Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.2 (PDK1)
 2,238 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rhabdomyosarcoma (RMS) is the most common paediatric soft-tissue sarcoma including two major subtypes, alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS). Increasing evidence suggests that oncogenesis of RMS involves multiple stages of signalling protein dysregulation which may include prolonged activation of serine/threonine kinases such as phosphoinositide-dependent kinase-1 (PDK-1) and AKT. To date, whether PDK-1/AKT pathway is activated in RMS is unknown. This study was to examine phosphorylation status of AKT and to evaluate a novel small molecular inhibitor, OSU-03012 targeting PDK-1 in RMS. We examined phosphorylation levels of AKT using ARMS and ERMS tissue microarray and immunohistochemistry staining. Our results showed phospho-AKT(Thr308) level is elevated 42 and 35% in ARMS and ERMS, respectively. Phospho-AKT(Ser473) level is also increased 43% in ARMS and 55% in ERMS. Furthermore, we showed that OSU-03012 inhibits cell viability and induces apoptosis in ARMS and ERMS cell lines (RH30, SMS-CTR), which express elevated phospho-AKT levels. Normal cells are much less sensitive to OSU-03012 and in which no detectable apoptosis was observed. This study showed, for the first time, that PDK-1/AKT pathway is activated in RMS and may play an important role in survival of RMS. PDK-1/AKT pathway may be an attractive therapeutic target for cancer intervention in RMS using OSU-03012.
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PMID:PDK-1/AKT pathway as a novel therapeutic target in rhabdomyosarcoma cells using OSU-03012 compound. 1784 13

The novel ideas of fundamental role of mitochondria in the maintenance of viability of malignant cells have been reviewed. The modern state of research is considered in detail, including: mitochondrial control of the cellular redox state, sites of reactive oxygen species (ROS) production in inner mitochondrial membrane and antioxidant protection systems. Specificities of the structural-functional mitochondrial remodelling in malignant tumors, the mechanisms of the energy metabolism reprogramming, enhancement of the ROS production and adaptation to the hypoxic conditions and metabolic stress are analyzed. The available data including our research on transplanted tumors indicate that cytotoxic action of sodium dichloroacetate (the inhibitor of pyruvate dehydrogenase kinase) depends on biological properties of tumors and intensity of structural-functional mitochondrial rearrangement. Dichloroacetate turned out to be effective for sarcoma 37, but not for Lewis lung carcinoma.
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PMID:[REPROGRAMMING OF MITOCHONDRIAL ENERGY METABOLISM IN MALIGNANT NEOPLASMS]. 2702 57