摘要:

In spite of progress made in surgical techniques and intensive care, only a slight improvement in the therapeutic control of gastric carcinoma has been achieved in the last 20 years. In this paper we present a review of controlled clinical trials on adjuvant chemotherapy and chemo-immunotherapy for gastric cancer and this topic is discussed in the light of our experience and that of the Gastrointestinal Group of the European Organization for Research and Treatment of Cancer. The results of adjuvant therapy are less satisfactory in Western countries than in Japan. The efficacy of the 5-fluorouracil + adriamycin + mitomycin C regimen in advanced gastric cancer has not been confirmed in an adjuvant setting. The therapeutic benefit reported in Japanese studies may be due to a chemotherapy started intraoperatively or during the immediate postoperative period and should also be considered in the light of a standardized surgical treatment. The new therapeutic trends, using recent chemotherapeutic associations tested in Phase I and II clinical trials or combining traditional chemotherapy with different types of immunostimulators, are discussed. Only when large-scale clinical studies have been made will it be possible to confirm their therapeutic efficacy.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

5-Fluorouracil (5-FU) remains the most effective chemotherapeutic agent in the management of patients with metastatic colorectal cancer. Leucovorin enhances its efficacy, but also its toxicity. Cited data suggest modulation of 5-FU toxicity by high dose allopurinol. In a prospective randomized trial we assessed the ability of allopurinol in a conventional dose to modulate the toxicity of 5-FU-leucovorin combination without compromising its efficacy in 50 patients with advanced colorectal cancer. Twenty-seven patients were randomized for allopurinol but had no benefit in terms of response or reduced toxicity over the other 23. Survival of responders with colon cancer was longer than that of non-responders (p= 0.013). Although allopurinol failed to reduce 5-FU-leucovorin toxicity, it did not lower its expected efficacy.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Seventeen consecutively treated patients with advanced gastric cancer were prescribed every 3 weeks intravenous cisplatin (20 mg/m2/day) and a continuous infusion of 5-fluorouracil (5-FU) (750 mg/m2/day) for 5 days. Twelve (71%) patients had been treated previously with other anticancer drugs. Seven (42%) patients showed a partial response and these responses persisted for over 4.4 months. Stabilization of the disease occurred in eight (47%) patients, and in two (12%) the disease progressed. At the time of analysis, mean survival of the responders was 8.2 months, while that of non-responders was 5.0 months. The toxicities were within acceptable limits and only a few had a grade III toxicity. This combined administration of cisplatin and 5-FU for 5 days is safe and effective for patients with advanced gastric cancer.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Two human gastric cancer xenograft lines (GC-YN and GC-SF) transplanted in nude mice were employed to evaluate and compare the anticancer effect of seven single anticancer agents and their various combinations. Mitomycin C, cisplatin (Briplatin) (CDDP) and 5-fluorouracil (5-FU) were screened out to be effective against GC-YN and only epirubicin (Farmorubicin) (EPIR) was effective against GC-SF. Combinations of two of these ‘effective' agents revealed that FP (5-FU + CDDP) is the most effective two-agent combination regimen against both lines, and some of those ‘ineffective' single agents showed synergistic effects against both lines when combined with 5-FU. Moreover, three-agent combinations composed of FP and one of the other five agents were also evaluated to select out the most effective regimen. All the combinations showed higher inhibition on the tumor growth of GC-YN than FP regimen, and FP + adriamycin (Adriacin) (ADR) and FP + EPIR were more effective against GC-SF than FP. However, taking toxic effects into consideration, the results suggest that CDDP + 5-FU + EPIR (FPEPIR) may be the regimen most worthy of clinical trial in the chemotherapy against human gastric cancer.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The aim of this in-vitro study was to evaluate the combination of busulfan with radiotherapy on TE-671 human medulloblastoma cells since unexpected clinical toxicity of busulfan was reported during the treatment of brain tumors, suggesting a possible radiopotentiation. The cytotoxicity of busulfan was determined by using colony forming assays, and doses inducing growth inhibitions of 10, 20 and 50% were selected to be tested in association: 6, 12 and 32 μmol/l for busulfan and 0.5, 1 and 3 Gy for irradiation. All possible combinations were considered within this frame and the results showed that the combination of busulfan with radiotherapy exerted an additive effect without potentiation.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The co-operative effects of recombinant human tumor necrosis factor (rH-TNF) and CPT-11, a new derivative of camptothecin, against the proliferation of human gynecologic tumor cell lines were examinedin vitro.The lshikawa cells were responsive to rH-TNF, the HHUA cells exhibited a minimal degree of responsiveness to rH-TNF, and the HeLa S3 and Caov-3 cells were unresponsive to rH-TNF. The HHUA, Ishikawa and Caov-3 cells were responsive to CPT-11, and the HeLa S3 cells were relatively sensitive to CPT-11 cytotoxicity. In all four cell lines, rH-TNF at clinically achievable concentrations exhibited synergy with CPT-11. The combination therapy of rH-TNF and CPT-11 will be a new approach against gynecologic cancers.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The effect of 22-oxa-1α,25-dihydroxyvitamin D3(22-oxa-1,25(OH)2D3) on the growth of autochthonous rat mammary tumors induced by 7, 12-dimethylbenz[a]anthracene (DMBA) was examined on the basis of our previous finding that this synthetic vitamin D3analog has a potent angiogenesis inhibitory effect. Two doses of 22-oxa-1,25(OH)2D3, 0.1 and 1μg/kg of body weight, due to the limited amount of the compound available, were used. The daily administration of 22-oxa-1,25(OH)2D3at the dose of 1 μg/kg/day resulted in significant inhibition of the growth of these mammary tumors at 1, 2 and 3 weeks after the administration of this agent, although the agent caused little or no regression of the tumors. After daily administration for 3 weeks, a significant antitumor effect was also observed in the group treated with 0.1 μg/kg/day. Treatment with 22-oxa-1,25(OH)2D3did not affect the serum calcium levels in the treated rats. The lower dose of 22-oxa-1,25(OH)2D3neither affected weight gain nor caused a decrease in body weight, while the higher dose, although having some effect on weight gain, did not induce a decrease in body weight. There were no significant differences in the weights of adrenals, uteri and ovaries between the treated groups and controls. These results suggest that 22-oxa-1,25(OH)2D3has a significant growth inhibitory effect on DMBA-induced autochthonous mammary tumors in rats, without producing severe side effects, including hypercalcemic activity. Additionally, it might be possible that the antitumor effect of 22-oxa-1,25(OH)2D3is due, in part, to the angrogenic response by the host tissues and since the agent exhibits remarkable antiangiogenic activity.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

A B16 melanoma line was repeatedly transplanted subcutaneously in C57BL/6 mice. On day 4 after every transplant, the animals were treated with doxorubicin (DXR), 10 mg/kg i.p. The aim of the work was to develop an in-vivo model of resistance to the antiblastic in order to analyze some possible mechanistic aspects of the process in the course of time. After 16 transplants and treatments the melanoma completely lost its sensitivity to the antiproliferative effects of maximal tolerated doses of DXR and showed over-expression of P-glycoprotein. Compared to the parental line, thein vitroresistance index was 4.6. After 27 transplants and treatments the melanoma did not increase itsin vitroresistance to DXR further, and this resistance was completely reversed by verapamil. The behavior of the antioxidant defenses (superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase, glutathlone reductase and glutathione) was evaluated after 4, 16 and 27 transplants and treatments with DXR. At no stage did the treated melanoma show any variation in the antioxidant enzymes. Compared to the parental counterpart its glutathione levels were elevated after four treatments (+80%), when, however, the line was still sensitive to thein vivoeffects of DXR, and after 16 treatments (+30%). Instead, no variation of the glutathione content was seen after 27 treatments with DXR. These results seem to exclude the possibility that hand, the low but, however, clinically significant resistance of the tumor to the antiblastic seems mainly related to the mechanisms linked to the P-glycoprotein over-expression.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The potential antitumor activity of a series of novel cyclopropyl compounds, which lack estrogen agonist activity, was evaluated in estogen receptor positive human breast cancer cells (MCF-7) in culture. The compounds were evaluated to determine their antiproliferative activity at a concentration of 1μM at 2, 4 and 6 days of treatment by hemocytometer using the Trypan Blue exclusion method to count viable cells. Estradiolinduced reversibility of the antiproliferative activity of these compounds was also evaluated. The activity of a series of 19 diaryl- and triarylcyclopropyl compounds was examined. Thirteen compounds inhibited the growth of MCF-7 cells while six were inactive. Five of the 13 active compounds produced antiproliferative activity which was reversed by 0.1 μM estradiol. Thus, several of these novel cyclopropyl compounds may be useful in the treatment of hormone-dependent breast cancer and other estrogendependent tumors.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

5‘-Chloro-5’-deoxyarabinosylcytosine (5‘-chloro-araC), a lipophilic and cytidine-deaminase resistant analog of the cytotoxic agent arabinosylcytosine (araC) was evaluated in terms of bioactivation, transformation and its cytotoxic activityin vitro.5’-Chloro-araC interferes with DNA synthesis (IC50= 2.8 μmol/l) and inhibits the growth of L1210 cells in suspension culture (IC50= 1.05 μmol/l) and in the soft agar assay (IC50= 0.65 μmol/l). Being phosphorylated to the triphosphate of araC-araCTP (5‘-triphosphate of araC), 5’-chloro-araC has the same mechanism of action as arabinosylcytosine. In alkaline solutions 5‘-chloro-araC is transformed to another (cytostatically inactive) araC analog—2’,5‘-anhydroarabinosylcytosine—but at physiological pH and temperature conditions, it has sufficient stability to be phosphorylated and thus activated. A lower rate of araCTP formation from 5’-chloro-araC explains the somewhat lower cytotoxic effect of this compound against various established cell linesin vitrocompared to araC. Lipophilicity that would allow an oral drug formulation and certain other superior physico-chemical and biochemical characteristics of 5‘-chloro-araC make this compound an interesting candidate for further investigations.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID