Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured the concentrations of MCNU and CBDCA in the serum, brain tumor and normal brain tissue. Six patients with malignant glioma were treated with intravenous chemotherapy using 80mg/m2 MCNU and 300mg/m2 CBDCA during surgery. After drug administration, specimens of serum, tumor and normal brain tissue were collected every 30 min and then the drug concentration in each sample was measured. The highest MCNU levels in all samples were obtained immediately after administration which followed by gradual decrease. On the contrary, the mean CBDCA levels in the tumor and normal tissue remained almost at a constant level, although serum CBDCA level declined rapidly as MCNU. As expected, MCNU seemed to have advantages in the treatment of brain tumors as it distributed with higher concentration in the tumor tissue than in the serum and normal brain tissue. On the contrary, CBDCA in the tumor tissue did not exceed the concentration in the serum. Nevertheless, it remained longer in the tumor tissue with a constant level, suggesting that CBDCA can achieve an effective area under the concentration versus time curve (AUC) in the brain tumor tissue to kill tumor cells.
 ...
PMID:[Clinical pharmacokinetics of carboplatin and MCNU in malignant brain tumor and normal brain tissues]. 803 Nov 57

A comparative exploration of the optimum regimens for CDDP and CBDCA therapy of malignant gynecologic tumors was conducted using both in vitro and in vivo approaches. In vitro, CBDCA exerted less cytotoxicity with short-time exposure, but over a longer time was as effective as CDDP. Pharmacokinetic studies demonstrated rapid binding of all administered CDDP to protein, while free-Pt was seen for many hours after CBDCA treatment. These results suggest that the gradual action of CBDCA leads to the appearance of cytotoxicity, and that in clinical use CBDCA affects the tumor cells for a long time. To increase the active dose of platinum, treatment with high doses of CDDP, or CBDCA, or the two platinum compounds with different pharmacokinetic behavior in combination, was designed for optimal therapeutic protocols. In the CDDP-alone treatment animals, renal toxicity was apparent with the increase in dose level. However, in the combination CDDP-and-CBDCA treatment animals, the total dose level could be elevated without causing toxicity. In the drug-sensitivity test, the combination therapy also exerted strong activity. The fact that the combined CDDP-and-CBDCA therapy appears to exert greater anti-tumor effects without any increment in adverse toxicity of these drugs is clinically promising.
 ...
PMID:Experimental studies of cis-diamminedichloroplatinum (II) and cis-diammine-1, 1-cyclobutandicarboxylate platinum (II) combination therapy for malignant gynecologic tumors. 813 80

The chemosensitivities of 77 samples of human head and neck cancer were examined by in vitro succinate dehydrogenase inhibition (SDI) test. The tumor tissues obtained at biopsy specimens were exposed to doxorubicin (DXR) and pirarubicin (THP). The average decrease of the enzyme activity by THP was significantly greater than that by DXR. In 60 cases of squamous cell carcinomas, the chemosensitivity of poorly differentiated type tended to be higher compared to the well differentiated type. It is suggested from there results that THP is a more effective anticancer drug than DXR against human head and neck cancers. Clinically good responses were obtained in a systemic chemotherapy of such as head and neck adenoid cystic carcinomas by combining THP with other anticancer drugs such as CDDP (or CBDCA) and CPA.
 ...
PMID:[Basic and clinical evaluation of the effect of pirarubicin against head and neck cancer--chemosensitivity test and a comparative study with doxorubicin]. 815 89

Two cell lines were established one from a primary site (OKK-TKp) and the other from a metastatic lymph node (OKK-TKm), from a maxillary squamous cell carcinoma (in the same patient). These cell lines were characterized with regard to morphology, chromosome numbers, tumorigenicity, growth kinetics, expression of tumor markers, sensitivity to immunological effector cells and anticancer agents. The two cell lines had the same modal chromosome number of 69, and formed tumors in nude mice. The median doubling time of OKK-TKp was 14.6 hrs and that of OKK-TKm was 24.3 hrs. Immunohistochemistry showed transferrin receptor (TfR), Ki-67, and epidermal growth factor receptor (EGFR) in OKK-TKm, but less or none in OKK-TKp. OKK-TKm was more sensitive to lysis by lymphokine-activated killer cells (LAK) on a 4-h 51Cr release assay, but was less sensitive to anticancer agents (CDDP, CBDCA) in modified MTT assay. We are convinced that these results are of value for understanding the mechanism of metastasis.
 ...
PMID:[Characterization of cell lines from metastatic maxillary cancer]. 816 39

