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  • 1
    ISSN: 1433-0563
    Keywords: Schlüsselwörter Nierenzellkarzinom ; Immuntherapie ; Prognose ; Zytokine ; Key words Renal cell carcinoma ; Immunotherapy ; Prognosis ; Cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The immunogenic potential of renal cell carcinoma and the resistance of its metastases against chemotherapy, radiation and hormonal treatment have led to the development of a great number and variety of different strategies, summarized under the term immunotherapy. Objective remissions can be expected in about 20–40 % of patients. Another 30–40 % show stable disease for a limited time, only occasionally for longer. Most results are from uncontrolled phase II studies. A cancer cure can usually not be expected, long-term remissions are rare (5 %), and high remission rates are only observed in studies with strong patient selection. Some authors have reported a higher survival rate in patients treated with IL-2 or IFN. Survival of patients with objective remissions is significantly improved. A standard therapy cannot be defined. Even presuming an increased survival rate, the toxicity, which can lead to a dramatic reduction in quality of life, and the high costs have to be considered carefully. We think that in view of the lack of therapeutic alternatives, the improving efficacy, the potential survival benefit, the reduction of toxicity and the perspectives, immunotherapy is essential in the treatment of metastatic renal cell carcinoma. Its use should be confined to clinical studies.
    Notes: Zusammenfassung Die Immunogenität des Nierenzellkarzinoms und die Resistenz seiner Metastasen gegen Chemo-, Strahlen- und Hormontherapien führten zur Etablierung einer Vielzahl von unterschiedlichen unter dem Begriff Immuntherapie zusammengefaßten Strategien. Die erzielbaren Remissionsraten liegen in der Regel zwischen 20 und 40 %. Zusätzlich kommt es bei 30–40 % der Patienten zu einer zeitlich limitierten, in Einzelfällen auch Jahre andauernden Stabilisierung der Erkrankung. Überwiegend handelt es sich hierbei um Ergebnisse unkontrollierter Phase-II-Studien. Heilungen sind in der Regel nicht zu erwarten, Langzeitremissionen sind selten (5 %) und hohe Remissionsraten können nur an selektionierten Patientenkollektiven erzielt werden. Einige Autoren beschreiben einen Überlebensvorteil für immuntherapierte Patienten gegenüber Nicht- oder Chemotherapierten. Gesichert ist ein Überlebensvorteil für Patienten mit objektiven Remissionen. Eine Standardtherapie läßt sich derzeit nicht definieren. Auch unter der Annahme eines Überlebensvorteils, müssen der Verlust an Lebensqualität bedingt durch die Toxizität der gängigen Therapieprotokolle sowie deren hohe Kosten berücksichtigt werden. Aufgrund des Fehlens therapeutischer Alternativen, einer zu erwartenden Verbesserung der momentan erreichbaren Remissionsraten und des von einigen Autoren berichteten Überlebensvorteil für immuntherapierte Patienten [15, 16, 26, 30, 31], halten wir die Immuntherapie für einen essentiellen Bestandteil in der Therapie des metastasierten Nierenzellkarzinoms. Die Anwendung sollte in der Regel im Rahmen klinischer Studien erfolgen.
    Type of Medium: Electronic Resource
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  • 2
    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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  • 3
    ISSN: 1433-8726
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A total of 385 patients (83% men, 52% aged 16–30) with urogenital (UG) trauma were treated in 19 urological clinics between April 1984 and December 1986. In all, 41% of the accidents were due to traffic; 13% to work and sports each; 8% to sexual activities; and 6% to violence. The distribution of injury severity included 40% light, 21% moderate and 39% severe. Of 427 UG lesions, 27% were combined with intraabdominal and 24% with pelvic injuries. The kidneys were involved in 51% of cases and the bladder, urethra, penis and scrotum, including its content, in ca. 10% each. Of the renal traumas, 49% were ruptures; 48% contusions; and 7% hilar lesions,a nd in 6% the complete destruction of the organ occurred. In all, 76% of these traumas were treated conservatively, whereas 8% each required reconstruction or nephrectomy. Amongst the urethral ruptures, 46% were complete; 39% partial posterior; and 11% ruptures of the penile urethra. In 43% of cases the treatment was conservative and in 41% a primary reconstruction was carried out. All intraperitoneal (43%) and 2/3 of the extraperitoneal bladder ruptures (57%) were operated on. Gross hematuria was found in 73% of the renal, 83% of the vesical and 73% of the urethral injuries. Microhematuria occurred in 24%, 9% and 13% of cases, whereas no hematuria was found in 3%, 5% and 13% of the kidney, bladder and urethral injuries, respectively. The injury-relevant sensitivity of the imaging methods was computed to be 95% for cystograms, 91% for urethrograms and 83% for angiograms. When used to screen trauma patients, the sensitivity proved to be 69% for the CT scan, 55% for the intravenous pyelogram (IVP) and 54% for sonography. Overall, 37% of 161 complications involved the UG tract, followed by neurological complications, those due to the operation or treatment, to infections or to organ failure. In all, 11% of patients remained in the hospital for only 1 day; 50% for up to 13 days; 20% for 14–60 days; and 17% for 〉60 days.
    Type of Medium: Electronic Resource
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  • 4
    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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