当前位置： SCI文献检索 > JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY期刊下所有文献 > Influence of recombinant tumour necrosis factor alpha on blood flow and antibody localisation in human tumour xenografts in nude mice.

Influence of recombinant tumour necrosis factor alpha on blood flow and antibody localisation in human tumour xenografts in nude mice.

Abstract：

:Mice with s.c. grafts of gastric carcinoma MKN45 or osteosarcoma 788T were injected i.v. with recombinant tumour necrosis factor alpha (rTNF alpha) and tumour blood flow rates were determined 4 h later as a fraction of the cardiac output g tissue-1. With MKN45, the tumour blood flow rate was significantly reduced from a mean of 1.86% cardiac output g-1 to 0.84% and 0.65% with 50 and 200 micrograms kg-1 rTNF alpha respectively. With 788T, the tumour blood flow rate was reduced at 50 micrograms kg-1 rTNF alpha from 1.13% cardiac output g-1 to 0.56%. There were essentially no changes in blood flow rates in other organs. The effect of rTNF alpha on localisation of monoclonal antibodies into these xenografts were examined. When a single dose of rTNF alpha (50 micrograms kg-1) was given at the same time as labelled NCRC-2 antibody there was a significant reduction in localisation into 788T osteosarcoma xenografts. In other tests, mice were injected daily for 3 days with 50 micrograms kg-1 rTNF alpha. They were injected i.v. with monoclonal antibody 4 h after the first injection and dissected on the 4th day. With 788T there was a small but not statistically significant reduction in the absolute amount of NCRC-2 antibody localising in tumour, although this reduction was greater when results were expressed as tumour-to-blood ratios. With MKN45 xenografts, treatment with rTNF alpha had little effect on tumour localisation of an anti-(carcinoembryonic antigen) monoclonal antibody (NCRC-24). These studies show that TNF can be administered so as to reduce tumour blood flow and with little effect on tumour localisation of antibody, suggesting that combination therapy with TNF and antibodies or their immunoconjugates is feasible. Other studies have suggested that TNF can increase antibody localisation into tumours, but this was not seen here, and in some cases administration could reduce tumour localisation. It appears that this method of enhancing antibody localisation may be critically dependent on scheduling, and therefore it may not be extensively applicable.

journal_name

J Cancer Res Clin Oncol

journal_title

Journal of cancer research and clinical oncology

authors

Pimm MV,Gribben SJ,Morris TM

doi

10.1007/BF01613286

subject

Has Abstract

pub_date

1991-01-01 00:00:00

pages

543-8

issue

eissn

0171-5216

issn

1432-1335

journal_volume

117

pub_type

杂志文章

在线工具

Influence of recombinant tumour necrosis factor alpha on blood flow and antibody localisation in human tumour xenografts in nude mice.