Changes of Drug Pharmacokinetics in Patients with Short Bowel Syndrome: A Systematic Review.

Background And Objectives: Short bowel syndrome is a clinical condition defined by malabsorption of nutrients and micronutrients, most commonly following extensive intestinal resection. Due to a loss of absorptive surfaces, the absorption of orally administered drugs is also often affected. The purpose of this study was to systematically review the published literature and examine the effects of short bowel syndrome on drug pharmacokinetics and clinical outcomes.

An Asian-centric human movement database capturing activities of daily living.

Assessment of human movement performance in activities of daily living (ADL) is a key component in clinical and rehabilitation settings. Motion capture technology is an effective method for objective assessment of human movement. Existing databases capture human movement and ADL performance primarily in the Western population, and there are no Asian databases to date.

Electroporation of NKG2D RNA CAR Improves Vγ9Vδ2 T Cell Responses against Human Solid Tumor Xenografts.

Vγ9Vδ2 T cell-based anticancer immunotherapy has shown some promise in early-phase clinical trials but there is still large room for improvement. Using the extracellular domain of the human NKG2D, a stimulatory receptor expressed by Vγ9Vδ2 T cells, we constructed NKG2D ligand-specific chimeric antigen receptors (CARs). We adopted a non-viral CAR approach via mRNA electroporation to modify Vγ9Vδ2 T cells and demonstrated that, upon interaction with the NKG2D ligand-positive cancer cells, the CARs substantially enhanced the cytotoxic activity of the modified cells toward multiple cultured solid tumor cell lines, including those resistant to Zometa treatment.

In Vitro Inhibition of Human Aldehyde Oxidase Activity by Clinically Relevant Concentrations of Gefitinib and Erlotinib: Comparison with Select Metabolites, Molecular Docking Analysis, and Impact on Hepatic Metabolism of Zaleplon and Methotrexate.

Gefitinib and erlotinib are epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) with activity against metastatic non-small cell lung cancer. Aldehyde oxidase-1 (AOX1) is a cytosolic drug-metabolizing enzyme. We conducted an experimental and molecular docking study on the effect of gefitinib, erlotinib, and select metabolites on the in vitro catalytic activity of AOX1, as assessed by carbazeran 4-oxidation, and determined the impact of AOX1 inhibition on hepatic metabolism of zaleplon and methotrexate.

Large-scale expansion of Vγ9Vδ2 T cells with engineered K562 feeder cells in G-Rex vessels and their use as chimeric antigen receptor-modified effector cells.

Vγ9Vδ2 T cells are a minor subset of lymphocytes in the peripheral blood that has been extensively investigated for their tolerability, safety and anticancer efficacy. A hindrance to the broad application of these cells for adoptive cellular immunotherapy has been attaining clinically appropriate numbers of Vγ9Vδ2 T cells. Furthermore, Vγ9Vδ2 T cells exist at low frequencies among cancer patients.

Clinical efficacy of a two-year oral health programme for infants and toddlers in Singapore.

Introduction: Dental caries, which is prevalent in Singapore preschoolers, is a disease that has a major impact on children's health and places a high cost on the society and health services. Oral health programmes for young children implemented in some parts of the world have been shown to be effective in the prevention of dental caries. We aimed to examine the clinical efficacy of a two-year oral health programme for infants and toddlers in Singapore.

Co-Expansion of Cytokine-Induced Killer Cells and Vγ9Vδ2 T Cells for CAR T-Cell Therapy.

Gamma delta (γδ) T cells and cytokine-induced killer (CIK) cells, which are a heterogeneous population of T lymphocytes and natural killer T (NKT) cells, have been separately expanded ex vivo and shown to be capable of targeting and mediating cytotoxicity against various tumor cells in a major histocompatibility complex-unrestricted manner. However, the co-expansion and co-administration of these immune cells have not been explored. In this study we describe an efficient method to expand simultaneously both CIK and Vγ9Vδ2 T cells, termed as CIKZ cells, from human peripheral blood mononuclear cells (PBMCs) using Zometa, interferon-gamma (IFN-γ), interleukin 2 (IL-2), anti-CD3 antibody and engineered K562 feeder cells expressing CD64, CD137L and CD86.

