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https://www.readbyqxmd.com/read/29781786/sitagliptin-rescues-memory-deficits-in-parkinsonian-rats-via-upregulating-bdnf-to-prevent-neuron-and-dendritic-spine-loss
#1
Jing Li, Shuhu Zhang, Chenye Li, Mei Li, Lan Ma
OBJECTIVES: Parkinson's disease (PD) is a neurodegenerative disease with high morbidity among adults worldwide that causes tremendous trouble to people's lives. The purpose of this study was to investigate the impact of sitagliptin on PD and its potential mechanism. METHODS: First, the memory of rats in each group was evaluated with the Morris water maze (MWM) test and the passive avoidance test. Then, both brain-derived neurotrophic factor (BDNF) protein and mRNA levels were detected by ELISA and qPCR assays, respectively...
May 21, 2018: Neurological Research
https://www.readbyqxmd.com/read/29781158/role-of-brain-derived-neurotrophic-factor-in-the-pathogenesis-of-distention-associated-abdominal-pain-in-bowel-obstruction
#2
Y Fu, Y M Lin, J H Winston, R Radhakrishnan, L-Y M Huang, X Z Shi
BACKGROUND: Previous studies found that visceral sensitivity is increased in bowel obstruction (BO). We hypothesized that mechanical stress-induced expression of BDNF in smooth muscle cells (SMC) of the distended bowel plays a critical role in visceral hypersensitivity in BO by altering voltage-gated K+ channel (Kv ) activity in sensory neurons. METHODS: Partial colon obstruction was maintained in rats for 7 days. Colon-projecting neurons in the dorsal root ganglia (DRG, T13 to L2) were isolated for electrophysiological and gene expression studies...
May 21, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29764494/precision-medicine-becomes-reality-tumor-type-agnostic-therapy
#3
REVIEW
Li Yan, Wei Zhang
Precision medicine just witnessed two breakthroughs in oncology in 2017. Pembrolizumab (Keytruda), Merck's anti-programmed cell death-1 (PD-1) monoclonal antibody (mAb), received accelerated approval in May 2017 by the US Food and Drug Administration for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having microsatellite instability-high (MSI-H) or deficient DNA mismatch repair (dMMR). Shortly after, nivolumab (Opdivo), Bristol-Myers Squibb's anti-PD-1 mAb, gained an accelerated approval in August 2017 for adult and pediatric patients with MSI-H or dMMR metastatic colorectal cancer that has progressed after standard chemotherapy...
March 31, 2018: Cancer communications
https://www.readbyqxmd.com/read/29753009/the-implications-of-trka-and-met-aberrations-in-de-novo-salivary-duct-carcinoma
#4
Hyang Joo Ryu, Yoon Woo Koh, Sun Och Yoon
Salivary duct carcinoma (SDC) is an aggressive carcinoma with poor prognosis. Although anti-HER2 therapy is a potential treatment option for HER2-positive SDC, other potential therapeutic targets are not known, in particular for HER2-negative cases. In this study, the recently identified receptor tyrosine kinases MET and tropomyosin-receptor kinase (Trk) were investigated as potential therapeutic targets. A total of 28 consecutive, surgically resected, de novo SDC cases were selected after evaluating histology and immunohistochemical expression of androgen receptor...
May 9, 2018: Human Pathology
https://www.readbyqxmd.com/read/29752549/promising-new-agents-for-colorectal-cancer
#5
REVIEW
Satya Das, Kristen K Ciombor, Sigurdis Haraldsdottir, Richard M Goldberg
Choosing the optimal treatment approach for patients with metastatic colorectal cancer (mCRC) demands that oncologists assess both clinical and genomic variables and individualize care based upon the findings. Clinically, choices depend on assessing the side of the colon in which the primary tumor originates, the sites and burden of metastatic disease, the patient's performance status, and their individual comorbidities. Genomic assessment of the tumor to discern the mutational status of genes such as RAS/RAF, HER2, and TRK, as well as assessing whether tumors have defective mismatch repair (dMMR) or high microsatellite instability (MSI-H), all factor in to potential treatment options and can determine clinical trial eligibility...
May 11, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29748024/expression-of-brain-derived-neurotrophic-factor-and-its-receptor-trkb-is-associated-with-poor-prognosis-and-a-malignant-phenotype-in-small-cell-lung-cancer
#6
Shinichi Kimura, Taishi Harada, Kayo Ijichi, Kentaro Tanaka, Renpeng Liu, Daisuke Shibahara, Yuko Kawano, Kohei Otsubo, Yasuto Yoneshima, Eiji Iwama, Yoichi Nakanishi, Isamu Okamoto
OBJECTIVES: TrkB is a receptor for brain-derived neurotrophic factor (BDNF) and is highly expressed in various cancers, with BDNF-TrkB signaling having been implicated in tumor progression and metastasis. The role of the BDNF-TrkB system in small cell lung cancer (SCLC), a neuroendocrine cancer, has remained unclear, however. We examined BDNF and TrkB expression in SCLC patients as well as the function of BDNF-TrkB signaling in SCLC cell lines. MATERIALS AND METHODS: BDNF and TrkB expression in tumor specimens of 58 SCLC patients and 20 non-small cell lung cancer (NSCLC) patients was examined by immunohistochemistry and was scored on the basis of the distribution and intensity of staining...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29741780/membrane-transport-at-an-organelle-interface-in-the-early-secretory-pathway-take-your-coat-off-and-stay-a-while-evolution-of-the-metazoan-early-secretory-pathway
#7
REVIEW
Michael G Hanna, Jennifer L Peotter, E B Frankel, Anjon Audhya
Most metazoan organisms have evolved a mildly acidified and calcium diminished sorting hub in the early secretory pathway commonly referred to as the Endoplasmic Reticulum-Golgi intermediate compartment (ERGIC). These membranous vesicular-tubular clusters are found tightly juxtaposed to ER subdomains that are competent for the production of COPII-coated transport carriers. In contrast to many unicellular systems, metazoan COPII carriers largely transit just a few hundred nanometers to the ERGIC, prior to COPI-dependent transport on to the cis-Golgi...
May 9, 2018: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/29729205/running-on-trk-to-neuroprotection-in-diabetic-retinopathy
#8
Rithwick Rajagopal
No abstract text is available yet for this article.
May 5, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29721977/brain-derived-neurotrophic-factor-as-a-treatment-option-for-retinal-degeneration
#9
Conor Daly, Rebecca Ward, Alison L Reynolds, Orla Galvin, Ross F Collery, Breandán N Kennedy
This review discusses the therapeutic potential of brain-derived neurotrophic factor (BDNF) for retinal degeneration. BDNF, nerve growth factor (NGF), neurotrophin 3 (NT-3) and NT-4/NT-5 belong to the neurotrophin family. These neuronal modulators activate a common receptor and a specific tropomyosin-related kinase (Trk) receptor. BDNF was identified as a photoreceptor protectant in models of retinal degeneration as early as 1992. However, development of effective therapeutics that exploit this pathway has been difficult due to challenges in sustaining therapeutic levels in the retina...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29683819/primary-and-metastatic-melanoma-with-ntrk-fusions
#10
Cecilia Lezcano, Alexander N Shoushtari, Charlotte Ariyan, Travis J Hollmann, Klaus J Busam
A number of oncogenic driver mutations have been identified in melanocytic nevi and melanoma, but translocations also play a role in tumorigenesis and provide potential therapeutic targets for malignant lesions. Various translocations, such as those involving the anaplastic lymphoma kinase (ALK), neurotrophic tropomyosin receptor kinase 1 (NTRK1), and NTRK3 have been reported in spitzoid melanocytic neoplasms leading to kinase-fusion proteins that result in immunohistochemically detectable ALK or NTRK expression...
April 20, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29683818/pan-trk-immunohistochemistry-identifies-ntrk-rearrangements-in-pediatric-mesenchymal-tumors
#11
Erin R Rudzinski, Christina M Lockwood, Bradley A Stohr, Sara O Vargas, Rachel Sheridan, Jennifer O Black, Veena Rajaram, Theodore W Laetsch, Jessica L Davis
Activating neurotrophic receptor kinase (NTRK) fusions define certain pediatric mesenchymal tumors, including infantile fibrosarcoma and cellular mesoblastic nephroma. Traditionally, molecular confirmation of these fusions has included either fluorescent in situ hybridization for ETV6 rearrangements or reverse-transcriptase polymerase chain reaction for the classic ETV6-NTRK3 fusion. However, these methods overlook variant NTRK rearrangements, which are increasingly appreciated as recurrent events in a subset of pediatric mesenchymal tumors...
April 20, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29661832/kinase-activity-in-the-olfactory-bulb-is-required-for-odor-memory-consolidation
#12
Michelle T Tong, Tae-Young P Kim, Thomas A Cleland
Long-term fear memory formation in the hippocampus and neocortex depends upon brain-derived neurotrophic factor (BDNF) signaling after acquisition. Incremental, appetitive odor discrimination learning is thought to depend substantially on the differentiation of adult-born neurons within the olfactory bulb (OB)-a process that is closely associated with BDNF signaling. We sought to elucidate the role of neurotrophin signaling within the OB on odor memory consolidation. Male mice were trained on odor-reward associative discriminations after bilateral infusion of the kinase inhibitor K252a, or vehicle control, into the OB...
May 2018: Learning & Memory
https://www.readbyqxmd.com/read/29617282/inhibiting-trk-proteins-in-clinical-cancer-therapy
#13
REVIEW
Allison M Lange, Hui-Wen Lo
Gene rearrangements resulting in the aberrant activity of tyrosine kinases have been identified as drivers of oncogenesis in a variety of cancers. The tropomyosin receptor kinase (TRK) family of tyrosine receptor kinases is emerging as an important target for cancer therapeutics. The TRK family contains three members, TRKA, TRKB, and TRKC, and these proteins are encoded by the genes NTRK1, NTRK2, and NTRK3, respectively. To activate TRK receptors, neurotrophins bind to the extracellular region stimulating dimerization, phosphorylation, and activation of downstream signaling pathways...
April 4, 2018: Cancers
https://www.readbyqxmd.com/read/29610391/application-of-genomics-to-identify-therapeutic-targets-in-recurrent-pediatric-papillary-thyroid-carcinoma
#14
Rebecca Ronsley, S Rod Rassekh, Yaoqing Shen, Anna F Lee, Colleen Jantzen, Jessica Halparin, Catherine Albert, Douglas S Hawkins, Shazhan Amed, Ralph Rothstein, Andrew J Mungall, David Dix, Geoffrey Blair, Helen Nadel, Steven J M Jones, Janessa Laskin, Marco A Marra, Rebecca J Deyell
Children with papillary thyroid carcinoma (PTC) may relapse despite response to radioactive iodine (RAI). Two children with multiply relapsed PTC underwent whole-genome and transcriptome sequencing. A TPM3-NTRK1 fusion was identified in one tumor, with outlier NTRK1 expression compared to the TCGA thyroid cancer compendium and to Illumina BodyMap normal thyroid. This patient demonstrated resolution of multiple pulmonary nodules without toxicity on oral TRK inhibitor therapy. A RET fusion was identified in the second tumor, another potentially actionable finding...
April 2018: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/29606586/larotrectinib-for-paediatric-solid-tumours-harbouring-ntrk-gene-fusions-phase-1-results-from-a-multicentre-open-label-phase-1-2-study
#15
Theodore W Laetsch, Steven G DuBois, Leo Mascarenhas, Brian Turpin, Noah Federman, Catherine M Albert, Ramamoorthy Nagasubramanian, Jessica L Davis, Erin Rudzinski, Angela M Feraco, Brian B Tuch, Kevin T Ebata, Mark Reynolds, Steven Smith, Scott Cruickshank, Michael C Cox, Alberto S Pappo, Douglas S Hawkins
BACKGROUND: Gene fusions involving NTRK1, NTRK2, or NTRK3 (TRK fusions) are found in a broad range of paediatric and adult malignancies. Larotrectinib, a highly selective small-molecule inhibitor of the TRK kinases, had shown activity in preclinical models and in adults with tumours harbouring TRK fusions. This study aimed to assess the safety of larotrectinib in paediatric patients. METHODS: This multicentre, open-label, phase 1/2 study was done at eight sites in the USA and enrolled infants, children, and adolescents aged 1 month to 21 years with locally advanced or metastatic solid tumours or CNS tumours that had relapsed, progressed, or were non-responsive to available therapies regardless of TRK fusion status; had a Karnofsky (≥16 years of age) or Lansky (<16 years of age) performance status score of 50 or more, adequate organ function, and full recovery from the acute toxic effects of all previous anticancer therapy...
