Lysosomal Zn 2+ Release Triggers Rapid, Mitochondria-Mediated, Non-Apoptotic Cell Death In Metastatic Melanoma, 2022 University of Michigan - Ann Arbor
Lysosomal Zn 2+ Release Triggers Rapid, Mitochondria-Mediated, Non-Apoptotic Cell Death In Metastatic Melanoma, Wanlu Du, Mingxue Gu, Meiqin Hu, Timothy Nold, Prateeksunder Pinchi, Wei Chen, Michael Ryan, Ahmed Bannaga, Haoxing Xu
Medical Student Research Symposium
During tumor progression, lysosome function is often maladaptively upregulated to match the high energy demand required for cancer cell hyper-proliferation and invasion. Here, we report that mucolipin TRP channel 1 (TRPML1), a lysosomal Ca2+ and Zn2+ release channel that regulates multiple aspects of lysosome function, is dramatically upregulated in metastatic melanoma cells compared with normal cells. TRPML-specific synthetic agonists (ML-SAs) are sufficient to induce rapid (within hours) lysosomal Zn2+-dependent necrotic cell death in metastatic melanoma cells while completely sparing normal cells. ML-SA-caused mitochondria swelling and dysfunction lead to cellular ATP depletion. While pharmacological inhibition or genetic silencing of TRPML1 ...
The Effects Of Thc On Hiv Tat Protein-Mediated Neuroinflammation, 2022 University of Mississippi
The Effects Of Thc On Hiv Tat Protein-Mediated Neuroinflammation, Camille Martin
Although antiretroviral therapies have allowed people living with human immunodeficiency virus (HIV) to achieve normal life expectancies, they cannot cure HIV nor the neurological symptoms associated with infection, termed neuroHIV. NeuroHIV describes a myriad of neurological disorders including mood disorders (depression and anxiety), cognitive impairment, neuropathic pain, and motor disinhibition. The mechanisms by which HIV promotes neurological impairment are not known, but may involve actions of its neurotoxic proteins. One such protein that has been well-characterized is the HIV trans-activator of transcription (Tat). Tat exerts neurotoxic effects via various means, one of which is to activate microglia, the macrophages of ...
Decreasing Time To Antibiotic Administration In Febrile Neutropenic Adult Oncology Patients In The Emergency Department: An Evidence-Based Quality Improvement Project, Kristin Murray
Introduction—Significance and Background: Febrile Neutropenia (FN) is the most common and serious complication of hematopoietic cancers and in patients receiving chemotherapy. Patients in this immunocompromised state have weakened immunity to fight off infection and a mortality rate of almost 10%. Thus, Infectious Diseases Society of America has identified the single most important determining factor of outcomes is the timing of antibiotic (TTA) administration and has identified the gold standard to be 60 minutes. Current practice does not follow guidelines and the current policy does not address the urgency of antibiotic administration.
Purpose: The purpose of this project is to ...
Non-Opioid Pharmacologic Agents In The Treatment Of Non-Cancer Chronic Pain In The Outpatient Setting, 2022 Sacred Heart University
Non-Opioid Pharmacologic Agents In The Treatment Of Non-Cancer Chronic Pain In The Outpatient Setting, Diane Eannotti
Opioid prescription related overdose deaths have increased substantially with evidence demonstrating only modest short-term benefits in chronic pain and thus represents the need to identify alternative treatments to opioids. A needs assessment performed for a federally qualified community health center revealed patients presently taking non-opioid pharmacologic agents in the treatment of chronic non-cancer pain (CNCP) needed additional education in managing multiple non-opioid medications. A targeted approach at improving patient experience and population health supporting the quadruple aim was undertaken with this project.
Purpose: The purpose of this quality improvement project consisted of performing medication management visits for 28 referred patients ...
