Database : MEDLINE
Search on : Phosphatidylinositol and 3-Kinases [Words]
References found : 31661 [refine]
Displaying: 1 .. 10   in format [Detailed]

page 1 of 3167 go to page                         

  1 / 31661 MEDLINE  
              next record last record
select
to print
Photocopy
Full text

[PMID]: 29373584
[Au] Autor:Zhao X; Li R; Jin H; Jin H; Wang Y; Zhang W; Wang H; Chen W
[Ad] Address:Tianjin Institute of Health and Environmental Medicine, Tianjin, China.
[Ti] Title:Epigallocatechin-3-gallate confers protection against corticosterone-induced neuron injuries via restoring extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3 kinase/protein kinase B signaling pathways.
[So] Source:PLoS One;13(1):e0192083, 2018.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Extensive studies suggested epigallocatechin-3-gallate (EGCG) has significant neuroprotection against multiple central neural injuries, but the underlying mechanisms still remain poorly elucidated. Here we provide evidence to support the possible involvement of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol-3 kinase/ protein kinase B (PI3K/AKT) pathways in EGCG-mediated protection against corticosterone-induced neuron injuries. As an essential stress hormone, corticosterone could induce obvious neurotoxicity in primary hippocampal neurons. Pre-treatment with EGCG ameliorated the corticosterone-induced neuronal injuries; however, it was blocked by pharmacological inhibitors for ERK1/2 (U0126) and PI3K/AKT (LY294002). Furthermore, the results confirmed that EGCG restored the corticosterone-induced decrease of ERK1/2 and PI3K/AKT phosphorylation, and attenuated the corticosterone-induced reduction of peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α) expression and ATP production. Taken together, these findings indicated that EGCG has significant neuroprotection against corticosterone-induced neuron injuries partly via restoring the ERK1/2 and PI3K/AKT signaling pathways as well as the PGC-1α-mediated ATP production.
[Mh] MeSH terms primary: Catechin/analogs & derivatives
Corticosterone/adverse effects
MAP Kinase Signaling System/drug effects
Neurons/drug effects
Phosphatidylinositol 3-Kinases/antagonists & inhibitors
Proto-Oncogene Proteins c-akt/metabolism
Signal Transduction
[Mh] MeSH terms secundary: Adenosine Triphosphate/biosynthesis
Animals
Catechin/pharmacology
Cells, Cultured
Hippocampus/cytology
Hippocampus/drug effects
Neuroprotective Agents/pharmacology
Phosphorylation
Rats
Rats, Wistar
Real-Time Polymerase Chain Reaction
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Neuroprotective Agents); 8L70Q75FXE (Adenosine Triphosphate); 8R1V1STN48 (Catechin); BQM438CTEL (epigallocatechin gallate); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); W980KJ009P (Corticosterone)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180127
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0192083

  2 / 31661 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 29346447
[Au] Autor:Chang HJ; Shin HS; Kim TH; Yoo JY; Teasley HE; Zhao JJ; Ha UH; Jeong JW
[Ad] Address:Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI, United States of America.
[Ti] Title:Pik3ca is required for mouse uterine gland development and pregnancy.
[So] Source:PLoS One;13(1):e0191433, 2018.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The PI3K/AKT signaling pathway plays a critical role in the maintenance of equilibrium between cell survival and apoptosis. The Pik3ca gene is mutated in a range of human cancers. It has been found to be oncogenic, and mutations lead to constitutive activation of the PI3K/AKT pathway. The expression patterns of PIK3CA proteins in the uterus of mice during early pregnancy indicate that it may play a role in the regulation of glandular epithelial cells, which is required to support uterine receptivity. To further investigate the role of Pik3ca in uterine function, Pik3ca was conditionally ablated only in the PGR-positive cells (Pgrcre/+Pik3caf/f; Pik3cad/d). A defect of uterine gland development and decidualization led to subfertility observed in Pik3cad/d mice. Pik3cad/d mice showed significantly decreased uterine weight compared to Pik3caf/f mice. Interestingly, a significant decrease of gland numbers were detected in Pik3cad/d mice compared to control mice. In addition, we found a decrease of Foxa2 expression, which is a known uterine gland marker in Pik3cad/d mice. Furthermore, the excessive proliferation of endometrial epithelial cells was observed in Pik3cad/d mice. Our studies suggest that Pik3ca has a critical role in uterine gland development and female fertility.
[Mh] MeSH terms primary: Phosphatidylinositol 3-Kinases/metabolism
Uterus/growth & development
[Mh] MeSH terms secundary: Animals
Blotting, Western
Cell Proliferation
Decidua/cytology
Decidua/growth & development
Embryo Implantation
Female
Fertility
Mice
Mice, Inbred C57BL
Mutation
Phosphatidylinositol 3-Kinases/genetics
Pregnancy
Real-Time Polymerase Chain Reaction
Uterus/cytology
Uterus/metabolism
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.1.137 (Pik3ca protein, mouse)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180119
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191433

