"Obesity-Associated" Breast Cancer in Lean Women: Metabolism and Inflammation as Critical Modifiers of Risk
Why is obesity only weakly associated with certain "obesity-driven" cancers? Recent population studies identify cohorts of high body mass index (BMI) subjects with unexpectedly reduced risk for breast and colon cancer, and normal BMI subjects with unexpectedly elevated risk for breast cancer, provoking hard thinking about cellular and molecular mechanisms that most strongly couple obesity to cancer occurrence or progression. Emerging work suggests that abnormal metabolism and its associated chronic inflammation make the difference. Type II diabetes, for example, is a chronic inflammatory disease with specific imbalances in...
Source: Cancer Prevention Research - May 1, 2017 Category: Cancer & Oncology Authors: Denis, G. V., Palmer, J. R. Tags: Editorial Source Type: research
Loss of BRCA1 in the Cells of Origin of Ovarian Cancer Induces Glycolysis: A Window of Opportunity for Ovarian Cancer Chemoprevention
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 the 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. Furthermore, when these cells wer...
Source: Cancer Prevention Research - April 2, 2017 Category: Cancer & Oncology Authors: Chiyoda, T., Hart, P. C., Eckert, M. A., McGregor, S. M., Lastra, R. R., Hamamoto, R., Nakamura, Y., Yamada, S. D., Olopade, O. I., Lengyel, E., Romero, I. L. Tags: Research Articles Source Type: research
Responsiveness of Brca1 and Trp53 Deficiency-Induced Mammary Preneoplasia to Selective Estrogen Modulators versus an Aromatase Inhibitor in Mus musculus
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 Brca1fl11/fl11/Cre/p53–/+ (54%) mice followed by Brca1WT/fl1...
Source: Cancer Prevention Research - April 2, 2017 Category: Cancer & Oncology Authors: Alothman, S. J., Wang, W., Goerlitz, D. S., Islam, M., Zhong, X., Kishore, A., Azhar, R. I., Kallakury, B. V., Furth, P. A. Tags: Research Articles Source Type: research
Metabolic Obesity, Adipose Inflammation and Elevated Breast Aromatase in Women with Normal Body Mass Index
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/m2) undergoing mastectomy for breast cancer risk reduction or treatment. WAT inflammation was defined by the presence of crown-like structures of the breast ...
Source: Cancer Prevention Research - April 2, 2017 Category: Cancer & Oncology Authors: Iyengar, N. M., Brown, K. A., Zhou, X. K., Gucalp, A., Subbaramaiah, K., Giri, D. D., Zahid, H., Bhardwaj, P., Wendel, N. K., Falcone, D. J., Wang, H., Williams, S., Pollak, M., Morrow, M., Hudis, C. A., Dannenberg, A. J. Tags: Research Articles Source Type: research
The Human Microbiome and Cancer
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. Several case–control metagenomics studies suggest that dysbiosis in the commensal micr...
Source: Cancer Prevention Research - April 2, 2017 Category: Cancer & Oncology Authors: Rajagopala, S. V., Vashee, S., Oldfield, L. M., Suzuki, Y., Venter, J. C., Telenti, A., Nelson, K. E. Tags: Minireview Source Type: research
Crown-like Structures in Breast Adipose Tissue from Normal Weight Women: Important Impact
Crown-like structures (CLS), composed of macrophages surrounding dead or dying adipocytes, are a histologic hallmark of the proinflammatory process by which adipose tissue contributes to the increased risk and worse prognosis of breast cancer in obese, postmenopausal patients. In this issue of Cancer Prevention Research, Iyengar and colleagues 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. This surprising observation suggests that some normal weight women may have similar mechanisms driving initiatio...
Source: Cancer Prevention Research - April 2, 2017 Category: Cancer & Oncology Authors: Berger, N. A. Tags: Editorial Source Type: research
The 4Ps of Breast Cancer Chemoprevention: Putting Proven Principles into Practice
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. Other tamoxi...
Source: Cancer Prevention Research - April 2, 2017 Category: Cancer & Oncology Authors: Jordan, V. C. Tags: Editorial Source Type: research
Aspirin-Induced Chemoprevention and Response Kinetics Are Enhanced by PIK3CA Mutations in Colorectal Cancer Cells
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. These parameters were fitted to a mathematical model to quantify the effects and unde...
Source: Cancer Prevention Research - March 1, 2017 Category: Cancer & Oncology Authors: Zumwalt, T. J., Wodarz, D., Komarova, N. L., Toden, S., Turner, J., Cardenas, J., Burn, J., Chan, A. T., Boland, C. R., Goel, A. Tags: Research Articles Source Type: research
Metformin Accumulation Correlates with Organic Cation Transporter 2 Protein Expression and Predicts Mammary Tumor Regression In Vivo
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. We used a rat model of HFD-induced overweight and mammary carcinogenesis to d...
