bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5271: Prostate cancer chemoprevention by dietary isothiocyanates is associated with suppression of lipogenesis
Authors: Singh Krishna B. , Singh Shivendra V. 
Published: July 2017

Abstract
Isothiocyanates (ITCs), including sulforaphane (SFN) and phenethyl isothiocyanate (PEITC), have been studied extensively for chemoprevention of prostate cancer using both in vitro and in vivo models, but the underlying mechanism is not fully understood. Dependence on fatty acid metabolism is progressively recognized as a unique trait of prostate cancer. Using in vitro and in vivo prostate cancer models, we demonstrate for the first time, that prostate cancer chemoprevention by ITCs is associated with suppression of fatty acid metabolism. Exposure of human prostate cancer cells to plasma achievable concentrations of SFN resulted in a marked decrease in levels of key fatty acid metabolism proteins, including acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), and carnitine palmitoyl transferase 1A (CPT1A), that was accompanied by suppression of their transcription. Consistent with the in vitro results, oral administration of prostate cancer chemopreventive concentrations of SFN (6 µmol per mouse, three times per week) resulted in downregulation of ACC1, FASN, and CPT1A proteins in prostate adenocarcinoma of TRAMP transgenic mice when compared with control. Levels of fatty acid metabolites (free fatty acid, triglycerides and phospholipids), lactate, and acetyl-CoA were also lower in the plasma and/or prostate adenocarcinoma of SFN-treated TRAMP mice in comparison with controls. Because fatty acid oxidation is an important step to supply energy to the prostate cancer cells, we explored the possibility of whether SFN could affect the fatty acid oxidation in prostate cancer cells. Indeed, SFN exposure significantly decreased the level of proteins involved in fatty acid oxidation in prostate cancer cells. Many of these changes were also observed with PEITC. In conclusion, it is reasonable to propose that suppression of fatty acid metabolism is an important mechanism in prostate cancer chemoprevention by ITCs. This study was supported by the grants RO1 CA115498-10 and RO1 CA101753-12 awarded by the National Cancer Institute.
Citation Format: Krishna B. Singh, Shivendra V. Singh. Prostate cancer chemoprevention by dietary isothiocyanates is associated with suppression of lipogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5271. doi:10.1158/1538-7445.AM2017-5271
Abstract 5283: Association between body mass index and prostate cancer among African American men
Authors: Pichardo Margaret S. , Smith Cheryl J. , Tang Wei , Dorsey Tiffany , Ambs Stefan 
Published: July 2017

Abstract
Prostate cancer (PCa) is a leading cause of cancer death in US men. Yet, the etiology of prostate cancer remains poorly understood, with only older age, African ancestry, family history of the disease, and multiple germline genetic variations being established disease risk factors. Prostate cancer occurs more often in African-American (AA) men and Caribbean men of African descent than in men of other race/ethnicities. While it has been previously suggested that obesity (measured using body mass index [BMI, kg/m2]) may worsen disease-related outcomes among prostate cancer patients, the relationship of obesity and prostate cancer risk, using race as a predictor, has not been fully explored. Using multivariable logistic regression, we estimated the risk of total PCa for 976 cases and 1,032 age-matched controls, with equal proportions of European-American (EA) and AA men. Among men in the NCI Maryland Prostate Cancer Case-Control Study, BMI was inversely associated with disease outcomes in AA men, but not among EA men. Consistent with previous literature, BMI in EA men was shown to be positively associated with overall prostate cancer risk. Our findings suggest an obesity paradox, where obesity may protect against incidence of PCa among AA men. Studies are needed to elucidate the underlying mechanisms responsible for the differential effects of obesity in AA and EA men with prostate cancer.
Citation Format: Margaret S. Pichardo, Cheryl J. Smith, Wei Tang, Tiffany Dorsey, Stefan Ambs. Association between body mass index and prostate cancer among African American men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5283. doi:10.1158/1538-7445.AM2017-5283
Abstract 5287: Recent trends in racial and regional disparities in cervical cancer incidence and mortality
Authors: Yoo Wonsuk , Kim Sangmi , Coughlin Steven , Bae Sejong , Partridge Edward , Huh Warner , Dilley Sarah , Chung Yunmi 
Published: July 2017

Abstract
Background: Although black and Hispanic women experienced greater cervical cancer rate reduction in recent years, they continue to have higher incidence rates than whites. Great variations also exist among geographic regions of the US, with the South having both the highest incidence and mortality rates compared to other regions. The present study explores the question of whether living in the South is associated with greater racial disparity in cervical cancer incidence and mortality by examining race- and region-specific rates and the trend between 2000 and 2012.
Methods: The Surveillance, Epidemiology, and End Results (SEER) 18 Program data was used. Incidence and mortality rates, annual percent changes, and disparity ratios of cervical cancer were calculated using SEER*Stat software and Joinpoint regression for four groups: US14-Non-Hispanic White (NHW), US14-Non-Hispanic Black (NHB), South-NHW, and South-NHB, where the South included 4 registries from Georgia and Louisiana.
Results: The incidence and mortality rates were much higher among NHB women compared to NHW in the South and the US. The degree of racial disparities between NHB and NHW women was greater in terms of mortality rates than incidence rates. For all age groups, NHB women in the South consistently had higher incidence rates than NHB women in the US14 region. The mortality disparity ratios was highest among NHB women, followed by NHW women in the South, NHW women in US14, and finally NHB women in the South.
Conclusions: Although racial disparity has been narrowed in recent years, there has been little change or even a growing gap between white women in the South and their counterparts in the US14 region. Age-specific analysis further indicated that the emerging regional gap observed among white women might be attributable to the excess number of new cases and deaths among young women.
Citation Format: Wonsuk Yoo, Sangmi Kim, Steven Coughlin, Sejong Bae, Edward Partridge, Warner Huh, Sarah Dilley, Yunmi Chung. Recent trends in racial and regional disparities in cervical cancer incidence and mortality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5287. doi:10.1158/1538-7445.AM2017-5287
Abstract 5292: Multitarget fecal miRNA test combined with fecal occult blood test and fecal miRNA test for colorectal cancer screening
Authors: Koga Yoshikatsu , Yamazaki Nobuyoshi , Kakugawa Yasuo , Matsuda Takahisa , Ito Masaaki , Saito Yutaka , Saito Hiroshi , Matsumura Yasuhiro 
Published: July 2017

Abstract
Background & Aims: The fecal immunochemical test (FIT) is used for colorectal cancer (CRC) screening worldwide. However, there are several issues of the false-positive and the false-negative. To overcome these problems, various molecular biological tests have been combined to FIT. In this context, multitarget fecal DNA test was approved by FDA in August 2014. In addition, multitarget fecal microbiota has been recently reported. We have reported the usefulness of fecal miRNA analysis to detect CRC. Here, we investigated the applicability of multitarget fecal miRNA test combined with FIT and fecal miRNA test using fecal RNA extracted from FIT residua.
Methods: In this study, 57 patients with invasive CRC, 33 patients with advanced adenoma, and 60 healthy individuals were enrolled. Each participant collected 10 mg fecal samples using the FIT sampling container for 2 days. After FIT was performed, total RNA was extracted from the residuum and miRNA expression was analyzed by using real-time RT-PCR. The sensitivity and specificity of the multitarget fecal miRNA test combined with FIT and fecal miRNA test was analyzed by using the decision tree analysis.
Results: Approximately 1μg RNA was extracted from 10 mg fecal sample. The expressions of miR-16, miR-92a, miR-106a, miR-142-3p, miR-223, and miR-451 in fecal samples were significantly higher in the patients with advanced neoplasm (including invasive CRC and advanced adenoma) than in the healthy individuals (P&lt;0.05). The sensitivity and the specificity of the FIT alone were 74.4% (67/90) and 93.3% (56/60), whereas those of the multitarget fecal miRNA test were 93.3% (83/90) and 91.7% (55/60). Moreover the multitarget fecal miRNA test could detect 81.8% of patients with advanced adenoma (27/33).
Conclusions: Multitarget fecal miRNA test combined with FIT and fecal miRNA test may be a useful new CRC screening method.
Citation Format: Yoshikatsu Koga, Nobuyoshi Yamazaki, Yasuo Kakugawa, Takahisa Matsuda, Masaaki Ito, Yutaka Saito, Hiroshi Saito, Yasuhiro Matsumura. Multitarget fecal miRNA test combined with fecal occult blood test and fecal miRNA test for colorectal cancer screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5292. doi:10.1158/1538-7445.AM2017-5292
Abstract 53: Antibody-drug conjugates (ADCs) of peptide-linked Indolino-Benzodiazepine (IGN) DNA-alkylator provides improved anti-tumor activity over that of a crosslinker
Authors: Miller Michael L. , Shizuka Manami , Ponte Jose F. , Lanieri Leanne , Vitharana Dilrukshi , Qiu Qifeng , Reid Emily E. , Archer Katie E. , Wu Rui , Maloney Erin K. , Ab Olga , Pinkas Jan , Chari Ravi V. 
Published: July 2017

Abstract
We recently disclosed highly active antibody-drug conjugates (ADCs) that incorporated the novel DNA alkylating indolino-benzodiazepine (termed IGN) dimer, DGN549 (IGN-P1). The stereochemistry of the alanyl moiety of the protease-cleavable alanine-alanine linker used was shown to impact ADC catabolism, bystander killing activity, and in vivo efficacy (Shizuka, et al., AACR 2016 #2959). Building upon these results, here we describe preclinical results from a head-to-head comparison of ADCs of the mono-imine containing DGN549 with its corresponding DNA cross-linking diimine version, IGN-P1 diimine. IGN-P1 diimine and DGN549 were conjugated to a folate receptor-α (FRα)-binding antibody and an EpCAM-binding antibody. The resulting ADCs demonstrated similar high in vitro potency (IC50 ~3-100 pM) and specificity towards several cancer cell lines. Further in vitro studies revealed that the DNA alkylating anti-FRα-DGN549 ADC demonstrated superior bystander cell-killing activity compared to its DNA crosslinking counterpart, anti-FRα-IGN-P1 diimine. In vivo, this improved bystander killing ability translated into better in vivo activity for the DNA alkylating ADC. In an endometrial tumor xenograft model established with Ishikawa cells, the anti-FRα-DGN549 induced complete regressions at a single dose of 140 µg/kg Ab dose (equivalent to 5 µg/kg linked IGN). The cross-linking anti-FRα-IGN-P1 diimine had to be used at twice the dose to achieve the same level of anti-tumor activity. The in vivo tolerability in CD-1 mice also displayed differences in the two ADCs. We found that the ADC of the DNA crosslinker was at least two-fold less tolerated than the corresponding ADC of the DNA alkylator. These results indicate that a ~4 fold greater therapeutic index can be achieved when using a DNA alkylating mono-imine DGN549 ADC as compared to the DNA crosslinking IGN-P1 diimine ADC.
Citation Format: Michael L. Miller, Manami Shizuka, Jose F. Ponte, Leanne Lanieri, Dilrukshi Vitharana, Qifeng Qiu, Emily E. Reid, Katie E. Archer, Rui Wu, Erin K. Maloney, Olga Ab, Jan Pinkas, Ravi V. Chari. Antibody-drug conjugates (ADCs) of peptide-linked Indolino-Benzodiazepine (IGN) DNA-alkylator provides improved anti-tumor activity over that of a crosslinker [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 53. doi:10.1158/1538-7445.AM2017-53
Abstract 5304: A serological biopsy using five stomach-specific circulating biomarkers for gastric cancer risk assessment: a multi-phase study
Authors: Tu Huakang , Sun Liping , Dong Xiao , Gong Yuehua , Xu Qian , Jing Jingjing , Bostick Roberd M. , Wu Xifeng , Yuan Yuan 
Published: July 2017

Abstract
Objective: We aimed to assess a serological biopsy using five stomach-specific circulating biomarkers—pepsinogen I (PGI), PGII, PGI/II ratio, anti-Helicobacter pylori (H. pylori) antibody, and gastrin-17 (G-17)—for identifying high-risk individuals and predicting risk of developing gastric cancer (GC).
Methods: Among 12112 participants with prospective follow-up from an ongoing population-based screening program using both serology and gastroscopy in China, we conducted a multi-phase study involving a cross-sectional analysis, a follow-up analysis, and an integrative risk prediction modeling analysis.
Results: In the cross-sectional analysis, the five biomarkers (especially PGII, the PGI/II ratio, and H. pylori sero-positivity) were associated with the presence of precancerous gastric lesions or GC at enrollment. In the follow-up analysis, low PGI levels and PGI/II ratios were associated with higher risk of developing GC, and both low (&lt;0.5 pmol/L) and high (2.0-4.7 or &gt;4.7 pmol/L) G-17 levels were associated with higher risk of developing GC, suggesting a J-shaped association. In the risk prediction modeling analysis, the five biomarkers combined yielded a C statistic of 0.801 (95% CI=0.787-0.815) and improved prediction beyond traditional risk factors (C statistic from 0.580 to 0.811, P&lt;0.001) for identifying precancerous lesions at enrollment, and higher serological biopsy score based on the five biomarkers at enrollment were associated with higher risk of developing GC during follow-up (P for trend &lt;0.001).
Conclusions: A serological biopsy composed of the five stomach-specific circulating biomarkers could be used to identify high-risk individuals for further diagnostic gastroscopy, and to stratify individuals’ risk of developing GC and thus to guide targeted screening/precision prevention.
Citation Format: Huakang Tu, Liping Sun, Xiao Dong, Yuehua Gong, Qian Xu, Jingjing Jing, Roberd M. Bostick, Xifeng Wu, Yuan Yuan. A serological biopsy using five stomach-specific circulating biomarkers for gastric cancer risk assessment: a multi-phase study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5304. doi:10.1158/1538-7445.AM2017-5304
Abstract 5313: Associations of calcium and dairy product intakes with colorectal cancer risk among older women: the Iowa Women's Health Study
Authors: Um Caroline , Prizment Anna , Lazovich DeAnn , Bostick Roberd M. 
Published: July 2017

