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)

We examined both in vitro and in vivo chemosensitivity of the human epidermoid carcinoma xenograft xeKB3-1-R which shows overexpression of the multidrug resistance gene (MDR1). XeKB3-1-R was sensitive to vincristine (VCR, 6%) and doxorubicin (DOX, 9%) in the adhesive tumor cell culture system in vitro. However, this xenograft showed decreased sensitivity to VCR (65%) and DOX (42%) in an in vivo chemosensitivity assay. The in vivo resistance of xeKB3-1-R to both VCR and DOX was reversed by coadministration of cyclosporin A (VCR 22%, DOX 11%). The xenograft xeKB3-1-R expressed significantly higher levels of MDR1 than xeKB3-1. The results confirmed that multidrug resistance in xeKB3-1-R was related to enhanced MDR1 expression in vivo. The observed discrepancies between in vitro and in vivo chemosensitivities suggest that the in vivo sensitivity assay more accurately reflects drug resistance as a result of low-level MDR1 overexpression in solid tumors.
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PMID:Advantage of in vivo chemosensitivity assay to detect vincristine-resistance in a human epidermoid carcinoma xenograft. 868 21

The effect of calmodulin antagonist trifluoperazine (TFP) on in vitro drug sensitivity of primary cultured lung cancer cells was studied in 28 cases with MTT assay. TFP was found to enhance significantly the anticancer activities of VCR, ADR and VP16 (P < 0.01 or < 0.05). But TFP could not sensitize tumor cells to DDP. TFP may therefore be useful as an adjunct in chemotherapy of lung cancer.
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PMID:[Effect of calmodulin antagonist on chemosensitivity of primary cultured lung cancer cells]. 869 72

Before CDDP was clinically used, combination chemotherapy regimens like BLM + MMC, VCR + MTX-LV + BLM, VCR + MTX-LV + BLM + MMC had been used for recurrent tumors of the head and neck. In a phase II study with CDDP, we experienced two patients with long-term survival (12, 15+) who were treated with CDDP as a second-line chemotherapy for recurrent tumors. Cisplatin was evaluated as a potentially curative agent. After that, CDDP based regimens have been used as neo-adjuvant setting (first-line chemotherapy). So it became quite difficult to make up a second-line chemotherapy since CDDP based regimens have been used as the first-line chemotherapy. We conducted basic research on second-line chemotherapy for recurrent head and neck cancer: (1) cross-resistance studies on head and neck cancer cell lines resistant to CDDP, 5-FU, MTX and BLM; (2) second line chemotherapy for CDDP + PEP combination chemotherapy, which was developed by us, in human KB cell line; and (3) effects of etoposide plus mitomycin C on head and neck squamous cell carcinoma in monolayer and multicellular tumor spheroid. Based on our long-term experience with chemotherapy for head and neck cancer, and the results of the above-mentioned basic research, we established a policy to select second-line chemotherapy for recurrent head and neck cancer, especially in cases previously treated with chemotherapy.
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PMID:[Head and neck cancer]. 875

The antitumor activity of S 16020-2, a new olivacine derivative, was investigated in vivo and compared with that of Adriamycin and elliptinium acetate in a panel of murine (P388 leukemia, M5076 sarcoma, Lewis lung carcinoma, and B16 melanoma) and human (NCI-H460 non-small-cell lung and MCF7 breast carcinomas) tumor models. S 16020-2 given i.v. was active against P388 leukemia implanted i.p., s.c., or intracerebrally. The therapeutic effect of an intermittent schedule (administration on days 1, 5, 9) was superior to that of single-dose treatment, allowing the i.v. administration of high total doses of S 16020-2 and resulting in the cure of 60% of mice in the i.p. P388 model. In this model, S 16020-2 was more active than elliptinium acetate and showed a better therapeutic index than Adriamycin: > or = 8 versus 2. A good therapeutic effect of S 16020-2 was also observed in three P388 leukemia sublines displaying the classic multidrug-resistance phenotype, namely, P388/VCR, P388/VCR-20, and P388/MDRC.04, the latter being totally insensitive to vincristine and Adriamycin. However, S 16020-2 was not active against the P388/ADR leukemia, a model highly resistant to adriamycin in vivo. S 16020-2 was both more active than Adriamycin and curative in the M5076 sarcoma and Lewis lung carcinoma implanted s.c. In the B16 melanoma implanted i.p. or s.c., S 16020-2 was less active than Adriamycin. Against the NCI-H460 human tumor xenograft, S 16020-2 demonstrated activity superior to that of Adriamycin (T/C = 20% versus 43% on day 21). Against the MCF7 breast cancer xenograft, S 16020-2 was active, but less so than Adriamycin (T/C = 23% versus 9% on day 21), whereas elliptinium acetate was marginally active (T/C = 49% on day 24). The hematological toxicity of S 16020-2 given to B6D2F1 mice at pharmacological dose appeared to be less severe than that of Adriamycin, particularly in bone-marrow stem cells. These results demonstrate that S 16020-2 is a highly active antitumor drug in various experimental tumor models and is markedly more efficient than elliptinium acetate. Because of its pharmacological profile, which is globally different from that of Adriamycin, S 16020-2 is considered an interesting candidate for clinical trials.
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PMID:In vivo antitumor activity of S 16020-2, a new olivacine derivative. 882 92

A 25-year-old male patient of invasive thymoma was referred to our institute on March'95. He had night coughs and on the annual chest X ray exam a large tumor was found in antero-superior mediastinum. At first his tumor was too large to be resected and left brachiocephalic vein was completely occluded. By needle biopsy it was proved to be thymoma, therefore, preoperative chemotherapy was planned. The tumor responded well to the two courses of ADOC (ADM, CDDP, VCR, CAP) therapy and the tumor seemed to become resectable. In June operation was performed and the tumor was resected completely. It appears that in case of stage Ill invasive thymoma, preoperative chemotherapy is one of the choices although it seems unresectable.
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PMID:[A case of invasive thymoma made resectable by preoperative chemotherapy]. 882 36

The aim of these experimental and clinical studies was to determine if verapamil helps overcome multidrug resistance in tumor cells and in cancer patients. The effect of the calcium channel blocker verapamil on the antiproliferative activity of epirubicin (Farmorubicin, Farmitalia) was followed up in in vitro studies on two constant human leukemia cell lines: CEM/O (P-gp negative) and CEM/VCR 1000 with a positive multidrug resistant (MDR) phenotype. The MTT assay was used to study the antiproliferative activity. Verapamil in concentrations of 3 and 10 micrograms/ml enhanced by 10-fold and 19-fold, respectively, the effect of epirubicin in CEM/VCR 1000 cells and had no significant effect on epirubicin activity in CEM/O. Eleven patients with measurable stage IV breast cancer, clinically resistant to anthracycline treatment, received the FEC combination (5-fluorouracil-epirubicin-cyclophosphamide) twice with verapamil pretreatment, p.o. at the doses of 1280-2560 mg. There were two complete remissions (soft tissue metastases), four partial remissions (soft tissue metastases and lung metastases), and three stable diseases. These studies confirm the possibilities of overcoming multidrug resistance by the administration of verapamil in tumor cells and in cancer patients.
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PMID:Does verapamil help overcome multidrug resistance in tumor cell lines and cancer patients? 887 36

S16020-2 is a new olivacine derivative which has recently shown a marked antitumor activity in various experimental models. This study was undertaken in order to measure the inhibition of the proliferation of various sensitive and resistant tumor cell lines, by S16020-2, and to obtain information concerning its mechanism of action. For a continuous exposure, S16020-2 was as cytotoxic as adriamycin (ADR) (mean IC50 of about 28 nM) and on average, 46 fold more potent than elliptinium acetate (ELP), against a panel of 20 non-multidrug resistant cell lines. With a short exposure (1 hour) followed by a post-incubation of 95 hours in drug-free medium, S16020-2 was 5 and 6 fold more cytotoxic than ADR for human lung A549 and murine melanoma B16 cells, respectively. Furthermore, S16020-2 inhibited more actively the formation of colonies issued from proliferating cells, compared to colonies issued from quiescent A549 cells. Because quiescent cells demonstrated a 3 fold lower level of topoisomerase II alpha (topo II) than proliferating cells, these results suggest that this enzyme could be a potential target for S16020-2. In addition, as demonstrated by flow cytometric studies, S16020-2 intercalated into DNA and induced a cell cycle arrest in G2. Cell lines displaying the multidrug resistance (MDR) phenotype, P388/ADR-1, P388/ADR, P388/VCR-20, KB-A1, DC-3F/AD, S1/tMDR, and Colo320DM, were more sensitive to S16020-2 than to ADR or ELP, as shown by the mean resistance factors, 8, 201, and 23 respectively. In addition, the two cell lines displaying the pure classical MDR phenotype, linked exclusively to the P-glycoprotein (P-gp) overexpression (P388/VCR-20 and S1/tMDR), were as sensitive to S16020-2 as their sensitive parental counterparts, although they were resistant to ADR. S16020-2 is thus one of the most potent olivacine and ellipticine derivative yet characterized. The good cytotoxicity of S16020-2 against cells displaying a P-gp-mediated multidrug resistance, and its antitumor activity in vivo delineate an important chemotherapeutic potential for this drug.
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PMID:In vitro cytotoxicity of S16020-2, a new olivacine derivative. 891 38

