bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2870: The inhibitory effects of propolin C and propolin G on human lung adenocarcinoma A549 cells through autophagy and apoptosis pathway
Authors: Hsu Hui-Chen , Ku Feng-Chuan , Chen Yu-Fen , Wang Hsiao-Feng , Lin Zhong-Zhe , Chen Yue-Wen , Tsai Meng-Geng 
Published: June 2012

Abstract
Propolis has been used empirically for centuries and it was always mentioned as an immunomodulatory agent. Propolis has over 150 constituents such as polyphenols (flavonoids, phenolic acids and their esters), terpenoids, steroids, and amino acids, but its composition varies qualitatively and quantitatively with the geographical and botanical origins. In Tawiwan, there are ten propolins (A-J) were isolated and characterized from the local propolins. Propolins, prenylflavanones are isolated and characterized from Taiwanese propolis have been shown inhibits certain cancer cell lines growth and induced apoptosis. In this study, human lung adenocarcinoma cell (A549) was used to investigate the anticancer activity of Proploins. Propolin C and propolin G could inhibit A549 cell growth by dose-dependent manner. The combination of propolin C with propolin G was more predominantly inhibited the cell viability. Propolin C or propolin G treatment alone could suppress Akt and p70S6K activation by blocking the PI3K/Akt/mTOR pathway. Moreover, the pro-apoptotic protein Bax and Bad expression were increased. The procaspase 9, procaspase 3, and PARP activated in cascade to lead to mitochondria-mediated apoptosis pathway of apoptosis. Flow cytometry assay showed that sub-G1 phase increased significantly in propolin G treatment but not in propolin C group. Both propolin C and G could promote LC3B increased within 6 hours treatment, moreover, and AVOs (acidic vesicular organelles) significantly increased by AO (Acridine orange) staining. Combination treatment had synergies effect to induce significantly apoptosis and autophagy in A549 cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2870. doi:10.1158/1538-7445.AM2011-2870
Abstract 2872: Induction of autophagy in hypoxic HT29 cells requires functional JNK1
Authors: Vasilevskaya Irina A. , Roberts David , O'Dwyer Peter J 
Published: June 2012

Abstract
BACKGROUND: Hypoxic HT29 colon cancer cell lines exhibit higher sensitivity to oxaliplatin when SEK1 function is impaired and higher resistance when MKK7 is down regulated (which in turn, cause more profound inhibition of JNK activation). We observed differential effects of JNK1/JNK2 modulation on oxaliplatin sensitivity of hypoxic HT29 cells to oxaliplatin treatment that implied a pro-survival function for JNK1. Further, we have shown that both oxaliplatin- and hypoxia-induced autophagy in these cells is diminished in the presence of JNK inhibitor SP600125, and that the cells are sensitized thereby.
PURPOSE: Here we investigate further how modulation of signaling through JNK influences autophagy in hypoxic HT29 cells treated with oxaliplatin, and expand the cellular model to additional colon cancer cell lines. We created a panel of HT29-derived cell lines stably expressing dominant negative constructs for SEK1 (HTS13), MKK7 (HTM9), JNK1 (HTJ1.3) and JNK2 (HTJ2.2). We also utilized 6 colon cancer cell lines (HCT116, LoVo, RKO1, SW480, DLD1 and HCT15) in which a dominant negative construct for JNK1 was introduced by viral delivery.
RESULTS: Our data demonstrate that in HTJ1.3 cells, hypoxic induction of autophagy is impaired. Silencing of JNK2 in these cells by viral delivery of shRNA does not affect either autophagy induction, or sensitivity to oxaliplatin. Downregulation of up-stream activators of JNK, as in the dnSEK1 or dnMKK7 derivatives, similarly does not affect autophagy induction, while still demonstrating differential effects on activation of JNK isoforms and its major target, c-Jun. Finally, we show that colon cancer cell lines differ in their ability initiate autophagy under hypoxia. Correspondingly, the introduction of dominant negative JNK1 causes some enhancement of oxaliplatin cytotoxicity in LoVo, RKO1 and HCT15 cell lines, which all demonstrate a greater propensity to autophagy under these circumstances.
CONCLUSIONS: Our data demonstrate that JNK1 plays a central role in autophagy induction under hypoxic conditions. Knockdown of JNK1 renders HT29 cells more sensitive to hypoxia due to impaired autophagy induction, and JNK2 is unable to substitute for JNK1 under these conditions. Our results also imply involvement of alternative JNK1 activators in autophagy induction by hypoxia. Finally, induction of autophagy and enhancement of oxaliplatin cytotoxicity, by this mechanism, appear to be model-specific in colon cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2872. doi:10.1158/1538-7445.AM2011-2872
Abstract 2875: Ceramide suffocates cancer cells to death: Regulation of mitophagy by ceramide signaling
Authors: Ogretmen Besim , Sentelle David , Senkal Can E. 
Published: June 2012

Abstract
Sphingolipid ceramide is a bioeffector molecule involved in the regulation of cell death. Endogenous ceramides contain different fatty acid chain lengths varying between C12-C26-ceramides. Ceramide synthase 1 (CerS1) selectively regulates the generation of C18-ceramide, which is down-regulated in the majority of tumors obtained from patients with head and neck squamous cell carcinomas (HNSCC). Reconstitution of C18-ceramide generation using a tetracycline inducible vector system for stable expression of CerS1 inhibits the growth of HNSCC cells and xenografts in culture and SCID mice, respectively. In this study, our goal was to determine mechanisms by which CerS1/C18-ceramide inhibits HNSCC tumor growth. Data revealed that reconstitution of C18-ceramide generation by wt-CerS1 induction, but not its catalytically inactive mutant, induces autophagy as detected by various techniques in HNSCC cells. Interestingly, soft agar studies showed that CerS1/C18-ceramide induction inhibits HNSCC cell growth, which is prevented by addition of the autophagy inhibitor 3-methyladenine. In addition, knockdown of Atg3 and Atg7 in HNSCC cells protected against cell death induced by exogenous addition of the C18-ceramide therapeutic analog, C18-pyridinium-ceramide (C18-Pyr-Cer). Additionally, Atg5-/- MEFs showed resistance to cell death when compared to wild type MEFs upon C18-Pyr-Cer exposure. Taken together these results suggest that autophagy is required for cell death. Electron microscopy showed that addition of C18-Pyr-Cer to UM-SCC-22A cells induced autophagosome formation and fusion with mitochondria. Mechanistically, our studies showed that CerS1/C18-ceramide-induced cell death/inhibition of tumor growth are mediated by mitochondrial damage and inhibition of respiration via induction of mitophagy. Inducible expression of CerS1/C18-ceramide and C18-Pyr-Cer treatment resulted in significant decreases in mitochondrial oxygen consumption rates. Furthermore, live and fixed cell imaging with mitochondrial markers MitoTracker Red colocalized with lysosomal marker LysoTracker Red upon C18-Pyr-Cer treatment and CerS1/C18-ceramide induction indicating mitochondrial fusion with lysosomes. Conversely, ceramide-mediated mitophagy was inhibited using LC3B siRNA, suggesting that mitochondria might be targeted to autophagosomes by ceramide signaling. In conclusion, we provide novel evidence here which suggest that C18-ceramide targets autophagosomes to mitochondria (mitophagy), which results in the modulation of respiration/oxygen consumption, leading to HNSCC growth inhibition and tumor suppression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2875. doi:10.1158/1538-7445.AM2011-2875
Abstract 2888: SOCS3-deficient cells are defective in the DNA damage response
Authors: Cacalano Nicholas A. , Jiang Sisi 
Published: June 2012

