Effect of passive smoking exposure on risk of type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies.

Objective: The effect of passive smoking exposure on the risk of type 2 diabetes has not been systematically studied. A meta-analysis was conducted to assess the association between passive smoking exposure and the risk of diabetes. Methods: We searched three major databases up to 31 October 2022 to identify relevant prospective cohort studies on the association between passive smoking and the risk of type 2 diabetes. The pooled relative risk (RR) and 95% confidence interval (CI) for the association between passive smoking exposure and the risk of type 2 diabetes were analyzed using a fixed-effect model. Results: Ten prospective cohort studies were included in this meta-analysis, with a total of 251,620 participants involved. The pooled RR showed a significantly positive association between nonsmokers exposed to passive smoking and type 2 diabetes as compared to non-smokers who were not exposed to passive smoking [RR = 1.27; 95% CI (1.19, 1.36); p < 0.001]. Sensitivity analysis indicated that the pooled RR was not substantially affected by any of the individual studies. Conclusion: Exposure to passive smoking increases the risk of type 2 diabetes. This study may have a positive effect on the prevention of type 2 diabetes. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023372532.

Inhibition of Human Sulfotransferases by Phthalate Monoesters.

Objective: This study aimed to investigate the inhibition of human important phase II metabolic enzyme sulfotransferases (SULTs) by phthalate monoesters, which are important metabolites of phthalate esters (PAEs). Method: Recombinant SULT-catalyzed metabolism of p-nitrophenol (PNP) was employed as the probe reactions of SULTs to investigate the inhibition of 8 kinds of phthalate monoesters towards SULT isoforms. An in vitro incubation system was utilized for preliminary screening, and 100 µM of phthalate monoesters was used. Inhibition kinetics were carried out to determine the inhibition of SULTs by phthalate monoesters. Result: Multiple phthalate monoesters have been demonstrated to exert strong inhibition potential towards SULT1A1, SULT1B1, and SULT1E1, and no significant inhibition of phthalate monoesters towards SULT1A3 was found. The activity of SULT1A1 was strongly inhibited by mono-hexyl phthalate (MHP), mono-octyl phthalate (MOP), mono-benzyl phthalate (MBZP), and mono-ethylhexyl phthalate (MEHP). Monobutyl phthalate (MBP), MHP, MOP, mono-cyclohexyl phthalate (MCHP), and MEHP significantly inhibited the activity of SULT1B1. MHP, MOP, and MEHP significantly inhibited the activity of SULT1E1. MOP was chosen as the representative phthalate monoester to determine the inhibition kinetic parameters (Ki) towards SULT1B1 and SULT1E1. The inhibition kinetic parameters (Ki) were calculated to be 2.23 µM for MOP-SULT1B1 and 5.54 µM for MOP-SULT1E1. In silico docking method was utilized to understand the inhibition mechanism of SULT1B1 by phthalate monoesters. Conclusions: All these information will be beneficial for understanding the risk of phthalate monoester exposure from a new perspective.

Short chain fatty acids for the risk of diabetic nephropathy in type 2 diabetes patients.

AIMS: This study aimed to explore relationships short chain fatty acids with diabetic nephropathy (DN) in type 2 diabetes (T2D) patients. METHODS: We extracted the clinical and omics data of 100 T2D patients and 100 DN patients from April 2018 to April 2019 from a tertiary hospital. Restricted cubic splines were used to examine full-range associations of short chain fatty acids with DN in T2D.Query Logistic regression was used to obtain odds ratio (OR) and confidence interval (CI). RESULTS: Acetate, butyrate and isovalerate were negatively correlated with DN. Isobutyrate was positively correlated with DN. Propionate ≥ 4.4 µg/mL and isobutyrate ≥ 1.4 µg/mL had threshold effects and their increasing levels above the cutoff points were associated with rapid rises in the risk of DN. The additive interaction between high propionate and high isobutyrate in serum significantly increased the risk of DN (OR34.35; 95%CI 7.11 to 166.08). Presence of hypertension further increased the OR of high propionate for DN to 8.27(95%CI 1.82 to 37.57) with a significant additive interaction. The additive interaction of the high isobutyrate and hypertension was not significant. CONCLUSIONS: Acetate, butyrate and isovalerate were negatively associated with DN. Isobutyrate was positively associated with DN. Serum high propionate and high isobutyrate worked independently and synergistically to increase the risk of DN in T2D. Presence of hypertension further amplified the effect of copresence of high propionate on DN risk.

Inhibition of hydroxylated polychlorinated biphenyls (OH-PCBs) on sulfotransferases (SULTs).

Polychlorinated biphenyls (PCBs) have been demonstrated as a kind of the persistent organic pollutants (POPs) that could exert complicated influences towards metabolism in human bodies. Since hydroxylated polychlorinated biphenyls (OH-PCBs) are important metabolites of PCBs, our study focuses on investigating the potential inhibitory capability of OH-PCBs on four human sulfotransferase (SULT) isoforms. P-nitrophenol (PNP) was utilized as nonselective probe substrate for this study, and recombinant SULT isoforms were utilized as the enzyme resources. Ultra-performance liquid chromatography (UPLC)-UV detecting system was used to analyze PNP and its metabolite PNP-sulfate. As result, 100 µM of most tested OH-PCBs significantly inhibited the activity of four SULT isoforms. Concentration-dependent inhibition of OH-PCBs towards SULTs was found, and half inhibition concentration values (IC50) of some inhibition processes were determined. Inhibition kinetics (inhibition kinetic type and parameters) were determined using 4'-OH-PCB106 as the representative OH-PCB, SULT1B1 and SULT1E1 as representative SULT isoforms. The inhibition kinetic parameters (Ki) were 1.73 µM and 1.81 µM for the inhibition of 4'-OH-PCB106 towards SULT1B1 and SULT1E1, respectively. In silico docking simulation was utilized to analyze the inhibition capability of 2'-OH-PCB5, 4'-OH-PCB9, 2'-OH-PCB12 towards SULT1A3.All these results obtained in this study are helpful for further understanding the toxicity of PCBs.

Hydroxylated polychlorinated biphenyls (OH-PCBs) exert strong inhibitory effects towards human carboxylesterases (CESs).

Polychlorinated biphenyls (PCBs) have been reported to pose a severe risk towards human health, and hydroxylated polychlorinated biphenyls (OH-PCBs) were potential substances basis for PCBs' toxicity. This study aims to determine the inhibition of OH-PCBs towards human carboxylesterases (CESs), including CES1 and CES2. For phenotypic analysis of CES1 and CES2 activity, we used the hydrolysis metabolism of 2-(2-benzoyl3-methoxyphenyl) benzothiazole (BMBT) and fluorescein diacetate (FD) catalyzed by human liver microsomes (HLMs) as the probe reactions. Preliminary inhibition screening showed that the inhibition potential of OH-PCBs towards CES1 and CES2 increased with the increased numbers of chlorine atoms in OH-PCBs. Both 2'-OH-PCB61 and 2'-OH-PCB65 showed concentration-dependent inhibition towards both CES1 and CES2. Lineweaver-Burk plots showed that 2'-OH-PCB61 and 2'-OH-PCB65 exerted non-competitive inhibition towards CES1 and competitive inhibition towards CES2. The inhibition kinetics parameters (Ki) were 6.8 µM and 7.0 µM for 2'-OH-PCB61 and 2'-OH-PCB65 towards CES1, respectively. The inhibition kinetics parameters (Ki) were 1.4 µM and 1.0 µM for 2'-OH-PCB61 and 2'-OH-PCB65 towards CES2, respectively. In silico docking methods elucidate the contribution of hydrogen bonds and hydrophobic contacts towards the binding of 2'-OH-PCB61 and 2'-OH-PCB65 with CES1 and CES2. All these results will provide a new perspective for elucidation of toxicity mechanism of PCBs and OH-PCBs.

Inhibition of UDP-glucuronosyltransferases (UGTs) by polycyclic aromatic hydrocarbons (PAHs) and hydroxy-PAHs (OH-PAHs).

Polycyclic aromatic hydrocarbons (PAHs) are known as one of the ubiquitous environmental pollutants caused by unavoidable combustion of by-products. Despite decades of research on adverse health effects towards humans, the effects of PAHs and their hydroxylated metabolites (OH-PAHs) on UDP-glucuronosyltransferases (UGTs) remain unclear. This study aimed to investigate inhibitory effects with structure-dependence of 14 PAHs and OH-PAHs towards the activity of 7 isoforms of UGTs using in vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) as the probe reaction. PAHs and OH-PAHs showed inhibitory effects towards different UGT isoforms with different extents. For inhibition kinetics determination, 1-HONAP, 4-HOPHE, 9-HOPHE, and 1-HOPYR were utilized as the representative compounds, and UGT1A6, UGT1A9 and UGT2B7 were chosen as the three representative UGT isoforms. The inhibitory effects of 4-HOPHE, 9-HOPHE and 1-HOPYR on three above UGT isoforms were the same: UGT1A9>UGT1A6>UGT2B; for 1-HONAP, that is UGT1A6>UGT1A9>UGT2B. Molecular docking methods were utilized to find the activity cavity of UGT1A9 and UGT2B7 binding with 1-HONAP and 1-HOPYR. Hydrogen bonds and hydrophobic contacts were mainly contributors to their interactions. In vitro-in vivo extrapolation (IVIVE) showed that high in vivo inhibition possibility exists for the inhibition of OH-PAHs on UGTs. All the results provide a novel viewpoint for an explanation of the toxicity of PAHs and OH-PAHs.

miR-195 Inhibits Tumor Progression by Targeting RPS6KB1 in Human Prostate Cancer.

PURPOSE: To investigate the involvement of hsa-miRNA-195-5p (miR-195) in progression and prognosis of human prostate cancer. EXPERIMENTAL DESIGN: qRT-PCR was performed to detect miR-195 expression in both prostate cancer cell lines and clinical tissue samples. Its clinical significance was statistically analyzed. The roles of miR-195 and its candidate target gene, ribosomal protein S6 kinase, 70 kDa, polypeptide 1 (RPS6KB1) in prostate cancer progression were confirmed on the basis of both in vitro and in vivo systems. RESULTS: miR-195 downregulation in prostate cancer tissues was significantly associated with high Gleason score (P = 0.001), positive metastasis failure (P < 0.001), and biochemical recurrence (BCR, P < 0.001). Survival analysis identified miR-195 as an independent prognostic factor for BCR-free survival of prostate cancer patients (P = 0.022). Then, we confirmed the tumor suppressive role of miR-195 through prostate cancer cell invasion, migration, and apoptosis assays in vitro, along with tumor xenograft growth, angiogenesis, and invasion in vivo according to both gain-of-function and loss-of-function experiments. In addition, RPS6KB1 was identified as a novel direct target of miR-195 through proteomic expression profiling combined with bioinformatic target prediction and luciferase reporter assay. Moreover, the reexpression and knockdown of RPS6KB1 could respectively rescue and imitate the effects induced by miR-195. Importantly, RPS6KB1 expression was closely correlated with aggressive progression and poor prognosis in prostate cancer patients as opposed to miR-195. Furthermore, we identified MMP-9, VEGF, BAD, and E-cadherin as the downstream effectors of miR-195-RPS6KB1 axis. CONCLUSION: The newly identified miR-195-RPS6KB1 axis partially illustrates the molecular mechanism of prostate cancer progression and represents a novel potential therapeutic target for prostate cancer treatment.

Combined overexpression of HIVEP3 and SOX9 predicts unfavorable biochemical recurrence-free survival in patients with prostate cancer.

BACKGROUND: To clarify the involvement of HIVEP3 and SOX9 coexpression in prostate cancer (PCa). METHODS: A small interfering RNA was used to knockdown SOX9 expression in a PCa cell line and to analyze the effects of SOX9 inhibition on the expression of HIVEP3 in vitro. Then, HIVEP3 and SOX9 expression patterns in the human PCa tissues were detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry. RESULTS: We found that the downregulation of SOX9 could inhibit the expression of HIVEP3 in the PCa cells in vitro. In addition, both HIVEP3 and SOX9 messenger RNA expression levels in the PCa tissues were significantly higher than those in the noncancerous prostate tissues (P=0.006 and P<0.001, respectively). Moreover, the immunohistochemical staining scores of HIVEP3 in the PCa tissues with PSA failure were significantly higher than those without (P=0.042); the increased SOX9 protein expression was more frequently found in the PCa tissues with a high Gleason score (P=0.045) and a high clinical stage (P=0.012). The tumors showing the HIVEP3-high/SOX9-high expression more frequently had PSA failure (P=0.024). When the patients with an HIVEP3 overexpression combined with the SOX9 overexpression, this group had a worse biochemical recurrence-free survival (P<0.001). Furthermore, the multivariate analysis showed that the HIVEP3/SOX9 coexpression was an independent predictor of an unfavorable biochemical recurrence-free survival. CONCLUSION: Our data offer the convincing evidence for the first time that a combined analysis of HIVEP3 and SOX9 may help to predict the tumor progression and prognosis of PCa patients. In particular, the overexpression of HIVEP3 in PCa might partly explain the poor prognosis of patients with an upregulation of SOX9.

Global analysis of the differentially expressed miRNAs of prostate cancer in Chinese patients.

BACKGROUND: Our recent study showed the global physiological function of the differentially expressed genes of prostate cancer in Chinese patients was different from that of other non-Chinese populations. microRNA are estimated to regulate the expression of greater than 60% of all protein-coding genes. To further investigate the global association between the transcript abundance of miRNAs and their target mRNAs in Chinese patients, we used microRNA microarray approach combined with bioinformatics and clinical-pathological assay to investigate the miRNA profile and evaluate the potential of miRNAs as diagnostic and prognostic markers in Chinese patients. RESULTS: A total of 28 miRNAs (fold change ≥ 1.5; P ≤ 0.05) were differentially expressed between tumor tissue and adjacent benign tissue of 4 prostate cancer patients.10 top Differentially expressed miRNAs were validated by qRT-PCR using all 20 tissue pairs. Compared to the miRNA profile of non-Chinese populations, the current study showed that miR-23b, miR-220, miR-221, miR-222, and miR-205 maybe common critical therapeutic targets in different populations. The integrated analysis for mRNA microarray and miRNA microarray showed the effects of specifically inhibiting and/or enhancing the function of miRNAs on the gene transcription level. The current studies also identified 15 specific expressed miRNAs in Chinese patients. The clinical feature statistics revealed that miR-374b and miR-19a have significant correlations with clinical-pathological features in Chinese patients. CONCLUSIONS: Our findings showed Chinese prostate cancer patients have a common and specific miRNA expression profile compared with non-Chinese populations. The miR-374b is down-regulated in prostate cancer tissue, and it can be identified as an independent predictor of biochemical recurrence-free survival.

MicroRNA-23b downregulates peroxiredoxin III in human prostate cancer.

To investigate the mechanism by which peroxiredoxin III (PRDX3) is altered in human prostate cancer (PCa), we used microRNA (miRNA) target prediction program and miRNA microarray to predict and identify miR-23b as a candidate miRNA that targets PRDX3. We showed that miR-23b suppresses PRDX3 protein expression in human DU145 cells under normal and hypoxic conditions. Additionally, the clinical significance of miR-23b and PRDX3 expression in PCa patients was also confirmed. In conclusion, our data suggest that the effects of PRDX3 in PCa progression may be caused by the regulation function of miR-23b, and consequently, miR-23b may be involved in the response of PCa cells to hypoxia stress.

SOXs in human prostate cancer: implication as progression and prognosis factors.

BACKGROUND: SOX genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the involvement of SOXs in the progression and prognosis of human prostate cancer (PCa). METHODS: The gene expression changes of SOXs in human PCa tissues compared with non-cancerous prostate tissues was detected using gene expression microarray, and confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. The roles of these genes in castration resistance were investigated in LNCaP xenograft model of PCa. RESULTS: The microarray analysis identified three genes (SOX7, SOX9 and SOX10) of SOX family that were significantly dis-regulated in common among four PCa specimens. Consistent with the results of the microarray, differential mRNA and protein levels of three selected genes were found in PCa tissues by QRT-PCR analysis and immunohistochemistry. Additionally, we found that the immunohistochemical staining scores of SOX7 in PCa tissues with higher serum PSA level (P = 0.02) and metastasis (P = 0.03) were significantly lower than those with lower serum PSA level and without metastasis; the increased SOX9 protein expression was frequently found in PCa tissues with higher Gleason score (P = 0.02) and higher clinical stage (P < 0.0001); the down-regulation of SOX10 tend to be found in PCa tissues with higher serum PSA levels (P = 0.03) and advanced pathological stage (P = 0.01). Moreover, both univariate and multivariate analyses showed that the down-regulation of SOX7 and the up-regulation of SOX9 were independent predictors of shorter biochemical recurrence-free survival. Furthermore, we discovered that SOX7 was significantly down-regulated and SOX9 was significantly up-regulated during the progression to castration resistance. CONCLUSIONS: Our data offer the convince evidence that the dis-regulation of SOX7, SOX9 and SOX10 may be associated with the aggressive progression of PCa. SOX7 and SOX9 may be potential markers for prognosis in PCa patients. Interestingly, the down-regulation of SOX7 and the up-regulation of SOX9 may be important mechanisms for castration-resistant progression of PCa.

Extracellular matrix metalloproteinase inducer: a novel poor prognostic marker for human seminomas.

OBJECTIVE: Extracellular matrix metalloproteinase inducer (EMMPRIN) is a glycosylated member of the immunoglobulin superfamily whose function in human seminomas is unknown. We have recently determined that EMMPRIN possesses the ability to stimulate fibroblast and endothelial cell matrix metalloproteinase production, and that its expression was frequently up-regulated in several tumours of the urinary system. Thus, EMMPRIN expression might be associated with the progression of human seminomas. The aim of this study was to investigate whether the presence of EMMPRIN in seminoma tissues might help to predict the patients' prognosis. METHODS: Paraffin-embedded tissues from 65 patients with seminomas and 20 normal testes were processed for immunohistochemical staining using a mouse monoclonal antibody generated against human EMMPRIN, as primary antibody, and a biotinylated goat-anti-mouse IgG, as secondary antibody. In addition, the correlation of EMMPRIN expression with clinicopathologic characteristics and patients' prognosis was also analysed. RESULTS: EMMPRIN was detected in cancerous tissues of 53 patients with seminoma, but not normal testes. Thirty- five patients showed weakly to moderately positive and 18 patients intensely positive expression. Moreover, positive EMMPRIN staining correlated significantly with various clinicopathological factors (increased TNM stage and higher histological differentiation type) as well as decreased tumour-specific survival (log-rank, p=0.02). In particular, EMMPRIN expression was an independent prognosticator as shown by Cox regression analysis (p<0.001). CONCLUSION: EMMPRIN expression in a primary tumour predicts an unfavourable prognosis in human seminoma, suggesting its crucial role in the progression of this tumour.

Identification of novel serological tumor markers for human prostate cancer using integrative transcriptome and proteome analysis.

The aim of this study was to identify novel serological tumor markers for human prostate cancer (PCa). We compared the gene expression profile of PCa tissues to adjacent benign tissues of prostate using gene expression microarray. 1207 genes that were consistently different from adjacent benign tissues of prostate (paired t test, P<0.05) were selected as differentially expressed genes (DEGs). Among them, 652 DEGs were upregulated in PCa, whereas 555 DEGs were downregulated in PCa. In addition, two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with MS was performed to screen for candidate markers in the proteome of PCa and adjacent benign tissues of prostate. A total of 89 spots were significantly up-regulated (ratio≥2, P<0.01) in PCa samples, whereas 66 spots were down-regulated (ratio≤-2, P<0.01). Sixty gene products were identified among these spots. Moreover, 14 potential candidate markers, which were identified as differentially expressed molecules by both gene expression microarray and 2D-DIGE, were chosen for validation and analysis by ELISA. The serum levels of three proteins correlated well with the 2D-DIGE results. Furthermore, the increased serum level of Inosine monophosphate dehydrogenase II (IMPDH2) was significantly associated with the clinicopathological features of the patients with PCa, suggesting its potential as a serological tumor marker. These results demonstrated that integrative transcriptome and proteome analysis could be a powerful tool for marker discovery in PCa. We suggest IMPDH2 as a novel serological tumor marker for detection of early PCa and evaluation of tumor progression.

Analysis of the specific pathways and networks of prostate cancer for gene expression profiles in the Chinese population.

The global physiological function of specifically expressed genes of prostate cancer in Chinese patients is unclear. This study aims to determine the genome-wide expression of genes related to prostate cancer in the Chinese population. Genes that were differentially expressed in prostate cancer were identified using DNA microarray technology. Expressions were validated by using real-time PCR. The identified genes were analyzed using the ingenuity pathway analysis (IPA) to investigate the gene ontology, functional pathway and network. A total of 1,444 genes (Fold time ≥ 1.5; P ≤ 0.05) were differentially expressed in prostate primary tumor tissue compared with benign tissue. IPA revealed a unique landscape where inductions of certain pathways were involved in Cell Cycle Regulation and proliferation. Network analysis not only confirmed that protein interactions lead to the deregulation of DNA Replication, Recombination and Repair, Cellular Compromise and Cell Cycle, Genetic Disorders and Connective Tissue Disorders, but it was also observed that many of the genes regulated by Myc contributed to the modulation of lipid Metabolism and Nucleic Acid Metabolism. Both pathway and network analysis exhibited some remarkable characteristics of prostate cancer for Chinese patients, which showed profound differences from that of other non-Chinese populations. These differences may provide new insights into the molecular cascade of prostate cancer that occurs in Chinese patients.

Expression of hedgehog pathway components is associated with bladder cancer progression and clinical outcome.

Hedgehog (Hh) pathway has been implicated in the tumorigenesis of a large number of human tumors. But its effects on the progression and prognosis of bladder cancer remain poorly understood. The aim of this study was to investigate expression patterns of Hh pathway components in bladder cancer and to elucidate their prognostic values in this tumor. The expression of sonic hedgehog (Shh), its receptor Patched (Ptch1), and downstream transcription factor Gli1 in 118 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between the expression of these three proteins and clinicopathologic features and prognosis. Immunohistochemical staining results showed the localizations of Shh and Ptch1 proteins to be mainly located in the cytoplasm of bladder cancer cells, whereas Gli1 was mainly localized in the nuclear of tumor cells. Additionally, positive expression of Shh, Ptch1 and Gli1 proteins was correlated with pathological stage (P = 0.006, 0.006 and 0.008, respectively), venous invasion (P = 0.01, 0.01 and 0.012, respectively) and lymph node metastasis (P = 0.009, 0.01 and 0.013, respectively), but not with other factors including age, gender, tumor grade and recurrence of superficial cancer. Moreover, patients with positive expression of Shh, Ptch1 and Gli1 proteins respectively showed poorer disease-free (P = 0.002, 0.002 and 0.001, respectively) and overall survival (all P < 0.001) than those with negative expression of these three proteins. Univariate and multivariate analysis of prognostic factors in bladder cancer patients indicated that the expression patterns of Shh, Ptch1 and Gli1 proteins were independent unfavorable prognostic factors (all P < 0.001). This is the first report describing about the correlation between Hh pathway and the prognosis of bladder cancer. Expression of Shh, Ptch1 and Gli1 proteins was greater in bladder cancers than in the adjacent normal tissues. The examination of their expression is potentially valuable in prognostic evaluation of bladder cancer.

Classical and alternative nuclear factor-κB pathways: a comparison among normal prostate, benign prostate hyperplasia and prostate cancer.

Nuclear factor-κB (NF-κB) is controlled by the classical and alternative NF-κB pathways, the role of which in prostate cancer (PCa) is not clearly defined. To provide this missing translational link, we compared the classical and alternative NF-κB pathways in normal prostate, benign prostate hyperplasia (BPH) and PCa. Prostate specimens were divided into three groups: group A, PCa (n = 68); group B, BPH (n = 60); and group C, normal prostates (n = 15). The gene expression levels of NF-κB1 and NF-κB2 were determined by real-time quantitative RT-PCR. Additionally, we analyzed the expression and sub-cellular localization of phosphorylated P50 (p-P50) and phosphorylated P52 (p-P52) proteins by immunohistochemical staining. Furthermore, associations were made between NF-κB pathway proteins and patients' prognosis. Compared with BPH and normal prostate tissues, the expression of NF-κB1 gene was differentially down-regulated by >1.5-fold, whereas NF-κB2 gene was differentially up-regulated by >2-fold in PCa tissues. The proportion of p-P50 positive patients in group A (26.5%) was significantly lower than in group B (88.3%, p = 0.005) and C (100%, p = 0.002). The proportion of p-P52 positive patients in group A (42.6%) was significantly higher than in group B (11.7%, p = 0.009) and C (6.7%, p = 0.008). Comparison of the survival curves in group A according to p-P52 expression showed a significant difference between positive and negative patients. The p-P52 positive patients showed worse prognosis (p = 0.019). Our findings suggest for the first time that the classical and alternative NF-κB pathways have an important role in PCa. p-P52 might be a predictor of poor prognosis for PCa.

[Multicenter case-control study of the relationship between smoking and bladder cancer in China].

OBJECTIVE: To explore the relationship between smoking and bladder cancer in China. METHODS: A multicenter case-control study was conducted from September 2005 to June 2008. A total of 432 bladder cancer patients, matched with 392 control cases, received a questionnaire including the type of exposure (active vs. passive smoking), the age of beginning and/or quitting smoking, smoking amount and time and depth of smoke inhalation. RESULTS: Both active smoking and passive smoking increased the incidence of bladder cancer (P < 0.05). Bladder cancer risk increased 1.89 times in active smokers and 1.88 times in passive smokers compared to non-smokers (P < 0.05). Smoke amount and time were significantly correlated with bladder cancer risk (P < 0.05). But the age of beginning smoking did not affect the bladder cancer risk (P > 0.05). Inhaling smoke into mouth or throat was also a risk factor for bladder cancer (P < 0.05). CONCLUSION: There is a strong association between smoking and bladder cancer. Active and passive smoking, smoke amount and time, and the depth of smoke inhalation are risk factors for bladder cancer. The best way of preventing bladder cancer is never smoking.