Analysis of Risk Factors for Recurrence after Transurethral Resection of Bladder Tumor in Patients with Non-Muscle Invasive Bladder Cancer: 2-Year Follow-Up Outcomes.

INTRODUCTION: The aim was to investigate the risk factors for recurrence after transurethral resection of bladder tumor (TURBT) in patients with non-muscle invasive bladder cancer (NMIBC) and to provide a basis for clinical prevention of recurrence of NMIBC. METHODS: From January 2012 to December 2020, 592 patients with NMIBC who underwent TURBT attending the Second Affiliated Hospital of Xi'an Jiaotong University were retrospectively included in this study. Patients were divided into relapse and relapse-free groups according to whether relapse occurred within 2 years. Ultimately, 72 patients were included in the relapse group and 350 patients were included in the relapse-free group. Observation indicators included age, sex, smoking, underlying disease (hypertension, diabetes, coronary heart disease), two or more lesions, tumor size, hematuria, pathology grading (low, medium, high), staging (Ta, T1), muscular invasion in initial pathology, tumor base (sessile, pedunculated), use of intravesical drug (pirarubicin, bacillus Calmette-Guerin [BCG], mitomycin, hydroxycamptothecin, gemcitabine). RESULTS: In this study, the 2-year recurrence rate of NMIBC patients after TURBT was 17.06%. There were significant differences in comparison of pirarubicin, BCG, and mitomycin treatment between the two groups (p < 0.05). To avoid missing risk factors for recurrence, factors with p < 0.1 were analyzed. The results of univariate logistic regression analysis showed that NMIBC patients with BCG treatment (OR = 5.088, 95% CI = 1.444-17.73, p = 0.012), high pathology grading (OR = 0.415, 95% CI = 0.197-0.880, p = 0.023), T1 stage (OR = 2.097, 95% CI = 0.996-4.618, p = 0.059), mitomycin treatment (OR = 5.029, 95% CI = 1.149-21.77, p = 0.031), and pirarubicin treatment (OR = 1.794, 95% CI = 1.079-3.030, p = 0.024) had significantly higher risk of recurrence within 2 years after TURBT. The results of multivariate logistic regression analysis showed that NMIBC patients with high pathology grading (OR = 0.4030, 95% CI = 0.1702-0.8426, p = 0.0241), pirarubicin treatment (OR = 1.961, 95% CI = 1.159-3.348, p = 0.0125), and BCG treatment (OR = 6.201, 95% CI = 1.275-29.73, p = 0.0190) had significantly higher risk of recurrence within 2 years after TURBT. CONCLUSION: Our study highlights the importance of postoperative surveillance and individualized treatment for patients with NMIBC. Our findings show that high pathology grading, pirarubicin treatment, and BCG treatment are independent risk factors for recurrence after TURBT in patients with NMIBC. However, caution is warranted when interpreting our findings due to the small sample size and the need for further research to confirm the negative impact of mitomycin and BCG on recurrence rates.

Circular RNA CSPP1 motivates renal cell carcinoma carcinogenesis and the Warburg effect by targeting RAC1 through microRNA-493-5p.

Circular RNAs (circRNAs) take on regulatory roles in renal cell carcinoma (RCC). The research's goal was to figure out circ-CSPP1's role and molecular mechanism in RCC. The results clarified that circ-CSPP1 expression was enhanced in RCC. Down-regulating circ-CSPP1 refrained the proliferation, migration, invasion, and Warburg effect (aerobic glycolysis), but accelerated apoptosis of RCC cells. The luciferase activity assay exhibited that circ-CSPP1 could perform as an endogenous sponge for miR-493-5p. Elevating miR-493-5p repressed RCC progression. The bioinformatics website starBase confirmed that ras-related C3 botulinum toxin substrate 1 (RAC1) was a target gene of miR-493-5p. Circ-CSPP1 up-regulated RAC1 by sponging miR-493-5p, and elevating RAC1 could turn around the effect of down-regulating circ-CSPP1 on RCC cells. Taken together, circ-CSPP1 is identified as a novel RCC-promoting RNA that could serve as a latent therapeutic target for RCC therapy.

The application of gemcitabine and pirarubicin in patients with non-muscle invasive bladder cancer.

