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HoC_1shot_test

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HoC_1shot700

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Contact inhibition of locomotion ( CIL ) is the process by which cells stop the continual migration in the same direction after collision with another cell . Highly invasive malignant cells exhibit diminished CIL when they contact stromal cells , which allows invasion of the tissue by tumors . We show that Nm23-H1 is essential for the suppression of Rac1 through inactivation of Tiam1 at the sites of cell-cell contact , which plays a pivotal role in CIL . U87MG cells show CIL when they contact normal glia . In spheroid confrontation assays U87MG cells showed only limited invasion of the glial population , but reduction of Nm23-H1 expression in U87MG cells abrogated CIL resulting in invasion . In U87MG cells , Nm23-H1 is translocated to the sites of contact with glia through association with α-catenin and N-cadherin . Mutants of Nm23-H1 , which lacked the binding ability with Tiam1 , or α-catenin did not restore CIL . Moreover , the expression of ephrin-B1 in tumor cells disrupted CIL and promoted invasion . As one mechanism , ephrin-B1 inhibits the association of Nm23-H1 with Tiam1 , which contributes for activation of Rac1 . These results indicate a novel function of Nm23-H1 to control CIL , and its negative regulation by ephrin-B1 . OUTPUT:

evading growth suppressors;activating invasion and metastasis

HoC_1shot701

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Recent evidence indicates that the estrogen receptor-α-negative , androgen receptor ( AR)-positive molecular apocrine subtype of breast cancer is driven by AR signaling . The MDA-MB-453 cell line is the prototypical model of this breast cancer subtype ; its proliferation is stimulated by androgens such as 5α-dihydrotestosterone ( DHT ) but inhibited by the progestin medroxyprogesterone acetate ( MPA ) via AR-mediated mechanisms . We report here that the AR gene in MDA-MB-453 cells contains a G-T transversion in exon 7 , resulting in a receptor variant with a glutamine to histidine substitution at amino acid 865 ( Q865H ) in the ligand binding domain . Compared with wild-type AR , the Q865H variant exhibited reduced sensitivity to DHT and MPA in transactivation assays in MDA-MB-453 and PC-3 cells but did not respond to non-androgenic ligands or receptor antagonists . Ligand binding , molecular modeling , mammalian two-hybrid and immunoblot assays revealed effects of the Q865H mutation on ligand dissociation , AR intramolecular interactions , and receptor stability . Microarray expression profiling demonstrated that DHT and MPA regulate distinct transcriptional programs in MDA-MB-453 cells . Gene Set Enrichment Analysis revealed that DHT- but not MPA-regulated genes were associated with estrogen-responsive transcriptomes from MCF-7 cells and the Wnt signaling pathway . These findings suggest that the divergent proliferative responses of MDA-MB-453 cells to DHT and MPA result from the different genetic programs elicited by these two ligands through the AR-Q865H variant . This work highlights the necessity to characterize additional models of molecular apocrine breast cancer to determine the precise role of AR signaling in this breast cancer subtype . OUTPUT:

sustaining proliferative signaling

HoC_1shot702

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Sirtuin proteins regulate diverse cellular pathways that influence genomic stability , metabolism and ageing . SIRT7 is a mammalian sirtuin whose biochemical activity , molecular targets and physiological functions have been unclear . Here we show that SIRT7 is an NAD(+)-dependent H3K18Ac ( acetylated lysine 18 of histone H3 ) deacetylase that stabilizes the transformed state of cancer cells . Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets , where it deacetylates H3K18Ac and promotes transcriptional repression . The spectrum of SIRT7 target genes is defined in part by its interaction with the cancer-associated E26 transformed specific ( ETS ) transcription factor ELK4 , and comprises numerous genes with links to tumour suppression . Notably , selective hypoacetylation of H3K18Ac has been linked to oncogenic transformation , and in patients is associated with aggressive tumour phenotypes and poor prognosis . We find that deacetylation of H3K18Ac by SIRT7 is necessary for maintaining essential features of human cancer cells , including anchorage-independent growth and escape from contact inhibition . Moreover , SIRT7 is necessary for a global hypoacetylation of H3K18Ac associated with cellular transformation by the viral oncoprotein E1A . Finally , SIRT7 depletion markedly reduces the tumorigenicity of human cancer cell xenografts in mice . Together , our work establishes SIRT7 as a highly selective H3K18Ac deacetylase and demonstrates a pivotal role for SIRT7 in chromatin regulation , cellular transformation programs and tumour formation in vivo . OUTPUT:

evading growth suppressors

HoC_1shot703

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Elevated phosphorylation of estrogen receptor α ( ERα ) at serines 118 ( S118 ) and 167 ( S167 ) is associated with favorable outcome for tamoxifen adjuvant therapy and may serve as surrogate markers for a functional ERα signaling pathway in breast cancer . It is possible that loss of phosphorylation at S118 and/or S167 could disrupt ERα signaling , resulting in aggressive ERα-independent breast cancer cells . To this end , MCF-7 breast cancer cells were stably transfected with an ERα-specific short hairpin RNA that reduced endogenous ERα . The resulting cell line was stably transfected with wild-type ERα ( ER-AB cells ) , or ERα containing serine to alanine mutation at S118 or S167 ( S118A cells and S167A cells , respectively ) . These stable cell lines expressed approximately equivalent ERα compared with parental MCF-7 cells and were evaluated for growth , morphology , migration/invasion , and ERα-regulated gene expression . S118A cells and S167A cells exhibited increased growth and migration/invasion in vitro . Forward- and side-scatter flow cytometry revealed that S167A cells were smaller in size , and both S118A and S167A cells exhibited less cellular complexity . S118A and S167A cells expressed pancytokeratin and membrane localization of β-catenin and did not express vimentin , indicating retention of epithelial lineage markers . Expression of ERα-target genes and other genes regulated by ERα signaling or involved in breast cancer were markedly altered in both S118A and S167A cells . In summary , attenuated phosphorylation of ERα at S118 and S167 significantly affected cellular physiology and behavior in MCF-7 breast cancer cells , resulting in increased growth , migration/invasion , compromised expression of ERα target genes , and markedly altered gene expression patterns . OUTPUT:

activating invasion and metastasis

HoC_1shot704

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Hepatocellular carcinoma ( HCC ) is the fifth most common cancer worldwide . Major risk factors of HCC include infection with hepatitis B or C viruses , alcohol and non-alcoholic fatty liver disease . HCC is difficult to diagnose at early stage , and has a very poor survival rate when diagnosed at a late stage . The majority of HCC-related deaths result from local invasion ( to cause liver failure ) or distant metastases . There is an urgent need to identify effective molecular targets for the treatment of the disease . As the target of an established class of therapeutic agent thiazolidinediones ( TZDs ) , peroxisome-proliferator-activated receptor γ ( PPARγ ) has been widely studied for its role in the development of HCC . A substantial body of evidence based on in vitro and in vivo models indicates that the activation of PPARγ is able to inhibit HCC cell proliferation and tumor growth through inducing cell cycle arrest and apoptosis via the regulation of a panel of downstream effector molecules . PPARγ activation also induces an inhibitory effect on HCC metastasis . Meanwhile , there is new evidence suggesting that PPARγ inhibition could also be anti-tumorigenic . In the present review , we summarize the available information on the role of PPARγ in HCC development and spread , and discuss whether PPARγ activation by TZDs could play a role in the treatment of HCC , summarizing both in vitro and in vivo . Considering the available data , PPARγ seems to exert beneficial effects against HCC and may therefore represent as a therapeutic target . OUTPUT:

resisting cell death;sustaining proliferative signaling;activating invasion and metastasis

HoC_1shot705

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: MicroRNAs ( miRNAs ) are small noncoding RNAs , 19-24 nucleotides in length , that regulate gene expression and are expressed aberrantly in most types of cancer . MiRNAs also have been detected in the blood of cancer patients and can serve as circulating biomarkers . It has been shown that secreted miRNAs within exosomes can be transferred from cell to cell and can regulate gene expression in the receiving cells by canonical binding to their target messenger RNAs . Here we show that tumor-secreted miR-21 and miR-29a also can function by another mechanism , by binding as ligands to receptors of the Toll-like receptor ( TLR ) family , murine TLR7 and human TLR8 , in immune cells , triggering a TLR-mediated prometastatic inflammatory response that ultimately may lead to tumor growth and metastasis . Thus , by acting as paracrine agonists of TLRs , secreted miRNAs are key regulators of the tumor microenvironment . This mechanism of action of miRNAs is implicated in tumor-immune system communication and is important in tumor growth and spread , thus representing a possible target for cancer treatment . OUTPUT:

activating invasion and metastasis;tumor promoting inflammation

HoC_1shot706

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Non-small cell lung cancer ( NSCLC ) , accounting for 80% of lung cancers , is the leading cause of all cancer deaths . Previously , we demonstrated that delta-tocotrienol inhibits NSCLC cell proliferation , invasion and induces apoptosis by down-regulation of the Notch-1 signaling pathway . The objective of this study was to investigate whether delta-tocotrienol , could enhance the anticancer effects of cisplatin . Treatment with a combination of delta-tocotrienol and cisplatin resulted in a dose-dependent , significant inhibition of cell growth , migration , invasiveness , and induction of apoptosis in NSCLC cells , as compared to the single agents . This was associated with a decrease in NF-κB DNA binding activity , decrease in Notch-1 , Hes-1 , Bcl-2 and increase in cleaved Caspase-3 and PARP expressions . These results suggest that down-regulation of Notch-1 , via inhibition of NF-κB signaling pathways by delta-tocotrienol and cisplatin , in combination , could provide a potential novel approach for tumor arrest in NSCLC , while lowering the effective dose of cisplatin . OUTPUT:

activating invasion and metastasis;resisting cell death;sustaining proliferative signaling

HoC_1shot707

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Geraniol ( GOH ) , a naturally occurring monoterpene , has been shown to have antiproliferative , cell cycle arrest and apoptosis-inducing effects , and represents a promising cancer chemopreventive agent . In the present study , we investigated the chemopreventive potential of GOH ( 50 and 100 mg kg(-1) body weight ) against 7,12-dimethylbenz[a]anthracene ( DMBA)/12-O-tetradecanoylphorbol 13-acetate ( TPA)-mediated skin tumorigenesis in Swiss albino mice . The topical treatment of GOH , 30 min prior to TPA ( 2 µg per 200 µl of acetone ) treatment significantly inhibited TPA-induced skin edema , hyperplasia , COX-2 induction and oxidative stress response . The GOH treatment also resulted in reduction of TPA-induced ornithine decarboxylase activity and [ (3) H ] thymidine incorporation by 53% ( P < 0.001 ) and 41% ( P < 0.001 ) , respectively . We found that GOH treatment significantly inhibited the tumor incidence and number of tumors ( P < 0.001 ) and extended the latency period from 4 weeks in DMBA/TPA treatment group to 10 weeks in GOH-pretreated mice . Furthermore , we observed that GOH treatment significantly suppressed the Ras/Raf/ERK1/2 signaling pathway in skin tumor . Consistently , GOH-treated skin tumors showed reduced expression of Bcl-2 and increased expression of Bax in these lesions . Thus , it was concluded that GOH inhibits DMBA/TPA-mediated skin tumorigenesis by attenuating the Ras proliferation pathway and inducing pro-apoptotic state via inhibition of oxidative stress response and inflammation . OUTPUT:

tumor promoting inflammation;resisting cell death

HoC_1shot708

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Circulating tumour cells ( CTCs ) shed into blood from primary cancers include putative precursors that initiate distal metastases . Although these cells are extraordinarily rare , they may identify cellular pathways contributing to the blood-borne dissemination of cancer . Here , we adapted a microfluidic device for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to single-molecule RNA sequencing , identifying Wnt2 as a candidate gene enriched in CTCs . Expression of WNT2 in pancreatic cancer cells suppresses anoikis , enhances anchorage-independent sphere formation , and increases metastatic propensity in vivo . This effect is correlated with fibronectin upregulation and suppressed by inhibition of MAP3K7 ( also known as TAK1 ) kinase . In humans , formation of non-adherent tumour spheres by pancreatic cancer cells is associated with upregulation of multiple WNT genes , and pancreatic CTCs revealed enrichment for WNT signalling in 5 out of 11 cases . Thus , molecular analysis of CTCs may identify candidate therapeutic targets to prevent the distal spread of cancer . OUTPUT:

activating invasion and metastasis

HoC_1shot709

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Glycolysis is the initial step of glucose catabolism and is up-regulated in cancer cells ( the Warburg Effect ) . Such shifts toward a glycolytic phenotype have not been explored widely in other biological systems , and the molecular mechanisms underlying the shifts remain unknown . With proteomics , we observed increased glycolysis in disused human diaphragm muscle . In disused muscle , lung cancer , and H(2)O(2)-treated myotubes , we show up-regulation of the rate-limiting glycolytic enzyme muscle-type phosphofructokinase ( PFKm , >2 fold , P<0.05 ) and accumulation of lactate ( >150% , P<0.05 ) . Using microRNA profiling , we identify miR-320a as a regulator of PFKm expression . Reduced miR-320a levels ( to ∼50% of control , P<0.05 ) are associated with the increased PFKm in each of these diverse systems . Manipulation of miR-320a levels both in vitro and in vivo alters PFKm and lactate levels in the expected directions . Further , miR-320a appears to regulate oxidative stress-induced PFKm expression , and reduced miR-320a allows greater induction of glycolysis in response to H(2)O(2) treatment . We show that this microRNA-mediated regulation occurs through PFKm's 3 ' untranslated region and that Ets proteins are involved in the regulation of PFKm via miR-320a . These findings suggest that oxidative stress-responsive microRNA-320a may regulate glycolysis broadly within nature . OUTPUT:

cellular energetics;tumor promoting inflammation

HoC_1shot710

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Epstein-Barr virus ( EBV ) induces an uncoordinated S-phase-like cellular environment coupled with multiple prophase-like events in cells replicating the virus . The EBV encoded Ser/Thr kinase BGLF4 has been shown to induce premature chromosome condensation through activation of condensin and topoisomerase II and reorganization of the nuclear lamina to facilitate the nuclear egress of nucleocapsids in a pathway mimicking Cdk1 . However , the observation that RB is hyperphosphorylated in the presence of BGLF4 raised the possibility that BGLF4 may have a Cdk2-like activity to promote S-phase progression . Here , we investigated the regulatory effects of BGLF4 on cell cycle progression and found that S-phase progression and DNA synthesis were interrupted by BGLF4 in mammalian cells . Expression of BGLF4 did not compensate Cdk1 defects for DNA replication in S. cerevisiae . Using time-lapse microscopy , we found the fate of individual HeLa cells was determined by the expression level of BGLF4 . In addition to slight cell growth retardation , BGLF4 elicits abnormal chromosomal structure and micronucleus formation in 293 and NCP-TW01 cells . In Saos-2 cells , BGLF4 induced the hyperphosphorylation of co-transfected RB , while E2F1 was not released from RB-E2F1 complexes . The E2F1 regulated activities of the cyclin D1 and ZBRK1 promoters were suppressed by BGLF4 in a dose dependent manner . Detection with phosphoamino acid specific antibodies revealed that , in addition to Ser780 , phosphorylation of the DNA damage-responsive Ser612 on RB was enhanced by BGLF4 . Taken together , our study indicates that BGLF4 may directly or indirectly induce a DNA damage signal that eventually interferes with host DNA synthesis and delays S-phase progression . OUTPUT:

genomic instability and mutation;sustaining proliferative signaling

HoC_1shot711

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: While human embryonic stem cells ( hESCs ) and human embryonal carcinoma cells ( hECCs ) have been studied extensively at the levels of the genome , transcriptome , proteome and epigenome our knowledge of their corresponding metabolomes is limited . Here , we present the metabolic signatures of hESCs and hESCs obtained by untargeted gas chromatography coupled to mass spectrometry ( GC-MS ) . Whilst some metabolites are common to both cell types , representing the self-renewal and house-keeping signatures , others were either higher ( e.g. , octadecenoic acid , glycerol-3-phosphate , 4-hydroxyproline ) or lower ( e.g. , glutamic acid , mannitol , malic acid , GABA ) in hESCs ( H9 ) compared to hECCs ( NTERA2 ) , these represent cell type specific signatures . Further , our combined results of GC-MS and microarray based gene expression profiling of undifferentiated and OCT4-depleted hESCs are consistent with the Warburg effect which is increased glycolysis in embryonic cells and tumor cells in the presence of O(2) while oxidative phosphorylation ( OXPHOS ) is impaired or even shut down . RNAi-based OCT4 knock down mediated differentiation resulted in the activation of the poised OXPHOS machinery by expressing missing key proteins such as NDUFC1 , UQCRB and COX , increase in TCA cycle activity and decreased lactate metabolism . These results shed light on the metabolite layer of pluripotent stem cells and could potentially establish novel metabolic markers of self renewal and pluripotency . OUTPUT:

cellular energetics

HoC_1shot712

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Inhibition of cell proliferation by fenoterol and fenoterol derivatives in 1321N1 astrocytoma cells is consistent with β(2)-adrenergic receptor ( β(2)-AR ) stimulation . However , the events that result in fenoterol-mediated control of cell proliferation in other cell types are not clear . Here , we compare the effect of the β(2)-AR agonists ( R,R')-fenoterol ( Fen ) and ( R,R')-4-methoxy-1-naphthylfenoterol ( MNF ) on signaling and cell proliferation in HepG2 hepatocarcinoma cells by using Western blotting and [ (3)H]thymidine incorporation assays . Despite the expression of β(2)-AR , no cAMP accumulation was observed when cells were stimulated with isoproterenol or Fen , although the treatment elicited both mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt activation . Unexpectedly , isoproterenol and Fen promoted HepG2 cell growth , but MNF reduced proliferation together with increased apoptosis . The mitogenic responses of Fen were attenuated by 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol ( ICI 118,551 ) , a β(2)-AR antagonist , whereas those of MNF were unaffected . Because of the coexpression of β(2)-AR and cannabinoid receptors ( CBRs ) and their impact on HepG2 cell proliferation , these Gα(i)/Gα(o)-linked receptors may be implicated in MNF signaling . Cell treatment with ( R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-napthalenylmethanone ( WIN 55,212-2 ) , a synthetic agonist of CB(1)R and CB(2)R , led to growth inhibition , whereas inverse agonists of these receptors blocked MNF mitogenic responses without affecting Fen signaling . MNF responses were sensitive to pertussis toxin . The β(2)-AR-deficient U87MG cells were refractory to Fen , but responsive to the antiproliferative actions of MNF and WIN 55,212-2 . The data indicate that the presence of the naphthyl moiety in MNF results in functional coupling to the CBR pathway , providing one of the first examples of a dually acting β(2)-AR-CBR ligand . OUTPUT:

