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Hormones & Cancer

Jian Wang, Huaqiang Liu, Lin Tian, Fachen Wang, Liangbo Han, Wei Zhang, Yun-An Bai
The microRNAs (miRNAs) have been suggested as a tumor suppressor in recent years. miR-15b was reported to exert an anti-oncogenic role in the proliferation, migration, and invasion of diverse tumor cells. However, the mechanisms underlying miR-15b-mediated biology of glioblastoma are still unclear. In the present study, the expression of miR-15b was down-regulated in glioblastoma tumor tissues and U87 and U251 cells, but insulin-like growth factor receptor 1 (IGF1R) expression became up-regulated in these tumor tissues and cells (all p < 0...
November 28, 2016: Hormones & Cancer
Shawna B Matthews, Carol A Sartorius
The vast majority of breast cancers are positive for estrogen receptor (ER) and depend on estrogens for growth. These tumors are treated with a variety of ER-targeted endocrine therapies, although eventual resistance remains a major clinical problem. Other steroid hormone receptors such as progesterone receptor (PR) and androgen receptor (AR) are emerging as additional prospective targets in breast cancer. The fundamental mechanism of action of these steroid receptors in gene regulation has been defined mainly by several breast cancer cell lines that were established in the late 1970s...
October 28, 2016: Hormones & Cancer
Stephania Casco, Elena Soto-Vega
Long-term childhood cancer survivors are at great risk of developing late adverse effects after treatment, such as, reduced growth, obesity, decreased fertility, high blood pressure, cardiovascular diseases, impaired glucose, another form of cancer, among others organ dysfunctions, some of them are part of the metabolic syndrome. Metabolic syndrome and cancer connection is still not entirely understood, but there are some notions about it. Metabolic alterations produced during childhood cancer are more likely determined by treatments like radiotherapy, chemotherapy, glucocorticoids therapy, and surgery...
December 2016: Hormones & Cancer
Hannah Oh, Zeina G Khodr, Mark E Sherman, Maya Palakal, Ruth M Pfeiffer, Laura Linville, Berta M Geller, Pamela M Vacek, Donald L Weaver, Rachael E Chicoine, Roni T Falk, Hisani N Horne, Daphne Papathomas, Deesha A Patel, Jackie Xiang, Xia Xu, Timothy Veenstra, Stephen M Hewitt, John A Shepherd, Louise A Brinton, Jonine D Figueroa, Gretchen L Gierach
Higher levels of circulating estrogens and estrogen metabolites (EMs) have been associated with higher breast cancer risk. In breast tissues, reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have also been linked to elevated breast cancer risk. However, it is unknown whether reduced TDLU involution mediates the risk associated with circulating EMs. In a cross-sectional analysis of 94 premenopausal and 92 postmenopausal women referred for clinical breast biopsy at an academic facility in Vermont, we examined the associations of 15 EMs, quantified using liquid chromatography-tandem mass spectrometry, with the number of TDLUs and acini count/TDLU using zero-inflated Poisson regression with a robust variance estimator and ordinal logistic regression models, respectively...
December 2016: Hormones & Cancer
Matthias Kroiss, Silviu Sbiera, Sabine Kendl, Max Kurlbaum, Martin Fassnacht
Mitotane is the only drug approved for treatment of the orphan disease adrenocortical carcinoma (ACC) and was recently shown to be the first clinically used drug acting through endoplasmic reticulum (ER)-stress induced by toxic lipids. Since mitotane has limited clinical activity as monotherapy, we here study the potential of activating ER-stress through alternative pathways. The single reliable NCI-H295 cell culture model for ACC was used to study the impact MG132, bortezomib (BTZ) and carfilzomib (CFZ) on mRNA and protein expression of ER-stress markers, cell viability and steroid hormone secretion...
September 8, 2016: Hormones & Cancer
Dannielle H Upton, Kirsty A Walters, Rachel E Allavena, Mark Jimenez, Reena Desai, David J Handelsman, Charles M Allan
Phosphatase and tensin homologue (PTEN) is a known tumour suppressor. To explore the role of Pten in ovarian tumorigenesis, we used transgenic (Tg) SOX2. Cre and AMH. Cre mouse models to direct global Pten haploinsufficiency (Pten (+/-)) or ovary-specific granulosa cell (GC) Pten disruption (Pten (GC) ). Pten mutant models were combined with progressively rising Tg-follicle-stimulating hormone (TgFSH) levels to study the tumorigenic potential of combined genetic/endocrine modification in vivo. Global Pten (+/-) mice exhibited grossly detectable tumours in multiple organs including uterine and mammary tissue and displayed reduced survival...
August 9, 2016: Hormones & Cancer
Ioannis Christakis, Wei Qiu, Angelica M Silva Figueroa, Samuel Hyde, Gilbert J Cote, Naifa L Busaidy, Michelle Williams, Elizabeth Grubbs, Jeffrey E Lee, Nancy D Perrier
Thymic carcinoids are rare neuroendocrine tumors that occur in 1-5 % of patients with multiple endocrine neoplasia type 1 (MEN1) and are a major cause of morbidity and mortality. The few published reports associate these tumors with male sex and smoking. Our objective was to describe cases of these tumors treated at our institution. We performed a retrospective chart review of all patients diagnosed with MEN1 at our tertiary referral center from 1980 to 2014. Patients with a histopathologic, fine-needle aspiration, or clinical diagnosis of a thymic carcinoid were included...
August 2016: Hormones & Cancer
Brenna M Zimmer, Michelle E Howell, Qin Wei, Linlin Ma, Trevor Romsdahl, Eileen G Loughman, Jonathan E Markham, Javier Seravalli, Joseph J Barycki, Melanie A Simpson
Prostate epithelial cells control the potency and availability of androgen hormones in part by inactivation and elimination. UDP-glucose dehydrogenase (UGDH) catalyzes the NAD(+)-dependent oxidation of UDP-glucose to UDP-glucuronate, an essential precursor for androgen inactivation by the prostate glucuronidation enzymes UGT2B15 and UGT2B17. UGDH expression is androgen stimulated, which increases the production of UDP-glucuronate and fuels UGT-catalyzed glucuronidation. In this study, we compared the glucuronidation potential and its impact on androgen-mediated gene expression in an isogenic LNCaP model for androgen-dependent versus castration-resistant prostate cancer...
August 2016: Hormones & Cancer
Gail P Risbridger, Renea A Taylor
Systems that model cancer form the backbone of research discovery, and their accuracy and validity are a key determinant to ensure successful translation. In many tumour types, patient-derived specimens are an important model of choice for pre-clinical drug development. In this review, we consider why this has been such a challenge for prostate cancer, resulting in relatively few patient-derived xenografts (PDXs) of prostatic tumours compared to breast cancers, for example. Nevertheless, with only a few patient specimens and PDXs, we exemplify in three vignettes how important new clinical insights were obtained resulting in benefit for future men with prostate cancer...
August 2016: Hormones & Cancer
Lei Wang, David M Lonard, Bert W O'Malley
Steroid receptor coactivator (SRC) family members (SRC-1, SRC-2, SRC-3) interact with nuclear receptors (NRs) and many transcription factors to enhance target gene transcription. Deregulation of SRCs is widely implicated in NR mediated diseases, especially hormone dependent cancers. By integrating steroid hormone signaling and growth factor pathways, SRC proteins exert multiple modes of oncogenic regulation in cancers and represent emerging targets for cancer therapeutics. Recent work has identified SRC-targeting agents that show promise in blocking tumor growth in vitro and in vivo, and have the potential to function as powerful and broadly encompassing treatments for different cancers...
August 2016: Hormones & Cancer
Jithma Prasad Abeykoon, Luke Mueller, Frank Dong, Ashish V Chintakuntlawar, Jonas Paludo, Rami Mortada
Thyroid nodules are classified into six cytological categories under the Bethesda classification system. Two of these categories, atypical of undetermined significance (AUS) and suspicious for a follicular neoplasm (SFN), are further labeled as "indeterminate" diagnosis. Starting in June, 2012, Kansas University-Wichita Endocrine clinic implemented Afirma® Gene Expression Classifier (AGEC) to evaluate the need for surgical resection of thyroid nodules in patients with an indeterminate diagnosis. Electronic medical records of patients who underwent thyroid nodule fine-needle aspiration from 2004-2014 were reviewed...
August 2016: Hormones & Cancer
Ali Shidfar, Tolulope Fatokun, David Ivancic, Robert T Chatterton, Seema A Khan, Jun Wang
The local endocrine environment of the breast may have stronger relations to breast cancer risk than systemic hormones. Nipple aspiration fluid (NAF) provides a window into this milieu. We hypothesized that the correlations between proteins and steroid hormones in NAF are stronger, and specific relationships may reveal links to breast cancer risk. NAF and blood samples were obtained simultaneously from 54 healthy women and from the contralateral unaffected breast of 60 breast cancer patients. The abundance of five proteins, superoxide dismutase (SOD1), C-reactive protein (CRP), chitinase-3-like protein 1 (YKL40), cathepsin D (CatD), and basic fibroblast growth factor (bFGF) in NAF was measured using ELISA...
August 2016: Hormones & Cancer
Amy E Baek, Erik R Nelson
As the most common cancer in women, one in eight will develop invasive breast cancer over their lifetime making it the second most common cause of cancer-related death among women. Of the many known risk factors for developing breast cancer, obesity stands out as prominent and modifiable. Interestingly, elevated cholesterol is highly associated with obesity and has emerged as an independent risk factor for breast cancer onset and recurrence. This indicates that cholesterol also contributes to the breast cancer pathogenicity of obesity...
