摘要:

Administration of vitamin A (retinol palmitate) causes a reduction of transplacentally induced leukemias. Subsequent to a transplacental application of ENU, addition of vitamin A as a suspension to drinking water leads to a reduction of leukemia incidence to 50% as well as to a corresponding decrease of this disease as a cause of death. Yet there is no influence of vitamin A on the adenomas of the lung arising in this experimental design.

ISSN:0030-2414    

DOI:10.1159/000225786

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Isogenic male BALB/c mice bearing Meth-A tumors in the ascites form were used. The effects of Lonidamine and irradiation both alone and in combination were studied. Lonidamine administered intra-peritoneally produced a significant enhancement of irradiation effects.

ISSN:0030-2414    

DOI:10.1159/000225883

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Lonidamine (LNA) has been investigated both alone and in combination with different chemotherapeutic agents in various types of tumors at an advanced stage. Acute and long-term treatments were studied. LNA has been shown to be devoid of the most typical side effects of currently used chemotherapeutic agents. It has revealed a characteristic profile of side effects, comprising myalgia, photosensitivity and altered hearing. LNA alone, tested in a limited number of patients, produced a partial remission in one ovary adenocarcinoma and a stabilization in two breast carcinomas and one microcytoma. When used in’ combination with chemotherapeutic agents, it potentiated them, particularly in brain metastases and lung adenocarcinoma

ISSN:0030-2414    

DOI:10.1159/000225884

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The Effect of gramicidin S (GS), a polypeptide antibiotic, on the growth of murine tumor cells such as allotransplantable sarcoma 180 (SI80) and Ehrlich ascites carcinoma (EAC) and Meth A fibrosarcoma (Meth A) was studied. GS inhibited the proliferation of EAC cells in culture and its effect on cell viability was dependent on the concentration of GS. On exposure to GS at concentrations ranging from 1 to 100 µg/ml for 10 min, EAC cells lost their transplantability in ddY mice depending on the concentration of GS. In particular, the transplantability of EAC cells was completely missing on exposure to GS at a concentration of 100 µg/ml. In the in vivo experiments, a daily intraperitoneal injection of GS exhibited a high inhibitory effect not only on the growth of subcutaneously implanted SI80 in ICR mice but on the growth of subcutaneously implanted syngeneic Meth A in BALB/c mice. In the studies using radioactively labeled DNA, RNA and protein precursors, GS at high concentrations inhibited the incorporation of all the precursors into EAC cell

ISSN:0030-2414    

DOI:10.1159/000225789

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The pharmacokinetics of lonidamine has been studied in cancer patients after single and chronic oral administrations. After single administration the plasma kinetics are highly variable, while the dose eliminated in the urine is over 70% in all subjects. This suggests an active but interindividually variable first-pass effect. After repeated administrations, both the residual plasma concentration before administration () and that obtained after drug intake () have been studied. The values range from 4.5 to 25 µg/ml and values from 0.4 to 7 µg/ml. In patients where a therapeutic response was noted, a mean value of 2.98 Hg/ml for C^?n was measured. In patients unresponsive to drug therapy the mean was 1.5 µg/

ISSN:0030-2414    

DOI:10.1159/000225885

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Established clones of initially normal hamster lung fibroblasts (DON) were examined over the course of long-term serial culture for the acquisition of growth properties usually ascribed to the transformed phenotype. With time, one clone (12A) expressed a full range of transformation-associated characteristics including proliferation in low serum medium, growth to high saturation density, multinucleate cell formation in response to cytochalasin B, karyotypic instability, anchorage independence, and tumorigenicity in nude mice. Gel electrophoretic analysis of selected passage levels of nontumorigenic and tumorigenic DON 12A cells revealed changes in peptide composition which were related, not to the acquisition of tumorigenicity, but to adaptation to long-term culture. These results indicate that any study utilizing long-term cell cultures should consider that alterations in gene expression which appear over the course of serial culture may be unrelated to specific phenotypic changes associated with transformation.

ISSN:0030-2414    

DOI:10.1159/000225790

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Lonidamine was given for 3 weeks at the dose of 150 mg three times daily to 6 male cancer patients. Serum follicle-stimulating and luteinizing hormone levels were significantly higher as compared to pretreatment values after 1 and 3 weeks of Lonidamine administration, while testosterone, prolactin, and thyroid-stimulating hormone levels remained unchanged.

ISSN:0030-2414    

DOI:10.1159/000225886

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

We have studied the cellular pharmacology of doxorubicin in a line of mouse sarcoma cells isolated from a dimethylbenzanthracene-induced autochthonous tumor. We have studied the cytotoxicity of the drugs as a function of the exposure dose and of the exposure time to the drug. Cytotoxicity was evaluated as the inhibition of the incorporation of [3H-methyl]-thymidine in the cellular nucleic acids. Intracellular drug concentrations were measured by spectrofluorometry. We have shown that the intracellular drug concentration was a linear function of the extracellular drug concentration up to 5 μg/ml; the cytotoxicity was an exponential function of the exposure dose up to 1 μg/ml, but it was not an exponential function of the exposure time: the cytotoxicity may therefore be very different for similar total drug exposures. Incubation with a low dose for a long time did not provide a cytotoxicity as high as that obtained with a high dose for a short period of time. These results emphasize the role of the peak concentration of doxorubicin for its maximal action in the target cel

ISSN:0030-2414    

DOI:10.1159/000225791

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

15 patients with metastatic cancer were treated with Lonidamine, a substituted indazole carboxylic acid active against the Lewis lung and Sarcoma 180 tumors. Single doses of 600 mg (350–400 mg/m2) mostly induced somnolence and gastro-intestinal side effects. Toxicity occurring during chronic administration of Lonidamine at doses ranging between 45 and 275 mg/m2 twice daily, mainly consisted of somnolence, myalgias, hyperesthesia and mild hair loss. Myalgias and hyperesthesias were markedly relieved with prednisone 5 mg twice daily. No laboratory abnormalities were seen. In 1 patient with breast cancer resistant to standard chemotherapeutic agents, a 30% reduction of measurable tumor masses was seen. In view of the lack of overlapping toxicity between Lonidamine and other chemotherapeutic drugs, and of its potential activity, it is suggested that phase II studies of Lonidamine be initiated at a dose of 135 mg/m2 twice dail

ISSN:0030-2414    

DOI:10.1159/000225887

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Lonidamine was studied in 31 patients with different types of advanced cancer. With one exception, patients were pretreated. Lonidamine was given at 6 dosage levels from 180 to 520 mg/m2 for at least 28 days. No toxicity on hematopoietic function was observed. Side effects consisted mostly in musculoskeletal discomfort, testicular pain in males and a reversible ototoxicity. In 2 patients conjunctivitis and photophobia occurred. Plasma Lonidamine levels were measured in 14 patients. Peak concentrations were observed from 1 to 2 h after administration and ranged from 3 to 35 μg/ml. Objective antitumoral effects were observed in only 2 patients with mycosis fungoides; a 3rd patient with mycosis fungoides was considered to have stable disease

ISSN:0030-2414    

DOI:10.1159/000225888

出版商:S. Karger AG    

年代:1984

数据来源: Karger