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The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines
In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We therefore performed immunophenotyping, copy number profiling, whole-exome sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype while three others, KRJ-I, L-STS and H-STS, did not. Instead, these three cell lines were identified as lymphoblastoid. Characterisation of remaining authentic GEPNET cell lines by copy number profiling showed that GOT1, among other chromosomal alterations, harboured losses on c...
Source: Endocrine-Related Cancer - February 14, 2018 Category: Endocrinology Authors: Hofving, T., Arvidsson, Y., Almobarak, B., Inge, L., Pfragner, R., Persson, M., Stenman, G., Kristiansson, E., Johanson, V., Nilsson, O. Tags: Research Source Type: research

PTGS2 polymorphism rs689466 favors breast cancer recurrence in obese patients
In conclusion, cyclooxygenase-2 genotyping may add to the prognostic evaluation of obese breast cancer patients. (Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - February 14, 2018 Category: Endocrinology Authors: Freitas-Alves, D. R., Vieira-Monteiro, H. d. A., Piranda, D. N., Sobral-Leite, M., da Silva, T. S. L., Bergmann, A., Santos Valenca, S., Perini, J. A., Vianna-Jorge, R. Tags: Research Source Type: research

DICER1 gene mutations in endocrine tumors
In this review, the importance of the DICER1 gene in the function of endocrine cells is discussed. There is conclusive evidence that DICER1 mutations play a crucial role in the development, progression, cell proliferation, therapeutic responsiveness and behavior of several endocrine tumors. We review the literature of DICER1 gene mutations in thyroid, parathyroid, pituitary, pineal gland, endocrine pancreas, paragangliomas, medullary, adrenocortical, ovarian and testicular tumors. Although significant progress has been made during the last few years, much more work is needed to fully understand the significance of DICER1 m...
Source: Endocrine-Related Cancer - February 8, 2018 Category: Endocrinology Authors: Solarski, M., Rotondo, F., Foulkes, W. D., Priest, J. R., Syro, L. V., Butz, H., Cusimano, M. D., Kovacs, K. Tags: Review Source Type: research

Inflammation and PD-L1 expression in pulmonary neuroendocrine tumors
In the light of novel cancer immune therapies, the status of antitumor inflammatory response and its regulation has gained much attention in patients with lung cancer. Ample datasets exist for non-small-cell lung cancer, but those for pulmonary neuroendocrine tumors are scarce and controversial. Here, tumor-associated inflammation, CD8+ cell infiltration and PD-L1 status were evaluated in a cohort of 57 resected carcinoids and 185 resected neuroendocrine carcinomas of the lung (58 large cell carcinomas and 127 small cell carcinomas). Data were correlated with clinicopathological factors and survival. Moderate or high tumor...
Source: Endocrine-Related Cancer - February 7, 2018 Category: Endocrinology Authors: Kasajima, A., Ishikawa, Y., Iwata, A., Steiger, K., Oka, N., Ishida, H., Sakurada, A., Suzuki, H., Kameya, T., Konukiewitz, B., Kloppel, G., Okada, Y., Sasano, H., Weichert, W. Tags: Research Source Type: research

miR-205 targets angiogenesis and EMT concurrently in anaplastic thyroid carcinoma
The current study aims to evaluate for the first time the inhibitory roles of miR-205 in the pathogenesis of anaplastic thyroid carcinoma. In addition, we investigated the mechanisms by which miR-205 regulates angiogenesis and epithelial-to-mesenchymal transition (EMT) in cancer. Two anaplastic thyroid carcinoma cell lines were transfected with the expression vector pCMV-MIR-205. Selected markers of angiogenesis and EMT including vascular endothelial growth factor A (VEGF-A) and zinc finger E-box-binding homeobox 1 (ZEB1) were investigated by Western blot. The interaction of miR-205 expression with EMT and angiogenesis wer...
Source: Endocrine-Related Cancer - February 7, 2018 Category: Endocrinology Authors: Vosgha, H., Ariana, A., Smith, R. A., Lam, A. K.-y. Tags: Research Source Type: research

Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial
Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with
Source: Endocrine-Related Cancer - February 7, 2018 Category: Endocrinology Authors: Pavel, M., Gross, D. J., Benavent, M., Perros, P., Srirajaskanthan, R., Warner, R. R. P., Kulke, M. H., Anthony, L. B., Kunz, P. L., Horsch, D., Weickert, M. O., Lapuerta, P., Jiang, W., Kassler-Taub, K., Wason, S., Fleming, R., Fleming, D., Garcia-Carbon Tags: Research Source Type: research

IAPs cause resistance to TRAIL-dependent apoptosis in follicular thyroid cancer
Follicular thyroid cancer’s (FTC) excellent long-term prognosis is mainly dependent on postoperative radioactive iodine (RAI) treatment. However, once the tumour becomes refractory, the 10-year disease-specific survival rate drops below 10%. The aim of our study was to evaluate the prognostic and biological role of the TRAIL system in FTC and to elucidate the influence of small-molecule-mediated antagonisation of inhibitor of apoptosis proteins (IAPs) on TRAIL sensitivity in vitro. Tissue microarrays were constructed from forty-four patients with histologically confirmed FTC. Expression levels of TRAIL and its recept...
Source: Endocrine-Related Cancer - February 7, 2018 Category: Endocrinology Authors: Werner, T. A., Nolten, I., Dizdar, L., Riemer, J. C., Schutte, S. C., Verde, P. E., Raba, K., Schott, M., Knoefel, W. T., Krieg, A. Tags: Research Source Type: research

Tetrac downregulates {beta}-catenin and HMGA2 to promote the effect of resveratrol in colon cancer
The molecular pathogenesis of colorectal cancer encompasses the activation of several oncogenic signaling pathways that include the Wnt/β-catenin pathway and the overexpression of high mobility group protein A2 (HMGA2). Resveratrol – the polyphenolic phytoalexin – binds to integrin αvβ3 to induce apoptosis in cancer cells via cyclooxygenase 2 (COX-2) nuclear accumulation and p53-dependent apoptosis. Tetraiodothyroacetic acid (tetrac) is a de-aminated derivative of l-thyroxine (T4), which – in contrast to the parental hormone – impairs cancer cell proliferation. In the current study, ...
Source: Endocrine-Related Cancer - February 7, 2018 Category: Endocrinology Authors: Nana, A. W., Chin, Y.-T., Lin, C.-Y., Ho, Y., Bennett, J. A., Shih, Y.-J., Chen, Y.-R., Changou, C. A., Pedersen, J. Z., Incerpi, S., Liu, L. F., Whang-Peng, J., Fu, E., Li, W.-S., Mousa, S. A., Lin, H.-Y., Davis, P. J. Tags: Research Source Type: research

Sex steroids in the tumor microenvironment and prostate cancer progression
This article reviews the clinical and basic research on the influence of sex steroids such as androgens, estrogens and progesterone within the prostate tumor microenvironment on the progression of prostate cancer. We review clinical studies to date evaluating serum sex steroids as prognostic biomarkers and discuss their respective biological effects within the prostate tumor microenvironment. We also review the link between genomic alterations and sex steroid levels within prostate tumors. Finally, we highlight the links between sex steroid levels and the function of the immune system within the tumor microenvironment. As ...
Source: Endocrine-Related Cancer - February 7, 2018 Category: Endocrinology Authors: Boibessot, C., Toren, P. Tags: Review Source Type: research

Runx2 overexpression compromises bone quality in acromegalic patients
In conclusion, this study demonstrates the key role of RUNX2 gene overexpression in causing bone impairment in acromegalic patients. It also suggests a therapeutic approach for the improvement of bone quality, focused on the osteoblastic lineage rather than the inhibition of osteoclastic activity. (Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - February 5, 2018 Category: Endocrinology Authors: Valenti, M. T., Mottes, M., Cheri, S., Deiana, M., Micheletti, V., Cosaro, E., Davi, M. V., Francia, G., Dalle Carbonare, L. Tags: Research Source Type: research

Sulforaphane metabolites cause apoptosis via microtubule disruption in cancer
Sulforaphane (SFN) inhibited growth in many cancers, but its half-life is 2 h in circulation. However, its metabolites, sulforaphane-cysteine (SFN-Cys) and sulforaphane-N-acetyl-cysteine (SFN-NAC) had longer half-lives and decreased the cell viability in both dose- and time-dependent manners in human prostate cancer. Flow cytometry assay revealed that these two SFN metabolites induced apoptosis with the features such as vacuolization, disappeared nuclear envelope, nuclear agglutination and fragmentation via transmission electron microscopy observation. Western blot showed that the sustained phosphorylation of ERK1/2 mediat...
Source: Endocrine-Related Cancer - February 5, 2018 Category: Endocrinology Authors: Zhou, Y., Yang, G., Tian, H., Hu, Y., Wu, S., Geng, Y., Lin, K., Wu, W. Tags: Research Source Type: research

Mesenteric fibrosis and palliative surgery in small intestinal neuroendocrine tumours
In conclusion, we confirmed known predictors of MF and mesenteric mass and suggest a role for sex hormones as women ≤52 years have less often a mesenteric mass. Furthermore, the presence of MF has no effect on survival in a multivariate analysis, and we found no benefit of metastasectomy of mesenteric mass or prophylactic surgery on overall survival. (Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - February 5, 2018 Category: Endocrinology Authors: Blažević, A., Zandee, W. T., Franssen, G. J. H., Hofland, J., van Velthuysen, M.-L. F., Hofland, L. J., Feelders, R. A., de Herder, W. W. Tags: Research Source Type: research

