Overexpression of SNHG12 regulates the viability and invasion of renal cell carcinoma cells through modulation of HIF1α.

BACKGROUND: Cumulative evidences demonstrated the aberrant overexpression of Small Nucleolar RNA Host Gene 12 (SNHG12) in diverse human cancer. However, the expression status and involvement of SNHG12 in renal cell carcinoma is still elusive. METHODS: The expression of SNHG12 was determined by q-PCR. The transcriptional regulation was interrogated by luciferase reporter assay. Cell viability was measured with CCK-8 kit. The anchorage-independent was evaluated by soft agar assay. Cell apoptosis was analyzed by Annexin V/7-AAD double staining. The migration and invasion were determined by trans-well assay and wound scratch closure. The in vivo tumor growth was monitored in xenograft mice model. Protein expression was quantified by immunoblotting. RESULTS: SNHG12 was aberrantly up-regulated in renal carcinoma both in vivo and in vitro. High expression of SNHG12 associated with poor prognosis. Deficiency of SNHG12 significantly suppressed cell viability, anchorage-independent growth and induced apoptosis. In addition, SNHG12 silencing inhibited migrative and invasive in vitro and xenograft tumor growth in vivo. Mechanistically, SNHG12 modulated HIF1α expression via competing with miR-199a-5p, which consequently contributed to its oncogenic potential. MiR-199a-5p inhibition severely compromised SNHG12 silencing-elicited tumor repressive effects. CONCLUSION: Our data uncovered a crucial role of SNHG12-miR-199a-5p-HIF1α axis in human renal cancer.

[Effects of long non-coding RNA RP1-90L14.1 on the biological behaviors of cancer prostate LNCaP cells and its regulating mechanisms].

OBJECTIVE: To investigate the effects of long non-coding RNA RP1-90L14.1 on the proliferation, migration and invasion of prostate cancer LNCaP cells and the expressions of GRIN2A and BACE2. METHODS: Using RT-PCR, we detected the expression of RP1-90L14.1 in LNCaP and LNCaP-AI cells, transiently transfected the RP1-90L14.1 overexpression plasmid (the RP1-90L14.1 group) and vector plasmid (the LNCaP-NC group) into the LNCaP cells, and cultured the two groups of cells with ordinary medium and phenol red-free activated carbon adsorption medium (PRF-ACA). Then we examined the proliferation, migration and invasiveness of the cells by CCK-8 and Transwell, and determined the mRNA and protein expressions of GRIN2A and BACE2 by RT-PCR and Western blot. RESULTS: The expression of RP1-90L14.1 was significantly higher in the LNCaP-AI than in the LNCaP cells (8.49 ± 0.43 vs 2.53 ± 0.95, P < 0.05), and so was that of LNCaP-RP1-90L14.1 in the RP1-90L14.1 than in the LNCaP-NC group after transfection (0.71 ± 0.22 vs 0.02 ± 0.01, P < 0.05). The optical densities (OD) of the cells were 51.95% and 50.69% higher in the RP1-90L14.1 than in the LNCaP-NC group after 72 hours of culture with ordinary medium and phenol red-free ACA (1.22 ± 0.08 vs 0.08 ± 0.05, P < 0.05; 0.79 ± 0.02 vs 0.53 ± 0.05, P < 0.05), and 51.72% and 60.23% higher in the former than in the latter after 96 hours (1.72 ± 0.07 vs 1.13 ± 0.05, P < 0.05; 1.18 ± 0.05 vs 0.73 ± 0.08, P < 0.05). The numbers of the migrating cells cultured with common medium and PRF-ACA were markedly higher in the RP1-90L14.1 than in the LNCaP-NC group after transfection (682.0 ± 42.7 vs 422.0 ± 37.1, P < 0.05; 419.0 ± 42.9 vs 251.0 ± 25.9, P < 0.05), and so were those of the invading cells (507.0 ± 22.2 vs 274.0 ± 19.6, P < 0.05; 352.0 ± 14.1 vs 216.0 ± 14.3, P < 0.05). Statistically significant differences were observed between the RP1-90L14.1 and LNCaP-NC groups in the mRNA and protein expressions of GRIN2A (5.13 ± 0.89 vs 2.09 ± 0.54, P < 0.05; 5.88 ± 0.29 vs 2.03 ± 0.22, P < 0.05) and BACE2 (5.82 ± 0.50 vs 2.53 ± 0.30, P < 0.05; 4.89 ± 0.19 vs 3.37 ± 0.13, P < 0.05). CONCLUSIONS: 　lncRNA RP1-90L14.1 may play important roles in the proliferation, migration and invasiveness of prostate cancer cells. RP1-90L14.1 can promote the expressions of GRIN2A and BACE2 and may have an endogenous competitive relation with GRIN2A and BACE2.

