Search

Die Pravalenz der Adipositas nimmt weltweit rapide zu. Die gesundheitlichen und okonomischen Konsequenzen dieser Entwicklung sind bedeutsam, da Adipositas mit zahlreichen Erkrankungen assoziiert ist. Neben einer Erhohung des Risikos fur Typ-II-Diabetes und kardiovaskulare Erkrankungen bestatigen grose prospektive Studien, dass Ubergewicht die Inzidenz und Mortalitat einer Reihe von bosartigen Tumoren erhoht. Zu diesen zahlen die Karzinome des Kolons, der Mamma (postmenopausal) und des Endometriums sowie das Nierenzellkarzinom und Adenokarzinome des Osophagus. Die gesteigerte Insulinresistenz und die daraus resultierende chronische Hyperinsulinamie, die hohere Bioverfugbarkeit von Steroidhormonen und lokale Entzundungsprozesse werden als potenzielle Mechanismen fur die adipositasassoziierte Entstehung und Progression von Tumoren angefuhrt. Auch einige aus dem Fettgewebe stammende Hormone, Adipozytokine, scheinen die Karzinogenese zu beeinflussen. Vieles deutet darauf hin, dass diatetische Interventionsstrategien das Risiko fur Krebserkrankungen vermindern und die Prognose verbessern.

Metastasis to bone is a frequent problem of advanced breast cancer. Particularly breast cancers, which do not express estrogen and progesterone receptors and which have no overexpression/amplification of the HER2- neu gene, so called triple-negative breast cancers, are considered as very aggressive and possess a bad prognosis. About 60% of all human breast cancers and about 74% of triple-negative breast cancers express receptors for gonadotropin- releasing hormone (GnRH), which might be used as a therapeutic target. Recently, we could show that bonedirected invasion of human breast cancer cells in vitro is time- and dose-dependently reduced by GnRH analogs. In the present study, we have analyzed whether GnRH analogs are able to reduce metastases of triple-negative breast cancers in vivo. In addition, we have evaluated the effects of GnRH analogs on tumor growth. To quantify formation of metastasis by triple-negative MDA-MB-435 and MDAMB- 231 human breast cancers, we used a real-time PCR method based on detection of human-specific alu sequences measuring accurately the amount of human tumor DNA in athymic mouse organs. To analyze tumor growth, the volumes of breast cancer xenotransplants into nude mice were measured. We could demonstrate that GnRH analogs significantly reduced metastasis formation by triple-negative breast cancer in vivo. In addition, we could show that GnRH analogs significantly inhibited the growth of breast cancer into nude mice. Side effects were not detectable. In conclusion, GnRH analogs seem to be suitable drugs for an efficacious therapy for triple-negative, GnRH receptorpositive human breast cancers to prevent metastasis formation. peerReviewed

In den letzten Jahren wurden zahlreiche Hinweise fur die Existenz von Stammzellen in Tumoren gefunden. Die Tumorstammzelltheorie besagt, dass Tumoren sich aus einer Subpopulation maligner Zellen entwickeln, die Stammzellcharakteristika aufweisen. Diese Zellen zeigen sowohl Zuge von Stammzellen als auch von Tumorzellen. So besitzen sie die Fahigkeit zu Selbsterneuerung, asymmetrischer Zellteilung und unabhangigem Wachstum, zeigen Resistenz gegenuber Apoptoseinduktion, sind tumorigen und haben metastatisches Potenzial. Die Entwicklung aus Tumorstammzellen konnte die Heterogenitat von Tumoren eines Gewebes sowie Rezidive nach Therapie erklaren. In diesem kurzen Uberblicksbeitrag berichten wir uber den Fortschritt in der Erforschung von Tumorstammzellen, dabei liegt der Schwerpunkt auf gynakologische Tumoren einschlieslich des Mammakarzinoms.

