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https://www.readbyqxmd.com/read/28646020/mcam-mediates-chemoresistance-in-small-cell-lung-cancer-via-the-pi3k-akt-sox2-signaling-pathway
#1
Satyendra C Tripathi, Johannes F Fahrmann, Muge Celiktas, Mitzi Aguilar, Kieren D Marini, Mohit Kumar Jolly, Hiroyuki Katayama, Hong Wang, Eunice N Murage, Jennifer B Dennison, D Neil Watkins, Herbert Levine, Edwin J Ostrin, Ayumu Taguchi, Samir M Hanash
Despite favorable responses to initial therapy, small cell lung cancer (SCLC) relapse occurs within a year and exhibits resistance to multiple drugs. Due to limited accessibility of patient tissues for research purposes, SCLC-patient derived xenografts (PDX) have provided the best opportunity to address this limitation. Here we sought to identify novel mechanisms involved in SCLC chemoresistance. Through in-depth proteomic profiling, we identified MCAM as a markedly upregulated surface receptor in chemoresistant SCLC cell lines and in chemoresistant PDX compared to matched treatment-naïve tumors...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28637746/early-protection-to-stress-mediated-by-cdk-dependent-pi3-5p2-signaling-from-the-vacuole-lysosome
#2
Natsuko Jin, Yui Jin, Lois S Weisman
Adaptation to environmental stress is critical for cell survival. Adaptation generally occurs via changes in transcription and translation. However, there is a time lag before changes in gene expression, which suggests that more rapid mechanisms likely exist. In this study, we show that in yeast, the cyclin-dependent kinase Pho85/CDK5 provides protection against hyperosmotic stress and acts before long-term adaptation provided by Hog1. This protection requires the vacuolar/endolysosomal signaling lipid PI3,5P2 We show that Pho85/CDK5 directly phosphorylates and positively regulates the PI3P-5 kinase Fab1/PIKfyve complex and provide evidence that this regulation is conserved in mammalian cells...
June 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28623178/adrenal-derived-stress-hormones-modulate-ozone-induced-lung-injury-and-inflammation
#3
Andres Henriquez, John House, Desinia B Miller, Samantha J Snow, Anna Fisher, Hongzu Ren, Mette C Schladweiler, Allen D Ledbetter, Fred Wright, Urmila P Kodavanti
Ozone-induced systemic effects are modulated through activation of the neuro-hormonal stress response pathway. Adrenal demedullation (DEMED) or bilateral total adrenalectomy (ADREX) inhibits systemic and pulmonary effects of acute ozone exposure. To understand the influence of adrenal-derived stress hormones in mediating ozone-induced lung injury/inflammation, we assessed global gene expression (mRNA sequencing) and selected proteins in lung tissues from male Wistar-Kyoto rats that underwent DEMED, ADREX, or sham surgery (SHAM) prior to their exposure to air or ozone (1ppm), 4h/day for 1 or 2days...
June 13, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28606920/single-cell-dynamics-determines-response-to-cdk4-6-inhibition-in-triple-negative-breast-cancer
#4
Uzma Asghar, Alexis R Barr, Ros Cutts, Matthew Beaney, Irina S Babina, Deepak Sampath, Jennifer Giltnane, Jennifer A Lacap, Lisa Crocker, Amy Young, Alex Pearson, Maria Teresa Herrera-Abreu, Chris Bakal, Nicholas C Turner
Purpose: Triple negative breast cancer (TNBC) is a heterogeneous subgroup of breast cancer that is associated with a poor prognosis. We evaluated the activity of CDK4/6 inhibitors across the TNBC subtypes, and investigated mechanisms of sensitivity. <p>Experimental design: A panel of cell lines representative of TNBC were tested for in vitro and in vivo sensitivity to CDK4/6 inhibition. A fluorescent CDK2 activity reporter was used for single cell analysis in conjunction with time-lapse imaging.</p> <p>Results: The luminal androgen receptor (LAR) subtype of TNBC was highly sensitive to CDK4/6 inhibition both in vitro [p<0...
June 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28605990/mir-25-protects-pc-12-cells-from-h2o2-mediated-oxidative-damage-via-wnt-%C3%AE-catenin-pathway
#5
Yi Guo, Shizhen Niu
OBJECTIVE: Spinal cord injury (SCI) is associated with modulation of different microRNAs (miRs). This study aims to explore the role of miR-25 in PC-12 cells to reveal the potential of miR-25 in SCI treatment. METHODS: SCI model was established in C57BL/6 mice, then miR-expression in the injured spinal cords were detected by qRT-PCR. PC-12 cells were exposed to H2O2 conditions to establish an in vitro model of SCI. PC-12 cells were transfected with expressing vector or antisense oligonucleotides (ASO) of miR-25...
