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Medullary thyroid cancer

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https://www.readbyqxmd.com/read/29158289/next-generation-panel-sequencing-identifies-nf1-germline-mutations-in-three-patients-with-pheochromocytoma-but-no-clinical-diagnosis-of-neurofibromatosis-type-1
#1
Laura Gieldon, Jimmy Rusdian Masjkur, Susan Richter, Roland Därr, Marcos Lahera, Daniela E Aust, Silke Zeugner, Andreas Rump, Karl Hackmann, Andreas Tzschach, Andrzej Januszewicz, Aleksander Prejbisz, Graeme Eisenhofer, Evelin Schroeck, Mercedes Robledo, Barbara Klink
Objective Our objective was to improve molecular diagnostics in patients with hereditary pheochromocytoma and paraganglioma (PPGL) by using next generation sequencing (NGS) multi-gene panel analysis. Derived from this study we here present three cases that were diagnosed with NF1 germline mutations but did not have a prior clinical diagnosis of Neurofibromatosis Type 1 (NF1). Design We performed genetic analysis of known tumor predisposition genes, including NF1, using a multi-gene NGS enrichment-based panel applied to a total of 1029 PPGL patients...
November 20, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29142006/characterization-of-neuroendocrine-tumors-in-heterozygous-mutant-menx-rats-a-novel-model-of-invasive-medullary-thyroid-carcinoma
#2
Sara Molatore, Andrea Kügler, Martin Irmler, Tobias Wiedemann, Frauke Neff, Annette Feuchtinger, Johannes Beckers, Mercedes Robledo, Frederico Roncaroli, Natalia S Pellegata
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...
November 15, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29136674/familial-hyperparathyroidism-disorders-of-growth-and-secretion-in-hormone-secretory-tissue
#3
Stephen J Marx, Delmar Muniz Lourenco
Six syndromes of familial hyperparathyroidism are compared: 1) Familial hypocalciuric hypercalcemia (FHH) expresses primary hyperparathyroidism (PHPT) beginning at birth with lifelong hypercalcemia. There is nonsuppressed PTH secretion from outwardly normal parathyroid glands. It reflects germline heterozygous mutation in CASR, GNA11, or AP2S1. 2) Neonatal severe primary hyperparathyroidism is severest of the six syndromes. It requires urgent total parathyroidectomy in infancy. It usually reflects biallelic inactivation of the CASR...
November 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29133048/structural-optimization-and-structure-activity-relationship-studies-of-n-phenyl-7-8-dihydro-6h-pyrimido-5-4-b-1-4-oxazin-4-amine-derivatives-as-a-new-class-of-inhibitors-of-ret-and-its-drug-resistance-mutants
#4
Jiao Yang, Kai Chen, Guo Zhang, Qiu-Yuan Yang, Yue-Shan Li, Shen-Zhen Huang, Yan-Lin Wang, Wei Yang, Xiao-Juan Jiang, Heng-Xiu Yan, Jing-Qiang Zhu, Rong Xiang, You-Fu Luo, Wei-Min Li, Yu-Quan Wei, Lin-Li Li, Sheng-Yong Yang
The RET tyrosine kinase is an important therapeutic target for medullary thyroid cancer (MTC), and drug resistance mutations of RET, particularly V804M and V804L, are a main challenge for the current targeted therapy of MTC based on RET inhibitors. In this investigation, we report the structural optimization and structure-activity relationship studies of N-phenyl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-amine derivatives as a new class of RET inhibitors. Among all the obtained kinase inhibitors, 1-(5-(tert-butyl)isoxazol-3-yl)-3-(4-((6,7,8,9-tetrahydropyrimido[5,4-b][1,4]oxazepin-4-yl)amino)phenyl)urea (17d) is a multi-kinase inhibitor and potently inhibits RET and its drug resistance mutants...
September 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29128180/notch3-as-a-novel-therapeutic-target-in-metastatic-medullary-thyroid-cancer
#5
Irene Lou, Scott Odorico, Xiao-Min Yu, April Harrison, Renata Jaskula-Sztul, Herbert Chen
BACKGROUND: Medullary thyroid cancer portends poor survival once liver metastasis occurs. We hypothesize that Notch3 overexpression in medullary thyroid cancer liver metastasis will decrease proliferation and growth of the tumor. METHODS: TT cells were modified genetically to overexpress Notch3 in the presence of doxycycline, creating the TT-Notch3 cell line. Mice were injected intrasplenically with either TT-Notch3 or control vector TT-TRE cells. Each cell line had 3 treatment groups: control with 12 weeks of standard chow, early DOX with doxycycline chow at day 0 and for 70 days thereafter, and late DOX with doxycycline chow at 8 weeks...
November 8, 2017: Surgery
https://www.readbyqxmd.com/read/29126344/genetic-and-epigenetic-of-medullary-thyroid-cancer
#6
Fatemeh Khatami, Seyed Mohammad Tavangar
Medullary thyroid carcinoma (MTC) is an infrequent, calcitonin producing neuroendocrine tumor and initiates from the parafollicular C cells of the thyroid gland. Several genetic and epigenetic alterations are collaterally responsible for medullary thyroid carcinogenesis. In this review article, we shed light on all the genetic and epigenetic hallmarks of MTC. From the genetic perspective, RET, HRAS, and KRAS are the most important genes that are characterized in MTC. From the epigenetic perspective, Ras-association domain family member 1A, telomerase reverse transcriptase promoter methylations, overexpression of histone methyltransferases, EZH2 and SMYD3, and wide ranging increase and decrease in non-coding RNAs can be responsible for medullary thyroid carcinogenesis...
November 11, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/29120653/-thyroid-carcinomas-the-present-view-on-diagnostics-and-therapy
#7
Petr Vlček, Dana Nováková, Rami Katra
Thyroid carcinoma (TC) represents 1-2 % of all human tumors, and is the seventh most common tumor. Women are in large majority among new patients. For women, this is the fifth most common tumor. In the Czech Republic, 1 143 new cases of TC were diagnosed in 2015. It is the tumor with the highest increase in incidence. Among newly diagnosed tumors, most of those are differentiated thyroid gland carcinomas (DTCs) originating from follicular thyroid cells. These tumors are follicular and papillary carcinomas and Hurthle carcinoma, accounting for 95 % of new cases...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29112684/cxcr4-cxcr7-cxcl12-axis-promotes-an-invasive-phenotype-in-medullary-thyroid-carcinoma
#8
Thomas A Werner, Christina M Forster, Levent Dizdar, Pablo E Verde, Katharina Raba, Matthias Schott, Wolfram T Knoefel, Andreas Krieg
BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare and challenging endocrine malignancy. Once spread, the therapeutic options are limited and the outcome poor. For these patients, the identification of new druggable biological markers is of great importance. Here, we investigated the prognostic and biological role of the C-X-C chemokine receptors type 4 and 7 (CXCR4/7) in MTC. METHODS: Eighty-six MTC and corresponding non-neoplastic thyroid specimens were immunohistochemically stained for CXCR4/7 using tissue microarray technology and expression levels correlated with clinicopathological variables...
November 7, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29108325/ratio-of-positive-lymph-nodes-the-prognostic-value-in-stage-iv-thyroid-cancer
#9
Tingyin Jiang, Chunling Huang, Yuan Xu, Yingrui Su, Guanjie Zhang, Long Xie, Liqun Huang, Shuchun You, Jinshun Zha
To assess the prognostic value of lymph node ratio (LNR) in patients with stage IV thyroid cancer based on the Surveillance, Epidemiology, and End Results (SEER) database. A total of 4,940 eligible patients were included for the analysis. Kaplan-Meier survival analysis and Cox proportional hazard regression were used to reveal the effect of LNR on overall survival (OS) and disease specific survival (DSS). The optimal cut-off value of LNR for predicting OS and DSS was determined by the time-dependent Receiver Operating Characteristic analysis...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29105562/reduced-retinoblastoma-protein-expression-is-associated-with-decreased-patient-survival-in-medullary-thyroid-cancer
#10
Anisley Valenciaga, Elizabeth G Grubbs, Kyle Porter, Paul E Wakely, Michelle D Williams, Gilbert J Cote, Vasyl V Vasko, Motoyasu Saji, Matthew D Ringel
BACKGROUND: The Retinoblastoma (RB) transcriptional corepressor 1 protein functions to slow cell cycle progression. Inactivation of RB by reduced expression and/or hyperphosphorylation allow for enhanced progression through cell cycle. Murine models develop medullary thyroid carcinoma (MTC) after generalized loss of RB; however, RB expression in MTC has been evaluated only in a small number of tumors with differing results. The objective of this study is to determine whether reduced expression of RB and/or overexpression of hyperphosphorylated RB predict MTC aggressive behavior...
November 4, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29079175/aberrant-expression-of-cd20-in-thyroid-cancer-and-its-clinicopathologic-significance
#11
Andrey Bychkov, Chan Kwon Jung
CD20 is the first line diagnostic marker of B-cells, which serves as the target of the therapeutic monoclonal antibodies in B-cell lymphomas and leukemias. Recently, aberrant CD20 expression has been described in a small series of papillary thyroid carcinomas (PTC). We aimed to evaluate CD20 immunoexpression and to perform clinicopathologic correlation in a large set of thyroid tumors, including a cohort of high-grade thyroid cancer. A total of 625 cases of thyroid tumor comprised tissue microarrays of 538 PTCs and 47 follicular adenomas, and whole-slide sections of 40 aggressive thyroid carcinomas (10 radioiodine-refractory PTCs, 8 poorly differentiated, 5 anaplastic and 17 medullary thyroid carcinomas) were immunostained with anti-CD20 monoclonal antibody...
October 24, 2017: Human Pathology
https://www.readbyqxmd.com/read/29077903/long-term-survivorship-in-multiple-endocrine-neoplasia-type-2b-diagnosed-before-and-in-the-new-millennium
#12
Friedhelm Raue, Henning Dralle, Andreas Machens, Thomas Bruckner, Karin Frank-Raue
Context: Recent long-term outcome and survival data are lacking for patients with multiple endocrine neoplasia type 2B (MEN2B). Objectives: To analyze long-term MEN2B outcome and define prognostic factors. Design, Setting, and Participants: Retrospective comparative study of 75 patients with MEN2B from two German tertiary referral centers. Patients diagnosed and treated before and after 2000 were compared for demographic, biochemical, surgical, and outcome parameters...
October 25, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29066476/role-of-cdkn2c-fluorescence-in-situ-hybridization-in-the-management-of-medullary-thyroid-carcinoma
#13
Maha El Naofal, Adriel Kim, Hui Yi Yon, Mohamed Baity, Zhao Ming, Jacquelin Bui-Griffith, Zhenya Tang, Melissa Robinson, Elizabeth G Grubbs, Gilbert J Cote, Peter Hu
Medullary thyroid carcinoma (MTC), an aggressive form of thyroid cancer, occurs sporadically in approximately 75% of MTCs. RET and RAS mutations play a role in about 40% and 15%, respectively, of sporadic MTCs and are predominant drivers in MTC pathways. These mutations are some of the most comprehensively described and screened for in MTC patients; however, in recent studies, other mutations in the CDKN2C gene (p18) have been implicated in the tumorigenesis of MTC. Comparative genomic hybridization analysis revealed that approximately 40% of sporadic MTC samples have loss of CDKN2C at chromosome 1p32 in addition to frequent losses of CDKN2D (p19) at chromosome 19p13...
September 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/29061021/-dye-tattooing-under-ultrasound-guidance-in-preoperative-localization-of-neck-recurrences-from-thyroid-cancer
#14
X W Zhang, B Zhang, L J Niu, D G Yan, Y Wang, L Zhu, Y B Zhang, Y Y He, Z G Xu, P Z Tang
Objective: To evaluate the efficacy and safety of the application of dye-tattooing under ultrasound guidance in preoperative localization of neck recurrences from thyroid cancer. Methods: Between October 2014 to September 2016, 25 patients with 34 lesions were enrolled. There were 22 cases of papillary thyroid carcinoma and three cases of medullary thyroid carcinoma, all of which could not be detected by computed tomography. Surgeons located the recurrent lesions using dye-tattooing under ultrasound guidance along with radiologist three days before the operation...
October 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/29057215/targeted-therapy-for-medullary-thyroid-cancer-a-review
#15
REVIEW
S R Priya, Chandra Shekhar Dravid, Raghunadharao Digumarti, Mitali Dandekar
Medullary thyroid cancers (MTCs) constitute between 2 and 5% of all thyroid cancers. The 10-year overall survival (OS) rate of patients with localized disease is around 95% while that of patients with regional stage disease is about 75%. Only 20% of patients with distant metastases at diagnosis survive 10 years which is significantly lower than for differentiated thyroid cancers. Cases with regional metastases at presentation have high recurrence rates. Adjuvant external radiation confers local control but not improved OS...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29049491/dermal-hyperneury-and-multiple-sclerotic-fibromas-in-multiple-endocrine-neoplasia-type-2a-syndrome
#16
Victoria Alegría-Landa, Margarita Jo-Velasco, Mercedes Robledo, Luis Requena
Importance: Multiple endocrine neoplasia type 2 (MEN 2) syndrome is an autosomal dominant, hereditary cancer disorder caused by germline mutations in the RET (formerly MEN2A, MEN2B) proto-oncogene located on chromosomal band 10q11.21. Two distinct clinical forms have been described as the following phenotypes: multiple endocrine neoplasia type 2A (MEN 2A) and multiple endocrine neoplasia type 2B (MEN 2B) syndromes. The common and necessary nexus that defines these 2 phenotypes is the presence of medullary thyroid carcinoma (MTC)...
October 18, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/29045520/overall-survival-analysis-of-exam-a-phase-iii-trial-of-cabozantinib-in-patients-with-radiographically-progressive-medullary-thyroid-carcinoma
#17
M Schlumberger, R Elisei, S Müller, P Schöffski, M Brose, M Shah, L Licitra, J Krajewska, M C Kreissl, B Niederle, E E W Cohen, L Wirth, H Ali, D O Clary, Y Yaron, M Mangeshkar, D Ball, B Nelkin, S Sherman
Background: Primary analysis of the double-blind, phase III Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM) trial demonstrated significant improvement in progression-free survival with cabozantinib versus placebo in patients with progressive medullary thyroid cancer (MTC). Final analysis of overall survival (OS), a key secondary endpoint, was carried out after long-term follow-up. Patients and methods: EXAM compared cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29044788/management-of-the-lateral-neck-compartment-in-patients-with-sporadic-medullary-thyroid-cancer
#18
Israel Pena, Gary L Clayman, Elizabeth G Grubbs, Jeffrey M Bergeron, Steven G Waguespack, Maria E Cabanillas, Ramona Dadu, Mimi I Hu, Bryan M Fellman, Yisheng Li, Neil D Gross, Stephen Y Lai, Erich M Sturgis, Mark E Zafereo
BACKGROUND: The purpose of this retrospective analysis was to evaluate the benefits of an elective lateral neck dissection (ELND) in patients with medullary thyroid cancer (MTC) without radiographically apparent lateral neck metastases. METHODS: Patients with sporadic MTC without radiographic evidence of lateral neck metastasis who underwent definitive surgery were divided into 2 groups based on surgical approach: no ELND (the observation group) and ipsilateral or bilateral ELND (the ELND group)...
October 16, 2017: Head & Neck
https://www.readbyqxmd.com/read/29033189/mir-375-a-prospective-regulator-in-medullary-thyroid-cancer-based-on-microarray-data-and-bioinformatics-analyses
#19
Lin Shi, Shi-Mei Zhao, Yu Luo, An-Wen Zhang, Li-Hua Wei, Zheng-Yi Xie, Yuan-Yuan Li, Wei Ma
BACKGROUND: This research aims to investigate the prospective molecular mechanism of miR-375 in Medullary Thyroid Cancer (MTC). MATERIAL AND METHODS: The expression level of miR-375 in MTC was explored with microarray data from Gene Expression Omnibus (GEO). To gather the putative target genes of miR-375, we selected eligible datasets in GEO, in which antagomir-375 and premir-375 were transfected to provide the miR-375-related genes. Subsequently, we attained the intersection of the results of GEO microarray data and 12 online target genes prediction database as the prospective target genes...
September 27, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29027612/penetrance-of-a-rare-familial-mutation-predisposing-to-papillary-thyroid-cancer
#20
Donika Saporito, Pamela Brock, Heather Hampel, Jennifer Sipos, Soledad Fernandez, Sandya Liyanarachchi, Albert de la Chapelle, Rebecca Nagy
Familial non-medullary thyroid cancer (FNMTC) is clinically defined as two or more first-degree relatives with NMTC and appears to follow an autosomal dominant inheritance pattern. Approximately 5-7% of NMTC is hereditary and affects multiple generations with a young age of onset. The primary aim of this study was to determine the age-specific penetrance of NMTC in individuals from a large family with FNMTC with a previously identified private mutation at 4q32, with a secondary aim to determine the penetrance for benign thyroid disease in this family...
October 12, 2017: Familial Cancer
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