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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Analytica Chimica Acta 114 (1980), S. 303-310 
    ISSN: 0003-2670
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Experimental Gerontology 25 (1990), S. 483-495 
    ISSN: 0531-5565
    Keywords: aging ; anemia ; erythropoiesis ; mathematical model
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1433-0385
    Keywords: Key words: Carcinomas ; Minimal residual cancer ; Immunocytochemistry ; Polymerase chain reaction ; Bone marrow ; Blood ; Lymph nodes. ; Schlüsselwörter: Carcinome ; minimale residuale Krebserkrankung ; Immuncytochemie ; Polymerasekettenreaktion ; Knochenmark ; Blut ; Lymphknoten.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. Während das Auftreten und die Häufigkeit von Lokalrezidiven bei der R0-Resektion solider Tumoren weitgehend in der Hand des Operateurs liegt, sind Fernrezidive nach derzeitigem Kenntnisstand auf die bereits prä- oder perioperativ erfolgte, systemische Disseminierung von Tumorzellen zurückzuführen. Das Vorliegen von einzelnen, disseminierten Tumorzellen – z. B. im Knochenmark als Indikatororgan – ist im Rahmen eines erweiterten Tumorstagings durch sensitive immuncytochemische und molekulare Methoden nachweisbar und wird zunehmend als klinisch relevanter Prognosefaktor angesehen. Im Gegensatz zu soliden Metastasen stellen isolierte mikrometastatische Tumorzellen aufgrund ihrer Zugänglichkeit für Makromoleküle und immunkompetente Effektorzellen geeignete Ziele für intravenös appplizierte Therapeutica dar. Der überwiegend nicht mitotisch aktive Zustand (G0-Phase) dieser Tumorzellen könnte eine Ursache für das Versagen einer adjuvanten Chemotherapie sein. Daher rücken adjuvante Therapiestrategien, die auch gegen ruhende Zellen wirksam sind, zunehmend in den Mittelpunkt des Interesses. Diese therapeutische Rationale ist mit dem Antikörper 17–1A bei Patienten mit colorectalem Carcinom im Stadium UICC III nach R0-Resektion randomisiert untersucht und bestätigt worden. Die Antikörpertherapie zeichnet sich dadurch aus, daß Antikörper sich im Gegensatz zur Chemotherapie auch gegen mitotisch nicht aktive Tumorzellen („dormant cells“) richten und zudem unabhängig von möglichen Chemotherapieresistenzen wirken. Als eine gegen den Zustand der minimalen residualen Krebserkrankung gerichtete Therapie wäre der adjuvante Einsatz von Antikörpern zukünftig auch als Kombinationsbehandlung mit der Chemotherapie parallel oder sequentiell sinnvoll. Ziel dieser Übersicht ist es, den momentanen Stand der Forschung auf dem Gebiet der Diagnostik und Therapie der minimalen residualen Krebserkrankung zu erläutern.
