Changes of immune microenvironment and prognosis of bladder cancer patients with positive urinary nuclear matrix protein 22 / 中国医师杂志

Objective:To explore the changes of immune microenvironment and prognosis of bladder cancer patients with positive urinary nuclear matrix protein 22 (NMP22).Methods:Retrospective analysis was made on 86 patients who were diagnosed with bladder cancer in Xuzhou Central Hospital from January 2019 to September 2020. All patients were tested for urinary NMP22 by colloidal gold method. The patients with positive test results were NMP22 positive group, and the patients with negative test results were NMP22 negative group. The expression of CD8, programmed cell death-ligand 1 (PD-L1), programmed cell death protein-1 (PD-1) and PanCK were detected by multiple fluorescent immunohistochemical method on the pathological tissue sections of all enrolled patients with bladder cancer after surgery. Follow-up data of enrolled patients were collected after discharge, and univariate and multivariate Cox analysis was performed on the follow-up data.Results:There were 69 patients in the NMP22 positive group and 17 patients in the NMP22 negative group. The percentage of CD8 and PD-L1 positive cells in NMP22 positive group was significantly higher than that in NMP22 negative group, and the difference was statistically significant (all P<0.05). Univariate analysis showed that tumor stage was correlated with bladder cancer progression ( HR=2.67, P=0.017). Multivariate analysis showed that positive NMP22 was significantly correlated with bladder cancer recurrence and disease progression (all P<0.05). Conclusions:The density of CD8 + T cells and PD-L1 in tumor parenchyma of urinary NMP22 positive bladder cancer patients was higher than that of NMP22 negative patients. Urinary NMP22 positive can be one of the bad prognostic factors of bladder cancer, and the patients with NMP22 positive should strengthen reexamination.

Expression comparison and clinical significance of PD-L1 (22C3) and PD-L1 (SP142) in triple negative breast cancer / 中华肿瘤杂志

Objective: To investigate the expression of programmed death ligand-1 (PD-L1, SP142) and PD-L1 (22C3) in triple-negative breast cancer (TNBC), and analyze their correlation with the clinicopathological factors and prognosis. Methods: The clinicopathologic data of 259 patients with TNBC treated in Cancer Hospital from August 2010 to December 2013 were collected. Whole section of surgical tissue samples were collected to conduct PD-L1 (SP142) and PD-L1 (22C3) immunohistochemical (IHC) staining. The PD-L1 expression in tumor cells and tumor infiltrating immune cells were visually assessed respectively, the relationship between PD-L1 expression and clinicopathologic characterizes were analyzed. Univariable and multivariable Cox proportional hazards regression models were used to test the correlations between PD-L1 expression and disease-free survival (DFS) and overall survival (OS). Results: The positive rates of SP142 (immune cell score, ICs≥1%) and 22C3 (combined positive score, CPS≥1) were 42.1%(109/259) and 41.3%(107/259) in TNBC tissues, respectively, with a total coincidence rate of 82.3%. The Kappa value of positive expression cases was 0.571 and the distribution difference of SP142 and 22C3 positive expression cases was statistically significant (P<0.001). The PD-L1 positive patients were less likely to have vascular invasion (P<0.05), but with higher histological grade and Ki-67 proliferation index (P<0.05). The recurrence/metastasis cases(8) of the patients with positive PD-L1 (SP142) was significantly lower than that of patients with negative PD-L1(SP142, 27, P=0.016). The positive expression of PD-L1 (SP142) patients were longer DFS (P=0.019). The OS of patients with positive PD-L1 (SP142) were longer than those with negative PD-L1 (SP142), but without significance (P=0.116). The positive expression of PD-L1 (22C3) was marginally associated with DFS and OS of patients (P>0.05). Conclusions: The expression of PD-L1 (22C3) is different from that of PD-L1 (SP142) in TNBC, and the two antibodies can't be interchangeable for each other in clinical tests. PD-L1 (SP142) status is an independent prognostic factor of DFS in TNBC. The DFS is significantly prolonged in patients with positive expression of PD-L1 (SP142).

Targeted inhibition of lncRNA CTB-191K22.5 reduces the proliferation and invasion of colorectal cancer SW480 cells and its mechanism / 国际外科学杂志

Objective:To explore the effect of down-regulation of long non-coding RNA (lncRNA) CTB-191K22.5 on the proliferation and invasion of colorectal cancer SW480 cells and the molecular mechanism.Methods:The TCGA database was used to analyze the expression differences of CTB-191K22.5 in colorectal cancer tissues and normal tissues. The CTB-191K22.5 inhibitor (Anti-CTB-191K22.5) and negative inhibitor (Control) were transfected into colorectal cancer SW480 cells, denoted as Observation group and Control group, real-time quantitative polymerase chain reaction (qRT) -PCR) was used to evaluate the inhibitory effect. MTT method and Transwell chamber method were used to evaluate the proliferation and invasion of SW480 cells. Western blot was used to evaluate the protein levels of PI 3K/AKT/mTOR signaling pathway in SW480 cells. The bioinformatics software starBase v2.0 was used to predict the target genes of CTB-191K22.5. qRT-PCR was used to evaluate the expression of CTB-191K22.5 target gene in SW480 cells. Measurement data were expressed as Mean±SD, and t-test was used for comparison between two groups. Results:Compared with normal tissues, the expression of CTB-191K22.5 in colorectal cancer tissues was significantly increased ( P<0.01). The expression of CTB-191K22.5 in SW480 cells of the Control group and Observation group were 6.60±0.85 and 1.08±0.21, respectively. The expression level of CTB-191K22.5 decreased after transfection with Anti-CTB-191K22.5 ( P<0.01). Compared with the Control group, the SW480 cell proliferation ability of the Observation group decreased ( P<0.01). The invasion numbers of SW480 cells in the Control group and Observation group were (135.4 ± 16.29) and (42.24±14.59), respectively. The invasion ability of SW480 cells decreased after transfection with Anti-CTB-191K22.5 ( P<0.01). Compared with the Control group, the expression levels of PI 3K/AKT/mTOR signaling pathway protein in SW480 cells in the Observation group decreased. miR-326 may be the target gene of CTB-191K22.5. Compared with the Control group, transfection with Anti-CTB-191K22.5 significantly increased the expression level of miR-326 in SW480 cells ( P<0.01). Conclusion:CTB-191K22.5 is highly expressed in colorectal cancer tissues, and down-regulation of CTB-191K22.5 may inhibit the proliferation and invasion of colorectal cancer SW480 cells by targeting miR-326.

Effect of miR-939-5p on the migration and proliferation of hepatocellular carcinoma by regulating the expression of USP22 gene / 国际外科学杂志

Objective To investigate the regulation of miR-939-5p on USP22 gene expression and its effect on liver cancer migration and proliferation.Methods The expression of miR-939-5p in hepatoma cell lines (HepG2,MHCC-97H,SMMC-7721,BEL-7404 and Huh7) and normal liver cell line LO2 was detected by realtime PCR (qPCR).The liver cancer cells with the lowest expression were used as experimental subjects,and transfected with miR-939-5p (Experimental group) or miR-NC (Control group).qPCR was used to detect the transfection efficiency of miR-939-5p.Transwell migration assay and MTT proliferation assay were used to detect the migration and proliferation of hepatoma cells after transfected miR-939-5p.Bioinformatics software predicted target genes for miR-939-5p.The dual luciferase reporter gene verified the interaction of miR-939-5p with the target gene.qPCR and Western blotting were used to detect the expression of target genes at mRNA and protein levels after over-expression of miR-939-5p.Measurement data were expressed as (Mean ± SD),and t test was used for comparison between groups.Results The expression of miR-939-5p was significantly lower in hepatoma cell lines than in normal hepatocytes (P ＜0.01),and the expression of miR-939-5p was the lowest in SMMC-7721 cells (P＜0.01).miR-939-5p was efficiently transfected into SMMC-7721 cells [(1.01 ±0.07) vs (20.12 ± 1.27),P ＜0.01].High expression of miR-939-5p inhibited the migration ability (P ＜ 0.01) and proliferative capacity of liver cancer SMMC-7721 cells (P ＜0.05).The USP22 gene may be a target gene of miR-939-5p.The luciferase reporter gene confirmed that miR-939-5p specifically binds to the 3'-UTR of USP22 mRNA (P ＜ 0.01).USP22 expression was decreased at mRNA and protein levels after high expression of miR-939-5p (P ＜ 0.01).Conclusions The expression of miR-939-5p was down-regulated in hepatocellular carcinoma cell lines,and miR-939-5p inhibited the migration and proliferation of liver cancer SMMC-7721 cells.The molecular mechanism was to interfere with the expression of USP22 gene.