The microbiome in PTEN hamartoma tumor syndrome
Germline PTEN mutations defining PTEN hamartoma tumor syndrome (PHTS) confer heritable predisposition to breast, endometrial, thyroid and other cancers with known age-related risks, but it remains impossible to predict if any individual will develop cancer. In the general population, gut microbial dysbiosis has been linked to cancer, yet is unclear whether these are associated in PHTS patients. In this pilot study, we aimed to characterize microbial composition of stool, urine, and oral wash from 32 PTEN mutation-positive individuals using 16S rRNA gene sequencing. PCoA revealed clustering of the fecal microbiome by cancer...
Source: Endocrine-Related Cancer - February 5, 2018 Category: Endocrinology Authors: Byrd, V., Getz, T., Padmanabhan, R., Arora, H., Eng, C. Tags: Research Source Type: research

Circulating miR-375 as a novel prognostic marker for metastatic medullary thyroid cancer patients
This study aimed to identify circulating miRNAs as novel non-invasive biomarkers for prognosis and vandetanib response in advanced medullary thyroid cancer (MTC) patients. We prospectively recruited two independent cohorts of locally advanced/metastatic MTC patients including a subgroup of vandetanib-treated subjects: a discovery cohort (n = 20), including matched plasma/tissue samples (n = 17/20), and a validation cohort, yielding only plasma samples (n = 17). Plasma samples from healthy subjects (n = 36) and MTC patients in remission (n = 9) were used as controls. MTC (n = 17 from 8 patients included in discovery cohort)...
Source: Endocrine-Related Cancer - February 5, 2018 Category: Endocrinology Authors: Romeo, P., Colombo, C., Granata, R., Calareso, G., Gualeni, A. V., Dugo, M., De Cecco, L., Rizzetti, M. G., Zanframundo, A., Aiello, A., Carcangiu, M. L., Gloghini, A., Ferrero, S., Licitra, L., Greco, A., Fugazzola, L., Locati, L. D., Borrello, M. G. Tags: Research Source Type: research

Receptor activities of persistent pollutant serum mixtures and breast cancer risk
Studies on associations between persistent organic pollutants (POPs) and breast cancer risk are inconclusive. The majority of studies have evaluated the effect of single compounds, without considering multiple exposures to and interactions between different POPs. The present study aimed at evaluating breast cancer risk related to combined effects of serum POP mixtures on cellular receptor functions. Data on breast cancer cases (n = 77) and controls (n = 84) were collected among Greenlandic Inuit women. Serum mixtures of lipophilic POPs (lipPOPs), perfluoroalkyl acids (PFAAs) and dioxin-like POPs were extracted. The effect ...
Source: Endocrine-Related Cancer - February 5, 2018 Category: Endocrinology Authors: Wielsoe, M., Bjerregaard-Olesen, C., Kern, P., Bonefeld-Jorgensen, E. C. Tags: Research Source Type: research

Genetic testing for indeterminate thyroid cytology: review and meta-analysis
Thyroid cancer is the most frequent endocrine malignancy, and its incidence is increasing. A current limitation of cytological evaluation of thyroid nodules is that 20–25% are reported as indeterminate. Therefore, an important challenge for clinicians is to determine whether an indeterminate nodule is malignant, and should undergo surgery, or benign, and should be recommended to follow-up. The emergence of precision medicine has offered a valuable solution for this problem, with four tests currently available for the molecular diagnosis of indeterminate cytologies. However, efforts to critically analyze the quality o...
Source: Endocrine-Related Cancer - February 5, 2018 Category: Endocrinology Authors: Vargas-Salas, S., Martinez, J. R., Urra, S., Dominguez, J. M., Mena, N., Uslar, T., Lagos, M., Henriquez, M., Gonzalez, H. E. Tags: Review Source Type: research

Anaplastic thyroid carcinoma: review of treatment protocols
Anaplastic thyroid carcinoma (ATC) is an orphan disease and in most patients fatal. So far no established treatment is available that prolongs survival. Several large retrospective studies have identified negative prognostic markers, analyzed efficacy of multimodal approaches such as radiotherapy with and without concurrent chemotherapy and chemotherapy protocols. Recently, single case reports have suggested some effectiveness of newer therapies targeting single somatic alterations in ATC. Overall, the conclusions that can be drawn from published retrospective studies and the scarce prospective approaches is that new treat...
Source: Endocrine-Related Cancer - February 5, 2018 Category: Endocrinology Authors: Tiedje, V., Stuschke, M., Weber, F., Dralle, H., Moss, L., Fuhrer, D. Tags: Review Source Type: research

Genetics of tumors of the adrenal cortex
This review describes the molecular alterations observed in the various types of tumors of the adrenal cortex, excluding Conn adenomas, especially the alterations identified by genomic approaches these last five years. Two main forms of bilateral adrenocortical tumors can be distinguished according to size and aspect of the nodules: primary pigmented nodular adrenal disease (PPNAD), which can be sporadic or part of Carney complex and primary bilateral macro nodular adrenal hyperplasia (PBMAH). The bilateral nature of the tumors suggests the existence of an underlying genetic predisposition. PPNAD and Carney complex are mai...
Source: Endocrine-Related Cancer - February 5, 2018 Category: Endocrinology Authors: Bonnet-Serrano, F., Bertherat, J. Tags: Review Source Type: research