Angiogenese bezeichnet das Wachstum von Blutgefasen aus einem vorgebildeten Kapillarsystem. Angiogenese ist ein physiologischer Prozess bei Entwicklung und Wachstum von Geweben und Organen. Die Blutgefasentwicklung wird durch eine Veranderung des Gleichgewichts zwischen pro- und antiangiogenen Faktoren induziert. Angiogenese spielt in der Kontrolle des Menstruationszyklus sowie bei Implantation und Wachstum der Plazenta eine wichtige Rolle. Bei vielen Erkrankungen in der Gynakologie und Geburtshilfe (z. B. ovarielles Hyperstimulationssyndrom, Endometriose, Praeklampsie) ist die Regulation angiogener Prozesse gestort. Angiogenese ist auch beim Wachstum und der Metastasierung maligner Tumoren von essentieller Bedeutung. Inhibitoren der Tumorangiogenese sind in den Blickpunkt neuer Therapiestrategien gekommen. Die Wirksamkeit des antiangiogenen Antikorpers Bevacizumab in der Behandlung von metastasierendem Brustkrebs wurde nachgewiesen. Der Beitrag gibt eine Ubersicht uber die Rolle der Angiogenese in der Reproduktionsmedizin und der gynakologischen Onkologie mit Akzentuierung der klinischen Relevanz.

Bei der fertilitatserhaltenden konservativen Therapie des gut differenzierten endometrioiden Endometriumkarzinoms des klinischen Stadiums IA sind hoch dosierte Gestagene uber mindestens 3, besser 6 Monate Mittel der Wahl. In der adjuvanten Therapie primar operierter Endometriumkarzinome mit hoher Rezidivrate haben endokrine Therapien bisher keine Wirksamkeit gezeigt. Auch fur adjuvante Chemotherapien ist die Datenlage noch schwach. Lediglich in einer Studie konnte fur gut operierte Endometriumkarzinome gezeigt werden, dass eine Chemotherapie einer perkutanen Strahlentherapie uberlegen ist. In den Stadien I und II muss die Wirksamkeit einer adjuvanten Chemotherapie (± Brachytherapie ± perkutaner Strahlentherapie) evaluiert werden.

Most cases of endometrial cancer (EC) become symptomatic at an early stage and have a good prognosis. EC has been traditionally treated with total abdominal hysterectomy plus bilateral salpingo-oophorectomy. For early stage, low grade cases (endometrioid, pT1a, pT1b; G1, G2) this is adequate therapy. For higher stages and grades, especially for type II EC (serous, clear cell) this therapy is insufficient. The efficacy of systematic pelvic and paraaortic lymphadenectomy for high risk EC, however, remains to be evaluated. External pelvic radiotherapy has been shown to improve local control in stage I and II EC, but has no positive effect on survival. A comparable improvement of local control can be achieved by vaginal brachytherapy with significantly less toxicity. Adjuvant chemotherapy is probably efficacious in EC. Its usefulness as exclusive adjuvant therapy or in combination with brachytherapy and/or external beam therapy remains to be evaluated by prospective trials.

BACKGROUND: According to current recommendations tocolysis for more than 48 h is only indicated in selected cases. The aim of this study was to analyse the relevance of long-term tocolysis with beta-2-mimetics (Fenoterol) at a single centre over a period of three years. METHODS: Tocolysis was performed in the case of isolated preterm contractions in 39 cases (56.5%) and in case of premature rupture of membranes in 30 cases (43.5%). RESULTS: 34 cases of tocolysis (49.3%) were started at 7 days 28 cases (40.6%). Neonatal complications occurred less with increasing gestational age: for

BACKGROUND: Postpartum haemorrhage is an important cause of maternal mortality. After failure of medical treatment, the application of uterine compressive sutures as described by Pereira to treat postpartum bleeding is an alternative to hysterectomy. MATERIAL AND METHODS: The uterus is compressed by multiple, superficially inserted sutures which are applied transversally and longitudinally around the uterus. Additionally the vascular flow is reduced. RESULTS: Five women underwent a Caesarean section and, in spite of treatment with oxytocin and sulprostone developed severe postpartum haemorrhage. Compression sutures of the uterus as described by Pereira were successful in all cases. The follow-up was uneventful in all cases. CONCLUSION: Compressive sutures of the uterus as described by Pereira are easy and quick to perform for treating uterine atony with postpartum bleeding.

Die Pravalenz der Adipositas nimmt in alarmierendem Ausmas zu. Gesundheitliche wie okonomische Konsequenzen sind bedeutsam, da Adipositas mit zahlreichen Erkrankungen assoziiert ist. Umfangreiche prospektive Studien zeigen, dass Adipositas auch mit mehreren Krebsarten signifikant assoziiert ist. Die IARC der WHO halt die Beweise hinsichtlich des kausalen Zusammenhanges von Ubergewicht und Karzinomen des Kolons, der Mamma (postmenopausal), des Endometriums, der Niere (Nierenzellkarzinom) und des Osophagus (Adenokarzinom) fur ausreichend. Zu den potenziellen pathogenetischen Mechanismen gehoren u. a. gesteigerte Insulinresistenz, chronische Hyperinsulinamie und die erhohte Bioverfugbarkeit von Steroidhormonen. Zudem konnte gezeigt werden, dass Adipozytokine in gewissem Mas am Prozess der Karzinogenese beteiligt sind. Am uberzeugendsten hat die Women’s Intervention Nutrition Study zeigen konnen, dass Lebensstilanderungen das Risiko fur ein erneutes Auftreten von Brustkrebs sogar vermindern konnen.

Das maligne Potenzial einiger Keimstrang-Stroma-Tumoren (z. B. Thekome, Fibrome, Gynandroblastome, Leydig-Zell-Tumoren) ist meist gering und die Prognose gunstig, andere Tumoren dieser Gruppe (z. B. Granulosazelltumoren, Sertoli-Leydig-Zell-Tumoren G2/G3 oder mit heterologen Elementen) konnen jedoch malignes Verhalten und letale Verlaufe zeigen. Mit Ausnahme der Fibrome sezernieren die meisten Steroide. Dies fuhrt in Abhangigkeit vom Alter zu Pseudopubertas praecox, Fertilitats- und Zyklusstorungen und postmenopausalen Blutungen. Haufig findet sich eine Hyperplasie oder ein Karzinom des Endometriums. Die Therapie besteht in der Resektion, deren Ausmas vom malignem Potenzial und vom Stadium abhangt. Ovarielle Keimzelltumoren aus totipotenten primordialen Keimzellen verhalten sich sehr heterogen. Insgesamt ist die Prognose bei sachgerechter Therapie sehr gunstig. Die Therapie folgt einem multimodalen Konzept. Neueste therapeutische Fortschritte zielen auf die Erhaltung der Fertilitat ab. Das intraoperative Staging ist entscheidend fur eine adaquate Behandlung ohne Beeintrachtigung der Fertilitat. Dabei ist mit der Einfuhrung der platinhaltigen Chemotherapie ein wichtiger Durchbruch erzielt worden. Mit Ausnahme von Patientinnen mit reinen Dysgerminomen Stadium I sowie malignen Teratomen Stadium I und niedrigem Differenzierungsgrad benotigen alle mit Keimzelltumoren Stadium I oder fortgeschrittenen Stadien eine adjuvante Chemotherapie mit Bleomycin, Etoposid und Cisplatin.

Die Therapie der einfachen Endometriumhyperplasie ohne Atypien ist nach Ausschluss eines Ostrogen produzierenden Tumors in der Regel konservativ durch Beseitigung der endokrinen Ursache oder symptomatisch durch adaquate Gestagengabe moglich. Auch bei der komplexen Hyperplasie ohne Atypien ist—insbesondere bei bestehendem Kinderwunsch—eine konservative Therapie moglich. Beim Vorliegen von Atypien ist die sicherste Therapie die Hysterektomie. Bei bestehendem Kinderwunsch kann bei hoher Compliance der Patientin und der Gewahrleistung engmaschiger histologischer Kontrollen eine konservative Therapie erwogen werden, bis der Kinderwunsch erfullt ist. Bei fruhesten Stadien und hochdifferenzierten invasiven Karzinomen sind bei Kinderwunsch erfolgreich konservative Therapien durchgefuhrt worden, allerdings wurden auch onkologisch ungunstige Verlaufe beschrieben. Der Nutzen einer adjuvanten endokrinen Therapie ist bis heute nicht belegt. Bei Rezidiven, die nicht mehr operativ oder strahlentherapeutisch beherrschbar sind, und bei metastasierten Fallen sollte bei gut differenzierten und Rezeptor-positiven Tumoren zunachst eine endokrine Therapie versucht werden, sofern keine akut lebensbedrohlichen Tumormanifestationen vorliegen. In den anderen Fallen oder beim Versagen einer endokrinen Therapie kommt eine Chemotherapie zum Einsatz, deren Effektivitat jedoch bei meist hoher Toxizitat begrenzt ist. Patientinnen mit disseminierten Endometriumkarzinomen sollten moglichst in Studien behandelt werden, um eine Verbesserung der unbefriedigenden Situation zu erreichen.

