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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radiotherapy and chemotherapy are often administered concurrently in an attempt to take advantage of postulated biochemical or molecular interactions between the two modalities. It is generally assumed that the drugs influence some mechanism of radioresistance rather than that radiation has any direct effect on the mechanisms of cell kill by chemotherapy. Many classes of drugs have been found to interact with radiation. Classic radiosensitizing agents include the halogenated pyrimidines and the nitroimidazoles; however, many conventional cytotoxic agents, such as hydroxyurea, 5-fluorouracil (5-FU) and cisplatin, also enhance cell kill by radiotherapy. Hydroxyurea has been shown to inhibit excision-repair of thymine dimers and single-strand DNA breaks induced by radiation. Exposure of cells to 5-FU following radiation produces synergistic cytotoxicity in several model systems. The precise cellular mechanisms by which 5-FU and radiotherapy interact have not been defined, although inhibition of repair of radiation-induced DNA damage has been postulated to occur. Cisplatin has also been shown to enhance the cytotoxicity of radiation in both cell culture and tumor-bearing animals, although the mechanisms of the interaction have not been defined. Hydroxyurea, 5-FU, and cisplatin also undergo a number of biochemical interactions that enhance their cytotoxic effects. Thus, a rationale exists for employing these drugs in combination with radiation. Additional studies are required to understand the mechanisms of drug-radiation interactions and to determine the optimal scheduling of these therapies.
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PMID:Biochemical pharmacology of chemotherapeutic drugs used as radiation enhancers. 150 77

Cisplatin (cis-dichlorodiammineplatinum (II)) acts as a tumor initiator in the mouse skin model of carcinogenesis. DNA transfection studies suggested that skin tumors initiated by cisplatin contained dominant transforming activity. Since the Harvey-ras (H-ras) gene is known to be activated by point mutations in chemically initiated mouse skin tumors, we used polymerase chain reaction (PCR) and direct DNA sequencing to analyze the DNA sequence of the H-ras gene in twelve different cisplatin-initiated skin tumors. The results of these studies indicated that cisplatin-initiated skin tumors were normal (wild-type) at codons 12, 13, 61 and 117. Thus the transforming activity associated with cisplatin initiated mouse skin tumors was not due to a mutant H-ras gene and this suggests the involvement of other transforming genes during initiation of the mouse skin with cisplatin.
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PMID:Analysis of the Harvey ras gene in cisplatin-initiated mouse skin tumors by polymerase chain reaction and direct DNA sequencing. 151 6

Cytotoxicity of thaliblastine (thalicarpine, TBL; NSC-68075) and/or cisplatin (DDP) in DDP-sensitive (O-342) and-resistant (O-342/DDP) rat ovarian tumor cell lines was comparatively determined using the MTT assay. The 50% inhibitory dose (ID50) of DDP was found to be 6.2 microM in O-342 cells and 23.4 microM in O-342/DDP cells, while, vice versa, the ID50 of TBL was 39.3 micrograms/ml in the sensitive line and 27.3 micrograms/ml in the resistant line. Furthermore, simultaneous exposure of cells to DDP and TBL showed a significant superiority over DDP alone in O-342 cells, as evaluated with variance analysis (P less than 0.001). This enhancing effect of TBL on DDP cytotoxicity, however, was not observed in the resistant cells.
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PMID:Antitumor activity of thaliblastine (NSC-68075) in experimental ovarian tumor cell lines sensitive and resistant to cisplatin. 153 81

In light of the discouraging results obtained with conventional chemotherapy of human colon cancer using 5-fluorouracil, we examined the effects of cis-diamminedichloroplatinum (cisplatin) alone and combined with 3'-deoxy-3'-azidothymidine (AZT) on chemotherapy of colorectal adenocarcinomas induced by dimethyldrazine in CD-1 mice. Thirteen weeks after a 20 week tumor induction period (15 mg/kg dimethylhydrazine weekly) groups of 19 mice were given either no therapy, or weekly cisplatin (6 mg/kg for 4 wks), AZT (400 mg/kg, wks 3 and 4), or cisplatin and AZT. Animals were autospied at death or after euthanasia on day 99 post initiation of therapy, their colons excised, fixed in buffered formalin and the number and volume of tumors measured. Cisplatin alone or with AZT decreased tumor size by 47-52%, and enhanced survival, leaving 55% of the mice alive at day 99 compared to 18% in controls. These therapeutic effects were amplified when animals were given chemotherapy during recovery from the effects of short-term dietary provision of the anti-carcinogenic steroid, dehydroepiandrosterone (DHEA). Our results suggest cisplatin is an effective chemotherapeutic agent against colon cancer in this murine model, and warrant further studies of its interaction with AZT and DHEA in enhancing this effect.
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PMID:Chemotherapy of murine colorectal carcinoma with cisplatin and cisplatin plus 3'-deoxy-3'-azidothymidine. 153 69