  3 / 31661 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 29320816
[Au] Autor:Ismail HAHA; Kang BH; Kim JS; Lee JH; Choi IW; Cha GH; Yuk JM; Lee YH
[Ad] Address:Department of Infection Biology, Chungnam National University School of Medicine, Daejeon 34134, Korea.
[Ti] Title:IL-12 and IL-23 Production in Toxoplasma gondii- or LPS-Treated Jurkat T Cells via PI3K and MAPK Signaling Pathways.
[So] Source:Korean J Parasitol;55(6):613-622, 2017 Dec.
[Is] ISSN:1738-0006
[Cp] Country of publication:Korea (South)
[La] Language:eng
[Ab] Abstract:IL-12 and IL-23 are closely related in structure, and have been shown to play crucial roles in regulation of immune responses. However, little is known about the regulation of these cytokines in T cells. Here, we investigated the roles of PI3K and MAPK pathways in IL-12 and IL-23 production in human Jurkat T cells in response to Toxoplasma gondii and LPS. IL-12 and IL-23 production was significantly increased in T cells after stimulation with T. gondii or LPS. T. gondii and LPS increased the phosphorylation of AKT, ERK1/2, p38 MAPK, and JNK1/2 in T cells from 10 min post-stimulation, and peaked at 30-60 min. Inhibition of the PI3K pathway reduced IL-12 and IL-23 production in T. gondii-infected cells, but increased in LPS-stimulated cells. IL-12 and IL-23 production was significantly reduced by ERK1/2 and p38 MAPK inhibitors in T. gondii- and LPS-stimulated cells, but not in cells treated with a JNK1/2 inhibitor. Collectively, IL-12 and IL-23 production was positively regulated by PI3K and JNK1/2 in T. gondii-infected Jurkat cells, but negatively regulated in LPS-stimulated cells. And ERK1/2 and p38 MAPK positively regulated IL-12 and IL-23 production in Jurkat T cells. These data indicate that T. gondii and LPS induced IL-12 and IL-23 production in Jurkat T cells through the regulation of the PI3K and MAPK pathways; however, the mechanism underlying the stimulation of IL-12 and IL-23 production by T. gondii in Jurkat T cells is different from that of LPS.
[Mh] MeSH terms primary: Interleukin-12/metabolism
Interleukin-23/metabolism
Lipopolysaccharides/immunology
MAP Kinase Signaling System/immunology
MAP Kinase Signaling System/physiology
Phosphatidylinositol 3-Kinases/immunology
Phosphatidylinositol 3-Kinases/physiology
Toxoplasma/immunology
[Mh] MeSH terms secundary: Cells, Cultured
Humans
Jurkat Cells
Mitogen-Activated Protein Kinase 3/metabolism
Mitogen-Activated Protein Kinase 3/physiology
Mitogen-Activated Protein Kinase 8/metabolism
Mitogen-Activated Protein Kinase 8/physiology
Mitogen-Activated Protein Kinase 9/metabolism
Mitogen-Activated Protein Kinase 9/physiology
Phosphorylation
p38 Mitogen-Activated Protein Kinases/metabolism
p38 Mitogen-Activated Protein Kinases/physiology
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Interleukin-23); 0 (Lipopolysaccharides); 187348-17-0 (Interleukin-12); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.1.24 (Mitogen-Activated Protein Kinase 9); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 8); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180112
[St] Status:MEDLINE
[do] DOI:10.3347/kjp.2017.55.6.613

  4 / 31661 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
SciELO Brazil full text

