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Zusammenfassung
Intrauterin wachstumsretardierte Neugeborene konnten ihr genetisches Wachstumspotential aufgrund einer intrauterinen Mangelversorgung nicht realisieren und werden deshalb zu klein oder zu leicht geboren. Das Merkmal „zu leicht” wird mit Hilfe von Gewichtsperzentilen quantifiziert. Kinder mit einem Gewicht< 10. Perzentile werden als „small for gestational age” (SGA) bezeichnet. Diese Einteilung berücksichtigt jedoch nicht die Proportionen eines Neugeborenen, so daß vor allem asymmetrisch retardierte Neugeborene, deren Gewicht zwar die 10. Perzentile noch überschreitet, die jedoch für ihre Körpergröße untergewichtig sind, nicht erfaßt werden. Der Ponderal Index (PI) dagegen berücksichtigt sowohl Gewicht als auch Länge des Neugeborenen. Kinder mit einem PI < 10. Perzentile werden als „low Ponderal Index” (LPI) klassifiziert. Aus pädiatrischen Studien ist bekannt, daß LPI-Kinder vermehrt durch Hypoglykämien, Hypothermien, Hypokalzämien und Mekoniumaspirationen/Aspirationspneumonien gefährdet sind. Langzeiterhebungen zeigten eine verzögerte körperliche Entwicklung und gehäuft motorische oder neurologische Verhaltensauffälligkeiten sowie schulische Probleme.
Fragestellung: Ziel der vorliegenden Arbeit war die Frage, ob Mangelgeborene, insbesondere LPI-Neugeborene, auch intrapartum einer erhöhten Gefährdung ausgesetzt sind.
Methoden: Hierzu wurden 3687 Neugeborene retrospektiv erfaßt, die anhand von Perzentilenkurven des betrachteten Kollektivs als SGA, LPI, SGA/LPI oder Vergleichskollektiv klassifiziert wurden.
Ergebnisse: Unterschiede im Geburtsmodus zwischen SGA- bzw. LPI-Mangelgeborenen und eutrophen Neugeborenen waren schwach ausgeprägt. Demgegenüber unterschied sich die Indikation, aufgrund deren ein geburtshilflicher Eingriff vorgenommen werden mußte deutlich. Bei 31 % aller operativ entbundenen LPI-Neugeborenen, 47 % der SGA-Neugeborenen und 52 % der SGA/LPI-Kinder erfolgte die operative Entbindung aus fetaler Indikation, im Vergleich zu 16 % des Normalkollektivs. Bezüglich des „fetal outcome”, das die Merkmale neonataler Säure-Basen-Status, Apgar-Wert, Verlegung in die Kinderklinik und perinatale Mortalität einbezog, verhielten sich die Gruppen SGA, LPI und SGA/LPI in gleicher Weise schlechter gegenüber dem Vergleichskollektiv. Die Unterschiede zwischen proportionierten (SGA) und dysproportionierten (LPI) Mangelgeborenen waren weniger deutlich.
Schlußfolgerungen: Es zeigte sich, daß das gegenwärtige engmaschige, geburtshilfliche Management mit nahezu permanenter CTG-Überwachung sub partu Probleme rechtzeitig erkennen und beherrschen ließ. Die Erfassung des niedrigen Ponderal Index war zur Erkennung und Vermeidung subpartaler geburtshilflicher Risikofaktoren nicht entscheidend.