We have established in vivo cisplatin-resistant mouse leukemia cell lines, L-1210/DDP and P388/DDP, in order to elucidate the mechanism of acquired resistance to cisplatin. Resistance indices were 22 and 14, respectively, when the cells were exposed to cisplatin for 48 h. Uptake of cisplatin by both resistant lines was significantly reduced, compared with values for the respective parent lines (17% for L-1210/DDP and 27% for P388/DDP, at 100 microM for 1 h). While glutathione contents in the resistant cells were 1.7-1.9 times higher than those in the sensitive ones, their reduction by preincubation with buthionine sulfoximine did not influence the sensitivity of the cells to cisplatin. In addition, the resistant lines did not show lower sensitivity to CdCl2 than the respective sensitive ones, suggesting that intracellular SH groups might contribute little to the mechanism of cisplatin resistance in these cells. Postincubation with DNA repair inhibitors, caffeine and aphidicolon, did not selectively enhance the sensitivity of the resistant cells to cisplatin. These results suggested that reduced drug uptake would be a primary mechanism of cisplatin resistance in L-1210/DDP and P388/DDP. Cross-resistance patterns to platinum complexes were quite different between L-1210/DDP and P388/DDP. Colon 26/DDP, another cisplatin-resistant mouse tumor showed a different pattern from those observed with L-1210/DDP and P388/DDP. In the development of new platinum complexes we should use plural resistant lines for examining cross-resistance patterns to candidate platinum complexes.
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PMID:Characterization of acquired resistance to cis-diamminedichloroplatinum(II) in mouse leukemia cell lines. 155 3

Cisplatin has played a major role in the treatment of germ cell tumors. However, it causes renal damage, severe nausea and vomiting. It is also neurotoxic and ototoxic. Carboplatin is an analog of cisplatin which, does not cause renal damage at therapeutic doses. It is not neurotoxic or ototoxic and it produces less gastrointestinal toxicity than cisplatin. We used carboplatin alone as an initial chemotherapy in a 36-year-old man with stage IIB seminoma. Following left radical orchiectomy the patient received 4 courses of carboplatin chemotherapy. After the first course of chemotherapy, tumor markers (LDH, beta-HCG) returned to the normal range. After 4 courses, the size of the retroperitoneal metastases was significantly reduced. The toxicity of 4 courses of carboplatin chemotherapy was generally milder than that of cisplatin-based combination chemotherapies such as PVB or VAB-6. There were no episodes of septicemia, thrombocytopenic bleeding or renal deterioration. The patient did not suffer from alopecia, neuropathy, symptomatic hearing loss, severe nausea or vomiting. Nine months after the completion of carboplatin chemotherapy, the patient remains well and free from disease progression. This case strongly suggests that single agent carboplatin therapy could be an effective and less-toxic treatment for advanced seminoma.
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PMID:[A case of advanced seminoma treated effectively with single agent carboplatin therapy]. 156 62

This prospective study was undertaken to evaluate the efficacy of continuous-infusion doxorubicin and cisplatin (CI-DOX/CPPD) for the treatment of children with incompletely resected hepatic cancer. Of the 46 evaluable patients, 32 had hepatoblastoma (70%) and 14 had hepatocellular carcinoma. Ten children had stage II tumors (microscopic residual), 25 were defined as stage III (gross residual), and 11 had distant metastasis (stage IV). Twelve patients underwent initial incomplete resection of their hepatic lesions and in the 34 others tumor biopsy specimens were obtained. Chemotherapy was administered and the majority of the children (70%) had an excellent clinical response with a decrease in both alpha-fetoprotein levels and measured tumor dimensions. The combination of CI-DOX/CPDD clearly facilitated surgical management, allowing for delayed hepatic resections in 20 of the 34 patients (59%) whose tumors were initially biopsied and considered to be unresectable. Overall survival in this study demonstrates a significant improvement in comparison to the historical controls. Twenty-one patients (46%) remain in complete clinical remission an average of 30 months following diagnosis (range, 17 to 40 months). The outcome of the children with hepatoblastoma was much better than those with hepatocellular carcinoma (63% v 17% survival). Survival of the 20 children who underwent delayed hepatic resections was not statistically different from the 12 patients whose hepatic tumors were removed at the initial laparotomy (41% v 58% survival). Although no obvious survival advantage was observed in those patients who underwent initial hepatic resections, there did appear to be an increased risk of postoperative complications in children whose tumors were resected following chemotherapy (8% v 25%).
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PMID:The surgical management of children with incompletely resected hepatic cancer is facilitated by intensive chemotherapy. 165 89

