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  • 11
    ISSN: 1432-1335
    Schlagwort(e): Key wordsMDM2 amplification ; Rb LOH ; p53 LOH ; p53 mutation ; Liposarcoma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Purpose: The present study aimed to investigate the status of alterations of the MDM2, Rb and p53 genes in a series of 45 liposarcomas. Furthermore, the possible correlation with histological and clinical parameters was studied. Methods: MDM2 amplification was examined by non-radioactive Southern blot hybridization with a human MDM2 cDNA probe. Mutations in the p53 gene were screened by polymerase chain reaction/single-strand conformation polymorphism analysis and direct sequencing. To study loss of heterozygosity (LOH) at the tumor-suppressor genes Rb and p53, we used four polymorphic intragenic Rb markers (introns 1, 17, 20, and 25) and two p53 markers (intron 1 and exon 4). Results: MDM2 amplification was found in 19 of 45 liposarcomas (42.2%). The frequency of LOH in Rb and p53 was nearly identical (22%). In 4 of 9 tumors (44.4%) with LOH, allelic loss was a concurrent event in both genes. Of 45 liposarcomas, 6 (13.3%) showed p53 mutations. Overall, alterations of the p53/MDM2/Rb pathway occurred in 30 of 45 liposarcomas (66.6%). In contrast to myxoid and pleomorphic variants, well-differentiated liposarcomas were characterized by a high frequency of MDM2 amplification, a lack of LOH of Rb and p53, and p53 mutations. Conclusions: Obviously MDM2 amplification and LOH at the Rb and p53 genes do not occur simultaneously in the oncogenesis of liposarcomas, as is the case for MDM2 amplification and p53 gene mutations (with one exception). We suggest that well-differentiated, myxoid and pleomorphic liposarcomas are characterized by a different pattern of molecular alterations.
    Materialart: Digitale Medien
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 388-394 
    ISSN: 1432-1335
    Schlagwort(e): p53 ; mdm2 ; p53 gene mutation ; Breast carcinoma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The aim of the study was to analyzep53 gene mutations and the expression of p53 and mdm2 proteins in 31 randomly selected invasive breast carcinomas. The results were then correlated with tumor grade, stage, estrogen receptor status, nodal status, and DNA ploidy. The expression of the proteins p53 and mdm2 was determined immunohistochemically using formalin-fixed, paraffin-embedded material. Screening for p53 mutation involved analysis of the highly conserved regions of thep53 gene (exons 5–9) by the polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) technique. PCR products with band shifts were directly sequenced. Immunohistochemical staining of p53 was positive in 9 cases (29.0%), only 2 of which showed ap53 gene mutation. These were identified as a C→G transversion at the second position of codon 278 in exon 8 and an A→G transition at the second position of codon 205 in exon 6. A third case with a mutation was observed (C→T transition, position 1 of codon 250 in exon 7) that did not show p53 immunohistochemically. Of the 9 p53-positive tumors, 2 were moderately differentiated (grade II). The remaining tumors were poorly differentiated (7/9). By contrast, p53-negative carcinomas were well differentiated (grade I) in most cases (P=0.02). DNA cytometry in 8 of the 9 p53-positive carcinomas revealed an aneuploid stem line. The majority of the p53-negative tumors were diploid (P=0.01). Mdm2 oncoprotein was detected in 10 tumors (32.2%), 4 of which were p53-positive, including the 3 with mutations. The grading of the mdm2-positive tumors was moderate or poor, G1 carcinomas were always noted to be mdm2-negative (P=0.04). Overexpression of p53 protein is a complex mechanism and does not merely indicate the detection of mutations in thep53 gene. This study has shown that p53 expression correlates with tumor grade and DNA ploidy. Mdm2 expression was also associated with the tumor grade. Immunohistological demonstration of the p53 protein alone is insufficient as a basis for comment on the functional state of thep53 gene and gene product. The interrelation between recognition of the p53 protein and gene mutation needs more careful assessment to define their roles in the control of neoplasia.