This study examines the effects of a combined modality regimen of long duration-low temperature whole body hyperthermia (6 h at 40.0 degrees C; LL-WBH), recombinant human tumor necrosis factor-alpha (TNF) and carboplatin (CBDCA) on a transplantable fibrosarcoma as well as normal tissue. We compare LL-WBH with short duration-high temperature whole body hyperthermia (2 h at 41.5 degrees; SH-WBH). LL-WBH alone had no significant effect on tumor growth. Tumor growth delay (TGD) with TNF alone (0.1 days) and that with CBDCA alone (1.3 days) were significantly increased to 2.6 days (P < 0.05) and 2.8 days (P < 0.05), respectively, when combined with LL-WBH. Although TNF+CBDCA produced minimally increased TGD of 1.9 days, the combination of LL-WBH+TNF+CBDCA produced a significantly greater TGD of 5.6 days, compared to the other dual combinations (P < 0.01). There was no difference between TGDs for SH-WBH and LL-WBH in combination with TNF+CBDCA. Trimodality treatment-induced normal tissue toxicities, characterized by body weight loss, diarrhea, foot edema, and myelosuppression, were significantly greater in rats treated with SH-WBH+TNF+CBDCA, compared to LL-WBH+TNF+CBDCA. Histopathological examination also demonstrated that SH-WBH+TNF+CBDCA caused severe damage to the lymphoid tissues, intestinal tract, and peripheral microvasulature. We observed minimal histopathological changes observed in rats treated with LL-WBH+TNF+CBDCA. These data suggest that LL-WBH in combination with TNF and CBDCA has a greater therapeutic efficacy than SH-WBH.
 ...
PMID:Therapeutic efficacy of long duration-low temperature whole body hyperthermia when combined with tumor necrosis factor and carboplatin in rats. 817 30

Drug therapy for cervical cancer is slowly undergoing evaluation in early disease stages, in which it is more likely to make an impact. Cisplatin has been the principal drug used in systemic therapy for all stages, with the possible exception of the radiosensitizer hydroxyurea. Nevertheless, current studies use cisplatin in this role as well. To a limited extent, substitution of carboplatin for cisplatin also has been explored. Conflicting interpretations of carboplatin trials nonetheless support continued study of this drug; its activity is reproducible and it can be combined with radiation therapy in practical dose schedules. The major question in the systemic nonendocrine treatment of endometrial cancer revolves around whether cisplatin adds to results achievable with doxorubicin. Carboplatin, documented as active against this neoplasm, represents a potentially advantageous cisplatin substitute for elderly patients. Moreover, if combination chemotherapy should prove disappointing, single-agent carboplatin may provide the best strategy for palliative therapy.
 ...
PMID:Platinum compounds in cervical and endometrial cancers: focus on carboplatin. 820 19

Carboplatin, a platinum analog with single-agent activity in previously untreated breast cancer, is characterized by comparatively less renal toxicity and emesis than cisplatin. We combined carboplatin at different dose levels [from 200 to 350 mg/m2 by intravenous (IV) infusion on day 1] with 5-fluorouracil (500 mg/m2 IV on days 1 and 8) and cyclophosphamide (500 mg/m2 IV on day 1), with all three drugs recycled every 28 days, to evaluate anti-tumor activity and toxicity of this novel combination [5-fluorouracil/carboplatin/cyclophosphamide (FCC)] in untreated locally advanced (LABC) or metastatic breast cancer (M+). Of 37 patients treated between March 1990 and August 1991 [LABC 25, M+ 8; World Health Organization (WHO) performance status, 0-1; median number of treatment cycles, 5; median follow-up, 20 months], 33 are evaluable for response and toxicity. The overall complete plus partial remission rate was 57% (LABC 68%, M+ 25%). The median duration of response was 19+ months. The cumulative carboplatin dose ranged from 800 to 2350 mg/m2 (median, 1450 mg/m2). In this series, no correlation was observed between the carboplatin dose level and response rate or toxicity. Leukopenia and thrombocytopenia represented the most frequent toxicities. WHO grades 3 and 4 neutropenia were documented in 34% and 8% of patients, respectively. Thrombocytopenia below 50 x 10(9)/l was observed in 8%. No renal toxicity was observed, and moderate emesis occurred in 67% of patients. These results indicate that FCC is an active and relatively safe combination for the treatment of advanced breast cancer in patients not previously treated with chemotherapy.
 ...
PMID:Carboplatin in combination as first-line therapy in advanced breast cancer. 822 14

