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  • Hodgkin's disease  (3)
  • Chemistry  (2)
  • Acetat  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 95 (1979), S. 115-122 
    ISSN: 1432-1335
    Keywords: Acetat ; Anaerobiose ; Lipogenese ; Oktanoat ; Pyruvate ; Tritiiertes Wasser ; Tumor ; Acetate ; Anaerobiosis ; Lipogenesis ; Octanoate ; Pyruvate ; Tritiated water ; Tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Anaerobic culture conditions (95% argon/5% CO2) caused a slightly greater increase in total lipids of Ehrlich ascites tumor cells than a gas phase of 20% O2, 75% N2, 5% CO2. Whereas the rate of [U-14C]acetate incorporation into total lipids and lipid-subclasses rose markedly in the absence of oxygen, a drastic decrease of [U-14C]pyruvate and [1-14C]octanoate incorporation as well as a 30% reduction of 3H incorporation into lipids from tritiated water were observed under these conditions. Since profound changes in the metabolic state of cells cause alterations in the specific activity of the acetyl-CoA pool but do not alter the specific activity of intracellular water, this precursor is considered to be an adequate monitor for lipogenesis under aerobic and anaerobic culture conditions. Therefore, it is concluded that Ehrlich ascites tumor cells are not able to reoxidize NADH/NADPH in the absence of oxygen by a stimulation of biosynthesis of fatty acids as is discussed to be the case in normal cells. The slight increase in total lipids of anaerobically cultured cells seems to be the result of an imbalance between normal uptake and impaired utilization of lipids from serum-supplemented culture medium.
    Notes: Zusammenfassung Unter anaeroben Kulturbedingungen, (95% Argon 5% CO2) stieg der Gesamtlipidgehalt in Ehrlich Ascites Tumorzellen etwas stärker an als unter aeroben Bedingungen (20% O2, 75% N2, 5% CO2). In Abwesenheit von Sauerstoff war der Einbau von [U-14C]Acetat in die Gesamtlipidfraktion als auch in einzelne Lipidklassen, deutlich erhöht, wohingegen ein drastischer Abfall der Einbauraten aus [U-14C]Pyruvat und [1-14C]Oktanoat sowie eine signifikante Verminderung des Einbaus von 3H-Wasser unter diesen Kulturbedingungen beobachtet wurde. Da die spezifische Aktivität von intrazellulärem Wasser auch unter tiefgreifenden Änderungen des metabolischen Zustandes der Zellen praktisch konstant bleibt, wird 3H-Wasser als die zuverlässigste Vorstufe zur Messung der Lipidbiosynthese unter aeroben und anaeroben Kulturbedingungen angesehen. Aus den Ergebnissen wird geschlossen, daß Ehrlich Ascites Tumorzellen nicht, wie es für Normalgewebe angenommen wird, in der Lage sind, NADH/NADPH bei Ausschluß von Sauerstoff durch erhöhte Fettsäuresynthese zu, reoxidieren. Der beobachtete Anstieg im Gesamtlipidgehalt von anaerob kultivierten Zellen erklärt sich wahrscheinlich durch ein Ungleichgewicht zwischen normaler Aufnahme und gehemmtem Abbau von exogenen Lipiden.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1569-8041
    Keywords: BEACOPP ; chemotherapy ; dose intensification ; hematotoxicity ; Hodgkin's disease ; practicability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Evidence is recently accumulating that the novelBEACOPP (bleomycin (B), etoposide (E), adriamycin (A), cyclophosphamide (C),vincristine (O), procarbazine (P), prednisone (P)) chemotherapy is a highlyeffective treatment for advanced stage Hodgkin's disease. Two dose variantsof BEACOPP are currently tested in a phase III randomized multicenter trialof the GHSG. To enable more extensive testing of BEACOPP we characterized itspracticability regarding schedule adherence, acute hematotoxicity and need forsupportive treatment. Patients and methods:Data of 858 patients (6592 therapy cycles)from 184 participating institutions were evaluated. Planned total drug dosesof the baseline variant (arm 1) were 80, 2400, 200, 5200, 11.2, 5600 and 4480mg/m2 for B, E, A, C, O, P and P, respectively. Compared to arm 1,the doses of E, A and C in the dose-intensified variant (arm 2) were escalatedby factor 2.0, 1.4, 1.92, respectively, using G-CSF assistance. Stepwise dosereductions were specified in case of dose-limiting toxicities. Both variantsare given in eight three-weekly courses. Results:Median dose adherence (dose actually given relative toplanned arm 1 dose) in arm 1 was 1.0 for all drugs. Relative dose escalationof E, A, and C actually maintained in arm 2 was 1.83, 1.37 and 1.77 (medians),respectively, and 70% of patients maintained elevated dose levelsthroughout the entire treatment. Dose-limiting toxicities occurred in25% of cycles in arm 2, most frequently due to leukocytopenia andthrombocytopenia. Time courses of leukocytes in arm 2 showed more severe butnot more prolonged leukocytopenia compared with arm 1. WHO grades 3–4infections were documented in 2.1% (arm 1) and 3.1% (arm 2) ofall cycles. Erythrocytes were transfused in 6% (arm 1) and 28%(arm 2), platelets in 〈1% (arm 1) and 6% (arm 2) of allcycles. Conclusions:Both BEACOPP schemes are practicable in a largemulticenter setting. Despite increased hematotoxicity, moderate doseescalation is safe for the majority of the patients with G-CSF assistance andstandard supportive treatment.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1569-8041
