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https://www.readbyqxmd.com/read/28934846/egfr-mutation-status-in-lung-adenocarcinoma-associated-malignant-pleural-effusion-and-efficacy-of-egfr-tyrosine-kinase-inhibitors
#1
Jiyoul Yang, Ok-Jun Lee, Seung-Myoung Son, Chang Gok Woo, Yusook Jeong, Yaewon Yang, Jihyun Kwon, Ki Hyeong Lee, Hye Sook Han
Purpose: Malignant pleural effusions (MPEs) are often observed in lung cancer, particularly adenocarcinoma. The aim of this study was to investigate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma-associated MPEs (LA-MPEs) and its correlation with efficacy of EGFR tyrosine kinase inhibitor (TKI) therapy. Methods: Samples comprised 40 cell blocks of pathologically-confirmed LA-MPEs collected before the start of EGFR TKI therapy. EGFR mutation status was re-evaluated by peptide nucleic acid clamping and the clinical outcomes of EGFR TKI-treated patients were analyzed retrospectively...
September 19, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28934818/effects-of-zinc-alpha2-glycoprotein-on-lipid-metabolism-of-liver-in-high-fat-diet-induced-obese-mice
#2
Guoqiang Fan, Yu Qiao, Shixing Gao, Jun Guo, Ruqian Zhao, Xiaojing Yang
Zinc alpha2 glycoprotein (ZAG) is a new type of adipokine involved in adipose tissue mobilization, however, little is known about its lipid metabolism effect in liver. Therefore, we investigated the effects of ZAG in the regulation of hepatic lipid accumulation. Mice were randomly divided into two groups; one was fed a normal diet and another was fed a high-fat diet for eight weeks to establish obesity model. After that, the normal diet group was divided into ND (injection of pcDNA3.1) and NDZ (injection of ZAG recombinant plasmid) and the high-fat diet group was divided into HF (injection of pcDNA3...
September 21, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28934742/elevated-apoptosis-in-the-liver-of-dairy-cows-with-ketosis
#3
Xiliang Du, Liang Chen, Dan Huang, Zhicheng Peng, Chenxu Zhao, Yuming Zhang, Yiwei Zhu, Zhe Wang, Xinwei Li, Guowen Liu
BACKGROUND/AIMS: Dairy cows with ketosis are characterized by oxidative stress and hepatic damage. The aim of this study was to investigate hepatic oxidative stress and the apoptotic status of ketotic cows, as well as the underlying apoptosis pathway. METHODS: The blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH) and gamma-glutamyl transferase (GGT) activities and the haptoglobin (HP), serum amyloid A (SAA) and serum apoptotic cytokeratin 18 neo-epitope M30 (CK18 M30) concentrations were determined by commercially available kits and ELISA kits, respectively...
September 21, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28934733/exosomes-from-human-induced-pluripotent-stem-cell-derived-mesenchymal-stromal-cells-hipsc-mscs-protect-liver-against-hepatic-ischemia-reperfusion-injury-via-activating-sphingosine-kinase-and-sphingosine-1-phosphate-signaling-pathway
#4
Yingdong Du, Dawei Li, Conghui Han, Haoyu Wu, Longmei Xu, Ming Zhang, Jianjun Zhang, Xiaosong Chen
BACKGROUND/AIMS: This study aimed to evaluate the effects of exosomes produced by human-induced pluripotent stem cell-derived mesenchymal stromal cells (hiPSC-MSCs-Exo) on hepatic ischemia-reperfusion (I/R) injury, as well as the underlying mechanisms. METHODS: Exosomes derived from hiPSC-MSCs were isolated and characterized both biochemically and biophysically. hiPSC-MSCs-Exo were injected systemically into a murine ischemia/reperfusion injury model via the inferior vena cava, and then the therapeutic effects were evaluated...
September 21, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28934680/a-phase-1-study-of-the-janus-kinase-2-jak2-v617f-inhibitor-gandotinib-ly2784544-in-patients-with-primary-myelofibrosis-polycythemia-vera-and-essential-thrombocythemia
#5
Srdan Verstovsek, Ruben A Mesa, Mohamed E Salama, Li Li, Celine Pitou, Fabio P Nunes, Gregory L Price, Jennifer L Giles, Deborah N D'Souza, Richard A Walgren, Josef T Prchal
Mutations in Janus kinase 2 (JAK2) are implicated in the pathogenesis of Philadelphia-chromosome negative myeloproliferative neoplasms, including primary myelofibrosis, polycythemia vera, and essential thrombocythemia. Gandotinib (LY2784544), a potent inhibitor of JAK2 activity, shows increased potency for the JAK2(V617F) mutation. The study had a standard 3+3 dose-escalation design to define the maximum-tolerated dose. Primary objectives were to determine safety, tolerability, and recommended oral daily dose of gandotinib for patients with JAK2(V617F)-positive myelofibrosis, essential thrombocythemia, or polycythemia vera...
