Source:http://linkedlifedata.com/resource/pubmed/id/15102664
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2004-4-22
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| pubmed:abstractText |
The objective of this Phase II study was to evaluate the pharmacodynamic and immune effects of intratumorally administered recombinant human interleukin-12 (IL-12) on regional lymph nodes, primary tumor, and peripheral blood. Ten previously untreated patients with head and neck squamous cell carcinoma were injected in the primary tumor two to three times, once/week, at two dose levels of 100 or 300 ng/kg, before surgery. We compared these patients with 20 control (non-IL-12-treated) patients. Toxicity was high, with unexpected dose-limiting toxicities at the 300 ng/kg dose level. Dose-dependent plasma IFN-gamma and IL-10 increments were detected. These cytokine levels were higher after the first injection than after the subsequent injections. A rapid, transient reduction in lymphocytes, monocytes, and all lymphocyte subsets, especially natural killer cells, was observed, due to a redistribution to the lymph nodes. In the enlarged lymph nodes of the IL-12-treated patients, a higher percentage of natural killer cells and a lower percentage of T-helper cells were found compared with control patients. The same pattern was detected in the infiltrate in the primary tumor. Real-time semiquantitative PCR analysis of peripheral blood mononuclear cells in the peripheral blood showed a transient decrease of T-bet mRNA. Interestingly, the peripheral blood mononuclear cells in the lymph nodes showed a 128-fold (mean) increase of IFN-gamma mRNA. A switch from the Th2 to a Th1 profile in the lymph nodes compared with the peripheral blood occurred in the IL-12-treated patients. In conclusion, in previously untreated head and neck squamous cell carcinoma patients, recombinant human IL-12 intratumorally showed dose-limiting toxicities at the dose level of 300 ng/kg and resulted in measurable immunological responses locoregionally at both dose levels.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
|
| pubmed:issn |
1078-0432
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
10
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2626-35
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:15102664-Adult,
pubmed-meshheading:15102664-Aged,
pubmed-meshheading:15102664-Area Under Curve,
pubmed-meshheading:15102664-Carcinoma, Squamous Cell,
pubmed-meshheading:15102664-Case-Control Studies,
pubmed-meshheading:15102664-Cytokines,
pubmed-meshheading:15102664-Female,
pubmed-meshheading:15102664-Head and Neck Neoplasms,
pubmed-meshheading:15102664-Humans,
pubmed-meshheading:15102664-Interferon-gamma,
pubmed-meshheading:15102664-Interleukin-10,
pubmed-meshheading:15102664-Interleukin-12,
pubmed-meshheading:15102664-Kinetics,
pubmed-meshheading:15102664-Leukocytes, Mononuclear,
pubmed-meshheading:15102664-Lymph Nodes,
pubmed-meshheading:15102664-Lymphocyte Subsets,
pubmed-meshheading:15102664-Male,
pubmed-meshheading:15102664-Middle Aged,
pubmed-meshheading:15102664-Polymerase Chain Reaction,
pubmed-meshheading:15102664-RNA, Messenger,
pubmed-meshheading:15102664-Recombinant Proteins,
pubmed-meshheading:15102664-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15102664-Th1 Cells,
pubmed-meshheading:15102664-Time Factors,
pubmed-meshheading:15102664-Treatment Outcome
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| pubmed:year |
2004
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| pubmed:articleTitle |
Intratumoral administration of recombinant human interleukin 12 in head and neck squamous cell carcinoma patients elicits a T-helper 1 profile in the locoregional lymph nodes.
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| pubmed:affiliation |
Department of Medical Oncology, UMC Nijmegen, Nijmegen, The Netherlands. C.vanherpen@onco.umcn.nl
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| pubmed:publicationType |
Journal Article,
Clinical Trial,
Research Support, Non-U.S. Gov't,
Clinical Trial, Phase II
|