Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor cells harboring stem-like/cancer stem cell (CSC) properties have been identified and isolated from numerous hematological and solid malignancies. These stem-like tumor cells can persist following conventional cytoreductive therapies, such as chemotherapy and radiotherapy, thereby repopulating the tumor and seeding relapse and/or metastasis. We have previously shown that natural killer (NK) cells preferentially target stem-like tumor cells via non- major histocompatibility complex (MHC) restricted mechanisms. Here, we demonstrated that the proteasome inhibitor, bortezomib, augments NK cell targeting of stem cell-like tumor cells against multiple solid human tumor-derived cancer lines and primary tissue samples. Mechanistically, this was mediated by the upregulation of cell surface NK ligands MHC class I chain-related protein A and B (MICA and MICB) on aldehyde dehydrogenases (ALDH)-positive CSCs. The increased expression of MICA and MICB on CSC targets thereby enhanced NK cell mediated killing in vitro and ex vivo from both human primary tumor and patient-derived xenograft samples. In vivo, the combination of bortezomib and allogeneic NK cell adoptive transfer in immunodeficient mice led to increased elimination of CSCs as well as tumor growth delay of orthotopic glioblastoma tumors. Taken together, our data support the combination bortezomib and NK transfer as a strategy for both CSC targeting and potentially improved outcomes in clinical cancer patients.
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PMID:Bortezomib Augments Natural Killer Cell Targeting of Stem-Like Tumor Cells. 3064 20

The study was carried out to evaluate characteristics of redox-status in erythrocytes of peripheral blood of patients with ovarian cancer, uterine body cancer and cervix cancer using evaluation of products of peroxide oxidation of lipids: diene conjugates, ketodienes, Schiff's bases by Volchegorskii, malonic di-aldehyde by L.I. Andreieva, content of products of oxidizing modification of proteins by E.E. Dubinina; activity of anti-oxidant enzymes: superoxiddismutase by Nishikimi, catalase, glutathione-S'-transferase, glutathionereductase and level of reduced glutathione by A.I. Karpischenko. The evaluation of architectonics of erythrocytes and rigidity of membrane was implemented using a scanning probing microscope SolverPro (NT-MDT, Zelenograd, Russia). The statistical processing of obtained data was implemented using non-parametric Mann-Whitney U-test. The increasing of products of initial stages of peroxide oxidation of lipids - diene conjugates and malonic di-aldehyde and decreasing of level of interim (ketodienes) and tertiary ( Schiff's bases) products of peroxide oxidation of lipids have been established. Against this background a multi-directional alteration of superoxiddismutase and decreasing of catalase occurred. Simultaneously, increasing of activity of glutathione-transferase and level of reduced glutathione under all analyzed localizations of neoplasm were noted. The level of products of oxidizing modification of proteins depended on localization of primary tumor and it was minimal in case of cervix cancer. Also such an alteration of cyto-architectonics of erythrocytes was established as development of reversible deformed echinocytes in patients in case of ovarian cancer and irreversible deformed spherocytes in patients with cervix cancer and uterine body cancer and also abrupt increasing of rigidity of membrane of erythrocytes. The obtained data permits to surmise as a capacity of para-neoplastic processes development of oxidative and carbonyl stress in erythrocytes of peripheral blood of patients with ovarian cancer, cervix cancer and uterine body cancer at extensive stage of disease. The mentioned stress is accompanied by formation of echinocytes and spherocytes and significant increasing of rigidity of membrane. However, intensity of these processes is determined by localization of primary neoplasm and it can be applied for characteristic of biological portrait of tumor in case of consideration of schemes of anti-oxidant therapy.
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PMID:[The characteristics of redox-status of peripheral part of erythron under various localizations of neoplasm of organs of female reproductive sphere.] 3080 92