August 31, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28934637/igf-system-targeted-therapy-therapeutic-opportunities-for-ovarian-cancer
#6
REVIEW
J A L Liefers-Visser, R A M Meijering, A K L Reyners, A G J van der Zee, S de Jong
The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models...
September 8, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28934561/epigenetic-mechanisms-regulating-adaptive-responses-to-targeted-kinase-inhibitors-in-cancer
#7
Steven P Angus, Jon S Zawistowski, Gary L Johnson
Although targeted inhibition of oncogenic kinase drivers has achieved remarkable patient responses in many cancers, the development of resistance has remained a significant challenge. Numerous mechanisms have been identified, including the acquisition of gatekeeper mutations, activating pathway mutations, and copy number loss or gain of the driver or alternate nodes. These changes have prompted the development of kinase inhibitors with increased selectivity, use of second-line therapeutics to overcome primary resistance, and combination treatment to forestall resistance...
September 15, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28934491/phosphorylation-regulates-human-pol%C3%AE-stability-and-damage-bypass-throughout-the-cell-cycle
#8
Federica Bertoletti, Valentina Cea, Chih-Chao Liang, Taiba Lanati, Antonio Maffia, Mario D M Avarello, Lina Cipolla, Alan R Lehmann, Martin A Cohn, Simone Sabbioneda
DNA translesion synthesis (TLS) is a crucial damage tolerance pathway that oversees the completion of DNA replication in the presence of DNA damage. TLS polymerases are capable of bypassing a distorted template but they are generally considered inaccurate and they need to be tightly regulated. We have previously shown that polη is phosphorylated on Serine 601 after DNA damage and we have demonstrated that this modification is important for efficient damage bypass. Here we report that polη is also phosphorylated by CDK2, in the absence of damage, in a cell cycle-dependent manner and we identify serine 687 as an important residue targeted by the kinase...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934469/hnrnp-l-controls-hpv16-rna-polyadenylation-and-splicing-in-an-akt-kinase-dependent-manner
#9
Naoko Kajitani, Jacob Glahder, Chengjun Wu, Haoran Yu, Kersti Nilsson, Stefan Schwartz
Inhibition of the Akt kinase activates HPV16 late gene expression by reducing HPV16 early polyadenylation and by activating HPV16 late L1 mRNA splicing. We identified 'hot spots' for RNA binding proteins at the early polyA signal and at splice sites on HPV16 late mRNAs. We observed that hnRNP L was associated with sequences at all HPV16 late splice sites and at the early polyA signal. Akt kinase inhibition resulted in hnRNP L dephosphorylation and reduced association of hnRNP L with HPV16 mRNAs. This was accompanied by an increased binding of U2AF65 and Sam68 to HPV16 mRNAs...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934393/neurofibromatosis-type-1-alternative-splicing-is-a-key-regulator-of-ras-erk-signaling-and-learning-behaviors-in-mice
#10
Hieu T Nguyen, Melissa N Hinman, Xuan Guo, Alok Sharma, Hiroyuki Arakawa, Guangbin Luo, Hua Lou
Appropriate activation of the Ras/extracellular signal-regulated kinase (ERK) protein signaling cascade within the brain is crucial for optimal learning and memory. One key regulator of this cascade is the Nf1 Ras GTPase activating protein (RasGAP), which attenuates Ras/ERK signaling by converting active Ras is bound to guanosine triphosphate, activating Ras into inactive Ras is bound to guanosine diphosphate, inactivating Ras. A previous study using embryonic stem cells and embryonic stem cell-derived neurons indicated that Nf1 RasGAP activity is modulated by the highly regulated alternative splicing of Nf1 exon 23a...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934384/short-syndrome-due-to-a-novel-de-novo-mutation-in-prkce-protein-kinase-c%C3%A9-impairing-torc2-dependent-akt-activation
#11
Diana Alcantara, Frances Elmslie, Martine Tetreault, Eric Bareke, Taila Hartley, Jacek Majewski, Kym Boycott, A Micheil Innes, David A Dyment, Mark O'Driscoll
SHORT syndrome is a rare, recognizable syndrome resulting from heterozygous mutations in PIK3R1 encoding a regulatory subunit of phosphoinositide-3-kinase (PI3K). The condition is characterized by short stature, intrauterine growth restriction, lipoatrophy and a facial gestalt involving a triangular face, deep set eyes, low hanging columella and small chin. PIK3R1 mutations in SHORT syndrome result in reduced signaling through the PI3K-AKT-mTOR pathway. We performed whole exome sequencing for an individual with clinical features of SHORT syndrome but negative for PIK3R1 mutation and her parents...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934369/in-vivo-activation-of-latent-hiv-with-a-synthetic-bryostatin-analog-effects-both-latent-cell-kick-and-kill-in-strategy-for-virus-eradication
#12
Matthew D Marsden, Brian A Loy, Xiaomeng Wu, Christina M Ramirez, Adam J Schrier, Danielle Murray, Akira Shimizu, Steven M Ryckbosch, Katherine E Near, Tae-Wook Chun, Paul A Wender, Jerome A Zack
The ability of HIV to establish a long-lived latent infection within resting CD4+ T cells leads to persistence and episodic resupply of the virus in patients treated with antiretroviral therapy (ART), thereby preventing eradication of the disease. Protein kinase C (PKC) modulators such as bryostatin 1 can activate these latently infected cells, potentially leading to their elimination by virus-mediated cytopathic effects, the host's immune response and/or therapeutic strategies targeting cells actively expressing virus...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28934360/pkacs-attenuate-innate-antiviral-response-by-phosphorylating-visa-and-priming-it-for-march5-mediated-degradation
#13
Bing-Ru Yan, Lu Zhou, Ming-Ming Hu, Mi Li, Heng Lin, Yan Yang, Yan-Yi Wang, Hong-Bing Shu
Sensing of viral RNA by RIG-I-like receptors initiates innate antiviral response, which is mediated by the central adaptor VISA. How the RIG-I-VISA-mediated antiviral response is terminated at the late phase of infection is enigmatic. Here we identified the protein kinase A catalytic (PKAC) subunits α and β as negative regulators of RNA virus-triggered signaling in a redundant manner. Viral infection up-regulated cellular cAMP levels and activated PKACs, which then phosphorylated VISA at T54. This phosphorylation abrogated virus-induced aggregation of VISA and primed it for K48-linked polyubiquitination and degradation by the E3 ligase MARCH5, leading to attenuation of virus-triggered induction of downstream antiviral genes...
September 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28934340/using-rna-seq-data-to-select-reference-genes-for-normalizing-gene-expression-in-apple-roots
#14
Zhe Zhou, Peihua Cong, Yi Tian, Yanmin Zhu
Gene expression in apple roots in response to various stress conditions is a less-explored research subject. Reliable reference genes for normalizing quantitative gene expression data have not been carefully investigated. In this study, the suitability of a set of 15 apple genes were evaluated for their potential use as reliable reference genes. These genes were selected based on their low variance of gene expression in apple root tissues from a recent RNA-seq data set, and a few previously reported apple reference genes for other tissue types...
2017: PloS One
https://www.readbyqxmd.com/read/28934284/correlation-of-dapk1-methylation-and-the-risk-of-gastrointestinal-cancer-a-systematic-review-and-meta-analysis
#15
Wenzheng Yuan, Jinhuang Chen, Yan Shu, Sanguang Liu, Liang Wu, Jintong Ji, Zhengyi Liu, Qiang Tang, Zili Zhou, Yifeng Cheng, Bin Jiang, Xiaogang Shu
OBJECTIVE: One of the critical mechanisms of gastrointestinal cancer pathogenesis is the silencing of death associated protein kinase 1 (DAPK1), which could be caused by aberrant methylation of the promoter. However, the relationship between DAPK1 methylation and the risk of gastrointestinal cancer is still controversial. Hence, we conducted this study to determine the potential correlation. METHODS: Eligible publications were searched in the Pubmed, Embase, and Cochrane Library through November 2016 according to the inclusion criteria and exclusion criteria...