[PMID]: 29267498
[Au] Autor:Ni XJ; Xu ZQ; Jin H; Zheng SL; Cai Y; Wang JJ
[Ad] Address:Transplantation Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
[Ti] Title:Ginsenoside Rg1 protects human renal tubular epithelial cells from lipopolysaccharide-induced apoptosis and inflammation damage.
[So] Source:Braz J Med Biol Res;51(2):e6611, 2017 Dec 11.
[Is] ISSN:1414-431X
[Cp] Country of publication:Brazil
[La] Language:eng
[Ab] Abstract:Ginsenoside Rg1, one of the most notable active components of Panax ginseng, has been widely reported to exert anti-inflammatory actions. This study aimed to reveal whether ginsenoside Rg1 also exhibits beneficial roles against lipopolysaccharide (LPS)-induced apoptosis and inflammation in human renal tubular epithelial cells, and to evaluate the potential role of the component on tubulointerstitial nephritis treatment. HK-2 cells were treated with various doses of ginsenoside Rg1 (0, 50, 100, 150, and 200 µM) in the absence or presence of 5 µg/mL LPS. Thereafter, CCK-8 assay, flow cytometry, western blot, migration assay, reactive oxygen species (ROS) assay, and ELISA were carried out to respectively assess cell viability, apoptosis, migration, ROS activity, and the release of inflammatory cytokines. As a result, ginsenoside Rg1 protected HK-2 cells from LPS-induced injury, as cell viability was increased, cell apoptosis was decreased, and the release of MCP-1, IL-1ß, IL-6, and TNF-α was reduced. Ginsenoside Rg1 functioned to HK-2 cells in a dose-dependent manner, and the 150 µM dose exhibited the most protective functions. Ginsenoside Rg1 had no significant impact on cell migration and ROS activity, while it alleviated LPS-induced ROS release and migration impairment. Furthermore, the down-regulations of p-PI3K, p-AKT, and up-regulations of PTEN, p-IκBα, p-p65, Bcl-3 induced by LPS were recovered to some extent after ginsenoside Rg1 treatment. In conclusion, ginsenoside Rg1 protects HK-2 cells against LPS-induced inflammation and apoptosis via activation of the PI3K/AKT pathway and suppression of NF-κB pathway.
[Mh] MeSH terms primary: Anti-Inflammatory Agents/pharmacology
Apoptosis/drug effects
Epithelial Cells/drug effects
Ginsenosides/pharmacology
Kidney Tubules/cytology
Lipopolysaccharides
Nephritis/prevention & control
[Mh] MeSH terms secundary: Analysis of Variance
Blotting, Western
Cell Line
Cell Migration Assays
Cell Survival/drug effects
Cytokines/analysis
Cytokines/drug effects
Enzyme-Linked Immunosorbent Assay
Humans
Kidney Tubules/drug effects
Phosphatidylinositol 3-Kinases/analysis
Phosphatidylinositol 3-Kinases/drug effects
Protective Agents/pharmacology
Proto-Oncogene Proteins c-akt/analysis
Proto-Oncogene Proteins c-akt/drug effects
Reactive Oxygen Species/analysis
Reproducibility of Results
[Pt] Publication type:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Name of substance:0 (Anti-Inflammatory Agents); 0 (Cytokines); 0 (Ginsenosides); 0 (Lipopolysaccharides); 0 (Protective Agents); 0 (Reactive Oxygen Species); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); PJ788634QY (ginsenoside Rg1)
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[Js] Journal subset:IM
[Da] Date of entry for processing:171222
[St] Status:MEDLINE

