M. Pomeranz

Relapsing Henoch-Schönlein Purpura Associated with a Tubo-Ovarian Abscess due to Morganella morganii

Henoch-Schönlein purpura is the most common vasculitis in children. It is frequently preceded by either viral or bacterial infections of the upper respiratory tract. We present a 15-year-old female who developed recurrent episodes of Henoch-Schönlein purpura. Eventual investigation of the patients abdominal pain, initially attributed to vasculitis involving the gastrointestinal tract, revealed a left tubo-ovarian abscess caused by Morganella morganii. Salpingo-oophorectomy resulted in complete remission of the disease process.

Placenta-breast cancer cell interactions promote cancer cell epithelial mesenchymal transition via TGFβ/JNK pathway

Women diagnosed with pregnancy associated breast cancer often have advanced cancer with metastases and reduced expression of ERα compared to non-pregnant women. Nevertheless, metastases to the placenta are uncommon. Previously, we demonstrated that breast cancer cells (MCF-7/T47D) migrated from ex vivo human placental explant implantation sites. We aimed to analyze the effect of factors produced during placental implantation or as a result of the interaction between the implanted placentae to cancer cells on cancer cells migration and aggressiveness. We collected supernatants from implanted placentae and placental-breast cancer cells cocultures and analyzed their effects on cancer cells phenotype and pathways. Supernatants collected from breast cancer cells served as controls. We found that supernatants collected from implanted placentae induced modest cancer cells migration that was not accompanied by epithelial to mesenchymal transition (EMT), supported breast cancer cells survival and elevated MCF-7 cell number. The coculture supernatant induced excessive motility and EMT of the MCF-7 cells. This EMT was mediated by Smad3 and JNK/ERK activation. Both placenta and coculture supernatants reduced ERα expression in the cancer cells. Finally, we showed that MCF-7 cocultured with the human placental explants underwent continuous activation of JNK and Smad3 pathways and the EMT process, which led to their migration away from the placental implantation sites. These findings may explain the reduced ERα and elevated metastases found in breast cancer during pregnancy and highlights pathways involved in it.

Hormone-dependent placental manipulation of breast cancer cell migration

BACKGROUND Breast cancer during pregnancy is often more advanced than in non-pregnant women. Nevertheless, no case of metastasis inside the placenta has been reported. Previously, we showed that placental-explants eliminated breast cancer cells from their surroundings, due to cell-death and elevated migration. Our objective was to find the underlying mechanisms of these phenomena. METHODS AND RESULTS Our model contained Michigan Cancer Foundation 7 (MCF7) or T47D cells co-cultured with and without human placental explants. Microarray analysis, validated by quantitative PCR, of MCF7 following their placental co-culture suggested activation of estrogen (E(2)) signaling. As extensive cross-talk exists between E(2) and progesterone, their involvement in mediating placental effects on breast cancer cells was tested. Indeed, addition of E(2) and progesterone receptor (ER and PR) inhibitors to the co-culture system reduced cancer cell motility, yet did not alter cell-cycle or death. E(2) and progesterone concentrations in placental media were found to be similar to those of early pregnancy blood levels. Interestingly, placental-breast cancer co-culture media contained lower progesterone (P < 0.05) and higher E(2) (200%, P < 0.05) levels than placentae cultured separately. Placental supernatant and E(2) and progesterone at placental levels were sufficient to increase MCF7 and T47D migration and invasion (P < 0.05), yet did not alter MCF7 cell-cycle or death. Furthermore, placental supernatant elevated p38 and Jun N-terminal kinase (JNK) phosphorylation in both cell lines (P < 0.05). Inhibitors of JNK, ER and PR reversed MCF7 and T47D motility induced by the placenta, suggesting their involvement. CONCLUSIONS We suggest that E(2) and progesterone contribute to cell migration away from placental areas. We hypothesize that they may increase metastatic spread to other organs in pregnancy.

Fluorescent in situ hybridization: an effective and less costly technique for genetic evaluation of products of conception in pregnancy losses

Objective.  In this study, we applied the fluorescent in situ hybridization (FISH) technique and compared the common numerical abnormalities with chromosomes 13, 16, 18, 21, X, and Y in spontaneous to artificial abortion. This would cover about 75% of the common aneuploidy in spontaneous abortion.

“In God we trust” and other factors influencing trial of labor versus Repeat cesarean section

Abstract Purpose: To investigate factors influencing womens decisions to undergo trial of labor after cesarean (TOLAC) or elective repeat cesarean delivery (ERCD) based on the Multidimensional Health Locus of Control (MHLC), religious observance and family planning. Materials and methods: Cross-sectional study of candidates for TOLAC or ERCD at two hospitals in Israel. Eligible women completed a demographic questionnaire and Form C of the MHLC scale. Results: The study included 197 women. Those who chose TOLAC (N = 101) were more religiously observant, wanted more children and had higher Internal and Chance health locus of control. Women who chose ERCD (N = 96) were more likely to be secular and had a higher health locus of control influenced by Powerful Others, notably physicians. Women not influenced by others were more likely to choose TOLAC. Conclusions: A woman’s choice of TOLAC or ERCD is influenced by her sense of control over her health, degree of religious observance and number of children desired. Healthcare providers can use this information to better understand, counsel and educate women regarding appropriate delivery decisions. Women who feel in control of their health, educated about delivery options and are less influenced by provider preference, might choose TOLAC; thus, reducing the rate of unnecessary ERCD.

