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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-9-21
pubmed:abstractText
Most cases of pancreatic cancer are inoperable when diagnosed. Since immunotherapy and antiangiogenic therapy have been reported to be promising for pancreatic cancer, we examined whether the combination of immunotherapy with dendritic cells (DCs) and the antiangiogenic drug TNP-470 induces tumor regression. Syngeneic mouse pancreatic adenocarcinoma cells were orthotopically inoculated into C57/BL6 mice. DCs with or without tumor lysate (TL) were administered i.p. at 4 and 5 weeks. TNP-470 was injected s.c. into tumor-bearing mice every other day from 4 weeks to 6 weeks. We compared anticancer effects in 6 groups: NT (no treatment), DC/TL- (DCs without TL), DC/TL+ (DCs pulsed with TL), TNP (TNP-470 alone), DC/TL-TNP (DC/TL- plus TNP-470) and DC/TL+TNP (DC/TL+ plus TNP-470). We measured tumor volume, mean vascular density (MVD) and vessel diameter by FITC-dextran using an intravital microscope; degrees of proliferation and apoptosis of cancer cells by PCNA and TUNEL; infiltrating lymphocytes and expression levels of VEGF and MMP-9 by immunohistochemistry and immunoblotting. Tumor volume and MVD were significantly suppressed in the treatment groups with prolonged survival rate, especially in the DC/TL+TNP group. There were no significant differences in apoptosis among the 6 groups except DC/TL+. The number of infiltrating CD4+ cells in the DC/TL+ group was higher than that in the NT group. VEGF expression was significantly suppressed in the treatment groups containing TNP-470, and MMP-9 was also suppressed in the groups containing DC/TL+. Our data suggested that TL-pulsed DCs combined with TNP-470 induced regression of mouse pancreatic cancer, possibly through induction of immune responses and suppression of angiogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
(c) 2005 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
499-505
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Combination therapy with tumor-lysate pulsed dendritic cells and antiangiogenic drug TNP-470 for mouse pancreatic cancer.
pubmed:affiliation
Second Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't