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Verhandlungen der Deutschen Gesellschaft für Innere Medizin 02/1975; 81:1627-9.
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Verhandlungen der Deutschen Gesellschaft für Innere Medizin 02/1975; 81:1624-6.
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DMW - Deutsche Medizinische Wochenschrift 12/1974; 99(48):2468-74. · 0.53 Impact Factor
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DMW - Deutsche Medizinische Wochenschrift 05/1974; 99(17):883-7. · 0.53 Impact Factor
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Onkologie 08/1970; 31(1-2):11-16. · 0.87 Impact Factor
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Breast Care 08/1970; 2(6):352-353. · 0.45 Impact Factor
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Onkologie 08/1970; 21(2):5-9. · 0.87 Impact Factor
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Onkologie 08/1970; 19(5):416-418. · 0.87 Impact Factor
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H. Wilke,
P. Preusser,
M. Stahl,
H.J. Meyer,
U. Fink,
W. Achterrath,
P. Busche,
J. Meyer,
A. Harstrick,
H.-J. Schmoll, S. Seeber
Onkologie 08/1970; 17(2):154-157. · 0.87 Impact Factor
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Onkologie 08/1970; 16(6):446-448. · 0.87 Impact Factor
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Onkologie 08/1970; 3(2):78-84. · 0.87 Impact Factor
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ABSTRACT: In chronic myelogenous leukemia (CML) malignant cells are characterised by the Philadelphia chromosome (Ph), resulting from a translocation t(9;22). The position of the breakpoint within the major breakpoint cluster region (M-bcr) on chromosome 22 has been shown to correlate with the clinical course of the disease or, more recently, thrombopoietic activity. We have therefore determined the breakpoint localisation in 53 Ph-positive CML patients. Following the 5′/3′-region definition of Inokuchi et al. Leukemia Research15, 1067 (1991) [1], 22 of our patients have 5′ and 31 of our patients have 3′ orientated breaks. No correlation was found between platelet counts and breakpoint localisation.
Leukemia Research.
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ABSTRACT: Two-dimensional polyacrylamide gel electrophoresis comparisons were made for the non-histone “Chromatin fraction II” proteins of normal, phytohemagglutinin-stimulated and acute leukemic lymphocytes. The “Chromatin fraction II” proteins were extracted from the nuclear residue fraction after initial treatment with (a) 0.075 M NaCl containing 0.025 M EDTA, pH 8; (b) 0.01 M Tris-HCl, pH 8; and (c) 0.4 N H2SO4. Most of the proteins found earlier in the “Chromatin fraction II” of rodent liver and hepatomas were also found in the human cells. Some changes such as the decrease in amount of protein BA of normal rodent cells were found in the comparison of normal and stimulated human cells. By comparison with normal lymphocytes, the phytohemagglutinin-treated cells had decreased spot densities and sizes for proteins BA and Bv and an increase in densities and sizes of proteins CB, C25, CS and CT. In the acute lymphocytic leukemic cells there was a decrease in spots A24, BA, Bv, CD and CD′ by comparison with the normal lymphocytes. Protein CG′ which was found earlier in the hepatomas was found in acute lymphocytic leukemic cells but not in the control or phytohemagglutinin-treated cells. These studies show that there is a loss in specific Chromatin proteins BA and Bv from the Chromatin of rapidly turning over cells. Concomitantly, increases are observed for the amounts of protein spots CB, C25, CS and CT in the actively growing cell samples.
Experimental Cell Research. 100(1):47-55.
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ABSTRACT: To evaluate the long-term impact of the reduction of Philadelphia chromosome (Ph)-positive metaphases by treatment of chronic myelogenous leukaemia (CML) with interferon (IFN) alpha, we examined the outcome of 62 patients who had been enrolled between 1984 and 1990 into 2 IFN trials at our institution. As best cytogenetic response, 9 patients had achieved a complete remission and an additional 9 patients a partial remission. The remaining 44 patients had obtained either a minimal (n=29) or no cytogenetic response (n=15). Of the total of 62 patients, 9 were still on schedule and responsive to IFN in January 1995, including 7 patients in ongoing complete cytogenetic remission. The overall 5-year survival rate after a median follow-up from diagnosis of 51 months (range 3-102 months) was 62% and the median survival was reached at month 87. The effect of cytogenetic remission on survival was examined by "landmark" studies showing a significant survival advantage for patients with karyotype responses. In conclusion, in the patients studied, cytogenetic improvement was found to translate into improved survival expectancy. Long-term control by IFN alpha of CML, however, was restricted to a small minority of patients, predominantly to those attaining a complete suppression of the leukaemic cell clone as judged by cytogenetic criteria.
European Journal Of Haematology 56(1-2):78-81. · 2.61 Impact Factor
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ABSTRACT: Forty-two patients with disseminated nonseminomatous testicular cancer were randomly entered to receive a two-armed chemotherapy regimen with mandatory crossover, consisting of either vinblastine-bleomycin or doxorubicin-cis-dichlorodiammineplatinum(II) (DDP) as initial therapy. Forty of these patients received at least four courses and were considered evaluable. Twenty-five of these patients received vinblastine-bleomycin and 15 received doxorubicin-DDP as initial treatment. The overall remission rate was 88%, with a complete remission rate of 68%. Thirty-two patients remain alive and 20 (50%) remain disease-free at 3+ to 18+ months, with a median duration of complete remissions of 9+ months. The response rate was not affected by prior chemotherapy or radiotherapy. Either treatment arm proved equally effective. However, response with doxorubicin-DDP therapy occurred in nine of 19 treatment courses when vinblastine-bleomycin therapy had failed, while response with vinblastine-bleomycin therapy occurred in only two of 11 treatment courses when doxorubicin-DDP therapy had failed. Thus, different patterns of cross-resistance between these alternative regimens may exist.
Cancer treatment reports 64(4-5):599-609.
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I Strohscheer,
R Kleinert,
C. Westphal,
J Schüller,
K. Werner,
O Anders,
H Wandt,
U. Poppy,
K Matthes,
M Kuliszkiewicz-Janus, [......],
G Schneider,
D. M. Rozynkowa,
H Kasparu,
G Gastl,
N Schwella,
H Wachter,
K Gabryś,
S Kleiner,
D Jakschies,
J Krauter
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ABSTRACT: The effects of resistance modifiers (RM) on the cytotoxicity of mafosfamide (MAF), bis-chloroethylnitrosourea (BCNU) and dacarbazine (DTIC) were evaluated by the MTT colorimetric assay in isolated lymphocytes and blast cells derived from patients with chronic lymphatic leukaemia (CLL; n = 28) and acute myeloid leukaemia (AML; n = 30), or from healthy donors (n = 19). Pentoxifylline (PTX) has been shown to restore sensitivity to alkylating drugs by interfering with DNA repair. PTX (10 microM) significantly sensitised leukaemic blasts to the cytotoxic effect of MAF. In 8 out of 30 AML samples, sensitisation ratios (SRs; i.e. cytotoxic drug ID50s in the presence or absence of RM) for MAF in the presence of PTX were > 2 ranging up to 4.2. Inhibition of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) by O6-benzylguanine (O6-BG; 50 microM) enhanced the cytotoxicity of DTIC in CLL lymphocytes. SRs > 2 for DTIC in the presence of O6-BG were observed in 7 out of 28 CLL specimens. Sensitisation was generally greater in the more chemo-resistant specimens. Ethacrynic acid (EA; 1 microM), an inhibitor of glutathione-S-transferases (GST), failed to influence the cytotoxicity of alkylating agents in any cell type. Also, all examined RMs did not sensitive leukaemic cells to the cytotoxic effect of BCNU. The data show significant chemosensitisation of leukaemic cells to alkylating agents by PTX and O6-BG, indicating a potential clinical use of these substances as RM in patients.
Anticancer research 13(6A):2155-9. · 1.73 Impact Factor
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ABSTRACT: Background: To define the maximum-tolerated dose (MTD) and to evaluate the dose-limiting toxicities (DLTs) of the combination of capecitabine and irinotecan in patients with metastatic colorectal cancer. Patients and methods: Thirty-seven patients with measurable metastatic colorectal cancer with no prior chemotherapy for metastatic disease were treated at three dose levels (DLs). For the first two dose levels, irinotecan (70 mg/m2) was administered once a week for 6 weeks in combination with 2 weeks of capecitabine at 1000 mg/m2 (DL1) or 1250 mg/m2 (DL2) twice daily, starting on days 1 and 22. In the last dose escalation step, the dose of irinotecan was increased to 80 mg/m2 (DL3). One cycle lasted 7 weeks. Results: In the subsequent phase I trial, 96 cycles of capecitabine and irinotecan were administered. At DL3, three out of six patients experienced DLTs (diarrhea, neutropenia, asthenia). In order to confirm the safety of the recommended dose, DL2 was extended to 15 patients. Five patients (33%) showed DLTs at this dose level, which was considered too high to embark on further clinical studies. Subsequently, the starting dose (DL1) was extended to a total of 16 patients, with diarrhea being the main toxicity. The overall response rate was 38% [95% confidence interval (CI) 21% to 58%], with a median response duration of 8.7 months (95% CI 6.4–11.5 months). Conclusions: The recommended doses for further studies are irinotecan 70 mg/m2 and capecitabine 1000 mg/m2. The combination of capecitabine and irinotecan appears to have significant therapeutic efficacy with manageable toxicity.