Sensitization of lidocaine on hepatoma H22-bearing mice treated by mitomycin / 肿瘤研究与临床

Objective To observe the sensitization of lidocaine on subcutaneous hepatoma H22-bearing mice and abdominal cavity H22 tumor-bearing mice treated by mitomycin. Methods According to the random number table method, the mice were divided into subcutaneous tumor-bearing group and abdominal cavity tumor-bearing group, with 15 mice in each group. The mice in the two groups were further divided into three subgroups: model group, mitomycin group, mitomycin+lidocaine group, with 5 mice in each subgroup. The day before the intraperitoneal injection, the density of H22 cells obtained from peritoneal culture of one mouse was adjusted to 5 ×106/ml. Subcutaneous tumor-bearing group mice were injected H22 cells into the right armpit, and abdominal cavity tumor-bearing group mice were injected H22 cells into the abdominal cavity, 0.2 ml per mouse. Intraperitoneal injection was given after inoculation for 24 h (the experiment day 1), followed by intraperitoneal injection on day 5 and 9. Univariate ANOVA analysis and t test were used to analyze the solid tumor weight and tumor inhibition rate on the 11th day of subcutaneous tumor-bearing mice, and the survival time and life extension rate within 60 days of abdominal cavity tumor-bearing mice. Results The solid tumor weight of subcutaneous tumor-bearing mice model group, mitomycin group and mitomycin + lidocaine group were (3.77 ±1.02) g, (1.67 ±0.28) g, (0.74 ±0.19) g, respectively, and the differences in the three groups were statistically different (F = 31.753, P < 0.01); compared with the subcutaneous model group, the subcutaneous solid tumor weights of mitomycin group and mitomycin +lidocaine group were decreased and the differences were both statistically different (t=2.10, P<0.01; t=3.04, P<0.01); the subcutaneous solid tumor weight of mitomycin+lidocaine group was lower than that of mitomycin group (t= 0.93, P= 0.034). The tumor inhibition rate of mitomycin group and mitomycin +lidocaine group reached 55.70％ and 80.37％ respectively. The survival time of abdominal cavity tumor-bearing mice in model group, mitomycin group and mitomycin + lidocaine group was (16.80±0.84) d, (28.80± 6.30) d, (40.40±12.86) d, respectively, and the differences in the three groups were statistically different (F=10.155, P=0.003); compared with the abdominal cavity tumor-bearing mice model group, the survival time of mice in mitomycin group and mitomycin + lidocaine group was prolonged (t= 12.00, P= 0.041; t= 23.60, P= 0.001), and it was found that survival time in mitomycin + lidocaine group was longer than that in mitomycin group (t=11.60, P=0.047). The life extension rate of mitomycin group and mitomycin+lidocaine group reached 71.43％ and 140.48％ respectively. Conclusion Lidocaine can increase the sensitization of mitomycin on hepatoma H22-bearing mice.

Role of Th22 cells and cytokine interlukin 22 secreted by Th22 in breast cancer / 中国医师进修杂志