  5 / 31661 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 29442036
[Au] Autor:Pivodová V; Zahler S; Karas D; Valentová K; Ulrichova J
[Ti] Title: study of 2,3-dehydrosilybin and its galloyl esters as potential inhibitors of angiogenesis.
[So] Source:Pharmazie;71(8):478-483, 2016 08 01.
[Is] ISSN:0031-7144
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:2,3-Dehydrosilybin exhibits substantial anticancer and antiangiogenic effects, which can be potentially improved by semi-synthetic modification such as esterification with gallic acid. The aim of this study was to examine the potential antiangiogenic effect of 2,3-dehydrosilybin and its galloyl esters (3-O-galloyl-2,3-dehydrosilybin; 7-O-galloyl-2,3-dehydrosilybin; 20-O-galloyl-2,3-dehydrosilybin and 23-O-galloyl-2,3-dehydrosilybin) and to determine which molecular mechanism could be responsible for their activity. The effect on cell proliferation, tube formation, signal transduction pathways (PI3K/Akt and ERK) and the cell cycle was studied in human microvascular endothelial cells (HMEC). The results showed that all compounds decreased the growth of HMEC, but the strongest effect was observed for 20-O-galloyl-2,3-dehydrosilybin at 5 µmol/l. In addition, at 5 and 10 µmol/l, this was the only compound that significantly inhibited HMEC tube formation. Based on an assessment of Akt and ERK1/2 expression, we suggest that 20-O-galloyl-2,3-dehydrosilybin influences the angiogenic process through the Akt pathway.
[Mh] MeSH terms primary: Angiogenesis Inhibitors/pharmacology
Silymarin/pharmacology
[Mh] MeSH terms secundary: Angiogenesis Inhibitors/chemical synthesis
Cell Cycle/drug effects
Cell Proliferation/drug effects
Endothelial Cells/drug effects
Esters/chemical synthesis
Esters/pharmacology
Gallic Acid/chemical synthesis
Gallic Acid/pharmacology
Humans
MAP Kinase Signaling System/drug effects
Microtubules/drug effects
Neovascularization, Pathologic/drug therapy
Oncogene Protein v-akt/drug effects
Phosphatidylinositol 3-Kinases/drug effects
Silymarin/chemical synthesis
Structure-Activity Relationship
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Angiogenesis Inhibitors); 0 (Esters); 0 (Silymarin); 4RKY41TBTF (silybin); 632XD903SP (Gallic Acid); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Oncogene Protein v-akt)
[Em] Entry month:1803
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[Js] Journal subset:IM
[Da] Date of entry for processing:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6579

  6 / 31661 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 29206995
[Au] Autor:Wyatt AW; Annala M; Aggarwal R; Beja K; Feng F; Youngren J; Foye A; Lloyd P; Nykter M; Beer TM; Alumkal JJ; Thomas GV; Reiter RE; Rettig MB; Evans CP; Gao AC; Chi KN; Small EJ; Gleave ME
[Ad] Address:Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive
[Ti] Title:Concordance of Circulating Tumor DNA and Matched Metastatic Tissue Biopsy in Prostate Cancer.
[So] Source:J Natl Cancer Inst;109(12), 2017 Dec 01.
[Is] ISSN:1460-2105
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Background: Real-time knowledge of the somatic genome can influence management of patients with metastatic castration-resistant prostate cancer (mCRPC). While routine metastatic tissue biopsy is challenging in mCRPC, plasma circulating tumor DNA (ctDNA) has emerged as a minimally invasive tool to sample the tumor genome. However, no systematic comparisons of matched "liquid" and "solid" biopsies have been performed that would enable ctDNA profiling to replace the need for direct tissue sampling. Methods: We performed targeted sequencing across 72 clinically relevant genes in 45 plasma cell-free DNA (cfDNA) samples collected at time of metastatic tissue biopsy. We compared ctDNA alterations with exome sequencing data generated from matched tissue and quantified the concordance of mutations and copy number alterations using the Fisher exact test and Pearson correlations. Results: Seventy-five point six percent of cfDNA samples had a ctDNA proportion greater than 2% of total cfDNA. In these patients, all somatic mutations identified in matched metastatic tissue biopsies were concurrently present in ctDNA. Furthermore, the hierarchy of variant allele fractions for shared mutations was remarkably similar between ctDNA and tissue. Copy number profiles between matched liquid and solid biopsy were highly correlated, and individual copy number calls in clinically actionable genes were 88.9% concordant. Detected alterations included AR amplifications in 22 (64.7%) samples, SPOP mutations in three (8.8%) samples, and inactivating alterations in tumor suppressors TP53 , PTEN , RB1 , APC , CDKN1B , BRCA2 , and PIK3R1 . In several patients, ctDNA sequencing revealed robust changes not present in paired solid biopsy, including clinically relevant alterations in the AR, WNT, and PI3K pathways. Conclusions: Our study shows that, in the majority of patients, a ctDNA assay is sufficient to identify all driver DNA alterations present in matched metastatic tissue and supports development of DNA biomarkers to guide mCRPC patient management based on ctDNA alone.
[Mh] MeSH terms primary: Circulating Tumor DNA/blood
Prostatic Neoplasms, Castration-Resistant/genetics
Prostatic Neoplasms, Castration-Resistant/pathology
[Mh] MeSH terms secundary: Adenomatous Polyposis Coli Protein/genetics
BRCA2 Protein/genetics
Biomarkers, Tumor/blood
Biomarkers, Tumor/genetics
Cyclin-Dependent Kinase Inhibitor p27/genetics
DNA Copy Number Variations
Humans
Liquid Biopsy
Male
Mutation
Neoplasm Metastasis
Nuclear Proteins/genetics
PTEN Phosphohydrolase/genetics
Phosphatidylinositol 3-Kinases/genetics
Receptors, Androgen/genetics
Repressor Proteins/genetics
Retinoblastoma Binding Proteins/genetics
Tumor Suppressor Protein p53/genetics
Ubiquitin-Protein Ligases/genetics
Wnt Signaling Pathway/genetics
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (APC protein, human); 0 (Adenomatous Polyposis Coli Protein); 0 (BRCA2 Protein); 0 (BRCA2 protein, human); 0 (Biomarkers, Tumor); 0 (CDKN1B protein, human); 0 (Circulating Tumor DNA); 0 (Nuclear Proteins); 0 (RB1 protein, human); 0 (Receptors, Androgen); 0 (Repressor Proteins); 0 (Retinoblastoma Binding Proteins); 0 (SPOP protein, human); 0 (TP53 protein, human); 0 (Tumor Suppressor Protein p53); 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.7.1.- (PIK3R1 protein, human); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 3.1.3.67 (PTEN Phosphohydrolase); EC 3.1.3.67 (PTEN protein, human)
[Em] Entry month:1712
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[Js] Journal subset:IM
[Da] Date of entry for processing:171206
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx118

