Increased IL-1α expression is correlated with bladder cancer malignant progression.

Introduction: To explore the function of interleukin 1α (IL-1α) in bladder cancer (BCa). Material and methods: Immunohistochemistry (IHC) was used to test the protein expression of IL-1α in BCa tissues. The relationship between IL-1α and clinical characteristics was analyzed by the Kaplan-Meier curve method. The gene and protein expression was tested by reverse transcription quantitative polymerase chain reaction (RT-q-PCR) and western blot, respectively. Colony formation and MTT assays were used to detect the potential of proliferation in vitro, and scratch and transwell chamber assays were used to detect the potential of invasion in vitro. Markers of proliferation such as Ki-67 and proliferating cell nuclear antigen (PCNA) and markers of invasion such as MMP-2 and MMP-9 were detected by western blot. Xenograft study was used for the in vivo experiment. Results: We found that IL-1α was highly expressed in BCa patients while highly expressed IL-1α was significantly related to short overall survival and progression-free survival in BCa as well. Moreover, knockdown of IL-1α might inhibit the ability of cancer cells to proliferate and invade or migrate both in vitro and in vivo. Conclusions: Our findings suggested that IL-1α might be a therapy target for BCa malignant progression.

Treatment and surveillance for non-muscle-invasive bladder cancer: a clinical practice guideline (2021 edition).

Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette-Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.

Nesfatin-1/Nucleobindin-2 Is a Potent Prognostic Marker and Enhances Cell Proliferation, Migration, and Invasion in Bladder Cancer.

In recent researches, high expression of nesfatin-1/nucleobindin-2 (NUCB2) is linked to poor prognosis in prostate and colon cancer due to the enhancement in proliferation, migration, and invasion. However, the role of nesfatin-1 in bladder cancer is not clear. In this study, we examined the expression of NUCB2 in bladder cancer using immunohistochemistry and observed that its high expression was associated with recurrence and metastasis. In addition, the transwell assay and wound healing assay showed that cell migration and invasion were decreased with NUCB2 knockdown in T24 and 5637 cells. In vivo, tumor growth and metastasis were inhibited with shRNA treatment in T24 cells. Those results showed that NUCB2 played an important role in bladder cancer and could be considered a potent prognostic factor in bladder cancer.

MAN1B1 is associated with poor prognosis and modulates proliferation and apoptosis in bladder cancer.

Bladder cancer (BC) has been regarded as the most common malignancy of the urinary system worldwide. With lack of investigations for molecular pathogenesis underlying that develop BC, the therapeutic efficacy of several therapeutic approaches existing is still unsatisfactory. Here, our study aimed to explore the potentially biological function of MAN1B1 on BC. In this study, MAN1B1 expression level in BC tissues and normal tissues was analyzed based on The Cancer Genome Atlas (TCGA) data and correlation between its expression and prognosis was determined using Kaplan-Meier analysis. Knockout of MAN1B1 was performed using silencing RNA and the efficacy of MAN1B1 knockout was identified using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. The BC cells proliferation was assessed by Cell Counting Kit-8 (CCK8) assay, and then the cells apoptosis was detected by Annexin V-fluorescein isothiocyanate (Annexin V-FITC)/propidium iodide (PI) staining and flow cytometry following MAN1B1 knocked down by small interfering RNA. Protein kinase B (AKT) signaling was evaluated by detecting related markers, namely AKT, p-AKT, 4E-BP-1 and Bax using western blot assay. As a result, the MAN1B1 expression was higher in BC tissues than those in normal tissues, besides, its overexpression was associated with poor prognosis. Moreover, MAN1B1 reduction by silencing RNA approach resulted in BC cells proliferation suppression and BC cells apoptosis promotion. Finally, AKT signaling activity was inhibited by MAN1B1 silencing. Taken together, these results unraveled that MAN1B1 may act on an oncogenic action in BC, which improved the likelihood of MAN1B1 taking on a promising prognostic biomarker and a potential target for treating BC.

