A computational method to predict carbonylation sites in yeast proteins.

Several post-translational modifications (PTM) have been discussed in literature. Among a variety of oxidative stress-induced PTM, protein carbonylation is considered a biomarker of oxidative stress. Only certain proteins can be carbonylated because only four amino acid residues, namely lysine (K), arginine (R), threonine (T) and proline (P), are susceptible to carbonylation. The yeast proteome is an excellent model to explore oxidative stress, especially protein carbonylation. Current experimental approaches in identifying carbonylation sites are expensive, time-consuming and limited in their abilities to process proteins. Furthermore, there is no bioinformational method to predict carbonylation sites in yeast proteins. Therefore, we propose a computational method to predict yeast carbonylation sites. This method has total accuracies of 86.32, 85.89, 84.80, and 86.80% in predicting the carbonylation sites of K, R, T, and P, respectively. These results were confirmed by 10-fold cross-validation. The ability to identify carbonylation sites in different kinds of features was analyzed and the position-specific composition of the modification site-flanking residues was discussed. Additionally, a software tool has been developed to help with the calculations in this method. Datasets and the software are available at https://sourceforge.net/projects/hqlstudio/ files/CarSpred.Y/.

Moxifloxacin monotherapy for treatment of complicated intra-abdominal infections: a meta-analysis of randomised controlled trials.

To evaluate the efficacy and safety of moxifloxacin monotherapy for treatment of complicated intra-abdominal infections. PubMed, EMBASE, Science Direct, ClinicalTrials.gov and Cochrane Central Register of Controlled Trials were searched to retrieve randomised controlled trials (RCTs) compared moxifloxacin monotherapy with other antibiotics in the treatment of complicated intra-abdominal infections from January 1999 to July 2011. A meta-analysis of all included randomised controlled trials was performed. Four randomised controlled trials including a total of 2444 patients with complicated intra-abdominal infections were included for meta-analysis. The results of the meta-analysis indicated that the moxifloxacin was associated with similar clinical cure rate (four RCTs, 1934 patients, OR = 0.80, 95% CI: 0.61, 1.04, p = 0.09), bacteriological success rates (four RCTs, 1484 patients, OR = 0.79, 95% CI: 0.59, 1.05, p = 0.11) and mortality (four RCTs, 2227 patients, OR = 0.91, 95% CI: 0.45, 1.83, p = 0.79) compared with the control group. The overall incidence of adverse events of moxifloxacin was significantly higher than that in the control group (three RCTs, 1367 patients, OR = 1.33, 95% CI: 1.07, 1.63, p = 0.008), although the incidence of drug-related adverse events (three RCTs, 1601 patients, OR = 1.13, 95% CI: 0.69, 1.85, p = 0.63) and serious adverse events (three RCTs, 1815 patients, OR = 1.23, 95% CI: 0.59, 2.60, p = 0.58) were similar between the compared treatment groups. Moxifloxacin is an effective and relatively safe option for the treatment of patients with intra-abdominal infections. Moxifloxacin monotherapy has similar efficacy to combination therapy.

A cross-sectional study on levels of secondhand smoke in restaurants and bars in five cities in China.

OBJECTIVES: To assess indoor secondhand smoke (SHS) exposure in restaurants and bars via PM(2.5) level measurements in five cities in China. METHODS: The study was conducted from July to September in 2007 in Beijing, Xi'an, Wuhan, Kunming and Guiyang. PM(2.5) concentrations were measured in 404 restaurants and bars using portable aerosol monitors. The occupant density and the active smoker density were calculated for each venue sampled. RESULTS: Among the 404 surveyed venues, 23 had complete smoking bans, nine had partial smoking bans and 313 (77.5%) had smoking observed during sampling. The geometric mean of indoor PM(2.5) levels in venues with smoking observed was 208 µg/m(3) and 99 µg/m(3) in venues without smoking observed. When outdoor PM(2.5) levels were adjusted, indoor PM(2.5) levels in venues with smoking observed were consistently significantly higher than those in venues without smoking observed (F=80.49, p<0.001). Indoor PM(2.5) levels were positively correlated with outdoor PM(2.5) levels (partial ρ=0.37 p<0.001) and active smoker density (partial ρ=0.34, p<0.001). CONCLUSIONS: Consistent with findings in other countries, PM(2.5) levels in smoking places are significantly higher than those in smoke-free places and are strongly related to the number and density of active smokers. These findings document the high levels of SHS in hospitality venues in China and point to the urgent need for comprehensive smoke-free laws in China to protect the public from SHS hazards, as called for in Article 8 of the Framework Convention on Tobacco Control, which was ratified by China in 2005.

A cross-sectional study on levels of second-hand smoke in restaurants and bars in five cities in China.

OBJECTIVES: To assess indoor second-hand smoke (SHS) exposure in restaurants and bars via PM(2.5) (fine particles 2.5 µm in diameter and smaller) level measurements in five cities in China. METHODS: The study was conducted from July to September in 2007 in Beijing, Xi'an, Wuhan, Kunming and Guiyang. Portable aerosol monitors were used to measure PM(2.5) concentrations in 404 restaurants and bars. The occupant density and the active smoker density were calculated for each venue sampled. RESULTS: Among the 404 surveyed venues, 23 had complete smoking bans, 9 had partial smoking bans and 313 (77.5%) were observed to have allowed smoking during sampling. The geometric mean of indoor PM(2.5) levels in venues with smoking observed was 208 µg/m(3) and 99 µg/m(3) in venues without observed smoking. When outdoor PM(2.5) levels were adjusted, indoor PM(2.5) levels in venues with smoking observed were consistently significantly higher than in venues without smoking observed (F=80.49, p<0.001). Indoor PM(2.5) levels were positively correlated with outdoor PM(2.5) levels (partial rho=0.37 p<0.001) and active smoker density (partial rho=0.34, p<0.001). CONCLUSIONS: Consistent with findings in other countries, PM(2.5) levels in smoking places are significantly higher than those in smoke-free places and are strongly related to the number and density of active smokers. These findings document the high levels of SHS in hospitality venues in China and point to the urgent need for comprehensive smoke-free laws in China to protect the public from SHS hazards, as called for in Article 8 of the Framework Convention on Tobacco Control, which was ratified by China in 2005.

The number of lymph node metastases influences survival and International Union Against Cancer tumor-node-metastasis classification for esophageal squamous cell carcinoma.

To study the influence of the number of metastatic lymph nodes (LNs) on survival and International Union Against Cancer tumor-node-metastasis (TNM) classification for esophageal carcinoma. The clinicopathological data on 1146 patients with esophageal squamous cell carcinoma who had undergone an esophagectomy were retrospectively studied. Survival was analyzed by the Kaplan-Meier method. By subclassifying the nodes (N) category according to the number of metastatic LNs as: N0 for no LN metastases; N1(1) for only one positive node; and N1(2) for >or=2 positive nodes. TNM staging was refined as stage IIa (T2-3N0M0), stage IIb (T1N1M0 and T2N1(1)M0), stage IIIa (T2N1(2)M0 and T3N1(1)M0), and stage IIIb (T3N1(2)M0 and T4NanyM0), and the survival was analyzed. LN metastases was found in 380 of 1146 (33.2%) treated esophageal cancer patients. In 4270 LNs harvested, metastases was detected in 807 (18.9%). The 5-year survival rates of the patients with 0, 1, and >or=2 positive nodes were 59.8, 33.4, and 9.4%, respectively. There was statistically significant difference among these three groups. The 5-year survival of the patients in stages T2N1M0 and T3N1M0 was significantly higher in the N1(1) group than in the N1(2) group (41.5 vs 24.1%, and 31.2 vs 6.8%, P<0.001). The 5-year survival rates of the patients in refined stage IIa, IIb, IIIa, and IIIb were 57.1, 42.2, 28.6, and 8.5%, with significant difference existing in each stage groups. The number of positive LNs significantly influenced survival of the patients with esophageal cancer. Three grade classification (0, 1, >or=2 positive nodes) could quite well demonstrate the effect of the number of LN metastases and the survival. The refined TNM classification based on the number of LN metastases could better reflect the prognosis of esophageal cancer. Our results offer a strong rationale for refining the International Union Against Cancer TNM classification for esophageal carcinoma.