Positive factors associated with quality of life among Chinese patients with renal carcinoma: a cross-sectional study.

Quality of life and positive psychological variables has become a focus of concern in patients with renal carcinoma. However, the integrative effects of positive psychological variables on the illness have seldom been reported. The aims of this study were to evaluate the quality of life and the integrative effects of hope, resilience and optimism on the quality of life among Chinese renal carcinoma patients. A cross-sectional study was conducted at the First Hospital of China Medical University. 284 participants completed questionnaires consisting of demographic and clinical characteristics, EORTC QLQ-C30, Adult Hope Scale, Resilience Scale-14 and Life Orientation Scale-Revised from July 2013 to July 2014. Pearson's correlation and hierarchical regression analyses were performed to explore the effects of related factors. Hope, resilience and optimism were significantly associated with quality of life. Hierarchical regression analyses indicated that hope, resilience and optimism as a whole accounted for 9.8, 24.4 and 21.9% of the variance in the global health status, functioning status and symptom status, respectively. The low level of quality of life for Chinese renal carcinoma patients should receive more attention from Chinese medical institutions. Psychological interventions to increase hope, resilience and optimism may be essential to enhancing the quality of life of Chinese cancer patients.

MiR-378 suppresses prostate cancer cell growth through downregulation of MAPK1 in vitro and in vivo.

Prostate cancer is one of the biggest health problems for the aging male. To the present, the roles of dysregulated microRNAs in prostate cancer are still unclear. Here, we evaluated the anti-proliferative role of miR-378 in prostate cancer. And, we found that the expression of miR-378 was significantly downregulated in clinical prostate cancer tissues. In vitro assay suggested that overexpression of miR-378-suppressed prostate cancer cell migration and invasion promoted cell apoptosis. Furthermore, we identified and validated MAPK1 as a direct target of miR-378. Ectopic expression of MAPK1 rescues miR-378-suppressed cell migration and invasion. In vivo assay demonstrated that the stably miR-378-overexpressed prostate cancer cells displayed a significantly reduction in tumor growth. Taken together, our data suggested that miR-378 may act as a potential therapeutic target against human prostate cancer.

PKC α regulates netrin-1/UNC5B-mediated survival pathway in bladder cancer.

BACKGROUND: Netrin-1 and its receptor UNC5B play important roles in angiogenesis, embryonic development, cancer and inflammation. However, their expression patttern and biological roles in bladder cancer have not been well characterized. The present study aims to investigating the clinical significance of PKC α, netrin-1 and UNC5B in bladder cancer as well as their association with malignant biological behavior of cancer cells. METHODS: Netrin-1 and UNC5B expression was examined in 120 bladder cancer specimens using immunohistochemistry and in 40 fresh cancer tissues by western blot. Immunofluorescence was performed in cancer cell lines. PKC α agonist PMA and PKC siRNA was employed in bladder cancer cells. CCK-8, wound healing assays and flow cytometry analysis were used to examine cell proliferation, migration and cell cycle, respectively. RESULTS: Netrin-1 expression was positively correlated with histological grade, T stage, metastasis and poor prognosis in bladder cancer tissues. Immunofluorescence showed elevated netrin-1 and decreased UNC5B expression in bladder cancer cells compared with normal bladder cell line. Furthermore, cell proliferation, migration and cell cycle progression were promoted with PMA treatment while inhibited by calphostin C. In addition, PMA treatment could induce while calphostin C reduce netrin-1 expression in bladder cancer cells. CONCLUSIONS: The present study identified netrin-1/UNC5B, which could be regulated by PKC signaling, was important mediators of bladder cancer progression.

High FOXM1 expression was associated with bladder carcinogenesis.

The forkhead box M1 (FOXM1) transcription factor plays crucial roles in regulating the proliferation, differentiation, and transformation of cells. Overexpression of FOXM1 is associated with a variety of aggressive solid carcinomas, including bladder cancer. However, the precise role and molecular mechanism responsible for the aggressive action of FOXM1 in bladder cancer remain unclear. Real-time quantitative PCR, Western blot and immunohistochemistry were used to explore FoxM1 expression in bladder cancer cell lines, primary bladder cancer clinical specimens and normal bladder tissues. FoxM1 expression was knocked down by small interfering RNA (siRNA) in T24 cells; proliferation, migration and invasion were assayed. FoxM1 expression was up-regulated in the majority of the bladder cancer tissue specimens at both mRNA and protein levels. Immunohistochemistry analysis showed that FoxM1 expression was significantly correlated with TNM stage and histological grade, metastasis. Experimentally, we found that down-regulation of FoxM1 inhibited cell proliferation, migration and invasion. These results suggested that FOXM1 up-regulation was associated with poor prognosis in bladder cancer, and therefore it might act as a prognostic marker and a new potential target for bladder cancer treatment.

Clinical significance of UNC5B expression in bladder cancer.

UNC5B is a membrane-bound receptor of the neural guidance factor netrin-1 family, with important roles in angiogenesis, neurogenesis, embryonic development, cancer, inflammation and various pathologies. However, its effect on bladder cancer has not been reported. To investigate the association of UNC5B expression with bladder cancer prognosis, 100 cases of clinical bladder cancer and adjacent noncancerous tissue samples, and four bladder cancer cell lines were selected using RT-PCR, Western blot, immunofluorescence and immunohistochemistry to investigate differential expression and cellular positioning of UNC5B, and its relationship with clinicopathological parameters. In 72 % of cases, UNC5B was expressed in both bladder cancer and adjacent noncancerous tissue samples. Expression of UNC5B in bladder cancer tissues increased significantly as cancer stage increased (P < 0.05); UNC5B emerged more in bladder cancer cell lines with lower degrees of malignancy than those with higher degrees of malignancy; UNC5B expression in bladder cancer cells was significantly reduced compared to normal bladder cells (P < 0.05). UNC5B mRNA was down-expressed in about 28 % of bladder cancer tissues. Low UNC5B expression was an independent risk factor for postoperative recurrence in patients with different stages and grades bladder cancer. Furthermore, patients with lower UNC5B expression in tumors had significantly higher recurrence rate after curative surgery and poorer prognosis than those with higher UNC5B expression, suggesting that UNC5B could be used to predict prognosis and recurrence.

Interactional expression of netrin-1 and its dependence receptor UNC5B in prostate carcinoma.

Acting via its receptor UNC5B, netrin-1, one of the major neuronal guidance cues, plays an important role in angiogenesis, neurogenesis, tissue morphogenesis, embryonic development, cancer, inflammation, and various pathologies. However, its role has not been reported in prostate carcinoma. To investigate the association of netrin-1 and UNC5B expression with prostate carcinoma, several human prostate carcinoma cell lines were cultured and the expression levels of netrin-1 and UNC5B were determined by real-time PCR and Western blot. Calphostin C, (the inhibitor of PKC α) and phorbol-12-myristate 13-acetate-PMA (the agonist of PKC α) were used to treat the prostate carcinoma cells, and the cell proliferation and invasion abilities were measured by CCK-8 and wound-healing assays. Proliferation of DU145 cells was affected by the recruitment of PMA and calphostin C in a dose-dependent manner. By immunofluorescence, we identified the localization of netrin-1 and UNC5B in prostate carcinoma cell lines (DU145, 22RV1, PC3, PC3M, and RWEP) and found that netrin-1 was highly expressed in the nucleolus but there was no expression of UNC5B. The co-localization expression of PKC α and UNC5B was confirmed by the confocal immunofluorescence. Higher netrin-1 and lower UNC5B expression in all prostate carcinoma cell lines indicated that netrin-1 and UNC5B could be used to predict metastasis.

The role of fascin in migration and invasion of urothelial carcinoma of the bladder.

