The high mobility group A2 (HMGA2), one ofnon-histone chromatin proteins, may alter chromatin structure and thereby regulate the transcription of several genes by either enhancing or suppressing transcription factors, and leading to malignant neoplasm formation. This paper focuses on the role of the HMGA proteins in human neoplastic diseases, and discusses the mechanisms by which they contribute to carcinogenesis, and diagnosis strategies based on targeting HMGA proteins.

Bladder cancer is a common type of tumor in the urinary system. Its incidence has been increasing and the disease has a high rate of recurrence. Cystoscopy and cytology are the main methods for the diagnosis and the early detection of recurrence for bladder transitional cell carcinoma. Since cystoscopy is expensive and invasive, and although cytology is non-invasive but it is not very sensitive, many tumor makers have recently been studied in the diagnosis of the disease. So how to choose tumor makers with high sensitivity and specificity for the diagnosis of the disease so that the patients with bladder cancer could be treated at the earliest stages is important, the biomarkers may play a very important role in clinical application. In this review we discussed the development of biomarkers for bladder cancer.

TROP2 (trophoblastic cell surface protein 2),a cell-surface glycoprotein,is named after its high expression only in trophoblast cells.Recent studies found that TROP2 protein is overexpressed in a variety of human epithelial cancers,and it is associated with the prognosis.However,the mechanism is still not clear.

Objective To explore the expression and significance of N-cadherin in urothelial bladder cancer and analyse its relation to clinicpathologic and prognosis of bladder cancer.Methods The expression of N-cadherin in 145 urothelial bladder cancer and 25 normal bladder tissues was detected by immunuhistochemisty,and correlations between N-cadherin and clinicopathologic features were analysed.Results The positive rate of N-cadherin protein was significantly higher in bladder cancer than in normal bladder tissue (P＜0.01).The positive rate of N-cadherin protein was 38.6％ in G1 bladder cancer,58.4％ in G2-G3 bladder cancer,and its difference was significant (P =0.028).The expression was significantly lower in non-muscle-invasive bladder cancer than in muscle invasive bladder cancer (45.7％ vs 64.7％,P=0.029).The muscle-invasive bladder cancer patients were followed up 4-103 months.Among those,the overall survival with positive expression of N-cadherin protein was 24.2％ (8/33),and the overall survival with negative expression of N-cadherin protein was 66.7 ％ (12/18).Kaplan-Meier analysis showed the positive expression of N-cadherin was significantly associated with overall survival of patients with muscle-invasive-bladder cancer (P=0.002 2).Multivariate Cox analysis showed that N-cadherin expression was an important prognostic factor.Conclusions The expression of N-cadherin protein was high in bladder cancer.The detection of the expression of N-cadherin protein is associated with the diagnosis and prognosis of bladder cancer.

One hundred and twenty five patients, who underwent cystoscopic examination, were randomly divided into two groups: the control group ( n = 62) received conventional cystoscopy, and the treatment group (n = 63) received rociverine 20 mg 1 h before cystoscpy.The pain levels were evaluated using numeric rating scale (NRS) in all patients.The average NRS during examination was 2.1 ±0.9 and 3.6 ± 1.8 in treatment group and control group respectively( P ＜0.01 ).The pain scores in control g roupwere still higher than those in treatment group 15 min and 1 d after procedure ( P ＜ 0.01 or 0.05,respectively).

Objective To explore the clinical significance of second transurethral resection (TUR) in patients with T1 urothelial cell carcinoma of the bladder.Methods The 142 cases with urothelial carcinoma were recruited.All patients underwent transurethral resection of bladder tumor (TURBT) and were diagnosed as stage T1 urothelial carcinoma of the bladder.The 68 of 142 cases underwent second TUR after the initial surgery.Tumor recurrence rate,progression rate and recurrence-free survival were compared.Results There were no statistical differences in age,gender,follow-up time,number of tumors,size of tumors or grade of tumors between patients with and without second TUR.Of the 68 cases that underwent second TUR,25 cases (36.8%) had residual tumor and 6 of them (8.8%) had muscle-invasive bladder cancer.After an average observation for 26.8 months,patients who underwent second TUR showed lower recurrence rate,higher recurrence-free rate and longer recurrence-free survival than patients without second TUR [37.1% vs.58.1%,x2=5.962,P=0.015;41% vs.35.1%,x2=8.502,P=0.004;21 months vs.12 months,U= 1584,P= 0.002].While the progression rate showed no statistical difference between them (14.5% vs.25.7%,x2 =2.570,P=0.109).Conclusions Second TUR provides an effective way to completely excise tumor.Second TUR is beneficial to the decrease of recurrence rate and improvement of recurrence-free survival.However,its effect on tumor progression needs further discussion.

Objective This study was to explore the expression and significance of HMA2 in bladder cancer , analyze its correlations to clinicopathologic and recurrence of bladder cancer. Methods The expression of HMGA2 protein in 148 specimens of bladder cancer and 30 specimens of normal bladder tissues was detected by immunohistochemtry, its correlations to clinicopathologic features was analyzed. Results There was no expression of HMGA2 protein in normal bladder tissues,while the expression level of HMGA2 protein was getting higher with the increase of tumor pathology grade and stage. The positive rate of HMGA2 protein was 21.3% in G1 bladder cancer, 60. 3% in G2 bladder cancer, 82.1% in G3 bladder cancer, its difference is significant (P＜0. 001). It was significantly lower in non-muscle invasive bladder cancer than in muscle invasive bladder cancer (43.3% vs 72. 7%, P=0. 003). The patients were followed up for 2～95 months, patients of recurrence was 64,HMGA2 protein expression was significantly higher in patients with recurrence than with non-recurrence (54.7% vs 25.0%, P=0. 007). Conclusions The expression of HMGA2 protein was highly in bladder cancer, the positive rate of HMGA2 protein expression was related with classification,TMN stage and recurrence, but not with sex, age, tumor number (P＞0. 05). The detection of the expression of HMGA2 protein is in favor of diagnosis and prognostic evaluation of bladder cancer.

Objective To discuss the techniques and clinical efficacy of laparoscopic partial cystectomy with bilateral pelvic lymphadenectomy for urachal adenocarcinoma. Methods From July 2006 to April 2008, 4 patients with urachal adenocarcinoma were managed by the laparoscopic procedure. Three patients were male, the other one was female, with a median age of 51 (range 42 to 66)years. The mean size of tumors was 3.4(rang 1.9 to 5.4)cm in diameter. Three of them were diagnosed as mucinous adenocarcinoma, the other one was adenocarcinoma. There was 1 patient at stage Ⅱ , and the other three as stage Ⅲ according to Sheldon Stage. Four patients were performed by transperitoneal approach. The boundaries of resection were similar to the open surgery, including resection of the tumor with normal margins, the peritoneum lateral to the two medial unbilical ligaments,the posterior sheath of the rectus muscle and the muscle fibers of the rectus muscle below it, and bilateral pelvic lymphanodes. Results The procedure was successfully in all 4 patients, with a mean operative time of 220(range 150 to 350)min, a mean estimated blood loss of 180 (range 120 to 290)ml.No significant intraoperative or postoperative complications occurred, except for an inferior epigastric artery injury in 1 case. The mean postoperative in-dwelling urinary catheter time was 6 (range 5 to 7)d, and the mean postoperative hospital stay was 6 (range 5 to 8)d. All 36 resected lymph nodes (range 8 to 11) were negative. At a median follow-up of 25(range 15 to 36) months, there was no evidence of recurrent disease by radiologic or cystoscopic evaluation. ConclusionLaparoscopic partial cystectomy and bilateral extended pelvic lymphadenectomy in selected patients with urachal tumors could be a safe, feasible, minimally invasive procedure.

Objective To investigate the clinical,pathological and histopatholo(g)ical features of primary bladder clear cell carcinoma and discuss the diagnosis and treatment of the disease. Methods The clinical and pathological features of one primary bladder clear cell carcinoma case retrospectively were analyzed,with the combination of reviewing reported literatures. Results The patient came to hospital with the chief complaint of urinary tract symptom and gradually developed gross hematuria.The tumor was located in the left wall of the bladder and was confirmed to be clear cell carcinoma by preoperative biopsy.Partial cysteetomy,ureteroneocystostomy and hysterectomy plus bilateral adnexectomy were performed.The patient received chemotherapy postoperatively and was tumor free 6 months post operatively. Conclusions Primary clear cell carcinoma of the bladder is a rare type of bladder adenocarcinoma.The diagnosis depends on the clinical and pathological study.Surgical operation is effective and the outcome of the disease is better than other non-urothelium carcinoma.

Objective To observe the expression and mechanism of monocyte chemoattractant protein-1 (MCP-1) in interstitial cystitis (IC) rats.Methods Twenty weight of 250-300 g of female SD rats were divided into IC group (n =10) and control group (n =10).IC group were treated by transurethral instillation with 10 mg/ml protamine sulfate (PS) 1 ml reserved for 45 min,and then instillation with 750 ug/ml of lipopolysaccharide (LPS) 1 ml reserved for 30 min.The same operations were repeated after 24 hours,and the rats were killed obtaining the bladder tissue and urine after three days.Control group was given PBS solution perfusion.MCP-1 and histamine (HA) expression levels in the rat bladder tissue and urine were detected by ELISA.The inflammation of bladder tissue was observed and inflammatory score was used by HE staining.MC degranulation count was used by MC special staining.MCP-1 expression and distribution in bladder tissue was observed by immunohistochemical method.The relationship between the MCP-1 and MC was detected by immunofluorescence method.Results By ELISA,the expression levels of MCP-1 and HA in the bladder tissue and urine in IC group were significantly increased compared with control group (P ＜0.01 ).More inflammatory cell infiltration in the bladder mucosa,edema mucosa,congestion and hemorrhage were seen by HE staining.The inflammatory score in IC and control group were (76.5 ±9.8) and (18.5± 9.8)/field (P ＜ 0.01 ).With MC special staining,degranulation MC count in IC and control group were (6.4±3.1 ) and (0.7 ±0.3)/field (P ＜0.01 ),and the degranulation in the bladder tissue of IC group was significantly higher than control group (P ＜ 0.01 ).MCP-1 has a higher expression in the bladder epithelium,and more MCP-1 were found gathering round MC surface by immunofluorescence.Conclusions MCP-1 is highly expressed in IC rats,and could induced activation of MC,which could release HA,aggravating the pathological process of inflammatory and fibrosis in IC.