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https://www.readbyqxmd.com/read/29161665/switchable-electrochemiluminescence-aptasensor-coupled-with-resonance-energy-transfer-for-selective-attomolar-detection-of-hg-2-via-cdte-cds-dendrimer-probe-and-au-nanoparticle-quencher
#1
Bahareh Babamiri, Abdollah Salimi, Rahman Hallaj
In the present study, an ultrasensitive electrochemiluminescence (ECL) aptasensing assay for selective detection of Hg(2+) was designed. In this electrochemiluminescence resonance energy transfer (ECL-RET) approach, Fe3O4@SiO2/dendrimers/QDs exhibited amplified ECL emissions (switch "on" state) and with the hybridization between T-rich ssDNA(S1) immobilized on the Fe3O4@SiO2/dendrimers/QDs and AuNPs modified with complementary aptamer (AuNPs-S2), the ECL of QDs nanocomposites was efficiently quenched (switch "off" state)...
November 10, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29159775/toxic-effects-of-phytol-and-retinol-on-human-glioblastoma-cells-are-associated-with-modulation-of-cholesterol-and-fatty-acid-biosynthetic-pathways
#2
Gustavo Facchini, Raffaela Silvestre Ignarro, Erika Rodrigues-Silva, André Schwambach Vieira, Iscia Lopes-Cendes, Roger Frigério Castilho, Fabio Rogerio
Glioblastoma (GBM) is the most common primary brain tumor. Genetic mutations may reprogram the metabolism of neoplastic cells. Particularly, alterations in cholesterol and fatty acid biosynthetic pathways may favor biomass synthesis and resistance to therapy. Therefore, compounds that interfere with those pathways, such as phytol (PHY) and retinol (RET), may be appropriate for cytotoxic approaches. We tested the effect of PHY or RET on the viability of human GBM cell lines (U87MG, A172 and T98G). Since the compounds showed a dose-dependent cytotoxic effect, additional analyses were performed with IC50 values...
November 20, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29159601/activating-fgfr1-mutations-in-sporadic-pheochromocytomas
#3
Jenny Welander, Małgorzata Łysiak, Michael Brauckhoff, Laurent Brunaud, Peter Söderkvist, Oliver Gimm
INTRODUCTION: Pheochromocytomas are neuroendocrine tumors of the adrenal glands. Up to 40% of the cases are caused by germline mutations in one of at least 15 susceptibility genes, making them the human neoplasms with the highest degree of heritability. Recurrent somatic alterations are found in about 50% of the more common sporadic tumors with NF1 being the most common mutated gene (20-25%). In many sporadic tumors, however, a genetic explanation is still lacking. MATERIALS AND METHODS: We investigated the genomic landscape of sporadic pheochromocytomas with whole-exome sequencing of 16 paired tumor and normal DNA samples and extended confirmation analysis in 2 additional cohorts comprising a total of 80 sporadic pheochromocytomas...
November 20, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/29158444/hnf1b-controls-epithelial-organization-and-cell-polarity-during-ureteric-bud-branching-and-collecting-duct-morphogenesis
#4
Audrey Desgrange, Claire Heliot, Ilya Skovorodkin, Saad U Akram, Janne Heikkilä, Veli-Pekka Ronkainen, Ilkka Miinalainen, Seppo J Vainio, Silvia Cereghini
Kidney development depends critically on proper ureteric bud branching giving rise to the entire collecting duct system. The transcription factor HNF1B is required for the early steps of ureteric bud branching. Yet, the molecular and cellular events regulated by HNF1B are poorly understood. We report that specific removal of Hnf1b from the ureteric bud leads to defective cell-cell contacts and apico-basal polarity during the early branching events. High resolution ex vivo imaging combined with a membranous fluorescent reporter strategy show decreased mutant cell-rearrangements during mitosis-associated cell dispersal and severe epithelial disorganisation...
November 20, 2017: Development
https://www.readbyqxmd.com/read/29152045/discovery-of-indolinone-based-multikinase-inhibitors-as-potential-therapeutics-for-idiopathic-pulmonary-fibrosis
#5
Zhenhua Huang, Heran Li, Qian Zhang, Fangzheng Lu, Mei Hong, Zhigang Zhang, Xiaocui Guo, Yuanju Zhu, Sanming Li, Hongzhuo Liu
Idiopathic pulmonary fibrosis (IPF) is a serious and deadly disease for which treatment options are limited. The recent approval of antifibrosis agent nintedanib represents one of the first therapeutic approaches for the treatment of IPF. Here, we report novel indolinone-based multikinase inhibitors that target angiogenesis and fibrosis pathways and may serve as potential therapeutics for IPF. KBP-7018 is a novel, tyrosine kinase-selective inhibitor with potent effects on three fibrotic kinases (c-KIT, PDGFR, and RET)...