Objective To investigate the role of Th22 cells and interlukin 22(IL-22) secreted by Th22 cells in the development of breast cancer. Methods The breast cancer model was established by in situ inoculation of 4T1 breast cancer cells in mice. The experimental group (20 cases) was injected with phosphoric acid buffer (PBS) 0.1 ml containing 4105 4T1 cells into the breast fat pad of mice, while the control group (20 cases) was injected with PBS 0.1 ml into the breast fat pad of mice without cells. Flow cytometry was used to detect Th22 cells in peripheral blood and enzyme linked immunosorbent assay (ELISA) was used to detect the level of IL-22 in serum. The difference of IL-22 levels between Th22 cells and serum was compared between the two groups, and the correlation between Th22 cells and IL-22 was analyzed. Real-time fluorescence quantitative PCR was used to detect the expression of IL-22. The phosphorylation of STAT3 in 4T1 cells treated with IL-22 was detected by Western blot. Results Tumors grew one week after in situ inoculation, and the expression of Th22 cells and IL-22 in serum was significantly increased and positively correlated with that in control group (r＝0.569, P＜0.01 or ＜0.05). The level of IL-22 mRNA in tumor group was significantly increased compared with that in normal group:(22.28 ± 2.52) ng/L vs. (18.92 ± 1.80) ng/L (P＜0.01), and STAT3 was phosphorylated by 4T1 cells after IL-22 treatment. Conclusions Th22 cells and cytokines IL-22 secreted by them can promote the occurrence and development of breast cancer by affecting STAT3 phosphorylation.

Expression of miRNA -22 in esophageal and gastric cancer tissues and cell lines / 中国基层医药

Objective To investigate the expression and clinical value of miRNA -22 in esophageal and gastric cancer tissues and cell lines.Methods Realtime -PCR was performed to detect the expression of miRNA -22 in human esophageal cancer cell lines ECA109,TE -1,TE -8,TE -13 and normal esophageal epithelial cells HEEC,48 cases of esophageal cancer tissues and matched adjacent normal tissues,human gastric cancer cell lines SGC -7901,MKN -45,NCI -N87,AGS,NUGC -3,SUN -1,normal human gastric mucosa cell line GES -1 and normal stomach fibroblastic cell NSFC,88 cases of gastric cancer tissues and matched adjacent normal tissues.Results The expression of miRNA -22 was much less in four esophageal cancer cell lines than that of immortalized normal esophageal epithelial cells HEEC,and the expression of miRNA -22 was much less in six gastric cancer cell lines than that of gastric mucosal epithelial cell line GES -1 and normal stomach fibroblastic cell line NSFC.The esophageal cancer tissues showed aberrant down regulation of miRNA -22 compared with the adjacent non -tumor tissues [(3.51 ±1.05)vs.(11.23 ±2.95),t =18.13,P <0.05].The gastric cancer tissues showed aberrant down regula-tion of miRNA -22 compared with the adjacent non -tumor tissues [(2.15 ±1.23)vs.(9.14 ±2.86),t =22.93, P <0.05].Conclusion The expression of miRNA -22 was much lower in esophageal and gastric cancer tissues and cell lines,which provided basement to nosogenesis,early diagnosis and create drug treatment of the cancers.

The expression and clinical significance of microRNA -22 in gastric cancer / 中国基层医药

Objective To investigate the expression and clinical value of miRNA -22 in gastric cancer tissues.Methods Real -time PCR was used to detect the miRNA -22 expression in gastric cancer tissues and matched adjacent tissues.The correlations of miRNA -22 expression with clinic pathological features were analyzed. Results 87.5%(77 /88)of the gastric tumor tissues showed aberrant down regulation of miRNA -22 compared with adjacent non -tumor tissues (χ2 =69.32,P 0.05 ). Conclusion The lower expression of miRNA -22 is associated with clinic pathological features.

