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https://www.readbyqxmd.com/read/29348306/novel-targeted-therapeutics-for-men2
#1
REVIEW
Sara Redaelli, Ivan Plaza-Menacho, Luca Mologni
The rearranged during transfection (RET) proto-oncogene was recognized as the multiple endocrine neoplasia type 2 (MEN2) causing gene in 1993. Since then, much effort has been put into a clear understanding of its oncogenic signaling, its biochemical function and ways to block its aberrant activation in MEN2 and related cancers. Several small molecules have been designed, developed or redirected as RET inhibitors for the treatment of MEN2 and sporadic MTC. However, current drugs are mostly active against several other kinases, as they were not originally developed for RET...
February 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29326158/reciprocal-spatiotemporally-controlled-apoptosis-regulates-wolffian-duct-cloaca-fusion
#2
Masato Hoshi, Antoine Reginensi, Matthew S Joens, James A J Fitzpatrick, Helen McNeill, Sanjay Jain
The epithelial Wolffian duct (WD) inserts into the cloaca (primitive bladder) before metanephric kidney development, thereby establishing the initial plumbing for eventual joining of the ureters and bladder. Defects in this process cause common anomalies in the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). However, developmental, cellular, and molecular mechanisms of WD-cloaca fusion are poorly understood. Through systematic analysis of early WD tip development in mice, we discovered that a novel process of spatiotemporally regulated apoptosis in WD and cloaca was necessary for WD-cloaca fusion...
January 11, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29324283/a-novel-electrochemiluminescent-biosensor-based-on-resonance-energy-transfer-between-poly-9-9-di-n-octylfluorenyl-2-7-diyl-and-3-4-9-10-perylenetetracar-boxylic-acid-for-insulin-detection
#3
Han Zhang, Fumei Zuo, Xingrong Tan, Shenghao Xu, Ruo Yuan, Shihong Chen
An electrochemiluminescencent (ECL) biosensor was designed for the determination of insulin using a novel ECL resonance energy transfer (ECL-RET) strategy. In this strategy, carboxyl poly(9,9-dioctyfluorenyl-2,7-diyl) dots (PFO dots) were worked as ECL donor and 3,4,9,10-perylenetetracar-boxylic acid (PTCA) exploited as ECL acceptor, and hydrogen peroxide (H2O2) employed as the coreactant. The ECL donor and ECL acceptor were separately labeled with primary antibody (Ab1) and secondary antibody (Ab2), forming a sensing interface to the analyte target, insulin...
December 27, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29321660/activated-alk-signals-through-the-erk-etv5-ret-pathway-to-drive-neuroblastoma-oncogenesis
#4
Lucille Lopez-Delisle, Cécile Pierre-Eugène, Caroline Louis-Brennetot, Didier Surdez, Virginie Raynal, Sylvain Baulande, Valentina Boeva, Sandrine Grossetête-Lalami, Valérie Combaret, Michel Peuchmaur, Olivier Delattre, Isabelle Janoueix-Lerosey
Activating mutations of the ALK receptor occur in a subset of neuroblastoma tumors. We previously demonstrated that Alk mutations cooperate with MYCN overexpression to induce neuroblastoma in mice and identified Ret as being strongly upregulated in MYCN/Alkmut tumors. By a genetic approach in vivo, we now document an oncogenic cooperation between activated Ret and MYCN overexpression in neuroblastoma formation. We show that MYCN/RetM919T tumors exhibit histological features and expression profiles close to MYCN/Alkmut tumors...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29290262/gcc2-alk-as-a-targetable-fusion-in-lung-adenocarcinoma-and-its-enduring-clinical-responses-to-alk-inhibitors
#5
Junhong Jiang, Xue Wu, Xiaoling Tong, Wangzhi Wei, Anan Chen, Xiaonan Wang, Yang W Shao, Jianan Huang
OBJECTIVES: ALK, RET and ROS1 fusions have been identified as treatable targets in 5%-15% of non-small-cell lung cancers, and thanks to the advanced sequencing technologies, their new partner genes have been steadily detected. Here we identified a rare fusion of ALK (GCC2-ALK) in a patient with advanced lung adenocarcinoma and monitored the treatment efficacy of ALK inhibitors on this patient. We further performed in vitro functional studies of this fusion protein for evaluating its oncogenic potential...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29282324/biphasic-functions-for-the-gdnf-ret-signaling-pathway-in-chemosensory-neuron-development-and-diversification
#6
Christopher R Donnelly, Amol A Shah, Charlotte M Mistretta, Robert M Bradley, Brian A Pierchala
The development of the taste system relies on the coordinated regulation of cues that direct the simultaneous development of both peripheral taste organs and innervating sensory ganglia, but the underlying mechanisms remain poorly understood. In this study, we describe a novel, biphasic function for glial cell line-derived neurotrophic factor (GDNF) in the development and subsequent diversification of chemosensory neurons within the geniculate ganglion (GG). GDNF, acting through the receptor tyrosine kinase Ret, regulates the expression of the chemosensory fate determinant Phox2b early in GG development...
December 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29251734/ligation-dependent-rt-pcr-a-new-specific-and-low-cost-technique-to-detect-alk-ros-and-ret-rearrangements-in-lung-adenocarcinoma
#7
Nicolas Piton, Philippe Ruminy, Claire Gravet, Vinciane Marchand, Élodie Colasse, Aude Lamy, Cécile Le Naoures Mear, Fréderic Bibeau, Florent Marguet, Florian Guisier, Mathieu Salaün, Luc Thiberville, Fabrice Jardin, Jean-Christophe Sabourin
Detection of anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 (ROS1), and rearranged during transfection (RET) gene rearrangements in lung adenocarcinoma is usually performed by immunohistochemistry (IHC) screening followed by fluorescence in situ hybridization (FISH), which is an expensive and difficult technique. Ligation-dependent reverse transcription polymerase chain reaction (RT-PCR) multiplex technique can detect gene rearrangements using probes specifically hybridized to either side of the break point...
December 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29239040/molecular-pathology-of-thyroid-tumours-of-follicular-cells-a-review-of-genetic-alterations-and-their-clinicopathological-relevance
#8
REVIEW
Giorgia Acquaviva, Michela Visani, Andrea Repaci, Kerry J Rhoden, Dario de Biase, Annalisa Pession, Tallini Giovanni
Thyroid cancer is the most common endocrine malignancy. Knowledge of the molecular pathology of thyroid tumours originating from follicular cells has greatly advanced in the past several years. Common molecular alterations, such as BRAF p.V600E, RAS point mutations, and fusion oncogenes (RET-PTC being the prototypical example), have been, respectively, associated with conventional papillary carcinoma, follicular-patterned tumours (follicular adenoma, follicular carcinoma, and the follicular variant of papillary carcinoma/non-invasive follicular thyroid neoplasm with papillary-like nuclear features), and with papillary carcinomas from young patients and arising after exposure to ionising radiation, respectively...
January 2018: Histopathology
https://www.readbyqxmd.com/read/29237911/functional-analysis-of-ret-with-multiple-endocrine-neoplasia-type-2
#9
Meihua Zhang, Yao Liu, Jie Fu, Ying Hu, Zheng Sun
BACKGROUND: Multiple endocrine neoplastic type 2 (MEN2) is an endocrine carcinoma syndrome which is caused by a germline activation mutation that occurs during transfection (RET) proto-oncogene transmission. MEN2A patients are affected by RET (C634Y, C634R) mutation; MEN2B patients are affected by RET (M918T) mutation. AIMS: We aim to identify RET mutations' (C634R and M918T) expression, location, and signaling activation during the disease's progression, which providing a theoretical basis for the study on etiology of multiple endocrine neoplasia...
2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/29218725/characterization-of-retinal-ganglion-cell-horizontal-cell-and-amacrine-cell-types-expressing-the-neurotrophic-receptor-tyrosine-kinase-ret
#10
Nadia Parmhans, Szilard Sajgo, Jingwen Niu, Wenqin Luo, Tudor Constantin Badea
We report the retinal expression pattern of Ret, a receptor tyrosine kinase for the Glial Derived Neurotrophic Factor (GDNF) family ligands (GFLs), during development and in the adult mouse. Ret is initially expressed in Retinal Ganglion Cells (RGCs), followed by Horizontal Cells (HCs) and Amacrine Cells (ACs), beginning with the early stages of postmitotic development. Ret expression persists in all three classes of neurons in the adult. Using RNA sequencing, immunostaining and random sparse recombination, we show that Ret is expressed in at least three distinct types of ACs, and ten types of RGCs...
December 8, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29212800/extracellular-retention-of-pdgf-b-directs-vascular-remodeling-in-mouse-hypoxia-induced-pulmonary-hypertension
#11
Philip Tannenberg, Ya-Ting Chang, Lars Muhl, Bàrbara Laviña, Hanna Gladh, Guillem Genové, Christer Betsholtz, Erika Folestad, Karin Tran-Lundmark
Pulmonary hypertension (PH) is a lethal condition and current vasodilator therapy has limited effect. Anti-proliferative strategies targeting platelet-derived growth factor (PDGF) receptors, such as imatinib, have generated promising results in animal studies. Imatinib is however a non-specific tyrosine kinase inhibitor and has in clinical studies caused unacceptable adverse events. Further studies are needed on the role of PDGF signaling in PH. Here, mice expressing a variant of PDGF-B with no retention motif (Pdgfbret/ret), resulting in defective binding to extracellular matrix, were studied...
December 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29201215/contrast-enhanced-computerized-tomography-combined-with-a-targeted-nanoparticle-contrast-agent-for-screening-for-early-phase-non-small-cell-lung-cancer
#12
Ninglu Yuan, Xiaohe Zhang, Yonghui Cao, Xiaojie Jiang, Si Zhao, Yingying Feng, Yimeng Fan, Zhitao Lu, Hongmei Gao
Non-small cell lung cancer (NSCLC) is a major cause of morbidity and mortality, and patients with NSCLC are frequently diagnosed at an advanced stage. This is primarily due to a lack of advanced and sensitive protocols for the detection of early stage NSCLC. Therefore, methods for the accurate diagnosis of early stage NSCLC are urgently required to improve survival rates. The present study investigated the use of contrast-enhanced computerized tomography (CECT) combined with a targeted nanoparticle contrast agent (TNCA) to diagnose early-stage NSCLC in a mice xenograft model...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29198084/-the-impact-of-molecular-profiling-using-next-generation-sequencing-in-advanced-lung-cancer
#13
Anna Belilovski Rozenblum, Maya Ilouze, Elizabeth Dudnik, Lior Soussan-Gutman, Addie Dvir, Nir Peled
BACKGROUND: In the last decade, important advances in understanding the lung cancer cellular signal pathways have led to the designing of targeted drugs that significantly prolong survival. Recent data shows that 64% of lung adenocarcinomas harbor at least one activating driver mutation, including treatable mutations such as RET, ERBB2 (HER-2) and ROS1 gene mutations, besides the regularly screened ALK and EGFR genes. Next-Generation Sequencing (NGS) reveals more clinically meaningful genomic alterations as compared to currently used diagnostic tests...
November 2017: Harefuah
https://www.readbyqxmd.com/read/29197384/involvement-of-the-bone-morphogenic-protein-smad-signaling-pathway-in-the-etiology-of-congenital-anomalies-of-the-kidney-and-urinary-tract-accompanied-by-cryptorchidism
#14
Kentaro Mizuno, Akihiro Nakane, Hidenori Nishio, Yoshinobu Moritoki, Hideyuki Kamisawa, Satoshi Kurokawa, Taiki Kato, Ryosuke Ando, Tetsuji Maruyama, Takahiro Yasui, Yutaro Hayashi
BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT), such as renal dysplasia, hydronephrosis, or vesicoureteral reflux, are the most common causes of end-stage renal disease. However, the genetic etiology of CAKUT remains unclear. In this study, we performed whole exome sequencing (WES) to elucidate the genetic etiology of symptomatic CAKUT and CAKUT accompanied by cryptorchidism. METHODS: Three patients with unilateral renal dysplasia accompanied by ipsilateral cryptorchidism were included in this analysis...
December 2, 2017: BMC Urology
https://www.readbyqxmd.com/read/29175871/ret-receptor-structure-and-function-in-men2
#15
Ivan Plaza-Menacho
It has been 25 years since the discovery of oncogenic germline RET mutations as the cause of Multiple Endocrine Neoplasia type II (MEN2). Intensive work over the last two and a half decades on RET genetics, signaling and cell biology have provided the current bases for the genotype-phenotype and functional correlations within this cancer syndrome. On the contrary, the structural and molecular basis for RET tyrosine kinase domain activation and oncogenic deregulation has remained largely elusive. Recent studies with a strong crystallographic and biochemical focus however have started to elucidate key insights into such molecular and atomic details revealing unexpected and private mechanisms of actions and molecular determinants not previously envisioned...
November 24, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29163356/sonic-hedgehog-signaling-in-thyroid-cancer
#16
REVIEW
Xiulong Xu, Yurong Lu, Yi Li, Richard A Prinz
Thyroid cancer is the most common malignancy of the endocrine system. The initiation of thyroid cancer is often triggered by a genetic mutation in the phosphortidylinositol-3 kinase (PI3K) or mitogen-activated protein kinase (MAPK) pathway, such as RAS and BRAF, or by the rearrangement of growth factor receptor tyrosine kinase genes such as RET/PTC. The sonic hedgehog (Shh) pathway is evolutionarily conserved and plays an important role in the embryonic development of normal tissues and organs. Gene mutations in the Shh pathway are involved in basal cell carcinomas (BCC)...
2017: Frontiers in Endocrinology
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
#17
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/29159601/activating-fgfr1-mutations-in-sporadic-pheochromocytomas
#18
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
#19
Audrey Desgrange, Claire Heliot, Ilya Skovorodkin, Saad U Akram, Janne Heikkilä, Veli-Pekka Ronkainen, Ilkka Miinalainen, Seppo J Vainio, Silvia Cereghini
Kidney development depends crucially 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 apicobasal 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 disorganization...
December 15, 2017: Development
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#20
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
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