The effects of a galectin-3 inhibitor on bladder pain syndrome in mice with cyclophosphamide-induced cystitis.

AIMS: To explore the effect of blocking galectin-3 in the bladder pain syndrome associated with interstitial cystitis. METHODS: A galectin-3 inhibitor was used to treat mice with cyclophosphamide-induced cystitis. The expression of galectin-3 in bladder tissues and urine was examined by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), respectively. Suprapubic-pelvic pain, bladder voiding, bladder pain-like nociceptive behavior, and referred hyperalgesia were assessed. The weights of the bladders were also measured, and inflammatory cell infiltration and inflammatory cytokine levels were examined by histopathological evaluation. The inflammatory cytokines interleukin 1ß (IL-1ß), nerve growth factor (NGF), IL-6, and tumor necrosis factor α (TNF-α) were measured by ELISA. RESULTS: Increases in galectin-3 levels, inflammation, bladder weight, and bladder pain-related symptoms were observed in bladders with cyclophosphamide-induced cystitis. Administration of the galectin-3 inhibitor significantly mitigated bladder pain-related symptoms and inflammatory response. In response to the 500 µM dose of the galectin-3 inhibitor, nociceptive behaviors, nociceptive score, and bladder-to-body weight ratios were reduced by 65.1%, 65.3%, and 40.3%, respectively, while 500 µM Gal-3 inhibitor increased pelvic pain threshold by 86.7%. Moreover, galectin-3 inhibitor treatment inhibited the inflammation. Compared to untreated CYP-induced mice, there were significant changes in the levels of IL-1ß (41.72 ± 2.05 vs. 18.91 ± 2.26 pg/mg tissues), NGF (9.64 ± 0.38 vs. 1.88 ± 0.05 pg/mg tissues), IL-6 (42.67 + 1.51 vs. 21.26 + 2.78 pg/mg tissues, and TNF-α (22.02 ± 1.08 vs. 10.70 ± 0.80 pg/mg tissues) in response to the highest dose of the Gal-3 inhibitor subgroup (500 µM), and 500 µM Gal-3 inhibitor reduced mast cell infiltration ratios by 71.8%. CONCLUSIONS: The galectin-3 inhibitor relieved pelvic pain, urinary symptoms, and bladder inflammation in mice with cyclophosphamide-induced cystitis. Thus, galectin-3 inhibitors may be novel agents in interstitial cystitis treatment.

Malignant glomus tumor of prostate: A case report.

We reported an 85-year-old patient with malignant glomus tumor (GT) of the prostate. He presented with urinary frequency for more than 2 years and gross hematuria for 7 days. Computed tomography scan showed that the prostate was markedly irregularly enlarged, and the boundary between the prostate and the posterior wall of the bladder was unclear. Bilateral kidneys and ureters were dilated. Biochemical examinations showed that the serum potassium was 7.24 mmol/L and the serum creatinine was 974.6 µmol/L. Transurethral diagnostic resection was performed after restoring homeostasis through several times of bedside blood filtration. The pathological diagnosis was malignant GT. The patient's renal function recovered after bilateral nephrostomy, and he refused further treatment and was out of contact after 9 months. We summarize the clinical and histopathological features of malignant GT of the prostate in order to improve the early recognition of the disease by clinicians.

Bergenin inhibits bladder cancer progression via activating the PPARγ/PTEN/Akt signal pathway.

Bladder cancer is one of the most common malignant tumors in the urinary system with high mortality and morbidity. Evidence revealed that bergenin could affect the development of cancer. Here, we aimed to investigate the effect of bergenin on bladder cancer progression and its mechanism. The effect of bergenin on cell function was first detected, followed by assessing the changes of the epithelial-mesenchymal transition (EMT) in bergenin-treated cells. The effect of bergenin on peroxisome proliferator-activated receptor γ (PPARγ)/phosphatase and tensin homolog (PTEN)/Akt signal pathway was measured by Western blotting, followed by the rescue experiments. The results showed that bergenin treatment significantly decreased cell viability and increased G1 phase arrest, accompanied by reduced expression of Ki67, cycling D1, and cycling B1 in bladder cancer cells. Apoptosis was induced by bergenin in bladder cancer cells, as evidenced by increased Bax and cleaved caspase 3 protein levels and decreased Bcl-2 level in bergenin-treated cells. Meanwhile, the inhibition of the invasion, migration, and EMT was also observed in bergenin-treated cells. Mechanism studies showed that bergenin treatment could activate PPARγ/PTEN/Akt signal pathway, as evidence by the increased nucleus PPARγ and phosphatase and tensin homolog (PTEN) expression and decreased Akt expression. Moreover, PPARγ inhibitor administration inverted the effects of bergenin on bladder cancer cell function, including the proliferation, apoptosis, invasion, and migration in bladder cancer cells. Our findings revealed that bergenin could inhibit bladder cancer progression via activating the PPARγ/PTEN/Akt signal pathway, indicating that bergenin may be a potential therapeutic medicine for bladder cancer treatment.

Influences of Different Operative Methods on the Recurrence Rate of Non-Muscle-Invasive Bladder Cancer.

PURPOSE: To compare the influence of three operative approaches [transurethral en bloc resection of bladder tumor by pin-shaped electrode (pin-ERBT), transurethral resection of bladder tumor (TURBT) and transurethral holmium laser resection of bladder tumor (HoLRBT)] on the recurrence rate of non-muscle-invasive bladder cancer (NMIBC) at low dimension (i.e. diameter below 3 cm). MATERIALS AND METHODS: A retrospective analysis was conducted for a total of 115 patients affected by solitary NMIBC, with a diameter <3 cm, who were submitted to operation between March 2013 to May 2017. The patients were divided according to the operative method applied (pin-ERBT, TURBT and HoLRBT groups, respectively). The 2-year recurrence rate was compared among the three groups, and multivariat Cox hazard model analysis was applied to analyze the influencing factor(s) for postoperative recurrence. RESULTS: The 2-year recurrence rate was 10.0% in ERBT, 38.5% in TURBT and 40.0% in HoLRBT group, with a significant difference (P =0.014). According to the Cox hazard model analysis, age(HR=1.058, 95% CI: 1.019~1.098，P=0.003), operative method(HR=2.974,6.508, 95% CI: 0.862~10.255,1.657~25.566, P=0.023), smoking(HR=2.399, 95% CI: 1.147~5.017, P=0.020) and pathological grade(HR=2.012,95% CI: 1.279~3.165, P=0.002) were risk factors for postoperative recurrence of bladder cancer. CONCLUSION: Pin-ERBT can prominently decrease the postoperative recurrence rate of solitary NMIBC with a diameter <3 cm.

Circular RNA cir-ITCH Is a Potential Therapeutic Target for the Treatment of Castration-Resistant Prostate Cancer.

cir-ITCH, a well-known tumor-suppressive circular RNA, plays a critical role in different cancers. However, its expression and functional role in prostate cancer (PCa) are unclear. Herein, we explored the potential mechanism and tumor-inhibiting role of cir-ITCH in PCa. Using reverse transcriptase polymerase chain reaction assay, we analyzed the expression of cir-ITCH in PCa and paired adjacent nontumor tissue samples resected during surgical operation, as well as in two cell lines of human PCa (LNCaP and PC-3) and the immortalized normal prostate epithelial cell line (RWPE-1). Cell viability and migration of PCa cell lines were evaluated using CCK-8 and wound-healing assays. Expression of key proteins of the Wnt/ß-catenin and PI3K/AKT/mTOR pathways was detected using western blotting. We found that cir-ITCH expression was typically downregulated in the tissues and cell lines of PCa compared to that in the peritumoral tissue and in RWPE-1 cells, respectively. The results showed that cir-ITCH overexpression significantly inhibits the proliferation, migration, and invasion of human PCa cells and that reciprocal inhibition of expression occurred between cir-ITCH and miR-17. Proteins in the Wnt/ß-catenin and PI3K/AKT/mTOR pathways were downregulated by overexpression of cir-ITCH both in androgen receptor-positive LNCaP cells and androgen receptor-negative PC-3 cells. Taken together, these data demonstrated that cir-ITCH plays a tumor-suppressive role in human PCa cells, partly through the Wnt/ß-catenin and PI3K/AKT/mTOR pathways. Thus, cir-ITCH may serve as a novel therapeutic target for the treatment of PCa, especially castration-resistant prostate cancer.

Induction of entosis in prostate cancer cells by nintedanib and its therapeutic implications.

Entosis is a homogeneous cell-in-cell phenomenon and a non-apoptotic cell death process. Tyrosine kinase inhibitors have been used in the treatment of prostate cancer and have already demonstrated efficacy in a clinical setting. The present study investigated the role of entosis in prostate cancer treated with the tyrosine kinase inhibitor nintedanib. Prostate cancer cells were treated with nintedanib in vitro and entosis was observed. Mice xenografts were created to evaluate whether nintedanib is able to induce entosis in vivo. The reverse transcription-quantitative polymerase chain reaction, western blotting and immunofluorescence were performed to investigate whether the entosis pathway is induced by nintedanib. It was also investigated whether entosis can contribute to cell survival and progression under nintedanib stress, and nintedanib was revealed to enhance prostate cancer cell entosis. Nintedanib-induced entosis in prostate cancer cells occurred through phosphoinositide 3-kinase/cell division cycle 42 (CDC42) inhibition, followed by the upregulation of epithelial (E-)cadherin and components of the Rho kinase (ROCK) signaling pathway. In addition, nintedanib-resistant cells exhibiting entosis had a higher invasive ability. In addition, in vivo treatment of mice xenografts with nintedanib also increased the expression of E-cadherin and components of the ROCK signaling pathway. Nintedanib can promote entosis during prostate cancer treatment by modulating the CDC42 pathway. Furthermore, prostate cancer cells acquired nintedanib resistance and survived by activating entosis.