Christopher Sherman

Uterine Wall Partial Thickness Necrosis Following Combined B-Lynch and Cho Square Sutures for the Treatment of Primary Postpartum Hemorrhage

I agree with the authors that the suture material used does not play a significant role in causing uterine necrosis, as the damage caused by the pressure suture would occur in the immediate postoperative period and would be related to the degree of tension and ischemia that the suture exerts on the myometrium. Also, it is good idea to establish a national registry of women who undergo placement of compression sutures, in order to document the efficacy and the long-term and short-term complications of this procedure.

MiR‐301a regulates E‐cadherin expression and is predictive of prostate cancer recurrence

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression post‐transcriptionally. Dysregulation of miRNA has been implicated in the development and progression of prostate cancer. Through next generation miRNA sequencing, we recently identified a panel of five miRNAs associated with prostate cancer recurrence and metastasis. Of the five miRNAs, miR‐301a had the strongest association with prostate cancer recurrence. Overexpression of miR‐301a in prostate cancer cells, PC3, and LNCaP resulted in increased growth both in vitro and in xenografted tumors. We therefore sought to examine its role in prostate carcinogenesis in greater detail.

A Pilot Study to Evaluate the Role of Magnetic Resonance Imaging for Prostate Cancer Screening in the General Population.

PURPOSE To our knowledge the role of magnetic resonance imaging as a first line screening test for prostate cancer is unknown. We performed a pilot study to evaluate the feasibility of prostate magnetic resonance imaging as the primary screening test for prostate cancer. MATERIALS AND METHODS We recruited unselected men from the general population. Prostate multiparametric magnetic resonance imaging and random or targeted biopsies were performed in all patients, in addition to prostate specific antigen testing. We compared the performance of prostate magnetic resonance imaging and prostate specific antigen test results to predict prostate cancer. RESULTS Of the 47 recruited patients 18 (38.3%) had cancer while 29 (61.7%) had no evidence of cancer. The adjusted OR of prostate cancer was significantly higher for magnetic resonance imaging score than for prostate specific antigen level (2.7, 95% CI 1.4-5.4, p = 0.004 vs 1.1, 95% CI 0.9-1.4, p = 0.21). Among the 30 patients with a normal prostate specific antigen (less than 4.0 ng/ml) the positive predictive value in those with a magnetic resonance imaging score of 4 or more was 66.7% (6 of 9) and the negative predictive value in those with a magnetic resonance imaging score of 3 or less was 85.7% (18 of 21, p = 0.004). CONCLUSIONS In this pilot study we determined the feasibility of using multiparametric prostate magnetic resonance imaging as the primary screening test for prostate cancer. Initial results showed that prostate magnetic resonance imaging was better to predict prostate cancer than prostate specific antigen in an unselected sample of the general population.

The role of placental malperfusion in the pathogenesis of preeclampsia in dichorionic twin and singleton pregnancies

INTRODUCTION In singletons, the pathogenesis of hypertensive disorders of pregnancy (HDP) is attributed to abnormal placentation, characterized by maternal vascular malperfusion (MVM) lesions. Whether MVM plays a similar role in twin pregnancies is unclear. The purpose of the study was to compared placental pathology findings between dichorionic-twin and singleton pregnancies complicated by HDP. METHODS Retrospective cohort study of women with dichorionic-twin or singleton pregnancies complicated by HDP who gave birth in a single tertiary center between 2001 and 2015. Placental abnormalities were classified into lesions associated with MVM, fetal vascular malperfusion, placental hemorrhage and chronic villitis. Placental findings and neonatal outcomes were compared between twin and singleton pregnancies. RESULTS A total of 144 women with twins and 768 women with a singleton pregnancy met the inclusion criteria. Compared with HDP singletons, twins with HDP had higher mean birth weights, were less likely to be small for gestational age and be born at <34 and at <32 weeks. Twins had lower odds for placental weight below <10th percentile (aOR 0.49, 95%CI 0.33-0.71), for MVM pathology (aOR 0.28, 95%CI 0.20-0.39) and for fetal vascular malperfusion pathology (aOR 0.65, 95%CI 0.45-0.93). These finding remained significant in the subpopulation of early onset HDP (<34 weeks) and small for gestational newborn. DISCUSSION Our findings support the hypothesis that MVM are less relevant to the pathogenesis of HDP in twin pregnancies and suggest that other placental or non-placental factors are responsible for the increased risk of HDP in twin pregnancies.

Abstract A079: MicroRNA-139 regulates prostate cancer aggressiveness by targeting IGF1R

Background: Dysregulated microRNA (miRNA) expression has been implicated in prostate cancer progression. We previously identified a panel of five miRNAs associated with biochemical recurrence and metastasis following prostatectomy based on NGS-based whole miRNome discovery and qPCR-based validation analysis. In this analysis, we examine the effect of miR-139-5p, one of the downregulated miRNAs identified in the panel, in greater detail. Methods: Using a cohort of 585 patients treated with radical prostatectomy, we examined the prognostic significance of miR-139 (dichotomized around the median) using the Kaplan Meier method and Cox proportional hazard models. We validated these results using The Cancer Genome Atlas (TCGA) data. We created cell lines that overexpressed miR-139 for functional assays. Finally, we examined pathways through which miR-139 may function using prediction algorithms and confirmed targets by Western blotting and reporter assays. Results: MiR-139 downregulation was significantly associated with a variety of accepted prognostic factors in prostate cancer, including Gleason score, pathologic stage, margin positivity, and lymph node status. MiR-139 was associated with prognosis: the cumulative incidence of biochemical recurrence and metastasis was significantly lower among patients with high miR-139 expression (p=0.0004 and 0.038, respectively). After adjusting for known prognostic factors, patients with high miR-139 expression had significantly lower risk of recurrence (HR 0.77, 95% 0.58-1.04). Validation in the TCGA dataset showed a significant association between dichotomized miR-139 expression and biochemical recurrence (OR 0.52, 95% CI 0.33-0.82). Overexpression of miR-139 in PC3 and DU145 prostate cancer cells led to a significant reduction in cell proliferation and migration compared to control cells. IGF1R was identified as a potential target of miR-139 based on previous work in colorectal and non-small cell lung cancers. Reduced luciferase reporter activity was observed upon co-transfection of the 3′ UTR of IGF1Rβ with miR-139 mimic compared to co-transfection with control mimic. Furthermore, Western blotting of PC3 cells overexpressing miR-139 revealed reduced IGF1Rβ protein expression, as well as reduced expression of its downstream pathway proteins pAKT and pERK. Cell cycle analysis indicated a significantly increased number of cells arrested in G2/M phase in PC3 cells overexpressing miR-139. This was accompanied by an increase in β-galactosidase stained senescent cells and p21 protein expression. Conclusions: miR-139 is associated with improved prognosis in patients with localized prostate cancer. This appears to be mediated through an IGF1R pathway leading to increased p21 expression, resulting in prostate cancer cell senescence from G2 arrest. Citation Format: Yutaka Amemiya, Christopher J. Wallis, Tania Benatar, Elizabeth Kobylecky, Linda Sugar, Christopher Sherman, Robert Nam, Arun K. Seth. MicroRNA-139 regulates prostate cancer aggressiveness by targeting IGF1R [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A079.