A. Schroer

Triple-negative breast cancers express receptors for growth hormone-releasing hormone (GHRH) and respond to GHRH antagonists with growth inhibition

Triple-negative breast cancers do not express receptors for estrogen or progesterone and do not overexpress HER2. These tumors have an unfavorable prognosis and at present chemotherapy is the only treatment option. Because the antagonists of growth hormone-releasing hormone (GHRH) have been shown to inhibit growth of a variety of cancers by endocrine and paracrine/autocrine mechanisms, we evaluated the expression of GHRH receptors in human specimens of triple-negative breast cancers and the response to GHRH by inxa0vitro models. In samples of triple-negative breast cancers we found mRNA expression for the GHRH receptor and its functional splice variant SV1 in 25 and 70% of the cases, respectively and for GHRH in 80% of the samples. Immunoreaction of SV1 was detected in the human triple-negative breast cancer cell line HCC1806 while HCC1937 was negative. The growth of HCC1806 was stimulated by GHRH(1-44)NH2 and inhibited by GHRH antagonist MZ-J-7-118. In addition, in HCC1806 MAP-kinases ERK-1/2 were activated by GHRH. Our findings suggest the existence of an autocrine loop consisting of GHRH and GHRH receptors in triple-negative breast cancers. Our inxa0vitro studies demonstrate that targeting the GHRH receptor may be a therapeutic option which should be evaluated in studies inxa0vivo.

Follicular and endocrine response to anastrozole versus clomiphene citrate administered in follicular phase to normoovulatory women: a randomized comparison

OBJECTIVEnTo compare the effect on follicular growth and endocrine parameters of follicular phase administration of anastrozole to healthy, normoovulatory women in doses of 1 or 5 mg, respectively, with the conventional dosing regimen for ovulation induction with clomiphene citrate (CC).nnnDESIGNnRandomized, assessor-blinded, single-center, three-armed study.nnnSETTINGnUniversity-affiliated, tertiary referral center.nnnPATIENT(S)nThirty-two, normoovulatory, normogonadotropic women.nnnINTERVENTION(S)nAdministration of anastrozole 1 mg (group A1), anastrozole 5 mg (group A5), or CC 50 mg (group CC50) from cycle days 3 to 7.nnnMAIN OUTCOME MEASURE(S)nNumber of follicles >or=15 mm and >or=10 mm on the day of the endogenous LH surge.nnnRESULT(S)nThe mean number of follicles >or=15 mm on the day of LH surge was 1.4 +/- 0.5, 1.0 +/- 0.4, and 0.8 +/- 0.4 in groups CC50, A1, and A5, respectively, which was statistically significant. Furthermore, a statistically significant difference between groups was found for the size of the growing follicular cohort (follicles >or=10 mm) on cycle days 8 and 10 and on the day of LH surge. The area under the curve (adjusted for baseline values on cycle day 3 and time frame of assessment) of follicular phase E(2) levels was significantly different among the groups that were compared (223.0 +/- 97.5, 69.2 +/- 40.0, and 83.4 +/- 36.4 for groups CC50, A1, and A5, respectively).nnnCONCLUSION(S)nCC 50 mg exerts a stronger stimulatory effect on follicular growth compared with anastrozole in doses of 1 or 5 mg. Anastrozole administration results in lower follicular phase E(2) levels.

Die radikale Primäroperation des fortgeschrittenen Ovarialkarzinoms

ZusammenfassungÜber 60% der Ovarialkarzinome werden im fortgeschrittenen Stadium FIGOxa0III/IV erkannt. Präoperativ ist eine Einschätzung der Tumorausdehnung nur unzureichend möglich. Die Prognose hängt im Wesentlichen von den operativen Möglichkeiten ab, Tumorfreiheit zu erreichen. Dafür ist eine große operative Erfahrung und ggf. ein interdisziplinäres Vorgehen notwendig, weswegen diese Operationen in spezialisierten Zentren geplant werden sollten. Von der Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-Ovar) wird ein standardisiertes Vorgehen empfohlen. Bei Tumorbefall sind Eingriffe im Oberbauch wie die Entfernung von Metastasen im Bereich des Diaphragmas, die Splenektomie oder Leberresektionen indiziert, die pelvine und paraaortale Lymphonodektomie soll durchgeführt werden, wenn insgesamt eine Tumorreduktion auf mindestens R1 zu erreichen ist. Durch die gesteigerte Radikalität des Primäreingriffs und die nachfolgende adjuvante platin- und taxanhaltige Chemotherapie wird die progressionsfreie Zeit wie auch die Überlebenszeit verlängert. Die Radikalität des Eingriffs muss auf das biologische Alter und den Allgemeinzustand der Patientin abgestimmt sein.AbstractMore than 60% of ovarian carcinomas are only recognized in the advanced FIGO III/IV stage. A preoperative estimation of the extent of the tumor is only insufficiently possible. The prognosis essentially depends on the operative possibilities to achieve complete resection of the tumor. Therefore, skillful operative techniques and should the occasion arise, an interdisciplinary cooperation are necessary, therefore surgery should be planned in specialized centers. The Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-OVAR) recommends a standardized procedure. In cases of tumors in the upper abdomen, operations such as the removal of metastases in the region of the diaphragm, splenectomy or liver resection are recommended. Pelvic and paraaortal lymphadonectomy should be carried out if a tumor reduction of at least level R1 can be attained. An increased radicality of the operation and the following adjuvant chemotherapy with platinum and taxan lead to an extension of the progression-free period as well as the overall survival rate. The radicality of the operation must be harmonized with the age and general condition of the patient.

Arguments for elective single-embryo transfer

Over the past 25 years, artificial reproductive techniques have significantly improved and are now a well-established practice. While pregnancy, without consideration of obstetric and neonatal outcomes, was the main focus of the practice in the past, today a practice is esteemed successful if a healthy baby is delivered in a short treatment time with low risks for the patient and the baby. Human reproduction itself is quite inefficient. During the period of conception, implantation and placentation to the delivery of a baby, a number of aberrations can occur, resulting either in no pregnancy or a loss of pregnancy. In order to compensate for the low implantation rate of human embryos, it is routine to transfer more than one embryo in each treatment cycle as a routine procedure. As a result, the incidence of multiple pregnancy (MP; twins and higher order pregnancies) after IVF/intracytoplasmic sperm injection is much higher (30%) than after natural conception (1%). The obstetric, neonatal and long-term con...