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Endocrine-related Cancer

Adrian F Daly, Emily Castermans, Lindsey Oudijk, Mirtha A Guitelman, Pablo Beckers, Iulia Potorac, Sebastian J C M M Neggers, Nathalie Sacre, Aj Van der Lely, Vincent Bours, Wouter W de Herder, Albert Beckers
Copy number variations (CNV), an important genetic mechanism in inherited tumor genetics, can affect large genetic regions or can be limited to smaller regions within genes, such deletions of single exons. Such exon deletions can be challenging to identify and sequencing can be normal in these cases. Multiplex ligation dependent probe amplification (MLPA) can identify CNV of individual exons. Mutations in the MAX gene are associated with a risk of sporadic and hereditary pheochromocytoma. As mutations in other pheochromocytoma related genes can also cause pituitary tumors (3P-Association), we studied whether MAX exon deletions were involved in the etiology of patients with an unexplained association of multiple endocrine neoplasia including pituitary adenoma and pheochromocytoma...
March 13, 2018: Endocrine-related Cancer
Luis V Syro, Fabio Rotondo, Leon D Ortiz, Kalman Kovacs
Temozolomide is an alkylating chemotherapeutic agent used in malignant neuroendocrine neoplasia, melanoma, brain metastases, and an essential component of adjuvant therapy in the treatment of glioblastoma multiforme and anaplastic astrocytoma. Since 2006 it has been used for the treatment of pituitary carcinomas and aggressive pituitary adenomas. Here, we discuss the current indications and results of temozolomide therapy in pituitary tumors, as well as frequently asked questions regarding temozolomide treatment, duration of therapy, dosage, tumor recurrence, and resistance...
March 13, 2018: Endocrine-related Cancer
Tiago Augusto, Georgina Correia-da-Silva, Cecília M P Rodrigues, Natércia Teixeira, Cristina Amaral
Aromatase inhibitors (AIs) are one of the principal therapeutic approaches for estrogen-receptor positive (ER+) breast cancer in postmenopausal women. They block estrogen biosynthesis through aromatase inhibition, thus preventing tumour progression. Besides the therapeutic success of the third-generation AIs, acquired-resistance may develop, leading to tumour relapse. This resistance is thought to be the result of a change in the behavior of ER in these breast cancer cells, presumably by PI3K/Akt pathway enhancement along with alterations in other signalling pathways...
March 12, 2018: Endocrine-related Cancer
Kwon Joong Na, Hongyoon Choi
Although papillary thyroid cancer (PTC) is curable with excellent survival rate, patients with dedifferentiated PTC suffer the recurrence or death. As cancer immune escape plays a critical role in cancer progression, we aimed to investigate the relationship between differentiation and immune landscape of PTC and its implications for immunotherapy. Using the Cancer Genome Atlas data, we estimated the immune cell enrichment scores and overall immune infiltration, ImmuneScore, to characterize the immune landscape of PTC...
March 5, 2018: Endocrine-related Cancer
Belinda van Zyl, Denise Tang, Nikola A Bowden
Ovarian cancer has poor survival rate due to a combination of diagnosis at advanced disease stages and disease recurrence as a result of platinum chemotherapy resistance. High grade serous ovarian cancer (HGSOC), the most common ovarian cancer subtype, is conventionally treated with surgery and paclitaxel/carboplatin combination chemotherapy. Initial response rates are 60-80%, but eventually the majority of patients become platinum resistant with subsequent relapses. Extensive research on individual biomarkers of platinum-resistance has revealed many potential targets for the development new treatments...
February 27, 2018: Endocrine-related Cancer
Minlu Zhang, Peng Peng, Kai Gu, Hui Cai, Guoyou Qin, Xiao-Ou Shu, Pingping Bao
The impact of some prognostic factors on breast cancer survival has been shown to vary with time since diagnosis. However, this phenomenon has not been evaluated in Asians. In the present study, 4886 patients were recruited from the Shanghai Breast Cancer Survival Study, a longitudinal study of patients diagnosed during 2002-2006, with a median follow-up time of 11.2 years. Cox model incorporating time-by-covariate interactions was used to describe the time-varying effects of prognostic factors related to overall survival and disease-free survival...
February 22, 2018: Endocrine-related Cancer
Vaishali I Parekh, Sita D Modali, James Welch, William Simonds, Lee Scott Weinstein, Electron Kebebew, Sunita K Agarwal
Extract: Pancreatic neuroendocrine tumors (PNETs/pNETs/p-NETs/PanNETs) are rare endocrine neoplasms that can be either functioning tumors that secrete hormones characteristic of their endocrine cell of origin, or nonfunctioning tumors. The most common functioning PNETs are the insulin-secreting b-cell tumors (insulinomas) that are mainly sporadic, but may also occur in 10% of patients with the hereditary tumor syndrome multiple endocrine neoplasia type 1 (MEN1) (OMIM ID: 131100). Patients with the MEN1 syndrome carry a heterozygous germline inactivating mutation in the MEN1 tumor suppressor gene and specific somatic loss of the normal MEN1 allele, leading to endocrine tumors mainly of the parathyroids, pituitary and pancreas (PNETs)...
