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Endocrine neoplasia

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https://www.readbyqxmd.com/read/28639308/discovery-of-novel-wtret-and-v804mret-inhibitors-from-hit-to-lead
#1
Luca Mologni, Martina Dalla Via, Adriana Chilin, Manlio Palumbo, Giovanni Marzaro
Oncogenic activation of the RET kinase has been found in several neoplastic diseases, like medullary thyroid carcinoma, multiple endocrine neoplasia, papillary thyroid carcinoma and non-small cells lung cancer. Currently approved RET inhibitors were not originally designed to be RET inhibitors and their potency against RET kinase has not been optimized. Hence, novel compounds able to inhibit both wtRET and its mutants (e.g. V804MRET) are needed. Herein we present the development and the preliminary evaluation of a new sub-micromolar wtRET/V804MRET inhibitor (69) endowed with 4-anilinopyridine structure, starting from our previously identified 4-anilinopyrimidine hit compound...
June 22, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28635633/new-insights-in-thyroid-cancer-and-p53-family-proteins
#2
REVIEW
Livia Manzella, Stefania Stella, Maria Stella Pennisi, Elena Tirrò, Michele Massimino, Chiara Romano, Adriana Puma, Martina Tavarelli, Paolo Vigneri
Thyroid cancers are common endocrine malignancies that comprise tumors with different clinical and histological features. Indeed, papillary and follicular thyroid cancers are slow-growing, well-differentiated tumors, whereas anaplastic thyroid cancers are undifferentiated neoplasias that behave much more aggressively. Well-differentiated thyroid carcinomas are efficiently cured by surgery and radioiodine, unlike undifferentiated tumors that fail to uptake radioactive iodine and are usually resistant to chemotherapy...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28617892/intestinal-heterotopic-pancreas-involved-by-simultaneous-panin-2-lesion-and-endocrine-microadenoma-a-unique-case
#3
Remus Cornea, Sorina Taban, Cristian Suciu, Codruta Lazureanu, Alis Dema
We hereby present the case of a 58-year-old male who underwent a total gastrectomy for gastric neoplasm. During the surgery, a tumor mass in the jejunum was identified, considered as metastasis, and resected. The histopathological examination of the jejunal lesion showed ectopic pancreas. In this area, two pathological distinct lesions were identified, one histologically compatible with pancreatic intraepithelial neoplasia (PanIN) type 2 lesion and the other with morphologic criteria for endocrine microadenoma...
June 2017: Journal of Gastrointestinal and Liver Diseases: JGLD
https://www.readbyqxmd.com/read/28614983/second-primary-cancer-in-patients-with-differentiated-thyroid-cancer-does-radioiodine-play-a-role
#4
Margarida Silva-Vieira, Sofia Carrilho-Vaz, Susana Esteves, Teresa C Ferreira, Edward Limbert, Lucília Salgado, Valeriano Leite
BACKGROUND: Well Differentiated Thyroid Cancer (WDTC) is the most common endocrine neoplasia and its incidence is rising. Studies have reported an increased risk of Second Primary Cancer (SPC) in WDTC survivors, but its relationship with radioiodine treatment (RAIT) and other risk factors remains controversial. We evaluated whether RAIT is an independent risk factor for SPC in WDTC patients. METHODS: This was a retrospective single-center study. We included 2031 patients with WDTC diagnosed between 1998 and 2009, treated and followed in our reference tertiary cancer center...
June 14, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28610401/oncogenesis-of-thyroid-cancer
#5
Enas Younis
Thyroid neoplasms encompass a variety of lesions that range from benign adenomas to malignancies. These latter can be well-differentiated, poorly differentiated or undifferentiated (anaplastic) carcinomas. More than 95% of thyroid cancers are derived from thyroid follicular cells, while 2-3% (medullary thyroid cancers, MTC) originate from calcitonin producing C-cells. Over the last decade, investigators have developed a clearer understanding of genetic alterations underlying thyroid carcinogenesis. A number of point mutations and translocations are involved, not only in its tumorigenesis, but also as have potential use as diagnostic and prognostic indicators and therapeutic targets...
