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https://www.readbyqxmd.com/read/28719467/pan-trk-immunohistochemistry-is-an-efficient-and-reliable-screen-for-the-detection-of-ntrk-fusions
#1
Jaclyn F Hechtman, Ryma Benayed, David M Hyman, Alexander Drilon, Ahmet Zehir, Denise Frosina, Maria E Arcila, Snjezana Dogan, David S Klimstra, Marc Ladanyi, Achim A Jungbluth
Activating neurotrophic tyrosine receptor kinase (NTRK) fusions, typically detected using nucleic-acid based assays, are highly targetable and define certain tumors. Here, we explore the utility of pan-TRK immunohistochemistry (IHC) to detect NTRK fusions. NTRK rearrangements were detected prospectively using MSK-IMPACT, a DNA-based next-generation sequencing assay. Transcription of novel NTRK rearrangements into potentially functional fusion transcripts was assessed via Archer Dx fusion assay. Pan-Trk IHC testing with mAb EPR17341 was performed on all NTRK rearranged cases and 20 cases negative for NTRK fusions on Archer...
July 17, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28695888/somatic-chromosomal-engineering-identifies-bcan-ntrk1-as-a-potent-glioma-driver-and-therapeutic-target
#2
Peter J Cook, Rozario Thomas, Ram Kannan, Esther Sanchez de Leon, Alexander Drilon, Marc K Rosenblum, Maurizio Scaltriti, Robert Benezra, Andrea Ventura
The widespread application of high-throughput sequencing methods is resulting in the identification of a rapidly growing number of novel gene fusions caused by tumour-specific chromosomal rearrangements, whose oncogenic potential remains unknown. Here we describe a strategy that builds upon recent advances in genome editing and combines ex vivo and in vivo chromosomal engineering to rapidly and effectively interrogate the oncogenic potential of genomic rearrangements identified in human brain cancers. We show that one such rearrangement, an microdeletion resulting in a fusion between Brevican (BCAN) and Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1), is a potent oncogenic driver of high-grade gliomas and confers sensitivity to the experimental TRK inhibitor entrectinib...
July 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28688957/discovery-of-highly-selective-%C3%AE%C2%BA-opioid-receptor-agonists-10%C3%AE-hydroxy-trk-820-derivatives
#3
Shinya Suzuki, Yuji Sugawara, Riichiro Tsuji, Ryuji Tanimura, Chihiro Kaneko, Natsumi Yuzawa, Mai Yagi, Koji Kawai
κ-Opioid receptor agonists with high selectivity over the μ-opioid receptor are attractive targets in the development of drugs for pain and pruritus. We previously reported the synthesis of 10α-hydroxy TRK-820 (1). In this study, we elucidated the biological properties of 1 and optimized its 6-acyl unit by modifying our synthetic route. Among the 10α-hydroxy TRK-820 derivatives prepared, 26 showed the most potent κ-opioid agonist activity (EC50=0.00466nM) and excellent selectivity and 22 was the most κ-selective agonist...
June 12, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28679060/protective-effects-of-green-tea-polyphenol-epigallocatechin-3-gallate-against-sevoflurane-induced-neuronal-apoptosis-involves-regulation-of-creb-bdnf-trk-b-and-pi3k-akt-mtor-signalling-pathways-in-neonatal-mice
#4
Mei-Li Ding, Hui Ma, Yi-Gang Man, Yan-Hong Lv
Epigallocatechin-3-gallate (EGCG), a polyphenol in green tea is an effective antioxidant and possesses neuroprotective effects. For neurogenesis and synaptic plasticity, brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are crucially involved. In this study we aimed to assess protective effects of EGCG against sevoflurane-induced neurotoxicity in neonatal mice. Distinct groups of C57BL/6 mice were given EGCG (25, 50 or 75 mg/kg b.wt) from postnatal day 3 (P3) to P21 and were subjected to sevoflurane (3 %; 6 h) exposure on P7...
