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)

Gamma linolenic acid (GLA) by itself shows anti-tumor activity on various neoplastic cells in culture. We investigated the combined effect of GLA and anticancer drugs on two human neuroblastoma cell lines. The cytotoxic effect of Vinca alkaloids such as vincristine (VCR), vindesine (VDS) and vinblastine (VBL) was about 2-fold enhanced when GLA was added simultaneously to the growth medium. On the other hand, that of platinating agents such as cisplatin (CDDP) and carboplatin (CBDCA) was inhibited by GLA supplementation. The cytotoxic activity of other anticancer agents was not affected by GLA. Pharmacokinetic studies on VCR and CDDP demonstrated that intracellular accumulation of [3H]-VCR was about 1.5-fold increased in the cells pretreated by GLA, while, on the contrary, that of CDDP was rather decreased; cellular efflux of either drug was not affected. Malon dialdehyde (MDA) formation induced by supplemented GLA was not influenced by either VCR or CDDP. These results indicate that GLA exerts differential effects on the kinetics of anticancer drugs.
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PMID:Gamma linolenic acid alters the cytotoxic activity of anticancer drugs on cultured human neuroblastoma cells. 216 61

Carboplatin, a second generation platinum complex, is less nephrotoxic and emetogenic than its parent compound. We have tested the objective response to and the toxicity of the combination carboplatin 330 mg m-2 on day 1 with etoposide 120 mg m-2 on days 1, 3 and 5, administered every 3 weeks in histologically proven inoperable non-small-cell lung cancer (NSCLC) patients with a good performance status. Thirty-one patients entered the study; 29 were evaluable for response, 24 after 3 courses and 5 after 2 courses of chemotherapy. An overall response rate of 21% was found including zero complete response and 6 partial responses. In addition, 3 minor responses (10%), 12 stable diseases (38%), and 9 progressive diseases (39%) were observed. The median survival was 48 weeks, including 68 weeks for non-metastatic (M0) patients and 27 weeks for metastatic (M+) patients. This regimen was well tolerated. Gastrointestinal toxicity never exceeded WHO grade II and renal function remained in the normal range for all cases. Haematological toxicity was low in the majority of the cases; nevertheless it proved to be the dose limiting toxicity as illustrated by two grade III anemia, one grade III leucopenia, one grade III and one grade IV thrombocytopenia. Carboplatin-etoposide combination is not more active, but clearly much less toxic than cisplatin-etoposide in NSCLC.
Med Oncol Tumor Pharmacother 1990
PMID:Carboplatin in combination with etoposide in inoperable non-small-cell lung cancer (NSCLC). 217 5

The effect of three second generation platinum complexes on proliferation of tumor cells (HeLa, C6) and nontumor cells (LEP) was studied, and compared with that of cis-DDP. The highest activity, comparable with cis-DDP, was exhibited by oxoplatinum. CBDCA was somewhat less active in this system, but had a greater effect on both lines of tumor cells than on nontumor cells. Cell proliferation was inhibited least of all by CHIP(IV). The differences observed are discussed from the point of view of the structure and oxidation state of the platinum complexes.
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PMID:The effect of second generation platinum cytostatics on mammalian cell proliferation. 218 63

We compared cis-platin (DDP) and its analogue, carboplatin (JM8, CBDCA) in their ability to inhibit spheroid growth. The activities of DDP and JM8 were also compared in an antimetabolic assay for their ability to inhibit (3H)-thymidine incorporation in multicellular tumor spheroids. The spheroids were derived from a squamous cell carcinoma cell line HN-1, originally derived from a tumor of the tongue. To produce equal levels of growth delay in spheroids, carboplatin was required at concentrations approximately 16 times that of DDP. Carboplatin also required much longer incubation periods than DDP to produce equivalent growth delay and proportions of cured spheroids. Reflecting the initial response to chemotherapy, the antimetabolic assay showed that carboplatin was required at higher concentrations and longer exposure times to produce equal inhibition of the nucleotide precursor thymidine. These findings may have implications for the clinical use of these drugs and in particular would support a role for carboplatin in the treatment of squamous cell carcinoma of the head and neck, since total free-drug exposure of patients to carboplatin may be up to 16-fold greater than with DDP, and the clinical side effects of carboplatin have been shown to be well tolerated. However, one must be cautious about applying in vitro data to clinical situations.
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PMID:Effectiveness of cis-platin and carboplatin in the chemotherapy of squamous cell carcinoma grown as multicellular spheroids. 219 88

