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https://www.readbyqxmd.com/read/27903527/standardized-flow-cytometry-for-highly-sensitive-mrd-measurements-in-b-cell-acute-lymphoblastic-leukemia
#1
Prisca Theunissen, Ester Mejstrikova, Lukasz Sedek, Alita J van der Sluijs-Gelling, Giuseppe Gaipa, Marius Bartels, Elaine Sobral da Costa, Michaela Kotrova, Michaela Novakova, Edwin Sonneveld, Chiara Buracchi, Paola Bonaccorso, Elen Oliviera, Jeroen G Te Marvelde, Tomasz Szczepanski, Ludovic Lhermitte, Ondrej Hrusak, Quentin Lecrevisse, Georgiana Emilia Grigore, Eva Fronkova, Jan Trka, Monika Brüggemann, Alberto Orfao, Jacques J M van Dongen, Vincent H J van der Velden
A fully-standardized EuroFlow 8-color antibody panel and laboratory procedure was stepwise designed to measure minimal residual disease (MRD) in B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) patients with a sensitivity of ≤10(-5), comparable to real-time quantitative (RQ)-PCR-based MRD detection via antigen-receptor rearrangements. Leukocyte markers and the corresponding antibodies and fluorochromes were selected based on their contribution in separating BCP-ALL cells from normal/regenerating BCP cells in multidimensional principal component analyses...
November 30, 2016: Blood
https://www.readbyqxmd.com/read/27871898/the-cannabinoid-beta-caryophyllene-bcp-induces-neuritogenesis-in-pc12-cells-by-a-cannabinoid-receptor-independent-mechanism
#2
Neife Aparecida Guinaim Santos, Nádia Maria Martins, Flávia Malvestio Sisti, Laís Silva Fernandes, Rafaela Scalco Ferreira, Osvaldo de Freitas, Antônio Cardozo Santos
Beta-caryophyllene (BCP) is a phytocannabinoid whose neuroprotective activity has been mainly associated with selective activation of cannabinoid-type-2 (CB2) receptors, inhibition of microglial activation and decrease of inflammation. Here, we addressed the potential of BCP to induce neuritogenesis in PC12 cells, a model system for primary neuronal cells that express trkA receptors, respond to NGF and do not express CB2 receptors. We demonstrated that BCP increases the survival and activates the NGF-specific receptor trkA in NGF-deprived PC12 cells, without increasing the expression of NGF itself...
November 18, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27856237/synthesis-anticancer-and-docking-studies-of-salicyl-hydrazone-analogues-a-novel-series-of-small-potent-tropomyosin-receptor-kinase-a-inhibitors
#3
Mohammad Sayed Alam, Sang-Un Choi, Dong-Ung Lee
A series of novel salicyl-hydrazone analogues were synthesized and evaluated for their in vitro cytotoxic activities in five human cancer cell lines, namely, lung cancer (A549), ovarian cancer (SK-OV-3), skin cancer (SK-MEL-2), colon cancer (HCT15) and pancreatic cancer (MIA-PaCa-2) cells, and for their in vitro tropomyosin receptor kinase A (TrkA) inhibitory activities. Each of the compounds showed significant cytotoxicity against all cancer cells. Compound 3i was found to be most potent against all cancer cell lines with IC50 values of 2...
November 3, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27843590/ntrk-gene-fusions-as-novel-targets-of-cancer-therapy-across-multiple-tumour-types
#4
REVIEW
Alessio Amatu, Andrea Sartore-Bianchi, Salvatore Siena
The tropomyosin receptor kinase (Trk) receptor family comprises 3 transmembrane proteins referred to as Trk A, B and C (TrkA, TrkB and TrkC) receptors that are encoded by the NTRK1, NTRK2 and NTRK3 genes, respectively. These receptor tyrosine kinases are expressed in human neuronal tissue and play an essential role in the physiology of development and function of the nervous system through activation by neurotrophins. Gene fusions involving NTRK genes lead to transcription of chimeric Trk proteins with constitutively activated or overexpressed kinase function conferring oncogenic potential...
2016: ESMO Open
https://www.readbyqxmd.com/read/27833955/neuro-neoplastic-interrelationships-in-colorectal-level-immunohistochemical-aspect-in-three-cases-and-review-of-the-literature
#5
Cristina Florescu, Octavian Istrătoaie, Georgică Costinel Târtea, Daniel Pirici, Costin Teodor Streba, Bogdan Cătălin, Ileana Puiu, Elena Anca Târtea, Daniel Cosmin Caragea, Mirela Corina Ghiluşi, Maria Victoria Comănescu, Ion Rogoveanu, Cristin Constantin Vere
Colorectal cancer represents a severe public health issue. Recent studies have shown the essential role played by nerves and their neurotransmitters in tumor initiation and progression. The aim of this study is to asses the expression of beta 2-adrenergic receptors (β2A) for adrenaline and noradrenaline, and the expression of M3 muscarinic receptors (M3R) for acetylcholine (neurotransmitters produced and released by sympathetic and parasympathetic afferents of the digestive tract and also by the enteric nervous system) in different tumor gradings of colorectal adenocarcinoma, and also the tropomyosin receptor kinase A (TrkA) for the nerve growth factor produced by the cells of colorectal adenocarcinoma...
2016: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/27830679/-effects-of-ischemia-on-the-expression-of-neurotrophins-and-their-receptors-in-rat-brain-structures-outside-the-lesion-site-including-on-the-opposite-hemisphere
#6
V G Dmitrieva, V V Stavchansky, O V Povarova, V I Skvortsova, S A Limborska, L V Dergunova
Neurotrophins stimulate the regeneration of neural tissue after lesions. It is also known that the sources of neurogenesis and cerebral function recovery are predominantly located in subcortical brain structures. The effects of ischemia on the expression of genes that encode neurotrophins (Bdnf, Ngf, Nt-3) and their receptors (TrkB, TrkA, TrkC, p75) in brain structures outside the lesion site were studied 3, 24, and 72 h after irreversible unilateral occlusion of the middle cerebral artery in rats. Changes in the mRNA expression of these genes were assessed by relative quantification using real-time RT-PCR...
September 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/27826105/klf7-transfected-schwann-cell-graft-transplantation-promotes-sciatic-nerve-regeneration
#7
Ying Wang, Wen-Yuan Li, Hua Jia, Feng-Guo Zhai, Wen-Rui Qu, Yong-Xia Cheng, Yan-Cui Liu, Ling-Xiao Deng, Su-Fen Guo, Zai-Shun Jin
Our former study demonstrated that Krüppel-like Factor 7 (KLF7) is a transcription factor that stimulates axonal regeneration after peripheral nerve injury. Currently, we used a gene therapy approach to overexpress KLF7 in Schwann cells (SCs) and assessed whether KLF7-transfected SCs graft could promote sciatic nerve regeneration. SCs were transfected by adeno-associated virus 2 (AAV2)-KLF7 in vitro. Mice were allografted by an acellular nerve (ANA) with either an injection of DMEM (ANA group), SCs (ANA+SCs group) or AAV2-KLF7-transfected SCs (ANA+KLF7-SCs group) to assess repair of a sciatic nerve gap...
November 5, 2016: Neuroscience
https://www.readbyqxmd.com/read/27826102/the-trka-receptor-mediates-experimental-thermal-hyperalgesia-produced-by-nerve-growth-factor-modulation-by-the-p75-neurotrophin-receptor
#8
Alla Khodorova, Grant D Nicol, Gary Strichartz
The p75 neurotrophin receptor (p75(NTR)) and its activation of the sphingomyelin signaling cascade are essential for mechanical hypersensitivity resulting from locally injected nerve growth factor (NGF). Here the roles of the same effectors, and of the tropomyosin receptor kinase A (TrkA) receptor, are evaluated for thermal hyperalgesia from NGF. Sensitivity of rat hind paw plantar skin to thermal stimulation after local sub-cutaneous injection of NGF (500ng) was measured by the latency for paw withdrawal (PWL) from a radiant heat source...
November 5, 2016: Neuroscience
https://www.readbyqxmd.com/read/27825832/nociceptor-like-rat-dorsal-root-ganglion-neurons-express-the-angiotensin-ii-at2-receptor-throughout-development
#9
Sergio Benitez, Alicia Seltzer, Cristian Acosta
AT2 receptor (AT2R) plays a functional role in foetal development. Its expression declines in most tissues soon after birth but stays high in sensory areas of the adult nervous system. In the dorsal root ganglia (DRG) the expression pattern of AT2R during development and the identity of the subpopulation expressing it remain unknown. Using a combination of semi-quantitative PCR, western blotting and immunohistochemistry we examined the expression of AT2R at mRNA and protein levels in rat DRGs from embryonic day 15 (E15) until postnatal day 30 (PN30)...
November 4, 2016: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/27825441/neurotrophin-signaling-is-required-for-glucose-induced-insulin-secretion
#10
Jessica Houtz, Philip Borden, Alexis Ceasrine, Liliana Minichiello, Rejji Kuruvilla
Insulin secretion by pancreatic islet β cells is critical for glucose homeostasis, and a blunted β cell secretory response is an early deficit in type 2 diabetes. Here, we uncover a regulatory mechanism by which glucose recruits vascular-derived neurotrophins to control insulin secretion. Nerve growth factor (NGF), a classical trophic factor for nerve cells, is expressed in pancreatic vasculature while its TrkA receptor is localized to islet β cells. High glucose rapidly enhances NGF secretion and increases TrkA phosphorylation in mouse and human islets...
