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Cancer Prevention Research

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https://www.readbyqxmd.com/read/29326285/prevalence-of-aflatoxin-associated-tp53r249s-mutation-in-hepatocellular-carcinoma-in-hispanics-in-south-texas
#1
Jingjing Jiao, Weibo Niu, Ying Wang, Keith Baggerly, Yuanqing Ye, Xifeng Wu, Dewitt Davenport, Jose Luis Almeda, Monica M Betancourt-Garcia, R Armour Forse, Heather L Stevenson, Gordon P Watt, Joseph B McCormick, Susan P Fisher-Hoch, Laura Beretta
We aimed to determine whether aflatoxin dietary exposure plays a role in the high incidence of hepatocellular carcinoma (HCC) observed among Hispanics in South Texas. We measured TP53R249S somatic mutation, hallmark of aflatoxin etiology in HCC, using droplet digital PCR and RFLP. TP53R249S mutation was detected in 3 of 41 HCC tumors from Hispanics in South Texas (7.3%). We also measured TP53R249S mutation in plasma cell-free DNA (cfDNA) from 218 HCC patients and 96 Hispanic subjects with advanced fibrosis or cirrhosis, from South Texas...
January 11, 2018: Cancer Prevention Research
https://www.readbyqxmd.com/read/29301746/cyclic-gmp-elevating-agents-suppress-polyposis-in-apc-min-mice-by-targeting-the-preneoplastic-epithelium
#2
Sarah K Sharman, Bianca N Islam, Yali Hou, Nagendra Singh, Franklin G Berger, Subbaramiah Sridhar, Wonsuk Yoo, Darren D Browning
The cGMP signaling axis has been implicated in the suppression of intestinal cancers but the inhibitory mechanism and the extent to which this pathway can be targeted remains poorly understood. The present study has tested the effect of cGMP-elevating agents on tumorigenesis in the ApcMin/+ mouse model of intestinal cancer. Treatment of ApcMin/+ mice with the receptor guanylyl-cyclase C (GCC) agonist linaclotide, or the phosphodiesterase-5 (PDE5) inhibitor sildenafil, significantly reduced the number of polyps per mouse (67% and 50% respectively)...
January 4, 2018: Cancer Prevention Research
https://www.readbyqxmd.com/read/29263155/molecular-predicators-of-duodenal-familial-adenomatous-polyposis-chemoprevention-do-chemopreventive-drugs-hit-their-presumed-molecular-targets
#3
EDITORIAL
Imad Shureiqi
Patients with familial adenomatous polyposis (FAP) have an increased risk of developing duodenal adenomas and adenocarcinomas. In previous trials, sulindac (a cyclooxygenase inhibitor) alone failed to significantly suppress duodenal tumorigenesis in FAP patients, but sulindac plus the tyrosine kinase inhibitor erlotinib significantly reduced duodenal polyp burden. Delker and colleagues report in this issue (beginning on page 4) on transcriptome analyses that aimed to identify the molecular targets mediating the response to sulindac-erlotinib...
December 19, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29246957/chemoprevention-of-preclinical-breast-and-lung-cancer-with-the-bromodomain-inhibitor-i-bet-762
#4
Di Zhang, Ana S Leal, Sarah Carapellucci, Kayla Zydeck, Michael B Sporn, Karen T Liby
Breast cancer and lung cancer remain the top two leading causes of cancer death in women. Due to limited success in reducing the high mortality of these diseases, new drugs and approaches are desperately needed. Cancer prevention is one such promising strategy that is effective in both preclinical and clinical studies. I-BET 762 is a new bromodomain inhibitor that reversibly targets BET (bromodomain and extra-terminal) proteins and impairs their ability to bind to acetylated lysines on histones, thus interrupting downstream transcription...
December 15, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29246956/marshalling-the-translational-potential-of-mc1r-for-precision-risk-assessment-of-melanoma
#5
Peter A Kanetsky, Jennifer L Hay
Melanoma rates have been increasing in the United States, and neither primary (sun protection and avoidance) nor secondary (skin examination) prevention is practiced consistently, even by those with melanoma risk factors. Inherited variation at MC1R is a robust marker for increased risk of melanoma, even among individuals with "sun-resistant" phenotypes. Although MC1R conveys important information about inherited melanoma risk for a broad spectrum of individuals, concerns that MC1R feedback could have negative consequences, including increased distress about melanoma, inappropriate use of health services, and development of a false sense of security are valid and require empirical examination...
