74,644 results match your criteria kinase akt


Development and validation of LC/MS/MS method for Triciribine and its monophosphate metabolite in plasma and RBC: Application to mice pharmacokinetic studies.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Apr 20;1174:122714. Epub 2021 Apr 20.

Ayma Therapeutics Incorporated, USA. Electronic address:

Triciribine (TCN) is a tricyclic nucleoside analog of adenosine and an inhibitor of Akt kinase. Triciribine 5'-monophosphate (TCNP) is a water-soluble analog of Triciribine and has progressed to Phase I and II clinical trials in oncology. TCNP is also an endogenous anabolite of TCN similar to other nucleoside phosphates. Read More

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Dasatinib inhibits proliferation of liver cancer cells, but activation of Akt/mTOR compromises dasatinib as a cancer drug.

Acta Biochim Biophys Sin (Shanghai) 2021 May 7. Epub 2021 May 7.

Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China.

Dasatinib is a multi-target protein tyrosine kinase inhibitor. Due to its potent inhibition of Src, Abl, the platelet-derived growth factor receptor (PDGFR) family kinases, and other oncogenic kinases, it has been investigated as a targeted therapy for a broad spectrum of cancer types. However, its efficacy has not been significantly extended beyond leukemia. Read More

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Antitumor and antimigration effects of Salvia clandestina L. extract on osteosarcoma cells.

Ann N Y Acad Sci 2021 May 7. Epub 2021 May 7.

Department of Biological and Environmental Science and Technologies (DiSTeBA), University of Salento, Lecce, Italy.

Salvia clandestina L. is a wild perennial species present in the Salento area of Italy. Here, we examined the in vitro effects of an aqueous extract of S. Read More

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Lansoprazole Alone or in Combination With Gefitinib Shows Antitumor Activity Against Non-small Cell Lung Cancer A549 Cells and .

Front Cell Dev Biol 2021 20;9:655559. Epub 2021 Apr 20.

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, China.

Lansoprazole (Lpz) is an FDA-approved proton pump inhibitor (PPI) drug for the therapy of acid-related diseases. Aiming to explore the new application of old drugs, we recently investigated the antitumor effect of Lpz. We demonstrated that the PPI Lpz played a tumor suppressive role in non-small cell lung cancer (NSCLC) A549 cells. Read More

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MAZ51 Blocks the Tumor Growth of Prostate Cancer by Inhibiting Vascular Endothelial Growth Factor Receptor 3.

Front Pharmacol 2021 20;12:667474. Epub 2021 Apr 20.

Department of Physiology, Aichi Medical University, Nagakute, Japan.

Vascular endothelial growth factor (VEGF) signaling plays a critical role in the carcinogenesis and tumor development of several cancer types. However, its pathological significance in prostate cancer, one of the most frequent and lethal malignancies in men, remains unclear. In the present study, we focused on a pathological role of the VEGF receptors (VEGFRs), and examined their expression and effects of MAZ51 (an inhibitor of the tyrosine kinase of VEGFR-3) on cell proliferation, migration, and tumor growth in human prostate cancer cells. Read More

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Integrated bioinformatic analysis and experiment confirmation of the antagonistic effect and molecular mechanism of ginsenoside Rh2 in metastatic osteosarcoma.

J Pharm Biomed Anal 2021 Apr 19;201:114088. Epub 2021 Apr 19.

Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China. Electronic address:

This study aimed to compare the gene expression variation of clinical primary osteosarcoma (OS) and metastatic OS, identify expression profiles and signal pathways related to disease classification, and systematically evaluate the potential anticancer effect and molecular mechanism of ginsenoside Rh2 on OS. A raw dataset (GSE14359), which excluded GSM359137 and GSM359138, was downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) and principal component analysis (PCA) were obtained with limma. Read More

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Modulation of Akt vs Stat3 activity by the focal adhesion kinase in non-neoplastic mouse fibroblasts.

Exp Cell Res 2021 May 3;404(1):112601. Epub 2021 May 3.

Department of Biomedical and Molecular Sciences and Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, K7L 3N6, Canada.

