bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 875: Risk factors for hepatocellular carcinoma (HCC) by race/ ethnicity in the United States
Authors: Makarova-Rusher Oxana V. , Altekruse Sean F. , McNeel Timothy S. , Graubard Barry I. , Duffy Austin G. , Ulahannan Susanna V. , Greten Tim F. , McGlynn Katherine A. 
Published: August 2015

Abstract
Background: Primary liver cancer is the sixth most common cancer worldwide, with HCC representing the majority of the cases. In the U.S., HCC rates are higher among Hispanics, Asians and blacks than among whites. Whether the higher risks are due to different distributions of risk factors is not clear. Thus, we conducted an analysis of HCC risk factors by race/ethnicity in the SEER-Medicare database for the years 2000-2009.
Methods: HCC cases (n = 8,116), identified by ICD-O morphology codes 8170-8175, were compared to a 5% random sample of cancer-free persons in the SEER areas (n = 313,525). Risk factors examined included type II diabetes (DM II), obesity, hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol-related disorders. Multivariate logistic regression analyses, which adjusted for age, location, gender, income and date of diagnosis as well as the other risk factors were used to compare risk factors by racial/ethnic group.
Results:
Risk factors by race/ethnicity
Risk factorWhiteBlackAsiansHispanicsN 6,120N 668N 971N 357%OR (95% CI)%OR (95% CI)%OR (95% CI)%OR (95% CI)Obesity6.31.06 (0.9-1.2)5.51.0 (0.7-1.5)0.70.2 (0.1-0.8)7.81.2 (0.7-1.9)DM II44.52.9 (2.8-3.1)41.81.3 (1.1-1.6)38.11.8 (1.5-2.1)54.62.0 (1.5-2.7)HBV1.83.8 (2.6-5.7)3.61.6 (0.7-3.7)17.717.1 (11.8-25.0)2.01.4 (0.2-11.1)HCV16.819.7 (17.1-22.6)34.036.8 (28.0-48.6)31.121.4 (15.4-29.9)22.716.0 (9.2-28.1)Alcohol cirrhosis11.44.7 (3.7-5.8)7.64.5 (2.4-8.5)4.03.8 (1.3-11.7)17.13.3 (1.7-6.8)Alcohol NOS13.12.7 (2.2-2.9)13.21.6 (1.1-2.4)3.72.0 (1.0-4.1)14.81.6 (0.8-3.0)Cirrhosis NOS33.345.5 (41.2-50.4)24.117.9 (12.3-25.9)36.836.9 (26.2-52.0)44.827.6 (18.9-40.3)
NOS not otherwise specified.
Conclusion: Major HCC risk factor profile is differ across race/ethnical groups. While diabetes is most common risk factor overall, it is most prevalent in Hispanics. HCC related to HCV is more common in blacks and Asians, and to HBV in Asians.
Citation Format: Oxana V. Makarova-Rusher, Sean F. Altekruse, Timothy S. McNeel, Barry I. Graubard, Austin G. Duffy, Susanna V. Ulahannan, Tim F. Greten, Katherine A. McGlynn. Risk factors for hepatocellular carcinoma (HCC) by race/ ethnicity in the United States. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 875. doi:10.1158/1538-7445.AM2015-875
Abstract 88: The Nkx3.1 homeobox gene maintains prostatic identity while its loss leads to prostate cancer initiation
Authors: Le Magnen Clémentine , Dutta Aditya , Abate-Shen Cory 
Published: August 2015

Abstract
Background
Maintenance of epithelial cell identity is tightly coordinated by tissue-specific gene expression programs, which are often deregulated during tumorigenesis. The homeodomain-containing transcription factor, Nkx3.1, is a key regulator of normal prostatic development and is frequently lost at early stages of prostate cancer initiation. In this study, we aim to elucidate detailed mechanisms governing Nkx3.1-driven maintenance of prostate identity and how deregulation of such can lead to prostate tumorigenesis.
Models and Methods
We evaluated the consequences of Nkx3.1 loss or gain of function in vivo using genetically-engineered mouse models and cell-recombination assays. RNA sequencing was performed to generate gene expression profiles, which were analyzed using Gene Set Enrichment analysis (GSEA), and validated by quantitative real-time PCR. In parallel, protein expression was assessed by immunofluorescence and western blot. Immunoprecipitation (IP) and chromatin-immunoprecipitation (ChIP) assays were performed using RWPE1 prostate epithelial cells.
Results
Here, we show that loss of function of Nkx3.1 leads to the progressive down-regulation of a prostate-specific gene expression program and to aberrant expression of genes that are not typically expressed in the prostate epithelium. Conversely, gain of function of Nkx3.1 in non-prostatic epithelium leads to the acquisition of a prostate-like morphology and expression of prostate-related genes. Our findings indicate that the underlying mechanism by which Nkx3.1 promotes prostatic identity is via epigenetic regulation of gene expression. In particular, we show that Nkx3.1 interacts with the histone methyl-transferase complex G9a/Glp. Finally, we demonstrate that this interaction is necessary for maintenance of prostate identity in vivo and that Nkx3.1 and G9a cooperate to control expression of genes that coordinate prostatic epithelial integrity.
Conclusions
Our results suggest that Nkx3.1 promotes prostatic identity by interacting with histone modifying enzymes to coordinate the expression of prostate-specific genes and that the loss of this function results in a failure to maintain prostate identity associated with early stages of prostate tumorigenesis.
Citation Format: Clémentine Le Magnen, Aditya Dutta, Cory Abate-Shen. The Nkx3.1 homeobox gene maintains prostatic identity while its loss leads to prostate cancer initiation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 88. doi:10.1158/1538-7445.AM2015-88
Abstract 883: Body mass, smoking habit, and hypertension and renal cell cancer survival
Authors: Lee Jung Eun , Kim Nayeon , Adami Hans-Olov , Lindblad Per 
Published: August 2015

Abstract
Background: A recent meta-analysis showed higher survival rate among over-weight and obese renal cell cancer (RCC) patients. Given that obesity, smoking and hypertension are well-established risk factors for RCC development, it is therefore important to know whether these factors are associated with RCC prognosis.
Objectives: We evaluated the associations of body mass index (BMI), smoking and hypertension with RCC survival in a population-based cohort of incident RCC cases assembled from a Swedish case-control study.
Methods: We analyzed a total of 371 RCC cases diagnosed in 1988-1992 with follow-up through Dec 31, 2011. Information on weight, height, smoking habit and hypertension was obtained through face-to-face interviews. Mortality information was determined through linkage to the National Cancer Registry; 298 deaths were identified, with 148 of those having RCC as the underlying cause of death, during an average of 9.9 years of follow-up. We calculated hazard ratios (HR)s and 95% confidence interval (CI)s using the Cox proportional hazards models.
Results: We confirmed that lifetime smoking and BMI at highest adult weight were associated with a worse overall survival among RCC patients. When we examined RCC-specific survival, the associations were not statistically significant; multivariate HR (95% CI) was 0.89 (0.54-1.49) for 20 or greater pack-years of smoking compared to never smokers. For BMI at highest adult weight, multivariate HR (95% CI) was 0.99 (0.53-1.87) comparing 35 or greater levels of BMI with less than 27 kg/m2 of BMI. History of hypertension was not associated with overall or RCC-specific survival.
Conclusions: We found a decreasing trend of overall survival with increasing prediagnostic BMI and lifetime smoking, but no significant associations of these factors and hypertension with RCC-specific survival among RCC patients.
Citation Format: Jung Eun Lee, Nayeon Kim, Hans-Olov Adami, Per Lindblad. Body mass, smoking habit, and hypertension and renal cell cancer survival. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 883. doi:10.1158/1538-7445.AM2015-883
Abstract 886: Health behaviors of cancer survivors: higher alcohol drinking, lower smoking and physical inactivity pattern in survivors with higher household income
Authors: Park Boyoung , Kong Sun-Young , Kim Jeongseon , Kim Yeol , Park In Hae , Jung So-Youn , Lee Eun Sook 
Published: August 2015

Abstract
Background: This study investigated the prevalence of smoking, alcohol consumption, and physical activity in cancer survivors and examined the sociodemographic factors affecting these health-related behaviors.
