Impacts of hyperthermic chemotherapeutic agent on cytotoxicity, chemoresistance-related proteins and PD-L1 expression in human gastric cancer cells.

Objective: Gastric cancer with peritoneal metastasis is considered to be final stage gastric cancer. One current treatment approach for this condition is combined cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the therapeutic mechanisms of HIPEC remain largely undescribed. Method: In order to assess the cellular effects of HIPEC in vitro, we treated AGS human gastric adenocarcinoma cells with or without 5-fluorouracil (5-Fu) at 37 °C or at 43 °C (hyperthermic temperature) for 1 h followed by incubation at 37 °C for 23 h. The impacts of hyperthermia/5-Fu on apoptosis, cell survival signals, oxidative stress, chemoresistance-related proteins and programmed death-ligand 1 (PD-L1) expression were measured. Results: Our results showed that hyperthermia potentiates 5-Fu-mediated cytotoxicity in AGS cells. Furthermore, the combination of 5-Fu and hyperthermia reduces levels of both phosphorylated STAT3 and STAT3, while increasing the levels of phosphorylated Akt and ERK. In addition, 5-Fu/hyperthermia enhances reactive oxygen species and suppresses superoxide dismutase 1. Chemoresistance-related proteins, such as multidrug resistance 1 and thymidylate synthase, are also suppressed by 5-Fu/hyperthermia. Interestingly, hyperthermia enhances 5-Fu-mediated induction of glycosylated PD-L1, but 5-Fu-mediated upregulation of PD-L1 surface expression is prevented by hyperthermia. Conclusion: Taken together, our findings provide insights that may aid in the development of novel therapeutic strategies and enhanced therapeutic efficacy of HIPEC.

Comparative study of Janus B2XY (X, Y = S, Se, Te) and F-BNBN-H monolayers for water splitting: revealing the positive and negative roles of the intrinsic dipole.

It is widely recognized that the intrinsic dipole in two-dimensional (2D) photocatalysts promotes hydrogen production during water splitting. Herein, we wonder whether the intrinsic dipole plays a negative role in water splitting. In this work, we make a comparative study of the structural, electronic, and photocatalytic properties of Janus B2XY (X, Y = S, Se, Te) and F-BNBN-H monolayers using first principles. Our theoretical results reveal that both B2XY and F-BNBN-H monolayers exhibit spatially separated conduction band minimum (CBM) and valence band maximum (VBM), as well as vacuum level differences at the opposite surfaces due to the intrinsic dipole. The F-BNBN-H monolayer has excellent redox ability for water splitting, because its CBM is located at the surface with a lower vacuum level and its VBM is distributed on the opposite surface possessing a higher vacuum level. By sharp contrast, B2XY monolayers have limited or vanishing redox ability, because their CBM is located at the surface with a higher vacuum level and their VBM is distributed on the opposite surface with a lower vacuum level. This work emphasizes the negative role of vacuum level differences of photocatalysts caused by the intrinsic dipole in water splitting.

Anti-Inflammatory Mechanism of An Alkaloid Rutaecarpine in LTA-Stimulated RAW 264.7 Cells: Pivotal Role on NF-κB and ERK/p38 Signaling Molecules.

Lipoteichoic acid (LTA) is a key cell wall component and virulence factor of Gram-positive bacteria. LTA contributes a major role in infection and it mediates inflammatory responses in the host. Rutaecarpine, an indolopyridoquinazolinone alkaloid isolated from Evodia rutaecarpa, has shown a variety of fascinating biological properties such as anti-thrombotic, anticancer, anti-obesity and thermoregulatory, vasorelaxing activity. It has also potent effects on the cardiovascular and endocrine systems. Herein, we investigated rutaecarpine's (Rut) anti-inflammatory effects in LTA-stimulated RAW macrophage cells. The Western blot and spectrophotometric results revealed that Rut inhibited the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and interleukin (IL)-1ß in the LTA-induced macrophage cells. Successively, our mechanistic studies publicized that Rut inhibited LTA-induced phosphorylation of mitogen-activated protein kinase (MAPK) including the extracellular signal-regulated kinase (ERK), and p38, but not c-Jun NH2-terminal kinase (JNK). In addition, the respective Western blot and confocal image analyses exhibited that Rut reserved nuclear transcription factor kappa-B (NF-κB) by hindering inhibitor of nuclear factor κB-α (IκBα) and NF-κB p65 phosphorylation and p65 nuclear translocation. These results indicate that Rut exhibits its anti-inflammatory effects mainly through attenuating NF-κB and ERK/p38 signaling pathways. Overall, this result suggests that Rut could be a potential therapeutic agent for the treatment of Gram-positive bacteria induced inflammatory diseases.

Chromium-Modified Ultrathin CoFe LDH as High-Efficiency Electrode for Hydrogen Evolution Reaction.

Hydrogen evolution reaction (HER) has a dominant function in energy conversion and storage because it supplies a most effective way for converting electricity into sustainable high-purity hydrogen. Layered double hydroxides (LDHs) have shown promising performance in the process of electrochemical water oxidation (a half-reaction for water splitting). Nevertheless, HER properties have not been well released due to the structural characteristics of related materials. Herein, a simple and scalable tactics is developed to synthesize chromium-doped CoFe LDH (CoFeCr LDH). Thanks to oxygen vacancy, optimized electronic structure and interconnected array hierarchical structure, our developed ternary CoFeCr-based layered double hydroxide catalysts can provide 10 mA cm-2 current density at -0.201 V vs. RHE with superior long-term stability in alkaline electrolyte. We anticipate that the simple but feasible polymetallic electronic modulation strategy can strengthen the electrocatalytic property of the layered double hydroxides established in the present study, based on a carbon neutral and hydrogen economy.

A comparison of test-retest reliability and random measurement error of the Barthel Index and modified Barthel Index in patients with chronic stroke.

OBJECTIVE: To compare the test-retest reliability and random measurement errors of the Barthel Index (BI) and modified Barthel Index (MBI) in patients with chronic stroke. METHOD: The intraclass correlation coefficient (ICC) and the minimal detectable change (MDC) were applied respectively to examine the test-retest reliability (about 2 weeks apart) and the random measurement errors. The MDC% was used to adjust the cut-off score for determining whether a real change had been achieved, if heteroscedasticity existed. RESULTS: A total of 60 patients participated. The BI and MBI both had high ICCs (0.94 and 0.94, respectively) with small MDCs (16.2 and 15.4, respectively) and MDC%s (21.2% and 19.0%, respectively), indicating that both measures have comparable reliability in repeated assessments. However, moderate associations (r = -0.47 for the BI and -0.59 for the MBI) were found between the means of tests and retests and the absolute values of change scores, indicating heteroscedasticity. These findings suggest that a fixed MDC value is not appropriate for determining the real change in both measures because the amount of random measurement error varies with the patients' ADL function. CONCLUSION: The MBI, which showed excellent test-retest reliability and relatively lower random measurement error than the BI, appears to be a better ADL measure. The MDC% adjusted value is recommended to determine whether the change scores are beyond random measurement error.IMPLICATIONS FOR REHABILITATIONThe MBI is recommended for clinical and research applications because it has better test-retest reliability and relatively lower random measurement error than those of the original BI.The MDC% adjusted value is recommended to determine whether the change scores are beyond random measurement error when the MBI or the BI is used.

Hierarchical iron molybdate nanostructure array for efficient water oxidation through optimizing electron density.

The water oxidation reaction plays a major role in many alternative-energy systems because it provides the electrons and protons required for the use of renewable electricity. We report the tuning of the iron molybdate (FeMoO4) electron structure via a coupled interface between the catalytic centers and the substrate. Our developed FeMoO4 catalysts can provide a 50 mA cm-2 current density at 1.506 V vs. RHE with excellent stability in 1.0 M KOH. The improved performance can be ascribed to the synergy of the optimized electronic structures and hierarchical nanostructure.

Ultrafast formation of an FeOOH electrocatalyst on Ni for efficient alkaline water and urea oxidation.

We report FeOOH supported on Ni foam which enables highly efficient UOR electrocatalysis and can be readily produced through a hydrolysis reaction. Our developed UOR catalyst as the anode can provide a current density of 200 mA cm-2 at 1.427 V vs. RHE, as well as remarkable operational stability, representing the best yet reported noble metal-free urea electrolyser.

Relative D3 vitamin deficiency and consequent cognitive impairment in an animal model of Alzheimer's disease: Potential involvement of collapsin response mediator protein-2.

Alzheimer's disease (AD) starts with memory impairments that can be observed before the appearance of significant neuropathology; thus, identifying mechanisms to stop AD progression is an urgent priority. Epidemiological and clinical data show that the consequences of vitamin D deficiency are relevant to disease risk and can be observed in the progression of many diseases, especially AD, whereas higher serum levels of vitamin D are associated with better cognitive test performance. However, the potential therapeutic strategy and underlying mechanisms of vitamin D supplementation against AD still need to be further investigated. In the present study, we found that 3xTg-AD mice with vitamin D supplementation exhibited an increase in serum vitamin D concentrations and improved cognition. We measured serum vitamin D binding protein (VDBP) concentrations and found that serum VDBP levels were increased in 3xTg-AD mice compared to B6129S control mice, but there was no significant difference between control- and vitamin D-treated 3xTg-AD groups. The vitamin D-mediated memory improvement may be accompanied by the suppression of increased hippocampal collapsin response mediator protein-2 (CRMP2) phosphorylation, and the restoration of CRMP2 phosphorylation by okadaic acid (OA) could abolish the beneficial effects of vitamin D. In addition, we found that CRMP2 was associated with NR2B and PSD-95 in 3xTg-AD mice with vitamin D supplementation. This CRMP2-NR2B interaction could be disrupted by a TAT-CBD3 peptide or OA, leading to attenuated memory protection in vitamin D-treated 3xTg-AD mice. Therefore, CRMP2 may be involved in vitamin D-mediated memory improvement in AD.

[Solitary Fibrous Tumours/Hemangiopericytomas of the Maters(Meninx):A Clinicopathologic Analysis].

To study the clinicopathologic characteristics,immunohistochemical features,differential diagnosis,and prognosis of solitary fibrous tumours(SFT)/hemangiopericytomas(HPC)in the maters(meninx). Methods A series of 7 cases previously diagnosed as SFT/HPC at the Department of Pathology,Peking Union Medical College Hospital,during the period from 2008 to 2018 were analyzed for clinical data,histopathology,and immunohistochemical findings.The patients were followed up and the relevant literatures were reviewed. Results These seven patients included two males and 5 females aged 22 to 77 years(mean,49 years).Headache was the most common symptom.The magnetic resonance imaging of SFT/HPC showed irregularly contoured masses and dural tail sign was observed at the periphery of the lesion in 4 cases.The major axis of the tumor ranged from 1.8 cm to 10 cm(mean,4 cm).The tumors were located in the mater in 6 cases and in the spinal meninx in 1 case.The tumors were surgically removed in all cases.Under light microscope,the tumors were formed by long round,oval or spindle cells,with rich branching vascular pattern and varying quantity of collagenous fibers bands in both sparse areas and dense areas.According the WHO classification,2 cases were in WHO grade Ⅰ,2 cases in WHO grade Ⅱ,and 3 cases in WHO grade Ⅲ.Immunohistochemistry of the paraffin-embedded tissues in all cases showed positive immunoreativity for CD34 and vimentin in all seven cases,along with positive signal transducer and activator of transcription 6 in 4 cases,negative epithelial membrane antigen and S-100 in 7 cases,and negative progestational hormone and somatostatin receptor 2 in 6 cases.The Ki-67 index ranged from 1% to 15%.Five patients with follow-up data(including 1 current case)were alive,while 2 patients were lost to follow-up. Conclusions The SFT/HPC are rare in the maters(meninx)and is clinically difficult to be differentiated from other meningioma.The combination of CD34 and signal transducer and activator of transcription 6 helps to diagnose this disease.

Leukoaraiosis and risk of intracranial hemorrhage and outcome after stroke thrombolysis.

BACKGROUND: The impact of leukoaraiosis on the risk of symptomatic intracerebral hemorrhage (SICH) after stroke thrombolysis is conflicting, and the data on Asian populations are lacking. Therefore, in this study, we assessed the association between leukoaraiosis and SICH, and the association between leukoaraiosis and the 90-day functional outcome in the Asian population. METHODS: Data were collected from a two-center prospective registry of acute ischemic stroke patients given intravenous tissue plasminogen activator between 2006 and 2014. A total of 614 pretreatment brain CT and 455 posttreatment MRI were retrospectively assessed using two different rating scales for the presence of leukoaraiosis. Outcome measures were the occurrence of SICH with three definitions and any hemorrhage after thrombolysis and functional outcome at 3 months. RESULTS: Of the 614 patients assessed, 30.3% showed severe leukoaraiosis on the baseline brain CT. The SICH rate was 4.6% - 7.2% based on different definitions, and overall, 24.9% of patients showed any post-tPA hemorrhage. No association was observed between the severity of leukoaraiosis and SICH, regardless of having used different leukoaraiosis rating scales or as assessment using different imaging modalities. However, severe leukoaraiosis was independently associated with poor functional outcome at 3 months (OR 1.96, 95% C1 1.24-3.11, P = 0.004) after adjustment for confounders. CONCLUSIONS: Our results showed no association between leukoaraiosis and the risk of SICH. Although the presence of severe leukoaraiosis predicted a poor functional outcome after stroke, IV thrombolysis might not be withheld in acute ischemic stroke patients solely based on the presence of severe leukoaraiosis on pre-thrombolytic CT scans.

Ror2, a Developmentally Regulated Kinase, Is Associated With Tumor Growth, Apoptosis, Migration, and Invasion in Renal Cell Carcinoma.

Renal cell carcinoma (RCC) represents one of the most resistant tumors to radiation and chemotherapy. Current therapies for RCC patients are inefficient due to the lack of diagnostic and therapeutic markers. The expression of novel tumor-associated kinases has the potential to dramatically shape tumor cell behavior. Identifying tumor-associated kinases can lend insight into patterns of tumor growth and characteristics. In the present study, we investigated the receptor tyrosine kinase-like orphan receptor 2 (Ror2), a new tumor-associated kinase, in RCC primary tumors and cell lines. Knockdown of Ror2 expression in RCC cells with specific shRNA significantly reduced cell proliferation and induced apoptosis. Using in vitro migration and Matrigel invasion assays, we found that cell migration and invasive ability were also significantly inhibited. In RCC, Ror2 expression correlated with expression of genes involved at the cell cycle and migration, including PCNA, CDK1, TWIST, and MMP-2. Furthermore, in vivo xenograft studies in nude mice revealed that administration of a Ror2 shRNA plasmid significantly inhibited tumor growth. These findings suggest a novel pathway of tumor-promoting activity by Ror2 within renal carcinomas, with significant implications for unraveling the tumorigenesis of RCC.

ß-Catenin promotes cell proliferation, migration, and invasion but induces apoptosis in renal cell carcinoma.

ß-Catenin (CTNNB1 gene coding protein) is a component of the Wnt signaling pathway that has been shown to play an important role in the formation of certain cancers. Abnormal accumulation of CTNNB1 contributes to most cancers. This research studied the involvement of ß-catenin in renal cell carcinoma (RCC) cell proliferation, apoptosis, migration, and invasion. Proliferation, cell cycle, and apoptosis were analyzed by using Cell Counting Kit-8 and by flow cytometry. Migration and invasion assays were measured by transwell analysis. Real-time polymerase chain reaction and Western blot analysis were used to detect the expression of CTNNB1, ICAM-1, VCAM-1, CXCR4, and CCL18 in RCC cell lines. It was found that CTNNB1 knockdown inhibited cell proliferation, migration, and invasion and induced apoptosis of A-498 cells. CTNNB1 overexpression promoted cell proliferation, migration, and invasion and inhibited apoptosis of 786-O cells. Moreover, knockdown of CTNNB1 decreased the levels of ICAM-1, VCAM-1, CXCR4, and CCL18 expression, but CTNNB1 overexpression increased the expression of ICAM-1, VCAM-1, CXCR4, and CCL18. Further in vivo tumor formation study in nude mice indicated that inhibition of CTNNB1 delayed the progress of tumor formation through inhibiting PCNA and Ki67 expression. These results indicate that CTNNB1 could act as an oncogene and may serve as a promising therapeutic strategy for RCC.

Increased Risk of Parkinson's Disease in Patients With Obstructive Sleep Apnea: A Population-Based, Propensity Score-Matched, Longitudinal Follow-Up Study.

Obstructive sleep apnea (OSA), characterized by repetitive episodes of apnea/hypopnea and hypoxia, is associated with systemic inflammation and induces metabolic, endocrine, and cardiovascular diseases. Inflammation might have an impact on neurodegenerative diseases. This study investigates the possible association between OSA and Parkinson's disease (PD). Random samples out of 1 million individuals were collected from Taiwan's National Health Insurance database. A total of 16,730 patients with newly diagnosed OSA from 2002 to 2008 were recruited and compared with a cohort of 16,730 patients without OSA matched for age, gender, and comorbidities using propensity scoring. All patients were tracked until a diagnosis of PD, death, or the end of 2011.During the mean 5.6-year follow-up period, the incidence rates of PD were 2.30 per 1000 person-years in the OSA cohort and 1.71per 1000 person-years in the comparison group. The incidence rate ratio (IRR) for PD was greater in older patients (≧ 65 years) and male patients with OSA than the controls, respective IRRs being 1.34 and 1.47. After adjustment for the comorbidities, patients with OSA were 1.37 times more likely to have PD than patients without (95% CI = 1.12-1.68, P < 0.05). Subgroup analysis showed that older patients and patients with coronary artery disease, stroke, or chronic kidney disease had a higher risk for PD than their counter parts. Log-rank analysis revealed that patients with OSA had significantly higher cumulative incidence rates of PD than the comparison group (P = 0.0048). Patients with OSA are at an increased risk for subsequent PD, especially elderly male patients.

[Study on the Crystal Structure of Cellulose in Bamboo with Synchrotron Radiation Wide Angle X-Ray Scattering].

The crystal structure of cellulose will directly affect the properties of bamboo fiber -reinforced composite, but the unit cell of native cellulose in bamboo has never been investigated. The most accepted model for the structure of native cellulose is Meyer-Misch model which provides a reference to understand the unit cell of native cellulose in bamboo. The native cellulose consists of two different crystal structures (Ⅰ(α) and Ⅰ(ß)) which exist in different plants with different proportions. Because of this situation, the crystal structure of bamboo cellulose should have a unique model. The moso bamboo (Phyllostachys edulis (Carr. ) H. de Lehaie)was selected. The crystal structure of cellulose of bamboo was investigated with two dimensional synchrotron radiation wide angle X-ray scattering (SR-WAXS). The values of the interplanar spacings of each peak were obtained from SR-WAXS patterns, and then crystal structure parameters were calculated according to monoclinic crystal system. The results show that the fibre axis of a bamboo cellulose unit cell with a monoclinic unit cell of a=8.35 Å, b (fiber axis)=10.38 Å, c=8.02 Å, ß=84.99°. This model has a two antiparallel arrangement for the chains in unit cell, with four glucose residues. Thus, the model may be used to provide a theoretical basis for high value-added bamboo fiber -reinforced composite.

