The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Graham P. Pidgeon - One of the best experts on this subject based on the ideXlab platform.
-
examination of thromboxane synthase as a prognostic factor and therapeutic target in non small Cell lung cancer
Molecular Cancer, 2011Co-Authors: Mary-clare Cathcart, Kathy Gately, Kenneth J Obyrne, Robert Cummins, Graham P. PidgeonAbstract:Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer Cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces Cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a Survival factor in the disease. TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall Survival. Cell proliferation/Survival and invasion was examined in NSCLC Cells following both selective TXS inhibition and stable TXS over-expression. TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB2 levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient Survival was observed. Selective TXS inhibition significantly reduced tumour Cell growth and increased apoptosis, while TXS over-expression stimulated Cell proliferation and invasiveness, and was protective against apoptosis. TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC.
-
examination of thromboxane synthase as a prognostic factor and therapeutic target in non small Cell lung cancer
Faculty of Health; Institute of Health and Biomedical Innovation, 2011Co-Authors: Mary-clare Cathcart, Kathy Gately, Kenneth J Obyrne, Robert Cummins, Graham P. PidgeonAbstract:Background: Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer Cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces Cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a Survival factor in the disease. Methods: TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB 2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall Survival. Cell proliferation/Survival and invasion was examined in NSCLC Cells following both selective TXS inhibition and stable TXS over-expression. Results: TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB 2levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient Survival was observed. Selective TXS inhibition significantly reduced tumour Cell growth and increased apoptosis, while TXS over-expression stimulated Cell proliferation and invasiveness, and was protective against apoptosis. Conclusion: TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC. © 2011 Cathcart et al; licensee BioMed Central Ltd.
Leongperng Chan - One of the best experts on this subject based on the ideXlab platform.
-
apigenin induces apoptosis via tumor necrosis factor receptor and bcl 2 mediated pathway and enhances susceptibility of head and neck squamous Cell carcinoma to 5 fluorouracil and cisplatin
Biochimica et Biophysica Acta, 2012Co-Authors: Leongperng Chan, Tzunghan Chou, Hsiouyu Ding, Pinru Chen, Fengyu Chiang, Polin Kuo, Chiahua LiangAbstract:Abstract Background Apigenin, a natural plant flavone, may have chemopreventive and therapeutic potentials for anti-inflammatory, antioxidant, and anti-cancer. Nevertheless, the anti-tumor effect of apigenin on human head and neck squamous Cell carcinoma (HNSCC) is not fully understood. Methods The antioxidant capacity and protective effects of apigenin against oxidative stress in murine normal embryonic liver BNLCL2 Cells are examined. Cell viability, morphologic change, clonogenic Survival, Cell cycle distribution, reactive oxygen species (ROS) production, glutathione formation, and death receptors- and Bcl-2-mediated caspase pathways of HNSCC SCC25 Cells and A431 Cells with apigenin are investigated. Results Apigenin inhibits the growth of SCC25 and A431 Cells and induces Cell cycle arrest in the G 2 /M phase. Apigenin has an antioxidant capacity as well as the ability to inhibit lipid peroxidation. It protects BNLCL2 Cells against oxidative damage, and is potentially able to prevent cancer. Apigenin increases intraCellular ROS levels and reduces levels of glutathione; it also induces Cell apoptosis via tumor necrosis factor receptor (TNF-R)-, TNF-related apoptosis-inducing ligand receptor (TRAIL-R)-, and Bcl-2-mediated caspase-dependent Cell death pathways in SCC25 Cells. The combination of apigenin with 5-fluorouracil (5-Fu) or cisplatin induces the dramatic death of SCC25 Cells. Conclusions Apigenin induces SCC25 Cell apoptosis via the up-regulation of both TNF-R and TRAIL-R signaling pathways, and has a synergistic effect on the inhibition of Cell proliferation in combination with 5-Fu or cisplatin. General significance These analytical findings suggest that apigenin may be a good therapeutic agent against HNSCC Cells.
Mary-clare Cathcart - One of the best experts on this subject based on the ideXlab platform.
-
examination of thromboxane synthase as a prognostic factor and therapeutic target in non small Cell lung cancer
Molecular Cancer, 2011Co-Authors: Mary-clare Cathcart, Kathy Gately, Kenneth J Obyrne, Robert Cummins, Graham P. PidgeonAbstract:Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer Cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces Cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a Survival factor in the disease. TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall Survival. Cell proliferation/Survival and invasion was examined in NSCLC Cells following both selective TXS inhibition and stable TXS over-expression. TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB2 levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient Survival was observed. Selective TXS inhibition significantly reduced tumour Cell growth and increased apoptosis, while TXS over-expression stimulated Cell proliferation and invasiveness, and was protective against apoptosis. TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC.
-
examination of thromboxane synthase as a prognostic factor and therapeutic target in non small Cell lung cancer
Faculty of Health; Institute of Health and Biomedical Innovation, 2011Co-Authors: Mary-clare Cathcart, Kathy Gately, Kenneth J Obyrne, Robert Cummins, Graham P. PidgeonAbstract:Background: Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer Cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces Cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a Survival factor in the disease. Methods: TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB 2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall Survival. Cell proliferation/Survival and invasion was examined in NSCLC Cells following both selective TXS inhibition and stable TXS over-expression. Results: TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB 2levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient Survival was observed. Selective TXS inhibition significantly reduced tumour Cell growth and increased apoptosis, while TXS over-expression stimulated Cell proliferation and invasiveness, and was protective against apoptosis. Conclusion: TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC. © 2011 Cathcart et al; licensee BioMed Central Ltd.
Kristopher T. Kahle - One of the best experts on this subject based on the ideXlab platform.
-
regulated phosphorylation of the k cl cotransporter kcc3 is a molecular switch of intraCellular potassium content and Cell volume homeostasis
Frontiers in Cellular Neuroscience, 2015Co-Authors: Norma C Adragna, Kristopher T. Kahle, Dandan Sun, Nagendra Babu Ravilla, Peter K Lauf, Gulnaz Begum, Arjun KhannaAbstract:The defense of Cell volume against excessive shrinkage or swelling is a requirement for Cell function and organismal Survival. Cell swelling triggers a coordinated homeostatic response termed regulatory volume decrease (RVD), resulting in K+ and Cl– efflux via the activation of K+ channels, volume-regulated anion channels (VRACs), and the K+-Cl– cotransporters, including KCC3. Here, we show genetic alanine (Ala) substitution at threonines (Thr) 991 and 1048 in the KCC3a isoform carboxyl-terminus, preventing inhibitory phosphorylation at these sites, not only significantly up-regulates KCC3a activity up to 25-fold in normally inhibitory isotonic conditions, but is also accompanied by reversal of activity of the related bumetanide-sensitive Na+-K+-2Cl– cotransporter isoform 1 (NKCC1). This results in a rapid (90 %) reduction in intraCellular K+ content (Ki) via both Cl-dependent (KCC3a + NKCC1) and Cl-independent (DCPIB [VRAC inhibitor]-sensitive) pathways, which collectively renders Cells less prone to acute swelling in hypotonic osmotic stress. Together, these data demonstrate the phosphorylation state of Thr991/Thr1048 in the KCC3a encodes a potent switch of transporter activity, Ki homeostasis, and Cell volume regulation, and reveal novel observations into the functional interaction among ion transport molecules involved in RVD.
Wasif N Khan - One of the best experts on this subject based on the ideXlab platform.
-
regulation of b lymphocyte development and activation by bruton s tyrosine kinase
Immunologic Research, 2001Co-Authors: Wasif N KhanAbstract:The generation and maintenance of B lymphocytes is controlled by biochemical signals tramsitted by the B Cell antigen receptor (BCR) complex. These signals are transduced by multiple cytoplasmic protein tyrosine kinases (PTKs) including Lyn, Syk, and Bruton's tyrosine kinase (BTK). Upon BCR engagement, these PTKs activate downstream effectors, including transcription factors that modulate gene expression. In turn activation of down stream effectors is critical for B Cell Survival, Cell cycle progression, and antibody production. Our studies focus on the role of BTK in these biological responses. We have discovered that BTK is required for activation of the BCR-responsive transcription factor, NF-κB. Furthermore, BTK-dependent activation of NF-κB isessential for reprogramming the expression of genes that control B Cell Survival and proliferation. The biochemical mechanisms by which BTK regulates signaling components that activate NF-κB, and the identification of BTK-responsive genes are under investigation. Elucidation of these regulatory mechanisms is expected to reveal new therapeutic targets for B Cell pathologies involving defects in BTK, including X-linked agammaglobulinemia (XLA).
-
bruton s tyrosine kinase is required for activation of iκb kinase and nuclear factor κb in response to b Cell receptor engagement
Journal of Experimental Medicine, 2000Co-Authors: James B Petro, S Jamshedur M Rahman, Dean W Ballard, Wasif N KhanAbstract:Mutations in the gene encoding Bruton's tyrosine kinase (btk) cause the B Cell deficiency diseases X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. In vivo and in vitro studies indicate that the BTK protein is essential for B Cell Survival, Cell cycle progression, and proliferation in response to B Cell antigen receptor (BCR) stimulation. BCR stimulation leads to the activation of transcription factor nuclear factor (NF)-kappaB, which in turn regulates genes controlling B Cell growth. We now demonstrate that a null mutation in btk known to cause the xid phenotype prevents BCR-induced activation of NF-kappaB. This defect can be rescued by reconstitution with wild-type BTK. This mutation also interferes with BCR-directed activation of IkappaB kinase (IKK), which normally targets the NF-kappaB inhibitor IkappaBalpha for degradation. Taken together, these findings indicate that BTK couples IKK and NF-kappaB to the BCR. Interference with this coupling mechanism may contribute to the B Cell deficiencies observed in XLA and xid.