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

Transcultural literacies in online collaboration: a case study of fanfiction translation from Russian into English

This study analyses the transcultural meaning-making and literacies that arise during the amateur translation of a fanfiction novel from Russian to English. We applied digital ethnography to make observations of the translation process and interviews with the participants. Transcultural meaning-making was identified during their discussions on how to adapt a Russian fanfiction novel for a global English-speaking readership. During the discussions the participants creatively mixed different linguistic and cultural resources. They also positioned themselves as mediators between two readerships, which pushed them to reflect on literary and philosophical traditions of the Russian and English-speaking cultures and engage in transcultural literacies.This work was supported by Ministerio de Ciencia, Innovación y Universidades [grant number Research project For-Vid, RT2018-100790-B-100]