Therapeutic resistance seen in aggressive forms of breast cancer remains challenging for current treatments. More than half of the patients suffer from a disease relapse, most of them with distant metastases. Cancer maintenance, resistance to therapy, and metastatic disease seem to be sustained by the presence of cancer stem cells (CSC) within a tumor. The difficulty in targeting this subpopulation derives from their dynamic interconversion process, where CSC can differentiate to non-CSC, which in turn de-differentiate into cells with CSC properties. Using fluorescent CSC models driven by the expression of ALDH1A 1(aldehyde dehydrogenase 1A1), we confirmed this dynamic phenotypic change in MDA-MB-231 breast cancer cells and to identify Serine/Threonine Kinase 2 (AKT2) as an important player in the process. To confirm the central role of AKT2, we silenced AKT2 expression via small interfering RNA and using a chemical inhibitor (CCT128930), in both CSC and non-CSC from different cancer cell lines. Our results revealed that AKT2 inhibition effectively prevents non-CSC reversion through mesenchymal to epithelial transition, reducing invasion and colony formation ability of both, non-CSC and CSC. Further, AKT2 inhibition reduced CSC survival in low attachment conditions. Interestingly, in orthotopic tumor mouse models, high expression levels of AKT2 were detected in circulating tumor cells (CTC). These findings suggest AKT2 as a promising target for future anti-cancer therapies at three important levels: (i) Epithelial-to-mesenchymal transition (EMT) reversion and maintenance of CSC subpopulation in primary tumors, (ii) reduction of CTC and the likelihood of metastatic spread, and (iii) prevention of tumor recurrence through inhibition of CSC tumorigenic and metastatic potential.

No abstract

No abstract

No abstract

No abstract

No abstract

Therapeutic or preventive research for coronavirus SARS-CoV2 is an extremely active topic of research since its outbreak in January 2020. In this paper we report the results from a virtual drug screening analysis that, to the best of our knowledge, is the widest work in terms of target proteins and compound library. Our study was focused on the repurposing of currently commercialized drugs, and especially those that can interact with multiple viral proteins and several binding sites within each protein. Additionally, we performed a second virtual screening analysis in which we compared our results to the predicted binding affinities for the drugs currently in clinical trials. We show that the best molecules in our screening compares favorably to those in clinical trials, suggesting their suitability for therapeutic or preventive applications.

In this paper, an analytical approach is used to determine the Flux-linkage characteristic of regular Switched Reluctance Machines (SRMs) considering simple geometry aspects. The proposed method is derived from an 8/6 SRM magnetic characteristic obtained by experimental tests and validated by FEM results. In order to reduce calculation time and expense, regarding simulation and implementation proposes, this analytical functions approach requires only few parameters, normally available or easily measured. An application example for a 6/4 SRM is presented to illustrate its use.