Abstract:
:We previously demonstrated a characteristically high sensitivity of pancreatic cancer cells to interferon alpha (IFN-alpha) gene transfer, which induced a more prominent growth suppression and cell death in pancreatic cancer cells than in other types of cancers and normal cells. The IFN-alpha protein can exhibit both direct cytotoxicity and indirect immunological antitumour activity. Here, we dissected and examined the two mechanisms, taking advantage of the fact that IFN-alpha did not show any cross-species activity in its in vivo effect. When a human IFN-alpha adenovirus was injected into subcutaneous xenografts of human pancreatic cancer cells in nude mice, tumour growth was significantly suppressed due to cell death in an adenoviral dose-dependent manner. The IFN-alpha protein concentration was markedly increased in the injected subcutaneous tumour, but leakage of the potent cytokine into the systemic blood circulation was minimal. When a mouse IFN-alpha adenovirus was injected into the same subcutaneous tumour system, all mice showed significant tumour inhibition, an effect that was dependent on the indirect antitumour activities of IFN-alpha, notably a stimulation of natural killer cells. Moreover, in this case, tumour regression was observed not only for the injected subcutaneous tumours but also for the untreated tumours at distant sites. This study suggested that a local IFN-alpha gene therapy is a promising therapeutic strategy for pancreatic cancer, due to its dual mechanisms of antitumour activities and lack of significant toxicity.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Ohashi M,Yoshida K,Kushida M,Miura Y,Ohnami S,Ikarashi Y,Kitade Y,Yoshida T,Aoki Kdoi
10.1038/sj.bjc.6602713subject
Has Abstractpub_date
2005-08-22 00:00:00pages
441-9issue
4eissn
0007-0920issn
1532-1827pii
6602713journal_volume
93pub_type
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journal_title:British journal of cancer
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doi:10.1054/bjoc.2001.1704
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doi:10.1038/bjc.1993.250
更新日期:1993-06-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章,meta分析
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pub_type: 杂志文章,随机对照试验
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pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:British journal of cancer
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