bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5225: PAR1 signaling on tumor cells limits tumor growth by maintaining a mesenchymal phenotype in pancreatic cancer
Authors: Tekin Cansu , Shi Kun , Spek Arnold , Bijlsma Maarten F. 
Published: August 2018

Abstract
Background: Pancreatic cancer is a dismal disease with limited treatment options. Importantly, in recent years an oncogenic role of protease-activated receptor 1 (PAR1) emerged in various cancer types, and PAR1 is generally accepted to promote tumor progression. PAR1 depletion in stroma limits cancer growth in an orthotopic pancreatic cancer model, suggesting that PAR1 would be a prognostic marker for PDAC.
Aim: To determine PAR1 expression in tumor compartment of PDAC microenvironment and its contribution to tumor progression and invasion.
Methods: Kaplan-Meier overall survival analysis for PAR1 expression on PDAC tumor expression sets was performed. In an orthotopic tumor model, short hairpin RNA mediated PAR1 (shPAR1) knockdown cells derived from p48-CRE/LSL-KRAS/p53flox/flox mice (KP cells) and Panc02 cells were used. Additionally, gene set enrichment analysis was done for EMT signatures on PDAC tumor and pancreatic cancer cell lines. Furthermore, in vitro migratory capacity and mRNA levels for emerging mesenchymal signatures were analyzed in PAR1 knockdown PANC-1 cell line.
Results: PAR1 expression does not associate with the overall survival of PDAC patients. However, tumor cell-specific PAR1 silencing potentiates pancreatic tumor growth but decreases metastatic potential in subsequent murine orthotopic pancreatic cancer model. Further analysis of PAR1 expression in PDAC tumors and pancreatic cancer cell lines show positive correlation with mesenchymal signatures and epithelial to mesenchymal transition genes. Indeed, PAR1 knockdown results in well-differentiated pancreatic tumors in vivo, with enhanced epithelial characteristics both in vitro and in vivo. Furthermore, decreased PAR1 activity decreases migratory capacity and in vitro metastatic potential in vivo.
Conclusion: Our results suggest that growth promoting effects of PAR1 in stromal cells are counterbalanced by the growth inhibitory contributions of PAR1 in tumor cells. Overall, tumor cell PAR1 is linked to the maintenance of a mesenchymal-like state and silencing PAR1 in this setup results in an increased epithelial phenotype of cancer cells with an increased proliferative index but a decreased metastatic potential.
Citation Format: Cansu Tekin, Kun Shi, Arnold Spek, Maarten F. Bijlsma. PAR1 signaling on tumor cells limits tumor growth by maintaining a mesenchymal phenotype in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5225.
Abstract 5227: Suppressive role of elevated estrogen on endometrial carcinogenesis
Authors: Asaka Ryoichi , Miyamoto Tsutomu , Ida Koichi , Takeuchi Hodaka , Ando Hirofumi , Yamada Yasushi , Mvunta David Hamisi , Kobara Hisanori , Kashima Hiroyasu , Shiozawa Tanri 
Published: August 2018

Abstract
Background: Although estrogen has been regarded as a risk factor for endometrial carcinoma, its concentration-dependent carcinogenetic effects remain unclear, because most endometrial carcinomas occur in post-menopausal women, whose serum estrogen levels are relatively low. Because impaired mismatch repair (MMR) was reportedly crucial in the early stages of endometrial carcinogenesis, we focused on the relationship between various estrogen concentration and MMR activity in normal and malignant endometrial glandular cells. In those cells, we reported that the protein and mRNA expression of both hMLH1 and hMSH2, the key factors of MMR, were up-regulated by estrogen stimulation. In addition, we demonstrated that the estrogen stimulation enhanced the MMR activity in those cells using in vitro MMR assay with the M13mp2 phage heteroduplex DNAs and that the proliferating cells without hMLH1/hMSH2 expressions implying “high risk” cells were more frequently observed under relative-low estrogen concentrations. In this study, to further confirm the role of E2 in vivo, we employed a mouse endometrial carcinoma model induced by intra-uterine injection of a carcinogen, N-methyl-N-nitrosourea (MNU) under various E2 concentrations.