OBJECTIVE: To investigate the value of gemcitabine and pirarubicin in patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: 405 patients with non-muscle invasive bladder cancer admitted to our hospital from January 2012 to December 2020 who underwent transurethral bladder tumor electronic resection were studied. 177 patients were treated with gemcitabine (Gemcitabine group) and 228 patients were treated with pirarubicin (Pirarubicin group) after surgery. The efficacy and adverse effects of the two groups were observed and the patients were followed up. RESULTS: No differences were found when comparing age, gender, smoking, bladder mass, number of masses, hypertension, diabetes, coronary artery disease, hematuria and tumor diameter between the 2 groups (P > 0.05). In the Gemcitabine group, bladder irritation signs, meatus hematuria, fever, nausea and vomiting were lower than those in the Pirarubicin group (P < 0.05). The recurrence rates were 6.21% and 12.28% at 1 year, 11.86% and 23.68% at 2 years, 15.82% and 25.88% at 3 years in the Gemcitabine and Pirarubicin groups respectively, with the Gemcitabine group having a significantly lower recurrence rate than the Pirarubicin group (P < 0.05). The tumor recurrence-free survival rate for 5 years of gemcitabine was significantly higher than that of the Pirarubicin group (P < 0.05). CONCLUSION: Gemcitabine and pirarubicin are both effective in treating patients with non-muscle invasive bladder cancer, with gemcitabine having a lower incidence of adverse reactions, a higher safety rating, a lower recurrence rate and an improved survival outcome.

Long-Term Survival and Prognostic Factors After Laparoscopic Radical Nephrectomy.

Purpose: Our study aims to investigate the long-term survival and prognostic factors of patients after laparoscopic radical nephrectomy. Methods: Totally, 245 patients with renal cell carcinoma in our hospital from January 2015 to February 2017 were analyzed retrospectively. The 5-year survival status of patients with renal cell carcinoma was under analysis and further based on univariate analysis, and its influencing factors were analyzed by Cox regression. Results: The average 5-year follow-up time of 245 patients with renal cell carcinoma was (4.88 ± 0.52) years. The mortality of 1 year, 3 years and 5 years were 2.45% (5/245), 6.35% (16/245) and 9.80% (24/245), respectively. The survival rates were 97.55% (239/245), 93.06% (228/245) and 90.61% (222/245). Univariate analysis showed that age, tumor diameter, hematuria, TNM stage and postoperative recurrence may be the influencing factors of 5-year survival of patients with renal cell carcinoma (P < .05). However, the following parameters, including gender, course of disease, and other clinical complications were not related to the 5-year survival of patients with renal cell carcinoma (P > .05). the influencing factors of 5-year survival status of patients with renal cell carcinoma were age, tumor diameter, hematuria, TNM stage, and postoperative recurrence. Conclusion: The study revealed the long-term survival of patients with renal cell carcinoma may be associated with age, tumor diameter, hematuria, TNM stage and postoperative recurrence.

Transcription factor p53-mediated activation of miR-519d-3p and downregulation of E2F1 attenuates prostate cancer growth and metastasis.

Prostate cancer (PCa) is a commonly diagnosed malignancy in men. The transcription factor p53, a well-known cancer suppressor, has been extensively analyzed in the progression of many tumor types, but its involvement in PCa remains not fully understood. Hence, this study aims to explore the possible molecular mechanism underlying p53 in the growth and metastasis of PCa. Based on bioinformatics analysis findings of GEPIA and starBase databases, p53 was demonstrated to be involved in the development of PCa by transcriptionally activating microRNA-519d-3p (miR-519d-3p) expression to suppress the expression of E2F transcription factor 1 (E2F1) and CD147. In order to verify this finding, clinically-obtained PCa tumor tissues were enrolled and commercially-purchased PCa cell lines were used to detect the cell viability, cycle, and apoptosis, as well as invasion and migration by CCK-8, flow cytometry, and Transwell assays respectively. The results of clinical tissue experiments and in vitro cell experiments showed that miR-519d-3p and p53 were poorly-expressed in PCa tissues and cell lines, while E2F1 was highly-expressed. Overexpression of miR-519d-3p led to inhibited PCa cell proliferation, invasion and migration, and p53 overexpression was found to promote miR-519d-3p expression to suppress the malignant characteristics of PCa cells, while the additional E2F1 overexpression restored the malignant traits. Moreover, ChIP analysis and dual-luciferase reporter assay confirmed the interactions among p53, miR-519d-3p, and E2F1. Mechanistically, it was found that p53 transcriptionally activated miR-519d-3p to suppress E2F1 expression. Finally, the in vitro results were further validated by in vivo experiments, which showed that miR-519d-3p prevents tumorigenesis and lymph node metastasis of PCa in nude mice via negatively regulation of E2F1 and CD147. Taken together, the findings uncover that the transcription factor p53 could upregulate miR-519d-3p expression to directly suppress the expression of E2F1, thus inhibiting PCa growth and metastasis. It highlights a novel therapeutic strategy against PCa based on the p53/miR-519d-3p/E2F1 regulatory pathway.