Triptorelin relieves lower urinary tract symptoms in Chinese advanced prostate cancer patients: a multicenter, non-interventional, prospective study.

BACKGROUND: Although triptorelin is increasingly used in China for biochemical castration, its effects on primary prostate cancer symptoms remain unclear. This study aimed to assess the prevalence of lower urinary tract symptoms (LUTS) in Chinese prostate cancer patients and the effectiveness of triptorelin on LUTS. METHODS: In this 48-week multicenter, non-interventional, prospective study, we enrolled patients with locally advanced or metastatic prostate cancer. Patients received triptorelin (15 mg) intramuscularly at baseline and at weeks 12, 24, and 36 with symptom assessment using the International Prostate Symptoms Score (IPSS). The primary endpoints were the prevalence of LUTS at baseline per IPSS categories and the percentage of patients with moderate to severe LUTS (IPSS > 7) at baseline, having at least a 3-point reduction of IPSS score at week 48. RESULTS: A total of 398 patients were included; 211 (53.0%) and 160 (40.2%) among them had severe and moderate LUTS, respectively. Of the patients with IPSS scores available at baseline and at week 48 (n = 213), 81.2% achieved a reduction in IPSS of at least 3 points. Of the patients with moderate to severe LUTS at baseline and IPSS scores available at baseline and at week 48 (n = 194), 86.6% achieved a total IPSS reduction of at least 3 points. CONCLUSIONS: The vast majority of Chinese patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin as part of their standard treatment have severe or moderate LUTS. Triptorelin therapy resulted in sustained improvement of LUTS in these patients.

LAMC1 mRNA promotes malignancy of hepatocellular carcinoma cells by competing for MicroRNA-124 binding with CD151.

Specific RNAs can function as sinks for endogenous miRNAs, known as competing endogenous RNAs (ceRNAs). Here, we confirm a miR-124 mediated ceRNA crosstalk between LAMC1 and CD151 in hepatocellular carcinoma (HCC). miR-124 negatively regulates LAMC1 expression through two miRNA binding sites within its 3' untranslated region (3'UTR) and suppresses migration and invasion of HCC cells through regulating LAMC1. The wild type LAMC1 miRNA response elements (MREs) facilitate expression of CD151, and this regulation is miR-124 dependent. In clinical hepatic tissues, LAMC1 and CD151 mRNAs exhibit positive correlation. Importantly, LAMC1 MREs promote HCC malignancy by absorbing miR-124 and by assisting CD151 expression. We conclude that LAMC1 mRNA acts as a trans regulator to stimulate CD151 expression by competing for miR-124 binding in HCC cells. © 2017 IUBMB Life, 69(8):595-605, 2017.

Expression profile of hydrogen sulfide and its synthases correlates with tumor stage and grade in urothelial cell carcinoma of bladder.

BACKGROUND: Hydrogen sulfide (H2S) is a newly discovered gas transmitter. It is synthesized by cystathionine ß-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MPST). Endogenous hydrogen sulfide has never been studied in bladder cancer. PURPOSE: We evaluated H2S production and its synthases expression levels in transitional cell carcinoma (urothelial cell carcinoma of bladder [UCB]) of human bladder tissue and cell lines. MATERIALS AND METHODS: Immunostaining was performed in urothelial cell lines and bladder specimens from 94 patients with UCB of different stages/grades. The expression levels/activities of CBS, CSE, and MPST of specimens and cell lines were analyzed by image semiquantity assay, western blot, and a sulfur-sensitive electrode. We tried to find the correlation between hydrogen sulfide and its synthases with tumor stage in UCB. All experiments were repeated at least 3 times. RESULTS: Immunoreactivity for CBS, CSE, and MPST was detected in malignant uroepithelium and muscular layer of all tissues examined and cultured cells. The expression levels of CBS, CSE, and MPST were associated with UCB stage/grade. Muscle-invasive bladder cancer samples showed the highest production of H2S (52.6±2.91 nmol/[mg·min]) among all tested samples and EJ cells (transitional cell carcinoma, grade IIIshowed the highest production of H2S among all tested cell lines (53.3±7.02nmol/[mg·min]). CONCLUSIONS: Protein levels and catalytic activities of CBS, CSE, and MPST increased with the increase of malignant degrees in human bladder tissues and human UCB cell lines. Our findings may promote the application of these novel enzymes to UCB diagnosis or treatment.

Association of endothelia nitric oxide synthase gene rs1799983 polymorphism with susceptibility to prostate cancer: a meta-analysis.

Genetic polymorphism of endothelial nitric oxide synthase (NOS3) rs1799983 (Glu298Asp) has been implicated to alter the risk of prostate cancer, but the results are controversial. Two investigators independently searched the PubMed, Cochrane Library, and Embase electronic databases up to September 30, 2013. Summary odds ratios (OR) and 95 % confidence interval (CI) for rs1799983 polymorphism and prostate cancer were calculated. Statistical analysis was performed with the software program Review Manage, version 5.0 and Stata 11.0. A total of 7 independent studies, including 1,792 cases and 2,411 controls, were identified. Our analysis suggested that rs1799983 was associated with prostate cancer risk in overall population under dominant model (OR = 1.15, 95%CI = 1.01-1.30, P = 0.03) and allelic model (OR = 1.11, 95%CI = 1.00-1.22, P = 0.04). In the subgroup analysis, we detected no association between rs1799983 polymorphism and prostate risk in Caucasian population under all the genetic models. This meta-analysis showed the evidence that NOS3 rs1799983 polymorphism was associated with a risk of prostate cancer development in overall populations.

Multilocular cystic renal cell carcinoma in lower pole moiety of a duplex kidney.

Multilocular cystic renal cell carcinoma (MCRCC) is an uncommon low-grade renal cell carcinoma with unique morphologic features. The 2004 World Health Organization classification of kidney tumors categorized MCRCC as a separate entity. The authors report the case of a 48-year-old man whose MCRCC originated from the lower portion of the duplex kidney (DK). Because the oncological outcome of MCRCC is favorable, regardless of tumor size and stage, patients with MCRCC might benefit from nephron-sparing surgery. It is important to distinguish larger MCRCCs from other renal cell carcinomas, especially when comorbid with DK, because the characteristic anatomy of DK warrants the nephron-sparing surgery. To the authors' knowledge, MCRCC in DK has not been reported previously in the English literature.

Antagonism of estrogen-mediated cell proliferation by raloxifene in prevention of ageing-related prostatic hyperplasia.

Estrogen has important roles in the initiation and development of benign prostatic hyperplasia (BPH). Regulators of the estrogen receptor (ER) are tissue- and cell-specific. We evaluated the effect of estrogen antagonist, raloxifene (Ral), on the prevention and treatment of BPH by investigating its effect on the proliferation of two different prostate cell lines: a stromal cell line, WPMY-1, and a benign prostatic hyperplasia epithelial cell line, BPH-1. We additionally evaluated its effect on prostatic hyperplasia induced by estrogen and androgen in a rat model. The effect of Ral on the prevention of prostatic hyperplasia was analyzed by haematoxylin and eosin staining and quantitative immunohistochemistry (IHC) for proliferating cell nuclear antigen and alpha-smooth muscle actin. In vitro and in vivo, tamoxifen (Tam), another anti-estrogen drug, and finasteride (Fin), a drug for the clinical treatment of BPH, served as efficacy controls. The in vitro data showed that neither Ral nor Tam alone affected the proliferation of WPMY-1 and BPH-1, but both antagonized the effect of oestradiol in promoting the proliferation of the two cells. Results from the IHC staining of the rat prostates indicated that, similar to Tam and Fin, Ral inhibited the proliferation of stromal cells in vivo. Interestingly, in contrast to Tam, both Ral and Fin inhibited the proliferation of epithelial cells. Furthermore, Ral treatment much strongly decreased the number of prostatic acini and the surrounding layers of smooth muscle cells than Fin (P < 0.05). Our data showed for the first time that Ral may have a role in the response of the rat prostate to selective ER modulators.