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The vagus nerve plays an essential role in homeostasis and inflammation. Clinically, peptic ulcer patients without helicobacter pylori (HP) infection may provide a population for studying the effect of vagal hyperactivity. There were interests in the association of gastrointestinal disease and urogenital disorders. Herein, we try to investigate subsequent risk of benign prostatic hyperplasia (BPH) in non-HP infected peptic ulcer patients. We identified 17,672 peptic ulcer admission male patients newly diagnosed in 1998–2007 from Taiwan Health Insurance Database, and 17,672 male comparison without peptic ulcer, frequency matched by age, and index-year. We assessed subsequent incidence of BPH in each cohort by the end of 2013, and then compared the risk of developing BPH between individuals with and without peptic ulcer. In addition, peptic ulcer patients underwent surgery were also examined. There were 2954 peptic ulcer patients and 2291 comparisons noted with the occurrence of BPH (25.35 and 16.70 per 1000 person-years, respectively). Compared to comparisons, peptic ulcer patients had a 1.45- and 1.26-fold BPH risk in multivariable Cox model and Fine and Gray model (95% CI 1.37–1.54 and 1.19–1.34). In age-stratified analysis, the highest risk of BPH was in 45–59 years (interaction p

Introduction The gold standard treatment for upper tract urothelial carcinomas (UTUC) is radical nephroureterectomy with bladder-cuff excision. However, the role of combination of ureterorenoscopy and laser ablation has recently become more essential. This study aimed to investigate the efficacy of Thulium laser ablation of UTUC and estimate clinical outcomes with subgroup analyses. Methods After obtaining informed consent, we retrospectively reviewed all patients who had undergone endoscopic Thulium laser ablation of UTUC as their primary treatment from Jun 2012, to Nov 2018. Sixty-eight patient were enrolled, and thirty-four patients were analyzed after selection by exclusion criteria. Comparisons with bivariate analyses between patients with and without recurrence were examined. Multivariable cox regression model were further applied. Further, Kaplan-Meier survival estimate were presented with comparison of the survival curves, we also combined two of three tumor characteristics (stage, size, and grade of tumor) for subgroup analyses. Results Fifteen patients (44%) had local tumor recurrence. Seven patients (21%) had recurrence at the urinary bladder. Two patients (6%) had lymph node or distal metastasis. A total of 4 patients (12%) had cancer-specific death. In bivariate analyses, statistical significance is noted for age, tumor grade and tumor size with p-values of 0.018, 0.047 and 0.014, respectively. In the multivariable analysis, statistical significance is noted for age and tumor size with p-values of 0.017, and 0.042, respectively. In Kaplan–Meier estimate for subgroup analysis, statistical significance is only noted in the tumor size + tumor grade group but almost achieved in the tumor size + biopsy stage group with p-value of 0.0275 and 0.0518, respectively. Conclusion In our experience, tumor size and tumor grade are influential recurrence factors. However, biopsy stage does not achieve statistical significance in both the recurrence analysis and survival estimate. In the subgroup analyses, tumor size is a more influential factor than tumor grade in the prognosis of local recurrence.

Introduction: End-stage renal disease has high prevalence in Taiwan, and peritoneal dialysis (PD) is one of the effective treatments. Although the open catheter placement method is more popular, the laparoscopic method is proven to be superior. We present our initial experience with laparoscopic PD catheter insertion. Materials and Methods: We set one 5-mm trocar over the periumbilicus with another assisting 5-mm trocar in a region about 3 cm lateral to the umbilicus. Abdominal exploration using laparoscopy is performed, and enterolysis is also performed if needed. The PD catheter is inserted through the assisted trocar deep into the Douglas pouch under vision. Finally, we check the final condition under laparoscopy and close the wound. Results: A total of thirty patients (median age 56.5 years old, 15 women) underwent this procedure. No intraoperative complications were noted, and the mean operation time was 32 min. Two postoperative complications were found (2/30, 6.7%). Delayed bleeding was noted due to abdominal wall vessel injury while setting the trocar. The vessel was sutured under laparoscopy, which stopped the bleeding. The other complication was tube dysfunction due to omentum wrapping. Laparoscopic revision of the tube was performed. All the complications could be resolved, and the PD was continued. The mid-term tube function at follow-up (at least 16 months) was acceptable in all cases. Conclusions: Laparoscopic-assisted PD catheter insertion is a feasible procedure that can reduce wound pain with acceptable PD function.

Perilla frutescens (L.) Britt Labiatae (Pl), known as “Zi-So” and widely grown in China (red cultivar, Rpl) and Japan (green cultivar, Gpl), is frequently served on “Sa-Shi-Mi” dishes. Considering ...

Taiwan produces large quantities of bananas in the southern area. Recently, due to the export quantity has been greatly reduced, in order to efficiently maintain the banana agriculture and economy, the development of alternate uses of bananas has become urgently in need. Bananas contain a fair amount of nutrients with low glycemic index. Currently, as the bread consumption is increasing, we tried to manufacture banana‐assorted breads. The desiccated powders of Musa sapientum var TC2‐425 Linn [(genomically, called as Musa (AAA) (MA)] and Musa basjoo “Nam Wa” (MB) were separately incorporated at 15%, 20%, and 25% (denoted as MA15‐MA25 and MB15‐MB25). Results indicated that MA exhibited higher contents of moisture, ash, crude protein, and lutein, while with lower crude fat, crude fibers, carbohydrate, sodium, total soluble sugars, and pectin. The contents of taste compounds (name, samples in decreasing order) were as follows: 5′‐CMP (MB25, MB20); 5′‐GMP (MA25, MA20); 5′‐AMP (MB25, MA15); 5′‐XMP (MA25, MA20); 5′‐IMP (MA25, MB20, MB25); and 5′‐UMP (MA20, MA25, MB20). Hedonic scoring (HS) indicated MA15, MA20, MB15, and MB20 were more acceptable. Textural profile analysis (TPA; for 0–6 days, only 0–4 days are shown) revealed that “flavor,” “mouthfeel,” “hardness,” “gumminess,” and “chewiness” were the determinant key roles. Conclusively, due to different chemical constituent of banana, different recipes must be considered. The bread acceptability is affected by the fermentative profile which in turn is governed by the contents of soluble sugars, pectin, taste compounds, and the overall activity of yeast cells., The bread acceptability is affected by the fermentative profile which in turn is governed by the contents of soluble sugars, pectin, and taste compounds. Hence, regarding the use of bananas in making the banana‐assorted breads, the recipes must be carefully designed by considering such factors.

Bicalutamide (Bic) is frequently used in androgen deprivation therapy (ADT) for treating prostate cancer. ADT-induced hypogonadism was reported to have the potential to lead to acute kidney injury (AKI). ADT was also shown to induce bladder fibrosis via induction of the transforming growth factor (TGF)-β level. We hypothesized that Bic can likely induce renal fibrosis. To understand this, a cell model was used to explore expressions of relevant profibrotic proteins. Results indicated that Bic initiated multiple apoptotic and fibrotic pathways, including androgen deprivation, downregulation of the androgen receptor → phosphatidylinositol-3-kinase → Akt pathway, upregulation of the extrinsic apoptotic pathway- tumor necrosis factor α → nuclear factor κB → caspase-3, increased expressions of fibrosis-related proteins including platelet-derived growth factor β, fibronectin and collagen IV, and enhanced cell migration. The endoplasmic reticular stress pathway and smooth muscle actin were unaffected by Bic. Co-treatment with testosterone was shown to have an anti-apoptotic effect against Bic, suggesting a better outcome of Bic therapy if administered with an appropriate testosterone intervention. However, since Bic was found to inhibit the membrane transport and consumption rates of testosterone, a slightly larger dose of testosterone is recommended. In conclusion, these pathways can be considered to be pharmaceutically relevant targets for drug development in treating the adverse effects of Bic.

