bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B54: A candidate gene study of smoking cessation
Authors: Stevens Victoria L. , Gapstur Susan M. , Sun Juzhong , Jacobs Eric J. , Gaudet Mia M. , Westmaas J. Lee , Patel Alpa V. 
Published: May 2019

Abstract
Background: Efforts to identify genes that influence smoking cessation have been largely unsuccessful to date. However, SNPs in the chromosome 15q25 region that encodes the nicotinic receptor subunits CHRNA5, CHRNA3, and CHRNB4 have been consistently and strongly associated with nicotine dependence as measured directly through dependence surveys or indirectly with smoking quantity (cigarettes per day, cpd). These SNPs have been found to either be modestly or not at all associated with smoking cessation as defined by a variety of different phenotypes. Despite the fact that nicotine dependence influences smoking cessation, these results suggest that cessation may be influenced by a wider range of genetic variants than just those that influence measures of nicotine dependence.
Methods: To identify genes important for smoking cessation, we defined a smoking cessation phenotype based on number of quit attempts; easy quitters achieved successful, long-term (&gt; 1 year) abstinence after their first quit attempt and difficult quitters reported ≥10 attempts before either continuing to smoke or quitting. We identified 1,500 easy quitters and 1,500 difficult quitters who were participants in the Cancer Prevention Study-3 (CPS-3), a large prospective study of cancer incidence and mortality conducted by the American Cancer Society. The association of 83 SNPs from 25 nicotine signaling and metabolism genes that had previously been associated with some aspect of smoking behavior with difficulty quitting was determined using logistic regression.
Results: Three SNPs in three separate genes were significantly associated with difficult quitting (p&lt;0.05). These were SLC6A3 rs2652511 [per allele odds ratio (OR)=0.89, 95% confidence intervals (CI): 0.80-0.99, p-trend=0.040], HTR1B rs6298 (per allele OR=0.88, 95% CI: 0.80-0.99, p-trend=0.034), and CHRNA5 rs16969968 (per allele OR=1.12, 95% CI: 1.00-1.22, p-trend=0.045). A genetic risk score based on number of risk alleles from these three SNPs was also associated with difficult quitting (OR=1.62, 95% CI:1.26-2.08, p=1.9 x 10-4 for score of 5-6 versus 0-2). None of the associations remained statistically significant after correction for multiple comparisons.
Conclusions: Although none of the SNPs investigated were statistically significantly associated with the number of quit attempts, these results suggest that examining this phenotype in future genome-wide association studies would be useful for the discovery of genes that could be targeted for the development of novel smoking cessation aids.
Citation Format: Victoria L. Stevens, Susan M. Gapstur, Juzhong Sun, Eric J. Jacobs, Mia M. Gaudet, J. Lee Westmaas, Alpa V. Patel. A candidate gene study of smoking cessation. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B54.
Abstract B57: Premenopausal plasma ferritin levels, HFE polymorphisms, and risk of breast cancer in the Nurses' Health Study II
Authors: Graff Rebecca E. , Eunyoung Cho , Lindström Sara , Kraft Peter , Willett Walter C. , Eliassen A Heather 
Published: May 2019

Abstract
Background: Evidence from the Nurses' Health Study II (NHSII) suggests that red meat consumption is associated with increased breast cancer risk in premenopausal women. Iron may be responsible by contributing to oxidative stress or effects on immune function.
Methods: We conducted a case-control study nested within the NHSII examining prediagnostic plasma ferritin (n=795 cases, 795 controls), 15 hemochromatosis gene (HFE) SNPs (n=772 cases, 1,368 controls), and breast cancer risk. Cases were diagnosed with cancer after providing blood samples between 1996 and 1999. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for ferritin levels by conditional logistic regression and for HFE SNPs by unconditional logistic regression.
Results: We did not observe a significant association between ferritin levels and breast cancer (top vs. bottom quartile multivariate OR: 1.05, 95% CI: 0.77-1.45, P-value for trend: 0.77). Results did not change when restricted to women who were premenopausal at blood draw, and were similar when cases were examined by hormone receptor status and menopausal status at diagnosis. No HFE SNPs were significantly associated with breast cancer in a log-additive manner. Among controls, ferritin levels were nominally associated with SNPs rs9366637 (P-value for trend: 0.04), rs6918586 (P-value for trend: 0.06) and rs13161 (P-value for trend: 0.07), but results did not remain significant after adjusting for multiple testing.
Conclusions: Ferritin levels and HFE SNPs were not associated with breast cancer risk in this population. Components of red meat other than iron are likely responsible for its positive association with breast cancer in premenopausal women.
Citation Format: Rebecca E. Graff, Cho Eunyoung, Sara Lindström, Peter Kraft, Walter C. Willett, A Heather Eliassen. Premenopausal plasma ferritin levels, HFE polymorphisms, and risk of breast cancer in the Nurses' Health Study II. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B57.
Abstract C13: Population-based evaluation of serum pepsinogen, anti-H. pylori IgG antibody and gastrin-17 tests for gastric cancer screening
Authors: Tu Huakang , Sun Liping , Gong Yuehua , Xu Qian , Long Qi , Bostick Roberd , Yuan Yuan 
Published: May 2019

Abstract
Objective: This study evaluated the role of multiple serological tests (including serum pepsinogen I (PGI), PGII, PGI/II ratio, anti-H. pylori IgG antibody, and gastrin-17 tests) individually and in combination in gastric cancer (GC) screening.
Design: Data were from the Zhuanghe Gastric Cancer Study, a 15-year, population-based endoscopic, gastric diseases screening program in northern China. From 1997 to 2011, esophagogastroduodenoscopies with gastric mucosal biopsies were conducted on 10,693 participants. All serum biomarkers were measured using ELISA, and gastric biopsies were evaluated using standardized criteria. Logistic regression was used to calculate odds ratios (OR) with 95 percent confidence intervals (95% CI) and produce receiver operator characteristic (ROC) curves with corresponding c statistics. In addition, results were replicated in an independent hospital-based population.
Results: PGI/II ratio monotonically decreased as gastric mucosa progresses from normal mucosa to precancerous conditions, and to GC, and a low PGI/II ratio (≥ 6.6) was associated with an increased risk of prevalent GC (OR = 2.34, 95% CI: 1.62, 3.39). PGI/II ratio individually or in combination with PGI, PGII, anti-H. pylori IgG antibody and gastrin-17 provided the same c statistic of 0.62 for screening for GC. PGI, PGII, anti-H. pylori IgG antibody or gastrin-17 tests individually provided c statistics less than or equal to 0.55. For identifying abnormal gastric conditions including GC, the five serological tests in combination provided adequate discriminatory performance (c = 0.77), and yielded a sensitivity of 84.0% and specificity of 50.0%. The results from the independent hospital-based population were similar.
Conclusion: Our results suggest that serum PGI, PGII, PGI/II ratio, anti-H. pylori IgG and gastrin-17 tests can be used as prescreening tests for patients at high risk for GC.
Citation Format: Huakang Tu, Liping Sun, Yuehua Gong, Qian Xu, Qi Long, Roberd Bostick, Yuan Yuan. Population-based evaluation of serum pepsinogen, anti-H. pylori IgG antibody and gastrin-17 tests for gastric cancer screening. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C13.
Abstract C29: Combination of SP17 with CA125 serologic measurement for detection of ovarian cancer
Authors: Chiriva-Internati Maurizio , Mirandola Leonardo , Yu Yuefei , Jenkins Marjorie R. , Cobos Everardo , Figueroa Jose A. , Nijman Hans W. , Kast W. Martin 
Published: May 2019

Abstract
Ovarian cancer (OC) is a serious healthy issue for women worldwide, ranking second for mortality rates among gynecological malignancies. CA125 (MUC16) is the only available biomarker to monitor disease and treatment response in OC but it suffers from poor performance for diagnostic purposes. As a consequence, increasing efforts are being made for the identification of novel tumor biomarkers to improve CA125 test specificity and sensitivity. More than 30 serum biomarkers have been studied alone or in combination with CA125. We have previously shown that SP17, a member of the cancer/testis antigen (CTA) family, is a potential biomarker that allows for the discrimination of the normal ovary from OC cells and for the tracking of OC disease in a xenograft mouse model. Here we hypothesized that SP17 serum levels could be exploited as a diagnostic test to detect early lesions of OC and to discriminate between malignant and benign lesions. We analyzed SP17 expression in primary ovarian tissues from ovarian cancer patients, benign ovarian lesions and healthy subjects through RT-PCR and immunohistochemistry. SP17 and CA125 levels were measured in the sera of the same subjects by ELISA. We found that SP17 expression was restricted to OC cells at the transcriptional and translational levels, and that the measurement of SP17 concentration in the serum afforded accurate discrimination between subjects with different prognoses allowing for predicting overall survival time. SP17 assay alone was superior to CA125 in discriminating between ovarian cancer and benign ovarian tumors: combining SP17 and CA125 assays, we obtained 96% sensitivity, 89% specificity and 97% PPV. SP17 is a novel serum biomarker for ovarian cancer. SP17 serum measurement in combination with CA125 affords improved positive predictive value for diagnostic purposes.
Citation Format: Maurizio Chiriva-Internati, Leonardo Mirandola, Yuefei Yu, Marjorie R. Jenkins, Everardo Cobos, Jose A. Figueroa, Hans W. Nijman, W. Martin Kast. Combination of SP17 with CA125 serologic measurement for detection of ovarian cancer. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C29.
Abstract C36: miR-22 represses Wnt Signaling in human colon cancer cells
Authors: Neha Chetlangia , Rao Srinivasa Rao , Karunagaran Devarajan 
Published: May 2019

Abstract
Background: Wnt signaling is an evolutionarily conserved pathway that plays an important role in processes like development, differentiation and metastasis. Aberrant activation of Wnt signaling has been implicated in various tumors, predominantly of breast and colon. MicroRNAs are short non-coding RNAs that are frequently deregulated in cancer. Expression of the microRNA miR-22 was reported to be significantly lower in colorectal cancer tissues than that in normal adjacent mucosa. Based on bioinformatics predictions, we identified several Wnt signaling intermediates as potential targets for miR-22. As Wnt signalling is constitutively active in colon cancer cell lines SW480 and SW620, we hypothesize that miR-22 might be a potential regulator of Wnt signaling in colon cancer.
Methods: Wnt signaling was stimulated in HEK293 cells by treating them with 25mM Lithium Chloride (LiCl). Wnt signaling activation was assayed using TOPFlash/FOPFlash luciferase activity in HEK293, SW480 and its metastatic derivative SW620, after overexpressing miR-22 using a plasmid construct. CyclinD1 promoter luciferase assay, Western blotting and quantitative RT-PCR were used to study the expression of downstream targets of Wnt signaling. Direct targets of miR-22 were validated by performing 3'-UTR luciferase assays. Plasmid constructs were used to overexpress or knockdown c-Myc.
Results: Overexpression of miR-22 resulted in decreased TOP-Flash luciferase activity in LiCl-treated HEK293 cells and the colon cancer cells SW480 and SW620. miR-22 repressed Wnt signaling target genes CyclinD1, c-Myc and TCF7L2, at both mRNA and protein levels. It also decreased the mesenchymal markers (Snail and Vimentin) at the protein level. Overexpression of miR-22 down-regulated BCL9L protein levels and also targeted the BCL9L 3' UTR, as demonstrated by luciferase reporter assay. In HEK293 cells, overexpression of c-MYC repressed miR-22 levels whereas knockdown of endogenous c-Myc by shRNA up-regulated miR-22 levels.
Conclusions: miR-22 inhibits Wnt signaling and potentially exerts this effect by targeting the Wnt activator BCL9L. The repression of mesenchymal markers by miR-22 suggests a role for it in Epithelial to Mesenchymal Transition. Further, the Wnt target gene c-Myc regulates the expression of miR-22, suggesting the existence of a positive feedback loop involving miR-22/Wnt Signaling/c-Myc by which miR-22 may indirectly regulate its own expression. Our findings therefore demonstrate a novel role for miR-22 in the regulation of Wnt signaling in colon cancer cells.
Citation Format: Chetlangia Neha, Srinivasa Rao Rao, Devarajan Karunagaran. miR-22 represses Wnt Signaling in human colon cancer cells. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C36.
Abstract C61: High fat triggers oncogenic K-Ras activity and a COX2 dependent feed-forward loop to induce pancreatic ductal adenocarcinoma development
Authors: Philip Bincy , Roland Christina L. , Daniluk Jarek , Liu Yan , Chatterjee Deyali , Gomez Sobeyda Berenice , Ji Baoan , Haojie Huang , Wang Huamin , Fleming Jason B. , Logsdon Craig D. , Cruz-Monserrate Zobeida 
Published: May 2019

Abstract
Obesity is a risk factor for Pancreatic Ductal Adenocarcinoma (PDAC), but the molecular mechanisms involved are unclear. Oncogenic mutation of K-Ras occurs early and nearly universally in patients with this disease. However, recent evidence indicates that oncogenic Ras is not fully active and for activity to surpass the threshold required to engage a Ras-inflammation feed-forward loop, it requires a stimulus. We hypothesized that high-fat intake acts as an inflammatory stimulus, increasing K-Ras activity and that cyclooxygenase -2 (COX2) expression is required in the inflammatory loop. LSL-K-Ras mice were crossed with elastase-CreER (acinar cell-specific) or Pdx1-Cre (pancreatic cell-specific) to “knock-in” expression of oncogenic K-Ras. Additionally, acinar cell-specific -Ras mice were crossed with COX2 conditional knockout mice. All mice were fed isocaloric diets with different amounts of fat and a COX2 inhibitor was administered to some acinar cell-specific -Ras mice. Pancreata were analyzed for Ras activity, Phospho-ERK levels, inflammation, fibrosis, PanIN and PDAC development. We observed that consumption of a high fat diet (HFD) led to increased K-Ras activity, PanIN formation, fibrotic stroma and PDAC development compared to a control diet. Additionally, we observed a significant reduction in the survival of mice fed a HFD. Genetic deletion of COX2 in acinar cells and COX2 systemic inhibition prevented the HFD-induced effects in acinar cell-specific -Ras mice. These findings indicated that a HFD stimulates activation of oncogenic K-Ras and initiates an inflammatory feed-forward loop requiring the expression of COX2 leading to pancreatic inflammation, fibrosis, PanINs and PDAC. This mechanism may explain the PDAC risks associated with consumption of a HFD.
Citation Format: Bincy Philip, Christina L. Roland, Jarek Daniluk, Yan Liu, Deyali Chatterjee, Sobeyda Berenice Gomez, Baoan Ji, Huang Haojie, Huamin Wang, Jason B. Fleming, Craig D. Logsdon, Zobeida Cruz-Monserrate. High fat triggers oncogenic K-Ras activity and a COX2 dependent feed-forward loop to induce pancreatic ductal adenocarcinoma development. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C61.
Abstract CN03-03: The impact of reduced tobacco smoking on lung cancer mortality in the United States during 1975-2000
Authors: Moolgavkar Suresh 
Published: May 2019

