Objective To investigate the expression of adenylate kinase 4 (AK4) in prostate cancer and its clinical significance.Methods The clinical data of 85 patients with prostate cancer who have underwent radical surgery were retrospectively analyzed.The expression of AK4 in prostate cancer tissues and corresponding paracancerous tissues was detected by immunohistochemistry to analyze the relationship with clinicopathological features.Results The positive rates of AK4 in prostate cancer and paracancerous tissues were 85.9％ and 38.8％ respectively,and the difference was statistically significant (P＜0.05).The abnormal expression of AK4 was correlated with recurrence and distant metastasis (all P＜0.05).The survival time of AK4-overexpressing patients with prostate cancer was significantly lower than that of AK4 low-expression patients,and the difference was statistically significant (P＜0.05).Conclusions The expression of AK4 in prostate cancer tissues is up-regulated,which is related to the distant metastasis of carcinoma and vascular tumor thrombus,which suggests that the expression of AK4 may indicate the poor prognosis of patients with prostate cancer.

Objective To investigate the expression of B7-H3 in muscle infiltration bladder transitional cell carcinoma and its clinical significance.Methods The clinical and pathological data of 115 patients with muscle infiltration bladder transitional cell carcinoma who underwent radical surgery were retrospectively analyzed.The expression of B7-H3 in bladder cancer tissues and corresponding paracancerous tissues was detected by immunohistochemical staining,and the relationship between B7-H3 and clinicopathological characteristics was analyzed.Results The positive expression of B7-H3 was mainly in the cytoplasm,presenting brownish yellow granules.B7-H3 had positive expression in all bladder cancer tissues but no expression in paracancerous tissues.The high positive rate of B7-H3 expression in bladder cancer was 68.7％.The abnormal expression of B7-H3 was correlated with the distant metastasis and intravascular tumor thrombi (all P＜0.05),but not with gender,age,tumor stage and grade,lymph node metastasis and recurrence (all P＞0.05).The survival analysis result showed that the survival time of the patients with high expression of B7-H3 in the bladder cancer tissues was significantly lower than that of patients with low expression of B7-H3,and the difference was statistically significant (P＜0.05).Conclusion The expression of B7-H3 in muscle infiltration bladder cancer tissues is up-regulated and is positively associated with the distant metastasis of bladder cancer and intravascular tumor thrombus.The expression of B7-H3 may indicate poor prognosis of the patients with bladder cancer.

Objective To analyze the features of onset, clinical pathological characteristics about the primary bladder mucinous adenocarcinoma.Methods From January 1990 to June 2015, we retrospectively reviewed the data from 15 patients diagnosed as primary bladder mucinous adenocarcinoma, including 10 male patients and 5 female patients.Their mean age was 58 years old, ranged from 41 to 78 years old.Among the fifteen patients, the initial symptoms included hematuria in 13 cases, lower abdominal pain in 1 case and urinary irritation symptom in 1 case.The ultrasound and CT scan revealed bladder tumors, which the size ranged from 2 to 6 cm.The location of bladder tumors included front wall in 12 cases, trigone zone in 2 cases and top wall in 1 case.Nine cases was suspected as tumor from urachal remnants.Eleven patients underwent partial cystectomy, three patients accepted the radical cystectomy and one case accepted transurethral resection of bladder tumor (TURBT).Result Pathological diagnosis was bladder mucinous adenocarcinoma in all patients, including nine from urachal remnant and the others from urothelimn.The tumor exhibited the mushroom liked prominence, which was associated with surface ulceration and infiltrated into the depth of bladder.Meanwhile, it was covered with thick mucinous substances.The histologic examination revealed the presence of andenoid structure, composed by various degree of diferenfiated mucinous cells.In cases with adenocarcinomas from urachus, the residue of urachal tissue could be noticed.The bladder mucous was intact or ulcerated.No sign of metaplasia was observed.In the pathological diagnosis, the classification included grade Ⅲ in 3 cases, grade Ⅱ in 7 cases and grade Ⅰ in 5 cases.Ten persons reported the information of the follow up.Eight of them, whose tumor originated from urachus, accepted bladder-sparing surgery.One died from acute myocardial infarction after 23 months postoperatively.And one died from cerebral hemorrhage 45 months postoperatively.The others have been followed up from 8 to 65 months with no sign of recurrence.In two cases with urothelial carcinoma, one was found the new urothelial carcinoma 50 months after TURBT and one died from cancer metastasis 29 months after partial cystectomy.Conclusions Primary mucinous adenocarcinoma of the bladder possess the relatively high malignant tendency.The hematuria is the main initial symptoms.The histologic examination revealed the presence of different differentiated mucinous cells and formed the andenoid structure.The case with urachal remnant adenocarcinoma has the better prognosis than other types.

