K. Blansit

The inhibition of miR-21 promotes apoptosis and chemosensitivity in ovarian cancer☆

BACKGROUND MicroRNAs have been implicated in tumorigenesis, drug resistance, and prognosis in cancer. We investigated the role of microRNA-21 (miR-21) in regulating ovarian cancer drug resistance. METHODS We used parental and cisplatin resistant ovarian cell lines to demonstrate the role of miR-21 in drug resistance and investigated the gene targets of miR-21. Fresh tumor specimens were used to validate our in vitro findings. RESULTS Cisplatin resistant ovarian cells were four-fold more resistant compared to the parental cell line. MiR-21 was overexpressed in the resistant cell line on microRNA microarray, which was subsequently validated with qRT-PCR. Using anti-microRNA inhibitors, we demonstrated that miR-21 attenuation reversed the drug resistant phenotype in both the resistant and parental cell lines. The inhibition of miR-21 induced apoptosis based on annexin V-FITC immunostaining. Using Western blot analysis, miR-21 knockdown enhanced the expression of tumor suppressor PDCD4, and attenuated apoptosis inhibitor c-IAP2. Using 101 specimens from advanced ovarian cancer patients enrolled in The Cancer Genome Atlas, we found that women with tumors that overexpressed miR-21 were associated with a shorter progression-free survival. CONCLUSION Our data suggest that miR-21 regulates drug resistance via apoptosis and cellular survival pathways. Targeting miR-21 may have clinical utility in the treatment of resistant ovarian cancer.

Robotic versus laparoscopic versus open surgery in morbidly obese endometrial cancer patients — A comparative analysis of total charges and complication rates

OBJECTIVE To compare the complications and charges of robotic vs. laparoscopic vs. open surgeries in morbidly obese patients treated for endometrial cancer. METHODS Data were obtained from the Nationwide Inpatient Sample from 2011. Chi-squared, Wilcoxon rank sum two-sample tests, and multivariate analyses were used for statistical analyses. RESULTS Of 1087 morbidly obese (BMI ≥40kg/m(2)) endometrial cancer patients (median age: 59years, range: 22 to 89), 567 (52%) had open surgery (OS), 98 (9%) laparoscopic (LS), and 422 (39%) robotic surgery (RS). 23% of OS, 13% of LS, and 8% of RS patients experienced an intraoperative or postoperative complication including: blood transfusions, mechanical ventilation, urinary tract injury, gastrointestinal injury, wound debridement, infection, venous thromboembolism, and lymphedema (p<0.0001). RS and LS patients were less likely to receive blood transfusions compared to OS (5% and 6% vs. 14%, respectively; p<0.0001). The median lengths of hospitalization for OS, LS, and RS patients were 4, 1, and 1days, respectively (p<0.0001). Median total charges associated with OS, LS, and RS were

MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer

39,281,

Bevacizumab in Treatment of High-Risk Ovarian Cancer—A Cost-Effectiveness Analysis

40,997, and

The centralization of robotic surgery in high-volume centers for endometrial cancer patients — A study of 6560 cases in the U.S.

45,030 (p=0.037), respectively. CONCLUSIONS In morbidly obese endometrial cancer patients, minimally invasive robotic or laparoscopic surgeries were associated with fewer complications and less days of hospitalization relative to open surgery. Compared to laparoscopic approach, robotic surgeries had comparable rates of complications but higher charges.

Survival differences in women with serous tubal, ovarian, peritoneal, and uterine carcinomas

OBJECTIVE To determine the role of miR-378 as a biomarker for anti-angiogenic therapy response in ovarian cancer. METHODS Expression of miR-378 was analyzed in ovarian cancer cell lines and human tumors vs. normal ovarian epithelial cells by qRT-PCR. After miR-378 transfection in SKOV3 cells, dysregulated genes were identified using microarray. Data from The Cancer Genome Atlas (TCGA) was utilized to correlate miR-378 expression with progression-free survival (PFS) among patients treated with anti-angiogenic therapy by using Kaplan-Meier and Cox proportional hazards. RESULTS MiR-378 was overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. Overexpressing miR-378 in ovarian cancer cells altered expression of genes associated with angiogenesis (ALCAM, EHD1, ELK3, TLN1), apoptosis (RPN2, HIPK3), and cell cycle regulation (SWAP-70, LSM14A, RDX). In the TCGA dataset, low vs. high miR-378 expression was associated with longer PFS in a subset of patients with recurrent ovarian cancer treated with bevacizumab (9.2 vs. 4.2months; p=0.04). On multivariate analysis, miR-378 expression was an independent predictor for PFS after anti-angiogenic treatment (HR=2.04, 95% CI: 1.12-3.72; p=0.02). Furthermore, expression levels of two miR-378 targets (ALCAM and EHD1) were associated with PFS in this subgroup of patients who received anti-angiogenic therapy (9.4 vs. 4.2months, p=0.04 for high vs. low ALCAM; 7.9 vs. 2.3months, p<0.01 for low vs. high EHD1). CONCLUSIONS Our data suggest that miR-378 is overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. MiR-378 and its downstream targets may serve as markers for response to anti-angiogenic therapy.

Comparison of bevacizumab alone or with chemotherapy in recurrent ovarian cancer patients

The objective of this study was to evaluate a cost-effectiveness strategy of bevacizumab in a subset of high-risk advanced ovarian cancer patients with survival benefit. Methods. A subset analysis of the International Collaboration on Ovarian Neoplasms 7 trial showed that additions of bevacizumab (B) and maintenance bevacizumab (mB) to paclitaxel (P) and carboplatin (C) improved the overall survival (OS) of high-risk advanced cancer patients. Actual and estimated costs of treatment were determined from Medicare payment. Incremental cost-effectiveness ratio per life-year saved was established. Results. The estimated cost of PC is

Applications for Oncologic Drugs: A Descriptive Analysis of the Oncologic Drugs Advisory Committee Reviews

535 per cycle; PCB + mB (7.5 mg/kg) is

Foreign- vs US-born Asians and the association of type I uterine cancer

3,760 per cycle for the first 6 cycles and then

The economic impact of surgical care for morbidly obese endometrial cancer patients: a nationwide study

3,225 per cycle for 12 mB cycles. Of 465 high-risk stage IIIC (>1 cm residual) or stage IV patients, the previously reported OS after PC was 28.8 months versus 36.6 months in those who underwent PCB + mB. With an estimated 8-month improvement in OS, the incremental cost-effectiveness ratio of B was