摘要:

A review on the chemotherapy in advanced pancreatic cancer is presented. Pancreatic cancer is an extremely chemotherapy resistant tumor and results of cytostatic drug treatment so far are unsatisfactory. For patients with locally advanced disease the combination of chemo- and radiotherapy may palliate some patients. To date no standard treatment is available and patients should be entered in clinical protocols assessing new treatment options.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

There is increasing evidence that copies of amplified oncogenes or drug-resistant genes located on extra-chromosomal DNA (e.g. double minutes and/or episomes) can be eliminated from mammalian tumor cell lines by treatment of the cells with low concentrations of hydroxyurea. However, amplified oncogenes or drug-resistant genes located in an intrachromosomal site (such as in a homogeneously staining region (HSR)) cannot be eliminated from the cells. A question which arises Is do primary human tumors have extra-chromosomal DNA present often enough to make elimination of that extrachromosomal DNA a potentially Important therapeutic strategy? To address that question we have reviewed published cytogenetic analyses of 200 tumors taken directly from patients to determine the percentage of primary human tumors which have amplified genes present on extrachromosomal DNA (present in the form of double minutes [DMs]) vs the percentage of tumors which have amplified genes located on an intrachromosomal site (in the form of HSRs). Of the 200 primary human tumors reviewed, 91% contained DMs only, 6.5% contained HSRs, and 2.5% contained both. Of interest, in a parallel review of 109 cell lines with cytogenetic and/or molecular evidence of gene amplification, 60.6% contained DMs, 26.6% contained HSRs, and 12.8% contained both. These data indicate that DMs are the predominant cytogenetic marker for gene amoplificaongoing efforts to eliminate amplified drug-resistant genes or oncogenes contained on DMs (or precursors of DMs) from tumor cells may be relevant forin vivosituations.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

A new approach to antitumor analog selection was evaluated usingin vitrocytotoxicity assays in tumor cells and heart cells. Eight anthracycline antibiotics and five non-anthracycline DNA intercalating agents were separately exposed to human 8226 myeloma cells and neonatal rat heart myoctesin vitro.Survival was measured after six days of culture by the MTT dye method for tumor cells and by ATP content for heart cells. Inhibitory drug concentrations in 50% of cells (IC50) were determined from log-linear dose-response curves for each agent. The IC50values in the tumor cells ranged from 0.002 μ/ml for idarubicin to 3.5 μ/ml for the primary metabolite of doxorubicin, doxorubicinol. In contrast, IC50values for anthracyclines in rat heart cells averaged approximately 357-fold higher than in the tumor cells. The heart cell/tumor IC50ratio was 114.4 for the parent anthracycline doxorubicin. Compounds with poor cytotoxic selectivity for tumor cells included doxorubicinol, amonafide, amsacrine and bisantrene. Compounds with reduced cardiotoxicity included the anthracyclines daunorubicin (IC50ratio of 550), esorubicin (IC50ratio of 1500) and the anthracene derivative mitoxantrone (IC50ratio of 500). These results show that simultaneous comparisons of cytotoxicity in heart cells and tumor cells can identify agents such as daunorubicin and mitoxantrone which are known to produce less cardiac toxicityin vivo.With further testing, this methodology may be applicable to preclinica screening programs to select active DNA Intercalating agents with low cardiotoxic potential.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Uterine sarcomas are rare tumors constituting 1–3% of all uterine malignancies. These tumors are characterized by aggressive growth and by poor overall prognosis. There is much controversy concerning diagnostic criteria and the great variation in histology, as well as the role of radiotherapy and chemotherapy in the management of these tumors. We report a case of endometrial stromal sarcoma of the uterus in a 45-year-old woman. Total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy was performed, followed by adjuvant radiotherapy and tamoxifen treatment. The patient has now been seen regularly for 2 years from the start of the treatment and at present there is no evidence of disease.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The antitumor action of bestatin is considered to be an indirect action mediated by T-cells. Therefore, we investigated the effects of bestatin on the differentiation and proliferation of human precursor T-cells using a colony formation technique. Bestatin did not increase the overall number of T-cell colonies, but it significantly increased in CD4+cell and significantly decreased in CD8+cell subpopulations. It also induced CD4+8+cells.These findings indicated that bestatin acts on precursor T-cells to induce the differentiation of these cells into CD4+cells.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We determined the effect of 1-hexylcarbamoyl-5-fluorouracil (HCFU), a masked compound of 5-fluorouracil, on the expression of heat shock protein (HSP) in heat-treated HeLa cells. We used a monoclonal anti-72-kDa heat shock protein antibody. At 37°C, HSP was predominant in the cytoplasm of cells and heating to 43 C for 30 min increased the synthesis of HSP in the nucleus. When HeLa cells were treated with heat and HCFU, at a concentration which showed evidence of synergy, nuclear staining of the cells decreased. Thus, the altered expression of HSP by HCFU is related to a synergism between heat and HCFU.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

