Jian-Ping Che

Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma

Long noncoding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has recently been identified to be involved in tumorigenesis of several cancers such as lung cancer, pancreatic cancer, and cervical cancer. However, the role of lncRNA MALAT1 in clear cell renal cell carcinoma (ccRCC) remains unclear. Expression levels of lncRNA MALAT1 in ccRCC tissues and renal cancer cell lines were evaluated by quantitative real-time PCR (qRT-PCR), and its association with overall survival of patients was analyzed by statistical analysis. Small interfering RNA (siRNA) was used to suppress MALAT1 expression in renal cancer cells. In vitro assays were conducted to further explore its role in tumor progression. The expression level of MALAT1 was higher in ccRCC tissues and renal cancer cells compared to adjacent non-tumor tissues and normal human proximal tubule epithelial cells HK-2. The ccRCC patients with higher MALAT1 expression had an advanced clinical features and a shorter overall survival time than those with lower MALAT1 expression. And multivariate analysis showed that the status of MALAT1 expression was an independent predictor of overall survival in ccRCC. Additionally, our data indicated that knockdown expression of MALAT1 decreased renal cancer cell proliferation, migration, and invasion. Our data suggested that lncRNA MALAT1 was a novel molecule involved in ccRCC progression, which provided a potential prognostic biomarker and therapeutic target.

Combination of quercetin and hyperoside has anticancer effects on renal cancer cells through inhibition of oncogenic microRNA-27a

Quercetin and hyperoside (QH) in combination (1:1 ratio) have previously been shown to inhibit the growth of human leukemia cells. Here, we investigated the anticancer activity of the same mixture in 786-O renal cancer cells. QH decreased the generation of reactive oxygen species (ROS) by up to 2.25-fold and increased the antioxidant capacity by up to 3-fold in 786-O cells (3.8-60 μg/ml), whereas IC50 values for viability were 18.2, 18.7 and 11.8 μg/ml, respectively. QH also induced caspase-3 cleavage (2-fold) and increased PARP cleavage. Specificity protein (Sp) transcription factors are overexpressed in cancer cells and regulate genes required for cell proliferation, survival and angiogenesis. QH treatment decreased the expression of Sp1, Sp3 and Sp4 mRNA and this was accompanied by decreased protein expression. Moreover, expression of the Sp-dependent anti-apoptotic survival gene survivin was also significantly reduced, both at the mRNA and protein levels. QH decreased microRNA-27a (miR-27a) and induced the zinc finger protein ZBTB10, an Sp-repressor, suggesting that interactions between QH and the miR-27a-ZBTB10 axis play a role in Sp downregulation. This was confirmed by transfection of cells with a specific mimic for miR-27a, which partially reversed the effects of QH. These findings are consistent with previous studies on botanical anticancer agents in colon cancer cells.

A comparative study of thulium laser resection of the prostate and bipolar transurethral plasmakinetic prostatectomy for treating benign prostatic hyperplasia

Thulium laser is a new generation of surgical laser. It is a minimally invasive technology with several advantages, including rapid vaporization and minimal tissue damage and bleeding. However, details regarding the safety and efficacy of thulium laser in treating BPH remains unknown. We performed a comparative study in 100 patients with BPH of the safety and efficacy of thulium laser resection of the prostate (TMLRP, n = 50) and bipolar transurethral plasmakinetic prostatectomy (TUPKP, n = 50). We found that the efficacy and indications were the same in TMLRP and TUPKP. In TUPKP, the morbidity of urethrostenosis was low, and was nearly bloodless in surgery and had higher safety. Nevertheless, TUPKP is more suitable for patients with larger prostate volume.

High Level of Circulating Endothelial Progenitor Cells Positively Correlates with Serum Vascular Endothelial Growth Factor in Patients with Renal Cell Carcinoma