OBJECTIVE: To analyze the relationship of the time interval between two deliveries, done by one obstetric team, on the delivery mode of the subsequent birth; to define the length of this interval; and to evaluate this time interval as a risk factor for increased perinatal mortality in a population-based cohort. METHODS: All singleton deliveries at ≥ 24 weeks' gestation in Lower Saxony, Germany, between 2001 and 2005 (a total of 317,663 deliveries including 402 cases of perinatal mortality) were analyzed. The mode of the previous and the subsequent delivery, the time interval between the two deliveries, the time of birth, the hospital volume, and the existence of an affiliated neonatal ward were investigated. RESULTS: When the first vaginal delivery was

Thus far the clinical benefits seen in breast cancer patients treated with drugs targeting the vascular endothelial growth factor (VEGF) pathway are only modest. Consequently, additional antiangiogenic approaches for treatment of breast cancer need to be investigated. Thrombospondin-2 (TSP-2) has been shown to inhibit tumor growth and angiogenesis with a greater potency than the related molecule TSP-1. The systemic effects of TSP-2 on tumor metastasis and the underlying molecular mechanisms of the antiangiogenic activity of TSP-2 have remained poorly understood. We generated a recombinant fusion protein consisting of the N-terminal region of TSP-2 and the IgG-Fc1 fragment (N-TSP2-Fc) and could demonstrate that the antiangiogenic activity of N-TSP2-Fc is dependent on the CD36 receptor. We found that N-TSP2-Fc inhibited VEGF-induced tube formation of human dermal microvascular endothelial cells (HDMEC) on matrigel in vitro and that concurrent incubation of anti-CD36 antibody with N-TSP2-Fc resulted in tube formation that was comparable to untreated control. N-TSP2-Fc potently induced apoptosis of HDMEC in vitro in a CD36-dependent manner. Moreover, we could demonstrate a CD36 receptor-mediated loss of mitochondrial membrane potential and activation of caspase-3 in HDMEC in vitro. Daily intraperitoneal injections of N-TSP2-Fc resulted in a significant inhibition of the growth of human MDA-MB-435 and MDA-MB-231 tumor cells grown in the mammary gland of immunodeficient nude mice and in reduced tumor vascularization. Finally, increased serum concentrations of N-TSP2-Fc significantly inhibited regional metastasis to lymph nodes and distant metastasis to lung as shown by quantitative real-time alu PCR. These results identify N-TSP2-Fc as a potent systemic inhibitor of tumor metastasis and provide strong evidence for an important role of the CD36 receptor in mediating the antiangiogenic activity of TSP-2. Electronic supplementary material The online version of this article (doi:10.1007/s10549-010-1085-7) contains supplementary material, which is available to authorized users.

Most cases of endometrial cancer (EC) become symptomatic at an early stage and have a good prognosis. EC has been traditionally treated with total abdominal hysterectomy plus bilateral salpingo-oophorectomy. For early stage, low grade cases (endometrioid, pT1a, pT1b; G1, G2) this is adequate therapy. For higher stages and grades, especially for type II EC (serous, clear cell) this therapy is insufficient. The efficacy of systematic pelvic and paraaortic lymphadenectomy for high risk EC, however, remains to be evaluated. External pelvic radiotherapy has been shown to improve local control in stage I and II EC, but has no positive effect on survival. A comparable improvement of local control can be achieved by vaginal brachytherapy with significantly less toxicity. Adjuvant chemotherapy is probably efficacious in EC. Its usefulness as exclusive adjuvant therapy or in combination with brachytherapy and/or external beam therapy remains to be evaluated by prospective trials.

According to current recommendations tocolysis for more than 48 h is only indicated in selected cases. The aim of this study was to analyse the relevance of long-term tocolysis with beta-2-mimetics (Fenoterol) at a single centre over a period of three years.Tocolysis was performed in the case of isolated preterm contractions in 39 cases (56.5%) and in case of premature rupture of membranes in 30 cases (43.5%).34 cases of tocolysis (49.3%) were started at30+0 weeks of gestation. The duration of tocolysis was48 h in nine cases (13%), 48 h 12 cases (17.4%), 3-7 days 20 cases (29%) and7 days 28 cases (40.6%). Neonatal complications occurred less with increasing gestational age: for28+0 weeks six of seven infants (85.7%), for 28+0 to 29+6 weeks six of 12 infants (50%), and for 30+0 to 33+6 weeks three of 42 infants (7.1%) suffered from complications. At this single centre long-term tocolysis was performed in 18 cases (26.1%) for28+0 and in 29 cases (42%) for32+0 weeks of gestation.The poor prognosis of extremely preterm infants improves rapidly with increasing gestational age, therefore long-term tocolysis should be considered as a therapeutic option in the case of an imminent birth.

Postpartum haemorrhage is an important cause of maternal mortality. After failure of medical treatment, the application of uterine compressive sutures as described by Pereira to treat postpartum bleeding is an alternative to hysterectomy.The uterus is compressed by multiple, superficially inserted sutures which are applied transversally and longitudinally around the uterus. Additionally the vascular flow is reduced.Five women underwent a Caesarean section and, in spite of treatment with oxytocin and sulprostone developed severe postpartum haemorrhage. Compression sutures of the uterus as described by Pereira were successful in all cases. The follow-up was uneventful in all cases.Compressive sutures of the uterus as described by Pereira are easy and quick to perform for treating uterine atony with postpartum bleeding.

In human solid cancer, the lymph node status is the most important prognostic indicator for the clinical outcome of patients. Follow-up data has shown that about 80% of metastasis follows an orderly pattern of progression via the lymphatic network while about 20% systemic metastasis occurs, bypassing the lymphatic system. Over the past few years, advances have been made in understanding the cellular and molecular aspects of physiological lymphangiogenesis and tumour-induced lymphangiogenesis, and the majority of studies point out to a positive correlation between tumour-induced lymphangiogenesis and lymphatic metastasis. However, the impact of intra- and peritumoural lymphatics on the tumour biology and the first steps of lymphatic metastasis, i.e. the invasion of tumour cells into the lymphatic vessels, are not well understood. We will give an outline of i. the physiological process of lymphangiogenesis, ii. tumour-induced lymphangiogenesis and lymphatic metastasis, iii. lymphatic invasion and the common pathways of tumourlymphangiogenesis and lymphatic invasion. The growing interest in this topic has brought up a number of new molecular players in the field, which may provide the basis for a rational therapy against the process of lymphatic dissemination of tumour cells.

Angiogenesis plays an important role for the growth and metastasis of malignant tumors. The "angiogenic switch" may even precede the development of other traits that contribute to the malignant phenotype. The switch to the angiogenic phenotype is thought to be induced by a change in the balance of positive and negative regulators of angiogenesis. The main emphasis of this review is to discuss the role of two potent endogenous inhibitors, thrombospondin-(TSP-)1 and TSP-2, for the development and progression of tumors. The recent identification of specific growth factors for lymphatic vessels and of new lymphatic-specific markers provided evidence for an active role of the lymphatic system during the metastasis process. Endogenous inhibitors of lymphangiogenesis have not yet been detected and until recently it was unclear whether or not the known endogenous angiogenesis inhibitors may also have some additional effects on lymphangiogenesis. The data provided indicate that angiogenesis inhibitors specifically inhibit tumor progression but fail to block the conversion of premalignant to malignant tumors. Moreover, angiogenesis inhibitors may have some elective effects on the formation of blood vessels but not on lymphatic vessels. These results will have implications for the further development and clinical use of angiogenesis inhibitors since they indicate that inhibitors might most efficiently be used to target early stages of tumor progression and in combination with specific inhibitors of lymphangiogenesis.