November 7, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27802234/changes-in-plasma-%C3%AE-ngf-and-its-receptors-expression-on-peripheral-blood%C3%A2-monocytes-during-alzheimer-s-disease-progression
#11
Lucia Crispoltoni, Anna Maria Stabile, Alessandra Pistilli, Massimo Venturelli, Giuliano Cerulli, Cristina Fonte, Nicola Smania, Federico Schena, Mario Rende
Alzheimer's disease (AD), the most common cause of dementia, is characterized by the deposition of extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles, and by neuroinflammation. During the pathogenesis of AD, monocyte-macrophage lineage cells become increasingly ineffective in clearing Aβ deposits, less able to differentiate, and shift toward pro-inflammatory processes. Beta-nerve growth factor (β-NGF) and its receptors, TrKA and p75NTR, produce several biological responses, including cell apoptosis and survival, and inflammation...
October 14, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27793712/albumin-hybrid-nanoparticles-loaded-with-tyrosine-kinase-a-inhibitor-gnf-5837-for-targeted-inhibition-of-breast-cancer-cell-growth-and-invasion
#12
Vahid Heravi Shargh, Hubert Hondermarck, Mingtao Liang
Novel albumin hybrid nanoparticles (Alb-HNPs) loaded with tyrosine kinase A (TrkA) inhibitor GNF-5837 were prepared and evaluated for antineoplastic efficacy in a panel of breast cancer cell lines. The nanomedicines (GNF-Alb-HNPs, hydrodynamic diameter ∼150nm) were formed through a unique polyelectrolyte complexation process where albumin and GNF-5837 were encapsulated by a stabilizing layer of oppositely charged chitosan and dextran sulfate polysaccharides. GNF-Alb-HNPs showed an excellent colloidal stability and a sustained drug release over more than 24h...
December 30, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27792755/blocking-nerve-growth-factor-signaling-reduces-the-neural-invasion-potential-of-pancreatic-cancer-cells
#13
Aditi A Bapat, Ruben M Munoz, Daniel D Von Hoff, Haiyong Han
Perineural invasion (PNI) is thought to be one of the factors responsible for the high rate of tumor recurrence after surgery and the pain generation associated with pancreatic cancer. Signaling via the nerve growth factor (NGF) pathway between pancreatic cancer cells and the surrounding nerves has been implicated in PNI, and increased levels of these proteins have been correlated to poor prognosis. In this study, we examine the molecular mechanism of the NGF signaling pathway in PNI in pancreatic cancer. We show that knocking down NGF or its receptors, TRKA and p75NTR, or treatment with GW441756, a TRKA kinase inhibitor, reduces the proliferation and migration of pancreatic cancer cells in vitro...
2016: PloS One
https://www.readbyqxmd.com/read/27779399/targeting-the-nerve-growth-factor-ngf-pathway-in-drug-discovery-potential-applications-to-new-therapies-for-chronic-pain
#14
Bryan H Norman, Jeff S McDermott
The neurotrophin nerve growth factor (NGF) has been implicated as a key mediator of chronic pain. NGF binds the tropomysin receptor kinase A (TrkA) and p75, resulting in the activation of downstream signaling pathways that have been linked to pro-nociception. While anti-NGF antibodies have demonstrated analgesia both preclinically and in patients, the mechanism of action of these agents remains unclear. We describe ligands targeting NGF, its receptors, and downstream/related targets. This Perspective highlights large and small molecule approaches to targeting the NGF-TrkA pathway both extra- and intracellularly...
October 25, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27775476/alteration-of-selected-neurotrophic-factors-and-their-receptor-expression-in-mouse-brain-response-to-whole-brain-irradiation
#15
Ewa Pius-Sadowska, Miłosz Piotr Kawa, Patrycja Kłos, Dorota Rogińska, Michał Rudnicki, Boehlke Marek, Piotr Waloszczyk, Bogusław Machaliński
Ionizing radiation can significantly affect brain function in children and young adults, particularly in the hippocampus where neurogenic niches are located. Injury to normal tissue is a major concern when whole-brain irradiation (WBI) is used to treat central nervous system (CNS) tumors, and the pathogenesis of this injury remains poorly understood. We assessed the expression of selected neurotrophins (NTs) and NT receptors (NTRs) in brains of young mice after a single 10 Gy gamma-ray exposure using morphological and molecular analyses [qRT-PCR, Western blot, immunohistochemistry (IHC)] to evaluate WBI-induced injury in its acute phase...