PURPOSE Although accumulated evidence indicates that circulating endothelial progenitor cells contribute to tumor neovascularization, to our knowledge the level of these cells and its correlation with serum vascular endothelial growth factor in patients with renal cell carcinoma have not been studied. We measured this level and investigated its clinical significance in patients with renal cell carcinoma. MATERIALS AND METHODS The level of circulating endothelial progenitor cells (percent of total peripheral blood mononuclear cells) was quantified by assaying the CD45(-)CD34(+)vascular endothelial growth factor receptor 2(+) cell phenotype in 53 patients with renal cell carcinoma, 33 with benign renal tumors and 40 healthy controls. Serum vascular endothelial growth factor was quantified. RESULTS The mean circulating endothelial progenitor cell level in patients with renal cell carcinoma was 0.281%, significantly higher than in patients with benign renal tumors and healthy controls (0.073% and 0.076%, respectively, each p <0.001). Patients with stage III-IV renal cell carcinoma had a statistically higher level of these cells than those with stage I-II (0.339% vs 0.243%, p <0.001). The mean level in patients with renal cell carcinoma greater than 7 cm was 0.331%, significantly higher than in those with tumors 4 or less and 4 to 7 cm (0.225% and 0.231%, respectively, each p <0.001). Mean serum vascular endothelial growth factor in patients with renal cell carcinoma was higher than in patients with benign renal tumors and healthy controls (315.5 vs 34.6 and 26.9 pg/ml, respectively, each p <0.001). The preoperative circulating endothelial progenitor cell level positively correlated with serum vascular endothelial growth factor in patients with renal cell carcinoma (r = 0.710, p <0.001). Levels of these cells and of vascular endothelial growth factor significantly decreased postoperatively compared to preoperatively (0.081% vs 0.297% and 31.69 vs 310.70 pg/ml, respectively, each p <0.001). CONCLUSIONS A high circulating endothelial progenitor cell level was found in patients with renal cell carcinoma, which positively correlated with serum vascular endothelial growth factor. Results support the potential use of circulating endothelial progenitor cells as a novel biomarker for renal cell carcinoma.

VPA inhibits renal cancer cell migration by targeting HDAC2 and down-regulating HIF-1α.

Cell migration plays major roles in human renal cancer-related death, but the molecular mechanisms remain unclear. Valproic acid (VPA) is a broad-spectrum inhibitor of class I and II histone deacetylases and shows great anticancer activity in a variety of human cancers. In this study, we found that VPA significantly inhibited cell migration but not proliferation of human renal cancer ACHN cells. Mechanistic studies found that VPA significantly inhibited the expression of HIF-1α. Knockdown of HIF-1α could obviously inhibited cell migration, while over-expression of HIF-1α markedly rescued the inhibition of VPA on cell migration. Further studies found that knockdown of HDAC2 completely mimicked the effects of VPA on HIF-1α and cell migration, and over-expression of HIF-1α could also rescue the effects of HDAC2 knockdown on cell migration. Collectively, these results indicated that the potential of specific inhibition of HDAC2 by small molecular chemicals may lead to future therapeutic agents in human renal cancer treatment.

Statin use and risk of kidney cancer: a meta‐analysis of observational studies and randomized trials

Clinical studies have shown that statin use may modify the risk of kidney cancer. However, these studies yielded different results. To quantify the association between statin use and risk of kidney cancer, we performed a detailed meta‐analysis of published studies regarding this subject.

Up-regulation of flotillin-2 is associated with renal cell carcinoma progression

Flotillin-2 (FLOT2) is a highly conserved protein isolated from caveolae/lipid raft domains that tether growth factor receptors linked to signal transduction pathway. FLOT2 has recently been identified to be involved in tumorigenesis of several cancers such as breast cancer, melanoma, and gastric cancer. However, the role of FLOT2 in renal cell carcinoma (RCC) remains unclear. The expression levels of FLOT2 in RCC patients and renal cancer cell lines were evaluated by quantitative real-time PCR (qRT-PCR) and Western blot. FLOT2 protein expression was also analyzed in archived paraffin-embedded RCC tissues using immunohistochemistry (IHC), and its association with overall survival of patients was analyzed by statistical analysis. Small-interfering RNA (siRNA) was used to suppress FLOT2 expression in RCC cell lines. In vitro assays were performed to further explore its role in tumor progression. The expression level of FLOT2 was higher in RCC tissues and cell lines than in corresponding adjacent normal tissues and normal human proximal tubule epithelial cell line HK-2. IHC analysis revealed high expression levels of FLOT2 in RCC specimens. The RCC patients with higher FLOT2 expression had an advanced clinical stage and poorer prognosis than those with lower FLOT2 expression. FLOT2 expression was an independent prognostic marker of overall RCC patient survival in a multivariate analysis. In vitro assays indicated that knockdown of FLOT2 reduced cell proliferation, migration, and invasion. Our data suggest that FLOT2 is a novel molecule involved in RCC progression, which provide a potential prognostic biomarker and therapeutic target.

