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https://www.readbyqxmd.com/read/29118225/activity-of-entrectinib-in-a-patient-with-the-first-reported-ntrk-fusion-in-neuroendocrine-cancer
#1
Darren Sigal, Marie Tartar, Marin Xavier, Fei Bao, Patrick Foley, David Luo, Jason Christiansen, Zachary Hornby, Edna Chow Maneval, Pratik Multani
Despite advances in genomic analysis, the molecular origin of neuroendocrine tumors (NETs) is complex and poorly explained by described oncogenes. The neurotrophic TRK family, including NTRK1, 2, and 3, encode the proteins TRKA, TRKB, TRKC, respectively, involved in normal nerve development. Because NETs develop from the diffuse neuroendocrine system, we sought to determine whether NTRK alterations occur in NETs and whether TRK-targeted therapy would be effective. A patient with metastatic well-differentiated NET, likely of the small intestine, was enrolled on the STARTRK2 trial (ClinicalTrials...
November 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29111205/hsa-mir-11181-regulates-wnt-signaling-pathway-through-targeting-of-apc2-transcripts-in-sw480-cell-line
#2
Sadat Dokanehiifard, Bahram M Soltani
Wnt signaling plays important roles in differentiation, morphogenesis and development. This signaling pathway is highly regulated at all levels and microRNAs are small noncoding RNAs regulating Wnt signaling. Here, we intended to investigate hsa-miR-11181 (a novel miRNA located in TrkC gene) effect on Wnt signaling pathway in SW480 cell line. TOP/FOP flash assay indicated up-regulation of Wnt signaling, following the overexpression of hsa-miR-11181, verified through RT-qPCR. Bioinformatics analysis predicted APC1, APC2 and Axin1 might be targeted by hsa-miR-11181...
October 27, 2017: Gene
https://www.readbyqxmd.com/read/29081732/lar-rptp-clustering-is-modulated-by-competitive-binding-between-synaptic-adhesion-partners-and-heparan-sulfate
#3
Seoung Youn Won, Cha Yeon Kim, Doyoun Kim, Jaewon Ko, Ji Won Um, Sung Bae Lee, Matthias Buck, Eunjoon Kim, Won Do Heo, Jie-Oh Lee, Ho Min Kim
The leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) are cellular receptors of heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans that direct axonal growth and neuronal regeneration. LAR-RPTPs are also synaptic adhesion molecules that form trans-synaptic adhesion complexes by binding to various postsynaptic adhesion ligands, such as Slit- and Trk-like family of proteins (Slitrks), IL-1 receptor accessory protein-like 1 (IL1RAPL1), interleukin-1 receptor accessory protein (IL-1RAcP) and neurotrophin receptor tyrosine kinase C (TrkC), to regulate synaptogenesis...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29018822/expression-of-neurotrophin-3-and-trkc-following-focal-cerebral-ischemia-in-adult-rat-brain-with-treadmill-exercise
#4
Jin-Young Chung, Min-Wook Kim, Wooseok Im, In Koo Hwang, Moon-Suk Bang, Manho Kim
Neurotrophin-3 (NT-3) is a neurotrophic factor that mainly binds to the tyrosine kinase C (trkC) receptor. NT-3 has been shown to have neuroprotective effects in focal cerebral ischemia. Exercise also has ability to induce functional recovery in focal cerebral ischemia. However, the relationship between NT-3, its receptor trkC, and exercise has not been revealed. In this study, we assessed the expressions of NT-3 and trkC in focal cerebral ischemia. We also assessed the expression of NT-3 and trkC with treadmill exercise in focal cerebral ischemia...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28924861/role-of-bdnf-and-neurotrophic-receptors-in-human-inner-ear-development
#5
L Johnson Chacko, M J F Blumer, E Pechriggl, H Rask-Andersen, W Dietl, A Haim, H Fritsch, R Glueckert, J Dudas, A Schrott-Fischer
The expression patterns of the neurotrophin, brain-derived neurotrophic factor, BDNF, and the neurotrophic receptors-p75NTR and Trk receptors-in the developing human fetal inner ear between the gestational weeks (GW) 9 to 12 are examined via in situ hybridization and immunohistochemistry. BDNF mRNA expression was highest in the cochlea at GW 9 but declined in the course of development. In contrast to embryonic murine specimens, a decline in BDNF expression from the apical to the basal turn of the cochlea could not be observed...
September 19, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28888073/selective-decline-of-neurotrophin-and-neurotrophin-receptor-genes-within-ca1-pyramidal-neurons-and-hippocampus-proper-correlation-with-cognitive-performance-and-neuropathology-in-mild-cognitive-impairment-and-alzheimer-s-disease
#6
Stephen D Ginsberg, Michael H Malek-Ahmadi, Melissa J Alldred, Shaoli Che, Irina Elarova, Yinghua Chen, Freddy Jeanneteau, Thorsten M Kranz, Moses V Chao, Scott E Counts, Elliott J Mufson
Hippocampal CA1 pyramidal neurons, a major component of the medial temporal lobe memory circuit, are selectively vulnerable during the progression of Alzheimer's disease (AD). The cellular mechanism(s) underlying degeneration of these neurons and the relationship to cognitive performance remains largely undefined. Here, we profiled neurotrophin and neurotrophin receptor gene expression within microdissected CA1 neurons along with regional hippocampal dissections from subjects who died with a clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), or AD using laser capture microdissection (LCM), custom-designed microarray analysis, and qPCR of CA1 subregional dissections...
September 9, 2017: Hippocampus
https://www.readbyqxmd.com/read/28884193/neurotrophin-trk-receptors-new-targets-for-cancer-therapy
#7
Jacopo Meldolesi
In the last few years, exciting reports have emerged regarding the role of the two types of neurotrophin receptors, p75(NTR) and Trks, not only in neurons, where they were discovered, but also in non-neural cells and, especially, in numerous cancers, including breast, lung, colon-rectum, pancreas, prostate, glioblastoma, neuroblastoma, myeloma, and lymphoid tumors. Traditionally, p75(NTR), activated by all neurotrophins and their precursors, is an inhibitor. In various cancers, however, activated p75(NTR) induces variable effects, from inhibition to stimulation of cell proliferation, dependent on their direct or coordinate/indirect mechanism(s) of action...
September 8, 2017: Reviews of Physiology, Biochemistry and Pharmacology
https://www.readbyqxmd.com/read/28865235/effect-of-electro-acupuncture-on-neuroplasticity-of-spinal-cord-transected-rats
#8
Xuyang Wang, Shiming Ju, Shiwen Chen, Wenwei Gao, Jun Ding, Gan Wang, Heli Cao, Hengli Tian, Xiaoli Li
BACKGROUND This study aimed to evaluate the effects of electro-acupuncture (EA) on neuroplasticity associated with the expressions of neurotrophic factors (NTFs) and their receptors in rats subjected to spinal cord transection (SCT). MATERIAL AND METHODS A total of 144 rats were randomly divided into 3 groups (n=48 per group): sham-operated group, SCT group, and EA (electro-acupuncture) group. Rats in SCT and EA groups received spinal cord transection at T10-T11 vertebral levels. Then, EA group rats received EA treatment...
September 2, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28829946/the-proprioceptive-system-masterminds-spinal-alignment-insight-into-the-mechanism-of-scoliosis
#9
Ronen Blecher, Sharon Krief, Tal Galili, Inbal E Biton, Tomer Stern, Eran Assaraf, Ditsa Levanon, Elena Appel, Yoram Anekstein, Gabriel Agar, Yoram Groner, Elazar Zelzer
Maintaining posture requires tight regulation of the position and orientation of numerous spinal components. Yet, surprisingly little is known about this regulatory mechanism, whose failure may result in spinal deformity as in adolescent idiopathic scoliosis. Here, we use genetic mouse models to demonstrate the involvement of proprioception in regulating spine alignment. Null mutants for Runx3 transcription factor, which lack TrkC neurons connecting between proprioceptive mechanoreceptors and spinal cord, developed peripubertal scoliosis not preceded by vertebral dysplasia or muscle asymmetry...
August 21, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28739680/bdnf-an-oncogene-or-tumor-suppressor
#10
REVIEW
Daniel P Radin, Parth Patel
Neurotrophins are a family of growth factors that are vital to the proper development of the central nervous system. Their effects on cells are governed by the expression and activation of the tyrosine kinase receptors TrkA, TrkB and TrkC. TrkB has been immensely implicated in mediating neuronal migration, development and differentiation. It has also been shown to protect several neuronal cell types from an array of cytotoxic stressors after activation by its conjugate ligand brain-derived neurotrophic factor (BDNF)...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28708822/an-ancient-neurotrophin-receptor-code-a-single-runx-cbf%C3%AE-complex-determines-somatosensory-neuron-fate-specification-in-zebrafish
#11
Philia Gau, Andrew Curtright, Logan Condon, David W Raible, Ajay Dhaka
In terrestrial vertebrates such as birds and mammals, neurotrophin receptor expression is considered fundamental for the specification of distinct somatosensory neuron types where TrkA, TrkB and TrkC specify nociceptors, mechanoceptors and proprioceptors/mechanoceptors, respectively. In turn, Runx transcription factors promote neuronal fate specification by regulating neurotrophin receptor and sensory receptor expression where Runx1 mediates TrkA+ nociceptor diversification while Runx3 promotes a TrkC+ proprioceptive/mechanoceptive fate...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28695340/tropomyosin-receptor-kinase-c-trkc-expression-in-medulloblastoma-relation-to-the-molecular-subgroups-and-impact-on-treatment-response
#12
Carsten Friedrich, Tarek Shalaby, Christoph Oehler, Martin Pruschy, Burkhardt Seifert, Daniel Picard, Marc Remke, Monika Warmuth-Metz, Rolf-Dieter Kortmann, Stefan Rutkowski, Michael A Grotzer, André O von Bueren
PURPOSE: High messenger RNA (mRNA) expression of the tropomyosin receptor kinase C gene (TrkC) has been associated with favorable survival in medulloblastoma patients. Untested is whether it plays a role through modulating the response to therapy or whether it might be a surrogate marker for a favorable molecular subgroup. METHODS: The medulloblastoma-derived cell line DAOY was stably transfected to overexpress TrkC (clone DAOY-TrkC) and compared to a control (clone DAOY-EV, empty vector transfected)...
July 10, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28625641/emergence-of-novel-and-dominant-acquired-egfr-solvent-front-mutations-at-gly796-g796s-r-together-with-c797s-r-and-l792f-h-mutations-in-one-egfr-l858r-t790m-nsclc-patient-who-progressed-on-osimertinib
#13
Sai-Hong Ignatius Ou, Jean Cui, Alexa B Schrock, Michael E Goldberg, Viola W Zhu, Lee Albacker, Philip J Stephens, Vincent A Miller, Siraj M Ali
Acquired epidermal growth factor receptor (EGFR) resistance mutations to osimertinib are common, including the EGFR C797S that abolishes the covalent binding of osimertinib to EGFR. Here we report the emergence of novel EGFR solvent front mutations at Gly796 (G796S/R) in addition to a hinge pocket L792F/H mutations, and C797S/G all in cis with T790M in a single patient on progression on osimertinib as detected by plasma circulating tumor DNA (ctDNA) assay in the course of clinical care. A 69-year-old Caucasian female former light-smoker presented with stage IV EGFR L858R positive adenocarcinoma who developed EGFR T790M mutation after 8 month treatment of erlotinib...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28614398/5-aza-2-deoxycytidine-in-the-medial-prefrontal-cortex-regulates-alcohol-related-behavior-and-ntf3-trkc-expression-in-rats
#14
Xiaomeng Qiao, Fangyuan Yin, Yuanyuan Ji, Yunxiao Li, Peng Yan, Jianghua Lai
Recent studies have indicated that DNA methylation plays an important role in the development of alcohol abuse. 5-Aza-2'-deoxycytidine (5-Aza-dc), an inhibitor of DNA methyltransferases, was FDA approved for myelodysplastic syndrome treatment. However, it is unclear whether 5-Aza-dc is involved in alcohol abuse. In this study, using a chronic alcohol exposure model in rats, 5-Aza-dc was injected into the medial prefrontal cortex (mPFC). Alcohol-drinking behavior and the anxiety related behavior were evaluated by two-bottle choice and open field test...
2017: PloS One
https://www.readbyqxmd.com/read/28604655/brain-derived-neurotrophic-factor-tropomyosin-related-kinase-b-signaling-pathway-contributes-to-the-aggressive-behavior-of-lung-squamous-cell-carcinoma
#15
COMPARATIVE STUDY
Keigo Ozono, Yoshihiro Ohishi, Hideya Onishi, Katsuya Nakamura, Junichi Motoshita, Masato Kato, Ryoichi Nakanishi, Masafumi Nakamura, Yoshinao Oda
The tropomyosin-related kinase (Trk) family consists of TrkA, TrkB, and TrkC, which play essential roles in tumor progression and/or suppression in various cancers. Little is known about the biological significance of the Trk family in human lung squamous cell carcinoma (SCC). Here we investigated the clinical significance of the protein expression of Trk family members in samples from 99 SCC patients, and we explored the relationship between invasion/proliferation activities and Trk expression using lung SCC cell lines to clarify the biological significance of the Trk family in lung SCC...
November 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28589908/activation-of-trka-receptor-elicits-mastocytosis-in-mice-and-is-involved-in-the-development-of-resistance-to-kit-targeted-therapy
#16
Min Yang, Zengkai Pan, Kezhi Huang, Guntram Büsche, Friedrich Feuerhake, Anuhar Chaturvedi, Danian Nie, Michael Heuser, Felicitas Thol, Nils von Neuhoff, Arnold Ganser, Zhixiong Li
The neurotrophins (NTs) play a key role in neuronal survival and maintenance. The TRK (tropomyosin-related kinase) tyrosine kinase receptors (TRKA, TRKB, TRKC) are high affinity receptors for NTs. There is increasing data demonstrating an important role of the TRK family in cancer initiation and progression. NTs have been known for many years to promote chemotaxis, maturation, and survival of mast cells. However, the role of NT signaling in the pathogenesis of mastocytosis is not well understood. In this study, we demonstrate that activation of TRKA by its ligand nerve growth factor (NGF) is potent to trigger a disease in mice with striking similarities to human systemic mastocytosis (SM)...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515680/trk-receptors-and-neurotrophin-cross-interactions-new-perspectives-toward-manipulating-therapeutic-side-effects
#17
Yazan Haddad, Vojtěch Adam, Zbyněk Heger
Some therapeutic side-effects result from simultaneous activation of homolog receptors by the same ligand. Tropomyosin receptor kinases (TrkA, TrkB and TrkC) play a major role in the development and biology of neurons through neurotrophin signaling. The wide range of cross-interactions between Trk receptors and neurotrophins vary in selectivity, affinity and function. In this study, we discuss new perspectives to the manipulation of side-effects via a better understanding of the cross-interactions at the molecular level, derived by computational methods...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28455963/trkc-promotes-colorectal-cancer-growth-and-metastasis
#18
Min Soo Kim, Kwang Wook Suh, Suntaek Hong, Wook Jin
The current work reveals that TrkC receptor is crucial to many aspects of tumorigenicity and metastasis of cancer. However, with only a few exceptions, such as colorectal cancer (CRC), where suppressing tumorigenic and metastatic ability via expression of TrkC as tumor suppressor have been proposed. These diverse lines of evidence led us to investigate whether TrkC is involved in CRC progression. By using mouse models and molecular biology analyses, we demonstrate that TrkC acts as an activator in tumorigenicity and metastasis of colorectal cancer...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28440877/brain-derived-neurotrophic-factor-neurotrophin-3-regulate-axon-initial-segment-location-and-affect-neuronal-excitability-in-cultured-hippocampal-neurons
#19
Yu Guo, Zi-Jun Su, Yi-Kun Chen, Zhen Chai
Plasticity of the axon initial segment (AIS) has aroused great interest in recent years because it regulates action potential initiation and neuronal excitability. AIS plasticity manifests as modulation of ion channels or variation in AIS structure. However, the mechanisms underlying structural plasticity of the AIS are not well understood. Here, we combined immunofluorescence, patch-clamp recordings, and pharmacological methods in cultured hippocampal neurons to investigate the factors participating in AIS structural plasticity during development...
July 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28404842/an-immortalized-human-dorsal-root-ganglion-cell-line-provides-a-novel-context-to-study-herpes-simplex-virus-1-latency-and-reactivation
#20
Nikki M Thellman, Carolyn Botting, Zachary Madaj, Steven J Triezenberg
A defining characteristic of alphaherpesviruses is the establishment of lifelong latency in host sensory ganglia with occasional reactivation causing recurrent lytic infections. As an alternative to rodent models, we explored the use of an immortalized cell line derived from human dorsal root ganglia. HD10.6 cells proliferate by virtue of a transduced tetracycline-regulated v-myc oncogene. In the presence of doxycycline, HD10.6 cells mature to exhibit neuronal morphology and express sensory neuron-associated markers such as neurotrophin receptors TrkA, TrkB, TrkC, and RET and the sensory neurofilament peripherin...
June 15, 2017: Journal of Virology
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