TMEM88 exhibits an antiproliferative and anti-invasive effect in bladder cancer by downregulating Wnt/ß-catenin signaling.

Transmembrane protein 88 (TMEM88) acts as a novel tumor-associated protein. The dysregulation of TMEM88 has been observed in several tumor types. However, the relevance of TMEM88 in tumorigenesis is still contradictory. This study assessed the relevance of TMEM88 in bladder cancer. TMEM88 levels were found to be significantly lower in bladder cancer tissue. Upregulation of TMEM88 resulted in a dramatic decrease in the cellular proliferative and invasive abilities of bladder cancer. Upregulation of TMEM88 decreased the level of active ß-catenin and prohibited the activation of the Wnt/ß-catenin pathway, an effect that was associated with downregulation of glycogen synthase kinase-3ß (GSK-3ß) phosphorylation. Suppression of GSK-3ß or overexpression of ß-catenin reversed the TMEM88-induced tumor-inhibiting effects in bladder cancer. Overexpression of TMEM88 prohibited the tumor formation and growth of bladder cancer cells in nude mice. In conclusion, this study demonstrates that TMEM88 exerts an antitumor function in bladder cancer through downregulation of Wnt/ß-catenin signaling.

[Research Advance on the Immune Escape of Acute Myeloid Leukemia--Review].

Acute myeloid leukemia (AML) is a kind of malignant hematological disease with high mortality. Patients 5-year survival rate is less than 25% and that of elderly patients is lower than 10%. Although the standardized chemotherapy or hematopoetic stem cell transplantation can significantly improve the therapeutic efficacy for AML, but disease recurrence is still a difficult problem in most patients. Chemotherapy combined with immunotherapy has been regarded as the most promising treatment for AML in recent years, but immunotherapy is prone to immune escape, which has become an important factor affecting the therapeutic efficacy. Therefore, understanding the mechanism of immune escape of AML and taking corresponding measures in time to improve the therapeutic effect and reduce the recurrence of AML are of great significance. In this review, the important cells that cause immune escape, such as myeloid-derived suppressor cells (MDSC), natural killer cells (NK), and cell surface inhibitory receptor PD-1 (programmed death 1), which mediate immune escape of AML cells are summarized, so as to provide valuable reference for research to improve the effect of AML immunotherapy.

Down-Regulation of Circular RNA_000926 Attenuates Renal Cell Carcinoma Progression through miRNA-411-Dependent CDH2 Inhibition.

Many studies have recognized that circular RNAs (circRNAs) can be promising targets for renal cell carcinoma (RCC) by acting as competing endogenous RNAs for miRNAs. This study intends to uncover the implication of a novel circRNA, circ_000926 in RCC, and how it affects tumorigenesis. Microarray-based circRNA/gene expression profiling of RCC was used to identify differentially expressed circRNAs/genes in RCC and normal tissues. miRNAs targeting the screened circRNAs/genes were predicted online, followed by analyzing circ_000926 expression in RCC. The crosstalk among circ_000926, miRNA-411 (miR-411), and CDH2 was then validated. The expression of circ_000926, miR-411, and cadherin 2 (CDH2) was up-regulated or down-regulated in RCC cells to unearth their effects on the biological behaviors of RCC cells. circ_000926 was highly expressed in RCC tissues and cell lines, whereas CDH2 was verified to be a target of miR-411. As a competing endogenous RNA, circ_000926 could directly bind to miR-411 to up-regulate CDH2. Down-regulation of circ_000926 resulted in inhibited growth, migration, and invasion abilities of RCC cells, as well as suppressed epithelial-mesenchymal transition and tumor growth. However, the inhibition of miR-411 or elevation of CDH2 reversed the antitumor effects induced by silencing circ_000926. Down-regulation of circ_000926 exerts an inhibitory effect on RCC progression through miR-411-dependent CDH2 inhibition, highlighting a potential target for RCC treatment.

Bone marrow-derived mesenchymal stromal cells promote resistance to tyrosine kinase inhibitors in chronic myeloid leukemia via the IL-7/JAK1/STAT5 pathway.

