Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1658953 (tumor vasculature)
 2,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Entrance of activated T cells into the tumor after adoptive transfer is a prerequisite for the efficacy of this form of immunotherapy. Because lymphocyte binding to vascular endothelium is the critical step in which lymphocyte extravasation into the tissue is controlled, we compared adhesion of tumor-infiltrating lymphocytes (TIL) to endothelial cells in tumors, peripheral lymph nodes, mucosa-associated lymphatic tissues, and inflamed synovium. Simultaneously, expression of the known homing-associated Ags both on TIL and tumor vasculature was analyzed. All TIL strongly expressed alpha 4-integrins, LFA-1 and CD44, whereas only a low level of L-selectin expression was detected. Tumor vasculature showed signs of activation in each patient on the basis of elevated levels of intercellular adhesion molecule-1, E-selectin, vascular cell adhesion molecule-1, and/or peripheral lymph node addressin (PNAd). TIL showed significantly enhanced binding to tumor vasculature in comparison with other endothelial specificities. Increased binding was not markedly due to up-regulation of the inflammation-induced endothelial cell adhesion molecules in tumors, because binding to inflamed synovium that expressed the same adhesion molecules was not enhanced. In summary, TIL show preferential binding to tumor vasculature and the binding is partially mediated by currently unknown mechanisms. In vitro analysis of endothelial cell binding properties may help to identify those TIL populations that will have the best potential to home back to tumor tissue after adoptive transfer.
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PMID:Tumor endothelium selectively supports binding of IL-2-propagated tumor-infiltrating lymphocytes. 775 43

The effects of intralesional injection of newly synthesized natural-type human tumor necrosis factor (nh-TNF) on experimental brain tumors in rats were investigated. The repeated injection of 5,000 U of nh-TNF into the tumor resulted in the prolongation of the survival time of the rats. More than half of the nh-TNF treated tumors were red, and were characterized by histopathological features of marked congestion of tumor vessels. Fibrin formations were also found in the tumor vessels. These histological findings were not observed in the control tumors. Furthermore, coagulative necrosis was observed in the center of some reddish tumors. Leukocytes adhering to vascular endothelium and infiltration of the leukocytes were also observed in the tumors of nh-TNF treated rats. In the immunohistochemical examination, these infiltrated cells were primarily polymorphonuclear leukocytes and macrophages. Expression of intercellular adhesion molecule-1 (ICAM-1) increased on the tumor endothelial cells after the administration of nh-TNF. These results suggest that repeated injection of nh-TNF has a therapeutic effect on brain tumors through its extensive influences on tumor vasculature.
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PMID:Antitumor activity of natural-type human tumor necrosis factor on experimental brain tumors in rats. 889 88