Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy with high incidence in the aging population. In addition, AML is one of the more common pediatric malignancies. Unfortunately, both of these patient groups are quite sensitive to chemotherapy toxicities. Investigation of blueberries specifically as an anti-AML agent has been limited, despite being a prominent natural product with no reported toxicity. In this study, blueberry extracts are reported for the first time to exert a dietary therapeutic effect in animal models of AML. Furthermore, in vitro studies revealed that blueberry extracts exerted anti-AML efficacy against myeloid leukemia cell lines as well as against primary AML, and specifically provoked Erk and Akt regulation within the leukemia stem cell subpopulation. This study provides evidence that blueberries may be unique sources for anti-AML biopharmaceutical compound discovery, further warranting fractionation of this natural product. More so, blueberries themselves may provide an intriguing dietary option to enhance the anti-AML efficacy of traditional therapy for subsets of patients that otherwise may not tolerate rigorous combinations of therapeutics.

In the current study, we have experimentally and comparatively investigated and compared malignant human cancer cells and tissues before and after irradiating of synchrotron radiation using Neutron Spin Echo Spectroscopy and Spin Noise Spectroscopy. It is clear that malignant human cancer cells and tissues have gradually transformed to benign human cancer cells and tissues under synchrotron radiation with the passage of time (Figures 1 and 2) [1–106].

When the patent of a small molecule drug expires, generics may be introduced. They are considered therapeutically equivalent once pharmaceutical equivalence (i.e. identical active substances) and bioequivalence (i.e. comparable pharmacokinetics) have been established in cross-over volunteer study. However this generic paradigm cannot be applied to complex drugs as biologics. For copies of biologics EMA, and FDA, have introduced a new regulatory biosimilar pathway which mandate clinical trials to show therapeutic equivalence. However for some complex drugs, such as iron-carbohydrate drugs, liposomal drugs, glatiramoids (named Non Biologic Complex Drugs [NBCD]), regulatory guidance is still mostly lacking. In this paper we will discuss therapeutic experiences with these different classes of complex drugs and their specificity, to provide scientific arguments for consideration for a new regulatory framework.

Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy with limited treatment options. Inflammation is often a contributing factor to the development and progression of AML, and related diseases, and can potentiate therapy failure. Previously, we had identified anti- inflammatory roles and anti-AML efficacy for blueberry extracts. The present study extended these observations to determine that the polyphenols Quercitin inhibited neutral Sphingomyelinase (N-SMase) activity and exerted anti-AML efficacy. Moreover, Quercitin was shown to exert combinatorial anti- AML efficacy with Nanoliposomal ceramide. Overall, this demonstrated that Quercitin could block the pro-inflammatory actions of N-SMase and augment the efficacy of anti- AML therapeutics, including ceramide-based therapeutics.

While the number of therapeutic biologics on the market has dramatically increased in the past decades, oral delivery of protein/peptide drugs is still one of the challenges for biopharmaceutical scientists. Transferrin (Tf), with its receptor-mediated transcytosis mechanism across intestinal epithelium, has been proven as a potential oral delivery carrier for different protein therapeutics. However, one of the major rate-limiting issues of Tf in oral absorption is that Tf Receptor (TfR) is selectively expressed on the basolateral surface instead of the apical surface of the intestinal epithelium, and thus, limits the mucosal transport capacity of Tf across the intestinal epithelium. To overcome this limitation and develop a more efficient oral delivery carrier, a novel transcytosis mechanism was proposed. The proposed transcytosis mechanism is composed of three major steps: apical binding and endocytosis of Tf with a cationic peptide carrier, intracellular cleavage of the linker between peptide and Tf, and basolateral exocytosis by TfR. The feasibility of the proposed approach was demonstrated when Tf was conjugated to poly-L-lysine (PLL) using a pHsensitive Nitrilo Triacetic Acid (NTA) linker in the presence of nickel (Ni2+). The results of Caco-2 transcytosis assay suggested that the transcytosis rate of histidine-tagged Tf could be unidirectionally increased from apical to basolateral compartment when co-incubated with Ni2+-NTA-PLL.