Increased Risk of Dementia in Patients With Erectile Dysfunction: A Population-Based, Propensity Score-Matched, Longitudinal Follow-Up Study.

Erectile dysfunction (ED) is a well-known predictor for future cardiovascular and cerebrovascular disease. However, the relationship between ED and dementia has rarely been examined. This study investigates the longitudinal risk for Alzheimer's disease and non-Alzheimer dementia in patients with ED. We collected a random sample of 1,000,000 individuals from Taiwan's National Health Insurance database. From this sample, we identified 4153 patients with newly diagnosed ED between 2000 and 2009 and compared them with a matched cohort of 20,765 patients without ED. All patients were tracked for 7 years from the index date to identify which of them subsequently developed dementia. During the 7-year follow-up period, the incidence rate of dementia in the ED cohort was 35.33 per 10,000 person-years. In the comparison groups, it was 21.67 per 10,000 person-years. After adjustment for patients characteristics and comorbidities, patients with ED were 1.68-times more likely to develop dementia than patients without ED (95% CI = 1.34-2.10, P < 0.0001). In addition, older patients and those with diabetes, hypertension, chronic kidney disease, stroke, depression, and anxiety were found to be at increased risk for dementia. Analyzing the data by dementia type, we found the hazard risk for Alzheimer's disease and non-Alzheimer dementia to be greater in patients with ED (adjusted HR 1.68, 95% CI = 1.31-2.16, P < 0.0001 and 1.63, 95% CI = 1.02-2.62, P = 0.0429, respectively). Log-rank test revealed that patients with ED had significantly higher cumulative incidence rates of dementia than those without (P < 0.0001). Patients with ED are at an increased risk for dementia later in life.

Development of a computerized Digit Vigilance Test and validation in patients with stroke.

OBJECTIVES: To develop a computerized Digit Vigilance Test (C-DVT) with lower random measurement error than that of the DVT and to examine the concurrent validity, ecological validity, and test-retest reliability of the C-DVT in patients with stroke. DESIGN: A cross-sectional study. PATIENTS: Forty-four patients with stroke. METHODS: We developed and tested the C-DVT. To examine the psychometric properties, the participants completed both the C-DVT and DVT twice with a 14-day interval. RESULTS: We developed the C-DVT on the basis of expert input and examinee feedback. C-DVT scores were highly correlated with DVT scores (ρ = 0.75), supporting the concurrent validity. The C-DVT scores were moderately correlated with the scores of the Barthel Index and the Activities of Daily Living Computerized Adaptive Testing system (ρ = -0.60~-0.57), supporting the ecological validity. The test-retest agreement of the C-DVT was excellent (intra-class correlation coefficient = 0.92). The random measurement error of the C-DVT (minimal detectable change percent change (MDC%) = 15.4%) was acceptable and lower than that of the DVT (33.0%). The practice effects of the C-DVT were statistically significant, but the effect size d was small (0.15). CONCLUSION: A C-DVT with a limited amount of random measurement error was developed. These preliminary findings show that the C-DVT demonstrates satisfactory concurrent validity, ecological validity, and test-retest reliability in patients with stroke.

Heat-shock protein 70 as a tumor antigen for in vitro dendritic cell pulsing in renal cell carcinoma cases.

Immunological functions of heat shock proteins (HSPs) have long been recognized. In this study we aimed to efficiently purify HSP70 from renal cell carcinoma and test it as a tumor antigen for pulsing dendritic cells in vitro. HSP70 was purified from renal cell carcinoma specimens by serial column chromatography on Con A-sepharose, PD-10, ADP-agarose and DEAE-cellulose, and finally subjected to fast protein liquid chromatography (FPLC). Dendritic cells derived from the adherent fraction of peripheral blood mononuclear cells were cultured in the presence of IL-4 and GM-CSF and exposed to tumor HSP70. After 24 hours, dendritic cells were phenotypically characterized by flow cytometry. T cells obtained from the non-adherent fraction of peripheral blood mononuclear cells were then co-cultured with HSP70-pulsed dendritic cells and after 3 days T cell cytotoxicity towards primary cultured renal cell carcinoma cells was examined by Cell Counting Kit-8 assay. Dendritic cells pulsed in vitro with tumor-derived HSP70 expressed higher levels of CD83, CD80, CD86 and HLA-DR maturation markers than those pulsed with tumor cell lysate and comparable to that of dendritic cells pulsed with tumor cell lysate plus TNF-α. Concomitantly, cytotoxic T-lymphocytes induced by HSP70-pulsed dendritic cells presented the highest cytotoxic activity. There were no significant differences when using homologous or autologous HSP70 as the tumor antigen. HSP70 can be efficiently purified by chromatography and induces in vitro dendritic cell maturation in the absence of TNF-α. Conspecific HSP70 may effectively be used as a tumor antigen to pulse dendritic cells in vitro.

Relationships between CYP1A1 genetic polymorphisms and bladder cancer risk: a meta-analysis.

This meta-analysis aims at evaluating the relationships between CYP1A1 genetic polymorphisms and bladder cancer risk. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched from inception through November 1st, 2013 without language restrictions. Meta-analysis was conducted with the use of the STATA 12.0 software. The relationships were evaluated by calculating the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). Eight case-control studies with a total of 2120 bladder cancer patients and 2061 healthy subjects met the inclusion criteria. Ten common polymorphisms in the CYP1A1 gene were assessed. The results of our meta-analysis suggested that CYP1A1 genetic polymorphisms might be strongly correlated with an increased risk of bladder cancer (allele model: OR=1.23, 95%CI=1.08-1.39, p=0.001; dominant model: OR=1.25, 95%CI=1.07-1.46, p=0.005; respectively), especially for 11599G>C, 2455A>G, 3810T>C, and 113T>C polymorphisms. A subgroup analysis was done to investigate the effect of ethnicity on an individual's risk of bladder cancer. Our results revealed positive significant correlations between CYP1A1 genetic polymorphisms and an increased risk of bladder cancer among Asians (allele model: OR=1.33, 95%CI=1.08-1.65, p=0.009; dominant model: OR=1.37, 95%CI=1.02-1.85, p=0.034; respectively), but not among Caucasians (all p<0.05). Our findings provide convincing evidence that CYP1A1 genetic polymorphisms may contribute to susceptibility to bladder cancer, especially for 11599G>C, 2455A>G, 3810T>C, and 113T>C polymorphisms among Asians.

Role of CDH1 promoter polymorphism and DNA methylation in bladder carcinogenesis: a meta-analysis.

Increasing scientific evidences suggest that CDH1 gene promoter polymorphism and DNA methylation may contribute to the development and progression of bladder cancer, but many existing studies have yielded inconclusive results. This meta-analysis aims to assess the role of CDH1 gene promoter polymorphism and methylation in bladder carcinogenesis. An extensive literature search for relevant studies was conducted in PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through April 1, 2013. This meta-analysis was performed using the STATA 12.0 software. The crude odds ratio with 95% confidence interval was calculated. Fifteen studies were included in this meta-analysis with a total of 824 bladder cancer patients and 818 healthy controls being assessed. Our meta-analysis revealed that the A variant of CDH1 -160C/A polymorphism was associated with an increased risk of bladder cancer. Further analysis by pathological subtype indicated that patients with invasive carcinoma had a higher frequency of CDH1 -160A variant than those with superficial carcinoma. We analyzed the methylation frequency of CDH1 gene in 608 bladder cancer samples and 338 normal bladder samples. Our data strongly suggest that the CDH1 promoter methylation frequencies in bladder cancer tissues were greater than those in normal control tissues. In conclusion, our meta-analysis indicates that promoter polymorphism and methylation of CDH1 gene may be involved in the development and progression of bladder cancer. CDH1 gene promoter polymorphism and methylation might be promising biomarkers for the diagnosis and prognosis of bladder cancer.