Chronic myeloid leukemia (CML) is caused by the fusion of the BCR activator of RhoGEF and GTPase activating protein (BCR) and ABL proto-oncogene, the nonreceptor tyrosine kinase (ABL) genes. Although the tyrosine kinase inhibitors (TKIs) imatinib (IM) and nilotinib (NI) have remarkable efficacy in managing CML, the malignancies in some patients become TKI-resistant. Here, we isolated bone marrow (BM)-derived mesenchymal stem cells (MSCs) from several CML patients by Ficoll-Hypaque density-gradient centrifugation for coculture with K562 and BV173 cells with or without TKIs. We used real-time quantitative PCR to assess the level of interleukin 7 (IL-7) expression in the MSCs and employed immunoblotting to monitor protein expression in the BCR/ABL, phosphatidylinositol 3-kinase (PI3K)/AKT, and JAK/STAT signaling pathways. We also used a xenograft tumor model to examine the in vivo effect of different MSCs on CML cells. MSCs from patients with IM-resistant CML protected K562 and BV173 cells against IM- or NI-induced cell death, and this protection was due to increased IL-7 secretion from the MSCs. Moreover, IL-7 levels in the BM of patients with IM-resistant CML were significantly higher than in healthy donors or IM-sensitive CML patients. IL-7 elicited IM and NI resistance via BCR/ABL-independent activation of JAK1/STAT5 signaling, but not of JAK3/STAT5 or PI3K/AKT signaling. IL-7 or JAK1 gene knockdown abrogated IL-7-mediated STAT5 phosphorylation and IM resistance in vitro and in vivo Because high IL-7 levels in the BM mediate TKI resistance via BCR/ABL-independent activation of JAK1/STAT5 signaling, combining TKIs with IL-7/JAK1/STAT5 inhibition may have significant utility for managing CML.

Overexpressing miR­335 inhibits DU145 cell proliferation by targeting early growth response 3 in prostate cancer.

MicroRNA­335 (miR­335) was reported to suppress cell proliferation in prostate cancer (PC), a common malignancy in males. The expression of early growth response 3 (EGR3) was determined to be elevated in human PC tissues; however, the possible effects and underlying mechanism of miR­335 on PC remains unknown. In the present study, miR­335 mimics and miR­335 inhibitors were respectively transfected into DU145 cells. Stable silencing of EGR3 was observed in DU145 cells following transfection with small interfering RNA. We also used Cell Counting Kit­8 and in vitro angiogenesis assays to determine the viability and revascularization potential of DU145 cells. The expression levels of EGR and caspase­3 activity were analyzed by immunohistochemistry and immunocytochemistry, respectively. We predicted the target of miR­335 by bioinformatics analysis and a dual­luciferase reporter gene assay. Western blot and quantitative real­time polymerase chain reaction analyses were performed to determine the protein and mRNA expression of molecules. miR­335 expression was downregulated in PC tissues and cell lines. Overexpression of miR­335 significantly reduced the viability and the formation of regenerative tubes of DU145 cells, and inhibited the expression of inflammatory factors. EGR3 was proposed as a possible target of miR­335, and was negatively regulated by miR­335. Silencing EGR3 suppressed the viability and angiogenesis of DU145 cells, and reduced the activity of caspase­3 and inflammatory factor expression. miR­335 inhibition along with EGR3 silencing EGR3 inhibited the cell proliferation. Furthermore, miR­335 inhibited the formation of a PC solid tumor xenograft in vivo. Thus, miR­335 may exert an antitumor effect on DU145 cells by regulating the expression of EGR3. The findings of the present study may provide insight into a novel therapeutic strategy for the treatment of prostatic carcinoma.

EZH2 enhances the invasive capability of renal cell carcinoma cells via activation of STAT3.

The enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) gene has been recognized to be a proto­oncogene and to be linked to human malignancies. However, the additional functions of EZH2 in renal cell carcinoma (RCC) are not completely understood. In the present study, a possible role of EZH2 in RCC was identified. EZH2 was demonstrated to promote the cell proliferation and invasion potential of 769­P cells, and inhibition of EZH2 was demonstrated to prevent these two processes in 786­O cells. Mechanically, EZH2 was demonstrated to increase the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and upregulate 72 kDa type IV collagenase (MMP­2) expression. When cells were treated with small interfering RNA targeting STAT3 or Stattic, a specific inhibitor of STAT3, the invasive ability of the cells was decreased and downregulation of MMP­2 was observed. Based on these results, in the present study it was hypothesized that EZH2 may serve a critical role in the progression of RCC. Its ability to facilitate invasion makes EZH2 a promising target for the management of advanced RCC.