August 2016: Hormones & Cancer
Catha Fischer, Ramanaiah Mamillapalli, Laura G Goetz, Elisa Jorgenson, Ysabel Ilagan, Hugh S Taylor
Bisphenol-A (BPA) is a ubiquitous estrogen-like endocrine disrupting compound (EDC). BPA exposure in utero has been linked to breast cancer and abnormal mammary gland development in mice. The recent rise in incidence of human breast cancer and decreased age of first detection suggests a possible environmental etiology. We hypothesized that developmental programming of carcinogenesis may involve an aberrant immune response. Both innate and adaptive immunity play a role in tumor suppression through cytolytic CD8, NK, and Th1 T-cells...
August 2016: Hormones & Cancer
Assumpta C Nwaneri, Lucien McBeth, Terry D Hinds
Prostate cancer (PC) is one of the leading causes of mortality amongst elderly men in the USA and is second only to lung cancer. African Americans (AA) are at an increased risk of developing PC and are more likely to die from the disease in comparison to Caucasian Americans (CA). Chromosomal alterations or genetic differences between AA and CA may account for the variances observed in PC progression. Importantly, mutations in the androgen receptor (AR) or the epidermal growth factor receptor (EGFR) may contribute to the disparity...
July 22, 2016: Hormones & Cancer
M H T Ettaieb, J C Duker, R A Feelders, E P M Corssmit, C W Menke-van der Houven van Oordt, H J L M Timmers, M N Kerstens, J W Wilmink, P M Zelissen, B Havekes, H R Haak
Adrenal Cortical Carcinoma (ACC) is a rare malignancy with an incidence of 1.0 per million per year in the Netherlands. Median survival varies according to the European Network for the Study of Adrenal Tumours (ENS@T) tumour stage. It is unknown whether time until development of metastases is of influence on prognosis. To asses this, data were retrospectively obtained from centres of the Dutch Adrenal Network. Patients who presented with ACC between January 1, 2004 and October 31, 2013 were included. Date of detection of metastases, number of metastases and affected organs were registered...
July 15, 2016: Hormones & Cancer
L I Velikanova, Z R Shafigullina, A A Lisitsin, N V Vorokhobina, K Grigoryan, E A Kukhianidze, E G Strelnikova, N S Krivokhizhina, L M Krasnov, E A Fedorov, I V Sablin, A L Moskvin, E A Bessonova
Urinary steroid profiling (USP) was studied using high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) methods in 108 patients with adrenocortical adenoma (ACA) and in 31 patients with adrenocortical carcinoma (ACC). Thirteen ACC and Cushing's syndrome (ACC-CS) patients had two types of USP as well as 18 ACC patients without hypercortisolism. These four types differed by androgen and glucocorticoid secretion of the adrenal cortex. Fifteen main ACC features were observed by GC-MS...
July 1, 2016: Hormones & Cancer
Mark Yarchoan, Changqing Ma, Andrea B Troxel, Stephen J Stopenski, Waixing Tang, Aaron B Cohen, Marina Pappas-Paxinos, Burles A Johnson, Emerson Y Chen, Michael D Feldman, Marcia S Brose
Sorafenib has an antitumor activity in patients with radioactive iodine-refractory differentiated thyroid carcinoma (RAIR-DTC). Prior research has implicated signaling through the MAPK and AKT/PI3K pathways in the progression of DTC. To assess whether the activity of these pathways is predictive of response to sorafenib, we retrospectively studied molecular tumor markers from these two pathways from a phase 2 study of sorafenib in RAIR-DTC. Tumor samples from 40 of 53 DTC subjects obtained prior to initiation of sorafenib were immunostained with DAB-labeled antibodies to phospho-AKT (pAKT), phospho-ERK (pERK), and phospho-S6 (pS6)...
June 2016: Hormones & Cancer
Cameron P Capper, James M Rae, Richard J Auchus
Breast and prostate cancers are malignancies in which steroid hormones drive cellular proliferation. Over the past century, this understanding has led to successful treatment strategies aimed to inhibit hormone-mediated tumor growth. Nonetheless, disease relapse and progression still pose significant clinical problems, with recurrent and metastatic tumors often exhibiting resistance to current drug therapies. The central role of androgens and estrogens in prostate and breast cancer etiology explains not only why endocrine therapies are often initially successful but also why many tumors ultimately become resistant...
June 2016: Hormones & Cancer
Matthias Kroiss, Timo Deutschbein, Wiebke Schlötelburg, Cristina L Ronchi, Bruno Neu, Hans-Helge Müller, Marcus Quinkler, Stefanie Hahner, Anke Heidemeier, Martin Fassnacht
Adrenocortical carcinoma (ACC) has a dismal prognosis in advanced stages. Despite treatment with the adrenal toxicant mitotane and/or aggressive chemotherapy, tumor control is often short-lived. Here, we examine trofosfamide as a salvage treatment of ACC in an observational cohort study within the German ACC registry. Response defined as progression-free survival (PFS) at first tumor evaluation was assessed by RECIST 1.1 or clinically, and PFS and overall survival (OS) were estimated by the Kaplan-Meier method...
June 2016: Hormones & Cancer
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