摘要:

Cisplatin-based chemotherapy considerably Improved the outcome of patients with metastatic germ cell tumors. Apart from Raynaud's phenomenon, a frequent side effect, vascular toxicity associated with chemotherapy for testicular cancer, has not been described precisely. Although major vascular complications such as myocardial infarction, stroke and pulmonary embolism seem to occur Infrequently, they raise concern with regard to the safety of chemotherapy. Also, potential late vascular toxicity has to be taken into account. Whereas a cause and effect relationship is probable for some vascular events following chemotherapy, some cases may represent coincidence or may be disease related. Presently, the very low incidence of major vascular events should not enter Into therapeutic decisions.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The anticancer drugs cisplatin and carboplatin have been shown to activate murine peritoneal macrophages In vivo and In vitro. These activated macrophages have enhanced tumoricidal activity mediated by extension and contact formation with the tumor cells leading to an Increase and transfer of lysosomes with eventual lysis of the tumor cells. Cisplatin (10 μg/ml) or carboplatin (50 μg/ml) for 2 and 24 h treatment of macrophages In vitro, In addition, show a significant increase In the release of various cytolytic factors, like hydrogen peroxide, superoxide anion, lnterieukin-1α, lysozyme and β-N-hexoseaminidase, that are also responsible for the destruction of tumor cells.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The novel anthracycllne N-benzyladriamycln-14-valerate (AD 198) circumvents P-glycoprotein (P-gp)- and altered topolsomerase ll-medlated drug resistance. Nevertheless, AD 198-reslstant (AD 198R) murlne J774.2 cells overexpressed P-gp, were cross-resistant to other drugs through reduced accumulation and were rendered sensitive by continuous exposure to verapamll. Intracellular AD 198 was, however, similar In sensitive and resistant cells. Consequently, the ability of P-gp to confer AD 198 resistance was examined. It was observed that (I) AD 198 resistance in AD 198Rcells grown without drug for 15 months declined by 60% with only a 10-15% loss of vlnblastlne cross-resistance and P-gp expression; (il) a cloned AD 198RP388 mouse leukemlc cell line did not express P-gp; and (ill) verapamll did not attenuate resistance against high-dose, short-term exposure to AD 198. Therefore, AD 198 resistance appeared to be P-gp- Independent despite P-gp overexpression. Antloxldant enzyme and topolsomerase II activities remained unchanged between sensitive and resistant cells. These results suggest that AD 198 resistance was conferred by a novel mechanism.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The In vitro antitumor activity of navelbine (NVB, KW- 2307), a newly synthesized vlnca alkaloid, was compared with that of adrlamycln (ADM) against human breast carcinomas Inoculated into nude mice at the maximum tolerated dose (MTO) and clinically equivalent dose (CED). The plasma levels of NVB after Intravenous Injection Into nude mice at doses of 1.2 and 4.8 mg/kg diminished rapidly during the early phase (0-1 h), followed by a very long shallow one. NVB was still detected 96 h after administration at a dose of 4.8 mg/kg. The pharmacokinetlc parameters of NVB In plasma Indicated that NVB extensively distributes to tissues. The CED of NVB was provisionally decided to be 4.8 mg/kg based on the comparison of AUC values at 24-oo h between human patients and nude mice. When compared by a single Injection of MTD (NVB, 16 mg/kg; ADM 12 mg/kg), NVB was effective against all four tumor lines, MC-2, MC-8, MMKY and H-31, while ADM was effective only against H- 31. On the other hand, the body weight loss by NVB was mild as compared with that by ADM, Indicating that the antitumor activity of NVB is superior to that of ADM at their MTDs. A single Injection of NVB at its CED (4.8 mg/ kg) produced a poor antitumor effect and no or little toxlclty In terms of body weight loss, as compared with those at MTD. However, when NVB was administered Intermittently at CED, It exhibited significant antitumor activity against three tumor lines. The body weight loss was still mild even on this Intermittent schedule. These results Indicate that NVB can offer antitumor activity against human breast carcinoma xenografts at its CED.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Multiparous SHN mice with spontaneous mammary tumors (5-10 mm In size) were given water extract of Guan-mu-tong (Gmt;Caulls arlstotochlae manshurlensis) (0.5%) ad libitum as drinking water for 10 days. This treatment retarded significantly the growth of mammary tumors compared with the controls. By contrast, normal mammary gland growth, histology of adrenals and ovaries, and body weight were affected little by the Gmt treatment. Gmt appears to be the first agent Inhibiting the growth of spontaneous mouse mammary tumors of palpable size by per os treatment.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Topoisomerase I (topo I) gene expression and cell sensitivity to camptothecin were investigated In seven human cancer cell lines not selected fn vitro for drug resistance. The cell lines were of different tumor origin, and included two ovarian carcinomas (A2780 and IGROV-1), a cervix squamous cell carcinoma (A431), an osteosarcoma (U2-OS), a gllobiastoma (GBM) and two different clones of a malignant melanoma (665/2/60 and 665/2/21). Topo I gene expression was evaluated by Northern blotting analysis and cell sensitivity to camptothecin was determined using the colony-forming assay after a 1 h exposure to the drug. A wide range of drug sensitivity levels was found among the examined cell lines. Cell doubling times end distribution In cell cycle phases were not correlated with camptothecin cytotoxlcity. In particular, the percent of untreated cells In S phase was not predictive of the drug sensitivity. No correlation was found between level of topo I gene expression and cell response to camptothecin. These results Indicate that the level of topo I expression Is not the only critical determinant of cell sensitivity to camptothecin In unselscted human cancer cell lines. Therefore, topo I gene expression may not be a useful predictive parameter of tumor response.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