November 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29145636/localization-and-functional-characterization-of-the-p-asn965ser-n965s-abca4-variant-in-mice-reveal-pathogenic-mechanisms-underlying-stargardt-macular-degeneration
#6
Laurie L Molday, Daniel Wahl, Marinko Sarunic, Robert S Molday
ABCA4 is a member of the superfamily of ATP-binding cassette (ABC) proteins that transports N-retinylidene-phosphatidylethanolamine (N-Ret-PE) across outer segment disc membranes thereby facilitating the removal of potentially toxic retinoid compounds from photoreceptor cells. Mutations in the gene encoding ABCA4 are responsible for Stargardt disease (STGD1), an autosomal recessive retinal degenerative disease that causes severe vision loss. To define the molecular basis for STGD1 associated with the p.Asn965Ser (N965S) mutation in the Walker A motif of nucleotide binding domain 1 (NBD1), we generated a p...
November 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#7
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29144541/genetic-landscape-of-papillary-thyroid-carcinoma-in-the-chinese-population
#8
Jialong Liang, Wanshi Cai, Dongdong Feng, Huajing Teng, Fengbiao Mao, Yi Jiang, Shanshan Hu, Xianfeng Li, Yujie Zhang, Baoguo Liu, Zhong Sheng Sun
Improvement in the clinical outcome of human cancers requires characterization of genetic alterations underlying their pathogenesis. Large-scale genomic and transcriptomic characterization of papillary thyroid carcinomas (PTCs) in Western populations has revealed multiple oncogenic drivers which are essential for understanding pathogenic mechanisms of this disease; while so far, the genetic landscape in Chinese patients with PTC remains uncharacterized. Here, we conducted a largescale genetic analysis of PTCs from patients in China to determine the mutational landscape of this cancer...
November 16, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29142006/characterization-of-neuroendocrine-tumors-in-heterozygous-mutant-menx-rats-a-novel-model-of-invasive-medullary-thyroid-carcinoma
#9
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/29142004/advances-in-the-management-of-men2
#10
Samuel Wells
Medullary thyroid carcinoma (MTC), a tumor derived from the neural crest, occurs either sporadically or as the dominant component of the type 2 multiple endocrine neoplasia (MEN) syndromes, MEN2A and MEN2B. The discovery that mutations in the RET protooncogene cause hereditary MTC was of great importance, since it led to the development of novel methods of diagnosis and treatment. For example, the detection of a mutated RET allele in family members at risk for inheriting MEN2A or MEN2B signaled that they would develop MTC, and possibly other components of the syndromes...
November 15, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29137260/pathologic-subtype-defined-prognosis-is-dependent-on-both-tumor-stage-and-status-of-oncogenic-driver-mutations-in-lung-adenocarcinoma
#11
Yu Dong, Ying Li, Bo Jin, Jie Zhang, Jinchen Shao, Hong Peng, Shichun Tu, Baohui Han
Previous studies have shown that the prognosis of lung adenocarcinoma is associated with pathological characterization. In this study, we investigated whether pathology-based prognosis was further influenced by both tumor stage and oncogenic driver mutations. To this end, we recruited a cohort of 465 lung adenocarcinoma patients in China. These patients were classified into 6 pathology-defined subtypes i.e., lepidic-predominant adenocarcinoma (LPA), acinar-predominant adenocarcinoma (APA), papillary-predominant adenocarcinoma (PPA), micropapillary-predominant adenocarcinoma (MPA), solid-predominant adenocarcinoma (SPA), and invasive mucinous adenocarcinoma (IMA)...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136674/familial-hyperparathyroidism-disorders-of-growth-and-secretion-in-hormone-secretory-tissue
#12
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/29134959/targeting-ret-driven-cancers-lessons-from-evolving-preclinical-and-clinical-landscapes
#13
REVIEW
Alexander Drilon, Zishuo I Hu, Gillianne G Y Lai, Daniel S W Tan
The gene encoding the receptor-tyrosine kinase RET was first discovered more than three decades ago, and activating RET rearrangements and mutations have since been identified as actionable drivers of oncogenesis. Several multikinase inhibitors with activity against RET have been explored in the clinic, and confirmed responses to targeted therapy with these agents have been observed in patients with RET-rearranged lung cancers or RET-mutant thyroid cancers. Nevertheless, response rates to RET-directed therapy are modest compared with those achieved using targeted therapies matched to other oncogenic drivers of solid tumours, such as sensitizing EGFR or BRAF(V600E) mutations, or ALK or ROS1 rearrangements...
November 14, 2017: Nature Reviews. Clinical Oncology
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
#14
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/29131865/associations-between-ret-tagsnps-and-their-haplotypes-and-susceptibility-clinical-severity-and-thyroid-function-in-patients-with-differentiated-thyroid-cancer
#15
Caiyun He, Jiangjun Ma, Yongle Jiang, Xuan Su, Xiao Zhang, Weichao Chen, Zulu Ye, Tiancheng Deng, Wenze Deng, Ankui Yang
BACKGROUND: It is unclear whether common genetic variants of the RET proto-oncogene contribute to disease susceptibility, clinical severity, and thyroid function in differentiated thyroid cancer (DTC). METHODS: A total of 300 DTC patients and 252 healthy controls were enrolled in this study. Seven RET tagging single nucleotide polymorphisms were genotyped using the KASPar platform. RESULTS: Subgroup analysis showed that concomitant thyroid benign diseases were less likely to occur in DTC subjects with the rs1799939 AG or AG plus AA genotypes (odds ratio (OR) = 1...