resisting cell death;sustaining proliferative signaling

HoC_1shot713

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Focal inflammation causes systemic fever . Cancer hyperthermia therapy results in shrinkage of tumors by various mechanisms , including induction of adaptive immune response . However , the physiological meaning of systemic fever and mechanisms of tumor shrinkage by hyperthermia have not been completely understood . In this study , we investigated how heat shock influences the adaptive immune system . We established a cytotoxic T lymphocyte ( CTL ) clone ( #IM29 ) specific for survivin , one of the tumor-associated antigens ( TAAs ) , from survivin peptide-immunized cancer patients ' peripheral blood , and the CTL activities were investigated in several temperature conditions ( 37-41�C ) . Cytotoxicity and IFN-γ secretion of CTL were greatest under 39�C condition , whereas they were minimum under 41�C . To address the molecular mechanisms of this phenomenon , we investigated the apoptosis status of CTLs , expression of CD3 , CD8 , and TCRαβ by flow cytometry , and expression of perforin , granzyme B , and Fas ligand by western blot analysis . The expression of perforin and granzyme B were upregulated under temperature conditions of 39 and 41�C . On the other hand , CTL cell death was induced under 41�C condition with highest Caspase-3 activity . Therefore , the greatest cytotoxicity activity at 39�C might depend on upregulation of cytotoxic granule proteins including perforin and granzyme B. These results suggest that heat shock enhances effector phase of the adaptive immune system and promotes eradication of microbe and tumor cells . OUTPUT:

resisting cell death

HoC_1shot714

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Src kinase is elevated in breast tumors that are ER/PR negative and do not overexpress HER2 , but clinical trials with Src inhibitors have shown little activity . The present study evaluated preclinical efficacy of a novel peptidomimetic compound , KX-01 ( KX2-391 ) , that exhibits dual action as an Src and pretubulin inhibitor . KX-01 was evaluated as a single-agent and in combination with paclitaxel in MDA-MB-231 , MDA-MB-157 , and MDA-MB-468 human ER/PR/HER2-negative breast cancer cells . Treatments were evaluated by growth/apoptosis , isobologram analysis , migration/invasion assays , tumor xenograft volume , metastasis , and measurement of Src , focal adhesion kinase ( FAK ) , microtubules , Ki67 , and microvessel density . KX-01 inhibited cell growth in vitro and in combination with paclitaxel resulted in synergistic growth inhibition . KX-01 resulted in a dose-dependent inhibition of MDA-MB-231 and MDA-MB-157 tumor xenografts ( 1 and 5 mg/kg , twice daily ) . KX-01 inhibited activity of Src and downstream mediator FAK in tumors that was coincident with reduced proliferation and angiogenesis and increased apoptosis . KX01 also resulted in microtubule disruption in tumors . Combination of KX-01 with paclitaxel resulted in significant regression of MDA-MB-231 tumors and reduced metastasis to mouse lung and liver . KX-01 is a potently active Src/pretubulin inhibitor that inhibits breast tumor growth and metastasis . As ER/PR/HER2-negative patients are candidates for paclitaxel therapy , combination with KX-01 may potentiate antitumor efficacy in management of this aggressive breast cancer subtype . OUTPUT:

inducing angiogenesis;resisting cell death;sustaining proliferative signaling;activating invasion and metastasis

HoC_1shot715

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Lentinula edodes mycelia ( L.E.M. ) is a dried powder extracted from shiitake mushrooms ( Lentinula edodes ) . We previously demonstrated that it has immunomodulatory effects . In this paper , the direct cytotoxic effects of the polysaccharide-rich fraction of L.E.M . ( L.E.M. ethanol precipitate ; LEP ) on HepG2 human hepatocellular carcinoma ( HCC ) cells were investigated . LEP directly killed the HepG2 cells efficaciously , but had only minor effects on normal rat hepatocytes and normal mouse dermal cells under the same conditions . Characteristic morphological changes associated with apoptosis such as shrinkage , rounding , and floating as well as chromatin condensation were confirmed ; terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling ( TUNEL ) staining was positive as determined by fluorescence microscopy analyses . The caspase-3 and -8 death receptor pathway was found largely responsible for the apoptotic death of HepG2 cells treated with LEP . In conclusion , LEP can directly induce apoptosis of HepG2 cells , and thus may have potential chemotherapeutic applications for the treatment of HCC . OUTPUT:

resisting cell death

HoC_1shot716

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Epigenetic deregulation of gene expression has a role in the initiation and progression of prostate cancer ( PCa ) . The histone methyltransferase MMSET/WHSC1 ( Multiple Myeloma SET domain ) is overexpressed in a number of metastatic tumors , but its mechanism of action has not been defined . In this work , we found that PCa cell lines expressed significantly higher levels of MMSET compared with immortalized , non-transformed prostate cells . Knockdown experiments showed that , in metastatic PCa cell lines , dimethylation of lysine 36 and trimethylation of lysine 27 on histone H3 ( H3K36me2 and H3K27me3 , respectively ) depended on MMSET expression , whereas depletion of MMSET in benign prostatic cells did not affect chromatin modifications . Knockdown of MMSET in DU145 and PC-3 tumor cells decreased cell proliferation , colony formation in soft agar and strikingly diminished cell migration and invasion . Conversely , overexpression of MMSET in immortalized , non-transformed RWPE-1 cells promoted cell migration and invasion , accompanied by an epithelial-mesenchymal transition ( EMT ) . Among a panel of EMT-promoting genes analyzed , TWIST1 expression was strongly activated in response to MMSET . Chromatin immunoprecipitation analysis demonstrated that MMSET binds to the TWIST1 locus and leads to an increase in H3K36me2 , suggesting a direct role of MMSET in the regulation of this gene . Depletion of TWIST1 in MMSET-overexpressing RWPE-1 cells blocked cell invasion and EMT , indicating that TWIST1 was a critical target of MMSET , responsible for the acquisition of an invasive phenotype . Collectively , these data suggest that MMSET has a role in PCa pathogenesis and progression through epigenetic regulation of metastasis-related genes . OUTPUT:

activating invasion and metastasis

HoC_1shot717

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Angiogenesis is critical for cancer growth and metastasis . Steps of angiogenesis are energy consuming , while vascular endothelial cells are highly glycolytic . Glioblastoma multiforme ( GBM ) is a highly vascular tumor and this enhances its aggressiveness . D-amino acid oxidase ( DAO ) is a promising therapeutic protein that induces oxidative stress upon acting on its substrates . Oxidative stress-energy depletion ( OSED ) therapy was recently reported ( El Sayed et al. , Cancer Gene Ther , 19 , 1-18 , 2012 ) . OSED combines DAO-induced oxidative stress with energy depletion caused by glycolytic inhibitors such as 3-bromopyruvate ( 3BP ) , a hexokinase II inhibitor that depleted ATP in cancer cells and induced production of hydrogen peroxide. 3BP disturbs the Warburg effect and antagonizes effects of lactate and pyruvate ( El Sayed et al. , J Bioenerg Biomembr , 44 , 61-79 , 2012 ) . Citrate is a natural organic acid capable of inhibiting glycolysis by targeting phosphofructokinase . Here , we report that DAO , 3BP and citrate significantly inhibited angiogenesis , decreased the number of vascular branching points and shortened the length of vascular tubules . OSED delayed the growth of C6/DAO glioma cells. 3BP combined with citrate delayed the growth of C6 glioma cells and decreased significantly the number and size of C6 glioma colonies in soft agar . Human GBM cells ( U373MG ) were resistant to chemotherapy e.g. cisplatin and cytosine arabinoside , while 3BP was effective in decreasing the viability and disturbing the morphology of U373MG cells . OUTPUT:

inducing angiogenesis

HoC_1shot718

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND It has been proven that metastasis-associated in colon cancer 1 ( MACC1 ) is a new gene that is related to the invasion and metastasis of tumors . MACC1 also regulates c-met expression . The aim of this study is to explore the expressions of MACC1 and hepatocyte growth factor receptor ( c-met ) , and its relationship with invasion , metastasis , and prognosis of non-small cell lung cancer ( NSCLC ) . METHODS MACC1 and c-met expressions were detected in 103 cases of NSCLC and 40 cases of neighboring normal lung cancer tissue using immunohistochemistry . RESULTS MACC1 and c-met expressions were significantly higher in lung cancer tissues than that in neighboring normal tissue ( P<0.001 ) . MACC1 and c-met expressions were associated with poor differentiation , advanced T stages , lymph node metastasis , and advanced TNM stages ( P<0.05 ) of NSCLC , but not with sex , age , smoking , and histological classification ( P>0.05 ) . In addition , a positive correlation between MACC1 and c-met expressions was observed ( r=0.403 , P<0.001 ) . The result from the Kaplan-Meier survival analysis showed that the five-year survival rate in patients with positive MACC1 and c-met expressions was remarkanly lower than that in patients with negative expressions ( P<0.05 ) . The result from the Cox regression analysis showed that MACC1 expression was an independent prognostic factor for NSCLC ( P=0.026 ) . CONCLUSIONS MACC1 and c-met have an important function in the differentiation , invasion , and metastasis of NSCLC . MACC1 and c-met have poor prognosis in patients with NSCLC . Moreover , MACC1 expression is an independent prognostic factor for NSCLC . OUTPUT:

activating invasion and metastasis

HoC_1shot719

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Epigenetic changes in pediatric neuroblastoma may contribute to the aggressive pathophysiology of this disease , but little is known about the basis for such changes . In this study , we examined a role for the DNA methyltransferase DNMT3B , in particular , the truncated isoform DNMT3B7 , which is generated frequently in cancer . To investigate if aberrant DNMT3B transcripts alter DNA methylation , gene expression , and phenotypic character in neuroblastoma , we measured DNMT3B expression in primary tumors . Higher levels of DNMT3B7 were detected in differentiated ganglioneuroblastomas compared to undifferentiated neuroblastomas , suggesting that expression of DNMT3B7 may induce a less aggressive clinical phenotype . To test this hypothesis , we investigated the effects of enforced DNMT3B7 expression in neuroblastoma cells , finding a significant inhibition of cell proliferation in vitro and angiogenesis and tumor growth in vivo . DNMT3B7-positive cells had higher levels of total genomic methylation and a dramatic decrease in expression of the FOS and JUN family members that comprise AP1 transcription factors . Consistent with an established antagonistic relationship between AP1 expression and retinoic acid receptor activity , increased differentiation was seen in the DNMT3B7-expressing neuroblastoma cells following treatment with all-trans retinoic acid ( ATRA ) compared to controls . Our results indicate that DNMT3B7 modifies the epigenome in neuroblastoma cells to induce changes in gene expression , inhibit tumor growth , and increase sensitivity to ATRA . OUTPUT:

inducing angiogenesis;sustaining proliferative signaling

HoC_1shot720

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Genetic and epigenetic changes in the von Hippel-Lindau ( VHL ) tumour suppressor gene are common in sporadic conventional ( clear cell ) renal cell carcinoma ( ccRCC ) . The effects on VHL expression are unknown but increased understanding may be relevant clinically , either in terms of prognosis or in therapy selection . We have examined the expression of VHL mutant RNA in 84 ccRCC tumours previously screened for mutations in genomic DNA , 56 of which contained 52 unique mutations or polymorphisms . Based on the predicted change to the primary amino acid sequence , 24 of the mutations were missense , 11 resulted in frameshifts with premature truncation , 9 resulted in immediate truncation at the site of the mutation and 2 were frameshifts which extended the reading frame beyond the normal stop codon . Nine tumours had intronic variants , including substitution of invariant residues at splice sites , deletion of nucleotides spanning the exon-intron junction , an intronic variant of unknown function and the polymorphism c.463+43A>G . Four variants were identified which were present in genomic DNA but not in mRNA . Three of these , all encoding apparent missense changes to the primary amino acid sequence , were located close to the ends of exons , reduced the strength of the splice site and function as null rather than missense variants . One nonsense variant was not detectable in mRNA but all other mutations resulting in premature truncation codons ( PTCs ) were , suggesting truncating VHL mutations may potentially generate truncated VHL protein . An intronic variant , c.341‑11T>A , previously regarded as of unknown function , is associated with an increased level of skipping of exon 2 and may , therefore , reduce production of pVHL . Our data show that the biological consequences of VHL mutations are not necessarily predictable from the sequence change of the mutation and that for the majority of VHL mutations , the potential for the generation of mutant protein exists . OUTPUT:

genomic instability and mutation

HoC_1shot721

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Although interleukin-28A ( IL-28A ) is believed to have an antiviral effect , its role in tumor migration requires further examination . The present study was intended to verify the effect of IL-28A on the migration of UMUC-3 bladder cancer cells . IL-28A and its receptor IL-28AR1 mRNA were detected in UMUC-3 cells . Although exogenous IL-28A showed no effect on cell proliferation , a wound-healing migration assay showed that the migration of UMUC-3 cells was induced by IL-28A . Furthermore , treatment of the cells with IL-28A significantly promoted MMP-9 expression via binding activities of NF-κB and AP-1 . IL-28A also induced the activation of p38MAPK and Jak2-Stat2 signaling . Using the p38MAPK inhibitor SB203580 and the dominant-negative plasmid DN-p38 , we found evidence that the inhibition of p38MAPK signaling suppressed the effects of IL-28A including wound-healing migration and MMP-9 expression by activation of NF-κB and AP-1 binding in UMUC-3 cells . However , Jak-2 inhibition by AG490 did not affect IL-28A-induced migration of UMUC-3 cells . Collectively , we suggest for the first time that the p38MAPK pathway mediates IL-28A-induced cell migration through MMP-9 expression by activating NF-κB and AP-1 binding motifs . OUTPUT:

sustaining proliferative signaling;activating invasion and metastasis

HoC_1shot722

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: We have evaluated DNA damage ( DNA adduct formation ) after feeding benzo[a]pyrene ( BP ) to wild-type ( WT ) and cancer-susceptible Xpa(-/-)p53(+/-) mice deficient in nucleotide excision repair and haploinsufficient for the tumor suppressor p53 . DNA damage was evaluated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry ( HPLC/ES-MS/MS ) , which measures r7,t8,t9-trihydroxy-c-10-(N ( 2)-deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene ( BPdG ) , and a chemiluminescence immunoassay ( CIA ) , using anti-r7,t8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene ( BPDE)-DNA antiserum , which measures both BPdG and the other stable BP-DNA adducts . When mice were fed 100 ppm BP for 28 days , BP-induced DNA damage measured in esophagus , liver and lung was typically higher in Xpa(-/-)p53(+/-) mice , compared with WT mice . This result is consistent with the previously observed tumor susceptibility of Xpa(-/-)p53(+/-) mice . BPdG , the major DNA adduct associated with tumorigenicity , was the primary DNA adduct formed in esophagus ( a target tissue in the mouse ) , whereas total BP-DNA adducts predominated in higher levels in the liver ( a non-target tissue in the mouse ) . In an attempt to lower BP-induced DNA damage , we fed the WT and Xpa(-/-)p53(+/-) mice 0.3% chlorophyllin ( CHL ) in the BP-containing diet for 28 days . The addition of CHL resulted in an increase of BP-DNA adducts in esophagus , liver and lung of WT mice , a lowering of BPdG in esophagi of WT mice and livers of Xpa(-/-)p53(+/-) mice and an increase of BPdG in livers of WT mice . Therefore , the addition of CHL to a BP-containing diet showed a lack of consistent chemoprotective effect , indicating that oral CHL administration may not reduce PAH-DNA adduct levels consistently in human organs . OUTPUT:

genomic instability and mutation

HoC_1shot723

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Nonmelanoma skin cancer ( NMSC ) is by far the most frequent type of cancer in humans . NMSC includes several types of malignancies with different clinical outcomes , the most frequent being basal and squamous cell carcinomas . We have used the Sleeping Beauty transposon/transposase system to identify somatic mutations associated with NMSC . Transgenic mice bearing multiple copies of a mutagenic Sleeping Beauty transposon T2Onc2 and expressing the SB11 transposase under the transcriptional control of regulatory elements from the keratin K5 promoter were treated with TPA , either in wild-type or Ha-ras mutated backgrounds . After several weeks of treatment , mice with transposition developed more malignant tumors with decreased latency compared with control mice . Transposon/transposase animals also developed basal cell carcinomas . Genetic analysis of the transposon integration sites in the tumors identified several genes recurrently mutated in different tumor samples , which may represent novel candidate cancer genes . We observed alterations in the expression levels of some of these genes in human tumors . Our results show that inactivating mutations in Notch1 and Nsd1 , among others , may have an important role in skin carcinogenesis . OUTPUT:

genomic instability and mutation

HoC_1shot724

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: A 34-year-old Japanese woman presented with left supraclavicular lymph node swelling . Computed tomography scans revealed a mass on the left lower lobe , pulmonary nodules , and pleural effusion . A lymph node biopsy revealed large-cell carcinoma with an epidermal growth factor receptor ( EGFR ) deletion mutation , L747-T751 in exon 19 . Although malignant pleural effusions carried the same EGFR mutation , progressive pleural effusions after treatment with chemotherapy , gefitinib , and erlotinib did not show any EGFR mutation . A cell line established from the pleural effusion 3 days before the patient expired also did not harbor the EGFR mutation . Histological sections of the lymph node of the patient were similar to those of the xenograft tumor of the cell line . There may be genetic heterogeneity in EGFR mutant tumors . OUTPUT:

genomic instability and mutation;sustaining proliferative signaling

HoC_1shot725

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND Colorectal cancer is one of the main cancers in the Western world . About 90% of the deaths arise from formation of distant metastasis . The expression of the newly identified gene metastasis associated in colon cancer 1 ( MACC1 ) is a prognostic indicator for colon cancer metastasis . Here , we analyzed for the first time the impact of single nucleotide polymorphisms ( SNPs ) in the coding region of MACC1 for clinical outcome of colorectal cancer patients . Additionally , we screened met proto-oncogene ( Met ) , the transcriptional target gene of MACC1 , for mutations . METHODS We sequenced the coding exons of MACC1 in 154 colorectal tumors ( stages I , II and III ) and the crucial exons of Met in 60 colorectal tumors ( stages I , II and III ) . We analyzed the association of MACC1 polymorphisms with clinical data , including metachronous metastasis , UICC stages , tumor invasion , lymph node metastasis and patients ' survival ( n = 154 , stages I , II and III ) . Furthermore , we performed biological assays in order to evaluate the functional impact of MACC1 SNPs on the motility of colorectal cancer cells . RESULTS We genotyped three MACC1 SNPs in the coding region . Thirteen % of the tumors had the genotype cg ( rs4721888 , L31V ) , 48% a ct genotype ( rs975263 , S515L ) and 84% a gc or cc genotype ( rs3735615 , R804T ) . We found no association of these SNPs with clinicopathological parameters or with patients ' survival , when analyzing the entire patients ' cohort . An increased risk for a shorter metastasis-free survival of patients with a ct genotype ( rs975263 ) was observed in younger colon cancer patients with stage I or II ( P = 0.041 , n = 18 ) . In cell culture , MACC1 SNPs did not affect MACC1-induced cell motility and proliferation . CONCLUSION In summary , the identification of coding MACC1 SNPs in primary colorectal tumors does not improve the prediction for metastasis formation or for patients ' survival compared to MACC1 expression analysis alone . The ct genotype ( rs975263 ) might be associated with a reduced survival for younger colon cancer patients in early stages . However , further studies with larger sample sizes are needed . OUTPUT:

activating invasion and metastasis

HoC_1shot726

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Breast cancer includes high number of molecular entities targetable by specific agents . In this study , array CGH and PIK3CA/AKT1 mutations were used to drive patients into targeted therapy . A prospective molecular analysis was offered to metastatic breast cancer patients for whom samples were collected prospectively or retrospectively either from frozen or paraffin-embedded tissue . Analyses were performed using array CGH ( Agilent platform ) and PIK3CA ( exon 10 and 21 ) and AKT1 mutations were explored by standard Sanger sequencing . One hundred and eight patients were included . Good quality CGH was obtained in 79% cases and was better for frozen samples . Genomic alterations were identified in 50% of patients including 11 PIK3CA and 8 AKT1 mutations . Eighteen treatments ( 17 patients ) were administered according to their molecular profile with evidence of activity in nine . Reasons for not providing a genomic-driven treatment included absence of progressive disease ( 38% ) , investigator's choice ( 9% ) , rapid PD ( 19% ) , and no drug access ( 21% ) . Array CGH correctly identified Her2 status in 97% cases ; failures were related to low % of tumour cells . Our study showed that array CGH is feasible in the context of daily practice and , in combination with PIK3CA/AKT1 mutations , identifies a significant number of actionable molecular alterations that allow driving patients into specific targeted agents . OUTPUT:

genomic instability and mutation

HoC_1shot727

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND : To quantify tumour angiogenesis , microvessel density ( MVD ) has been widely used . We here present a novel angiogenesis marker , microvessel proliferation ( MVP ) , based on dual immunohistochemical staining of nestin and Ki-67 . Immature endothelial cells express nestin , and when co-expressed with the proliferation marker Ki-67 , the number of proliferating immature blood vessels can be measured . MATERIALS AND METHODS : Microvessel proliferation was evaluated in 178 breast cancer samples and estimated by vascular proliferation index ( VPI ) , the ratio between the number of vessels containing proliferating endothelial cells and the total number of immature vessels . RESULTS : High VPI was strongly associated with several markers of aggressive breast cancer , such as negative oestrogen receptor ( ER ) status ( p=0.003 ) , high tumour cell proliferation by Ki-67 ( p=0.004 ) , high p53 expression ( p=0.001 ) , and five profiles for the basal-like phenotype ( odds ratios ( OR ) ; range 3.4-6.3 ) . Also , high VPI was significantly associated with interval detected breast cancer compared with screening detected lesions ( p<0.0005 ) , and adverse outcome in univariate and multivariate survival analysis ( p=0.034 and p=0.022 , respectively ) . CONCLUSION : Microvessel proliferation is a novel marker of ongoing angiogenesis and was associated with aggressive tumour features , basal-like phenotypes , interval presentation , and prognosis in this series of breast cancer . OUTPUT:

sustaining proliferative signaling;inducing angiogenesis

HoC_1shot728

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Liver cancer , predominantly hepatocellular carcinoma ( HCC ) , represents a complex and fatal malignancy driven primarily by oxidative stress and inflammation . Due to dismal prognosis and limited therapeutic intervention , chemoprevention has emerged as a viable approach to reduce the morbidity and mortality of HCC . Pomegranate fruit is a rich source of phytochemicals endowed with potent antioxidant and anti-inflammatory properties . We previously reported that pomegranate phytochemicals inhibit diethylnitrosamine ( DENA)-initiated hepatocarcinogenesis in rats though nuclear factor E2-related factor 2 ( Nrf2)-mediated antioxidant mechanisms . Since Nrf2 also acts as a key mediator of the nuclear factor-kappaB ( NF-κB)-regulated inflammatory pathway , our present study investigated the anti-inflammatory mechanisms of a pomegranate emulsion ( PE ) during DENA-induced rat hepatocarcinogenesis . Rats were administered with PE ( 1 or 10 g/kg ) 4 weeks before and 18 weeks following DENA initiation . There was a significant increase in hepatic expressions of inducible nitric oxide synthase , 3-nitrotyrosine , heat shock protein 70 and 90 , cyclooxygenase-2 and NF-κB in DENA-exposed rat livers . PE dose-dependently suppressed all aforementioned elevated inflammatory markers . A conspicuous finding of this study involves lack of cardiotoxicity of PE as assessed by monitoring cardiac function using noninvasive echocardiography . Our results provide substantial evidence that suppression of the inflammatory cascade through modulation of NF-κB signaling pathway may represent a novel mechanism of liver tumor inhibitory effects of PE against experimental hepatocarcinogenesis . Data presented here coupled with those of our earlier study underline the importance of simultaneously targeting two interconnected molecular circuits , namely , Nrf2-mediated redox signaling and NF-κB-regulated inflammatory pathway , by pomegranate phytoconstituents to achieve chemoprevention of HCC . OUTPUT:

tumor promoting inflammation

HoC_1shot729

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Bioenergetic profiling of tumors is a new challenge of cancer research and medicine as therapies are currently being developed . Meanwhile , methodological means must be proposed to gather information on tumor metabolism in order to adapt these potential therapies to the bioenergetic specificities of tumors . Studies performed on tumors and cancer cell lines have shown that cancer cells bioenergetics is highly variable . This profile changes with microenvironmental conditions ( eg. substrate availability ) , the oncogenes activated ( and the tumor suppressors inactivated ) and the interaction with the stroma ( i.e. reverse Warburg effect ) . Here , we assessed the power of metabolic footprinting ( MFP ) to unravel the bioenergetics and associated anabolic changes induced by three oncogenes , c-Myc , KLF4 and Oct1 . The MFP approach provides a quantitative analysis of the metabolites secreted and consumed by cancer cells . We used ultra performance liquid chromatography for quantifying the amino acid uptake and secretion . To investigate the potential oncogene-mediated alterations in mitochondrial metabolism , we measured oxygen consumption rate and ATP production as well as the glucose uptake and lactate release . Our findings show that c-Myc deficiency initiates the Warburg effect along with a reduction of mitochondrial respiration . KLF4 deficiency also stimulated glycolysis , albeit without cellular respiration impairment . In contrast , Oct1 deficiency reduced glycolysis and enhanced oxidative phosphorylation efficiency . MFP revealed that c-Myc , KLF4 and Oct1 altered amino acid metabolism with specific patterns . We identified isoleucine , α-aminoadipic acid and GABA ( γ-aminoisobutyric acid ) as biomarkers related . Our findings establish the impact of Oct1 , KLF4 and c-Myc on cancer bioenergetics and evidence a link between oncosecretomics and cellular bioenergetics profile . OUTPUT:

cellular energetics

HoC_1shot730

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Colorectal tumors are continuously exposed to an inflammatory environment , which together with mitogenic signals sustain several cancer hallmarks . Nuclear factor-kappa B ( NFκB ) is a major regulator of inflammation and variation in NFκB-associated genes could potentially be used as biomarkers to identify patients with increased risk of colorectal cancer ( CRC ) development , and/or a rapidly progressing disease . In this study , 348 CRC cases and 806 randomly selected healthy individuals from southeastern Sweden were examined with regard to seven polymorphisms in NFκB pathway-associated genes . Log-rank-tests and Cox proportional hazard regression analysis examined the association between the polymorphisms and CRC-specific survival , whereas chi-square tests and logistic regression analysis were used to test for associations between the polymorphisms and CRC susceptibility . Gene expression and loss of heterozygosity analyses of TNFAIP3 were carried out in a subset of tumors to assess its role as a tumor suppressor in CRC . Heterozygous and polymorphic TNFAIP3 ( rs6920220 ) , heterozygous NLRP3 ( Q705K ) and polymorphic NFκB -94 ATTG ins/del genotypes were found to be associated with poorer survival in patients diagnosed with invasive CRC ( aHR = 5.2 , 95% CI : 2.5-10.9 , P &lt ; 0.001 ) . TNFAIP3 mRNA levels were significantly decreased in tumors compared with adjacent non-neoplastic mucosa ( P &lt ; 0.0001 ) and loss of heterozygosity of 6q23.3 ( TNFAIP3 ) was detected in 17% of cases , whereas only 2.5% of the investigated specimens displayed TNFAIP3 gene mutations . We propose that TNFAIP3 ( rs6920220 ) , NLRP3 ( Q705K ) and NFκB -94 ATTG ins/del polymorphisms are associated with poor survival in patients with advanced CRC and may be used as prognostic markers . Experimental results indicate that TNFAIP3 may act as a tumor suppressor in CRC . OUTPUT:

genomic instability and mutation

HoC_1shot731

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Interleukin-23 ( IL-23 ) plays an essential role in the mucosal immune system . It has been suggested that IL-23 is able to induce carcinogenesis as well as inflammation and a recent study revealed that IL-23R is expressed in colorectal carcinoma cells . However , neither the differences in the IL-23R expression among the patients nor the concrete functions of IL-23 in colorectal carcinoma cells have been revealed . The aim of the present study was to examine the characteristics of IL-23R expression in colorectal carcinoma and the direct effects of IL-23 on colorectal cancer cells . We examined the IL-23R expression in human colorectal cancer tissue samples by immunohistochemistry . Cell proliferation and invasion assays under IL-23 stimulation were performed using cultured cells derived from colorectal cancer . ELISA and real-time PCR were used to evaluate the transforming growth factor ( TGF)-β production due to IL-23 stimulation . All of the TNM stage IV patients were positive for IL-23R . IL-23R expression in the carcinoma tissue was also relatively high at the deepest point of invasion in certain cases . The proliferative and invasive activities and/or TGF-β production of DLD-1 cells increased by IL-23 stimulation , whereas no change was observed in the activities of MIP101 and KM12c cells . IL-23 directly enhanced the malignancy of the colon carcinoma cells . An autocrine mechanism via TGF-β production may underlie these effects . IL-23 is therefore a potential target for cancer immunotherapy . However , the homogeneity in IL-23R expression and the effects of IL-23 on colorectal carcinoma cells should be considered . OUTPUT:

activating invasion and metastasis

HoC_1shot732

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND To investigate the dynamics of inter- and intratumoral molecular alterations during tumor progression in recurrent gliomas . METHODOLOGY/PRINCIPAL FINDINGS To address intertumoral heterogeneity we investigated non-microdissected tumor tissue of 106 gliomas representing 51 recurrent tumors . To address intratumoral heterogeneity a set of 16 gliomas representing 7 tumor pairs with at least one recurrence , and 4 single mixed gliomas were investigated by microdissection of distinct oligodendroglial and astrocytic tumor components . All tumors and tumor components were analyzed for allelic loss of 1p/19q ( LOH 1p/19q ) , for TP53- mutations and for R132 mutations in the IDH1 gene . The investigation of non-microdissected tumor tissue revealed clonality in 75% ( 38/51 ) . Aberrant molecular alterations upon recurrence were detected in 25% ( 13/51). 64% ( 9/14 ) of these were novel and associated with tumor progression . Loss of previously detected alterations was observed in 36% ( 5/14 ) . One tumor pair ( 1/14 ; 7% ) was significant for both . Intratumoral clonality was detected in 57% ( 4/7 ) of the microdissected tumor pairs and in 75% ( 3/4 ) of single microdissected tumors. 43% ( 3/7 ) of tumor pairs and one single tumor ( 25% ) revealed intratumoral heterogeneity . While intratumoral heterogeneity affected both the TP53- mutational status and the LOH1p/19q status , all tumors with intratumoral heterogeneity shared the R132 IDH1- mutation as a common feature in both their microdissected components . CONCLUSIONS/SIGNIFICANCE The majority of recurrent gliomas are of monoclonal origin . However , the detection of divertive tumor cell clones in morphological distinct tumor components sharing IDH1- mutations as early event may provide insight into the tumorigenesis of true mixed gliomas . OUTPUT:

genomic instability and mutation

HoC_1shot733

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The tumor suppressor gene p53 has been implicated in the regulation of epithelial-mesenchymal transition ( EMT ) and tumor metastasis by regulating microRNA ( miRNA ) expression . Here , we report that mutant p53 exerts oncogenic functions and promotes EMT in endometrial cancer ( EC ) by directly binding to the promoter of miR-130b ( a negative regulator of ZEB1 ) and inhibiting its transcription . We transduced p53 mutants into p53-null EC cells , profiled the miRNA expression by miRNA microarray and identified miR-130b as a potential target of mutant p53 . Ectopic expression of p53 mutants repressed the expression of miR-130b and triggered ZEB1-dependent EMT and cancer cell invasion . Loss of an endogenous p53 mutation increased the expression of miR-130b , which resulted in reduced ZEB1 expression and attenuation of the EMT phenotype . Furthermore , re-expression of miR-130b suppressed mutant p53-induced EMT and ZEB1 expression . Importantly , the expression of miR-130 was significantly reduced in EC tissues , and patients with higher expression levels of miR-130b survived longer . These data provide a novel understanding of the roles of p53 gain-of-function mutations in accelerating tumor progression and metastasis through modulation of the miR-130b-ZEB1 axis . OUTPUT:

activating invasion and metastasis;genomic instability and mutation

HoC_1shot734

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND Agricultural products and by products provide the primary materials for a variety of technological applications in diverse industrial sectors . Agro-industrial wastes , such as cotton and curaua fibers , are used to prepare nanofibers for use in thermoplastic films , where they are combined with polymeric matrices , and in biomedical applications such as tissue engineering , amongst other applications . The development of products containing nanofibers offers a promising alternative for the use of agricultural products , adding value to the chains of production . However , the emergence of new nanotechnological products demands that their risks to human health and the environment be evaluated . This has resulted in the creation of the new area of nanotoxicology , which addresses the toxicological aspects of these materials . PURPOSE AND METHODS Contributing to these developments , the present work involved a genotoxicological study of different nanofibers , employing chromosomal aberration and comet assays , as well as cytogenetic and molecular analyses , to obtain preliminary information concerning nanofiber safety . The methodology consisted of exposure of Allium cepa roots , and animal cell cultures ( lymphocytes and fibroblasts ) , to different types of nanofibers . Negative controls , without nanofibers present in the medium , were used for comparison . RESULTS The nanofibers induced different responses according to the cell type used . In plant cells , the most genotoxic nanofibers were those derived from green , white , and brown cotton , and curaua , while genotoxicity in animal cells was observed using nanofibers from brown cotton and curaua . An important finding was that ruby cotton nanofibers did not cause any significant DNA breaks in the cell types employed . CONCLUSION This work demonstrates the feasibility of determining the genotoxic potential of nanofibers derived from plant cellulose to obtain information vital both for the future usage of these materials in agribusiness and for an understanding of their environmental impacts . OUTPUT:

genomic instability and mutation

HoC_1shot735

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: 22Rv1 is a common prostate cancer cell line used in xenograft mouse experiments as well as in vitro cell culture assays to study aspects of prostate cancer tumorigenesis . Recently , this cell line was shown to harbor multiple copies of a gammaretrovirus , called XMRV , integrated in its genome . While the original prostate cancer xenograft CWR22 is free of any retrovirus , subsequently generated cell lines 22Rv1 and CWR-R1 , carry this virus and additionally shed infectious gammaretroviral particles in their supernatant . Although XMRV most likely was generated by recombination events in cell culture this virus has been demonstrated to infect human cells in vitro and 22Rv1 as well as CWR-R1 cells are now considered biosafety 2 reagents . Here , we demonstrate that 22Rv1 cells with reduced retroviral transcription show reduced tumor angiogenesis and increased necrosis of the primary tumor derived from xenografted cells in scid mice when compared to the parental cell line . The presence of XMRV transcripts significantly increases secretion of osteopontin ( OPN ) , CXCL14 , IL13 and TIMP2 in 22Rv1 cells . Furthermore , these data are supported by in vitro cell invasion and differentiation assays . Collectively , our data suggest that the presence of XMRV transcripts at least partially contributes to 22Rv1 characteristics observed in vitro and in vivo with regard to migration , invasion and tumor angiogenesis . We propose that data received with 22Rv1 cells or equivalent cells carrying xenotropic gammaretroviruses should be carefully controlled including other prostate cancer cell lines tested for viral sequences . OUTPUT:

inducing angiogenesis;resisting cell death;activating invasion and metastasis

HoC_1shot736

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Metastatic cancer is extremely difficult to treat , and the presence of metastases greatly reduces a cancer patient's likelihood of long-term survival . The ZEB1 transcriptional repressor promotes metastasis through downregulation of microRNAs ( miRs ) that are strong inducers of epithelial differentiation and inhibitors of stem cell factors . Given that each miR can target multiple genes with diverse functions , we posited that the prometastatic network controlled by ZEB1 extends beyond these processes . We tested this hypothesis using a mouse model of human lung adenocarcinoma metastasis driven by ZEB1 , human lung carcinoma cells , and human breast carcinoma cells . Transcriptional profiling studies revealed that ZEB1 controls the expression of numerous oncogenic and tumor-suppressive miRs , including miR-34a . Ectopic expression of miR-34a decreased tumor cell invasion and metastasis , inhibited the formation of promigratory cytoskeletal structures , suppressed activation of the RHO GTPase family , and regulated a gene expression signature enriched in cytoskeletal functions and predictive of outcome in human lung adenocarcinomas . We identified several miR-34a target genes , including Arhgap1 , which encodes a RHO GTPase activating protein that was required for tumor cell invasion . These findings demonstrate that ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression and provide a compelling rationale to develop miR-34a as a therapeutic agent in lung cancer patients . OUTPUT:

activating invasion and metastasis

HoC_1shot737

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Identifying genomic alterations driving breast cancer is complicated by tumor diversity and genetic heterogeneity . Relevant mouse models are powerful for untangling this problem because such heterogeneity can be controlled . Inbred Chaos3 mice exhibit high levels of genomic instability leading to mammary tumors that have tumor gene expression profiles closely resembling mature human mammary luminal cell signatures . We genomically characterized mammary adenocarcinomas from these mice to identify cancer-causing genomic events that overlap common alterations in human breast cancer . Chaos3 tumors underwent recurrent copy number alterations ( CNAs ) , particularly deletion of the RAS inhibitor Neurofibromin 1 ( Nf1 ) in nearly all cases . These overlap with human CNAs including NF1 , which is deleted or mutated in 27.7% of all breast carcinomas . Chaos3 mammary tumor cells exhibit RAS hyperactivation and increased sensitivity to RAS pathway inhibitors . These results indicate that spontaneous NF1 loss can drive breast cancer . This should be informative for treatment of the significant fraction of patients whose tumors bear NF1 mutations . OUTPUT:

genomic instability and mutation

HoC_1shot738

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The metastasis-associated lung adenocarcinoma transcript 1 , MALAT1 , is a long non-coding RNA ( lncRNA ) that has been discovered as a marker for lung cancer metastasis . It is highly abundant , its expression is strongly regulated in many tumor entities including lung adenocarcinoma and hepatocellular carcinoma as well as physiological processes , and it is associated with many RNA binding proteins and highly conserved throughout evolution . The nuclear transcript MALAT-1 has been functionally associated with gene regulation and alternative splicing and its regulation has been shown to impact proliferation , apoptosis , migration and invasion . Here , we have developed a human and a mouse knockout system to study the loss-of-function phenotypes of this important ncRNA . In human tumor cells , MALAT1 expression was abrogated using Zinc Finger Nucleases . Unexpectedly , the quantitative loss of MALAT1 did neither affect proliferation nor cell cycle progression nor nuclear architecture in human lung or liver cancer cells . Moreover , genetic loss of Malat1 in a knockout mouse model did not give rise to any obvious phenotype or histological abnormalities in Malat1-null compared with wild-type animals . Thus , loss of the abundant nuclear long ncRNA MALAT1 is compatible with cell viability and normal development . OUTPUT:

sustaining proliferative signaling

HoC_1shot739

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: FMS-like tyrosine kinase 3 ( FLT3 ) normally functions in the survival/proliferation of hematopoietic stem/progenitor cells , but its constitutive activation by internal tandem duplication ( ITD ) mutations correlates with a poor prognosis in AML . The development of FLT3 tyrosine kinase inhibitors ( TKI ) is a promising strategy , but resistance that arises during the course of treatment caused by secondary mutations within the mutated gene itself poses a significant challenge . In an effort to predict FLT3 resistance mutations that might develop in patients , we used saturation mutagenesis of FLT3/ITD followed by selection of transfected cells in FLT3 TKI . We identified F621L , A627P , F691L and Y842C mutations in FLT3/ITD that confer varying levels of resistance to FLT3 TKI . Western blotting confirmed that some FLT3 TKI were ineffective at inhibiting FLT3 autophosphorylation and signaling through MAP kinase , STAT5 and AKT in some mutants . Balb/c mice transplanted with the FLT3/ITD Y842C mutation confirmed resistance to sorafenib in vivo but not to lestaurtinib . These results indicate a growing number of FLT3 mutations that are likely to be encountered in patients . Such knowledge , combined with known remaining sensitivity to other FLT3 TKI , will be important to establish as secondary drug treatments that can be substituted when these mutants are encountered . OUTPUT:

genomic instability and mutation;sustaining proliferative signaling

HoC_1shot740

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Increasing evidence shows that estrogens are involved in lung cancer proliferation and progression , and most human lung tumors express estrogen receptor β ( ERβ ) as well as aromatase . To determine if the aromatase inhibitor anastrozole prevents development of lung tumors induced by a tobacco carcinogen , alone or in combination with the ER antagonist fulvestrant , ovariectomized female mice received treatments with the tobacco carcinogen 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone ( NNK ) along with daily supplements of androstenedione , the substrate for aromatase . Placebo , anastrozole and/or fulvestrant were administered in both an initiation and a promotion protocol of lung tumorigenesis . The combination of fulvestrant and anastrozole given during NNK exposure resulted in significantly fewer NNK-induced lung tumors ( mean = 0.5 ) compared with placebo ( mean = 4.6 , P &lt ; 0.001 ) , fulvestrant alone ( mean = 3.4 , P &lt ; 0.001 ) or anastrozole alone ( mean = 2.8 , P = 0.002 ) . A significantly lower Ki67 cell proliferation index was also observed compared with single agent and control treatment groups . Beginning antiestrogen treatment after NNK exposure , when preneoplastic lesions had already formed , also yielded maximum antitumor effects with the combination . Aromatase expression was found mainly in macrophages infiltrating preneoplastic and tumorous areas of the lungs , whereas ERβ was found in both macrophages and tumor cells . Antiestrogens , especially in combination , effectively inhibited tobacco carcinogen-induced murine lung tumorigenesis and may have application for lung cancer prevention . An important source of estrogen synthesis may be inflammatory cells that infiltrate the lungs in response to carcinogens , beginning early in the carcinogenesis process . ERβ expressed by inflammatory and neoplastic epithelial cells in the lung may signal in response to local estrogen production . OUTPUT:

sustaining proliferative signaling

HoC_1shot741

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: A glycolytic profile unifies a group of pheochromocytomas and paragangliomas ( PHEOs/PGLs ) with distinct underlying gene defects , including von Hippel-Lindau ( VHL ) and succinate dehydrogenase B ( SDHB ) mutations . Nevertheless , their tumor aggressiveness is distinct : PHEOs/PGLs metastasize rarely in VHL- , but frequently in SDHB-patients . To date , the molecular mechanisms causing the more aggressive phenotype in SDHB-PHEOs/PGLs remain largely unknown . Recently , however , an excellent model to study aggressive PHEOs ( mouse tumor tissue ( MTT ) cells ) has been developed from mouse PHEO cells ( MPC ) . We employed this model for a proteomics based approach to identify changes characteristic for tumor aggressiveness , which we then explored in a homogeneous set of human SDHB- and VHL-PHEOs/PGLs . The increase of glucose transporter 1 in VHL , and of hexokinase 2 in VHL and SDHB , confirmed their glycolytic profile . In agreement with the cell model and in support of decoupling of glycolysis , the Krebs cycle and oxidative phosphorylation ( OXPHOS ) , SDHB tumors showed increased lactate dehydrogenase levels . In SDHB-PGLs OXPHOS complex activity was increased at complex III and , as expected , decreased at complex II . Moreover , protein and mRNA expression of all tested OXPHOS-related genes were higher in SDHB- than in VHL-derived tumors . Although there was no direct evidence for increased reactive oxygen species production , elevated superoxide dismutase 2 expression may reflect elevated oxidative stress in SDHB-derived PHEOs/PGLs . For the first time , we show that despite dysfunction in complex II and evidence for a glycolytic phenotype , the Warburg effect does not seem to fully apply to SDHB-PHEOs/PGLs with respect to decreased OXPHOS . In addition , we present evidence for increased LDHA and SOD2 expression in SDHB-PHEOs/PGLs , proteins that have been proposed as promising therapeutic targets in other cancers . This study provides new insight into pathogenic mechanisms in aggressive human PHEOs/PGLs , which may lead to identifying new diagnostic and prognostic markers in the near future . OUTPUT:

cellular energetics;tumor promoting inflammation

HoC_1shot742

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND To assess the potential mechanisms that may underlie increased local failure in triple negative ( TN ) breast cancers , an analysis was performed of the risk of residual carcinoma after lumpectomy with correlation to pathologic factors , including molecular phenotype . METHODS A review of pathologic specimens was performed for women with invasive breast cancer treated with lumpectomy followed by reexcision . Data were collected on age ; tumor size , grade , and nodal stage ; estrogen receptor , progesterone receptor , and human endothelial growth factor receptor 2 ( Her2 ) ; extensive intraductal component ; lymphovascular invasion ; margins ; and reexcision findings . Univariate and multivariate logistic regression analyses were performed to evaluate for associations between pathologic features of the lumpectomy specimen and reexcision findings . Molecular phenotypes were defined by conventionally used immunohistochemical pattern . RESULTS Data were collected on 369 patients with breast cancer . The median age was 57 years , median tumor size was 1.5 cm , 36% had positive margins , 32% had positive lymph nodes , 73.5% had the luminal A subtype , 9.5% had the luminal B subtype , 4.5% were Her2-enriched , and 12.5% were TN . Overall , 32% of patients had invasive cancer in their reexcision specimens , and 51% of those with the TN subtype had residual invasive disease on reexcision compared with 30% to 31% for other subtypes . On univariate analysis , age , tumor size , margin status , lymphovascular invasion , nodal status , and TN subtype were associated with elevated risk of residual invasive cancer . On multivariate analysis using a forward stepwise model , TN subtype maintained significance , with an odds ratio of 3.28 ( P = .002 ) . CONCLUSION TN subtype has a statistically significant association with an increased risk of residual tumor . This suggests the putative increase in the risk of local failure in TN patients may be related to increased residual tumor burden . OUTPUT:

activating invasion and metastasis

HoC_1shot743

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The role of energy deregulation and altered/adapted metabolism in tumor cells is an increasingly important issue in understanding cancer . Hereditary leiomyomatosis and renal cell carcinoma ( HLRCC ) is an aggressive form of RCC characterized by germline mutation of fumarate hydratase ( FH ) , followed by somatic loss of the remaining wild-type allele and known to be a highly metastatic and lethal malignancy compared to other RCCs . The intrinsic loss of normal tricarboxylic acid ( TCA ) cycle presumably aids tumorigenesis due to the necessary metabolic alterations required and the enforced dependence on glycolysis derived energy , mimicking the Warburg effect . Thus , there is considerable utility in establishing a preclinical cell model from these tumors to study energy metabolism deregulation , as well as developing new targeted therapeutic approaches for TCA cycle enzyme-deficient cancers . Here , we describe a new immortalized cell line , UOK268 , derived from a patient's primary HLRCC-associated kidney cancer . This represents the first primary renal cell line to model TCA cycle gene loss and provides a perfect partner cell line to our previously described metastasis-derived HLRCC-associated cell line , UOK262 . We identified a novel germline FH missense mutation , p.His192Asp , and the subsequent loss of heterozygosity in UOK268 . The UOK268 cell line expressed mutant FH protein , which localized to the mitochondria , but with loss of almost all catalytic activity . The UOK268 cells had severely compromised oxidative phosphorylation and increased glycolytic flux . Ingenuity pathways analysis of human mitochondria-focused cDNA microarray ( hMitChip3 ) gene chip data confirmed the altered mRNA expression patterns of genes involved in several important pathways , such as lipid metabolism , apoptosis , and energy production/glycolysis . UOK268 provides a unique model of a primary cell line demonstrating an enforced , irreversible Warburg effect and , combined with UOK262 , provides a unique invitro preclinical model for studying the bioenergetics of the Warburg effect in human cancer . OUTPUT:

genomic instability and mutation;cellular energetics;resisting cell death

HoC_1shot744

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Focal adhesion kinase ( FAK ) is an important mediator of extracellular matrix integrin signaling , cell motility , cell proliferation and cell survival . Increased FAK expression is observed in a variety of solid human tumors and increased FAK expression and activity frequently correlate with metastatic disease and poor prognosis . Herein we identify miR-7 as a direct regulator of FAK expression. miR-7 expression is decreased in malignant versus normal breast tissue and its expression correlates inversely with metastasis in human breast cancer patients . Forced expression of miR-7 produced increased E-CADHERIN and decreased FIBRONECTIN and VIMENTIN expression in breast cancer cells . The levels of miR-7 expression was positively correlated with E-CADHERIN mRNA and negatively correlated with VIMENTIN mRNA levels in breast cancer samples . Forced expression of miR-7 in aggressive breast cancer cell lines suppressed tumor cell monolayer proliferation , anchorage independent growth , three-dimensional growth in Matrigel , migration and invasion . Conversely , inhibition of miR-7 in the HBL-100 mammary epithelial cell line promoted cell proliferation and anchorage independent growth . Rescue of FAK expression reversed miR-7 suppression of migration and invasion. miR-7 also inhibited primary breast tumor development , local invasion and metastatic colonization of breast cancer xenografts . Thus , miR-7 expression is decreased in metastatic breast cancer , correlates with the level of epithelial differentiation of the tumor and inhibits metastatic progression . OUTPUT:

activating invasion and metastasis

HoC_1shot745

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Both the deregulation of microRNAs and epidermal growth factor receptor ( EGFR ) are emerging as important factors in non-small-cell lung cancer ( NSCLC ) . Here , miR-133b was found to be associated with tumor stage , the extent of regional lymph node involvement , stage , visceral pleura or vessel invasion and EGFR mRNA expression in Chinese patients with NSCLC . Bioinformatic analysis and luciferase reporter assay revealed that miR-133b can interact specifically with the 3'-UTR of EGFR mRNA . Functionally , miR-133b transfection showed regulatory activity in translationally repressing EGFR mRNA . Moreover , miR-133b transfection may modulate apoptosis , invasion and sensitivity to EGFR-TKI through the EGFR signaling pathways , especially in EGFR-addicted NSCLC cells . Taken together , our findings show that miR-133b can inhibit cell growth of NSCLC through targeting EGFR and regulating its downstream signaling pathway . This finding has important implications for the development of targeted therapeutics for a number of EGFR-addicted cancers . OUTPUT:

sustaining proliferative signaling;activating invasion and metastasis;resisting cell death

HoC_1shot746

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Objective . The present study was performed to investigate the effect of N-desulfated heparin on basic fibroblast growth factor ( bFGF ) expression , tumor angiogenesis and metastasis of gastric carcinoma . Methods . Human gastric cancer SGC-7901 tissues were orthotopically implanted into the stomach of NOD SCID mice . Twenty mice were randomly divided into two groups which received either intravenous injection of 0.9% NaCl solution ( normal saline group ) or 10 mg/kg N-desulfated heparin ( N-desulfated heparin group ) twice weekly for three weeks . In vitro , human gastric carcinoma SGC-7901 cells were treated with N-desulfated heparin in different concentration ( 0.1 mg/mL , 1 mg/mL , N-desulfated heparin group ) , and treated with medium ( control group ) . Results . In vivo , the tumor metastasis rates were 9/10 in normal saline group and 2/10 in N-desulfated heparin group ( P &lt ; 0.05 ) . The intratumoral microvessel density was higher in normal saline group than in N-desulfated heparin group ( P &lt ; 0.05). bFGF expression in gastric tissue was inhibited by N-desulfated heparin ( P &lt ; 0.05 ) . There was no bleeding in N-desulfated heparin group . In vitro , N-desulfated heparin inhibited significantly bFGF protein and mRNA expression of gastric carcinoma cells ( P &lt ; 0.05 ) . Conclusions . N-desulfated heparin can inhibit the metastasis of gastric cancer through inhibiting tumor bFGF expression and tumor angiogenesis with no obvious anticoagulant activity . OUTPUT:

activating invasion and metastasis;inducing angiogenesis

HoC_1shot747

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVES Lymph node metastasis is among the most important prognostic factors for patients with esophageal squamous cell carcinoma after curative esophagectomy ; however , the extent of lymphadenectomy is still controversial . The objective of the present study was to determine the frequency of lymphatic metastases and to study the pattern of lymph node metastasis in a large study population . METHODS The data from 1361 patients with thoracic esophageal squamous cell carcinoma who underwent curative R0 esophagectomy were retrospectively examined . Logistic regression analysis was used to identify the factors associated with lymph node metastasis . RESULTS Of the 1361 patients , 714 ( 52.5% ) were found to have lymph node metastasis . The frequency of lymph node metastasis increased as the tumor invasion increased . Paratracheal nodes were the most frequent metastasis nodes ( 15.9% ) . The frequency of lymph node metastasis was 9.8% in the neck , 18.0% in the upper mediastinum , 18.9% in the middle mediastinum , 11.8% in the lower mediastinum , and 28.4% in the abdomen . Of these 714 patients , 424 ( 31.2% ) presented with 1 field involvement , 255 ( 18.7% ) with 2 fields , and 35 ( 2.6% ) with 3 fields involvement . Logistic regression analysis revealed tumor length ( P<.001 ) , tumor invasion ( P<.001 ) , tumor differentiation ( P=.003 ) , and lymphovascular invasion ( P<.001 ) were risk factors for lymph node metastasis . Tumor location ( P<.001 ) , tumor invasion ( P=.003 ) , lymphovascular invasion ( P=.004 ) , and paratracheal lymph node involvement ( P=.002 ) were identified as risk factors for cervical lymph node metastasis . CONCLUSIONS Metastases were more frequent in the abdomen than in the neck . Total mediastinal and upper abdominal lymphadenectomy should be carefully conducted . Certain factors , such as tumor location , depth of tumor invasion , lymphovascular invasion , and paratracheal lymph node involvement , might be helpful in determining the need to perform cervical lymphadenectomy in individual patients . OUTPUT:

