Linked Life Data

9973211

Source:http://linkedlifedata.com/resource/pubmed/id/9973211

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-2-25
pubmed:abstractText
The selective induction of tumor vascular collapse represents an exciting approach to cancer treatment. However, clinical evaluation of tumor necrosis factor-alpha (TNF), an agent that accomplishes this goal, has been limited by systemic toxicity, and clinical approaches using bacterial components to induce TNF production have also been disappointing. Our laboratory has developed synthetic low molecular weight inducers of TNF, including 5,6-dimethylxanthenone-4-acetic acid (DMXAA), as an alternative strategy. DMXAA induces rapid vascular collapse in transplantable murine tumors and induces TNF synthesis in vitro in both murine and human systems. We show here that the extent of DMXAA-induced TNF synthesis is greater in tumors than that in the spleen, liver, or serum. As shown by in situ hybridization studies of the murine Colon 38 tumor, DMXAA induced tumor as well as host cells to express TNF mRNA. The distribution of cells containing TNF mRNA in tumor tissues after DMXAA administration contrasted significantly with that obtained after lipopolysaccharide (LPS) treatment, although splenic and hepatic tissues showed a similar distribution of TNF mRNA-positive cells. In the Colon 38 tumor, the action of LPS was limited to host cells in the periphery of the vessels. DMXAA treatment induced 7-fold higher peak TNF levels in tumor than in serum. In contrast, LPS treatment induced 9-fold higher TNF levels in serum than in tumor. DMXAA induced 35-fold higher TNF activity in the Colon 38 tissue than did LPS. One ovarian, one squamous, and three melanoma human tumor xenografts implanted in athymic nude mice expressed TNF mRNA of human and murine origin in response to DMXAA, confirming that DMXAA can activate both host and tumor cells. The use of low molecular weight agents to induce TNF synthesis in situ in the tumor represents a novel approach to TNF-mediated therapy of cancers.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
633-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9973211-Animals, pubmed-meshheading:9973211-Antineoplastic Agents, pubmed-meshheading:9973211-Carcinoma, Squamous Cell, pubmed-meshheading:9973211-Female, pubmed-meshheading:9973211-Humans, pubmed-meshheading:9973211-Lipopolysaccharides, pubmed-meshheading:9973211-Liver, pubmed-meshheading:9973211-Melanoma, pubmed-meshheading:9973211-Mice, pubmed-meshheading:9973211-Mice, Inbred C57BL, pubmed-meshheading:9973211-Mice, Inbred DBA, pubmed-meshheading:9973211-Mice, Nude, pubmed-meshheading:9973211-Neoplasm Transplantation, pubmed-meshheading:9973211-Ovarian Neoplasms, pubmed-meshheading:9973211-RNA, Messenger, pubmed-meshheading:9973211-Spleen, pubmed-meshheading:9973211-Stimulation, Chemical, pubmed-meshheading:9973211-Transplantation, Heterologous, pubmed-meshheading:9973211-Tumor Necrosis Factor-alpha, pubmed-meshheading:9973211-Xanthenes, pubmed-meshheading:9973211-Xanthones
pubmed:year
1999
pubmed:articleTitle
Stimulation of tumors to synthesize tumor necrosis factor-alpha in situ using 5,6-dimethylxanthenone-4-acetic acid: a novel approach to cancer therapy.
pubmed:affiliation
Auckland Cancer Society Research Centre, University of Auckland School of Medicine, New Zealand.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't