Abstract
Calcium has been consistently modestly associated with lower risk of colorectal cancer, which remains the second leading cause of cancer deaths among men and women combined in the United States. Dairy products, a major source of dietary calcium, have also been consistently inversely associated with colorectal cancer, although inconsistencies in relation to high-fat dairy products have been noted. Limited evidence suggests that dairy products may contain components other than calcium and fat, such as insulin-like growth factor 1 (IGF-1), that may be independently directly associated with risk of colorectal and other cancers.
Data from the Iowa Women’s Health Study, a prospective cohort study, were used to investigate associations of calcium, dairy products, and the non-calcium component of dairy products with colorectal cancer incidence. Dietary data were collected using a semiquantitative food frequency questionnaire (FFQ) mailed to 55 – 69 year-old women in 1986 who had a valid Iowa driver’s license. Among participants with no history of cancer at baseline and who satisfactorily completed their FFQ (n=35,221), through follow up in 2012, 1,731 incident cases of colorectal cancer were documented via the Iowa SEER registry. To investigate total dairy and total, whole, and non-fat milks independent of their calcium components, we used the residuals from linear regression models of their associations with dietary calcium. Associations of the calcium and dairy product variables with colorectal cancer incidence were estimated using multivariable Cox proportional hazards regression.
For those in the highest relative to those in the lowest quintiles of intakes, the adjusted hazards ratios and 95% confidence intervals (CI) were 0.81 (CI 0.67-0.98; P-trend 0.004) for total calcium, 0.85 (CI 0.68-1.03; P-trend 0.07) for dietary calcium, and 0.85 (CI 0.68-1.06; P-trend 0.16) for supplemental calcium. For total dairy and total milk, the corresponding findings were 0.79 (CI 0.66-0.94; P-trend 0.01) and 0.82 (CI 0.69-0.96; P-trend 0.09), respectively. Low-fat dairy products, non-fat milk, and residuals of total dairy products and total and non-fat milk were not associated with colorectal cancer.
These results are consistent with previous findings of lower colorectal cancer risk with higher intakes of calcium and dairy products, but provide little support for the hypothesis that the non-calcium, non-fat component of dairy products may be associated with colorectal cancer.
Citation Format: Caroline Um, Anna Prizment, DeAnn Lazovich, Roberd M. Bostick. Associations of calcium and dairy product intakes with colorectal cancer risk among older women: the Iowa Women's Health Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5313. doi:10.1158/1538-7445.AM2017-5313
Abstract 5325A: Fruit and vegetable intake and risk of breast cancer: Pooled analysis of the Nurses’ Health Study and the Nurses’ Health Study II
Authors: Farvid Maryam S. , Willett Walter C. , Eliassen A. Heather 
Published: July 2017

