LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 3 of total 3

Search options

  1. Article ; Online: Important Metabolites in Maintaining Folate Cycle, Homocysteine, and Polyamine Metabolism Associated with Ranibizumab Treatment in Cultured Human Tenon's Fibroblasts.

    Munirah Md Noh, Siti / Hamimah Sheikh Abdul Kadir, Siti / Vasudevan, Sushil

    Biomolecules

    2019  Volume 9, Issue 6

    Abstract: The anti-fibrotic properties of ranibizumab have been well documented. As an antagonist to vascular endothelial growth factor (VEGF), ranibizumab works by binding and neutralizing all active VEGF-A, thus limiting progressive cell growth and proliferation. ...

    Abstract The anti-fibrotic properties of ranibizumab have been well documented. As an antagonist to vascular endothelial growth factor (VEGF), ranibizumab works by binding and neutralizing all active VEGF-A, thus limiting progressive cell growth and proliferation. Ranibizumab application in ocular diseases has shown remarkable desired effects; however, to date, its antifibrotic mechanism is not well understood. In this study, we identified metabolic changes in ranibizumab-treated human Tenon's fibroblasts (HTFs). Cultured HTFs were treated for 48 h with 0.5 mg/mL of ranibizumab and 0.5 mg/mL control IgG antibody which serves as a negative control. Samples from each group were injected into Agilent 6520 Q-TOF liquid chromatography/mass spectrometer (LC/MS) system to establish the metabolite expression in both ranibizumab treated cells and control group. Data obtained was analyzed using Agilent Mass Hunter Qualitative Analysis software to identify the most regulated metabolite following ranibizumab treatment. At
    MeSH term(s) Adolescent ; Adult ; Aged ; Cells, Cultured ; Female ; Fibroblasts/cytology ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Folic Acid/metabolism ; Homocysteine/metabolism ; Humans ; Male ; Metabolomics ; Middle Aged ; Polyamines/metabolism ; Ranibizumab/pharmacology ; Tendons/cytology ; Young Adult
    Chemical Substances Polyamines ; Homocysteine (0LVT1QZ0BA) ; Folic Acid (935E97BOY8) ; Ranibizumab (ZL1R02VT79)
    Language English
    Publishing date 2019-06-22
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom9060243
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Effects of ranibizumab on TGF-β1 and TGF-β2 production by human Tenon's fibroblasts: An in vitro study.

    Noh, Siti Munirah Md / Abdul Kadir, Siti H Sheikh / Crowston, Jonathan G / Subrayan, Visvaraja / Vasudevan, Sushil

    Molecular vision

    2015  Volume 21, Page(s) 1191–1200

    Abstract: Purpose: Inhibiting exaggerated wound healing responses, which are primarily mediated by human Tenon's fibroblast (HTF) migration and proliferation, has become the major determining factor for a successful trabeculectomy. Antivascular endothelial growth ...

    Abstract Purpose: Inhibiting exaggerated wound healing responses, which are primarily mediated by human Tenon's fibroblast (HTF) migration and proliferation, has become the major determining factor for a successful trabeculectomy. Antivascular endothelial growth factor (anti-VEGF) has showed promising results as a potential antifibrotic candidate for use concurrently in trabeculectomy. Preliminary cohort studies have revealed improved bleb morphology following trabeculectomy augmented with ranibizumab. However, the effects on HTFs remain unclear. This study was conducted to understand the effects of ranibizumab on transforming growth factor (TGF)-β1 and transforming growth factor (TGF)-β2 expression by HTFs.
    Methods: The effect of ranibizumab on HTF proliferation and cell viability was determined using 3-(4,5-dimethylthiazone-2-yl)-2,5-diphenyl tetrazolium (MTT) assay. Ranibizumab at concentrations ranging from 0.01 to 0.5 mg/ml were administered for 24, 48, and 72 h in serum and serum-free conditions. Supernatants and cell lysates from samples were assessed for TGF-β1 and TGF-β2 mRNA and protein levels using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA).
    Results: At 48 h, 0.5 mg/ml of ranibizumab significantly induced cell death under serum-free culture conditions (p<0.05). Ranibizumab caused a significant reduction in TGF-β1 mRNA, but not for TGF-β2. However, the total protein production of TGF-β1 and TGF-β2 was unaffected by this anti-VEGF treatment.
    Conclusions: Exposure of HTFs to an intravitreal dose of ranibizumab significantly suppresses cell viability in vitro; however, the application seemed unable to affect the ultimate production of TGF-β. Therefore, we highlighted ranibizumab as a potential antiscarring agent that acts via a different mechanism when used synergistically with another antifibrotic agent. Understanding the mechanism of actions of ranibizumab offers an additional view of a possible new rational therapeutic strategy.
    MeSH term(s) Angiogenesis Inhibitors/pharmacology ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cicatrix/etiology ; Cicatrix/pathology ; Cicatrix/prevention & control ; Fibroblasts/cytology ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Gene Expression Regulation ; Humans ; Primary Cell Culture ; RNA, Messenger/antagonists & inhibitors ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Ranibizumab/pharmacology ; Signal Transduction ; Tenon Capsule/cytology ; Tenon Capsule/drug effects ; Tenon Capsule/metabolism ; Trabeculectomy/adverse effects ; Transforming Growth Factor beta1/antagonists & inhibitors ; Transforming Growth Factor beta1/biosynthesis ; Transforming Growth Factor beta1/genetics ; Transforming Growth Factor beta2/biosynthesis ; Transforming Growth Factor beta2/genetics ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances Angiogenesis Inhibitors ; RNA, Messenger ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta2 ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Ranibizumab (ZL1R02VT79)
    Language English
    Publishing date 2015
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2017540-1
    ISSN 1090-0535 ; 1090-0535
    ISSN (online) 1090-0535
    ISSN 1090-0535
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: Effects of ranibizumab on the extracellular matrix production by human Tenon's fibroblast.

