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  • 32P-Orthophosphat  (2)
  • Phase II study  (2)
  • paclitaxel  (2)
  • 1
    Digitale Medien
    Digitale Medien
    Paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil plus leucovorin in the second-line treatment of metastatic breast cancer: Results of a phase II study (1998)
    Springer
    Annals of oncology 9 (1998), S. 45-50 
    Details
    ISSN: 1569-8041
    Schlagwort(e): metastatic breast cancer ; paclitaxel ; weekly 24-hour 5-FU/leucovorin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Purpose: To evaluate the antitumor activity in terms of response rate (RR), time to progression (TTP) and survival of paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil (5-FU)/leucovorin in pretreated metastatic breast cancer (MBC). Patients and methods: Fifty-four patients with bidimensionally measureable disease were included during phase II. Thirty-two had anthracycline resistant disease. Treatment consisted of 5-FU (24-hour i.v. infusion) 2.0 g/m2, leucovorin (two-hour i.v. infusion prior to 5-FU) 500 mg/m2, weekly for six weeks (day 1, 8, 15, 22, 29, 36) and paclitaxel (three-hour i.v. infusion) 175 mg/m2 was administered additionally on days 1 and 22, q 50 days. Results: We observed complete remissions in 4% of patients (2 of 54), partial remissions in 55% (30 of 54), stable disease in 37% (20 of 54) and progressive disease in 4% (2 of 54). The overall RR was 59% (95% CI 48%–72%). The RR in 32 patients with anthracycline resistant disease was 59% (19 of 32). The median duration of response was 12 months (3–22), median TTP eight months (2–22) and median survival time 15 months (2–28). Neutropenia was common, but of CTC grade 2 or 3 in most patients. Nonhematologic toxicities mostly consisted of CTC grade 1 and 2 myalgia, diarrhea, mucosits, nausea and vomiting. Conclusions: Paclitaxel combined with weekly 24-hour infusional 5-FU/leucovorin is well tolerated in the second line treatment of MBC. High efficacy was documented even in the treatment of anthracycline resistant disease, which warrants further evaluation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008292332166
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  • 2
    Digitale Medien
    Digitale Medien
    Phase II trial of aclacinomycin A in acute leukemia and various solid tumors (1983)
    Springer
    Journal of cancer research and clinical oncology 105 (1983), S. 162-165 
    Details
    ISSN: 1432-1335
    Schlagwort(e): Aclacinomycin A ; Phase II study ; Refractory neoplasms
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Aclacinomycin A (ACM) is a new anthracycline antibiotic with a reduced cardiac toxicity in animal models. A phase II study was performed in a total of 25 patients, 23 of whom are evaluable for response. All suffered from recurrent and advanced tumors. Pretreatment consisted of at least four different chemotherapeutic agents (range: 4–9). Lung cancer patients (3/9) were irradiated to the mediastinum. Eighteen patients were pretreated with doxo- or daunomycin. The dose for solid tumors was 2–3 mg/kg given on 3 consecutive days every 3 weeks. Leukemia patients received a daily dose of 20 mg/m2, and standard response criteria were used. Marked reductions of leukocyte counts were achieved in leukemia patients. The overall response rate was about 15% in solid tumors, but major objective responses (CR+PR) have not been observed. Myelosuppression was commonly moderate in solid tumor patients, nausea and vomiting were rare, and alopecia was not induced. Cumulative cardiotoxicity was not evaluated in this trial. Treatment with ACM requires further investigation in acute leukemias and solid tumors, not pretreated with anthracycline antibiotics.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00406927
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  • 3
    Digitale Medien
    Digitale Medien
    Isolation of rapidly labelled nuclear RNA of high specific activity from human leukaemic cells (1973)
    Springer
    Journal of molecular medicine 51 (1973), S. 677-679 
    Details
    ISSN: 1432-1440
    Schlagwort(e): Human Leukaemia ; 32P-orthophosphate ; nuclear RNA ; Menschliche Leukämie ; 32P-Orthophosphat ; nucleare RNA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Es werden Methoden zur Präparation von nuklearer RNA hoher spezifischer Aktivität aus menschlichen Leukämiezellen beschrieben. Das Inkubationsmedium basiert auf Hepes-Puffer und der Verwendung von dialysiertem Kalbsserum zur Verbesserung der Bedingungen für den32P-Orthophosphat-Einbau in die hochmolekulare Kern-RNA. Die erreichten spezifischen Aktivitäten erlauben detaillierte Nucleotid- und Oligonucleotidanalysen der verschiedenartigen Ribonucleinsäurespezies in menschlichen Leukämiezellen.