Methods: MNU was injected into the uterine cavity of 29 CD-1 mice at 6 weeks of age, and E2 was administered by pellets or orally. Uteri were removed for histological examinations 24 weeks later, and serum E2 levels were measured. The immunohistochemical expression of MMR proteins in uterine epithelia was investigated.
Results: Of 29 mice, 8, 8, 8, and 5 showed atrophic, normal, hyperplastic, and carcinomatous endometria, respectively. The mean E2 levels of each group were 0.2pg/ml, 3.8pg/ml, 190.0pg/ml, and 6.7pg/ml, with significant differences. The expression of the MMR proteins was stronger in mice with elevated E2.
Conclusions: Elevated E2 levels preferentially induced endometrial hyperplasia rather than carcinoma, and this may be mediated by MMR proteins. These results indicate that modest E2 is needed, whereas elevated E2 levels are not necessarily advantageous for carcinogenesis, suggesting the importance of low-chronic (un-opposed) estrogen in human endometrial carcinogenesis.
Citation Format: Ryoichi Asaka, Tsutomu Miyamoto, Koichi Ida, Hodaka Takeuchi, Hirofumi Ando, Yasushi Yamada, David Hamisi Mvunta, Hisanori Kobara, Hiroyasu Kashima, Tanri Shiozawa. Suppressive role of elevated estrogen on endometrial carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5227.
Abstract 5240: Functional and therapeutic significance of ESR1 gene fusions in breast cancer
Authors: Lei Jonathan T. , Shao Jieya , Zhang Jin , Iglesia Michael , Chan Doug W. , Cao Jin , Anurag Meenakshi , Singh Purba , He Xiaping , Kosaka Yoshimasa , Matsunuma Ryoichi , Crowder Robert , Hoog Jeremy , Phommaly Chanpheng , Goncalves Rodrigo , Romalho Susana , Peres Raquel M. , Punturi Nindo , Schmidt Cheryl , Bartram Alex , Jou Eric , Lai W V. , Hampton Oliver , Rogers Anna , Tobias Ethan , Parikh Poojan , Davies Sherri R. , Li Shunqiang , Ma Cynthia X. , Suman Vera , Hunt Kelly K. , Watson Mark A. , Hoadley Katherine A. , Thompson E A. , Chen Xi , Kavuri Shyam M. , Creighton Chad J. , Maher Christopher A. , Perou Charles M. , Haricharan Svasti , Ellis Matthew J. 
Published: August 2018

Abstract
RNA sequencing detects estrogen receptor alpha gene (ESR1) fusion transcripts in estrogen receptor positive (ER+) breast cancer but their role in disease pathogenesis remains unclear. Herein we examined multiple in-frame and out-of-frame ESR1 fusions and found only two, both identified in advanced endocrine treatment resistant disease, encoded stable and functional in-frame fusion proteins. In both examples, ESR1-e6&gt;YAP1 and ESR1-e6&gt;PCDH11X, the N-terminal, DNA binding and dimerization motifs encoded by exons 2-6 were fused to C-terminal sequences from the partner gene. Functional properties included estrogen-independent growth, constitutive expression of ER target genes, anti-estrogen resistance, induction of cellular motility in vitro and the development of lung metastasis in vivo. Chromatin immunoprecipitation and RNA sequencing experiments showed both fusions uniquely activated a metastasis-associated transcriptional program. ESR1-e6&gt;YAP1 and ESR1-e6&gt;PCDH11X-induced growth remained sensitive to a CDK4/6 inhibitor, palbociclib, and a patient-derived xenograft (PDX) expressing the ESR1-e6&gt;YAP1 fusion was also responsive. Transcriptionally active ESR1 fusions therefore trigger both endocrine therapy resistance and metastatic progression explaining the association with fatal disease progression, although CDK4/6 inhibitor treatment is predicted to be effective.
Citation Format: Jonathan T. Lei, Jieya Shao, Jin Zhang, Michael Iglesia, Doug W. Chan, Jin Cao, Meenakshi Anurag, Purba Singh, Xiaping He, Yoshimasa Kosaka, Ryoichi Matsunuma, Robert Crowder, Jeremy Hoog, Chanpheng Phommaly, Rodrigo Goncalves, Susana Romalho, Raquel M. Peres, Nindo Punturi, Cheryl Schmidt, Alex Bartram, Eric Jou, W V. Lai, Oliver Hampton, Anna Rogers, Ethan Tobias, Poojan Parikh, Sherri R. Davies, Shunqiang Li, Cynthia X. Ma, Vera Suman, Kelly K. Hunt, Mark A. Watson, Katherine A. Hoadley, E A. Thompson, Xi Chen, Shyam M. Kavuri, Chad J. Creighton, Christopher A. Maher, Charles M. Perou, Svasti Haricharan, Matthew J. Ellis. Functional and therapeutic significance of ESR1 gene fusions in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5240.
Abstract 5247: Aspirin use and estrogen receptor-negative breast cancer risk in African American women
Authors: Bertrand Kimberly A. , Bethea Traci N. , Gerlovin Hanna , Coogan Patricia , Adams-Campbell Lucile L. , Rosenberg Lynn , Palmer Julie R. 
Published: August 2018

Abstract
Introduction: Use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been hypothesized to be associated with reduced risk of breast cancer; however, results of epidemiological studies have been mixed. Further, few previous studies investigated these associations among African American women and no studies that included African Americans evaluated whether associations differ by estrogen receptor (ER) status.
Methods: To assess the relation of aspirin use to risk of ER+ and ER- breast cancer in African American women, we conducted a prospective analysis within the Black Women's Health Study, an ongoing nationwide cohort of 59,000 black women that began in 1995. On baseline and biennial follow-up questionnaires, women reported regular aspirin use (defined as use at least three days per week) and years of use. Acetaminophen use was queried similarly. Among women with available information on aspirin use, 1701 invasive breast cancers occurred during follow-up through 2015, including 962 ER+ and 492 ER- tumors. All cancers were confirmed through pathology reports or state cancer registry data. We used age-stratified Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of aspirin use with risk of ER+ and ER- breast cancer. All models adjusted for age at menarche, oral contraceptive use, parity, age at first birth, estrogen plus progestin use, body mass index, alcohol consumption, and use of other NSAIDs.
Results: Compared to never use, current regular use of aspirin was associated with lower risk of breast cancer overall (HR 0.87; 95% CI 0.76, 1.00). The association was driven by a statistically significant inverse association for ER- breast cancer (HR 0.76; 95% CI 0.58, 0.99); for ER+ breast cancer, the corresponding HR was 0.92 (95% CI 0.77, 1.09). In contrast, we found no associations with acetaminophen use.
Conclusions: Our observation of reduced risk of ER- breast cancer in relation to current regular use of aspirin is consistent with anti-inflammatory effects of aspirin, rather than hormone-dependent pathways. Aspirin may represent a potential opportunity for chemoprevention of ER- breast cancer; however, these findings require corroboration in additional studies.
Citation Format: Kimberly A. Bertrand, Traci N. Bethea, Hanna Gerlovin, Patricia Coogan, Lucile L. Adams-Campbell, Lynn Rosenberg, Julie R. Palmer. Aspirin use and estrogen receptor-negative breast cancer risk in African American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5247.
Abstract 5253: Dietary fiber intake and lung cancer risk: A pooled analysis of 1.44 million individuals in 10 cohorts
Authors: Yang Jae Jeong , Yu Danxia , Xiang Yong-Bing , Blot William , Robien Kim , Sinha Rashmi , Park Yikyung , White Emily , Takata Yumie , Johansson Mattias , Zheng Wei , Shu Xiao-Ou 
Published: August 2018

Abstract
Background: Dietary fiber has been shown to have various health benefits, including anti-inflammation. However, the role of dietary fiber on lung cancer risk has not been well characterized. In this pooled analysis of 10 prospective cohort studies from the US, Europe, and Asia, we evaluated the association between dietary fiber intake and risk of lung cancer and further, potential effect modifications by tobacco smoking, alcohol drinking, and demographic factors (e.g., sex and race/ethnicity).
Methods: Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated within each cohort using Cox proportional hazard models with adjustment for major lung cancer risk factors. Risk estimates from each cohort were pooled using random-effects meta-analysis. To reduce potential reverse causation due to preclinical dietary changes, all analyses were conducted excluding the first two years of observation.
Results: A total of 18,822 incident lung cancer cases were identified among 1,445,850 participants during mean follow-ups of 9.4 years. After adjustment for lung cancer risk factors (i.e., age, total energy, smoking status, smoking pack-years, gender, race/ethnicity, education, obesity status, diabetes, family history of lung cancer, alcohol consumption, physical activity level, menopausal status in women, and intake of saturated and polyunsaturated fat), dietary fiber intake was inversely associated with lung cancer risk (HR [95% CI] = 0.90 [0.83-0.99] for highest vs. lowest quintile and 0.93 [0.89-0.97] per 10g/day increase). Stratified analyses showed a significant inverse association in men (HRs [95% CIs] per 10g/day increase = 0.92 [0.85-1.00]), women (0.94 [0.90-0.99]), whites (0.92 [0.88-0.95]), smokers (0.92 [0.88-0.97]), and alcohol drinkers (0.89 [0.86-0.94]). However, no significant association was found in Blacks (1.05 [0.92-1.19]), Asians (0.99 [0.85-1.16]), never smokers (0.97 [0.88-1.07]), and never drinkers (0.99 [0.94-1.05]) (P interaction = 0.06 for sex, 0.004 for race, 0.17 for tobacco smoking, and &lt;0.001 for alcohol drinking).
Conclusion: Our findings suggest that a high-fiber diet was associated with a lower risk of lung cancer among whites, smokers, and alcohol drinkers. Further research is needed to determine if the association between dietary fiber intake and lung cancer risk reflects a causal relation.
Citation Format: Jae Jeong Yang, Danxia Yu, Yong-Bing Xiang, William Blot, Kim Robien, Rashmi Sinha, Yikyung Park, Emily White, Yumie Takata, Mattias Johansson, Wei Zheng, Xiao-Ou Shu. Dietary fiber intake and lung cancer risk: A pooled analysis of 1.44 million individuals in 10 cohorts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5253.
Abstract 5260: Alcohol consumption and risk of gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma: A prospective analysis from the NIH-AARP Diet and Health cohort
Authors: Wang ShaoMing , Freedman Neal D. , Loftfield Erikka , Hua Xing , Abnet Christian C. 
Published: August 2018

Abstract
Objective: The 2016 WCRF Continuous Update Project reported that consumption of alcoholic drinks probably causes gastric cancer, but the magnitude of the association was small, there was moderate heterogeneity among the studies included in the meta-analysis, and most studies were from Asian populations, with only 401 cases from North American studies. Therefore, we re-evaluated the association between alcohol intake and gastric cancer in a large US cohort that has accrued more than 1300 gastric cancer cases.
Methods: We prospectively investigated the associations of alcohol consumption with gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA) in 490,605 members aged 50-71 years at baseline in the NIH-AARP Diet and Health Study cohort. Alcohol consumption was assessed during the baseline questionnaire in 1995/1996 and evaluated as grams of ethanol intake and as a categorical variable: never, up to or including one drink/day, one to three drinks/day, and greater than three drinks/day. We used Cox proportional hazard regression to calculate the hazard ratios and 95% confidence intervals for associations between alcohol intake and risk of gastric adenocarcinomas with adjustment for several potential confounders.
Results: Through 2011, 662 incident cases of GCA and 713 of GNCA occurred in the cohort. We found no association between higher alcohol consumption and GCA or GNCA, regardless of whether analyzed as total alcoholic beverage intake or the individual beverage types of beer, wine and liquor and no evidence for a dose-response. Furthermore, we observed no association by stratum of sex, ethnic group, educational level, or smoking status. Although there were no overall associations, we found some evidence for lower risk of GNCA among people who drank up to one drink per day (HR=0.81, 95%CIs:0.67-0.97) compared to nondrinkers.
Conclusion: Alcohol consumption was not associated with increased risk of gastric cardia adenocarcinoma or gastric non-cardia adenocarcinoma in this large US prospective cohort.
Citation Format: ShaoMing Wang, Neal D. Freedman, Erikka Loftfield, Xing Hua, Christian C. Abnet. Alcohol consumption and risk of gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma: A prospective analysis from the NIH-AARP Diet and Health cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5260.
Abstract 5270: Associations of circulating 25-hydroxyvitamin D3 concentrations with incident, sporadic colorectal adenoma risk according to common vitamin D-binding protein isoforms
Authors: Gibbs David C. 
