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Protein Kinase

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https://www.readbyqxmd.com/read/29458221/thyroid-stimulating-hormone-stimulated-human-adipocytes-express-thymic-stromal-lymphopoietin
#1
Loretta Ma, AnneMarie Gagnon, Anne Landry, Timothea Le, Fengxia Xiao, Cathy Sun, Heather A Lochnan, Dylan Burger, Alexander Sorisky
When recombinant human (rh) thyroid-stimulating hormone (TSH) is administered to thyroid cancer survivors, an acute extra-thyroidal effect raises pro-inflammatory cytokines and activates platelets. Thymic stromal lymphopoietin (TSLP) is a cytokine recently implicated in platelet activation. Our aim was to measure platelet microparticle levels after rhTSH stimulation in vivo, and to investigate TSLP expression in TSH-stimulated human adipocytes in culture. Blood samples for total and platelet microparticle analysis were obtained from thyroid cancer survivors before (day 1) and after rhTSH administration (day 5)...
February 19, 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29458087/ngf-fak-signal-pathway-is-implicated-in-angiogenesis-after-acute-cerebral-ischemia-in-rats
#2
Hai-Ting Zhao, Yu-Hu Zhang, Ying-Hui Zhang, Yue Shen, Yi-Dan Zhang, Fang-Fang Bi, Bo Xiao, Hao Zhang, Wen Ye, Hong-Hai Zhang, Yi-Wei Liao
Neurogenesis in the cerebral infarction after an ischemic event is important to the rehabilitation of patients. However, the mechanism of angiogenesis around cerebral ischemia is not clear. Our study designed to test whether the nerve growth factor (NGF)-P-focal adhesion kinase (FAK) signaling pathway for associations with angiogenesis plays a key role in post-acute cerebral ischemia of rats. Firstly, we implanted the Matrigel, a carrier of basement membrane matrix, into the abdominal skin of rats to identify the relevant components of the NGF-P-FAK signaling pathway related to angiogenesis...
February 16, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29458077/reciprocal-regulation-of-the-cadherin-11-stat3-axis-by-caveolin-1-in-mouse-fibroblasts-and-lung-carcinoma-cells
#3
M Geletu, R Mohan, R Arulanandam, A Berger-Becvar, I R Nabi, P T Gunning, L Raptis
Caveolin-1 (Cav1) is an integral plasma membrane protein and a complex regulator of signal transduction. The Signal Transducer and Activator of Transcription-3 (Stat3) is activated by a number of receptor and non-receptor tyrosine kinases and is positively implicated in cancer. Despite extensive efforts, the relationship between Cav1 and Stat3 has been a matter of controversy. We previously demonstrated that engagement of E- or N-cadherin or cadherin-11 cell to cell adhesion molecules, as occurs with confluence of cultured cells, triggers a dramatic increase in the levels of tyr705 phosphorylated ie activated Stat3, by a mechanism requiring the cRac1 small GTPase...
February 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29458018/5-chloro-n4-2-isopropylsulfonyl-phenyl-n2-2-methoxy-4-4-4-methylpiperazin-1-yl-methyl-1h-1-2-3-triazol-1-yl-phenyl-pyrimidine-2-4-diamine-wy-135-a-novel-alk-inhibitor-induces-cell-cycle-arrest-and-apoptosis-through-inhibiting-alk-and-its-downstream-pathways
#4
Mengting Han, Jiwei Shen, Lijing Wang, Yu Wang, Xin Zhai, Yao Li, Meiqiao Liu, Zengqiang Li, Daiying Zuo, Yingliang Wu
Anaplastic lymphoma kinase (ALK)-positive cancers have rising morbidity and mortality in recent years, and novel chemotherapeutic drugs with no drug resistance and high activity for treating ALK-positive cancers are needed urgently. In this study, we investigated the anti-cancer effect of 5-chloro-N4-(2-(isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(4-((4-methylpiperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)phenyl)pyrimidine-2,4-diamine (WY-135), a novel ALK inhibitor, on nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) positive cancer cell line Karpas299 and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) positive cancer cell line H2228...
February 16, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29457907/deletion-of-adipose-triglyceride-lipase-links-triacylglycerol-accumulation-to-a-more-aggressive-phenotype-in-a549-lung-carcinoma-cells
#5
Tamara Tomin, Katarina Fritz, Juergen Gindlhuber, Linda Waldherr, Bettina Pucher, Gerhard G Thallinger, Daniel K Nomura, Matthias Schittmayer, Ruth Birner-Gruenberger
Adipose triglyceride lipase (ATGL) catalyzes the rate limiting step in triacylglycerol breakdown in adipocytes but is expressed in most tissues. The enzyme was shown to be lost in many human tumors, and its loss may play a role in early stages of cancer development. Here we report that loss of ATGL supports a more aggressive cancer phenotype in a model system where ATGL was deleted in A549 lung cancer cells by CRISPR/Cas9. We observed that loss of ATGL led to triacylglycerol accumulation in lipid droplets, and higher levels of cellular phospholipid and bioactive lipid species (lyso- and ether-phospholipids)...
