Publications by authors named "Aaron Sellers"

Introduction: The FDA has restrictions on cigarettes; however, little cigars and cigarillos (LCCs) remain largely absent from these regulations. Due to their low prices and flavoring, many engage in dual use of both LCCs and cigarettes. Dual use is particularly prevalent among low income racial/ethnic minority groups.

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Returning to the community after incarceration is a particularly vulnerable time with significantly increased risk of death in the first 2 weeks. The elevated risk of death persists as long as 2 years, with cardiovascular disease (CVD) among the leading causes. African-Americans, especially African-American men, have higher rates of incarceration and community supervision (e.

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Introduction: Drug overdoses are the leading cause of accidental death in the United States. It is imperative to explore predictors of opioid overdose in order to facilitate targeted treatment and prevention efforts. The present study was conducted as an exploratory examination of the factors associated with having a past opioid overdose.

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Background: Individuals in the criminal justice system demonstrate high rates of cigarette use (70-80%) and low adherence to smoking cessation medication. Educational approaches have not been shown to promote adherence or cessation, though medication sampling has boosted both use and cessation. The objective of the present study was to determine whether In vivo nicotine replacement therapy (NRT) sampling approach increases NRT adherence among criminal justice smokers during a subsequent quit attempt.

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A chemically defined anti-CXCR4-auristatin antibody-drug conjugate (ADC) was synthesized that selectively eliminates tumor cells overexpressing the CXCR4 receptor. The unnatural amino acid p-acetylphenylalanine (pAcF) was site-specifically incorporated into an anti-CXCR4 immunoglobulin G (IgG) and conjugated to an auristatin through a stable, non-cleavable oxime linkage to afford a chemically homogeneous ADC. The full-length anti-CXCR4 ADC was selectively cytotoxic to CXCR4(+) cancer cells in vitro (half maximal effective concentration (EC50 )≈80-100 pM).

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Antibody drug conjugates (ADCs) are monoclonal antibodies designed to deliver a cytotoxic drug selectively to antigen expressing cells. Several components of an ADC including the selection of the antibody, the linker, the cytotoxic drug payload and the site of attachment used to attach the drug to the antibody are critical to the activity and development of the ADC. The cytotoxic drugs or payloads used to make ADCs are typically conjugated to the antibody through cysteine or lysine residues.

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Using an expanded genetic code, antibodies with site-specifically incorporated nonnative amino acids were produced in stable cell lines derived from a CHO cell line with titers over 1 g/L. Using anti-5T4 and anti-Her2 antibodies as model systems, site-specific antibody drug conjugates (NDCs) were produced, via oxime bond formation between ketones on the side chain of the incorporated nonnative amino acid and hydroxylamine functionalized monomethyl auristatin D with either protease-cleavable or noncleavable linkers. When noncleavable linkers were used, these conjugates were highly stable and displayed improved in vitro efficacy as well as in vivo efficacy and pharmacokinetic stability in rodent models relative to conventional antibody drug conjugates conjugated through either engineered surface-exposed or reduced interchain disulfide bond cysteine residues.

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We describe here the development of site-specific antibody-polymer conjugates (APCs) for the selective delivery of small interference RNAs (siRNAs) to target cells. APCs were synthesized in good yields by conjugating an aminooxy-derivatized cationic block copolymer to an anti-HER2 Fab or full-length IgG by means of genetically encoded p-acetyl phenylalanine (pAcF). The APCs all showed binding affinity comparable to that of HER2 as their native counterparts and no significant cellular cytotoxicity.

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