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BackgroundPatient-derived organoids and xenografts (PDXs) have emerged as powerful models in functional diagnostics with high predictive power for anticancer drug response. However, limitations such as engraftment failure and time-consuming for establishing and expanding PDX models followed by testing drug efficacy, and inability to subject to systemic drug administration for ex vivo organoid culture hinder realistic and fast decision-making in selecting the right therapeutics in the clinic. The present study aimed to develop an advanced PDX model, namely MiniPDX, for rapidly testing drug efficacy to strengthen its value in personalized cancer treatment.MethodsWe developed a rapid in vivo drug sensitivity assay, OncoVee® MiniPDX, for screening clinically relevant regimens for cancer. In this model, patient-derived tumor cells were arrayed within hollow fiber capsules, implanted subcutaneously into mice and cultured for 7 days. The cellular activity morphology and pharmacokinetics were systematically evaluated. MiniPDX performance (sensitivity, specificity, positive and negative predictive values) was examined using PDX as the reference. Drug responses were examined by tumor cell growth inhibition rate and tumor growth inhibition rate in PDX models and MiniPDX assays respectively. The results from MiniPDX were also used to evaluate its predictive power for clinical outcomes.ResultsMorphological and histopathological features of tumor cells within the MiniPDX capsules matched those both in PDX models and in original tumors. Drug responses in the PDX tumor graft assays correlated well with those in the corresponding MiniPDX assays using 26 PDX models generated from patients, including 14 gastric cancer, 10 lung cancer and 2 pancreatic cancer. The positive predictive value of MiniPDX was 92%, and the negative predictive value was 81% with a sensitivity of 80% and a specificity of 93%. Through expanding to clinical tumor samples, MiniPDX assay showed potential of wide clinical application.ConclusionsFast in vivo MiniPDX assay based on capsule implantation was developed-to assess drug responses of both PDX tumor grafts and clinical cancer specimens. The high correlation between drug responses of paired MiniPDX and PDX tumor graft assay, as well as translational data suggest that MiniPDX assay is an advanced tool for personalized cancer treatment.

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Oxidative stress is considered to be a major cause of cellular injuries in a variety of chronic health problems, such as carcinogenesis and neurodegenerative disorders. Caffeic acid phenethyl ester (CAPE), derived from the propolis of honeybee hives, possesses a variety of biological and pharmacological properties including antioxidant and anticancer activity. In the present study, we focused on the diverse antioxidative functionalities of CAPE and its related polyphenolic acid esters on cellular macromolecules in vitro. The effects on human erythrocyte membrane ghost lipid peroxidation, plasmid pBR322 DNA, and protein damage initiated by the water-soluble initiator 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) and hydrogen peroxide (H(2)O(2)) were monitored by formation of hydroperoxides and by DNA nicking assay, single-cell alkaline electrophoresis, and SDS-polyacrylamide gel electrophoresis. Our results showed that CAPE and its related polyphenolic acid esters elicited remarkable inhibitory effects on erythrocyte membrane lipid peroxidation, cellular DNA strand breakage, and protein fragmentation. The results suggest that CAPE is a potent exogenous cytoprotective and antigenotoxic agent against cell oxidative damage that could be used as a template for designing novel drugs to combat diseases induced by oxidative stress components, such as various types of cancer.

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Graphical abstract Schematic diagram of the mechanism by which H 2 S inhibits VSMC proliferation targeting on the FOXO1. H 2 S persulfidates FOXO1 at Cys457, which reduces FOXO1 phosphorylation at Ser256, prevents the FOXO1 nucleus exclusion to the cytoplasm, and further protecting against ET-1-induced VSMC proliferation.