MiR-34b suppresses the proliferation of bladder cancer BIU-87 cells / 肿瘤

Objective: To investigate the effect of microRNA-34b (miR-34b) on the proliferation of bladder cancer BIU-87 cells, and to exploreObjective: To investigate the effect of microRNA-34b (miR-34b) on the proliferation of bladder cancer BIU-87 cells, and to explore Methods: The expression levels of miR-34b in bladder cancer BIU-87 cells, SV-HUC-1 cells and renal tubular epithelial HK-2 cells were determined by real-time fluorescent quantitative PCR. After transfection with miR-34b mimic, the proliferation rate and clone formation rate of BIU-87 cells were detected by MTT assay and clone formation assay, respectively. After co-transfection with miR-34b mimic and ubiquitin-specific peptidase 22 (USP22)-wide type (WT) or USP22-mutation type (Mut), the specific binding ability of miR-34b to 3'-untranslated region (3'-UTR) in USP22 gene was examined by luciferase reporter system. The expression levels of USP22 mRNA and protein in BIU-87 cells after transfection with miR-34b mimic were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. Results: The expression level of miR-34b in human bladder cancer BIU-87 cells was lower than those in SV-HUC-1 cells and renal tubular epithelial HK-2 cells (both P < 0.05). The proliferation rate and clone formation rate of BIU-87 cells in miR-34b mimic transfection group were lower than those of blank control cells (BIU-87 cells without any transfection) and negative control cells [BIU-87 cells transfected with miRNA mimic negative control (miRNA mimic NC)] (all P < 0.05). The result of luciferase reporter system indicated that miR-34b targeted 3'-UTR in USP22 gene. The luciferase activity of BIU-87 cells in co-transfection with miR-34b mimic and recombinant vector USP22-WT group was decreased (P < 0.05). The expression level of USP22 protein in BIU-87 cells in miR-34b mimic transfection group were lower than those in the blank control and the negative control groups (all P < 0.05). Conclusion: miR-34b can suppress the proliferation of bladder cancer BIU-87 cells. This effect may be related to the expression of USP22.

The validation of EORTC QLQ-STO22 scale in patients with gastric cancer in China / 肿瘤研究与临床

Objective To test the effectiveness, reliability and acceptability of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-STO22 scale in gastric cancer patients in China. Methods One hundred and twenty-eight cases were collected in the Affiliated Cancer Hospital of Xiangya School of Medicine of Central South University from September 2014 to April 2015. All the patients completed the EORTC QLQ-STO22 and EORTC QLQ-C30 scales and given the Zubrod-ECOG-WHO (ZPS) score. Karen Bach coefficient and Pearson correlation test were used for statistical analysis while using ZPS score to detect EORTC QLQ-STO22 in validity. After score was standardized, P<0.05 represented the difference had statistical significance. Results The Karen Bach coefficient was 0.607-0.830, confirming that the EORTC QLQ-STO22 scale had good reliability. A number of enhanced analysis showed that the scale had good convergent validity and divergent validity. In the same or similar dimension, EORTC QLQ-C30 and EORTC QLQ-STO22 scales had good correlation and the correlation scores were higher than 0.400. The patients were divided into four groups according to ZPS score, with ZPS score increase, the overall quality of life scores were decreasing and entries associated with symptoms were increasing, showing difference between different groups(P<0.05). Conclusion The EORTC QLQ-STO22 scale shows high reliability and validity that can be used for assessing the quality of life of patients with advanced gastric cancer in China.

Clinical significance of combined detection with urinary nuclear matrix protein 22 and cytokeratin 20 mRNA in the monitoring of bladder tumor recurrence / 重庆医学

Objective To detect the expression of urinary nuclear matrix protein 22(NMP22) and cytokeratin 20(CK20) mRNA in the monitoring of bladder tumor recurrence ,and to explore the clinical value of combined detection of urinary NMP22 and CK20 mRNA in the monitoring of bladder tumor recurrence .Methods Enzyme‐linked immunosorbent assay(ELISA) and nested reverse transcriptase polymerase chain reaction(Nested RT‐PCR) were used to detect the expression of NMP22 and CK20 mRNA in the u‐rine of 46 patients with recurrent bladder cancer tumor (recurrent group) ,66 patients without recurrent tumor (no‐recurrent group) and 40 healthy volunteers(control group) respectively .Results The expression of NMP22 and CK20 mRNA in the urine of control group were negative .There was statistically significant difference between the positive expression rate of NMP 22 and CK20 mRNA in the urines of the recurrent group[78 .3% (36/46) ,80 .4% (37/46))] and that of the no‐recurrent group[6 .1% (4/62) , 6 .1% (4/62)] and the control group respectively (P0 .05) .The expression level of NMP22 in recurrent tumor increased obviously along with the progression of the pathological grade and clinical classification of tumor (P0 .05) .Conclusion The positive expression of CK20 mRNA may also indicate tumor multiplicity .Combined detection of NM P22 and CK20 mRNA significantly increases the sensitivity and specificity in clinical detection .

Overexpression of heat shock protein 22 inhibits the growth of hematopoietic malignant tumor cells / 白血病·淋巴瘤

Objective To investigate the effects of overexpression of heat shock protein 22(HSP22) in hematopoietic malignant tumor cell lines.Methods A lentiviral system was used to mediate transduction of HSP22 complementary DNA-containing expression vector or empty vector into K562 and Namalwa cells.The transduction effeciency was tested by fluorescence microscope scan and flow cytometry.Semi-quantitative RT-PCR and Western blot were used to identify the expression levels of HSP22 mRNA and protein.Growth curve analysis,cell cycle analysis,colony-forming assay,tumor growth in nude mice and apoptosis analysis were used to evaluate the role of HSP22 in K562 and Namalwa cells.Results Lentivector expression systemmediated delivery of HSP22 into K562 and Namalwa cells can inhibit colony forming of K562 and Namalwa cells,the average numbers of colonies per well were 108,72,125 and 80 for K562-V,K562-H,Namalwa-V and Namalwa-H respectively (P =0.000 16 and 0.000 37 for K562 and Namalwa respectively).HSP22 transduction can also inhibit proliferation of Namalwa cells in vitro (P =0.015,0.042 and 0.048 for day 5,6 and 7 respectively) and K562 cells in vivo (P =0.022 for day 21).No significant difference in cell cycle and apoptosis was found in K562 and Namalwa cells compared with controls (all P ＞ 0.05).Conclusion Overexpression of HSP22 could inhibit the growth of hematopoietic malignant tumor cell lines K562 and Namalwa.

Effects of decitabine on heat-shock protein 22 expression in malignant hematopoietic cells / 白血病·淋巴瘤

Objective To investigate the effects and possible mechanisms of decitabine on heat-shock protein 22 (HSP22) expression in hematopoietic tumor cell lines and bone marrow samples from patients with hematopoietic tumor.Methods The expression of HSP22 in 13 hematopoietic tumor cell lines,20 primary patients' samples and 10 normal donor' samples were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).After HSP22 induction with a demethylating agent decitabine (2 μmol/L),the methylation of the HSP22 promoters in hematopoietic tumor cell lines,healthy donors and bone marrow samples from patients with hematopoietic tumor were detected by methylation specific PCR (MSP).Results Expression of HSP22 was not detected in 13 hematopoietic tumor cell lines,20 primary patients' samples or 10 healthy donors' samples.Decitabine can induce the expression of HSP22 in hematopoietic tumor cell lines and bone marrow samples from patients with hematopoietic tumor.Decitabine can maintain partially demethylation of HSP22 promoters in hematopoietic tumor cell lines.HSP22 promoters were highly methylated in BMMC of the healthy donors and patients with hcmatopoictic tumor.Conclusion Decitabine can induce the expression of HSP22 in hematopoietic tumor cells partly by demethylation of HSP22 promoters.

Clinical value of NMP22 and cytology in bladder cancer / 国际外科学杂志

Objective To investigate the clinical applications of nuclear matrix protein 22 (NMP22) and urine cytology in early diagnosis,monitoringrecurrence and determining prognosis of bladder cancer.Methods Ninty-six urine specimens,including 45 cases before the resection of bladder cancer (pathologically confirmed),20 cases after the resection of bladder cancer and 31 cases with benign urinary tract condition,were both selected in detecting NMP22 by enzyme-linked i mmunosorbent assay (ELISA),and the results were compared with urinary cytology by x2 test.Results The NMP22 content of 45 cases before the resection of bladder cancer was 9.3 to 112.5 U/mL,the median was 48.7 U/mL.The NMP22 content of 31 cases with benign urinary tract condition was from 2.1 to 14.7 U/mL,the median was 7.9 U/mL.The NMP22 content of 20 cases after the resection of bladder cancer was from 4.3 to 18.7 U/mL,the median was 8.9 U/mL.The median of NMP22 before the resection of bladder cancer was significantly higher than the median in patients with benign urinary,the difference was statistically significant (P ＜0.05).Considering NMP22 ≥ 10 U/mL as the critical value,the sensitivity of the NMP22 in diagnosing bladder cancer was 82.2％ and the specificity was 70.9％.And the sensitivity of urine cytology was 31.1％ and the specificity was 100％.The recurrence of 9 cases was confirmed by cystoscopy in 20 cases after the resection of bladder cancer.Conclusion The NMP22 can be a effective biomarker in the early screeningand postoperative follow-up of bladder cancer.

Patients with a negative cystoscopy and negative Nmp22® Bladderchek® test are at low risk of missed transitional cell carcinoma of the bladder: a prospective evaluation

OBJECTIVES: Urine based tumor markers have uncertain utility in diagnosis or surveillance of patients with bladder cancer while cytology is commonly used. We evaluated whether cytology provides additional diagnostic information in patients with a negative NMP22® BladderChek® test (BladderChek) and negative cystoscopy. MATERIALS AND METHODS: We performed subset analyses of 2 large prospective multi-center databases evaluating BladderChek for UCB detection and surveillance. These cohorts were analyzed for presence of cancer and result of urine cytology in setting of a negative cystoscopy and negative BladderChek. Subsequently, we prospectively performed cystoscopy, cytology and BladderChek on 434 patients at our institution being evaluated for UCB. RESULTS: In the detection database (n = 1331), 1065 patients had a negative cystoscopy and BladderChek. There were 3 cancers (stages Ta, Tis and T1) and cytology was atypical in one and reactive in two. In the surveillance cohort (n = 668) patients, 437 patients had negative cystoscopy and BladderChek. Cancer was found in 2 patients (stages Tis and Ta). The patient with Tis has dysplastic cytology and Ta tumor had reactive cytology. In our cohort of 434 patients, 288 pts had negative cystoscopy and BladderChek. One cancer was missed, a Ta ureteral urothelial carcinoma with a reactive cytology. CONCLUSIONS: In patients with negative cystoscopy and BladderChek, very few cancers are missed and cytology was not effective in detection. Use of a point-of-care test in conjunction with cystoscopy in lieu of cytology could decrease cost, provide immediate results, improve negative predictive value and reduce the uncertainty that results from inconclusive cytologic results.

Usefulness of the NMP22BladderChek Test for Screening and Follow-up of Bladder Cancer

PURPOSE: We evaluated the usefulness of the nuclear matrix protein 22 BladderChek (NMP22BC) test for the screening and follow-up of bladder cancer. MATERIALS AND METHODS: From February 2006 to September 2009, we enrolled 1,070 patients who had hematuria or who were being followed up for bladder cancer. We compared the sensitivity and specificity of the NMP22BC test with those of urine cytology. RESULTS: The sensitivity of the NMP22BC test (77.5%) was significantly higher than that of urine cytology (46.3%). The specificity of the NMP22BC test was 88.8%, compared with 97.9% for urine cytology. The sensitivity of the NMP22BC test (81.8%) in non-muscle-invasive bladder cancer was higher than that of cytology (36.4%). However, the sensitivity of the NMP22BC test and of urine cytology in invasive bladder cancer were 57.1% and 92.9%, respectively. The sensitivity of the NMP22BC test was higher for low-grade bladder cancer (83.9%) than for high-grade (62.5%), and the sensitivity of cytology was higher for high-grade bladder cancer (66.7%) than for low-grade (37.5%). Follow-up bladder cancer was detected in 262 patients. The sensitivity of the NMP22BC test in that group (72.7%) was decreased and the specificity (91.7%) was increased. The sensitivity of cytology (54.5%) in the follow-up group was increased and the specificity (95.6%) was decreased. The presence of pyuria was significantly associated with the lower specificity of the NMP22BC test. CONCLUSIONS: The greater sensitivity of the NMP22BC test may be more useful for the diagnosis of non-muscle-invasive bladder cancer and low-grade bladder cancer than for the diagnosis of invasive or high-grade bladder cancer. If the NMP22BC test is performed in the absence of pyuria, it may play a compensatory role for urine cytology.

EMP3 Overexpression in Primary Breast Carcinomas is not Associated with Epigenetic Aberrations

Epithelial membrane protein 3 (EMP3) is a trans-membrane signaling molecule with important roles in the regulation of apoptosis, differentiation and invasion of cancer cells, but the detailed is largely still unknown. We analyzed the mRNA levels and methylation statuses of EMP3 in 63 primary breast carcinomas and assessed their correlations with clinicopathologic variables. The expression of EMP3 mRNA in primary breast carcinomas was significantly higher than the expression of 20 normal breast tissues (p<10(-7)). EMP3 overexpression in breast carcinomas was significantly related to histological grade III (p=3.9X10(-7)), lymph node metastasis (p= 0.003), and strong Her-2 expression (p=3.3X10(-6)). Hypermethylation frequencies of EMP3 were detected in 36.5% of breast carcinomas by methylation-specific polymerase chain reaction. However, no significant correlations were found between methylation status of EMP3 and mRNA expression levels as well as other clinical parameters. In conclusion, EMP3 may be a novel marker of tumor aggressiveness. Overexpression of EMP3 in primary breast carcinoma is not associated with DNA methylation.

Expression of imprinted tumor suppressor gene SLC22A18 in breast eancer / 中华普通外科杂志

Objective To investigate the expression of sLc22A1 8,an impfinted tumor suppressor gene,in breast cancer and explore the relationship between expression of SLC22A18 and the pathogenesis of breast cancer. Methods Real-time quantitative reverse transcriptase-polymerase chain reaction was applied on 46 cases of infiltrating duetal breast carcinoma(IDC),46 csges of corresponding adjacent noncancerous tissues and 20 benign breast tissues in order to detect mRNA expression of SLC22A18 gene.Protein expression was detected by immunohistochemistry.Statistical analysis was carried out to analyse the correlation between SLC22A18 gene expression and various elinical parameters in these breast cancer patients. Results SLC22A18 mRNA expression in 46 IDC tissues Was lower than that in all corresponding adjacent non-cancerous tissues(Z=-4.900,P＜0.01).SLC22A18 mRNA expression was lower in breast cancer eases,when compared with that in benign cases(Z=-3.182,P＜0.01).SLIC22A18 mRNA expression in 40 IDCs Was lower than that in 6 dutal carcinoma in situ(part of IDC)(Z=-2.022,P＜0.05).There was a decreased or completely diminished SLC22A18 protein expression in breast cancer.A significant difference of SLC22A18 protein expression was also observed in IDC and benign groups(P＜0.05).Neither mRNA nor protein expression of SLC22A18 gene correlated with clinieopathologic parameters such as age of patients,size of tumor,ehnical stage,pathologic subtype,histologlc grade or lymph node metastasis(P＞0.05).Condusion Decreased expression of SLC22A18 gene may play an important role in the carcinogenesis of IDC.

Clinical significance of NMP 22 in early diagnosis of bladder cancer / 中华泌尿外科杂志

10 U/ml was determined as positive value.Urinary NMP 22 protein was elevated in 22 cases.Bladder cancer was diagnosed in 11 cases.The sensitivity and specificity of the NMP 22 test were 100%(11/11) and 81%(46/57),respectively.Cystoscopy alone identified 35% of the cancers (4/11).Among 22 cases with elevated NMP 22,1 case was dignosized as bladder cancer during 1 year visit. Conclusions Urine NMP 22 is a new useful marker in early diagnosis of bladder cancer.

Urine nuclear matrix protein 22 and bladder tumor antigen test in the screening of bladder tumor recurrence / 中华泌尿外科杂志

Objective To evaluate the quantitative determination of urine nuclear matrix protein 22 (NMP-22) and bladder tumor antigen (BTA) in the screening of bladder tumor recurrence. Methods 90 patients who had undergone TURBT were recruited in this study.Standard ELISA test was used to determine the quantity of NMP-22 in urine and urine BTA stat test was also performed.the findings were analyed with reference to the cystoscopic and pathological results. Results In comparison with the results of cystoscopy,urine NMP-22 test might denote 77% (32/43) recurrence of bladder cancer and this positive rate would increase to 93% (40/43) with the combined use of urine NMP-22 and BTA test. Conclusions Examination of NMP-22 in urine is a rapid and effective means of detecting the recurrence of bladder cancer.With the combined use of BTA test,urine NMP-22 determination might be a useful non-invasive method in screening the recurrence of bladder cancer,and the conventional invasive cystoscopy might be avoided.