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Medullary thyroid cancer

Valeria La Pietra, Stefania Sartini, Lorenzo Botta, Alessandro Antonelli, Silvia Martina Ferrari, Poupak Fallahi, Alessio Moriconi, Vito Coviello, Luca Quattrini, Yi-Yu Ke, Hsieh Hsing-Pang, Federico Da Settimo, Ettore Novellino, Concettina La Motta, Luciana Marinelli
It is now known that "gain of function" mutations of RET (REarranged during Transfection) kinase are specific and key oncogenic events in the onset of thyroid gland cancers such as the Medullary Thyroid Carcinoma (MTC). Although a number of RET inhibitors exist and are capable of inhibiting RET variants, in which mutations are outside the enzyme active site, the majority becomes dramatically ineffective when mutations are within the protein active site (V804L and V804M). Pursuing a receptor-based virtual screening against the kinase domain of RET, we found that compound 5 is able to inhibit efficiently both wild type and V804L mutant RET...
March 2, 2018: European Journal of Medicinal Chemistry
Lynn Jakobs
BACKGROUND: Medullary thyroid cancer (MTC) is a rare cancer that has historically been managed by endocrinologists. In 2011, the first of several multi- targeted tyrosine kinase inhibitors was approved as treatment for MTC. These drugs have changed the management of MTC to teams that include oncologists and oncology nurses. OBJECTIVES: This article illustrates MTC diagnostics, surveillance, management of adverse drug reactions, and disease progression through a case study...
April 1, 2018: Clinical Journal of Oncology Nursing
Lingbin Du, Youqing Wang, Xiaohui Sun, Huizhang Li, Xinwei Geng, Minghua Ge, Yimin Zhu
BACKGROUND: Thyroid cancer is the most common malignant disease of the endocrine system. Previous studies indicate a rapid increase in the incidence of thyroid cancer in recent decades, and this increase has aroused the great public concern. The aim of this study was to analyze the trends in incidence, mortality and clinical-pathological patterns of thyroid cancer in Zhejiang province. METHODS: Population-based incidence and mortality rates of thyroid cancer were collected from eight cancer registries in Zhejiang from 2000 to 2012...
March 15, 2018: BMC Cancer
Maura Massimino, Douglas B Evans, Marta Podda, Claudio Spinelli, Paola Collini, Natalia Pizzi, Archie Bleyer
In adolescents and young adults, thyroid cancer accounts for 13% of all invasive neoplasms, being three times more frequent in females, but overdiagnosis and overtreatment are common. There are two therapeutic approaches, one radical and no longer preferred in all instances, and the other conservative. Permanent complications of surgery and metabolic irradiation can affect quality of life and carry an economic burden. The overall survival rate approaches 100% for patients with differentiated thyroid cancer regardless of the extent of treatment...
March 12, 2018: Pediatric Blood & Cancer
Anna Angelousi, Nikolaos Settas, Fabio R Faucz, Charalampos Lyssikatos, Martha Quezado, Narjes Nasiri-Ansari, Constantine A Stratakis, Eva Kassi
Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor hereditary in 35% of cases. The most common syndromic form is in the context of the multiple endocrine neoplasia type 2 (MEN 2) syndromes in association with other tumors and due to germline RET mutations. We describe a 57-year-old female patient diagnosed with sporadic MTC. The patient had a history of other neoplasias, such as acute myeloid leukemia, for which she had received chemotherapy, and two other solid tumors, peritoneal mesothelioma and meningioma...
October 2017: Hormones: International Journal of Endocrinology and Metabolism
Ankit A Shah, Preeti P Jain, Anjaney S Dubey, Ghanish N Panjwani, Hiral A Shah
Context: To share clinicopathological data of thyroid carcinoma from a high volume Tertiary Care Centre in East India. Aim: To share the epidemiology and clinicopathological presentation of thyroid cancer at a high volume Tertiary Care Center in East India. Settings and Design: Retrospective observational study. Subjects and Methods: Forty-two consecutive patients of thyroid neoplasm diagnosed by fine needle aspiration cytology (FNAC) and primarily underwent surgical treatment from July 2005 to June 2012 were included...
January 2018: Journal of Cancer Research and Therapeutics
Cristina Romei, Raffaele Ciampi, Francesca Casella, Alessia Tacito, Liborio Torregrossa, Clara Ugolini, Fulvio Basolo, Gabriele Materazzi, Paolo Vitti, Rossella Elisei
Purpose: Medullary Thyroid Cancer (MTC) whose pathogenesis is strictly related to RET proto-oncogene alterations, has been shown to have a heterogenic RET mutation profile in subpopulations of MTC. The aim of our study was to investigate the RET somatic mutation profile in primary MTC and in the corresponding metastatic tissues in a series of advanced metastatic cases. Results: This study demonstrated that in about 20% of cases a different RET mutation profile can be found when comparing primary tumor and its corresponding metastases...
February 9, 2018: Oncotarget
P W Shield, S J Crouch, D J Papadimos, M D Walsh
INTRODUCTION: We evaluated immunohistochemical staining for thyroid peroxidase (TPO), a glycoprotein found in the apical plasma membrane of thyroid follicular cells, as a marker for metastatic PTC in FNA samples and compared results with thyroglobulin (Tg) and thyroid transcription factor 1 (TTF1) staining. METHODS: Cell block sections prepared from 100 FNA specimens were stained with a rabbit monoclonal antibody to TPO (EP159). The FNAs included 64 metastatic malignancies from non-thyroid primary sites, including 18 lung, and 36 cases of thyroid tumours (29 PTC, six cases of medullary thyroid carcinoma and one thyroid anaplastic carcinoma)...
March 6, 2018: Cytopathology: Official Journal of the British Society for Clinical Cytology
Judit Kocsis, Éva Szekanecz, Ali Bassam, Andrea Uhlyarik, Zsuzsanna Pápai, Gábor Rubovszky, Emese Mezősi, Károly Rucz, Ildikó Garai, Endre Nagy, Iván Uray, Zsolt Horváth
BACKGROUND: Medullary thyroid cancer (MTC) is a rare disease, the prognosis of advanced and metastatic disease is poor and few therapeutic options are available in this setting. Based on the results of phase II and III studies with sorafenib in differentiated thyroid cancer and the lack of availability of registered tyrosine kinase inhibitors, vandetabin and cabozantinib in Hungary, we designed a uncontrolled, prospective efficacy and safety study of patients with metastatic MTC treated with first-line sorafenib in five Hungarian oncology centers...
March 5, 2018: Experimental and Clinical Endocrinology & Diabetes
Jung Bum Choi, Seul Gi Lee, Min Jhi Kim, Tae Hyung Kim, Eun Jeong Ban, Cho Rok Lee, Jandee Lee, Sang-Wook Kang, Jong Ju Jeong, Kee-Hyun Nam, Woong Youn Chung
Recently, dynamic risk stratification has been found to be more valuable than static anatomic staging system in nonmedullary thyroid cancer and this strategy has also been accepted in medullary thyroid cancer (MTC). The present study was designed to compare the clinical usefulness of response to initial therapy stratification with a traditional anatomic staging system.From August 1982 to December 2012, a total of 144 MTC patients underwent thyroidectomy in Yonsei University Hospital. Among them, 117 (82.2%) patients with complete clinical data and sustained follow-up were enrolled in this study...
January 2018: Medicine (Baltimore)
Lian-Jie Ren, Hua-Jing Wu, Li-Han Sun, Xue Xu, Li-Ying Mo, Lei Zhang, Jun-Ying Zhang, Chun-Yong Wu
Cabozantinib (CBZ) could be used for the treatment of progressive, metastatic medullary thyroid cancer. Its major oxidative metabolite is cabozantinib N-oxide (CBN) which contains a structural alert associated with mutagenicity, yet the pharmacokinetics study lacks the simultaneous investigation of CBN and dose proportionality. In current study a simple LC-MS/MS method was developed and validated for the simultaneous estimation and pharmacokinetic investigation of CBZ and CBN in rat plasma. The analytes were separated on a Waters Atlantics C18 column (2...
March 3, 2018: Biomedical Chromatography: BMC
Lei Zhang, Wen Liu, Qun Wang, Qinpei Li, Huijuan Wang, Jun Wang, Tieshan Teng, Mingliang Chen, Ailing Ji, Yanzhang Li
Medullary thyroid cancer (MTC) is a relatively rare thyroid cancer responsible for a substantial fraction of thyroid cancer mortality. More effective therapeutic drugs with low toxicity for MTC are urgently needed. Orphan nuclear receptor 4A1 (NR4A1) plays a pivotal role in regulating the proliferation and apoptosis of a variety of tumor cells. Based on the NR4A1 protein structure, 2-imino-6-methoxy-2H-chromene-3-carbothioamide (IMCA) was identified from the Specs compounds database using the protein structure-guided virtual screening approach...
March 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Saurabh Arora, Nishikant Avinash Damle, Girish Kumar Parida, Abhinav Singhal, Harish Nalli, Shreya Dattagupta, Chandrasekar Bal
The prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells. Few other malignancies have shown expression of PSMA. We present a case of 35-year-old man with medullary thyroid carcinoma, post total thyroidectomy and bilateral neck dissection, now presenting with rising calcitonin levels (doubling time 9 months) and local neck recurrence with negative I-MIBG scan. We decided to perform Ga-PSMA-HBED-CC PET/CT scan to assess PSMA expression and explore the therapeutic option in view of rising serum calcitonin...
