OBJECTIVES ARID1A is a recently identified tumor suppressor participating in chromatin remodeling. Somatic inactivating mutations of ARID1A and loss of its expression occur most frequently in ovarian clear cell and endometrioid carcinomas and uterine endometrioid carcinomas. Since endometriosis is thought to be a precursor of most ovarian clear cell and endometrioid carcinomas, we undertook an analysis of ARID1A expression of these tumors arising within an endometriotic cyst (endometrioma). MATERIALS/METHODS Our immunohistochemical study set consisted of 47 endometriotic cysts containing clear cell carcinoma in 24 cases, well-differentiated ovarian endometrioid carcinoma in 20 and mixed clear cell and endometrioid carcinoma in 3. RESULTS ARID1A loss was observed in 31 (66%) of 47 carcinomas and therefore these cases were informative for determining the temporal sequence of loss of ARID1A expression in tumor progression. In 16 of the 47 cases, ARID1A immunoreactivity was retained in both the endometriotic cyst and the carcinoma and thus these cases were not informative. All of the 31 informative cases showed loss of ARID1A immunoreactivity in the carcinoma and in the endometriotic cyst epithelium in direct continuity with the carcinoma but not in the cyst epithelium that was not adjacent to the tumor. CONCLUSIONS The findings in this study provide cogent evidence that loss of ARID1A function as shown by loss of expression, presumably due to mutations, is an early molecular event, occurring before malignant transformation, in the development of the majority of ovarian clear cell and endometrioid carcinomas arising in endometriomas.

Recent reports have shown that peroxisome proliferatoractivated receptor (PPAR

Objective: The aim of this study was to investigate the prognostic role of the pretreatment neutrophil-to-lymphocyte ratio (NLR) as a predictive marker prior to treatment of cervical cancer with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT).Methods: Fifty-six patients with squamous cell carcinoma (SCC) of the uterine cervix who underwent RT or CCRT from 2005 to 2013 at this Hospital were retrospectively identified using electronic databases.Patients were divided into a high NLR group (≥ 2.5) and a low NLR group (< 2.5). The efficacy of RT and CCRT in the two groups was compared.Result: Of the 56 patients, 35 were in the high NLR group and 21 were in the low NLR group. In comparison to a high NLR, a low NLR was significantly associated with a complete response (P < 0.001).When cancer was divided into stages I/II and III/IV, patients with a low NLR had a significantly better therapeutic outcome than those with a high NLR (P < 0.05). Multivariate analysis showed that only the NLR was a significant prognostic factor for progression-free survival (PFS). Patients with a high NLR had a significantly shorter PFS and overall survival than those with a low NLR.Conclusion: Results showed that a low NLR before treatment can predict a good response to RT or CCRT by all stages of uterine cervical cancer. The NLR may be a promising parameter on which to base the choice of a therapeutic strategy to treat SCC of the uterine cervix.

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BACKGROUND.It was recently reported that high expression of peroxisome proliferator‐activated receptor γ (PPARγ) and low expression of cyclooxygenase‐2 (COX‐2) might be involved in the inhibition of ovarian tumor progression and confirmed that PPARγ activation could suppress COX‐2 expression via the nuclear factor‐κB pathway in ovarian cancer cells.METHODS.The current study investigated whether meloxicam, a selective COX‐2 inhibitor, and ciglitazone, a ligand for PPARγ, inhibit the growth of human ovarian cancer cell lines and aimed to elucidate the molecular mechanism of their antitumor effect. Tumor growth and survival were examined in female nu/nu mice xenografted with subcutaneous OVCAR‐3 tumors or with intraperitoneal DISS tumors and treated with meloxicam (162 ppm in diet, every day) or ciglitazone (15 mg/kg intraperitoneally once a week).RESULTS.Both meloxicam and ciglitazone treatments significantly suppressed the growth of OVCAR‐3 tumors xenotransplanted subcutaneously and significantly prolonged the survival of mice with malignant ascites derived from DISS cells as compared with controls. Meloxicam treatment decreased COX‐2 expression in tumors by 2.5‐fold compared with that observed in untreated tumors. Although ciglitazone treatment did not alter COX‐2 expression in tumors, it reduced the expression of microsomal prostaglandin (PG) E synthase, which converts COX‐derived PGH2 to PGE2. Both meloxicam and ciglitazone decreased PGE2 levels in serum as well as in ascites. Reduced microvessel density and induced apoptosis were found in solid OVCAR‐3 tumors treated with either meloxicam or ciglitazone.CONCLUSIONS.These results indicate that both meloxicam and ciglitazone produce antitumor effects against ovarian cancer in conjunction with reduced angiogenesis and induction of apoptosis. Cancer 2007; 110:791–800. © 2007 American Cancer Society.