Protective Effects of SP600125 on Renal Ischemia-Reperfusion Injury in Rats

BACKGROUND Ischemia/reperfusion injury (IRI) has a negative effect on renal allograft survival. Using a rat model of kidney IRI in this study, we investigated the overall effect of selective c-Jun N-terminal kinase (JNK) inhibitor SP600125 on renal IRI events. METHODS All 45 Fisher rats were anesthetized and renal IRI model was established by 45 min clamp of bilateral renal pedicles and 24 h reperfusion. Vehicle solution or SP600125 solution was intraperitoneally injected 45 min before ischemia, respectively. Analysis of renal histology, function, reactive oxygen species (ROS) expression, JNK phosphorylation status, as well as intra-renal pro-inflammatory cytokines expression was evaluated in this study. RESULTS After IRI, the levels of blood urea nitrogen, creatinine, tissue malondialdehyde, TNF-α, IL-1β, IL-6 were all elevated significantly, while superoxide dismutase, catalase activity were decreased. Histologic findings showed severe devastating lesions and increased rodent cell apoptosis; SP600125 effectively improved morphologic features, reversed above-mentioned parameters, and significantly attenuated c-Jun phosphorylation, as well as intra-renal pro-inflammatory cytokines expression compared with vehicle-treated group. CONCLUSION These data demonstrate that inhibition of c-Jun with SP600125 is capable of attenuating renal IRI, which might be a novel therapy target.

Photoselective Vaporization Versus Transurethral Resection of the Prostate for Benign Prostatic Hyperplasia: A Meta-Analysis

PURPOSE To determine whether photoselective vaporization has advantages over transurethral resection of the prostate (TURP) in terms of effectiveness and safety for treatment of patients with benign prostatic hyperplasia. MATERIALS AND METHODS MEDLINE, EMBASE, and the Cochrane Controlled Trial Register were searched for randomized controlled trials. The risk ratio, mean difference, and their corresponding 95% confidence intervals were calculated for dichotomous and continuous outcomes, respectively. Risk of bias of enrolled trials was assessed according to Cochrane Handbook. RESULTS A total of five trials were enrolled. There was no significant difference in the International Prostate Symptom Score and maximum flow rate between photoselective vaporization and TURP at 6-, 12-, and 24-month follow-up. Photoselective vaporization was associated with significantly lower risk of capsule perforation, transurethral resection syndrome, and clot retention, significantly lower transfusion requirements, a shorter catheterization time, and a shorter length of hospital stay. TURP was associated with a shorter operative time and a lower risk of reoperation. In addition, there was no difference in risk of acute urinary retention and urethral/bladder neck sclerosis between photoselective vaporization and TURP. CONCLUSIONS Photoselective vaporization and TURP provide comparable improvements in functional results, including International Prostate Symptom Score and maximum flow rate at 6-, 12-, and 24-month follow-up. Photoselective vaporization offers advantages over TURP in terms of intraoperative safety; however, TURP is found to have a shorter operative time and lower reoperative risk.

Nrf2 sensitizes prostate cancer cells to radiation via decreasing basal ROS levels

Androgen deprivation therapy (ADT) was reported to lower basal ROS level in prostate cancer (PCa) and to sensitize PCa to radiation. We aimed to seek for the underlying molecular mechanism and to develop novel additive treatments to ADT in this regard. We simulated human androgen milieu in vitro and tested the ROS level in PCa cells undergoing ADT. We also tested the Nrf2 level in PCa cells with or without ADT. Genetic and pharmaceutical upregulation of Nrf2 was applied in vitro and in vivo in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without castration to investigate whether Nrf2 overexpression supplemented the effect of ADT in PCa. We first discovered that androgen deprivation increased basal ROS level in PCa cells with AR expression. We then found that genetic Nrf2 upregulation lowered basal ROS similar to ADT. Also, SFN sensitized PCa cell to radiation via upregulation of Nrf2. We then found that Nrf2 level in control TRAMP groups was lower than castration or SFN groups. The SFN treated TRAMP mice showed similar level of Nrf2 to castration. Genetic and pharmaceutical upregulation of Nrf2 lowered the ROS in PCa cells and sensitized PCa cells to radiation similar to ADT, implicating possible administration of SFN in place of ADT for PCa patients requiring radiotherapy.