In recent years, second-look transurethral resection of bladder tumors (TURBT) has been recommended for patients with stage T1 bladder cancer after the initial TURBT for restaging and deciding the subsequent treatment. However, we believe that second-look TURBT has therapeutic benefits, such as low incidence of recurrence and progression. Therefore, we compare the differences in long-term outcome between patients who did and did not accept second-look TURBT for stage T1 bladder cancer. We assessed 504 patients diagnosed with urothelial carcinoma who underwent initial TURBT between January 2012 and December 2016 at a single medical center; of these patients, 177 were diagnosed with T1 bladder cancer during the initial TURBT, and we excluded no muscle from the specimen in the initial TURBT. The patients were categorized into groups 1 and 2 based on the acceptance of second-look TURBT, which was performed within 4–14 weeks after the initial TURBT. Group 1 underwent second-look TURBT, but group 2 did not. Both groups were followed-up for recurrence-free survival (RFS) and progression-free survival (PFS), and the risk factors for recurrence and progression were analyzed. In total, 93 (52.5%) patients in group 1 underwent second-look TURBT, and 84 (47.5%) in group 2 did not. The 2-year RFS rates were 74.6% and 60.0% and the PFS rates were 91.2% and 87.5% in groups 1 and 2, respectively. This study demonstrated higher recurrence-free and progression-free survival rates for patients who underwent second-look TURBT. This result emphasizes the importance of second-look TURBT in stage T1 bladder cancer not only for restaging but also for therapeutic benefit.

Rhizoma Alpinia officinarum (Hance) Farw, Zingiberaceae (AO), a ginger family herb exhibiting stimulant and a carminative bioactivity, is widely used in European and Asian countries as spicy condiment and medicinal uses. Allyl isothiocyanate (AITC) is the main pungent taste of native Wasabi (Wasabia japonica). The cytotoxicity of AITC has been implicated in thymus, adrenals, and white blood cells. Considering food safety, apparently a safer substitute for wasabi is worthy commercialized. Previously, we found AO crude paste to be rather feasible for use as a "Wasabi-substitute" in fresh meat and cold salads. A process linking cold ethyl acetate (EtAc) extraction with silica gel adsorption and reversed phase high-performance liquid chromatography (RP-HPLC) (mobile phase, 75% methanol) was used to isolate galangal acetate, the Wasabi-like taste constituent. AO contained abundant galangal acetate (3.84 ± 0.07%) compared to A. galangal (0.57 ± 0.16%), and as already confirmed by thin layer chromatography (TLC), gas chromatography (GC)/mass spectrometry (MS)/MS and Nuclear Magnetic Resonance Spectroscopy (NMR), galangal acetate was particularly thermally labile. The steam distilled essential oil (SDEO) of AO (0.14% on wet basis) contained 80 compounds (number of component, %): monoterpene hydrocarbon (21, 13.83%); oxygenated monoterpene (17, 27.08%); sesquiterpene hydrocarbon (20, 31.03%), and oxygenated sesquiterpene (20, 21.85%), respectively. However, no spicy wasabi-like constituent remained in SDEO. Alternatively, n-hexane, EtAc, and methanol extracts of AO all showed potent DPPH- and superoxide anion-scavenging activity. Conclusively, SDEO although contains 80 volatiles, galangal acetate is absent due to thermal instability. Galangal acetate exhibits pleasant "Wasabi-like taste" for which we have successively developed an integrated process for mass production.

To investigate bladder preservation therapy with a well tolerated strategy, 30 patients with bladder cancer underwent concomitant chemoradiotherapy with weekly carboplatin. The 2-year overall survival was 75% for all patients, 43% and 95% for patients without adjuvant chemotherapy or with adjuvant chemotherapy separately. This strategy was well tolerated with 7% of Grade 3/4 late bladder toxicity.The purpose of this study was to determine the feasibility and clinical effectiveness of concurrent weekly carboplatin chemotherapy in conjunction with definite radiation with or without adjuvant chemotherapy in the treatment of muscle-invasive bladder cancer.Between April 2010 and December 2013, 30 patients with muscle-invasive bladder cancer were evaluated retrospectively in this study. Concurrent chemoradiotherapy (CCRT) with weekly carboplatin was initiated. CCRT was followed by 2 courses of carboplatin and gemcitabine limited to patients with Eastern Cooperative Oncology Group performance status3 and age80 years.Thirty patients were treated and all completed the CCRT protocol. Seven of 8 patients (88%) achieved a pathological complete response (pCR) with CCRT alone, and 18 of 22 patients (82%) treated with CCRT followed by adjuvant chemotherapy had a pCR. The median follow-up was 23.2 (range, 8.3-40.7) months. The median progression-free survival was 15.9 months for the CCRT group, and not sufficient to evaluate CCRT followed by adjuvant chemotherapy. The median overall survival with CCRT was 18.8 months, and had not yet been reached for CCRT with adjuvant chemotherapy. The protocol was well tolerated for adverse events.Our study has shown that concomitant chemotherapy using weekly carboplatin in the management of muscle-invasive bladder cancer is feasible and well tolerated, even in older patients. Additional adjuvant chemotherapy with 2 cycles of carboplatin and gemcitabine should be encouraged in physically fit patients. These results provide a basis for randomized studies to compare this approach with conventional therapy for patients who wish to preserve the bladder.

Sinomenine is an alkaloid derived from Sinomenium acutum. Recent studies have found that sinomenine can inhibit various cancers by inhibiting the proliferation, migration and invasion of tumors and inducing apoptosis. This study aims to investigate the effect and mechanism of sinomenine on inhibiting the migration and invasion of human lung adenocarcinoma cells in vitro. The results demonstrate that viabilities of A549 and H1299 cells were inhibited by sinomenine in a dose-dependent manner. When treated with sub-toxic doses of sinomenine, cell migration and invasion are markedly suppressed. Sinomenine decreases the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9, and the extracellular inducer of matrix metalloproteinase (EMMPRIN/CD147), but elevates the expression of reversion-inducing cysteine-rich proteins with kazal motifs (RECK) and the tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. In addition, sinomenine significantly increases the expression of the epithelial marker E-cadherin but concomitantly decreases the expression of the mesenchymal marker vimentin, suggesting that it suppresses epithelial&ndash, mesenchymal transition (EMT). Moreover, sinomenine downregulates oncogenic microRNA-21 (miR-21), which has been known to target RECK. The downregulation of miR-21 decreases cell invasion, while the upregulation of miR-21 increases cell invasion. Furthermore, the downregulation of miR-21 stimulates the expression of RECK, TIMP-1/-2, and E-cadherin, but reduces the expression of MMP-2/-9, EMMPRIN/CD147, and vimentin. Taken together, the results reveal that the inhibition of A549 cell invasion by sinomenine may, at least in part, be through the downregulating expression of MMPs and miR-21. These findings demonstrate an attractive therapeutic potential for sinomenine in lung cancer anti-metastatic therapy.

Immunotherapy using bacille Calmette-Guerin (BCG) instillation is the mainstay treatment modality for superficial urothelial cancer (UC) through toll-like receptor (TLR) activation of cognitive immune response. We investigated the roles of TLR7 in the activation of apoptosis in UC cells after BCG treatment. The in vitro cytotoxicity effect of BCG on UC cells was measured by a modified 3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyl tetrazolium assay. Expressions of TLR7 mRNA and protein in native UC cells prior to and after BCG treatment were analyzed using real-time quantitative polymerase chain reaction and western blot methods. Phagocytotic processes after BCG treatment in UC cells were observed microscopically using a specific immunostain, subsequent cellular apoptosis-related signals induced by TLR7 were analyzed by western blot. Low-grade UC cells, TSGH8301, showed significant cellular death (4.23-fold higher than the high-grade UC cells T24 and J82) when treated with BCG and the BCG cytotoxicity was displayed in a dose–time-dependent manner. TSGH8301 cells had the highest content of TLR7 mRNA, 7.2- and 4.5-fold higher than that of T24 and J82 cells, respectively. TLR7 protein expression was also significantly increased in TSGH8301 cells. Phagocytosis-related markers, including beclin 1, ATG2, and LC3, were increased when TSGH8301 cells were treated by BCG. Interleukin-1 receptor-associated kinases 2 and 4 were also increased markedly in TSGH8301 cells. On the contrary, cellular apoptosis of TSGH8301 cells decreased by 34% when TLR7 activation was suppressed by the TLR antagonist IRS661 after BCG treatment. Our findings suggest that well differentiated TCC cells have higher expression of TLR7 and BCG can drive cellular death of TCC cells directly via TLR7 activation and related apoptotic pathway.

Arsenic may affect the function of proximal convoluted tubules and glomeruli, but epidemiological data on the association between arsenic ingestion and end-stage renal disease (ESRD) are limited. Therefore, we conducted a nationwide population-based study in Taiwan, where the incidence of ESRD is the highest in the world, to study the potential association. Using the National Health Insurance Database in Taiwan, we constructed a cohort of 362,505 members with age ≥ 40 years in 1998. We identified patients of ESRD newly diagnosed between January 1, 1998 and December 31, 2010 and performed Cox proportional hazard regressions to identify risk factors for ESRD and evaluate their effects. Arsenic levels in drinking water were assessed on the basis of a nationwide census survey conducted by the government, of which measurement reports were available for 311 townships. We identified 5442 new patient of ESRD during the study period and found that residents of areas with arsenic levels ≥ 50 μg/L in the drinking water had a hazard ratio (HR) of 1.14 (95% confidence interval [CI]: 1.08–1.21) for ESRD. After adjusting for sex, age, income, and comorbidities, we found an adjusted HR of 1.12 (95% CI: 1.06–1.19), which was still statistically significant. Furthermore, the effect was modified by comorbidities, with more prominent effects on patients with less than three comorbidities (adjusted HR = 1.51; 95% CI: 1.22–1.86 for low comorbidity score). In conclusion, a high arsenic level in drinking water was a risk factor for ESRD, independent of other documented risk factors. Reducing high-risk comorbidities in patients with early-stage renal dysfunction is important for slowing the progression of the disease to ESRD, even in the endemic area of arsenic exposure.

Corylin is a main compound isolated from Psoralea corylifolia L. (Fabaceae). A variety of pharmacological effects such as antioxidant, anti-proliferation, and anti-inflammatory properties of corylin have been reported. Nevertheless, the effect of corylin in microbial infection and sepsis remains unclear. In the present study, we investigated the anti-inflammatory effects of corylin. Our experimental results demonstrated that corylin inhibited the production of TNF-α, IL-6 and NO by both LPS-activated RAW 264.7 cells and LPS-activated murine peritoneal macrophages. Moreover, corylin suppressed the expression levels of iNOS and COX-2, reduced the production of PGE2 and HMGB1, blocked the translocation of HMGB1 from the nucleus to cytosol, and decreased the phosphorylation of MAPKs in LPS-activated RAW 264.7 cells as well as suppressed the activity of NF-κB in LPS-activated J-Blue cells. In addition, the administration of corylin reduced the production of NO and TNF-α, decreased LPS-induced liver damage markers (AST and ALT) and kidney damage markers (BUN and CRE), attenuated infiltration of inflammatory cells and tissue damage of lung, liver and kidney, and enhanced the survival rate of LPS-challenged mice. Taken together, these results show the anti-inflammatory properties of corylin on LPS-induced inflammation and sepsis. Corylin could potentially be a novel anti-inflammatory and immunosuppressive drug candidate in the treatment of sepsis and septic shock.

Several previous studies have investigated the association between the SULT1A1 Arg213His polymorphism and the risk of bladder cancer in various populations. However, these results remain inconsistent. Therefore, we performed this meta-analysis to evaluate the relationship between the SULT1A1 Arg213His polymorphism and the risk of bladder cancer. An extensive literature search was performed to identify all eligible studies regarding this association. The odds ratios (ORs) with 95 % confidence intervals (CIs) were used to estimate the strength of risk under fixed and random effects models. We identified and included eight case-control studies including 2,036 cases and 2,273 controls. No significant association was found between the SULT1A1 Arg213His polymorphism and the risk of bladder cancer under the dominant model; however, those with the SULT1A1 Arg/Arg genotype had a significantly increased risk (OR = 1.218, 95 % CI = 1.067-1.392, P = 0.0044) under the recessive model. In the subgroup analysis of ethnicity, a significant association was observed in Caucasians under the recessive model (OR = 1.269, 95 % CI = 1.069-1.506, P = 0.007). Furthermore, an increased risk of bladder cancer was observed between the Arg213His polymorphism and never smokers in the recessive model (OR = 1.428, 95 % CI = 1.079-1.890, P = 0.013). The results of this meta-analysis indicate that the SULT1A1 Arg213His polymorphism is associated with the risk bladder cancer under a recessive model; however, a possibly higher risk for Caucasians with the Arg/Arg genotype and never smokers needs further investigation.

Background: Pivotal phase III data have shown the efficacy and safety of degarelix (240 mg starting dose/80 mg maintenance dose [240/80 mg]) in North American and European patients with prostate cancer (PCa). This open-label, multicenter, single-arm trial has evaluated the efficacy and safety of degarelix in Taiwanese patients with PCa.Methods: Eligible patients received degarelix 240/80 mg monthly for 6 months. The primary objective was the efficacy of degarelix in achieving and maintaining serum testosterone below castrate levels (≤0.5 ng/mL). Secondary objectives included changes in serum testosterone and PSA, and safety.Results: One hundred and ten patients were allocated to treatment. Over six months, degarelix maintained serum testosterone at castrate levels; from Days 28-168, the cumulative probability of sustained castrate level testosterone was 97.2% (95% CI: 91.6-99.1%), meeting the primary objective. Degarelix rapidly suppressed serum testosterone levels, with castrate levels achieved by Days 3 in 93.5% of patients. PSA decreased rapidly from baseline, with a median reduction of 92.4% by Day 28. Degarelix was well tolerated, with the most frequent adverse events (AEs) being mild to moderate injection site reactions (ISRs), occurring mostly with the initial dose of degarelix. There were no immediate-onset systemic hypersensitivity reactions observed.Conclusions: In Taiwanese patients with PCa, a monthly degarelix 240/80 mg/mL dose regimen rapidly decreased testosterone and PSA levels, and maintained testosterone at castrate levels (≤ 0.5 ng/ mL) over 6 months. The safety profile of degarelix was consistent with that expected for elderly men with PCa undergoing androgen deprivation therapy (ADT).

Solasodine, a naturally occurring aglycone of glycoalkaloid in eggplant (Solanum melongena), was found to inhibit proliferation in various tumor cells. However, the effect of solasodine on cancer cell metastasis remains unclear. This study investigates the suppression mechanism of solasodine on motility of human lung cancer cell A549 in vitro. Results show that solasodine reduces viability of A549 cells. Treatment with non-toxic doses of solasodine suppresses markedly cell invasion. Solasodine reduces the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9 and extracellular inducer of matrix metalloproteinase (EMMPRIN), but increases the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK), as well as tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Immunoblotting assays indicate that solasodine is effective in suppressing PI3K and Akt phosphorylation. Moreover, solasodine downregulates oncogenic microRNA-21 (miR-21), which has been known to target RECK. Downregulation of miR-21 by miR-21 inhibitor increases RECK expression and decreases cell invasion, suggesting that downregulation of miR-21 by solasodine may contribute to elevate RECK expression and subsequently inhibiting cell invasion. Taken together, the results reveal that inhibition of A549 cell invasion by solasodine may be, at least in part, through blocking MMP expression. Solasodine also reduces PI3K/Akt signaling pathways and downregulates expression of miR-21. These findings demonstrate an attractive therapeutic potential for solasodine in lung cancer anti-metastatic therapy.

Arsenic exposure and cigarette smoking are environmental risk factors for urothelial carcinoma (UC). Vascular endothelial growth factor (VEGF) is the key regulator of angiogenesis in various malignancies. This study investigates the joint effect of arsenic exposure, cigarette smoking, and VEGF polymorphisms on UC risk. This was a hospital-based case-control study consisting of 730 histopathologically confirmed UC cases, including 470 bladder cancers, 260 upper urinary tract UCs (UUTUCs), and 850 age-matched controls, recruited from September 1998 to December 2009. UC risk was estimated by odds ratios and 95% confidence intervals using unconditional logistic regression. Ever smokers with high arsenic exposure had significantly increased risks of 5.7 and 6.4 for bladder cancer and UUTUC, respectively. Moreover, ever smokers with high arsenic exposure carrying 1 or 2 risk genotypes of the VEGF gene had a significantly increased risk of 6.6 for bladder cancer and a strikingly higher risk of 9.9 for UUTUC. Additionally, UUTUC cases with high arsenic exposure carrying 1 or 2 risk genotypes of the VEGF gene had a non-significant increased risk of advanced tumor stage. Our findings suggest that arsenic exposure, cigarette smoking, and risk genotypes of VEGF contribute to a higher risk of UUTUC than of bladder cancer.

BackgroundUrothelial carcinoma (UC) is prevalent worldwide. Dysregulation of cell growth is a critical event of tumorigenesis and has not been assessed systemically in UC. We thus assessed the published transcriptome of urinary bladder urothelial carcinoma (UBUC) and identified insulin-like growth factor-binding protein-5 (IGFBP-5) as the most significantly upregulated gene associated with the regulation of cell growth. Moreover, validated by using public domain data set, IGFBP-5 expression also significantly predicted worse outcome. IGFBP-5 is one of the binding proteins that regulate insulin-like growth factors (IGFs) and its significance has not been comprehensively evaluated in UCs.MethodsUsing immunohistochemistry, we evaluated the IGFBP-5 expression status and its associations with clinicopathological features and survival in 340 cases of upper urinary tract urothelial carcinoma (UTUC) and 295 cases of UBUC. Western blot analysis was used to evaluate IGFBP-5 protein expression in human urothelial cell (HUC) lines.ResultsIGFBP-5 overexpression was significantly associated with advanced pT stage (pConclusionsIGFBP-5 plays an important role in tumour progression in UC. Its overexpression is associated with advanced tumour stage and conferred poorer clinical outcome.

To evaluate the associations between exposure to arsenic in drinking water and the progression of chronic kidney disease (CKD), we conducted a study in Taiwan. We recruited 8854 participants from a nationwide health screening program from 2000 to 2009 who were at least 20 years old and had two checkups in a 24-month period with at least 12 months apart. We defined CKD as having an estimated glomerular filtration rate (eGFR) 5ml/min/1.73m2/year. Arsenic levels were assessed on the basis of a governmental nationwide survey. Of the 8854 participants, 1341 exhibited rapid progression. Participants who lived in areas with arsenic levels≥50μg/L had a higher risk of rapid progression, with an odds ratio of 1.22 (95% confidence interval: 1.05-1.42, p

