BackgroundWhile several molecular markers of bladder cancer prognosis have been identified, the limited value of current prognostic markers has created the need for new molecular indicators of bladder cancer outcomes. The aim of this study was to identify genetic signatures associated with disease prognosis in bladder cancer.ResultsWe used 272 primary bladder cancer specimens for microarray analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Microarray gene expression analysis of randomly selected 165 primary bladder cancer specimens as an original cohort was carried out. Risk scores were applied to stratify prognosis-related gene classifiers. Prognosis-related gene classifiers were individually analyzed with tumor invasiveness (non-muscle invasive bladder cancer [NMIBC] and muscle invasive bladder cancer [MIBC]) and prognosis. We validated selected gene classifiers using RT-PCR in the original (165) and independent (107) cohorts. Ninety-seven genes related to disease progression among NMIBC patients were identified by microarray data analysis. Eight genes, a progression-related gene classifier in NMIBC, were selected for RT-PCR. The progression-related gene classifier in patients with NMIBC was closely correlated with progression in both original and independent cohorts. Furthermore, no patient with NMIBC in the good-prognosis signature group experienced cancer progression.ConclusionsWe identified progression-related gene classifier that has strong predictive value for determining disease outcome in NMIBC. This gene classifier could assist in selecting NMIBC patients who might benefit from more aggressive therapeutic intervention or surveillance.

Results strongly suggest that inactivation of RUNX3 by the methylation of its promoter region is a significant risk factor for invasive bladder tumors, tumor progression and cancer specific survival. RUNX3 promoter methylation status could be a promising marker for assessing the prognosis of human bladder tumors.

Dysregulated bone morphogenetic proteins (BMP) may contribute to the development and progression of renal cell carcinoma (RCC). Herein, we report that BMP-6 promotes the growth of RCC by interleukin (IL)-10-mediated M2 polarization of tumor-associated macrophages (TAM). BMP-6-mediated IL-10 expression in macrophages required Smad5 and STAT3. In human RCC specimens, the three-marker signature BMP-6/IL-10/CD68 was associated with a poor prognosis. Furthermore, patients with elevated IL-10 serum levels had worse outcome after surgery. Together, our results suggest that BMP-6/macrophage/IL-10 regulates M2 polarization of TAMs in RCC.

BackgroundNew biological prognostic predictors have been studied; however, some factors have limited clinical application due to tissue-specific expression and high cost. There is the need for a promising predictive factor that is simple to detect and that is closely linked to oncological outcomes in patients with urothelial bladder cancer (BC) who have undergone radical cystectomy (RC). Therefore, we investigated the clinical prognostic value of the preoperative De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) on oncological outcomes in patients with urothelial BC after RC.MethodsWe retrospectively evaluated clinicopathological data of 118 patients with non-metastatic urothelial BC after RC between 2008 and 2013 at a single center. The association between the De Ritis ratio and clinicopathological findings was assessed. The potential prognostic value of the De Ritis ratio was analyzed using the Kaplan-Meier method, and multivariate Cox analyses were performed to identify the independent predictors of metastasis-free survival, cancer-specific survival, and overall survival.ResultsAccording to the receiver operating curve of the De Ritis ratio for metastasis, we stratified the patients into 2 groups using a threshold of 1.3. A high De Ritis ratio was more likely to be associated with old age and the female sex. Kaplan-Meier estimates revealed that patients with a high De Ritis ratio had inferior metastasis-free survival, cancer-specific survival, and overall survival outcomes (P = 0.012, 0.024, and 0.022, respectively). Multivariate analysis revealed that a high De Ritis ratio was an independent prognostic factor for metastasis (hazard ratio [HR], 2.389; 95% confidence interval [CI], 1.161–4.914; P = 0.018), cancer-related death (HR, 2.755; 95% CI, 1.214–6.249; P = 0.015), and overall death (HR, 2.761; 95% CI, 1.257–6.067; P = 0.011).ConclusionsAn elevated De Ritis ratio was significantly associated with worse prognosis in patients who underwent RC for urothelial BC. This ratio might further improve the predictive accuracy for prognosis in BC.

BACKGROUND: Human adipose tissue is routinely discarded as medical waste. However, this tissue may have valuable clinical applications since methods have been devised to effectively isolate adipose-derived extracellular matrix (ECM), growth factors (GFs), and stem cells. In this review, we analyze the literature that devised these methods and then suggest an optimal method based on their characterization results. METHODS: Methods that we analyze in this article include: extraction of adipose tissue, decellularization, confirmation of decellularization, identification of residual active ingredients (ECM, GFs, and cells), removal of immunogens, and comparing structural/physiological/biochemical characteristics of active ingredients. RESULTS: Human adipose ECMs are composed of collagen type I-VII, laminin, fibronectin, elastin, and glycosaminoglycan (GAG). GFs immobilized in GAG include basic fibroblast growth factor (bFGF), transforming growth factor beta 1(TGF-b1), insulin like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), BMP4 (bone morphogenetic protein 4), nerve growth factor (NGF), hepatocyte growth factor (HGF), and epithermal growth factor (EGF). Stem cells in the stromal-vascular fraction display mesenchymal markers, self-renewal gene expression, and multi-differentiation potential. CONCLUSION: Depending on the preparation method, the volume, biological activity, and physical properties of ECM, GFs, and adipose tissue-derived cells can vary. Thus, the optimal preparation method is dependent on the intended application of the adipose tissue-derived products. Keywords Human adipose tissue Á Extracellular matrix Á Growth factors Á Adipose-derived stem cell Á Optimum method So Young Chun and Jeong Ok Lim have contributed equally to this work.

Strong carcinogens, such as 1,2-dichloroethane, benzene, and ethylbenzene, were eliminated by more than 85% by using this activated carbon fiber filter and the risks from these compounds decreased to an almost negligible level. We suggest using every measure, including these filters, to protect the health of operating room personnel.

Appropriate patient selection for active surveillance is challenging. Our study of 217 patients demonstrated that the preoperative absolute neutrophil and lymphocyte counts were better predictors of aggressive oncologic features than were the neutrophil-to-lymphocyte ratio in the assessment of low-risk prostate cancer patients. Our findings suggest that routine hematologic workup could be used to further stratify low-risk prostate cancer patients. Introduction The neutrophil-to-lymphocyte ratio (NLR) has emerged as a ubiquitous prognostic biomarker in cancer-related inflammation, specifically in patients with metastatic castration-resistant prostate cancer (PCa). We evaluated the clinical utility of the preoperative NLR, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) as a risk stratification tool for patients with low-risk PCa. Materials and Methods We identified 217 low-risk PCa patients with preoperative hematologic data who had met the criteria for active surveillance but had undergone robot-assisted radical prostatectomy at our institution from 2006 to 2015. Logistic regression models were constructed to determine whether the baseline NLR, ANC, and ALC were associated with upstaging, upgrading, and biochemical recurrence (BCR). Survival analyses were performed using the Kaplan-Meier method. Results On multivariate analysis, a higher prostate-specific antigen level (odds ratio [OR], 1.554; 95% confidence interval [CI], 1.148–2.104), a greater number of positive cores (OR, 2.098; 95% CI, 1.043–2.104), and a higher ALC (OR, 4.311; 95% CI, 1.258–14.770) were associated with upstaging. More importantly, the 5-year biochemical recurrence-free survival was significantly lower in the high ANC group (ANC > 4.0 × 109/L) compared with that of the low ANC group (P = .011). The NLR was not associated with upstaging, upgrading, or BCR in our study cohort (P = .368, P = .573, and P = .504, respectively). The only significant association with upgrading was patient age (OR, 1.106; 95% CI, 1.043–1.173). Conclusion NLR was not useful in predicting adverse pathologic outcomes in our patients with low-risk PCa. However, relative neutrophilia and lymphocytosis might indicate an early manifestation of harboring a more aggressive PCa.

Purpose: Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy is effective in the prevention of recurrence and progression in many cases of nonmuscle invasive bladder cancer, but many patients fail to respond. The aim of this study was to identify gene sets of markers that could predict the response to BCG immunotherapy in primary pT1 bladder cancer using microarray gene expression profiling.Experimental Design: We used 80 patients with primary pT1 bladder cancer treated with BCG immunotherapy as training (48) and test (32) sets. Microarray gene expression profiling was done in the training set to identify genes differentially expressed between responder and nonresponder to BCG immunotherapy according to the events (recurrence or progression). Using a real-time reverse-transcriptase PCR, our findings were validated in the test set.Results: In the training set, 424 and 287 genes were significantly associated with recurrence-and progression-free survival, respectively. Functional annotation of these genes included cell-mediated immune response, inflammatory response, cellular growth, and proliferation. From these predictive gene signatures, 24 genes (12 in recurrence and 12 in progression) with the highest score of expression ratio were extracted for validation in the test set. In multivariate regression analyses, predictive gene signatures were the only independent predictors of recurrence (hazard ratio, 3.38; P = 0.048) or progression (hazard ratio, 10.49; P = 0.048) in the test set.Conclusions: Predictive gene signatures have diagnostic value for determining the response to intravesical BCG immunotherapy in primary pT1 bladder cancer. Clin Cancer Res; 16(7); 2131-7. ©2010 AACR.