Methods: We used data from the fourth and fifth Korean National Health and Nutrition Examination Survey conducted between 2007 and 2012, which identified 1,153 cancer cases and 34,368 non-cancer controls ≥ 20 years of age. We used a structured questionnaire to obtain information concerning cancer diagnosis and sociodemographic characteristics.
Results: The proportion of cancer survivors who were current drinkers, heavy drinkers, current smokers, or engaged in physical activity were 49.1, 9.0, 9.2, or 50.7%, respectively. Compared with non-cancer controls, cancer survivors were less likely to be current drinkers, heavy drinkers, or current smokers (odds ratio [OR] = 0.56; 95% confidence interval [CI], 0.47-0.66; OR = 0.58; 95% CI, 0.44-0.78; and OR = 0.44, 95% CI, 0.34-0.59, respectively). Cancer survivors with higher household incomes had higher odds of current drinking and heavy drinking (P trend = 0.04 and 0.03, respectively) and were less likely to be current smokers or physically inactive (P trend &lt;0.01 and 0.03, respectively). Age, gender, employment status, the type of cancer, and the duration of cancer diagnosis affected the health behaviors. Furthermore, we confirmed that these unhealthy behaviors are interrelated. Conclusions: We found that household income had a bidirectional effect on health behaviors and confirmed an aggregation of unhealthy lifestyles. Identification of survivors vulnerable to unhealthy lifestyles would allow intervention programs to be more effective.
Citation Format: Boyoung Park, Sun-Young Kong, Jeongseon Kim, Yeol Kim, In Hae Park, So-Youn Jung, Eun Sook Lee. Health behaviors of cancer survivors: higher alcohol drinking, lower smoking and physical inactivity pattern in survivors with higher household income. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 886. doi:10.1158/1538-7445.AM2015-886
Abstract 89: Pin1 suppresses androgen receptor activity
Authors: Van der Steen Travis , Huang Haojie , Tindall Donald 
Published: August 2015

Abstract
Reactivation of the androgen receptor (AR) is the hallmark of prostate cancer (PCa) progression to the castration resistant prostate cancer (CRPC) phenotype. Currently, treatment for CRPC strives to impede the full-length AR (AR-FL) from becoming activated through targeting the ligand binding domain (LBD) via androgen deprivation therapy or treatment with antiandrogens. However, these options can give rise to AR-variants (AR-Vs) that lack the LBD and are unresponsive to treatment. Therefore, targeting the N-terminus of AR, which is conserved between AR-FL and AR-Vs, is critical for identifying new treatment options. Phosphorylation of serine 81 (AR-pS81) in the N-terminus of AR is critical for AR activation, stability and recruitment to the chromatin. Similar phosphorylation sites can be observed in the N-terminus of both AR-FL and AR-Vs. Expression of Pin1, a proline isomerase, exhibits a strong correlation with progression and relapse of PCa. Also, suppression of Pin1 in PCa decreases cell proliferation rates, suggesting that Pin1 may play a pivotal role in PCa progression. Pin1 isomerizes proline residues from trans to cis when the adjacent serine/threonine residue is phosphorylated. Dephosphorylation by phosphatases occurs when a pS-P motif is in the trans conformation. Therefore, Pin1 isomerization of AR pS81-P82 from trans to cis could prevent dephosphorylation and result in constitutive or enhanced AR activity. Stable cell lines with Pin1 knockdown were generated via shRNA targeting the 5′ UTR of Pin1 that express either AR-FL and/or AR-Vs. Pin1 knockdown was confirmed by western blots, and AR activity was monitored by expression of several AR regulated genes. Additionally, AR recruitment to chromatin was assayed by ChIP and Re-Chip. Loss of Pin1 resulted in a 60% reduction of endogenous PSA expression, and AR was unable to induce PSA expression when treated with androgens. However, suppression of AR activity was not due to decreased recruitment of AR to chromatin. Phosphorylation of AR-pS81 was decreased by loss of Pin1, while protein stability and mRNA expression was not altered. These data suggest that Pin1 may play a critical role in regulating the transcriptional activity of AR by altering the accessibility of AR to interact with transcriptional machinery needed to maintain AR activity. (Funding for this project was provided by the T.J. Martell Foundation).