December 15, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29246955/a-bet-bromodomain-inhibitor-suppresses-adiposity-associated-malignant-transformation
#6
Debrup Chakraborty, Vanessa Benham, Vladislav Jdanov, Blair Bullard, Ana S Leal, Karen T Liby, Jamie J Bernard
Almost half a million of all new cancers have been attributed to obesity and epidemiological evidence implicates visceral adipose tissue (VAT) and high-fat diets (HFD) in increasing cancer risk. We demonstrated that VAT-derived fibroblast growth factor 2 (FGF2) from mice fed a HFD or obese individuals stimulates the malignant transformation of epithelial cells. Mechanism-based strategies to prevent this VAT-enhanced tumorigenesis have not been explored. Clinical studies have indicated that bromodomain inhibitors have considerable potential as therapeutic agents for cancer by inhibiting the activity of several oncogenes including c-Myc however, their chemopreventive activity is unknown...
December 15, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29222347/pioglitazone-inhibits-periprostatic-white-adipose-tissue-inflammation-in-obese-mice
#7
Miki Miyazawa, Kotha Subbaramaiah, Priya Bhardwaj, Xi K Zhou, Hanhan Wang, Domenick J Falcone, Dilip D Giri, Andrew J Dannenberg
Obesity is associated with an increased incidence of high-grade prostate cancer (PC) and poor prognosis for PC patients. Recently, we showed that obesity-related periprostatic white adipose tissue (WAT) inflammation, characterized by crown-like structures (CLS) consisting of dead or dying adipocytes surrounded by macrophages, was associated with high-grade PC. It's possible, therefore, that agents that suppress periprostatic WAT inflammation will alter the development or progression of PC. Pioglitazone, a ligand of PPARγ is used to treat diabetes and possesses anti-inflammatory properties...
December 8, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29222346/adiposity-inflammation-and-breast-cancer-pathogenesis-in-asian-women
#8
Neil M Iyengar, I-Chun Chen, Xi K Zhou, Dilip D Giri, Domenick J Falcone, Lisle A Winston, Hanhan Wang, Samantha Williams, Yen-Shen Lu, Tsu-Hsin Hsueh, Ann-Lii Cheng, Clifford A Hudis, Ching-Hung Lin, Andrew J Dannenberg
Obesity is associated with white adipose tissue (WAT) inflammation in the breast, elevated levels of the estrogen biosynthetic enzyme, aromatase, and systemic changes that predispose to breast cancer development. We examined whether WAT inflammation and its associated systemic effects correlate with body fat levels in an Asian population where body mass index (BMI) is not an accurate assessment of obesity and cancer risk. We also investigated whether biologic differences could account for the greater proportion of premenopausal estrogen receptor (ER)-positive breast cancer in Asian versus western countries...
December 8, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29167285/macrophagic-crown-like-structures-are-associated-with-an-increased-risk-of-breast-cancer-in-benign-breast-disease
#9
Jodi M Carter, Tanya L Hoskin, M Alvaro Pena, Rushin Brahmbhatt, Stacey J Winham, Marlene H Frost, Melody Stallings-Mann, Derek C Radisky, Keith L Knutson, Daniel W Visscher, Amy C Degnim
In breast adipose tissue, macrophages that encircle damaged adipocytes form "crown-like structures of breast" (CLS-B). While CLS-B have been associated with breast cancer, their role in benign breast disease and early carcinogenesis is not understood. We evaluated breast biopsies from three age-matched groups (n = 86 each, mean age 55 y), including normal tissue donors of the Susan G. Komen for the Cure® Tissue Bank (KTB), and subjects in the Mayo Clinic Benign Breast Disease (BBD) Cohort who developed cancer (BBD cases) or did not develop cancer (BBD controls, median follow-up 14 y)...
November 22, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29158340/effects-of-black-raspberry-on-dibenzo-a-l-pyrene-diol-epoxide-induced-dna-adducts-mutagenesis-and-tumorigenesis-in-the-mouse-oral-cavity
#10
Kun-Ming Chen, Joseph B Guttenplan, Yuan-Wan Sun, Timothy Cooper, Nora Ae Shalaby, Wieslawa Kosinska, Gabrielle Benitez, Cesar Aliaga, Junjia Zhu, Jason Liao, Krishne Gowda, Shantu Amin, Gary Stoner, Karam El-Bayoumy
We previously showed that metabolic activation of the environmental and tobacco smoke constituent dibenzo[a,l]pyrene (DB[a,l]P) to its active fjord region diol epoxide (DB[a,l]PDE) is required to induce DNA damage, mutagenesis and squamous cell carcinoma (SCC) in the mouse oral cavity. In contrast to procarcinogens which were employed previously to induce SCC, DB[a,l]PDE does not require metabolic activation to exert its biological effects and thus, this study was initiated to examine, for the first time, whether black raspberry powder (BRB) inhibits post-metabolic processes such as DNA damage, mutagenesis and tumorigenesis...