INTRODUCTION: To investigate the roles of fascin in migration and invasiveness in bladder urothelial carcinoma. MATERIALS AND METHODS: Immunohistochemical detection of fascin in urothelial carcinoma samples and inhibition the expression of fascin in the urothelial carcinoma cell line were performed, then the differences in cell behaviors before and after silencing of the fascin gene were tested. RESULTS: In our study, we found that overexpression of fascin was more frequent in urothelial carcinoma tissues (p < 0.001). Fascin expression was positively correlated with histological grade (p = 0.024) and pT stage (p < 0.001). After transfection of fascin shRNA, the expressions of fascin in 5637 cells and BIU87 cells were efficiently decreased according to real-time RT-PCR and Western blot analysis. When fascin was inhibited, a significant decrease in migration and invasion, and increase in adhesion were observed in 5637 cells and BIU87 cells. However, there was no significant change in the proliferation of 5637 cells or BIU87 cells with or without inhibition of the fascin gene. CONCLUSIONS: Fascin expression can be used as a predictor for transformation and progression of urothelial carcinoma, and reduction of fascin levels may represent a novel therapeutic strategy for urothelial carcinoma of the bladder.

[Expressions of netrin-1 and UNC5B in prostate cancer and their clinical significance].

OBJECTIVE: To search for a new diagnostic biomarker for prostate cancer by comparing the differences in the expressions of netrin-1 and UNC5B in prostate cancer cells with different invasive abilities. METHODS: We examined the expressions of netrin-1 and UNC5B in five prostate cancer cell lines DU145, 22RV1, PC3, PC3M and RWPE-1 using RT-PCR and Western blot, and positioned the ligands netrin-1 and its receptor UNC5B in the prostate cancer cells by immunofluorescence. RESULTS: Both netrin-1 and UNC5B were expressed in the prostate cancer cells, and the expression of netrin-1 was significantly increased in highly invasive cells (P < 0.05), while that of UNC5B in RWPE-1 (normal) cells (P < 0.05). CONCLUSION: The expressions of netrin-1 and UNC5B are closely related to the infiltration and progression of prostate cancer, and expected to be as potential biomarkers for predicting the malignancy degree of prostate cancer.

[Clinical efficacy of daily low-dose tadalafil on erectile dysfunction-no sexual life].

OBJECTIVE: Erectile dysfunction-no sexual life (ED-NS) is defined as the inability to have enough penile erection hardness and duration so as to have enough confidence in attempting sexual intercourse for more than six months. This study was to investigate the effect of daily low-dose tadalafil on ED-NS. METHODS: We treated 35 ED-NS patients aged 17-35 (25.9 +/- 3.9) years with oral tadalafil at 5 mg qd for 3 months and followed them up for another 3 months after drug withdrawal. We obtained the scores of the patients on Self-estimation Index of Erectile Function-No Sexual Life (SIEF-NS) and compared them before and after medication and at 3 months after drug withdrawal. RESULTS: The patients' SIEF-NS scores were 43.2 +/- 7.1 after medication and 42.1 +/- 7.4 at 3 months after drug withdrawal, both significantly higher than 21.2 +/- 5.9 before treatment (P < 0.05), though there was no significant difference between the former two scores (P > 0.05). CONCLUSION: Daily medication of low-dose tadalafil can significantly improve the erectile function of the patients with ED-NS.

Overexpression of RIN1 associates with tumor grade and progression in patients of bladder urothelial carcinoma.

Ras and Rab interactor 1 (RIN1) is an effector of H-Ras, which plays an important role in the development and progression of carcinomas, but it has not been reported in bladder cancer. Hence, the association of RIN1 expression with prognosis of bladder urothelial carcinoma (UC) was examined. RIN1 mRNA and protein expression in 20 paired UCs and the adjacent normal tissues was detected by quantitative reverse transcription polymerase chain reaction and Western blot. The expression of RIN1 protein in 96 specimens of UCs and 22 specimens of adjacent normal bladder tissues were analyzed by immunohistochemistry. The overall survival (OS) was assessed by univariate and multivariate analysis. Moreover, the progression-free survival (PFS) and recurrence-free survival (RFS), classified by the clinicopathologic features with RIN1 expression, were assessed by multivariate analysis. RIN1 mRNA and protein level was higher in UCs than in the adjacent normal tissues (P < 0.01). Enhanced RIN1 immunoexpression was associated with high histologic grades (P = 0.046), cancer progression (P = 0.047) as well as Ki-67 expression (P = 0.023). Furthermore, the 5-year survival rate was 29% in the subgroup with high level of RIN1 expression, while it was 43% in the subgroup with normal level of RIN1 expression (P < 0.05). Importantly, RIN1 level was revealed as the significant independent prognostic factor for death (P = 0.023) and progression (P = 0.003), but a weak contribution for recurrence (P = 0.063). Collectively, RIN1 expression could be a potential prognostic predictor for UC patients.

Ursolic acid overcomes Bcl-2-mediated resistance to apoptosis in prostate cancer cells involving activation of JNK-induced Bcl-2 phosphorylation and degradation.

Androgen-independent prostate cancers express high levels of Bcl-2, and this over-expression of Bcl-2 protects prostate cancer cells from undergoing apoptosis. Ursolic acid (UA) has demonstrated an anti-proliferative effect in various tumor types. The aim of this study is to evaluate the difference between UA-induced apoptosis in androgen-dependent prostate cancer cell line LNCaP cells and androgen-independent prostate cancer cell line LNCaP-AI cells and to reveal the molecular mechanisms underlying the apoptosis. We found that UA treatment in vitro can effectively induce apoptosis in LNCaP and LNCaP-AI cells. UA can overcome Bcl-2-mediated resistance to apoptosis in LNCaP-AI cells. Intrinsic apoptotic pathways can be triggered by UA treatment because c-Jun N-terminal kinase (JNK) is activated and subsequently provokes Bcl-2 phosphorylation and degradation, inducing activation of caspase-9. Although further evaluation is clearly needed, the present results suggest the potential utility of UA as a novel therapeutic agent in advanced prostate cancer.

[Diagnosis and management of scrotal Paget's disease: report of 23 cases].

OBJECTIVE: To explore the clinical manifestation, management, recurrence factors and prognosis of scrotal Paget's disease. METHODS: We retrospectively analyzed the clinical and pathological data of 23 cases of scrotal Paget's disease diagnosed and treated in our hospital from 1996 to 2008. RESULTS: The disease was confined to one side of the scrotum in 15, and involved the whole scrotum and penis in 8 of the cases. Three patients showed enlarged inguinal lymph nodes in the same side, and 2 in both sides. All the cases were confirmed by biopsy and treated by surgery. Post-operative follow-up was conducted for 2-68 months, which revealed 5 cases of local recurrence and 1 case of death for systemic metastasis. CONCLUSION: Biopsy is proved to be important for the early diagnosis of scrotal Paget's disease, and extended excision of local lesion is a preferred management.

Mineralocorticoid receptor blockade and calcium channel blockade have different renoprotective effects on glomerular and interstitial injury in rats.

We hypothesized that combination treatment with the mineralocorticoid receptor antagonist eplerenone and the calcium channel blocker amlodipine elicits better renoprotective effects than monotherapy with either drug, via different mechanisms in Dahl salt-sensitive (DS) hypertensive rats. DS rats were fed a high-salt diet (4% NaCl) for 10 wk and were treated with vehicle (n = 12), eplerenone (50 mg x kg(-1) x day(-1), p.o., n = 12), amlodipine (3 mg x kg(-1) x day(-1), p.o., n = 12), or eplerenone plus amlodipine (n = 12) after 2 wk of salt feeding. Vehicle-treated DS rats developed proteinuria, which was attenuated by eplerenone or amlodipine. Interestingly, eplerenone attenuated the glomerulosclerosis and podocyte injury, but amlodipine did not. Conversely, treatment with amlodipine markedly improved interstitial fibrosis, while the effect of eplerenone was minimal. Combination treatment markedly improved proteinuria, glomerulosclerosis, podocyte injury, and interstitial fibrosis in DS rats. Renal hypoxia estimated by pimonidazole, vascular endothelial growth factor expression, and density of peritubular endothelial cells was exacerbated by salt feeding. Amlodipine, either as monotherapy or in combination, ameliorated the renal hypoxia, whereas eplerenone treatment had no effect. In conclusion, both eplerenone and amlodipine attenuated renal injuries in high salt-fed DS rats, but the targets for renoprotection differed between these two drugs, with eplerenone predominantly acting on glomeruli and amlodipine acting on interstitium. The combination of eplerenone and amlodipine improved renal injury more effectively than either monotherapy in high salt-fed DS rats, presumably by achieving their own renoprotective effects.

Livin may serve as a marker for prognosis of bladder cancer relapse and a target of bladder cancer treatment.

OBJECTIVES: To evaluate the expression of Livin in bladder cancer, investigate its clinical and prognostic implications, and explore the effect of gene Livin transfection on the proliferation and apoptosis in bladder cancer cells. METHODS: The expression of Livinalpha and beta was detected in 48 bladder cancer samples (G(1) in 23 cases, G(2) in 17 cases, and G(3) in 8 cases. Of the 48 cases, 17 developed relapse) and 15 non-tumor bladder tissues by Western blot and reverse transcription PCR (RT-PCR). Livinalpha-pcDNA3.1(+) was constructed and transfected into T24, BIU-87 and EJ bladder cancer cells. The clone activity of the transfected cells was detected by colony formation analysis. MTT was used to determine the cell proliferation assay. Flow cytometry and acridine orange staining were used to examine apoptosis. Caspase 3 activity assay was also measured. RESULTS: Expression of Livinalpha, but not beta, was detected in 19 of the 48 bladder cancer samples; G(1) was 39.13%, G(2) and G(3) were 41.18% and 37.50%, respectively, which showed no significant (P > 0.05), but not in 15 non-tumor bladder tissues. The positive rate of Livinalpha was significant higher in relapse tumors (58.82%) than in primary tumors (29.03%) (P < 0.05). By the end of 2 years follow-up, the relapse rate in Livin positive patients was 68.42%, and 37.93% in Livin negative group. The difference between the two groups was significant (P < 0.05). Additionally, overexpression of Livinalpha clearly stimulated cell proliferation and inhibited chemical induced apoptosis in bladder cancer cells. CONCLUSIONS: Livin may serve as a promising marker to identify the relapse risk in bladder cancer, and targeting Livin could offer a therapeutic benefit in apoptosis-inducing treatment.

[Diagnosis and treatment for the corticomedullary mixed tumor of adrenal gland].

OBJECTIVE: To study and summarize the diagnosis and treatment for the corticomedullary mixed tumor of adrenal gland. METHODS: The clinical data of 25 cases of adrenal corticomedullary mixed tumor from January 2000 to April 2008 were analyzed retrospectively, which including 9 males and 16 females. The ages were from 25 to 60 years old, and the average age was 39 years old. Thirteen cases had paroxysmal hypertension and 11 cases had central obesity, as well as 8 cases with hypokalemia. There were different degree abnormalities in plasma endocrine hormones in laboratory examination. Every case underwent b-ultrasound and CT normal plus extensive scan to make the diagnosis. RESULTS: Adrenalectomy was performed in the 25 cases, which contain 9 cases of open operations and 16 cases of endoscopic adrenalectomies. All of the cases had blood pressure fluctuation during dissection of the adrenal tumors, with the highest blood pressure reached to 230/140 mm Hg (1 mm Hg = 0.133 kPa). Postoperative histopathological study revealed that the pathological changes was corticomedullary mixed tumor of adrenal gland, which was supported by immunohistochemical study. CONCLUSIONS: In cases with complex phenomenon that can't explain with single cortical or medullary changes, it must beware of the mixed pathological changes in adrenal gland.

[The clinical analysis of 62 cases of the urothelial inverted papilloma].

OBJECTIVE: To investigate the clinical manifestation, biological behavior, diagnosis and treatment of the urothelial inverted papilloma. METHODS: Sixty-two cases of urothelial inverted papilloma were analyzed retrospectively from January 1990 to August 2008. Of the 62 patients, 51 were men and 11 were women. The average age at presentation was 56.4 years old. Fifty-six cases were solitary tumors and 6 were multiple. The most common compliant was macroscopic hematuria. The tumor located at the ureter in 5 cases. Of these cases, 4 were treated by local excision, 1 by nephroureterectomy. One case of multiple ureteral inverted papilloma with coexistent bladder inverted papilloma was treated by total cystectomy. The tumor located at the bladder in 52 cases, with 44 treated by transurethral resection of bladder tumor, 6 by partial cystectomy, 2 by total cystectomy. Four cases had the tumor located at the urethra, with 1 treated by transurethral resection of tumor, 3 by tumorectomy. RESULTS: The postoperative pathological diagnosis of all the 62 cases was inverted papilloma, synchronous urothelial carcinoma in 7. Follow-up data were available in 49 cases. Two cases had a recurrence at 7 months and 79 months, respectively. Three case of subsequent transitional cell carcinoma developed 18 months, 2 years and 6 years later, respectively. CONCLUSIONS: Inverted urothelial papilloma is a kind of benign tumor. It should be differentiated from malignant urothelial tumors. Surgical operation is the main treatment choice. Cystoscopic surveillance and followup are necessary after the operation regularly.

[The clinical study for reducing bladder cancer recurrence after surgical treatment for renal pelvic carcinoma].

OBJECTIVE: To investigate the clinical methods for reducing bladder cancer recurrence after surgical treatment for renal pelvic carcinoma. METHODS: From October 1997 to December 2007, the data of 227 patients undergoing total nephroureterectomy for clinically localized transitional cell carcinoma of the renal pelvis with follow-up results were analyzed retrospectively, including 126 cases of male and 101 cases of female, and the age was 34 to 78 years old. There were 2 kinds of technique used in the dissection of bladder wall circumferentially around the ureteral orifice. Technique A was dissection along the ipsilateral ureter to the bladder wall. Technique B was dissection along the vas deferens to the bladder wall circumferentially around the ipsilateral ureteral orifice and division of the lateral vesical ligament to reach the seminal vesicle. Prophylactic intravesical chemotherapy included 3 method. Method 1 was intraoperative intravesical chemotherapy and then administrated once a week, 10 times in total. Method 2 was intraoperative intravesical chemotherapy and then administrated once a week from the 4(th) week after operation, 10 times in total. Method 3 was intravesical chemotherapy was given once a week from the 4(th) week after operation, 10 times in total. The time of follow-up was 1 to 10 years with regular cystoscopy. Chi-square test and Logistic regression were used to analyzed the recurrence rate of bladder cancer. RESULTS: Recurrence rate of bladder cancer was 27.8% (63/227). The recurrence rates of bladder cancer in patients using technique A and B were 18.0% (7/39) and 12.5% (3/24), respectively (P < 0.05). The postoperative recurrence rates of bladder cancer in patients using 3 kinds of intravesical chemotherapy regimen were 17.9% (11/67), 20.8% (10/48) and 33.3% (17/51), respectively. There was significant difference between the recurrence rates of patients using method 1 and method 3 intravesical chemotherapy (P < 0.05). CONCLUSION: Complete removal of the bladder mucosa circumferentially around the ureteral orifice, administration of the intraoperative intravesical chemotherapy instillation and instillation once a week may be a useful approach to reduce the recurrence of bladder cancer after operation for renal pelvic carcinoma.

Inhibition of miR-34a-5p can rescue disruption of the p53-DAPK axis to suppress progression of clear cell renal cell carcinoma.

DAPK, a transcriptional target of the p53 protein, has long been characterized as a tumor suppressor that acts as a negative regulator in multiple cellular processes. However, increasing studies have suggested that the role of DAPK may vary depending on cell type and cellular context. Thus far, the expression and function of DAPK in clear cell renal cell carcinoma (ccRCC) remain ambiguous. Since ccRCC behaves in an atypical way with respect to p53, whether the p53-DAPK axis functions normally in ccRCC is also an intriguing question. Here, tissue specimens from 61 ccRCC patients were examined for DAPK expression. Functional studies regarding apoptosis, growth, and migration were used to determine the role of DAPK in renal cancer cells. The validity of the p53-DAPK axis in ccRCC was also determined. Our study identified DAPK as a negative regulator of ccRCC, and its expression was reduced in certain subgroups. However, the p53-DAPK axis was disrupted due to upregulation of miR-34a-5p under stressed conditions. miR-34a-5p was identified as a novel repressor of DAPK acting downstream of p53. Inhibition of miR-34a-5p can correct the p53-DAPK axis disruption by upregulating DAPK protein and may have potential to be used as a therapeutic target to improve outcomes for ccRCC patients.