July 5, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28673205/nerve-growth-factor-is-associated-with-sexual-pain-in-women-with-endometriosis
#5
Bo Peng, Hong Zhan, Fahad Alotaibi, Ghadeer M Alkusayer, Mohamed A Bedaiwy, Paul J Yong
Endometriosis is present in 1 in 10 reproductive-age women, and half experience deep dyspareunia (pelvic pain with sexual intercourse). Our objective was to investigate nerve growth factor (NGF) and its receptors (TrkA/p75NTR) in endometriosis-associated deep dyspareunia. A total of 32 women with endometriosis in the posterior pelvic compartment (cul-de-sac/uterosacrals) were included, either with (n = 17) or without (n = 15) deep dyspareunia symptoms confirmed by endovaginal ultrasound-assisted palpation on examination...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28672981/neurotrophic-factor-and-trk-signaling-mechanisms-underlying-the-promotion-of-motor-recovery-after-acute-spinal-cord-injury-in-rats
#6
Hua Fang, Chong Liu, Miao Yang, Huafeng Li, Fangxiang Zhang, Weijing Zhang, Jianping Zhang
Neurotrophic factor (NF) and Trk signaling mechanisms underlying the promotion of motor recovery following acute spinal cord injury (SCI) in rats were investigated. Thirty-six adult Sprague-Dawley rats of both genders were randomly divided into three groups: Sham-operated, model, and NF/Trk. Each group consisted of 12 rats, with four subgroups in each group: 1, 3, 5 and 7 days. Sham-operated rats received a laminectomy without SCI, while in model group rats, SCI was induced using an improved version of the Allen's method...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28650560/uncovering-the-role-of-brain-derived-neurotrophic-factor-bdnf-trkb-signaling-in-head-and-neck-malignancies
#7
REVIEW
Juliana Kern de Moraes, Vivian Petersen Wagner, Felipe Paiva Fonseca, Pablo Agustin Vargas, Caroline Brunetto de Farias, Rafael Roesler, Manoela Domingues Martins
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that was first known as responsible for sustain the growth, function and plasticity of neural cells. BDNF exerts its effects by binding to the tyrosine kinase receptor B (TrkB). The BDNF/TrkB axis has been reported to be overexpressed in several neurogenic and non-neurogenic tumors. Its higher expression was associated with a poor prognosis to patients affected by different human malignancies, tumor growth, invasion and metastasis; epithelial-mesenchymal transition (EMT) and resistance to chemotherapy...
June 26, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28646880/6-shogaol-a-neuroactive-compound-of-ginger-jahe-gajah-induced-neuritogenic-activity-via-ngf-responsive-pathways-in-pc-12-cells
#8
Syntyche Ling Sing Seow, Sok Lai Hong, Guan Serm Lee, Sri Nurestri Abd Malek, Vikineswary Sabaratnam
BACKGROUND: Ginger is a popular spice and food preservative. The rhizomes of the common ginger have been used as traditional medicine to treat various ailments. 6-Shogaol, a pungent compound isolated from the rhizomes of jahe gajah (Zingiber officinale var officinale) has shown numerous pharmacological activities, including neuroprotective and anti-neuroinflammatory activities. The aim of this study was to investigate the potential of 6-shogaol to mimic the neuritogenic activity of nerve growth factor (NGF) in rat pheochromocytoma (PC-12) cells...
June 24, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28643709/comparison-of-central-corneal-thickness-with-four-noncontact-devices-an-agreement-analysis-of-swept-source-technology
#9
Erhan Ozyol, Pelin Özyol
PURPOSE: The purpose of this study was to compare the central corneal thickness (CCT) measurements of four noncontact devices in healthy eyes. MATERIALS AND METHODS: In a sample of 45 healthy controls, CCT was measured using an optical biometer (IOLMaster 700) based on swept-source optical coherence tomography (SS-OCT), high-resolution rotating Scheimpflug camera system (Pentacam HR), spectral-domain OCT (SD-OCT) device with an anterior segment module (Spectralis), and noncontact pachymetry (NCP) device (Topcon TRK-2P)...