  7 / 31661 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 29028222
[Au] Autor:Choi HJ; Joo HS; Won HY; Min KW; Kim HY; Son T; Oh YH; Lee JY; Kong G
[Ad] Address:Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea; Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University,
[Ti] Title:Role of RBP2-Induced ER and IGF1R-ErbB Signaling in Tamoxifen Resistance in Breast Cancer.
[So] Source:J Natl Cancer Inst;110(4), 2018 Apr 01.
[Is] ISSN:1460-2105
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Background: Despite the benefit of endocrine therapy, acquired resistance during or after treatment still remains a major challenge in estrogen receptor (ER)-positive breast cancer. We investigated the potential role of histone demethylase retinoblastoma-binding protein 2 (RBP2) in endocrine therapy resistance of breast cancer. Methods: Survival of breast cancer patients according to RBP2 expression was analyzed in three different breast cancer cohorts including METABRIC (n = 1980) and KM plotter (n = 1764). RBP2-mediated tamoxifen resistance was confirmed by invitro sulforhodamine B (SRB) colorimetric, colony-forming assays, and invivo xenograft models (n = 8 per group). RNA-seq analysis and receptor tyrosine kinase assay were performed to identify the tamoxifen resistance mechanism by RBP2. All statistical tests were two-sided. Results: RBP2 was associated with poor prognosis to tamoxifen therapy in ER-positive breast cancer (P = .04 in HYU cohort, P = .02 in KM plotter, P = .007 in METABRIC, log-rank test). Furthermore, RBP2 expression was elevated in patients with tamoxifen-resistant breast cancer (P = .04, chi-square test). Knockdown of RBP2 conferred tamoxifen sensitivity, whereas overexpression of RBP2 induced tamoxifen resistance invitro and invivo (MCF7 xenograft: tamoxifen-treated control, mean [SD] tumor volume = 70.8 [27.9] mm3, vs tamoxifen-treated RBP2, mean [SD] tumor volume = 387.9 [85.1] mm3, P < .001). Mechanistically, RBP2 cooperated with ER co-activators and corepressors and regulated several tamoxifen resistance-associated genes, including NRIP1, CCND1, and IGFBP4 and IGFBP5. Furthermore, epigenetic silencing of IGFBP4/5 by RBP2-ER-NRIP1-HDAC1 complex led to insulin-like growth factor-1 receptor (IGF1R) activation. RBP2 also increased IGF1R-ErbB crosstalk and subsequent PI3K-AKT activation via demethylase activity-independent ErbB protein stabilization. Combinational treatment with tamoxifen and PI3K inhibitor could overcome RBP2-mediated tamoxifen resistance (RBP2-overexpressing cells: % cell viability [SD], tamoxifen = 89.0 [3.8]%, vs tamoxifen with BKM120 = 41.3 [5.6]%, P < .001). Conclusions: RBP2 activates ER-IGF1R-ErbB signaling cascade in multiple ways to induce tamoxifen resistance, suggesting that RBP2 is a potential therapeutic target for ER-driven cancer.
[Mh] MeSH terms primary: Breast Neoplasms/metabolism
Carcinoma, Ductal, Breast/metabolism
Drug Resistance, Neoplasm
Neoplasm Proteins/physiology
Receptors, Estrogen/metabolism
Retinoblastoma-Binding Protein 2/physiology
[Mh] MeSH terms secundary: Adaptor Proteins, Signal Transducing/metabolism
Analysis of Variance
Animals
Antineoplastic Agents, Hormonal/therapeutic use
Breast Neoplasms/chemistry
Breast Neoplasms/drug therapy
Breast Neoplasms/pathology
Carcinoma, Ductal, Breast/chemistry
Carcinoma, Ductal, Breast/drug therapy
Carcinoma, Ductal, Breast/pathology
Carrier Proteins/metabolism
Cohort Studies
Colorimetry
Disease-Free Survival
Drug Resistance, Neoplasm/genetics
Female
Heterografts
Humans
Kaplan-Meier Estimate
MCF-7 Cells
Mice
Mice, Inbred NOD
Mice, SCID
Neoplasm Proteins/metabolism
Neoplastic Stem Cells
Nuclear Proteins/metabolism
Phosphatidylinositol 3-Kinases/antagonists & inhibitors
Phosphatidylinositol 3-Kinases/metabolism
Receptor, ErbB-2/metabolism
Receptor, IGF Type 1/metabolism
Retinoblastoma-Binding Protein 2/metabolism
Tamoxifen/therapeutic use
Tumor Burden
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Adaptor Proteins, Signal Transducing); 0 (Antineoplastic Agents, Hormonal); 0 (Carrier Proteins); 0 (IGFBP5-interacting protein, human); 0 (Neoplasm Proteins); 0 (Nuclear Proteins); 0 (Receptors, Estrogen); 0 (nuclear receptor interacting protein 1); 094ZI81Y45 (Tamoxifen); EC 1.14.11.27 (Retinoblastoma-Binding Protein 2); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.10.1 (Receptor, ErbB-2); EC 2.7.10.1 (Receptor, IGF Type 1)
[Em] Entry month:1710
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[Js] Journal subset:IM
[Da] Date of entry for processing:171014
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx207

