The Significance of INHBE Expression in the Cancer Cells of Clear-Cell Renal Cell Carcinoma.

BACKGROUND: Activins and inhibins are structurally related dimeric glycoprotein hormones belonging to the transforming growth factor-ß superfamily but whether they are also involved in malignancy is far from clear. No study has reported the expression of INHBE in kidney cancer. The purpose of this study was to examine the expressions of INHBE in the tumor tissue of patients with clear-cell renal cell carcinoma (ccRCC) and to explore the pathologic significance. METHODS: The INHBE mRNA expression in the tumor tissue of ccRCC patients was analyzed by using RNA sequencing data from the TCGA database. To examine the expression of inhibin ßE protein, 241 ccRCC patients were recruited and immunohistochemistry was performed on the tumor tissue of these patients along with 39 normal renal samples. The association between the inhibin ßE expression level and patient's clinicopathological indices was evaluated. RESULTS: In the normal renal tissue, inhibin ßE was found to be expressed mainly by renal tubular epithelial cells. In the tumor tissue, inhibin ßE was expressed mainly in cancer cells. The expressions of INHBE mRNA and protein in the tumor tissue of ccRCC patients increased significantly compared with those in normal renal samples. There was a significant correlation between the level of inhibin ßE in the tumor tissue and tumor grade. Patients with a lower inhibin ßE expression in the tumor tissue were found to have a longer overall survival and disease-specific survival. CONCLUSIONS: INHBE might be involved in the pathogenesis of ccRCC and function as a tumor promoter.

A theoretical study on the excited-state deactivation paths for the A-5FU dimer.

The photostability of DNA plays a key role in the normal function of organisms. A-5FU is a base pair derivative of the A-T dimer where the methyl group is replaced by a F atom. Here, accurate static TDDFT calculations and non-adiabatic dynamic simulations are used to systematically investigate the excited-state decay paths of the A-5FU dimer related to the proton transfer and the out-of-plane twisting deformation motion of A and 5FU in the 1ππ* and 1nπ* states. CC2 is used to check the accuracy of the current TDDFT calculations. Our results show that the deformation of the C[double bond, length as m-dash]C or C[double bond, length as m-dash]N double bond in A and 5FU provides an efficient pathway for the depopulation of the lowest excited states, which can compete with the excited-state proton transfer paths in the dimer. This finding indicates that monomer-like decay paths could be important for the photostability of weakly hydrogen-bonded DNA base pairs and provide a new insight into the excited-state decay paths in base pairs and their analogues.

[Subsequent retroperitoneoscopy for patients with previous ipsilateral retroperitoneal surgery].

OBJECTIVE: To evaluate the feasibility and clinical results of subsequent retroperitoneoscopic surgery for patients with previous ipsilateral retroperitoneal surgery through frank incision. METHODS: A total of 10 patents were selected for subsequent laparoscopic surgery through retroperitoneal approach. Among them, there were recurrent renal cysts (n = 4) including a history of open surgery (n = 1) and retroperitoneal surgery (n = 3) and nonfunctional kidneys (n = 6) including open nephropyelopolasty (n = 3), retroperitoneoscopic nephropyelopolasty (n = 1) and retroperitoneoscopic ureterolithotomy (n = 2). The mean surgical duration was (12-85) 38.6 months. All patients underwent retroperitoneoscopy. Decortication was performed for renal cysts and nephrectomy for nonfunctional kidneys. RESULTS: All operations were successfully performed with a mean surgical duration of 97 (40-185) minutes and a mean volume of blood loss 125 (20-460) ml. Among 4 cases with intraoperative peritoneal rupture, one case had renal cyst on ventral side. After enlargement, the procedure was performed through peritoneal cavity. The mean postoperative hospital stay was 5.6 (3-9) days. Nine patients received a mean follow-up period of 21.5 (3-47) months. All symptoms were relieved without any occurrence of postoperative complications. CONCLUSION: For patients with previous ipsilateral retroperitoneal surgery, retroperitoneoscopy may be feasible for properly selected cases.

By Increasing the Expression and Activation of STAT3, Sustained C5a Stimulation Increases the Proliferation, Migration, and Invasion of RCC Cells and Promotes the Growth of Transgrafted Tumors.

