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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
May 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28495796/phosphorylation-of-nhe3-s-719-regulates-nhe3-activity-through-the-formation-of-multiple-signaling-complexes
#7
Rafiquel Sarker, Boyoung Cha, Olga Kovbasnjuk, Robert Cole, Sandra Gabelli, Chung Ming Tse, Mark Donowitz
Casein kinase 2 (CK2) binds to the NHE3 C-terminus and constitutively phosphorylates a down-stream site (S719) that accounts for 40% of basal NHE3 activity. The role of CK2 in regulation of NHE3 activity in polarized Caco-2/bbe cells was further examined by mutation of NHE3-S(719) to A (not phosphorylated) or D (phosphomimetic). NHE3-S719A but not -S719D had multiple changes in NHE3 activity consisting of a) reduced basal NHE3 activity: specifically, inhibition of the PI3-K/ AKT-dependent component. b) reduced acute stimulation of NHE3 activity by LPA/LPA5R stimulation...
May 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28495456/crosstalk-between-stat5-activation-and-pi3k-akt-functions-in-normal-and-transformed-mammary-epithelial-cells
#8
REVIEW
Patrick D Rädler, Barbara L Wehde, Kay-Uwe Wagner
Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) have been shown to function downstream of several peptide hormones and cytokines that are required for postnatal development and secretory function of the mammary gland. As part of an extended network, these signal transducers can engage in crosstalk with other pathways to facilitate synergistic, and sometimes antagonistic, actions of different growth factors. Specifically, signaling through the JAK2/STAT5 cascade has been demonstrated to be indispensable for the specification, proliferation, differentiation, and survival of secretory mammary epithelial cells...
May 8, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28485890/inhibition-of-endoplasmic-reticulum-stress-apoptosis-by-estrogen-protects-human-umbilical-vein-endothelial-cells-through-the-pi3-kinase-akt-signaling-pathway
#9
Yu Wang, Xin Yang, Xiao-Dong Li, Yong-Fen Qi, Xiao-Jing He, Yan-Jie Wang
OBJECTIVES: We aimed to investigate whether the cardioprotective effect of estrogen is mediated by inhibiting the apoptosis induced by endoplasmic reticulum stress (ERS) and to explore the underlying signaling pathway responsible for this effect. METHODS: The effect of estrogen on ERS apoptosis, the mechanism responsible for that effect, and the ERS signaling pathways were examined in human umbilical vein endothelial cells (HUVECs) and measured using western blot or Hoechst stains...
May 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28485480/shikonin-inhibited-migration-and-invasion-of-human-lung-cancer-cells-via-suppression-of-c-met-mediated-epithelial-to-mesenchymal-transition
#10
Yei-San Hsieh, Chiung-Ho Liao, Wan-Shen Chen, Jih-Tung Pai, Meng-Shih Weng
Epithelial-to-mesenchymal transition (EMT) is a major process to regulate cell migration and invasion. Inhibition of epidermal growth factor receptor (EGFR)-mediated EMT by tyrosine kinase inhibitors (TKIs) is a strategy to prevent lung cancer invasion. However, drug resistance is emerged and accelerated invasion through other signaling bypassing EGFR after TKIs therapy. c-Met signaling pathway is highly activated in EGFR-mutated lung cancer cells. Targeting c-Met signaling pathway may be a strategy to suppress EGFR-independent migration and invasion for lung cancer therapy...
May 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28477431/ehrho1-regulates-plasma-membrane-blebbing-through-pi3-kinase-in-entamoeba-histolytica
#11
Ravi Bharadwaj, Ranjana Arya, Sudha Bhattacharya, Alok Bhattacharya
The protozoan parasite Entamoeba histolytica causes amoebiasis, a major public health problem in developing countries. Motility of E. histolytica is important for its pathogenesis. Blebbing is an essential process contributing to cellular motility in many systems. In mammalian cells, formation of plasma membrane blebs is regulated by Rho-GTPases through its effectors, such as ROCK, mDia1 and acto-myosin proteins. In the present study, we have illuminated the role of EhRho1 in bleb formation and motility of E...
May 6, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28477117/studies-of-atm-kinase-activity-using-engineered-atm-sensitive-to-atp-analogues-atm-as
#12
Masato Enari, Yuko Matsushima-Hibiya, Makoto Miyazaki, Ryo Otomo
Ataxia-telangiectasia mutated (ATM) protein is a member of the phosphatidylinositol 3-phosphate kinase (PI3-K)-related protein kinase (PIKK) family and is implicated in the initiation of signaling pathways following DNA double strand breaks (DSBs) elicited by exposure to ionizing irradiation (IR) or radiomimetic compounds. Loss of function of the ATM gene product results in the human genetic disorder ataxia-telangiectasia (A-T) characterized by neurodegeneration, immunodeficiency, genomic instability, and cancer predisposition...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28477068/the-role-of-mir-130a-in-cancer
#13
REVIEW
He-da Zhang, Lin-Hong Jiang, Da-Wei Sun, Jian Li, Zhen-Ling Ji
MicroRNAs (miRs) are short and highly conserved non-coding RNAs molecules consisting of 18-25 nucleotides that regulate gene expression at post-transcriptional level by direct binding to complementary binding sites within the 3'untranslated region (3'UTR) of target mRNAs. New evidences have demonstrated that miRNAs play an important role in diverse physiological processes, including regulating cell growth, apoptosis, metastasis, drug resistance, and invasion. In chromosomes 11 and 22 of the miR-130 family, paralogous miRNA sequences, miR-130a and miR-130b are situated, respectively...
May 5, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28476872/integrative-analysis-identifies-a-novel-axl-pi3-kinase-pd-l1-signaling-axis-associated-with-radiation-resistance-in-head-and-neck-cancer
#14
Heath D Skinner, Uma Giri, Liang P Yang, Manish Kumar, Ying Liu, Michael D Story, Curtis R Pickering, Lauren A Byers, Michelle D Williams, Jing Wang, Li Shen, Suk Y Yoo, You Hong Fan, David P Molkentine, Beth M Beadle, Raymond E Meyn, Jeffrey N Myers, John V Heymach
Purpose: The primary cause of death due to head and neck squamous cell carcinoma (HNSCC) is local treatment failure. The goal of this study was to examine this phenomenon using an unbiased approach.Experimental Design: We utilized human papilloma virus (HPV)-negative cell lines rendered radiation-resistant (RR) via repeated exposure to radiation, a panel of HPV-negative HNSCC cell lines and three cohorts of HPV-negative HNSCC tumors (n = 68, 97, and 114) from patients treated with radiotherapy and subjected to genomic, transcriptomic, and proteomic analysis...
May 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28469544/fucoxanthin-prevents-h2o2-induced-neuronal-apoptosis-via-concurrently-activating-the-pi3-k-akt-cascade-and-inhibiting-the-erk-pathway
#15
Jie Yu, Jia-Jia Lin, Rui Yu, Shan He, Qin-Wen Wang, Wei Cui, Jin-Rong Zhang
Background: As a natural carotenoid abundant in chloroplasts of edible brown algae, fucoxanthin possesses various health benefits, including anti-oxidative activity in particular. Objective: In the present study, we studied whether fucoxanthin protected against hydrogen peroxide (H2O2)-induced neuronal apoptosis. Design: The neuroprotective effects of fucoxanthin on H2O2-induced toxicity were studied in both SH-SY5Y cells and primary cerebellar granule neurons. Results: Fucoxanthin significantly protected against H2O2-induced neuronal apoptosis and intracellular reactive oxygen species...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28469402/integrative-analysis-of-microrna-mediated-gene-signatures-and-pathways-modulating-white-blood-cell-count-in-childhood-acute-lymphoblastic-leukemia
#16
Ritika Ramani, Gail Megason, Jason Schallheim, Cynthia Karlson, Vani Vijayakumar, Srinivasan Vijayakumar, Chindo Hicks
MicroRNAs (miRNAs) regulate the expression of protein-coding genes and represent potential biomarkers for childhood acute lymphoblastic leukemia (ALL). However, information linking miRNAs with their messenger RNA (mRNA) target genes modulating white blood cell (WBC) count is lacking. Here, we analyzed miRNAs and gene expression data from pediatric patients with ALL to identify a signature of miRNAs involved in ALL and their mRNA target genes, molecular networks, and biological pathways modulating WBC. We discovered a signature of miRNAs differentially expressed in ALL and a signature of mRNA target genes distinguishing patients with high WBC from patients with low WBC...