activating invasion and metastasis

HoC_1shot748

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: MDSCs and Tregs play an essential role in the immunosuppressive networks that contribute to tumor-immune evasion . The mechanisms by which tumors promote the expansion and/or function of these suppressive cells and the cross-talk between MDSC and Treg remain incompletely defined . Previous reports have suggested that MDSC may contribute to Treg induction in cancer . Herein , we provide evidence that tumor-induced gr-MDSCs , endowed with the potential of suppressing conventional T Lc , surprisingly impair TGF-β1-mediated generation of CD4(+)CD25(+)FoxP3(+) iTregs . Furthermore , gr-MDSCs impede the proliferation of nTregs without , however , affecting FoxP3 expression . Suppression of iTreg differentiation from na�ve CD4(+) cells by gr-MDSC occurs early in the polarization process , requires inhibition of early T cell activation , and depends on ROS and IDO but does not require arginase 1 , iNOS , NO , cystine/cysteine depletion , PD-1 and PD-L1 signaling , or COX-2 . These findings thus indicate that gr-MDSCs from TB hosts have the unanticipated ability to restrict immunosuppressive Tregs . OUTPUT:

avoiding immune destruction;sustaining proliferative signaling

HoC_1shot749

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND Cholangiocarcinoma , a type of malignant tumor , originates from epithelial cells of the bile duct . Perineural invasion is common path for cholangiocarcinoma metastasis , and it is highly correlated with postoperative recurrence and poor prognosis . It has been reported that muscarinic acetylcholine receptor M3 ( mAChR M3 ) is widely expressed in digestive tract cancer , and may play an important role in the proliferation , differentiation , transformation and carcinogenesis of tumors . This study was to explore the effect of mAChR M3 on the growth of cholangiocarcinoma cells in vitro and provide a new approach to the pathogenesis and treatment of cholangiocarcinoma . METHODS Streptavidin-biotin complex immunohistochemistry was carried out to assess the expression of mAChR M3 in surgical specimens of cholangiocarcinomas ( 40 cases ) and normal bile duct tissues ( 9 ) , as well as to investigate nerve infiltration . The cholangiocarcinoma cells were treated with different concentrations of selective M-receptor agonist pilocarpine and M-receptor blocker atropine sulfate to induce changes in cell proliferation . The experimental data were analyzed by the Chi-square test . RESULTS The strongly-positive expression rate of mAChR M3 was much higher in poorly-differentiated ( 69% , 9/13 ) than in well- and moderately-differentiated cholangiocarcinomas ( 30% , 8/27 ) ( X2=5.631 , P<0.05 ) . The strongly-positive mAChR M3 expression rate in hilar cholangiocarcinoma ( 50% , 14/28 ) was higher than that in cholangiocarcinomas from the middle and lower common bile duct ( 25% , 3/12 ) ( X2=2.148 , P<0.05 ) . Cholangiocarcinomas with distant metastasis had a strongly-positive expression rate ( 75% , 9/12 ) , which was much higher than those without distant metastasis ( 29% , 8/28 ) ( X2=7.410 , P<0.01 ) . The absorbance value in the pilocarpine+atropine group was significantly higher than the corresponding value in the pilocarpine group . CONCLUSIONS The expression of mAChR M3 is influenced by the extent of differentiation , distant metastasis and the site of cholangiocarcinoma . It also plays a key role in the proliferation and metastasis of cholangiocarcinoma . OUTPUT:

activating invasion and metastasis

HoC_1shot750

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Colorectal cancer represents one of the most challenging diseases . Increasing evidence indicates that aberrant expression of microRNAs ( miRNAs ) is related to pathogenesis of colorectal cancer . Cancer cells reprogram metabolic pathways to sustain higher proliferation rates . Whether mechanisms underlying the role of miRNA in colorectal cancer are involved in metabolic reprogramming and the mechanisms through which miRNAs alter cancer metabolism are as yet unknown . Herein , we show that miR-124 , miR-137 and miR-340 are associated with poor prognosis of colorectal cancer . Expression of these miRNAs inhibits the growth of colorectal cancer cells . PKM ( pyruvate kinase isozyme ) alternative splicing proteins ( PTB1/hnRNAPA1/hnRNAPA2 ) , which control the inclusion of exon 9 ( PKM1 ) or exon 10 ( PKM2 ) , are targeted by miR-124 , miR-137 and miR-340 . Consequently , miR-124 , miR-137 and miR-340 switch PKM gene expression from PKM2 to PKM1 . High ratios of PKM1/PKM2 inhibit the glycolysis rate , but elevate the glucose flux into oxidative phosphorylation . These results demonstrate that miRNAs ( miR-124 , miR-137 and miR-340 ) impair colorectal cancer growth by counteracting the Warburg effect due to regulating alternative splicing of the PKM gene . OUTPUT:

cellular energetics

HoC_1shot751

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Mesenchymal stem cells ( MSCs ) are generally used in tissue engineering , regenerative medicine and therapy for immune disorder disease . MSCs are also employed as drug carriers for tumor therapy due to their ability to migrate to tumor tissue . However , due to the immunosuppressive function of MSCs , the application of MSCs in prostate cancer therapy remains limited . In this study , we investigated the underlying mechanism by which MSCs enable prostate cancer cells to escape from immune surveillance in the inflammatory microenvironment . Firstly , we demonstrated that compared with the control groups , MSCs pretreated with IL-1α effectively promoted the growth of the mouse prostate cancer cell line RM-1 invivo . Furthermore , when RM-1 prostate cancer cells were co-injected with MSCs pretreated with IL-1α , tumor incidence significantly increased in allogeneic recipients . In addition , we investigated the mechanism through which MSCs promote the ability of RM-1 cells to escape from immune injury . The results revealed that IL-1α led to the upregulation of TGF-β in MSCs . The inflammatory cytokine-induced promotive effect of MSCs on RM-1 cells in vivo was inhibited by TGF-β siRNA . The results of our study suggest that inflammatory cytokines induce the immunosuppressive function of MSCs which enables prostate cancer cells to escape from immune injury . OUTPUT:

sustaining proliferative signaling;tumor promoting inflammation;avoiding immune destruction

HoC_1shot752

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Glioblastoma is one of the most lethal and common malignant human brain tumors , with aggressive proliferation and highly invasive properties . Honokiol derived from Magnolia officinalis is able to cross the blood-brain barrier ( BBB ) and the blood-cerebrospinal fluid barrier ( BCSFB ) , suggesting a strong possibility that it could be an effective drug for the treatment of brain tumors , including glioblastoma . Thus , we investigated the effects of honokiol on the expression of adhesion molecules in TNF-α-stimulated endothelial cells , and cancer growth and invasion were determined in T98G human glioblastoma cells . Honokiol dose-dependently inhibited the expression of intercellular adhesion molecule-1 ( ICAM-1 ) and vascular cell adhesion molecule-1 ( VCAM-1 ) in human umbilical vein endothelial cells ( HUVECs ) stimulated with TNF-α for 6 h . Pretreatment with honokiol significantly reduced the adhesion of T98G cells to HUVECs . Moreover , honokiol inhibited the invasion of T98G cells , suggesting that honokiol has an anti-metastatic effect . In addition , honokiol increased the cytotoxicity of T98G cells in a dose- and time-dependent manner as assayed by MTT . TUNEL assay showed that honokiol significantly induced apoptosis in T98G cells at doses of 10 �M or more . The induction of apoptotic cell death was mediated by the downregulation of the anti-apoptotic protein Bcl-2 and the upregulation of the pro-apoptotic protein Bax . Taken together , the results of this study suggest that honokiol exerts an anticancer effect by preventing metastasis and inducing apoptotic cell death of brain tumor cells . OUTPUT:

activating invasion and metastasis;resisting cell death

HoC_1shot753

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The insulin-like growth factor ( IGF ) pathway represents one of the most studied molecular regulatory networks in oncology . Clinical trials investigating the therapeutic value of anti-IGF1 receptor ( IGF1R ) therapies in cancer , including prostate cancer , are ongoing . However , the multiple functions of the IGF network in the prostate are not entirely known . To elucidate the effects of IGF and insulin ( INS ) on prostate cells , we stimulated prostate cancer ( PC3 , DU145 , LNCaP , DUCaP ) and noncancerous prostate cells ( EP156T , RWPE-1 ) and observed differing responses : whereas cancer cells responded to IGF and INS exposure by way of enhanced cell proliferation and glucose consumption , basal to luminal differentiation was induced in noncancerous cells . The same diverse responses were observed when the growth factor receptors IGF1R or INSR were overexpressed . Down-regulation of IGF1R or INSR isoform A ( INSRA ) also inhibited only proliferation of cancer cells . The proliferative response induced by the INSR in cancer cells was mediated solely by the INSRA . Moreover we observed that the receptors of the IGF network mutually influence their expression and exert redundant functions , thus underscoring the functional molecular network formed by IGF , INS , IGF1R , and INSR . Collectively we found that both IGF1R and INSRA have oncogenic effects in prostate cancer , but the IGF network also has important physiological functions in the noncancerous prostate . These data provide new insights into the biology of the IGF network in the prostate , thereby facilitating the design and interpretation of clinical studies investigating IGF1R targeting agents . OUTPUT:

sustaining proliferative signaling

HoC_1shot754

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND Although basal cell carcinoma ( BCC ) is the most common type of skin cancer , the incidence of metastasis is exceedingly low . OBJECTIVE Case presentation of a basal cell carcinoma arising on the dorsum of the foot with inguinal and pelvic lymph node metastases . METHOD Case presentation with literature review . RESULT On the basis of our review of Japanese literature , the risk factors for BCC metastasis are occurrence on the genitalia , diameter of more than 3 cm , deep invasion of tumor cells into extradermal structures , and infiltrative/morpheic histological type . CONCLUSION Although metastasis from BCC is extremely rare , the prognosis of metastatic BCC is often poor . Careful follow-up is recommended in cases with high risk factors . OUTPUT:

activating invasion and metastasis

HoC_1shot755

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Hesperetin , a flavonoid from citrus fruits , has several bioactivities such as anti-inflammatory , antihypertensive , antiatherogenic effects . However , studies elucidating the role and the mechanism(s) of action of hesperetin in cervical cancer are sparse . In this study , we investigated the mechanism of the antiproliferative and apoptotic actions exerted by hesperetin on human cervical cancer SiHa cells . The viability of SiHa cells was evaluated using the MTT assay , apoptosis by acridine orange/ethidium bromide , propidium iodide , TUNEL assay , and Annexin V-Cy3 , cell cycle distribution and mitochondrial transmembrane potential using flow cytometry , and apoptotic marker genes using quantitative real-time PCR . The treatment of SiHa cells with hesperetin ( IC(50,) 650μm ) showed a marked concentration- and time-dependent inhibition of proliferation and induced the G2/M phase in a dose-dependent manner after 24h . There was an attenuation of mitochondrial membrane potential with increased expression of caspase-3 , caspase-8 , caspase-9 , p53 , Bax , and Fas death receptor and its adaptor protein Fas-associated death domain-containing protein ( FADD ) , indicating the participation of both death receptor- and mitochondria-related mechanisms . Furthermore , hesperetin-induced apoptosis was confirmed by TUNEL and Annexin V-Cy3 . This study shows that hesperetin exhibits a potential anticancer activity against human cervical cancer cell lines in vitro through the reduction in cell viability and the induction of apoptosis . Altogether , these data sustain our contention that hesperetin has anticancer properties and merits further investigation as a potential therapeutic agent . OUTPUT:

sustaining proliferative signaling;resisting cell death

HoC_1shot756

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Placental Growth Factor ( PGF ) is a key molecule in angiogenesis . Several studies have revealed an important role of PGF primarily in pathological conditions ( e.g. : ischaemia , tumour formation , cardiovascular diseases and inflammatory processes ) suggesting its use as a potential therapeutic agent . However , to date , no information is available regarding the genetics of PGF variability . Furthermore , even though the effect of environmental factors ( e.g. : cigarette smoking ) on angiogenesis has been explored , no data on the influence of these factors on PGF levels have been reported so far . Here we have first investigated PGF variability in two cohorts focusing on non-genetic risk factors : a study sample from two isolated villages in the Cilento region , South Italy ( N=871 ) and a replication sample from the general Danish population ( N=1,812 ) . A significant difference in PGF mean levels was found between the two cohorts . However , in both samples , we observed a strong correlation of PGF levels with ageing and sex , men displaying PGF levels significantly higher than women . Interestingly , smoking was also found to influence the trait in the two populations , although differently . We have then focused on genetic risk factors . The association between five single nucleotide polymorphisms ( SNPs ) located in the PGF gene and the plasma levels of the protein was investigated . Two polymorphisms ( rs11850328 and rs2268614 ) were associated with the PGF plasma levels in the Cilento sample and these associations were strongly replicated in the Danish sample . These results , for the first time , support the hypothesis of the presence of genetic and environmental factors influencing PGF plasma variability . OUTPUT:

inducing angiogenesis

HoC_1shot757

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Curcumin ( diferuloylmethane ) is a polyphenol derived from the plant turmeric ( Curcuma longa ) , which is commonly used as a spice . Although anti-carcinogenic , anti-oxidant , anti-inflammation , and anti-angiogenic properties have been reported , the effect of curcumin on breast cancer metastasis is unknown . Matrix metalloproteinase-9 ( MMP-9 ) is a major component in cancer cell invasion . In this study , we investigated the inhibitory effect of curcumin on 12-O-tetradecanoylphorbol-13-acetate ( TPA)-induced MMP-9 expression and cell invasion and the molecular mechanisms involved in MCF-7 cells . Our results showed that curcumin inhibits TPA-induced MMP-9 expression and cell invasion through suppressing NF-κB and AP-1 activation . Also , curcumin strongly repressed the TPA-induced phosphorylation of p38 and JNK and inhibited TPA-induced translocation of PKCα from the cytosol to the membrane , but did not affect the translocation of PKCδ . These results indicate that curcumin-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the PKCα , MAPK and NF-κB/AP-1 pathway in MCF-7 cells . Curcumin may have potential value in restricting breast cancer metastasis . OUTPUT:

activating invasion and metastasis

HoC_1shot758

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND Angiogenesis plays an important role in the progression of colorectal cancer ( CRC ) . Studies have indicated vascular endothelial growth factor ( VEGF ) is the predominant angiogenic factor . Cyclin D1 ( CCND1 ) induces production of VEGF and is required for migration of blood vessels . Our aim was to determine the roles of CCND1 and VEGF overexpression in CRC patients . METHODS We analyzed clinicopathological features , VEGF and CCND1 expressions by immunohistochemical ( IHC ) staining in 100 stage I-III CRC patients ( 44 were postoperative relapsed ; 56 were postoperative non-relapsed ) to determine the correlation between clinicopathologic features and co-existence of CCND1 and VEGF . Furthermore , the clinical outcomes of co-existence of CCND1 and VEGF were investigated . RESULTS Multivariate analysis showed vascular invasion ( P = 0.019 ) , VEGF overexpression ( P = 0.033 ) , and high postoperative serum carcinoembryonic antigen ( CEA ) levels ( P = 0.022 ) were independent predictors of postoperative relapse . Co-existence of CCND1 and VEGF overexpression had significantly poorer disease-free survival rates ( P  = 0.004 ) and overall survival rates ( P = 0.001 ) than other phenotypes . CONCLUSIONS Co-existence of CCND1 and VEGF overexpression would potentially assist in TNM staging systems to predict the prognosis of these patients who would benefit from intensive follow-up and therapeutic programs . OUTPUT:

inducing angiogenesis

HoC_1shot759

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting the immunogenicity of developing tumors . Although the full process depends on innate and adaptive immunity , it remains unclear whether innate immunity alone is capable of immunoediting . To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity , we compared the incidence and immunogenicity of 3'methylcholanthrene-induced sarcomas in syngeneic wild-type , RAG2(-/-) , and RAG2(-/-)x γc(-/-) mice . We found that innate immune cells could manifest cancer immunoediting activity in the absence of adaptive immunity . This activity required natural killer ( NK ) cells and interferon γ ( IFN-γ ) , which mediated the induction of M1 macrophages . M1 macrophages could be elicited by administration of CD40 agonists , thereby restoring editing activity in RAG2(-/-)x γc(-/-) mice . Our results suggest that in the absence of adaptive immunity , NK cell production of IFN-γ induces M1 macrophages , which act as important effectors during cancer immunoediting . OUTPUT:

avoiding immune destruction

HoC_1shot760

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Cellular senescence has emerged as a critical tumor suppressive mechanism in recent years , but relatively little is known about how senescence occurs . Here , we report that secreted Frizzled-related protein 1 ( SFRP1 ) , a secreted antagonist of Wnt signaling , is oversecreted upon cellular senescence caused by DNA damage or oxidative stress . SFRP1 is necessary for stress-induced senescence caused by these factors and is sufficient for the induction of senescence phenotypes . We present evidence suggesting that SFRP1 functions as a secreted mediator of senescence through inhibition of Wnt signaling and activation of the retinoblastoma ( Rb ) pathway and that cancer-associated SFRP1 mutants are defective for senescence induction . OUTPUT:

enabling replicative immortality;genomic instability and mutation;tumor promoting inflammation