Abstract
The SOCS family of proteins are negative feedback inhibitors of cytokine and growth factor signal transduction, targeting primarily the STAT family of transcription factors. Several SOCS genes, including SOCS1 and SOCS3 are hypermethylated and silenced in solid tumors, which is believed to impart a growth advantage via hyperactivation of the STAT pathway. Despite the growing role of SOCS in the pathogenesis of cancer, very little is known of their role in modulating tumor cell responses to therapy. We recently identified an unexpected function for SOCS3 in the context of the DNA damage response. We found that cells lacking SOCS3 are sensitive to ionizing radiation (IR) in a clonogenic survival assay due to impaired p21 (Cip1/Waf-1) upregulation, which results in failure of the radiation-induced G1-S checkpoint. Normal cell cycle arrest and p21 upregulation could be restored in SOCS3-/- MEFs by overexpression of a phosphorylation-deficient, dominant-negative (DN) mutant of STAT3. Two STAT3-dependent genes known to suppress p21 expression, c-Myc and BCL6 are overrepresented in SOCS3-deficient MEFs. Likewise, human tumor cells that repress SOCS3 expression by epigenetic silencing are also more radiosensitive than their SOCS3+ counterparts. In agreemwnt with our data in MEFs, c-Myc and BCL6 are overexpressed in human tumor cells that silence SOCS3 expression by promoter hypermethulation, suggesting that tumors lacking SOCS3 may be more vulnerable to IR-based therapies due to impaired cell cycle arrest and DNA repair. Our data suggest that therapeutic targeting of SOCS3 in tumor cells could sensitize cells to IR and improve the effectiveness of radiotherapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2888. doi:10.1158/1538-7445.AM2011-2888
Abstract 2895: The epithelial to mesenchymal transition is associated with alterations in the mitogenic signaling pathways that drive cancer cell proliferation
Authors: Corsino Patrick E. , Law Mary , Jahn Stephan , Davis Brad , Law Brian 
Published: June 2012

Abstract
The Epithelial to Mesenchymal Transition (EMT), by facilitating the metastatic process, is an important step in tumor progression for many types of cancer. We have developed a mouse tumor model, driven by the HER2/neu oncogene, whereby this process can be studied robustly both in vivo and in cell culture. This system has revealed significant changes in mitogenic signaling networks that occur during EMT. Post-EMT cancer cells acquired increased responsiveness to HGF, PDGF, and LPA. This change in responsiveness was accompanied by a decrease of Her2, c-Src and IRS-1 levels, as well as an increase in Axl, PDGFR and c-Met levels. Perturbations in these signaling cascades results in the differential sensitivity to certain anti-cancer therapeutics. Post-EMT cells were less sensitive than Pre-EMT cells to the MEK inhibitor U0126. Furthermore, while Pre-EMT cells exhibited cell cycle arrest in response to rapamycin, Post-EMT cell proliferation was stimulated. These observations may have significant bearing on the efficacy of targeted therapeutic agents in patients with metastatic breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2895. doi:10.1158/1538-7445.AM2011-2895
Abstract 2902: Phosphorylation of 12 lipoxygenase at Tyrosines 19 and 614 regulates its activity during beta4 integrin signaling
Authors: Dilly Ashok Kumar , Tang Keqin Tang , Guo Yande Guo , Joshi Sangeeta , Ekambaram Prasanna , Maddipati Krishna Rao , Cai Yinlong , Tucker Stephanie , Honn Kenneth 
Published: June 2012

Abstract
12-Lipoxygenase (12-LOX) converts arachidonic acid to 12(S)-hydroxyeicosatetraenoic acid 12(S)-HETE, an eicosanoid implicated in tumor angiogenesis, growth, and metastasis. We have demonstrated previously that 12-LOX interacts with integrin beta4 cytoplasmic domain by using yeast two hybrid system. Integrins are involved in metastasis by mediating attachment and migration of cells, as well as through transducing signals. Increased expression of 12-LOX and beta4 integrin have been documented in a number of carcinomas. The purpose of this study is to find out the mechanisms underlying the signaling pathways in 12-LOX mediated cancer progression. The phosphorylation of beta4 integrin, Src, and 12-LOX were analyzed using specific antibodies against phospho-tyrosine, phospho-beta4 integrin, Phospho-Src (pSrc). c-Src activity and association was determined in beta4 integrin immunoprecipitate. The HEK293 cells transiently transfected with wild type or dominant negative (DN) Src were used as in vitro models to study the regulation of 12-LOX activity. The 12-LOX product 12(S)-HETE was analyzed by using an analytical liquid chromatography-tandem mass spectrometry.12-LOX tyrosine phosphorylation sites mutants viz., 19, 295, and 614 were used to study the effect on its activity upon beta4 ligation. We show here that the cytoplasmic domain of beta4 integrin, can interact specifically with pSrc after beta4 integrin ligation in A431 cells. Herein we report that beta4 integrin ligation resulted in significant increase in 12(S)-HETE level in A431 cells, compared to that of unligated beta4 integrin. An increase in Src kinase activity was found in beta4 integrin ligation of A431 cells and inhibition of Src kinase by PP2 or DN Src significantly reduced 12(S)-HETE production. The ligation of beta4 integrin induces src activation, which resulted in tyrosine phosphorylation of 12-LOX. The residues that are important for 12-LOX activity and tyrosine phosphorylation were mapped to Y19 and Y614. We examined that 12-LOX mutants (Y19F and Y614F), showed 70% less enzymatic activity, compared to wild type 12-LOX. Furthermore, we showed that the 12-LOX activity modulated by these residues impacts migration in HUVEC cells. To our knowledge, this is the first report to show that Src kinase activity is required for beta4 integrin mediated regulation of 12-LOX, which may in turn regulate metastatic potential of cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2902. doi:10.1158/1538-7445.AM2011-2902
Abstract 2924: IGF-IR inibition induces MAPK signaling in prostate carcinoma cells
Authors: Morris Brandon L. , Young Talearia , van Golen Cynthia M. 
Published: June 2012

Abstract
Prostate carcinoma, the most common malignancy in men, metastasizes primarily to bone. Multiple factors, including integrins, chemokines, and growth factors are implicated in the regulation of this process. In our laboratory, we are interested in the role of the insulin-like growth factor (IGF) family of proteins in the regulation of tumor metastasis to bone. Metastatic prostate carcinoma cells express the type I IGF receptor (IGF-IR) and are responsive to IGF ligands. Therefore, it has been suggested that inhibitors against the IGF-IR may be effective against prostate carcinoma bone metastasis.
Our hypothesis is that IGF-IR inhibitors will prevent prostate carcinoma growth and survival signaling. PC-3, LNCaP, and bone-adapted C42B prostate carcinoma cells were plated in a 96-well growth assay and treated with/without IGF-I and/or neutralizing antibody against the IGF-IR. Predictably, IGF-I treatment leads to an increase in cell number over a period of 4 d; however, inhibition of the IGF-IR enhances, rather than diminishes, this effect on growth. To further understand this paradoxical finding, Western immunoblotting was performed to analyze the effect of IGF-IR inhibition on IGF-IR expression and signaling. PC-3 cells were treated with increasing concentrations of a neutralizing antibody against the IGF-IR. With increasing concentrations of the neutralizing antibody, IGF-IR and Akt expression levels remain unchanged. In contrast, p44/p42 MAPK expression and activation increases with increasing concentrations of the IGF-IR neutralizing antibody. These data suggest that IGF-IR inhibition induces an upregulation of the p44/p42 MAPK pathway in PC-3 prostate carcinoma cells.
The data collected indicate that our original hypothesis was incorrect. Our current hypothesis is that treatment of prostate carcinoma cells with the IGF-IR neutralizing antibody induces receptor internalization supporting prolonged signaling rather than lysosomal degradation. We are currently investigating this hypothesis using immunofluorescence and confocal microscopy.This work was supported by NIH/NCRR 2 P20 RR016472-09 (INBRE) and the Children's Neuroblastoma Cancer Foundation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2924. doi:10.1158/1538-7445.AM2011-2924
Abstract 2927: Regulation of Na+/H+ exchanger 1 (NHE1) expression by hyperactivation of Akt in PTEN-null mouse embryonic fibroblasts
Authors: James Joanne , Kumar Jaspal Kaur , Clement Marie Veronique 
Published: June 2012

