Trophoblast invasion: tuning through LIF, signalling via Stat3

Aberrant activity of the signal transducer and activator of transcription 3 (Stat3) is believed to be essential for neoplastic cell behaviour and thus for the malignancy of tumor cells [Bowman T, Garcia R, Turkson J, Jove R. STATs in oncogenesis. Oncogene 2000;19:2474-88]. Extravillous trophoblast cells resemble malignancies in their invasive and destructive features, excluding the fact of sequential restriction to the first trimester of pregnancy. Trophoblast cells from term placentas have reduced invasive capacity [Hohn HP, Denker HW. Experimental modulation of cell-cell adhesion, invasiveness and differentiation in trophoblast cells. Cells Tissues Organs 2002;172:218-36]. Constitutively activated Stat3 DNA-binding activity in choriocarcinoma cells, carcinomatous derivates of trophoblast cells, have been reported to correlate with its invasiveness [Corvinus FM, Fitzgerald JS, Friedrich K, Markert UR. Evidence for a correlation between trophoblast invasiveness and STAT3 activity. Am J Reprod Immunol 2003;50:316-21]. Here we demonstrate using RNAi that Stat3 activation is necessary in the invasive phenotype of trophoblast cells and can be controlled via Leukemia Inhibitory Factor (LIF). LIF provides a soluble extracellular signal that stimulates invasion in trophoblast and Jeg-3 choriocarcinoma cells. Loss of LIF-mediated invasion in these cells subsequent to STAT3 knock-down strongly suggests that STAT3 plays a crucial role in mediating this invasion

STAT3 and SOCS3 expression patterns during murine placenta development

<p>Signal transducers and activators of transcription 3 (Stat3) has been identified as an important signal transducer in the invasive phenotype of the trophoblasts cells in<em> in vitro</em> studies. However, the <em>in situ</em> distribution and patterns of expression of this molecule in trophoblast cells during the development of the placenta are still under-elucidated. Mice uteri of gestational ages between 7 and 14 days of pregnancy (dop) were fixed in methacarn and processed with immunoperoxidase techniques for detection of Stat3 and its phosphorylation at serine (p-ser727) residues, as well as the suppressor of cytokine signaling 3 (Socs3) expression. Stat3 was observed at 7 through 9 dop in both the antimesometrial and mesometrial deciduas, while continued immunoreactivity between 10 and 13 dop was seen only in the mesometrial decidua. In the placenta, Stat3 was detected in the cytotrophoblast cells of labyrinth and giant trophoblast cells between 10 and 14 dop. Immunoreactivity for Stat3 was also seen in trophoblast cells surrounding the maternal blood vessels. On days 10 and 11 of pregnancy, p-ser727 was detectable in the mesometrial decidua and in giant trophoblasts, while during 12-14 dop in the spongiotrophoblast region. In addition, Socs3 was immunodetected in maternal and placental tissues, principally in the giant trophoblast cells during the whole period of the study. The present <em>in situ</em> study shows the distribution of Stat3, its serine activation and Socs3 in different maternal and fetal compartments during murine placental development, thus further supporting the idea that they play a role during physiological placentation in mice.</p><p> </p

Translation individualisierter Diagnose- und Therapiekonzepte in die Klinik am Beispiel kardiologischer Erkrankung: Greifswald Approach to Individualized Medicine (GANI_MED)

Item does not contain fulltextBreast cancer during pregnancy (BCP), although rare, is becoming more common and treatment should be as similar as possible to that for nonpregnant young patients with breast cancer. A group of specialists convened to review current guidelines and provide guidance on how recent advances in breast cancer diagnosis and treatment can be adapted for pregnant patients. The majority of patients with BCP will be considered for treatment during the pregnancy. Premature delivery should be avoided whenever possible. Most treatments, including sentinel lymph node biopsy, systemic therapy with taxanes, platinum agents, or dose-dense treatment can be safely given during pregnancy, after careful risk/benefit assessment for mother and child. Chemotherapy is contraindicated during the first trimester because of a higher risk of fetal malformations but is feasible in the second and third trimesters. Other treatments such as radiation therapy or anti-human epidermal growth receptor 2 treatment are in general not indicated during pregnancy but might be considered in some instances. Patient data should be collected in a systematic way whenever possible

Breast Cancer Diagnosed During Pregnancy: Adapting Recent Advances in Breast Cancer Care for Pregnant Patients

Item does not contain fulltextBreast cancer during pregnancy (BCP), although rare, is becoming more common and treatment should be as similar as possible to that for nonpregnant young patients with breast cancer. A group of specialists convened to review current guidelines and provide guidance on how recent advances in breast cancer diagnosis and treatment can be adapted for pregnant patients. The majority of patients with BCP will be considered for treatment during the pregnancy. Premature delivery should be avoided whenever possible. Most treatments, including sentinel lymph node biopsy, systemic therapy with taxanes, platinum agents, or dose-dense treatment can be safely given during pregnancy, after careful risk/benefit assessment for mother and child. Chemotherapy is contraindicated during the first trimester because of a higher risk of fetal malformations but is feasible in the second and third trimesters. Other treatments such as radiation therapy or anti-human epidermal growth receptor 2 treatment are in general not indicated during pregnancy but might be considered in some instances. Patient data should be collected in a systematic way whenever possible

ESMO Expert Consensus Statements on the management of breast cancer during pregnancy (PrBC)

Abstract: The management of breast cancer during pregnancy (PrBC) is a relatively rare indication and an area where no or little evidence is available since randomized controlled trials cannot be conducted. In general, advances related to breast cancer (BC) treatment outside pregnancy cannot always be translated to PrBC, because both the interests of the mother and of the unborn should be considered. Evidence remains limited and/or conflicting in some specific areas where the optimal approach remains controversial. In 2022, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process on this topic to gain insights from a multidisciplinary group of experts and develop statements on controversial topics that cannot be adequately addressed in the current evidence-based ESMO Clinical Practice Guideline. The aim of this consensus-building process was to discuss controversial issues relating to the management of patients with PrBC. The virtual meeting included a multidisciplinary panel of 24 leading experts from 13 countries and was chaired by S. Loibl and F. Amant. All experts were allocated to one of four different working groups. Each working group covered a specific subject area with two chairs appointed: 1. PrBC: incidence, epidemiology, biology and pathology, diagnostic work-up, staging and risk assessment, prognosis (Chairs: Vincent Vandecaveye, Fedro Peccatori). 2. Clinical pharmacology of systemic agents during pregnancy: management of localized disease and (neo) adjuvant therapies, management of systemic disease (Chairs: Giuseppe Curigliano, Peter Schmid). 3. Obstetric care and fetal/newborn follow-up and outcomes: metastases to fetus, management of pregnancy during anti-cancer therapy, lactation, psychological support (Chairs: Elyce Cardonick, Mathilde van Gerwen). Planning, preparation and execution of the consensus process was conducted according to the ESMO standard operating procedures