A normally, relatively sensitive P 388 developed resistance within few passages (P 388/Mitox) by in vivo treatment with suboptimal doses (1 mg/kg i.v.) of mitoxantrone. This resistance remained stable over 50 generations without further drug treatment. Immunization with irradiated cells (30 Gy) 7 days before tumor challenge led to partial rejection, proving that there was a higher immunogenicity of the resistant line in comparison to the parenteral P 388 line. The P 388/Mitox showed cross-resistance towards doxorubicin, daunorubicin and vincristine. Cis-DDP and bleomycin had in the resistant line significantly better antineoplastic efficacy than in the source P 388 and should be taken into consideration as second-line therapy following development of clinical mitoxantrone resistance. Nifedipine, a calcium channel blocker, and the immunosuppressive agent ciclosporin A were able to overcome resistance partially, but the mechanisms are still unclear. The P 388/Mitox can be considered as an interesting in vivo model for further research concerning resistance mechanisms and reversal of resistance.
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PMID:Development of a mitoxantrone-resistant P 388 in vivo: approaches to overcome resistance. 170 Aug 51

We investigated the clinical effects and toxicity of chemotherapy with Cisplatin (CDDP) for head and neck cancer as the third joint research project of the Tokai Meeting for Head and Neck Tumors. The cases were examined at the cooperating institutions from September 1986 to March 1988. The subjects were 93 cases consisting of 66 patients (intravenous infusion: 47 cases; intraarterial infusion: 19 cases) of PP therapy (CDDP + PEP), 16 cases of PF therapy (CDDP + 5-FU) and 11 cases of PPV therapy (CDDP + PEP + VCR). The regimens of PP therapy were: CDDP 50-100 mg/body x 1 day, PEP 5 mg/body x 5 days (i.v.), and CDDP 10-20 mg/body x 5 days, PEP 5-10 mg/body x 5 days (i.a.). In the regimen of PF therapy, CDDP 80-100 mg/body x 1 day and 5-FU 750-1,000 mg/body x 5 days were administered. In the regimen of PPV therapy, CDDP 80-100 mg/body x 1 day, PEP 5 mg/body x 5 days and VCR 1 mg/body x 1 day were administered. As a rule, two courses of each of the regimens were performed. The total dose of CDDP in intraarterial infusion of PP therapy was significantly less than in intravenous infusion. The major results were as follows: 1) Total response rate was 57.0% on the average, and this was not significantly different among the regimens. 2) The response rate of intraarterial infusion of PP therapy was as high as that for intravenous infusion in spite of the lower CDDP dose. 3) The response rate of oral cavity was significantly higher than that of nasal cavity and paranasal sinuses. 4) In the squamous cell carcinoma, the response rate of the well differentiated type was significantly higher than that of the poorly differentiated type. 5) The leukocyte counts significantly decreased with the intravenous infusion of PP therapy, PF therapy and PPV therapy. 6) The platelet counts significantly decreased with PPV therapy. 7) There were no significant changes with time with Ccr and PaO2 of PP therapy. 8) The frequency of toxicities such as nausea and vomiting was high in the intravenous infusion of PP therapy, PF therapy and PPV therapy. However, the frequency of toxicity was low in the intraarterial infusion of PP therapy.
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PMID:[Clinical effects and toxicity of chemotherapy with cisplatin for head and neck cancer--the multi-institutional joint research in Tokai district]. 170 33

The effect of cis-DDP (cis-diamminedichloroplatinum(II)), trans-DDP (trans-diamminedichloroplatinum(II)), SPC (spermine-platinum(II) complex), and K2PtCl4 on the ribomononucleotide and RNA metabolism was studied. When Ehrlich ascites tumor cells were preincubated with the aforementioned compounds and then labeled with [C14]uridine a clear-cut suppression of the radioactive labeling of RNA was observed. As radioactivity incorporated into the pool of the free uridine nucleotides in the cells treated with platinum compounds was even higher in comparison with that of the non-treated cells a conclusion may be drawn with certainty that the platinum compounds studied inhibit RNA biosynthesis. It was also found that under the effect of these compounds in the in vivo-assessed rate of the conversion of uridine nucleotides into cytidine nucleotides was considerably diminished. Using NaH14CO3 as a radioactive precursor it was shown that platinum compounds also inhibited purine biosynthesis de novo, in particular the conversion of IMP into GMP and AMP. The pronounced inhibitory effect of the platinum compounds on essential steps of the pyrimidine and purine biosynthesis de novo may be at least partly responsible for the firmly established inhibition in the present study of RNA biosynthesis by platinum compounds. The inhibition of the synthesis of the mononucleotides and RNA by the platinum compounds may be closely related to their cytostatic and cytotoxic activities.
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PMID:The effect of some platinum compounds on the biosynthesis of RNA and its precursors. 170 15


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