2017: PloS One
https://www.readbyqxmd.com/read/29130501/tert-promoter-hypermethylation-is-associated-with-metastatic-disease-in-abdominal-paraganglioma
#16
Fredrika Svahn, C Christofer Juhlin, Johan O Paulsson, Omid Fotouhi, Jan Zedenius, Catharina Larsson, Adam Stenman
Telomere maintenance, a hallmark of cancer for cell immortalization, is commonly achieved by telomerase activation through induction of the telomerase reverse transcriptase (TERT) gene. Pheochromocytomas (PCC) and abdominal paragangliomas (PGL) (together PPGL) are endocrine tumours for which TERT promoter mutations and telomerase activation have been previously reported [1]. Only 10-15% of PPGL metastasize, however in the absence of metastases, the identification of malignant disease is a diagnostic dilemma...
November 11, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/29130105/tumor-molecular-profiling-of-nsclc-patients-using-next-generation-sequencing
#17
Nikolaos Tsoulos, Eirini Papadopoulou, Vasiliki Metaxa-Mariatou, Georgios Tsaousis, Chrisoula Efstathiadou, Georgia Tounta, Aikaterini Scapeti, Eugenia Bourkoula, Pavlos Zarogoulidis, George Pentheroudakis, Stylianos Kakolyris, Ioannis Boukovinas, Pavlos Papakotoulas, Elias Athanasiadis, Theofanis Floros, Anna Koumarianou, Vasileios Barbounis, Anca Dinischiotu, George Nasioulas
Non‑small cell lung cancer (NSCLC) is the most common type of lung cancer and a tumor with a broad spectrum of targeted therapies already available or in clinical trials. Thus, molecular characterization of the tumor using next generation sequencing (NGS) technology, has become a key tool for facilitating treatment decisions and the clinical management of NSCLC patients. The performance of a custom 23 gene multiplex amplification hot spot panel, based on Ion AmpliSeq™ technology, was evaluated for the analysis of tumor DNA extracted from formalin-fixed and paraffin-embedded (FFPE) tissues...
December 2017: Oncology Reports
https://www.readbyqxmd.com/read/29129392/targeting-obesity-and-cachexia-identification-of-the-gfral-receptor-mic-1-gdf15-pathway
#18
Samuel N Breit, Vicky Wang-Wei Tsai, David A Brown
Macrophage inhibitory cytokine-1/growth differentiation factor 15 (MIC-1/GDF15) is a divergent transforming growth factor (TGFβ) superfamily cytokine implicated in biological and disease processes including metabolism, cancer, and chronic inflammation, but whose receptor has remained elusive. Four laboratories have recently identified GFRAL, an orphan receptor of the glial-derived neurotrophic factor (GDNF) receptor α family, as the receptor for MIC-1/GDF15, signaling though the coreceptor Ret. These data identify a new systemic to central nervous system (CNS) circuit that regulates metabolism in response to stress and which could be targeted to treat both severe obesity and anorexia/cachexia syndrome...
November 9, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29128428/clinical-and-translational-implications-of-ret-rearrangements-in-non-small-cell-lung-cancer
#19
REVIEW
Roberto Ferrara, Nathalie Auger, Edouard Auclin, Benjamin Besse
Since the discovery in 2012 of RET rearrangements in non-small cell lung cancer (NSCLC), at least 12 different fusion variants have been identified, with KIF5B-RET being the most frequent and the best characterized. Unlike ALK and ROS1 rearrangements, RET fusion genes cannot be adequately detected by immunohistochemistry, although fluorescence in situ hybridization and reverse transcriptase PCR are fully complementary diagnostic tools. In large retrospective studies, RET rearrangements correlate with adenocarcinoma histology, never-smoking status, younger age, more advanced stage disease, potentially higher chemo-sensitivity (in particular to pemetrexed-based regimens), and coexistence of other genomic alterations...
November 8, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29128185/correct-extent-of-thyroidectomy-is-poorly-predicted-preoperatively-by-the-guidelines-of-the-american-thyroid-association-for-low-and-intermediate-risk-thyroid-cancers
#20
Mashaal Dhir, Kelly L McCoy, N Paul Ohori, Cameron D Adkisson, Shane O LeBeau, Sally E Carty, Linwah Yip
BACKGROUND: Recent guidelines from the American Thyroid Association recommend thyroid lobectomy for intrathyroidal differentiated thyroid cancers <4 cm. Our aim was to examine histology from patients with cytologic results that were positive or suspicious for malignancy to assess the extent of initial thyroidectomy based on criteria from the 2015 American Thyroid Association guidelines. METHODS: We studied consecutive patients who had either a positive or suspicious for malignancy cytologic diagnosis and under prior American Thyroid Association guidelines underwent initial total thyroidectomy ± lymphadenectomy...
November 8, 2017: Surgery
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