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  • 1
    Digitale Medien
    Digitale Medien
    P-GLYCOPROTEIN EXPRESSION IN CLASSICAL MULTI-DRUG RESISTANT LEUKAEMIA CELLS DOES NOT CORRELATE WITH ENHANCED CHLORIDE CHANNEL ACTIVITY (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 21 (1994), S. 0 
    Details
    ISSN: 1440-1681
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: 1. P-glycoprotein (Pgp) is an ATP-dependent drug efflux pump responsible for classical multi-drug resistance (MDR).2. Pgp is part of a supergene family of membrane transport proteins that includes the cystic fibrosis gene product.3. Transfection of cells with the MDRl gene has been previously shown to generate volume-regulated chloride channel activity in association with Pgp expression.4. We have used whole-cell patch clamping to examine the drug-sensitive T lymphoblastic cell line CEM-CCRF and its classical MDR derivative CEM/VLB100. The results suggest that expression of Pgp is not associated with increased chloride channel activity in this multi-drug resistant cell line.5. We were unable to confirm previously reported results in MDRl transfected cell lines that suggested that Pgp was associated with the presence of volume-regulated chloride channels.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1440-1681.1994.tb02475.x
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  • 2
    Digitale Medien
    Digitale Medien
    Differential effects of estrogen, tamoxifen and the pure antiestrogen ICI 182,780 in human drug-resistant leukemia cell lines (1993)
    Springer
    Cancer chemotherapy and pharmacology 33 (1993), S. 123-129 
    Details
    ISSN: 1432-0843
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract ICI 182,780, a potent, new steroidal antiestrogen without apparent agonist activity, appears to be a potent modulator of the classic multidrug resistance (MDR) phenotype in the CEM/A7, CEM/VLB100 and K562/VIN100 MDR cell lines. This reagent had no effect on the respective parental CCRF-CEM and K562 cell lines. The use of 1.25 μM ICI 182,780 resulted in a 6- to 7-fold decrease in doxorubicin resistance in the CEM/A7 and CEM/VLB100 cell lines. A dose-response effect was observed at ICI 182,780 concentrations of up to 5 μM. As compared with tamoxifen (TAM), ICI 182,780 was 2 and 4 times more effective in the K562/VIN100 and CEM/A7 cell lines, respectively. ICI 182,780 at 0.625 μM increased [3H]-daunomycin uptake (P〈0.0001) as effectively as 5 μM TAM in the resistant CEM/A7 line. Drug-efflux studies showed that 5 μM ICI 182,780 significantly decreased drug efflux as compared with 5 μM TAM (P〈0.0001). Estradiol (EST) at 10 μM increased doxorubicin resistance by 1.2–1.3 times in the CEM/A7 and CEM/VLB100 cell lines and significantly decreased drug accumulation (P=0.002) and retention (P〈0.001) in the CEM/A7 cell line. However, the addition of 10 μM EST to 1–2 μM ICI 182,780 did not inhibit the ability of ICI 182,780 to modulate doxorubicin resistance in the two resistant cell lines. Using reverse-phase high-performance liquid chromatography (HPLC) to measure lipophilicity, we found no apparent association between the ability of ICI 182,780, TAM or EST to modulate resistance and their relative hydrophobicity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00685329
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  • 3
    Digitale Medien
    Digitale Medien
    Etoposide, carboplatin, cyclophosphamide and vincristine in previously untreated patients with small-cell lung cancer (1990)
    Springer
    Cancer chemotherapy and pharmacology 25 (1990), S. 367-370 
    Details
    ISSN: 1432-0843
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The efficacy and toxicity of 120 mg/m2 etoposide and 100 mg/m2 carboplatin given i.v. daily x 3 together with 750 mg/m2 cyclophosphamide and 14 mg/m2 vincristine given i.v. on day 1 (ECCO) in a regimen given every 28 days for 6 courses was assessed in 90 (40 limited stage, 50 extensive stage) previously untreated patients with small-cell lung cancer. Mediastinal irradiation using 50 Gy in 25 fractions was given to limitedstage patients without progression after 3 courses of chemotherapy. Cranial irradiation with 30 Gy in 10 fractions was given to all patients attaining a complete response (CR). Objective responses were seen in 83% [CR, 60%; partial response (PR), 23%] of patients with limited and 76% (CR, 22%; PR, 54%) of those with extensive disease. The median relapse-free survival for objective responders with limited disease was 13.4 months, with a median of 8.0 months for extensive-stage patients. The median relapse-free survival for patients achieving a CR was 13.4 months, with a median of 7.8 months for those undergoing a PR. The median survival was 13.3 months for patients with limited disease, with a median of 9.6 months for those with extensive disease. The median survival following a CR was 18.2 months, with a median survival of 9.9 months for those showing a PR. The combination was well tolerated, with either no nausea or nausea only (WHO grade 0 or 1) in 56% of patients and minimal mucositis, renal toxicity, neurotoxicity or ototoxicity. Neutropenia measuring 〈1.0×109 WBC/l (WHO grade 3 or 4) was seen in 74% of patients, with two deaths due to infection occurring during neutropenia. Thrombocytopenia of 〈50×109 platelets/l (WHO grade 3 or 4) occurred in 24% of patients. ECCO is a new, active, welltolerated program for previously untreated patients with small-cell lung cancer.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00686239
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  • 4
    Digitale Medien
    Digitale Medien
    Patients' beliefs about cancer management (1996)
    Springer
    Supportive care in cancer 4 (1996), S. 110-117 
    Details
    ISSN: 1433-7339
    Schlagwort(e): Beliefs ; Patients ; Cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The results of a questionnaire answered by 205 medical patients are reported (100 patients with cancer and 105 with other medical conditions). The questionnaire examined beliefs and preferences regarding various aspects of cancer, including expectations of medical management and treatment. The issues examined relate to beliefs and preferences about information giving, trust of doctors' control of decision making, expectations of help, expectations of treatment, the treatment of cancer pain including morphine use, and issues of terminal care. Some patients appear to hold the inconsistent beliefs that doctors should tell them all they want to know, but that doctors do not know a lot of what they would like to be told. They were also ambivalent about who should make decisions, patient or doctor, suggesting a preference for collaborative consensus decision making. It may be important to inform patients more clearly about what doctors can and cannot reasonably be expected to know and do. Some incorrect beliefs about management were related to fear about having cancer. The results suggest the need for better communication between patients and their professional carers and the need for accessible health information about cancer management to be available to the general public.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01845760
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  • 5
    Digitale Medien
    Digitale Medien
    Phase II study of 10-EdAM in patients with squamous cell carcinoma of the head and neck, previously untreated with chemotherapy (1992)
    Springer
    Investigational new drugs 10 (1992), S. 31-34 
    Details
    ISSN: 1573-0646
    Schlagwort(e): head and neck cancer ; 10 EdAM ; edatrexate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Fifteen patients with advanced head and neck cancer not curable with radiation or surgery were entered into a phase II study of 10-EdAM. None of the patients had received prior chemotherapy. 10-EdAM was administered intravenously at a dose of 80 mg/m2 each week. Four patients were not eligible for evaluation. Two died before completing four cycles of chemotherapy, one refused further treatment and one developed hepatic toxicity resulting in withdrawal. Of the remaining patients, three had a partial response. The major toxicities were leukopenia and mucositis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01275477
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  • 6
    Digitale Medien
    Digitale Medien
    Induction of insulin‐like growth factor binding protein expression by ICI 182,780 in a tamoxifen‐resistant human breast cancer cell line (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 231-242 
    Details
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; ICI 182 ; 780 ; IGFBPs ; tamoxifen resistance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Earlier studies in our laboratory demonstrated that the steroidal antiestrogen ICI 182,780 is very effective in abolishing the tamoxifen‐resistant proliferation of MCF 7/5‐23 cells [1]. In addition, preliminary binding studies showed that ICI 182,780 increased the binding of insulin‐like growth factor (IGF)‐I to the MCF 7/5‐23 cells, although this finding was not the result of an increase in the expression of the insulin‐like growth factor‐I receptor (IGF‐IR). Hence, we reasoned that the inhibition of tamoxifen‐resistant cell growth by ICI 182,780 might have been due to increased expression of insulin‐like growth factor binding proteins (IGFBPs). We observed the up‐regulation of non‐insulin‐suppressible IGF‐I binding in both the tamoxifen‐sensitive MCF 7/5‐21 cell line (1.5‐fold) and the tamoxifen‐resistant MCF 7/5‐23 cell line (2.5‐fold) after 5 days of treatment with ICI 182,780 (10−7 M) in serum‐free medium, suggesting a role for cell‐associated IGFBPs. Affinity cross‐linking experiments confirmed the presence of an IGF‐I:IGFBP complex of approximately 38‐kDa in tamoxifen or ICI 182,780‐treated cells. Western ligand blots showed higher levels of a soluble 30‐kDa IGFBP in media conditioned by either of the subclones that had been treated with ICI 182,780, an effect consistently opposed by estrogen (E2:10−9 M). RT‐PCR showed higher levels of IGFBP‐5 mRNA than any of the other known IGFBPs, suggesting that this was the major IGFBP subtype. The protein was subsequently identified by Western immunoblotting as IGFBP‐5. In conclusion, we postulate that this may be a mechanism contributing to the greater potency of ICI 182,780 in the growth inhibition of the MCF 7/5‐23, tamoxifen‐resistant cell line.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1006274712664
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