Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemic heart disease remains the leading cause of death worldwide. Ischemic pre-, post-, and remote conditionings trigger endogenous cardioprotection that renders the heart resistant to ischemic-reperfusion injury (IRI). Mimicking endogenous cardioprotection by modulating genes involved in cardioprotective signal transduction provides an opportunity to reproduce endogenous cardioprotection with better possibilities of translation into the clinical setting. Genes and signaling pathways by which conditioning maneuvers exert their effects on the heart are partially understood. This is due to the targeted approach that allowed identifying one or a few genes associated with IRI and cardioprotection. Genes critical for signaling pathways in cardioprotection include protectomiRs (e.g., microRNA 125b*), ZAC1 transcription factor, pro-inflammatory genes such as cycloxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), antioxidant enzymes such as hemoxygenase (HO)-1, extracellular and manganese superoxidase dismutases (ec-SOD and Mg-SOD), heat shock proteins (HSPs), growth factors such as insulin like growth factor (IGF)-1 and hepatocyte growth factor (HGF), antiapoptotic proteins such as Bcl-2 and Bcl-xL, pro-apoptotic proteins such as FasL, Bcl-2, Bax, caspase-3 and p53, and proangiogenic genes such as TGFbeta, sphingosine kinase 1 (SPK1), and PI3K-Akt. By identifying the gene expression profiles of IRI and ischemic conditioning, one may reveal potential gene targets responsible for cardioprotection. In this manuscript, we review the current state of the art of gene therapy in cardioprotection and propose that gene expression analysis facilitates the identification of individual genes associated with cardioprotection. We discuss signaling pathways associated with cardioprotection that can be targeted by gene therapy to achieve cardioprotection.
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PMID:Cardioprotection by gene therapy: A review paper on behalf of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology. 2597 96

Introduction: Myelodysplastic syndromes (MDS) comprise a heterogeneous group of myeloid neoplasms with diverse clinical courses. The revised version of the international prognostic scoring system (IPSS-R) provides risk stratification into 5 different groups. Areas covered: For lower-risk patients, red blood cell transfusions and iron chelation are the backbone of supportive care. In addition, erythropoiesis-stimulating agents (ESA) are used to ameliorate anemia. Lenalidomide is approved for the treatment of lower-risk patients with del(5q) who are transfusion-dependent. Patients with higher-risk disease should be offered allogeneic stem cell transplantation whenever possible. If they are unfit for transplantation or an appropriate donor cannot be found, hypomethylating agents may be used. Expert opinion: New therapeutic options for lower-risk patients include thrombopoietin analogues, the TGF-beta family ligand trapping drug Luspatercept, and the telomerase inhibitor Imetelstat. Combinations of hypomethylating agents (HMA) with other compounds, and inhibitors of bcl2, such as venetoclax are being developed for higher-risk patients. Finally, hypomethylating agents in combination with donor lymphocytes may lead to long-term remission following molecular or hematological relapse after allogeneic SCT.
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PMID:Novel therapies in low- and high-risk myelodysplastic syndrome. 3135 75


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