Carboplatin (CBDCA; commercial name: Paraplatin) is a platinum complex having 1-cyclobutanedicarboxylic acid group at the two chlorine positions of cisplatin (CDDP). In the preclinical studies, CBDCA was proved to be almost equally effective to various murine tumors compared to cisplatin. Compared to cisplatin, of which free platinum was not detected from 2 hr after administration, the free type of more than 85% of total platinum concentration remained in the blood even 8 hrs after administration. Total urine excretion at 2-4 hrs after administration of CBDCA was about 57-82%, indicating CBDCA's relative rapid urine excretion compared to CDDP. In the clinical trials in Japan, appreciable clinical responses were observed in head and neck, small cell lung, ovarian, uterine cervical cancers, testicular tumor and malignant lymphoma. The renal toxicity was considerably slight, resulting in almost no hydration during treatment. Nausea and vomiting were also slight and there were no hearing-loss and neurotoxicities. The dose-limiting factor (DLF) in the phase I study was myelosuppression. From these results, it was found that carboplatin's antitumor efficacies were almost identical with cisplatin and much less toxic than cisplatin. Carboplatin will serve as a useful antitumor drug in current cancer chemotherapy.
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PMID:[Development of carboplatin]. 220 18

To investigate whether each of cisplatin (CDDP) and carboplatin (CBDCA) was AUC (Area Under the Curve)-dependent or time-dependent drug, Human Tumor Clonogenic Assays (HTCA) were performed in various exposure times of CDDP or CBDCA using PC-9 cells. From the result of this study, it was shown that CDDP and CBDCA were AUC dependent drugs. Furthermore, to evaluate the combination effect of CDDP and CBDCA, we carried out HTCA using PC-9 and PC-14 (human lung adenocarcinoma cell lines) cells, and evaluated the combination effect by the median effect analysis of Chou, T.C. and Talalay, P. The combination effects were above the additive effects at the AUC ratios of free Pt in the exposure medium of 3.2, 6.5, 13.1 (CBDCA/CDDP). Especially in the combination of 3 hours exposure of CBDCA followed by 1 hour exposure of CDDP, the Combination Index by median effect analysis was from 0.74 to 0.86 at the AUC ratio of 13.1. But the combination effect was antagonistic at that of 19.5. CDDP and CBDCA, which are AUC dependent drugs, have shown different side effects in previous clinical practice. And the combination effect of both drugs is more than additive effect at the AUC ratios of free Pt of 3.2, 6.5, 13.1 (CBDCA/CDDP). It is considered that the combination chemotherapy of CDDP and CBDCA for patients of lung adenocarcinoma may be useful.
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PMID:[Probability of the combination use of cisplatin and carboplatin]. 227 19

Previously, we reported on the resistance to cis-diamminedichloroplatinum(II) (cis-DDP) of tumor cells in IgM immunocytoma tumors. In vitro cell lines were established, from tumors both sensitive and resistant to cis-DDP. The cultured cells obtained from the parent tumor were designated IgM-I, and those from a cis-DDP resistant tumor IgM/cDDP. In vitro dose response studies showed a difference in cis-DDP sensitivity with a resistance factor of approximately 20 at a relative survival of the tumor cells of 50 percent. The resistance factor was determined both in an assay with continuous cis-DDP exposure for 72 h, and in a clonogenic assay after an exposure for 1 h to various dosages of cis-DDP. The IgM/cDDP cells showed cross-resistance, in vitro and in vivo, to the currently used cis-DDP analogs carboplatin (CBDCA or JM8) and iproplatin (CHIP or JM9). Cross-resistance was also observed against the recently developed platinum(IV) compound tetraplatin. In addition, the cell line IgM/cDDP was resistant to other drugs interacting with DNA, such as doxorubicin (DXR), mitomycin C (MMC) and melphalan (L-PAM). For two non DNA-interacting drugs, vincristine (VCR), a mitosis inhibitor, and VP-16, a topoisomerase inhibitor, both cell lines were equally sensitive.
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PMID:Resistance of in vitro grown IgM immunocytoma cells to cis-diamminedichloroplatinum (II) (cis-DDP) and cross-resistance to other DNA interacting drugs. 234 18

Antitumor activity of a new platinum complex, (R)-(-)-2-aminomethylpyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II) (DWA 2114 R) against cisdiamminedichloroplatinum (II) (CDDP)-resistant tumor was examined in in vitro and in vivo experiments. CDDP-resistant line was established from L 1210 mouse leukemia cells by continuous exposure to CDDP in dose-escalation manner. Six clones were isolated from parental resistant line and one of these clones, clone f, which was found to be highly resistant (30-40 fold) to CDDP, was used in the following experiments. Clone f showed 4-7 fold cross-resistance to DWA 2114 R and 11-19 fold to cisdiammine-1, 1-cyclobutanedicarboxylatoplatinum (II) (CBDCA) in in vitro growth inhibition assay. DWA 2114 R showed the most effective antitumor activity against mice transplanted with the resistant cells in the increase of life span (ILS%). About 100% of ILS and cured mice were observed in the treatment with DWA 2114 R. On the other hand, CDDP or CBDCA showed a little increase in the survival time (less than 40% of ILS) and all mice died. These results suggest that DWA 2114 R seemed to be more effective against CDDP-resistant tumors clinically than CDDP and CBDCA.
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PMID:[Antitumor activity of a new platinum complex, (R)-(-)-2-aminomethylpyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II), against cisdiamminedichloroplatinum (II)-resistant murine leukemia cell line]. 240 58

Carboplatin, an analog of cisplatin, was evaluated in a phase II study involving 25 patients with advanced testicular tumor and 45 with transitional cell carcinoma (TCC) of the urinary tract; 21 and 38 cases, respectively, were evaluable for response. Prior treatment with cisplatin-based chemotherapy had occurred in 7 of the testicular cancer patients and in 11 with TCC. The response rate (complete + partial response) in testicular tumors was 47.6%. The best response rate was observed in seminomas (70.0%), whereas the response rate in nonseminomas was 27.3%. The seminoma patients had mainly stage IIIA or less than IIIA disease, with metastatic lesions restricted to the lymph nodes. Three responses were seen in patients previously treated with cisplatin. In TCC, the response rate was 18.4%. Good-risk patients were treated with a dose of 400 mg/m2 every 4 weeks, whereas poor-risk patients received a lower dose of 300 mg/m2. The response rates for good-risk patients were 50.0% in testicular lesions and 26.1% in TCC. For poor-risk patients, the response rates were 40.0% and 6.7%, respectively. Carboplatin was well tolerated, with no significant renal impairment or ototoxicity detected. Nausea and vomiting were experienced by 51.7% of patients, but the severity was low; half of these patients demonstrated WHO grade I toxicity. However, myelosuppression was severe. In conclusion, carboplatin demonstrated activity in both testicular tumors and TCC and is worthy of further study, especially in combination with other active drugs.
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PMID:Phase II trial of carboplatin in patients with advanced germ-cell testicular tumors and transitional cell carcinomas of the urinary tract. 246 79

The antitumor activities of five anticancer drugs, at IC50 dosages cisplatin (CDDP), adriamycin (ADM), etoposide (VP-16), mitomycin C (MMC) and carboplatin (CBDCA) were studies an 7,12-dimethylbenz (a) anthracene induced rat ovarian cancer cell line (DMBA-OC-1) and a human ovarian serous adenocarcinoma cell line (KOC-1S). The IC50 dosage of anticancer drugs for DMBA-OC-1 was: CDDP 0.2 microgram/ml. ADM 0.04 microgram/ml, VP-16 3.0 microgram/ml, MMC 0.1 microgram/ml and CBDCA 10.0 micrograms/ml. The results of our study except those for MMC were parallel with those published on in vivo studies. The IC50 dosages of DMBA-OC-1 did not have enough antitumor activity for KOC-1S, whereas the original KOC-1S tumor strongly resisted the combination chemotherapy (CDDP, ADM and cyclophosphamide). Therefore, our findings suggested the possibility of the separation of multiple drug resistant clones from KOC-1S. These two cell lines had quite different antitumor activity characteristics.
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PMID:[Effects of anticancer agents on 7, 12-dimethylbenz (a) anthracene induced rat ovarian cancer cell line (DMBA-OC-1) and human ovarian serous adenocarcinoma cell line (KOC-1S)]. 251 Dec 56


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