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Endocrine-related Cancer

Sung Gwe Ahn, Chang Ik Yoon, Jae Hoon Lee, Hye-Sun Lee, So Eun Park, Yoon Jin Cha, Chihwan Cha, Soong June Bae, Kyung-A Lee, Joon Jeong
On the basis of TP53 mutations and standardized uptake values (SUVs) from 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET), we sought to enhance our knowledge of the biology underlying low progesterone receptor (PR) expression in estrogen receptor (ER)-positive/human epidermal growth factor receptor-2 (HER2)-negative tumors. This study included 272 patients surgically treated for ER-positive, HER2-negative breast cancer and who had undergone TP53 gene sequencing. Of these, 229 patients also underwent 18F-FDG PET or PET/CT...
November 1, 2018: Endocrine-related Cancer
Xiang Zhang, Ya Hu, Mengyi Wang, Ronghua Zhang, PeiPei Wang, Ming Cui, Zhe Su, Xiang Gao, Quan Liao, Yupei Zhao
Parathyroid carcinoma (PCa) is a rare endocrine neoplasia that typically has unfavourable outcomes. The contribution of long non-coding RNAs (lncRNAs) to the development of malignant and benign parathyroid tumours remains largely unknown. In this study, we explored transcriptomic profiling of lncRNA and mRNA expression in 6 PCa, 6 parathyroid adenoma (PAd) and 4 normal parathyroid (PaN) tissues. In total, 2641 lncRNA transcripts and 2165 mRNA transcripts were differentially expressed between PCa and PAd. Enrichment analysis demonstrated that dysregulated transcripts were involved mainly in the extracellular matrix (ECM)-receptor interaction and energy metabolism pathways...
November 1, 2018: Endocrine-related Cancer
Giorgio Secreto, Alessandro Girombelli, Vittorio Krogh
The aim of this review is to highlight the pivotal role of androgen excess in the development of breast cancer. Available evidence suggests that testosterone controls breast epithelial growth through a balanced interaction between its two active metabolites: cell proliferation is promoted by estradiol while it is inhibited by dihydrotestosterone. A chronic overproduction of testosterone (e.g. ovarian stromal hyperplasia) results in an increased estrogen production and cell proliferation that are no longer counterbalanced by dihydrotestosterone...
November 1, 2018: Endocrine-related Cancer
Jonathan Wesley Nyce
A here-to-fore unknown tumor suppression mechanism reached its greatest expression in humans, having evolved to protect during the twenty-five-year lifespan of primitive humans. It depends upon high levels of circulating DHEAS and its importation into cells that have experienced inactivation of TP53, whereupon DHEAS is desulfated to DHEA, an uncompetitive inhibitor of Glucose-6-phosphate Dehydrogenase (G6PD). Uncompetitive inhibition of G6PD becomes irreversible in the presence of high levels of inhibitor and substrate (G6P)...
October 1, 2018: Endocrine-related Cancer
Martin K Bakht, Iulian Derecichei, Yinan Li, Rosa-Maria Ferraiuolo, Mark J Dunning, So Won Oh, Abdulkadir Hussein, Hyewon Youn, Keith F Stringer, Chang Wook Jeong, Gi Jeong Cheon, Cheol Kwak, Keon Wook Kang, Alastair Lamb, Yuzhuo Wang, Xuesen Dong, Lisa Porter
Prostate-specific membrane antigen (PSMA) is overexpressed in most prostate adenocarcinoma (AdPC) cells and acts as a target for molecular imaging. However, some case reports indicate that PSMA-targeted imaging could be ineffectual for delineation of neuroendocrine (NE) prostate cancer (NEPC) lesions due to the suppression of the PSMA gene (FOLH1). These same reports suggest that targeting somatostatin receptor type 2 (SSTR2) could be an alternative diagnostic target for NEPC patients. This study evaluates the correlation between expression of FOLH1, NEPC marker genes and SSTR2...