First trimester human placenta prevents breast cancer cell attachment to the matrix: The role of extracellular matrix.

The extracellular matrix (ECM) affects cancer cell characteristics. Its detachment from the ECM induces cell apoptosis, termed anoikis. Cancer cells can develop anoikis resistance, a necessary step for metastasis, by switching integrins, over‐expressing growth factor receptors, and inducing epithelial mesenchymal transition (EMT). The placenta is a non‐supportive microenvironment for cancer cells. We showed that breast cancer cells (BCCL) were eliminated from placental implantation sites. During implantation, the placenta manipulates its surrounding matrix, which may induce BCCL elimination. Here, we explored the effect of placenta‐induced ECM manipulations on BCCL. During experiments, BCCL (MCF‐7/T47D) were cultured on placenta/BCCL‐conditioned ECM (Matrigel used for first trimester placenta/BCCL culture and cleared by NH4OH). After culturing the cells, we analyzed cancer cell phenotype (death, count, aggregation, MMP) and signaling (microarray analysis and pathway validation). We found that the BCCL did not attach to previous placental implantation sites and instead, similarly to anoikis‐resistant cells, migrated away, displayed increased MMP levels/activity, and formed aggregates in distant areas. T47D were less affected than the MCF‐7 cells, since MCF‐7 also showed modest increases in cell death, EMT, and increased proliferation. Microarray analysis of the MCF‐7 highlighted changes in the integrin, estrogen, EGFR, and TGFβ pathways. Indeed, placental ECM reduced ERα, induced Smad3/JNK phosphorylation and increased integrin‐α5 expression (RGD‐dependent integrin) in the BCCL. Addition of RGD or TGFβR/JNK inhibitors reversed the phenotypic changes. This study helps explain the absence of metastases to the placenta and why advanced cancer is found in pregnancy, and provides possible therapeutic targets for anoikis‐resistant cells.

Adnexal Torsion during Pregnancy: Pregnancy Outcomes after Surgical Intervention—A Retrospective Case-Control Study

STUDY OBJECTIVE To investigate the pregnancy and neonatal outcomes of surgical treatment for adnexal torsion (AT) during pregnancy. DESIGN A retrospective case-control study (Canadian Task Force classification II-2). SETTING A tertiary care academic medical center. MEASUREMENTS AND MAIN RESULTS The study group included all parturients who underwent surgery for suspected AT during pregnancy from January 2005 to January 2017. The control group included parturients with an uneventful pregnancy matched by maternal age, parity, multiple gestation, and pregnancy complications. The primary outcome was gestational age at delivery. Secondary outcomes were perinatal outcomes and intraoperative and immediate postoperative complications. Among 85 study group patients with suspected AT, 78 (91.7%) underwent laparoscopy and 7 (8.3%) laparotomy. Torsion was diagnosed in 84 patients (98.8%). The gestational age at delivery was similar between the study and control groups (38.7 ± 1.5 vs 38.6 ± 1.6 weeks, respectively; p = .908) as was preterm labor (5.8% in both groups, p = 1.00). There was no significant difference between the study and control groups in pregnancy and neonatal outcomes, including Apgar scores, mean cord blood pH (7.25 ± 0.1 and 7.26 ± 0.08, respectively), and birth weight (3040 ± 473 g and 3115 ± 584 g, respectively). In the study group, the mean gestational age at surgery was 11.2 ± 6 weeks (range, 4-34 weeks). The average operative time was 40.2 ± 22 minutes. In the postoperative follow-up, 3 (3.5%) patients had a first trimester miscarriage. A previous cesarean delivery was a risk factor for ovarian torsion during pregnancy (p = .012). CONCLUSION Adnexal detorsion with or without additional surgical procedures during pregnancy did not affect the gestational age at delivery and did not appear to increase fetal or maternal complication rates.

Placenta-conditioned extracellular matrix (ECM) activates breast cancer cell survival mechanisms: A key for future distant metastases: Placental ECM affects breast cancer cell hallmarks

The extracellular matrix (ECM) affects cancer cell characteristics. Inability of normal epithelial cells to attach to the ECM induces apoptosis (anoikis). Cancer cells are often anoikis resistant, a prerequisite for their metastatic spread. Previously we demonstrated that the placenta manipulates its surrounding ECM in a way that prevents breast cancer cells (BCCL) attachment and induces their motility and aggregation. This fits with the fact that although breast cancer during pregnancy is often advanced, metastasis to the placenta is rarely observed. Placental intervillous space provides suitable conditions for cancer cell arrival. Yet, the outcome of the short communication between the placental ECM to the BCCL and its effect on BCCL malignant potential are unknown, and are the focus of our study. In the current study we analyzed the effect of placental ECM on BCCL survival pathways and drug resistance. Microarray analysis suggested activation of the NF‐κB and stress response pathways. Indeed, the placenta‐conditioned ECM induced autophagy in ERα + BCCL, inactivated the NF‐κB inhibitor (IκB) and increased integrin α5 in the BCCL. The autophagy mediated MCF‐7 and T47D migration and the placental ECM‐BCCL interactions reduced the BCCL sensitivity to Taxol. We also demonstrated by using siRNA that integrin α5 was responsible for the MCF‐7 autophagy and suggest this molecule as a suitable target for therapy.