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

The cytostatic and cytocidal effects of a newly synthesized tetravalent platinum drug (CBDCA-ox) on two experimental ascites tumors as well as on normal tissues of the mouse were investigated. It was found that CBDCA-ox exhibited only negligible acute toxicity in comparison with its reduced analog. Also hemotoxicity of this tetravalent drug was markedly lower than that of CBDCA. The comparison of antitumor activity of CBDCA and CBDCA-ox tested against LS/BL lymphosarcoma and EAT tumor cells strongly supports the view that CBDCA-ox deserves further preclinical testing.
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PMID:Evaluation of cytotoxic and antitumor effects of a tetravalent analog of carboplatin. 273 8

(Glycolate-o,o') diammineplatinum (II) (254-S) is one of the platinum derivatives showing high activity against rodent solid tumors and lack of renal toxicity. We have used a human tumor clonogenic assay (HTCA) as a disease-oriented drug screening model for new antitumor drugs, in order to test the antitumor activity of 254-S against non-small cell lung carcinoma (NSCLC) and to compare its activity with that of cisplatin (CDDP) and of carboplatin (CBDCA). The overall in vitro response rate (defined as less than 50% survival of tumor colony forming units) for 254-S was observed in 10/29 and 20/30 evaluable specimens isolated freshly from NSCLC patients with continuous exposure at 1 and 10 micrograms/ml, respectively, indicating a positive dose-response relationship. Dose dependent cytotoxicity was also confirmed in 4 human tumor cell lines derived from NSCLC patients. The antitumor activity of 254-S was 3.6-fold that of CBDCA, but two-fifths that of CDDP. A comparison of these in vitro results with the toxic properties of 254-S such as low nephrotoxicity suggests that 254-S is a promising new drug against NSCLC.
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PMID:Antitumor activity of a new platinum compound (glycolate-o,o') diammineplatinum (II) (254-S), against non-small cell lung carcinoma grown in a human tumor clonogenic assay system. 283 98

It is difficult to predict the adequate doses of effective drugs which must be administered in cancer chemotherapy. We have developed a successive colony-forming assay in order to analyze changes of drug sensitivity in human cancer cell lines, and it is used as a model of cancer chemotherapy. Presently, widely used methods include the clonog ceni assay as in vitro sensitivity test established by Salmon and Hamberger et al., for revealing effective drugs. However, formation of a second colony using initial colony-forming cells has not yet been performed. We therefore analyzed the changes occurring in drug sensitivity in 2nd and 3rd colony-forming assays. Using a human lung adenocarcinoma cell line PC-9 (established by Hayata at the Surgical Department in Tokyo Medical School), we measured the changes in sensitivity to CDDP and its derivatives. After picking up the colony-forming cells by micropipette and culturing them in culture medium, we tried to incubate them for 1 hour with the anticancer drug, and then replate them in soft agar. This technique is called "2nd colony-forming assay". We were able to carry this out three times. The results obtained showed that the anti-tumor effect of 254S was the same as that of CDDP, whereas that of CBDCA was less than either of them. Although these tendencies were noticeable even in the 2nd colony-forming assay, the sensitivities to CDDP and its derivatives were diminished in the 3rd colony-forming assay.
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PMID:[Analysis of drug sensitivity by successive colony-forming assay]. 303 6

Carboplatin was evaluated in a phase II study involving 109 patients with genitourinary cancer. A total of 21 cases of advanced testicular tumor, 38 of transitional cell carcinoma (TCC) of the urinary tract and 25 of prostatic cancer were evaluable for response. The response rate in testicular tumors was 48%, with 70% in seminomas and 27% in nonseminomas. Three responses were observed in patients previously treated with cisplatin. In TCC, the response rate was 18%. No response was observed in prostatic cancer. Carboplatin was well tolerated with no significant renal impairment and ototoxicity detected. Nausea and vomiting were experienced by 50% of patients but the severity was low. Severe myelosuppression, thrombocytopenia and leukopenia were observed. In conclusion, carboplatin has demonstrated activity in both testicular tumors and TCC of the urinary tract and is worthy of further study, especially in combination with other active drugs.
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PMID:[Phase II study of carboplatin in genitourinary cancer. Urological Cooperative Study Group on Carboplatin]. 304 77

Forty-six patients with previously untreated, advanced ovarian cancer received carboplatin (JM8, CBDCA) and chlorambucil (CLB) to assess the efficacy and toxicity of this combination. Carboplatin 300 mg m-2 was given on day 1 with CLB 10 mg daily for 7, 10 or 14 days; 6 treatment courses were given at 4-6 weekly intervals in the absence of disease progression. Tumour response was assessed, where possible, by restaging laparotomy after 6 treatment cycles. Five complete and 16 partial remission were seen in 37 evaluable patients giving an overall response rate of 57%. The median survival of all patients was 15 months. The major toxicity was myelosuppression. Nausea and vomiting were generally minor (WHO, grades I or II) and most courses were given on an outpatient basis. Leucopenia was the major factor causing treatment delays, particularly with the 10 and 14 day CLB regimens. Thrombocytopenia was minimal in the early chemotherapy cycles but the data suggest that cumulative toxicity may occur. This combination may provide a satisfactory degree of efficacy with less toxicity than cisplatin-based regimens.
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PMID:A pilot study of carboplatin (JM8, CBDCA) and chlorambucil in combination for advanced ovarian cancer. 306 98

The combination of Cis-dichlorodiammineplatinum (II) (CisDDPt) + 5-Fluorouracil (5-FU) was compared with two CisDDPt analogues + 5-FU [Iproplatin (CHIP) + 5-FU and Carboplatin (CBDCA) + 5-FU] for relative efficacy against advanced stage squamous cell lung tumors (LC-12) in Balb/c mice. At equitoxic dosages, the numbers of regressions and cures were similar for the three combinations (5-FU/CISDDPt 2/10 PR's, 2/10 CR's, 2/10 cures; 5-FU/CBDCA 1/10 PR's, 5/10 CR's, 3/10 cures; 5-FU/CHIP 1/10 PR's, 3/10 CR's, 3/10 cures). The tumor growth delay among the mice not cured was slightly superior in the 5-FU/CisDDPt regimen. All the agents were active singly against this tumor model. Based on these results, the substitution of CBDCA or CHIP for CisDDPt in a FU regimen did not offer a cytotoxic advantage. Because of different dose limiting toxicities for the platinum compounds the possibility exists that these analogues could be used in drug combinations in substitution for CisDDPt.
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PMID:Chemotherapy of the squamous cell lung cancer LC-12 with 5-fluorouracil, cisplatin, carboplatin or iproplatin combinations. 306 84

The antitumor effect of vinblastine (VBL), vincristine (VCR), etoposide (VP-16), teniposide (VM-26), cisplatin (CDDP), CBDCA (JM-8, Carboplatin), CHIP (JM-9), DWA2114R and recombinant human tumor necrosis factor (TNF) on four human testicular cancers heterotransplanted in nude mice were studied. The treatments with CDDP, CBDCA or CHIP significantly reduced the transplanted tumors. Combination chemotherapy with CDDP, bleomycin and VBL or VCR or VP-16 or VM-26 also revealed significant tumor regression. The antitumor effect of TNF on human testicular xenografts was much more evident when it was given intratumorally than when given intravenously. Teratoma was resistant to TNF even when it was administered intratumorally. Those results are briefly discussed and compared with the clinical results of chemotherapy. Several problems in anticancer drug sensitivity test against human tumor xenografts are also discussed.
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PMID:[Anti-cancer drug sensitivity test against human testicular cancer xenograft--comparison with clinical results of chemotherapy]. 324 64

Carboplatin and iproplatin, two new analogues of cisplatin, appear to have comparable activity in the treatment of advanced ovarian cancer, but minimal nephro- and neurotoxicities. Hyperthermia can potentiate the cytoxicity of cisplatin in vitro and in vivo, but systemic treatment with the combination has proven unsafe in patients. To provide the rationale for an alternative approach, we evaluated the relative degree of additivity between hyperthermia and the three platinum analogues in vitro against a human ovarian adenocarcinoma cell line, UACC-66. All drug and heat treatments were simultaneous for 1 h. Platinum analogue concentrations covered a five-log range from 0.001 to 100 micrograms/ml and hyperthermia temperatures included 38.5 degrees, 40 degrees, 41.5 degrees, and 43 degrees C. A tumor clonogenic assay was used to quantitate heat-drug interactive effects against the UACC-66 cells, and statistical analysis was performed using the median-effect equation of Chou. When combined with heat, the in vitro concentrations of the three platinum analogues were between 5% and 25% of those required at 37 degrees C to inhibit 50%-70% of the UACC-66 tumor colony-forming units. For each drug when combined with heat, a 3 degrees C incremental increase in temperature (i.e., from 37 degrees C to 40 degrees C or from 40 degrees C to 43 degrees C) was associated with a ten-fold decrease in ID50 drug concentration. We conclude that the synergistic effects of both carboplatin and iproplatin with hyperthermia at all temperatures above 37 degrees C provide a rationale for design of clinical trials in patients with ovarian cancer using these hyperthermia-drug combinations.
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PMID:Potentiation of platinum analogue cytotoxicity by hyperthermia. 328 6

We investigated the antitumor activity of cis-diammine[1,1-cyclobutanedicarboxylato]platinum(II) (CBDCA, JM8) and cis-dichloro-trans-dihydroxybis(isopropylammine)platinum(IV) (CHIP, JM9) for the cis-DDP-sensitive and -resistant IgM immunocytoma in the LOU/M Wsl rat. The optimal dose for the antitumor effect of cis-diamminedichloroplatinum (cis-DDP) in this tumor model is 1 mg/kg body weight. In order to determine the dose range for antitumor activity of JM8 and JM9, tumor-bearing rats were treated i.p. (twice weekly) with 2, 4, 8, 16, or 32 mg/kg JM8 or with 2, 4, or 8 mg/kg JM9. The maximal antitumor activity of JM8 was found at a dose of 4-8 mg/kg and that of JM9, at 4 mg/kg. Doses of 16 or 32 mg/kg JM8 did not increase the antitumor activity. Recurrence of tumors was observed in JM8- and JM9-treated rats. It was demonstrated that these relapses during treatment with JM8 or JM9 involved tumor cell populations almost completely resistant against therapy with the respective drugs. The growth of cis-DDP-resistant tumors was not influenced by the analog JM9 (4 and 8 mg/kg). Only a high dose of JM8 (32 mg/kg) caused growth retardation of the cis-DDP-resistant IgM subline. The JM8-resistant tumor was resistant to treatment with cis-DDP (1 and 2 mg/kg). The JM9-resistant tumor was also resistant to this treatment (1 mg/kg); however, at a dose of 2 mg/kg cis-DDP, growth retardation of the tumor occurred. We conclude that cis-DDP, JM8, and JM9 induce resistance in the IgM immunocytoma tumor system; tumors resistant for cis-DDP were not sensitive to the treatment with JM8 or JM9. Although JM9 reacts in vitro distinctly differently with DNA than cis-DDP and JM8, no differences were found in the induction of Pt resistance. In this study tumor cells were readily made resistant, which allows us to study in more detail the induction of (cross-) resistance by cis-DDP, JM8, and JM9.
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PMID:Resistance and cross-resistance of the IgM immunocytoma in the LOU/M Wsl rat for cisplatin, carboplatin, and iproplatin. 329 40

A 56-year-old housewife was incidentally discovered to have an abnormal shadow in the right B6 area upon a chest X-ray film being taken. A transcutaneous lung biopsy of the mass revealed adenocarcinoma of the lung (WHO classification). A brain computed tomography (CT) scan demonstrated multiple brain metastasis. Following whole brain irradiation, carboplatin (CBDCA) (450 mg/m2) was administered by intravenous drip infusion on March 7, 1986. After three weeks of initial treatment with CBDCA, the size of the tumor in the primary site was found to have decreased on the chest X-ray film by more than 50%, following which, similar doses of CBDCA were administered twice, and reduced (330 mg/m2) doses three times every three to four weeks. She showed a partial response and, for seven months after the beginning of the CBDCA treatment, no progression was seen on the chest X-ray film. It is suggested that there is a need for further phase II studies of CBDCA against non-small cell lung cancer.
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PMID:A case report of adenocarcinoma of the lung in which a partial response was achieved by carboplatin. 330 80


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