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https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#1
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/29142004/advances-in-the-management-of-men2
#2
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/29130501/tert-promoter-hypermethylation-is-associated-with-metastatic-disease-in-abdominal-paraganglioma
#3
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/29129392/targeting-obesity-and-cachexia-identification-of-the-gfral-receptor-mic-1-gdf15-pathway
#4
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/29114471/beyond-alk-and-ros1-ret-ntrk-egfr-and-braf-gene-rearrangements-in-non-small-cell-lung-cancer
#5
REVIEW
Anna F Farago, Christopher G Azzoli
The discovery of gene rearrangements involving the receptor tyrosine kinase genes ALK and ROS1 has revolutionized management of the subset of non-small cell lung cancers characterized by these alterations. The oncogenic fusion proteins expressed in these tumors drive cancer cell growth and survival, and targeted inhibition of this signaling can lead to dramatic and durable responses in patients. While the best characterized gene fusions in non-small cell lung cancer (NSCLC) involve ALK and ROS1, fusions involving other kinases including RET, NTRK, EGFR and BRAF are now established as additional targetable drivers...
October 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29106982/distinct-trka-and-ret-modulated-negative-and-positive-neuropathic-behaviors-in-a-mouse-model-of-resiniferatoxin-induced-small-fiber-neuropathy
#6
Yu-Lin Hsieh, Hung-Wei Kan, Hao Chiang, Yi-Chen Lee, Sung-Tsang Hsieh
Neurotrophic factors and their corresponding receptors play key roles in the maintenance of different phenotypic dorsal root ganglion (DRG) neurons, the axons of which degenerate in small fiber neuropathy, leading to various neuropathic manifestations. Mechanisms underlying positive and negative symptoms of small fiber neuropathy have not been systematically explored. This study investigated the molecular basis of these seemingly paradoxical neuropathic behaviors according to the profiles of TrkA and Ret with immunohistochemical and pharmacological interventions in a mouse model of resiniferatoxin (RTX)-induced small fiber neuropathy...
October 26, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29089297/ccr5-myeloid-derived-suppressor-cells-are-enriched-and-activated-in-melanoma-lesions
#7
Carolin Blattner, Viktor Fleming, Rebekka Weber, Bianca S Himmelhan, Peter Altevogt, Christoffer Gebhardt, Torsten J Schulze, Hila Razon, Elias Hawila, Gizi Wildbaum, Jochen Utikal, Nathan Karin, Viktor Umansky
Accumulation of myeloid-derived suppressor cells (MDSC) in melanoma microenvironment is supported by chemokine receptor/chemokine signaling. Although different chemokines were suggested to be involved in this process, the role of CCR5 and its ligands is not established. Using a ret transgenic mouse melanoma model, we found an accumulation of CCR5+ MDSC in melanoma lesions associated with both increased concentrations of CCR5 ligands and tumor progression. Tumor-infiltrating CCR5+ MDSC displayed higher immunosuppressive activity than their CCR5- counterparts...
October 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/29066476/role-of-cdkn2c-fluorescence-in-situ-hybridization-in-the-management-of-medullary-thyroid-carcinoma
#8
Maha El Naofal, Adriel Kim, Hui Yi Yon, Mohamed Baity, Zhao Ming, Jacquelin Bui-Griffith, Zhenya Tang, Melissa Robinson, Elizabeth G Grubbs, Gilbert J Cote, Peter Hu
Medullary thyroid carcinoma (MTC), an aggressive form of thyroid cancer, occurs sporadically in approximately 75% of MTCs. RET and RAS mutations play a role in about 40% and 15%, respectively, of sporadic MTCs and are predominant drivers in MTC pathways. These mutations are some of the most comprehensively described and screened for in MTC patients; however, in recent studies, other mutations in the CDKN2C gene (p18) have been implicated in the tumorigenesis of MTC. Comparative genomic hybridization analysis revealed that approximately 40% of sporadic MTC samples have loss of CDKN2C at chromosome 1p32 in addition to frequent losses of CDKN2D (p19) at chromosome 19p13...
September 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/29063141/cmpx-affects-virulence-in-pseudomonas-aeruginosa-through-the-gac-rsm-signaling-pathway-and-by-modulating-c-di-gmp-levels
#9
Anjali Y Bhagirath, Deepti Somayajula, Yanqi Li, Kangmin Duan
Pseudomonas aeruginosa is an ubiquitous organism which is able to infect and colonize many types of hosts including humans. Colonization of P. aeruginosa in chronic infections leads to the formation of biofilms, which are difficult to eradicate. P. aeruginosa is capable of regulating its virulence factors in response to external environment triggers and its signaling mechanism involves two-component regulatory systems and small molecules such as bis-(3'-5')-cyclic dimeric guanosine monophosphate. PA1611-RetS-GacS/A-RsmA/Y/Z is a key regulatory pathway in P...
October 23, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#10
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29047216/uteroplacental-insufficiency-in-rats-induces-renal-apoptosis-and-delays-nephrogenesis-completion
#11
James Sm Cuffe, Jessica F Briffa, Shannyn Rosser, Andrew L Siebel, Tania Romano, Deanne H Hryciw, Mary E Wlodek, Karen M Moritz
AIM: Uteroplacental insufficiency in rats reduces nephron endowment, leptin concentrations and programs cardiorenal disease in offspring. Cross-fostering growth restricted (Restricted) offspring onto a mother with normal lactation restores leptin concentrations and nephron endowment. This study aimed to determine if the reduced nephron endowment in Restricted offspring is due to delayed glomerular formation and dysregulation of renal genes regulating branching morphogenesis, apoptosis or leptin signalling...
October 19, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/29045838/p75-is-required-for-the-establishment-of-postnatal-sensory-neuron-diversity-by-potentiating-ret-signaling
#12
Zhijiang Chen, Christopher R Donnelly, Bertha Dominguez, Yoshinobu Harada, Weichun Lin, Alan S Halim, Tasha G Bengoechea, Brian A Pierchala, Kuo-Fen Lee
Producing the neuronal diversity required to adequately discriminate all elements of somatosensation is a complex task during organogenesis. The mechanisms guiding this process during dorsal root ganglion (DRG) sensory neuron specification remain poorly understood. Here, we show that the p75 neurotrophin receptor interacts with Ret and its GFRα co-receptor upon stimulation with glial cell line-derived neurotrophic factor (GDNF). Furthermore, we demonstrate that p75 is required for GDNF-mediated Ret activation, survival, and cell surface localization of Ret in DRG neurons...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29045518/negative-hyper-selection-of-metastatic-colorectal-cancer-patients-for-anti-egfr-monoclonal-antibodies-the-pressing-case-control-study
#13
C Cremolini, F Morano, R Moretto, R Berenato, E Tamborini, F Perrone, D Rossini, A Gloghini, A Busico, G Zucchelli, C Baratelli, E Tamburini, M Tampellini, E Sensi, G Fucà, C Volpi, M Milione, M Di Maio, G Fontanini, F De Braud, A Falcone, F Pietrantonio
Background: Refining the selection of metastatic colorectal cancer (mCRC) patients candidates for anti-EGFR monoclonal antibodies beyond RAS and BRAF testing is a challenge of precision oncology. Several uncommon genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than EGFR or downstream signaling pathways, have been suggested by preclinical and retrospective studies. Patients and methods: We conducted this multicenter, prospective, case-control study to demonstrate the negative predictive impact of a panel of rare genomic alterations (PRESSING panel), including HER2/MET amplifications, ALK/ROS1/NTRK1-3/RET fusions, and HER2/PI3K/PTEN/AKT1 mutations...
September 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29031858/involvement-of-integrin-%C3%AE-1-fak-signaling-in-the-analgesic-effects-induced-by-glial-cell-line-derived-neurotrophic-factor-in-neuropathic-pain
#14
Hong-Jun Wang, Ge Song, Jian Liang, Yuan-Yuan Gao, Cun-Jin Wang
Treatment of neuropathic pain (NP) continues to be a clinical challenge and the underlying mechanisms of NP remain elusive. More evidence suggests that glial cell line-derived neurotrophic factor (GDNF) has potent anti-nociceptive effects on NP, but the underlying mechanisms are still largely unknown. Recent data have shown that integrin β1 plays an important part in NP induction, and that the activity of integrin β1 signaling is associated with the phosphorylation of the conserved threonines in the cytoplasmic domain and recruitment of focal adhesion kinase (FAK) to the integrin β1 tail and phosphorylation...
October 12, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29031851/constitutive-ret-signaling-leads-to-long-lasting-expression-of-amphetamine-induced-place-conditioning-via-elevation-of-mesolimbic-dopamine
#15
Jaakko Kopra, Marian Villarta-Aguilera, Mari Savolainen, Samo Weingerl, Timo T Myöhänen, Saara Rannanpää, Michael F Salvatore, Jaan-Olle Andressoo, T Petteri Piepponen
Addictive drugs enhance dopamine release in the striatum, which can lead to compulsive drug-seeking after repeated exposure. Glial cell line-derived neurotrophic factor (GDNF) is an important regulator of midbrain dopamine neurons, and may play a mechanistic role in addiction-related behaviors. To elucidate the components of GDNF-signaling that contribute to addiction-related behaviors of place preference and its extinction, we utilized two genetically modified GDNF mouse models in an amphetamine-induced conditioned place preference (CPP) paradigm and evaluated how the behavioral findings correlate with dopamine signaling in the dorsal and ventral striatum...
October 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29018141/vitamin-d-regulation-of-gdnf-ret-signaling-in-dopaminergic-neurons
#16
Renata A N Pertile, Xiaoying Cui, Luke Hammond, Darryl W Eyles
1,25(OH)2D3 (vitamin D) appears essential for the normal development of dopaminergic neurons. Vitamin D affects dopamine synthesis and metabolism as well as expression of glial cell line-derived neurotrophic factor (GDNF), which is crucial for the survival of dopaminergic neurons. We investigated the role of vitamin D on GDNF and its receptors protooncogene tyrosine-protein kinase receptor Ret (C-Ret) and GDNF family receptor alpha 1 (GFRα1) signaling. To this end, we used a developmental vitamin D-deficient rat model and SH-SY5Y cells transfected with vitamin D receptor (VDR)...
October 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28979811/a-novel-multi-target-inhibitor-harboring-selectivity-of-inhibiting-egfr-t790m-sparing-wild-type-egfr
#17
Xiaoping Song, Xin Qi, Qiang Wang, Weiming Zhu, Jing Li
Non-Small Cell Lung Cancer (NSCLC) is driven by a variety of deregulated kinases and the development of multi-target inhibitor for multiple signaling pathways or multiple steps is required. Here, we reported that ZWM026, an indolocarbazoles analogue, derived from mangrove in coastal marine wetland, exhibited selectivity and reversibility against T790M mutant over wild-type EGFR in naturally occurring NSCLC cells and constructed NIH-3T3 cells. It simultaneously inhibited activities of HER2, HER3, HER4 and RET but was different from current multi-target kinase inhibitors...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28961547/electrochemiluminescent-quaternary-cu-zn-in-s-nanocrystals-as-a-sensing-platform-enzyme-free-and-sensitive-detection-of-the-flt3-gene-based-on-triple-signal-amplification
#18
Yingying Sun, Xiaohui Wu, Kai Zhang, Qunxiang Ren, Renguo Xie
A new near-infrared electrochemiluminescence resonance energy transfer (NECL-RET) strategy for enzyme-free amplified DNA detection was designed. In this strategy, the quaternary Cu-Zn-In-S nanocrystals (NCs) were applied as the ECL donor and gold nanostars (AuNSs) were used as the acceptor. The flowerlike MoS2/GO/o-MWNTs nanostructure was synthesized and used as an outstanding substrate to immobilize the NCs. ECL measurements demonstrated that the NCs assembled on the MoS2/GO/o-MWNTs film resulted in ECL intensity amplified by ~2...
September 21, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28949508/high-sensitive-electrochemiluminescence-c-peptide-biosensor-via-the-double-quenching-of-dopamine-to-the-novel-ru-ii-organic-complex-with-dual-intramolecular-self-catalysis
#19
Haijun Wang, Liyu Peng, Yaqin Chai, Ruo Yuan
Here, a novel Ru(II)-organic complex (Ru-PEI-ABEI) with high electrochemiluminescence (ECL) efficiency was proposed to construct a sensitive quenching-typed ECL biosensor for C-peptide (C-P) measurement based on the double quenching effect of dopamine (DA). The high ECL efficiency of Ru-PEI-ABEI was originated from the dual intramolecular self-catalysis including intramolecular coreaction between polyethylenimine (PEI) and Ru(bpy)2(mcbpy)(2+), and intramolecular ECL resonance energy transfer (ECL-RET) from N-(aminobutyl)-N-(ethylisoluminol) (ABEI) to Ru(bpy)2(mcbpy)(2+), which would generate a strong initial ECL signal...
October 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28938186/electrochemiluminescence-resonance-energy-transfer-system-between-gnrs-and-ru-bpy-3-2-application-in-magnetic-aptasensor-for-%C3%AE-amyloid
#20
Hong Ke, Haifeng Sha, Yinfang Wang, Weiwei Guo, Xin Zhang, Zhiming Wang, Chusen Huang, Nengqin Jia
Electrochemiluminescent (ECL) assay has gradually drawn increasing interest in the biomedical analysis. This paper proposed a new methodology for ultrasensitive and facile detection of Alzheimer's disease marker β-amyloid (Aβ) by fabricating a sandwich-type ECL sensing platform. Herein, electrochemiluminescence resonance energy transfer (ECL-RET) was employed to determine Aβ concentration, which can be attributed to the quenching effect from RET between Ru(bpy)3(2+) and gold nanorods (GNRs) acting as ECL-RET electron donor and acceptor, respectively...
September 14, 2017: Biosensors & Bioelectronics
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