Human galectin-1 is a member of the galectin family, proteins with conserved carbohydrate-recognition domains that bind galactoside. Galectin-1 is highly expressed in various tumors and participates in various oncogenic processes. However, detailed descriptions of the function of galectin-1 in urinary bladder urothelial carcinoma have not been reported. Our previous cohort investigation showed that galectin-1 is associated with tumor invasiveness and is a possible independent prognostic marker of urinary bladder urothelial carcinoma. The present study aimed to clarify the relevance of galectin-1 expression level to tumor progression and invasion. In order to decipher a mechanism for the contribution of galectin-1 to the malignant behavior of urinary bladder urothelial carcinoma, two bladder cancer cell lines (T24 and J82) were established with knockdown of galectin-1 expression by shRNA. Bladder cancer cells with LGALS1 gene silencing showed reduced cell proliferation, lower invasive capability, and lower clonogenicity. Extensive signaling pathway studies indicated that galectin-1 participated in bladder cancer cell invasion by mediating the activity of MMP9 through the Ras-Rac1-MEKK4-JNK-AP1 signaling pathway. Our functional analyses of galectin-1 in urinary bladder urothelial carcinoma provided novel insights into the critical role of galectin-1 in tumor progression and invasion. These results revealed that silencing the galectin-1-mediated MAPK signaling pathway presented a novel strategy for bladder cancer therapy.

Vascular endothelial growth factor A (VEGF-A) is a key mediator in the neovascularization of cancers. We have found that VEGF-A was expressed at significantly higher levels in high-grade transitional cell carcinoma (TCC) cells than low-grade TCC cells in our previous study. In the present study, promoter methylation pattern was assessed and quantified by bisulfite genomic sequencing (BGS) and specific VEGF-A CpG sites in low-grade, but not in high-grade, TCC cells were observed. Reporter assays indicated that hypermethylation of nine CpG sites can inhibit the transcriptional activity of the VEGF-A gene. Subsequent chromatin immunoprecipitation (ChIP) assay revealed down-regulation of transcription activity of VEGF-A with increasing binding of methyl-CpG-binding protein 2 (MBD2) and trimethyl-histone H3 (Lys9) proteins to these CpG sites in low-grade TCC cells during hypermethylation. Furthermore, treatment of low-grade TCC cells with DNA methyltransferase inhibitor and histone deacetylase inhibitor can restore the expression of VEGF-A and promote the invasive ability of low-grade TCC cells. Hypermethylation with lower expression levels of VEGF-A in low-grade TCC tumors than high-grade TCC tumors was also confirmed in clinical specimens by reverse transcriptase-PCR and pyrosequencing analyses. Our findings are the first results indicating that VEGF-A expression is suppressed in low-grade TCC tumors by promoter hypermethylation. This offers a new perspective on the role of VEGF-A in TCC tumor behavior.

Objective Extraperitoneal laparoscopic radical prostatectomy (ELRP) has been established as a minimally invasive and viable alternative to the open procedure. Herein, we summarize the initial experience of single surgeon who performed 20 procedures for clinically localized prostate cancer. Materials and Methods Between February 2006 and June 2009, 20 patients underwent an ELRP. Demographic data, including age, preoperative prostate-specific antigen (PSA), prostate volume, Gleason score, and ASA score were collected. A five-trocar extraperitoneal technique was used. Surgical parameters, pathological staging, postoperative complications, hospital stay, continence state, and oncological control during follow-up were retrospectively reviewed. Results The mean age was 67.5 (54–81) years. Mean preoperative PSA was 24.6 ± 15.8 ng/mL and prostate volume was 47.8 ± 22.5 (17–92) mL. The mean operative time was 325 ± 58 (220–465) min. Mean blood loss was 450 ± 300 (250–3000) mL. The mean postoperative hospitalization was 10.4 ± 4.9 (5–25) days. The one major complication that occurred was deep-venous thrombosis, and venous filter implantation was applied. In addition, one had anastomosis disruption, and three had bladder neck contracture. All patients had transient stress urinary incontinence but almost 80% were continent 9 months later. Biochemical failure was noted in five patients, and they received adjuvant hormone or radiation therapy. All patients are alive except one who had pelvic lymph node involvement (N1) with bony metastasis; that patient died 34 months postoperatively. Conclusion A major benefit of ELRP compared to the transperitoneal approach is avoiding potential risks of intraperitoneal injury. In addition, it can also isolate urine leakage due to a negligent interrupted suture at anastomosis. From our 5-year short-term follow-up, it provides equal efficacy in tumor control as does a radical prostatectomy. We think that as experience accumulates, better postoperative oncological and functional outcomes are expected.