Source: Cancer Prevention Research - March 1, 2017 Category: Cancer & Oncology Authors: Checkley, L. A., Rudolph, M. C., Wellberg, E. A., Giles, E. D., Wahdan-Alaswad, R. S., Houck, J. A., Edgerton, S. M., Thor, A. D., Schedin, P., Anderson, S. M., MacLean, P. S. Tags: Research Articles Source Type: research
Inhibitory Effects of {gamma}- and {delta}-Tocopherols on Estrogen-Stimulated Breast Cancer In Vitro and In Vivo
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-, -, and -tocopherols as well as a natural -tocopherol–rich mixture of tocopherols, -TmT, on estrogen-stimulated MCF-7 cells in...
Source: Cancer Prevention Research - March 1, 2017 Category: Cancer & Oncology Authors: Bak, M. J., Das Gupta, S., Wahler, J., Lee, H. J., Li, X., Lee, M.-J., Yang, C. S., Suh, N. Tags: Research Articles Source Type: research
Activation of TRPA1 Channel by Antibacterial Agent Triclosan Induces VEGF Secretion in Human Prostate Cancer Stromal Cells
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. This mechanism involves an increase in intracellular calcium levels due to the direct activation of a membrane ion...
Source: Cancer Prevention Research - March 1, 2017 Category: Cancer & Oncology Authors: Derouiche, S., Mariot, P., Warnier, M., Vancauwenberghe, E., Bidaux, G., Gosset, P., Mauroy, B., Bonnal, J.-L., Slomianny, C., Delcourt, P., Dewailly, E., Prevarskaya, N., Roudbaraki, M. Tags: Research Articles Source Type: research
Immunohistochemical Phenotype of Breast Cancer during 25-Year Follow-up of the Royal Marsden Tamoxifen Prevention Trial
In conclusion, the preventive effects of tamoxifen result in reduced ER-positive but not ER-negative tumors and reduced ER expression in the ER-positive cases largely confined to the posttreatment period. Overall reductions in PgR expression are explained by lower frequency of ER-positive cases. Impact on Ki67, HER2, and EGFR was modest. Cancer Prev Res; 10(3); 171–6. ©2017 AACR. (Source: Cancer Prevention Research)
Source: Cancer Prevention Research - March 1, 2017 Category: Cancer & Oncology Authors: Detre, S. I., Ashley, S., Mohammed, K., Smith, I. E., Powles, T. J., Dowsett, M. Tags: Research Articles Source Type: research
{beta}-Carotene 9',10' Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model
This study suggests that genetic variables impacting carotenoid metabolism and accumulation can impact anticancer activity and that future efforts devoted to understanding the interface between tomato carotenoid intake, host genetics, and metabolism will be necessary to clearly elucidate their interactive roles in human prostate carcinogenesis. Cancer Prev Res; 10(2); 161–9. ©2016 AACR. (Source: Cancer Prevention Research)
Source: Cancer Prevention Research - February 1, 2017 Category: Cancer & Oncology Authors: Tan, H.-L., Thomas-Ahner, J. M., Moran, N. E., Cooperstone, J. L., Erdman, J. W., Young, G. S., Clinton, S. K. Tags: Research Articles Source Type: research
Xanthohumol Prevents DNA Damage by Dietary Carcinogens: Results of a Human Intervention Trial
Xanthohumol (XN) is a hop flavonoid contained in beers and soft drinks. In vitro and animal studies indicated that XN has DNA and cancer protective properties. To find out if it causes DNA protective effects in humans, an intervention trial was conducted in which the participants (n = 22) consumed a XN containing drink (12 mg XN/P/d). We monitored prevention of DNA damage induced by representatives of major groups of dietary carcinogens [i.e., nitrosodimethylamine (NDMA) benzo(a)pyrene (B(a)P) and the heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)]. Lymphocytes were collected before, during, and a...
Source: Cancer Prevention Research - February 1, 2017 Category: Cancer & Oncology Authors: Pichler, C., Ferk, F., Al-Serori, H., Huber, W., Jäger, W., Waldherr, M., Misik, M., Kundi, M., Nersesyan, A., Herbacek, I., Knasmueller, S. Tags: Research Articles Source Type: research
Unlocking Aspirin's Chemopreventive Activity: Role of Irreversibly Inhibiting Platelet Cyclooxygenase-1
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. This process may be driven by platelet-induced epithelial–mesenchymal transition (EMT), as assessed using confocal microscopy, based upon changes in cell morphology, growth characteristics and fibronect...
Source: Cancer Prevention Research - February 1, 2017 Category: Cancer & Oncology Authors: Lichtenberger, L. M., Fang, D., Bick, R. J., Poindexter, B. J., Phan, T., Bergeron, A. L., Pradhan, S., Dial, E. J., Vijayan, K. V. Tags: Research Articles Source Type: research