  8 / 31661 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 28453696
[Au] Autor:Böger C; Krüger S; Behrens HM; Bock S; Haag J; Kalthoff H; Röcken C
[Ad] Address:Department of Pathology, Christian-Albrechts-University, Kiel, Germany
[Ti] Title:Epstein-Barr virus-associated gastric cancer reveals intratumoral heterogeneity of PIK3CA mutations.
[So] Source:Ann Oncol;28(5):1005-1014, 2017 05 01.
[Is] ISSN:1569-8041
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Background: Recent whole-genome sequencing identified four molecular subtypes of gastric cancer (GC), of which the subgroup of Epstein-Barr virus-associated GC (EBVaGC) showed a significant enrichment of PIK3CA mutations. We here aimed to validate independently the enrichment of PIK3CA mutations in EBVaGC of a Central European GC cohort, to correlate EBV status with clinico-pathological patient characteristics and to test for a major issue of GC, intratumoral heterogeneity. Patients and methods: In a first step, 484 GCs were screened for EBV and PIK3CA hot spot mutations of exon 9/20 using EBER in situ hybridization and pyrosequencing, respectively. Secondly, an extended sequencing of PIK3CA also utilizing next generation sequencing was carried out in all EBVaGCs and 96 corresponding lymph node metastases. Results: Twenty-two GCs were EBER-positive, all being of latency type I. Intratumoral heterogeneity of EBER-positivity was found in 18% of EBVaGCs. Twenty-three GCs held PIK3CA mutations in hot spot regions of exon 9 or 20, being significantly more common in EBVaGCs (P < 0.001). Subsequent extended sequencing of PIK3CA of EBVaGCs showed that 14% harvested three to five different PIK3CA genotypes (including wildtype) in the same primary tumor, albeit in histologically and spatially distinct tumor areas, and that intratumoral heterogeneity of PIK3CA was also present in the corresponding lymph node metastases. Conclusions: Our findings unravel issues of tumor heterogeneity and illustrate that the assessment of the EBV status in tissue biopsies might carry the risk of sampling errors, which may significantly hamper adequate molecular tumor classification in a more clinical setting. Moreover, this is the first report of intratumoral heterogeneity of PIK3CA mutations in GC, and our findings lead to the conclusion that PIK3CA mutant and -wildtype tumor subclones are skilled to metastasize independently to different regional lymph nodes.
[Mh] MeSH terms primary: Adenocarcinoma/genetics
Class I Phosphatidylinositol 3-Kinases/genetics
Epstein-Barr Virus Infections/genetics
Stomach Neoplasms/genetics
[Mh] MeSH terms secundary: Adenocarcinoma/mortality
Adenocarcinoma/secondary
Adenocarcinoma/virology
Aged
Epstein-Barr Virus Infections/mortality
Epstein-Barr Virus Infections/pathology
Epstein-Barr Virus Infections/virology
Female
Gene Frequency
Genetic Association Studies
Genetic Heterogeneity
Genetic Predisposition to Disease
High-Throughput Nucleotide Sequencing
Humans
Kaplan-Meier Estimate
Lymphatic Metastasis
Male
Molecular Diagnostic Techniques
Mutation
Stomach Neoplasms/mortality
Stomach Neoplasms/pathology
Stomach Neoplasms/virology
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases); EC 2.7.1.137 (PIK3CA protein, human)
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[Js] Journal subset:IM
[Da] Date of entry for processing:170429
[St] Status:MEDLINE
[do] DOI:10.1093/annonc/mdx047