    Notes: Summary. The incidence of local relapse after complete (R0) resection of solid tumors is largely determined by the skill of the surgeon, whereas metastatic relapse in distant organs is caused by pre- or perioperative systemic dissemination of tumor cells. The presence of individual disseminated tumor cells – e. g., in bone marrow as indicator organ – can be detected by sensitive immunocytochemical and molecular methods and is increasingly considered as a clinically relevant prognostic indicator. In contrast to solid metastases, isolated micrometastatic tumor cells are appropriate targets for intravenously applied anti-cancer therapeutics because they are easily accessible to macromolecules and immunologic effector cells. The majority of these tumor cells appear to be nonproliferating (i. e., in the G0 phase of the cell cycle), which may explain the failure of adjuvant chemotherapy. Adjuvant therapeutic strategies aimed at quiescent tumor cells are therefore of increasing interest. This therapeutic rationale has been tested and confirmed in a randomized clinical trial using antibody 17–1A in patients with non-metastatic colorectal carcinoma (UICC stage III). The antibody therapy kills also quiescent tumor cells (“dormant cells”) and is independent from a potential chemotherapy resistance of the tumor cells. As treatment for minimal residual cancer, the clinical use of antibody therapy could be envisaged in conjunction with chemotherapy, applied either in parallel or sequentially. The aim of this review is to present and discuss the current state of research in the field of diagnosis and therapy of minimal residual cancer.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Archives of gynecology and obstetrics 254 (1993), S. 786-789 
    ISSN: 1432-0711
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Early dissemination of malignant cells is the main cause for metastatic relapse in patients with solid tumours. By use of monoclonal antibodies (mAbs) specific for cytokeratins, disseminated individual epithelial tumour cells can now be identified in mesenchymal organs such as bone marrow. Further to characterize such cells in patients with prostate cancer, an immunocytochemical procedure was developed for simultaneous labelling of cytokeratin component no. 18 (CK18) and prostate specific antigen (PSA). In a first step, cells were incubated with mAb ER-PR8 against PSA and secondary gold-conjugated goat anti-mouse antibodies. In a second step, biotinylated mAb CK2 to CK18 was applied as primary antibody and subsequently incubated with complexes of streptavidin-conjugated alkaline phosphatase, which were developed with the Newfuchsin substrate. The binding of gold-labelled antibodies was visualized by silver enhancement. The sensitivity and specificity of the technique was demonstrated on cryostat sections of hyperplastic prostatic tissue, and cytological preparations of LNCaP prostatic tumour cells. Double staining was restricted to cells derived from the secretory epithelium of the prostate. Cross-reactivity between both detection systems was excluded by several controls, including the use of unrelated antibodies of the same isotype and the staining of CK18+/PSA− HT29 colon carcinoma cells. CK18+ cells co-expressing PSA were found in bone marrow aspirates from 5 out of 13 patients with carcinomas of the prostate, a finding that is consistent with the relative fraction of double-positive LNCaP cells. The specificity of CK18 for epithelial tumour cells in bone marrow was supported by negative staining of 12 control aspirates from patients with benign prostatic hypertrophy. In conclusion, the approach presented appears to be a reliable method to phenotype individual prostatic carcinoma cells.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1434-0879
    Keywords: Prostate cancer ; Micrometastasis ; Bone marrow ; Double immunocytochemistry ; Cytokeratin ; Prostate-specific antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Monoclonal antibodies (mAbs) specific for cytokeratins are potent probes for the identification of disseminated individual epithelial tumour cells in mesenchymal organs such as bone marrow. We have used a monoclonal antibody (mAB) against cytokeratin 18 (CK18) for the detection of individual metastatic tumour cells in bone marrow aspirates from 84 patients with carcinoma of the prostate. CK18+cells were detected in a sensitivity of 1 per 8×105 marrow cells using the alkaline phosphatase anti-alkaline phosphatase (APAAP) system for staining. We were able to detect CK18+tumour cells in the marrow of 33% of patients with stage N0M0 prostate cancers. The incidence of CK18+cells showed a significant correlation with established risk factors, such as local tumour extent, distant metastases and tumour differentiation. For further characterization of such cells in patients with prostate cancer, we developed an immunocytochemical procedure for simultaneous labelling of cytokeratin component no. 18 (CK18) and prostate-specific antigen (PSA). In a first step, cells were incubated with a murine mAb against PSA, followed by goldconjugated goat anti-mouse antibodies. In a second step, a biotinylated mAb to CK18 was applied as primary antibody and subsequently incubated with complexes of streptavidin-conjugated alkaline phosphatase, which were developed with Newfuchsin substrate. The binding of gold-labelled antibodies was visualized by silver enhancement. CK18+cells co-expressing PSA were found in bone marrow aspirates from 5 out of 14 patients with carcinomas of the prostate. The specificity of CK18 for epithelial tumour cells in bone marrow was supported by negative staining of 12 control aspirates from patients with benign prostatic hyperplasia (BPH). Thus the prostatic origin of CK+cells in bone marrow of patients with prostate cancer has been directly demonstrated for the first time in this work. In conclusion, the approaches presented appear to be reliable methods of identifying and phenotyping individual prostatic carcinoma cells and may help to identify those patients with prostate cancer who are at high risk of relapse.
    Type of Medium: Electronic Resource
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