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  • 1
    Electronic Resource
    Electronic Resource
    Expression of MDR1/p-glycoprotein and multidrug resistance-associated protein in childhood solid tumours (1997)
    Springer
    Virchows Archiv 430 (1997), S. 99-105 
    Details
    ISSN: 1432-2307
    Keywords: Multidrug resistance ; P-glycoprotein Neuroblastoma ; Nephroblastoma ; Reverse transcriptase polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the expression of MDR1/p-glycoprotein in paediatric tumours using reverse transcriptase polymerase chain reaction (RT-PCR), RNA dot blot analysis, and immunohistochemistry on formalin fixed paraffin-embedded material with JSB-1 and C-219 monoclonal antibodies, and compared these three techniques. The expression of multidrug resistance-associated protein (MRP) gene was examined by RT-PCR assay. We studied MDR1/p-glycoprotein and MRP expression in 13 samples from 10 neuroblastoma patients, 11 samples from 10 nephroblastoma patients, 2 rhabdomyosarcomas, 1 adrenocortical carcinoma and 10 benign tumours or tumour-like lesions. Eleven of 13 neuroblastomas, 7 of 11 nephroblastomas, 2 rhabdomyosarcomas, 1 adrenocortical carcinoma, and 7 of 10 benign tumours or tumour-like lesions showed MDR1 PCR products. By RNA dot blot analysis, MDR1 transcripts were detectable in 11 of 34 specimens. Immunohistochemically, we detected positive reaction products for JSB-1 in 26 of 36 samples. There was a significant correlation between the immunoreactivity for JSB-1 and the expression of MDR1 mRNA expression by RTPCR (P=0.0001). However, the presence of p-glycoprotein immunostaining does not correlate with the MDR1 expression shown by RT-PCR in every case. As for MRP mRNA expression, 9 of 13 neuroblastomas and 10 of 11 nephroblastomas revealed PCR products.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01008030
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  • 2
    Electronic Resource
    Electronic Resource
    p53 gene mutations and expression of p53 and mdm2 proteins in invasive breast carcinoma (1997)
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 388-394 
    Details
    ISSN: 1432-1335
    Keywords: Key words p53 ; mdm2 ; p53 gene mutation ; Breast carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the study was to analyze p53 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 the p53 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 a p53 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 the p53 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 the p53 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01240122
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Prognostic implication of immunodetection of P glycoprotein in Ewing's sarcoma (1993)
    Springer
    Journal of cancer research and clinical oncology 119 (1993), S. 185-189 
    Details
    ISSN: 1432-1335
    Keywords: P glycoprotein ; Ewing's sarcoma ; Multidrug resistance ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Increased expression of P glycoprotein is associated with multidrug resistance in many cell lines. P glycoprotein has been detected in different human tumors. To assess the implication of multidrug resistance in the prognosis of Ewing's sarcoma the expression of P glycoprotein was studied immunohistochemically in pre- and post-therapeutic tumor tissues of 21 cases treated according to the CESS 81 or 86 protocol. The response to chemotherapy was evaluated histologically. Formalin-fixed, paraffin-embedded and fresh frozen sections were immunostained with a monoclonal antibody to P glycoprotein, clone JSB 1, using the double APAAP method. P glycoprotein was detected in 12 cases of 21 (57%) in either pre- or postchemotherapy tumor tissues. From the 21 cases 8 revealed a good morphological response to chemotherapy (33%); 10 of the 13 non-responders were positive for P glycoprotein (77%), but only 2 of the 8 responders (25%). The difference was statistically significant (P〈0.05). Comparing P glycoprotein expression with the clinical outcome, we found that 7 of 12 positive cases had died (58%). From the negative cases only 3 of 9 had died (33%). However, judged by the the Kaplan Meyer life tables, these data were not significant. In conclusion our results suggest that the immunodetection of P glycoprotein indicates a poor response to chemotherapy and probably a bad clinical outcome for Ewing's sarcoma patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01624429
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    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    p53 gene mutations and expression of p53 and mdm2 proteins in invasive breast carcinoma (1997)
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 388-394 
    Details
    ISSN: 1432-1335
    Keywords: p53 ; mdm2 ; p53 gene mutation ; Breast carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01240122
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
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