摘要:

The effect of the new hypoxic cell sensitizer, 1[2-hydroxy-1(hydroxymethyl)-ethoxy]methyl-2-nitroimidazole (RP-170), combined with heat against EMT6/KU cells, was determined under conditions of in vitro hypoxia. Heat-induced cytotoxicity for the EMT6/KU cells was increased to a greater extent under conditions of hypoxia and a normal pH of the medium. Hypoxia also reduced the surviving fraction of the cells treated either with RP-170 alone or with RP-170 plus heat. The concomitant treatment of RP-170 and heat inhibited the clonogenic activity of the EMT6/KU cells under conditions of in vitro hypoxia in all experimental groups, with a significant difference (p < 0.05). Therefore, RP-170 combined with exposure to heat may be an effective treatment for hypoxic cells in a solid tumor, as these cells are resistant to radiation and/or to many chemotherapeutic agents.

ISSN:0030-2414    

DOI:10.1159/000227428

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Recent studies have demonstrated that intraperitoneal instillation of dialysis solutions and drug additives may adversely affect the function of peritoneal cell populations. Therefore the aim of the present investigation was to examine the short-term effects of antineoplastic agents on human peritoneal mesothelial cells (HPMC). We have assessed the integrity of HPMC membrane and mechanisms of intracellular potassium transport. There was no evidence of significant cytotoxicity (as measured by 86Rb release) during a 60-min exposure of HPMC to either methotrexate (10-6-10-4M), doxorubicin (10-7-10-5M) or mitoxantrone (10-7-10-5 M). In HPMC exposed to doxorubicin (10-6M) the intracellular transport of potassium, as assessed with 86Rb as its analogue, was not affected. Methotrexate (10-5M) diminished Na, K-ATPase activity and simultaneously enhanced the 86Rb transport via furosemide-sensitive pathway. Mitoxantrone reduced the furosemide-sensitive 86Rb influx in a dose-dependent manner and at a concentration of 10-4M it also impaired the ouabain-dependent 86Rb influx. These data demonstrate that antineoplastic agents interfere with HPMC function which might contribute to the onco-static-induced peritoneal toxicity.

ISSN:0030-2414    

DOI:10.1159/000227429

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Using a rapid technique to assess drug-induced cell toxicity, a fibrosarcoma cell line was exposed in vitro to increasing concentrations of embelin, a benzo-quinone derivative of Embelia ribes Burm., and simultaneously inoculated with [3H]-thymidine. After regular time intervals, the cells were examined for incorporation of the labelled thymidine in DNA, lipid peroxide and glutathione levels. A dose-dependent decrease in labelled thymidine uptake, lipid peroxide and glutathione levels was observed on embelin administration.

ISSN:0030-2414    

DOI:10.1159/000227430

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The effect of recombinant human tumor necrosis factor alpha (TNF-α) on tumor growth and tumor cell proliferation of a human renal cell carcinoma transplanted into nude mice as well as on the body weight of the tumor-bearing animals has been studied. Due to differences of the effect of TNF-α after intravenous and intraperitoneal injection reported in the literature the influence of the two routes of application was presently studied. There was no effect on tumor growth with either route of application. Only the mode of growth showed a tendency to an increased rate of growth at the beginning of the treatment and a following increased growth deceleration. A slight change of the 3H-thymidine labeling index and the mitotic index was observed only after intraperitoneal injection of TNF-α indicative of a more cytostatic than cytotoxic effect of the drug. This is supported by the lack of an increase of necrotic cells. Although a rather high dose of TNF-α was applied, no effect on the body weight of the animals, i.e. no toxic effect of the treatment, has been fo

ISSN:0030-2414    

DOI:10.1159/000227431

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Human recombinant tumor necrosis factor (TNF) suspended in lipiodol (TNF/lipiodol emulsion) was injected via the hepatic artery, and its antitumor effects on VX2 tumor inoculated into the liver were evaluated. In TNF/lipio-dol-treated rabbits, soft-X-ray study revealed an accumulation of lipiodol in the liver tumor and the TNF concentration in the tumors was significantly higher than in rabbits treated with free TNF. 7 days after the various treatments, the tumor growth ratio evaluated macroscopically was found to be significantly lower in TNF/lipiodol emulsion-treated rabbits compared to rabbits treated with either free TNF or lipiodol (p < 0.05). Microscopically, the necrotic-area ratio of the tumors in the TNF/lipiodol emulsion-treated group was also significantly greater than in any other group (p < 0.01). Pathohistolog-ically, liver tumors treated with TNF/lipiodol emulsion revealed massive necrosis associated with occlusive thromboangitis in the tumor vessels and fibrous capsule formation around the tumor. In these rabbits, the elevation of serum transaminase after the treatment was transient and tissue damage in the surrounding noncancerous liver tissue was minimal. These findings therefore suggest that the intraarterial infusion of TNF/lipiodol emulsion may produce prominent antitumor effects, possibly due to the retention of TNF in the tumors, which causes damage to the endothelium of the tumor vessels.

ISSN:0030-2414    

DOI:10.1159/000227432

出版商:S. Karger AG    

年代:1995

数据来源: Karger

ISSN:0030-2414    

DOI:10.1159/000227433

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Sixteen patients with histologically confirmed inoperable hepatocellular carcinoma were treated with vindesine 3 mg/m2 i.v. weekly. Anemia, leukopenia and neuritis were documented but no severe or life-threatening toxicity was seen. There were no objective responses among the 14 evaluable patients. Eight had a no change status (median duration of 16 weeks, range 6-33), while the remaining 6 had progressive disease as their best evaluation. The median survival time was 20 weeks. Vindesine does not have a therapeutic effect in patients with advanced hepatocellular carcinoma.

ISSN:0030-2414    

DOI:10.1159/000227434

出版商:S. Karger AG    

年代:1995

数据来源: Karger

ISSN:0030-2414    

DOI:10.1159/000227435

出版商:S. Karger AG    

年代:1995

数据来源: Karger