Objective To investigate the histopathologic characteristics of bladder tumor and provide theoretical basis for the reasonable selection of treatment modality.Methods This retrospective study collected the pathological data of 4 200 bladder tumor from May 2001 to October 2014.There were 3 443 male and 757 female, and the average diameter of these tumors was (1.8 ± 0.6) cm (ranged 0.2 to 6.5 cm).Among all cases, 3 214 (76.5％) cases were solitary tumor while 986 (23.5％) were multiple tumors.The histologic subtype, pathological grade and stage, the existence of vascular and lymphovascular invasion, tumor in situ, abnormal variants and rare subtypes were recorded and analyzed.Results 162 cases (3.9％)were benign tumors and 4 038 cases (96.1％)were malignant tumors including 4 008 cases of urothelial cancer (UC), 18 cases of primary adenocarcinoma and 12 cases of primary bladder squamous carcinoma.Furthermore, 2 460 (61.4％)cases were high grade UC while 1 548(38.6％)cases were low grade.320 cases were found intravascular tumor embolus or lymphovascular tumor thrombus and 391 (9.3％)cases were found metaplasia of squamous epithelium.Moreover, there were 230 cases of squamous differentiation, 120 cases of glandular differentiation, 110 cases of both squamous and glandular differentiation, and 39 cases (0.9％)of other rare subtypes or variations.On pathological stage, 112 (2.8 ％) cases were carcinoma in situ, 548 (13.7％)cases were Ta, 2 599(65.1％)cases were T1, 480(12％)cases were T2, 92 cases(2.3％)were T3 and 23 cases(0.6％)were T4 stage, with the rest cases being unable to be accurate staging.Multiple Logistic regression analysis revealed that lymphovascular invasion was related to tumor grade , pathological stage and abnormal differentiation (P ＜ 0.02).Moreover, UC with squamous and glandular differentiation were related with tumor recurrence and progression (P =0.02).Conclusions Most bladder tumors were high grade and low stage urothelial cancer with various forms of differentiation.Squamous and glandular differentiation were most common variation which should be avoided to diagnosed as hybrid carcinoma.Lymphovascular tumor thrombus and abnormal differentiation were correlated with tumor stage and grade.

Objective To study the clinical and histopathologic features of small renal carcinoma (diameter≤4 cm)and provide theoretical basis for evaluating the safety,efficacy and prognosis of nephron sparing surgery.Methods This retrospective study collected the pathological data of 490 patients with small renal cell carcinoma,who were treated in our hospital,from May 2000 to October 2014.We recorded and analyzed the tumor size,histological subtype,Fuhrman grading,pathological stage,the existence of mulifocality,vascular invasion,tumor psuedocapsule,hemorrhage or necrosis and distant metastasis.Results The median diameter of tumor was (3.2 ± 0.6) cm,ranged 0.6 to 4.0 cm.Of all the subjects,422 (86.1％) were clear cell carcinoma,32 (6.5％) were chromophobe cell carcinoma,23 (4.7％) were papillary carcinoma and 13 (2.7％) were other rare types.Among the 422 clear cell carcinoma cases,27 were Fuhrman grade Ⅰ,157 were Ⅰ-Ⅱ grade,210 were grade Ⅱ,21 were Ⅱ-Ⅲ grade,7 were grade Ⅲ and no one was grade Ⅳ.Multifocal tumors were found in 18 cases (3.7％) and tumor embolus of renal vein was found in 6 cases (1.2％).Intact psuedocapsule were found in 326 (66.5％) tumors with the thickness ranged from 0.2 to 1.0 mm.Tumor infiltration without the psuedocapsule penetration were found in 82 cases (16.7％),penetrated into the psuedocapsule were found in 11 cases (2.2％),infringement of perirenal fat were found in 9 cases (1.8％).Hemorrhage and necrosis were found in 240 cases (48.9％),synchronous lung metastases occurred in 3 patients (0.6％).Logistic regression analysis revealed that tumor invasion and pseudocapsule penetration were related to Fuhrman Ⅱ-Ⅲ,Ⅲ and tumor diameter (P =0.04).Moreover,tumor size was related with histological grade and renal capsule invasion (P =0.02).Nevertheless,there was no relationship among tumor size,renal vein embolus or mulifocality (P =0.35).Conclusions Although most small renal tumors are high differentiation and low grade,but rare cases are aggressive with infringement of perirenal fat or early distant metastasis,suggesting heterogeneity in its biological behavior.Most small renal tumors have obvious psuedocapsule.When the tumor size is greater than 3.0 cm and its Fuhrman classification was high,the psuedocapsule and perirenal fat are more likely to be infiltrated.Nephron sparing surgery should remove the tumor and its surface adipose tissue entirely.