  9 / 31661 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 29348617
[Au] Autor:Miranda AM; Lasiecka ZM; Xu Y; Neufeld J; Shahriar S; Simoes S; Chan RB; Oliveira TG; Small SA; Di Paolo G
[Ad] Address:Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, 10032, USA.
[Ti] Title:Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures.
[So] Source:Nat Commun;9(1):291, 2018 01 18.
[Is] ISSN:2041-1723
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Defects in endolysosomal and autophagic functions are increasingly viewed as key pathological features of neurodegenerative disorders. A master regulator of these functions is phosphatidylinositol-3-phosphate (PI3P), a phospholipid synthesized primarily by class III PI 3-kinase Vps34. Here we report that disruption of neuronal Vps34 function in vitro and in vivo impairs autophagy, lysosomal degradation as well as lipid metabolism, causing endolysosomal membrane damage. PI3P deficiency also promotes secretion of unique exosomes enriched for undigested lysosomal substrates, including amyloid precursor protein C-terminal fragments (APP-CTFs), specific sphingolipids, and the phospholipid bis(monoacylglycero)phosphate (BMP), which normally resides in the internal vesicles of endolysosomes. Secretion of these exosomes requires neutral sphingomyelinase 2 and sphingolipid synthesis. Our results reveal a homeostatic response counteracting lysosomal dysfunction via secretion of atypical exosomes eliminating lysosomal waste and define exosomal APP-CTFs and BMP as candidate biomarkers for endolysosomal dysfunction associated with neurodegenerative disorders.
[Mh] MeSH terms primary: Amyloid beta-Protein Precursor/metabolism
Exosomes/metabolism
Lipids/analysis
Lysosomes/metabolism
Neurons/metabolism
[Mh] MeSH terms secundary: Amyloid beta-Protein Precursor/chemistry
Animals
Autophagy/genetics
Biomarkers/metabolism
Cell Line, Tumor
Class III Phosphatidylinositol 3-Kinases/genetics
Class III Phosphatidylinositol 3-Kinases/metabolism
HEK293 Cells
Humans
Lysophospholipids/metabolism
Mice, Inbred C57BL
Mice, Knockout
Monoglycerides/metabolism
Neurodegenerative Diseases/diagnosis
Neurodegenerative Diseases/metabolism
Peptide Fragments/metabolism
Phosphatidylinositol Phosphates/metabolism
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Amyloid beta-Protein Precursor); 0 (Biomarkers); 0 (Lipids); 0 (Lysophospholipids); 0 (Monoglycerides); 0 (Peptide Fragments); 0 (Phosphatidylinositol Phosphates); 0 (bis(monoacylglyceryl)phosphate); 0 (phosphatidylinositol 3-phosphate); EC 2.7.1.137 (Class III Phosphatidylinositol 3-Kinases)
[Em] Entry month:1803
[Cu] Class update date: 180306
[Lr] Last revision date:180306
[Js] Journal subset:IM
[Da] Date of entry for processing:180120
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02533-w

