| Differential antitumor effect of interleukin-12 family cytokines on orthotopic hepatocellular carcinoma. | |
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MedLine Citation:
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PMID: 20440753 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most difficult cancers to treat. The interleukin (IL)-12 family cytokines, including IL-12, IL-23 and IL-27, display overlapping, but not redundant, roles in regulating lymphocyte subpopulations. IL-12 is known as a potent antitumor cytokine, whereas the results of the antitumor effect of IL-23 and IL-27 are inconsistent. The present study aimed to directly compare the relative antitumor efficacy of these three IL-12 family cytokines on HCC. METHODS: A murine orthotopic BNL HCC model, in which the tumor is located in an environment heavily populated with different lymphocyte subsets, was established. The hepatotropic adeno-associated virus serotype 8 (AAV8) vector was used to deliver the cytokine genes aiming to achieve sustained cytokine expression in the liver. RESULTS: AAV8/IL-12 treatment significantly reduced hepatic metastases and prolonged survival time, whereas treatment with AAV8/IL-23 or AAV8/IL-27 had only moderate antitumor effects at a high dose. The antitumor efficacy of these cytokines was positively correlated with their ability to regulate hepatic T cells, natural killer cells and natural killer T cells, with IL-12 greatly increasing the number and activation status of these cells, whereas IL-27 had no effect and IL-23 had a negative effect. AAV8/IL-12 treatment also resulted in a marked decrease in tumor vessel density, which was not observed with AAV8/IL-23 and AAV8/IL-27 treatment. CONCLUSIONS: The data obtained in the present study highlight the importance of local lymphocytes and anti-angiogenesis for influencing the antitumor activity of these three IL-12 family cytokines and suggest that IL-12 is the best candidate for treating HCC. |
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Authors:
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Chia-Hui Lo; Chia-Ming Chang; Shih-Wen Tang; Wen-Yu Pan; Cheng-Chieh Fang; Yin Chen; Ping-Yi Wu; Kai-Yun Chen; Hsin-I Ma; Xiao Xiao; Mi-Hua Tao |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The journal of gene medicine Volume: 12 ISSN: 1521-2254 ISO Abbreviation: J Gene Med Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-04 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9815764 Medline TA: J Gene Med Country: England |
Other Details:
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Languages: eng Pagination: 423-34 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 John Wiley & Sons, Ltd. |
Affiliation:
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Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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