Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

The thymus is a central lymphoid organ with crucial role in generating T cells and maintaining homeostasis of the immune system. More than 30 peptides, initially referred to as “thymic hormones,” are produced by this gland. Although the majority of them have not been proven to be thymus-speciWc, thymic peptides comprise an eVective group of regulators, mediating important immune functions. Thymosin fraction Wve (TFV) was the Wrst thymic extract shown to stimulate lymphocyte proliferation and diVerentiation. Subsequent fractionation of TFV led to the isolation and characterization of a series of immunoactive peptides/polypeptides, members of the thymosin family. Extensive research on prothymosin (proT) and thymosin 1 (T1) showed that they are of clinical signiWcance and potential medical use. They may serve as molecular markers for cancer prognosis and/or as therapeutic agents for treating immunodeWciencies, autoimmune diseases and malignancies. Although the molecular mechanisms underlying their eVect are yet not fully elucidated proT and T1 could be considered as candidates for cancer immunotherapy. In this review, we will focus in principle on the eventual clinical utility of proT, both as a tumor biomarker and in triggering anticancer immune responses. Considering the experience acquired via the use of T1 to treat cancer patients, we will also discuss potential approaches for the future introduction of proT into the clinical setting

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Synthesis, Biological Evaluation and Stability Studies of Some Novel Aza-Acridine Aminoderivatives

Several new amino-substituted aza-acridine derivatives bearing a basic side chain have been designed and synthesized. The antiproliferative activity of the target compounds has been evaluated against three cancer cell lines—namely HCT-116 (colorectal), the uterine sarcoma MES-SA, and its doxorubicin-resistant variant MES-SA/Dx5. A limited number of the new acridines showed marginal cytotoxicity against the tested cell lines; nevertheless, these analogues possessed a similar substitution pattern. The moderate biological activity of these derivatives was attributed to their instability in aqueous media, which has been studied by mass spectrometry and computational chemistry experiments at the density functional level of theory (DFT)

Molecular responses to therapeutic proteasome inhibitors in multiple myeloma patients are donor-, cell type-and drug-dependent

Proteasome is central to proteostasis network functionality and its overactivation represents a hallmark of advanced tumors; thus, its selective inhibition provides a strategy for the development of novel antitumor therapies. In support, proteasome inhibitors, e.g. Bortezomib or Carfilzomib have demonstrated clinical efficacy against hematological cancers. Herein, we studied proteasome regulation in peripheral blood mononuclear cells and erythrocytes isolated from healthy donors or from Multiple Myeloma patients treated with Bortezomib or Carfilzomib. In healthy donors we found that peripheral blood mononuclear cells express higher, as compared to erythrocytes, basal proteasome activities, as well as that proteasome activities decline during aging. Studies in cells isolated from Multiple Myeloma patients treated with proteasome inhibitors revealed that in most (but, interestingly enough, not all) patients, proteasome activities decline in both cell types during therapy. In peripheral blood mononuclear cells, most proteostatic genes expression patterns showed a positive correlation during therapy indicating that proteostasis network modules likely respond to proteasome inhibition as a functional unit. Finally, the expression levels of antioxidant, chaperone and aggresomes removal/autophagy genes were found to inversely associate with patients' survival. Our studies will support a more personalized therapeutic approach in hematological malignancies treated with proteasome inhibitors. © Papanagnou et al