2017: Biomarker Insights
https://www.readbyqxmd.com/read/28468873/subversion-of-host-responses-to-energy-insufficiency-by-us3-supports-hsv-1-replication-during-stress
#17
Elizabeth I Vink, James R Smiley, Ian Mohr
Cellular stress responses to energy insufficiency can impact virus reproduction. In particular, activation of the host AMP-activated protein kinase (AMPK) by low energy could limit protein synthesis by inhibiting mTORC1. Although many herpesviruses, including herpes simplex virus-1 (HSV-1), stimulate mTORC1, how HSV-1-infected cells respond to energy availability, a physiological indicator regulating mTORC1, has not been investigated. In addition, the impact of low energy stress on productive HSV-1 growth and viral genetic determinants potentially enabling replication under physiological stress remain undefined...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28466814/association-of-leukemia-inhibitory-factor-gene-polymorphism-and-in-vitro-fertilization-outcome-in-a-population-in-northern-iran
#18
M Alipour, F Mashayekhi, Z Salehi
Several studies have been demonstrated that endometrial leukemia inhibitory factor (LIF) is important in embryo implantation. LIF is a secreted glycoprotein with a variety of biological functions including stimulation of cell proliferation, differentiation and survival that are all essential for blastocyete development and implantation. The LIF receptor activates several signaling pathways in diverse cell types, including Jak/STAT, MAPK and PI3-kinase pathways in the endometrium of fertile woman. It has been suggested that the initial lower expression of LIF in proliferative phase may be one of the causes for multiple failure of implantation...
March 31, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28464236/neuroprotection-by-plumbagin-involves-bdnf-trkb-pi3k-akt-and-erk1-2-jnk-pathways-in-isoflurane-induced-neonatal-rats
#19
Jun-Hui Yuan, Feng Pan, Jie Chen, Cai-Er Chen, Deng-Pan Xie, Xing-Zhu Jiang, Su-Juan Guo, Jun Zhou
OBJECTIVES: This study was designed to assess the effects of plumbagin on isoflurane-induced neurotoxicity. METHODS: Neonatal Sprague Dawley rat pups were treated with plumbagin (50, 100 or 150 mg/kg body weight, orally) from postnatal day 2. The pups on postnatal day 7 were subjected to isoflurane (0.75%) exposure for 6 h. Neuronal apoptosis in the hippocampal tissues was detected by TUNEL assay and FluroJade B staining following isoflurane exposure. Protein expressions were analysed by immunoblotting...
May 2, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28458712/total-flavonoids-extracted-from-oxytropis-falcata-bunge-improve-insulin-resistance-through-regulation-on-the-ikk%C3%AE-nf-%C3%AE%C2%BAb-inflammatory-pathway
#20
Lixia Yang, Zhicheng Wang, Liangen Jiang, Wen Sun, Qiang Fan, Tonghua Liu
Background. Insulin resistance (IR) is the main etiology of type 2 diabetes mellitus (T2DM). It has been known that total flavonoid extracts can markedly improve the hypoglycemic symptoms caused by IR. Nevertheless, the relevant molecular mechanism remains unclarified. Aim. This study aimed to investigate the antihyperglycemic effects and mechanism of the total flavonoid extract from Oxytropis falcata Bunge. Methods. STZ-induced T2DM rats (n = 35) were divided into 5 groups: model, low-, medium-, and high-dose total flavonoids, and pioglitazone groups...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
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