Adhesion of cells to each other and to the extracellular matrix (ECM) are both required for cellular functions. Cell-to-cell adhesion is mediated by cadherins and their engagement triggers the activation of Stat3, which offers a potent survival signal. Adhesion to the ECM on the other hand, activates FAK which attracts and activates Src, as well as receptor tyrosine kinases (RTKs), the PI3k/Akt and Ras/Erk pathways. Read More

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The Kidney-Related Effects of Polystyrene Microplastics on Human Kidney Proximal Tubular Epithelial Cells HK-2 and Male C57BL/6 Mice.

Environ Health Perspect 2021 May 6;129(5):57003. Epub 2021 May 6.

Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Background: Understanding the epidemic of chronic kidney disease of uncertain etiology may be critical for health policies and public health responses. Recent studies have shown that microplastics (MPs) contaminate our food chain and accumulate in the gut, liver, kidney, muscle, and so on. Humans manufacture many plastics-related products. Read More

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Reduced kinase D‑interacting substrate of 220 kDa (Kidins220) in pancreatic cancer promotes EGFR/ERK signalling and disease progression.

Int J Oncol 2021 Jun 6;58(6). Epub 2021 May 6.

Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.

Kidins220 is a transmembrane scaffold protein involved in several types of cancer. The aim of the present study was to examine the role of Kidins220 in tumorigenesis and disease progression of pancreatic cancer. The relevant signalling pathways including EGFR, EMT, and MMP were also investigated. Read More

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Decreased muscle-derived musclin by chronic resistance exercise is associated with improved insulin resistance in rats with type 2 diabetes.

Physiol Rep 2021 May;9(9):e14823

Faculty of Sport and Health Science, Ritsumeikan University, Kusatsu, Shiga, Japan.

Chronic resistance exercise induces improved hyperglycemia in patients with type 2 diabetes mellitus. Musclin, a muscle-derived secretory factor, is involved in the induction of insulin resistance via the downregulation of the glucose transporter-4 (GLUT-4) signaling pathway in skeletal muscles. However, whether musclin affects the mechanism of resistance exercise remains unclear. Read More

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Melatonin ameliorates myocardial injury by reducing apoptosis and autophagy of cardiomyocytes in a rat cardiopulmonary bypass model.

PeerJ 2021 15;9:e11264. Epub 2021 Apr 15.

Department of Cardiac Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Background: Myocardial injury is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to test the hypothesis that melatonin could attenuate myocardial injury in a rat CPB model.

Methods: Eighteen male Sprague-Dawley rats were randomly divided into three groups,  = 6 for each group: the sham operation (SO) group, CPB group and melatonin group. Read More

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[Doxorubicin directly induced fibrotic change of cardiac fibroblasts].

Nihon Yakurigaku Zasshi 2021 ;156(3):146-151

Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine.

Doxorubicin (DOX)-induced cardiomyopathy has a poor prognosis. No early detection or effective treatment methods are available in clinical. The mechanisms of cardiotoxicity were considered as oxidative stress and apoptosis in cardiomyocytes. Read More

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January 2021

Honokiol regulates endoplasmic reticulum stress by promoting the activation of the sirtuin 1-mediated protein kinase B pathway and ameliorates high glucose/high fat-induced dysfunction in human umbilical vein endothelial cells.

Authors:
Hong Ye Ying Meng

Endocr J 2021 Apr 29. Epub 2021 Apr 29.

Department of Cardiology, Hefei Binhu Hospital, Hefei City, Anhui Province, 230011, China.

Honokiol plays an important role in anti-oxidation, but its role in diabetic vascular complications is unclear. In this study, the effects of honokiol in high glucose/high fat (HG/HF)-induced human umbilical vein endothelial cells (HUVECs) were explored. After pre-treatment with honokiol, the cells were transferred to an HG/HF medium, and cell viability and apoptosis were respectively measured by methyl tetrazolium and flow cytometry. Read More

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Estrogen Receptor β Is Involved in Acquired Resistance to EGFR-tyrosine Kinase Inhibitors in Lung Cancer.

Anticancer Res 2021 May;41(5):2371-2381

Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan;

Background/aim: Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has posed serious clinical problems in the treatment of lung adenocarcinoma (LADC) patients harboring relevant EGFR mutations. In this study, we explored the role of estrogen receptor β (ERβ) in the development of acquired resistance to EGFR-TKIs in human LADC.

Materials And Methods: First, the role of ERβ in erlotinib resistance of LADC cell lines (PC9/ER) was examined. Read More

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Combined Targeting of AKT and mTOR Synergistically Inhibits Formation of Primary Colorectal Carcinoma Tumouroids : A 3D Tumour Model for Pre-therapeutic Drug Screening.

Anticancer Res 2021 May;41(5):2257-2275

Institute of Biochemistry and Signal Transduction, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

Background: Pre-therapeutic analysis of three-dimensional spheroid cultures of primary tumour samples is a promising approach of assessing susceptibility to potential treatment. The phosphatidylinositol-3-kinase/AKT serine/threonine kinase/mammalian target of rapamycin (PI3K/AKT/mTOR) signalling pathway is frequently activated in colorectal cancer (CRC). In previous work, we showed combined inhibition of AKT and mTOR to be highly synergistic in cell lines from patients with hepatocellular carcinoma and cholangiocarcinoma in vitro as well as in vivo in murine xenograft tumour models. Read More

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Mitochondrial Disruption Is Involved in the Effect of Nuclear Factor of Activated T cells, Cytoplasmic 4 on Aggravating Cardiomyocyte Hypertrophy.

J Cardiovasc Pharmacol 2021 May;77(5):557-569

Department of Pharmacy, School of Medicine, Guangxi University of Science and Technology, Liuzhou, Guangxi, People's Republic of China; and.

Abstract: Nuclear factor of activated T cells, cytoplasmic 4 (NFATc4), a nuclear transcription factor, has been implicated in cardiac hypertrophy through the enhancement of hypertrophic gene expression. However, the role of NFATc4 in mitochondrial modulation is mostly unknown. The current study aimed to investigate the role of NFATc4 in regulating mitochondrial function during phenylephrine (PE)-induced cardiac hypertrophy. Read More

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Ilex kudingcha C.J. Tseng Mitigates Phenotypic Characteristics of Human Autism Spectrum Disorders in a Drosophila Melanogaster Rugose Mutant.

Neurochem Res 2021 May 5. Epub 2021 May 5.

Center for Supporting Pharmaceutical Education, Daiichi University of Phamacy, Fukuoka, 815-8511, Japan.

Autism spectrum disorders (ASD) have heterogeneous etiologies involving dysfunction of central nervous systems, for which no effective pan-specific treatments are available. Ilex kudingcha (IK) C.J. Read More

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AKIP1 promotes glioblastoma viability, mobility and chemoradiation resistance via regulating CXCL1 and CXCL8 mediated NF-κB and AKT pathways.

Am J Cancer Res 2021 15;11(4):1185-1205. Epub 2021 Apr 15.

Department of Neurosurgery, The First Clinical College of Harbin Medical University Nangang District, Harbin 150001, China.

This study aimed to investigate the interaction of A-kinase-interacting protein 1 (AKIP1) with C-X-C motif chemokine ligand (CXCL)1, CXCL2, CXCL8, and their effects on regulating glioblastoma multiforme (GBM) malignant behaviors. AKIP1 expression was modified by pcDNA and pGPH1 vectors in U-87 MG and U-251 MG cells. Subsequently, multiple compensative experiments were conducted via adding CXCL1, CXCL2 and CXCL8 in the pGPH1-AKIP1 (AKIP1 knockdown) transfected U-87 MG and U-251 MG cells, respectively. Read More

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LRIG1 is a conserved EGFR regulator involved in melanoma development, survival and treatment resistance.

Oncogene 2021 May 4. Epub 2021 May 4.

Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Umeå, Sweden.

Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a pan-negative regulator of receptor tyrosine kinase (RTK) signaling and a tumor suppressor in several cancers, but its involvement in melanoma is largely unexplored. Here, we aim to determine the role of LRIG1 in melanoma tumorigenesis, RTK signaling, and BRAF inhibitor resistance. We find that LRIG1 is downregulated during early tumorigenesis and that LRIG1 affects activation of the epidermal growth factor receptor (EGFR) in melanoma cells. Read More

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The genomic landscape of carcinomas with mucinous differentiation.

Sci Rep 2021 May 4;11(1):9478. Epub 2021 May 4.

Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 20, New York, NY, 10065, USA.

Mucinous carcinomas can arise in any organ with epithelial cells that produce mucus. While mucinous tumors from different organs are histologically similar, it remains to be elucidated whether they share molecular alterations. Here we analyzed a total of 902 patients across six cancer types by comparing mucinous and non-mucinous samples, integrating text mining of pathology reports, gene expression, methylation, mutational and copy-number profiling. Read More

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Bioactive glass activates VEGF paracrine signaling of cardiomyocytes to promote cardiac angiogenesis.

Mater Sci Eng C Mater Biol Appl 2021 May 26;124:112077. Epub 2021 Mar 26.

National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, PR China; School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641, PR China; Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou 510006, PR China; Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou 510006, PR China; Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, PR China. Electronic address:

The heart contains a wide range of cell types, which are not isolated but interact with one another via multifarious paracrine, autocrine and endocrine factors. In terms of cardiac angiogenesis, previous studies have proved that regulating the communication between cardiomyocytes and endothelial cells is efficacious to promote capillary formation. Firstly, this study investigated the effect and underlying mechanism of bioactive glass (BG) acted on vascular endothelial growth factor (VEGF) paracrine signaling in cardiomyocytes. Read More

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Genetic alterations and their therapeutic implications in epithelial ovarian cancer.

BMC Cancer 2021 May 4;21(1):499. Epub 2021 May 4.

ACT Genomics, Co. Ltd., 3F., No.345, Xinhu 2nd Rd., Neihu Dist, Taipei City, 114, Taiwan.

Background: Genetic alterations for epithelial ovarian cancer are insufficiently characterized. Previous studies are limited regarding included histologies, gene numbers, copy number variant (CNV) detection, and interpretation of pathway alteration patterns of individual patients.

Methods: We sequenced 410 genes to analyze mutations and CNV of 82 ovarian carcinomas, including high-grade serous (n = 37), endometrioid (n = 22) and clear cell (n = 23) histologies. Read More

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Integration of Metabolomics and Gene Expression Profiling Elucidates IL4I1 as Modulator of Ibrutinib Resistance in ABC-Diffuse Large B Cell Lymphoma.

Cancers (Basel) 2021 Apr 29;13(9). Epub 2021 Apr 29.

Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL). B-cell NHLs rely on Bruton's tyrosine kinase (BTK) mediated B-cell receptor signaling for survival and disease progression. However, they are often resistant to BTK inhibitors or soon acquire resistance after drug exposure resulting in the drug-tolerant form. Read More

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Co-Targeting PIM Kinase and PI3K/mTOR in NSCLC.

Cancers (Basel) 2021 Apr 29;13(9). Epub 2021 Apr 29.

Department of Clinical Medicine, Trinity Translational Medicine Institute, St. James's Hospital, Dublin, Ireland.

PIM kinases are constitutively active proto-oncogenic serine/threonine kinases that play a role in cell cycle progression, metabolism, inflammation and drug resistance. PIM kinases interact with and stabilize p53, c-Myc and parallel signaling pathway PI3K/Akt. This study evaluated PIM kinase expression in NSCLC and in response to PI3K/mTOR inhibition. Read More

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Novel antiadipogenic effect of menadione in 3T3-L1 cells.

Chem Biol Interact 2021 May 1:109491. Epub 2021 May 1.