Towards optimal personalized diet and vitamin supplementation in NET patients
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - February 5, 2018 Category: Endocrinology Authors: de Hosson, L. D., Stelwagen, J., Bouma, G., Sijtema, B., Huitema, S., van Faassen, H. J. R., de Bock, G. H., de Groot, D. J. A., Campmans-Kuijpers, M. J. E., Kema, I. P., de Vries, E. G. E., Walenkamp, A. M. E. Tags: Research Letter Source Type: research

Higher prevalence of lymph node metastasis in prostate cancer in patients with diabetes
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - February 5, 2018 Category: Endocrinology Authors: Lutz, S. Z., Todenhofer, T., Wagner, R., Hennenlotter, J., Ferchl, J. M., Scharpf, M. O., Martus, P., Staiger, H., Fritsche, A., Stenzl, A., Haring, H.-U., Heni, M. Tags: Research Letter Source Type: research

Nfe2l1-silenced insulinoma cells acquire aggressiveness and chemoresistance
The transcription factor nuclear factor erythroid 2-like 1 (NFE2L1 or NRF1) is involved in various critical cell processes such as maintenance of ubiquitin-proteasome system and regulation of the cellular antioxidant response. We previously determined that pancreatic β-cell-specific Nfe2l1-knockout mice had hyperinsulinemia and that silencing of Nfe2l1 in mouse islets or MIN6 insulinoma β-cells induced elevated basal insulin release and altered glucose metabolism. Hypoglycemia is a major issue with aggressive insulinomas, although a role of NFE2L1 in this pathology is not defined. In the present work, we studied ...
Source: Endocrine-Related Cancer - January 31, 2018 Category: Endocrinology Authors: Fu, J., Zheng, H., Cui, Q., Chen, C., Bao, S., Sun, J., Li, L., Yang, B., Wang, H., Hou, Y., Xu, Y., Xu, Y., Zhang, Q., Pi, J. Tags: Research Source Type: research

Copy number profiling of oncogenes in ductal carcinoma in situ of the male breast
Characterizing male breast cancer (BC) and unraveling male breast carcinogenesis is challenging because of the rarity of this disease. We investigated copy number status of 22 BC-related genes in 18 cases of pure ductal carcinoma in situ (DCIS) and in 49 cases of invasive carcinoma (IC) with adjacent DCIS (DCIS-AIC) in males using multiplex ligation-dependent probe amplification (MLPA). Results were compared to female BC and correlated with survival. Overall, copy number ratio and aberration frequency including all 22 genes showed no significant difference between the 3 groups. Individual unpaired analysis revealed a signi...
Source: Endocrine-Related Cancer - January 31, 2018 Category: Endocrinology Authors: Vermeulen, M. A., Doebar, S. C., van Deurzen, C. H. M., Martens, J. W. M., van Diest, P. J., Moelans, C. B. Tags: Research Source Type: research

The role of the AR/ER ratio in ER-positive breast cancer patients
The significance of androgen receptor (AR) in breast cancer (BC) management is not fully defined, and it is still ambiguous how the level of AR expression influences oestrogen receptor-positive (ER+) tumours. The aim of the present study was to analyse the prognostic impact of AR/ER ratio, evaluated by immunohistochemistry (IHC), correlating this value with clinical, pathological and molecular characteristics. We retrospectively selected a cohort of 402 ER+BC patients. On each tumour, IHC analyses for AR, ER, PgR, HER2 and Ki67 were performed and AR+ cases were used to calculate the AR/ER value. A cut-off of ≥2 was sele...
Source: Endocrine-Related Cancer - January 31, 2018 Category: Endocrinology Authors: Rangel, N., Rondon-Lagos, M., Annaratone, L., Osella-Abate, S., Metovic, J., Mano, M. P., Bertero, L., Cassoni, P., Sapino, A., Castellano, I. Tags: Research Source Type: research

Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum
Small intestinal neuroendocrine tumours (SI-NETs) are neoplasms characterized by their ability to secrete biogenic amines and peptides. These cause distinct clinical pathology including carcinoid syndrome, marked by diarrhoea and flushing, as well as fibrosis, notably mesenteric fibrosis. Mesenteric fibrosis often results in significant morbidity by causing intestinal obstruction, oedema and ischaemia. Although advancements have been made to alleviate symptoms of carcinoid syndrome and prolong the survival of patients with SI-NETs, therapeutic options for patients with mesenteric fibrosis are still limited. As improved ins...
Source: Endocrine-Related Cancer - January 31, 2018 Category: Endocrinology Authors: Blažević, A., Hofland, J., Hofland, L. J., Feelders, R. A., de Herder, W. W. Tags: Review Source Type: research

Detection and monitoring of circulating tumor DNA in adrenocortical carcinoma
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - January 31, 2018 Category: Endocrinology Authors: Garinet, S., Nectoux, J., Neou, M., Pasmant, E., Jouinot, A., Sibony, M., Orhant, L., Pipoli da Fonseca, J., Perlemoine, K., Bricaire, L., Groussin, L., Soubrane, O., Dousset, B., Libe, R., Letourneur, F., Bertherat, J., Assie, G. Tags: Research Letter Source Type: research

8th edition of the AJCC/TNM staging system of thyroid cancer: what to expect (ITCO#2)
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - January 31, 2018 Category: Endocrinology Authors: Lamartina, L., Grani, G., Arvat, E., Nervo, A., Zatelli, M. C., Rossi, R., Puxeddu, E., Morelli, S., Torlontano, M., Massa, M., Bellantone, R., Pontecorvi, A., Montesano, T., Pagano, L., Daniele, L., Fugazzola, L., Ceresini, G., Bruno, R., Rossetto, R., T Tags: Research Letter Source Type: research

RET-mediated modulation of tumor microenvironment and immune response in multiple endocrine neoplasia type 2 (MEN2)
Medullary thyroid carcinomas (MTC) arise from thyroid parafollicular, calcitonin-producing C-cells and can occur either as sporadic or as hereditary diseases in the context of familial syndromes, including multiple endocrine neoplasia 2A (MEN2A), multiple endocrine neoplasia 2B (MEN2B) and familial MTC (FMTC). In a large fraction of sporadic cases, and virtually in all inherited cases of MTC, activating point mutations of the RET proto-oncogene are found. RET encodes for a receptor tyrosine kinase protein endowed with transforming potential on thyroid parafollicular cells. As in other cancer types, microenvironmental facto...
Source: Endocrine-Related Cancer - January 18, 2018 Category: Endocrinology Authors: Castellone, M. D., Melillo, R. M. Tags: Thematic Review Source Type: research

Non-mammalian models of multiple endocrine neoplasia type 2
Twenty-five years ago, RET was identified as the primary driver of multiple endocrine neoplasia type 2 (MEN2) syndrome. MEN2 is characterized by several transformation events including pheochromocytoma, parathyroid adenoma and, especially penetrant, medullary thyroid carcinoma (MTC). Overall, MTC is a rare but aggressive type of thyroid cancer for which no effective treatment currently exists. Surgery, radiation, radioisotope treatment and chemotherapeutics have all shown limited success, and none of these approaches have proven durable in advanced disease. Non-mammalian models that incorporate the oncogenic RET isoforms a...
Source: Endocrine-Related Cancer - January 18, 2018 Category: Endocrinology Authors: Das, T. K., Cagan, R. L. Tags: Thematic Review Source Type: research

Structure and function of RET in multiple endocrine neoplasia type 2
It has been twenty-five years since the discovery of oncogenic germline RET mutations as the cause of multiple endocrine neoplasia type 2 (MEN2). Intensive work over the last two and a half decades on RET genetics, signaling and cell biology has provided the current bases for the genotype–phenotype and functional correlations within this cancer syndrome. On the contrary, the structural and molecular basis for RET tyrosine kinase domain activation and oncogenic deregulation has remained largely elusive. Recent studies with a strong crystallographic and biochemical focus have started to elucidate key insights into such...
Source: Endocrine-Related Cancer - January 18, 2018 Category: Endocrinology Authors: Plaza-Menacho, I. Tags: Thematic Review Source Type: research

Patient quality of life and prognosis in multiple endocrine neoplasia type 2
Multiple endocrine neoplasia type 2 (MEN2) refers to the autosomal-dominant neuroendocrine tumour syndromes, MEN type 2A (MEN2A) and MEN type 2B (MEN2B). They are typified by the development of medullary thyroid cancer (MTC), phaeochromocytoma and parathyroid hyperplasia in MEN2A and MTC, phaeochromocytomas, ganglioneuromatosis and skeletal abnormalities in MEN2B. The aggressiveness of MTC is variable according to genotype, and although it is still the major cause of mortality in both conditions, prognosis has improved dramatically in those diagnosed and treated at a young age thanks to predictive genetic testing. Neverthe...
Source: Endocrine-Related Cancer - January 18, 2018 Category: Endocrinology Authors: Grey, J., Winter, K. Tags: Thematic Review Source Type: research

Novel targeted therapeutics for MEN2
The rearranged during transfection (RET) proto-oncogene was recognized as the multiple endocrine neoplasia type 2 (MEN2) causing gene in 1993. Since then, much effort has been put into a clear understanding of its oncogenic signaling, its biochemical function and ways to block its aberrant activation in MEN2 and related cancers. Several small molecules have been designed, developed or redirected as RET inhibitors for the treatment of MEN2 and sporadic MTC. However, current drugs are mostly active against several other kinases, as they were not originally developed for RET. This limits efficacy and poses safety issues. Ther...
Source: Endocrine-Related Cancer - January 18, 2018 Category: Endocrinology Authors: Redaelli, S., Plaza-Menacho, I., Mologni, L. Tags: Thematic Review Source Type: research

Advances in risk-oriented surgery for multiple endocrine neoplasia type 2
Genetic association studies hinge on definite clinical case definitions of the disease of interest. This is why more penetrant mutations were overrepresented in early multiple endocrine neoplasia type 2 (MEN2) studies, whereas less penetrant mutations went underrepresented. Enrichment of genetic association studies with advanced disease may produce a flawed understanding of disease evolution, precipitating far-reaching surgical strategies like bilateral total adrenalectomy and 4-gland parathyroidectomy in MEN2. The insight into the natural course of the disease gleaned over the past 25 years caused a paradigm shift in MEN2...
Source: Endocrine-Related Cancer - January 18, 2018 Category: Endocrinology Authors: Machens, A., Dralle, H. Tags: Thematic Review Source Type: research

A comprehensive review on MEN2B
MEN2B is a very rare autosomal dominant hereditary tumor syndrome associated with medullary thyroid carcinoma (MTC) in 100% cases, pheochromocytoma in 50% cases and multiple extra-endocrine features, many of which can be quite disabling. Only few data are available in the literature. The aim of this review is to try to give further insights into the natural history of the disease and to point out the missing evidence that would help clinicians optimize the management of such patients. MEN2B is mainly characterized by the early occurrence of MTC, which led the American Thyroid Association to recommend preventive thyroidecto...
Source: Endocrine-Related Cancer - January 18, 2018 Category: Endocrinology Authors: Castinetti, F., Moley, J., Mulligan, L., Waguespack, S. G. Tags: Thematic Review Source Type: research

Looking beyond the thyroid: advances in the understanding of pheochromocytoma and hyperparathyroidism phenotypes in MEN2 and of non-MEN2 familial forms
Over the last years, the knowledge of MEN2 and non-MEN2 familial forms of pheochromocytoma (PHEO) has increased. In MEN2, PHEO is the second most frequent disease: the penetrance and age at diagnosis depend on the mutation of RET. Given the prevalence of bilateral PHEO (50% by age 50), adrenal sparing surgery, aimed at sparing a part of the adrenal cortex to avoid adrenal insufficiency, should be systematically considered in patients with bilateral PHEO. Non-MEN2 familial forms of PHEO now include more than 20 genes: however, only small phenotypic series have been reported, suggesting that phenotypic features of isolated h...
Source: Endocrine-Related Cancer - January 18, 2018 Category: Endocrinology Authors: Guerin, C., Romanet, P., Taieb, D., Brue, T., Lacroix, A., Sebag, F., Barlier, A., Castinetti, F. Tags: Thematic Review Source Type: research

Advances in the management of MEN2: from improved surgical and medical treatment to novel kinase inhibitors
Medullary thyroid carcinoma (MTC), a tumor derived from the neural crest, occurs either sporadically or as the dominant component of the type 2 multiple endocrine neoplasia (MEN) syndromes, MEN2A and MEN2B. The discovery that mutations in the RET protooncogene cause hereditary MTC was of great importance, since it led to the development of novel methods of diagnosis and treatment. For example, the detection of a mutated RET allele in family members at risk for inheriting MEN2A or MEN2B signaled that they would develop MTC, and possibly other components of the syndromes. Furthermore, the detection of a mutated allele create...
Source: Endocrine-Related Cancer - January 18, 2018 Category: Endocrinology Authors: Wells, S. A. Tags: Thematic Review Source Type: research

The evolving clinical, genetic and therapeutic landscape of multiple endocrine neoplasia type 2
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - January 18, 2018 Category: Endocrinology Authors: Moodley, S., Weber, F., Mulligan, L. M. Tags: Editorials Source Type: research

A unifying biology of sex steroid-induced apoptosis in prostate and breast cancers
Prostate and breast cancer are the two cancers with the highest incidence in men and women, respectively. Here, we focus on the known biology of acquired resistance to antihormone therapy of prostate and breast cancer and compare laboratory and clinical similarities in the evolution of the disease. Laboratory studies and clinical observations in prostate and breast cancer demonstrate that cell selection pathways occur during acquired resistance to antihormonal therapy. Following sex steroid deprivation, both prostate and breast cancer models show an initial increased acquired sensitivity to the growth potential of sex ster...
Source: Endocrine-Related Cancer - January 16, 2018 Category: Endocrinology Authors: Maximov, P. Y., Abderrahman, B., Curpan, R. F., Hawsawi, Y. M., Fan, P., Jordan, V. C. Tags: Review Source Type: research

Long noncoding RNAs: emerging players in thyroid cancer pathogenesis
Thyroid cancer continues to be the most common malignancy of endocrine glands. The incidence of thyroid cancer has risen significantly over the past 4 decades and has emerged as a major health issue. In recent years, significant progress has been achieved in our understanding of the molecular mechanisms of thyroid carcinogenesis, resulting in significant diagnostic, prognostic and therapeutic implications; yet, it has not reached a satisfactory level. Identifying novel molecular therapeutic targets and molecules for diagnosis and prognosis is expected to advance the overall management of this common malignancy. Long noncod...
Source: Endocrine-Related Cancer - January 16, 2018 Category: Endocrinology Authors: Murugan, A. K., Munirajan, A. K., Alzahrani, A. S. Tags: Review Source Type: research

Characterization of neuroendocrine tumors in heterozygous mutant MENX rats: a novel model of invasive medullary thyroid carcinoma
Rats affected by the MENX syndrome spontaneously develop multiple neuroendocrine tumors (NETs) including adrenal, pituitary and thyroid gland neoplasms. MENX was initially reported to be inherited as a recessive trait and affected rats were found to be homozygous for the predisposing Cdkn1b mutation encoding p27. We here report that heterozygous MENX-mutant rats (p27+/mut) develop the same spectrum of NETs seen in the homozygous (p27mut/mut) animals but with slower progression. Consequently, p27+/mut rats have a significantly shorter lifespan compared with their wild-type (p27+/+) littermates. In the tumors of p27+/mut rat...
Source: Endocrine-Related Cancer - January 10, 2018 Category: Endocrinology Authors: Molatore, S., Kugler, A., Irmler, M., Wiedemann, T., Neff, F., Feuchtinger, A., Beckers, J., Robledo, M., Roncaroli, F., Pellegata, N. S. Tags: Research Source Type: research

Classification of gastrointestinal stromal tumor syndromes
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, thought to derive from neoplastic outgrowth of the interstitial cells of Cajal. Building on recent advances in recognition, classification and diagnosis, the past two decades have seen a changing paradigm with molecular diagnostics and targeted therapies. KIT and PDGFRA mutations account for 85–90% of GIST carcinogenesis. However, the remaining 10–15% of GISTs, which until recently were called KIT/PDGFRA wild-type GISTs, have been found to have one of the several mutations, including in the SDHA, B, C, ...
Source: Endocrine-Related Cancer - January 10, 2018 Category: Endocrinology Authors: Gopie, P., Mei, L., Faber, A. C., Grossman, S. R., Smith, S. C., Boikos, S. A. Tags: Review Source Type: research

Notch pathway inhibition targets chemoresistant insulinoma cancer stem cells
This study was aimed to characterise and target INS CSCs in order to develop novel targeted therapies. Highly invasive and tumourigenic human and canine INS CSC-like cells were successfully isolated. These cells expressed stem cell markers (OCT4, SOX9, SOX2, CD133 and CD34), exhibited greater resistance to 5-fluorouracil (5-FU) and demonstrated a more invasive and tumourigenic phenotype in vivo compared to bulk INS cells. Here, we demonstrated that Notch-signalling-related genes (NOTCH2 and HES1) were overexpressed in INS CSC-like cells. Protein analysis showed an active NOTCH2-HES1 signalling in INS cell lines, especially...
Source: Endocrine-Related Cancer - January 8, 2018 Category: Endocrinology Authors: Capodanno, Y., Buishand, F. O., Pang, L. Y., Kirpensteijn, J., Mol, J. A., Argyle, D. J. Tags: Research Source Type: research

Neoadjuvant palbociclib on ER+ breast cancer (N007): clinical response and EndoPredicts value
The purpose of the study was to test the efficacy of neoadjuvant palbociclib therapy and to evaluate its impact on cell cycle arrest and changes in EndoPredict (EP) scores before and after treatment. Postmenopausal women with histologically proven ER+ve, HER2–ve invasive breast cancer, 2 cm or greater, were enrolled in an open-label, single-arm study. Twenty eligible patients were given letrozole 2.5 mg per day together with palbociclib 125 mg per day for 3 out of 4 weeks in repeated cycles for 16 weeks (4 cycles) before surgery. The primary end points were clinical response rates (cRR) and preoperative endocrine pro...
Source: Endocrine-Related Cancer - January 8, 2018 Category: Endocrinology Authors: Chow, L. W. C., Morita, S., Chow, C. Y. C., Ng, W.-K., Toi, M. Tags: Research Source Type: research

Enhancement of mammary tumour growth by IGFBP-3 involves impaired T cell accumulation
This study aimed to examine how IGFBP-3 promotes tumour growth by influencing the immune tumour microenvironment in healthy and obese mice. Syngeneic EO771 cells, which lack detectable IGFBP-3 expression, were grown as orthotopic tumours in WT and IGFBP-3-null C57BL/6 mice placed on either a control chow or a high-fat diet (HFD), and examined by quantitative PCR and immunohistochemistry. In WT mice, increased stromal expression of IGFBP-3 was positively associated with tumour growth, supporting the hypothesis that IGFBP-3 in the microenvironment promotes tumour progression. Examining markers of immune cell subsets, gene ex...
Source: Endocrine-Related Cancer - January 8, 2018 Category: Endocrinology Authors: Scully, T., Scott, C. D., Firth, S. M., Sedger, L. M., Pintar, J. E., Twigg, S. M., Baxter, R. C. Tags: Research Source Type: research

The next step: mechanisms driving adrenocortical carcinoma metastasis
Endocrine tumors have the peculiarity to become clinically evident not only due to symptoms related to space occupation by the growing lesion, similarly to most other tumors, but also, and most often, because of their specific hormonal secretion, which significantly contributes to their pathological burden. Malignant endocrine tumors, in addition, have the ability to produce distant metastases. Here, we critically review the current knowledge about mechanisms and biomarkers characterizing the metastatic process in adrenocortical carcinoma (ACC), a rare endocrine malignancy with a high risk of relapse and metastatization ev...
Source: Endocrine-Related Cancer - January 8, 2018 Category: Endocrinology Authors: Lalli, E., Luconi, M. Tags: Review Source Type: research

TSC2 rare germline variants in non-tuberous sclerosis patients with neuroendocrine neoplasias
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - January 8, 2018 Category: Endocrinology Authors: Asprino, P. F., Linck, R. D. M., Cesar, J., Freitas, F. P., Koyama, F. C., Riechelmann, R. S. P., Costa, F. P., Hoff, P. M. G., Galante, P. A. F., Meyer, D., Camargo, A. A., Sabbaga, J. Tags: Research Letter Source Type: research

Bortezomib sensitizes thyroid cancer to BRAF inhibitor in vitro and in vivo
In this study, BRAFV600E-bearing TC cells were treated with BRAFV600E inhibitor, Vemurafenib alone or in combination with the proteasome inhibitor, Bortezomib. The combination of both drugs showed synergistic effects as evidenced by cell growth inhibition (P
Source: Endocrine-Related Cancer - December 21, 2017 Category: Endocrinology Authors: Tsumagari, K., Abd Elmageed, Z. Y., Sholl, A. B., Green, E. A., Sobti, S., Khan, A. R., Kandil, A., Murad, F., Friedlander, P., Boulares, A. H., Kandil, E. Tags: Research Source Type: research

ROS-induced near-homozygous genomes in thyroid cancer
A near-homozygous genome (NHG) is especially seen in a subset of follicular thyroid cancer of the oncocytic type (FTC-OV). An NHG was also observed in the metabolically relatively quiescent cell lines XTC.UC1, a model for FTC-OV, and in FTC-133, -236 and -238, the latter three derived from one single patient with follicular thyroid cancer. FTC-236 subclones showed subtle whole-chromosome differences indicative of sustained reciprocal mitotic missegregations. Reactive oxygen species (ROS) scavenger experiments reduced the number of chromosomal missegregations in XTC.UC1 and FTC-236, while pCHK2 was downregulated in these ce...
Source: Endocrine-Related Cancer - December 21, 2017 Category: Endocrinology Authors: Corver, W. E., Demmers, J., Oosting, J., Sahraeian, S., Boot, A., Ruano, D., Wezel, T. v., Morreau, H. Tags: Research Source Type: research

Knockdown of BRCA2 enhances cisplatin and cisplatin-induced autophagy in ovarian cancer cells
Clinical implications of the BRCA2 expression level on treatments of ovarian cancer are controversial. Here, we demonstrated that platinum-resistant cancer had a higher percentage of high BRCA2 level (87.5% vs 43.6%, P = 0.001), and that patients with a low BRCA2 level in cancer tissues had longer progression-free survival (with a median time of 28.0 vs 12.0 months, P
Source: Endocrine-Related Cancer - December 18, 2017 Category: Endocrinology Authors: Wan, B., Dai, L., Wang, L., Zhang, Y., Huang, H., Qian, G., Yu, T. Tags: Research Source Type: research

A novel model to predict positive prostate biopsy based on serum androgen level
This study aims to develop a novel model for predicting positive prostate biopsy based on serum androgen levels. This study included 253 Japanese patients who underwent prostate biopsy at our institution. TT and FT, %FT (=FT/TT), age, PSA, prostate volume (PV) and PSA density (PSAD = PSA/PV) were assessed for association with prostate biopsy findings. The following results were obtained. Of 253 patients, 145 (57.3%) had positive biopsies. Compared to the negative biopsy group, the positive biopsy group demonstrated higher age, PSA and PSAD but lower PV, FT and %FT by univariate analysis. Multivariate logistic regression an...
Source: Endocrine-Related Cancer - December 18, 2017 Category: Endocrinology Authors: Ujike, T., Uemura, M., Kawashima, A., Nagahara, A., Fujita, K., Miyagawa, Y., Nonomura, N. Tags: Research Source Type: research

Differentiated thyroid cancer: millions spent with no tangible gain?
The incidence of differentiated thyroid cancer (DTC) has rapidly increased worldwide over the last decades. It is unknown if the increase in diagnosis has been mirrored by an increase in thyroidectomy rates with the concomitant economic impact that this would have on the health care system. DTC and thyroidectomy incidence as well as DTC-specific mortality were modeled using Poisson regression in New South Wales (NSW), Australia per year and by sex. The incidence of 2002 was the point from which the increase in rates was assessed cumulatively over the subsequent decade. The economic burden of potentially avoidable thyroidec...
Source: Endocrine-Related Cancer - December 18, 2017 Category: Endocrinology Authors: Furuya-Kanamori, L., Sedrakyan, A., Onitilo, A. A., Bagheri, N., Glasziou, P., Doi, S. A. R. Tags: Research Source Type: research