February 21, 2018: Endocrine-related Cancer
Nevena Gajovic, Milena Jurisevic, Jelena Pantic, Gordana D Radosavljevic, Nebojsa Arsenijevic, Miodrag Lukic, Ivan Jovanovic
Diabetic patients have higher incidence and mortality of cancer. Recent study revealed that hyperglycemia-induced oxidative stress is involved in the acceleration of tumor metastasis. We used model of high dose streptozotocin-induced diabetes to investigate its effect on tumor growth and modulation of antitumor immune response of 4T1 murine breast cancer in BALB/c mice. Diabetes accelerated tumor appearance, growth and weight, which was associated with decreased NK cells cytotoxicity against 4T1 tumor cells in vitro...
February 19, 2018: Endocrine-related Cancer
Joseph Shulan, Leonid Vydro, Arthur B Schneider, Dan Mihailescu
With increasing numbers of childhood cancer survivors who were treated with radiation, there is a need to evaluate potential biomarkers that could signal an increased risk of developing thyroid cancer. We aimed to examine the relationships between thyrotropin and thyroglobulin levels and the risk of developing thyroid nodules and cancer in a cohort of radiation exposed children. 806 subjects who were irradiated in the neck area as children were examined and followed for up to 25 years. All subjects underwent a clinical examination, measurements of thyrotropin, thyroglobulin levels and thyroid imaging...
February 16, 2018: Endocrine-related Cancer
Carolyn M Klinge
The human genome is 'pervasively transcribed' leading to a complex array of non-coding RNAs (ncRNAs) that far outnumber coding mRNAs. ncRNAs have regulatory roles in transcription and post-transcriptional processes as well numerous cellular functions that remain to be fully described. Best characterized of the 'expanding universe' of ncRNAs are the ~ 22 nucleotide microRNAs (miRNAs) that base-pair to target mRNA's 3' untranslated region within the RNA-induced silencing complex (RISC) and block translation and may stimulate mRNA transcript degradation...
February 12, 2018: Endocrine-related Cancer
Kosmas Daskalakis, Olov Norlen, Andreas Karakatsanis, Per Hellman, Rolf Larsson, Peter Nygren, Peter Stalberg
Small intestinal endocrine tumours (SI-NETs) are generally considered resistant to systemic treatment. To date, predictive markers for drug activity are lacking. Tumour samples from 27 patients with SI-NETs were analyzed ex vivo for sensitivity to a panel of cytotoxic drugs and targeted agents using a short-term total cell kill assay. Samples of renal cancer, colorectal cancer (CRC), ovarian cancer, and chronic lymphocytic leukemia (CLL) were included for comparison. For the SI-NET subset, drug sensitivity was analyzed in relation to clinico-pathological variables and pre-treatment biomarkers...
February 12, 2018: Endocrine-related Cancer
Isabel Amendoeira, Tiago Maia, M Sobrinho-Simões
The 2017 edition of the WHO book on Classification of Tumours of Endocrine Organs includes a new section entitled "Other encapsulated follicular-patterned thyroid tumours", in which the newly created NIFTP (Non-invasive follicular thyroid neoplasm with papillary-like nuclear features) is identified and detailed described. Despite deleting the word "carcinoma" from its name, NIFTP is not a benign tumor either, and is best regarded as a neoplasm with "very low malignant potential"...
February 9, 2018: Endocrine-related Cancer
Mark A White, Efrosini Tsouko, Chenchu Lin, Kimal Rajapakshe, Jeffrey M Spencer, Sandi R Wilkenfeld, Sheiva S Vakili, Thomas L Pulliam, Dominik Awad, Fotis Nikolos, Rajasekhara Reddy Katreddy, Benny Abraham Kaipparettu, Arun Sreekumar, Xiaoliu Zhang, Edwin Cheung, Cristian Coarfa, Daniel E Frigo
Despite altered metabolism being an accepted hallmark of cancer, it is still not completely understood which signaling pathways regulate these processes. Given the central role of androgen receptor (AR) signaling in prostate cancer, we hypothesized that AR could promote prostate cancer cell growth in part through increasing glucose uptake via the expression of distinct glucose transporters. Here, we determined that AR directly increased the expression of SLC2A12, the gene that encodes the glucose transporter GLUT12...
February 5, 2018: Endocrine-related Cancer
Antonio De la Vieja, Pilar Santisteban
Iodide (I-) metabolism is crucial for the synthesis of thyroid hormones (THs) in the thyroid and the subsequent action of these hormones in the organism. I- is principally transported by the sodium iodide symporter (NIS) and by the anion exchanger PENDRIN, and recent studies have demonstrated the direct participation of new transporters including anoctamin 1 (ANO1), cystic fibrosis transmembrane conductance regulator (CFTR) and sodium multivitamin transporter (SMVT). Several of these transporters have been found expressed in various tissues, implicating them in I- recycling...
February 1, 2018: Endocrine-related Cancer
Marta Kaczmarek-Ryś, Katarzyna Ziemnicka, Andrzej Pławski, Bartlomiej Budny, Michał Michalak, Szymon Hryhorowicz, Justyna Hoppe-Gołebiewska, Pawel Borun, Monika Gołąb, Malgorzata Czetwertynska, Maria Sromek, Marlena Szalata, Marek Ruchala, Ryszard Słomski
The clinical course of medullary thyroid carcinoma (MTC) associated with the MEN2A syndrome as well as of sporadic MTC shows considerable heterogeneity. The disease picture varies between the same RET proto-oncogene mutation carriers but also among sporadic MTC patients with no RET germinal mutations, which suggests the involvement of additional modulators of the disease. However, genetic factors responsible for this heterogeneity of the MTC clinical course remain still unknown. The aim of this study was to determine if polymorphic variants or specific haplotypes of the RET gene may modify the MTC clinical course...
January 31, 2018: Endocrine-related Cancer
Andreas Machens, Kerstin Lorenz, Frank Weber, Henning Dralle
There is evidence in the literature that some RET (REarranged during Transfection) variants commonly associated with multiple endocrine neoplasia type 2A (MEN2A) may be more frequent in certain European countries: p.L790F in Germany; p.Y791F in Poland; and p.V804 in France and Italy. This investigation of 189 German medullary thyroid cancer families was undertaken to explore the geographic epidemiology of these three RET variants, based on place of residence of the last common ancestor grouped by Roman and Slavic historic settlement areas...
January 29, 2018: Endocrine-related Cancer
Douglas A Gibson, Frances Collins, Fiona L Cousins, Arantza Esnal Zufiaurre, Philippa T Saunders
Endometrial cancer (EC) is the most common gynaecological malignancy. Obesity is a major risk factor for EC and is associated with elevated cholesterol. 27-Hydroxycholesterol (27HC) is a cholesterol metabolite that functions as an endogenous agonist for Liver X Receptor (LXR) and a selective estrogen receptor modulator (SERM). Exposure to estrogenic ligands increases risk of developing EC however the impact of 27HC on EC is unknown. Samples of stage 1 EC (n=126) were collected from post-menopausal women undergoing hysterectomy...
January 25, 2018: Endocrine-related Cancer
Päivi Järvensivu, Taija Heinosalo, Janne Hakkarainen, Pauliina Kronqvist, Niina Saarinen, Matti Poutanen
Hydroxysteroid (17-beta) dehydrogenase type 1 (HSD17B1) converts low active estrogen estrone to highly active estradiol. Estradiol is necessary for normal postpubertal mammary gland development; however, elevated estradiol levels increase mammary tumorigenesis. To investigate the significance of the human HSD17B1 enzyme in the mammary gland, transgenic mice universally overexpressing human HSD17B1 were used (HSD17B1TG mice). Mammary glands obtained from HSD17B1TG females at different ages were investigated for morphology and histology, and HSD17B1 activity and estrogen receptor activation in mammary gland tissue were assessed...
January 25, 2018: Endocrine-related Cancer
Amandine Berdelou, Livia Lamartina, Michele Klain, Sophie Leboulleux, Martin Schlumberger
Distant metastases from thyroid cancer of follicular origin are uncommon. Treatment includes levothyroxine administration, focal treatment modalities with surgery, external radiation therapy and thermal ablation, and radioiodine in patients with uptake of 131I in their metastases. Two thirds of distant metastases become refractory to radioiodine at some point, and when there is a significant tumor burden and documented progression on imaging, a treatment with a kinase inhibitor may provide benefits.
January 25, 2018: Endocrine-related Cancer
Katja Kiseljak-Vassiliades, Yu Zhang, Stacey Bagby, Adwitiya Kar, Nikita Pozdeyev, Mei Xu, Katherine Gowan, Vibha Sharma, Christopher D Raeburn, Maria Albuja-Cruz, Kenneth L Jones, Lauren Fishbein, Rebecca Schweppe, Hilary L Somerset, Todd M Pitts, Stephen Leong, Margaret Wierman
Adrenocortical cancer (ACC) is an orphan malignancy that results in heterogeneous clinical phenotypes and molecular genotypes. There are no curative treatments for this deadly cancer with 35% survival at five years. Our understanding of the underlying pathobiology and our ability to test novel therapeutic targets has been limited due to the lack of preclinical models. Here, we report the establishment of two new ACC cell lines and corresponding patient derived xenograft (PDX) models. CU-ACC1 cell line and PDX were derived from a perinephric metastasis in a patient whose primary tumor secreted aldosterone...
January 25, 2018: Endocrine-related Cancer
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