In the rapidly advancing field of synthetic biology, there exists a critical need for technology to discover targeting moieties for therapeutic biologics. Here we present INSPIRE-seq, an approach that utilizes a nanobody library and next-generation sequencing to identify nanobodies selected for complex environments. INSPIRE-seq enables the parallel enrichment of immune cell-binding nanobodies that penetrate the tumor microenvironment.
View Article and Find Full Text PDFCanine soft tissue sarcoma (STS) has served as a preclinical model for radiation, hyperthermia, experimental therapeutics, and tumor microenvironmental research for decades. Stereotactic body radiotherapy (SBRT) demonstrates promising results for the control of various tumors in human and veterinary medicine; however, there is limited clinical data for the management of STS with SBRT. In this retrospective study, we aimed to define overall efficacy and toxicity of SBRT for the treatment of macroscopic canine STS to establish this preclinical model for comparative oncology research.
View Article and Find Full Text PDFIsoniazid is a potent and selective therapeutic prodrug agent used to treat infections by Mycobacterium tuberculosis. Although it has been used clinically for over five decades its full mechanism of action is still being elucidated. Essential to its mechanism of action is the activation of isoniazid to a reactive intermediate, the isonicotinyl acyl radical, by the catalase-peroxidase KatG.
View Article and Find Full Text PDFIn support of the potential use of advanced oxidation and reduction process technologies for the removal of carcinogenic nitro-containing compounds in water reaction rate constants for the hydroxyl radical and hydrated electron with a series of low molecular weight nitramines (R(1)R(2)-NNO(2)) have been determined using a combination of electron pulse radiolysis and transient absorption spectroscopy. The hydroxyl radical reaction rate constant was fast, ranging from 0.54-4.
View Article and Find Full Text PDFMethyl isothiocyanate (MITC), a toxic and corrosive skin and respiratory irritant, is a common soil fumigant byproduct which has become an atmospheric, aqueous, and soil contaminant. The work described here examines the degradation and potential removal of MITC from contaminated waters via free radical reactions. We have measured the oxidizing hydroxyl radical ((·)OH) reaction rate constant with MITC over a range of temperatures relevant to wastewater treatment conditions, determining a room temperature value of (5.
View Article and Find Full Text PDFTemperature-dependent kinetics for the reactions of hydroxyl radicals and hydrated electrons with the anti-cancer drug nedaplatin have been determined using a combination of electron pulse radiolysis and absorption spectroscopy. Under physiological pH and chloride concentrations, the kinetics was well described by the equations [Formula: see text]and [Formula: see text]corresponding to Arrhenius activation energies of 15.88 +/- 1.
View Article and Find Full Text PDFArrhenius parameters for the reactions of oxidizing hydroxyl radicals and reducing hydrated electrons with cisplatin, transplatin and carboplatin in aqueous solution have been determined using pulsed electron radiolysis and absorption spectroscopy techniques. Under physiological pH and chloride concentration conditions, hydroxyl radical reaction rate constants of (9.99 +/- 0.
View Article and Find Full Text PDFAbsolute rate constants and degradation efficiencies for hydroxyl radical reactions with seven low-molecular-weight nitrosamines in water have been evaluated using a combination of electron-pulse radiolysis/absorption spectroscopy and steady-state radiolysis/GCMS measurements. The hydroxyl radical oxidation rate constants were found to depend upon nitrosamine size and to have a very good linear correlation with the number of methylene groups in these compounds. This correlation, given by In(k x OH) = (19.
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