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Der Bedarf labordiagnostischer Masnahmen in der Schwangerschaft ergibt sich einerseits aus der Notwendigkeit, Risikofaktoren fur eine Infektionsgefahrdung zu diagnostizieren, und andererseits auftretende Infektionen moglichst fruhzeitig zu erkennen, bevor eine Ausweitung mit vielseitigen generalisierten Symptomen und moglichen Komplikationen eintritt. Dafur stehen mikrobiologische, serologische sowie biochemische labordiagnostische Methoden zur Verfugung, wobei mikrobiologische und serologische Untersuchungen uberwiegend im Rahmen von Screeninguntersuchungen zur Definierung bzw. Erkennung von infektionsgefahrdeten Risikogruppen oder zur Spezifizierung einer manifesten Infektion dienen. Biochemische labordiagnostische Masnahmen werden hauptsachlich zur allgemeinen Infektionsdiagnostik eingesetzt.

The regulatory influence of medroxyprogesterone acetate (MPA) on estrogen and androgen receptors of the human breast cancer cell lines MCF-7 and EFM-19 was explored in conjunction with the growth-promoting properties of these steroids. In the absence of steroidal stimulation, up to 1 microM MPA had no effect on the proliferation of the MCF-7 cell strain used and of EFM-19 cells. Under stimulation with 10 nM 17 beta-estradiol or 1 microM dihydrotestosterone, dose-dependent inhibition of the cell proliferation rates by 0.1-1 microM MPA was observed. Binding of MPA to the androgen receptor (Kd = 2.1 nM) but not to the estrogen receptor was demonstrable. During incubation of MCF-7 or EFM-19 cells with 1 microM MPA for 7 days, the estrogen and androgen receptor contents were down-regulated by approximately 50% and 60%, respectively. Likewise, the number of androgen-binding sites was reduced to 35% of the untreated controls after incubation of MCF-7 cells with 1 microM synthetic progestin R5020 for 7 days. The results indicate down-regulation of estrogen and androgen receptors by progestins in the absence of stimulatory effects on the proliferation of mammary carcinoma cells.

Eine hormonelle Substitutionstherapie (HST) mit Ostrogenen fuhrt zu einer geringradigen Erhohung des Mammakarzinomrisikos, wenn diese uber einen Zeitraum von uber 10 Jahren durchgefuhrt wird. Zu diesem Ergebnis kommt die uberwiegende Zahl der vorliegenden Studien. Die Gesamtmortalitat und die mammakarzinombedingte Mortalitat sind jedoch reduziert. Dies hangt moglicherweise damit zusammen, das unter einer HST weniger maligne Tumoren mit einer geringeren Ausbreitung auftreten. Gestagene haben keinen Einflus auf das durch Ostrogene leicht erhohte Mammakarzinomrisiko. Eine HST kann bei einigen Frauen zu einer Dichtezunahme des Drusenparenchyms fuhren und somit die Fruherkennung von Mammakarzinomen bzw. von intramammaren Rezidiven nach brusterhaltender Therapie behindern. Derzeit liegen keine umfangreichen Informationen zur Sicherheit einer HST nach Mammakarzinom vor, so dasuber den Einsatz der Therapie erst nach Abwagen des potentiellen Rezidivrisikos gegenuber dem Nutzen gemeinsam mit der Patientin entschieden werden kann.

In the present study we used the well known antiviral properties of interferon alpha 2b in condylomata acuminata. Firstly we investigated 3 different application forms. We found that 1. the local INF application in gel was completely ineffective, 2. the injection of INF into the base of the warts was effective but too painful for routine therapy, 3. the systemic treatment by s.c.-injection had an excellent compliance and a high efficacy. In the second part of the study we treated 16 patients with our own s.c.-regimen of 3 x 5 mill. U and 6 x 2 mill. U INF alpha 2b within 5 weeks. 60% showed a complete response, 30% a partial response; these were treated surgical afterwards. In none of the patients a relapse occurred at a median follow-up of 11 months. The observed side-effects were poor. We consider the systemic treatment with interferon for condylomata acuminata to be highly effective and well tolerated. The relapse rate is very poor.

