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Medullary thyroid cancer

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https://www.readbyqxmd.com/read/29774010/efficacy-of-vandetanib-in-treating-locally-advanced-or-metastatic-medullary-thyroid-carcinoma-according-to-recist-criteria-a-systematic-review-and-meta-analysis
#1
Pierpaolo Trimboli, Marco Castellana, Camilla Virili, Francesco Giorgino, Luca Giovanella
Background: Vandetanib is the most largely used tyrosine kinase inhibitor (TKI) in patients with locally advanced and/or metastatic medullary thyroid cancer (MTC). Here, we conducted a systematic review on its efficacy and attempted to perform a meta-analysis adopting standardized RECIST criteria as end-points. Methods: The terms "medullary thyroid" and "protein kinase inhibitor" (then including all TKIs) were searched in PubMed, ClinicalTrials...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29753028/pituitary-somatolactotropes-evade-an-oncogenic-response-to-ras
#2
Allyson K Roof, Tammy Trudeau, Arthur Gutierrez-Hartmann
Distinct cell types have been shown to respond to activated Ras signaling in a cell-specific manner. In contrast to its pro-tumorigenic role in some human epithelial cancers, oncogenic Ras triggers differentiation of pheochromocytoma cells and medullary thyroid carcinoma cells. Furthermore, we have previously demonstrated that in pituitary somatolactotropes, activated Ras promotes differentiation and is not sufficient to drive tumorigenesis. These findings demonstrate that lactotrope cells have the ability to evade the tumorigenic fate that is often associated with persistent activation of Ras/ERK signaling, and suggest that there may be differential expression of inhibitory signaling molecules or negative cell cycle regulators that act as a brake to prevent the tumorigenic effects of sustained Ras signaling...
May 9, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29739896/quantitative-proteomics-analysis-of-sporadic-medullary-thyroid-cancer-reveals-fn1-as-a-potential-novel-candidate-prognostic-biomarker
#3
Shaohua Zhan, Jinming Li, Tianxiao Wang, Wei Ge
BACKGROUND: Sporadic medullary thyroid cancer (MTC) is a rare neuroendocrine tumor. Currently, although the diagnosis of sporadic MTC is relatively simple, the need to discover novel candidate prognostic biomarkers for sporadic MTC and investigate the underlying mechanism involved in this rare disease is urgent. MATERIALS AND METHODS: We employed tandem mass tag-based liquid chromatography-mass spectrometry to identify and analyze differentially expressed proteins (DEPs) in sporadic MTC...
May 8, 2018: Oncologist
https://www.readbyqxmd.com/read/29721199/rapid-methods-to-create-a-positive-control-and-identify-the-pax8-ppar%C3%AE-rearrangement-in-fna-thyroid-samples-by-molecular-biology
#4
Emilia Vuttariello, Elio Biffali, Raimondo Pannone, Anna Capiluongo, Mario Monaco, Valentina Sica, Concetta Aiello, Marco Matuozzo, Maria Grazia Chiofalo, Gerardo Botti, Gennaro Chiappetta
Thyroid cancer is the most common malignancy of the endocrine system and includes well-differentiated forms, namely papillary and follicular carcinomas, and the poorly differentiated and undifferentiated forms that result from the transformation of thyroid follicular cells (anaplastic carcinomas). Notably, 5-10% of all thyroid cancers are medullary thyroid cancers that arise from parafollicular cells also known as C cells. The most common genetic mutations in papillary and follicular thyroid cancers are point mutations of the BRAF or RAS genes, while the most common chromosomal alterations are RET/PTC and PAX8/PPARγ rearrangements...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29704768/management-of-treatment-related-toxicities-in-advanced-medullary-thyroid-cancer
#5
REVIEW
Marcia S Brose, Keith C Bible, Laura Q M Chow, Jill Gilbert, Carolyn Grande, Francis Worden, Robert Haddad
Progress in the treatment of advanced medullary thyroid cancer (MTC) has resulted from the approval of 2 drugs within the past 5 years, vandetanib and cabozantinib. These multikinase inhibitors (MKIs) possess overlapping specificities for multiple kinase targets implicated in the progression of MTC. Both drugs are associated with toxicities, including hypertension, hemorrhage/perforation, diarrhea and other gastrointestinal events, several dermatologic events, and hypothyroidism. In addition, vandetanib is uniquely associated with QTc prolongation through interaction with myocardial potassium channels, and cabozantinib is uniquely associated with hand-foot skin reaction...
April 22, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29696039/thrombosis-in-thyroid-cancer
#6
REVIEW
Arash Ordookhani, Abbas Motazedi, Kenneth D Burman
Background: The number of studies on venous thromboembolism (VTE) and thyroid cancer is very scarce and existing data are contradictory. This paper reviews VTE in thyroid cancer. Methods: The following words were used for a comprehensive literature review using MEDLINE database: Blood coagulation factors; thyroid hormones; blood coagulation tests; venous thromboembolism; receptors thyroid hormone; hemostasis; fibrinolysis; bleeding; blood coagulation disorders; thyroid neoplasms; Thyroid cancer, papillary; Thyroid cancer, follicular; Thyroid carcinoma, anaplastic; Thyroid cancer, Hurthle cell; Familial medullary thyroid carcinoma; venous thrombosis; Pulmonary embolism; Blood coagulation factors...
January 2018: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29693796/a-phase-1-study-of-cabozantinib-in-children-and-adolescents-with-recurrent-or-refractory-solid-tumors-including-cns-tumors-trial-advl1211-a-report-from-the-children-s-oncology-group
#7
Meredith K Chuk, Brigitte C Widemann, Charles G Minard, Xiaowei Liu, AeRang Kim, Melanie Brooke Bernhardt, Rachel A Kudgus, Joel M Reid, Stephan D Voss, Susan Blaney, Elizabeth Fox, Brenda J Weigel
BACKGROUND: We conducted a phase 1 trial to determine the maximum tolerated dose (MTD), toxicity profile, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary activity of cabozantinib in children with refractory or relapsed solid tumors. METHODS: Patients received cabozantinib tablets on a continuous dosing schedule in a rolling-six escalating phase 1 trial design. PK and PD studies were performed. RESULTS: Forty-one patients, median (range) age 13 (4-18) years, received cabozantinib to achieve a weekly cumulative dose equivalent to 30 (n = 6), 40 (n = 23)...
April 25, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29692901/primary-high-grade-calcitonin-negative-neuroendocrine-carcinoma-of-the-thyroid-a-very-rare-cancer
#8
Joseph A Chorny, John J Orrego, José Manuel Cameselle-Teijeiro
Most medullary thyroid carcinomas (MTCs) are low grade and produce calcitonin. There are some calcitonin-negative MTCs that produce only calcitonin gene-related peptide (CGRP). Rarely, MTCs are negative for calcitonin and CGRP peptides, but contain their corresponding mRNAs. Primary thyroid neuroendocrine neoplasms other than MTCs are extremely rare. We describe a primary high-grade neuroendocrine carcinoma that was negative for CGRP and calcitonin at both the protein and mRNA levels. A 42-year-old woman presented with a rapidly enlarging thyroid mass replacing most of the left lobe and isthmus...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29688429/ef24-a-curcumin-analog-and-zstk474-emphasizes-the-effect-of-cabozantinib-in-medullary-thyroid-cancer
#9
Loris Bertazza, Francesca Sensi, Elisabetta Cavedon, Sara Watutantrige-Fernando, Simona Censi, Jacopo Manso, Federica Vianello, Eric Casal Ide, Maurizio Iacobone, Raffaele Pezzani, Caterina Mian, Susi Barollo
XL184 is a small-molecule kinase inhibitor recently included in first-line systemic therapy for patients with advanced, progressive medullary thyroid cancer (MTC). EF24 is a curcumin analog with a high bio-availability, and ZSTK474 is an inhibitor of the PI3K signaling pathway. We investigated the effect of these compounds, alone and in combination, in two RET-mutated TT and MZ-CRC-1 MTC cell lines, and in six mostly RET wild-type human MTC primary cultures. Low IC50 values demonstrated the efficacy of the drugs, while the Combination Index revealed a significant synergistic effect of combinations of XL184+ZSTK474 and XL184+EF24...
April 23, 2018: Endocrinology
https://www.readbyqxmd.com/read/29687244/a-population-pharmacokinetic-model-of-cabozantinib-in-healthy-volunteers-and-patients-with-various-cancer-types
#10
Steven Lacy, Bei Yang, Jace Nielsen, Dale Miles, Linh Nguyen, Matt Hutmacher
PURPOSE: An integrated population pharmacokinetic (popPK) model was developed to describe the pharmacokinetics (PK) of tyrosine kinase inhibitor cabozantinib in healthy volunteers (HVs) and patients with various cancer types and to identify any differences in cabozantinib PK across these populations. METHODS: Plasma concentration data used to develop the popPK model were obtained from nine clinical trials (8072 concentrations from 1534 HVs or patients) of cabozantinib in HVs and patients with renal cell carcinoma (RCC), medullary thyroid carcinoma (MTC), glioblastoma multiforme, castration-resistant prostate cancer, or other advanced malignancies...
April 23, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29672841/mutant-myo1f-alters-the-mitochondrial-network-and-induces-tumor-proliferation-in-thyroid-cancer
#11
Chiara Diquigiovanni, Christian Bergamini, Cecilia Evangelisti, Federica Isidori, Andrea Vettori, Natascia Tiso, Francesco Argenton, Anna Costanzini, Luisa Iommarini, Hima Anbunathan, Uberto Pagotto, Andrea Repaci, Giulia Babbi, Rita Casadio, Giorgio Lenaz, Kerry J Rhoden, Anna Maria Porcelli, Romana Fato, Anne Bowcock, Marco Seri, Giovanni Romeo, Elena Bonora
Familial aggregation is a significant risk factor for the development of thyroid cancer and Familial Non-Medullary Thyroid Cancer (FNMTC) accounts for 5-7% of all NMTC. Whole Exome Sequencing analysis in the family affected by FNMTC with oncocytic features where our group previously identified a predisposing locus on chromosome 19p13.2, revealed a novel heterozygous mutation (c.400G>A, NM_012335; p.Gly134Ser) in exon 5 of MYO1F, mapping to the linkage locus. In the thyroid FRTL-5 cell model stably expressing the mutant MYO1F p...
April 19, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29663329/prophylactic-thyroidectomy-in-children-with-multiple-endocrine-neoplasia-type-2
#12
F P Prete, T Abdel-Aziz, C Morkane, C Brain, T R Kurzawinski
BACKGROUND: In patients with multiple endocrine neoplasia type 2 (MEN2) syndrome, genetic testing offers early diagnosis, stratifies the risk of developing medullary thyroid cancer (MTC) and informs the timing of thyroidectomy. The efficacy of treatment, which depends on timely and safe surgery, is not well established. METHODS: This was a retrospective review of diagnostic and clinicopathological outcomes of prophylactic thyroidectomy in children with MEN2 between 1995 and 2013 in the UK...
April 17, 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29663167/structural-studies-on-radiopharmaceutical-dota-minigastrin-analogue-cp04-complexes-and-their-interaction-with-cck2-receptor
#13
Piotr F J Lipiński, Piotr Garnuszek, Michał Maurin, Raphael Stoll, Nils Metzler-Nolte, Artur Wodyński, Jan Cz Dobrowolski, Marta K Dudek, Monika Orzełowska, Renata Mikołajczak
BACKGROUND: The cholecystokinin receptor subtype 2 (CCK-2R) is an important target for diagnostic imaging and targeted radionuclide therapy (TRNT) due to its overexpression in certain cancers (e.g., medullary thyroid carcinoma (MTC)), thus matching with a theranostic principle. Several peptide conjugates suitable for the TRNT of MTC have been synthesized, including a very promising minigastrin analogue DOTA-(DGlu)6 -Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 (CP04). In this contribution, we wanted to see whether CP04 binding affinity for CCK-2R is sensitive to the type of the complexed radiometal, as well as to get insights into the structure of CP04-CCK2R complex by molecular modeling...
April 16, 2018: EJNMMI Research
https://www.readbyqxmd.com/read/29657136/blu-667-targets-ret-altered-cancers
#14
(no author information available yet)
Findings from a phase I study indicate that the investigational RET inhibitor BLU-667 is safe and well tolerated, inducing good responses in patients with RET-altered medullary thyroid cancer or non-small cell lung cancer.
April 15, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29657135/precision-targeted-therapy-with-blu-667-for-ret-driven-cancers
#15
Vivek Subbiah, Justin F Gainor, Rami Rahal, Jason D Brubaker, Joseph L Kim, Michelle Maynard, Wei Hu, Qiongfang Cao, Michael P Sheets, Douglas Wilson, Kevin J Wilson, Lucian DiPietro, Paul Fleming, Michael Palmer, Mimi I Hu, Lori Wirth, Marcia S Brose, Sai-Hong Ignatius Ou, Matthew Taylor, Elena Garralda, Stephen Miller, Beni Wolf, Christoph Lengauer, Timothy Guzi, Erica K Evans
The receptor tyrosine kinase, rearranged during transfection (RET), is an oncogenic driver activated in multiple cancers including non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC). No approved therapies have been designed to target RET; treatment has been limited to multi-kinase inhibitors (MKIs) which can have significant off-target toxicities and limited efficacy. BLU-667 is a highly potent and selective RET inhibitor designed to overcome these limitations...
April 15, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29656518/genotype-specific-progression-of-hereditary-medullary-thyroid-cancer
#16
Andreas Machens, Kerstin Lorenz, Frank Weber, Henning Dralle
Although already 25 years into the genomic era, age-related progression of hereditary medullary thyroid cancer (MTC), the prevalence of which is estimated at 1 in 80,000 inhabitants, remains to be delineated for most unique RET (REarranged during Transfection) mutations. Included in this study were 567 RET carriers. The age-related progression of MTC across histopathological groups (normal thyroid/C-cell hyperplasia; node-negative MTC; node-positive MTC) was statistically significant for 13 unique RET mutations (p...
April 14, 2018: Human Mutation
https://www.readbyqxmd.com/read/29644341/uptake-of-99m-tc-mibi-by-sclerosing-pneumocytoma-raising-a-false-suspicion-of-metastasis-from-medullary-thyroid-carcinoma
#17
Georgios E Papadakis, Flavian Tabotta, Igor Levotanec, Michel Gonzalez, John O Prior, Stefano La Rosa, Gerasimos P Sykiotis
Technetium-99m methoxy isobutyl isonitrile (99m Tc-MIBI; sestamibi) single-photon emission computed tomography (SPECT)/computed tomography (CT) performed for preoperative localization of parathyroid adenomas or for other indications can reveal incidentalomas. Interpretation of such findings can be challenging, particularly when thyroid or other endocrine tumors are also present. Preoperative staging of a 59-year-old female patient with medullary thyroid carcinoma (MTC) showing moderate hypermetabolism on 18 F-fluorodeoxyglucose positron emission tomography/CT also detected a slightly hypermetabolic pulmonary nodule (standardized uptake value normalized by body weight max = 2...
April 1, 2018: Journal of the Endocrine Society
https://www.readbyqxmd.com/read/29643661/unusual-metastasis-of-medullary-thyroid-carcinoma-to-the-breast-a-cytological-and-histopathological-correlation
#18
Parul Tanwar, Jatin S Gandhi, Anila Sharma, Manoj Gupta, Partha S Choudhary
Breast metastases are a relatively rare condition and account for approximately 0.5-2% of all breast tumors. Recognition of metastatic tumors in the breast is important because it would prevent unnecessary mutilating surgery and would lead to appropriate treatment of the primary tumor. Breast metastases from medullary thyroid cancer (MTC) are very rare with only 21 reported cases in the literature. Some MTCs mimic primary invasive lobular carcinoma of the breast histopathologically and radiologically, making the distinction between the two diagnostically challenging...
April 2018: Journal of Cytology
https://www.readbyqxmd.com/read/29615431/clinical-significance-of-ret-and-ras-mutations-in-sporadic-medullary-thyroid-cancer-a-meta-analysis
#19
Huy Gia Vuong, Toru Odate, Hanh T T Ngo, Thong Quang Pham, Thao T K Tran, Kunio Mochizuki, Tadao Nakazawa, Ryohei Katoh, Tetsuo Kondo
There are ongoing debates with respect to the prognostic roles of molecular biomarkers in sporadic medullary thyroid carcinoma (MTC). In this study, we aimed at investigating the prognostic value of RET and RAS mutations - the two most common mutations in sporadic MTCs. A search was conducted in four electronic databases. Relevant data were extracted and pooled into odds ratios (OR), mean differences (MD) and corresponding 95% confidence intervals (CI) using the random-effect model. We used Egger's regression test and visual of funnel plots to assess the publication bias...
April 3, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29608439/quantitative-analysis-of-the-benefits-and-risk-of-thyroid-nodule-evaluation-in-patients-%C3%A2-70-years-old
#20
Zhihong Wang, Chirag M Vyas, Olivia Van Benschoten, Matt A Nehs, Francis D Moore, Ellen Marqusee, Jeffrey F Krane, Matthew I Kim, Howard T Heller, Atul A Gawande, Mary C Frates, Peter M Doubilet, Gerard M Doherty, Nancy L Cho, Edmund S Cibas, Carol B Benson, Justine A Barletta, Ann Marie Zavacki, P Reed Larsen, Erik K Alexander, Trevor E Angell
BACKGROUND: In older patients, thyroid nodules are frequently detected and referred for evaluation, though usually prove to be benign disease or low-risk cancer. Therefore, management should be guided not solely by malignancy risk, but also by the relative risks of any intervention. Unfortunately, few such data are available for patients ≥70 years old. METHODS: All consecutive patients ≥70 years old assessed by ultrasound (US) and fine-needle aspiration (FNA) between 1995 and 2015 were analyzed...
April 2, 2018: Thyroid: Official Journal of the American Thyroid Association
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