ISSN:0959-4973    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The mitomycins are antitumor antibiotics that are under investigation now for more than 30 years. Mitomycin C (MMC) is the best investigated subtype. It serves as a prototype for drugs with bioreductive alkylation, which is a unique feature of this class. MMC is mainly active under anaerobic circumstances. The pharmacokinetics are linear in a two-compartment model. The main toxicities of MMC are thrombocytopenia and leucocytopenia. Rare but severe side effects are a hemolytic uremic syndrome, pneumonitis and cardiac failure. MMC has a wide clinical antitumor spectrum with efficacy in various tumor types such as gastric cancer, pancreatic cancer, breast cancer, non-small cell lung cancer, cervical cancer, prostate cancer and bladder cancer. Still, the above mentioned side effects prevent a more widespread use. The most important features of the drug will be reviewed.

ISSN:0959-4973    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Numerous reports on colon carcinogenesis reveal gender differences in the incidence and location of tumors. A large number of the presented studies suggest that sex-steroids have a considerable effect on tumorigenesis of the large bowel. To clarify the, so far, not fully understood mechanisms and somewhat conflicting information about the possible hormone action, it is important to discuss two points: first, the reliability of the currently used experimental animal models; and second, what is known concerning the role of sex steroids in colon carcinogenesis.

ISSN:0959-4973    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The effect of cisplatin (CDDP) in combination with etoposide (VP16) was examined on four human cell lines (one colon adenocarcinoma, LoVo; one ovarian carcinoma, IGROV-1; two small cell lung cancers, NCI-H146 and NCI-N592; and two murine leukemias, P388 and L1210). Simultaneous exposure to CDDP and subtoxic concentrations of VP16 for 1 h produced a cell killing in all cell lines comparable to that achieved by CDDP alone. Sequential exposure of NCI-H146 and NCI-N592 to CDDP for 1 h followed by VP16 for 96 h again produced an additive effect. When two of these cell lines were treated inin vivomodels (i.p. P388 leukemia, s.c. NCI-N592) with sub-optimal doses of the two drugs, a potentiation of the antitumor effects of the two drugs in simultaneous combination was evidenced by the increase in survival time and in the number of ‘cures' in P388 leukemia bearing mice and by the inhibition of tumor size in NCI-N592. This comparative study, using the same cell linesin vitroandin vivo, indicates that the CDDP-VP16 potentiation observedin vivodoes not reflect a specific interaction at the cellular-biochemical level. The results support the therapeutic interest of this combination (presumably as a result from favorable pharmacological interactions) even despite the lack of potentiation at cellular level, under comparable conditions of treatment.

ISSN:0959-4973    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

During a phase III open study of depot leuprolide for stage D2 cancer of the prostate, we studied the effect of depot leuprolide on chronic leuprolide users. To determine whether there was a transient elevation of testosterone or luteinizing hormone (LH) 4–24 h and 3–5 days following the monthly injections, we monitored the changes of testosterone and LH before injection and 24 h post-injection in 10 patients who have been under depot leuprolide Rx for 24–36 weeks, and in 35 patients before injection and 3–5 days post-injection who have received depot leuprolide for 8–24 weeks prior to monitoring. Comparison of the data between pre-injection within 24 h and 3–5 days post-injection showed no significant changes of testosterone and LH values between these levels for either testosterone (P = 0.31) or LH (P = 0.45). We therefore conclude that there was no 'acute on chronic' effect of depot formulation in chronic users of depot leuprolide.

ISSN:0959-4973    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Two cases of severe delayed neurologic toxicity related to the administration of intrathecal (IT) combination chemotherapy including thiotepa (TSPA) are presented. Both cases developed axonal neuropathy with motor predominance in the lower extremities 1 and 6 months after IT chemotherapy was administered. Neurologic tox-icities have been described with IT-methotrexate, IT-cytosine arabinoside and IT-TSPA. To our knowledge, however, axonal neuropathy following administration of these three agents has not been previously described. In spite of the fact that TSPA is a useful IT agent, its combination with MTX, ara-C and radiotherapy could cause severe neurotoxicity. This unexpected complication indicates the need for further toxicology research on IT-TSPA.