In a 28-year-old patient with a large uterine leiomyoma, complete tumor regression was achieved by the LHRH agonist Zoladex (ICI 118.630) when administered three times. During the follow-up period of three months, new myoma growth did not occur. On the basis of this case study, it is necessary to discuss a new therapy concept for the differentiated treatment of uterine leiomyomata in young women with a desire for pregnancy.

Von 110 Patientinnen wurden nach Abschlus der Primarbehandlung im Rahmen der Tumornachsorge (No evidence of disease) (NED) Stadium des Karzinoms, die TPA und CEA Plasmakonzentrationen uberwacht. 29% zeigten dabei TPA-Konzentrationen uber dem bisher etablierten „cut off level“ von 85 U/1. Oberhalb 120 U/1 befanden sich noch 9% der Werte. CEA wurde nur in 3,6% oberhalb des „cut off limit“ von 5,0 µg/1 bestimmt. Anamnestische Daten der Patientinnen sowie die Auswertung 12 weiterer Laborparameter sollten Aufschlus uber unspezifische Veranderungen der Tumormarker TPA und CEA geben. Die Untersuchungen zeigten einen eindeutigen Zusammenhang zwischen dem Alter der Patientinnen und ihrer mittleren TPA-Plasmakonzentration (Abb. 1). Das Signifikanz-niveau mit dem Chi-Quadrat-Test betrug 99%.

A urinary chorionic gonadotrophin (hCG) preparation, mitogenic for ovarian carcinoma cells, was analysed by gel filtration through Sephadex G-100 Superfine. The resulting fractions were tested for hCG and for properties of the epidermal growth factor (EGF) by radioimmunoassays (RIA) in comparison with their ability to stimulate the growth of EFO27nu ovarian carcinoma cells. The elution profile of the RIA activities for hCG corresponded to molecular weights of 12 and 71 kDa, whereas the mitogenic activity was found in peak fractions eluting at 7, 11 and 52 kDa, indicating the presence of mitogenic substances distinct from hCG or its β-subunit. In comparison experiments, radiolabelled recombinant human EGF eluted at 7 kDa from the column. The profile of EGF immunoreactivity determined in the eluant fractions of hCG preparation A correlated with the mitogenic potential. Eluant fractions with growth-promoting activity competed with 125I-labelled EGF in binding to EFO-27nu cells; the inhibition of EGF binding was correlated with the mitogenic potential and the EGF immunoreactivity. We assume that the 7 kDa component of the gel filtration eluate corresponds to monomeric EGF; the high molecular weight mitogens may represent EGF precursor protein fragments of various molecular size classes. Journal of Endocrinology (1989) 123, 333–340

In der Verlaufskontrolle und Nachsorge von Patientinnen mit malignen gynakologischen Erkrankungen hat in den letzten Jahren neben den klinisch-rontgenologischen Methoden die Bestimmung von Tumormarkern an Bedeutung gewonnen. Fortschritte der Hybridomtechnik fuhrten in den letzten 3–4 Jahren auf der Basis monoklonale Antikorper zur Beschreibung verschiedener neuer tumorassoziierte Antigene im menschlichen Mammakarzinomgewebe. Von Kufe wurde erstmals 1984 ein monoklonaler Mausantikorper mit der Bezeichnung DF 3 beschrieben, der gegen eine Membran-angereicherte Fraktion eines in die Leber metastasierten Mammakarzinoms reagierte (Kufe et al. 1984). Immunhistochemische Untersuchungen ergaben eine Korrelation zwischen zytoplasmatischer Verteilung des Antigens und zunehmender Entdifferenzierung mit Verlust sekretorischer Funktionsfahigkeit benigner und maligner Zellveranderungen.

