Efficacy of CDK4/6 inhibitors in preclinical models of malignant pleural mesothelioma

Background There is no effective therapy for patients with malignant pleural mesothelioma (MPM) who progressed to platinum-based chemotherapy and immunotherapy. Methods We aimed to investigate the antitumor activity of CDK4/6 inhibitors using in vitro and in vivo preclinical models of MPM. Results Based on publicly available transcriptomic data of MPM, patients with CDK4 or CDK6 overexpression had shorter overall survival. Treatment with abemaciclib or palbociclib at 100 nM significantly decreased cell proliferation in all cell models evaluated. Both CDK4/6 inhibitors significantly induced G1 cell cycle arrest, thereby increasing cell senescence and increased the expression of interferon signalling pathway and tumour antigen presentation process in culture models of MPM. In vivo preclinical studies showed that palbociclib significantly reduced tumour growth and prolonged overall survival using distinct xenograft models of MPM implanted in athymic mice. Conclusions Treatment of MPM with CDK4/6 inhibitors decreased cell proliferation, mainly by promoting cell cycle arrest at G1 and by induction of cell senescence. Our preclinical studies provide evidence for evaluating CDK4/6 inhibitors in the clinic for the treatment of MPM

Design evolution of the Giant Magellan Telescope Integral Field Spectrograph, GMTIFS

We report the design evolution for the GMT Integral Field Spectrograph, (GMTIFS). To support the range of operating modes – a spectroscopic channel providing integral field spectroscopy with variable spaxel scales, and a parallel imaging channel Nyquist sampling the LTAO corrected field of view - the design process has focused on risk mitigation for the demanding operational tolerances. We summarise results from prototype components, confirming concepts are meeting the necessary specifications. Ongoing review and simulation of the scientific requirements also leads to new demonstrations of the science that will be made possible with this new generation of high performance AO assisted instrumentation

Gemini multiconjugate adaptive optics system review - I. Design, trade-offs and integration

International audienc

Gemini multiconjugate adaptive optics system review - II. Commissioning, operation and overall performance

The Gemini multiconjugate adaptive optics system-GeMS, a facility instrument mounted on the Gemini South telescope, delivers a uniform, near diffraction limited images at near-infrared wavelengths (0.95-2.5 μm) over a field of view of 120 arcsec. GeMS i

DNA Methylation: Biological Implications and Modulation of Its Aberrant Dysregulation

The alteration of the DNA methylation pattern is often related to the onset of diseases based on epigenetic dysregulation, primarily cancer. In this scenery the development of DNA methyltransferase inhibitors is one of the most attractive challenges for anticancer therapy. The present chapter proposes a comprehensive classification of the DNA methyltransferase inhibitors known in literature, on the basis of their natural or synthetic nature and their mechanism of action