Thyroid hormone receptor represses miR-17 expression to enhance tumor metastasis in human hepatoma cells.

MicroRNAs (miRNAs) are thought to control tumor metastasis through direct interactions with target genes. Thyroid hormone (T3) and its receptor (TR) are involved in cell growth and cancer progression. However, the issue of whether miRNAs participate in T3/TR-mediated tumor migration is yet to be established. In the current study, we demonstrated that T3/TR negatively regulates mature miR-17 transcript expression, both in vitro and in vivo. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays localized the regions responding to TR-mediated repression to positions -2234/-2000 of the miR-17 promoter sequence. Overexpression of miR-17 markedly inhibited cell migration and invasion in vitro and in vivo, mediated via suppression of matrix metalloproteinases (MMP)-3. Moreover, p-AKT expression was increased in miR-17-knockdown cells that led to enhanced cell invasion, which was blocked by LY294002. Notably, low miR-17 expression was evident in highly metastatic cells. The cell migration ability was increased by T3, but partially reduced upon miR-17 overexpression. Notably, TRα1 was frequently upregulated in hepatocellular carcinoma (HCC) samples and associated with low overall survival (P=0.023). miR-17 expression was significantly negatively associated with TRα1 (P=0.033) and MMP3 (P=0.043) in HCC specimens. Data from our study suggest that T3/TR, miR-17, p-AKT and MMP3 activities are interlinked in the regulation of cancer cell metastasis.

Regulation of ovarian cancer progression by microRNA-187 through targeting Disabled homolog-2.

MicroRNAs (miRNAs) play important roles in tumorigenesis by regulating oncogenes and tumor-suppressor genes. In this study, miR-187 and miR-200a were found to be expressed at higher levels in ovarian cancers than in benign tumors. In patients with ovarian cancer, however, higher levels of miR-187 and miR-200a expression were paradoxically associated with better OS and recurrence-free survival. Further, multivariate analysis showed that miR-187 served as an independent prognostic factor for patients with ovarian cancer (n=176). Computational prediction and microarray results indicated that miR-187 directly targeted Disabled homolog-2 (Dab2), and luciferase reporter assays confirmed that the target site of miR-187 was located at the 3'-UTR of the Dab2 gene. Generally considered as a tumor-suppressor gene, Dab2 may actually promote tumor progression in advanced cancers through epithelial-to-mesenchymal transition (EMT). Ectopic expression of miR-187 in cancer cells promoted cell proliferation, but continued overexpression of miR-187 suppressed Dab2 and inhibited migration. Suppression of miR-187 upregulated Dab2, which, by inhibiting E-cadherin levels while stimulating vimentin and phospho-FAK levels, promoted EMT. Reduced ovarian cancer Dab2 histoscores correlated with high miR-187 levels and improved outcomes of patients. Collectively, these results demonstrate distinct dual roles of Dab2 in cell proliferation and tumor progression. In the initial steps of tumorigenesis, upregulated miR-187 suppresses Dab2, promoting cell proliferation. During the later stages, however, continued increased levels of miR-187 inhibits the Dab2-dependent EMT that is associated with tumor invasiveness, which is presumed to be the reason why cancers with high miR-187 levels were associated with better survivals.

Age factor and implication of human papillomavirus type-specific prevalence in women with normal cervical cytology.

The prevalence and genotype distribution of human papillomavirus (HPV) infection in women with normal cervical cytology varies widely according to the population studied. Two non-overlapping population-based cohort studies of women aged ≥30 years for the periods 2008-2009 (n=5026) and 2004-2005 (n=10 014) were analysed. The prevalence rate of HPV was 11·0% (95% CI 10·5-11·6). HPV infection was significantly associated with age, menopausal status, and inversely associated with hormone replacement therapy. There was an increasing trend of α3/α15, α5/α6, and multiple HPV infections with increasing age. The five most common types were HPV52, 18, 53, 58 and 70, while HPV16, 31, 33 ranked 21st, 25th, and 16th, respectively, in the merged cohort with normal cytology (n=14 724). HPV16, 31, and 33 were significantly associated with abnormal cytology, which could have resulted in their rarity in the total merged cohort (n=15 040).

Prognostic factors and adjuvant therapy in uterine carcinosarcoma.

PURPOSE OF INVESTIGATION: The objective of this retrospective study was to investigate prognostic variables and impact of adjuvant therapy in uterine carcinosarcoma. METHODS: The clinical information and pathological confirmation were reviewed for cases with uterine carcinosarcoma from 1984 to 2005. A total of 45 patients were eligible for analysis. RESULTS: The median follow-up for survivors was 84 months. Five-year overall survival and progression-free survival (PFS) rates were 36.5% and 33.8%, respectively for Stage I-IV. Distant site metastasis with/without pelvic failure occurred in 83.3% of those with recurrence/progression. By multivariate analysis, older age (p = 0.001) and more than half of myometrial invasion (p = 0.002) were significant predictors of death, while only myometrial invasion (p = 0.022) was significantly associated with PFS. Stratified analyses demonstrated a monotonic trend of chemotherapy or chemoradiation to decrease death. CONCLUSIONS: Our results suggested that age and depth of myometrial invasion were significant prognostic factors, and chemotherapy or chemoradiation seemed to be beneficial for uterine carcinosarcoma.

Ovarian endometrioid carcinoma with diffuse pigmented peritoneal keratin granulomas: a case report and review of the literature.

The presence of keratin granulomas in peritoneal cavity associated with ovarian endometrioid carcinoma, which might be related to leakage from the ovarian tumor, is rarely reported. Its clinical significance has not yet been well investigated. We report a case presenting with intermittent abdominal pain after an acute episode 1 month before a complex adnexal tumor was noted. Comprehensive cytoreductive surgery was performed. The ovarian tumor was an endometrioid adenocarcinoma with squamous differentiation. There were diffuse brownish flecks over the omental surface and pelvic peritoneum, which contained fragments of degenerated squamous cells, keratin, and numerous foreign body giant cells. Extensive multiple sections were examined for these implants. DNA flow cytometry and various immunostaining studies (HER-2/neu, p53, CK-7, and cytokeratin [AE1/AE3]) were performed. Since viable epithelial cells in the implants could be differentially identified against mesothelial or granulomatous components by CK-7 staining and DNA aneuploidy was demonstrated on primary ovarian tumor, four courses of chemotherapy were administered. The patient has been free of disease for 18 months since diagnosis.

False-positive fluorine-18 fluorodeoxy-D-glucose positron emission tomography imaging caused by retained gauze in a woman with recurrent ovarian cancer: a case report.

We report a case of a 47-year-old woman with a false-positive [18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) result caused by retained gauze during resection of liver metastasis for a Stage IV ovarian cancer at primary cytoreductive surgery. She achieved complete remission and remained free of progression for seven years. Owing to elevation of CA-125, computed tomography and PET studies were performed, and both showed two potentially resectable lesions. One was located ventral to the diaphragmatic surface of the left hepatic lobe and the other was around the gauze at the right hepatorenal fossa. During surgical intervention, the left supraheptic tumor was excised and the gauze with surrounding granulation was removed. However, the former proved to be recurrent ovarian cancer with the latter proven false-positive. This case demonstrates that PET results should be interpreted with caution in differentiating a benign inflammatory process from malignant abnormalities, especially in regions with a high probability of granulomatous lesions.