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3. Amyloid Beta Leads to Decreased Acetylcholine Levels and Non-Small Cell Lung Cancer Cell Survival via a Mechanism That Involves p38 Mitogen-Activated Protein Kinase and Protein Kinase C in a p53-Dependent and -Independent Manner.

Author

Al Khashali, Hind, Ray, Ravel, Darweesh, Ban, Wozniak, Caroline, Haddad, Ben, Goel, Stuti, Seidu, Issah, Khalil, Jeneen, Lopo, Brooke, Murshed, Nayrooz, Guthrie, Jeffrey, Heyl, Deborah, and Evans, Hedeel Guy

Subjects
NON-small-cell lung carcinoma, MITOGEN-activated protein kinases, CELL survival, AMYLOID, PROTEIN kinase C, ACETYLCHOLINE, ACETYLCHOLINESTERASE, CANCER cells
Abstract

Several studies have shown an inverse correlation between the likelihood of developing a neurodegenerative disorder and cancer. We previously reported that the levels of amyloid beta (Aβ), at the center of Alzheimer's disease pathophysiology, are regulated by acetylcholinesterase (AChE) in non-small cell lung cancer (NSCLC). Here, we examined the effect of Aβ or its fragments on the levels of ACh in A549 (p53 wild-type) and H1299 (p53-null) NSCLC cell media. ACh levels were reduced by cell treatment with Aβ 1–42, Aβ 1–40, Aβ 1–28, and Aβ 25–35. AChE and p53 activities increased upon A549 cell treatment with Aβ, while knockdown of p53 in A549 cells increased ACh levels, decreased AChE activity, and diminished the Aβ effects. Aβ increased the ratio of phospho/total p38 MAPK and decreased the activity of PKC. Inhibiting p38 MAPK reduced the activity of p53 in A549 cells and increased ACh levels in the media of both cell lines, while opposite effects were found upon inhibiting PKC. ACh decreased the activity of p53 in A549 cells, decreased p38 MAPK activity, increased PKC activity, and diminished the effect of Aβ on those activities. Moreover, the negative effect of Aβ on cell viability was diminished by cell co-treatment with ACh. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Regulation of Vascular Endothelial Growth Factor Signaling by Nicotine in a Manner Dependent on Acetylcholine-and/or β-Adrenergic-Receptors in Human Lung Cancer Cells

Author

Al Khashali, Hind, primary, Darweesh, Ban, additional, Ray, Ravel, additional, Haddad, Ben, additional, Wozniak, Caroline, additional, Ranzenberger, Robert, additional, Goel, Stuti, additional, Khalil, Jeneen, additional, Guthrie, Jeffrey, additional, Heyl, Deborah, additional, and Evans, Hedeel Guy, additional

Published
2023
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10. Achieving Tactical and Strategic Synergy in Optimizing Reproductive Health Care for Active-Duty Service Women The Military Active-Duty Reproductive + Sexual Health (MARSH) Research Program & Multiphase Optimization Strategy (MOST)

Author

Department of Family Medicine (FAM), SOM, Ryan Landoll, Sara E. Vargas, Kate M. Guthrie, Jeffrey Quinlan, Madison F. Clark, Francis Obuseh, Amelia Ozemoya, Department of Family Medicine (FAM), SOM, Ryan Landoll, and Sara E. Vargas, Kate M. Guthrie, Jeffrey Quinlan, Madison F. Clark, Francis Obuseh, Amelia Ozemoya

Abstract

Achieving Tactical and Strategic Synergy in Optimizing Reproductive Health Care for Active-Duty Service Women The Military Active-Duty Reproductive + Sexual Health (MARSH) Research Program & Multiphase Optimization Strategy (MOST) Ryan R. Landoll, PhD, ABPP, Lt Col, USAFR, Sara E. Vargas, PhD, Kate M. Guthrie, PhD, Jeffrey Quinlan, MD, Madison F. Clark, BS, Francis Obuseh, DrPH, & Amelia Ozemoya, MHS FUTURE DIRECTIONS RESULTS MULTIPHASE OPTIMIZATION STRATEGY (MOST) THE PROBLEM MARSH RESEARCH PROGRAM (Collins, 2018) The views expressed herein are solely those of the study team individually and are not representative of their respective institutions, to include the Uniformed Services University, Department of Defense or United States Government Focusing on DHA and DoD Priorities Ensuring Local Command Support Listening to Healthcare Providers and Service Members Unintended Pregnancies among U.S. Service Members High-risk Service Members untested for HIV in past year Cities with Military Installations in Top 20 for STIs nationally Think Talking to a Provider about Sexual Health Will be Negative • HIV/STI/Pregnancy Basic Training • Skills-Building Videos Beyond the Basics • Narrative Videos Stories from the Field • Interactive Scenarios Difficult Conversations • Goal Setting My Goals • Behavioral Risk Game Know Your Risk Q&A and Resources App Components • Formed in 2017 in partnership with The Miriam Hospital, affiliated with Brown University • Initially funded by the USU Women’s Health Research Consortium, with data collection endorsed by USD/P&R, employs mixed-method design • Has developed partnerships with 12 tri-service Military Treatment Facilities and over 40 collaborators, leverages civilian, military and academic partnerships • Intentional, data-driven, iterative and scientific approach to dissemination and implementation of sexual health resources “The amount of information available, it's a one stop area for any questions one may have” Needs assessment informe, RITM0040115, N/A

Published
2023

11. Phosphorylation of IGFBP-3 by Casein Kinase 2 Blocks Its Interaction with Hyaluronan, Enabling HA-CD44 Signaling Leading to Increased NSCLC Cell Survival and Cisplatin Resistance

Author

Coleman, Kai-ling, primary, Chiaramonti, Michael, additional, Haddad, Ben, additional, Ranzenberger, Robert, additional, Henning, Heather, additional, Al Khashali, Hind, additional, Ray, Ravel, additional, Darweesh, Ban, additional, Guthrie, Jeffrey, additional, Heyl, Deborah, additional, and Evans, Hedeel Guy, additional

Published
2023
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15. Abstract 1350: Investigating the Role of Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Regulating the Levels of Soluble Amyloid Precursor Protein α (sAPPα) in Lung Cancer Cell Media

Author

Al khashali, Hind, primary, Ray, Ravel, additional, Coleman, Kai-ling, additional, Atali, Sarah, additional, Haddad, Ben, additional, Wareham, Jadziah, additional, Guthrie, Jeffrey, additional, Heyl-Clegg, Deborah, additional, and Evans, Hedeel, additional

Published
2023
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35. D-Amino Acid Analogues of the Antimicrobial Peptide CDT Exhibit Anti- Cancer Properties in A549, a Human Lung Adenocarcinoma Cell Line

Author

Guy Evans, Hedeel, W. Guthrie, Jeffrey, Jujjavarapu, Murali, Hendrickson, Nathan, Eitel, Anna, Park, Yeji, Garvey, Jennifer, Newman, Rebecca, Esckilsen, Daniel, and L. Heyl, Deborah

Abstract

Introduction: The importance of the antitumor activity of some antimicrobial peptides (AMPs) is being increasingly recognized. The antimicrobial peptide, tachyplesin, has been shown to exhibit anticancer properties and a linear, cysteine deleted analogue (CDT), was found to retain its antibacterial function. Objectives: The objective was to test CDT and related analogues against normal mammalian, bacterial, and cancer cells to determine their effectiveness and then utilize specific assays to determine a possible mechanism of action. Methods: We used sequence reversal and D-amino acids to synthesize four CDT analogues by solid phase peptide synthesis. A number of assays were used including liposome dye-leakage, antibacterial activity against both Gram-positive and Gram-negative bacterial strains, hemolytic assays, methyl thiazolyl tetrazolium (MTT), and apoptosis to examine their effectiveness as both AMPs and anti-cancer peptides (ACPs). We then tested the analogues for their ability to inhibit proliferation of the human lung cancer cell line, A549. Results: We found that D-CDT exhibited the best bactericidal properties of those tested and was not damaging to red blood cells. Both D-CDT and reverse D-CDT showed a dose-dependent reduction of cell viability. However, D-CDT was most effective with an IC50 of 9.814 μM, a value 9-fold lower than that calculated for reverse D-CDT (90.16 μM). Apoptosis does not appear to be a mechanism by which D-CDT exerts its anticancer properties since > 100 μM was required to increase activation of caspase 3. Moreover, the ERK1/2 pathway is also unlikely since only a modest (20%) decrease of activity was observed with > 100 μM D-CDT. However, D-CDT was found to operate via a hyaluronan (HA)-dependent mechanism as pretreatment of the cells with hyaluronidase decreased the cytotoxic effects of D-CDT on A549 cells and increased its IC50 29-fold to 283.9 μM. Conclusion: D-CDT is both an effective AMP and ACP, and likely exerts its anticancer effects through both membranolytic as well as an HA-mediated mechanism.

Published
2017
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37. Technical Support DLA Apparel Research Network

Author

IIT RESEARCH INST ROME NY, Guthrie, Jeffrey D., IIT RESEARCH INST ROME NY, and Guthrie, Jeffrey D.

Abstract

The Defense Logistics Agency's Research and Development Enterprise Division established a network of universities, equipment suppliers, apparel manufacturers, industry consultants and software developers. The focus of this network, known as the Apparel Research Network, is to optimize the military clothing supply chain. Coordinating research activities of these diverse organizations is a daunting task. The Defense Logistics Agency's Research and Development Enterprise Division employs the DoD's Advanced Materials and Processes Technology Information Analysis Center (AMPTIAC) to directly assist the ARN program management with meeting coordination, technical oversight support, and assistance in technology transfer. This report describes the contents of that support from April 2001 to May 2002.

Published
2002

40. Selection and analytical applications of aptamers

Author

Hamula, Camille L.A., Guthrie, Jeffrey W., Zhang, Hongquan, Li, Xing-Fang, and Le, X. Chris

Subjects
*RNA, *MEDICAL equipment, *NUCLEIC acids, *GENES
Abstract

Abstract: Advances in systematic evolution of ligands by exponential enrichment (SELEX), a selection protocol for aptamers, have resulted in increased applications of DNA and RNA aptamers in developing analytical techniques. We review recent developments in SELEX techniques as well as new aptamer-based bioanalytical applications. [Copyright &y& Elsevier]

Published
2006
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41. Assays for cytokines using aptamers

Author

Guthrie, Jeffrey W., Hamula, Camille L.A., Zhang, Hongquan, and Le, X. Chris

Subjects
*NUCLEIC acid analysis, *CYTOKINES, *NUCLEOTIDE sequence, *CELLULAR immunity
Abstract

Abstract: Aptamers are short nucleic acid sequences that are used as ligands to bind their targets with high affinity. They are generated via the combinatorial chemistry procedure systematic evolution of ligands by exponential enrichment (SELEX). Aptamers have shown much promise towards detection of a variety of protein targets, including cytokines. Specifically, for the determination of cytokines and growth factors, several assays making use of aptamers have been developed, including aptamer-based enzyme-linked immunosorbent assays, antibody-linked oligonucleotide assay, fluorescence (anisotropy and resonance energy transfer) assays, and proximity ligation assays. In this article, the concept of aptamer selection using SELEX and the assay formats using aptamers for the detection of cytokines are discussed. [Copyright &y& Elsevier]

Published
2006
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42. Characterization of a cyclodextrinoligonucleotide complex by capillary electrophoresis using laser-induced fluorescence.

Author

Guthrie JW, Ryu JH, Le XC, and Wiebe LI

Subjects
Borates chemistry, Electrophoresis, Capillary, Fluoresceins chemistry, Fluorescence, Hydrogen-Ion Concentration, Lasers, Temperature, Arabinonucleotides chemistry, Oligonucleotides chemistry, beta-Cyclodextrins chemistry
Abstract

Purpose: Cyclodextrins (CDs) have been identified as a viable alternative to viral vectors for use in therapeutic applications. Here, the stability of the complex formed between the a multiply charged, cationic, fully substituted heptakis-(6-amino-2-galactosyl)cyclodextrin (BCDX12) with a multiply charged 12-mer hexachlorofluorescein tagged arabinopolynucleotide (Hex-PAH) have been evaluated., Methods: The stability of complexes of Hex-PAH and BCD-X12 was studied with respect to mole ratio (1:1, 1:2, and 1:5 Hex-PAH:BCD-X12), pH, buffer concentration, temperature, and agitation using capillary electrophoresis with laser induced fluorescence detection (CE/LIF). Two neutral CDs and an additional cationic CD were also tested under the same analytical conditions to determine their ability to form complexes., Results: Hex-PAH:BCDX12 complexes at mole ratios of 1:2 were stable in 10 mM (160 mM total borate concentration) sodium tetraborate buffer at pH 7.5 and at temperatures of 4 degrees C and 25 degrees C over 48 hours. However, the Hex-PAH:BCD-X12 complex was less stable at 37 degrees C and at higher buffer concentrations and pH values. Strong vortex mixing prior to analysis was found to disrupt the complex. Of the four CDs tested for their ability to complex with Hex-PAH, only BCDX12 formed stable complexes with Hex-PAH under the test conditions., Conclusions: Capillary electrophoresis was found to be well suited to test the stability of cyclodextrin-nucleotide complexes. CE/LIF indicated that only a single Hex- PAH:BCD-X12 complex was formed at all formulation ratios, and that the complexes were electrophoretically identical to each other, and increasing the molar ratio beyond 1:2 did not contribute measurably to complex stability. Storage temperature and agitation conditions were found to influence complex stability. Since no stable complexes were formed with neutral cyclodextrins, the results support the hypothesis of a 'charge associated' complex rather than an inclusion complex, although inclusion complexes cannot be excluded on the basis of these studies.

Published
2007

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