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  • 1
    ISSN: 1434-0879
    Keywords: Renal cell carcinoma ; Prognosis ; p53 ; mdm-2 ; Survival ; Proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The clinical course of renal cell carcinoma (RCC) is highly variable. Overexpression of the p53 protein has been suggested as a possible prognostic parameter in RCC. Overexpression of the mdm-2 oncogene product has been shown to interact with the p53 function. To investigate the immunohistochemical overexpression of mdm-2 protein in comparison with that of p53 protein in RCC, 50 nonpapillary pT3 RCCs were immunostained for p53 protein (DO-7) and mdm-2 (1172). Tumor growth fraction (Ki-67 labeling index; MIB-1) was determined by immunohistochemistry. p53 positivity was detected in 16% of tumors. mdm-2 overexpression was seen in 30% of RCCs. There was a significant association between p53 and mdm-2 immunostaining (P=0.0006), suggesting that mdm-2 protein may contribute to p53 protein stabilization in RCC. p53 overexpression was associated with a high Ki-67 LI (P=0.0002), suggesting that p53 overexpression is involved in growth control in RCC. Survival analysis showed that Ki-67 LI (P=0.04) and p53 overexpression were associated with poor prognosis (P=0.0021), whereas mdm-2 overexpression was not related to patient outcome (P=0.73). A Cox regression analysis revealed tumor stage (P〈0.001) and p53 overexpression (P〈0.05) to be independent prognostic parameters. It is concluded that p53 but not mdm-2 may be of practical relevance in predicting patient prognosis in RCC.
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  • 2
    ISSN: 1434-0879
    Keywords: Bladder neoplasms ; Flow cytometry ; Fluorescence in situ hybridization ; Chromosome Y ; Chromosome X ; Chromosome 1 ; Chromosome 7 ; Chromosome 9 ; Chromosome 17 ; Aneuploidy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Detection of molecular alterations is of potential significance for diagnosis and prognosis in bladder cancer. Fluorescence in situ hybridization (FISH) allows visualization and quantitation of genes and chromosomes on a cell by cell level and can easily be applied to urinary cells. To evaluate the sensitivity of FISH for detection of DNA aberrations in bladder cancer, formalin-fixed tissues of 293 tumors were examined by FISH and flow cytometry (FCM). Centromere probes for the chromosomes X, Y, 1, 7, 9, and 17 were used for FISH analysis. FISH was more sensitive for detection of quantitative DNA aberrations than FCM. An aberration of at least one chromosome was found in 107 of 108 tumors (99%), which were tetraploid, aneuploid, or multiploid, and in 29 of 49 tumors (59%), which were diploid, by FCM. The frequency of FISH aberrations showed greater differences between pTa (47%) and pT1 tumors (85%;P〈0.0001) than between stages pT1 and pT2-4 (98%). The marked genetic difference between pTa and pT1 tumors argues against the concept of grouping pTa and pT1 tumors together as “superficial bladder cancer.” The frequency of tumors with chromosomal aberrations detected by FISH increased with the number of chromosomes examined. Aneusomy was seen in 68% of grade 1 tumors examined for ≥4 chromosomes, suggesting that the cytological diagnosis of bladder cancer recurrences could be substantially improved by FISH.
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  • 3
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Prostatakarzinom ; Zytogenetik ; Gen-Amplifikation ; Polysomie ; Key words Prostate cancer ; Cytogenetics ; Gene amplification ; Polysomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Development and progression of tumors is driven by a malfunction of specific genes. Although prostate cancer is one of the most frequent tumors, little is known about the genes involved. Cytogenetic and molecular examinations have shown that chromosomal deletions most frequently involve 7q, 8p, 10q, 13q, 16q, 17p and the Y chromosome. These loci may carry tumor suppressor genes with relevance for prostate cancer. DNA sequence copy number gains were most frequently observed at chromosomes 7, 8q, and 11q. These regions may carry currently un-known oncogenes. There is increasing evidence for a clinical relevance of genetic alterations. Polysomies of several chromosomes were shown to be associated with poor prog-nosis of prostate cancer patients. Androgen receptor amplification can be found in hormone-refractory carcinomas which may re-spond to total androgen blockage. For the future it is hoped that the identification of the genes involved in prostate cancer and the determination of their function could allow for significant improvements of treatment strategies for prostate cancer patients.
    Notes: Zusammenfassung Entstehung und Progression von Tumoren werden durch Funktionsstörungen von spezifischen Genen gesteuert. Obwohl das Prostatakarzinom zu den häufigsten Tumoren gehört, ist über die bei diesem Tumor involvierten Gene wenig bekannt. Zytogenetische und molekulare Untersuchungen haben gezeigt, daß chromosomale Deletionen besonders häufig das Y-Chromosom, 7q, 8p, 10q, 13q, 16q und 17p betreffen. Diese Loci dürften für das Prostatakarzinom relevante Tumorsuppressorgene enthalten. Häufige DNS-Sequenzvermehrungen von Chromosom 7, 8q und 11q deuten auf die Lokalisation von möglichen Onkogenen hin. Bereits heute bestehen Anhaltspunkte für eine Prognoserelevanz genetischer Veränderungen. Der Nachweis von Polysomien in Primärtumoren deuten auf eine ungünstige Prognose hin. Eine Amplifikation des Androgenrezeptors spricht für einen Hormontherapie-resistenten Tumor, welcher möglicherweise besonders gut auf eine totale Androgenblockade ansprechen wird. Die Identifikation der alterierten Gene und die Entschlüsselung ihrer Funktion könnte in Zukunft zu deutlich verbesserten Behandlungsstretegien für Patienten mit Prostatakarzinom führten.
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  • 4
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Mikrovaskulitis ; Panarteriitis nodosa ; Alveoläre Kapillaritis ; Mikroaneurysmen ; ANCA ; Key words Microvasculitis ; Polyarteriitis nodosa ; Alveolar capillaritis ; Microaneurysms ; Antineutrophil cytoplasmic autoantibodies (ANCA)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In contrast to the panarteriitis nodosa macroform, the lung is frequently involved in p-ANCA-positive microvasculitis. Alveolar capillaritis, which may improve under immunosuppressive therapy, is a characteristic feature of this microvasculitis. We report on an 82-year-old patient who was admitted to the hospital because of severe hemoptysis due to microvasculitis. He died 3 weeks later despite therapy with steroids and cyclophosphamide. At autopsy alveolocapillary microaneurysms were found that may be residues of alveolar capillaritis.
    Notes: Zusammenfassung Im Unterschied zur Makroform der Panarteriitis nodosa befällt die pauci-immune p-ANCA-positive Mikrovaskulitis (Mikroform der Panarteriitis nodosa) häufig auch die Lunge. Kennzeichnend ist eine alveoläre Kapillaritis, die sich unter immunosuppressiver Therapie zurückbilden kann. Wir berichten über einen 82 jährigen Patienten, der wegen schwerer Lungenblutungen bei Mikrovaskulitis hospitalisiert wurde und nach 3 Wochen trotz entsprechender Therapie verstarb. Autoptisch waren keine frischen Kapillarveränderungen mehr nachweisbar. Stattdessen wurden alveolokapilläre Aneurysmen gefunden, die möglicherweise Residuen der Kapillaritis darstellen.
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  • 5
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Although prostate cancer initially responds and regresses in response to androgen-depletion therapy, most human prostate cancers will re-grow as an androgen-independent tumour. The goal of our study was to apply functional genomics to identify gene expression changes involved in this process. Two ...
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