Malignant mesothelioma (MM) is an aggressive asbestos‐related cancer of the serous membranes. Despite intensive treatment regimens, MM is still a fatal disease, mainly due to the intrinsic resistance to current therapies and the lack of predictive markers and new valuable molecular targets. Protein arginine methyltransferase 5 (PRMT5) inhibition has recently emerged as a potential therapy against methylthioadenosine phosphorylase (MTAP)‐deficient cancers, in which the accumulation of the substrate 5'‐methylthioadenosine (MTA) inhibits PRMT5 activity, thus sensitizing the cells to further PRMT5 inhibition. Considering that the MTAP gene is frequently codeleted with the adjacent cyclin‐dependent kinase inhibitor 2A (CDKN2A) locus in MM, we assessed whether PRMT5 could represent a therapeutic target also for this cancer type. We evaluated PRMT5 expression, the MTAP status and MTA content in normal mesothelial and MM cell lines. We found that both administration of exogenous MTA and stable PRMT5 knock‐down, by short hairpin RNAs (shRNAs), selectively reduced the growth of MTAP‐deleted MM cells. We also observed that PRMT5 knock‐down in MTAP‐deficient MM cells reduced the expression of E2F1 target genes involved in cell cycle progression and of factors implicated in epithelial‐to‐mesenchymal transition. Therefore, PRMT5 targeting could represent a promising new therapeutic strategy against MTAP‐deleted MMs.
Malignant mesothelioma (MM) is a very aggressive asbestos-related cancer, whose incidence is increasing worldwide. Unfortunately, no effective therapies are currently available and the prognosis is extremely poor. Recently, the anti-helminthic drug pyrvinium pamoate has attracted a strong interest for its anti-cancer activity, which has been demonstrated in many cancer models. Considering the previously established inhibitory effect of pyrvinium pamoate on the Wnt/β-catenin pathway and given the important role of this pathway in MM, we investigated the potential anti-tumor activity of this drug in MM cell lines. We observed that pyrvinium pamoate significantly impairs MM cell proliferation, cloning efficiency, migration, and tumor spheroid formation. At the molecular level, our data show that pyrvinium pamoate down-regulates the expression of β-catenin and Wnt-regulates genes. Overall, our study suggests that the repurposing of pyrvinium pamoate for MM treatment could represent a new promising therapeutic approach.
Assisted reproductive technologies (ARTs) are widely used as a tool to improve reproductive performance in both humans and animals. In particular, in the veterinary field, ARTs are used to improve animal genetics, recover endangered animals, and produce offspring in the event of subfertility or infertility in males or females. However, the use of ARTs did not improve the fertilization rate in some animals due to various factors such as the difficulty in reproducing an anatomical and humoral substrate typical of the natural condition or due to the increase in catabolites and their difficult elimination. The
in vitro
environment allows the production and increase in the concentration of substances, including reactive oxygen species (ROS), which could be harmful to gametes. If produced in high concentration, the ROS becomes deleterious, both
in vitro
and
in vivo
systems. It has been seen that the use of antioxidants can help neutralize or counteract the production of ROS. The present study aims to report the latest findings regarding the use of antioxidants in ARTs of some domestic species, such as dogs, cats, and horses, compared to other animal species, such as cattle, in which ARTs have instead developed more widely.
SARS-CoV-2 (COVID-19) belongs to the same coronavirus group (Beta-coronavirus) as SARS and MERS viruses that caused two of the more severe epidemics in recent years. Horseshoe bats (genus Rhinolophus) have been identified as the natural reservoirs of SARS-related coronaviruses (CoVs) and the likely origin of SARS-CoV-2. The intermediate host is thought to be the pangolin. The purpose of this review is to draw attention to the relationship between COVID-19 and different malignancies, and to discuss the similarities in their pathogenesis, and the possible repurposing of cancer drugs for the treatment of COVID-19. Along with antiviral and anti-inflammatory drugs, several anti-cancer drugs can be potentially repurposed in the management of COVID-19. The pathogenesis of COVID-19 and cancer shares certain similarities, including inflammation, immunological dysregulation, and coagulopathy. Blood parameters in COVID-19 patients upon admission show lymphocytopenia, and elevated C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and D-dimer levels in most of the patients. Currently, RT-PCR is the gold-standard laboratory test for COVID-19 confirmation in suspected cases.
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