The tumour-associated antigen was determined in the plasma of patients with squamous cell carcinoma (SCC) of the uterine cervix by radioimmunoassay. Setting a limit of 2 ng/ml, levels were abnormal in 13.4% of healthy controls, in 14% of patients with carcinoma in situ and in 62% of patients with invasive cervical SCC. The incidence of elevated SCC antigen levels and the absolute antigen plasma concentration were dependent upon the tumour load, increasing significantly with advanced stage disease. Abnormal SCC antigen values in operable cervical cancer declined to normal within one week after radical hysterectomy with pelvic lymphadenectomy. In cases of radiotherapy antigen values took 4-6 weeks after the start of treatment to return to normal. The success of both treatment modalities was announced by an early rise in the SCC antigen in the initial phase of therapy, followed by normalisation. After successful primary treatment and a complete remission during further follow-up SCC antigen in plasma was only increased in 3.8% of the cases. Retrospective evaluations in ten patients with progressive disease showed the reappearance of abnormal SCC titers and further increase preceeding the clinically detectable relapse or progression, with a median interval of 8 weeks. The present study indicates that SCC antigen determination is not useful for the early diagnosis of cervical cancer, but it is a potential means for monitoring the efficacy of individual anticancer therapy of SCC of the uterine cervix and for detecting recurrent disease.

The proliferation of three mammary carcinoma cell lines was explored for the effectiveness of dihydrotestosterone (DHT) and the antiandrogenic substances cyproterone acetate (CPA) or hydroxyflutamide. The cell growth, determined in multiple experimental cultures of the estrogen-sensitive lines MCF-7 and EFM-19, was stimulated by 10(-9) M to 10(-6) M DHT, whereas estrogen-resistant MFM-21 cells were unresponsive to the hormonal factors applied. Growth-promoting effects of 10(-8) M to 10(-6) M CPA were detected in cultures of those cell lines which were sensitive to estrogen and androgen. Competition experiments with DHT and the antiandrogens suggested involvement of the androgen receptor in the stimulation of cell growth by CPA. Participation of the estrogen receptor was excluded by lack of competition between CPA and the enhancement of proliferation by estradiol-17 beta. At the receptor level the antiandrogens were able to compete with androgen binding. The results of the study demonstrate androgenic properties of CPA in regard to the growth of human mammary carcinoma cells.

CA 15.3 is an antigenic determinant associated with human mammary carcinomas. Two murine monoclonal antibodies have been raised against the determinants, and an immunoradiometric assay (IRMA-Kit, Centocor, USA) has been developed to determine the antigen levels in plasma of cancer patients. Based on the 99% confidence limit of healthy women, plasma values above 30 U/ml are considered abnormal. Plasma samples from 357 women were examined in the present study. Healthy females (n = 84) ranged below the cut-off level between < 10 and 29 U/ml. Higher values were found in 12.5% of benign breast diseases and in 23.6% of breast cancer patients, including all stages. Depending on the stage of the disease, there were elevated levels in 11% of operable breast cancer patients preoperatively, in 7% of the cases with no evidence of disease after primary treatment and in 63.5% ofpatients with disseminated mammary carcinoma. In metastasized breast cancer the frequency and the degree of abnormal titers were closely related to the extent of the metastatic disease. Follow-up examinations of 63 patients under cytotoxic therapy showed CA 15.3 changes correlating well with the clinical course in up to 90% of the antigen positive cases. The present data indicate that CA 15.3 may be useful in the surveillance of breast cancer patients. However in our study one third of the patients with metastatic breast cancer did not show any increase in CA 15.3 and must be regarded as antigen negative.

Das Gestagen Medroxyprogesteronacetat (MPA) wird vielfach in der endokrinen Therapie des metastasierten Mammakarzinoms eingesetzt. Ein Teilaspekt der therapeutischen Wirksamkeit von MPA wird in der Verminderung der Serumspiegel von Androgenen und Glukokortikoiden durch die Suppression der Nebennierenrinde gesehen. Die davon unabhangige Hemmung des Tumorwachstums auf zellularer Ebene wird in der vorliegenden Arbeit untersucht. Dabei wird besonders die Interaktion von MPA mit den stimulierenden Steroiden 17s-Oestradiol (E2) und Dihydrotestosteron (DHT) berucksichtigt.

The plasma levels of CA 12-5 were determined by radioimmunoassay in 50 healthy volunteers, 53 pregnant women, 10 patients with benign lesions of the ovary, in 37 patients with recurrent or primary ovarian cancer, in 34 patients with no recurrent ovarian carcinomas and in a small number of patients with other types of malignancies. Furthermore we investigated the amniotic fluid of 71 pregnant women with regard to their CA 12-5 concentration. Elevated Ca 12-5 values were found in 2% of normal controls, in 80% of patients with primary ovarian cancer stage III and IV, in 69% of patients with recurrent ovarian carcinoma, in 6% of pregnant women and in 100% in very high concentration in the amniotic fluid. The elevation of CA 12-5 were dependent on the histology of the tumor. Observations of patients under therapy (surgery or systemic cancerostatic treatment) demonstrated a correlation between CA 12-5 concentration and tumor activity.

Klinische Studien uber TPA untersuchen meist dessen Relevanz als Tumormarker bei unterschiedlichen malignen Erkrankungen. Doch wird TPA auch als Indikator fur allgemein proliferative Aktivitat angesehen.

The radiation included 50 Gy to the thoracic wall and the regional lymph node areas (beginning ~ 12 days after mastectomy). The adjuvant polychemotherapy was administered in form of combined treatment with adriamycin (day I ,i.v., 40 mg/m 2 ) and cyclophosphamide (days 3-6,per os,200 mg/m 2 ) over a 12 month period (~ 8 max. 12 cycles), beginning ~ 12 days after radiation (groups IA and IIA) or ~ 12 days after mastectomy (group IIB). Results: Adjuvant chemotherapy appears to delay the time of recurrence for about two years. The frequency or recurfence is not influenced. The radiotherapy reduces the frequency of thoracic wall recurrences in patients with high grade of positive lymph node, the time of recurrence is delayed for about 10months. Data according to the menopausal status, the histological grading and the steroid hormone receptor levels are shown as well as the side effects of adjuvant treatment. Universit~tsfrauenklinik K~in, Kerpener Str. 34, 5 K~in 41, * Strahlentherapeutisches Institut der Universit~t K@in Bre 13 RISK OF BREAST CANCER IN PATIENTS WITH MASTOPATHY A LONG TERM FOLLOW-UP. W.Friedl, C.Tschahargane, P.Schlag

Cyproterone acetate (CPA) is a synthetic steroidal compound with multiple endocrine effects in different types of hormone dependent tissues. CPA was used for the palliative treatment of breast cancer. 34% partial remissions or status of no change were observed in a group of 41 patients as described before (Schulz, K.-D. et al. Verh. Dtsch. Krebs Ges 3, 187, 1982). The present study was designed to investigate the way of action of CPA. Systemic endocrine effects were monitored under prolonged CPA treatment. Serum levels of cortison (C), androstendione (A), dehydroepiandrostetone (DHEA), dihydrotestosterone (DHT), testosterone (T), estradiol (E2), prolactin (Prl), FSH and LH were determind. The androgens A, DHEA, DHT and T decreased 30-50% during CPA treatment. Postmenopausally elevated levels of FSH and LH dropped to the range of 20mIU/ml. C, E2 and Prl were not altered significantly. Permanent cell lines from human mammary carcinomas were incubated with CPA in vitro in a dose range from Ing/ml to l~g/ml. At concentrations higher than 100ng/ml the cell proliferation was inhibited significantly. Thus the clinical benefit of CPAtreatment may be the consequence of direct interference with proliferation at the cellular level and of systemic endocrine effects, which in turn may reduce the amount of organotrophic growth factors favouring tumor cell proliferation.