Cellular senescence is a terminal differentiation state that has been proposed to have a role in both tumour suppression and ageing. This view is supported by the fact that accumulation of senescent cells can be observed in response to oncogenic stress as well as a result of normal organismal ageing. Thus, identifying senescent cells in in vivo and in vitro has an important diagnostic and therapeutic potential. The molecular pathways involved in triggering and/or maintaining the senescent phenotype are not fully understood. As a consequence, the markers currently utilized to detect senescent cells are limited and lack specificity. In order to address this issue, we screened for plasma membrane-associated proteins that are preferentially expressed in senescent cells. We identified 107 proteins that could be potential markers of senescence and validated 10 of them (DEP1, NTAL, EBP50, STX4, VAMP3, ARMX3, B2MG, LANCL1, VPS26A and PLD3). We demonstrated that a combination of these proteins can be used to specifically recognize senescent cells in culture and in tissue samples and we developed a straightforward fluorescence-activated cell sorting-based detection approach using two of them (DEP1 and B2MG). Of note, we found that expression of several of these markers correlated with increased survival in different tumours, especially in breast cancer. Thus, our results could facilitate the study of senescence, define potential new effectors and modulators of this cellular mechanism and provide potential diagnostic and prognostic tools to be used clinically.

Objectives:To analyze the overall trends in cancer incidence and mortality in Saudi Arabia between 1990 and 2016.Methods:Data were retrieved through a Global Burden of Disease (GBD, 2016) database (Viz Hub) that is developed by the Institute for Health Metrics and Evaluation at the University of Washington.Results:The incidence of cancer increased around 26-fold for thyroid cancer; approximately 10-fold in breast, colon, bladder and uterine cancers; 8-fold for prostate cancer; 5-fold for renal cancer; 4-fold for pancreatic and ovarian cancer; 3.5-fold for lung cancer; 3-fold for liver cancer, and 2 folds for lymphoma, leukemia and gastric cancer. There was also an increase in the percentage of mortality due to cancer during this period. However, we noticed that the percentage of deaths due to cancer decreased after 70 years of age in Saudi Arabia population.Conclusion:The increases in the incidence of different types of cancer in the past decade could be due to the revolutionary change in socioeconomic status that has occurred in Saudi Arabia; therefore, a national plan should be established for cancer prevention, screening and therapy. Concerning mortality, the decrease in its percentage among elderly people could be due to biological factors that should be investigated in the future.

Abstractp53 is a tumor suppressor that prevents the emergence of transformed cells by inducing apoptosis or senescence, among other responses. Its functions are regulated tightly by posttranslational modifications. Here we show that Bruton's tyrosine kinase (BTK) is a novel modulator of p53. We found that BTK is induced in response to DNA damage and p53 activation. BTK induction leads to p53 phosphorylation, which constitutes a positive feedback loop that increases p53 protein levels and enhances the transactivation of its target genes in response to stress. Inhibiting BTK reduced both p53-dependent senescence and apoptosis. Further, BTK expression also upregulated DNA damage signals and apoptosis. We conclude that despite being involved in oncogenic signals in blood malignancies, BTK has antineoplastic properties in other contexts, such as the enhancement of p53's tumor suppressor responses. Along with evidence that BTK expression correlates with good prognosis in some epithelial tumors, our findings may encourage a reevaluation of the clinical uses of BTK inhibitors in cancer therapy.