Publications by authors named "Jessica Newton-Northup"

Phage display is a versatile method often used in the discovery of peptides that targets disease-related biomarkers. A major advantage of this technology is the ease and cost efficiency of affinity selection, also known as biopanning, to identify novel peptides. While it is relatively straightforward to identify peptides with optimal binding affinity, the pharmacokinetics of the selected peptides often prove to be suboptimal.

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Background: The melanocortin 4 antagonist TCMCB07 is safe and effective in reversing cachexia caused by sepsis or cancer in rodents. The safety and pharmacokinetics of TCMCB07 are demonstrated in healthy beagle dogs.

Hypothesis/objectives: The objectives of this study were to investigate the safety, peak plasma concentrations, and potential for efficacy of TCMCB07 in pet dogs with naturally occurring cachexia over a 4-week time period.

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During the development of a melanocortin (MC) peptide drug to treat the condition of cachexia (a hypermetabolic state producing lean body mass wasting), we were confronted with the need for peptide transport across the blood-brain barrier (BBB): the MC-4 receptors (MC4Rs) for metabolic rate control are located in the hypothalamus, i.e., behind the BBB.

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The melanocortin-4 receptor (MC4R) antagonistic peptide TCMCB07 was developed for the treatment of cachexia. The objectives of this study were to examine pharmacokinetics and safety of TCMCB07 administered subcutaneously to healthy dogs. Dogs were treated with high- (2.

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Ovarian cancer is often diagnosed at late stages due to current inadequate detection. Therefore, the development of new detection methods of ovarian cancer is needed. This may be achieved by phage nanoparticles that display targeting peptides for optical imaging.

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Bacteriophage (phage) display technology is a powerful strategy for the identification of peptide-based tumor targeting agents for drug discovery. Phage selections performed in vitro often result in many phage clones/peptides with similar properties and often similar sequence. However, these phage and corresponding peptides are selected, validated, and characterized outside the complicated milieu of a living animal.

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Metal-free click chemistry has become an important tool for pretargeted approaches in the molecular imaging field. The application of bioorthogonal click chemistry between a pretargeted trans-cyclooctene (TCO) derivatized monoclonal antibody (mAb) and a (99m)Tc-modified 1,2,4,5-tetrazine for tumor imaging was examined in vitro and in vivo. The HYNIC tetrazine compound was synthesized and structurally characterized, confirming its identity.

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Ovarian cancer is among the leading causes of cancer deaths in women, and is the most fatal gynecological malignancy. Poor outcomes of the disease are a direct result of inadequate detection and diagnostic methods, which may be overcome by the development of novel efficacious screening modalities. However, the advancement of such technologies is often time-consuming and costly.

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The often fatal outcome of ovarian cancer (OC) is related to inadequate detection methods, which may be overcome by development of nuclear imaging agents. Cancer targeting peptides have been identified using in vivo bacteriophage (phage) display technology; however, the majority of these ligands target tumor vasculature. To overcome this problem, a two-tier phage display method was employed to select an ovarian cancer targeting peptide with good pharmacokinetic and imaging properties.

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Purpose: Clinical use of most radiolabeled targeting agents has been limited because of the uptake and retention in kidney and/or liver. We hypothesized that bacteriophage (phage) display could be exploited to select for peptide sequences with fast clearance and low kidney uptake with the added ability to redirect phage clearance away from the reticuloendothelial system towards the kidney possessing rapid kidney clearance.

Procedures: In vivo phage display was performed to identify peptides displayed on phage that were excreted rapidly into the urine of mice.

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Galectin-3 (gal-3) is involved in the metastatic cascade and interacts with the cancer-associated carbohydrate, Thomsen-Freidenreich (TF) antigen during early stages of metastatic adhesion and tumor formation. Our laboratory previously utilized bacteriophage display to select a peptide, G3-C12, with high specificity and affinity for gal-3 that was able to inhibit cancer cell adhesion. We hypothesized that G3-C12 would inhibit TF/gal-3 and gal-3/gal-3 interactions in vitro and in vivo and would moderate early steps of the metastatic cascade leading to reduced carcinogenesis in vivo.

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Bacteriophage (phage) display has been exploited for the purpose of discovering new cancer specific targeting peptides. However, this approach has resulted in only a small number of tumor targeting peptides useful as in vivo imaging agents. We hypothesize that in vivo screening for tumor uptake of fluorescently tagged phage particles displaying multiple copies of an in vivo selected tumor targeting peptide will expedite the development of peptide based imaging agents.

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Introduction: Two-step and three-step pretargeting systems utilizing biotinylated prostate tumor-homing bacteriophage (phage) and (111)In-radiolabeled streptavidin or biotin were developed for use in cancer radioimaging. The in vivo selected prostate carcinoma-specific phage (G1) displaying up to five copies of the peptide IAGLATPGWSHWLAL was the focus of the present study.

Methods: The ability of G1 phage to extravasate and target prostate tumor cells was investigated using immunohistochemistry.

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