ISSN:0959-4973    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The interaction of 5-fluorouracil (S-FU) and cisplatin (CDDP) was studied in Bp8 ascites sarcoma cells growing in mice. By density gradient centrifugation in PercollTMsolution, non-viable cells were separated from viable cells. Single drug treatment with doses of 12 and 36 mg/kg body weight of 5-FU and 0.4 and 0.8 mg/kg body weight of CDOP did not yield non-viable cells during the time period studied (96 h). Combination of the drugs increased the non-viable cells to about 10–25% depending on the doses given. This indicates a supra-additive cytotoxic effect. Analysis of the distribution of viable cells in the different cell cycle phases by flow cytometry showed an accumulation of cells in the S-phase after 5-FU and in the S- and G2-phases of the CDDP or combined 5-FU-CDDP treatment. Similar analysis of non-viable cells showed a similar cell cycle distribution, which suggests that supra-additive cytotoxicity is not cell cycle specific. By labeling the DNA of the tumor cells with [1257]-deoxyuridine and using whole body measurement, the cell loss was studied. No changes in cell loss after single drug and combined treatment were found during the observation time. The molecular basis for the interaction between 5-FU and CDDP should be elucidated.

ISSN:0959-4973    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

It has been demonstrated that the flavonoid quercetin (3,3',4',5–7-pentahydroxyflavone) (Q) inhibits the growth of several cancer cell lines and that the antiproliferative activity of this substance is mediated by a so-called type II estrogen binding site (type II EBS). We investigated the effects of quercetin and cisplatin (CDDP) alone and in combination on the proliferation of the ovarian cancer cell line OVCA 433. Both drugs exhibited a dose-related growth inhibition in a range of concentrations between 0.01 and 2.5 μM and 0.01 and 2.5 μg/ml for Q and CDDP respectively. The combination of the two drugs resulted in a synergistic antiproliferative activity. Two other flavonoids tested, i.e., rutin (3-rhamnosylglucoside of quercetin) and hesperidin [7-b rutinoside of hesperetin (3'-5–3-hydroxy-4-methoxyflavone)] were ineffective both alone and in combination with CDDP. Since both rutin and hesperidin do not bind to type II EBS it can be hypothesized that Q synergizes with CDDP by acting through an interaction with these binding sites.

ISSN:0959-4973    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

To elucidate the potential mechanisms of anemia induced by cisplatin (CDDP) we have evaluated hemolysis, dyserythropoiesis, ferrokinetics and cytotoxicity on erythroid progenitors in 12 patients treated by a CDDP-containing combination chemotherapy and in 6 patients treated by a similar combination but without CDDP. Eight patients, from the CDDP treated group, experienced a pronounced anemia. None had signs of hemolysis. Ferrokinetic study showed a very deep and protracted decrease ofS9Fe incorporation during the chemotherapy cycle and the following 2 weeks. These results, along with a normal medullary erythroblastic cellularity, suggest that CDDP induces a deep but transient erythropoiesis alteration leading to anemia in some cases.

ISSN:0959-4973    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

A recombinant plasmid carrying the long terminal repeat (LTR) of the human immunodeficiency virus 1 (HIV-1) linked to the reporter chloramphenicol acetyl transferase (CAT) gene was stably introduced into human fibroblasts. The transfectant cells expressed CAT activity from the HIV LTR. The response to anti-neoplastic drugs, i.e. cisplatin, a platin derivative, and hexadecylphosphocho-line, was studied. It was found that at 5 x 10-6M concentrations cisplatin stimulates by 2.2-fold the expression of CAT from the HIV LTR. Our results extend our observations on the effect of cisplatin on HIV LTR in rodent fibroblast cells and suggest caution against therapy including cisplatin in the treatment of AIDS patients.

ISSN:0959-4973    

出版商:OVID    

年代:1990

数据来源: OVID