Among the proinflammatory mediators, platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) is a major primary and secondary messenger involved in intracellular and extracellular communication. Evidence suggests that PAF plays a significant role in oncogenic transformation, tumor growth, angiogenesis, and metastasis. However, PAF, with its receptor (PAFR) and their downstream signaling targets, has not been thoroughly studied in cancer. Here, we characterized the PAFR expression pattern in 4 normal human ovarian surface epithelial (HOSE) cell lines, 13 ovarian cancer cell lines, paraffin blocks (n = 84), and tissue microarrays (n = 230) from patients with ovarian cancer. Overexpression of PAFR was found in most nonmucinous types of ovarian cancer but not in HOSE and mucinous cancer cells. Correspondingly, PAF significantly induced cell proliferation and invasion only in PAFR-positive cells (i.e., OVCA429 and OVCA432), but not in PAFR-negative ovarian cells (HOSE and mucinous RMUG-L). The dependency of cell proliferation and invasion on PAFR was further confirmed using PAFR-specific small interfering RNA gene silencing probes, antibodies against PAFR and PAFR antagonist, ginkgolide B. Using quantitative multiplex phospho-antibody array technology, we found that tyrosine phosphorylation of EGFR/Src/FAK/paxilin was coordinately activated by PAF treatment, which was correlated with the activation of phosphatidylinositol 3-kinase and cyclin D1 as markers for cell proliferation, as well as matrix metalloproteinase 2 and 9 for invasion. Specific tyrosine Src inhibitor (PP2) reversibly blocked PAF-activated cancer cell proliferation and invasion. We suggest that PAFR is an essential upstream target of Src and other signal pathways to control the PAF-mediated cancer progression. [Cancer Res 2008;68(14):5839-48]

C-CPE treatment of EOC cells leads to altered TJ function. Further research is needed to determine the potential clinical applications of C-CPE in EOC drug delivery strategies.

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BRCA1/BRCA2 mutations are common and the hallmarks of high-grade serous ovarian carcinoma. We found that MIR182, a negative BRCA1 regulator, is significantly overexpressed in high-grade serous ovarian carcinoma. To examine whether overexpression of MIR182 and its target genes, including BRCA1, HMGA2 (high-mobility group A2), FOXO3 and MTSS1, are associated with high-grade serous ovarian carcinoma tumor types and clinical outcome, we studied MIR182 by in situ hybridization and its target gene expression by immunohistochemistry in 117 cases of advanced ovarian cancer. We found that high-grade serous ovarian carcinoma had significantly higher MIR182 (P ¼ 0.0003) and HMGA2 (P ¼ 0.04) expression, and significantly lower BRCA1 (Po0.0001) and FOXO3 (Po0.001) expression than normal controls. MIR182 is significantly correlated with MTSS1 expression (r ¼ 0.31; Po0.001), whereas other target genes did not show a significant correlation with MIR182, indicating a complicated regulatory mechanisms of these genes in high-grade serous ovarian carcinoma. Among the examined MIR182 target genes, only HMGA2 was significantly associated with serous type carcinomas (Po0.01), ascites (Po0.01) and high death rate (P ¼ 0.02). FOXO3 expression was associated with lower-stage disease (P ¼ 0.04) and solid growth pattern (P ¼ 0.03). MIR182 expression is significantly higher in high-grade serous ovarian carcinoma than in fallopian tubes. Modern Pathology (2012) 25, 1644-1653; doi:10.1038/modpathol.2012.118; published online 13 July 2012Keywords: miR-182; ovarian cancer; BRCA1; HMGA2; MTSS1 High-grade serous ovarian carcinoma is an aggressive and deadly form of ovarian cancer, yet its pathogenesis is poorly understood. Despite significant efforts of clinical researchers, the survival rate of women with high-grade serous ovarian carcinoma has not changed in the past 50 years. 1 These tumors are often high-grade and aggressive at presentation, with a poor prognosis. Recent recognition of the existence of high-grade serous ovarian carcinoma precursor lesions, serous tubal intraepithelial carcinoma, 2,3 in the distal (fimbriated) ends of the fallopian tubes has renewed hope that we will be able to identify early tumorigenic events leading to high-grade serous ovarian carcinoma and reveal new opportunities for early detection and treatment that may decrease the mortality rate among women with this cancer.BRCA1 and BRCA2 mutations are a hallmark of high-grade serous ovarian carcinoma tumorigenesis. 4 Women with germline BRCA1/2 mutations have a 30-70% chance of developing high-grade serous ovarian carcinoma by age 70. 5 Germline BRCA mutations, 6 somatic mutations and epigenetic inactivation of BRCA1/2 (via methylation) can be found in nearly 30% of high-grade serous ovarian carcinoma cases. 7 BRCA1 has a broader role upstream of BRCA2, participating in various cellular

The ABSST is a valuable tool to identify MS patients with urinary symptoms who will likely follow up for genitourinary evaluation. However, other barriers beyond awareness exist and prevent patients from being evaluated.

When voiding symptoms or urinary retention is the primary indication for intervention after anti-incontinence surgery, urodynamic findings are not predictive of outcomes after intervention to relieve obstruction. If storage symptoms are the main indication for intervention, urodynamics may be valuable for patient counseling.

Bladder outlet obstruction (BOO) in women can be either anatomic or functional. Anatomic causes for BOO are often readily apparent by history and physical exam. On the other hand, causes for functional obstruction, including dysfunctional voiding, primary bladder neck obstruction, and detrusor-external sphincter dyssynergia, are more difficult to establish. Because the appropriate treatment for functional obstruction drastically varies according to etiology, making an accurate diagnosis is paramount. Videourodynamics, interpreted in the context of individual clinical symptoms, remains the diagnostic gold standard in women with functional obstruction.

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