May 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28605116/phaeochromocytoma-in-multiple-endocrine-neoplasia-type-2-ret-codon-specific-penetrance-and-changes-in-management-during-the-last-four-decades
#6
L Mucha, G Leidig-Bruckner, K Frank-Raue, Th Bruckner, M Kroiss, F Raue
OBJECTIVES: We describe phaeochromocytoma penetrance in multiple endocrine neoplasia type 2 (MEN2) according to RET protooncogene-specific mutations, and report changes in phaeochromocytoma diagnosis and management from 1968 to 2015. DESIGN: This retrospective chart review included 309 MEN2 patients from one specialised ambulatory care centre. Phaeochromocytoma patients were categorised by diagnosis date: early, 1968-1996, n = 40; and recent, 1997-2015, n = 45. RESULTS: Phaeochromocytoma was diagnosed in 85/309 patients with RET mutations in the following exons (phaeos/all carriers, %): exon 11 (56/120, 46·6%); exon 16 (7/17, 41·2%), exon 10 (14/47, 29·8%), and exon 13-15 (2/116, 1·7%)...
June 12, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28597079/men1-mutations-and-potentially-men1-targeting-mirnas-are-responsible-for-menin-deficiency-in-sporadic-and-men1-syndrome-associated-primary-hyperparathyroidism
#7
Vince Kornél Grolmusz, Katalin Borka, Annamária Kövesdi, Kinga Németh, Katalin Balogh, Csaba Dékány, András Kiss, Anna Szentpéteri, Beatrix Sármán, Anikó Somogyi, Éva Csajbók, Zsuzsanna Valkusz, Miklós Tóth, Péter Igaz, Károly Rácz, Attila Patócs
Inherited, germline mutations of menin-coding MEN1 gene cause multiple endocrine neoplasia type 1 (MEN1), while somatic MEN1 mutations are the sole main driver mutations in sporadic primary hyperparathyroidism (PHPT), suggesting that menin deficiency has a central role in the pathogenesis of PHPT. MiRNAs are small, noncoding RNAs posttranscriptionally regulating gene expression. Our aim was to investigate both the role of MEN1 mutations and potentially MEN1-targeting miRNAs as the underlying cause of menin deficiency in MEN1-associated and sporadic PHPT tissues...
June 8, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28589571/laparoscopic-total-pancreatectomy-for-multiple-endocrine-neoplasia-type-1-syndrome-associated-multifocal-non-functioning-pancreatic-neuroendocrine-tumor-a-case-report
#8
Palanisamy Senthinathan, Samrat Vijaykumar Jankar, Sandeep C Sabnis, Vivek Kaje, Sivakumar Srivatsan Gurumurthy, Natesan Anand Vijai, Vaiyapurigounder Palanisamy Nalankilli, Palanivelu Praveen Raj, Ramakrishanan Parthasarathi, Subbiah Rajapandian, Chinnusamy Palanivelu
Pancreatic neuroendocrine tumors are rare, accounting for less than 3% of all pancreatic tumors. Although laparoscopic pancreas-preserving surgery for managing sporadic pancreatic neuroendocrine tumors has been described in the literature, laparoscopic total pancreatectomy has rarely been reported. We present a 30-year-old man who was incidentally diagnosed with multiple endocrine neoplasia type 1 syndrome with parathyroid hyperplasia and a non-functioning pancreatic neuroendocrine tumor. He underwent laparoscopic total pancreatectomy with splenectomy...
June 6, 2017: Asian Journal of Endoscopic Surgery
https://www.readbyqxmd.com/read/28582344/androgen-receptor-expression-in-endometrial-carcinoma
#9
Sara L Zadeh, Linda R Duska, Anne M Mills
Endometrial carcinoma (ECA) is frequently hormonally driven and can be treated with endocrine-based therapy, yet hormone receptor status is not routinely assessed. In particular, little is known about the significance of androgen receptor (AR) in ECA. Androgen has antiproliferative effects in the healthy endometrium and could serve a similar role to progesterone in curbing the progression of estrogen-dependent neoplasia. There may also be a subset of ECA that benefits from androgen antagonistic therapy. We herein investigate AR expression across ECA subtypes and compare its expression to estrogen receptor (ER) and progesterone receptor (PR)...
June 2, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/28578594/novel-somatic-ret-mutation-questioning-the-causality-of-the-ret-i852m-germline-sequence-variant-in-multiple-endocrine-neoplasia-2a
#10
Jes Sloth Mathiesen, Thomas V O Hansen, Åse Krogh Rasmussen, Tina Duelund Hjortshøj, Katalin Kiss, Stine Rosenkilde Larsen, Lotte Nylandsted Krogh, Anja Lisbeth Frederiksen, Anne Pernille Hermann, Christian Godballe
"Letter to the Editor" format requires no Abstract.
June 3, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28569245/genetic-diagnosis-of-a-chinese-multiple-endocrine-neoplasia-type-2a-family-through-whole-genome-sequencing
#11
Zhen-Fang DU, Peng-Fei Li, Jian-Qiang Zhao, Zhi-Lie Cao, Feng Li, Ju-Ming Ma, Xiao-Ping Qi
Approximately 98% of patients with multiple endocrine neoplasia type 2A (MEN 2A) have an identifiable RET mutation. Prophylactic or early total thyroidectomy or pheochromocytoma/parathyroid removal in patients can be preventative or curative and has become standard management. The general strategy for RET screening on family members at risk is to sequence the most commonly affected exons and, if negative, to extend sequencing to additional exons. However, different families with MEN 2A due to the same RET mutation often have significant variability in the clinical exhibition of disease and aggressiveness of the MTC, which implies additional genetic loci exsit beyond RET coding region...
June 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28567607/pancreatic-neuroendocrine-tumors-in-men1-disease-a-mono-centric-longitudinal-and-prognostic-study
#12
S Chiloiro, F Lanza, A Bianchi, G Schinzari, M G Brizi, A Giampietro, V Rufini, F Inzani, A Giordano, G Rindi, A Pontecorvi, L De Marinis
PURPOSE: Multiple endocrine neoplasia type 1 (MEN1) is an inherited endocrine neoplastic syndrome associated with a greater risk of endocrine tumor development like pancreatic neuroendocrine tumors (p-NET), with different clinical characteristics from sporadic ones. This paper aims to compare clinical, hystological and morphological aspects of p-NET in patients affected from MEN1 (MEN1+) and not-affected ones (MEN1-). METHODS: We performed a retrospective observational study...
May 31, 2017: Endocrine
https://www.readbyqxmd.com/read/28566601/challenging-differential-diagnosis-of-hypergastremia-and-hyperglucagonemia-with-chronic-renal-failure-report-of-a-case-with-multiple-endocrine-neoplasia-type-1
#13
Takaaki Murakami, Takeshi Usui, Yuji Nakamoto, Akio Nakajima, Yuki Mochida, Sumio Saito, Takahiro Shibayama, Nobuhisa Yamazaki, Tomonobu Hatoko, Tomoko Kato, Shin Yonemitsu, Seiji Muro, Shogo Oki
A 53-year-old woman developed end-stage renal failure during a 15-year clinical course of primary hyperparathyroidism and was referred to our hospital for evaluation of suspected multiple endocrine neoplasia type 1 (MEN1). Genetic testing revealed a novel deletion mutation at codon 467 in exon 10 of the MEN1 gene. Systemic and selective arterial calcium injection (SACI) testing revealed hyperglucagonemia and hypergastrinemia with positive gastrin responses. A pathological examination revealed glucagonoma and a lymph node gastrinoma...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28562256/sporadic-insulinoma-presenting-as-early-morning-night-terrors
#14
Daniel Beisang, Gregory P Forlenza, Mark Luquette, Kyriakie Sarafoglou
A 16-year-old boy with a recent diagnosis of night terrors was evaluated for recurrent early morning hypoglycemia after an early morning seizure. Evaluation in clinic with critical laboratories identified hyperinsulinemic hypoglycemia. Additional investigation revealed a sporadic insulinoma as the etiology of his hypoglycemia and all symptoms were resolved after pancreaticoduodenectomy. The importance of obtaining critical laboratory samples is highlighted and appropriate radiologic, medical, and pathologic testing is discussed...
May 24, 2017: Pediatrics
https://www.readbyqxmd.com/read/28553188/incidental-detection-of-synchronous-medullary-thyroid-carcinoma-with-bilateral-adrenal-pheochromocytoma-on-iodine-123-metaiodobenzylguanidine-scintigraphy-leading-to-diagnosis-of-multiple-endocrine-neoplasia-2a
#15
Asif Ali Fakhri, Paul David Rodrigue, Mustafa Aladin, Aun Hussain
We report a case of a 29-year-old female with the family history of medullary thyroid carcinoma (MTC) presenting with hematuria and tachycardia, who was found to have bilateral adrenal masses on abdominal computed tomography and biochemical testing compatible with pheochromocytoma. Iodine-123 (I-123) metaiodobenzylguanidine (MIBG) scintigraphy for preoperative planning prior to planned adrenalectomy revealed incidental synchronous unifocal MTC, along with expected bilateral adrenal pheochromocytomas. Pathology confirmed these findings, and subsequent genetic testing confirmed a rearranged during transfection proto-oncogene mutation on exon 11, confirming the clinical diagnosis of multiple endocrine neoplasia 2A (MEN 2A)...
April 2017: World Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28553179/peptide-receptor-radionuclide-therapy-with-177-lu-dotatate-for-metastatic-neuroendocrine-tumor-occurring-in-association-with-multiple-endocrine-neoplasia-type-1-and-cushing-s-syndrome
#16
Chinna Naik, Sandip Basu
Neuroendocrine tumor (NET) occurring in association with other endocrine syndromes forms a distinct entity. The aim was to assess the therapy response profile of the routine peptide receptor radionuclide therapy (PRRT) in this relatively uncommon but clinically challenging subgroup of patients. A retrospective analysis was undertaken from the case records from those who were treated with (177)Lu-DOTATATE for metastatic NET. In addition to assessing the therapeutic efficacy, emphasis was also given to study lesional sites and scan pattern...
April 2017: World Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28506408/genetics-of-medullary-thyroid-cancer-an-overview
#17
REVIEW
Giacomo Accardo, Giovanni Conzo, Daniela Esposito, Claudio Gambardella, Marco Mazzella, Filomena Castaldo, Carlo Di Donna, Andrea Polistena, Nicola Avenia, Vittorio Colantuoni, Dario Giugliano, Daniela Pasquali
Medullary thyroid carcinoma (MTC) represents 3-5% of thyroid cancers. 75% is sporadic and 25% is the dominant component of the hereditary multiple endocrine neoplasia (MEN) type 2 syndromes. Three different subtypes of MEN2, such as MEN2A, MEN2B, and Familial MTC (FMTC) have been defined, based on presence or absence of hyperparathyroidism, pheocromocytoma and characteristic clinical features. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC, but there are many other mutational patterns involved...
May 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/28504695/epigenetic-pathway-inhibitors-represent-potential-drugs-for-treating-pancreatic-and-bronchial-neuroendocrine-tumors
#18
K E Lines, M Stevenson, P Filippakopoulos, S Müller, H E Lockstone, B Wright, S Grozinsky-Glasberg, A B Grossman, S Knapp, D Buck, C Bountra, R V Thakker
Cancer is associated with alterations in epigenetic mechanisms such as histone modifications and methylation of DNA, and inhibitors targeting epigenetic mechanisms represent a novel class of anti-cancer drugs. Neuroendocrine tumors (NETs) of the pancreas (PNETs) and bronchus (BNETs), which may have 5-year survivals of <50% and as low as 5%, respectively, represent targets for such drugs, as >40% of PNETs and ~35% of BNETs have mutations of the multiple endocrine neoplasia type 1 (MEN1) gene, which encodes menin that modifies histones by interacting with histone methyltransferases...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28503312/germline-and-somatic-genetic-changes-in-multicentric-tumors-obtained-from-a-patient-with-multiple-endocrine-neoplasia-type-1
#19
Akane Naruoka, Sumiko Ohnami, Takeshi Nagashima, Masakuni Serizawa, Keiichi Ohshima, Shumpei Ohnami, Kenichi Urakami, Yasue Horiuchi, Yoshimi Kiyozumi, Masato Abe, Takashi Nakajima, Teiichi Sugiura, Katsuhiko Uesaka, Masatoshi Kusuhara, Ken Yamaguchi
Multiple endocrine neoplasia type 1 (MEN1) is a hereditary cancer syndrome caused by germline mutations of the MEN1 gene located in chromosome 11q13. In patients with MEN1, multicentric tumors develop in the involved organs; however, precise evaluation of genetic changes in these multicentric tumors has not been performed. In the present study, using whole-exome sequencing, we analyzed germline and somatic genetic changes in blood cells, two pancreatic endocrine tumors and one duodenal tumor obtained from a patient with MEN1 gastrinoma...
2017: Human Genome Variation
https://www.readbyqxmd.com/read/28501573/alterations-of-dna-methylation-in-parathyroid-tumors
#20
REVIEW
Vito Guarnieri, Lucia Anna Muscarella, Chiara Verdelli, Sabrina Corbetta
Parathyroid tumors are common endocrine neoplasias associated with primary hyperparathyroidism, a metabolic disorder characterized by parathormone hypersecretion. Parathyroid neoplasia are frequently benign adenomas or multiple glands hyperplasia, while malignancies are rare. The epigenetic scenario in parathyroid tumors has just begun to be decoded: DNA methylation, histones and chromatin modifiers expression have been investigated so far. The main findings suggest that DNA methylation and chromatin remodeling are active and deregulated in parathyroid tumors, cooperating with genetic alterations to drive the tumor phenotype: the tumor suppressors menin and parafibromin, involved in parathyroid tumorigenesis, interact with chromatin modifiers, defining distinct epigenetic derangements...
May 10, 2017: Molecular and Cellular Endocrinology
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