HoC_1shot761

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: We show that sufficient concentrations of gold nanoparticles produced by an original synthesis method in EMT-6 and CT-26 cancer cells make it possible to detect the presence , necrosis and proliferation of such cells after inoculation in live mice . We first demonstrated that the nanoparticles do not interfere with the proliferation process . Then , we observed significant differences in the tumor evolution and the angiogenesis process after shallow and deep inoculation . A direct comparison with pathology optical images illustrates the effectiveness of this approach . OUTPUT:

sustaining proliferative signaling;inducing angiogenesis

HoC_1shot762

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The development of targeted therapies and immunotherapies has markedly advanced the treatment of metastasized melanoma . While treatment with selective BRAF(V600E) inhibitors ( like vemurafenib or dabrafenib ) leads to high response rates but short response duration , CTLA-4 blocking therapies induce sustained responses , but only in a limited number of patients . The combination of these diametric treatment approaches may further improve survival , but pre-clinical data concerning this approach is limited . We investigated , using Tyr::CreER(T2)PTEN(F-/-)BRAF(F-V600E/+) inducible melanoma mice , whether BRAF(V600E) inhibition can synergize with anti-CTLA-4 mAb treatment , focusing on the interaction between the BRAF(V600E) inhibitor PLX4720 and the immune system . While PLX4720 treatment strongly decreased tumor growth , it did not induce cell death in BRAF(V600E)/PTEN(-/-) melanomas . More strikingly , PLX4720 treatment led to a decreased frequency of tumor-resident T cells , NK-cells , MDSCs and macrophages , which could not be restored by the addition of anti-CTLA-4 mAb . As this effect was not observed upon treatment of BRAF wild-type B16F10 tumors , we conclude that the decreased frequency of immune cells correlates to BRAF(V600E) inhibition in tumor cells and is not due to an off-target effect of PLX4720 on immune cells . Furthermore , anti-CTLA-4 mAb treatment of inducible melanoma mice treated with PLX4720 did not result in enhanced tumor control , while anti-CTLA-4 mAb treatment did improve the effect of tumor-vaccination in B16F10-inoculated mice . Our data suggest that vemurafenib may negatively affect the immune activity within the tumor . Therefore , the potential effect of targeted therapy on the tumor-microenvironment should be taken into consideration in the design of clinical trials combining targeted and immunotherapy . OUTPUT:

avoiding immune destruction

HoC_1shot763

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND The presence of distant metastases from colorectal cancer ( CRC ) does not preclude curative treatment . Early detection of pulmonary metastases at a potentially curable stage could improve survival . The aim of the present study was to assess the prognostic significance of commonly reported clinicopathologic features to identify high-risk patients who would likely benefit from more intensive chest surveillance for pulmonary metastases . MATERIAL AND METHOD A total of 351 consecutive patients , with surgical stages I-III colorectal cancer , who underwent curative resection at Phramongkutklao hospital from 1999 to 2005 , were followed regularly according to the established guidelines with routine physical examination , serum carcinoembryonic antigen ( CEA ) and colonoscopic surveillance . Imaging studies for detecting metastases were computed tomography ( CT ) , plain film radiography , and ultrasonograpy . Clinical and pathologic features were analyzed for their association with pulmonary metastasis . RESULTS There were 145 patients who had been operated for longer than five years after curative intent surgery . Of these , nineteen patients were lost to follow-up or died from other causes that were unrelated to colorectal cancer . Pulmonary metastases were detected in 26 patients by either CXR or CT scan . Median time to pulmonary metastasis was 19 months ( 95 percent CI , 12-35 ) . According to an univariate analysis , with log-rank test , identified four factors associated with pulmonary metastasis : Tumor stage T4 , Nodal stage N2 , elevation of serum CEA &gt ; 3.4 ng/ml and presence of lymphovascular invasion(LVI) . According to a multivariate analysis , with Cox regression , found an elevation of serum CEA &gt ; 3.4 ng/ml which was an independent factor that was significantly associated with pulmonary metastasis ( Hazard ratio ( HR ) , 8.9 ; 95 percent CI , 3.6-22 ; p &lt ; 0.01 ) . The present study revealed that 50 percent of patients who had more than one of these risk factors would eventually develop pulmonary metastases . CONCLUSION An elevation of serum CEA &gt ; or = 3.4 ng/ml was found as an independent factor that was significantly associated with pulmonary metastasis whereas tumor stage T4 , nodal stage N2 and presence of lymphovascular invasion ( LVI ) were not independent clinicopathologic features associated with subsequent pulmonary metastases . Chest CT scan has greater sensitivity than chest radiography in detection of pulmonary metastasis and should be considered as an imaging study of choice for intensive chest surveillance for patients who had more than one of these risk factors . OUTPUT:

activating invasion and metastasis

HoC_1shot764

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Depression is the most common psychiatric syndrome in cancer patients and adversely affects anti-cancer immune system and life quality of patients . Antidepressant desipramine ( DMI ) is clinically prescribed in the auxiliary treatment of cancer patients . Increasing evidences suggest that DMI has a broad spectrum of target-off biological effects , such as anticancer properties . Our previous study revealed that DMI at the clinical relevant concentrations could induce CHOP-dependent apoptotic death in C6 glioma cells . In this study , we further explored the pro-autophagic effect of DMI in C6 glioma cells and its underlying mechanism . Treatment with DMI could induce autophagic cell death characterized by the formation of autophagosome and the elevated level of autophagic protein Beclin-1 and cellular redistribution of marker LC3 . Meanwhile , DMI inhibited the activation of PI3K-AKT-mTOR pathway which is considered as a negative regulator of autophagy . Furthermore , DMI activated PERK-eIF2α and ATF6 of endoplasmic reticulum ( ER ) stress pathway , while knockdown of PERK with the PERK-specific short interfering RNA ( siRNA ) could obviously attenuate the autophagy . The results strongly suggested that DMI could induce autophagy through the PERK-ER stress pathway in C6 glioma cells . Our findings provided new insights into another beneficial potential of antidepressant DMI in the adjuvant therapy of cancer . OUTPUT:

resisting cell death

HoC_1shot765

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Therapy-induced senescence ( TIS ) , a cytostatic stress response in cancer cells , is induced inefficiently by current anticancer agents and radiation . The mechanisms that mediate TIS in cancer cells are not well defined . Herein , we characterize a robust senescence response both in vitro and in vivo to the quinone diaziquone ( AZQ ) , previously identified in a high-throughput senescence-induction small-molecule screen . Using AZQ and several other agents that induce senescence , we screened a series of cyclin-dependent kinase inhibitors and found that p27(Kip1) was induced in all investigated prostate cancer cell lines . The ubiquitin-ligase Skp2 negatively regulates p27(Kip1) and , during TIS , is translocated to the cytoplasm before its expression is decreased in senescent cells . Overexpression of Skp2 blocks the effects of AZQ on senescence and p27(Kip1) induction . We also find that stable long-term short hairpin RNA knockdown of Skp2 decreases proliferation but does not generate the complete senescence phenotype . We conclude that Skp2 participates in regulating TIS but , alone , is insufficient to induce senescence in cancer cells . OUTPUT:

enabling replicative immortality

HoC_1shot766

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Dendritic cells ( DCs ) and natural killer ( NK ) cells are central components of innate immunity for controlling tumor growth . The therapeutic effects of certain anti-myeloma drugs are partially mediated by targeting the innate immune response . In addition , novel types of natural compounds have been developed that efficiently modulate the activity of both the cellular and humoral compartments of immunity . MGN-3 is known as an activator of natural killer cells , inducer of apoptosis and cytokine production , and modulator of dendritic cell maturation and differentiation in vitro . We have performed a randomized , placebo-controlled study to examine the effects of MGN-3 on innate immune system parameters in 48 multiple myeloma patients . We performed immunophenotypic analysis of peripheral blood samples , determined NK cell activity , and assessed the cytokine profiles of plasma before and during 3months of treatment . The results demonstrate a clear increase in NK activity in MGN-3-treated patients compared to the placebo group , an increased level of myeloid DCs in peripheral blood , and augmented concentrations of T helper cell type 1-related cytokines . The present study suggests that MGN-3 may represent an immunologically relevant product for activating innate immunity in multiple myeloma patients and warrants further testing to demonstrate clinical efficacy . OUTPUT:

avoiding immune destruction

HoC_1shot767

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: AIM To elucidate the roles of receptor tyrosine kinases RET and VEGFR2 and the RAF/MEK/ERK signaling cascade in cancer treatment with sorafenib . METHODS The cell lines A549 , HeLa , and HepG2 were tested . The enzyme activity was examined under cell-free conditions using 384-well microplate assays . Cell proliferation was evaluated using the Invitrogen Alarmar Blue assay . Gene expression was analyzed using the Invitrogen SYBR Green expression assays with a sequence detection system . Protein expression analysis was performed using Western blotting . RESULTS Sorafenib potently suppressed the activities of cRAF , VEGFR2 , and RET with IC(50) values of 20.9 , 4 and 0.4 nmol/L , respectively . Sorafenib inhibited cRAF , VEGFR2 , and RET via non-ATP-competitive , ATP-competitive and mixed-type modes , respectively . In contrast , sorafenib exerted only moderate cytotoxic effects on the proliferation of the 3 cell lines . The IC(50) values for inhibition of A549 , HeLa , and HepG2 cells were 8572 , 4163 , and 8338 nmol/L , respectively . In the 3 cell lines , sorafenib suppressed the cell proliferation mainly by blocking the MEK/ERK downstream pathway at the posttranscriptional level , which in turn regulated related gene expression via a feed-back mechanism . CONCLUSION This study provides novel evidence that protein kinases RET and VEGFR2 play crucial roles in cancer treatment with sorafenib . OUTPUT:

sustaining proliferative signaling

HoC_1shot768

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The cadherins are a family of cell surface glycoproteins responsible for cell adhesion which play an important role in cell morphology , contact inhibition and signal transduction during tumorigenesis . Protocadherin 8 ( PCDH8 ) , a member of the cadherin family , has been reported to act as a tumor suppressor involved in oncogenesis in breast cancer . In this study , we aimed to investigate the epigenetic inactivation of PCDH8 and its tumor suppressor function in gastric cancer . The expression of PCDH8 was markedly reduced or silenced in gastric cancer cell lines compared with normal gastric cells or tissues . Methylation of the PCDH8 gene promoter was observed in 100% ( 4/4 ) of cell lines and 55.38% ( 36/65 ) of the primary gastric cancer by methylation-specific PCR , but not in normal gastric mucosa ( 0/10 ) . Methylated PCDH8 was significantly associated with lymph node metastasis in a logistic regression analysis . The demethylation reagent 5-aza-2'-deoxycytidine was able to restore or upregulate PCDH8 expression in gastric cancer cell lines . Ectopic expression of PCDH8 in silenced gastric cancer cells significantly inhibited cell migration and induced apoptosis . For the first time , our study demonstrates the epigenetic inactivation of PCDH8 by promoter methylation and its tumor suppressor function in human gastric cancer . Thus , PCDH8 could be identified as a candidate tumor suppressor in human gastric cancer . OUTPUT:

activating invasion and metastasis;resisting cell death

HoC_1shot769

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Therapy-induced cellular senescence ( TCS ) , characterized by prolonged cell cycle arrest , is an in vivo response of human cancers to chemotherapy and radiation . Unfortunately , TCS is reversible for a subset of senescent cells , leading to cellular reproliferation and ultimately tumor progression . This invariable consequence of TCS recapitulates the clinical treatment experience of patients with advanced cancer . We report the findings of a clinicopathological study in patients with locally advanced non-small cell lung cancer demonstrating that marker of in vivo TCS following neoadjuvant therapy prognosticate adverse clinical outcome . In our efforts to elucidate key molecular pathways underlying TCS and cell cycle escape , we have previously shown that the deregulation of mitotic kinase Cdk1 and its downstream effectors are important mediators of survival and cell cycle reentry . We now report that aberrant expression of Cdk1 interferes with apoptosis and promotes the formation of polyploid senescent cells during TCS . These polyploid senescent cells represent important transition states through which escape preferentially occurs . The Cdk1 pathway is in part modulated differentially by p21 and p27 two members of the KIP cyclin-dependent kinase inhibitor family during TCS . Altogether , these studies underscore the importance of TCS in cancer therapeutics . OUTPUT:

enabling replicative immortality;resisting cell death

HoC_1shot770

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The aberrant activation of sonic hedgehog ( SHH ) pathway contributes to initiation and progression of various malignancies . However , the roles and underlying mechanisms of SHH signaling pathway in invasion and metastasis of liver cancer have not been well understood . In this study , we found that SHH signaling was activated and correlated with invasion and metastasis in hepatocellular carcinoma ( HCC ) . Enhanced SHH signaling by recombinant human SHH N-terminal peptide ( rSHH-N ) promoted hepatoma cell adhesion , migration and invasion , whereas blockade of SHH signaling with SHH neutralizing antibody or cyclopamine suppressed hepatoma cell adhesion , migration and invasion . Furthermore , matrix metalloproteinase ( MMP)-2 and MMP-9 expressions and activities were upregulated and downregulated by rSHH-N and SHH signaling inhibitor , respectively . The rSHH-N-mediated hepatoma cell migration and invasion was blocked by MMP-specific inhibitors or neutralizing antibodies to MMP-2 and MMP-9 . In addition , phosphorylations of AKT and focal adhesion kinase ( FAK ) were increased and decreased by rSHH-N and SHH signaling inhibitor , respectively . Further investigations showed that activation of AKT and FAK were required for rSHH-N-mediated upregulation of MMP-2 and MMP-9 , cell migration and invasion . Finally , we found that SHH protein expression was positively correlated with phosphorylatd FAK Tyr397 , phosphorylatd AKT Ser473 , MMP-2 and MMP-9 protein expressions in HCC samples . Taken together , our findings suggest that SHH pathway induces cell migration and invasion through FAK/AKT signaling-mediated MMP-2 and MMP-9 production and activation in liver cancer . OUTPUT:

activating invasion and metastasis

HoC_1shot771

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: PURPOSE This study investigated the impact of specific mutations in codon 12 of the Kirsten-ras ( KRAS ) gene on treatment efficacy in patients with metastatic colorectal cancer ( mCRC ) . PATIENTS Overall , 119 patients bearing a KRAS mutation in codon 12 were evaluated . All patients received cetuximab-based first-line chemotherapy within the Central European Cooperative Oncology Group ( CECOG ) , AIO KRK-0104 or AIO KRK-0306 trials . RESULTS Patients with KRAS codon 12 mutant mCRC showed a broad range of outcome when treated with cetuximab-based first-line regimens . Patients with tumors bearing a KRAS p.G12D mutation showed a strong trend to a more favorable outcome compared to other mutations ( overall survival 23.3 vs. 14-18 months ; hazard ratio 0.66 , range 0.43-1.03 ) . An interaction model illustrated that KRAS p.G12C was associated with unfavorable outcome when treated with oxaliplatin plus cetuximab . CONCLUSION The present analysis suggests that KRAS codon 12 mutation may not represent a homogeneous entity in mCRC when treated with cetuximab-based first-line therapy . OUTPUT:

genomic instability and mutation

HoC_1shot772

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Anal canal cancer is a rare tumor without clear treatment evidence in the metastatic setting . In terms of the bad prognosis of patients with metastatic anal cancer , further therapeutic options are urgently needed . In this paper we present the case of a 64-year-old man suffering from undifferentiated squamous cell carcinoma with liver metastases . After progression on cisplatin and fluorouracil , tumor tissue was analyzed with respect to anti-EGFR therapy with cetuximab . There was no KRAS mutation and the EGFR expression level in the tumor tissue was 2+ ; ideal conditions for the immunotherapy . Encouraged by these results we started a therapy using FOLFIRI in combination with cetuximab . Fortunately the patient showed a partial response after 6 cycles . On patient's preference we did a therapy break of 6 weeks . Within this time period the disease was progressive indicating its aggressiveness . However , the same immunotherapy was able to stabilize the disease for a further 3 months . The patient died 21 months after diagnosis because of liver failure . Nevertheless , from our perspective the combination of FOLFIRI and cetuximab is quite a promising therapeutic option for patients with metastatic anal cancer . Potential predictive factors of the immunochemotherapy are discussed in this paper . OUTPUT:

genomic instability and mutation;activating invasion and metastasis

HoC_1shot773

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: We examined how well the human papillomavirus ( HPV ) E6 oncogene can function in the absence of the E7 oncogene during the carcinogenic process in human keratinocytes using a common HPV variant strongly associated with cervical cancer : the Asian-American E6 variant ( AAE6 ) . This E6 variant is 20 times more frequently detected in cervical cancer than the prototype European E6 variant , as evidenced by independent epidemiological data . Using cell culture and cell-based functional assays , we assessed how this variant can perform crucial carcinogenesis steps compared to the prototype E6 variant . The ability to immortalize and transform primary human foreskin keratinocytes ( PHFKs ) to acquire resilient phenotypes and the ability to promote cell migration were evaluated . The immortalization capability was assayed based on population doublings , number of passages , surpassing mortality stages 1 and 2 , human telomerase reverse transcriptase ( hTERT ) expression , and the ability to overcome G(1) arrest via p53 degradation . Transformation and migration efficiency were analyzed using a combination of functional cell-based assays . We observed that either AAE6 or prototype E6 proteins alone were sufficient to immortalize PHFKs , although AAE6 was more potent in doing so . The AAE6 variant protein alone pushed PHFKs through transformation and significantly increased their migration ability over that of the E6 prototype . Our findings are in line with epidemiological data that the AA variant of HPV16 confers an increased risk over the European prototype for cervical cancer , as evidenced by a superior immortalization , transformation , and metastatic potential . OUTPUT:

enabling replicative immortality;activating invasion and metastasis

HoC_1shot774

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Biallelic mutations in MCPH1 cause primary microcephaly ( MCPH ) with the cellular phenotype of defective chromosome condensation . MCPH1 encodes a multifunctional protein that notably is involved in brain development , regulation of chromosome condensation , and DNA damage response . In the present studies , we detected that MCPH1 encodes several distinct transcripts , including two major forms : full-length MCPH1 ( MCPH1-FL ) and a second transcript lacking the six 3 ' exons ( MCPH1Δe9-14 ) . Both variants show comparable tissue-specific expression patterns , demonstrate nuclear localization that is mediated independently via separate NLS motifs , and are more abundant in certain fetal than adult organs . In addition , the expression of either isoform complements the chromosome condensation defect found in genetically MCPH1-deficient or MCPH1 siRNA-depleted cells , demonstrating a redundancy of both MCPH1 isoforms for the regulation of chromosome condensation . Strikingly however , both transcripts are regulated antagonistically during cell-cycle progression and there are functional differences between the isoforms with regard to the DNA damage response ; MCPH1-FL localizes to phosphorylated H2AX repair foci following ionizing irradiation , while MCPH1Δe9-14 was evenly distributed in the nucleus . In summary , our results demonstrate here that MCPH1 encodes different isoforms that are differentially regulated at the transcript level and have different functions at the protein level . OUTPUT:

genomic instability and mutation;sustaining proliferative signaling

HoC_1shot775

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND Chemokines are involved in multiple aspects of pathogenesis and cellular trafficking in tumorigenesis . In this study , we report that the latest member of the C-X-C-type chemokines , CXCL17 ( DMC/VCC-1 ) , recruits immature myeloid-derived cells and enhances early tumor progression . METHODOLOGY/PRINCIPAL FINDINGS CXCL17 was preferentially expressed in some aggressive types of gastrointestinal , breast , and lung cancer cells . CXCL17 expression did not impart NIH3T3 cells with oncogenic potential in vitro , but CXCL17-expressing NIH3T3 cells could form vasculature-rich tumors in immunodeficient mice . Our data showed that CXCL17-expressing tumor cells increased immature CD11b(+)Gr1(+) myeloid-derived cells at tumor sites in mice and promoted CD31(+) tumor angiogenesis . Extensive chemotactic assays proved that CXCL17-responding cells were CD11b(+)Gr1(high)F4/80(-) cells ( ≈ 90% ) with a neutrophil-like morphology in vitro . Although CXCL17 expression could not increase the number of CD11b(+)Gr1(+) cells in tumor-burdened SCID mice or promote metastases of low metastatic colon cancer cells , the existence of CXCL17-responding myeloid-derived cells caused a striking enhancement of xenograft tumor formation . CONCLUSIONS/SIGNIFICANCE These results suggest that aberrant expression of CXCL17 in tumor cells recruits immature myeloid-derived cells and promotes tumor progression through angiogenesis . OUTPUT:

inducing angiogenesis;activating invasion and metastasis

HoC_1shot776

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: UNLABELLED BACKGROUND We aimed to develop a mouse spontaneous liver metastasis model from an orthotopically implanted human colon cancer cell line stably expressing a human sodium/iodide symporter ( NIS ) reporter gene , which can be imaged with single-photon emission computed tomography ( SPECT ) using 99mTcO4- . METHODS A recombinant plasmid containing a constitutively driven NIS gene ( pcDNA3-NIS ) was transfected into the human colon cancer cell line HCT116 , and stable cell lines were established . The stable cells were subcutaneously injected into the nude mice . When the diameter reached 10 mm , the xenografts were excised , cut into small fragments , and orthotopically implanted into the cecal walls of another nude mice. 99mTcO4- SPECT/CT imaging was initiated 8 weeks later and repeated every 1 to 2 weeks . RESULTS The production and function of NIS protein was confirmed in vitro by Western blotting and 99mTcO4- uptake assay . On SPECT/CT imaging , focal 99mTcO4- uptake was detected in the liver . Necropsy revealed local growth of the orthotopic colon xenografts with extensive invasion , microscopic serosal metastasis , and metastatic foci in the corresponding hepatic regions showing focal 99mTcO4- uptake . Immunohistochemistry revealed high levels of NIS expression in cells forming liver tumor , indicating that the liver tumor cells originated from the orthotopic colon xenografts . CONCLUSIONS The present proof-of-concept study provided a rationale for employing a radionuclide reporter gene for the specific visualization of spontaneous liver metastasis in living mice . This unique animal model of clinically relevant and externally detectable liver metastasis will be a powerful tool for investigating tumor biology and developing novel therapies for cancer metastasis . OUTPUT:

activating invasion and metastasis

HoC_1shot777

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Cancer cells convert glucose preferentially to lactate even in the presence of oxygen ( aerobic glycolysis-Warburg effect ) . New concepts in cancer treatment aim at inhibition of aerobic glycolysis . Pyruvate dehydrogenase converts pyruvate to acetylCoA thus preventing lactate formation . Therefore , the aim of this study was to evaluate compounds that could activate pyruvate dehydrogenase in cancer cells . We investigated the effects of ( R)-(+)-α-lipoic acid ( LPA ) and dichloroacetate ( DCA ) , possible activators of pyruvate dehydrogenase , on suppression of aerobic glycolysis and induction of cell death . The neuroblastoma cell lines Kelly , SK-N-SH , Neuro-2a and the breast cancer cell line SkBr3 were incubated with different concentrations ( 0.1-30 mM ) of LPA and DCA . The effects of both compounds on cell viability/proliferation ( WST-1 assay ) , [ 18F]-FDG uptake , lactate production and induction of apoptosis ( flow cytometric detection of caspase-3 ) were evaluated . Furthermore , NMRI nu/nu mice that had been inoculated s.c. with SkBr3 cells were treated daily for four weeks with LPA ( i.p , 18.5 mg/kg ) starting at day 7 p.i. . Tumor development was measured with a sliding calliper and monitored via [ 18F]-FDG-PET . Residual tumors after therapy were examined histopathologically . These data suggests that LPA can reduce ( 1 ) cell viability/proliferation , ( 2 ) uptake of [ 18F]-FDG and ( 3 ) lactate production and increase apoptosis in all investigated cell lines . In contrast , DCA was almost ineffective . In the mouse xenograft model with s.c . SkBr3 cells , daily treatment with LPA retarded tumor progression . Therefore , LPA seems to be a promising compound for cancer treatment . OUTPUT:

cellular energetics;resisting cell death

HoC_1shot778

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The epidermal growth factor receptor ( EGFR ) is a member of the HER family receptors and its activation induced by its natural ligand EGF results in colon cancer growth and progression . Panitumumab ( pmAb ) is a fully human IgG2 anti-EGFR antibody that blocks the EGFR actions . In the present study , we evaluated the effects of pmAb on the EGF-mediated cellular responses in a panel of colon cancer cells ( HCT-8 , HT-29 , DLD-1 and HCT-116 ) . HCT-1116 and DLD-1 cells showed no significant EGF-dependent cell proliferation ; HT-29 and HCT-8 exhibited an EGF-dependent proliferation , with HCT-8 cells to be the most responsive with significant EGFR phosphorylation upon treatment with EGF . The effects of pmAb were then evaluated in the most EGF-responsive cells , HCT-8 . In that respect , pmAb impedes the signaling cascade mediated by EGFR intracellular phosphorylation and activity of focal adhesion kinase ( FAK ) as well as the EGF-induced invasive and migratory potential of colon cancer cells . At the level of matrix effectors implicated in colon cancer progression we report that pmAb is a potent inhibitor of constitute and EGF-mediated gene expression of certain matrix effectors , such as membrane-type 1 metalloproteinase ( MT1-MMP ) , extracellular metalloproteinases inducer ( EMMPRIN ) , urokinase plasminogen activator ( uPA ) and syndecan-4 . The obtained data demonstrated that pmAb is a specific blocker of EGF-mediated EGFR activation , resulting in a significant inhibition of colon cancer cell proliferation in early stages of growth , migration and invasiveness as well as of matrix effector implicated in cancer progression . OUTPUT:

sustaining proliferative signaling;activating invasion and metastasis

HoC_1shot779

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Hypoxia in the tumor microenvironment plays a central role in the evolution of immune escape mechanisms by tumor cells . In this study , we report the definition of miR-210 as a miRNA regulated by hypoxia in lung cancer and melanoma , documenting its involvement in blunting the susceptibility of tumor cells to lysis by antigen-specific cytotoxic T lymphocytes ( CTL). miR-210 was induced in hypoxic zones of human tumor tissues . Its attenuation in hypoxic cells significantly restored susceptibility to autologous CTL-mediated lysis , independent of tumor cell recognition and CTL reactivity . A comprehensive approach using transcriptome analysis , argonaute protein immunoprecipitation , and luciferase reporter assay revealed that the genes PTPN1 , HOXA1 , and TP53I11 were miR-210 target genes regulated in hypoxic cells . In support of their primary importance in mediating the immunosuppressive effects of miR-210 , coordinate silencing of PTPN1 , HOXA1 , and TP53I11 dramatically decreased tumor cell susceptibility to CTL-mediated lysis . Our findings show how miR-210 induction links hypoxia to immune escape from CTL-mediated lysis , by providing a mechanistic understanding of how this miRNA mediates immunosuppression in oxygen-deprived regions of tumors where cancer stem-like cells and metastatic cellular behaviors are known to evolve . OUTPUT:

avoiding immune destruction;activating invasion and metastasis

HoC_1shot780

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Senescence , an inherent tumor suppressive mechanism , is a critical determinant for chemotherapy . In the present study , we show that the monocarboxylate transporter 2 ( MCT2 ) protein was tumor-selectively expressed in human colorectal malignancies and knockdown of MCT2 induces mitochondrial dysfunction , cell-cycle arrest , and senescence without additional cellular stress in colorectal cancer cell lines . Moreover , the reactive oxygen species ( ROS ) scavenger , N-acetylcysteine , blocked MCT2 knockdown-induced growth arrest and cellular senescence , indicating a pivotal role of ROS in this pathway . Dramatic induction of mitochondrial superoxide generation and decrease in ATP production was observed , indicating that mitochondrial dysfunction is the major mechanism underlying MCT2 knockdown-induced ROS generation . Senescence-associated DNA damage was also evident from the increase in promyelocytic leukemia bodies , γH2AX foci , and SAHF . Conversely , overexpression of MCT2 prevented doxorubicin-induced ROS accumulation ( P = 0.0002 ) and cell growth inhibition ( P = 0.001 ) . MCT2 knockdown suppressed KRAS mutant colorectal tumor growth in vivo . In addition , MCT2 knockdown and cytostatic drug combination further enhanced the antitumor effect . These findings support the use of MCT2 as a promising target for inhibition of colorectal cancer . OUTPUT:

enabling replicative immortality;sustaining proliferative signaling;tumor promoting inflammation;genomic instability and mutation

HoC_1shot781

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVE To investigate the relationship between lymphangiogenesis and lymphatic metastasis in cervical squamous carcinoma . METHODS Eighty cases of invasive cervical squamous cancer were selected as objects of our study . Double immunohistochemical staining with antibodies against lymphatic vessel endothelial hyaluronan receptor 1 and Ki-67 was used to label the lymphatic vessels and mark the proliferative lymphatic vessels in cervical squamous cancer . The peritumoral lymphatic vessel density and intratumoral lymphatic vessel density was assessed . The lymphatic vessels proliferation index was evaluated by calculating Ki-67 proliferation index ( PI ) to reflect the lymphangiogenesis of cervical squamous cancer . Then the correlation between lymphangiogenesis and clinicopathologic features of cervical squamous cancer was analyzed . RESULTS The LVD of cervical cancer ( 15.23 � 3.6 ) was clearly higher than that of the adjacent normal cervical subepithelial tissues ( 9.9 � 2.5 , P &lt ; 0.001 ) . The peritumoral lymphatic vessel density of cervical cancer ( 18.75 � 4.3 ) was significantly higher than the intratumoral lymphatic vessel density of cervical cancer ( 11.71 � 4.9 , P &lt ; 0.001 ) . Lymphatic PI ( LPI ) of cervical cancer ( 0.258 � 0.07 ) was higher than that of the adjacent normal cervical subepithelial tissues ( 0.068 � 0.08 , P &lt ; 0.001 ) . The peritumoral lymphatic vessel PI of cervical cancer ( 0.324 � 0.06 ) was notably higher than the intratumoral lymphatic vessel PI of cervical cancer ( 0.232 � 0.06 , P &lt ; 0.001 ) . Peritumoral lymphatic vessel density and peritumoral lymphatic vessel were clearly associated with the lymph node metastasis ( P = 0.001 and P = 0.002 , respectively ) and lymphovascular space invasion ( P = 0.024 and P = 0.01 , respectively ) . CONCLUSIONS The high density of peritumoral lymphatic vessels is a potential predictor of more aggressive phenotype of cervical squamous cancer . OUTPUT:

inducing angiogenesis;activating invasion and metastasis

HoC_1shot782

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Cellular senescence can be a functional barrier to carcinogenesis . We hypothesized that inflammation modulates carcinogenesis through senescence and DNA damage response ( DDR ) . We examined the association between senescence and DDR with macrophage levels in inflammatory bowel disease ( IBD ) . In vitro experiments tested the ability of macrophages to induce senescence in primary cells . Inflammation modulating microRNAs were identified in senescence colon tissue for further investigation . OUTPUT:

enabling replicative immortality

HoC_1shot783

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Background . An important goal of personalized cancer therapy is to tailor specific therapies to the mutational profile of individual patients . However , whole genome sequencing studies have shown that the mutational profiles of cancers evolve over time and often differ between primary and metastatic sites . Activating point mutations in the PIK3CA gene are common in primary breast cancer tumors , but their presence in breast cancer bone metastases has not been assessed previously . Results . Fourteen patients with breast cancer bone metastases were biopsied by three methods : CT-guided bone biopsies ; bone marrow trephine biopsies ; and bone marrow aspiration . Samples that were positive for cancer cells were obtained from six patients . Three of these patients had detectable PIK3CA mutations in bone marrow cancer cells . Primary tumor samples were available for four of the six patients assessed for PIK3CA status in their bone metastases . For each of these , the PIK3CA mutation status was the same in the primary and metastatic sites . Conclusions . PIK3CA mutations occur frequently in breast cancer bone metastases . The PIK3CA mutation status in bone metastases samples appears to reflect the PIK3CA mutation status in the primary tumour . Breast cancer patients with bone metastases may be candidates for treatment with selective PIK3CA inhibitors . OUTPUT:

genomic instability and mutation;activating invasion and metastasis

HoC_1shot784

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Multiple myeloma ( MM ) is classically illustrated by a desynchronized cytokine system with rise in inflammatory cytokines . There are recent reports which emphasized the potential role of angiogenesis in the development of MM. Role of cyclooxygenase 2 ( COX-2 ) is well documented in the pathogenesis of solid tumors , but little is known about its occurrence and function in hematologic neoplasms . Involvement of neoangiogenesis is reported in the progression of MM , and angiopoietins probably contribute to this progression by enhancing neovascularization . Circulatory and mRNA levels of angiogenic factors and cyclooxygenase were determined in 125 subjects ( 75 MM patients and 50 healthy controls ) by using enzyme-linked immunosorbent assay and quantitative PCR . We observed significant increase for angiogenic factors ( Ang-1 , Ang-2 , hepatocyte growth factor , and vascular endothelial growth factor ) and cyclooxygenase at circulatory level , as well as at mRNA level , as compared to healthy controls except insignificant increase for Ang-1 at circulatory level . We have also observed the significant positive correlation of all angiogenic factors with cyclooxygenase . The strong association found between angiogenic factors and COX-2 in this study may lead to the development of combination therapeutic strategy to treat MM. Therefore , targeting COX-2 by using its effective inhibitors demonstrating antiangiogenic and antitumor effects could be used as a new therapeutic approach for treatment of MM . OUTPUT:

inducing angiogenesis;tumor promoting inflammation

HoC_1shot785

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: MAP17 is a small 17 kDa non-glycosylated membrane protein previously identified as being overexpressed in carcinomas . Breast tumor cells that overexpress MAP17 show an increased tumoral phenotype with enhanced proliferative capabilities both in the presence or the absence of contact inhibition , decreased apoptotic sensitivity , and increased migration . MAP17-expressing clones also grow better in nude mice . The increased malignant cell behavior induced by MAP17 is associated with an increase in reactive oxygen species ( ROS ) production , and the treatment of MAP17-expressing cells with antioxidants results in a reduction in the tumorigenic properties of these cells . The MAP17-dependent increase in ROS and tumorigenesis relies on its PDZ-binding domain because disruption of this sequence by point mutations abolishes the ability of MAP17 to enhance ROS production and tumorigenesis . MAP17 is overexpressed in a great variety of human carcinomas , including breast tumors . Immunohistochemical analysis of MAP17 during cancer progression demonstrates that overexpression of the protein strongly correlates with tumoral progression . Generalized MAP17 overexpression in human carcinomas indicates that MAP17 can be a good marker for tumorigenesis and , especially , for malignant progression . OUTPUT:

tumor promoting inflammation;genomic instability and mutation

HoC_1shot786

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND Coronins are a family of highly evolutionary conserved proteins reportedly involved in the regulation of actin cytoskeletal dynamics , although only coronin 3 has been shown to be related to cancer cell migration . In glioblastoma cells , the knockdown of coronin 3 inhibits cell proliferation and invasion . Coronin 3 is also associated with the aggression and metastasis of hepatocellular carcinoma . In this paper , we analyze the migration , invasion and metastasis abilities of gastric cancer cells after up- or down-regulation of coronin 3 , and explore the mechanism of coronin 3 in the process of gastric cancer metastasis . RESULTS The expression of coronin 3 was higher in the highly metastatic sub-cell line MKN28-M , which we established in our laboratory . We also demonstrated that the expression of coronin 3 was remarkably higher in lymph lode metastases than in primary gastric cancer tissues , and over-expression of coronin 3 was correlated with the increased clinical stage and lymph lode metastasis . Recombinant lentiviral vectors encoding shRNAs were designed to down-regulate coronin 3 expression in gastric cancer cell lines . Stable knockdown of coronin 3 by this lentiviral vector could efficiently inhibit the migration and invasion of MKN45 gastric cancer cells . In contrast , up-regulation of coronin 3 significantly enhanced migration and invasion of MKN28-NM cells . In addition , knockdown of coronin 3 significantly reduced liver metastasis in mice after tail vein injection of gastric cancer cells . The Human Tumor Metastasis PCR Array was used to screen the metastasis-associated genes identified by the down-regulation of coronin 3 , and the results suggested that , following the knockdown of coronin 3 , the tumor cell migration and invasion were inhibited by the reduced expression of MMP-9 and cathepsin K. CONCLUSION Coronin 3 is highly expressed in gastric cancer metastases and can promote the metastatic behaviors of gastric cancer cells , including their migration and invasion . OUTPUT:

activating invasion and metastasis

HoC_1shot787

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Immunosenescence , the progressive decline of adaptive immunity and chronic inflammation with ageing has been demonstrated to be the main factor responsible for infections , cancer and autoimmune conditions in the elderly . Senescence-accelerated mouse ( SAM ) was used to study the protective effects of Pu-erh tea in the elderly . The senile-prone sub-strain , SAM-P8 mice were administered individually with ripened or crude Pu-erh tea at 125 , 250 or 500mg/kg . The results showed that Pu-erh tea significantly increased the fractions of na�ve T lymphocytes , CD8(+)CD28(+) T lymphocytes and NK cells in the peripheral blood , but decreased the levels of IL-6 in aged mice . These data suggested that the Pu-erh tea reversed the immunosenescence by restoring the immune deficiency and decreasing pro-inflammatory cytokine . Thus , long term drinking of Pu-erh tea may be beneficial for the aged population in terms of increasing the body's resistance to infection and cancer . OUTPUT:

avoiding immune destruction

HoC_1shot788

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The aim of this work was to characterize the antitumoral activity of the plant compound 7-epi-nemorosone in prostate carcinoma cell lines . Prostate cancer is the most frequently diagnosed malignancy and the second-leading cause of cancer death in men . In spite of the current therapeutic options for this cancer entity , many patients die due to metastases in distant organs and acquired chemotherapy resistance . Thus , approaches to provide improvements in outcome and quality of life for such patients are urgently needed . Recently , the polyisoprenylated benzophenone 7-epi-nemorosone , originally collected by honeybees from Clusia rosea and Clusia grandiflora ( Clusiaceae ) , has been described to be a potent antitumoral agent . Here , its activity in prostate carcinoma is reported. 7-epi-nemorosone was isolated from Caribbean propolis employing RP-HPLC techniques . Its cytotoxicity was assessed using the MTT proliferation assay in human androgen-dependent prostate carcinoma LNCaP cells including an MDR1(+) sub-line . No cross-resistance was detected . FACS-based cell cycle analysis revealed a significant increase in the sub-G0/G1 , G1 , and depletion in the S phase populations . A concomitant down-regulation of cyclins D1/D3 and CDK 4/6 in LNCaP cells was detected by Western blot . Annexin-V-FITC labeling and caspase-3 cleavage assays showed that 7-epi-nemorosone induced apoptotic events . Major signal transduction elements such as p38 MAPK and Akt/PKB as well as androgen receptor AR and PSA production were found to be down-regulated after exposure to the drug . ERK1/2 protein levels and phosphorylation status were down-regulated accompanied by up-regulation but inhibition of the activity of their immediate upstream kinases MEK1/2 . Additionally , Akt/PKB enzymatic activity was effectively inhibited at a similar concentration as for MEK1/2 . Here , we demonstrate for the first time that 7-epi-nemorosone exerts cytotoxicity in an androgen-dependent prostate carcinoma entity by targeting the MEK1/2 signal transducer . OUTPUT:

sustaining proliferative signaling;resisting cell death

HoC_1shot789

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: It is well established that aberrant production of inflammatory mediators has been associated with most the toxic manifestations and the genesis of different chronic diseases including cancer . The basic aim of the present study is to investigate the effects of soy isoflavones ( SIF ) on 12-O-tetradecanoylphorbol-13-acetate ( TPA)-induced cutaneous inflammatory responses and to explore the underlying molecular mechanisms . We have studied the protective effects of SIF against TPA induced oxidative stress , pro-inflammatory cytokines level , activation of NF-κB , expression of COX-2 and ki-67 in mouse skin . Animals were divided into five groups I-V ( n=6 ) . Groups II , III and IV received topical application of TPA at the dose of 10 nmol/0.2 ml of acetone/animal/day , for 2 days . Animals of the groups III and IV were pre-treated with SIF 1.0 μg ( D1 ) and 2.0 μg ( D2 ) topically 30 min prior to each TPA administration , while groups I and V were given acetone ( 0.2 ml ) and SIF ( D2 ) , respectively . We have found that SIF pretreatment significantly inhibited TPA induced oxidative stress , proinflammatory cytokines production and activation of NF-κB . SIF also inhibited the expression of COX-2 and ki-67 . Histological findings further supported the protective effects of SIF against TPA-induced cutaneous damage . Thus , our results suggest that inhibitory effect of SIF on TPA-induced cutaneous inflammation includes inhibition of proinflammatory cytokines , attenuation of oxidative stress , activation of NF-κB and expression of COX-2 . OUTPUT:

tumor promoting inflammation

HoC_1shot790

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Contact inhibition is a crucial mechanism regulating proliferation in vitro and in vivo . Although it is generally accepted that contact inhibition plays a pivotal role in maintaining tissue homeostasis , the molecular mechanisms of contact inhibition are still not fully understood . FoxM1 is known as a proliferation-associated transcription factor and is upregulated in many cancer types . Vice versa , anti-proliferative signals , such as TGF-β and differentiation signals decrease FoxM1 expression . Here we investigated the role of FoxM1 in contact inhibition in fibroblasts . We show that protein expression of FoxM1 is severely and rapidly downregulated upon contact inhibition , probably by inhibition of ERK activity , which then leads to decreased expression of cyclin A and polo-like kinase 1 . Vice versa , ectopic expression of FoxM1 prevents the decrease in cyclin A and polo-like kinase 1 and causes a two-fold increase in saturation density indicating loss of contact inhibition . Hence , we show that downregulation of FoxM1 is required for contact inhibition by regulating expression of cyclin A and polo-like kinase 1 . OUTPUT:

evading growth suppressors

HoC_1shot791

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: AIM To investigate whether luteolin , a highly prevalent flavonoid , reverses the effects of epithelial-mesenchymal transition ( EMT ) in vitro and in vivo and to determine the mechanisms underlying this reversal . METHODS Murine malignant melanoma B16F10 cells were exposed to 1% O(2) for 24 h . Cellular mobility and adhesion were assessed using Boyden chamber transwell assay and cell adhesion assay , respectively . EMT-related proteins , such as E-cadherin and N-cadherin , were examined using Western blotting . Female C57BL/6 mice ( 6 to 8 weeks old ) were injected with B16F10 cells ( 1�10(6) cells in 0.2 mL per mouse ) via the lateral tail vein . The mice were treated with luteolin ( 10 or 20 mg/kg , ip ) daily for 23 d . On the 23rd day after tumor injection , the mice were sacrificed , and the lungs were collected , and metastatic foci in the lung surfaces were photographed . Tissue sections were analyzed with immunohistochemistry and HE staining . RESULTS Hypoxia changed the morphology of B16F10 cells in vitro from the cobblestone-like to mesenchymal-like strips , which was accompanied by increased cellular adhesion and invasion . Luteolin ( 5-50 μmol/L ) suppressed the hypoxia-induced changes in the cells in a dose-dependent manner . Hypoxia significantly decreased the expression of E-cadherin while increased the expression of N-cadherin in the cells ( indicating the occurrence of EMT-like transformation ) , which was reversed by luteolin ( 5 μmol/L ) . In B16F10 cells , luteolin up-regulated E-cadherin at least partly via inhibiting the β3 integrin/FAK signal pathway . In experimental metastasis model mice , treatment with luteolin ( 10 or 20 mg/kg ) reduced metastatic colonization in the lungs by 50% . Furthermore , the treatment increased the expression of E-cadherin while reduced the expression of vimentin and β3 integrin in the tumor tissues . CONCLUSION Luteolin inhibits the hypoxia-induced EMT in malignant melanoma cells both in vitro and in vivo via the regulation of β3 integrin , suggesting that luteolin may be applied as a potential anticancer chemopreventative and chemotherapeutic agent . OUTPUT:

activating invasion and metastasis

HoC_1shot792

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: p21 is a potent cyclin-dependent kinase inhibitor that plays a role in promoting G1 cell cycle arrest and cellular senescence . Consistent with this role , p21 is a downstream target of several tumour suppressors and oncogenes , and it is downregulated in the majority of tumours , including breast cancer . Here , we report that protein arginine methyltransferase 6 ( PRMT6 ) , a type I PRMT known to act as a transcriptional cofactor , directly represses the p21 promoter . PRMT6 knock-down ( KD ) results in a p21 derepression in breast cancer cells , which is p53-independent , and leads to cell cycle arrest , cellular senescence and reduced growth in soft agar assays and in severe combined immunodeficiency ( SCID ) mice for all the cancer lines examined . We finally show that bypassing the p21-mediated arrest rescues PRMT6 KD cells from senescence , and it restores their ability to grow on soft agar . We conclude that PRMT6 acts as an oncogene in breast cancer cells , promoting growth and preventing senescence , making it an attractive target for cancer therapy . OUTPUT:

enabling replicative immortality;sustaining proliferative signaling

HoC_1shot793

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The molecular mechanism mediating expression of senescent cell antigen-aggregated or cleaved band 3 and externalized phosphatidylserine ( PS ) on the surface of aged erythrocytes and their premature expression in certain anemias is not completely elucidated . The erythrocytes with these surface modifications undergo macrophage-mediated phagocytosis . In this study , the role of protein kinase C ( PKC ) isoforms in the expression of these surface modifications was investigated . Inhibition of PKC α by 30 μM rottlerin ( R30 ) and 2.3 nM G� 6976 caused expression of both the senescent cell marker-externalized PS measured by FACS analysis and aggregated band 3 detected by western blotting . In contrast to this observation , but in keeping with literature , PKC activation by phorbol-12-myristate-13-acetate ( PMA ) also led to the expression of senescence markers . We explain this antithesis by demonstrating that PMA-treated cells show reduction in the activity of PKC α , thereby simulating inhibition . The reduction in PKC α activity may be attributed to the known downregulation of PMA-activated PKC α , caused by its membrane translocation and proteolysis . We demonstrate membrane translocation of PKC α in PMA-treated cells to substantiate this inference . Thus loss of PKC α activity either by inhibition or downregulation can cause surface modifications which can trigger erythrophagocytosis . OUTPUT:

enabling replicative immortality

HoC_1shot794

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Ovarian cancer-related angiogenesis is a complex process orchestrated by many positive and negative regulators . Many growth factors are involved in the development of the tumor-associated vasculature , and from these , endocrine gland-derived vascular endothelial growth factor ( EG-VEGF ) seems to play a crucial role . EG-VEGF is the first organ-specific angiogenic factor and its effects are restricted to the endothelial cells of the endocrine glands . Although EG-VEGF was detected in both normal and neoplastic ovaries , its clinical significance remains controversial . In the present study , we analyzed 30 patients with epithelial ovarian cancer , and the immunohistochemical expression of EG-VEGF was compared with the conventional clinico-pathological parameters of prognosis . Neoplastic cells of the ovarian carcinoma expressed EG-VEGF in 73.33% of the cases , as a cytoplasmic granular product of reaction . We found a strong correlation between the expression of EG-VEGF at protein level and tumor stage , grade , and microscopic type . The expression of EG-VEGF was found in patients with stage III and IV , but not in stage II . The majority of serous adenocarcinoma , half of the cases with clear cell carcinoma and two cases with endometrioid carcinoma showed definite expression in tumor cells . No positive reaction was found in the cases with mucinous carcinoma . Our results showed that EG-VEGF expression is an indicator not only of the advanced stage , but also of ovarian cancer progression . Based on these data , we concluded that EG-VEGF expression in tumor cells of the epithelial ovarian cancer is a good marker of unfavorable prognosis and could be an attractive therapeutic target in patients with advanced-stage tumors , refractory conventional chemotherapy . OUTPUT:

inducing angiogenesis

HoC_1shot795

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: UNLABELLED Hepatocellular carcinoma ( HCC ) is a major liver malignancy . We previously demonstrated that deregulation of epigenetic regulators is a common event in human HCC . Suppressor of variegation 3-9 homolog 1 ( SUV39H1 ) , the prototype of histone methyltransferase , is the major enzyme responsible for histone H3 lysine 9 trimethylation , which , essentially , is involved in heterochromatin formation , chromosome segregation , and mitotic progression . However , the implication of SUV39H1 in hepatocarcinogenesis remains elusive . In this study , we found that SUV39H1 was frequently up-regulated in human HCCs and was significantly associated with increased Ki67 expression ( P &lt ; 0.001 ) and the presence of venous invasion ( P = 0.017 ) . To investigate the role of SUV39H1 in HCC development , both gain- and loss-of-function models were established . SUV39H1 overexpression remarkably enhanced HCC cell clonogenicity , whereas knockdown of SUV39H1 substantially suppressed HCC cell proliferation and induced cell senescence . In addition , ectopic expression of SUV39H1 increased the migratory ability of HCC cells , whereas a reduced migration rate was observed in SUV39H1 knockdown cells . The significance of SUV39H1 in HCC was further demonstrated in a nude mice model ; SUV39H1 knockdown drastically inhibited in vivo tumorigenicity and abolished pulmonary metastasis of HCC cells . We also identified microRNA-125b ( miR-125b ) as a post-transcriptional regulator of SUV39H1 . Ectopic expression of miR-125b inhibited SUV39H1 3'-untranslated-region-coupled luciferase activity and suppressed endogenous SUV39H1 expression at both messenger RNA and protein levels . We have previously reported frequent down-regulation of miR-125b in HCC . Interestingly , miR-125b level was found to be inversely correlated with SUV39H1 expression ( P = 0.001 ) in clinical specimens . Our observations suggested that miR-125b down-regulation may account for the aberrant SUV39H1 level in HCC . CONCLUSION Our study demonstrated that SUV39H1 up-regulation contributed to HCC development and metastasis . The tumor-suppressive miR-125b served as a negative regulator of SUV39H1 . OUTPUT:

enabling replicative immortality;activating invasion and metastasis

HoC_1shot796

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Chronic inflammation is a risk factor for the development of colon cancer , providing genotoxic insults , growth and pro-angiogenic factors that can promote tumorigenesis and tumor growth . Immunomodulatory agents can interfere with the inflammation that feeds cancer , but their impact on the transformed cell is poorly understood . The calcium/calcineurin signaling pathway , through activation of NFAT , is essential for effective immune responses , and its inhibitors cyclosporin A ( CsA ) and FK506 are used in the clinics to suppress immunity . Moreover , the kinases GSK3β and mTOR , modulated by PI-3K/Akt , can inhibit NFAT activity , suggesting a cross-talk between the calcium and growth factor signaling pathways . Both NFAT and mTOR activity have been associated with tumorigenesis . We therefore investigated the impact of calcineurin and PI-3K/mTOR inhibition in growth of human colon carcinoma cells . We show that despite the efficient inhibition of NFAT1 activity , FK506 promotes tumor growth , whereas CsA inhibits it due to a delay in cell cycle progression and induction of necroptosis . We found NFκB activation and mTORC1 activity not to be altered by CsA or FK506 . Similarly , changes to mitochondrial homeostasis were equivalent upon treatment with these drugs . We further show that , in our model , NFAT1 activation is not modulated by PI3K/mTOR . We conclude that CsA slows cell cycle progression and induces necroptosis of human carcinoma cell lines in a TGFβ- , NFAT- , NFκB- and PI3K/mTOR-independent fashion . Nevertheless , our data suggest that CsA , in addition to its anti-inflammatory capacity , may target transformed colon and esophagus carcinoma cells without affecting non-transformed cells , promoting beneficial tumoristatic effects . OUTPUT:

sustaining proliferative signaling;tumor promoting inflammation

HoC_1shot797

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Proline- , glutamic acid- and leucine-rich protein-1/modulator of non-genomic activity of estrogen receptor ( ER ) ( PELP1/MNAR ) is a novel nuclear receptor ( NR ) co-activator that plays an essential role in the actions of ER . Emerging findings suggest that PELP1/MNAR is a novel proto-oncogene , whose expression is deregulated in several hormone-responsive cancers , including endometrial cancer . In this study , we demonstrate that PELP1/MNAR is widely expressed in endometrial carcinoma cell lines . To investigate its possible role in endometrial carcinoma progression , we adopted an RNA interference technology to downregulate PELP1/MNAR expression in Ishikawa endometrial carcinoma cells . PELP1/MNAR downregulation substantially reduced cell proliferation , and the cells in which PELP1/MNAR expression was knocked down also exhibited a decreased migration and invasion ability , as shown by Boyden chamber and invasion assays . The results showed that the expression of MMP-2 and MMP-9 was also decreased . These results suggest that PELP1/MNAR plays a role in endometrial cancer progression and metastasis , and that PELP1/MNAR may be a potential therapeutic target for endometrial cancer . OUTPUT:

activating invasion and metastasis;sustaining proliferative signaling

HoC_1shot798

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVE To construct the eukaryotic expression vector for Max interacting protein 1 ( Mxi1 ) . METHODS The full length cDNA of Mxi1 gene obtained from fetal lymphocyte and KG1 cells were inserted into plasmid pDs-red2-N1 respectively to generate pDs-red2-N1/Mri1 ( wild/mutation type ) . Then the recombinant vector was transfected into Cos-7 cells via liposome. 48 hours post transfection , mRNA of Mri1 gene was detected by RT-PCR and Mxi1 protein expression was detected by flow cytometry and fluorescence microscope in the Cos-7 cells . RESULTS The eukaryotic expression vector of Mxi1 was constructed and transfected into eukaryotic cells successfully . The expression of red fluorescence protein in the transfected Cos-7 cells was observed under fluorescence microscope which implied the expression of Mxi1 . The transfect efficiency of both wild and mutation type were in a high level in 3 days after transfected , which lasted to 6 d . RT-PCR amplified the total RNA extracted from the transfected Cos-7 cells could find increased mRNA level of Mxi1 gene . CONCLUSION We successfully constructed the eukaryote expression vector for Mri1 gene ; Cos-7 cells transfected with the vector via liposome could express Mxi1 protein . These could be useful for the further study of the Myc gene modulation . OUTPUT:

genomic instability and mutation

HoC_1shot799

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: TGF-β derived from bone fuels melanoma bone metastases by inducing tumor secretion of prometastatic factors that act on bone cells to change the skeletal microenvironment . Halofuginone is a plant alkaloid derivative that blocks TGF-β signaling with antiangiogenic and antiproliferative properties . Here , we show for the first time that halofuginone therapy decreases development and progression of bone metastasis caused by melanoma cells through the inhibition of TGF-β signaling . Halofuginone treatment of human melanoma cells inhibited cell proliferation , phosphorylation of SMAD proteins in response to TGF-β , and TGF-β-induced SMAD-driven transcription . In addition , halofuginone reduced expression of TGF-β target genes that enhance bone metastases , including PTHrP , CTGF , CXCR4 , and IL11 . Also , cell apoptosis was increased in response to halofuginone . In nude mice inoculated with 1205Lu melanoma cells , a preventive protocol with halofuginone inhibited bone metastasis . The beneficial effects of halofuginone treatment were comparable with those observed with other anti-TGF-β strategies , including systemic administration of SD208 , a small-molecule inhibitor of TGF-β receptor I kinase , or forced overexpression of Smad7 , a negative regulator of TGF-β signaling . Furthermore , mice with established bone metastases treated with halofuginone had significantly less osteolysis than mice receiving placebo assessed by radiography . Thus , halofuginone is also effective in reducing the progression of melanoma bone metastases . Moreover , halofuginone treatment reduced melanoma metastasis to the brain , showing the potential of this novel treatment against cancer metastasis . Cancer Res ; 72(23) ; 6247-56. �2012 AACR . OUTPUT:

activating invasion and metastasis;sustaining proliferative signaling;resisting cell death