International journal of molecular medicine
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Gene therapy and virotherapy are among the approaches currently used to treat malignant tumors. Gene therapy and virotherapy use a specific therapeutic gene that causes death in cancer cells. In early attempts at gene therapy, therapeutic genes were driven by ubiquitous promoters such as the CMV promoter, which induce non-specific toxicity to normal cells and tissues in addition to the cancer cells. ⋯ In this review, we describe cancer and/or tissue-specific gene therapy systems for the treatment of cancer. In particular, we will discuss three systems for gene therapy and virotherapy: i) tissue-specific promoter systems, ii) cancer-specific promoter systems, and iii) oncolytic virotherapy. We will also discuss the major challenges of cancer-targeting vector systems and future directions in this area.
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Hepatocellular dysfunction occurs early in sepsis and this appears to be caused by Kupffer cell-derived TNF-alpha production from the liver as a result of the increased release of the sympathetic neurotransmitter, norepinephrine, from the gut. Ghrelin, a novel stomach-derived peptide, is down-regulated in sepsis and administration of ghrelin into rodents decrease pro-inflammatory cytokines, attenuates hepatic and other organ injuries and improves survival. Ghrelin's beneficial effect in sepsis is mediated by the inhibition of the sympathetic nervous system (SNS), as evidenced by the reduced gut-derived norepineprine (NE) release in sepsis after ghrelin treatment. ⋯ To further confirm the effect of NE on MKP-1, normal rats were infused with NE for 2 h through the portal vein and MKP-1 mRNA from the liver was examined. Infusion with NE produced a significant 73.7% decrease in MKP-1 mRNA. Therefore, ghrelin's inhibitory effect on gut-derived NE release in sepsis leading to the downregulation of pro-inflammatory cytokines is mediated by MKP-1.