摘要:

Suramin is a polysulfonated naphthylurea currently investigated for the treatment of advanced malignancy. We have previously reported that suramin was a potent inducer of the differentiation of the human colic adenocarcinoma cell clone HT29-D4 (Fantiniet al., J Biol Chem, 1989; 264: 10282–10286). In this report, we show that chronic suramin treatment of these cells is associated with a lysosomal storage disease. We have tested five suramin-related compounds for their ability to induce HT29-D4 differentiation and we looked at their action on the lysosomal apparatus. We conclude that one of the derivatives used is a more potent differentiation inducer than suramin, while it does not elicit any perturbation of the lysosomal system.

ISSN:0959-4973    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Low level cytotoxic stress greatly accelerates the loss of unstably amplified dihydrofolate reductase (dhfr) genes from methotrexate-resistant mouse cell lines. To understand this drug-induced loss of amplified genes, the highly methotrexate-resistant mouse R500 cell line was flow sorted into two subpopulations with higher and lower averagedhfrgene dosage respectively. The subpopula-tion with higher levels of gene amplification was much more sensitive to low level cytotoxic stress as judged by both cloning efficiency and growth in the presence of low concentrations of cytotoxic drugs. These results suggest that high levels of gene amplification can confer hypersensitivity to cytotoxic Stressors such as anticancer drugs.

ISSN:0959-4973    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Doxorubicin (DXR) and ME2303, a new fluorine-containing (C'-2) anthracycline derivative, were studied for their tissue distributions—particularly in the plasma, liver and bone marrow—following administration at the maximum tolerated doses to normal mice and mice bearing hepatic metastases of Lewis lung carcinoma. ME2303 was rapidly metabolized and disappeared rapidly from the plasma, liver and bone marrow. Its metabolites—the product of esterolysis (M1) and its reduced derivative at the C-14 position (M2)—remained for a long period except in bone marrow. On the other hand DXR remained in the analyzed tissues for a long period; an especially large amount of DXR was found in the bone marrow even at 24 h after administration of the drug while, in the case of ME2303, by this time even its metabolites had disappeared. The concentrations of M1 and DXR in the liver at 2 h were about 50− and 300-fold higher than their plasma concentrations. The tissue distributions in the normal mice and hepatic-metastases-bearing mice showed no significant differences. Regarding the antitumor effects of ME2303, M1, M2 and DXR in the hepatic-metastases-bearing mice, ME2303 was the most effective compound, and M1 was also active; DXR showed only a marginal effect, and M2 showed no effect.

ISSN:0959-4973    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We have recently found that membranes ofSpiroplasmaspp. strain MQ-1 (hereafter referred to as MQ-1) induce both tumor necrosis factorα (TNFα) secretion by bone marrow macrophages and blast transformation of lymphocytes via a mechanism different from that operated by bacterial lipopolysaccharide (LPS). This report presents evidence indicating that the MQ-1-derived membrane component(s) which activates bone marrow macrophages to secrete TNFα is, at least in part, protein. This conclusion is supported by our findings that TNFα secretion was reduced following exposure of MQ-1 membranes to elevated temperatures, extreme acidic pH treatment and incubation with protease K or pronase. Furthermore, following lipid extraction of MQ-1 membranes, most of both induction of TNFα secretion and blast transformation activities appeared in the ‘protein’ fraction. When membranes were chromatographed on a phenyl-Sephar-ose column, two major peaks were obtained, one containing most of the TNFα induction activity and the other the mitogenic activity. Neither peak coeluted with the peak of bulk membrane lipids. The possibility that the spiroplasma membrane component inducing TNFα secretion is acylated protein is discussed.

ISSN:0959-4973    

出版商:OVID    

年代:1990

数据来源: OVID

ISSN:0959-4973    

出版商:OVID    

年代:1990

数据来源: OVID

ISSN:0959-4973    

出版商:OVID    

年代:1990

数据来源: OVID