October 1, 2018: Endocrine-related Cancer
Frederic Castinetti, Frederique Albarel, Francoise Archambeaud, Jerome Bertherat, Benjamin Bouillet, Perrine Buffier, Claire Briet, Bertrand Cariou, Philippe Caron, Olivier Chabre, Philippe Chanson, Christine Cortet, Christine Do Cao, Delphine Drui, Magali Haissaguerre, Segolene Hescot, Frederic Illouz, Emmanuelle Kuhn, Najiba Lahlou, Emilie Merlen, Veronique Raverot, Sarra Smati, Bruno Verges, Françoise Borson-Chazot
The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPI). However, the use of ICPI has a risk of side-effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a consensus document on ICPI-related endocrine toxicity...
October 1, 2018: Endocrine-related Cancer
Ji Won Kim, Dharmendra K Yadav, Soo Jin Kim, Moo-Yeol Lee, Jung-Min Park, Bum Seok Kim, Mi-Hyun Kim, Hyeung-Geun Park, Keon Wook Kang
GV1001, a 16-amino acid fragment of the human telomerase reverse transcriptase catalytic subunit (hTERT), has been developed as an injectable formulation of cancer vaccine. Here, we revealed for the first time that GV1001 is a novel ligand for gonadotropin-releasing hormone receptor (GnRHR). The docking prediction for GV1001 against GnRHR showed high binding affinity. Binding of GV1001 to GnRHR stimulated the Gαs-coupled cAMP signaling pathway and antagonized Gαq-coupled Ca2+ release by leuprolide acetate (LA), a GnRHR agonist...
October 1, 2018: Endocrine-related Cancer
Samuel M O'Toole, David S Watson, Tatiana V Novoselova, Lisa E L Romano, Peter King, Teisha Y Bradshaw, Clare L Thompson, Martin M Knight, Tyson V Sharp, Michael R Barnes, Umasuthan Srirangalingam, William Drake, J Paul Chapple
Primary cilia are sensory organelles involved in regulation of cellular signalling. Cilia loss is frequently observed in tumors, yet the responsible mechanisms and consequences for tumorigenesis remain unclear. We demonstrate that cilia structure and function is disrupted in human pheochromocytomas - endocrine tumours of the adrenal medulla. This is concomitant with transcriptional changes within cilia mediated signalling pathways that are associated with tumorigenesis generally and pheochromocytomas specifically...
September 7, 2018: Endocrine-related Cancer
Neil Portman, Sarah Alexandrou, Emma Carson, Shudong Wang, Elgene Lim, Catherine Elizabeth Caldon
Three inhibitors of CDK4/6 kinases were recently FDA approved for use in combination with endocrine therapy, and they significantly increase the progression-free survival of patients with advanced Estrogen Receptor positive (ER+) breast cancer in the first-line treatment setting. As the new standard-of-care in some countries, there is the clinical emergence of patients with breast cancer that is both CDK4/6 inhibitor and endocrine therapy resistant. The strategies to combat these cancers with resistance to multiple treatments are not yet defined and represent the next major clinical challenge in ER+ breast cancer...
September 1, 2018: Endocrine-related Cancer
Xianhui Ruan, Xianle Shi, Qiman Dong, Yang Yu, Xiukun Hou, Xinhao Song, Xi Wei, Lingyi Chen, Ming Gao
There is no effective treatment for patients with poorly differentiated papillary thyroid cancer or anaplastic thyroid cancer (ATC). Anlotinib, a multi-kinase inhibitor, has already shown antitumor effects in various types of carcinoma in a phase I clinical trial. In this study, we aimed to better understand the effect and efficacy of anlotinib against thyroid carcinoma cells in vitro and in vivo. We found that anlotinib inhibits the cell viability of papillary thyroid cancer and ATC cell lines, likely due to abnormal spindle assembly, G2/M arrest, and activation of TP53 upon anlotinib treatment...
August 23, 2018: Endocrine-related Cancer
Paraskevi Xekouki, Emily Jane Lodge, Jakob Matschke, Alice Santambrogio, John R Apps, Ariane Sharif, Thomas S Jacques, Simon Aylwin, Vincent Prevot, Ran Li, Jörg Flitsch, Stefan R Bornstein, Marily Theodoropoulou, Cynthia Andoniadou
Tumours of the anterior pituitary can manifest from all endocrine cell types but the mechanisms for determining their specification are not known. The Hippo kinase cascade is a crucial signalling pathway regulating growth and cell fate in numerous organs. There is mounting evidence implicating this in tumour formation, where it is emerging as an anti-cancer target. We previously demonstrated activity of the Hippo kinase cascade in the mouse pituitary and nuclear association of its effectors YAP/TAZ with SOX2-expressing pituitary stem cells...
August 23, 2018: Endocrine-related Cancer
Veronica Vella, Maria Luisa Nicolosi, Patrizia Cantafio, Michele Massimino, Rosamaria Lappano, Paolo Vigneri, Roberto Ciuni, Pietro Gangemi, Andrea Morrione, Roberta Malaguarnera, Antonino Belfiore
Patients with thyroid cancers refractory to radioiodine (RAI) treatment show a limited response to various therapeutic options and a low survival rate. The recent use of multikinase inhibitors has also met limited success. An alternative approach relies on drugs that induce cell differentiation, as the ensuing increased expression of the cotransporter for sodium and iodine (NIS) may partially restore sensitivity to radioiodine. The inhibition of the ERK1/2 pathway has shown some efficacy in this context. Aggressive thyroid tumors overexpress the isoform A of the insulin receptor (IR-A) and its ligand IGF-2; this IGF-2/IR-A loop is associated with de-differentiation and stem-like phenotype, resembling RAI refractory tumors...
August 18, 2018: Endocrine-related Cancer
Christina Schug, Sarah Urnauer, Carsten Jäckel, Kathrin Alexandra Schmohl, Mariella Tutter, Katja Steiger, Nathalie Schwenk, Markus Schwaiger, Ernst Wagner, Peter Jon Nelson, Christine Spitzweg
Based on their excellent tumor-homing capacity, genetically engineered mesenchymal stem cells (MSCs) are under investigation as tumor-selective gene delivery vehicles. Transgenic expression of the sodium iodide symporter ( NIS ) in genetically engineered MSCs allows noninvasive tracking of MSC homing by imaging of functional NIS expression as well as therapeutic application of 131 I. The use of tumor-stroma activated promoters can improve tumor-specific MSC-mediated transgene delivery. The essential role of transforming growth factor B1 (TGFB1) and the SMAD downstream target in the signaling between tumor and the surrounding stroma makes the biology of this pathway a potential option to better control NIS expression within the tumor milieu...
August 18, 2018: Endocrine-related Cancer
Han-Wei Lin, Ying-Cheng Chiang, Nai-Yun Sun, Yu-Li Chen, Chi-Fang Chang, Yi-Jou Tai, Chi-An Chen, Wen-Fang Cheng
The role of chitinase-3-like protein 1 (CHI3L1) in ovarian cancer and the possible mechanisms were elucidated. CHI3L1 is a secreted glycoprotein and associated with inflammation, fibrosis, asthma, extracellular tissue remodeling and solid tumors. Our previous study showed CHI3L1 could be a potential prognostic biomarker for epithelial ovarian cancer and protect cancer cells from apoptosis. Therefore, clinical data and quantitation of CHI3L1 of ovarian cancer patients, tumor spheroid formation, side-population assays, Aldefluor and apoptotic assays, ELISA, RT-PCR, immunoblotting, and animal experiments were performed in two ovarian cancer cells lines, OVCAR3 and CA5171, and their CHI3L1-overexpressing and knockdown transfectants...
August 18, 2018: Endocrine-related Cancer
Eva Baxter, Karolina Windloch, Greg Kelly, Jason S Lee, Frank Gannon, Donal Brennan
Up to 80% of endometrial and breast cancers express oestrogen receptor alpha (ERα). Unlike breast cancer, anti-oestrogen therapy has had limited success in endometrial cancer, raising the possibility that oestrogen has different effects in both cancers. We investigated the role of oestrogen in endometrial and breast cancers using data from The Cancer Genome Atlas (TCGA) in conjunction with cell line studies. Using phosphorylation of ERα (ERα-pSer118) as a marker of transcriptional activation of ERα in TCGA datasets, we found that genes associated with ERα-pSer118 were predominantly unique between tumour types and have distinct regulators...
