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  • 1
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1433-8726
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary For a variety of human malignancies such as breast cancer and cancer of the prostate, p53 oncoprotein overexpression indicating an alteration of the p53 tumorsuppressor gene has been described as a prognostic factor for a poor clinical outcome. To investigate the overexpression of p53 oncoprotein in transitional-cell carcinoma of the bladder, 58 bladder cancer specimens of different clinical stages and histological grades were investigated using an immunohistochemical approach. A correlation between p53 positivity and tumor stage was observed, with an increase from 38.5% of superficial (Ta) tumors to 83.3% of muscle-invasive (T3/T4) tumors staining positively for p53 oncoprotein. Furthermore, an increase from 46.7% of G1 tumors to 75% of G3 tumors was observed. In 22 of 25 (87%) informative patients the results of the immunohistochemical staining could be verified by the determination of p53 mutations as detected by polymerase chain reaction (PCR)-directed analysis of restriction-fragment-length polymorphisms (RFLP). To determine the prognostic value of p53 immunohistochemistry for the clinical course of superficial bladder cancer, the overexpression of p53 oncoprotein was investigated in 41 patients with superficial bladder tumors (T1) undergoing complete transurethral tumor resection. The detection of p53 protein was correlated with further clinically important variables such as sex, age, histological grading, former instillation therapy, and immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating-cell nuclear antigen; monoclonal antibody PC10). After a median follow-up period of 54 months, 7 of 8 patients for whom more than 20% of cells stained positively for p53 had disease progression as compared with only 1 of 33 patients who were negative for p53 detection (P〈0.01; chi-square test). For other urological tumors such as prostate cancer, the results of immunohistochemistry are more difficult to interpret and require definite confirmation on the DNA level.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1433-0563
    Keywords: Key words Renal cell cancer • Biological prognostic factors • Risk stratification ; Schlüsselwörter Nierenparenchymkarzinome • Prognosefaktoren • Risikostratifizierung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Beobachtung sehr unterschiedlicher klinischer Verläufe für Patienten mit Nierenzellkarzinomen, die ein identisches pathologisches Stadium, eine vergleichbare histologische Differenzierung sowie ein ähnliches Wachstumsmuster aufweisen, scheint die Existenz von Tumoren mit unterschiedlichem biologischen Potential zu belegen. Letzteres wird durch gegenwärtig zur Verfügung stehende Klassifikationssysteme nicht in so ausreichendem Maße determiniert, daß eine ihnen entsprechende Charakterisierung einzelner Tumoren die Basis für eine validierte bzw. individualisierte Therapieentscheidung darstellen könnte. Die Notwendigkeit hierzu ergibt sich aber aus der Einführung modifizierter operativer Strategien im Sinne einer sich zunehmend etablierenden organerhaltenden Chirurgie, sowie aus der jüngst beschriebenen Applikation einer sich am biologisch sicher noch besser charakterisierbaren Progressionsrisiko bestimmter Subgruppen von Patienten mit Nierenzellkarzinom ausrichtenden adjuvant-systemischen Therapie (Immun-Chemotherapie). Hieraus ergibt sich für den klinisch orientierten Grundlagenforscher bzw. den grundlagenwissenschaftlich orientierten Kliniker das Bedürfnis, prognostisch bedeutsame Variablen in Ergänzung zu „klassischen“ Prognosefaktoren (T-Stadium, histologischer Differenzierungsgrad, Wachstumsmuster) zu identifizieren, die das biologische Aggressivitätspotential des einzelnen Tumors so valide abzuschätzen erlauben, daß sich hieraus die Möglichkeit eines an den einzelnen Patienten individuell adaptierten therapeutischen Vorgehens ergibt. Diesbezüglich wurden in der jüngeren Vergangenheit verschiedenste biologische Parameter unter Einschluß des Nachweises von Alterationen auf chromosomaler/DNA-Ebene, aber auch der Veränderung physiologischer Proteinexpression, als potentielle Progressionsmarker bzw. biologische Prognosefaktoren diskutiert. Ziel der vorliegenden Abhandlung ist eine Bestandsaufnahme bezüglich der gegenwärtigen Verfügbarkeit solcher biologischer Variablen, denen künftig eine klinische Bedeutung in Verbindung mit dem Ziel einer individualisierten Therapie des Nierenzellkarzinomes zukommen könnte.
    Notes: Summary The observation of extremely variable clinical courses for patients with renal cell carcinomas of an identical pathological stage as well as a comparable histological differentiation resp. growth pattern strongly indicates the existence of tumors harboring different biological aggressiveness. Currently available histopathological classification systems do not predict the biological behaviour of renal cell cancer as sufficiently as the establishment of a therapeutical strategy adjusted to the individual patient would require. The need for a more refined characterization of the biological potential of the indidual tumor results from the introduction of modified operative strategies as organ-preserving surgery, for example, as well as from the recently suggested application of an adjuvant systemic therapy adapted to the individual risk for tumor recurrence resp. the development of progressive disease. Therefore, the clinically orientated basic scientist and the basic scientifically orientated clinician intensively try to determine prognostically important biological variables which would allow to better predict the biological aggressiveness of a single tumor in addition to “classical” prognostic parameters (T-stage, histological grading, growth patterns). In this context, several biological parameters including the identification of alterations on the DNA-, RNA- and protein level have been discussed as possible biological prognostic markers for renal cell cancer. The present review tries to reflect currently available biological characteristics of RCC which might gain clinical importance with regard to an individualized therapy in the near future.
    Type of Medium: Electronic Resource
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