2‘,2’-difluorodeoxycytidine (known as dFdC, Gemcitabine and LY188011) is a new analog of deoxycytidine which has demonstrated excellent antineoplastic activity against many kinds of solid tumors and leukemic cell lines. We were interested in the comparison of the antineoplastic activity of this new antimetabolite with cytosine arabinoside (ARA-C) against HL-60 myeloid, RPMI-8392 B-lymphoid and Molt-3 T-lymphoid leukemic cell lines. Ourin vitroexperiments showed that dFdC was a more potent cytostatic drug than ARA-C against all the leukemic lines with IC50ranging from 3 to 10 nM for dFdC and from 26 to 52 nM for ARA-C for a 48 h exposure. The cytotoxicity of both drugs was evaluated by clonogenic assay and dFdC was found to be 100 times more potent than ARA-C against all the leukemic cell lines for both a 2 h and a 24 h exposure. The recovery of DNA synthesis after drug removal was much slower for dFdC than for ARA-C. However, in contrast to cytostatic and cytotoxicity results ARA-C was a more potent inhibitor of DNA synthesis than dFdC for all the leukemic cell lines for short exposure. Uptake and elimination of the drugs showed that dFdC accumulated to a higher degree in the leukemic cells than ARA-C and that elimination of this difluoro analog was slower than that of ARA-C. These results indicate that dFdC has more potentin vitroantileukemic activity than ARA-C.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Scanning electron microscopic studies revealed that ascites Dalton's lymphoma cells are distributed singly (25–30%) or in groups of 2–3 cells (55–60%) and 5 or more cells (10–15%) connected together. The percentage of single cells and groups of 2–3 or more cells changes with tumor growth. The number of single cells is maximal 72 h after tumor transplantation. Control tumor cells revealed the presence of blebs—ruffles all over the cells. Cisplatin treatment of the cellsin vivobrings about definite changes in the arrangement of blebs—ruffles over the cells. At the later stages of cisplatin treatment disintegration and breaking of the plasma membrane occurs, which ultimately results in the lysis of tumor cells.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

In vitroandin vivoeffects of ginsenoside Rh2on human ovarian tumor growth were examined by using a cell line (HRA) derived from ascites of a patient with serous cystadenocarcinoma of the ovary. The HRA cell proliferationin vitrowas inhibited in a dose-dependent manner with dosages of 10–100 μM of ginsenoside RH2. DNA, RNA and protein synthesis by the HRA cells was inhibited in a dose-dependent manner at more than 15 μM of ginsenoside RH2. However, the growth of HRA cells transplanted in nude mice was not significantly inhibited by ginsenoside RH2. On the contrary, when cisplatin was administered together with 10 μM (but not 1 μM or 100 μM) ginsenoside RH2, the tumor growth was significantly inhibited 31 days after inoculation and the survival was also significantly prolonged, compared with not only the untreated group but also the groups given cisplatin alone or ginsenoside RH, alone. This indicates synergistic effects between cisplatin and ginsenoside RH2. From monitoring of body weight and hematocrit, concentrations of ginsenoside RH2used in this study did not seem to cause any adverse effect.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

To date, random anticancer drug screening has proven to be relatively inefficient and non-specific with respect to selecting active compounds for most tumor types (except for leukemia/lymphoma). Although large numbers of compounds from diverse sources were evaluated for many years in the P388 mouse leukemia model, only a few clinically useful drugs have been identified by thisin vivoscreening method. Thus, there is intense interest in the development of more effectivein vitroscreening models for new anticancer drugs. In the present paper we have compared the discriminating power for fresh human tumors from patients, human tumor cell lines developed from 11 patients and murine P388 leukemia in tumor colony forming assays as indicators of cytotoxicity for a series of anthracene antitumor agents. Two of a series of 21 novel bisantrene analogs, R6 (N, N1-bis[2-(dimethylamino)ethyl]-9,10-anthracenebis(methylamine)) and R26 (N, N1-bis(1-ethyl-3-piperidinyl)-9,10-anthracene-bis(methylamine)) produced significant cytotoxicity against the 11 human tumor cell lines and were therefore selected for additionalin vitroandin vivostudies. R26 was specifically selected for further testing since it had Ion or doxorubicin-resistant 8226 myeiomd ten lines, in contrast to the cell line data, only one of the 22 fresh human tumors showed significantin vitrosensitivity (i.e.in vitro, whereas mitoxantrone and bisantrene were highly active in this model at a concentration of 0.2 μM. In order to compare thein vitrodata with antitumor activityin vivo, R26, the most active bisantrene analog, and mitoxantrone, the most active of the two anthracene parent compounds, were tested against P388 leukemia and M5076 ovarian sarcoma in mice. In both models mitoxantrone showed significant activity whereas R26 produced minimal or no antitumor effects. We conclude that fresh human tumors, but not defined human tumor cell lines, predict thein vivocytotoxicity of a series of anthracene anticancer agents. Although this conclusion may not apply to the screening of other classes of antitumor agents, we propose anin vitroscreening process which first utilizes numerous human tumor cell lines of many different biologies (to screen a large number of new compounds each year), followed by confirmatory tests in fresh human tumors using colony forming assays to screen up to a smaller number of 1000 compounds. Finally appropriatein vivotumor model based on histologic pecificity would be used to screen a few consistently active new compounds for advancement to clinical trials. Thus, the first screening stage would be highly sensitive and non-specific, the secondin vitrostage more specific and the thirdin vivostage relevant by histologic tumor type.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID