ABSTRACT
OBJECTIVE: The objective of this study is to identify and validate novel therapeutic target(s) in ovarian cancer. BACKGROUND: Development of targeted therapeutics in ovarian cancer has been limited by molecular heterogeneity. Although gene expression datasets are available, most of them lack appropriate pair-matched controls to define the alterations that result in the transformation of normal ovarian cells to cancerous cells. METHODS: We used microarray to compare the gene expression of treatment-naïve ovarian cancer tissue samples to pair-matched normal adjacent ovarian tissue from 24 patients. Ingenuity Pathway Analysis (IPA) was used to identify target pathways for further analysis. Integrin-linked kinase (ILK) expression in SKOV3 and OV90 cells was determined using Western blot. ILK was knocked down using CRISPR/Cas9 constructs. Subcutaneous xenograft study to determine the effect of ILK knockdown on tumor growth was performed in NOD SCID gamma mice. RESULTS: Significant upregulation of the ILK pathway was identified in 22 of the 24 cancer specimens, identifying it as a potential player that could contribute to the transformation of normal ovarian cells to cancerous cells. Knockdown of ILK in SKOV3 cells resulted in decreased cell proliferation and tumor growth, and inhibition of downstream kinase, AKT (protein kinase B). These results were further validated using an ILK-1 chemical inhibitor, compound 22. CONCLUSION: Our initial findings validate ILK as a potential therapeutic target for molecular inhibition in ovarian cancer, which warrants further investigation.
ABSTRACT
OBJECTIVE: The objective of this study was to determine if high-dose antibiotic prophylaxis with cefazolin decreases the risk of surgical site infection (SSI) after a cesarean delivery. METHODS: We performed a retrospective cohort study of women who underwent a cesarean section. Two preoperative antibiotic regimens were compared: low dose versus high dose. The primary outcome was SSI. A sample size of 343 patients per group was calculated for a 50% reduction in risk for SSI. RESULTS: Seven hundred and thirty women were included with an incidence of SSI of 5%. Women who received the high-dose antibiotic regimen had lower rates of risk factors for SSI. The only exception was skin incision closure with staples. The rate of SSI did not differ between the low-dose and high-dose groups, even after adjusting for confounding variables [aOR 1.78, 95% CI (0.82-3.9)]. CONCLUSIONS: Higher doses of antibiotic prophylaxis did not decrease the rates of SSI after cesarean delivery.
