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TP-38 is a recombinant chimeric targeted toxin composed of the EGFR binding ligand TGF-alpha and a genetically engineered form of the Pseudomonas exotoxin, PE-38. After in vitro and in vivo animal studies that showed specific activity and defined the maximum tolerated dose (MTD), we investigated this agent in a Phase I trial. The primary objective of this(More)
Molecular size is one of the key determinants of transvascular transport of therapeutic agents in tumors. However, there are no data in the literature on the molecular size dependence of microvascular permeability in tumors. Therefore, we measured microvascular permeability to various macromolecules in the human colon adenocarcinoma LS174T transplanted in(More)
Many brain tumors are highly resistant to chemotherapy, presumably due to the presence of a tight blood-tumor barrier. For a better understanding of the regulation of this barrier by the brain environment, a new intravital microscopy model was established by transplanting tumor tissue into cranial windows in both rats and mice. The model was characterized(More)
To date, most quantitative information on tumor angiogenesis, micro-circulation, and transport has been derived from rodent tumors grown in transparent chamber preparations. In this paper we present a chamber technique adapted to immunodeficient mice for the study of human tumor xenografts. Microcirculatory parameters in severe combined im-munodeficient(More)
Magneto-optic (MO) imaging produces images of magnetic flux leakage from surface and sub-surface defects. The presence of domain boundaries in the MO sensor produces a characteristic artefact in the images that renders detection of cracks difficult. This paper presents two different approaches for the removal of domain boundaries in MO images. The first(More)
The goal of this investigation was to measure changes in vascular permeability, pore cutoff size, and number of transvascular transport pathways as a function of time and in response to vascular endothelial growth factor (VEGF), placenta growth factor (PIGF-1 and PIGF-2), or basic fibroblast growth factor (bFGF). Two human and two murine tumors were(More)
The effects of glutamate and its agonists and antagonists on the swelling of cultured astrocytes were studied. Swelling of astrocytes was measured by [3H]-O-methyl-D-glucose uptake. Glutamate at 0.5, 1 and 10 mmol/L and trans-1-aminocyclopentane-1, 3-dicarboxylic acid (trans-ACPD), a metabotropic glutamate receptor (mGluR) agonist, at 1 mmol/L caused a(More)
Molecular charge is one of the main determinants of transvascular transport. There are, however, no data available on the effect of molecular charge on microvascular permeability of macromolecules in solid tumours. To this end, we measured tumour microvascular permeability to different proteins having similar size but different charge. Measurements were(More)
Electric field mediated gene delivery or electrotransfection is a widely used method in various studies ranging from basic cell biology research to clinical gene therapy. Yet, mechanisms of electrotransfection are still controversial. To this end, we investigated the dependence of electrotransfection efficiency (eTE) on binding of plasmid DNA (pDNA) to(More)
Plasmids may have unique advantages as a gene delivery system. However, a major obstacle is the low in vivo transduction efficiency. In this study, an electroporation-based gene transduction approach was taken to study the effect of interleukin (IL)-2 or IL-12 gene transduction on the growth of experimental murine tumors. Significant intratumoral gene(More)