October 24, 2016: Radiation Research
https://www.readbyqxmd.com/read/27772781/congenital-insensitivity-to-pain-with-anhidrosis-a-report-of-two-siblings-with-a-novel-mutation-in-trka-ntrk1-gene-in-a-saudi-family
#16
Hussein Algahtani, Muhammad Imran Naseer, Mohammad Al-Qahtani, Shireen Abubakr Abdulrahman, Faisal Boker, Bader Shirah
Congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV (HSAN type IV) is an extremely rare autosomal recessive disorder with an estimated incidence of 1 in 25,000. It was first described in 1963, and since then several case reports and review articles have been published. In this article, we report two brothers with clinical features of CIPA, who presented with recurrent episodes of hyperthermia, anhidrosis, profound loss of pain sensitivity, and unconscious self-mutilation of fingers, lip and tongue...
November 15, 2016: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/27753790/self-assembling-peptide-reduces-glial-scarring-attenuates-posttraumatic-inflammation-and-promotes-neurite-outgrowth-of-spinal-motor-neurons
#17
Kei Ando, Shiro Imagama, Zenya Ito, Kazuyoshi Kobayashi, Tetsuro Hida, Hiroaki Nakashima, Kenyu Ito, Mikito Tsushima, Yoshimoto Ishikawa, Akiyuki Matsumoto, Koji Nishida, Yoshihiro Nishida, Naoki Ishiguro
STUDY DESIGN: Self-assembling peptide gel (SPG-178) provides new evidence for the role of a scaffold for treatment of the spinal cord through induction of neuroprotective factors. OBJECTIVE: To verify the reproducibility of SPG-178 as scaffold after spinal cord injury, we examine the characteristics of SPG-178 and protective effect on neural cells in vitro and in vivo. SUMMARY OF BACKGROUND DATA: The central nervous system extracellular matrix may play a role in maintenance of the neuronal network by inhibiting axonal growth and suppressing formation of additional inadequate synapses...
October 15, 2016: Spine
https://www.readbyqxmd.com/read/27742705/nerve-growth-factor-is-critical-requirement-for-in-vitro-angiogenesis-in-gastric-endothelial-cells
#18
Amrita Ahluwalia, Michael K Jones, Tomasz Brzozowski, Andrzej S Tarnawski
Angiogenesis is critical for the healing of gastric mucosal injury and is considered to be primarily regulated by vascular endothelial growth factor (VEGF), the fundamental pro-angiogenic factor. The role of nerve growth factor (NGF) in gastric angiogenesis is unknown. We examined: the expression of NGF and its TrkA receptor in endothelial cells (ECs) isolated from gastric mucosa of rats (GMECs); the effect of NGF treatment on in vitro angiogenesis in GMECs; and, the mechanisms underlying NGF's pro-angiogenic actions...
October 13, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27732851/hypofunctional-trka-accounts-for-the-absence-of-pain-sensitization-in-the-african-naked-mole-rat
#19
Damir Omerbašić, Ewan St J Smith, Mirko Moroni, Johanna Homfeld, Ole Eigenbrod, Nigel C Bennett, Jane Reznick, Chris G Faulkes, Matthias Selbach, Gary R Lewin
The naked mole-rat is a subterranean rodent lacking several pain behaviors found in humans, rats, and mice. For example, nerve growth factor (NGF), an important mediator of pain sensitization, fails to produce thermal hyperalgesia in naked mole-rats. The sensitization of capsaicin-sensitive TRPV1 ion channels is necessary for NGF-induced hyperalgesia, but naked mole-rats have fully functional TRPV1 channels. We show that exposing isolated naked mole-rat nociceptors to NGF does not sensitize TRPV1. However, the naked mole-rat NGF receptor TrkA displays a reduced ability to engage signal transduction pathways that sensitize TRPV1...
October 11, 2016: Cell Reports
https://www.readbyqxmd.com/read/27704743/research-progress-of-the-role-and-mechanism-of-extracellular-signal-regulated-protein-kinase-5-erk5-pathway-in-pathological-pain
#20
Li-Na Yu, Li-Hong Sun, Min Wang, Min Yan
Extracellular signal-regulated protein kinase 5 (ERK5), also known as big mitogen-activated protein kinase 1 (MAPK1), is an important member of ERK family, which is a subfamily of the large MAPK family. ERK5 is expressed in many tissues, including the dorsal root ganglion (DRG) neurons and the spinal cord. In this review, we focus on elaborating ERK5-associated pathway in pathological pain, in which the ERK5/CREB (cyclic adenosine monophosphate (cAMP)-response element-binding protein) pathway plays a crucial role in the transduction of pain signal and contributes to pain hypersensitivity...
2016: Journal of Zhejiang University. Science. B
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