    Notizen: Summary Methods are presented which provide the preparation of highly labelled nuclear RNA from cells of the different forms of human leukaemia. An incubation medium is described that is based on Hepes buffer and on the use of exhaustively dialyzed fetal calf serum offering suitable conditions for the uptake of32P-orthophosphate into the RNA of leukaemic nuclei. The specific activities reached may allow more detailed nucleotide and oligonucleotide analyses of the various RNA species present in human leukaemic cells.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01468172
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  • 4
    Digitale Medien
    Digitale Medien
    Differences in nuclear RNA labelling patterns of BURKITT lymphoma, leukaemic lymphosarcoma and various human leukaemias (1973)
    Springer
    Journal of molecular medicine 51 (1973), S. 680-684 
    Details
    ISSN: 1432-1440
    Schlagwort(e): BURKITT lymphoma ; leukaemic lymphosarcoma ; chronic myelotic leukaemia (CML) ; acute myeloblastic leukaemia (AML) ; chronic lymphocytic leukaemia (CLL) ; 32P-orthophosphate ; nuclear RNA ; Burkitt-Lymphom ; leukämische Lymphosarcomatose ; akute myeloische Leukämie (AML) ; chronischmyeloische Leukämie (CML) ; chronisch-lymphatische Leukämie (CLL) ; 32P-Orthophosphat ; nucleare RNA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Aus Zellen des Burkitt-Lymphoms, eukämischer Lymphosarcomatose, chronisch-lymphatischer Leukämie, chronisch-myeloischer und akuter myeloischer Leukämie wurden nach sechsstündiger32P-Markierung in einem phosphatarmen Medium Zellkerne mit Hilfe des Zitronensäure-Verfahrens isoliert und die nucleare RNA mit der heißen Phenol-SDS-Methode extrahiert. Nach Fraktionierung der kernspezifischen Nucleinsäuren über Zucker-Dichtegradienten fanden sich markante Unterschiede in der32P-Radioaktivitätsverteilung. Insbesondere war eine differente Markierung der nuclearen 45S RNA, welche als Vorläufer ribosomaler 28S und 18S RNA gilt, festzustellen. Die niedrigsten spezifischen Aktivitäten des ribosomalen Vorläufers fanden sich bei der CML, die höchsten bei AML, leukämischem Lymphosarkom und Burkitt-Tumor. Bemerkenswert erscheint die aktive Synthese präribosomaler (45S/35S) RNA in Zellen der CLL, deren DNA-Syntheserate äußerst niedrig ist. Zur Klärung der Frage, ob die im Nucleolus der unreifen Zellen gebildeten hochmolekularen Nucleinsäuren quantitative oder qualitative Unterschiede zwischen myeloischen und lymphatischen Zellen aufweisen, sind strukturchemische Untersuchungen im Gange.
    Notizen: Summary Nuclear RNA was isolated from citric acid nuclei derived from AML, CML, CLL, leukaemic lymphosarcoma and BURKITT lymphoma cells after 6 hours incubation with32P-orthophosphate in a phosphate-free medium. In fractionations on sucrose density gradients, marked differences were found in the distribution of the32P-radioactivity mainly in the 45S fraction containing the ribosomal precursor RNA. The lowest specific activities of nuclear 45S RNA were found in CML; very high labelling accurred in cells of AML, leukaemic lymphosarcoma and BURKITT lymphoma. In CLL cells which are known for lack in DNA synthesis, pre-ribosomal 45S and 35S RNA were labelled to a remarkable extent. Studies are in progress in order to define possible differences in nuclear RNA structures between lymphocytic and granulocytic cell lines.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01468173
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  • 5
    Digitale Medien
    Digitale Medien
    Phase II evaluation of fractionated low and single high dose cisplatin in various tumors (1984)
    Springer
    Journal of cancer research and clinical oncology 107 (1984), S. 57-60 
    Details
    ISSN: 1432-1335