BACKGROUND: Contradictive results about the direct role of C5a/C5aR1 axis in different cancer cells have been reported. The direct effect of C5a on human renal cell carcinoma (RCC) cells and the underlying mechanism are not clear. The aim of this study is to investigate the role of C5a/C5aR1 axis in RCC cells and its working mechanism. METHODS: RCC cells were infected with lentivirus Lenti-C5a, which was designed to over-express secretory C5a in the cells, or directly treated with recombinant C5a, the influence of these treatments in the cells and the underlying mechanism were explored. RESULTS: Transfection of RCC cells with Lenti-C5a markedly increased the production of C5a and significantly increased the proliferation, migration, and invasion of RCC cells, but direct addition of C5a to the cell culture medium had no such effects though it indeed induced a transient intracellular calcium rise. RCC cells were found to express carboxypeptidase D and M, which reportedly to inactivate C5a. Also, the RCC cells stably transfected with Lenti-C5a produced larger transgrafted tumors in nude mice compared with the non-transfected or control virus transfected cells. In addition, over-expression of C5a significantly increased the expression and phosphorylation of STAT3 as well as the phosphorylated JNK level. Furthermore, the effect of C5a over-expression on RCC cells' proliferation, migration, and invasion could be blocked by Stattic, a STAT3-specific inhibitor. CONCLUSION: Chronic over-activation of C5a/C5aR1 axis could directly increase RCC cells' proliferation, migration, and invasion and thus contribute directly to the progression of the disease. Over-activation of STAT3 pathway is among the underlying mechanism.

KDF1, a Novel Tumor Suppressor in Clear Cell Renal Cell Carcinoma.

KDF1 has been identified as a key regulator of epidermal proliferation and differentiation, but it is unknown whether KDF1 is involved in the pathogenesis of malignancy. No study has reported the expression and function of KDF1 in renal cancer. To explore the pathologic significance of KDF1 in clear cell renal cell carcinoma (ccRCC), the expression level of KDF1 protein in the tumor tissue of ccRCC patients was examined by immunohistochemistry and Western blot while the expression level of KDF1 mRNA was analyzed by using the data from TCGA database. In vitro cell experiments and allogeneic tumor transplantation tests were performed to determine the effects of altered KDF1 expression on the phenotype of ccRCC cells. Both the KDF1 mRNA and protein were found to be decreasingly expressed in the tumor tissue of ccRCC patients when compared with the adjacent non-tumor control tissue. The expression level of KDF1 in the tumor tissue was found to correlate negatively with the tumor grade. Patients with higher KDF1 in the tumor tissue were found to have longer overall survival and disease-specific survival time. KDF1 was shown to be an independent factor influencing the disease-specific survival of the ccRCC patients. Overexpression of KDF1 was found to inhibit the proliferation, migration and invasion of ccRCC cells, which could be reversed by decreasing the expression of KDF1 again. ccRCC cells with KDF1 overexpression were found to produce smaller transgrafted tumors. These results support the idea that KDF1 is involved in ccRCC and may function as a tumor suppressor.

[A comparative study of nephrectomy and radical nephrectomy for renal cell carcinoma].

OBJECTIVE: To compare the clinical efficacy and safety of nephrectomy versus radical nephrectomy for renal cell carcinoma (RCC). METHODS: A total of 134 patients with renal carcinoma without metastasis in lymphatic system and distant sites were recruited. In random, 69 cases of renal cell carcinoma were elected for nephrectomy and the others radical nephrectomy. The operating time, blood loss, fasting time, postoperative hospital stay, information of tumor recurrence and metastasis, survival time without tumor, survival rate and perioperative complication were compared between two groups. RESULTS: In cases of nephrectomy, the operating time ranged from 60 - 135 minutes and blood loss 70 - 100 ml. In 4 cases, membrana pleuro-peritonealis was damaged. The fasting time ranged from 6 - 24 hours and postoperative hospital stay 5 - 8 days; the staging of all 69 cases was detected; follow-up studies ranged from 5 - 15 years, finding 1 case tumor metastasis in adrenal body and 1 case recurrent tumor in cases of radical nephrectomy, operating time ranged from 105 - 185 minutes and blood loss 150 - 2000 ml. Membrana pleuro-peritonealis was breached in 3 cases. The fasting time ranged from 12 - 90 hours and postoperative hospital stay 8 - 12 days. The staging of all 65 cases was detected. Follow-up studies of 5 - 15 years revealed 1 case of tumor metastasis in brain and 1 case of recurrent tumor. There was no significant difference in perioperative complication, tumor recurrence, tumor metastasis and survival time without tumor between those two groups (P > 0.05). The blood loss, operating time, fasting and postoperative hospital stay were less than that in radical nephrectomy group (P < 0.05). CONCLUSION: In patients without metastasis in lymphatic system and distant sites, nephrectomy is both effective and safe. It has the advantages of a short operating time, a short postoperative hospital stay and less damage and blood loss than radical nephrectomy.