Micro-ribonucleic acids (miRNAs) are endogenous single-stranded small non-coding RNAs. miRNAs bind to a com-plementary site in the 3' untranslated region of their target mRNAs through canonical base pairing, which can direct the degradation or translational repression of these transcripts. Thus, miRNAs can effectively silence the protein expression of target genes post-transcrip-tionally. miRNAs may also regulate the expression of oncogenes and tumor suppressor genes and could be involved in almost all known hallmarks of cancinogenesis. In this paper, we discuss the following in detail:(1) biogenesis and main functions of cellular miR-NAs, (2) stability and detectability of exosomal miRNAs in biological fluids;and (3) feasibility of miRNAs as a potential new class of biomarkers derived from urinary exosome in the malignancy of urinary system. Finally, we summarize studies on urinary exosomal miRNAs as potential biomarkers of prostate, bladder, and kidney cancers.

Tumor-derived heat shock protein-peptide complex 96 (HSPPC-96) containing tumor antigenic peptides can elicit po-tent tumor-specific and protective immunity. Autologous HSPPC-96 vaccine has been shown to effectively prolong recurrence-free sur-vival and increase the overall survival of many tumors, thereby suggesting extensive future applications. However, as an autologous tu-mor-derived individual vaccine, the development of HSPPC-96 vaccine is challenged by the lack of an adequate autologous tumor, lim-ited efficacy for advanced-stage cancer, etc. This paper summarized the progress, future perspectives, and challenges in the clinical de-velopment of HSPPC-96 vaccine immunotherapy.

Objective: To investigate the molecular changes in bladder urothelial carcinoma via different pathways. Methods:Polymerase-chain reaction (PCR) or coamplification at low denaturation temperature-PCR and Sanger direct sequencing were per-formed to detect the status of fgfr3, p53, and h-ras gene mutations in 88 tissue samples of human bladder cancer and 10 normal control tissues. The relative mRNA expression levels of motility-related protein-1 (MRP-1)/CD9 and the relationship between genes and tumor recurrence were also determined. Logistic regression and relative analyses were conducted to compare the significance and interrelation of genes among tumor recurrences. Results:The mutation rate of p53 increased as pathological grades and stages increased. Recurrence rate was higher in patients with MT-p53 genotype than in patients with WT-p53 genotype. Conversely, the mutation rate of fgfr3 gene decreased as pathological grades and stages increased. Recurrence rate was also higher in patients with WT-fgfr3 genotype than in pa-tients with MT-fgfr3 genotype. In low-grade and early stage tumors, MT-fgfr3/WT-p53 was the most prevalent genotype;in high-grade and late stage tumors, WT-fgfr3/MT-p53 was the most prevalent genotype. The mutations of h-ras were mainly observed in low-grade tumors in early stages. Moreover, the relative mRNA levels of MRP-1/CD9 decreased as pathological grades and stages increased. The mRNA levels of MRP-1/CD9 were negatively correlated with p53 mutations and positively correlated with fgfr3 mutations. Logistic re-gression analysis results showed that patients with WT-fgfr3 genotypes exhibited 3.88 times higher relative risk of tumor recurrence than those with MT-fgfr3 genotypes;by contrast, patients with MT-p53 genotypes exhibited 4.53 times higher relative risk of tumor re-currence than those with WT-p53 genotypes. Conclusion:Fgfr3 and h-ras gene mutations may play important roles in tumorigenesis of low-grade and early stage bladder cancer. p53 gene mutation and mRNA levels of MRP-1/CD9 may be implicated in the tumorigenesis of high-grade tumors in late stage of bladder cancer. In general, the two variants of urothelial carcinoma exhibit distinct genetic defects. fgfr3 gene mutation revealed a pathway of favorable prognosis, and p53 gene mutation demonstrated a pathway associated with poor prognosis.

Objective To investigate the clinical and pathological characteristics of nephrogenic adenoma. Methods Eleven patients were diagnosed as nephrogenic adenoma including 5 men and 6 women, aged 37-78 years (56 on average). The pathological findings in all cases of nephrogenic adenoma were presented with a review of the literature. Results Eleven cases of nephrogenic adenomas were evaluated, 2 cases were in ureter and 9 cases were in the bladder. Eight of the 9 bladder cases underwent TUR-BT surgery in continuous epidural anesthesia, 1 case underwent partial cystectomy with general anesthesia. A right ureteroscopy and left ureterolithotomy were performed respectively in continuous epidural anesthesia for the 2 cases in ureter. The final diagnosis was based on histopathological findings. For all of cases, 8 cases were diagnosed as nephrogenic adenomas, 2 cases as atypical nephrogenic adenoma and 1 case as nephrogenic adenoma with malignant transformation. The microscopic appearance of nephrogenic adenoma demonstrated that morphology closely resembled aberrant tubules of the kidney. In addition, atypical nephrogenic adenomas appeared as the presence of cytologic atypia, including nuclear enlargement, nuclear hyperchromasia and prominent nucleoli. The morphologic changes of nephrogenic adenomas with malignant transformation were that tumor cells retained the basic structural characteristics of typical nephrogenic adenomas, and the similar morphological cells lost adhesion ability among cells and presented diffuse solid growth in the surrounding area.Intravesical perfusion was further performed for treating the patients with atypical nephrogenic adenomas or nephrogenic adenomas with malignant transformation. The mean patient follow up was 46 months (range, 24- 104 months), and there was only 1 case of recurrence. Conclusions Nephrogenic adenoma is an uncommon benign lesion of the urinary tract. The symptoms and cystoscopic manifestations are not unique. We reported one patient of nephrogenic adenomas with malignant transformation and provided some evidence for malignant alteration in morphology and invasive behavior. All patients underwent local excision of the lesions. Intravesical perfusion was further performed for treating the patients of atypical nephrogenic adenomas or nephrogenic adenomas with malignant transformation. Whether it is nephrogenic adenoma or atypical nephrogenic adenoma, long-term follow-up after treatment is necessary.

Objective To construct a naive human Fab fragment phage display library,from which the anti-gp96 antibodies may be panned by the gp96 purified from the tissue of urothelial carcinoma in the urinary bladder and provide a basis to new therapy for the malignant tumors.Methods Peripheral blood lymphocytes were isolated from 800 ml of blood,which was obtained from four healthy blood donors.The heavy chain Fd and light chain cDNA synthesized from the total RNA of lympbocytes were amplified by PCR with variable regions 5' and 3' primers of heavy and light chain, and the amplification products were ligated into the phagemid vector pComb3, then the ligated sample was transformed into competent E.coli XL1-Blue by electroperation.The transformed cells were infected with VCSM13 helper phage to yield recombinant phage antibody Fabs.The phagemids abstracted from amplified E.coli were cut with endonucleases such as Sac Ⅰ,Xba Ⅰ,Xho Ⅰ and Spe Ⅰ, and both the phage antibody Fabs and phage-raids abstracted from amplified E.coil were amplified by PCR to monitor the insertion of the genes of light chain or heavy chain Fd fragment.The gp96 purified from the urothelial carcinoma tissue of the bladder by affinity chromatog-raphy on eoncanavalin-A sephnrose and DEAE-sephnrose ion exchange chromatography were utilized as antigens to process three rounds of panning to the original Fab antibody library.Results The quantity of total RNA and cDNA were qualified.By combination of light chain and heavy chain genes, an antibody library containing 6.6×106 clones was obtained, and both the cutting of enzymes and PCR showed that there were the genes of light chain or heavy chain Fd fragment in the phagemids.The gp96 protein was obtained from urothelial carcinoma tissue in the urinary bladder.After having been panned by gp96, the original antibody library gained enrichment by 68 times.Conclusion Utilizing the technology of phage surface display, specific antibody can be gained from the human naive Fab phage display library,which can be used for immunological therapy for tumors.