Abstract
The serine/threonine kinase, Akt, plays a key role in regulating the signaling of a multitude of biological processes including cell proliferation, differentiation, migration and survival. In addition, many human cancers commonly display aberrant hyperactivated Akt survival pathway, a phenomenon that is frequent in tumours that have impaired or deletion of the PTEN tumour suppressor gene. Interestingly, we have recently demonstrated that an increase in intracellular O2− could replace the removal of growth factors resulting in the activation of Akt through the inhibition of the tumour suppressor PTEN and inducing an increased expression of the Na+/H+ exchanger 1 (NHE1), mimicking the phenotype of PTEN-null mouse embryonic fibroblasts. The Na+/H+ exchanger 1 (NHE1) is a membrane antiporter that has been described to promote cell survival via a dual mechanisms- defending cell volume and pHi through Na+/H+ exchange and by functioning as a scaffold for the recruitment of a signalplex involving, PI3-Kinase, ERM and Akt. In the present study, we asked whether the hyperactivity of Akt found in cells that have lost the expression of PTEN could influence the expression of NHE-1. We show that the PTEN-null mouse embryonic fibroblast model displayed an increased expression of Na+/H+ exchanger 1 (NHE1) and hyperactivated Akt compared to its PTEN wildtype counterpart. Moreover the half-life of NHE-1 was shown to increase in PTEN-null fibroblasts compared to the wildtype mouse embryonic fibroblasts. Hence, we hypothesized that Akt hyperactivation could influence the stability of NHE-1 expression. Indeed, using drugs such as LY294002 and Wortmannin to inhibit the activation of AKT, we showed that activated Akt had an effect on NHE-1 expression as the decrease in NHE-1 expression correlated with the dephosporylation of Akt, both at the mRNA and protein levels. Similarly, by silencing Akt gene expression, a more prominent decrease in NHE-1 protein expression was observed. Taken together, our data suggest that hyperactivated Akt may play a crucial role in the stability of NHE-1 in PTEN null fibroblasts, a phenomenon not observed in wildtype fibroblasts. Results from these studies could establish that Akt may be involved in the regulation of NHE-1 expression in tumours that have lost the expression of PTEN.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2927. doi:10.1158/1538-7445.AM2011-2927
Abstract 293: Characterization of renal tumor-initiating cells in human renal carcinoma cell lines
Authors: Wang Lin , Park Paul , Zhang Huina , Marca Frank La , Lin Chia-Ying 
Published: June 2012

Abstract
High aldehyde dehydrogenase activity (ALDH) has been used as a putative marker for the tumor- initiating subpopulation in many cancer types. We previously showed that tumor-initiating cells in human osteosarcoma OS99-1 cell line can be identified using ALDH. In the current study we sought to determine whether ALDH can be also used as a marker to isolate tumor-initiating populations from human renal carcinoma cell lines. By using a xenograft model in which cells from human renal carcinoma cell line ACHN and Caki-2 were grown in NOD/SCID mice, we identified a subset of renal cells that were highly tumorigenic based on the high aldehyde dehydrogenase activity. Isolated cancer cells with relatively high aldehyde dehydrogenase activity (ALDHbr cells) revealed a greater colony-forming efficiency, higher proliferative output, the ability to grow in non-adhesive spheroids, the capability to undergo adipogenic and osteogenic differentiation, and increased expression of stem cell marker genes Oct3/4A, Nanog and Pax-2. In vivo experiments showed that ALDHbr cells were enriched with greater tumorigenicity compared to their counterparts with low ALDH activity (ALDHlo cells), generating new tumors with as few as 25 cells. The isolation of renal tumor-initiating cells by their high ALDH activity may lead to a new insight into the study of how renal cell carcinoma may take place, and may lead to effective prognostic and therapeutic strategies for the treatment of patients with kidney cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 293. doi:10.1158/1538-7445.AM2011-293
Abstract 2956: Prognostic value of PCNA expression in salivary gland cancer in consideration of different histological subtypes
Authors: Stenner Markus , Demgensky Ariane , Molls Christoph , Hardt Aline , Klussmann Jens P. 
Published: June 2012

Abstract
Background: The expression of the cell proliferation-related marker Proliferating Cell Nuclear Antigen (PCNA) has shown to be a significant prognostic indicator in various human cancers. Its role in malignant tumors of the major salivary glands remains unclear.
Methods: We analysed the expression of PCNA in 159 patients with parotid gland cancer (12 different histological subtypes) by means of immunohistochemistry. Patients were divided into two groups due to the median PCNA expression level. The experimental findings were correlated with clinicopathological and survival parameters. The mean follow-up time was 56.6 months.
Results: Cytoplasmic expression of PCNA was found in 89% of cases. A high cytoplasmic expression of PCNA was found in 47% of the examined tumors. High cytoplasmic PCNA expression was an independent prognostic indicator for a significant poorer 5-year disease-free survival rate (50.6% versus 73.8%, p=0.036) as well as overall survival rate (57.0% versus 78.8%, p=0.006).
Conclusion: The correlation between cytoplasmic PCNA expression and survival probabilities of salivary gland cancer might make this an effective tool in patient follow-up, prognosis and therapy in future.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2956. doi:10.1158/1538-7445.AM2011-2956