The pulmonary toxicity of multi-wall carbon nanotubes in mice 30 and 60 days after inhalation exposure.

The pulmonary toxicity, induced by multi-wall carbon nanotubes in mice, was studied after 30-day and 60-day inhalation exposure. The mice were exposed to multi-wall carbon nanotubes aerosol with weighted mean concentration of 32.61 mg/m3, once in very two days, 6 hours in an exposure day. After 30-day and 60-day inhalation exposure, the pulmonary toxicity of multi-wall carbon nanotubes was assessed using biochemical indices in bronchoalveolar lavage fluid and pathological examination. It was found that the aerosolized multi-wall carbon nanotubes did not induce obvious pulmonary toxicity in 30-day exposure group, but induced severe pulmonary toxicity in 60-day exposure group.

Identification a novel set of 6 differential expressed genes in prostate cancer that can potentially predict biochemical recurrence after curative surgery.

PURPOSE: Approximately, 30% patients after radical prostatectomy (RP) will undergo post-operative biochemical recurrence (BCR). Present stratification method by TNM staging and Gleason score was not adequate to screen high-risk patients. In this study, we intended to identify a novel set of differentially expressed gene (DEG) signature that can predict BCR after RP. MATERIALS/PATIENTS: 358 patients after RP with follow-up data were extracted from The Cancer Genome Atlas (TCGA), among which 61 patients had undergone BCR. Key DEGs were confirmed by the intersection of GSE35988 and TCGA_PCa dataset, and their gene expression data were also extracted from TCGA_PCa dataset. Kaplan-Meier plot and Cox proportion hazard regression model were applied to assess the relationship between risk score and survival outcome (BCR). RESULTS: 310 DEGs were confirmed in two prostate cancer dataset. 6 DEGs (SMIM22, NINL, NRG2, TOP2A, REPS2, and TPCN2) were selected to construct a risk score formula. The risk score was a powerful predictive factor independent of TNM stage (HR 3.045, 95% CI 1.655-5.602, p < 0.001). CONCLUSION: In this study, a novel 6-gene signature with robust predictive ability on post-operative BCR was constructed and 4 genes (SMIM22, NRG2, NINL and TPCN2) in the 6-gene signature were not reported to be associated with prostate cancer.

The incidence proportion of erectile dysfunction in patients treated with cryotherapy for prostate cancer: a meta-analysis.

OBJECTIVES: With the maturity of cryotherapy for prostate cancer, the complications after operation are also decreasing, which can improve the prognosis of patients. However, erectile dysfunction (ED) is still one of the main complications after cryotherapy. Therefore, we performed a meta-analysis to evaluate the incidence of erectile dysfunction in patients after cryotherapy. MATERIALS AND METHODS: A comprehensive literature search was performed in August 2018. PUBMED and EMBASE databases were searched to collect studies reporting the incidence rate of ED after cryotherapy from 2002 to 2018. Two reviewers independently screened the literatures, extracted data and assessed the risk of bias of included studies. Pooled ratio and its 95% confidence intervals (95% CIs) were performed by Stata 12.1. RESULTS: Of the 157 articles identified on August 1st 2018, 23 studies which reported ED after cold ablative therapy were identified, however, only 12 used validated outcome measures and met inclusion criteria. A total of 12 studies were included in this meta-analysis. Overall, the results of this meta-analysis showed that the pooled incidence rate of ED was 0.27 (95% CI 0.26-0.28) which means that the incidence rate of ED after cryotherapy for prostate cancer was not high, but we still found that there are great heterogeneity between the 12 articles. By subgroup analysis, we found a statistically significant incidence rate of ED in primarily localized PCa which was 0.49 (95% CI 0.30-0.68), which is clearly lower than the incidence of recurrent prostate cancer after failed primary radiotherapy 0.61 (95% CI 0.43-0.79). CONCLUSION: ED is one of the major complications after cryotherapy for PCa. Furthermore, subgroup analysis revealed a higher incidence rate in PCa undergoing radiotherapy. Significantly, with the development of cryotherapy technology, the incidence of ED after cryotherapy for prostate cancer is decreasing. While we still need further researches to advance knowledge in this field.

IL-21 modulates CD4+ CD25+ regulatory T-cell homeostasis in experimental autoimmune encephalomyelitis.

The homeostasis of CD4+ CD25+ regulatory T cells (Tregs) depends on the cytokine interleukin (IL)-2. As IL-21 shares sequence homology with IL-2 and the IL-21 receptors contain a gamma-chain common to IL-2, we hypothesized that IL-21 could also affect the homeostasis of Tregs. We tested this hypothesis in experimental autoimmune encephalomyelitis (EAE), an animal model of relapsing-remitting human multiple sclerosis. We show that blockade of IL-21 in SJL/J mice before and after the induction of EAE enhances the influx of inflammatory cells into the central nervous system (CNS). The blockade of IL-21 leads to proliferation of proteolipid peptide (PLP(139-151))-autoreactive CD4+ T cells, which are capable to cause severe EAE in adoptively transferred recipient mice. Conversely, Tregs from mice where IL-21 was blocked, lose their capacity to prevent EAE induced PLP(139-151)-reactive T cells. Notably, direct effects of IL-21 on Tregs are confirmed by studies of blockade of IL-21 in mice expressing a green fluorescent protein 'knocked' into a Foxp3 allele, in which a reduction of the number of Tregs and a downregulation of their frequency and expression of Foxp3 are observed. These data suggest a role of the IL-21/IL-21R axis in the homeostasis of Tregs in CNS autoimmunity.

A closer look at the in vitro electrochemical characterisation of titanium alloys for biomedical applications using in-situ methods.

Titanium (Ti) and its alloys are widely used in several biomedical applications, particularly as permanent orthopaedic implants. Electrochemical testing provides a means to perform accelerated corrosion testing, however whilst results from polarisation testing for Ti and its alloys to date have been generally useful, they are also rather limited on the basis of several reasons. One reason is that the polarisation curves for Ti and its alloys in simulated body fluids all appear rather similar, and they do not present a classical 'breakdown' or pitting potential, making discrimination between alloys difficult. Of practical relevance however, are two key issues; (1) how do Ti alloys respond to a breakdown event? (i.e. do they readily 'repassivate'?), and, (2) what is that actual rate of Ti ion loss from exposure to physiological conditions? The answers to these questions are probed herein. Several Ti alloys of either unique composition or different fabrication method were studied, including commercially pure Ti (cp-Ti), Ti-6Al-4V, Ti-29Nb-13Ta-4.5Zr (TNTZ), selective laser melted Ti-6Al-4V, direct laser deposited cp-Ti, Ti-35Nb-15Zr, and Ti-25Nb-8Zr. Results reveal that both fabrication method and alloying influence 'repassivation' behaviour. Furthermore, atomic emission spectroelectrochemistry as applied to cp-Ti indicated actual dissolution currents of ∼2-3µA/cm-2 (i.e. ∼9µm/yr) in the range of the corrosion potential, also revealing such dissolution is persistent, even with cathodic polarisation, and definitively revealing that the presence of hydrogen peroxide and albumin activate anodic dissolution of Ti. STATEMENT OF SIGNIFICANCE: We believe the paper makes a significant and important contribution to the field of permanent implant biomaterials. Whilst we concede that the paper does not include any in vivo work, the timeliness of the work, and the completely new nature of the findings, we believe carries the impact required for Acta Biomaterialia. Key highlights include:All of the above combine to produce a manuscript that we believe has wide appeal, and can be used as both a port of reference to those working with Ti biomaterials, and also those wishing to apply useful characterisation techniques to their own work (with two very novel methods demonstrated herein, along with the unique information they provide).