  10 / 31661 MEDLINE  
              first record previous record
select
to print
Photocopy
Full text

[PMID]: 28455143
[Au] Autor:Li H; Li B; Larose L
[Ad] Address:Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada; The Research Institute of McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
[Ti] Title:IRE1α links Nck1 deficiency to attenuated PTP1B expression in HepG2 cells.
[So] Source:Cell Signal;36:79-90, 2017 Aug.
[Is] ISSN:1873-3913
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:PTP1B, a prototype of the non-receptor subfamily of the protein tyrosine phosphatase superfamily, plays a key role in regulating intracellular signaling from various receptor and non-receptor protein tyrosine kinases. Previously, we reported that silencing Nck1 in human hepatocellular carcinoma HepG2 cells enhances basal and growth factor-induced activation of the PI3K-Akt pathway through attenuating PTP1B expression. However, the underlying mechanism by which Nck1 depletion represses PTP1B expression remains unclear. In this study, we found that silencing Nck1 attenuates PTP1B expression in HepG2 cells through down-regulation of IRE1α. Indeed, we show that silencing Nck1 in HepG2 cells leads to decreased IRE1α expression and signaling. Accordingly, IRE1α depletion using siRNA in HepG2 cells enhances PI3K-dependent basal and growth factor-induced Akt activation, reproducing the effects of silencing Nck1 on activation of this pathway. In addition, depletion of IRE1α also leads to reduced PTP1B expression, which was rescued by ectopic expression of IRE1α in Nck1-depleted cells. Mechanistically, we found that silencing either Nck1 or IRE1α in HepG2 cells decreases PTP1B mRNA levels and stability. However, despite miR-122 levels, a miRNA targeting PTP1B 3' UTR and inducing PTP1B mRNA degradation in HepG2 cells, are increased in both Nck1- and IRE1α-depleted HepG2 cells, a miR-122 antagomir did not rescue PTP1B expression in these cells. Overall, this study highlights an important role for Nck1 in fine-tuning IRE1α expression and signaling that regulate PTP1B expression and subsequent activation of the PI3K-Akt pathway in HepG2 cells.
[Mh] MeSH terms primary: Adaptor Proteins, Signal Transducing/deficiency
Adaptor Proteins, Signal Transducing/metabolism
Endoribonucleases/metabolism
Oncogene Proteins/deficiency
Oncogene Proteins/metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism
Protein-Serine-Threonine Kinases/metabolism
[Mh] MeSH terms secundary: Adaptor Proteins, Signal Transducing/chemistry
Animals
Enzyme Activation/drug effects
Fibroblasts/drug effects
Fibroblasts/metabolism
Gene Silencing/drug effects
HeLa Cells
Hep G2 Cells
Humans
Mice
MicroRNAs/metabolism
Oncogene Proteins/chemistry
Phosphatidylinositol 3-Kinases/metabolism
Phosphorylation/drug effects
Protein Binding/drug effects
Protein Domains
Protein Tyrosine Phosphatase, Non-Receptor Type 1/genetics
Proto-Oncogene Proteins c-akt/metabolism
RNA Stability/drug effects
RNA, Messenger/genetics
RNA, Messenger/metabolism
Signal Transduction/drug effects
Thapsigargin/pharmacology
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Adaptor Proteins, Signal Transducing); 0 (MIRN122 microRNA, human); 0 (MicroRNAs); 0 (Nck protein); 0 (Oncogene Proteins); 0 (RNA, Messenger); 67526-95-8 (Thapsigargin); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (ERN1 protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.1.- (Endoribonucleases); EC 3.1.3.48 (PTPN1 protein, human); EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
[Em] Entry month:1803
[Cu] Class update date: 180306
[Lr] Last revision date:180306
[Js] Journal subset:IM
[Da] Date of entry for processing:170430
[St] Status:MEDLINE


page 1 of 3167 go to page                         
   


Refine the search
  Database : MEDLINE Advanced form   

    Search in field  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/PAHO/WHO - Latin American and Caribbean Center on Health Sciences Information