Linked Life Data

18049332

Source:http://linkedlifedata.com/resource/pubmed/id/18049332

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2007-11-30
pubmed:abstractText
We evaluated the impact and mechanism of interleukin (IL)-18 alone or in combination with IL-12 or tumor necrosis factor-alpha when delivered intratumorally via polylactic acid microspheres (PLAMs). C57BL6 mice with established B16 melanomas underwent a single intratumoral injection of IL-12, tumor necrosis factor-alpha, or IL-18 PLAM, alone or in combination. Tumor draining lymph nodes and splenocytes were assessed for specific antitumor response by FACS analysis and IFN-gamma release assay and enzyme-linked immunosorbent spot. Mice with established pulmonary metastases were killed for enumeration of pulmonary metastatic nodules after treatment of the primary tumor. Intratumoral treatment with IL-12 in combination with IL-18 led to significant tumor suppression compared with either cytokine alone. FACS analysis revealed the combination of IL-12 and IL-18 resulted in an increase in the percentage of CD3+ cells within the tumor draining lymph node, attributable to increases in both CD4+ and CD8+ T cells. Both IFN-gamma release assay and enzyme-linked immunosorbent spot demonstrated a significant and substantial increase in tumor-specific response with the combination. Treatment of the primary tumor with IL-12 and IL-18 PLAM led to a significant decrease in pulmonary metastases and improvement in survival compared with either cytokine alone. The systemic effects were abrogated after depletion of CD8+ or natural killer cells, but not CD4+ cells. IL-12 and IL-18, when released intratumorally in a sustained fashion as can be accomplished through the use of PLAM, demonstrate both local effects on tumor growth and the generation of a tumor-specific response capable of eradicating distant disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1524-9557
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
808-16
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18049332-Animals, pubmed-meshheading:18049332-CD4-Positive T-Lymphocytes, pubmed-meshheading:18049332-CD8-Positive T-Lymphocytes, pubmed-meshheading:18049332-Cell Line, Tumor, pubmed-meshheading:18049332-Coculture Techniques, pubmed-meshheading:18049332-Drug Therapy, Combination, pubmed-meshheading:18049332-Female, pubmed-meshheading:18049332-Injections, Intralesional, pubmed-meshheading:18049332-Interferon-gamma, pubmed-meshheading:18049332-Interleukin-12, pubmed-meshheading:18049332-Interleukin-18, pubmed-meshheading:18049332-Killer Cells, Natural, pubmed-meshheading:18049332-Lactic Acid, pubmed-meshheading:18049332-Lung Neoplasms, pubmed-meshheading:18049332-Lymph Nodes, pubmed-meshheading:18049332-Melanoma, Experimental, pubmed-meshheading:18049332-Mice, pubmed-meshheading:18049332-Mice, Inbred C57BL, pubmed-meshheading:18049332-Nanocapsules, pubmed-meshheading:18049332-Polymers, pubmed-meshheading:18049332-Spleen, pubmed-meshheading:18049332-Survival Analysis, pubmed-meshheading:18049332-T-Lymphocytes, pubmed-meshheading:18049332-Treatment Outcome, pubmed-meshheading:18049332-Tumor Necrosis Factor-alpha
pubmed:articleTitle
Generation of a tumor-specific systemic response after intratumoral injection of IL-12 and IL-18-loaded polylactic acid microspheres.
pubmed:affiliation
Division of Surgical Oncology, University of Michigan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109-0932, USA. msabel@umich.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural