Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1658953 (tumor vasculature)
 2,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokine and antiangiogenic gene therapies have proved effective in implanted hepatocellular carcinoma (HCC) models in which small tumor burdens were established in small rodents. These models, however, may not reflect human HCCs, which are frequently detected at a stage when tumors are large and multifocal. In addition, HCC in patients is often associated with viral hepatitis. To investigate the effectiveness of a mixture type of gene therapy strategy on large tumor burdens, we used the woodchuck model in which woodchuck hepatitis virus-induced HCCs are large and multifocal, simulating the conditions in humans. Adenoviruses encoding antiangiogenic factors (pigment epithelium-derived factor and endostatin) or cytokines (GM-CSF and IL-12) were delivered via the hepatic artery separately or in combination into woodchuck livers bearing HCCs. Our results showed that the mixture type of strategy, which contained two cytokines and two antiangiogenic factors, had better antitumor effects on large tumors as compared with monotherapy either with antiangiogenic or cytokine genes. The immunotherapy recruited significant levels of CD3(+) T cells that infiltrated the tumors, whereas the antiangiogenesis-based therapy significantly reduced tumor vasculature. The mixture type of gene therapy achieved both effects. In addition, it induced high levels of natural killer cells and apoptotic cells and reduced the levels of immunosuppressive effectors in the tumor regions. Hence, antiangiogenic therapy may provide the advantage of reducing immune tolerance in large tumors, making them more vulnerable to the immune reactions. Our study implies that in the future, the combination therapy may prove effective for the treatment of patients with advanced HCC.
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PMID:Combining antiangiogenic therapy with immunotherapy exerts better therapeutical effects on large tumors in a woodchuck hepatoma model. 2067 98

This study aimed to explore the potential therapeutic effects of the combination of pigment epithelium-derived factor (PEDF) and radiation on lung cancer. The Lewis lung cancer (LLC) allografts in nude mice were treated with radiation, PEDF and PEDF combined with radiation. The morphologic changes of tumor vasculature and the hypoxic fraction of tumor tissues were evaluated. Significant inhibition of tumor growth was observed when radiation was applied between the 3rd and 7th day (the vasculature normalization window) after the initiation of PEDF treatment. During the vasculature normalization window, the tumor blood vessels in PEDF-treated mice were less tortuous and more uniform than those in the LLC allograft tumor treated with phosphate-buffered saline. Meanwhile, the thickness of the basement membrane was remarkably reduced and pericyte coverage was significantly increased with the PEDF treatment. We also found that tumor hypoxic fraction decreased during the 3rd to the 7th day after PEDF treatment, suggesting improved intratumoral oxygenation. Taken together, our results show that PEDF improved the effects of radiation therapy on LLC allografts by inducing a vascular normalization window from the 3rd to the 7th day after PEDF treatment. Our findings provide a basis for treating lung cancer with the combination of PEDF and radiation.
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PMID:Pigment epithelium-derived factor enhances tumor response to radiation through vasculature normalization in allografted lung cancer in mice. 2559 9