Gene profiling after knocking-down expression of nucleostemin in Hela cells using oligonucleotide DNA microarray.

Nucleostemin (NS) is preferentially and exclusively expressed in the stem cells and cancer cells, but not in differentiated adult tissues and cells. NS is likely to take part in controlling the proliferation and differentiation switch in stem cells and progenitor cells. Its deregulation in cancer also contributes to the elevated proliferation and undifferentiation of cancer cells. However, the mechanisms by which NS helps to maintain both cancer and stem cells in undifferentiated state remain unclear. In this study, we carried out gene profilings using oligonucleotide DNA microarray after knocking down the expression of NS in Hela cells. Of the 21,329 genes, 200 genes were found differentially expressed in NS silenced Hela cells with > 2 fold ratio (either > 2 or < 0.5). Category analysis indicated these differential genes were mainly related with cancer pathogenesis, cell death, cell growth and proliferation. NS related gene pathway analysis suggested NS was mostly involved in the networks of cell cycle and differentiation controls. p53 may not be the only partner of NS in its regulated pathways. c-Myc may directly or indirectly interact with it to control the proliferation and differentiation switch in cancer cells. Our study provides a general view of the NS-target genes, and indicates the possible pathways in which NS plays its role in proliferation control.

Controlling the corrosion and cathodic activation of magnesium via microalloying additions of Ge.

The evolution of corrosion morphology and kinetics for magnesium (Mg) have been demonstrated to be influenced by cathodic activation, which implies that the rate of the cathodic partial reaction is enhanced as a result of anodic dissolution. This phenomenon was recently demonstrated to be moderated by the use of arsenic (As) alloying as a poison for the cathodic reaction, leading to significantly improved corrosion resistance. The pursuit of alternatives to toxic As is important as a means to imparting a technologically safe and effective corrosion control method for Mg (and its alloys). In this work, Mg was microalloyed with germanium (Ge), with the aim of improving corrosion resistance by retarding cathodic activation. Based on a combined analysis herein, we report that Ge is potent in supressing the cathodic hydrogen evolution reaction (reduction of water) upon Mg, improving corrosion resistance. With the addition of Ge, cathodic activation of Mg subject to cyclic polarisation was also hindered, with beneficial implications for future Mg electrodes.

[Clinical significance of the preoperative neutrophil lymphocyte ratio in the evaluation of the prognosis of laryngeal carcinoma].

OBJECTIVE: To explore the effect of preoperative neutrophil lymphocyte ratio (NLR) on the prognosis of patients with laryngeal carcinoma. METHODS: Clinical data of 202 patients with laryngeal carcinoma treated from January 2004 to October 2009 were retrospective analyzed to determine the optimal critical value of NLR. To study whether NLR is an independent factor affecting the recurrence and 5-year survival rate of patients with laryngeal cancer after surgery, single factor and multivariate analyses were performed. The factors included age, gender, T stage, pathological differentiation, lymph node metastasis, primary tumor site and NLR value. The relationship between NLR and cervical lymph node metastasis was analyzed. RESULTS: The optimal critical value of NLR was 2.85, by which cases were divided into high NLR group (NLR≥2.85) and low NLR group (NLR<2.85). Single factor and multivariate analyses indicated that T staging, lymph node metastasis, primary tumor location, and NLR were the independent factors affecting the recurrence of laryngeal carcinoma. T stage and lymph node metastasis were the independent factors affecting 5-year survival rate of laryngeal carcinoma. The increase of NLR value increased the rate of cervical lymph node metastasis. CONCLUSION: Preoperative NLR level influences the recurrence and cervical lymph node metastasis of laryngeal carcinoma and can be considered a prognosis factor of laryngeal cancer.

Application of biotin-avidin system, determination of circulating immune complexes, and evaluation of antibody response in different hydatidosis patients.

The avidin-biotin-peroxidase complex enzyme-linked immunosorbent assay (ABC-ELISA) and standard ELISA were used for the detection of Echinococcus granulosus antibody in sera of 101 patients operated on for hydatid disease, 40 patients with miscellaneous nonhydatid diseases, and 61 normal subjects. Sensitivity and specificity of the two procedures were comparable and the geometric mean antibody titer detected with ABC-ELISA was higher than with standard ELISA. The ABC-ELISA is a sensitive, specific, simple, and convenient method for diagnosing hydatidosis.

[Measurement of the single muscle fiber action potentials and jitter value in tibialis anterior muscles of rabbits in situ].

With a home-made jitter data processing board and microcomputer for recording extracellular single fiber action potential (SF-AP), variations of the time intervals of the SF-AP pairs, or the jitters, from two adjacent muscle fibers in the unique motor unit in tibialis' anterior in response to repeated stimuli were measured. The jitter distribution of 936 recorded from 7 rabbits was positively showed with a percentile value of P75-P25 of 54.99-14.61 microseconds. The data suggested that the lower limit was smaller than that of skeletal muscles in normal human and that there exists also some differences in the jitter values of SFEMG between human and rabbit muscles.

[Effects of poria cocos on ototoxicity induced by kanamycin in guinea-pigs].

In order to prevent the ototoxicity of kanamycin (KM), the effects of Poria Cocos (PC) on the ototoxicity induced by KM in guinea-pigs was observed by infusing the PC decoction into the guinea-pigs with comparing the difference in the general intoxicating symptom, prayer's reflex (PR) threshold, brainstem auditory evoked potentials (BAEPs) and the absence rate of outer hair cells in the first turn of cochlea. The results suggested that the ototoxicity of KM was retarded by giving the PC decoction. On 7th day after given KM, PR threshold of 4,6,8 kHz in the medicated group and control group were 4.7 +/- 1.5 dB, 5.7 +/- 2.4 dB, 2.7 +/- 1.2 dB and 10.5 +/- 3.2 dB, 12.1 +/- 3.7 dB, 8.5 +/- 2.7 dB respectively. BAEPs threshold on 13th day given KM raised 22.7 +/- 9.7 dB in the medicated group and 51.3 +/- 14.4 dB in control group. The absence rate of outer hair cells in first turn of cochlea were 39.4% and 67.4% respectively. The results suggested that PC might be antagonistic to the ototoxicity of KM in guinea-pigs.

Influence of lactuside B on the expression of AQP4 and TRPM7 mRNAs in the cerebral cortex after cerebral ischemia injury.

AIM: This study aimed to determine the effect of Lactuside B isolated from Pterocypsela alata on the expression of AQP4 and TRPM7 mRNAs after cerebral ischemic injury. MATERIALS AND METHODS: Brain ischemia injury was established by occluding the MCA (middle cerebral artery) for 2 h, followed by reperfusion in rats. The neurologic deficit scores were used to determine the success of the model. All drugs were intraperitoneally administered once a day (5 ml/kg). Eight animals from each group were investigated for the Na+ level, and the others were examined for AQP4 and TRPM7 mRNA changes. RESULTS: Compared with the model group, the neurologic deficit scores and Na+ levels decreased in the lactuside B groups (p < 0.05 vs. p < 0.01). All lactuside B groups had significantly decreased AQP4 and TRPM7 mRNA expression compared with the model group (p < 0.05 vs. < 0.01). Dose dependence was observed between low and medium doses. CONCLUSIONS: Lactuside B protected against cerebral edema and nerve cell damage caused by cerebral ischemic injury by decreasing the expression of AQP4 and TRPM7 mRNAs in the cerebral cortex of rats.

The roles of MAPKs in rabbit nucleus pulposus cell apoptosis induced by high osmolality.

BACKGROUND: Earlier work has suggested that the p38 MAPK, JNK1/2 and ERK1/2 signal pathway existed in nucleus pulposus cells and the cell growth, differentiation and apoptosis were regulated by them. Because osmotic fluctuations are inevitable in the physicochemical environment of intervertebral disc cells, high osmolality could activate p38 MAPK, JNK1/2 and ERK1/2 signal pathway. The effects of high osmolality on the catabolic program and proliferation of nucleus pulposus cells are still not clear. AIM: To explore the possible roles of MAPKs in rabbit nucleus pulposus cell apoptosis induced by high osmolality. MATERIALS AND METHODS: Rabbit nucleus pulposus cells were cultured and divided into different group at random. The cells were pretreated with inhibitor for p38 MAPK, JNK1/2 and ERK1/2 signal pathway respectively. In next step, the cells were cultured in different osmolality environment for different time at 37°C in 5% carbon dioxide incubator. After treatments, ratio of apoptosis was measured by flow cytometry, and western blotting was performed to quantify the expression of the activated forms of p38 MAPK, JNK1/2 and ERK1/2. Furthermore, immunofluorescence analysis with confocal microscopy was performed to confirm the hyperosmolality effects on activation of p38 MAPK, JNK1/2 and ERK1/2 signal pathways in nucleus pulposus cells. RESULTS: Our results show that in 500 and 600 mOsm/kg medium, rabbit nucleus pulposus cell apoptosis increased, and a persistent phosphorylation of p38 MAPK, JNK1/2 and ERK1/2 proteins were observed. In the same condition, the apoptotic cells death remarkably decreased when the p38 MAPK and JNK1/2 signal pathways were blocked by their inhibitors SB203580, SP600125 repectively. On the other side, the apoptotic cells death rate reraised greatly when the ERK1/2 signal pathways were blocked by its inhibitor PD98059. CONCLUSIONS: High osmolality activated p38MAPK, JNK1/2 and ERK1/2 in rabbit nucleus pulposus cell, and the activated p38 MAPK and JNK1/2 induced cell apoptosis, on the contrary, the activated ERK1/2 made the cell survived.

The significance of fragile histidine triad protein as a molecular prognostic marker of bladder urothelial carcinoma.

OBJECTIVES: The role and clinical significance of fragile histidine triad (FHIT) gene in the pathogenesis of bladder urothelial carcinoma (UC) and the potential of Fhit protein as a prognostic biomarker for UC were investigated. METHODS: FHIT expression was determined according to semiquantitative immunohistochemical staining for Fhit protein levels in normal bladder and bladder UC tissues. Associations between FHIT expression, clinicopathological features and survival were evaluated. RESULTS: This study evaluated 42 cases of normal bladder and 125 cases of bladder UC; bladder UC cases had a median follow-up of 53.5 months. Immuno histochemistry showed that 95.2% of normal cases and 47.2% of bladder UC cases, respectively, were positive for Fhit protein; this difference was statistically significant. There was a significant association between negative FHIT expression in bladder UC and advanced tumour stage, high pathological grade, large tumour size, tumour recurrence and reduced survival time, but no association with age, gender, tumour number or tumour shape. CONCLUSIONS: The FHIT gene may have an important role in the pathogenesis of bladder UC and was expressed at lower levels in bladder UC compared with normal bladder tissue. Using Fhit protein as a biomarker could provide important information about patient prognosis.