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https://www.readbyqxmd.com/read/27904650/cabozantinib-in-the-treatment-of-advanced-renal-cell-carcinoma-clinical-trial-evidence-and-experience
#1
REVIEW
Jose Manuel Ruiz-Morales, Daniel Y C Heng
The treatment of metastatic renal cell carcinoma (mRCC) is rapidly changing. During first-line treatment with targeted therapy, patients ultimately develop resistance to therapy and the disease progresses. Recently, cabozantinib has demonstrated a better response rate, progression-free survival and overall survival compared with everolimus after failure of prior targeted therapy in patients with advanced or metastatic renal cell carcinoma (RCC). Cabozantinib is a small-molecule tyrosine kinase inhibitor (TKI)...
December 2016: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/27902697/a-novel-zebrafish-ret-heterozygous-model-of-hirschsprung-disease-identifies-a-functional-role-for-mapk10-as-a-modifier-of-enteric-nervous-system-phenotype-severity
#2
Tiffany A Heanue, Werend Boesmans, Donald M Bell, Koichi Kawakami, Pieter Vanden Berghe, Vassilis Pachnis
Hirschsprung disease (HSCR) is characterized by absence of enteric neurons from the distal colon and severe intestinal dysmotility. To understand the pathophysiology and genetics of HSCR we developed a unique zebrafish model that allows combined genetic, developmental and in vivo physiological studies. We show that ret mutant zebrafish exhibit cellular, physiological and genetic features of HSCR, including absence of intestinal neurons, reduced peristalsis, and varying phenotype expressivity in the heterozygous state...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27896649/the-micropapillary-hobnail-variant-of-papillary-thyroid-carcinoma-a-review-of-series-described-in-the-literature-compared-to-a-series-from-one-southern-italy-pathology-institution
#3
REVIEW
Antonio Ieni, Valeria Barresi, Roberta Cardia, Luana Licata, Flavia Di Bari, Salvatore Benvenga, Giovanni Tuccari
Papillary thyroid carcinoma (PTC) has a good prognosis with a 10-yr survival greater than 90%. Recently, a micro-papillary pattern with hobnail appearance (MPHC) in PTC has been indicated as associated with poor prognosis, but this suggestion is based only on a few cases from geographical areas different from ours. Two-hundred ninety-nine consecutive PTC cases were collected between the years of 1992 and 2014 at our institution. The corresponding histologic sections (at least 6 for each case) were stained with hematoxylin and eosin and reviewed independently by two pathologists to reach a consensus on the identification and quantification of the MPHC...
November 28, 2016: Reviews in Endocrine & Metabolic Disorders
https://www.readbyqxmd.com/read/27883960/a-dual-potential-electrochemiluminescence-ratiometric-sensor-for-sensitive-detection-of-dopamine-based-on-graphene-cdte-quantum-dots-and-self-enhanced-ru-ii-complex
#4
Xiaomin Fu, Xingrong Tan, Ruo Yuan, Shihong Chen
A novel dual-potential ratiometric electrochemiluminescence (ECL) sensor was designed for detecting dopamine (DA) based on graphene-CdTe quantum dots (G-CdTe QDs) as the cathodic emitter and self-enhanced Ru(II) composite (TAEA-Ru) as the anodic emitter. TAEA-Ru was prepared by linking ruthenium(II) tris(2,2'-bipyridyl-4,4'-dicarboxylato) with tris(2-aminoethyl)amine. Firstly, 3-aminopropyltriethoxysilane founctionalized G-CdTe QDs was used as the substrate for capturing target DA via the specific recognition of the diol of DA to the oxyethyl group of APTES...
November 11, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27881454/cabozantinib-is-active-in-patients-with-advanced-ret-rearranged-nsclc
#5
(no author information available yet)
Cabozantinib achieved an overall response rate of 28% in patients with RET-rearranged NSCLC.
