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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 25 (1969), S. 489-490 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Ascites tumour cells have been employed to study the reactivity of Zn++ on nucleic acid biosynthesis. 10−4 M Zn++ caused a selective inhibition of DNA synthesis of intact cells. The rate of RNA- and protein-biosynthesis, however, remained unchanged. The activity of DNA polymerase as well as DNA dependent RNA polymerase was strongly affected by Zn++ in vitro.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1569-8041
    Keywords: metastatic breast cancer ; paclitaxel ; weekly 24-hour 5-FU/leucovorin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1569-8041
    Keywords: biochemical modulation ; 5-fluorouracil ; methotrexate ; pancreatic cancer ; phosphonacetyl-L-aspartate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To evaluate the effect of biochemical modulation by PALA and methotrexate on the therapeutic activity of 5-fluorouracil (5-FU) in patients with advanced pancreatic adenocarcinoma. Patients and methods: The treatment protocol consisted of phosphonacetyl-L-aspartate (PALA) 250 mg/m2 i.v. 15-minute infusion followed by methotrexate 200 mg/m2 i.v. 30-minute infusion on day 1 and 5-FU 600 mg/m2 i.v. push on day 2. Folinic acid was given at 15 mg/m2 p.o. every six hours for eight doses, starting 24 hours after methotrexate infusion. Cycles were repeated every two weeks. Results: Thirty patients with advanced chemotherapy-naive pancreatic cancer were included; 26 had measurable disease. Median age 56 years (27–72); median PS 1 (0–2). One PR (3.9%) was achieved; nine patients had stable disease. Median time to progression was 91 days. Median survival was 177 days and one year survival was 13.3% (4 of 30 patients). Treatment was well tolerated; diarrhea WHO grade 2 or 3 occurred in six patients; stomatitis WHO grade 2 and 3 in nine patients. Conclusions: Modulation of 5-FU by PALA and MTX given in this dose and schedule appears to be ineffective in patients with advanced pancreatic adenocarcinoma.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1335
    Keywords: Key words Bendamustine ; Breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A phase II pilot study of bendamustine as salvage treatment in patients with advanced breast cancer was performed to determine the objective response rates and make further observations on the toxicity of this drug. A group of 37 patients, pretreated with chemotherapy for advanced disease, entered the trial. Treatment consisted of 150 mg/m2 bendamustine on days 1 and 2 of a 4-week treatment course. Patients continued to receive treatment until complete remission and then two further courses, until tumour progression or unacceptable toxicity ensued. A total of 36 patients received at least one treatment course and were assessable for toxicity; 33 patients were evaluable for treatment results. Dose-limiting grade 3 and 4 WHO toxicity occurred in 5 and 3 patients respectively; 27% of patients entered complete or partial tumour remission. The median time to tumour progression was 2 months with a range of 1–14 months. The efficacy of bendamustine was apparently independent of pretreatment with anthracyclines, suggesting a lack of cross-resistance between bendamustine and anthracyclines. It can be concluded that bendamustine in the dose and application schedule used here is active in the salvage therapy of women with advanced breast cancer. The toxicity was acceptable. Future studies have to confirm the data of this pilot trial and to define the role of bendamustine in the combination chemotherapy of metastatic breast cancer that has been suggested by previous trials.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Der Onkologe 5 (1999), S. 47-54 
    ISSN: 1433-0415
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Die zytostatische Chemotherapie ist etablierter Bestandteil im Behandlungskonzept des kolorektalen Karzinoms. Im metastasierten Stadium führt eine auf 5-Fluorouracil-basierende Chemotherapie zu einer signifikant längeren Überlebenszeit und zu einer deutlichen Reduktion tumorbedingter Symptome. In den letzten Jahren wurden zudem mehrere Substanzklassen, die eine relevante Aktivität beim kolorektalen Karzinom zu besitzen scheinen und damit potentiell das therapeutische Arsenal erheblich erweitern könnten, entwickelt und klinisch geprüft. Im folgenden Artikel wird ein Überblick über den derzeitgen Entwicklungsstand der wichtigsten neuen Substanzen für die Therapie des kolorektalen Karzinoms gegeben.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 71 (1968), S. 361-367 
    ISSN: 1432-1335
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Vinblastin senkt den 14C-Leucin-Einbau in Asciteszellen. Vinblastin und Vincristin hemmen die DNS-, RNS-und besonders die Proteinbiosynthese in leukämischen Rinderlymphocyten und führen auch in zellfreien Systemen zu einer Hemmung der Proteinbiosynthese. Im Bereich des Nucleinsäurestoffwechsels inaktivieren sie vornehmlich die DNS-abhängige RNS-Polymerase, in Ganzzellen setzen sie den intracellulären Nucleosidgehalt herab.—Das zum Vergleich eingesetzte Colchicin besitzt ähnliche Angriffspunkte.
    Notes: Summary 14C-leucine-incorporation by ascites cells is diminished by Vinblastine. RNA-, DNA-and especially proteinbiosynthesis of leukemic lymphocytes are inhibited by Vinblastine and Vincristine. Further, a similar mode of inhibition of proteinbiosynthesis as well as the inactivation of DNA dependent RNA-Polymerase was displayed by cell free systems. The intracellular content of nucleosides was reduced in intact cells.—Similar results have been obtained by employing Colchicine as a reference substance.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 72 (1969), S. 137-143 
    ISSN: 1432-1335
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Der Einfluß des 4-Hydroxy-pentenals auf die Biosynthese von monomeren und polymeren Nucleotiden wird anhand zellfreirr Systeme untersucht. Es werden vor allem Angriffspunkte an der Nucleotidphosphorylierung und an der DNA-Polymerase gefunden. Bei Untersuchungen der Wirksamkeit des HPE in einem zellfreien Ribonucleotid-Reduktase-System kann kein deutlicher Effekt an der ADP-Reduktase gesehen werden. Wie die Biosynthese der DNS eines natürlich proliferierenden Gewebes in Gegenwart von HPE verläuft, wird an regenerierender Rattenleber geprüft.
    Notes: Summary Cell free systems have been employed to study the effect of 4-hydroxy-pentenale on monomer and polymer nucleotide biosynthesis. It appears that the phosphorylation of nucleotides as well as DNA polymerase is affected by HPE. However, this compound caused no significant inhibition of ADP-reductase-system. Of further interest seemed to be the DNA synthesis of regenerating rat liver in presence of HPE.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 73 (1969), S. 67-74 
    ISSN: 1432-1335
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Einwirkung von Vinblastin und Vincristin auf vier zellfreie Systeme von leukämischen Rinderlymphocyten wird beschrieben: DNS-abhängige RNS-Polymerase, Proteinbiosynthese und Uridin-Kinase. Beide Alkaloide inaktivieren die pH-5. Enzymfraktion der Proteinbiosynthese und hemmen stark die DNS-abhängige RNS-Poly-merase. Die DNS-Polymerase und die Uridin-Kinase werden hingegen nur schwach beeinflußt.
    Notes: Summary The influence of vinblastine and vincristine on four cell free systems derived from leukemic lymphocytes is described. The systems used were: DNA dependent RNA polymerase, DNA polymerase, uridine kinase and protein-biosynthesis. Both alkaloids strongly inactivate pH-5-enzymes and DNA-dependent RNA polymerase. In contrast, DNA polymerase and uridine kinase are not influenced to a great extent.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 47 (1969), S. 1118-1119 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The influence of some substances used in combination therapy of Morbus Hodgkin — Vinblastine, phenylbutazone, prednisolone and procarbazine — on ATP-nucleosidtransferases of leukemic cells have been examinated. Procarbazine and prednisolone do not influence the reactions of nucleosidephosphorylation. In contrary phenylbutazone and especially vinblastine are diminishing the amounts of triphosphates in leukemic cells.
    Notes: Zusammenfassung Einige beim Morbus Hodgkin meist im Sinne einer Kombinationstherapie angewendeten Substanzen—Vinblastin, Phenylbutazon, Procarbazin und Prednisolon — wurden auf ihren Einfluß auf die ATP-Nucleosidphosphotransferasen von Leukosezellen geprüft. Procarbazin und Prednisolon beeinflussen die Phosphorylierungsreaktionen nicht. Hingegen nehmen unter Phenylbutazon und besonders unter Vinblastin die Mengen der gebildeten Triphosphate ab.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Ascites cells derived from various transplantation tumours and leukemic lymphocytes have been employed to study the in-vitro effects of E. coli L-asparaginase on protein and nucleic acid biosynthesis. Bovine lymphocytes obtained from a cow suffering from chronic lymphatic leukemia showed a marked inhibition of14C-thymidine incorporation not reversible by L-asparagine and L-glutamine addition. With Walker ascites and Yoshida ascites of the rat, this effect has been found to be accompanied by a comparable inhibition of14C-leucine uptake, while in cells from mouse crocker ascites under the same conditions only14C-leucine incorporation was decreased. Although some specific investigations have been performed on nucleic acid biosynthesis in presence of L-asparaginase, the mechanisms of action — with respect to the rapid inhibition of14C-thymidine uptake into lymphatic cells — are still unknown.
    Notes: Zusammenfassung Die Wirkung von E. coli-L-Asparaginase auf die Nucleinsäure- und Proteinbiosynthese wurde an Zellsuspensionen lymphatischer Leukämiezellen und verschiedener Transplantationstumoren untersucht. Hierbei wurde beobachtet, daß dieses Enzym eine deutliche Senkung des14C-Thymidineinbaus an Leukämiezellen des Rindes hervorruft, ein Effekt, welcher durch Zusatz von L-Asparagin und L-Glutamin nicht aufhebbar war. Bei Zellen des Walker- und Yoshida-Ascitestumors der Ratte fanden sich eine Hemmung der14C-Thymidin- und14C-Leucininkorporation, während die L-Asparaginase bei Asciteszellen des Crocker-Sarkoms der Maus lediglich eine Senkung des14C-Leucineinbaus bewirkte. Die Ursache für das Verhalten des14C-Thymidineinbaus bei bestimmten Tumorzellen bleibt zunächst ungeklärt.
    Type of Medium: Electronic Resource
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