    Materialart: Digitale Medien
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  • 13
    ISSN: 1432-2307
    Schlagwort(e): Key words p53 alterations ; Synovial sarcoma ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Alterations to p53 seem to be of prognostic significance in soft tissue sarcomas, but their significance for synovial sarcomas has not been studied. We analysed 34 synovial sarcomas in 19 patients for p53 alterations (p53 gene mutations + p53 immunopositivity) and examined this factor for its prognostic value in a group of 15 primary tumours. DNA was prepared from paraffin-embedded tumour material by a modified proteinase K/phenol/chloroform extraction. p53 gene mutations of exons 5–8 were analysed by the PCR-SSCP-sequencing method. p53 protein expression was evaluated by immunohistochemistry using the murine monoclonal antibody DO1. We found two missense mutations (5.9%) and ten p53 immunopositive cases (29.4%). Both tumours with p53 mutations showed p53 protein expression. There was no significant correlation between p53 alteration and histological subtype, age, sex, or tumour size. The 5-year survival rate was 24.1%. Overall survival was significantly reduced in patients having synovial sarcomas with p53 alterations (P〈0.001). In the multivariate Cox’s analysis, only p53 alterations (P=0.032) and tumour size (P=0.023) emerged as independent prognostic factors. We suggest that p53 alterations may be a useful prognostic indicator in synovial sarcomas, allowing rational clinical treatment and follow-up.
    Materialart: Digitale Medien
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  • 14
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 275 (1972), S. 124-134 
    ISSN: 1432-1912
    Schlagwort(e): Isolated Perfused Rat Brain ; High-Energy Phosphates ; Glycolytic Pathway ; Phenobarbital ; Ischemia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The concentrations of P-creatine, creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6-P, fructose diphosphate, dihydroxyacetone-P, α-glycero-P, lactate and pyruvate were measured in the isolated perfused rat brain as well as in rat brain in vivo. Similar levels were observed in the isolated brain and in intact animals, and the values measured were in good accordance with those described in the literature. Only the pyruvate and lactate content were significantly higher in the isolated brain but the lactate/pyruvate ratio remained unchanged. An anesthetic or ischemia caused just the same effects on energy metabolism of the isolated rat brain as described for intact animals. Thus, 1.5 mM phenobarbital in the perfusion medium produced a statistically significant increase in P-creatine and glucose levels as well as a decrease of pyruvate, lactate and α-glycero-P levels. After ischemia of the isolated brain the concentrations of high-energy phosphates, glycogen, glucose, and pyruvate fell considerably concomitantly with significant accumulations of creatine, AMP, α-glycero-P and lactate. The results indicate that the isolated perfused rat brain may be a useful tool for studying cerebral metabolism.
    Materialart: Digitale Medien
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  • 15
    Digitale Medien
    Digitale Medien
    Springer
    The European physical journal 8 (1999), S. 649-654 
    ISSN: 1434-6052
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Physik
    Notizen: Abstract. Transverse momentum event–by–event fluctuations are studied within the string–hadronic model of high energy nuclear collisions, LUCIAE. Data on non–statistical $p_T$ fluctuations in p+p interactions are reproduced. Fluctuations of similar magnitude are predicted for nucleus–nucleus collisions, in contradiction to the preliminary NA49 results. The introduction of a string clustering mechanism (Firecracker Model) leads to a further, significant increase of $p_T$ fluctuations for nucleus–nucleus collisions. Secondary hadronic interactions, as implemented in LUCIAE, cause only a small reduction of $p_T$ fluctuations.
    Materialart: Digitale Medien
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  • 16
    ISSN: 1573-0638
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Pädagogik
    Materialart: Digitale Medien
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  • 17
    Digitale Medien
    Digitale Medien
    Springer
    Chromatographia 41 (1995), S. 612-615 
    ISSN: 1612-1112
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 18
    Digitale Medien
    Digitale Medien
    Springer
    Chromatographia 42 (1996), S. 352-353 
    ISSN: 1612-1112
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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