Haige Chen

Single-nucleotide polymorphisms of GPX1 and MnSOD and susceptibility to bladder cancer: a systematic review and meta-analysis

Reactive oxygen species-related damage plays a critical role in carcinogenesis. Glutathione peroxidase 1 (GPX1) and mitochondrial superoxide dismutase (MnSOD) are two key antioxidant enzymes in the defense system against reactive oxygen species. This systematic review and meta-analysis was designed to evaluate the association of single-nucleotide polymorphisms in GPX1 and MnSOD genes with susceptibility to bladder cancer risk. Online databases of PubMed, Embase, China National Knowledge Infrastructure, and SinoMed were searched to identify eligible studies. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were calculated to estimated the association strength. The fixed effects model and random effects model were used to pool the data from different studies. By pooling all eligible studies, we found that the GPX1 Pro198Leu polymorphism was associated with a significantly increased risk of bladder cancer (Leu vs. Pro, OR = 2.111, 95 % CI = 1.020–4.368, heterogeneity (p < 0.001); LeuPro/LeuLeu vs. ProPro, OR = 1.876, 95 % CI = 1.011–3.480, heterogeneity (p < 0.001)). No significant association of MnSOD Ala-9Val polymorphism with cancer risk was observed (AlaVal/ValVal vs. AlaAla, OR = 0.966, 95 % CI = 0.754–1.239, heterogeneity (p = 0.390); Vla vs. Ala, OR = 1.038, 95 % CI = 0.782–1.377, heterogeneity (p = 0.015)). This systematic review and meta-analysis demonstrated that the GPX1 Pro198Leu polymorphism significantly increased susceptibility to bladder cancer, while the MnSOD Ala-9Val polymorphism was not associated with bladder cancer risk.

Catalpol Inhibited the Proliferation of T24 Human Bladder Cancer Cells by Inducing Apoptosis Through the Blockade of Akt-Mediated Anti-apoptotic Signaling

Catalpol is an iridoid glucoside extracted from the traditional Chinese medicinal plant called Rehmannia glutinosa, and it is reported to possess a variety of pharmacological activities. The goal of this research was to explore the effect of catalpol on the human bladder cancer cells T24. The cells were treated for different durations with various concentrations of catalpol. Then the viability, mobility, and invasiveness of the cells were determined by MTT assay and flow cytometry, respectively. Catalpol was found to significantly suppress the proliferation, migration, and invasiveness of T24 bladder cancer cells in a dose- and time-dependent manner. The results also revealed that catalpol promoted apoptosis and caused the cell-cycle arrest at G2/M phase. Furthermore, the catalpol-mediated apoptosis was found to involve the modulation of PI3K/Akt pathway and inhibit the expression of anti-apoptotic B cell lymphoma-2 (Bcl-2) family proteins. Also, the expressions of Bcl-2 proapoptotic effectors, Bcl-2-associated X protein, and Bcl-2 associated death promoter were up-regulated in the cells treated with catalpol. The enzymes involved in the ultimate process of apoptosis, active caspase-3 and poly ADP ribose polymerase were elevated, and the latter was observed to be cleaved, indicating that catalpol-accelerated cell apoptosis involved a caspase-dependent pathway. These results suggest that catalpol might serve to be a promising therapeutic agent for the treatment of human bladder cancer.

Preoperative prognostic nutritional index is a significant predictor of survival in patients with localized upper tract urothelial carcinoma after radical nephroureterectomy.

BACKGROUND Patients nutritional and immunological status have a potentially significant role in survival outcome in patients with malignant tumors. We investigated the prognostic value of preoperative prognostic nutritional index (PNI) in patients with localized upper tract urothelial carcinoma (UTUC) undergoing radical nephrouretectomy (RNU). PATIENTS AND METHODS A total of 425 patients with nonmetastatic UTUC (Ta-4N0/+M0) who underwent RNU were evaluated. PNI was calculated as 10 × serum albumin concentration (g/dl) + 0.005 × lymphocyte counts (number/mm3). The associations of preoperative PNI level with clinical and pathologic variables were analyzed. RESULTS The optimal cutoff value of PNI for cancer-specific survival (CSS) stratification was determined to be 46.78. Multivariate analysis identified low PNI as an independent prognostic factor for CSS (HR = 1.98, 95% CI: 1.31-2.99, P = 0.001) and overall survival (HR = 1.74, 95% CI: 1.20-2.53, P = 0.004). The estimated c-index of the multivariate model for CSS and overall survival increased from 0.777 and 0.767 to 0.791 and 0.774, respectively, when PNI added, which was higher than hypoalbuminemia (albumin<37.75g/l) or neutrophil-to-lymphocyte ratio >2.955 added. CONCLUSIONS Preoperative PNI was an independent prognostic factor for predicting survival in patients with UTUC undergoing RNU. Preoperative PNI may become a useful biomarker, particularly because of its low associated cost and easy accessibility.

