New synergistic combination therapy approaches with HDAC inhibitor quisinostat, cisplatin or PARP inhibitor talazoparib for urothelial carcinoma.

Urothelial carcinoma (UC) urgently requires new therapeutic options. Histone deacetylases (HDAC) are frequently dysregulated in UC and constitute interesting targets for the development of alternative therapy options. Thus, we investigated the effect of the second generation HDAC inhibitor (HDACi) quisinostat in five UC cell lines (UCC) and two normal control cell lines in comparison to romidepsin, a well characterized HDACi which was previously shown to induce cell death and cell cycle arrest. In UCC, quisinostat led to cell cycle alterations, cell death induction and DNA damage, but was well tolerated by normal cells. Combinations of quisinostat with cisplatin or the PARP inhibitor talazoparib led to decrease in cell viability and significant synergistic effect in five UCCs and platinum-resistant sublines allowing dose reduction. Further analyses in UM-UC-3 and J82 at low dose ratio revealed that the mechanisms included cell cycle disturbance, apoptosis induction and DNA damage. These combinations appeared to be well tolerated in normal cells. In conclusion, our results suggest new promising combination regimes for treatment of UC, also in the cisplatin-resistant setting.

Evidence of the synergetic role of charged species and atomic oxygen in the molecular etching of PTFE surfaces for hydrophobic surface synthesis.

The transformation of a poly(tetrafluoroethylene) (PTFE) hydrophobic surface into a superhydrophobic one using a low pressure RF plasma is explored using optical emission spectrometry (OES), X-ray photoelectron spectroscopy (XPS), water contact angle (WCA) measurements, mass measurements, and atomic force microscopy (AFM). It is shown that the increase in contact angle is due to an increase of roughness provoked by a chemical etching of the surface. We propose a molecular mechanism for etching that requires the simultaneous presence of atomic oxygen and negatively charged species (electrons) at the PTFE surface.

Prognostic factors in ossiculoplasty.

OBJECTIVE: To analyze predictive factors of outcome after ossiculoplasty using a standard ossicular prosthesis system. STUDY DESIGN: Retrospective review of 140 ossiculoplasties, performed by the same senior surgeon, with titanium prostheses. SETTINGS: Academic hospital and tertiary referral center. PATIENTS: All patients undergoing ossiculoplasty with Spiggle and Theis or Kurz titanium total and partial prostheses. Documented, postoperative follow-up had to be provided. A total of 129 patients (140 ears; 53 men and 76 women) were evaluated. INTERVENTIONS: These included ossiculoplasties using 75 Spiggle and Theis prostheses (30 partial and 45 total) and 65 Kurz prostheses (35 partial and 30 total). MAIN OUTCOME MEASURES: Mean preoperative and postoperative air-bone gaps and the changes in mean hearing loss were analyzed using a four-frequency (500, 1,000, 2,000, and 3,000 Hz) pure tone average. Success rate was defined as postoperative air-bone gap within 20 dB. A one-way analysis of variance was used to analyze group differences. A multivariate statistical analysis was then undertaken to define the significant factors. RESULTS: There were no statistical difference between the Spiggle and Theis and the Kurz prostheses. Multivariate statistical analysis has identified the predictive value of the presence or absence of the malleus handle and the mucosal status of the middle ear in the prognosis of ossiculoplasties. CONCLUSION: Anatomical and technical factors diversely affect the functional outcome of tympano-ossiculoplasties. A better knowledge of their predictive value will enable accurate, preoperative, individual assessment when counseling patients with regard to the success of any proposed intervention. The use of these factors will also permit precise matching of future series to allow accurate comparisons.