As the results of adjuvant chemotherapy In the treatment of advanced rectal cancer are unsatisfactory, more effective regimens and routes of administration are being tried. Submucosal anal Injection of methotrexate (MXT) has given encouraging results In the treatment of pelvic malignancies. This communication studies the MXT level In serum and rectal cancer tissue after either anal submucosal or parenteral MXT administration. Twenty four patients, mean age 46.4 years (16 men and eight women), with stage C rectal cancer were divided into two equal, age- and sex-matched groups. MXT (50 mg) was administered to each patient intravenously in one group and Into the anal submucosa in the other. A blood sample was taken 30, 60 and 120 mln after Injection, and again after 24 h. A tumor sample was also taken each 30 and 60 mln of injection. The serum and tissue MXT levels were determined using a radlolmmunoassay kit. The serum MXT concentration was significantly higher after parenteral than after anal Injection. Meanwhile, the concentration of MXT In tumor tissue was higher after anal administration. In conclusion, the anal route of administration of MXT, by inducing a high MXT concentration in the tumor tissue associated with a low serum level, might achieve satisfactory therapeutic results In advanced rectal cancer, with minimal side effects.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Three monoclonal antibodies (mAb), MRK16, MM4.17 and MCS7, directed against distinct epltopes on the external domain of human P-glycoproteln (Pgp), were used to follow Its expression on multldrug resistant (MDR)- cells. The linear MM4.17 epitope and conformatlonal MRK16 epitope showed a 4-fold higher expression at 37°C than at 4°C, while the detection of the conformatlonal MCS7 epitope did not change. Inhibition of Pgp function, by a short pretreatment of the MDR-cells with resistance-modulating agents (RMA), such as SDZ PSC 833 and SDZ 280-446, could not be related to depletion of Pgp from the cell surface, since their expression of the MM4.17 and MRK16 epltopes was found unchanged. However, a substantially higher expression of MC57 epitopes was found on RMA-treated cells than on untreated ones. Since this effect correlated to the strength of different RMA In reversing the MDR phenotype, MC57 epltopes might be more efficiently expressed on Inactivated) forms of the Pgp molecules, suggesting that RMA might Inhibit Pgp function by disturbing the conformation of individual Pgp molecules, their topographical distribution or polymerization status In the membrane.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

In spite of the Improvement on chemotherapy results In treating testicular cancer and the Introduction of adjuvant chemotherapy to node negative (as well as node positive) breast cancer patients, there Is still present a wide spectrum of early and late toxic manifestations. The combination of cisplatin, vinblastine and bleomycin given to testicular cancer might result In cariovascular, neurological, gastrointestinal and renal problems. Late effects of cyclophosphamide, methotrexate and 5-fluorouracll given to breast cancer patients might cause obesity, amenorrhea and Infertility. We report a persistent asymptomatic indirect hyperbilirubinemia which was observed in two cancer patients (breast; testls) 3 and 14 months following the cessation of chemotherapy. Metastatic liver disease and Involvement of other sites, as well as other causes of hyperbilirubinemia, were excluded. The exact cause of the Indirect hyperbilirubinemia remained obscure.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID