Sinularin stabilizes FOXO3 protein to trigger prostate cancer cell intrinsic apoptosis.

Sinularin, a natural product that purified from soft coral, exhibits anti-tumor effects against various human cancers. However, the mechanisms are not well understood. In this study, we demonstrated that Sinularin inhibited the viability of human prostate cancer cells in a dose-dependent manner and displayed significant cytotoxicity only at high concentration against normal prostate epithelial cell RWPE-1. Flow cytometry assay demonstrated that Sinularin induced tumor cell apoptosis. Further investigations revealed that Sinularin exerted anti-tumor activity through intrinsic apoptotic pathway along with up-regulation of pro-apoptotic protein Bax and PUMA, inhibition of anti-apoptotic protein Bcl-2, mitochondrial membrane potential collapses, and release of mitochondrial proteins. Furthermore, we illustrated that Sinularin induced cell apoptosis via up-regulating PUMA through inhibition of FOXO3 degradation by the ubiquitin-proteasome pathway. To explore how Sinularin suppress FOXO3 ubiquitin-proteasome degradation, we tested two important protein kinases AKT and ERK that regulate FOXO3 stabilization. The results revealed that Sinularin stabilized and up-regulated FOXO3 via inhibition of AKT- and ERK1/2-mediated FOXO3 phosphorylation and subsequent ubiquitin-proteasome degradation. Our findings illustrated the potential mechanisms by which Sinularin induced cell apoptosis and Sinularin may be applied as a therapeutic agent for human prostate cancer.

Case report: Complete response of a bladder cancer patient with multiple hepatic and pelvic metastases treated by nab-paclitaxel combined with sintilimab.

This article described a patient with metastatic bladder cancer (mBC) who was successfully treated with nab-paclitaxel plus sintilimab. Localized muscle-invasive bladder cancer (MIBC) was discovered in a 56-year-old man who received radical cystectomy and platinum-based adjuvant chemotherapy. Eleven months after cystectomy, this patient developed numerous hepatic and pelvic metastases and progressed to mBC. The patient was given an anti-PD-1 antibody (sintilimab 200mg, q3w) in combination with Nab-paclitaxel (100mg, qw) for mBC. Complete remission (CR) was achieved after nine cycles of therapy, and the patient had no severe side effects during the treatment. The disease remained in CR after 41 months of follow-up. This case suggests that nab-paclitaxel combined with sintilimab is a safe and effective option in treatment of mBC.

Atypical granular cell tumor of the urinary bladder: A case report.

BACKGROUND: Granular cell tumor (GCT) is a neurogenic tumor mainly occurring in the head and neck. GCT in the genitourinary system is extremely rare and only sporadic cases of urinary bladder GCT have been reported. Most urinary bladder GCT cases are benign and only two malignant cases have been reported. Due to its rarity, no consensus criteria for the treatment of urinary bladder GCT are available at present. CASE SUMMARY: A 62-year-old Chinese woman was found to have a urinary bladder tumor without any clinical manifestations on physical examination. Cystoscopy revealed a semispherical shaped lesion measuring approximately 4.0 cm in diameter at the junction of the left wall and roof of the bladder, which was covered with normal bladder mucosa. Computed tomography scan demonstrated a high-density lesion on the left wall of the bladder, measuring approximately 2.9 cm × 2.4 cm with clear boundaries. Contrast-enhanced pelvic magnetic resonance imaging revealed a space-occupying lesion on the left wall of the bladder (non-mucosal origin/ external pressure), which was preliminarily suspected to be a desmoplastic fibroma or leiomyoma. In the context of the above findings, a pre-operative diagnosis of bladder leiomyoma was made. The patient consequently underwent a laparoscopic partial cystectomy. The resected bladder mass looked yellowish and well-demarcated, measuring 4.0 cm × 3.5 cm and infiltrated the muscular layer. The diagnosis of urinary bladder GCT was finally made by postoperative pathology, with positive immunohistochemical S-100 staining and negative pancytokeratin. The patient has been followed for 6 mo so far, with no tumor recurrence detected. CONCLUSION: This case highlights the biological feature and differential diagnosis of urinary bladder GCT at the pathological and molecular levels. Transurethral resection of the bladder tumor and partial cystectomy are recommended in most urinary bladder GCT cases, while radical cystectomy is recommended in malignant cases.

Guide sheath-assisted ureteroscope lithotripsy for upper ureteral calculi: An observational study on 81 cases.

The present study assessed the clinical efficacy of guide sheath-assisted ureteroscope lithotripsy in the treatment of upper ureteral calculi. A total of 81 patients with upper ureteral calculi underwent ureteroscope lithotripsy assisted by a guide sheath between January 2012 and June 2014; of these, 63 patients were successfully treated with simple rigid ureteroscope lithotripsy assisted by a ureteral access sheath, and 18 patients were successfully treated with rigid and flexible ureteroscope lithotripsy assisted by a guide sheath. At 1 day after the surgery, ultrasound examination of kidneys, ureters and bladder, and urinary system computed tomography were used to re-check for residual stones, and 69 patients had stones with a diameter of <2 mm in the renal pelvis, while 12 had stones of 2-4 mm in diameter. The operation time was 30-115 min (average, 56.0±4.8 min); all patients underwent a successful surgical procedure. A total of 7 patients had an elevated temperature 37.4-39.1°C (mean temperature, 37.7±0.3°C) after the surgery, but no other major complications were noted. After 1 month, the residual stones were completely discharged, so that the stone clearance rate was 100%. All patients were followed up for 3-12 months and no associated complications occurred. Overall, ureteroscope lithotripsy assisted by a guide sheath for the treatment of upper ureteral calculi had the benefit of water injection and reflux functions, as well as enhanced vision, reduced pressure within the renal pelvis, good discharge of stones as well as an improved efficiency and success rate compared with simple ureteroscopic lithotripsy.

Cell studies of hybridized carbon nanofibers containing bioactive glass nanoparticles using bone mesenchymal stromal cells.

Bone regeneration required suitable scaffolding materials to support the proliferation and osteogenic differentiation of bone-related cells. In this study, a kind of hybridized nanofibrous scaffold material (CNF/BG) was prepared by incorporating bioactive glass (BG) nanoparticles into carbon nanofibers (CNF) via the combination of BG sol-gel and polyacrylonitrile (PAN) electrospinning, followed by carbonization. Three types (49 s, 68 s and 86 s) of BG nanoparticles were incorporated. To understand the mechanism of CNF/BG hybrids exerting osteogenic effects, bone marrow mesenchymal stromal cells (BMSCs) were cultured directly on these hybrids (contact culture) or cultured in transwell chambers in the presence of these materials (non-contact culture). The contributions of ion release and contact effect on cell proliferation and osteogenic differentiation were able to be correlated. It was found that the ionic dissolution products had limited effect on cell proliferation, while they were able to enhance osteogenic differentiation of BMSCs in comparison with pure CNF. Differently, the proliferation and osteogenic differentiation were both significantly promoted in the contact culture. In both cases, CNF/BG(68 s) showed the strongest ability in influencing cell behaviors due to its fastest release rate of soluble silicium-relating ions. The synergistic effect of CNF and BG would make CNF/BG hybrids promising substrates for bone repairing.