Human iPS cell-derived fibroblast-like cells as feeder layers for iPS cell derivation and expansion.

Mouse embryonic fibroblasts (MEFs) are commonly used as feeder cells for the generation of human induced pluripotent stem cells (hiPSCs). However, medical applications of cell derivatives of hiPSCs generated with a MEF feeder system run the risk of having xeno-factor contamination due to long-term cell culturing under an animal factor-containing environment. We developed a new method for the derivation of human fibroblast-like cells (FLCs) from a previously established hiPSC line in an FLC differentiation medium.

Genetic rearrangements of variable di-residue (RVD)-containing repeat arrays in a baculoviral TALEN system.

Virus-derived gene transfer vectors have been successfully employed to express the transcription activator-like effector nucleases (TALENs) in mammalian cells. Since the DNA-binding domains of TALENs consist of the variable di-residue (RVD)-containing tandem repeat modules and virus genome with repeated sequences is susceptible to genetic recombination, we investigated several factors that might affect TALEN cleavage efficiency of baculoviral vectors. Using a TALEN system designed to target the AAVS1 locus, we observed increased sequence instability of the TALE repeat arrays when a higher multiplicity of infection (MOI) of recombinant viruses was used to produce the baculoviral vectors.

Zinc finger nuclease-expressing baculoviral vectors mediate targeted genome integration of reprogramming factor genes to facilitate the generation of human induced pluripotent stem cells.

Integrative gene transfer using retroviruses to express reprogramming factors displays high efficiency in generating induced pluripotent stem cells (iPSCs), but the value of the method is limited because of the concern over mutagenesis associated with random insertion of transgenes. Site-specific integration into a preselected locus by engineered zinc-finger nuclease (ZFN) technology provides a potential way to overcome the problem. Here, we report the successful reprogramming of human fibroblasts into a state of pluripotency by baculoviral transduction-mediated, site-specific integration of OKSM (Oct3/4, Klf4, Sox2, and c-myc) transcription factor genes into the AAVS1 locus in human chromosome 19.

Targeted transgene insertion into the AAVS1 locus driven by baculoviral vector-mediated zinc finger nuclease expression in human-induced pluripotent stem cells.

Background: The AAVS1 locus is viewed as a 'safe harbor' for transgene insertion into human genome. In the present study, we report a new method for AAVS1 targeting in human-induced pluripotent stem cells (hiPSCs).

Methods: We have developed two baculoviral transduction systems: one to deliver zinc finger nuclease (ZFN) and a DNA donor template for site-specific gene insertion and another to mediate Cre recombinase-mediated cassette exchange system to replace the inserted transgene with a new transgene.

Baculoviral transduction facilitates TALEN-mediated targeted transgene integration and Cre/LoxP cassette exchange in human-induced pluripotent stem cells.

Safety and reliability of transgene integration in human genome continue to pose challenges for stem cell-based gene therapy. Here, we report a baculovirus-transcription activator-like effector nuclease system for AAVS1 locus-directed homologous recombination in human induced pluripotent stem cells (iPSCs). This viral system, when optimized in human U87 cells, provided a targeted integration efficiency of 95.

Inhibition of neuronal nitric oxide synthase activity promotes migration of human-induced pluripotent stem cell-derived neural stem cells toward cancer cells.

The breakthrough in derivation of human-induced pluripotent stem cells (hiPSCs) provides an approach that may help overcome ethical and allergenic challenges posed in numerous medical applications involving human cells, including neural stem/progenitor cells (NSCs). Considering the great potential of NSCs in targeted cancer gene therapy, we investigated in this study the tumor tropism of hiPSC-derived NSCs and attempted to enhance the tropism by manipulation of biological activities of proteins that are involved in regulating the migration of NSCs toward cancer cells. We first demonstrated that hiPSC-NSCs displayed tropism for both glioblastoma cells and breast cancer cells in vitro and in vivo.