    Schlagwort(e): Cisplatin ; Phase II study ; Solid tumors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Seventy-three evaluable patients with advanced measurable solid tumors were given cisdichlorodiammineplatinum (II) (DDP) at a dose of 20 mg/M2 IV for 1–5 days every 3 weeks, and 19 patients who failed on this low dose DDP protocol received a single high dose of 100 mg/M2 IV once every 3 weeks. Forty-six patients had received prior chemotherapy, and 29 patients were untreated. Results included four complete responses (5.5%) in malignant melanoma, spindle-cell sarcoma, adrenal carcinoma, and bladder carcinoma lasting 2 to 4 months. In 21 patients (28.8%), partial responses were achieved. Twenty-two patients (30.1%) showed stable disease and 26 (35.6%) had tumor progression. A response rate of 25% (4/16 patients) was found for malignant melanoma, 45.5% (5/11) for nonsmall-cell lung cancer, and 35.3% (6/17) for sarcomas of various types. One patient with teratocarcinoma, who relapsed on low-dose DDP, had another partial remission for 4 months after high-dose therapy. Toxicity was most commonly seen with gastrointestinal side effects and myelosuppression. Cumulative nephrotoxicity was prevented by prehydration and/or treatment with furosemide or mannitol.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00395492
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  • 6
    Digitale Medien
    Digitale Medien
    Comparative antitumor efficacy of docetaxel and paclitaxel in nude mice bearing human tumor xenografts that overexpress the multidrug resistance protein (MRP) (1997)
    Springer
    Annals of oncology 8 (1997), S. 1221-1228 
    Details
    ISSN: 1569-8041
    Schlagwort(e): docetaxel ; MRP ; multidrug resistance ; nude mice ; paclitaxel
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Multidrug resistance has been associated with expression ofthe multidrug resistance protein (MRP). Recently, MRP-expression has beendetected in human tumor samples of patients with breast cancer andnon-small-cell lung cancer. Since taxoids are the most active drugs in thetreatment of both tumor entities, the antitumor efficacies of paclitaxel anddocetaxel were compared in nude mice bearing human tumor xenografts thatexpress MRP. Materials and methods: Athymic nude mice (nu/nu) bearing tumor xenograftsof parental human sarcoma HT1080 or MRP-expressing HT1080/DR4 cells (asconfirmed by Northern blot analysis) were treated with the maximum tolerateddoses (MTD) of doxorubicin ([Dx] 10 mg/kg i.v. push), paclitaxel ([PC] 50mg/kg three-hour i.v. infusion), or docetaxel ([DC] 40 mg/kg three-hour i.v.infusion). In vitro, the activity of doxorubicin, paclitaxel and docetaxelwas evaluated by the sulphorhodamine B (SRB) assay using the pyridineanalogue PAK-104P (5 µM), a potent inhibitor of MRP-function. Results: At their MTDs both taxoids showed significant activity againstMRP-negative HT1080 xenografts with response rates of 80% (40%CR) for PC and 100% (60% CR) for DC. In contrast, DC wassignificantly more active than PC in nude mice bearing doxorubicin resistantMRP-expressing HT1080/DR4 tumor xenografts (overall response rates:100% (60% CR) for DC; 10% (0% CR) for PC;0% for Dx). Since treatment of mice with the MTD of PC or DC yieldedsimilar overall toxicity (maximum weight loss for HT1080: PC 8.6 ±2.2%; DC 7.5 ± 2.2% and for HT1080/DR4: PC 11.6± 3.0%; DC 7.5 ± 1.8%, respectively), theseresults demonstrate the increase in the therapeutic index for docetaxelagainst MRP-expressing tumors. In vitro, HT1080/DR4 cells were 270-fold,6.4-fold and 2.8-fold more resistant than parental cells to doxorubicin, PCand DC, respectively. Pyridine analogue PAK-104P completely restored drugsensitivity to PC and DC, while no effect of PAK-104P on parental HT1080cells was observed. Conclusions: Both taxoids, when given at their MTDs, showed significantefficacy against parental HT1080 tumor xenografts. However, docetaxel at itsMTD was significantly more active against MRP-expressing tumor xenografts thanpaclitaxel. Furthermore, in vitro resistance of HT1080/DR4 cells was higherfor PC (6.4-fold) than for DC (2.8-fold). Since PAK-104P completely restoredsensitivity to both taxoids, the observed resistance appears to be related toMRP. These data suggest, that docetaxel is not as readily transported by MRPas paclitaxel leading to an increased therapeutic ratio in MRP-expressingtumors in vivo. Therefore, docetaxel may have therapeutic advantages in theclinical treatment of MRP-expressing tumors.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008290406221
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