June 12, 2017: Journal of Spinal Cord Medicine
https://www.readbyqxmd.com/read/28597147/mir-338-3p-inhibits-tnf-%C3%AE-induced-lipogenesis-in-human-sebocytes
#6
Jia Liu, Linggai Cao, Yue Feng, Yuhua Li, Tao Li
OBJECTIVE: To suppress TNF-α-induced lipogenesis in sebocytes (associated with acne development) with microRNA-338-3p (miR-338-3p) and to explore the underlying mechanisms. RESULTS: TNF-α increased lipid droplet formation in sebocytes which were used as in vitro model of inflammation-induced acne. Flow cytometry and TLC assays validated that miR-338-3p could suppress TNF-α-induced lipid droplet formation, down-regulate the expression of PREX2a, and inactivate AKT signaling in sebocytes...
June 9, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28597105/role-of-aspirin-in-breast-cancer-survival
#7
REVIEW
Wendy Y Chen, Michelle D Holmes
Chemotherapy and hormonal therapy have significantly decreased breast cancer mortality, although with considerable side effects and financial costs. In the USA, over three million women are living after a breast cancer diagnosis and are eager for new treatments that are low in toxicity and cost. Multiple observational studies have reported improved breast cancer survival with regular aspirin use. Furthermore, pooled data from five large randomized trials of aspirin for cardiovascular disease showed that subjects on aspirin had decreased risk of cancer mortality and decreased risk of metastatic cancer...
July 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28589905/nicotine-induces-ep4-receptor-expression-in-lung-carcinoma-cells-by-acting-on-ap-2%C3%AE-the-intersection-between-cholinergic-and-prostanoid-signaling
#8
Yu Fan, Ke Wang
It was demonstrated that nicotine increased non-small cell lung cancer cell proliferation through nicotinic acetylcholine receptor -mediated signals. However, the detailed mechanism remains incompletely understood. We evaluated whether nicotine increased EP4 receptor expression in lung carcinoma cells by activating on AP-2α. METHODS: The non-small cell lung cancer cells of A549 and H1838 were cultured and treated with EP4 inhibitor AH23848, also with EP4 and control siRNAs. The extracellular signal-regulated kinases inhibitor PD98059, the p38 mitogen-activated protein kinase inhibitor SB239063, the α7 nicotinic acetylcholine receptor inhibitor α-bungarotoxin, the α4 nicotinic acetylcholine receptor inhibitor dihydro-β-erythroidine, the PI3K inhibitor wortmannin, the PKC inhibitor calphostin C, and the PKA inhibitor H89 have been used to evaluate the effects on proliferations...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28578669/vegf-isoforms-have-differential-effects-on-permeability-of-human-pulmonary-microvascular-endothelial-cells
#9
Khadija Ourradi, Thomas Blythe, Caroline Jarrett, Shaney L Barratt, Gavin I Welsh, Ann B Millar
BACKGROUND: Alternative splicing of Vascular endothelial growth factor-A mRNA transcripts (commonly referred as VEGF) leads to the generation of functionally differing isoforms, the relative amounts of which have potentially significant physiological outcomes in conditions such as acute respiratory distress syndrome (ARDS). The effect of such isoforms on pulmonary vascular permeability is unknown. We hypothesised that VEGF165a and VEGF165b isoforms would have differing effects on pulmonary vascular permeability caused by differential activation of intercellular signal transduction pathways...
June 2, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28573491/p2x7-receptor-large-pore-signaling-in-avian-m%C3%A3-ller-glial-cells
#10
Robson X Faria, Hercules R Freitas, Ricardo A M Reis
ATP is a pleiotropic molecule that promotes extra- and intracellular signaling to regulate numerous functions. This nucleotide activates purine and pyrimidine receptors at the plasma membrane, categorized as ionotropic P2X or G-protein-coupled receptor (GPCR) P2Y receptors. P2X are ligand-gated ion channel receptors, expressed in both retinal neurons and Müller cells leading to neuron-glia communication, calcium waves and neurovascular coupling. However, how P2X pore is formed upon ATP activation and how signaling pathways regulates the complex is still a matter of controversy...
June 1, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28566443/hypoinsulinaemic-hypoketotic-hypoglycaemia-due-to-mosaic-genetic-activation-of-pi3-kinase
#11
Sarah Maria Leiter, Victoria Er Parker, Alena Welters, Rachel Knox, Nuno Rocha, Graeme R Clark, Felicity Payne, Luca Lotta, Julie Harris, Julio Guerrero-Fernández, Isabel González-Casado, Sixto García-Miñaur, Gema Gordo, N J Wareham, Victor Martínez-Glez, Michael Allison, Stephen O'Rahilly, Ines Barroso, Thomas Meissner, Susan Davies, Khalid Hussain, Karen Temple, Ana-Carol Barreda-Bonis, Sebastian Kummer, Robert Kenneth Semple
OBJECTIVE: Genetic activation of the insulin signal-transducing kinase AKT2 causes syndromic hypoketotic hypoglycaemia without elevated insulin. Mosaic activating mutations in class 1A phospatidylinositol-3-kinase (PI3K), upstream from AKT2 in insulin signalling, are known to cause segmental overgrowth, but the metabolic consequences have not been systematically reported. We assess the metabolic phenotype of 22 patients with mosaic activating mutations affecting PI3K, thereby providing new insight into the metabolic function of this complex node in insulin signal transduction...
May 31, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28561224/variant-pik3r1-hypermorphic-mutation-and-clinical-phenotypes-in-a-family-with-short-statures-mild-immunodeficiency-and-lymphoma
#12
Fabian Hauck, Thomas Magg, Ana Krolo, Ivan Bilic, Tatjana Hirschmugl, Martin Laass, Angela Rösen-Wolff, Hella Luksch, Kaan Boztug, Joachim Roesler
Background Heterozygous point mutations in the GT splice donor consensus sequence of exon 11 of the PIK3R1 gene (coding for p85α, p55α, and p50α regulatory subunits of PI3K) lead to exon skipping and thereby to an aberrant protein that leaves PI3K hyperactivated. Several patients with this particular variant of PI3 kinase delta syndrome (APDS) suffering from sinopulmonary infections and lymphoproliferation have been described. Methods (Whole exome) sequencing, evaluation of cellular and clinical phenotypes...
May 2017: Klinische Pädiatrie
https://www.readbyqxmd.com/read/28554304/ginsenoside-rb1-exerts-antidiabetic-action-on-c2c12-muscle-cells-by-leptin-receptor-signaling-pathway
#13
Mohammad Reza Tabandeh, Seyed Ahmad Hosseini, Maryam Hosseini
CONTEXT: Ginsenoside Rb1 improves insulin sensitivity and glucose uptake in muscle cells via different signaling pathways; however, it is not clear that it has any effect on leptin signaling in skeletal muscle. OBJECTIVES: The aim of this study was to investigate the effect of ginsenoside Rb1 on leptin receptors expression and main signaling pathways of leptin (STAT3, PI3 kinase and ERK kinase) in C2C12 skeletal muscle cells. MATERIALS AND METHODS: C2C12 myotubes were incubated with various concentrations of Rb1 (0...
August 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28554203/the-expanding-significance-of-inositol-polyphosphate-multikinase-as-a-signaling-hub
#14
REVIEW
Eunha Kim, Hyoungjoon Ahn, Min Gyu Kim, Haein Lee, Seyun Kim
The inositol polyphosphates are a group of multifunctional signaling metabolites whose synthesis is catalyzed by a family of inositol kinases that are evolutionarily conserved from yeast to humans. Inositol polyphosphate multikinase (IPMK) was first identified as a subunit of the arginine-responsive transcription complex in budding yeast. In addition to its role in the production of inositol tetrakis- and pentakisphosphates (IP4 and IP5), IPMK also exhibits phosphatidylinositol 3-kinase (PI3-kinase) activity...
