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Gerd Jakse - One of the best experts on this subject based on the ideXlab platform.
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Differential expression of the lung resistance-related protein/major vault protein in the histological compartments of Nephroblastomas
International Journal of Oncology, 2001Co-Authors: Thomas Efferth, Marc Eric Bode, Hans-gunther Schulten, Paul Thelen, Bernd Granzen, Antonius J. M. C. Beniers, Rolf Mertens, Olaf Gefeller, Rolf-hermann Ringert, Gerd JakseAbstract:Nephroblastomas (Wilms' tumors) are curable with survival rates above 80%. Some tumors, however, fail to respond to therapy and those patients have a poor prognosis. In a search for molecular markers of drug resistance, we investigated the expression of lung resistance protein (LRP) in tissue samples from 32 children with Nephroblastoma by means of immunohistochemistry. LRP is a human major vault protein (MVP) and is associated with multidrug resistance of tumors. LRP/MVP expression was found in the blastemal and epithelial compartments but to a significantly lesser extent in the stromal compartment of Wilms' tumors. Expression was generally heterogeneous with respect to staining intensity and percentage of positive cells. We found significant relationships between LRP/MVP expression and chemotherapeutic pre-treatment of tumors and tumor stage. The immunohistochemical results were validated with a real-time RT-PCR technique and a significant association between protein and mRNA expression was observed.
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differential expression of the lung resistance related protein major vault protein in the histological compartments of Nephroblastomas
International Journal of Oncology, 2001Co-Authors: Thomas Efferth, Marc Eric Bode, Hans-gunther Schulten, Paul Thelen, Bernd Granzen, Antonius J. M. C. Beniers, Rolf Mertens, Olaf Gefeller, Rolf-hermann Ringert, Gerd JakseAbstract:Nephroblastomas (Wilms' tumors) are curable with survival rates above 80%. Some tumors, however, fail to respond to therapy and those patients have a poor prognosis. In a search for molecular markers of drug resistance, we investigated the expression of lung resistance protein (LRP) in tissue samples from 32 children with Nephroblastoma by means of immunohistochemistry. LRP is a human major vault protein (MVP) and is associated with multidrug resistance of tumors. LRP/MVP expression was found in the blastemal and epithelial compartments but to a significantly lesser extent in the stromal compartment of Wilms' tumors. Expression was generally heterogeneous with respect to staining intensity and percentage of positive cells. We found significant relationships between LRP/MVP expression and chemotherapeutic pre-treatment of tumors and tumor stage. The immunohistochemical results were validated with a real-time RT-PCR technique and a significant association between protein and mRNA expression was observed.
Alex Rufle - One of the best experts on this subject based on the ideXlab platform.
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KIT, PDGFRα and EGFR analysis in Nephroblastoma
Virchows Archiv : an international journal of pathology, 2008Co-Authors: Sylvia C. Wetli, Dieter Harms, Ivo Leuschner, Alex Rufle, Anja Foerster, Michel P. Bihl, Norbert Graf, Roikos Furtwaengler, Michael Paulussen, Jakob BrinerAbstract:Nephroblastoma prognosis has dramatically improved, but an unfavourable prognostic subgroup warrants development of novel therapeutic strategies. Selective KIT, PDGFRα and epidermal growth factor receptor (EGFR) tyrosine kinase inhibition evolved as powerful targeted therapy for gastrointestinal stromal tumours and non-small-cell lung cancer. To investigate a potential role for tyrosine kinase inhibition, we analyzed 209 Nephroblastomas for immunohistochemical KIT and EGFR expression, 63 Nephroblastomas for mutations in KIT exons 9, 11, 13, EGFR exons 18, 19, 20 and 21, and all 209 Nephroblastomas for PDGFRα exons 12, 14 and 18. Twenty-two tumours (10.5%) expressed KIT, 31 (14.8%) EGFR, and 10 (4.8%) both KIT and EGFR, respectively. KIT expression was relatively more common among high-risk tumours (6/27; 22.3%) compared to low-/intermediate-risk tumours (26/181; 14.4%). Nine patients deceased, four of which had high-risk tumours with KIT expression in two of four and EGFR expression in one of four. There were no KIT, PDGFRα or EGFR mutations. Our results suggest no significant contribution of KIT, EGFR or PDGFRα mutations to Nephroblastoma pathogenesis. Despite a trend towards association of immunohistochemical KIT and EGFR expression with poor outcome in high-risk Nephroblastomas, statistical analysis did not yield significant correlations in this subgroup. Therefore, it remains open if KIT, PDGFRα or EGFR tyrosine kinase inhibition constitute a therapeutic target in Nephroblastoma in the absence of KIT, PDGFRα or EGFR mutations.
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Wnt signaling pathway analysis in renal cell carcinoma in young patients
Modern Pathology, 2007Co-Authors: Elisabeth Bruder, Dieter Harms, Ivo Leuschner, Norbert Graf, Jakob Briner, Holger Moch, David Ehrlich, Pedram Argani, Barbara Selle, Alex RufleAbstract:Renal cell carcinomas in young patients constitute a morphologically and genetically heterogeneous group. Twenty percent belong to the newly recognized Xp11.2 translocation-associated family and rare tumors arise from Nephroblastoma. Aberrant Wnt signaling through β-catenin mutation has been implicated in Nephroblastoma pathogenesis and has been found to synergize with WT1 mutations. To characterize Wnt signaling activity in renal cell carcinomas in young patients, we gathered 34 tumors (three clear cell, ten Xp11.2 translocation associated, five papillary, two chromophobe, two collecting duct, one neuroblastoma associated, eight unclassified renal cell carcinomas, and three carcinomas combined with Nephroblastoma) from patients less than 22 years. Expression of β -catenin, its homologue γ -catenin, and of WT1 was assessed by immunohistochemistry in 30 tumors, and sequence analysis of CTNNB1 , CTNNG1 , and WT1 genes was performed in 25 tumors. Cytoplasmic β -catenin accumulation was demonstrated in two papillary carcinomas, one neuroblastoma-associated carcinoma, and two carcinomas arising from Nephroblastoma. The pattern of γ -catenin expression paralleled that of β -catenin but its signal intensity was lower in 22, equal in 7, and stronger only in 1 tumor, respectively. Four tumors showed nuclear WT1 expression. One Xp11.2 translocation-associated carcinoma presented a rare intronic CTNNB1 single nucleotide polymorphism and cytoplasmic β -catenin accumulation. There were no further CTNNB1 or CTNNG1 sequence alterations. A WT1 mutation was found in the Nephroblastoma component of a carcinoma arising from Nephroblastoma. These findings suggest Wnt signaling pathway activation only in a minority of renal cell carcinomas in young patients. CTNNB1 mutations are rare events. Cytoplasmic β -catenin accumulation in an Xp11.2-associated carcinoma suggests potential interaction of Wnt signaling components with microphthalmia transcription factor family also in Xp11.2 translocation carcinomas. WT1 mutation in the Nephroblastoma component of a mixed-type renal cell carcinoma provides direct evidence for clonal independence of Nephroblastoma and carcinoma components in this exceptional tumor.
Thomas Efferth - One of the best experts on this subject based on the ideXlab platform.
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Differential expression of the lung resistance-related protein/major vault protein in the histological compartments of Nephroblastomas
International Journal of Oncology, 2001Co-Authors: Thomas Efferth, Marc Eric Bode, Hans-gunther Schulten, Paul Thelen, Bernd Granzen, Antonius J. M. C. Beniers, Rolf Mertens, Olaf Gefeller, Rolf-hermann Ringert, Gerd JakseAbstract:Nephroblastomas (Wilms' tumors) are curable with survival rates above 80%. Some tumors, however, fail to respond to therapy and those patients have a poor prognosis. In a search for molecular markers of drug resistance, we investigated the expression of lung resistance protein (LRP) in tissue samples from 32 children with Nephroblastoma by means of immunohistochemistry. LRP is a human major vault protein (MVP) and is associated with multidrug resistance of tumors. LRP/MVP expression was found in the blastemal and epithelial compartments but to a significantly lesser extent in the stromal compartment of Wilms' tumors. Expression was generally heterogeneous with respect to staining intensity and percentage of positive cells. We found significant relationships between LRP/MVP expression and chemotherapeutic pre-treatment of tumors and tumor stage. The immunohistochemical results were validated with a real-time RT-PCR technique and a significant association between protein and mRNA expression was observed.
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differential expression of the lung resistance related protein major vault protein in the histological compartments of Nephroblastomas
International Journal of Oncology, 2001Co-Authors: Thomas Efferth, Marc Eric Bode, Hans-gunther Schulten, Paul Thelen, Bernd Granzen, Antonius J. M. C. Beniers, Rolf Mertens, Olaf Gefeller, Rolf-hermann Ringert, Gerd JakseAbstract:Nephroblastomas (Wilms' tumors) are curable with survival rates above 80%. Some tumors, however, fail to respond to therapy and those patients have a poor prognosis. In a search for molecular markers of drug resistance, we investigated the expression of lung resistance protein (LRP) in tissue samples from 32 children with Nephroblastoma by means of immunohistochemistry. LRP is a human major vault protein (MVP) and is associated with multidrug resistance of tumors. LRP/MVP expression was found in the blastemal and epithelial compartments but to a significantly lesser extent in the stromal compartment of Wilms' tumors. Expression was generally heterogeneous with respect to staining intensity and percentage of positive cells. We found significant relationships between LRP/MVP expression and chemotherapeutic pre-treatment of tumors and tumor stage. The immunohistochemical results were validated with a real-time RT-PCR technique and a significant association between protein and mRNA expression was observed.
Dominique Martin-coignard - One of the best experts on this subject based on the ideXlab platform.
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Wilms' tumor in patients with 9q22.3 microdeletion syndrome suggests a role for PTCH1 in Nephroblastomas.
European Journal of Human Genetics, 2012Co-Authors: Bertrand Isidor, Franck Bourdeaut, Delfine Lafon, Ghislaine Plessis, Elodie Lacaze, Caroline Kannengiesser, Sylvie Rossignol, Olivier Pichon, Annaig Briand, Dominique Martin-coignardAbstract:Nephroblastoma (Wilms' tumor; WT) is the most common renal tumor of childhood. To date, several genetic abnormalities predisposing to WT have been identified in rare overgrowth syndromes. Among them, abnormal methylation of the 11p15 region, GPC3 and DIS3L2 mutations, which are responsible for Beckwith-Wiedemann, Simpson-Golabi-Behmel and Perlman syndromes, respectively. However, the underlying cause of WT remains unknown in the majority of cases. We report three unrelated patients who presented with WT in addition to a constitutional 9q22.3 microdeletion and dysmorphic/overgrowth syndrome. The size of the deletions was variable (ie, from 1.7 to 8.9 Mb) but invariably encompassed the PTCH1 gene. Subsequently, we identified a somatic PTCH1 nonsense mutation in the renal tumor of one patient. In addition, by array comparative genomic hybridization method, we analyzed the DNA extracted from the blood samples of nine patients with overgrowth syndrome and WT, but did not identify any deleterious chromosomal imbalances in these patients. These findings strongly suggest that patients with constitutional 9q22.3 microdeletion have an increased risk of WT, and that PTCH1 have a role in the pathogenesis of Nephroblastomas.
William W. Carlton - One of the best experts on this subject based on the ideXlab platform.
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Incidence, histopathologic and electron microscopic features of spontaneous Nephroblastomas in rats.
Toxicology letters, 1992Co-Authors: Manik Chandra, William W. CarltonAbstract:Primary renal neoplasms in the rats are uncommon. Nephroblastoma is the only renal embryonal tumor of the rat; all other tumors are reported in older rats. The occurrence of spontaneous Nephroblastoma in rats has been reported. However, metastasis from the Nephroblastoma in rat is extremely rare. Data from 2669 Sprague-Dawley control rats and 1060 Fischer-344 rats were reviewed and evaluated to determine the incidence and pathology of Nephroblastoma. This tumor was observed in three Sprague-Dawley rats. Metastasis was observed in the lungs and renal lymph nodes in two different rats. No case of Nephroblastoma was observed in Fischer-344 rats. Detailed histopathological and electron microscopic features of these neoplasms are described and discussed.