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Lactate dehydrogenase A, an unexplored target for cancer treatment

Par : Contributeur(s) : Type de matériel : TexteTexteLangue : français Détails de publication : 2023. Sujet(s) : Ressources en ligne : Abrégé : Several recent studies have reported the association, for several types of cancers, between cancer aggressiveness and the expression of one of the enzymes responsible for the interconversion between pyruvate and lactate in the final stage of glycolysis—lactate dehydrogenase A (LDHA). LDHA favors the conversion of pyruvate to lactate, while lactate dehydrogenase B (LDHB) favors the opposite reaction. Several more or less specific LDHA inhibitors have been identified, but no clinical trial seems to have been undertaken to date. We carried out a preliminary study using The Cancer Genome Atlas (TCGA) database to analyze the association between the aggressiveness of the most lethal cancers and the level of expression of LDHA and LDHB genes (the criterion used to assess aggressiveness at the clinical level being overall survival of patients). A significant link between overall survival and a low level of expression of the LDHA gene was noted in pancreatic adenocarcinomas and glioblastomas, but not in bronchopulmonary carcinomas, adenocarcinomas or squamous cell carcinomas, nor in breast or colorectal cancers. Furthermore, high expression of the LDHB gene was associated with a favorable prognosis in patients with glioblastomas. Data in the literature, supported by our study, suggest that LDHA is a potential target for therapeutic development in oncology, at least for pancreatic cancer and glioblastoma, provided that the molecules chosen are sufficiently selective for LDHA.
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Several recent studies have reported the association, for several types of cancers, between cancer aggressiveness and the expression of one of the enzymes responsible for the interconversion between pyruvate and lactate in the final stage of glycolysis—lactate dehydrogenase A (LDHA). LDHA favors the conversion of pyruvate to lactate, while lactate dehydrogenase B (LDHB) favors the opposite reaction. Several more or less specific LDHA inhibitors have been identified, but no clinical trial seems to have been undertaken to date. We carried out a preliminary study using The Cancer Genome Atlas (TCGA) database to analyze the association between the aggressiveness of the most lethal cancers and the level of expression of LDHA and LDHB genes (the criterion used to assess aggressiveness at the clinical level being overall survival of patients). A significant link between overall survival and a low level of expression of the LDHA gene was noted in pancreatic adenocarcinomas and glioblastomas, but not in bronchopulmonary carcinomas, adenocarcinomas or squamous cell carcinomas, nor in breast or colorectal cancers. Furthermore, high expression of the LDHB gene was associated with a favorable prognosis in patients with glioblastomas. Data in the literature, supported by our study, suggest that LDHA is a potential target for therapeutic development in oncology, at least for pancreatic cancer and glioblastoma, provided that the molecules chosen are sufficiently selective for LDHA.

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