bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2590: Curcumin inhibits prostate cancer metastasis in vivo by targeting the inflammatory cytokines CXCL1 and -2.
Authors: Killian Peter H. , Kronski Emanuel , Astigiano Simonetta , Barbieri Ottavia , Sommerhoff Christian P. , Nerlich Andreas G. , Pfeffer Ulrich , Bachmeier Beatrice E. 
Published: August 2014

Abstract
In America and Western Europe prostate cancer is the second leading cause of death in men. Emerging evidence suggests that chronic inflammation is a major risk factor for the development and metastatic progression of prostate cancer.
We previously reported that the chemopreventive polyphenol Curcumin inhibits the expression of the pro-inflammatory cytokines CXCL1 and -2 leading to diminished formation of breast cancer metastases. Here we analyse the effects of Curcumin on prostate carcinoma growth, apoptosis and metastasis. We show that Curcumin inhibits translocation of NFκB to the nucleus through the inhibition of the IκB-kinase, IKKβ, leading to stabilization of the inhibitor of NFκB, IκBα, in PC3 prostate carcinoma cells. Inhibition of NFκB activity reduces expression of CXCL1 and -2 and abolishes the autocrine/paracrine loop that links the two chemokines to NFκB. The combination of Curcumin with the synthetic IKKβ inhibitor, SC-541, shows no additive or synergistic effects indicating that the two compounds share the target. Treatment of the cells with Curcumin as wells as siRNA based knock-down of CXCL1 and -2 induce apoptosis, inhibit proliferation, and down-regulate several important metastasis-promoting factors like COX2, SPARC, and EFEMP. In an orthotopic mouse model of haematogenous metastasis, treatment with Curcumin inhibits statistically significantly formation of lung metastases.
In conclusion, chronic inflammation can induce a metastasis prone phenotype in prostate cancer cells by maintaining a positive pro-inflammatory and pro-metastatic feed-back loop between NFκB and CXCL1/-2. Curcumin disrupts this feed-back loop by the inhibition of NFκB signalling leading to reduced metastasis formation in vivo.
Citation Format: Peter H. Killian, Emanuel Kronski, Simonetta Astigiano, Ottavia Barbieri, Christian P. Sommerhoff, Andreas G. Nerlich, Ulrich Pfeffer, Beatrice E. Bachmeier. Curcumin inhibits prostate cancer metastasis in vivo by targeting the inflammatory cytokines CXCL1 and -2. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2590. doi:10.1158/1538-7445.AM2013-2590
Abstract 2591: Global gene expression regulated by phenethyl isothiocyanate in human colon cancer SW480 cells.
Authors: Mi Lixin , Wang Xiantao , Li Xin , Chung Fung-Lung 
Published: August 2014

Abstract
Phenethyl isothiocyanate (PEITC), a promising chemopreventive compound originated from cruciferous vegetables, is known to inhibit proliferation of colon cancer cells through inducing apoptosis and cell cycle arrest. Although exact mechanisms are unclear, it seems that PEITC may have multiple molecular targets and play multiple roles in a variety of events. Some of our recent studies indicate that a key mechanism of apoptosis induction by PEITC may be through covalent modification of its target proteins, such as tubulin. Numerous studies also reported that PEITC may induce apoptotic signals through gene transcriptional regulation. However, systematic studies on PEITC-induced gene expression profile, particularly in colon cancer cells, are rare. In this study, we examined overall gene expression profile of SW480 cells at different time points after PEITC treatment using cDNA microarray. Results showed that PEITC induced significant changes in expression of several apoptosis-related genes, such as BIM, DEDD2, GADD45B, HSPB8, SYK, PIK3C2A, CTNNB1, LGALS8, and NOXA. Furthermore, these changes were confirmed by real-time polymerase chain reaction at transcript level and immunoblot at protein level. Considering significant roles of these genes in signaling transduction leading to downstream events, such as apoptosis, the findings of this study may shed lights on the molecular mechanisms by which PEITC exert its anti-carcinogenic effects. (Supported by NCI grant CA100853)
Citation Format: Lixin Mi, Xiantao Wang, Xin Li, Fung-Lung Chung. Global gene expression regulated by phenethyl isothiocyanate in human colon cancer SW480 cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2591. doi:10.1158/1538-7445.AM2013-2591
Abstract 2592: Helicobacter pylori induces phosphorylation of STAT3 Tyr705 and Ser727 in human gastric epithelial cells.
Authors: Piao Juan-Yu , Lee Hee-Geum , Ji Hyeon-Geum , Han Hyeong-Joon , Ngo Hoang Kieu Chi , Kim Do-Hee , Kim Su-Jung , Lee Sung-Young , Surh Young-Joon 
Published: August 2014

Abstract
Helicobacter pylroi (H. pylori) infection has been considered to be one of the high risk factors of gastritis and gastric cancer, but its pathogenic implication is still poorly understood. Recent studies indicate that constitutive activation of the signal transducer and activator of transcription 3 (STAT3) plays an important role in inflammation-associated carcinogenesis. In our previous study, we found that the phosphorylation of STAT3 at Tyr705 was increased in H. pylori plus high salt diet-induced gastritis in a mouse model. The similar results were observed in human gastric AGS cells co-cultured with H. pylori. Interestingly, H. pylori induced phosphorylation of STAT3 at not only Tyr705 but also Ser727. However, the phosphorylation of two residues exhibited different profiles in human gastric epithelial cells upon H. pylori treatment. The phosphor-Tyr705 increased at early time of H. pylori infection and then decreased immediately, but phosphor-Ser727 increased thereafter which was first discovered in our present study. Phosphorylation of STAT3 is an essential event for inducing the expression of anti-apoptotic/survival proteins, such as Bcl-XL, BcL-2, survivin and c-Myc which contribute to gastric carcinogenesis. Levels of all these proteins were elevated in H. pylori-infected AGS cells. In conclusion, H. pylori induces phosphorylation of STAT3 at both Tyr705 and Ser727 residues. The role of phospohorylation of STAT3 at the Serine 727 residue in H. pylori-induced gastritis and gastric cancer is under investigation.
Citation Format: Juan-Yu Piao, Hee-Geum Lee, Hyeon-Geum Ji, Hyeong-Joon Han, Hoang Kieu Chi Ngo, Do-Hee Kim, Su-Jung Kim, Sung-Young Lee, Young-Joon Surh. Helicobacter pylori induces phosphorylation of STAT3 Tyr705 and Ser727 in human gastric epithelial cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2592. doi:10.1158/1538-7445.AM2013-2592
Abstract 2596: Inhibition of PI3K-mTOR pathway using combination of chloroquine and aspirin regimen leads to apoptosis in pancreatic cancer cells.
Authors: Thakkar Arvind , Grandhi B. Karthik , Wang Jeffrey , Prabhu Sunil 
Published: August 2014

Abstract
Pancreatic cancer ranks as the fourth most deadly form of cancer in the United States with approximately 37,000 deaths each year. The present study aims to evaluate the combinatorial chemopreventive effects of low doses of chloroquine (CQ) and aspirin (ASP) alone and in combination CQA (CQ+ASP) on three pancreatic cancer cell lines, MIA PaCa-2, Panc-1 and BxPC-3. Results demonstrated that low doses of CQ (6.25μM) and ASP (1mM) alone did not reduce cell viability, whereas combination CQA reduced cell viability by ∼80% (P&lt;0.001). CQA combination blocked cell cycle progression at G0/G1 checkpoint. The CQA treatment for 24 h inhibited the NF-κB p50 DNA binding activity by ∼45% (P&lt;0.01) in MIA PaCa-2 and BxPC-3 cells, but no NF-κB inhibition observed in Panc-1 cells. Mechanistic studies revealed that treatment with CQA combination increased the expression of LC3-II protein, indicates inhibition of autophagy. In order to verify the involvement of PI3K and mTOR pathway in CQA-induced apoptosis, we used PI3K inhibitor (3-MA) and mTOR inhibitor (Rapamycin) and analyzed by cell viability assay. The inhibition of PI3K by 3-MA pretreatment enhanced the cell growth inhibition of CQA treatment, whereas the inhibition of m-TOR by rapamycin pretreatment attenuated CQA induced reduction in cell viability. Overall, our results for the first time, illustrate that low dose CQA combinations impart synergistic suppressive activity than chemopreventive agents alone, thus confirming the importance of novel combination chemoprevention strategies against pancreatic cancer.
Citation Format: Arvind Thakkar, B. Karthik Grandhi, Jeffrey Wang, Sunil Prabhu. Inhibition of PI3K-mTOR pathway using combination of chloroquine and aspirin regimen leads to apoptosis in pancreatic cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2596. doi:10.1158/1538-7445.AM2013-2596
Abstract 2597: Prospective study of the relationship between coffee and tea with colorectal cancer risk: The PLCO cancer screening trial.
Authors: Dominianni Christine , Huang Wen-Yi , Berndt Sonja , Hayes Richard B. , Ahn Jiyoung 
Published: August 2014

Abstract
Coffee and tea are commonly consumed and carry several potential anticancer components which could reduce the risk of colorectal cancer risk; however, the relationships of coffee and tea consumption with colorectal cancer risk remain unclear. We prospectively examined the relations of coffee and tea intake to colorectal cancer risk in 53,480 men and women in the intervention arm of the NCI-Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. The majority of these men and women (82.3%) received flexible sigmoidoscopy screening at baseline. Coffee and tea intakes were assessed by a food frequency questionnaire at study baseline. Six-hundred and twenty-two incident colorectal cancer cases were ascertained during a median follow-up of 11.4 years. Greater coffee intake was not associated with risk of colorectal cancer. The relative risks for &lt;1 cup/day, 1 cup/day, 2-3 cups/day and ≥4 cups/day, respectively, were 0.89 (95% CI=0.65-1.20), 0.92 (95% CI=0.68-1.25), 1.02 (95% CI=0.76-1.36) and 1.08 (95% CI=0.78-1.49); p for trend = 0.16. Associations were also not detected for ≥4 cups of coffee/day when stratifying by cancer site (proximal, distal and rectal, p for heterogeneity = 0.53) or stage of disease (stage I, stage II and stage III/IV, p for heterogeneity = 0.86). Furthermore, associations remained unchanged in subsets of participants for either caffeinated or decaffeinated coffee or when stratifying by several colorectal cancer risk factors. Similarly, greater tea intake was not associated with colorectal cancer risk. The relative risks for &lt;1 cup/day, 1 cup/day and ≥2 cups/day were 1.02 (95% CI=0.82-1.27), 1.14 (95% CI=0.83-1.58) and 0.76 (95% CI=0.53-1.10), respectively; p for trend = 0.15. There were also no associations observed for ≥2 cups of tea/day by cancer site (proximal, distal and rectal, p for heterogeneity = 0.79) or stage of disease (stage I, stage II and stage III/IV, p for heterogeneity = 0.44). The associations were also not modified by several colorectal cancer risk factors. In conclusion, the findings of this study do not provide evidence to suggest that drinking coffee or tea is beneficial in protecting against colorectal cancer.
Citation Format: Christine Dominianni, Wen-Yi Huang, Sonja Berndt, Richard B. Hayes, Jiyoung Ahn. Prospective study of the relationship between coffee and tea with colorectal cancer risk: The PLCO cancer screening trial. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2597. doi:10.1158/1538-7445.AM2013-2597
Abstract 2602: Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression through paracrine neuregulin 1/HER3 signaling.
Authors: Wever Olivier De , Boeck Astrid De , Hendrix An , Denys Hannelore , Braems Geert , Bracke Marc 
Published: August 2014

Abstract
Objective: Bone marrow-derived mesenchymal stem cells (BM-MSC) migrate to primary tumors and drive tumor progression. This study aimed to identify the molecular mechanisms associated with these heterotypic cellular interactions and analyse their relevance in colorectal cancer (CRC).
Design: Paracrine interactions of BM-MSC with CRC cells were studied using collagen invasion assays, cell counts, flow cytometric cell-cycle analysis and tumor xenograft models. The role of neuregulin 1 (NRG1) and the human epidermal growth factor receptor (HER) family pathways were investigated using tyrosine kinase assays, mass spectrometry, pharmacological inhibition, antibody-mediated neutralisation and RNA interference. Transmembrane NRG1 (tNRG1), HER2 and HER3 expression was analysed in primary CRCs (n = 54), adjacent normal colorectal tissues (n = 4), liver metastases (n = 3) and adjacent normal liver tissues (n = 3) by immunohistochemistry.
Results: BM-MSC stimulate invasion, survival and tumorigenesis of CRCs through release of soluble NRG1, activating the HER2/HER3-dependent PI3K/AKT signaling cascade in CRC cells. Tumor-associated mesenchymal cells (T-MC) in CRCs demonstrate high tNRG1 expression. HER2 and HER3 show membrane localization in cancer cells of CRC tissue. High tNRG1 expression in T-MC is significantly associated with advanced UICC stage (P = .005) and invasion depth (P = .04) and decreased 5-year progression-free-survival (PFS) (P = .01).
Conclusion: Paracrine NRG1/HER3 signals initiated by BM-MSC promote CRC cell progression, and high tNRG1 expression is associated with poor prognosis.
Citation Format: Olivier De Wever, Astrid De Boeck, An Hendrix, Hannelore Denys, Geert Braems, Marc Bracke. Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression through paracrine neuregulin 1/HER3 signaling. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2602. doi:10.1158/1538-7445.AM2013-2602
Abstract 2608: Regulation of response to oxaliplatin by wnt/β-catenin in colon cancer cell lines.
Authors: Lee Myung Ah , Park Jin Hee 
Published: August 2014

Abstract
Background: Oxaliplatin is the standard treatment chemotherapy agent in patients with metastatic colorectal cancer. However, most patients developed the progressive disease after treatment with oxaliplatin due to chemotherapy resistance. Unfortunately the mechanism of resistance of oxaliplatin is unclear. Wnt/β-catenin signaling pathway may play a role in oncogenesis in many cancer and also involve in the control the cancer progression and metastasis throughout the interaction with the tumor microenvironment. In this study, we investigated the response to oxaliplatin regulated by wnt/β-catenin pathway in colon cancer cell line.
Method: We used SNU-C2A and HCT116 human colon cancer cell lines. After comparing β-catenin expression in SNU-C2A and HCT116 cells through western blot, we exposed these two cell lines to gradient concentrations of oxaliplatin for 48hrs to examine the sensitivity. The viability was determined by Neutral Red uptake assay (NR assay). To construct a gene silenced cell line, a siRNA against β-catenin was transfected in HCT116 cells. Besides, we stimulated SNU-C2A cells with human recombinant Wnt3a (rhWnt3a) protein to up regulate the β-catenin and estimated the change of sensitivity for oxaliplatin,respectively. We also constructed a HCT116-cis cell line which showed oxaliplatin-resistance. It has been made by long-term exposure to oxaliplatin.
Result: β-catenin was highly expressed in HCT116 cell line relatively higher than in SNU-C2A cell line. Through the sensitivity test to oxalipatlin, we confirmed that SNU-C2A cells were more sensitive to oxaliplatin than HCT116 cells. When we transfected β-catenin siRNA into the HCT116 cell line, the cell viability was decreased about 20-50% after oxaliplatin treatment. After rhWnt3a treatment,we confirmed the expression of β-catenin and c-myc was up regulated in SNU-C2A cell line by western blot. After treatment with oxaliplatin, we found that the cell viability was reduced in SNU-C2A cells with β-catenin overexpressing. Moreover,HCT116-cis, oxaliplatin-resistance induced cell line, showed not only the increased protein level of β-catenin but also the upper viability for oxaliplatin compared with HCT116.
Conclusion Based on our data, β-catenin is one of the crucial factors to determine the resistance for oxaliplatin in colon cancer cells. Currently we are conducting the analysis with human tissue, and exploring the possible mechanism of resistance developmend to oxaliplatin.
Citation Format: Myung Ah Lee, Jin Hee Park. Regulation of response to oxaliplatin by wnt/β-catenin in colon cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2608. doi:10.1158/1538-7445.AM2013-2608
Abstract 2609: Astrocytes decrease the radiosensitivity of glioblastoma stem-like cells.
Authors: Rath Barbara H. , Camphausen Kevin , Tofilon Philip J. 
Published: August 2014

Abstract
Radiotherapy remains a primary treatment modality for glioblastoma (GBM). However, despite their extensive biological heterogeneity, although some GBMs respond better than others, they all essentially fail radiotherapy. This relatively homogeneous clinical response in a background of inter-tumor heterogeneity suggests that the microenvironment may play a significant role in determining their radioresponse. Data now suggest that glioblastoma stem-like cells (GSCs) play a critical role in GBM development and maintenance. Therefore, towards developing a model system for investigating the role of the microenvironment in GBM radioresponse, we have used human GSCs grown in co-culture with human astrocytes. For these studies GSCs were seeded into the lower compartment of Boyden chambers with astrocytes in the upper compartment. GSC numbers were determined at times out to 18 days after seeding according to ATP content. The proliferation rate of GSCs in co-culture was similar to that obtained when astrocytes were not included in the upper chamber, indicating that astrocytes had no effect on the growth rate of GSCs. To determine whether astrocytes influence GSC radiosensitivity, 48h after co-culture initiation GSCs were irradiated with doses up to 6 Gy; ATP content of the cells were defined 11 days later and radiation survival curves generated. The resulting survival curves showed that the GSCs irradiated under co-culture conditions were significantly less sensitive than those irradiated in the absence of astrocytes. To begin to address the mechanisms responsible for the increased radioresistance of co-cultured GSCs, radiation-induced γ-H2AX nuclear foci were defined in GSCs grown with and without astrocyte co-culture. The initial level of γ-H2AX foci in GSCs was reduced significantly in co-cultures as compared to GSCs cultured in the absence of astrocytes suggesting the induction of fewer DNA double strand breaks. In addition, gene expression profiles generated from GSCs grown in co-culture were significantly different from control GSCs suggesting that astrocytes induced phenotypic modifications. Finally, profiling of astrocyte conditioned media revealed increased levels of a variety of chemokines/growth factors, including a number of which that have already been linked to radioresponse such as HGF, IL-6 and EGF. Taken together, these results are consistent with an astrocyte-mediated radioprotection of GBM cells and provide additional support for a critical role of the microenvironment in contributing to GBM radioresistance.
Citation Format: Barbara H. Rath, Kevin Camphausen, Philip J. Tofilon. Astrocytes decrease the radiosensitivity of glioblastoma stem-like cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2609. doi:10.1158/1538-7445.AM2013-2609
Abstract 2611: The developmental patterning gene HOXA9 promotes ovarian cancer growth via paracrine effects on mesenchymal stem cells and peritoneal fibroblasts.
Authors: Ko Song Yi , Barengo Nicolas , Ladanyi Andras , Lee Ju-Seog , Marini Frank , Lengyel Ernst , Naora Honami 
Published: August 2014

Abstract
As is the case in normal organogenesis, it is increasingly recognized that tumor growth is regulated by cross-talk between epithelial and stromal cells. Whereas the ability of cancer-associated fibroblasts (CAFs) to stimulate tumor cell growth has been extensively studied, it is not clear whether CAFs are reciprocally controlled by developmental programs that are activated in tumor cells. Epithelial ovarian cancers (EOCs) frequently colonize peritoneal surfaces that overlie connective and adipose tissues. We found that expression of HOXA9, a homeobox gene that is normally expressed in the developing female reproductive tract, is strongly associated with poor outcomes in EOC patients and in mouse xenograft models of EOC. Whereas HOXA9 promoted EOC growth in vivo, HOXA9 did not stimulate autonomous tumor cell growth in vitro. Expression of HOXA9 in EOC cells induced normal peritoneal fibroblasts and adipose mesenchymal stem cells (MSCs) to express CAF markers and to stimulate growth of EOC and endothelial cells. These effects of HOXA9 were due in substantial part to its transcriptional activation of the gene encoding TGF-β2 that acted in a paracrine manner on peritoneal fibroblasts and adipose MSCs to induce CXCL12, IL-6 and VEGF-A expression. These results indicate that HOXA9 expression in EOC cells promotes a microenvironment that is permissive for tumor growth.
Citation Format: Song Yi Ko, Nicolas Barengo, Andras Ladanyi, Ju-Seog Lee, Frank Marini, Ernst Lengyel, Honami Naora. The developmental patterning gene HOXA9 promotes ovarian cancer growth via paracrine effects on mesenchymal stem cells and peritoneal fibroblasts. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2611. doi:10.1158/1538-7445.AM2013-2611