Preoperative serum pre-albumin as an independent prognostic indicator in patients with localized upper tract urothelial carcinoma after radical nephroureterectomy

Purpose To investigate the prognostic value of preoperative pre-albumin and albumin level in patients with localized upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy. Methods and Materials Between January 2003 and June 2013, we evaluated data on 425 patients with nonmetastatic UTUC (Ta-4N0/+M0) who underwent radical nephroureterectomy at our institution. Low pre-albumin level was defined as <20 mg/dl, while hypoalbuminemia was defined as albumin <35 g/L. The associations of preoperative low pre-albumin level and hypoalbuminemia with clinical and pathologic variables were assessed. Univariable and multivariable analyses using the Cox regression model were performed to determine prognostic factors that were associated with cancer specific survival (CSS) and overall survival (OS). The Harrell concordance index with variables only or combined pre-albumin data were used to evaluate the prognostic accuracy. Results Compared with patients with high pre-albumin level, patients with low pre-albumin level were more likely to have older age, higher tumor stage, higher rate of diabetes, regional lymph node metastasis and lymphovascular invasion. Meanwhile, hypoalbuminemia was only associated with diabetes. Multivariate analysis identified decreased preoperative pre-albumin level as an independent prognostic factor for CSS (HR 1.85, 95% CI 1.14-3.00, p=0.013) and OS (HR 1.73, 95% CI 1.12-2.70, p=0.015), but not preoperative hypoalbuminemia. The estimated c-index of the multivariate model for CSS and OS increased from 0.771 and 0.760 without pre-albumin to 0.775 and 0.765 when pre-albumin added. Conclusions Low preoperative pre-albumin level but not preoperative hypoalbuminemia is a negative independent prognostic factor for survival outcome in patients with UTUC undergoing radical nephroureterectomy.

Prognostic value of preoperative plasma fibrinogen level and platelet-to-lymphocyte ratio (F-PLR) in patients with localized upper tract urothelial carcinoma

Purpose Hemostatic factors is thought to have a potentially significant role in progression and metastasis of malignant tumors. We investigated the prognostic value of preoperative plasma fibrinogen level and platelet-to-lymphocyte ratio (PLR) in localized upper tract urothelial carcinoma (UTUC). Materials and Methods A total of 481 patients who underwent radical nephroureterectomy for localized UTUC (pTa-4N0M0) were identified between January 2002 and June 2013. Patients were assigned a F-PLR score of 0, 1, or 2 based upon the presence of elevated plasma fibrinogen level, an elevated PLR, or both. The association between F-PLR score and clinicopathological variables was analysed. Results The optimal cut-off value of plasma fibrinogen and PLR for overall survival stratification was determined to be 4.22 and 241.2. Kaplan–Meier analysis revealed significant differences in cancer specific survival (CSS) and overall survival (OS) among patients with F–PLR scores of 0, 1 and 2. Multivariate analysis identified higher F–PLR score as an independent risk factor for CSS (P < 0.001) and OS (P < 0.001). The estimated c-index of the multivariate model for CSS and OS increased from 0.772 and 0.756 to 0.799 and 0.784 when F–PLR score added, which was higher than fibrinogen level, PLR or neutrophil-to-lymphocyte ratio added. Conclusions Preoperative F-PLR score is a negative independent prognostic factor for survival outcomes in patients with localized upper tract urothelial carcinoma. Preoperative F-PLR score may become a useful biomarker, particularly because of its low associated cost and easy accessibility.

Thyroid-Like Follicular Carcinoma of the Kidney in a Patient with Skull and Meningeal Metastasis: A Unique Case Report and Review of the Literature

AbstractThyroid-like follicular carcinoma of the kidney (TLFCK) is an extremely rare subtype of renal cell carcinoma with close resemblance to the well-differentiated thyroid follicular neoplasms. TLFCK has not been included in the 2004 World Health Organization (WHO) classification due to the limited data available. Only 27 cases have been reported in the literature to date.Herein, we report a unique case of TLFCK that presented as a striking skull and meningeal metastasis 5 years after the initial diagnosis; this is the first case of TLFCK with such a novel metastasis pattern. A 68-year-old woman was found to have a right renal lesion using computed tomography (CT) during her regular clinical follow-up visit for bladder cancer, but she exhibited no obvious clinical symptoms. The CT scan showed a 4.4-cm diameter, slightly lobulated soft tissue mass in the right lower kidney, the pathological findings of which showed a TLFCK. Five years later, the patient had progressed to skull and meningeal metastasis.Both the renal tumor and the metastasis lesion were composed almost entirely of follicles with a dense, colloid-like material that resembled thyroid follicular carcinoma. However, no lesion was found in the thyroid gland. The neoplastic epithelial cells were strongly immunoreactive for cytokeratin 7 (and vimentin but negative for thyroid transcription factor-1 and thyroglobulin.This is the first reported case of TLFCK to consist of widespread metastases to the skull and meninges and provides evidence that this rare variant of renal cell carcinoma has uncertain malignant potential and can be more clinically aggressive than previously believed.

Curcumin inhibits cell proliferation and motility via suppression of TROP2 in bladder cancer cells

Bladder cancer (BC) has become a serious health problem and represents the second most commonly diagnosed urological tumor. Curcumin is a principal active natural component of turmeric and has long been used in Asia as a traditional herbal medicine. Curcumin suppresses cell growth in various types of cancer, including BC, by regulating numerous molecular signaling pathways. The human trophoblast cell surface antigen 2 (Trop2) belongs to the tumor-associated calcium signal transducer gene family. Trop2 has been described as a cancer driver and is deregulated in various types of cancer. However, whether Trop2 is involved in curcumin-induced BC cell inhibition remains to be elucidated. The present study hypothesized that Trop2 may be a promising target of curcumin in BC cells. It was found that Trop2 was closely involved in curcumin-induced cell proliferation suppression, mobility inhibition, apoptosis, and cell cycle arrest in BC cells. Curcumin decreased the expression of Trop2 and its downstream target cyclin E1, and increased the level of p27. The overexpression of Trop2 enhanced the oncogenic activity of BC cells, whereas downregulation of the expression of Trop2 suppressed cell proliferation and mobility, increased apoptosis, and sensitized BC cells to curcumin treatment. Therefore, Trop2 may be a promising target of curcumin in BC cells and the inhibition of Trop2 may be an important method for the therapeutic management of patients with BC.