    Md Noh, Siti Munirah / Sheikh Abdul Kadir, Siti H / Bannur, Zakaria M / Froemming, Gabriele Anisah / Abdul Hamid Hasani, Narimah / Mohd Nawawi, Hapizah / Crowston, Jonathan G / Vasudevan, Sushil

    Experimental eye research

    2014  Volume 127, Page(s) 236–242

    Abstract: Anti-Vascular Endothelial Growth Factors (Anti-VEGF) agents have received recent interest as potential anti-fibrotic agents for their concurrent use with trabeculectomy. Preliminary cohort studies have revealed improved bleb morphology following ... ...

    Abstract Anti-Vascular Endothelial Growth Factors (Anti-VEGF) agents have received recent interest as potential anti-fibrotic agents for their concurrent use with trabeculectomy. Preliminary cohort studies have revealed improved bleb morphology following trabeculectomy augmented with ranibizumab. The effects of this humanized monoclonal antibody on human Tenon's fibroblast (HTF), the key player of post trabeculectomy scar formation, are not fully understood. This study was conducted to understand the effects of ranibizumab on extracellular matrix production by HTF. The effect of ranibizumab on HTF proliferation and cell viability was determined using MTT assay (3-(4,5-dimethylthiazone-2-yl)-2,5-diphenyl tetrazolium). Ranibizumab at concentrations ranging from 0.01 to 0.5 mg/mL were administered for 24, 48 and 72 h in serum and serum free conditions. Supernatants and cell lysates from samples were assessed for collagen type 1 alpha 1 and fibronectin mRNA and protein level using quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). After 48-h, ranibizumab at 0.5 mg/mL, significantly induced cell death under serum-free culture conditions (p < 0.05). Ranibizumab caused significant reduction of collagen type 1 alpha 1 (COL1A1) mRNA, but not for fibronectin (FN). Meanwhile, COL1A1 and FN protein levels were found upregulated in treated monolayers compared to control monolayers. Ranibizumab at 0.5 mg/mL significantly reduced cell viability in cultured HTF. From this study, we found that single application of ranibizumab is inadequate to induce the anti-fibrotic effects on HTF, suggesting the importance of adjunctive therapy. Further studies are underway to understand mechanism of actions of ranibizumab on HTF.
    MeSH term(s) Angiogenesis Inhibitors/pharmacology ; Antibodies, Monoclonal, Humanized/pharmacology ; Cell Culture Techniques ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Collagen Type I/genetics ; Collagen Type I/metabolism ; Enzyme-Linked Immunosorbent Assay ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Fibronectins/genetics ; Fibronectins/metabolism ; Fluorescent Antibody Technique, Indirect ; Gene Expression Regulation/physiology ; Glaucoma, Open-Angle/surgery ; Humans ; RNA, Messenger/genetics ; Ranibizumab ; Real-Time Polymerase Chain Reaction ; Tenon Capsule/cytology ; Trabeculectomy ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Vimentin/metabolism
    Chemical Substances Angiogenesis Inhibitors ; Antibodies, Monoclonal, Humanized ; Collagen Type I ; Fibronectins ; RNA, Messenger ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Vimentin ; collagen type I, alpha 1 chain ; Ranibizumab (ZL1R02VT79)
    Language English
    Publishing date 2014-08-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80122-7
    ISSN 1096-0007 ; 0014-4835
    ISSN (online) 1096-0007
    ISSN 0014-4835
    DOI 10.1016/j.exer.2014.08.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top