2017: PloS One
https://www.readbyqxmd.com/read/28934276/enhanced-pyruvate-dehydrogenase-activity-improves-cardiac-outcomes-in-a-murine-model-of-cardiac-arrest
#16
Lin Piao, Yong-Hu Fang, Manfred M Kubler, Michael W Donnino, Willard W Sharp
RATIONALE: Post-ischemic changes in cellular metabolism alter myocardial and neurological function. Pyruvate dehydrogenase (PDH), the limiting step in mitochondrial glucose oxidation, is inhibited by increased expression of PDH kinase (PDK) during ischemia/reperfusion injury. This results in decreased utilization of glucose to generate cellular ATP. Post-cardiac arrest (CA) hypothermia improves outcomes and alters metabolism, but its influence on PDH and PDK activity following CA are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28934275/activation-of-phosphatidylinositol-3-kinase-akt-snail-signaling-pathway-contributes-to-epithelial-mesenchymal-transition-induced-multi-drug-resistance-to-sorafenib-in-hepatocellular-carcinoma-cells
#17
Jiejie Dong, Bo Zhai, Weihua Sun, Fengli Hu, Hao Cheng, Jun Xu
Sorafenib, an orally available kinase inhibitor, is the standard first-line systemic drug for advanced hepatocellular carcinoma (HCC), and it exerts potent inhibitory activity against epithelial-mesenchymal transition (EMT) and multidrug resistance (MDR) by inhibiting mitogen-activated protein kinase (MAPK) signaling in HCC. However, after long-term exposure to sorafenib, HCC cells exhibit EMT and resistance to sorafenib. The activation of AKT by sorafenib is thought to be responsible for the development of these characteristics...
2017: PloS One
https://www.readbyqxmd.com/read/28934221/stage-specific-requirement-of-platelet-derived-growth-factor-receptor-%C3%AE-in-embryonic-development
#18
Chen Qian, Carol Wing Yan Wong, Zhongluan Wu, Qiuming He, Huimin Xia, Paul Kwong Hang Tam, Kenneth Kak Yuen Wong, Vincent Chi Hang Lui
BACKGROUND: Platelet-derived growth factor receptor alpha (PDGFRα) is a cell-surface receptor tyrosine kinase for platelet-derived growth factors. Correct timing and level of Pdgfra expression is crucial for embryo development, and deletion of Pdgfra caused developmental defects of multiple endoderm and mesoderm derived structures, resulting in a complex phenotypes including orofacial cleft, spina bifida, rib deformities, and omphalocele in mice. However, it is not clear if deletion of Pdgfra at different embryonic stages differentially affects these structures...
2017: PloS One
https://www.readbyqxmd.com/read/28934205/a-rab5-gtpase-module-is-important-for-autophagosome
#19
Fan Zhou, Shenshen Zou, Yong Chen, Zhanna Lipatova, Dan Sun, Xiaolong Zhu, Rui Li, Zulin Wu, Weiming You, Xiaoxia Cong, Yiting Zhou, Zhiping Xie, Valeriya Gyurkovska, Yutao Liu, Qunli Li, Wenjing Li, Jie Cheng, Yongheng Liang, Nava Segev
In the conserved autophagy pathway, the double-membrane autophagosome (AP) engulfs cellular components to be delivered for degradation in the lysosome. While only sealed AP can productively fuse with the lysosome, the molecular mechanism of AP closure is currently unknown. Rab GTPases, which regulate all intracellular trafficking pathways in eukaryotes, also regulate autophagy. Rabs function in GTPase modules together with their activators and downstream effectors. In yeast, an autophagy-specific Ypt1 GTPase module, together with a set of autophagy-related proteins (Atgs) and a phosphatidylinositol-3-phosphate (PI3P) kinase, regulates AP formation...
September 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28934193/oxidative-stress-prefrontal-cortex-hypomyelination-and-cognitive-symptoms-in-schizophrenia
#20
REVIEW
D A Maas, A Vallès, G J M Martens
Schizophrenia (SZ) is a neurodevelopmental disorder with a broad symptomatology, including cognitive symptoms that are thought to arise from the prefrontal cortex (PFC). The neurobiological aetiology of these symptoms remains elusive, yet both impaired redox control and PFC dysconnectivity have been recently implicated. PFC dysconnectivity has been linked to white matter, oligodendrocyte (OL) and myelin abnormalities in SZ patients. Myelin is produced by mature OLs, and OL precursor cells (OPCs) are exceptionally susceptible to oxidative stress...
July 18, 2017: Translational Psychiatry
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