To our knowledge, this is the first study to examine relationships between LBM, liver mass/function and epirubicin PK and toxicity. This exploratory work investigates the notion of organs and tissues having distinctive contributions to the distribution and metabolism of antineoplastic drugs.

Conventional bone composites consistently fail to mimic the chemical composition and integrated organic/inorganic structure of natural bone, lacking sufficient mechanics as well as inherent osteoconductivity and osteoinductivity. Through a facile surface coating process, the strong adhesive, tannic acid (TA), is adhered to the surface of the natural bone component, hydroxyapatite (HA), with and without the immobilization of in situ formed silver nanoparticles. Residual functional groups available on the immobilized TA substituents are subsequently covalently linked to the citrate‐based biodegradable polymer, poly(octamethylene citrate) (POC), effectively bridging the organic and inorganic phases. Due to the synergistic effects of the tannin and citrate components, the obtained citrate‐based tannin‐bridged bone composites (CTBCs) exhibit vastly improved compression strengths up to 323.0 ± 21.3 MPa compared to 229.9 ± 15.6 MPa for POC‐HA, and possess tunable degradation profiles, enhanced biomineralization performance, favorable biocompatibility, increased cell adhesion and proliferation, as well as considerable antimicrobial activity. In vivo study of porous CTBCs using a lumbar fusion model further confirms CTBCs' osteoconductivity and osteoinductivity, promoting bone regeneration. CTBCs possess great potential for bone regeneration applications while the immobilized TA additionally preserves surface bioconjugation sites to further tailor the bioactivity of CTBCs.

Purpose: Combinations of tyrosine kinase inhibitors (TKI) with gemcitabine have been attempted with little added benefit to patients. We hypothesized that TKIs designed to bind to ATP-binding pockets of growth factor receptors also bind to transporter proteins that recognize nucleosides.Experimental Design: TKI inhibition of uridine transport was studied with recombinant human (h) equilibrative (E) and concentrative (C) nucleoside transporters (hENT, hCNT) produced individually in yeast. TKIs effects on uridine transport, gemcitabine accumulation, regulation of hENT1 activity, and cell viability in the presence or absence of gemcitabine were evaluated in human pancreatic and lung cancer cell lines.Results for 24 hours reduced hENT1 activity which was reversed by subsequent incubation in drug-free media for 24 hours. Greater cytotoxicity was observed when gemcitabine was administered before erlotinib, gefitinib, or vandetanib than when administered together and synergy, evaluated using the CalcuSyn Software, was observed in three cell lines resulting in combination indices under 0.6 at 50% reduction of cell growth.Conclusions: Vandetanib inhibited hENT1, hENT2, hCNT1, hCNT2, and hCNT3, whereas erlotinib inhibited hENT1 and hCNT3 and gefitinib inhibited hENT1 and hCNT1. The potential for reduced accumulation of nucleoside chemotherapy drugs in tumor tissues due to inhibition of hENTs and/or hCNTs by TKIs indicates that pharmacokinetic properties of these agents must be considered when scheduling TKIs and nucleoside chemotherapy in combination.