February 27, 2018: Clinical Nuclear Medicine
S Jayakody, J Reagh, M Bullock, A Aniss, R Clifton-Bligh, D Learoyd, B Robinson, L Delbridge, S Sidhu, A J Gill, M Sywak
INTRODUCTION: Medullary thyroid cancer (MTC) is a rare tumour of neuroendocrine origin with a more aggressive profile than differentiated thyroid cancer. Familial cases of MTC are associated with RET mutations whilst RAS mutations appear to be a frequent finding in RET negative tumours. The aims of this study were to analyse survival outcomes in MTC and to evaluate the role of RAS immunohistochemistry in the identification of sporadic disease. MATERIALS AND METHODS: A retrospective cohort study of consecutive patients with MTC was undertaken...
February 26, 2018: World Journal of Surgery
George E Naoum, Michael Morkos, Brian Kim, Waleed Arafat
Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15-20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC...
February 19, 2018: Molecular Cancer
Marra Aghajani, Susannah Graham, Charles McCafferty, Christina Abdel Shaheed, Tara Roberts, Paul DeSouza, Tao Yang, Navin Niles
BACKGROUND: Evidence has shown that PD-L1 overexpression is associated with poor prognosis and resistance to immune therapies in several human cancers. However, data on the prognostic significance of PD-L1 expression in thyroid cancer is limited and remains controversial. In this systematic review and meta-analysis, we aimed to comprehensively evaluate the clinicopathological significance and prognostic value of PD-L1 expression in non-medullary thyroid cancers. SUMMARY: Electronic databases, including Medline/PubMed, EMBASE and the Cochrane Library, were searched up until July 5th, 2017...
February 17, 2018: Thyroid: Official Journal of the American Thyroid Association
David Lindquist, Fernando C Alsina, Carl Herdenberg, Catharina Larsson, Jo Höppener, Na Wang, Gustavo Paratcha, Miklós Tarján, Tibor Tot, Roger Henriksson, Håkan Hedman
Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) are characterized by genomic rearrangements and point mutations in the proto-oncogene RET. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a suppressor of various receptor tyrosine kinases, including RET. LRIG1 expression levels are associated with patient survival in many cancer types. In the present study, we investigated whether the oncogenic RET mutants RET2A (C634R) and RET2B (M918T) were regulated by LRIG1, and the possible effects of LRIG1 expression in thyroid cancer were investigated in three different clinical cohorts and in a RET2B-driven mouse model of MTC...
February 9, 2018: International Journal of Oncology
Bernard Peene, Annick Van den Bruel, Carolien Moyson, Brigitte Decallonne
Objective Thyroid cancer incidence is increasing. The rise is most pronounced for microcancers (≤10 mm, T1a). In 2006, landmark European and American guidelines for the management of thyroid cancer were published. We studied thyroid cancer characteristics and initial management before and after 2006. Methods We conducted a retrospective observational study of non-medullary thyroid cancer patients that underwent thyroidectomy in two Belgian referral centres comparing pre-, per- and post-operative management in a cohort before and after 2006...
February 12, 2018: Acta Clinica Belgica
Minerva A Romero Arenas, Thereasa A Rich, Samuel M Hyde, Naifa L Busaidy, Gilbert J Cote, Mimi I Hu, Robert F Gagel, Paul W Gidley, Camilo Jimenez, Michael E Kupferman, Susan K Peterson, Steven I Sherman, Anita Ying, Roland L Bassett, Steven G Waguespack, Nancy D Perrier, Elizabeth G Grubbs
BACKGROUND: No guidelines exist regarding physicians' duty to inform former patients about novel genetic tests that may be medically beneficial. Research on the feasibility and efficacy of disseminating information and patient opinions on this topic is limited. METHODS: Adult patients treated at our institution from 1950 to 2010 for medullary thyroid cancer, pheochromocytoma, or paraganglioma were included if their history suggested being at-risk for a hereditary syndrome but genetic risk assessment would be incomplete by current standards...
February 9, 2018: Annals of Surgical Oncology
Tania Jaber, Samuel M Hyde, Gilbert J Cote, Elizabeth G Grubbs, Wesley H Giles, Cathy A Stevens, Ramona Dadu
Context: Germline RET K666N mutation has been described as a pathogenic mutation with low disease penetrance for medullary thyroid cancer (MTC) without other features of MEN2A. We describe a patient with homozygous RET K666N mutation with MTC and bilateral pheochromocytoma (PHEO). Case Description: A 59-year-old female was diagnosed with MTC after biopsy of two thyroid nodules. Coincident biochemical and radiologic testing was suspicious for bilateral PHEO, confirmed after bilateral adrenalectomy...
February 2, 2018: Journal of Clinical Endocrinology and Metabolism
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