Instituto de Investigaciones Bioquímicas de Bahía Blanca, Universidad Nacional Del Sur (UNS)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca, Argentina. Departamento de Biología, Bioquímica y Farmacia, UNS, Bahía Blanca, Argentina. Electronic address:

Inhibition of adipocyte differentiation can be used as a strategy for preventing adipose tissue expansion and, consequently, for obesity management. Since reactive oxygen species (ROS) have emerged as key modulators of adipogenesis, the effect of menadione (a synthetic form of vitamin K known to induce the increase of intracellular ROS) on 3T3-L1 preadipocyte differentiation was studied. Menadione (15 μM) increased ROS and lipid peroxidation, generating mild oxidative stress without affecting cell viability. Read More

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Direct Effects of Lipopolysaccharide on Human Pancreatic Cancer Cells.

Pancreas 2021 Apr;50(4):524-528

From the Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.

Objectives: Obesity, a risk factor for pancreatic adenocarcinoma (PDAC), is often accompanied by a systemic increase in lipopolysaccharide (LPS; metabolic endotoxemia), which is thought to mediate obesity-associated inflammation. However, the direct effects of LPS on PDAC cells are poorly understood.

Methods: The expression of toll-like receptor 4, the receptor for LPS, was confirmed in PDAC cell lines. Read More

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Morin protects against acrylamide-induced neurotoxicity in rats: an investigation into different signal pathways.

Environ Sci Pollut Res Int 2021 May 3. Epub 2021 May 3.

Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, 25240, Erzurum, Turkey.

The presented study investigates the effects of morin against toxicity induced by acrylamide (ACR) in the brains of Sprague Dawley rats. In this study, neurotoxicity was induced by orally administering 38.27 mg/kg/b. Read More

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Suppressive effect of tamarixetin, isolated from , on degranulation and eicosanoid production in bone marrow-derived mast cells.

Allergol Immunopathol (Madr) 2021 1;49(3):42-49. Epub 2021 May 1.

Division of Korean Medicine Development, National Development Institute of Korean Medicine, Gyeongsan, Republic of Korea;

Background: The aim of this study was to evaluate the inhibitory effect of tamarixetin on the production of inflammatory mediators in IgE/antigen-induced mouse bone marrow-derived mast cells (BMMCs).

Materials And Methods: The effects of tamarixetin on mast cell activation were investigated with regard to degranulation, eicosanoid generation, Ca2+ influx, and immunoblotting of various signaling molecules.

Results: Tamarixetin effectively decreased degranulation and the eicosanoid generation such as leukotriene C and prostaglandin D in BMMCs. Read More

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Accelerated Bone Regeneration by Adrenomedullin 2 Through Improving the Coupling of Osteogenesis and Angiogenesis via β-Catenin Signaling.

Front Cell Dev Biol 2021 14;9:649277. Epub 2021 Apr 14.

Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Both osteogenic differentiation and the pro-angiogenic potential of bone marrow mesenchymal stem cells (BMSCs) contribute to bone regeneration during distraction osteogenesis (DO). Adrenomedullin 2 (ADM2), an endogenous bioactive peptide belonging to the calcitonin gene-related peptide family, exhibits various biological activities associated with the inhibition of inflammation and the attenuation of ischemic-hypoxic injury. However, the effects and underlying mechanisms of ADM2 in osteogenic differentiation and the pro-angiogenic potential of BMSCs, along with bone regeneration, remain poorly understood. Read More

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PI3K/AKT Signal Pathway: A Target of Natural Products in the Prevention and Treatment of Alzheimer's Disease and Parkinson's Disease.

Front Pharmacol 2021 15;12:648636. Epub 2021 Apr 15.

Department of Pharmacy, Cancer Institute, Phase I Clinical Trial Centre, Changsha Central Hospital Affiliated to University of South China, School of Pharmacy, University of South China, Changsha, China.

Alzheimer's disease (AD) and Parkinson's disease (PD) are two typical neurodegenerative diseases that increased with aging. With the emergence of aging population, the health problem and economic burden caused by the two diseases also increase. Phosphatidylinositol 3-kinases/protein kinase B (PI3K/AKT) signaling pathway regulates signal transduction and biological processes such as cell proliferation, apoptosis and metabolism. Read More

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