[Preventive strategies and causes of common complications of ureteroscopy].

OBJECTIVE: To discuss the causes of common complications of ureteroscopy and how to prevent them. METHODS: A total of 768 cases of common complications of ureteroscopy were retrospectively analyzed from February 2004 to February 2009. RESULTS: The intra-operative complications were failed entry (n = 6, 0.78%), ureterostoma injury and ureterostoma submucosa pseudocana (n = 12, 1.56%), ureteral perforation (n = 16, 2.08%), stone displacement (n = 13, 1.87%) and ureteral mucosa evulsion (n = 3, 0.39%). And the post-operative complications were lumbago or renal colic (n = 11, 1.43%), infection (n = 9, 1.17%)and severe hematuria (n = 5, 0.65%). CONCLUSION: Skillful operative techniques and strict indications are key to reducing complications of ureteroscopy.

Purple sweet potato anthocyanin exerts antitumor effect in bladder cancer.

Bladder cancer (BC) is the most common malignant disease. The developing of economically sustainable and available agents for the treatment of BC is required. Purple sweet potato anthocyanin (PSPA) has been shown to have antitumor abilities. The present study aimed to evaluate the potential role of PSPA in BC treatment. CCK-8 assay was used to assess the viability of BC cells. Flow cytometry assays were performed to evaluate the mitochondrial membrane potential (MMP), cell apoptosis and cell-cycle distribution. Real-time PCR (RT-PCR) and western blot analysis were performed to determine the expression of the target genes. The results of this study revealed that PSPA reduced the viability of BC in a dose-dependent manner. The MMP collapse was aggravated by the PSPA treatment. The apoptosis rate was higher in the PSPA groups than that in the control group. The expression of the pro-apoptosis genes, including cleaved caspase-3, Fas, Fasl, Bcl-2-associated X proteins (Bax) and anti-apoptotic gene (Bcl-2) was induced and decreased by PSPA, respectively. The cell-cycle progression was suppressed by the presence of PSPA. The activation of the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt (PI3K/Akt) signaling pathway was suppressed by PSPA treatment during BC treatment. The PI3K/Akt signaling was closely related to the antitumor effect of PSPA in BC. The present study provided evidence regarding the treatment of BC and enhanced the understanding of the potential role that PSPA plays in cancer prevention.

Lycium barbarum polysaccharides inhibit proliferation and migration of bladder cancer cell lines BIU87 by suppressing Pi3K/AKT pathway.

The aim of this study was to verify whether Lycium barbarum polysaccharides inhibits proliferation and migration of BIU87 cells through Pi3K/AKT pathway. Different concentrations of Lycium barbarum polysaccharides were used to incubate with BIU87cells. LY-294002 and IGF-1 were used to inhibit and activate Pi3K/AKT pathway respectively. MTT were used to investigate the proliferation of BIU87cells. Transwell chambers and wound healing were used to test the migratory ability of BIU87cells. Western blotting were used to investigate the expressions of P21,P27,MMP-2, MMP-9, AKT and p-AKT in BIU87cells. Compared with the control group, the proliferation and migration of BIU87cells and the expression of p-AKT were significantly decreased in the study group; the inhibitory effect of the downregulation of p-AKT by LY-294002on the induction of BIU87cells proliferation and migration was identical to that of Lycium barbarum polysaccharides; upregulation of p-AKT by IGF-1 reversed the Lycium barbarum polysaccharides-induced inhibition of BIU87cells dedifferentiation. In conclusion, LBP inhibits the proliferation and migration of BIU87 cells by suppressing Pi3K/AKT signaling pathway.