May 31, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28542127/functional-screen-analysis-reveals-mir-3142-as-central-regulator-in-chemoresistance-and-proliferation-through-activation-of-the-pten-akt-pathway-in-cml
#15
Lifen Zhao, Yujia Shan, Bing Liu, Yang Li, Li Jia
Chronic myeloid leukemia (CML) is caused by the constitutively active BCR-ABL tyrosine kinase. Although great progress has been made for improvement in clinical treatment during the past decades, it is common for patients to develop chemotherapy resistance. Therefore, further exploring novel therapeutic strategies are still crucial for improving disease outcome. MicroRNAs (miRNAs) represent a novel class of genes that function as negative regulators of gene expression. Recently, miRNAs have been implicated in several cancers...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28538623/impact-of-a-novel-pi3-kinase-inhibitor-in-preventing-mitochondrial-dna-damage-and-damage-associated-molecular-pattern-accumulation-results-from-the-biochronicity-project
#16
George E Black, Kyle K Sokol, Donald M Moe, Jon Simmons, David Muscat, Victor Pastukh, Gina Capley, Olena Gorodnya, Mykhalo Ruchko, Mark B Roth, Mark Gillespie, Matthew J Martin
BACKGROUND: Despite improvements in the management of severely injured patients, development of multiple organ dysfunction syndrome (MODS) remains a morbid complication of traumatic shock. One of the key attributes of MODS is a profound bioenergetics crisis, for which the mediators and mechanisms are poorly understood. We hypothesized that metabolic uncoupling using an experimental PI3-kinase inhibitor, LY294002 (LY), may prevent mitochondrial abnormalities that lead to the generation of mitochondrial DNA (mtDNA) damage and the release of mtDNA damage associated molecular patterns (DAMPs) METHODS: 16 swine were studied using LY294002 (LY), a non-selective PI3-KI: Animals were assigned to Trauma only (TO, N=3); LY drug only (LYO, N=3); and Experimental (N=10), trauma + drug (LY+T) groups...
May 22, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28532828/expression-of-apelin-and-apelin-receptor-apj-in-porcine-ovarian-follicles-and-in%C3%A2-vitro-effect-of-apelin-on-steroidogenesis-and-proliferation-through-apj-activation-and-different-signaling-pathways
#17
A Rak, E Drwal, Ch Rame, K Knapczyk-Stwora, M Słomczyńska, J Dupont, E L Gregoraszczuk
Apelin was thought to be an adipocyte-specific hormone, but recent studies indicate a link between apelin and female reproductive function. Using real-time PCR, immunoblotting, immunohistochemistry and ELISA, we demonstrated expression of apelin and its receptor (APJ) in ovarian follicles of different sizes from mature pigs. Apelin concentration in the follicular fluid, and expression of both apelin and APJ, increased with follicular growth; greatest values were found in large follicles. Immunohistochemistry revealed the positive staining for apelin and APJ in membranes of granulosa, than theca cells...
July 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28512269/oscillating-expression-of-interleukin-16-in-multiple-myeloma-is-associated-with-proliferation-clonogenic-growth-and-pi3k-nfkb-mapk-activation
#18
Julia Templin, Djordje Atanackovic, Daniel Hasche, Sabarinath Venniyil Radhakrishnan, Tim Luetkens
Multiple myeloma (MM) is an incurable hematologic malignancy emerging from a plasma cell clone located in the bone marrow and is characterized by a high rate of fatal relapses after initially effective treatment. We have previously identified Interleukin-16 (IL-16) as an important factor promoting the proliferation of MM cells. We demonstrate here an upregulated, periodic expression, and secretion of IL-16 by MM cells leading to high extracellular IL-16 levels. The level of IL-16 released from a given MM cell line correlated with its proliferative activity...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28502694/phase-ii-trial-of-the-pi3-kinase-inhibitor-buparlisib-bkm-120-with-or-without-enzalutamide-in-men-with-metastatic-castration-resistant-prostate-cancer
#19
Andrew J Armstrong, Susan Halabi, Patrick Healy, Joshi J Alumkal, Carolyn Winters, Julie Kephart, Rhonda L Bitting, Carey Hobbs, Colleen F Soleau, Tomasz M Beer, Rachel Slottke, Kelly Mundy, Evan Y Yu, Daniel J George
BACKGROUND: Phosphatidylinositol-3-kinase (PI3K) and androgen receptor pathway activation is common in metastatic castration resistant prostate cancer (mCRPC). Buparlisib is an oral, pan-class I PI3 kinase inhibitor. METHODS: This was a multisite single arm phase II trial of buparlisib 100 mg ± enzalutamide daily in men with mCRPC whose disease progressed on or who were not candidates for docetaxel. The primary end-point was the rate of radiographic/clinical progression-free survival (PFS) at 6 months...
May 11, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28500219/mechanisms-of-enhanced-phrenic-long-term-facilitation-in-sod1-g93a-rats
#20
Nicole L Nichols, Irawan Satriotomo, Latoya L Allen, Ashley M Grebe, Gordon S Mitchell
Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease, causing muscle paralysis and death from respiratory failure. Effective means to preserve/restore ventilation are necessary to increase the quality and duration of life in ALS patients. At disease end-stage in a rat ALS model (SOD1(G93A) ), acute intermittent hypoxia (AIH) restores phrenic nerve activity to normal levels via enhanced phrenic long-term facilitation (pLTF). Mechanisms enhancing pLTF in end-stage SOD1(G93A) rats are not known...
June 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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