Published: August 2018

Abstract
25-hydroxyvitamin D3 (25[OH]D3), the main circulating form of vitamin D, is inversely associated with incident, sporadic colorectal adenoma. We investigated whether this association differs by two functional variants in the vitamin D binding protein gene (GC) that encode for common protein isoforms (Gc1s, Gc1f, Gc2) linked to differences in vitamin D metabolism. We pooled data from three US colonoscopy-based case-control studies (418 adenoma cases, 524 polyp-free controls), and estimated 25(OH)D3-adenoma associations, by GC isoforms, using multivariable logistic regression. Consistent with previous studies, mean-adjusted 25(OH)D3 concentrations were lowest among Gc2 homozygotes (20.7 ng/mL, 95% CI: 26.2, 28.0) and highest among Gc1 (combined Gc1s and Gc1f) homozygotes (27.1 ng/mL, 95% CI: 18.6, 22.7). Higher 25(OH)D3 concentrations were inversely associated with colorectal adenoma among those with the Gc2 isoform (per 10 ng/mL increase in 25(OH)D3 odds ratio = 0.71; 95% confidence interval: 0.56, 0.90), but not among those with only Gc1 isoforms (odds ratio = 1.07; 95% confidence interval: 0.87, 1.32) (Pinteraction = 0.03). These novel findings suggest that the vitamin D-incident, sporadic colorectal adenoma association may differ by common GC isoforms, and that those with the Gc2 isoform may particularly benefit from maintaining higher circulating 25(OH)D3 concentrations for adenoma prevention.
Citation Format: David C. Gibbs. Associations of circulating 25-hydroxyvitamin D3 concentrations with incident, sporadic colorectal adenoma risk according to common vitamin D-binding protein isoforms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5270.
Abstract 5275: Comparing self-reported cognitive function among Caucasian and African American breast cancer survivors
Authors: Lewis Kayla A. , Vo Jacqueline B. , Royston Kendra J. , Gisiger-Camata Silvia , Meneses Karen 
Published: August 2018

Abstract
Approximately 35% of breast cancer survivors (BCS) report changes in cognitive function after cancer treatment. The purpose of this abstract is to compare self-reported cognitive changes between Caucasian (CAU) and African American (AA) BCS who participated in the Think Well program.
Think Well is an educational program to increase awareness of cognitive function and promote healthy living. Sixteen Think Well seminars were delivered in-person to urban and rural counties throughout North Central Alabama. Following each seminar, participants completed an evaluation of demographic information and cognitive changes. Descriptive statistics and chi-squared tests were used. Data were analyzed using SPSS v23.
Among BCS who completed the evaluation, 82 (54%) were CAU, and 62 (41%) were AA. Many BCS were employed (32%) or disabled/retired (51%). CAU were more likely to be married than AA BCS (p&lt;0.01). More CAU self-reported “poor/below average” in domains of memory, ability to think, speed of problem solving, and ability to pay attention than AA BCS (p&lt;0.01). CAU were more likely than AA BCS to report “moderately” or “very much/extremely” in changes in ability to think (p&lt;0.01), speed of problem solving (p=0.02), and ability to pay attention (p=0.01) since completion of breast cancer treatment.
CAU BCS self-reported poorer cognitive function and changes since cancer treatment. Differences in self-reported changes between AA and CAU may be contributed to geographic location, racial differences in perception of cognitive function, or marital status. Race-related stigmas may affect self-reporting of cognitive function. Future research is warranted to examine factors that contribute to racial differences in cognitive function and interventions aimed at improving cognitive function among both AA and CAU BCS.
Acknowledgement: Think Well is supported by a grant from the North Central Alabama Affiliate of Susan G. Komen. Authors are also supported by funding: Susan G. Komen Graduate Traineeship in Disparities Research, Robert Wood Johnson Foundation Future of Nursing Scholarship, and American Cancer Society Doctoral Degree Scholarship in Cancer Nursing (DSCN-17-076-01).
Citation Format: Kayla A. Lewis, Jacqueline B. Vo, Kendra J. Royston, Silvia Gisiger-Camata, Karen Meneses. Comparing self-reported cognitive function among Caucasian and African American breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5275.