Abstract
Fruit and vegetable intake has been hypothesized to protect against breast cancer, but the overall evidence has not been supportive. Using pooled data from the Nurses’ Health Study and the Nurses’ Health Study II cohorts, we evaluated fruit and vegetable intake in relation to breast cancer risk. Diet was assessed every 4 years using semi-quantitative food frequency questionnaires. Cox proportional hazards regression, adjusting for multiple breast cancer risk factors, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs)for each category, using the lowest quintile of intake as the reference category. Among 182,204 women aged 27 to 66 years, we prospectively identified 10,973 invasive breast cancer cases during follow-up from 1980 through 2012 for the Nurses’ Health Study and from 1991 through 2013 for the Nurses’ Health Study II. Fruit and vegetable intake was significantly associated with a lower risk of breast cancer. The pooled multivariate HR (95% CIs) for highest (3.2 servings/day) versus lowest (0.4 serving/day) quintile intake of total fruit intake was 0.93 (0.86-0.99; Ptrend=0.03) and for highest (4.9 servings/day) versus lowest (1.5 servings/day) quintile intake of total vegetable was 0.92 (0.86-0.99; Ptrend=0.02). We also observed that a higher intake of yellow/orange vegetables, cruciferous vegetable, fruits and vegetables rich in vitamin C, fruits and vegetables rich in α-carotene, fruits and vegetables rich in β-carotene, and fruits and vegetables rich in lutein was each associated with a lower breast cancer risk. In addition, the association with vegetable intake was stronger for both estrogen and progesterone receptor negative (HR=0.91; 95%CIs=0.87-0.95) than both estrogen and progesterone receptor positive cancers (HR=0.98; 95%CIs=0.96-1.00; Pheterogeneity=0.003). Our findings support an association of a higher fruit and vegetable intake with a lower breast cancer risk.
Citation Format: Maryam S. Farvid, Walter C. Willett, A. Heather Eliassen. Fruit and vegetable intake and risk of breast cancer: Pooled analysis of the Nurses’ Health Study and the Nurses’ Health Study II [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5325A. doi:10.1158/1538-7445.AM2017-5325A
Abstract 5326: EZH2 regulation through lysine 63 linked ubiquitination in prostate cancer
Authors: Lu Wenfu , Lu Shenji , Li Bo , Xie Yingqiu , Izban Michael G. , Ballard Billy R. , Sathyanarayana Sandeep A. , Adunyah Samuel E. , Matusik Robert J. , Chen Zhenbang 
Published: July 2017

Abstract
Enhancer of zeste homolog 2 (EZH2) plays crucial roles on the development of cells and tissues as well as the progression of prostate cancer (PCa) and castration resistant prostate cancer (CRPC). EZH2 can upregulate and activate progenitor genes including androgen receptor (AR) and the target genes. However, the mechanisms by which EZH2 is regulated in PCa remain elusive. Literature reports that tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) is essential for both normal tissue development and regulation of oncogenic signaling pathways in cancers. In this study, we reported that EZH2 is regulated by PTEN and SKP2 network in PCa. Specifically, we showed that the aberrant upregulation of EZH2 and histone H3 lysine 27 trimethylation (H3K27me3) in both Pten null mouse embryonic fibroblasts (MEFs) in vitro and prostate tumors of Pten null mice in vivo, as compared to the controls. EZH2 levels were negatively correlated with TRAF6 in human PCa cells upon SKP2 dysregulation. Immunofluorescence (IF) staining results showed a co-localization of EZH2 and TRAF6 in nucleus of PC3 cells, and co-immunoprecipitation (co-IP) analysis further confirmed a physical binding of EZH2 and TRAF6 in PC3 cells. Ectopic expression of TRAF6 promoted the K63-linked polyubiquitination of EZH2 to decrease EZH2 and H3K27me3 levels in PCa cells. Conversely, TRAF6 knockdown resulted in a reduction of EZH2 polyubiquitination with an increase of EZH2 and H3K27me3 levels in PCa cells. Furthermore, the catalytically dead mutant TRAF6 C70A abolished the TRAF6-mediated polyubiquitination of human EZH2 in vivo in 293T cells and in vitro in the recombinant human EZH2 protein, as compared with TRAF6 WT. Together, we report for the first time a novel mechanism on EZH2 ubiquitination and an important signaling network of SKP2-TRAF6-EZH2-H3K27me3 in PCa cells. Our findings provide valuable clues on the mechanism and efficiency of targeting EZH2 in PCa and CRPC .
Note: This abstract was not presented at the meeting.
Citation Format: Wenfu Lu, Shenji Lu, Bo Li, Yingqiu Xie, Michael G. Izban, Billy R. Ballard, Sandeep A. Sathyanarayana, Samuel E. Adunyah, Robert J. Matusik, Zhenbang Chen. EZH2 regulation through lysine 63 linked ubiquitination in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5326. doi:10.1158/1538-7445.AM2017-5326