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)

Human tumor cells from 22 patients with squamous cell carcinomas of the oral cavity were cultivated in vitro and then subjected to sensitivity tests to cytotoxic drugs such as methotrexate, 5-fluorouracil, cisplatin and bleomycin. Tumor cell proliferation showed drug-specific reaction patterns and time-dose-dependent variations. While the effect of methotrexate on cell proliferation was insignificant, 5-fluorouracil caused a growth suppression of 50%. Cisplatin and bleomycin suppressed cell growth by more than 90%.
 ...
PMID:[Resistance of isolated cells from squamous cell carcinomas of the oral cavity to cytotoxic drugs]. 172 15

A total of 248 analyzable patients with Stages III-IV ovarian epithelial cancer (114 with and 134 without prior chemotherapy) were randomized to one of four cisplatin (DDP)-hexamethylmelamine (HMM) regimens. In each, HMM, 200 mg/m2 was given orally daily on days 8-21 of each 21-day cycle. DDP was given i.v. on Day 1 at a dose of 37.5 mg/m2 (regimens A and B) or 75 mg/m2 (regimens C and D). In addition, since pyridoxine administration has been reported to reduce the neurotoxicity of HMM, that agent was given at a dose of 300 mg/m2 orally on Days 1-21 in regimens B and D. Randomization was stratified for performance status (0-1, 2-3) and largest tumor diameter at entry (greater than 2- less than or equal to 10 cm, greater than 10 cm) for previously untreated patients, and for performance status and time from initial diagnosis to entry on study (less than or equal to 1 year, greater than 1 year) for previously treated patients. The overall response rate (PR + CR) was 54%, with 25% of patients achieving a complete response. The 61% response rate with the higher dose DDP regimens was significantly greater than the 47% response rate with the lower dose regimens (p = 0.031). Multivariate analysis identified higher DDP dose, age less than 60 years, no prior chemotherapy, small tumor bulk and favorable tumor grade as significant prognosticators for response. The overall median response duration was 8.3 months (range 1-70 months). Prior chemotherapy, pyridoxine administration, recent diagnosis, and large tumor size were identified by multivariate analysis as factors adversely affecting response duration. Patients treated with the higher dose DDP regimens had more severe nausea, vomiting, and neurotoxicity. This study demonstrates that the combination of DDP + HMM is an effective regimen for advanced ovarian carcinoma that yields response rates comparable to other more complex regimens, and that there is a dose-response relationship for DDP in ovarian cancer. Although pyridoxine administration significantly reduced neurotoxicity, its adverse effect on response duration suggests that the agent should not be administered with DDP or HMM. The mechanism by which pyridoxine may unfavorably affect response duration deserves further investigation.
 ...
PMID:Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group. 173 9

Three model systems involving LOX human malignant melanoma cells in nude rats were used to compare the chemosensitivity of tumors growing in different tissues. Groups of 4-18 rats with either s.c. xenografts, lung tumor colonies, or bone metastases were treated with cisplatin, doxorubicin, dacarbazine, or mitozolomide. The antitumor effect in the s.c. model was expressed as specific growth delay, and in the experimental metastasis studies as relative increase in life span (RILS), calculated on the basis of observed disease-free survival. Cisplatin had a moderate but significant effect on the progression of LOX tumor growth in all three systems. Doxorubicin was clearly more efficacious, but for both drugs tumor-free survivors were rare or absent. Importantly, for each of the compounds the levels of response were roughly the same in all three models, with specific growth delay and RILS values in the range of 0.2-0.3 for cisplatin and 0.5-0.9 for doxorubicin. In contrast, a significant site-dependent difference in sensitivity of the LOX tumors was observed for two alkylating agents. Thus, dacarbazine, which temporarily caused complete regression of s.c. xenografts (specific growth delay = 21.0), showed a moderate activity in the lung tumor model (RILS = 1.0) but had only a limited effect (RILS = 0.4) on bone metastases. Mitozolomide gave a curative effect in 6 of 10 animals with s.c. and in 4 of 4 animals with lung tumors, whereas in the bone metastasis model it was only slightly superior to doxorubicin (RILS = 1.1). In preliminary attempts to elucidate the underlying mechanisms, no site-dependent differences in drug distribution and in two cellular detoxifying systems were detected. The data demonstrate the usefulness of the LOX models for studying the clinically relevant problem of site-dependent tumor response to chemotherapy.
 ...
PMID:Site-dependent differences in sensitivity of LOX human melanoma tumors in nude rats to dacarbazine and mitozolomide, but not to doxorubicin and cisplatin. 173 96

DDP treatment (1.2 mg/kg x 5) prolonged the mean survival time (MST) of rats bearing an experimental ovarian tumor (0-342) from 16.4 to 51.1 days, with one of ten rats surviving more than 90 days. Administration of D,L - buthionine sulfoximine (BSO) (24 and 2 h prior to DDP, respectively) before the last two doses of DDP had no significant effect on DDP therapeutic activity, while daily combination of DDP with BSO (BSO 2 h prior to DDP) throughout the treatment significantly increased MST to 69 days (p less than 0.05, vs. DDP alone), with three of ten rats surviving more than 90 days. In the DDP resistant counterpart (0-342/DDP), on the other hand, DDP alone showed only a slight increase of MST (11.6 days in DDP group vs. 10.7 days in control group), addition of BSO to DDP treatment further prolonged MST to 13.3 days (p less than 0.01 vs. DDP alone). The formation of DNA interstrand cross links (DNA-ISCL) was found to be higher in 0-342 than in 0-342/DDP cells in vitro with a maximum at 24 h following 1 h exposure to DDP. BSO depleted the intracellular GSH level in a dose - and time - dependent manner in the two cell lines. Pretreatment with BSO resulted in a 7.4% increase in DNA-ISCL by DDP in 0-342 cells but a 39% increase in 0-342/DDP cells, which may partially account for chemosensitization of BSO to DDP in vivo. Our result that the chemosensitizing effect of BSO, through depletion of cellular GSH, is more significant in the DDP sensitive O-342 tumor than in its DDP resistant subline in vivo underlines that BSO should be used as a chemosensitizer in combination with DDP at the beginning of chemotherapy for clinical trial.
 ...
PMID:Augmentation of cisplatin (DDP) cytotoxicity in vivo by DL-buthionine sulfoximine (BSO) in DDP-sensitive and-resistant rat ovarian tumors and its relation to DNA interstrand cross links. 177 64

The present work investigates the effect of cis-DDP (DDP, diamminedichloroplatinum(II)), trans-DDP, SPC (spermine platinum(II) complex), and K2PtCl4 on the activity of the CTP synthetase in the cytosol of Ehrlich ascites tumor cells. To study their in vitro effect, the platinum compounds were supplemented to the incubation mixture for the enzyme assay. A concentration dependent inhibition of the CTP synthetase was found which was strongest in the case of trans-DDP. When ascites cells collected from mice, pretreated in vivo with platinum compounds, were used, the enzyme assay showed that the inhibition is strongest in the case of cis-DDP and K2PtCl4 (about 90% inhibition). This distinct inhibitory effect of the platinum compounds in the present experiments may be explained with the metabolic conversions of the compounds in the organism to their more active forms and/or with the inhibition of the protein biosynthesis under their influence because the lifetime of the CTP synthetase is short. This last assertion is proved in this work by control experiments with the antibiotic cycloheximide, which is an inhibitor of the protein biosynthesis.
 ...
PMID:The effect of some platinum compounds on the activity of the CTP synthetase of Ehrlich ascites tumor cells: in vitro and in vivo studies. 177 27

The activity of Etoposide (VP16) in combination chemotherapy against four human transitional cell carcinoma cell lines of bladder (TCCaB) was determined by in vitro colony formation assay. Four anti-tumor agents (methotrexate: MTX, vinblastine: VBL, adriamycin: ADM, cisplatin: DDP) were used for combination chemotherapy with VP16. The ADM + VP16 combination exhibited a strong synergistic antitumor effect against the human TCCaBs compared with other combinations in this study. The combination chemotherapy of ADM + VP16 may be useful as a new chemotherapeutic regimen for advanced bladder cancer.
 ...
PMID:[The activity of etoposide (VP16) in combination chemotherapy against human bladder cancer cells in vitro]. 178 27

The study reported here was undertaken to determine the nephrotoxicosis associated with the administration of cisplatin, an antineoplastic agent, to dogs when administered during 6-hour saline solution diuresis. Cisplatin (70 mg/m2 of body surface, IV, every 21 days) was given to 61 dogs with malignant neoplasia with a total of 185 doses in 1 (n = 9 dogs), 2 (n = 26 dogs), 3 (n = 4 dogs), 4 (n = 9 dogs), 5 (n = 2 dogs), and 6 (n = 11 dogs) treatments. The cisplatin was given over a 20-minute period after 0.9% NaCl solution (saline solution) was administered IV for 4 hours at a rate of 18.3 ml/kg of body weight/h. After the cisplatin infusion, saline solution diuresis was continued at the same rate for 2 hours. Before each treatment with cisplatin, dogs were evaluated with at least a physical examination, CBC, determination of serum urea nitrogen concentration, and in most cases, determination of serum creatinine concentration and urine specific gravity. Four of the 61 dogs (6.6%) developed clinically evident renal disease after 2 (1 dog), 3 (2 dogs), and 4 (1 dog) doses of cisplatin were administered. Three of the 4 dogs had preexisting disease of the urinary tract prior to the start of treatment. The survival time in dogs that developed renal disease (median, 145 days; range, 15 to 150 days) was similar to that of all dogs in this study (median, 154 days; range, 30 to 500 days), with 13 dogs still alive at the conclusion of the study.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Prevalence of nephrotoxicosis associated with a short-term saline solution diuresis protocol for the administration of cisplatin to dogs with malignant tumors: 61 cases (1987-1989). 178 22

(R)-(-)-1,1-(2-amino-methylpyrrorodine)-platinum(II) (DWA2114R), cis-1,1-cyclobutanedicarboxylato(2R)-2-methyl-1,4-butanediammin eplatinum(II) (NK121; CI-973) and glycolate-o,-o'-diammine platinum(II) (254-S; NSC375101D) are new platinum compounds developed in Japan. We studied the antitumor effects of these compounds on the cisplatin (cis-diamminedichloroplatinum, DDP)-resistant human leukemia cell line, K562/DDP. K562/DDP cells were 10-fold resistant to DDP, while the cells showed minimal cross-resistance to carboplatin (2.1-fold) and DWA2114R (3.3-fold), and were as sensitive to NK121 (1.6-fold) and 254-S (1.0-fold) as the parent cells. Increases in exposure time of K562 cells to DWA2114R resulted in progressive shifting of the dose-response curve to the left, or more effective cell growth inhibition of the cells. Time dependency indices (ID80 obtained from dose-response curve after 1 hr-exposure of K562 cells to drug followed by 72 hr-culture without drug/ID80 after 24 hr-exposure) of DDP, NK121 and 254-S were 10, 8 and 20, respectively. A multidrug resistant cell-line, MOLT-3/TMQ200, was as sensitive to platinum compounds as the parent MOLT-3 cells. Little or no influence of tumor cell density was observed in the growth inhibition of MOLT-3 or K562 cells induced by these new compounds even if cells were concentrated to a density of 10(8) cells/ml. These results indicate that NK121 and 254-S may overcome the drug resistance developed in the patients after treatment with DDP. The antitumor effect of DWA2114R is more dependent not only on drug-concentration but also on exposure time than that of DDP, suggesting that continuous infusion rather than bolus administration appears the favorable schedule in clinical trials.
 ...
PMID:Antitumor activities of new platinum compounds, DWA2114R, NK121 and 254-S, against human leukemia cells sensitive or resistant to cisplatin. 180 4

Chemotherapy according to the MACC protocol (Methotrexate, Adriamycin, Cyclophosphamide, CCNU) was applied in 32 patients with squamous cell bronchial carcinoma. The following criteria were used for the evaluation of the effect of therapy: response to therapy (evaluation of decrease in tumor mass), duration of response and survival time. A positive response to therapy was achieved in 3 (9.4%) cases. In 22 (68.7%) the condition remained unchanged, while in 7 (21.9%) cases there came to a progression of the disease. Mean duration of survival was 15.1 +/- 8.2 months. More than a half of the patients lived for a year (59.4%), while 12.5% and 9.4% survived two and three years, respectively. By comparison of the results with findings from literature it seems that the application of chemotherapy in the combination of Cisplatin and Vindesin is more effective in the case of poorly differentiated squamous cell bronchial carcinoma.
 ...
PMID:[Evaluation of the results of chemotherapy in squamous cell bronchial carcinoma]. 180 89

The Lung Cancer Study Group conducted a phase II pilot study of concurrent chemotherapy and radiation therapy (chemoradiotherapy) before surgery in 85 eligible patients with non-small-cell cancer limited to the chest but in whom attempted resection would have been likely to leave residual disease (advanced stage IIIA and minimal stage IIIB disease). Cisplatin, 75 mg/m2, was given on days 1 and 29; fluorouracil, 1 g/m2 per 24 hours, was administered as a continuous infusion on days 1 through 4 and on days 29 through 32; and thoracic radiation, 30 Gy in 15 fractions, was administered on days 1 through 19. Two patients achieved a complete response and 46 patients had a partial response for an overall response rate of 56%. Toxicity from chemoradiotherapy was moderate but acceptable. Eight weeks after therapy was initiated, 54 patients underwent thoracotomy and tumor resection was attempted: 29 (34%) had complete resection and 15 (18%) had incomplete resection. Although surgical dissection was generally more difficult than in patients not pretreated with chemoradiotherapy, there was no apparent increase in postoperative complications. In 8 patients (9%), no viable tumor was detected pathologically in the resection specimen. Of the 18 patients whose tumors were completely resected and had disease recurrence, none had recurrence only in the chest, 12 (67%) had recurrence only in distant sites, and 3 developed second primary tumors. Median survival of all patients was 13 months. The overall results do not indicate a major benefit from this preoperative chemoradiotherapy regimen in patients with advanced but potentially resectable non-small-cell lung cancer. These results suggest a need to define better the relative roles of preoperative radiotherapy and chemotherapy.
 ...
PMID:Preoperative chemotherapy (cisplatin and fluorouracil) and radiation therapy in stage III non-small-cell lung cancer: a phase II study of the Lung Cancer Study Group. 184 20


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