bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 19: Structural insight for the role of Fas binding to FADD and oligomerization degree of Fas/FADD complex in death inducing signaling complex formation
Authors: Yan Qi , McDonald Jay M. , Song Yuhua 
Published: July 2012

Abstract
Fas death receptor-activated signaling pathways regulate apoptosis in a variety of cells, including cholangiocarcinoma and other cancer cells. Fas binding to Fas-associated death domain (FADD) activates FADD-caspase-8 binding to form the death-inducing signaling complex (DISC) to trigger apoptosis (Nature reviews 9:231-241, 2008, Cell 81:505-512, 1995). The Fas-Fas association exists primary as a dimer in the Fas-FADD complex and the Fas-FADD tetramer complex has the tendency to form higher oligomers (Nature 457:1019-1022, 2009). The importance of the oligomerized Fas-FADD complex in DISC formation has been confirmed (Nat Struct Mol Biol. 2010 Oct 10). This study sought to provide structural insight for the role of Fas binding to FADD and the oligomerization of Fas/FADD complex in activating FADD-procaspase-8 binding. In this study, we determined the conformational and motion changes of FADD by binding to Fas for the Fas-FADD complex in either dimer or tetramer behavior with molecular dynamics (MD) simulations. The conformational and motion changes in FADD by binding to Fas could directly affect FADD binding to procaspase-8. Results show Fas binding to FADD stabilized FADD conformation, including the increased stability of the critical residues in FADD death effector domain (DED) for FADD-procaspase-8 binding. Fas binding to FADD resulted in the decreased degree of both correlated and anti-correlated motion of the residues in FADD and caused the reversed correlated motion between FADD DED and FADD death domain. The exposure of procaspase-8 binding residues in FADD that allows FADD to interact with procaspase-8 was observed with Fas binding to FADD. We also observed the different degree of the conformational and motion changes of FADD in the Fas-FADD complex with the different degree of oligomerization. The increased conformational stability and the decreased degree of the correlated motion of the residues in FADD in Fas-FADD tetramer complex were observed compared to those in Fas-FADD dimer complex. This study provided structural evidence for the role of Fas binding to FADD and the oligomerization degree of Fas/FADD complex in DISC formation to signal apoptosis. The structural information should facilitate the identification of novel strategies and targets that regulate DISC formation and, thereby, modulate apoptosis.
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 19. doi:10.1158/1538-7445.AM2011-19
Abstract 1902: Aspirin, nonsteroidal antiinflammatory drugs (NSAIDs) acetaminophen and risk of pancreatic cancer
Authors: Tan Xiang-Lin , Reid Lombardo Kaye M. , Bamlet William R. , Robinson Dennis P. , Anderson Kristin , Petersen Gloria M. 
Published: July 2012

Abstract
Background: Aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) show indisputable promise as cancer chemoprevention agents. While aspirin and NSAID use have been suggested to lower risk of developing pancreatic cancer, the results of several epidemiological studies are not in consensus. Methods: Using a case-control design, we examined the association between aspirin, NSAID and acetaminophen use and the risk of pancreatic cancer. We enrolled 904 histological or clinically documented pancreatic ductal adenocarcinoma cases, and 1,223 age and gender matched healthy clinic-based controls evaluated at Mayo Clinic from April 2004 and September 2010. All subjects were ≥ 55 years old and self-reported by questionnaire their use of aspirin, NSAIDs, and acetaminophen at ages 41-60, along with extensive epidemiologic and demographic information. Multivariate logistic regression analysis was used to estimate risk of pancreatic cancer after adjusting for potential confounders. Results: The use of aspirin was associated with a decreased risk of pancreatic cancer. The unadjusted odds ratio (OR) associated with aspirin use ≥ 1 day/month, compared with never or &lt; 1 day/month, was 0.79 [95% confidence interval (CI) 0.65. 0.96, p = 0.015]. This effect remained significant [OR 0.71, 95% CI 0.58,0.87, p = 0.0008], after adjusting for the potential confounders of body mass index and smoking status (never, former, current). The inverse relationship was stronger among former smokers (OR 0.61, 95% CI 0.46, 0.82, p =0.0008) than never and current smokers, although there was not a statistically significant interaction (Pintereaction = 0.333). NSAID and acetaminophen use was not associated with the risk of pancreatic cancer. Conclusions: Results from this large case-control study suggest that aspirin use, but not non-aspirin NSAID use, was associated with lower risk of developing pancreatic cancer and was more pronounced among former smokers than never and current smokers.
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 1902. doi:10.1158/1538-7445.AM2011-1902
Abstract 1915: Specialty supplements and prostate cancer risk in the vitamins and lifestyle (VITAL) cohort
Authors: Brasky Theodore M. , Kristal Alan R. , Navarro Sandi L. , Lampe Johanna W. , Patterson Ruth E. , Peters Ulrike , White Emily 
Published: July 2012

Abstract
Although there is evidence from studies of prostate cancer cell lines and rodent models that several supplements may have anti-inflammatory, anti-oxidant, or other anti-cancer properties, few epidemiologic studies have examined the association between non-vitamin, non-mineral, specialty supplement use and prostate cancer risk. Participants, 50-76 years, were 35,239 male members of the VITamins And Lifestyle (VITAL) cohort who were residents of western Washington State, and who completed an extensive baseline questionnaire in 2000-2002. Participants responded about their frequency (days/week) and duration (years) of specialty supplement uses. 1,602 incident invasive prostate cancers were obtained from the Surveillance, Epidemiology, and End Results registry. Multivariate-adjusted hazards ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox proportional hazards models. Any use of grapeseed supplements was associated with a 41% (HR 0.59, 95% CI: 0.40-0.86) reduced risk of total prostate cancer. Although not statistically different, the association was somewhat stronger for low-grade (HR 0.58, 95% CI: 0.33-1.03) than high-grade tumors (HR 0.82, 95% CI: 0.34-2.00). There were no associations for use of chondroitin, co-enzyme Q10, fish oil, garlic, ginkgo biloba, ginseng, glucosamine, or saw palmetto. Grapeseed may be a potential chemopreventive agent, however as current evidence is limited, it should not yet be promoted for prevention of prostate cancer.
This work is supported by NCI grants R25-CA94880, R01-CA142545, and K05-CA154337
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 1915. doi:10.1158/1538-7445.AM2011-1915
Abstract 1916: Divergent trends for gastric cancer incidence by anatomic subsite in U.S. adults
Authors: Camargo M. Constanza , Anderson William F. , King Jessica B. , Correa Pelayo , Thomas Cheryll C. , Rosenberg Philip S. , Eheman Christie R. , Rabkin Charles S. 
Published: July 2012

Abstract
Background and aims: Age-specific analyses for noncardia gastric cancer reveal divergent trends among United States (U.S.) whites: rates are declining in older adults (over age 40) but rising in younger persons. To further investigate this heterogeneity, we evaluated incidence trends by anatomic subsite, age, and race/ethnicity.
Methods: Gastric cancer incidence data for 1976-2007 were obtained from the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program and the Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR). Incidence rates and estimated annual percentage change (EAPC) were obtained by gastric subsite, age group (25-39, 40-59, and 60-84 years), and race/ethnicity.
Results: Based on data from the nine oldest SEER registries (covering about 10% of the U.S. population), long term age-specific incidence rates for corpus cancer increased between 1976 and 2007 with EAPCs of 1.0%/yr (95% CI, 0.1-1.9) for whites and 3.5%/yr (95% CI, 1.8-5.2) for blacks. All other subsite-specific rates decreased in whites and blacks, whereas all noncardia subsites including corpus cancer declined among other races. In the shorter term, age-specific analyses using combined data from NPCR and SEER registries (covering 89.4% of the U.S. population), corpus cancer significantly increased among younger and middle-aged whites from 1999 to 2007; in ethnic-specific analyses, the increase was significant among non-Hispanic whites aged 40-59 years. Age-specific rates for all subsites declined or were stable in this period among blacks and other races.
Conclusions: Long- and short-term incidence trends for noncardia gastric cancers indicate a shifting distribution by anatomic subsite, age and race/ethnicity, consistent with changing risk factor exposures and warranting further investigation.
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention and the National Cancer Institute.
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 1916. doi:10.1158/1538-7445.AM2011-1916
Abstract 2004: Effect of epigenetic drugs on melanocytes and melanoma cell lines phenotype and aggressiveness
Authors: Molognoni Fernanda , Monteiro Ana Carolina , Morais Alice Santana , Souza Camila Ferreira , Cruz Adriana Taveira , Melisso Fabiana Marcelino , Liang Gangning , Jones Peter Anthony , Jasiulionis Miriam Galvonas 
Published: July 2012

Abstract
Melanoma is the most aggressive skin cancer because of its high resistance to currently available therapy. Like other types of cancer, melanoma is influenced by many factors, including genetic and epigenetic alterations. There are few available models that mimic different steps of melanoma progression. In this way, our laboratory developed a mouse model to study melanoma genesis. Different melanoma cell lines (i.e. 4C11- and 4C11+) were obtained as result of sequential anchorage blockade cycles of a non-tumorigenic melanocyte lineage, melan-a. Melan-a submitted to 2, 3 and 4 deadhesion cycles were also established (2C, 3C and 4C), are not tumorigenic and represent distinct phases of tumor progression. Melan-a, 4C, 4C11- and 4C11+ cells present differences in epigenetic profile, including global and gene specifc DNA methylation, posttranslational histone modifications as well DNA methyltransferases expression. Therefore, we have been interested in determining the separate and combined effects of 5-Aza-2’-deoxycytidine (5-Aza-CdR, inhibitor of DNA methylation) and Trichostatin A (TSA, inhibitor of histone deacetylases) treatment on cell phenotype and tumor characteristics. Our group already showed that TSA or 5-Aza-2’-deoxycytidine treatment causes changes in melanoma cells (4C11- and 4C11+) morphology and in in vivo tumor growth. Interestingly, TSA treatment was more efficient in diminishing 4C11- (non-metastatic melanoma) tumor growth in vivo than 5-Aza-CdR. On the other hand, 5-Aza-CdR treatment was more efficient to decrease 4C11+ (metastatic melanoma) tumor growth in vivo. Moreover, when treated with 5-Aza-CdR and TSA, 4C11- cells (a non-metastatic melanoma) give rise to hemorrhagic invasive tumors in vivo. This kind of treatment might lead to over expression of genes related to invasiveness and metastasis. We already have some candidate genes to investigate as γ-synuclein. Taken together these findings could contribute to a better understanding of epigenetic drugs treatment on melanoma and may have important clinical applications.
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 2004. doi:10.1158/1538-7445.AM2011-2004
Abstract 2005: Modulation of tumor suppressor gene DNA-methylation by quercetin and dietary indoles
Authors: Samuel Temesgen , Fadlalla Khalda , Yehualaeshet Teshome , Turner Timothy 
Published: July 2012

Abstract
Epidemiological and preclinical research provide strong evidence for the anticancer properties of bioactive dietary compounds abundantly found in fruits, vegetables and other fiber-rich food stuff. However, the mechanisms by which nutritional intake of such dietary compounds prevent oncogenesis is largely unknown. We hypothesize that synergistic activities of different dietary compounds through epigenetic mechanisms underlie some of the chemopreventive functions of the dietary compounds. We undertook a preliminary study to examine the effects of Quercetin, Indole-3-Carbinol (I3C) and diindolylmethane (DIM) on promoter methylation profiles of selected genes known to be suppressed by methylation in colorectal cancer. Quercetin is a polyphenolic flavonoid, while I3C and DIM are dietary indoles, DIM being a derivative of I3C. The genes queried in this study were p16INK4a, E-cadherin (CDH1), and IGFBP7. p16INK4a is a cell cycle regulator silenced in up to 40-50% of colorectal carcinomas. E-cadherin is a tumor suppressor and metastasis regulator protein the loss of which promotes wnt-signaling, which is dysregulated in the majority of colorectal cancers. IGFBP7 has recently been identified as a p53-responsive gene frequently silenced in colorectal and gastric cancers. In this study, RKO colorectal cancer cells were treated with the three dietary compounds, vehicle (DMSO), or the demethylating compound 5-azacytidine. DNA was harvested and bisulfite converted. Methylation of the gene promoters was examined by methylation-specific PCR using primer sets that amplify only methylated DNA. Gel electrophoresis and Real-time PCR were used to assess the relative abundance of methylated DNA in control and treated samples. Preliminary results show that the dietary compounds can reverse the methylated-promoter phenotype, with the indole compounds having higher potency compared to quercetin especially in demethylating the CDH1 gene promoter. Further experiments will elucidate the molecular mechanisms through which the compounds modulate gene methylation.
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 2005. doi:10.1158/1538-7445.AM2011-2005
Abstract 2007: Epigenetic reactivation of CCN5/WISP2 by combined effect of green tea polyphenol and epigenetic modulators in highly aggressive breast cancer cells
Authors: Chattopadhyay Indranil , Majumder Monami , De Archana , Banerjee Snigdha , Vanveldhuizen Peter , Banerjee Sushanta 
Published: July 2012

Abstract
CCN5/WISP-2 has been considered as an antiinvasive gene because CCN5/WISP-2 silencing augments the invasive phenotypes in vitro. One of the major functions of the CCN5 protein is to block aggressive behavior, such as the mesenchymal-to-epithelial transition (MET) of cancer cells. CCN5/WISP-2 is constitutively expressed in less aggressive human breast cancer cells, whereas its expression is undetected in the highly aggressive breast cancer cells. Dietary green tea polyphenol, (−)-epigallocatechin-3-gallate (EGCG), is believed to be an anticancer agent in part through its regulation of epigenetic processes. Our studies were aimed to address the epigenetic mechanisms of CCN5 reactivation by EGCG in highly aggressive breast cancer cells. In our current studies, we found that EGCG can reactivate CCN5 expression in highly aggressive breast cancer cell line (MDA-MB-231) and augments mesenchymal-epithelial transition process by modulating multiple EMT regulators. Combination studies using EGCG with the epigenetic modulators including the histone deacetylase (HDAC) inhibitor, trichostatin (TSA) and the DNA methyltransferase (DNMT) inhibitor such as 5-aza-2’-deoxycytidine (5- aza), revealed a synergistic effect of reactivation of CCN5 expression in highly aggressive breast cancer cells. Our findings help to assess the key mechanisms of EGCG chemoprevention and therapy by impacting epigenetic pathways toward aggressive breast tumors.
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 2007. doi:10.1158/1538-7445.AM2011-2007
Abstract 2008: Effect of histone deacetylase inhibitor in combination with 5-fluorouracil on pancreas cancer and cholangiocarcinoma cell line
Authors: Yamada Shinichiro , Shimada Mitsuo , Utsunomiya Tohru , Morine Yuji , Imura Satoru , Ikemoto Tetsuya , Hanaoka Jun , Mori Hiroki , Kanamoto Mami , Iwahashi Shuichi , Saito Yu , Asanoma Michihito 
Published: July 2012

Abstract
Background: Histone deacetylase (HDAC) is well known to be associated with epigenetic regulation and carcinogenesis, and its inhibitors (HDACIs) induce the differentiation or apoptosis of cancer cells. Valproic acid (VPA) is one of the HDACIs, and it is clinically available as an oral antiepilepsy drug. We have reported that VPA augmented the anti-tumor effects of gemcitabine (GEM) in pancreas cancer cell lines and a cholangiocarcinoma cell line (2010 ASCO-GI), and we plan the clinical trial of combination therapy, S-1, that is a novel oral fluoropyrimidine derivative consisting of 5-fluorouracil (5-FU) prodrug tegafur, and VPA. We examined the augment effects of VPA with a combination of 5-FU in vitro.
Methods: A human pancreas cancer cell line (SUIT-2) and a cholangiocarcinoma cell line (HuCCT1) were used. The anticancer effects of VPA combined with 5-FU in SUIT-2 and HuCCT1. The cell viability was evaluated by MTT assay.
Results: Pancreas cancer cell line (SUIT-2): In 5-FU alone group, no effect of 5-FU was observed in dose of 1.0μM, and 17% and 30% of proliferation-inhibitory effects were observed in dose of 2.5 and 5.0μM, respectively. VPA (0.5mM) weakly suppressed cell viability by 13%. In combination of 5-FU and VPA, 19% of inhibitory effect was observed in dose of 5-FU 1.0μM/VPA 0.5mM, respectively.
Cholangiocarcinoma cell line: 5-FU (1.0μM) did not suppress the cell viability, 5-FU (2.5μM) suppressed by 23%. VPA (0.5mM) did not suppress the cell viability, while VPA (1.0mM) weakly decreased it by 11%. 5-FU (1.0μM) and VPA (0.5mM) reduced by 30%, which significantly augmented the anticancer effect of 5-FU alone or VPA alone (P&lt;0.01).
Conclusion: VPA augmented the anti-tumor effect of 5-FU in both a pancreas cancer cell line and a cholangiocarcinoma cell line. Therefore, 5-FU plus VPA is suggested to be a promising therapeutic option for both pancreas cancer and cholangiocarcinoma.
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 2008. doi:10.1158/1538-7445.AM2011-2008
Abstract 2009: Histone deacetylase inhibitors (HDI) down-regulate Ron kinase and synergize with Ron knockdown or Ron monoclonal antibody 41A10to treat pancreatic cancer
Authors: Zou Yi , Howell Gillian , Brattain Michael G. 
Published: July 2012

Abstract
Receptor tyrosine kinase Ron (recepteur d'origine nantais) has been reported to be overexpressed in a panel of pancreatic cancer cells, as well as in tissue samples from pancreatic cancer patients and has been correlated to late stages of pancreatic cancer. Here we hypothesize that Ron kinase can be served as a potential therapeutic target. Our study showed that Ron-specific shRNA significantly altered oncogenic signaling as reflected by reduced pRon, pAkt and pERK in conjunction with reduced cell motility, as evidenced by wound healing assays and transwell assays. Ron knockdown also reduced HIF1α expression. HIF1α is constitutively expressed in many pancreatic cancer cells and has been reported to be a transcription factor for Ron and CXCR4 gene expression, indicating the reciprocal control for these two proteins. Targeting HIF1α and Ron may represent a novel therapeutic strategy for Ron-overexpressing pancreatic cancer patients. Histone deacetylase (HDAC) inhibitors have been reported to target HIF1α gene expression and alter the interaction of HSP70/90 with their client proteins through disruption of HSP70/HSP90 by HDAC6. We demonstrate here that HDAC inhibitors TSA and Panobinostat significantly reduced HIF1α, Ron kinase and CXCR4 expression in pancreatic cancer cells, which was associated with attenuation of pAkt and pERK. Thus our work indicates that HDAC inhibitor therapy targets both Ron and HIF1α. Our future work will demonstrate that Panobinostat can synergize with Ron knockdown or Ron monoclonal antibody to reduce cell growth by colony formation assay. Molecular mechanism will also be investigated. Ron, HIF1α and CXCR4 were reported to increase tumor metastasis. Whether HDI such as Panobinostat alone or in combination with Ron knockdown or Ron monoclonal antibody can reduce metastasis through downregulation of these metastasis related genes will be further investigated.
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 2009. doi:10.1158/1538-7445.AM2011-2009