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H Schueller

Publications and source records attributed to H Schueller.

4 recordsLinked to original sources
PubMed2006

Non-sufficient cell cycle control as possible clue for the resistance of human malignant glioma cells to clinically relevant treatment conditions.

OBJECTIVES: Human gliomas have a catastrophic prognosis with a median survival in the range of one year even after therapeutic treatment. Relatively high resistance towards apoptotic stimuli is the characteristic feature of malignant gliomas. Since cell cycle control has been shown to be the key mechanism controlling both apoptosis and proliferation, this study focuses on DNA damage analysis and protein expression patterns of essential cell cycle regulators P53 and P21waf1/cip1 in glioma under clinically relevant therapeutic conditions. MATERIAL AND METHODS: U87MG cell line, characterised by wild p53-phenotype relevant for the majority of primary malignant glioblastomas, was used. Glioma cells underwent either irradiation or temozolomide treatment alone, or combined radio/chemo treatment. DNA damage was analysed by the "Comet Assay". Expression rates of target proteins were analysed using "Western-Blot" technique. RESULTS AND CONCLUSIONS: "Comet Assay" demonstrated extensive DNA damage caused by temozolomide treatment alone and in combination with irradiation, correlating well with the low survival rate observed under these treatment conditions. In contrast, irradiation alone resulted in a relatively low DNA damage, correlating well with a high survival rate and indicating a poor therapeutic efficiency of irradiation alone. Unusually low up-regulation of P53 and P21waf1/cip1 expression patterns was produced by the hereby tested stressful conditions. A deficit in cell cycle control might be the clue to the high resistance of malignant glioma cells to established therapeutic approaches.

Antineoplastic Agents, Alkylating↗
PubMed2003

Preclinical evaluation of a radiosensitizing effect of gemcitabine in p53 mutant and p53 wild type bladder cancer cells.

OBJECTIVES: Despite clinical use, the radiosensitizing effect of gemcitabine (2'2'-difluorodeoxycytidine) in human transitional cell carcinoma (TCC) has not been shown to date. We investigated gemcitabine as a radiosensitizer for human TCC cells. METHODS: Monolayer cultures of RT112 (G1, p53 wild type), RT4 (G1-G2, p53 wild type), T24 (G3, p53, mutant type), and SUP (G4, p53 mutant type) cells were incubated in medium with gemcitabine. Electron beam radiation was applied alone, simultaneous, or 3, 6, 12, and 24 hours after gemcitabine. Jurkat leukemia cells were used as controls for radiation toxicity. Cell survival was determined 6, 12, 24, 48, and 72 hours after radiation by microculture tetrazolium assay. DNA damage was evaluated by flow cytometric assessment of poly(ADP-ribose) polymerase, and apoptosis was determined by terminal-deoxynucleotidyltransferase-mediated dUTP nick-end labeling and flow cytometric assessment after annexin-V and propidium iodide labeling. RESULTS: In all TCC cell lines, radiation alone caused only little and insignificant growth inhibitory effects at 10 Gy. Gemcitabine alone had a dose-dependent cytotoxic and apoptosis inducing effect on all TCC cell lines independent of p53 status. Assays combining radiation with gemcitabine in different dose and time schedules demonstrated no radiosensitizing effect in TCC cells. CONCLUSIONS: Gemcitabine is effective in TCC cell lines independent of p53 status. A radiosensitizing effect could not be demonstrated. Again, p53 status was not predictive of the radioresponse in the bladder cancer cell lines. Clinical studies with gemcitabine and radiotherapy might nevertheless yield different results but should be performed with utmost caution.

Animals↗
PubMed1983

The carbon tip electrode.

The development of the carbon tip electrode and its low chronic threshold behavior are described. Compared to presently used electrode material, carbon tip electrodes result in lower chronic stimulation thresholds. In a group of 43 patients, chronic pulse generator output has been favorably reduced in association with this type of electrode. Thus the use of activated carbon tip electrodes may result in the routine implantation of low output pacemakers.

Animals↗