June 2017: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/28612521/could-modafinil-prevent-psychostimulant-addiction-an-experimental-study-in-rats
#10
Verônica Tironi Dias, Luciana Taschetto Vey, Higor Zuquetto Rosa, Lívia Ferraz D'avila, Raquel Cristine Silva Barcelos, Marilise Escobar Burger
Addiction is a serious health problem which leads to general social impairment. The period of adolescence plays a significant role in drug abuse liability. Psychostimulants, such as modafinil (MOD), are majorly used by teenagers seeking improvements in cognition, which contributes to its indiscriminate use. This study aimed to investigate the influence of MOD (64 mg/kg by gavage, once a day) treatment during adolescence [post-natal day (PND) 28-42] on amphetamine (AMPH, 4 mg/kg i.p.)-conditioned place preference (CPP) in early adulthood (PND 60)...
June 14, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28609318/biochemical-and-pharmacological-characterization-of-a-mice-model-of-complex-regional-pain-syndrome
#11
Vaskar Das, Jeffrey S Kroin, Mario Moric, Asokumar Buvanendran
BACKGROUND AND OBJECTIVES: Complex regional pain syndrome is a challenging disease to treat. Recently, a mouse fracture model of complex regional pain syndrome has been developed that has many signs of the clinical syndrome. However, many aspects of the sensory neuron biochemistry and behavioral and pharmacological characterization of this model remain to be clarified. METHODS: Mice were randomly assigned to fracture/cast or control (naive) groups. Fracture/cast mice underwent a closed distal tibia facture, with hindlimb wrapped in casting tape for 3 weeks...
July 2017: Regional Anesthesia and Pain Medicine
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
#12
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...
June 12, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28602824/distribution-of-bdnf-and-trkb-isoforms-in-growing-antler-tissues-of-red-deer
#13
M Colitti
Antlers are the cranial appendages of deer that regenerate each year. This renewal provides a model to explore molecules involved in mammalian organ regeneration. The cellular distributions of the brain-derived neurotrophic factor (BDNF) and the isoforms of its cognate receptor Trk tyrosine kinase receptor (TrkB) were localized by immunohistochemistry in sections of growing red deer antler. BDNF and TrkB full length were widely expressed in the integument, perichondrium, periosteum and bone. The truncated isoform receptor was particularly evidenced in integument and vascular inner dermis, but very light reaction was observed in cartilage and bone, both at the site of endochondral and intramembranous ossification...
June 7, 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
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
#14
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/28583910/dramatic-responses-seen-with-trk-inhibitor
#15
(no author information available yet)
Presenting data on 50 of 55 patients with advanced TRK fusion-positive tumors, researchers reported that 76% of patients responded to the selective pan-TRK inhibitor larotrectinib, and 12% of patients experienced complete responses; 93% of responders remain on therapy. The targeted therapy was well tolerated, with just 13% of patients requiring a dose modification. None of the patients discontinued treatment due to adverse events.
June 5, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28578312/a-next-generation-trk-kinase-inhibitor-overcomes-acquired-resistance-to-prior-trk-kinase-inhibition-in-patients-with-trk-fusion-positive-solid-tumors
#16
Alexander Drilon, Ramamoorthy Nagasubramanian, James F Blake, Nora Ku, Brian B Tuch, Kevin Ebata, Steve Smith, Veronique Lauriault, Gabrielle R Kolakowski, Barbara J Brandhuber, Paul D Larsen, Karyn S Bouhana, Shannon L Winski, Robyn Hamor, Wen-I Wu, Andrew Parker, Tony H Morales, Francis X Sullivan, Walter E Dewolf, Lance A Wollenberg, Paul R Gordon, Dorothea N Douglas-Lindsay, Maurizio Scaltriti, Ryma Benayed, Sandeep Raj, Bethany Hanusch, Alison M Schram, Philip Jonsson, Michael F Berger, Jaclyn F Hechtman, Barry S Taylor, Steve Andrews, S Michael Rothenberg, David M Hyman
Larotrectinib, a selective TRK tyrosine kinase inhibitor (TKI), has demonstrated histology-agnostic efficacy in patients with TRK fusion-positive cancers. While responses to TRK inhibition can be dramatic and durable, duration of response may eventually be limited by acquired resistance. LOXO-195 is a novel, selective TRK TKI designed to overcome acquired resistance mediated by recurrent kinase domain (solvent front and xDFG) mutations identified in multiple patients who have developed resistance to TRK TKIs...
June 3, 2017: Cancer Discovery
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/28476569/design-and-synthesis-of-a-fluorinated-quinazoline-based-type-ii-trk-inhibitor-as-a-scaffold-for-pet-radiotracer-development
#18
Vadim Bernard-Gauthier, Anne Mahringer, Matthew Vesnaver, Gert Fricker, Ralf Schirrmacher
NTRK1/2/3 fusions have recently been characterized as low incidence oncogenic alterations across various tumor histologies. Tyrosine kinase inhibitors (TKIs) of the tropomyosin receptor kinase family TrkA/B/C (encoded by NTRK1/2/3) are showing promises in the clinic for the treatment of cancer patients whose diseases harbor NTRK tumor drivers. We describe herein the development of [(18)F]QMICF ([(18)F]-(R)-9), a quinazoline-based type-II pan-Trk radiotracer with nanomolar potencies for TrkA/B/C (IC50=85-650nM) and relevant TrkA fusions including TrkA-TPM3 (IC50=162nM)...
June 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28469194/kai-xin-san-series-formulae-alleviate-depressive-like-behaviors-on-chronic-mild-stressed-mice-via-regulating-neurotrophic-factor-system-on-hippocampus
#19
Yue Zhu, Cheng Chao, Xiuzhu Duan, Xiaoxuan Cheng, Pei Liu, Shulan Su, Jinao Duan, Tina Tingxia Dong, Karl Wah-Keung Tsim
Kai-xin-san (KXS) is a famous Chinese medicinal formula applied for treating stress-related psychiatric diseases with the symptoms such as depression, forgetfulness and dizziness. In clinic, the composition ratio of KXS is always varied and KXS series formulae are created. Here, we aim to compare the anti-depressive effect of different ratios of KXS and reveal its action mechanism on regulation of neurotrophic factor system. Firstly, daily intra-gastric administration of chemically standardized extracts of KXS series formulae for seven days significantly alleviated the depressive symptoms of chronic unpredictable mild stressed mice displayed by enhanced sucrose consumptions and decreased immobile time of forced swimming coupled with increased locomotor activities...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28456118/dna-interaction-antimicrobial-anticancer-activities-and-molecular-docking-study-of-some-new-vo-ii-cr-iii-mn-ii-and-ni-ii-mononuclear-chelates-encompassing-quaridentate-imine-ligand
#20
Laila H Abdel-Rahman, Ahmed M Abu-Dief, Moustafa O Aboelez, Azza A Hassan Abdel-Mawgoud
The present study was conducted to synthesis of some new imine Cr(III), VO(II), Mn(II) and Ni(II) complexes derived from the condensation of 2-amino phenol with 2-hydroxynapthaldehyde were synthesized. The prepared HNPN imine ligand was analyzed by its melting point, IR, (1)H NMR and (13)C NMR spectroscopies. The investigated HNPN imine complexes were characterized by elemental analysis, FT IR, UV-vis and thermal analysis (TGA) under nitrogen atmosphere from ambient temperature to 750°C. The experimental results revealed that the investigated complexes contain hydrated water molecules...
May 2017: Journal of Photochemistry and Photobiology. B, Biology
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