March 29, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29606584/an-active-drug-for-trk-positive-paediatric-solid-tumours
#16
Lucas Moreno
No abstract text is available yet for this article.
March 29, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29601870/anti-gm1-ganglioside-antibodies-modulate-membrane-associated-sphingomyelin-metabolism-by-altering-neutral-sphingomyelinase-activity
#17
Akihiro Ueda, Sayuri Shima, Kenitiroh Murate, Kouichi Kikuchi, Ryunosuke Nagao, Toshiki Maeda, Eri Muto, Yoshiki Niimi, Yasuaki Mizutani, Tatsuro Mutoh
Previous studies have shown that patients with Guillain-Barré syndrome express autoantibodies against ganglioside GM1 (GM1), although its pathogenic significance for the development of the disease remains to be elucidated. nSMase2 is the best characterized neutral sphingomyelinase (nSMase) found in neuronal cells. Activation of this enzyme leads to ceramide production, which is a known second messenger of the cell-death program in neuronal cells. We have explored the effects of anti-GM1 antibodies on sphingomyelin metabolism of PC12 cells stably transfected with human trk cDNA (PCtrk cells) by determining their effects on nSMase2 activity...
March 27, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29599313/the-novel-selective-pan-trk-inhibitor-ono-7579-exhibits-antitumor-efficacy-against-human-gallbladder-cancer-in-vitro
#18
Makoto Kawamoto, Keigo Ozono, Yasuhiro Oyama, Akio Yamasaki, Yoshinao Oda, Hideya Onishi
We previously reported that brain-derived neurotrophic factor (BDNF)/neurotrophic receptor tyrosine kinase 2 (NTRK2/TRKB) signaling contributes to induction of malignant phenotype of gallbladder cancer (GBC). Recently, pan-TRK inhibitors have been evaluated and their dramatic clinical activity is being shown for a variety of cancer types harboring an NTRK rearrangement in phase I trials. ONO-7579 is an oral pan-TRK inhibitor currently under investigation in phase I/II clinical trial for TRK-rearranged solid tumors...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29596897/mechanisms-of-neurotrophin-trafficking-via-trk-receptors
#19
REVIEW
Emily Scott-Solomon, Rejji Kuruvilla
In neurons, long-distance communication between axon terminals and cell bodies is a critical determinant in establishing and maintaining neural circuits. Neurotrophins are soluble factors secreted by post-synaptic target tissues that retrogradely control axon and dendrite growth, survival, and synaptogenesis of innervating neurons. Neurotrophins bind Trk receptor tyrosine kinases in axon terminals to promote endocytosis of ligand-bound phosphorylated receptors into signaling endosomes. Trk-harboring endosomes function locally in axons to acutely promote growth events, and can also be retrogradely transported long-distances to remote cell bodies and dendrites to stimulate cytoplasmic and transcriptional signaling necessary for neuron survival, morphogenesis, and maturation...
March 26, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29563190/tropomyosin-receptor-kinase-a-novel-target-in-screened-neuroendocrine-tumors
#20
Elke Tatjana Aristizabal Prada, Vera Heinzle, Thomas Knösel, Svenja Nölting, Gerald Spoettl, Julian Maurer, Christine Spitzweg, Martin Angele, Nina Schmidt, Felix Beuschlein, Günter K Stalla, Rainer Blaser, Klaus A Kuhn, Christoph J Auernhammer
Tropomyosin receptor kinase (Trk) inhibitors are investigated as a novel targeted therapy in various cancers. We investigated the in vitro effects of the pan-Trk inhibitor GNF-5837 in human neuroendocrine tumor (NET) cells. The human neuroendocrine pancreatic BON1, bronchopulmonary NCI-H727 and ileal GOT1 cell lines were treated with GNF-5837 alone and in combination with everolimus. Cell viability decreased in a time- and dose-dependent manner in GOT1 cells in response to GNF-5837 treatment, while treatment in BON1 and NCI-H727 cells showed no effect on cellular viability...
March 21, 2018: Endocrine-related Cancer
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