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Cancer Prevention Research

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https://www.readbyqxmd.com/read/28325828/the-prolyl-isomerase-pin1-is-a-novel-target-of-6-7-4-trihydroxyisoflavone-for-suppressing-esophageal-cancer-growth
#1
Tae Gyu Lim, Sung-Young Lee, Zhaoheng Duan, Mee-Hyun Lee, Hanyong Chen, Fangfang Liu, Kangdong Liu, Sung Keun Jung, Dong Joon Kim, Ann M Bode, Ki Won Lee, Zigang Dong
Intake of soy isoflavones is inversely associated with the risk of esophageal cancer. Numerous experimental results have supported the anti-cancer activity of soy isoflavones. The current study aimed to determine the anti-esophageal cancer activity of 6,7,4'-trihydroxyisoflavone (6,7,4'-THIF), a major metabolite of daidzein, which is readily metabolized in the human body. Notably, 6,7,4'-THIF inhibited proliferation and increased apoptosis of esophageal cancer cells. Based on a virtual screening analysis, Pin1 was identified as a target protein of 6,7,4'-THIF...
March 21, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28325827/sessile-serrated-polyps-and-colon-cancer-prevention
#2
Shahrooz Rashtak, Rafaela Rego, Seth R Sweetser, Frank A Sinicrope
Evidence suggests that up to one fifth of colorectal carcinomas (CRC) develop from serrated polyps, named for their pattern of colonic crypts, and include the sessile serrated adenoma/polyp (SSA/P) that has malignant potential. SSA/Ps are typically located in the proximal colon and have molecular features of hypermethylation of CpG islands in gene promoters and activating point mutations (V600E) in the BRAF oncogene. Both of these features are seen in sporadic CRCs with microsatellite instability (MSI) which is potentially consistent with an origin of these cancers from precursor SSA/Ps...
March 21, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28325826/a-phase-ii-randomized-double-blind-presurgical-trial-of-polyphenon-e-in-bladder-cancer-patients-to-evaluate-pharmacodynamics-and-bladder-tissue-biomarkers
#3
Jason R Gee, Daniel R Saltzstein, KyungMann Kim, Jill M Kolesar, Wei Huang, Thomas C Havighurst, Barbara W Wollmer, Jeanne Stublaski, Tracy Downs, Hasan Mukhtar, Margaret House, Howard L Parnes, Howard H Bailey
We performed a phase 2 pharmacodynamic, prevention trial of Polyphenon E® (a green tea polyphenol formulation primarily consisting of epigallocatechin gallate (EGCG)) in patients prior to bladder cancer surgery. Patients with a bladder tumor were randomized to receive Polyphenon E® containing either 800 or 1200 mg of EGCG or placebo for 14 to 28 days prior to TURBT or cystectomy. The primary objective was to compare the post-intervention EGCG tissue levels in patients receiving Polyphenon E® as compared to placebo...
March 21, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28292742/fatty-acid-synthesis-intermediates-represent-novel-noninvasive-biomarkers-of-prostate-cancer-chemoprevention-by-phenethyl-isothiocyanate
#4
Krishna B Singh, Shivendra V Singh
Increased de novo synthesis of fatty acids is a distinctive feature of prostate cancer, which continues to be a leading cause of cancer-related deaths among American men. Therefore, inhibition of de novo fatty acid synthesis represents an attractive strategy for chemoprevention of prostate cancer. We have shown previously that dietary feeding of phenethyl isothiocyanate (PEITC), a phytochemical derived from edible cruciferous vegetables such as watercress, inhibits incidence and burden of poorly-differentiated prostate cancer in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model...
March 14, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28283467/responsiveness-of-brca1-and-trp53-deficiency-induced-mammary-preneoplasia-to-selective-estrogen-modulators-versus-an-aromatase-inhibitor-in-mus-musculus
#5
Sahar J Alothman, Weisheng Wang, David S Goerlitz, Md Islam, Xiaogang Zhong, Archana Kishore, Redha I Azhar, Bhaskar V Kallakury, Priscilla A Furth
An intervention study initiated at age 4 months compared the impact of tamoxifen (25 mg), raloxifene (22.5 mg), and letrozole (2.5 mg) administered by 60-day release subcutaneous pellet on mammary preneoplasia prevalence at age 6 months in conditional genetically engineered mouse models with different Breast cancer 1 (Brca1) gene dosages targeted to mammary epithelial cells and germline Tumor protein P53 (Trp53) haploinsufficiency (10-16/cohort). The proportion of unexposed control mice demonstrating mammary preneoplasia at age 6 months was highest in Brca1(fl11/fl11/Cre/p53-/+) (54%) mice followed by Brca1(WT/fl11/Cre/p53-/+) mice (30%)...
March 10, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28274936/no-decreased-risk-of-gastrointestinal-cancers-in-users-of-metformin-in-the-netherlands-a-time-varying-analysis-of-metformin-exposure
#6
Roy G de Jong, Andrea M Burden, Sander de Kort, Myrthe van Herk-Sukel, Pauline A Vissers, Paddy K Janssen, Harm R Haak, Ad A M Masclee, Frank de Vries, Maryska L Janssen-Heijnen
Previous studies on metformin use and gastrointestinal (GI) cancer risk have yielded inconclusive results on metformin's chemoprotective effects. We aimed to evaluate GI cancer risk in users of metformin in The Netherlands using a time-varying approach in a large population-based database. A cohort study was performed using the NCR-PHARMO database. Patients using ≥1 non-insulin anti-diabetic drug (NIAD) during 1998-2011 were included (N=57,621). Exposure to NIADs was modelled time-varyingly. Cox regression analysis estimated hazard ratios (HRs) of GI cancers in current metformin users versus current users of other NIADs...
March 8, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28274935/crown-like-structures-in-breast-adipose-tissue-from-normal-weight-women-significant-impact
#7
Nathan A Berger
Crown-like structures (CLS), composed of macrophages surrounding dead or dying adipocytes, are a histologic hallmark of the pro-inflammatory process by which adipose tissue contributes to the increased risk and worse prognosis of breast cancer in obese, post menopausal patients. In this issue of Cancer Prevention Research, Iyengar et al report the intriguing finding that CLS, can be identified in a significant proportion of normal BMI women undergoing mastectomy for breast cancer risk reduction or therapy (1)...
March 8, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28270386/metabolic-obesity-adipose-inflammation-and-elevated-breast-aromatase-in-women-with-normal-body-mass-index
#8
Neil M Iyengar, Kristy A Brown, Xi Kathy Zhou, Ayca Gucalp, Kotha Subbaramaiah, Dilip D Giri, Heba Zahid, Priya Bhardwaj, Nils K Wendel, Domenick J Falcone, Hanhan Wang, Samantha Williams, Michael Pollak, Monica Morrow, Clifford A Hudis, Andrew J Dannenberg
Obesity is associated with breast white adipose tissue (WAT) inflammation, elevated levels of the estrogen biosynthetic enzyme, aromatase, and systemic changes that have been linked to the pathogenesis of breast cancer. Here, we determined whether metabolic obesity, including changes in breast biology and systemic effects, occurs in a subset of women with normal body mass index (BMI). Breast WAT and fasting blood were collected from 72 women with normal BMI (<25 kg/m(2)) undergoing mastectomy for breast cancer risk reduction or treatment...
March 7, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28264838/loss-of-brca1-in-the-cells-of-origin-of-ovarian-cancer-induces-glycolysis-a-window-of-opportunity-for-ovarian-cancer-chemoprevention
#9
Tatsuyuki Chiyoda, Peter C Hart, Mark A Eckert, Stephanie M McGregor, Ricardo R Lastra, Ryuji Hamamoto, Yusuke Nakamura, S Diane Yamada, Olufunmilayo I Olopade, Ernst Lengyel, Iris L Romero
Mutations in the breast cancer susceptibility gene 1 (BRCA1) are associated with an increased risk of developing epithelial ovarian cancer. However, beyond the role of BRCA1 in DNA repair, little is known about other mechanisms by which BRCA1 impairment promotes carcinogenesis. Given that altered metabolism is now recognized as important in the initiation and progression of cancer, we asked whether loss of BRCA1 changes metabolism in the cells of origin of ovarian cancer. The findings show that silencing BRCA1 in ovarian surface epithelial and fallopian tube cells increased glycolysis...
March 6, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28246081/the-4ps-of-breast-cancer-chemoprevention-putting-proven-principles-into-practice
#10
EDITORIAL
V Craig Jordan
The pioneering Royal Marsden Tamoxifen Prevention Trial recruited 2,471 eligible high-risk women to be randomized to either placebo or tamoxifen (20 mg daily) for 8 years. Breast cancer incidence was evaluated at a median of 18.4 years from the start of the study. There was a 32% reduction in estrogen/progesterone receptor (ER/PR)-positive breast cancers after tamoxifen treatment finished. Translational research, to study "the good, the bad, and the ugly of tamoxifen" in the 1980s, subsequently ensured women's safety from possible increases in osteoperosis, coronary heart disease, and endometrial cancer...
February 28, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28154203/metformin-accumulation-correlates-with-organic-cation-transporter-2-protein-expression-and-predicts-mammary-tumor-regression-in-vivo
#11
L Allyson Checkley, Michael C Rudolph, Elizabeth A Wellberg, Erin D Giles, Reema S Wahdan-Alaswad, Julie A Houck, Susan M Edgerton, Ann D Thor, Pepper Schedin, Steven M Anderson, Paul S MacLean
Several epidemiologic studies have associated metformin treatment with a reduction in breast cancer incidence in prediabetic and type II diabetic populations. Uncertainty exists regarding which patient populations and/or tumor subtypes will benefit from metformin treatment, and most preclinical in vivo studies have given little attention to the cellular pharmacology of intratumoral metformin uptake. Epidemiologic reports consistently link western-style high fat diets (HFD), which drive overweight and obesity, with increased risk of breast cancer...
February 2, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28100469/immunohistochemical-phenotype-of-breast-cancer-during-25-year-follow-up-of-the-royal-marsden-tamoxifen-prevention-trial
#12
Simone I Detre, Susan Ashley, Kabir Mohammed, Ian E Smith, Trevor J Powles, Mitch Dowsett
The randomized, double-blinded Royal Marsden Tamoxifen Breast Cancer Prevention Trial in healthy high-risk women started in 1986 and is still blinded. Eligible participants (n = 2,471) were randomly assigned to tamoxifen (20 mg/d) or placebo for 8 years. Analysis in 2006 showed a 30% risk reduction of estrogen receptor (ER)-positive invasive breast cancer mostly in the posttreatment period. Biomarker analysis in this population may identify any subgroup-specific preventive effects tamoxifen. After a median follow-up of 18...
January 18, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28096237/the-human-microbiome-and-cancer
#13
REVIEW
Seesandra V Rajagopala, Sanjay Vashee, Lauren M Oldfield, Yo Suzuki, J Craig Venter, Amalio Telenti, Karen E Nelson
Recent scientific advances have significantly contributed to our understanding of the complex connection between the microbiome and cancer. Our bodies are continuously exposed to microbial cells, both resident and transient, as well as their byproducts, including toxic metabolites. Circulation of toxic metabolites may contribute to cancer onset or progression at locations distant from where a particular microbe resides. Moreover, microbes may migrate to other locations in the human body and become associated with tumor development...
January 17, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28154202/aspirin-induced-chemoprevention-and-response-kinetics-are-enhanced-by-pik3ca-mutations-in-colorectal-cancer-cells
#14
Timothy J Zumwalt, Dominik Wodarz, Natalia L Komarova, Shusuke Toden, Jacob Turner, Jacob Cardenas, John Burn, Andrew T Chan, C Richard Boland, Ajay Goel
This study was designed to determine how aspirin influences the growth kinetics and characteristics of cultured colorectal cancer cells that harbor a variety of different mutational backgrounds, including PIK3CA- and KRAS-activating mutations, and the presence or absence of microsatellite instability. Colorectal cancer cell lines (HCT116, HCT116 + Chr3/5, RKO, SW480, HCT15, CACO2, HT29, and SW48) were treated with pharmacologically relevant doses of aspirin (0.5-10 mmol/L) and evaluated for proliferation and cell-cycle distribution...
March 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28096238/activation-of-trpa1-channel-by-antibacterial-agent-triclosan-induces-vegf-secretion-in-human-prostate-cancer-stromal-cells
#15
Sandra Derouiche, Pascal Mariot, Marine Warnier, Eric Vancauwenberghe, Gabriel Bidaux, Pierre Gosset, Brigitte Mauroy, Jean-Louis Bonnal, Christian Slomianny, Philippe Delcourt, Etienne Dewailly, Natalia Prevarskaya, Morad Roudbaraki
Accruing evidence indicates that exposure to environmental compounds may adversely affect human health and promote carcinogenesis. Triclosan (TCS), an antimicrobial agent widely used as a preservative in personal care products, has been shown to act as an endocrine disruptor in hormone-dependent tissues. Here, we demonstrate a new molecular mechanism by which TCS stimulates the secretion by human prostate cancer stromal cells of vascular endothelial growth factor (VEGF), a factor known to promote tumor growth...
March 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28096236/inhibitory-effects-of-%C3%AE-and-%C3%AE-tocopherols-on-estrogen-stimulated-breast-cancer-in-vitro-and-in-vivo
#16
Min Ji Bak, Soumyasri Das Gupta, Joseph Wahler, Hong Jin Lee, Xiaowei Li, Mao-Jung Lee, Chung S Yang, Nanjoo Suh
Estrogens have been implicated as complete carcinogens for breast and other tissues through mechanisms involving increased cell proliferation, oxidative stress, and DNA damage. Because of their potent antioxidant activity and other effects, tocopherols have been shown to exert antitumor activities in various cancers. However, limited information is available on the effect of different forms of tocopherols in estrogen-mediated breast cancer. To address this, we examined the effects of α-, γ-, and δ-tocopherols as well as a natural γ-tocopherol-rich mixture of tocopherols, γ-TmT, on estrogen-stimulated MCF-7 cells in vitro and in vivo For the in vivo studies, MCF-7 cells were injected into the mammary fat pad of immunodeficient mice previously implanted with estrogen pellets...
March 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28052934/fixed-dose-combinations-of-pioglitazone-and-metformin-for-lung-cancer-prevention
#17
Donna E Seabloom, Arthur R Galbraith, Anna M Haynes, Jennifer D Antonides, Beverly R Wuertz, Wendy A Miller, Kimberly A Miller, Vernon E Steele, Mark Steven Miller, Margie L Clapper, M Gerard O'Sullivan, Frank G Ondrey
Combination treatment with pioglitazone and metformin is utilized clinically in the treatment of type II diabetes. Treatment with this drug combination reduced the development of aerodigestive cancers in this patient population. Our goal is to expand this treatment into clinical lung cancer chemoprevention. We hypothesized that dietary delivery of metformin/pioglitazone would prevent lung adenoma formation in A/J mice in a benzo[a]pyrene (B[a]P)-induced carcinogenesis model while modulating chemoprevention and anti-inflammatory biomarkers in residual adenomas...
February 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/27998883/unlocking-aspirin-s-chemopreventive-activity-role-of-irreversibly-inhibiting-platelet-cyclooxygenase-1
#18
Lenard M Lichtenberger, Dexing Fang, Roger J Bick, Brian J Poindexter, Tri Phan, Angela L Bergeron, Subhashree Pradhan, Elizabeth J Dial, K Vinod Vijayan
The mechanism by which aspirin consumption is linked to significant reductions in the incidence of multiple forms of cancer and metastatic spread to distant tissues, resulting in increased cancer patient survival is not well understood. In this study, using colon cancer as an example, we provide both in vitro (cell culture) and in vivo (chemically induced mouse model of colon cancer) evidence that this profound antineoplastic action may be associated with aspirin's ability to irreversibly inhibit COX-1-mediated platelet activation, thereby blocking platelet-cancer cell interactions, which promote cancer cell number and invasive potential...
February 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/27965287/clinical-challenges-associated-with-universal-screening-for-lynch-syndrome-associated-endometrial-cancer
#19
Amanda S Bruegl, Kari L Ring, Molly Daniels, Bryan M Fellman, Diana L Urbauer, Russell R Broaddus
Universal testing for Lynch syndrome is now a routine component of the diagnostic work-up of endometrial cancer patients. The purpose of this study was to identify prospectively the barriers to universal screening based on a tissue testing approach [microsatellite instability (MSI) analysis, IHC for DNA mismatch repair proteins, and MLH1 methylation analysis]. Endometrial carcinoma patients (n = 213) prospectively underwent microsatellite instability and IHC testing for expression of DNA mismatch repair (MMR) proteins...
February 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/27965286/identifying-and-creating-the-next-generation-of-community-based-cancer-prevention-studies-summary-of-a-national-cancer-institute-think-tank
#20
REVIEW
Worta McCaskill-Stevens, Deborah C Pearson, Barnett S Kramer, Leslie G Ford, Scott M Lippman
In late 2015, the NCI Division of Cancer Prevention convened cancer prevention research experts and stakeholders to discuss the current state of cancer prevention research, identify key prevention research priorities for the NCI, and identify studies that could be conducted within the NCI Community Oncology Research Program. Goals included identifying cancer prevention research opportunities offering the highest return on investment, exploring the concept of precision prevention and what is needed to advance this area of research, and identifying possible targets for prevention...
February 2017: Cancer Prevention Research
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