    Keywords: chemotheapy ; dose escalation ; efficacy ; Hodgkin's disease ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The BEACOPP chemotherapy regimen for advanced Hodgkin's disease employs a rearranged schedule permitting a shortened three-week cycle. With haematological growth factor support, the dosages of cyclophosphamide, etoposide and adriamycin could be moderately escalated. The 3-armed multicentre HD9 trial (recruitment 1993-1998; 1300 patients randomised) aimed to compare BEACOPP with the standard COPP/ABVD chemotherapy and to detect and measure the gain in efficacy, if any, due to moderate dose escalation of BEACOPP. Eight cycles were given, followed by local irradiation. The most recent interim analysis, with 689 evaluable patients, circa 40% of all expected events and a median observation time of 27 months, showed significant differences in progression rate (P) and in two-year freedom from treatment failure (F) between the treatment arms, with escalated BEACOPP (P = 2%, F = 89%) better than baseline BEACOPP (P = 9%, F = 81%) better than COPP/ABVD (P = 13%, F = 72%). Survival was not significantly different. Acute toxicity was more severe due to dose escalation, but remained manageable. These preliminary results suggest that BEACOPP improves efficacy. Moderate dose escalation is feasible with G-CSF support and appears likely to make a worthwhile improvement in the cure rate. The results must await confirmation (or otherwise) by the final analysis including all randomised patients and sufficiently mature data.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Annals of oncology 9 (1998), S. 73-78 
    ISSN: 1569-8041
    Keywords: chemotherapy ; dose response relationship ; Hodgkin's disease ; randomised clinical trials ; statistical models ; tumour growth kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this article we summarize the theoretical arguments which led us in the German Hodgkin's Disease Study Group to introduce the BEACOPP-regimen and to initiate a large randomised trial to investigate the role of moderate dose escalation in the treatment of advanced stage Hodgkin's disease. Although some indications for a role of dose were available in the early 1990s no prospective randomised trial had been undertaken. In order to obtain an impression of the shape of the essential dose response characteristic we developed a novel statistical model that could be used to analyse a set of data in which dose variations had occured. The model took tumour growth and chemotherapy effects into account. The model could be applied to clinical data on tumour control and treatment given in a patient population. The model was fitted to the data of 706 patients which had received COPP/ABVD-like regimens. It revealed considerable heterogeneity in chemosensitivity and a positive slope of the doseresponse relationship. The model was used to simulate the effect of various treatment strategies with dose escalation and schedule changes. On the basis of such simulations we predicted that shortening cycle intervals from 4 to 3 weeks should lead to small benefits (about 3% in five-year tumour control rates). In contrast, we predicted that a moderate average dose escalation by 30% of a standard chemotherapy would lead to a potential benefit in the order of 10%-15% in tumour control at five years. Subsequently we searched for a treatment scheme that would permit such a dose escalation. The BEACOPP-scheme was invented to allow the three major myelotoxic substances (cyclophsphamide, adriamycin and etoposide) to be given in the beginning of a cycle. These three substances were then subject to dose escalation in a dose finding trial. G-CSF was introduced to compensate for the myelotoxic effects. The dose level found feasible for a large multicentre setting turned out to be in the required magnitude. The HD9 trial of the GHSG was then initiated to examine whether the predicted dose response curve really exists.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Polymer Science 2 (1959), S. 297-301 
    ISSN: 0021-8995
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: The manner in which changes in air pressure affect the thermal and oxidative degradation of a methylphenylsilicone was investigated as a function of time. A closed, gas-circulating system of 1500-cc. volume, incorporating a magnetic balance for following loss of weight in the sample, was employed. Finely ground samples were heated at 400°C. for 7 hours with initial pressures of air ranging from 700 to 50 mg. Hg. Mass spectrometric and infrared analyses identified the gaseous and the volatile products. At all pressures, low molecular weight silicones represented a major portion of the weight loss. Final weight losses in air approximated 10%, and approached, at the lowest pressure (50 mm.), the 7% observed in argon. Water and benzene were evolved, the latter at a rate that decreased with decrease in pressure. Traces of phenol, formaldehyde, propane, and higher molecular weight hydrocarbons were also given off. The evolution of carbon dioxide, carbon monoxide, methane, and hydrogen and the consumption of oxygen were followed in detail. Changes in air pressure from 700 to 300 mm. did not alter appreciably the rates of product evolution, oxygen consumption, and of weight loss. At lower presures (300 to 50 mm.), however, the molar ratio of the total noncondensed gases generated to total oxygen consumed increased, indicating a possible change in reaction mechanism.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Acta Polymerica 44 (1993), S. 50-53 
    ISSN: 0323-7648
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: Die Synthese eines Diels-Alder-Leiterpolymers mit Imino- und Etherbrücken wird beschrieben. Der Strukturnachweis wird durch hochaufgelöste 13C-NMR-Spektroskopie geführt, wobei Modellverbindungen eine wichtige Rolle zukommt. Die Molekulargewichte erreichen Werte bis zu M̄n = 52000. Dies sind die höchsten, die bisher für doppelsträngige Polymere erreicht wurden. Schließlich wird die Einkristallstrukturanalyse der Modellverbindung 8 vorgestellt.
    Notes: The synthesis of a Diels-Alder ladder polymer with imino and ether bridges is described. The structure proof is based upon a comparison of its high resolution 13C-NMR spectrum with those of model compounds. The molecular weights can reach values as high as M̄n = 52000 which are the highest ones observed so far for a double stranded polymer. The X-ray structure of model compound 8 is also presented.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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