Increased risk of subsequent benign prostatic hyperplasia in non-Helicobacter pylori-infected peptic ulcer patients: a population-based cohort study.

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 < 0.05). Regarding surgery types, peptic ulcer patients who underwent simple suture surgery (i.e.: with integrated vagus nerve) had a significant higher BPH risk than comparison (HR 1.50 and 95% CI 1.33-1.74; SHR 1.26 and 95% CI 1.07-1.48), while patients underwent truncal vagotomy/pyloroplasty showed a lower incidence of BPH. In this study, non-HP-infected male peptic ulcer patients were found to have an increased risk of subsequent BPH. Indicating that there might be a role of vagus nerve. Based on the limitations of retrospective nature, further studies are required.

Manufacturing technology of banana-assorted breads: The fermentative characteristics affected by different banana cultivars.

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.

Sinomenine Inhibits Migration and Invasion of Human Lung Cancer Cell through Downregulating Expression of miR-21 and MMPs.

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-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.

Therapeutic benefit of second-look transurethral resection of bladder tumors for newly diagnosed T1 bladder cancer: a single-center experience.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Renal Damaging Effect Elicited by Bicalutamide Therapy Uncovered Multiple Action Mechanisms As Evidenced by the Cell Model.

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)-ß 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 ß, 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.

Proteomic Identification of the Galectin-1-Involved Molecular Pathways in Urinary Bladder Urothelial Carcinoma.

Among various heterogeneous types of bladder tumors, urothelial carcinoma is the most prevalent lesion. Some of the urinary bladder urothelial carcinomas (UBUCs) develop local recurrence and may cause distal invasion. Galectin-1 de-regulation significantly affects cell transformation, cell proliferation, angiogenesis, and cell invasiveness. In continuation of our previous investigation on the role of galectin-1 in UBUC tumorigenesis, in this study, proteomics strategies were implemented in order to find more galectin-1-associated signaling pathways. The results of this study showed that galectin-1 knockdown could induce 15 down-regulated proteins and two up-regulated proteins in T24 cells. These de-regulated proteins might participate in lipid/amino acid/energy metabolism, cytoskeleton, cell proliferation, cell-cell interaction, cell apoptosis, metastasis, and protein degradation. The aforementioned dys-regulated proteins were confirmed by western immunoblotting. Proteomics results were further translated to prognostic markers by analyses of biopsy samples. Results of cohort studies demonstrated that over-expressions of glutamine synthetase, alcohol dehydrogenase (NADP⁺), fatty acid binding protein 4, and toll interacting protein in clinical specimens were all significantly associated with galectin-1 up-regulation. Univariate analyses showed that de-regulations of glutamine synthetase and fatty acid binding protein 4 in clinical samples were respectively linked to disease-specific survival and metastasis-free survival.

Associations between arsenic in drinking water and occurrence of end-stage renal disease with modifications by comorbidities: A nationwide population-based study in Taiwan.

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≥40years 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≥50µg/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 protects LPS-induced sepsis and attenuates LPS-induced inflammatory response.

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.

Solasodine inhibits invasion of human lung cancer cell through downregulation of miR-21 and MMPs expression.

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.

Associations between arsenic in drinking water and the progression of chronic kidney disease: A nationwide study in Taiwan.

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)<90ml/min/1.73m2 or renal dysfunction demonstrated by proteinuria and a rapid progression of CKD as a decline in 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<0.01) after adjusting for hypertension, diabetes mellitus, proteinuria, and anemia. The results showed that a high arsenic level in drinking water was a risk factor for rapid progression of CKD, independent of most of the documented risk factors. Screening and intervention programs should be implemented in endemic areas of exposure to reduce the risk.

Role of galectin-1 in urinary bladder urothelial carcinoma cell invasion through the JNK pathway.

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.

Integrated Process for Production of Galangal Acetate, the "Wasabi-Like" Spicy Compound, and Analysis of Essential Oils of Rhizoma Alpinia officinarum (Hance) Farw.

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.

An Effective and Well Tolerated Strategy of Bladder Preservation Therapy in Cisplatin-Ineligible Patients With Muscle-Invasive Bladder Cancer.

UNLABELLED: 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. BACKGROUND: 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. PATIENTS AND METHODS: 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 status < 3 and age < 80 years. RESULTS: 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. CONCLUSION: 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.

Mesoporous Europium-Doped Titania Nanoparticles (Eu-MTNs) for Luminescence-Based Intracellular Bio-Imaging.

Monodisperse and mesoporous europium (Eu)-doped titania nanoparticles (denoted as Eu-MTNs) were prepared by a co-synthesis method with the presence of a cationic surfactant (i.e., CTAB). A maximum loading amount of 8 mol% of Eu could be successfully incorporated into the framework of MTNs. The synthesized Eu-MTNs samples were characterized with X-ray diffraction (XRD) and scanning electron microscopy (SEM), with their luminescent property examined by photoluminescence (PL). Under ultraviolet irradiation, the Eu-MTNs samples exhibit several characteristic luminescence corresponding to 5D0-7F(j) for Eu+3 ions, which can be attributed to the energy transfer from titania nanocrystallite to Eu3+ ions dispersed in amorphous mesoporous titania region. The potential intracellular bio-imaging application of the synthesized Eu-MTN nanoparticles was demonstrated with a breast cancer cell line (i.e., BT-20). High biocompatibility and strong luminescence of the Eu-MTNs show great potential in biomedical applications.

Benign prostatic hyperplasia complicated with T1DM can be alleviated by treadmill exercise-evidences revealed by the rat model.

BACKGROUND: Both benign prostatic hyperplasia (BPH) and Type-1 diabetes mellitus (T1DM) share similar epidemiologic features and are all associated with the insulin-like growth factor (IGF)-mediated hormonal imbalance. The purpose of this study is to understand whether exercise (EX) could alleviate DM and DM + BPH. METHODS: Sprague-Dawley rats were divided into eight groups: normal control, EX, BPH, BPH + EX, DM, DM + EX, BPH + DM, and BPH + DM + EX. T1DM was induced by intraperitoneal (ip) injection of streptozotocin (65 mg/kg) in Week 2, and BPH was induced by successive ip injections of Sustanon® (testosterone, 3.5 mg/head) plus estradiol (0.1 mg/head) from Week 3 to Week 9. Treadmill exercise training (20 m/min, 60 min per time) was performed three times per week for 6 weeks. RESULTS: In BPH + EX, EX maintained at a constant body weight (BW); and suppressed stromal layer thickening, collagen deposition, blood glucose (BG), levels of testosterone (Ts), 5α-reductase(5αRd), dihydrotestosterone (DHT), androgen receptor (AR), serum hydrogen peroxide, TBARs, and interleukin-6 (IL-6). EX recovered testes size and substantially increased nitric oxide (NO) levels. In DM + EX group, EX decreased BW, PW, nuclear proliferation, inflammatory cell aggregation, collagen deposition, and BG. As contrast, EX upregulated insulin, IGF, Ts, NO, 5αRd, AR, and DHT, and substantially reduced PSA. In BPH + DM + EX, EX maintained BW at a subnormal level, slightly suppressed prostate stromal inflammation, collagen deposition, and BG, moderately restored sIn and IGF. Although failed to suppress Ts, EX highly upregulated 5αRd and suppressed DHT and AR, together with highly upregulated NO resulting in substantially reduced PSA. CONCLUSION: EX, by remodeling androgen and NO expressions, can effectively alleviate BPH, DM, and BPH + DM.

Bacille Calmette-Guerin can induce cellular apoptosis of urothelial cancer directly through toll-like receptor 7 activation.

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.

Galectin-1 dysregulation independently predicts disease specific survival in bladder urothelial carcinoma.

PURPOSE: Galectin-1 is highly expressed in various tumors and participates in various oncogenic processes. Our previous proteomics investigation demonstrated that galectin-1 is up-regulated in high compared to nonhigh grade lesions. Thus, in the current cohort study we clarified the correlation of galectin-1 over expression with various clinicopathological features and prognosis. MATERIALS AND METHODS: We selected 185 cases of consecutively treated primary localized bladder urothelial carcinoma for study. Transurethral resection of bladder tumor was performed in all patients followed by radical cystectomy in those with T2 to T4 tumors. Pathological slides were examined to determine cytoplasmic galectin-1 immuno-expression and correlate galectin-1 dysregulation with various clinicopathological factors and disease specific survival. RESULTS: Positive galectin-1 immuno-expression in tumors was significantly linked to pT status (p = 0.0295), histological grade (p = 0.037), vascular invasion (p = 0.0287) and nodal status (p = 0.0012). Galectin-1 over expression in tumors significantly predicted disease specific survival at the univariate (p = 0.0002) and multivariate levels (p = 0.03, HR 2.438, 95% CI 1.090-5.451). In situ hybridization indicated that the LGALS1 gene was amplified in 43 specimens in an independent cohort of 56 snap frozen tumor specimens. Association analysis showed that an increased LGALS1 mRNA level was linked to bladder urothelial carcinoma invasiveness (p = 0.016) and LGALS1 gene amplification was significantly associated the amount of GAL-1 protein in tumors (p <0.0001). On the univariate level gene amplification was also closely linked to disease specific survival (p = 0.0006). CONCLUSIONS: These results reveal that galectin-1 over expression is a possible independent factor for bladder cancer prognosis.

α-Solanine inhibits invasion of human prostate cancer cell by suppressing epithelial-mesenchymal transition and MMPs expression.

α-Solanine, a naturally occurring steroidal glycoalkaloid found in nightshade (Solanum nigrum Linn.), was found to inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism involved in suppression of cancer cell metastasis by α-solanine remains unclear. This study investigates the suppression mechanism of α-solanine on motility of the human prostate cancer cell PC-3. Results show that α-solanine reduces the viability of PC-3 cells. When treated with non-toxic doses of α-solanine, cell invasion is markedly suppressed by α-solanine. α-Solanine also significantly elevates epithelial marker E-cadherin expression, while it concomitantly decreases mesenchymal marker vimentin expression, suggesting it suppresses epithelial-mesenchymal transition (EMT). α-Solanine 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), and tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Immunoblotting assays indicate α-solanine is effective in suppressing the phosphorylation of phosphatidylinositide-3 kinase (PI3K), Akt and ERK. Moreover, α-solanine downregulates oncogenic microRNA-21 (miR-21) and upregulates tumor suppressor miR-138 expression. Taken together, the results suggest that inhibition of PC-3 cell invasion by α-solanine may be, at least in part, through blocking EMT and MMPs expression. α-Solanine also reduces ERK and PI3K/Akt signaling pathways and regulates expression of miR-21 and miR-138. These findings suggest an attractive therapeutic potential of α-solanine for suppressing invasion of prostate cancer cell.

Association between the SULT1A1 Arg213His polymorphism and the risk of bladder cancer: a meta-analysis.

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.