The single most common cause leading to the diagnosis of endometrial cancer is postmenopausal bleeding. Although most patients with early-stage disease (FIGO stage I and II) can be cured, prognosis worsens considerably with increasing stage. While serum CA 125 levels are elevated only in a significant proportion of patients with advanced disease, recently a new serum marker (OVX1) for the detection of early-stage endometrial cancer was reported. Serum OVX1 levels were measured using an OVX1 radioimmunoassay (RIA) or enzyme immunoassay (EIA) in 192 patients with endometrial cancer. CA 125 levels were measured in 112 patients using the CIS ELSA CA 125 kit. Apparently healthy females had mean serum OVX1 levels measured with the OVX1–EIA of 1.34 ± 0.74 U/ml, while patients with endometriosis had mean OVX1 serum levels of 3.15 ± 2.45 U/ml. The mean OVX1 serum level for endometrial cancer patients was 2.00 ± 1.32 U/ml. These values were 2.76 ± 1.62, 6.10 ± 4.66, and 5.37 ± 3.49, respectively, using the OVX1–RIA assay. Applying a cutoff value of 2.8 U/ml, serum OVX1–EIA levels in endometrial cancer patients were increased in 25 of 127 patients (19.7%) with stage I disease, 5 of 17 patients with stage II (29.4%), 5 of 22 patients (22.7%) with stage III, and 4 of 11 patients (36.4%) with stage IV disease. Using the OVX1–RIA and a cutoff of 7.2 U/ml, serum levels were increased in 22 of 127 (17.3%) stage I, 6 of 17 (35.3%) stage II, 5 of 22 (22.7%) stage III, and 6 of 11 (54.5%) stage IV patients. Serum CA 125 levels, determined in a total of 112 patients, were elevated above 35 U/ml in 12 of 79 patients (15.2%) with stage I, 4 of 12 patients (33.3%) with stage II, 8 of 13 patients (61.5%) with stage III, and all of 8 patients (100%) with stage IV disease. While a good correlation between serum CA 125 levels and the clinical stage of the disease was found, no correlation could be detected for OVX1 and stage.
Cis-diammine dichloro platinum (II) (CDDP), is a highly potent antineoplastic agent that is used in the treatment of ovarian cancer. However, the clinical use of CDDP is restricted by its severe side effects. In order to reduce these side effects and to enhance its therapeutic efficacy, we developed specific immunoconjugates consisting of the murine monoclonal antibody OC125 and CDDP, using diethylene triamine pentaacetic acid (DTPA) as a linker.
The coupling efficiencies of the different preparations synthesized, varied between 1.10±0.42 and 2.65±1.60 mol of CDDP per mol of antibody protein. Despite the chemical modification of the antibody molecule, specific binding activity of the OC125-CDDP conjugates toward the CA125 antigen was maintained as was demonstrated by means of immunohisto-/cytochemical staining of frozen sections of ovarian cancer tissue, amniotic epithelium, and the CA125 positive ovarian cancer cell line NIH:OVCAR 3.
The antiproliferative activity of the immunoconjugates was tested against the human ovarian cancer cell lines NIH:OVCAR3 and SKOV 3, applying a kinetic crystal violet microassay.
Despite the promising results obtained with the specific immuno-staining of the target cells, no significant antiproliferative activity of our immunoconjugates against the cell lines tested was observed.
One possible explanation for the lack of antitumor activity could be the fact that CA125 is released in large amounts by the NIH:OVCAR 3 cells. This may have prevented an efficient immunotargeting of the cancer cells by the formation of soluble immune complexes.
Identification of insulin and insulin-like growth factor I (IGF I) receptors in ovarian cancer
(1994)
Abstract
The objective of this study was to test if specific insulin and insulin-like growth factor I (IGF I) receptors are expressed in ovarian cancer tissue. Thirteen tissue specimens from primary ovarian cancers, 1 specimen from a primary peritoneal carcinoma, 10 specimens from metastatic lesions of ovarian carcinomas, and 4 specimens from recurrent ovarian cancers together with 13 normal ovaries were tested for their content of insulin and IGF-I receptors, by the application of specific insulin and IGF-I receptor radioimmunoassays. The insulin receptor (IR) and IGF-I receptor (IGF R) content in the primary tumors varied between 23.8-321.4 and 16.4-554.2 ng/0.1 mg DNA, respectively. Metastatic lesions contained between 12.3 and 226.7 ng IR/0.1 mg DNA and between 7.5 and 459.4 ng IGF R/0.1 mg DNA. In recurrent tumors the receptor concentrations were in the range of 41.5-79.8 and 48.9-160.9 ng/0.1 mg DNA for insulin and IGF-I receptors, respectively. Normal ovarian tissue contained between 12.2 and 150.1 ng IR and between 21.4 and 420.1 ng IGF R per 0.1 mg DNA, respectively. As both insulin and IGF-I receptors are present in ovarian cancer tissue, the effects of insulin and IGF-I as potential growth factors in ovarian cancer should be further investigated.
Copyright © 1994 Academic Press. All rights reserved.