Citation Format: Travis Van der Steen, Haojie Huang, Donald Tindall. Pin1 suppresses androgen receptor activity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 89. doi:10.1158/1538-7445.AM2015-89
Abstract 891: FGF21 prevents high fat diet-induced pancreatic cancer in mice expressing oncogenic Kras
Authors: Lu Weiqin , Yang Yaying , Wang Xiaojie , Liu Yan , Luo Yongde , Wolff Robert A. , Abbruzzese James L. , Logsdon Craig D. 
Published: August 2015

Abstract
The genetic landscape of pancreatic cancer shows nearly ubiquitous mutations of Kras. However, expression of mutant Kras alone is not sufficient to drive pancreatic ductal adenocarcinoma (PDAC) in adult mice. Obesity is a metabolic disorder and is a risk factor for PDAC. One of the main factors that contributes to the development of obesity is high-fat consumption. Recent studies have demonstrated that High-Fat-Diet (HFD) can promote oncogenic Kras mediated development of pancreatic intraepithelial neoplasia and PDAC. However, it is not clear why mice with oncogenic KrasG12D expression are predisposed to HFD mediated pancreatic carcinogenesis. Here, we report that Ras activity dramatically reduces the expression of fibroblast growth factor 21 (FGF21). FGF21 is a key mediator of fatty acid oxidation and lipid metabolism. Pharmacological doses of FGF21 lower serum free fatty acids and lead to weight loss in obese mice. FGF21 is highly expressed in pancreatic acinar cells and is a potential autocrine factor. High levels expression of FGFR1 and β-Klotho, key components for specific sites of FGF21 action, were observed on normal control mouse pancreatic acinar cells using both qRT-PCR and immunohistochemistry technics. FGF21 levels were dramatically reduced (∼6-fold) by Cre-mediated knock-in of oncogenic KrasG12D within one week and further decreased by more than 100-fold within 7 months. This effect of KrasG12D may have been mediated by decreased expression of pancreatic transcription factor Mist1, which was also observed. To dissect obesity and oncogenic KrasG12D mediated PDAC, we fed adult KrasG12D expressing mice with HFD or HFD+FGF21. We observed that KrasG12D expressing mice fed with HFD+FGF21 for 9 weeks significantly lower body weight and pancreatic triglyceride, as well as dramatically fewer PanIN lesions and tumor, compared with KrasG12D mice on a HFD without FGF21. FGF21 treatment extended survival of KrasG12D expressing mice on a HFD. Our results suggest that pancreas-derived FGF21 is an important metabolic regulator which is silenced by oncogenic KrasG12D expression and plays an important role in preventing HFD induced PDAC in KrasG12D expressing mice.
Citation Format: Weiqin Lu, Yaying Yang, Xiaojie Wang, Yan Liu, Yongde Luo, Robert A. Wolff, James L. Abbruzzese, Craig D. Logsdon. FGF21 prevents high fat diet-induced pancreatic cancer in mice expressing oncogenic Kras. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 891. doi:10.1158/1538-7445.AM2015-891
Abstract 893: Metabolomic profiling of APCΔ14/+ mice maintained on a methyl donor deficient diet reveals alterations to methionine and fatty acid metabolism associated with cancer protection
Authors: Hanley Matthew P. , Rosenberg Daniel W. 
Published: August 2015

Abstract
Our laboratory has previously demonstrated that administration of a diet deficient in methyl donor nutrients (folic acid, methionine, choline and vitamin B12) reduces tumor multiplicity by greater than 95% in ApcMin/+ mice. However, the mechanism by which this dramatic cancer protection is afforded is unknown. To begin to identify the metabolic consequences of methyl donor deficiency, we have conducted an LC/MS-based metabolic profiling analysis of colonic mucosa collected from ApcΔ14/+ mice fed a methyl donor deficient (MDD) diet for 17 weeks. Methyl donor deficiency causes significant alterations to a number of key metabolic pathways, including those involved in the methionine cycle, fatty acid oxidation, and tryptophan catabolism. We observed significant reductions in methionine (65% reduction, p&lt;0.001) and betaine (70% reduction, p&lt;0.001), accompanied by large increases in homocysteine (88.6-fold increase, p&lt;0.001) and S-adenosylmethionine (17.2-fold increase, p&lt;0.001), confirming that dietary methyl donor deficiency alters one-carbon metabolites in the colon. MDD mice were found to have reduced levels of acyl-carnitines and free carnitine (58% reduction, p&lt;0.001). Additionally, we detected a reduction in the critical metabolic component, acetyl CoA, suggesting decreased transport of fatty acids into the mitochondria for use in fatty acid oxidation (FAO). Finally, we observed changes in the mucosal levels of tryptophan (32% reduction, p = 0.02), kynurenine (2.8-fold increase, p = 0.008) and indolepropionate (5.1-fold increase, p = 0.005), that were retained for seven weeks beyond active methyl donor deficiency. Taken together, these findings suggest that dietary methyl donor deficiency significantly disrupts the methionine cycle, inhibits fatty acid transport and oxidation, and may induce long-term changes to tryptophan metabolism. This study has improved our understanding of the molecular mechanisms underlying the cancer protection conveyed by dietary methyl donor deficiency and has identified metabolic pathways that are candidate targets for chemopreventive intervention.
Citation Format: Matthew P. Hanley, Daniel W. Rosenberg. Metabolomic profiling of APCΔ14/+ mice maintained on a methyl donor deficient diet reveals alterations to methionine and fatty acid metabolism associated with cancer protection. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 893. doi:10.1158/1538-7445.AM2015-893
Abstract 904: Lifetime genistein alters mammary tumors’ response to anti-estrogen tamoxifen treatment by affecting immune function in rats
Authors: Zhang Xiyuan , Cook Katherine , Hilakivi-Clarke Leena 
Published: August 2015

Abstract
Consistent with the human data showing that soy intake reduces the risk of breast cancer recurrence, we have previously reported that childhood and lifelong genistein (GEN) intake enhanced response of mammary tumors to tamoxifen (TAM) treatment and prevented recurrence in rats. Mammary tumor recurrence was also inhibited by starting GEN consumption in adulthood. Since GEN is shown to alter immune functions, and tumor immune responses can determine cancer outcome, we examined several immune markers in the tumor prior to TAM treatment.
Female Sprague-Dawley rats were fed control AIN93G diet or AIN93G diet supplemented with 500 ppm GEN either during childhood (between postnatal days 15 and 30), adulthood (from 55 days to end of the study), or both. Mammary tumors were induced by DMBA at the age of 48 days, and when a tumor reached a size of 1.4 cm in diameter (criteria for starting TAM treatment in the previous study), rats were euthanized (n = 15 per group), and blood and mammary tumors were collected.
We determined the expression of CD8-alpha (present in cytotoxic T lymphocytes) and Foxp3, TGFβ1 and TGF2 (present in regulatory T-cells, Treg) in mammary tumors from rats with varying lifetime exposures to GEN. Compared with the control rats, expression of CD8-alpha mRNA was significantly increased by GEN intake at any time during the life cycle, suggesting an elevation in cytotoxic T-cells density infiltrating the tumor. Foxp3 and TGF-β1 mRNA were significantly reduced by GEN consumption. Increased Treg levels in tumors result in the suppression of immune responses; therefore, a reduction in Foxp3 and TGF-β1 may indicate a decrease in immune suppression. TGF-2 mRNA expression was significantly increased in the tumors of rats that consumed GEN only as adults. In the serum, interleukin (IL)-1 and IL-6 levels were significantly elevated in rats that consumed GEN only during childhood, whilst IL-6 was reduced in rats consuming GEN during lifetime or only as adults. IL-12 that is reported to stimulate cellular immunity, was increased in the rats that consumed GEN during lifetime or as adults.
Our findings suggest that the ability of GEN intake to prevent mammary cancer recurrence is associated with improved immune responses in the tumor.
Citation Format: Xiyuan Zhang, Katherine Cook, Leena Hilakivi-Clarke. Lifetime genistein alters mammary tumors’ response to anti-estrogen tamoxifen treatment by affecting immune function in rats. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 904. doi:10.1158/1538-7445.AM2015-904