The prognostic impact of lymphovascular invasion for upper urinary tract urothelial carcinoma: A propensity score-weighted analysis.

Lymphovascular invasion (LVI) predicts poor survival in patients with pathologically localized or locally advanced upper urinary tract urothelial carcinoma (UT-UC). However, LVI is associated with high tumor grade, tumor necrosis, advanced tumor stage, tumor location, concomitant carcinoma in situ, lymph node metastasis, and sessile tumor architecture. These factors might interfere with the analysis of the impact of LVI on oncological prognosis. To address this, this study aimed to clarify the relationship between LVI and patient prognosis in UT-UC using propensity score weighting. Data were collected from 789 patients with UT-UC treated with radical nephroureterectomy without chemotherapy. We evaluated the significance of LVI in predicting metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) using propensity score weighting. All weighted baseline characteristics included in the propensity score model were balanced between the LVI (+) and LVI (-) groups. The MFS, CSS, and OS were all significantly poorer in the LVI (+) group. For patients without LVI, the 5-year MFS, CSS, and OS rates were 65.3%, 73.1%, and 67.3%, respectively, whereas the corresponding rates were 50.2%, 63.8 %, and 54.6%, respectively, for patients with LVI. (all P < .001). For patients without LVI, the 10-year MFS, CSS, and OS rates were 61.5%, 69.6%, and 59.2%, respectively, whereas those for patients with LVI were 44.5%, 57.0%, and 42.7%, respectively (all P < .001). LVI is an important pathological feature that predicts metastasis development and worse survival outcome after radical surgery in UT-UC patients.

Unusual presentation of upper urinary tract urothelial carcinoma in Taiwan: Direct comparison from Taiwan-Japan UTUC Collaboration Cohort.

OBJECTIVES: To carry out a comparison of upper urinary tract urothelial carcinoma characteristics and behavior between patients in Taiwan and Japan. METHODS: A Taiwan urinary tract urothelial carcinoma cohort was obtained from Kaohsiung Chang Gung Memorial Hospital, and a Japan urinary tract urothelial carcinoma cohort from Hirosaki University Hospital. The inclusion criteria were urinary tract urothelial carcinoma patients who underwent radical nephroureterectomy. Those who received perioperative chemotherapy were excluded. Finally, 765 patients in the Taiwan cohort and 325 in the Japan cohort were analyzed. The end-point of this study was to study the natural course of urinary tract urothelial carcinoma within 5 years between these two groups. RESULTS: The main finding was that urinary tract urothelial carcinoma patients in Taiwan were younger (P < 0.001), more were women (P < 0.001), with low-stage disease (P < 0.001), with more chronic kidney disease (P < 0.001), with less smoking history (P < 0.001), with more bladder cancer history (P = 0.002), with more multifocal (P < 0.001) and less high-grade disease (P = 0.015), as well as less lymphovascular invasion (P < 0.001) and more squamous differentiation (P < 0.001). However, the multivariate Cox regression analysis showed no racial difference in oncologic outcome, such as intravesical recurrence, systemic recurrence or cancer-specific death in primary and propensity-matched cohorts. Bladder cancer history was found to be the most important factor predicting intravesical recurrences, whereas stage was strongly associated with systemic recurrence and cancer specific mortality. CONCLUSIONS: The clinical characteristics of urinary tract urothelial carcinoma in Taiwan are significantly different from those of urinary tract urothelial carcinoma in Japan. However, there is no racial difference in stage-specific oncologic outcome after standard nephroureterectomy.

TGF-ßI Regulates Cell Migration through Pluripotent Transcription Factor OCT4 in Endometriosis.

Transforming growth factor (TGF-ß)/TGF-ß receptor signal is known to promote cell migration. Up-regulation of TGF-ß in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-ß/TGF-ß receptor and OCT4 affect endometriotic cell migration still remain largely unknown. Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls. We found the mRNA levels of TGF-ß receptor I (TGF-ß RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low-migratory normal or hyperplastic endometrium. Positive correlations between TGF-ß RI and OCT4, and either TGF-ß RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues. TGF-ßI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-ßI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A. Furthermore, TGF-ßI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-ßI-induced cell migration activity evidenced by wound-closure assay, transwell assay, and confocal image of F-actin cellular distribution. In conclusion, the present findings demonstrate that the niche TGF-ß plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell migration. These findings would be useful for developing therapeutic strategies targeting TGF-ß-OCT4 signaling to prevent endometriosis in the future.

Expression of the pluripotent transcription factor OCT4 promotes cell migration in endometriosis.

OBJECTIVE: To identify the impact of the pluripotent transcription factor OCT4 in endometrial cell migration and endometriosis. DESIGN: The OCT4 expression and cell migration study. SETTING: Research institution and reproductive medical clinic. PATIENT(S): Nine subjects with normal endometrium, 3 subjects with normal myometrium, 36 patients with hyperplastic endometrium, and 58 patients with endometriosis. INTERVENTION(S): The expression of OCT4 messenger RNA in normal endometrium, normal myometrium, hyperplastic endometrium, and ectopic endometriotic tissues was analyzed using reverse transcription and quantitative real-time polymerase chain reaction (PCR). The effect of OCT4 expression on the migration activity of the endometrial cells was examined. MAIN OUTCOME MEASURE(S): Reverse transcription and quantitative real-time PCR, Western blotting, and wound closure and transwell assays. RESULT(S): The expression of OCT4 and NANOG messenger RNA was significantly higher in ectopic endometriotic tissues, compared with that of the normal endometrium, the normal myometrium, and the hyperplastic endometrium. The level of OCT4 messenger RNA in endometriotic tissues was positively correlated with the expression of genes associated with cell migration. Overexpression of the OCT4 protein in primary human endometriotic stromal cells and human RL95-2 and HEC1A endometrial carcinoma cell lines resulted in decreased levels of E-CADHERIN, the increased expression of the VIMENTIN, TWIST, and SLUG proteins, and an increase in the migration activity of endometrial cells in transwell and wound closure assays. CONCLUSION(S): The transcription of the OCT4 gene is significantly up-regulated in human ectopic endometriotic tissues. The expression of OCT4 may contribute to the pathology of ectopic endometrial growth by stimulating the migration activity of endometrial cells.

Antioxidant effects of black rice extract through the induction of superoxide dismutase and catalase activities.

Our ex vivo study revealed that BRE had significantly stronger ability to inhibit LDL oxidation than white rice extract (WRE). The purpose of this study was to investigate whether black rice extract (BRE) supplementation might ameliorate oxidative stress and enhance antioxidant enzyme activities in HepG2 cells and in C57BL/6 mice. In the cellular study, superoxide anions (O2*-) and reactive oxygen species (ROS) in the BRE group were significantly suppressed. The BRE group also showed significant increases in superoxide dismutase (SOD) and catalase (CAT) activities by 161.6% and 73.4%, respectively. The major components responsible for the free-radical-scavenging and antioxidative properties might be cyanidin-3-O-glucoside chloride and peonidin-3-O-glucuside chloride. In the animal study, male C57BL/6 mice were divided into three groups (control, BRE, and WRE). Plasma HDL-cholesterol was significantly higher, and thiobarbituric, acid-reactive substances were significantly lower in the BRE group, whereas plasma levels of total cholesterol and triglyceride were not affected by BRE supplementation. Increased hepatic SOD and CAT activities were observed in BRE-treated mice as compared to the control mice. However, no changes were detected for the protein expression of antioxidant enzymes by Western blot analysis. Our data suggest that antioxidative effects exerted by BRE are mediated through decreases in free-radical generation as well as increases in SOD and CAT activities both in vitro and in vivo.