MicroRNA-590-3p promotes cell proliferation and invasion by targeting inositol polyphosphate 4-phosphatase type II in human prostate cancer cells.

Inositol polyphosphate 4-phosphatase type II emerges as a tumor suppressor in prostate cancer, and its loss of expression is associated with poor prognosis for prostate cancer. However, the mechanism of downregulation of inositol polyphosphate 4-phosphatase type II in prostate cancer development has not yet been fully clarified. In this study, microRNA-590-3p was found to be upregulated in both prostate cancer tissues and cell lines. Overexpression of microRNA-590-3p by microRNA-590-3p mimics promoted prostate cancer cell proliferation and invasion and accelerated the growth of xenografted tumors, while microRNA-590-3p inhibitors contributed to inhibition of cellular proliferation and invasion as well as tumor growth. A dual-luciferase reporter assay and expression analysis further confirmed that inositol polyphosphate 4-phosphatase type II was a direct target of microRNA-590-3p. Enforced expression of microRNA-590-3p led to repression of inositol polyphosphate 4-phosphatase type II messenger RNA and protein expression, as well as upregulation of p-Akt, p-FoxO3a, and cyclin D1 and downregulation of p21 expression in prostate cancer cell lines. Overexpression of inositol polyphosphate 4-phosphatase type II could reduce microRNA-590-3p-induced cell proliferation and invasion as well as tumor growth, and decrease microRNA-590-3p-mediated upregulation of cyclin D1 and downregulation of p21 expression in prostate cancer cells. Taken together, our findings reveal that microRNA-590-3p is a potential onco-microRNA that participates in carcinogenesis of human prostate cancer by suppressing inositol polyphosphate 4-phosphatase type II expression and involving the Akt/FoxO3a pathway. MicroRNA-590-3p may represent a potential therapeutic target for prostate cancer patients.

Expression of netrin-1 by hypoxia contributes to the invasion and migration of prostate carcinoma cells by regulating YAP activity.

Hypoxia is a hallmark of solid tumor growth microenvironment and appropriates the major contributor for the failure and poor prognosis of clinical tumor treatment, including prostate cancer (PCa). Ectopic expression of netrin-1 is reportedly associated with the progression of several carcinomas. Here, we aimed to investigate the role of netrin-1 in hypoxic metastasis potential of prostate carcinoma. Here, hypoxia induced the up-regulation of netrin-1 mRNA and protein expression in prostate cancer cell lines PC3 and DU145. Importantly, knockdown of netrin-1 dramatically suppressed cell invasion, migration and epithelial-to-mesenchymal transition (EMT) of PC3 and DU145 cells under hypoxia. Furthermore, hypoxia treatment increased the activity of Yes-associated protein (YAP) by increasing YAP expression in the nucleus and inhibiting p-YAP levels. However, YAP activation was notably restrained following netrin-1 down-regulation. Interestingly, interrupting YAP expression attenuated hypoxia-triggered cell invasion, migration and EMT of DU145 cells. More importantly, restoring YAP expression strikingly antagonized the inhibitory effects of netrin-1 decrease on the metastatic potential of prostate cancer cells. Together, these results indicate that netrin-1 may function as a positive regulator of hypoxia-triggered malignant behavior in PCa by activating the YAP signaling. Accordingly, netrin-1 could be a promising therapeutic agent against prostate carcinoma.

Anxiety and decreased social support underline poorer quality of life of parent living kidney donors.

INTRODUCTION: A growing body of published work suggests that the parent-child relationship can be inherently coercive, such that the expectation that a living parent will not hesitate to donate a kidney to their children, makes informed consent difficult if not impossible to ascertain. The present study was designed to explore whether the emotional response and social resources have a similar effect on health-related quality of life among parent and sibling living kidney donors. METHODS: This was a cross-sectional study. A total of 98 living kidney donors (60 parent donors, 38 sibling donors) completed an assessment including emotional response, social support and quality of life. RESULTS: Depression, anxiety, subjective social support and quality of life scores were much poorer for parent than sibling donors. Parent donors also showed more anxiety and poorer physical functioning than their counterparts in the general population. Hierarchical multiple regression analyses suggested that anxiety and decreased social support in the parent group were negatively associated with physical and mental function. In the sibling group, the main indicator of improved physical state was higher education level. DISCUSSION: Current results raised new concerns for the quality of life of parent donors as emotional response and social support differentially affected parent versus sibling quality of life. Therefore, stricter standards for physical selection, as well as emotional and supportive intervention, are needed for parent donors.