摘要:

A phase 11 trial of citrovorum factor, 500 mg/m2/week, plus 5-fluorouracil, 400 mg/m2/week on day 1, and cisplatin, 20 mglm2lweek on day 2, was carried out in a group of 40 patients with metastatic colorectal carcinoma. A partial response with a mean duration of 8.4+ months was achieved in 24% of patients, a minimal response with a mean duration of 5.4 months was obtained in 6% of patients, and a stabilization of 6.2 months was achieved in 41%. Ten patients (29%) progressed. A 38% partial response rate was seen in patients with advanced rectal carcinoma, whereas no response was obtained in patients with colon cancer. Interestingly, 5 partial responses were seen in 12 patients pretreated with 5-fluorouracil. The overall survival was 9.8+ months. The mean survival of patients who achieved a partial response was 12.0+ months, whereas patients who progressed survived a mean of 6.6+ months. Patients with colon cancer had a mean survival of 8.1 + months, and those with rectal cancer survived a mean of 11A + months. This difference was not statistically significant. The treatment was generally very well tolerated, with patients showing mostly grade 1-2 gastrointestinal and Ior hematological toxicity.

ISSN:0735-7907    

DOI:10.3109/07357909209024811

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Tiazofurin is effective in treating end-stage leukemic patients (Tricot et al., Cancer Res 49:3696-3701, 1989). In sensitive tumors, the active metabolite of tiazofurin, TAD, potently inhibits IMP dehydrogenase activity, resulting in reduced guanylate pools. To elucidate tiazofurin activity in human solid tumors, we examined its activity in human colon carcinoma HT-29. Tiazofurin exhibited an LC50of 35 pM in cultured HT-29 cells. Incubation of HT-29 cells with 100 pM tiazofurin for 2 h resulted in TAD formation (9.3 nmollg cells) and in a 64% decrease in GTP pools. For biochemical and chemotherapy studies, athymic nude mice were transplanted s.c. with HT-29 cells. Twenty-four days later, mice were injected i.p. with tiazofurin (500 mg/kg); 6 h later, tumors were removed and analyzed. These tumors formed 17 nmollg of TAD with decreased GTP pools (56%). To study oncolytic activity, transplanted mice were treated 24 h later with tiazofurin (500 mg/kg, once a day for 10 days). To examine the effectiveness of tiazofurin in established tumors, the drug was administered to mice 14 days after tumor implantation (500 mglkg, once a day for 5 days, course repeated 4 times with a 10-day rest). Both treatment schedules resulted in significant antitumor activity. This study illustrates the potential usefulness of tiazofurin in treating human colon carcinoma.

ISSN:0735-7907    

DOI:10.3109/07357909209024812

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

We analyzed the pattern of alpha-fetoprotein (AFP) synthesis in 40 consecutive human hepatocarcinomas (HCC) in relation to hepatitis B viral (HBV) infection. In addition, histopathological characteristics of liver parenchyma and the tumor itself were examined. Elevated AFP (>20 nglml) were found in 90% of HCC patients and in none of the controls. In 35% of HCC cases, serum AFP was above 100,000 nglml. AFP levels were significantly higher in patients seropositive for hepatitis B surface antigen (HBsAg) compared with their negative counterparts (mean log[AFP]: 4.28±1.67 vs. 3.28±1.96, respectively; geometric mean (GM): 19,322.6 nglml and 1939.5 nglml, respectively; p<0.05). Furthermore, serum AFP levels were higher in HCC patients with liver cirrhosis than in those without (log[AFP] :4.43±1.58 vs. 3.23±1.98, respectively; p<0.05). However, the relationship of cirrhosis with AFP was confounded by the high prevalence ofHBsAg in cirrhotic HCC patients. There was no correlation of AFP with either liver necrosis (abnormal AFP in 45% of cases; mean log[AFP]: 3.99±1.91 vs. 3.75±1.85 forHCC0 with and without necrosis, respectively; 0.05

ISSN:0735-7907    

DOI:10.3109/07357909209024813

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909209024814

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909209024815

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The development of effective low-LET radiation therapy for cancer has been hindered by the lack of consistent differential responses to radiation between tumor and normal tissues. One major difference between many solid tumors and the surrounding normal stroma is the presence of hypoxic foci in solid tumors due to the inadequate supply of nutritional needs as a result of the breakdown of micro-vasculature. Consequently, failure of conventional radiotherapy and local recurrences are in part attributed to the radioresistant hypoxic cell populations, present in the tumor. Local cure I control rates of a tumor can be increased only by an effective increase in the radiation dose. At the same time, an increase in such a dose would damage the oxic normal stroma, more than the hypoxic tumor cells. Hence, specific modification of tumor radiosensitivity by the use of chemical radiosensitizers, in combination with conventional radiotherapy, is an attractive alternative. Many clinicians and radiotherapists are skeptical about the outcome of using radiosensitizers in patients. Nevertheless, a vast amount of information is currently available regarding the first-and second-generation radiosensitizers both in murine and in human tumors. As a result, it is hoped that eventually a radio-sensitizing drug would be discovered! synthesized that will overcome the drawbacks so far encountered in their use in the clinic.In this article, the development of chemical radiosensitizers since the early sixties, the basis for their selection, their mechanism(s) of action, and the results obtained with the various groups of radiosensitizers are reviewed.

ISSN:0735-7907    

DOI:10.3109/07357909209024816

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909209024817

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909209024818

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

erbB-2 protein is believed to be a cell membrane receptor for the recently identified ligand gp30. When overexpressed, erbB-2 is an indicator of poor prognosis in adenocarcinomas of breast, stomach, lung, and endometrium. Even more important, clinical data suggest that erbB-2 overexpression may be an indicator of poor response to at least some commonly used adjuvant regimens. However, there is preliminary evidence that these tumors might respond as well to doxorubicin regimen as do erbB-2 negative tumors, at least in gastric cancer. The efficacy of doxorubicin-containing regimen in the treatment of tumors with erbB-2 overexpression needs to be explored further by retrospective analysis of finished clinical trials. Combination of chemotherapeutics with reagents that block erbB-2 signal transduction pathway may be another effective approach.

ISSN:0735-7907    

DOI:10.3109/07357909209024819

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909209024820

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor