bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2153: Metformin and aspirin synergistically inhibit mTOR and JAK/STAT3 signaling pathway and induce cell death in pancreatic cancer cells
Authors: Yue Wen , Lin Yong , Chen Chunxia , Carpizo Darren R. , DiPaola Robert S. , Tan Xiang-Lin 
Published: May 2015

Abstract
Epidemiological studies have correlated a decreased risk of pancreatic cancer with patients who take either metformin or aspirin. In addition, animal studies have shown that either metformin or aspirin inhibits pancreatic tumor formation as well as the progression of pancreatic intraepithelial neoplasia (PanIN). Since the combination of metformin and aspirin and their potential synergistic effects on pancreatic cancer cells have not been investigated, we evaluated the effects of metformin and aspirin, alone or in combination, on cell viability, migration, and apoptosis in pancreatic cancer cell lines PANC-1 and BxPC3. Cell viability and migration were determined using the MTT assay, colony formation, and the wound-healing assay, and the molecular changes in the mTOR and JAK/STAT3 and apoptotic signaling pathways were evaluated. The synergistic effects of the combination of metformin with aspirin were assessed using a method based on isobologram analyses. We observed that the combination of metformin and aspirin at low concentrations showed significant synergistic effects on the inhibition of cell viability, migration and colony formation in both PANC-1 and BxPC-3 cells. We also found that the combination of metformin and aspirin significantly inhibited the phosphorylation of mTOR, S6K, JAK2 and STAT3. Furthermore, the combination of metformin and aspirin significantly inhibited the expression of Bcl-2 and Mcl-1, which are the downstream targets of STAT3, in both mRNA and protein levels. We also observed increased apoptosis as measured by caspase 3 and poly (ADP-ribose) polymerase (PARP) cleavage in PANC-1 cells treated with the combination of metformin and aspirin. These results suggest that metformin and aspirin synergistically induce cell death in pancreatic cancer cells associated with down-regulating Bcl-2 and Mcl-1 through the STAT3 pathway. Our results support the continued investigation of the combination of metformin and aspirin as chemopreventative or therapeutic agents in pancreatic cancer tumor models.
Citation Format: Wen Yue, Yong Lin, Chunxia Chen, Darren R. Carpizo, Robert S. DiPaola, Xiang-Lin Tan. Metformin and aspirin synergistically inhibit mTOR and JAK/STAT3 signaling pathway and induce cell death in pancreatic cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2153. doi:10.1158/1538-7445.AM2014-2153
Abstract 2154: Notoginseng suppresses azoxymethane/dextran sulphate sodium-induced colitis and colitis-associated colorectal carcinogenesis
Authors: Wang Chong-Zhi , Yuan Chun-Su 
Published: May 2015

Abstract
Colorectal cancer remains one of the most prevalent cancers and a leading cause of cancer related death in the US. Many currently used chemotherapeutic agents are derived from botanicals. Identifying the herbal sources, including those from ginseng family, to develop better preventive or therapeutic agents remains an essential step in advancing the management of the cancer. Patients suffering from inflammatory bowel disease are at a high risk of developing colorectal cancer. To evaluate the anti-cancer potential of botanicals, we evaluated the effects of notoginseng on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis. One week after A/J mice received AOM, the animals received DSS for 8 days, or were supplemented with notoginseng extract, at 30 or 90 mg/kg. DSS-induced colitis was scored with the disease activity index (DAI). The severity of the inflammatory lesions was evaluated by a colon tissue histological assessment. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were also investigated. We observed that the effects of notoginseng on the reduction of colon inflammation, expressed in the DAI score, were in a dose-related manner (p &lt; 0.01). Notoginseng inhibited the reduction of colon length and loss of bodyweight in a dose-related manner (all p &lt; 0.05). The histological assessment of colitis and the inflammatory related immunohistochemical data of iNOS and COX-2 also supported the pharmacological observations. Our data suggest that notoginseng is a promising candidate in preventing and treating colitis and inflammation-associated colon carcinogenesis. (This work was supported in part by the NIH/NCCAM grants AT004418 and AT005362).
Citation Format: Chong-Zhi Wang, Chun-Su Yuan. Notoginseng suppresses azoxymethane/dextran sulphate sodium-induced colitis and colitis-associated colorectal carcinogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2154. doi:10.1158/1538-7445.AM2014-2154
Abstract 2165: Parents' ages at birth and risk of hormone-related cancer among women in the California Teachers Study
Authors: Lu Yani , Luo Jianning , Wang Sophia , Ma Huiyan , Sullivan-Halley Jane , Reynolds Peggy , Bernstein Leslie 
Published: May 2015

Abstract
Childbearing age has increased in Western countries over the last several decades. The immediate effects of advanced parental age on the health of offspring have been extensively studied. However, few studies have examined the effect of parental age at birth on the risk of adult-onset cancer. We explored the association between parental age at birth and the risk of adult-onset hormone-related cancers (i.e., breast cancer, ovarian cancer and endometrial cancer) in the prospective California Teachers Study cohort of 133,479 female teachers and administrators. Between 1995 and 2010, 5359 women were diagnosed with breast cancer, 515 women were diagnosed with ovarian cancer, and 1110 women were diagnosed with endometrial cancer. Multivariate adjusted relative risks (RR) and 95% confidence intervals (CI) were estimated by fitting Cox proportional hazards models. After mutual adjustment for paternal age/maternal age at birth, no association was observed for maternal age at birth for any of the three types of cancer. However, compared to those born to a father whose age at his daughter's birth was 25-29 years, women born to a father under age 20 years had 35% greater risk of breast cancer (RR=1.35, 95% CI=1.03-1.76) and more than 2 times greater risk of ovarian cancer (RR=2.26, 95% CI=1.14-4.50); women born to a father whose age at childbirth was 30-34 years had 25% greater risk of endometrial cancer (RR=1.25, 95% CI=1.05-1.48) than women whose father was 25-29 years. In an interaction model, relative to daughters born to a mother younger than 25 year and a father between 25-29 years, relative risk was elevated for those born to a mother younger than 25 and a father younger than 20 years (RR=1.37, 95% CI=1.07-1.76), or to a father older than 34 years old regardless of mother's age (mother &lt;25 or ≥25 years old; RR=1.31 and 1.12 respectively). Lower ovarian cancer risk was observed among women born to a mother ≥25 years and a father between 25-29 years (RR=0.66, 95% CI=0.48-0.90); no association was observed for endometrial cancer. These findings indicate that parental age at birth, especially paternal age at birth, may affect the adult-onset cancer risk of daughters, especially breast cancer.
Citation Format: Yani Lu, Jianning Luo, Sophia Wang, Huiyan Ma, Jane Sullivan-Halley, Peggy Reynolds, Leslie Bernstein. Parents' ages at birth and risk of hormone-related cancer among women in the California Teachers Study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2165. doi:10.1158/1538-7445.AM2014-2165
Abstract 2168: Components of metabolic syndrome and total cancer mortality
Authors: Gathirua-Mwangi Wambui G. , Zhang Jianjun 
Published: May 2015

Abstract
Metabolic syndrome becomes more and more common primarily due to the epidemic of overweight and obesity in both developed and developing countries. Epidemiologic studies have shown that obesity increases the risk of several cancers. However, it largely remains unclear whether the components of metabolic syndrome are associated with total cancer mortality. Therefore, we sought to evaluate this important question in the Third National Health and Nutrition Examination Survey (NHANES). Data on demographics, socioeconomics, lifestyle factors, and the components of metabolic syndrome were collected among 19,296 men and women aged 18 years or older (pregnant women excluded). Cancer mortality outcomes of these subjects were determined by linkage to the National Death Index (NDI), and the most recent year of the linkage was in 2010. A total of 1,111 cases of all sites of cancer have been documented during this period of time. Weighted Cox proportional hazards regression was used to compute relative risks (RR) with 95% confidence intervals (CIs) for total cancer mortality in relation to the components of metabolic syndrome. After adjustment for age, sex, race, education, marital status, and cigarette smoking, subjects in the highest quartile (Q) of serum glucose experienced a 25% increased risk of total cancer when compared with those in the lowest quartile [RR (95% CI): 1.250 (1.247-1.253)]. The significant positive association was also observed for systolic blood pressure [Q4 vs. Q1: RR (95% CI): 1.278 (1.274-1.282)]. Conversely, a reduced risk of total cancer was found for high-density lipoprotein (HDL) cholesterol [Q4 vs. Q1: RR (95% CI): 0.798 (0.796-0.800)]. No apparent effect was detected for waist circumference and serum triglyceride. To our knowledge, the present study is among the first to demonstrate that some components of metabolic syndrome modulate the risk of total cancer among a representative population in the US. Our findings offer novel evidence for the potential role of metabolic syndrome in cancer carcinogenesis and mechanistic data for the associations between obesity and the risk of some cancers.
Citation Format: Wambui G. Gathirua-Mwangi, Jianjun Zhang. Components of metabolic syndrome and total cancer mortality. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2168. doi:10.1158/1538-7445.AM2014-2168
Abstract 2174: Association of diabetes and obesity with risk of esophageal and gastric adenocarcinoma in the Iowa Women's Health Study (IWHS)
Authors: LaBore Bryan P. , Prizment Anna E. , Ondrey Frank G. , Anderson Kristin E. 
Published: May 2015

Abstract
Incidence rates of esophageal and gastric cancers have increased rapidly in developing countries during the past four decades. The rate of esophageal adenocarcinomas has approximately tripled among US whites and now exceeds that of esophageal squamous cell carcinomas. Incidence of gastric cardia adenocarcinomas has also risen significantly during this period, though to a lesser extent. These cancers often respond poorly to treatment, highlighting the importance of identifying modifiable risk factors with a view to prevention. The association between diabetes and gastroesophageal adenocarcinoma has been examined in only a few studies and findings are inconsistent. While obesity is a significant risk factor for esophageal and gastric adenocarcinomas, few analyses have been conducted in prospective cohorts. We examined the association between diabetes, BMI, and waist circumference and incidence of esophageal, non-cardia gastric and gastric cardia adenocarcinomas in a large prospective cohort of postmenopausal women. A mailed survey at baseline (1986) collected information on self-reported diabetes and anthropometric measures and included a detailed food-frequency questionnaire. The 34,466 initially cancer free women were followed for 24 years with annual cancer incidence obtained through the State Health Registry of Iowa, part of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program; 83 women developed gastroesophageal adenocarcinoma. Associations were examined using proportional hazards regression models: hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Significant associations were observed in age-adjusted models for diabetes (yes/no) [HR: 2.09, 95% CI: 1.01-4.34], body mass index (kg per meters squared) [HR: 1.09, 95% CI: 1.03-1.15], and waist circumference (cm) [HR: 1.24, 95% CI: 1.01-1.53]. Additionally, a positive association between diabetes and adenocarcinoma of the gastroesophageal junction was found in both age-adjusted [HR: 3.43, 95% CI: 1.32-8.90] and multivariate-adjusted models [HR: 3.00, 95% CI: 1.13-7.99]. An inverse association was found with increasing daily fiber intake (g/day) and all gastroesophageal adenocarcinomas [HR: 0.84, 95% CI: 0.73-0.96]. These findings support the view that diabetes, body mass index and waist circumference increase risk of gastroesophageal adenocarcinoma while increased fiber intake may decrease risk.
Citation Format: Bryan P. LaBore, Anna E. Prizment, Frank G. Ondrey, Kristin E. Anderson. Association of diabetes and obesity with risk of esophageal and gastric adenocarcinoma in the Iowa Women's Health Study (IWHS). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2174. doi:10.1158/1538-7445.AM2014-2174
Abstract 2178: Rotating night shift work and cancer mortality in the nurses' health study
Authors: Gu Fangyi , Han Jiali , Hankinson Sue , Schernhammer Eva , Group Nurses' Health Study 
Published: May 2015

Abstract
Rotating night-shift work is common in western societies, but epidemiological studies on shift work and cancer mortality are limited.
In a prospective closed cohort of 74,914 registered US nurses, the Nurses' Health Study, we examined the impact of rotating night-shift work on total-cancer and cancer-specific mortality. Rotating night-shift work was defined as having worked at least 3 nights per month. Cox proportional hazards models adjusting for age, smoking, BMI, and other important confounders, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
During 22 years of follow-up, we documented 5,123 cancer deaths. Overall, we observed no association between rotating night-shift work and total-cancer mortality (HR15+years=1.07; 95% CI, 0.97-1.19; Ptrend=0.17). However, women with 15 or more years of night-shift work had a significant increase in lung cancer mortality (multivariable HR=1.25; 95% CI, 1.04-1.50) and a borderline significant increase in colorectal cancer mortality (MV HR=1.32; 95% CI, 0.97-1.81). The increase in lung cancer mortality was limited to current smokers. We observed no increase in breast cancer mortality (HR15+years=1.03; 95%CI, 0.76-1.38; Ptrend=0.97). For cancers with fewer than 200 deaths, we observed a non-significant increase in mortality from kidney cancer, myeloma and leukemia among women with 6-14 and 15+ years of rotating night-shift work: the HRs were 1.58 (95% CI, 0.92-2.71) and 1.36 (95% CI, 0.72-2.56) for kidney cancer, 1.66 (95% CI, 0.98-2.81) and 1.47 (95% CI, 0.79-2.77) for myeloma, 1.25 (95% CI, 0.70-2.23) and 1.53 (95% CI, 0.83-2.83) for leukemia, respectively.
We conclude that after adjusting for important confounders, the impact of rotating night-shift work on cancer mortality appears modest. Women working rotating night-shifts for more than 15 years had modestly increased colorectal and lung cancer mortality but the increase in lung cancer mortality was largely limited to current smokers and it is possible that these observations remain residually confounded by smoking. Additional studies are warranted to confirm our findings.
Citation Format: Fangyi Gu, Jiali Han, Sue Hankinson, Eva Schernhammer, Nurses' Health Study Group. Rotating night shift work and cancer mortality in the nurses' health study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2178. doi:10.1158/1538-7445.AM2014-2178
Abstract 2203: Pathway analysis of genome-wide association study data highlights taste transduction and metabolic pathways and esophageal squamous cell carcinoma susceptibility
Authors: Hyland Paula L. , Zhang Han , Yang Qi , Lin Shih-Wen , Maeder Dennis , Hu Nan , Tang Ze-Zhong , Su Hua , Wang Lemin , Wang Chaoyu , Ding Ti , Fan Jin-Hu , Qiao You-Lin , Wheeler William , Giffen Carol , Burdett Laurie , Wang Zhaoming , Chanock Stephen J. , Dawsey Sanford M. , Freedman Neal D. , Abnet Christian C. , Goldstein Alisa M. , Yu Kai , Taylor Philip R. 
Published: May 2015

Abstract
Background: In China, esophageal cancer is the fourth leading cause of cancer death and essentially all cases are histologically esophageal squamous cell carcinoma (ESCC). Agnostic pathway-based analyses applied to GWAS data can identify biological pathways and/or groups of genes enriched with disease-associated variants whose individual effect sizes may be too small to be detected by standard single locus methods. Methods: We used the adaptive rank-truncated product (ARTP) method to analyze 1,827 pathways containing 69,420 genes in GWAS data from 1942 ESCC cases and 2111 controls with Chinese ancestry. Pathways were retrieved from five databases: KEGG, BioCarta, Reactome, HumanCys and NCI-Nature curated. Statistical significance was determined by permutation. Results: Associations with ESCC risk (P&lt;0.001) were observed for 60 pathways, which included overlapping pathways from different sources predominantly associated with cell cycle control and signaling, DNA repair, and apoptosis. After excluding genes with previous GWAS hits from the pathway analysis, the KEGG taste transduction pathway and the KEGG metabolic pathways were significantly associated with risk of ESCC (P&lt;0.001). The most significant genes (P&lt;0.001) in these pathways were TAS2R13, TAS2R42, TAS2R14, TAS2R46 and TAS2R50, and MTAP, GAPDH, DCTD, POLD2 and AMDHD1, respectively. Significance: This approach provides new insights into the collective role of genetic variants and ESCC risk in Han Chinese and suggests that genetic alterations associated with taste transduction and metabolic pathways may contribute to cancer susceptibility.
Citation Format: Paula L. Hyland, Han Zhang, Qi Yang, Shih-Wen Lin, Dennis Maeder, Nan Hu, Ze-Zhong Tang, Hua Su, Lemin Wang, Chaoyu Wang, Ti Ding, Jin-Hu Fan, You-Lin Qiao, William Wheeler, Carol Giffen, Laurie Burdett, Zhaoming Wang, Stephen J. Chanock, Sanford M. Dawsey, Neal D. Freedman, Christian C. Abnet, Alisa M. Goldstein, Kai Yu, Philip R. Taylor. Pathway analysis of genome-wide association study data highlights taste transduction and metabolic pathways and esophageal squamous cell carcinoma susceptibility. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2203. doi:10.1158/1538-7445.AM2014-2203
Abstract 2213: Uncommon CHEK2 missense variant and reduced risk of pancreatic cancer
Authors: Scelo Ghislaine , McKay James , Holcatova Ivana , Janout Vladimir , Foretova Lenka , Fabianova Eleonora , Chabrier Amelie , Gaborieau Valerie , Brennan Paul 
Published: May 2015

Abstract
CHEK2 is a cell cycle control gene encoding for checkpoint kinase 2, which acts as a tumor suppressor by causing arrest or apoptosis in response to unrepaired DNA damage. Inherited mutations in the CHEK2 gene have been reported to increase the risk of several cancers, although a paradoxical decrease in risk of tobacco-related lung and head and neck cancers was reported. An association between CHEK2 mutations and pancreatic cancer risk has not been reported. Missense variant rs17879961 (replacement of T by C, resulting in the change of Isoleucine by Threonine at position 157 of the protein [I157T]) has been shown to be very rare in the US and western Europe populations (&lt;1%) while more common in central Europe countries (∼5%). We genotyped 585 pancreatic cancer cases and 664 controls recruited in central Europe (Czech Republic and Slovakia). The heterozygous (T/C) genotype was observed in 2.1% of cases and 4.4% of controls. After adjustment for age, sex, and center of recruitment, T/C genotype was associated with a significantly lower incidence of pancreatic cancer than the common T/T genotype (odds ratio [OR]=0.41, 95% confidence interval [CI] 0.20-0.83, p=0.0132). ORs were of similar magnitude by smoking status, diabetes history, and body mass index categories, while an apparent difference by drinking status with observed: OR=0.24 (95% CI 0.09-0.64) for non-drinkers versus OR=0.88 (95%CI 0.31-2.53), p for heterogeneity=0.078. This counter-intuitive halving of the pancreatic cancer risk for CHEK2 rs17879961 T/C carriers warrants replication and functional studies to elucidate mechanisms involved.
Citation Format: Ghislaine Scelo, James McKay, Ivana Holcatova, Vladimir Janout, Lenka Foretova, Eleonora Fabianova, Amelie Chabrier, Valerie Gaborieau, Paul Brennan. Uncommon CHEK2 missense variant and reduced risk of pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2213. doi:10.1158/1538-7445.AM2014-2213