February 19, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29457883/mapping-the-h-nox-hk-binding-interface-in-vibrio-cholerae-by-hydrogen-deuterium-exchange-mass-spectrometry
#6
Yirui Guo, Anthony T Iavarone, Matthew M Cooper, Michael A Marletta
Heme-nitric oxide/oxygen binding (H-NOX) proteins are a group of hemoproteins that bind diatomic gas ligands such as nitric oxide (NO) and oxygen (O2 ). H-NOX proteins typically regulate histidine kinases (HK) located within the same operon. It has been reported that NO-bound H-NOXs inhibit cognate histidine kinase autophosphorylation in bacterial H-NOX/HK complexes, however, a detailed mechanism of NO-mediated regulation of the H-NOX/HK activity remains unknown. In this study, the binding interface of Vibrio cholerae (Vc) H-NOX/HK complex was characterized by hydrogen/deuterium exchange mass spectrometry (HDX-MS) and further validated by mutagenesis, leading to a new model for NO-dependent kinase inhibition...
February 19, 2018: Biochemistry
https://www.readbyqxmd.com/read/29457866/epigenetic-effects-of-metformin-from-molecular-mechanisms-to-clinical-implications
#7
REVIEW
S C Bridgeman, G C Ellison, P E Melton, P Newsholme, Cds Mamotte
There is a growing body of evidence that links epigenetic modifications to type 2 diabetes. Researchers have more recently investigated effects of commonly used medications, including those prescribed for diabetes, on epigenetic processes. This work reviews the influence of the widely used antidiabetic drug metformin on epigenomics, microRNA levels and subsequent gene expression and potential clinical implications. Metformin may influence the activity of numerous epigenetic modifying enzymes, mostly via modulating the activation of AMP-activated protein kinase (AMPK)...
February 19, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29457836/deptor-suppresses-lipogenesis-and-ameliorates-hepatic-steatosis-and-acute-on-chronic-liver-injury-in-alcoholic-liver-disease
#8
Hanqing Chen, Feng Shen, Alex Sherban, Allison Nocon, Yu Li, Hua Wang, Ming-Jiang Xu, Xianliang Rui, Jinyan Han, Bingbing Jiang, Donghwan Lee, Na Li, Farnaz Keyhani-Nejad, Jian-Gao Fan, Feng Liu, Amrita Kamat, Nicolas Musi, Leonard Guarente, Pal Pacher, Bin Gao, Mengwei Zang
Alcoholic liver disease (ALD) is characterized by lipid accumulation and liver injury. However, how chronic alcohol consumption causes hepatic lipid accumulation remains elusive. The present study demonstrates that activation of the mechanistic target of rapamycin complex 1 (mTORC1) plays a causal role in alcoholic steatosis, inflammation and liver injury. Chronic-plus-binge ethanol feeding led to hyperactivation of mTORC1, as evidenced by increased phosphorylation of mTOR and its downstream kinase S6K1 in hepatocytes...
February 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29457784/hiv-latency-is-reversed-by-acss2-driven-histone-crotonylation
#9
Guochun Jiang, Don Nguyen, Nancie M Archin, Steven A Yukl, Gema Méndez-Lagares, Yuyang Tang, Maher M Elsheikh, George R Thompson, Dennis J Hartigan-O'Connor, David M Margolis, Joseph K Wong, Satya Dandekar
Eradication of HIV-1 (HIV) is hindered by stable viral reservoirs. Viral latency is epigenetically regulated. While the effects of histone acetylation and methylation at the HIV long-terminal repeat (LTR) have been described, our knowledge of the proviral epigenetic landscape is incomplete. We report that a previously unrecognized epigenetic modification of the HIV LTR, histone crotonylation, is a regulator of HIV latency. Reactivation of latent HIV was achieved following the induction of histone crotonylation through increased expression of the crotonyl-CoA-producing enzyme acyl-CoA synthetase short-chain family member 2 (ACSS2)...
February 19, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29457680/chronic-lead-exposure-enhances-the-sympathoexcitatory-response-associated-with-p2x4-receptor-in-rat-stellate-ganglia
#10
Gaochun Zhu, Zhenying Chen, Bo Dai, Chaoran Zheng, Huaide Jiang, Yurong Xu, Xuan Sheng, Jingjing Guo, Yu Dan, Shangdong Liang, Guilin Li
Chronic lead exposure causes peripheral sympathetic nerve stimulation, including increased blood pressure and heart rate. Purinergic receptors are involved in the sympathoexcitatory response induced by myocardial ischemia injury. However, whether P2X4 receptor participates in sympathoexcitatory response induced by chronic lead exposure and the possible mechanisms are still unknown. The aim of this study was to explore the change of the sympathoexcitatory response induced by chronic lead exposure via the P2X4 receptor in the stellate ganglion (SG)...
February 19, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29457552/reciprocal-regulation-of-yap-taz-by-the-hippo-pathway-and-the-small-gtpase-pathway
#11
Ju-Won Jang, Min-Kyu Kim, Suk-Chul Bae
Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) (YAP/TAZ) are transcriptional coactivators that regulate genes involved in proliferation and transformation by interacting with DNA-binding transcription factors. Remarkably, YAP/TAZ are essential for cancer initiation or growth of most solid tumors. Their activation induces cancer stem cell attributes, proliferation, and metastasis. The oncogenic activity of YAP/TAZ is inhibited by the Hippo cascade, an evolutionarily conserved pathway that is governed by two kinases, mammalian Ste20-like kinases 1/2 (MST1/2) and Large tumor suppressor kinase 1/2 (LATS1/2), corresponding to Drosophila's Hippo (Hpo) and Warts (Wts), respectively...
February 18, 2018: Small GTPases
https://www.readbyqxmd.com/read/29457462/determination-of-site-specific-phosphorylation-ratios-in-proteins-with-targeted-mass-spectrometry
#12
Lennard J M Dekker, Lona Zeneyedpour, Sandor Snoeijers, Jos Joore, Sieger Leenstra, Theo M Luider
We show that parallel reaction monitoring (PRM) can be used for exact quantification of phosphorylation ratios of proteins using stable isotope labelled peptides. We have compared two different PRM approaches on a digest of a U87 cell culture, namely direct-PRM (tryptic digest measured by PRM without any further sample preparation) and TiO2-PRM (tryptic digest enriched with TiO2 cartridges, followed by PRM measurement); these approaches are compared for the following phosphorylation sites: Neuroblast differentiation-associated protein (AHNAK S5480-p), Calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D T337-p) and Epidermal growth factor receptor (EGFR S1166-p)...
February 19, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29456860/protein-kinase-inhibitors-for-acute-leukemia
#13
REVIEW
Yuan Ling, Qing Xie, Zikang Zhang, Hua Zhang
Conventional treatments for acute leukemia include chemotherapy, radiation therapy, and intensive combined treatments (including bone marrow transplant or stem cell transplants). Novel treatment approaches are in active development. Recently, protein kinase inhibitors are on clinical trials and offer hope as new drugs for acute leukemia treatment. This review will provide a brief summary of the protein kinase inhibitors in clinical applications for acute leukemia treatment.
2018: Biomarker Research
https://www.readbyqxmd.com/read/29456854/novel-braf-mutation-in-melanoma-a-case-report
#14
Serena Trubini, Alessandro Ubiali, Carlo Terenzio Paties, Luigi Cavanna
In melanoma, a number of specific genetic and genomic aberrations have been identified to be important in tumorigenesis. In particular, the mutant B-Raf proto-oncogene, Serine/Threonine kinase (BRAF) gene is the target of tailored therapy with kinase inhibitor molecules. Identification of the array of mutations in patients with melanoma will be useful in determining a genetic profile of the tumor with potential implications for treatment decisions. A rare aminoacidic insertion in codon 599 of the BRAF gene (c...
March 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29456853/crizotinib-associated-toxic-epidermal-necrolysis-in-an-alk-positive-advanced-nsclc-patient
#15
Shaoyu Yang, Liming Wu, Xin Li, Jie Huang, Jianbo Zhong, Xueqin Chen
Crizotinib is an oral small-molecule inhibitor of anaplastic lymphoma kinase (ALK) tyrosine-kinase that has been approved for treating patients with advanced echinoderm microtubule associated protein like 4-ALK rearranged non-small-cell lung cancer (NSCLC). Toxic epidermal necrolysis (TEN) is a rare adverse event associated with crizotinib. The present study reported a case of a 75-year-old Chinese male patient with advanced NSCLC with ALK fusion, who developed TEN after 56 days of crizotinib treatment and demised due to this dermatological adverse event...
March 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29456817/s100a9-aggravates-bleomycin-induced-dermal-fibrosis-in-mice-via-activation-of-erk1-2-mapk-and-nf-%C3%AE%C2%BAb-pathways
#16
Xue Xu, Zhiyong Chen, Xiaoxia Zhu, Dandan Wang, Jun Liang, Cheng Zhao, Xuebing Feng, Jiucun Wang, Hejian Zou, Lingyun Sun
Objectives: This study aims to investigate the pathogenicity and possible mechanisms of S100A9 function in mice models of scleroderma. Materials and Methods: The content of S100A9 in the skin tissues of mice with scleroderma was determined. Different concentrations of bleomycin (BLM) and S100A9 were subcutaneously injected into the backs of mice simultaneously, and then pathological changes in the skin of these mice were monitored. Specifically, the levels of inflammatory cytokines and alpha smooth muscle actin (α-SMA), the activation of extracellular regulated kinase 1/2 (ERK1/2), mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathways, and the expression of the receptor for advanced glycation end-product (RAGE) in the skin were determined...
February 2018: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29456744/cardamonin-enhances-the-anti-proliferative-effect-of-cisplatin-on-ovarian-cancer
#17
Peiguang Niu, Daohua Shi, Shusheng Zhang, Yanting Zhu, Jintuo Zhou
The mammalian target of rapamycin (mTOR) is well-known as a promising therapeutic target in various cancer cells. mTOR activation decreases the sensitivity of ovarian cancer to cisplatin. Cardamonin inhibits the proliferation of various cancer cells by mTOR suppression. The present study examined whether cardamonin combined with cisplatin is efficacious for the anti-proliferation of ovarian cancer cells. The anti-proliferative effect was determined by MTT and cell cycle assays. Activation of the mTOR signal pathway and the expression of anti-apoptotic proteins were evaluated by western blot analysis...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29456742/mir302a-inhibits-the-proliferation-of-esophageal-cancer-cells-through-the-mapk-and-pi3k-akt-signaling-pathways
#18
Daokui Xia, Shumei Tian, Zhen Chen, Wenchao Qin, Quan Liu
MicroRNAs (miRNAs/miRs) are involved in the regulation of various types of cancer, either as oncogenes or tumor suppressors. miR302a has been reported that it could suppress tumor cell proliferation by inhibiting Akt in prostate cancer. The present study examined the effect of miR302a on proliferation and invasion in esophageal cancer cell lines. The expression levels of miR302a in esophageal cancer cell lines was determined by reverse transcription-polymerase chain reaction. Subsequently, miR302a mimics were transfected into esophageal cancer cells, and cell viability and invasion were assessed by MTT and Transwell assays...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29456739/effects-of-pha-665752-and-vemurafenib-combination-treatment-on-in-vitro-and-murine-xenograft-growth-of-human-colorectal-cancer-cells-with-braf-v600e-mutations
#19
Jie Zhi, Zhongxin Li, Jian Lv, Bo Feng, Donghai Yang, Liang Xue, Zhaolong Zhao, Yanni Zhang, Jianhua Wu, Yingchao Jv, Yitao Jia
It remains unknown whether blockade of B-Raf proto-oncogene, serine/threonine kinase (BRAF)V600E signaling and MET proto-oncogene, receptor tyrosine kinase (c-Met) signaling is effective in suppressing the growth of human colorectal cancer (CRC) cells. The present study investigated the effects of the vemurafenib alone and in combination with c-Met inhibitor PHA-665752 on the growth of human CRC cells in vitro and in mouse xenografts. HT-29 and RKO CRC cell lines with BRAFV600E mutations and mice bearing HT-29 xenografts were treated with vemurafenib in the absence or presence of PHA-665752...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29456722/fucosterol-exhibits-selective-antitumor-anticancer-activity-against-hela-human-cervical-cell-line-by-inducing-mitochondrial-mediated-apoptosis-cell-cycle-migration-inhibition-and-downregulation-of-m-tor-pi3k-akt-signalling-pathway
#20
Hongye Jiang, Jie Li, Aiyue Chen, Yinguang Li, Meng Xia, Peng Guo, Shuzhong Yao, Shuqin Chen
Cervical cancer greatly contributes to cancer-associated mortalities worldwide. The growing incidence of cervical cancer is of primary concern, and has signaled the need for multiple treatment options. Despite preliminary responses to chemotherapy and/or surgical interventions, the tumors consistently relapse. Previously, natural products gained attention for their diverse bioactivities, which include however are not limited to, neuroprotective, antimicrobial and anticancer effects. The present study evaluated the anticancer activity of fucosterol against a panel of human cancer cell lines...
March 2018: Oncology Letters
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