From 1987 to 1991, 100 evaluable patients with advanced head and neck carcinomas (T2-4, N0-3) were treated with radiotherapy and simultaneous carboplatin. Tumors were located in the oral cavity in 33 patients, oropharynx in 8 patients, and hypopharynx in 7 patients. Four patients had a tumor of the epipharynx, 3 of the larynx, and 45 had involvement of two or more compartments. Radiotherapy was performed in a fractionation of 5 x 2 Gy/week up to a dose of 50 Gy. Carboplatin was administered in a dose of 60 or 70 mg/m2 from days 1-5 and 29-33. After a 2-week interval, tumor involution was evaluated and a decision was made on the patients' operability. In cases of inoperability, radiotherapy was continued up to a dose of 70-74 Gy. Thirty patients underwent surgery after 50 Gy. Eight patients showed a histologically complete remission (CR), 7 showed microscopic residual tumor, and 15 showed macroscopic tumor. Seventy patients were treated with radiotherapy and concomitant carboplatin only. Thirty-nine of them achieved a CR and 30 a partial remission (PR). The residual tumor was operable in 8 of the latter patients. Only a minor response was achieved in the remaining patient. At the end of the treatment 77 patients achieved a CR with this combined modality. From 1990 to 1992, 20 patients with locally advanced head and neck carcinomas underwent hyperfractionated accelerated radiotherapy (2 x 1.6 Gy/day, 5 days per week: total dose, 64-67.2 Gy) and simultaneous intravenous carboplatin (60 mg/m2, days 1-5 and 29-33) in a pilot study. Fifteen patients had T4 and 5 had T3 tumors. Six weeks after the end of treatment, 16 patients (80%) had CR, and PR was seen in the other 4 patients (20%). Overall and disease-free survival at 1 year was 82 and 81%, respectively. Although acute side effects were more pronounced compared with conventional irradiation, this treatment regimen is feasible and the initial CR rate of 80% is encouraging. Because of the results achieved with hyperfractionated accelerated radiotherapy, we initiated a multicenter randomized study in November 1991. Patients with advanced head and neck carcinomas are either randomized for conventional radiotherapy with carboplatin or hyerfractionated accelerated irradiation with carboplatin. Results will be forthcoming.
 ...
PMID:Combined radiochemotherapy with carboplatin in the treatment of advanced head and neck carcinomas. 823 96

Twenty-six patients with a variety of tumor types were treated according to a phase 1 experimental treatment protocol consisting of repetitive cycles of cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (carboplatin, 200-480 mg/m2) at day 1 and cis-diamminedichloroplatinum(II) (cisplatin, 50-100 mg/m2) at day 3. Buccal cells were collected in one or two treatment cycles prior to carboplatin, 24 h after carboplatin, just prior to cisplatin, and approximately 24 h after cisplatin administration. Drug-induced DNA modification was visualized at the single cell level by anti-serum NKI-A59 and quantitated by microdensitometry. All (39 of 39) treatments with carboplatin, and almost all (33 of 35) treatments with cisplatin resulted in an increase in nuclear stain. Interindividual variation in drug-induced, adduct-specific nuclear stain amounted to a factor of 5-8 for carboplatin and 5-12 for cisplatin. This drug-induced increase was, however, not related to the dose of either carboplatin or cisplatin, suggesting that large interindividual differences in DNA adduct formation and/or repair obscured the effects of dose variation within the relatively small range used for the drugs (2.4 for carboplatin and 2.0 for cisplatin). This explanation was strengthened by the good reproducibility of the immunocytochemical assay and by the reasonable correlation between carboplatin-induced nuclear stain in cycles 1 and 2 (correlation coefficient, 0.69; P = 0.009). Mean carboplatin-induced nuclear stain was significantly higher in the first cycle than in the second cycle (P = 0.0001) but this difference was no longer significant when drug-induced nuclear stain was corrected for carboplatin dose. Differences in cisplatin-induced nuclear stain between cycle 1 and cycle 2 were small and not significant. Carboplatin-induced nuclear stain was significantly higher in the partial responders than in the nonresponders (P < 0.0001, two cycles combined); the level of statistical significance remained the same after dose correction. Cisplatin-induced nuclear stain did not differ significantly between partial responders and nonresponders; this result might, however, be confounded to some extent by remaining carboplatin-induced nuclear stain at the moment of cisplatin administration. It is concluded that determination of the extent of platinum-induced DNA modification might be helpful in predicting the tumor response in cancer patients.
 ...
PMID:Drug-induced DNA modification in buccal cells of cancer patients receiving carboplatin and cisplatin combination chemotherapy, as determined by an immunocytochemical method: interindividual variation and correlation with disease response. 824 22

The in vitro antitumor activities of a new platinum complex, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) monohydrate (DWA2114R), against various human tumor lines (23 solid tumor lines and 6 hematopoietic malignant lines) were examined in comparison with those of cis-diammine (1,1-cyclobutanedicarboxylato) platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP). The growth inhibitory activities of the compounds were estimated by MTT assay after the incubation of cells under continuous exposure to the drug. The mean concentrations (microM) of DWA2114R, CBDCA and CDDP needed to inhibit the proliferation of cells by 50% (IC50) were 64.0, 55.1 and 6.8 against solid tumor lines and 8.5, 7.4 and 1.7 against hematopoietic malignant lines, respectively. Comparing the drug sensitivity of the solid tumor lines by type, ovarian cancer was found to be the most susceptible to all three compounds. The susceptibilities of other tumors were in the order prostate, breast and colon cancers for DWA2114R and CBDCA but colon, prostate and breast cancers for CDDP. The correlations of the mean IC50 values for all three combinations of the two compounds were statistically evaluated. A significant correlation was shown between DWA2114R and CBDCA, or CBDCA and CDDP, but not between DWA2114R and CDDP. These results suggest that DWA2114R is almost equivalent in effect to CBDCA which is several times less potent than CDDP, but also that the in vitro cell line subpanel specificity of DWA2114R is in certain respects different from CDDP, in contrast with CBDCA.
 ...
PMID:In vitro antitumor activity of a new platinum complex, DWA2114R against human tumor cell lines. 829 43


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>