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Breast cancer AND estrogen

Aarifa Nazmeen, Smarajit Maiti
N-ethyl-N-nitrosourea (ENU) is highly used in rodent models of tumerogenesis/carcinogenesis. Xenografting human-cancer tissues/cells with estradiol (E2) treatment is also used to generate rodent-models of gynaecological cancers. The altered metabolic-redox environment leading to establishment of pre-tumorigenesis condition and their mechanism are less studied. Here, female Wister rats were treated with these drugs at their pre-tumerogenic dosage (one group ENU single intra-peritoneal dose of 90 mg/kg b.w. and another group were implanted with human breast tumor (stage-IIIB) and fed with 2...
October 12, 2018: Molecular Biology Reports
Wen-Bo Zhou, Xin-Xin Zhang, Yun Cai, Wu Sun, Hao Li
Tamoxifen (TMX) is an antiestrogen drug that is used in the treatment and prevention of all stages of estrogen-dependent breast cancer. Adverse effects of TMX include hepatotoxicity. In this study, we investigated the therapeutic effects of osthole, isolated from medicinal plants especially Fructus Cnidii, on TMX-induced acute liver injury in mice. Mice were injected with osthole (100 mg/kg, ip) or vehicle, followed by TMX (90 mg/kg, ip) 24 h later. We showed that a single injection of TMX-induced liver injury and oxidative stress...
October 12, 2018: Acta Pharmacologica Sinica
Tatsuro Yamamoto, Chiyomi Sakamoto, Hiroaki Tachiwana, Mitsuru Kumabe, Toshiro Matsui, Tadatoshi Yamashita, Masatoshi Shinagawa, Koji Ochiai, Noriko Saitoh, Mitsuyoshi Nakao
Long-term estrogen deprivation (LTED) of an estrogen receptor (ER) α-positive breast cancer cell line recapitulates cancer cells that have acquired estrogen-independent cell proliferation and endocrine therapy resistance. Previously, we have shown that a cluster of non-coding RNAs, Eleanors (ESR1 locus enhancing and activating non-coding RNAs) formed RNA cloud and upregulated the ESR1 gene in the nuclei of LTED cells. Eleanors were inhibited by resveratrol through ER. Here we prepared another polyphenol, glyceollin I from stressed soybeans, and identified it as a major inhibitor of the Eleanor RNA cloud and ESR1 mRNA transcription...
October 12, 2018: Scientific Reports
Melissa A Maczis, Michael Maceyka, Michael R Waters, Jason Newton, Manjulata Singh, Madisyn F Rigsby, Tia H Turner, Mohammad A Alzubi, J Chuck Harrell, Sheldon Milstien, Sarah Spiegel
In breast cancer, 17β-estradiol (E2) plays critical roles mainly by binding to its canonical receptor, estrogen receptor (ER) α66, and eliciting genomic effects. E2 also triggers rapid, non-genomic responses. E2 activates sphingosine kinase 1 (SphK1), increasing sphingosine-1-phosphate (S1P) that binds to its receptors leading to important breast cancer signaling. However, the E2 receptor responsible for SphK1 activation has not yet been identified. Here we demonstrate in triple negative breast cancer cells, which lack the canonical ERα66 but express the novel splice variant ERα36, that ERα36 is the receptor responsible for E2-induced activation of SphK1 and formation and secretion of S1P and dihydro-S1P, the ligands for S1PRs...
October 12, 2018: Journal of Lipid Research
Sarah Croessmann, Luigi Formisano, Lisa Kinch, Paula I Gonzalez-Ericsson, Dhivya R Sudhan, Rebecca J Nagy, Aju Mathew, Eric H Bernicker, Massimo Cristofanilli, Jie He, Richard E Cutler, Alshad S Lalani, Vincent A Miller, Richard B Lanman, Nick Grishin, Carlos L Arteaga
PURPOSE: We examined the role of ERBB2 activating mutations in endocrine therapy resistance in estrogen receptor positive (ER+) breast cancer. Design ERBB2 mutation frequency was determined from large genomic databases. Isogenic knock-in ERBB2 mutations in ER+ MCF7 cells and xenografts were used to investigate estrogen-independent growth. Structural analysis was used to determine the molecular interaction of HER L755S with HER3. Small molecules and siRNAs were used to inhibit PI3Kα, TORC1 and HER3...
October 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Clinton Yam, Rashmi K Murthy, Gaiane M Rauch, James L Murray, Ronald S Walters, Vicente Valero, Abenaa M Brewster, Robert C Bast, Daniel J Booser, Sharon H Giordano, Francisco J Esteva, Wei Yang, Gabriel N Hortobagyi, Stacy L Moulder, Banu Arun
Background Imatinib mesylate is a potent inhibitor of the Abl, KIT and platelet derived growth factor (PDGF) receptor tyrosine kinases. Preclinical data suggest that combining imatinib mesylate with anti-estrogen therapy may be synergistic in hormone receptor-positive breast cancer. We report results of the first phase II trial evaluating the efficacy of the novel combination of imatinib mesylate and letrozole in the treatment of postmenopausal women with metastatic breast cancer. Patients and Methods 45 postmenopausal women with hormone receptor-positive metastatic breast cancer whose tumors demonstrated c-kit and/or PDGFR-β positivity were treated with imatinib mesylate 400 mg PO twice daily and letrozole 2...
October 11, 2018: Investigational New Drugs
Xiao Zhang, Jian Yang, Haoyang Cai, Yifeng Ye
Objective: To compare the prognosis of young breast cancer patients with the older ones. Patients and methods: Utilizing the Surveillance, Epidemiology, and End Results database, we identified 150,588 female breast cancer patients diagnosed during 2003-2014, including 6,668 patients younger than 35 years and 143,920 patients aged between 35 and 60 years. Kaplan- Meier analysis was performed to compare the prognosis of these two groups. Univariate and multivariate Cox proportional hazard models were utilized to identify independent prognostic factors and calculate the HR and 95% CI...
2018: Cancer Management and Research
Olfat G Shaker, Mahmoud A Senousy
BACKGROUND: Genetic susceptibility for breast cancer (BC) is still poorly understood. A combination of multiple low-penetrant alleles of cancer-related genes and gene-gene interactions (epistasis) contributes to BC risk. Genetic variants in receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), chitinase-3-like protein 1 (CHI3L1), and vitamin D receptor (VDR) genes are implicated in breast carcinogenesis; however, the influence of their epistatic effects on BC susceptibility has not yet been studied...
September 19, 2018: Clinical Breast Cancer
Hong Zhang, Shimin Pei, Bin Zhou, Huanan Wang, Hongchao Du, Di Zhang, Degui Lin
Canine mammary tumor (CMT) has always been an ideal animal model for human breast cancer (HBC) research, however, there is a lack of various established CMT cell lines corresponding to HBC cell lines. This study was designed to establish a new type of CMT cell line. The primary tumor, CMT-7364, was identified as the intraductal papillary carcinoma, and showed negative immunoreactivity to estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor-2 (HER-2) by immunohistochemistry (IHC) analysis...
October 2018: Tissue & Cell
Evelyn Jiagge, Aisha Souleiman Jibril, Melissa Davis, Carlos Murga-Zamalloa, Celina G Kleer, Kofi Gyan, George Divine, Mark Hoenerhoff, Jessica Bensenhave, Baffour Awuah, Joseph Oppong, Ernest Adjei, Barbara Salem, Kathy Toy, Sofia Merajver, Max Wicha, Lisa Newman
PURPOSE: Population-based incidence rates of breast cancers that are negative for estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2/ neu (triple-negative breast cancer [TNBC]) are higher among African American (AA) compared with white American (WA) women, and TNBC prevalence is elevated among selected populations of African patients. The extent to which TNBC risk is related to East African versus West African ancestry, and whether these associations extend to expression of other biomarkers, is uncertain...
October 2018: Journal of Global Oncology
Thu H Truong, Carol A Lange
Steroid hormone receptors (SR) have a multitude of functions in human biology and disease progression. The SR family of related ligand-activated transcription factors includes androgen (AR), estrogen (ER), glucocorticoid (GR), mineralocorticoid (MR), and progesterone receptors (PRs). Antiestrogen or ER-targeted therapies to block ER action remain the primary treatment for luminal breast cancers. Although this strategy is successful, approximately 40% of patients eventually relapse due to endocrine resistance...
October 10, 2018: Endocrinology
V L Maruthanila, R Elancheran, Nand Kishor Roy, Anupam Bhattacharya, Ajaikumar B Kunnumakkara, S Kabilan, Jibon Kotoky
BACKGROUND: Breast cancer is one of the most common cancers diagnosed among women. It is now recognized that two receptors mediate estrogen action and the presence of estrogen receptor alpha (ERα) correlates with better prognosis and the likelihood of response to hormonal therapy. ERα is an attractive target for the treatment of breast cancer. Most of the drug currently used for the breast cancer treatment that has numerous side effects and often unsuccessfully to remove the tumour completely...
October 8, 2018: Current Computer-aided Drug Design
Coby Basal, Emily Vertosick, Theresa A Gillis, Qing Li, Ting Bao, Andrew Vickers, Jun J Mao
PURPOSE: Arthralgia is common among women with breast cancer on adjuvant aromatase inhibitor (AI) therapy. Pain is associated with falls in the general population; however, little is known about the relationship between arthralgia and falls among AI users. Our objective was to determine whether joint pain severity and interference predict future falls. METHODS: We conducted a prospective cohort study of postmenopausal women with stage I-III estrogen receptor-positive breast cancer who were prescribed a third-generation AI...
October 10, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Arunkumar Karthikayan, Sathasivam Sureshkumar, Dharanipragada Kadambari, Chellappa Vijayakumar
OBJECTIVE: This study was conducted to assess the serum 25-hydroxy (OH) vitamin D levels in patients with breast cancer compared to healthy controls and to identify its association with aggressive breast cancer phenotypes. MATERIALS AND METHODS: Serum 25-OH vitamin D levels of 78 breast cancer patients and 78 matched healthy controls were estimated using ELISA. The cases and controls were matched with respect to age, menopausal status, parity, weight, height and co-morbidities...
August 2018: Archives of Endocrinology and Metabolism
Joseph H Huntley, Lee A Richter, Amanda L Blackford, Oluseyi Aliu, Craig E Pollack
OBJECTIVE: To evaluate how often women with a history of breast cancer who are taking hormone therapy (HT) filled prescriptions for topical estrogens and whether this frequency varied over time and by type of HT used. METHODS: We performed a retrospective cohort study using medical and outpatient drug claims from a large commercial claims database for the years 2010-2015. Women younger than age 65 years taking HT for breast cancer were classified as users of 1) tamoxifen only, 2) aromatase inhibitor(s) only, or 3) any other or multiple HTs...
October 5, 2018: Obstetrics and Gynecology
Ang Gao, Tonghua Sun, Gui Ma, Jiangran Cao, Qingxia Hu, Ling Chen, Yanxin Wang, Qianying Wang, Jiafu Sun, Rui Wu, Qiao Wu, Jiaxi Zhou, Lin Liu, Junjie Hu, Jin-Tang Dong, Zhengmao Zhu
The elucidation of molecular events that confer tamoxifen resistance to estrogen receptor α (ER) positive breast cancer is of major scientific and therapeutic importance. Here, we report that LEM4 overexpression renders ER+ breast cancer cells resistant to tamoxifen by activating the cyclin D-CDK4/6 axis and the ERα signaling. We show that LEM4 overexpression accelerates tumor growth. Interaction with LEM4 stabilizes CDK4 and Rb, promotes Rb phosphorylation and the G1/S phase transition. LEM4 depletion or combined tamoxifen and PD0332991 treatment significantly reverses tamoxifen resistance...
October 9, 2018: Nature Communications
Shuning Wang, Xiaoju Li, Wangqian Zhang, Yuan Gao, Kuo Zhang, Qiang Hao, Weina Li, Zhaowei Wang, Meng Li, Wei Zhang, Yingqi Zhang, Cun Zhang
Estrogen receptor alpha (ERα), which has been detected in over 70% of breast cancer cases, is a driving factor for breast cancer growth. For investigating the underlying genes and networks regulated by ERα in breast cancer, RNA-seq was performed between ERα transgenic MDA-MB-231 cells and wild type MDA-MB-231 cells. A total of 267 differentially expressed genes (DEGs) were identified. Then bioinformatics analyses were performed to illustrate the mechanism of ERα. Besides, by comparison of RNA-seq data obtained from MDA-MB-231 cells and microarray dataset obtained from estrogen (E2) stimulated MCF-7 cells, an overlap of 126 DEGs was screened...
October 5, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Gaetano Verde, Lara I De Llobet, Roni H G Wright, Javier Quilez, Sandra Peiró, François Le Dily, Miguel Beato
Breast cancer prognosis and response to endocrine therapy strongly depends on the expression of the estrogen and progesterone receptors (ER and PR, respectively). Although much is known about ERα gene ( ESR1 ) regulation after hormonal stimulation, how it is regulated in hormone-free condition is not fully understood. We used ER-/PR-positive breast cancer cells to investigate the role of PR in ESR1 regulation in the absence of hormones. We show that PR binds to the low-methylated ESR1 promoter and maintains both gene expression and DNA methylation of the ESR1 locus in hormone-deprived breast cancer cells...
October 5, 2018: Cancers
Matteo Lambertini, Giulia Viglietti, Evandro de Azambuja
PURPOSE OF THE REVIEW: This manuscript aims at providing an updated overview on the role of adding ovarian function suppression to tamoxifen or an aromatase inhibitor as adjuvant endocrine therapy in premenopausal women with estrogen receptor (ER)-positive early breast cancer. RECENT FINDINGS: Until recently, tamoxifen alone was the only standard adjuvant treatment option for premenopausal women with ER-positive disease. However, recent important evidence has contributed to significantly modify the endocrine treatment landscape in this setting...
October 5, 2018: Current Opinion in Oncology
Patricia A Cronin, Anya Romanoff, Emily C Zabor, Michelle Stempel, Anne Eaton, Lillian M Smyth, Alice Y Ho, Monica Morrow, Mahmoud El-Tamer, Mary L Gemignani
BACKGROUND: Low incidence of breast cancer in men (BCM) (< 1% of all breast cancers) has led to a paucity of outcome data. This study evaluated the impact of age on BCM outcomes. METHODS: For this study, BCM patients treated between 2000 and 2011 were stratified by age (≤ 65 or > 65 years). Kaplan-Meier methods were used to compare overall survival (OS) and breast cancer-specific survival (BCSS). Competing-risk methods analyzed time to second primary cancers (SPCs), with any-cause death treated as a competing risk...
October 8, 2018: Annals of Surgical Oncology
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