A retrospective analysis of treatment results of 242 children with Wilms tumor treated in the years 1962-1989 is presented. The patients (pts) were divided into 4 groups according to methods of treatment that changed with the time. Group I consisted of patients treated between 1962-1965. Surgery followed by radiotherapy (RTX) and monochemotherapy (CHT) (ACTD) were the main treatment methods. Group II consisted of 68 patients treated between 1966-1974. In this group, surgery was followed by RTX and CHT (multiple courses of ACTD + VCR). Group III included 68 patients treated between 1975-1982. Preoperative RTX (20 Gy) and CHT (ACTD) were administered. RTX (total 35 Gy) and adjuvant CHT were continued after surgery. Group IV consisted of 62 patients treated in 1982-1989. Preoperative CHT (ACTD, VCR +/- ADR) was introduced. Adjuvant treatment depended on stage and histology of the tumor. The treatment results were as follows: 27, 66.1, 38.2 and 85.4% of survival, respectively. This points to the beneficial role of induction CHT, delayed surgery with adjusting the intensity of further adjuvant treatment to stage and tumor histology.
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PMID:[Progress in the treatment of children with Wilms' tumor in the Department of Pediatric Oncology at the Institute of Mother and Child]. 892 68

Anti-cancer drugs and cytotoxic cytokines such as members of the TNF/Fas-ligand family play a predominant role in apoptosis induction in tumor cells, and are critical in cancer therapy. In this study we used the human breast-carcinoma cell line MCF7, its derivatives MCF7Adr (resistant to adriamycin) and R-A1 (resistant to TNF), to determine the impact of acquired drug and cytokine resistance on susceptibility to Fas-induced cytotoxicity and Fas-antigen expression. While MCF7 and R-A1 cells were killed by anti-Fas in the presence of IFN-gamma, MCF7Adr was found to be resistant to Fas-mediated apoptosis. This resistance was correlated with a loss of surface Fas-protein expression. Fas-gene transfer in MCF7Adr resulted in high sensitivity to Fas-mediated cytotoxicity, indicating that the Fas signalling pathway is virtually intact in this cell line. Over-expression of the MDR1 gene in MCF7 following gene transfer did not affect Fas expression and anti-Fas sensitivity, suggesting that the P-gp-mediated multidrug-resistance phenotype is not directly involved in the loss of Fas expression, contrary to what has been observed by others in T-cell lines. Furthermore, the down-regulation of Fas expression and subsequent resistance to anti-Fas were observed in drug-resistant human ovarian-carcinoma IGR-OV1/VCR cells and leukemic lymphoblast CEM/VLB cells, suggesting that the alteration of Fas expression following drug-resistance selection is not restricted to one cell type.
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PMID:Impairment of Fas-antigen expression in adriamycin-resistant but not TNF-resistant MCF7 tumor cells. 894 27

A 15-year-old boy had metastasis to the spinal cord and then to the lung after an operation to remove a primary medulloblastoma. A medulloblastoma developed at the age of 10 years. The tumor was completely resected and the brain and spinal cord were irradiated. At the age of 13 years, metastasis to the sacral spinal cord developed and was treated with radiotherapy and intramedullary injection of methotrexate. At the age of 15 years, metastasis to the lung developed and was treated with chemotherapy (CBDCA, VP-16) followed by radiotherapy. Three months after the end of that therapy, the disease recurred but another course of radiotherapy and chemotherapy (VCR) was successful. Chemotherapy and radiotherapy were effective against metastatic lesions of medulloblastoma. With improvement in the survival rate among patients with medulloblastoma, we can expect incidence of extraneural metastases to increase. In addition to recurrence of the primary lesion and intramedullary dissemination, these metastatic lesions also require attention.
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PMID:[A patient with lung metastasis of medulloblastoma]. 897 84


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