Medical Pharmacology Commons^™

Partial Treatment Response To Capmatinib In Met-Amplified Metastatic Intrahepatic Cholangiocarcinoma: Case Report & Review Of Literature, Daniel S Lefler, Marni Brisson Tierno, Babar Bashir

Department of Medical Oncology Faculty Papers

Cholangiocarcinoma is a highly morbid gastrointestinal malignancy for which available therapies are limited. Standard of care includes cytotoxic chemotherapies such as gemcitabine, platinum agents, nab-paclitaxel, and fluoropyrimidine analogues. However, tolerability of these regimens varies, and patients who do not tolerate chemotherapy have limited targeted therapies and immunotherapy options. In cholangiocarcinoma, mesenchymal-epithelial transition factor (MET) amplification may present an additional opportunity for a targeted therapeutic approach, especially considering emerging data in non-small cell lung cancer. In this case, we present a metastatic cholangiocarcinoma patient with high-level MET gene amplification for whom capmatinib, a tyrosine kinase inhibitor with activity against c-MET, …

Sorafenib, Rapamycin, And Venetoclax Attenuate Doxorubicin-Induced Senescence And Promote Apoptosis In Hct116 Cells, Homood M. As Sobeai, Munirah Alohaydib, Ali R. Alhoshani, Khalid Alhazzani, Mashal M. Almutairi, Tareq Saleh, David A. Gewirtz, Moureq R. Alotiabi

Pharmacology and Toxicology Publications

Emerging evidence has shown that the therapy-induced senescent growth arrest in cancer cells is of durable nature whereby a subset of cells can reinstate proliferative capacity. Promising new drugs named senolytics selectively target senescent cells and commit them into apoptosis. Accordingly, senolytics have been proposed as adjuvant cancer treatment to cull senescent tumor cells, and thus, screening for agents that exhibit senolytic properties is highly warranted. Our study aimed to investigate three agents, sorafenib, rapamycin, and venetoclax for their senolytic potential in doxorubicin-induced senescence in HCT116 cells. HCT116 cells were treated with one of the three agents, sorafenib …

Modified Ysk12-Mend-Sirna In Dendritic Cells For Cancer Immunotherapy, Syed S. Alam

UROP Posters

Tumors may induce tolerogenesis through signaling dendritic cells to produce tolerogenic molecules, such as indoleamine 2, 3-dioxygenase 1 (IDO1). Tumor-associated immunosuppression is associated with higher mortality in patients. Small interfering RNA (siRNA) has been shown to silence specific target genes in the target cell. The siRNA associated with these genes could support a gene knockdown of these immunosuppressors and reduce mortality. Delivery of these therapeutic nucleic acids is difficult in vivo because siRNA is easily broken down inside the cell and the bloodstream through present nucleases. Use of liposome polymers has been reviewed extensively in literature. YSK12-C4, a lipid nanoparticle …

Crispr-Krispr: A Method To Identify On-Target And Random Insertion Of Donor Dnas And Their Characterization In Knock-In Mice, Masayuki Tanaka, Keiko Yokoyama, Hideki Hayashi, Sanae Isaki, Kanae Kitatani, Ting Wang, Hisako Kawata, Hideyuki Matsuzawa, Channabasavaiah B. Gurumurthy, Hiromi Miura, Masato Ohtsuka

Journal Articles: Pharmacology & Experimental Neuroscience

CRISPR tools can generate knockout and knock-in animal models easily, but the models can contain off-target genomic lesions or random insertions of donor DNAs. Simpler methods to identify off-target lesions and random insertions, using tail or earpiece DNA, are unavailable. We develop CRISPR-KRISPR (CRISPR-Knock-ins and Random Inserts Searching PRotocol), a method to identify both off-target lesions and random insertions. CRISPR-KRISPR uses as little as 3.4 μg of genomic DNA; thus, it can be easily incorporated as an additional step to genotype founder animals for further breeding.

Ecdysoneless Overexpression Drives Mammary Tumorigenesis Through Upregulation Of C-Myc And Glucose Metabolism, Bhopal C. Mohapatra, Sameer Mirza, Aditya Bele, Channabasavaiah B. Gurumurthy, Mohsin Raza, Irfana Saleem, Matthew D. Storck, Aniruddha Sarkar, Sai Sundeep Kollala, Surendra K. Shukla, Siddesh Southekal, Kay-Uwe Wagner, Fang Qiu, Subodh M. Lele, Mansour A. Alsaleem, Emad A. Rakha, Chittibabu Guda, Pankaj K. Singh, Robert D. Cardiff, Hamid Band, Vimla Band

Journal Articles: Pharmacology & Experimental Neuroscience

Ecdysoneless (ECD) protein is essential for embryogenesis, cell-cycle progression, and cellular stress mitigation with an emerging role in mRNA biogenesis. We have previously shown that ECD protein as well as its mRNA are overexpressed in breast cancer and ECD overexpression predicts shorter survival in patients with breast cancer. However, the genetic evidence for an oncogenic role of ECD has not been established. Here, we generated transgenic mice with mammary epithelium-targeted overexpression of an inducible human ECD transgene (ECDTg). Significantly, ECDTg mice develop mammary hyperplasia, preneoplastic lesions, and heterogeneous tumors with occasional lung metastasis. ECDTg tumors exhibit epithelial to mesenchymal transition …

A Study Of The Analysis Of Hemp-Derived Oil Products: Development Of A Method For The Analysis Of Phytocannabinoids In Medicinal Products, Erin Johnson

Theses and Dissertations--Pharmacology and Nutritional Sciences

Human interactions with cannabis have a history spanning millennia as a source of fiber, food, and medicine. The plant came across Asia, Europe, and Africa with the movements of people and travelers eventually coming to the Americas with European explorers. In colonizing North America, cannabis fiber was key to the production of canvas and ropes for ships. Although fiber was the driver for cannabis production in the United States, medicinal uses were prevalent and propelled the eventual regulations. The Pure Food and Drug Act of 1906 mandated accurate labeling on drugs such as cannabis followed by the Marihuana Tax Act …

Effects Of The Selective Gsk3b Inhibitor, Tideglusib, On Ethanol Consumption, Anxiety-Like Behavior, Taste Preference, And Downstream Proteins, Sam Gottlieb, Douglas Bledsoe, Jessica L. Maltman, Alanna Morgan, Jennifer T. Wolstenholme, Michael F. Miles

Graduate Research Posters

Background: We have shown modulations in glycogen synthase kinase 3 beta (GSK3B) abundance or activity regulate ethanol consumption, suggesting potential as a therapeutic target for alcohol use disorder (AUD). Here we report the GSK3B inhibitor tideglusib’s actions on ethanol consumption, basal behaviors, and modulation of GSK3B targets.

Methods: C57BL/6J males and females received i.g. 200mg/kg tideglusib, except drinking-in-the-dark (males;100mg/kg i.p.). Drinking-in-the-dark (DID): Mice given 20% ethanol 4-hours, 4-days/week x 3 weeks and then i.p. tideglusib or vehicle x 4 days in a Latin Square design with ethanol consumption measured daily. Light/Dark Box: Mice gavaged with tideglusib or vehicle …

Multimodal Medicine: Pain Control Potential, Tyler Ostlund

Master of Science in Nursing Family Nurse Practitioner

Due to the continual problem with overuse of, overdose on, and abuse of opioid medications for the past three decades it is paramount that effective, cheap, and above all safe forms of pain control are studied and applied. Multimodal pain management utilizes a combination of pharmacological and non pharmacological therapies in synergy to control pain and reduce dependence on strictly opioids. Combining the effects of medications or therapies that focus on treating different types or sources of pain such as inflammatory pain, neurological pain, etc. With the adoption of this method of pain management, the longstanding effects of the opioid …

Steroid-Refractory Lichenoid Eruption Associated With Pembrolizumab In A Patient With Non-Small Cell Lung Cancer, Leon Kou, Sanjay Agarwal, Alyssa Miceli, Logan Kolb, Karthik Krishnamurthy, Shawn Schmieder

HCA Healthcare Journal of Medicine

Programmed cell death receptor 1 (PD-1) inhibitors are promising and effective treatments for various cancers. Cutaneous adverse events, such as lichenoid drug eruptions, are well-known common side effects associated with PD-1 inhibitors. Lichenoid drug eruptions associated with PD-1 inhibitors show rapid improvement with high potency topical steroids and do not require cessation of the offending drug. We present the case of an 84-year-old female with progressive pembrolizumab therapy-associated lichenoid eruption that was resistant to several treatments and ultimately required discontinuation of pembrolizumab and treatment with methotrexate to resolve. This report includes histological findings of the pembrolizumab-associated lichenoid eruption.

Adipose-Specific Pparα Knockout Mice Have Increased Lipogenesis By Pask–Srebp1 Signaling And A Polarity Shift To Inflammatory Macrophages In White Adipose Tissue, Terry D. Hinds, Jr., Zachary A. Kipp, Mei Xu, Frederique B. Yiannikouris, Andrew J. Morris, Donald F. Stec, Walter Wahli, David E. Stec

Pharmacology and Nutritional Sciences Faculty Publications

The nuclear receptor PPARα is associated with reducing adiposity, especially in the liver, where it transactivates genes for β-oxidation. Contrarily, the function of PPARα in extrahepatic tissues is less known. Therefore, we established the first adipose-specific PPARα knockout (Ppara^FatKO) mice to determine the signaling position of PPARα in adipose tissue expansion that occurs during the development of obesity. To assess the function of PPARα in adiposity, female and male mice were placed on a high-fat diet (HFD) or normal chow for 30 weeks. Only the male Ppara^FatKO animals had significantly more adiposity in the inguinal white …

Evaluation Of Cost Savings Opportunity With The Use Of An Alternative Factor Vii Product Within A Tertiary Academic Medical Center And Health System, Kevin Rivera Jr., Pharmd, Anthony Renzoni Pharmd, Bcps, Bcemp, Evan Zahn Pharmd, Bcccp, Bcemp

Posters

• Eptacog alpha is the factor VII product on formulary
• It is approved by the FDA to treat bleeding in adults or children with hemophilia A or B with inhibitors •
• Additional approved uses include Glanzmann’s Disease, and factor VII deficiency and off label uses include cardiac surgery, and trauma salvage therapy
• Eptacog beta is an alternative recombinant factor VII product approved by the Food and Drug Administration in 2020 to treat bleeding in patients 12 years old or greater with hemophilia A or B with inhibitors
• In evaluating contracting pricing for each of these factor agents eptacog beta is potentially …

Modulating The Tumor Microenvironment To Improve Immunotherapy Treatments, Lleayem Nazario-Johnson, David Rowley

Senior Honors Projects

Advances in immunotherapy are revolutionizing the treatments of certain cancers, especially those in the blood. However, wider applications for eradicating solid tumors have been slow to emerge. A likely reason is the presence of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment that secrete immunosuppressive molecules which attenuate the attack of immune cells. We hypothesize that small molecule Wnt/Beta- Catenin inhibitors can be used to modulate the immunosuppressive actions of MDSCs and increase the effectiveness of immunotherapy treatments, such as with chimeric antigen receptor (CAR) T-cells. The Wnt/Beta-Catenin Pathway has been shown to be a crucial driving force behind the …

Preclinical Development Of Epicertin, A Novel Biotherapeutic For The Treatment Of Ulcerative Colitis., Micaela Ann Reeves

Electronic Theses and Dissertations

Epicertin (EPT) is a recombinant variant of the cholera toxin B subunit with a C-terminal KDEL endoplasmic retention motif. Previously, orally administered EPT demonstrated mucosal healing activity in acute and chronic dextran sulfate sodium colitis models, indicating its therapeutic potential for ulcerative colitis (UC) treatment. However, oral dosing with EPT requires neutralization of gastric acid prior to administration, hindering its facile application in the treatment of chronic diseases like UC. One solution to this issue is that EPT may also be administered intracolonically without losing efficacy. This work describes the determination of a target intracolonic dose of EPT for future …

Assessing The Role Of Arsenic Exposure And Mirna-186 In Skin Tumorigenesis And Chromosomal Instability., Angeliki Lykoudi

Electronic Theses and Dissertations

Chronic arsenic exposure through drinking water is a global health issue, affecting more than 200 million people. Arsenic is a group I human carcinogen and causes chromosomal instability (CIN). Arsenic exposure is the second most cause of skin cancer after UV radiation. MiR-186 is overexpressed in arsenic-induced squamous cell carcinoma relative to premalignant hyperkeratosis. Predicted targets of miR-186 are cell cycle regulators. Thus, we hypothesize that miR-186 overexpression drives malignant transformation of HaCaT cells by induction of CIN. Stable clones of HaCaT transfected with pEP-miR-186 expression vector or empty vector were maintained under puromycin selection were exposed to 0 or …

Race And Drug Toxicity: A Study Of Three Cardiovascular Drugs With Strong Pharmacogenetic Recommendations., Travis J. O'Brien, Kevin Fenton, Alfateh Sidahmed, April Barbour, Arthur F Harralson

Pharmacology and Physiology Faculty Publications

No abstract provided.

Cancer Vaccines And Immunotherapy For Tumor Prevention And Treatment, Jagmohan Singh, Wilbur Bowne, Adam E. Snook

Kimmel Cancer Center Faculty Papers

In this editorial, we highlight articles published in this Special Issue of Vaccines on "Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment", recent developments in the field of cancer vaccines, and the potential for immunotherapeutic combinations in cancer care. This issue covers important developments and progress being made in the cancer vaccine field and possible future directions for exploring new technologies to produce optimal immune responses against cancer and expand the arena of prophylactic and therapeutic cancer vaccines for the treatment of this deadly disease.

Editorial: Recent Advances In Cardiotoxicity Testing, Tamer M. A. Mohamed, Javid Moslehi, Jonathan Satin

Physiology Faculty Publications

No abstract provided.

Dextromethorphan-Quinidine Is Helpful For Pseudobulbar Affect Disorder In Stroke Patients, Michael Francis, Mira Hamame, Md, Mariam Nasrallah, Md, Alison Nesbitt, Do, James Peter Meza, Md, Phd

Clinical Research in Practice: The Journal of Team Hippocrates

An informed consent article using

Hammond FM, Alexander DN, Cutler AJ, et al. PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury. BMC Neurology. 2016;16:89. https://doi.org/10.1186/s12883-016-0609-0

for a patient with pseudobulbar affect following stroke

Lysergic Acid Diethylamide Induces Increased Signalling Entropy In Rats’ Prefrontal Cortex, Aurora Savino, Charles D. Nichols

School of Medicine Faculty Publications

Psychedelic drugs are gaining attention from the scientific community as potential new compounds for the treatment of psychiatric diseases such as mood and substance use disorders. The 5-HT2A receptor has been identified as the main molecular target, and early studies pointed to an effect on the expression of neuroplasticity genes. Analysing RNA-seq data from the prefrontal cortex of rats chronically treated with lysergic acid diethylamide (LSD), we describe the psychedelic-induced rewiring of gene co-expression networks, which become less centralised but more complex, with an overall increase in signalling entropy typical of highly plastic systems. Intriguingly, signalling entropy mirrors, at the …

Gestational Diabetes Triggers Postpartum Cardiac Hypertrophy Via Activation Of Calcineurin/Nfat Signaling, Nirmal Verma, Sarah Srodulski, Sathya Velmurugan, Amanda Hoskins, Vivek K. Pandey, Florin Despa, Sanda Despa

Pharmacology and Nutritional Sciences Faculty Publications

Population-based studies identified an association between a prior pregnancy complicated by gestational diabetes mellitus (GDM) and cardiac hypertrophy and dysfunction later in life. It is however unclear whether GDM initiates this phenotype and what are the underlying mechanisms. We addressed these questions by using female rats that express human amylin (HIP rats) as a GDM model and their wild-type (WT) littermates as the normal pregnancy model. Pregnant and two months postpartum HIP females had increased left-ventricular mass and wall thickness compared to non-pregnant HIP females, which indicates the presence of concentric hypertrophy. These parameters were unchanged in WT females during …

Substance Abuse Relapse Is Not About Willpower But Is The Culmination Of Psychological And Socioeconomic Stress, Paul A. Steffes

Clinical Research in Practice: The Journal of Team Hippocrates

The author reflects on the impact of non-judgmental listening on patient care outcomes.

Does Hiv Status Confer A Higher Risk Of Acquiring Covid-19? Using Clinical Decision Science To Combat Patients’ Anxiety, Camilo Guzman

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using

del Amo J, Polo R, Moreno S, et al. “Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy.” Annals of Internal Medicine. 2020;173(7):536-541. doi.org/10.7326/m20-3689

for a patient with HIV and concerns about COVID-19 for immunocompromised individuals.

Analysis Of Potentially Toxic Contaminants In Milk Powder, Magdalena Mititelu, Lucian Hîncu, Emma Adriana Ozon, Daniela Luiza Baconi, Ioana Paunica, Oana Denisa Bălălău

Journal of Mind and Medical Sciences

The aim of this study was to identify potentially toxic contaminants in milk powder. Powdered milk contains a range of toxic and non-toxic substances that are present in a wide variety, also having very different origins. A number of seven milk powder samples from different producers sold on the Romanian market were analyzed, the samples that were collected from the original packaging: P1, P 2, P3, P4, P5, P6 and P7. The concentration of the following elements was analyzed using the X-ray (XRF) fluorescence method: potassium (K), chlorine (Cl), calcium (Ca), phosphorus (P) and aluminum (Al). The vast majority of …

Mental Health Or Cardiac Health. Is There A Reason To Choose? Cardiac Arrhythmias Induced By Atomoxetine And Methylphenidate, Gabriel Cismaru, Viorel Lupu

Journal of Mind and Medical Sciences

The current treatment of Attention Deficit Disorder and Attention Deficit with Hyperactivity consists mainly in the administration of Straterra (Atomoxetine) Concerta and Ritalin (Methylphenidate). The FDA warned that the products might increase systolic, diastolic blood pressure, and lead to ventricular arrhythmias. Arrhythmic events and sudden cardiac death were described in adults with preexistent heart disease. However, studies on children have failed to demonstrate a clear association between the arrhythmic events and these drugs, as demonstrated in adults. What should the attitude of the pediatric psychiatrist be towards the administration of these products? What examination should be made by the psychiatrist …

Serotonin 5-Ht2a Receptor Activity Mediates Adipocyte Differentiation Through Control Of Adipogenic Gene Expression, Bangning Yu, Diana M. Battaglia, Timothy P. Foster, Charles D. Nichols

School of Medicine Faculty Publications

Serotonin 5-HT2 receptors are expressed in many tissues and play important roles in biological processes. Although the 5-HT2A receptor is primarily known for its role in central nervous system, it is also expressed in peripheral tissues. We have found that 5-HT2A receptor antagonists inhibit human subcutaneous primary adipocyte differentiation. We also show that siRNA knockdown of the 5-HT2A receptor blocks differentiation. Using gene expression analysis in combination with receptor antagonists we found that activity of 5-HT2A receptors is necessary very early in the differentiation process to mediate expression of adipogenic genes, including peroxisome proliferator-activated receptor gamma (ppar-γ), adipocyte protein 2 …

Contribution Of The Ledgf/P75 Protein Interactome To Prostate Cancer Chemoresistance, Greisha Lee Ortiz Hernández

Loma Linda University Electronic Theses, Dissertations & Projects

Prostate Cancer (PCa) progression leads to an advanced stage called metastatic castration resistant PCa (mCRPC), for which currently there is no cure in spite of advances in treatment with new generation anti-androgen drugs and chemotherapy with taxanes such as docetaxel (DTX). Our laboratory demonstrated previously that the stress oncoprotein Lens Epithelium Derived Growth Factor of 75 kD (LEDGF/p75) is upregulated in clinical prostate tumors and contributes to DTX-resistance in mCRPC cells. However, little is known about the molecular mechanisms by which LEDGF/p75 promotes taxane resistance. The C-terminus of LEDGF/p75 contains a domain called the Integrase Binding Domain (IBD), which in …

Decreasing Unintentional Pregnancies For Tennesseans, Paula M. Todd

Electronic Theses and Dissertations

In 2018, 49% of all pregnancies in the United States were unintended, with women with a lower- income status being five times more likely to experience an unplanned pregnancy. Tennessee has a high rate of unintended pregnancies, particularly among the uninsured, low-income, and rural teen populations; some 22% of these unintended pregnancies end in abortion. Oral or transdermal contraceptives that are affordable and accessible for women of childbearing age can reduce unintentional pregnancies. The addressed gap in clinical practice was that contraceptives are not currently available over the counter in Tennessee pharmacies without a prescription, which necessitates a costly medical …

Can 3d Printers Create Viable Personalized Therapy In The Treatment Of Diabetes?, Lyla White

Holster Scholar Projects

This study aimed to use 3D printing techniques to create a drug tablet containing two commonly used active ingredients (metformin and glyburide) for treating diabetes in a single pill. The hypothesis was that both drugs can be given in doses not available commercially and that these pills will have appropriate hardness, and extended-release dissolution. I was able to create 48 tablets that contained evenly dispersed active ingredient powder and met the weight requirements with consistency between tablets. Unfortunately, we had to substitute the usual bulk excipient for another because it was incompatible with the metformin and the replacement (mannitol) may …

The Concise Guide To Pharmacology 2021/22: Catalytic Receptors, Stephen Ph Alexander, Doriano Fabbro, Eamonn Kelly, Alistair Mathie, John A Peters, Emma L Veale, Jane F Armstrong, Elena Faccenda, Simon D Harding, Adam J Pawson, Christopher Southan, Jamie A Davies, Annie Beuve, Peter Brouckaert, Clare Bryant, John C Burnett, Richard W Farndale, Andreas Friebe, John Garthwaite, Adrian J Hobbs, Gavin E Jarvis, Michaela Kuhn, David Macewan, Tom P Monie, Andreas Papapetropoulos, Lincoln R Potter, Harald H H W Schmidt, Csaba Szabo, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will …

Role Of Limonene In An Experimental Model Of Rotenone Induced Parkinson’S Disease, Lujain Mohamad Bader Eddin

Theses

Parkinson's disease (PD) is one of the prevalent neurodegenerative diseases in elderly population. The symptoms of PD often begin with motor and cognitive impairment that are attributed to the dopaminergic neurons degeneration. Rotenone (ROT) is a naturally derived pesticide that is used in agriculture to control pests. It is a neurotoxin well-established for use in resembling PD symptoms in research. Limonene (LMN) is a plant derived monoterpene extracted from citrus peel with a wide range of therapeutic effects. Due to the shortage in available therapeutic agents that can cure or halt the progressive degeneration of PD, the main aim of …