November 23, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27873490/egf-induced-ret-inhibitor-resistance-in-ccdc6-ret-lung-cancer-cells
#6
Hyun Chang, Ji Hea Sung, Sung Ung Moon, Han Soo Kim, Jin Won Kim, Jong Seok Lee
PURPOSE: Rearrangement of the proto-oncogene rearranged during transfection (RET) has been newly identified potential driver mutation in lung adenocarcinoma. Clinically available tyrosine kinase inhibitors (TKIs) target RET kinase activity, which suggests that patients with RET fusion genes may be treatable with a kinase inhibitor. Nevertheless, the mechanisms of resistance to these agents remain largely unknown. Thus, the present study aimed to determine whether epidermal growth factor (EGF) and hepatocyte growth factor (HGF) trigger RET inhibitor resistance in LC-2/ad cells with CCDC6-RET fusion genes...
January 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/27872141/differential-roles-of-ret-isoforms-in-medullary-and-papillary-thyroid-carcinomas
#7
Eric Y Lian, Sarah M Maritan, Jessica G Cockburn, Katayoon Kasaian, Mathieu Jf Crupi, David Hurlbut, Steven Jones, Sam Wiseman, Lois M Mulligan
The RET receptor tyrosine kinase mediates cell proliferation, survival and migration in embryogenesis, and is implicated in transformation and tumour progression in multiple cancers. RET is frequently mutated and constitutively activated in familial and sporadic thyroid carcinomas. As a result of alternative splicing, RET is expressed as two protein isoforms, RET9 and RET51, which differ in their unique C-terminal amino acids. These isoforms have distinct intracellular trafficking and associated signaling complexes, but functional differences are not well defined...
November 21, 2016: Endocrine-related Cancer
https://www.readbyqxmd.com/read/27869424/-study-of-medullary-thyroid-carcinoma-from-a-proband
#8
Laura Morlán Herrador, Antonio de Arriba, Gloria Miguel, Marta Ferrera, José I Labarta
Thyroid cancer is an uncommon type of cancer, accounting less than 1% of all cancers in adults, and 0.5-3% of all cancers in children. There are four different types: papillary carcinoma (80-90% of cases), follicular (5-10%), medullary (5%) and anaplastic cell (2-3%). Eighty per cent of cases of medullary thyroid cancer are sporadic, but 20% are associated with an inherited syndrome that is divided into three groups: multiple endocrine neoplasia type 1, multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma...
December 1, 2016: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/27865871/clinical-impact-of-hybrid-capture-based-next-generation-sequencing-on-changes-in-treatment-decisions-in-lung-cancer
#9
Anna Belilovski Rozenblum, Maya Ilouze, Elizabeth Dudnik, Addie Dvir, Lior Soussan-Gutman, Smadar Geva, Nir Peled
INTRODUCTION: Targeted therapy significantly prolongs survival in lung adenocarcinoma. Current diagnostic guidelines include only EGFR and ALK testing. Next-generation sequencing (NGS) reveals more actionable genomic alterations (GAs) than stan dard diagnostic methods. Data on the influence of hybrid capture-based (HC-based) NGS on treatment are limited, and we investigated its impact on treatment decisions/clinical outcomes. METHODS: This retrospective study included patients with advanced lung cancer on whom HC-based NGS was performed between 11/2011-10/2015...
November 9, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27864876/kinase-gene-fusions-in-defined-subsets-of-melanoma
#10
Jacqueline Turner, Kasey Couts, Jamie Sheren, Siriwimon Saichaemchan, Witthawat Ariyawutyakorn, Izabela Avolio, Ethan Cabral, Magdelena Glogowska, Carol Amato, Steven Robinson, Jennifer Hintzsche, Allison Applegate, Eric Seelenfreund, Rita Gonzalez, Keith Wells, Stacey Bagby, John Tentler, Aik-Choon Tan, Joshua Wisell, Marileila Varella-Garcia, William Robinson
Genomic rearrangements resulting in activating kinase fusions have been increasingly described in a number of cancers including malignant melanoma, but their frequency in specific melanoma subtypes has not been reported. We used break-apart fluorescence in-situ hybridization (FISH) to identify genomic rearrangements in tissues from 59 patients with various types of malignant melanoma including acral lentiginous, mucosal, superficial spreading, and nodular. We identified four genomic rearrangements involving the genes BRAF, RET, and ROS1...
November 19, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27864651/all-in-the-family-analyzing-the-impact-of-family-history-in-addition-to-genotype-on-medullary-thyroid-carcinoma-aggressiveness-in-men2a-patients
#11
Kristin L Long, Carol Etzel, Thereasa Rich, Samuel Hyde, Nancy D Perrier, Paul H Graham, Jeffrey E Lee, Mimi I Hu, Gilbert J Cote, Robert Gagel, Elizabeth G Grubbs
Several guidelines for patients with multiple endocrine neoplasia 2A (MEN2A) take into account genotype and family history of medullary thyroid carcinoma (MTC) disease aggressiveness. We sought to determine if an association exists independent of genotype, which could provide important information for counseling MEN2A patients in management of their MTC. Pedigrees of patients with ≥5 family members with MEN2A were retrospectively reviewed. Analysis was performed among kindreds with the most frequently observed codon mutation (RET 634)...
November 18, 2016: Familial Cancer
https://www.readbyqxmd.com/read/27853024/extraskeletal-osteosarcoma-of-the-orbit-a-clinicopathologic-case-report-and-review-of-literature
#12
V M D S de Maeyer, P A F A Kestelyn, Akash D Shah, C M Van Den Broecke, H G N Denys, C E Decock
Primary extraskeletal osteosarcoma (EOS) is an extremely rare malignancy. In this report, the clinical course of a 32-year-old man presenting with proptoses is described. Medical history included Hirschsprung disease (HD), horseshoe kidney, azoospermia, and vertebral anomalies. Imaging of the orbit showed an oval, well-defined heterogeneous mass adjacent to the lateral wall of the orbit. The patient underwent a lateral orbitotomy and complete excision of the mass. The mass was not attached to the bone. Histopathologic and immunohistochemical examination confirmed the diagnosis of an EOS...
September 2016: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/27849670/ret-ptc3-rearrangement-in-papillary-thyroid-carcinoma-possible-marker-of-tumor-progression
#13
Sergei V Jargin
No abstract text is available yet for this article.
November 15, 2016: Annals of Surgery
https://www.readbyqxmd.com/read/27849443/fusion-oncogenes-are-the-main-genetic-events-found-in-sporadic-papillary-thyroid-carcinomas-from-children
#14
Maria Isabel Cunha Vieira Cordioli, Lais Moraes, André Uchimura Bastos, Paloma Besson, Maria Teresa de Seixas Alves, Rosana Delcelo, Osmar Monte, Carlos A Longui, Adriano Namo Cury, Janete Cerutti
BACKGROUND: Previous studies reported significant differences in the clinical presentation and outcomes of papillary thyroid carcinoma (PTC) in pediatric patients compared to adults. Previous studies have suggested that the clinicopathological differences observed between pediatric and adult PTC may be due the existence of distinct genetic alterations. However, the knowledge of genetic events in pediatric PTC is based primarily on studies in radiation-exposed PTC or in few studies that enrolled predominantly adolescent patients...
November 16, 2016: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/27847096/a-cohort-study-on-10-year-survival-of-sporadic-medullary-thyroid-carcinoma-with-somatic-ret-mutation
#15
Li-Lun Chuang, Daw-Yang Hwang, Kun-Bow Tsai, Hon-Man Chan, Feng-Yu Chiang, Pi-Jung Hsiao
Somatic rearranged during transfection (RET) mutations are reported in 40-50% of sporadic medullary thyroid carcinoma (sMTC) patients with prognostic significance. As there is a lack of somatic RET mutations reported previously for the Taiwanese population, we tried to assess the presence of somatic RET mutations and evaluate the potential outcome predictors for our sMTC patients. We collected data from seven sMTC patients from the years 1997 to 2005 and analyzed their clinic-pathological features up to 2015...
November 2016: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/27842445/cabozantinib-in-genitourinary-malignancies
#16
Tian Zhang, Se Eun Park, Cierra Hong, Daniel J George
Cabozantinib inhibits a variety of cellular receptors including VEGFR1-3, MET, AXL, RET, FLT3 and KIT. These signaling pathways have been shown to be important in genitourinary malignancies. Along its clinical development, it has shown most activity in advanced renal cell carcinoma; the METEOR study compared cabozantinib to everolimus and showed clinically and statistically significant improvements in both progression-free survival and overall survival. Herein, we review the development of cabozantinib in the genitourinary malignancies of renal cell carcinoma, prostate adenocarcinoma and urothelial carcinoma...
November 15, 2016: Future Oncology
https://www.readbyqxmd.com/read/27836695/clinical-validation-of-a-next-generation-sequencing-genomic-oncology-panel-via-cross-platform-benchmarking-against-established-amplicon-sequencing-assays
#17
Sabah Kadri, Bradley C Long, Ibro Mujacic, Chao J Zhen, Michelle N Wurst, Shruti Sharma, Nadia McDonald, Nifang Niu, Sonia Benhamed, Jigyasa Tuteja, Tanguy Seiwert, Kevin White, Megan E McNerney, Carrie Fitzpatrick, Y Lynn Wang, Larissa V Furtado, Jeremy P Segal
Next-generation sequencing (NGS) genomic oncology profiling assays have emerged as key drivers of personalized cancer care and translational research. However, validation of these assays to meet strict clinical standards has been historically problematic because of both significant assay complexity and a scarcity of optimal validation samples. Herein, we present the clinical validation of 76 genes from a novel 1212-gene large-scale hybrid capture cancer sequencing assay (University of Chicago Medicine OncoPlus) using full-data comparisons against multiple clinical NGS amplicon-based assays to yield dramatic increases in per-sample data comparison efficiency compared with previously published validations...
November 8, 2016: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27834132/surgical-management-of-medullary-thyroid-carcinoma-in-pediatric-age
#18
Claudio Spinelli, Leonardo Rossi, Silvia Strambi, Jessica Piscioneri, Rossella Elisei, Maura Massimino, Paolo Miccoli
Medullary thyroid carcinoma (MTC) is a rare, accounting for 5% of thyroid malignancies. It is a neuroendocrine tumor wich origins from thyroid parafollicular cells. It may be sporadic, mostly in adult patients, or inherited as autosomal dominant pattern, mostly in pediatric patients. As familial cancer, MTC may presented isolated as familial medullary thyroid carcinoma (FMTC) - 10% of cases - or, most often, as part of multiple endocrine neoplasm type 2 (MEN 2A or MEN 2B) syndromes - 90% of cases. The therapy for sporadic or hereditary MTC is surgical resection and consists in total thyroidectomy associated with central compartment lymph nodal dissection; the radicality of this intervention is fundamental to obtain a definitive cure...
November 11, 2016: Current Pediatric Reviews
https://www.readbyqxmd.com/read/27834083/molecular-diagnosis-using-residual-liquid-based-cytology-materials-for-patients-with-nondiagnostic-or-indeterminate-thyroid-nodules
#19
Hyemi Kwon, Won Gu Kim, Markus Eszlinger, Ralf Paschke, Dong Eun Song, Mijin Kim, Suyeon Park, Min Ji Jeon, Tae Yong Kim, Young Kee Shong, Won Bae Kim
BACKGROUND: Molecular analysis for common somatic mutations in thyroid cancer can improve diagnostic accuracy of fine-needle aspiration cytology (FNAC) in the nondiagnostic or indeterminate category of thyroid nodules. In this study, we evaluated the feasibility of molecular diagnosis from residual liquid-based cytology (LBC) material after cytological diagnosis. METHODS: This prospective study enrolled 53 patients with thyroid nodules diagnosed as nondiagnostic, atypia of undetermined significance (AUS), or follicular lesion of undetermined significance (FLUS) after FNAC...
November 4, 2016: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27826534/fusion-gene-and-splice-variant-analyses-in-liquid-biopsies-of-lung-cancer-patients
#20
REVIEW
Cristina Aguado, Ana Giménez-Capitán, Niki Karachaliou, Ana Pérez-Rosado, Santiago Viteri, Daniela Morales-Espinosa, Rafael Rosell
Obtaining a biopsy of solid tumors requires invasive procedures that strongly limit patient compliance. In contrast, a blood extraction is safe, can be performed at many time points during the course disease and encourages appropriate therapy modifications, potentially improving the patient's clinical outcome and quality of life. Fusion of the tyrosine kinase genes anaplastic lymphoma kinase (ALK), C-ROS oncogen 1 (ROS 1), rearranged during transfection (RET) and neurotrophic tyrosine kinase 1 (NTRK1) occur in 1-5% of lung adenocarcinomas and constitute therapeutic targets for tyrosine kinase inhibitors...
October 2016: Translational Lung Cancer Research
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