lipid-a has been researched along with Carcinoma* in 2 studies
2 other study(ies) available for lipid-a and Carcinoma
| Article | Year |
|---|---|
Evidence for control of nitric oxide synthesis by intracellular transforming growth factor-beta1 in tumor cells. Implications for tumor development.
Transforming growth factor-beta1 (TGF-beta1) has been shown to down-regulate NO synthesis in a variety of normal cells. In the present study, we investigated the influence of TGF-beta1 upon NO production in tumor cells and its consequences for tumor development. During the growth of PROb colon carcinoma cells intraperitoneally injected in syngeneic BDIX rats, intratumoral concentration of TGF-beta1 increases while NO concentration stays very low. Tumor regression induced by intraperitoneal injections of a lipid A is associated with a decrease in TGF-beta1 and an increase in NO intratumoral concentration. In these tumors, PROb tumor cells are the NO- and TGF-beta1-secreting cells. Using PROb cells transfected with an expression vector coding for TGF-beta1 antisense mRNA, we demonstrate in vitro that there is an inverse correlation between the amount of TGF-beta1 secreted and the ability of PROb cells to secrete NO. As the same results were obtained in the presence of an anti-TGF-beta type II receptor neutralizing antibody, and as exogenous TGF-beta1 is without any effect on NO secretion by PROb cells, TGF-beta1 apparently down-regulates NO synthesis in PROb cells by an intracellular mechanism. These results suggest that endogenous TGF-beta1 constitutes a potential target in a search for new antitumoral agents. Topics: Activin Receptors, Type I; Animals; Carcinoma; Colonic Neoplasms; Down-Regulation; Female; Immunotherapy; Intracellular Fluid; Lipid A; Male; Neoplasm Transplantation; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Protein Serine-Threonine Kinases; Rats; Rats, Inbred Strains; Receptor, Transforming Growth Factor-beta Type I; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta; RNA, Antisense; Second Messenger Systems; Transfection; Transforming Growth Factor beta; Tumor Cells, Cultured | 1999 |
Activation of tumor-infiltrating macrophages by a synthetic lipid A analog (ONO-4007) and its implication in antitumor effects.
ONO-4007 is a novel synthetic analog of lipid A subunit and has been shown to exert antitumor activities on various experimental tumors with less toxicity than lipopolysaccharide. It remains unclear, however, what biological activities of this compound are relevant to its antitumor effects. We therefore investigated the activation of macrophages by ONO-4007 in vitro and in vivo and its implication in antitumor effects, using mouse MM46 mammary tumor as an experimental model. Intravenous injection of ONO-4007 produced significant therapeutic effects on this solid tumor. ONO-4007 could stimulate glycogen-elicited peritoneal macrophages in vitro, not only to produce tumor necrosis factor (TNF), but also to exert cytocidal activities against MM46 cells in vitro. Substantial TNF production was induced in tumor tissue by i. v. injection of ONO-4007, and its successive administration to tumor-bearing mice gave tumor-infiltrating macrophages a prominent in vitro tumoricidal activity and primed them for in vitro TNF secretion. These results suggest that activation of tumor-infiltrating macrophages to a direct tumoricidal state as well as to TNF secretion in tumor tissues may be at least some of the antitumor effects of this novel lipid A analog. Topics: Animals; Antineoplastic Agents; Carcinoma; Dose-Response Relationship, Drug; Injections, Intravenous; Lipid A; Macrophage Activation; Macrophages, Peritoneal; Male; Mammary Neoplasms, Experimental; Mice; Mice, Inbred C3H; Neoplasm Transplantation; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha | 1994 |