Abstract
A consortium of six groups using common inputs and independent models estimated the number of U.S. lung cancer deaths averted over the period 1975-2000 in the United States as a result of changes in smoking behavior beginning in the mid-fifties, and also the number of deaths that could have been averted had tobacco control been completely effective in eliminating smoking in 1965, following the issuance of the first Surgeon General's report (SGR) on Smoking and Health in 1964. Our results suggest that approximately 795,000 lung cancer deaths were averted, 550,000 among males and 245,000 among females. However, this total number represents only about 30% of the lung cancer deaths that could potentially have been averted during this period. Enhanced tobacco control efforts are necessary to reduce further the burden of lung cancer in the U.S. population.
Citation Format: Suresh Moolgavkar. The impact of reduced tobacco smoking on lung cancer mortality in the United States during 1975-2000. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr CN03-03.
Abstract CN04-03: Stemming the rising tide of liver and esophageal cancer
Authors: Thompson Patricia A. 
Published: May 2019

Abstract
Obesity has been convincingly linked to non-viral/non-alcoholic liver carcinogenesis (HCC) and to esophageal adenocarcinoma (EAC). Both HCC and EAC have five-year survival rates below 50% with little to no advancement in treatment options over the past decade. In obesity-associated HCC and EAC, bile acids and their biology as signaling molecules are emerging as potentially shared mechanistic factors generally in gastrointestinal cancers and in particular in the liver and in the esophagus. Emerging work on the role of bile acid-based therapeutics for the prevention of cancer risk factor intermediates will be presented. This will include status of clinical trials with bile acid based drugs, their molecular targets and novel opportunities for drugs targeting metabolic disturbances in the obese as prevention agents for HCC and EAC.
Citation Format: Patricia A. Thompson. Stemming the rising tide of liver and esophageal cancer. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr CN04-03.
Abstract CN07-02: Local transdermal therapy for DCIS and for breast cancer prevention
Authors: Khan Seema A. 
Published: May 2019

Abstract
Pharmacological breast cancer prevention is efficacious but has had low uptake by high risk women. The breast is a skin appendage, with a well-developed internal lymphatic circulation; preliminary studies have shown that small molecules which penetrate the skin concentrate well in the breast with low systemic exposure. We conducted a Phase II randomized trial comparing oral tamoxifen to 4-OHT gel applied to the breast skin, in women needing surgical resection of core-biopsy proven DCIS. Our goal was to assess relative breast tissue drug concentration and anti-proliferative efficacy in DCIS lesions. Although the study was halted early due to interruption in drug supply, preliminary results demonstrate good skin penetration, low systemic concentrations, and reduction in cell proliferation similar to that achieved with oral tamoxifen. These data support the continued investigation of this mode of drug delivery to the breast, with the potential for decreasing the toxicity of proven prevention agents, and for expanding the prevention drug portfolio to effective drugs that penetrate the skin, but systemic use is constrained by toxicity.
Citation Format: Seema A. Khan. Local transdermal therapy for DCIS and for breast cancer prevention. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr CN07-02.
Abstract CN08-03: 3-D electron microscopy in cellular and molecular imaging: Applications to cancer
Authors: Subramaniam Sriram 
Published: May 2019

Abstract
Emerging methods in 3-D biological electron microscopy provide powerful tools and great promise to bridge a critical gap in imaging in the biomedical size spectrum. This comprises a size range of considerable interest that includes cellular protein machines, giant protein and nucleic acid assemblies, small subcellular organelles and bacteria. These objects are generally too large and/or too heterogeneous to be investigated by high resolution X-ray and NMR methods; yet the level of detail afforded by conventional light and electron microscopy is often not adequate to describe their structures at resolutions high enough to be useful in understanding the chemical basis of biological function. The long-term mission of our research program is to obtain an integrated molecular understanding of cellular architecture by combining novel technologies for 3-D biological imaging with advanced methods for image segmentation and computational analysis. I will review our recent progress in imaging and modeling dynamic biological systems, with particular emphasis on applications to signal transduction, HIV/AIDS and cancer.
Lab website: http://electron.nci.nih.gov
Citation Format: Sriram Subramaniam. 3-D electron microscopy in cellular and molecular imaging: Applications to cancer. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr CN08-03.