November 20, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29138137/the-next-frontier-head-and-neck-cancer-immunoprevention
#11
J Silvio Gutkind, Jack D Bui
Restoring T cell-mediated antitumor immunity by targeting immune checkpoint inhibitors in head and neck squamous cell carcinoma (HNSCC) results in immunomodulation and durable remissions. However, the overall response rate to these immunotherapies in HNSCC is only approximately 20%. This raises the possibility that immunologic intervention earlier in the HNSCC continuum, such as in oral premalignant lesions (OPL) could elicit an increased therapeutic response. New experimental studies suggest that immune therapies can be used for HNSCC prevention rather than therapy...
November 14, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29133307/the-anti-inflammatory-effect-of-personalized-omega-3-fatty-acid-dosing-for-reducing-prostaglandin-e2-in-the-colonic-mucosa-is-attenuated-in-obesity
#12
Zora Djuric, D Kim Turgeon, Ananda Sen, Jianwei Ren, Kirk Herman, Devon Ramaswamy, Lili Zhao, Mack T Ruffin, Daniel P Normolle, William L Smith, Dean E Brenner
This clinical trial developed a personalized dosing model for reducing prostaglandin E2 (PGE2) in colonic mucosa using ω-3 fatty acid supplementation. The model utilized serum eicosapentaenoic acid (EPA, ω-3):arachidonic acid (AA, ω-6) ratios as biomarkers of colonic mucosal PGE2 concentration. Normal human volunteers were given low and high ω-3 fatty acid test doses for 2 weeks. This established a slope and intercept of the line for dose versus serum EPA:AA ratio in each individual. The slope and intercept was utilized to calculate a personalized target dose that was given for 12 weeks...
November 13, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29118162/does-mutated-k-ras-oncogene-attenuate-the-effect-of-sulindac-in-colon-cancer-chemoprevention
#13
Photini F S Rice, Kevin G Ehrichs, Mykella S Jones, Hwudarw Chen, Chiu-Hsieh Hsu, Edward R Abril, Raymond B Nagle, David G Besselsen, Jennifer K Barton, Natalia A Ignatenko
The non-steroidal anti-inflammatory drug (NSAID) Sulindac has been successfully used alone or in combination with other agents to suppress colon tumorigenesis in patients with genetic predisposition, and also showed its efficacy in prevention of sporadic colon adenomas. At the same time, some experimental and clinical reports suggest that a mutant K-RAS oncogene may negate Sulindac anti-tumor efficacy. To directly assess Sulindac activity at suppressing premalignant lesions carrying K-RAS mutation, we utilized a novel mouse model with an inducible colon-specific expression of the mutant K-ras oncogene (K-ras G12D)...
November 8, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29118161/dietary-nutrient-intake-ethnicity-and-epigenetic-silencing-of-lung-cancer-genes-detected-in-sputum-in-new-mexican-smokers
#14
Shuguang Leng, Maria A Picchi, Huining Kang, Guodong Wu, Piotr T Filipczak, Daniel E Juri, Xiequn Zhang, W James Gauderman, Frank D Gilliland, Steven A Belinsky
Lung cancer (LC) gene methylation detected in sputum assesses field cancerization and predicts LC incidence. Hispanic smokers have higher LC susceptibility compared to non-Hispanic Whites (NHW). We aimed to identify novel dietary nutrients affecting LC gene methylation and determine the degree of ethnic disparity in methylation explained by diet. Dietary intakes of 139 nutrients were assessed using a validated Harvard food frequency questionnaire in 327 Hispanics and 1502 NHWs from the Lovelace Smokers cohort (LSC)...
November 8, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29109117/chemoprevention-with-cyclooxygenase-and-epidermal-growth-factor-receptor-inhibitors-in-familial-adenomatous-polyposis-patients-mrna-signatures-of-duodenal-neoplasia
#15
Don A Delker, Austin C Wood, Angela K Snow, N Jewel Samadder, Wade S Samowitz, Kajsa E Affolter, Kenneth M Boucher, Lisa M Pappas, Inge J Stijleman, Priyanka Kanth, Kathryn R Byrne, Randall W Burt, Philip S Bernard, Deborah W Neklason
To identify gene expression biomarkers and pathways targeted by sulindac and erlotinib given in a chemoprevention trial with a significant decrease in duodenal polyp burden at 6 months (P < 0.001) in familial adenomatous polyposis (FAP) patients, we biopsied normal and polyp duodenal tissues from patients on drug versus placebo and analyzed the RNA expression. RNA sequencing was performed on biopsies from the duodenum of FAP patients obtained at baseline and 6-month endpoint endoscopy. Ten FAP patients on placebo and 10 on sulindac and erlotinib were selected for analysis...
November 6, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29101208/nf-kappab-at-the-crossroads-of-normal-mammary-gland-biology-and-the-pathogenesis-and-prevention-of-brca1-mutated-breast-cancer
#16
M A Christine Pratt, Andrea Sau, Miguel A Cabrita
Recent studies have shown that progesterone receptor (PR)-expressing cells respond to progesterone in part through the induction of the receptor activator of NF-kappaB ligand (RANKL) in which acts in a paracrine manner to induce expansion of a RANK-expressing luminal progenitor cell population. The RANK+ population in human breast tissue from carriers of BRCA1 mutations (BRCA1mut/+) as well as the luminal progenitor population in Brca1-deficient mouse mammary glands is abnormally amplified. Remarkably, mouse Brca1+/- and human BRCA1mut/+ progenitor cells are able to form colonies in vitro in the absence of progesterone demonstrating a hormone-independent proliferative capacity...
November 3, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29089332/chemopreventive-and-antitumor-efficacy-of-curcumin-in-a-spontaneously-developing-hen-ovarian-cancer-model
#17
Kazim Sahin, Cemal Orhan, Mehmet Tuzcu, Nurhan Sahin, Hakki Tastan, Ibrahim Hanifi Ozercan, Osman Guler, Nermin Kahraman, Omer Kucuk, Bulent Ozpolat
We investigated the effect of daily dietary curcumin intake on the development and progression of spontaneous ovarian cancer in a galline (hen) model, as the chicken is the only nonhuman animal in which ovarian cancer spontaneously develops with a high prevalence. At the end of 12 months, ovarian cancer had spontaneously developed in 39% (35/90) of control hens not fed curcumin (n = 90). In comparison, it spontaneously developed in 27% (24/90) and 17% (15/90) of hens given curcumin at 25.8 (n=90) and 53.0 mg/day (n=90), respectively (P = 0...
October 31, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29089331/prevalence-of-aflatoxin-associated-tp53r249s-mutation-in-hepatocellular-carcinoma-in-hispanics-in-south-texas
#18
Jingjing Jiao, Weibo Niu, Ying Wang, Keith A Baggerly, Yuanqing Ye, Xifeng Wu, Dewitt Davenport, Jose Luis Almeda, Monica M Betancourt-Garcia, R Armour Forse, Heather L Stevenson, Gordon P Watt, Joseph B McCormick, Susan P Fisher-Hoch, Laura Beretta
We aimed to determine whether aflatoxin dietary exposure plays a role in the high incidence of hepatocellular carcinoma (HCC) observed among Hispanics in South Texas.We measured TP53R249S somatic mutation, hallmark of aflatoxin etiology in HCC, using droplet digital PCR and restriction fragment length polymorphism. TP53R249S mutation was detected in 3 out of 41 HCC tumors from Hispanics in South Texas (7.3%). We also measured TP53R249S mutation in plasma cell free DNA (cfDNA) from 218 HCC patients and 96 Hispanic subjects with advanced fibrosis or cirrhosis, from South Texas...
October 31, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29074537/genetic-variants-in-metabolic-signaling-pathways-and-their-interaction-with-lifestyle-factors-on-breast-cancer-risk-a-random-survival-forest-analysis
#19
Su Yon Jung, Jeanette C Papp, Eric M Sobel, Zuo-Feng Zhang
Genetic variants in the insulin-like growth factor-I (IGF-I)/insulin resistance axis may interact with lifestyle factors, influencing postmenopausal breast cancer risk, but these interrelated pathways are not fully understood. In this study, we examined 54 single-nucleotide polymorphisms (SNPs) in genes related to IGF-I/insulin phenotypes and signaling pathways and lifestyle factors in relation to post-menopausal breast cancer, using data from 6,567 postmenopausal women in the Women's Health Initiative Harmonized and Imputed Genome-Wide Association Studies...
October 26, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29074536/a-novel-application-of-structural-equation-modeling-estimates-the-association-between-oxidative-stress-and-colorectal-adenoma
#20
Ronald C Eldridge, Michael Goodman, Roberd M Bostick, Veronika Fedirko, Myron Gross, Bharat Thyagarajan, W Dana Flanders
In vitro evidence implicates oxidative stress in many adverse health conditions, including colorectal neoplasia. In human studies, however, oxidative stress is measured by imperfect biomarkers, which are inconsistently associated with health outcomes. Structural equation modeling (SEM) offers one possible solution by modeling a latent (unobserved) construct from multiple biomarkers. Our goal was to investigate the association of a latent oxidative stress variable with colorectal adenoma. Using SEM, we analyzed pooled data from two cross-sectional studies of colorectal adenoma (n=526) that measured five plasma biomarkers of oxidative stress and inflammation that comprised the latent oxidative stress variable: F2-isoprostanes (FIP), fluorescent oxidation products (FOP), mitochondrial DNA (MtDNA) copy number, γ-tocopherol (Gtoc), and C-reactive protein (CRP)...
October 26, 2017: Cancer Prevention Research
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