No abstract

The JAK-STAT signalling pathway regulates cellular processes like cell division, cell death and immune regulation. Dysregulation has been identified in solid tumours and STAT3 activation is a marker for poor outcome. The aim of this study was to explore potential therapeutic strategies by targeting this pathway in bladder cancer (BC). High STAT3 expression was detected in 51.3% from 149 patient specimens with invasive bladder cancer by immunohistochemistry. Protein expression of JAK, STAT and downstream targets were confirmed in 10 cell lines. Effects of the JAK inhibitors Ruxolitinib and BSK-805, and STAT3/5 inhibitors Stattic, Nifuroxazide and SH-4-54 were analysed by cell viability assays, immunoblotting, apoptosis and cell cycle progression. Treatment with STAT3/5 but not JAK1/2 inhibitors reduced survival, levels of phosphorylated STAT3 and Cyclin-D1 and increased apoptosis. Tumour xenografts, using the chicken chorioallantoic membrane (CAM) model responded to Stattic monotherapy. Combination of Stattic with Cisplatin, Docetaxel, Gemcitabine, Paclitaxel and CDK4/6 inhibitors showed additive effects. The combination of Stattic with the oncolytic adenovirus XVir-N-31 increased viral replication and cell lysis. Our results provide evidence that inhibitors against STAT3/5 are promising as novel mono- and combination therapy in bladder cancer.

No abstract

Minimal invasive treatments such as arthroscopic techniques may be adequate to restore the anatomy and functional integrity of the thumb CMC (carpometacarpal) joint. In this paper, we reported the interposition of autologous fat tissue in combination with arthroscopic synovectomy/debridement for early stage of the thumb CMC joint osteoarthritis. Twelve patients with a mean age of 46 years with early radiological stages of thumb CMC joint osteoarthritis were included. Evaluation of outcome was measured prior and 3, 12, and 24 months after surgery including, Visual Analog Scale (VAS), QuickDASH, grip and pinch strength, range of motion (ROM), and patient satisfaction. Pain at rest (or with load) was reduced from preoperative 4,7 (8,7) to 2 (5,9) at 3 to 6 months; 1,4 (4,3) at 12 months; and 0,75 (2,7) at 2 years after the surgery. Initial preoperative QuickDASH value of 52 points reduced to 33 (17-65) at 6 months, 23 (2-70) at 12 months, and 20 (11-29) at 24 months after the surgery. Grip strength and thumb pinch with respect to the contralateral untreated thumb was reduced in the first 12 months but recovered subsequently. ROM was equal to the contralateral thumb. Three patients suffered from tendinitis and required surgical treatment. One patient indicated prolonged pain symptoms. No infections were noted and no donor-site morbidity or side effects were detected. Arthroscopic synovectomy combined with autologous fat graft is a reliable surgical option for early thumb CMC joint osteoarthritis and that effect continues for more than 24 months.