August 18, 2018: Endocrine-related Cancer
Lautaro Zubeldia-Brenner, Catalina De Winne, Sofia Perrone, Santiago Andres Rodriguez-Segui, Christophe Willems, Ana Maria Ornstein, Isabel Maria Lacau-Mengido, Hugo Vankelecom, Carolina Cristina, Damasia Becú-Villalobos
Preclinical and clinical studies support that Notch signaling may play an important oncogenic role in cancer, but there is scarce information for pituitary tumors. We therefore undertook a functional study to evaluate Notch participation in pituitary adenoma growth. Tumors generated in nude mice by subcutaneous GH3 somatolactotrope cell injection were treated in vivo with DAPT, a γ-secretase inhibitor, thus inactivating Notch signaling. This treatment led to pituitary tumor reduction, lower prolactin and GH tumor content, and a decrease in angiogenesis...
August 18, 2018: Endocrine-related Cancer
Milena Doroszko, Marcin Chrusciel, Joanna Stelmaszewska, Tomasz Slezak, Slawomir Anisimowicz, Ursula Plöckinger, Marcus Quinkler, Marco Bonomi, Slawomir Wolczynski, Ilpo Huhtaniemi, Jorma Toppari, Nafis A Rahman
Aberrantly expressed G protein-coupled receptors in tumors are considered as potential therapeutic targets. We analyzed the expressions of receptors of gonadotropin-releasing hormone (GNRHR), luteinizing hormone/chorionic gonadotropin (LHCGR) and follicle-stimulating hormone (FSHR) in human adrenocortical carcinomas and assessed their response to GnRH antagonist therapy. We further studied the effects of the GnRH antagonist cetrorelix acetate (CTX) on cultured adrenocortical tumor (ACT) cells (mouse Cα1 and Y-1, and human H295R), and in vivo in transgenic mice (SV40 T-antigen expression under inhibin α promoter) bearing Lhcgr and Gnrhr in ACT...
January 1, 2019: Endocrine-related Cancer
Bruno Heidi Nozima, Thais Biude Mendes, Gustavo José da Silva Pereira, Rodrigo Pinheiro Araldi, Edna Sadayo Miazato Iwamura, Soraya Soubhi Smaili, Gianna Maria Griz Carvalheira, Janete Maria Cerutti
We previously proposed that high expression of FAM129A can be used as a thyroid carcinoma biomarker in preoperative diagnostic exams of thyroid nodules. Here, we identify that FAM129A expression is increased under nutrient and growth factor depletion in a normal thyroid cell line (PCCL3), overlapping with increased expression of autophagy-related protein and inhibition of AKT/mTOR/p70S6K. Supplementation of insulin, TSH and serum to the medium was able to reduce the expression of both FAM129A and autophagy-related protein and reestablish the AKT/mTOR/p70S6K axis...
January 1, 2019: Endocrine-related Cancer
Xi Wei, Shang Cai, Rebecca J Boohaker, Joshua Fried, Ying Li, Linfei Hu, Yi Pan, Ruifen Cheng, Sheng Zhang, Ye Tian, Ming Gao, Bo Xu
Anaplastic thyroid cancer (ATC) is an aggressive cancer with poor clinical prognosis. However, mechanisms driving ATC aggressiveness is not well known. Components of the DNA damage response (DDR) are frequently found mutated or aberrantly expressed in ATC. The goal of this study is to establish the functional link between histone acetyltransferase lysine (K) acetyltransferase 5 (KAT5, a critical DDR protein) and ATC invasiveness using clinical, in vitro and in vivo models. We analyzed the expression of KAT5 by immunohistochemistry and assessed its relationship with metastasis and overall survival in 82 ATC patients...
January 1, 2019: Endocrine-related Cancer
Lingfan Xu, Enze Ma, Tao Zeng, Ruya Zhao, Yulei Tao, Xufeng Chen, Jeff Groth, Chaozhao Liang, Hailiang Hu, Jiaoti Huang
ATM is a well-known master regulator of double strand break (DSB) DNA repair and the defective DNA repair has been therapeutically exploited to develop PARP inhibitors based on the synthetic lethality strategy. ATM mutation is found with increased prevalence in advanced metastatic castration-resistant prostate cancer (mCRPC). However, the molecular mechanisms underlying ATM mutation-driving disease progression are still largely unknown. Here, we report that ATM mutation contributes to the CRPC progression through a metabolic rather than DNA repair mechanism...
January 1, 2019: Endocrine-related Cancer
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