Medicinal Plant Extracts And Natural Compounds For The Treatment Of Cutaneous Lupus Erythematosus: A Systematic Review, 2022 UMass Chan Medical School
Medicinal Plant Extracts And Natural Compounds For The Treatment Of Cutaneous Lupus Erythematosus: A Systematic Review, Janet E. Lubov, Aisha S. Jamison, Becky Baltich Nelson, Alice A. Amudzi, Kelly N. Haas
Cutaneous lupus erythematosus (CLE) is a group of autoimmune connective tissue disorders that significantly impact quality of life. Current treatment approaches typically use antimalarial medications, though patients may become recalcitrant. Other treatment options include general immunosuppressants, highlighting the need for more and more targeted treatment options. The purpose of this systematic review was to identify potential compounds that could be repurposed for CLE from natural products since many rheumatologic drugs are derived from natural products, including antimalarials. This study was registered with PROSPERO, the international prospective register of systematic reviews (registration number CRD42021251048). We comprehensively searched Ovid Medline, Cochrane Library ...
Efforts To Increase The Ketamine-Like Activity Of The Rapid-Acting Antidepressant Ro-25-6981 (Mi-4) By Increasing Ampa Potentiation, 2022 Roseman University of Health Sciences
Efforts To Increase The Ketamine-Like Activity Of The Rapid-Acting Antidepressant Ro-25-6981 (Mi-4) By Increasing Ampa Potentiation, Nathan Heger
Annual Research Symposium
The small molecule ketamine has generated much interest due to its rapid antidepressant effects. Despite having a rapid onset, ketamine has poor bioavailability, short duration of action, toxicities with long-term use, and a high potential for abuse. The molecule MI-4 (RO 25-6981) has also been shown to have both a rapid and sustained antidepressant effect. Most of the research into the mechanism of the rapid onset of MI-4 and ketamine has focused on their interaction with the NMDA receptor in addition to some monoamine transporters. Some recent publications have shown a significant role of AMPA receptors in the ketamine antidepressant ...
In-Silico Determination Of Phytochemicals Against Spike Protein Of Covid-19, 2022 Institute of Microbiology and Molecular genetics, University of the Punjab, Lahore, Pakistan.
In-Silico Determination Of Phytochemicals Against Spike Protein Of Covid-19, Muhammad Irfan, Muhammad Adil, Areej Fatima, Arooj Fatima, Ammara Khalid, Muhammad Bilal
Journal of Bioresource Management
Spike protein is present on the exterior of SARS-CoV-2 that mediates the binding of virus with human ACE2 receptor. S-protein has the ability to mutate in a short span of time. Using S-protein as a therapeutic target, Covid-19 infection can be prevented. Many plant-derived phytochemicals are found effective to treat viral infections. In this study, we selected top 10 phytochemicals following the Lipinski’s rule of five from total 82 candidate phytochemicals. The binding energies were determined through molecular docking of the phytochemical ligands. Top three compounds having maximal interactions and lowest binding energies were visualized. We suggested Dictamnine, Deoxypodophyllotoxin ...
Targeting Gastrointestinal Cancers With Chimeric Antigen Receptor (Car)-T Cell Therapy, 2022 Thomas Jefferson University
Targeting Gastrointestinal Cancers With Chimeric Antigen Receptor (Car)-T Cell Therapy, Ross E Staudt, Robert D Carlson, Adam E. Snook
Department of Pharmacology and Experimental Therapeutics Faculty Papers
The immune system is capable of remarkably potent and specific efficacy against infectious diseases. For decades, investigators sought to leverage those characteristics to create immune-based therapies (immunotherapy) that might be far more effective and less toxic than conventional chemotherapy and radiation therapy for cancer. Those studies revealed many factors and mechanisms underlying the success or failure of cancer immunotherapy, leading to synthetic biology approaches, including CAR-T cell therapy. In this approach, patient T cells are genetically modified to express a chimeric antigen receptor (CAR) that converts T cells of any specificity into tumor-specific T cells that can be expanded to ...
Partial Treatment Response To Capmatinib In Met-Amplified Metastatic Intrahepatic Cholangiocarcinoma: Case Report & Review Of Literature, 2022 Thomas Jefferson University
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, provided ...
Effects Of The Selective Gsk3b Inhibitor, Tideglusib, On Ethanol Consumption, Anxiety-Like Behavior, Taste Preference, And Downstream Proteins, 2022 Virginia Commonwealth University
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 ...
Modified Ysk12-Mend-Sirna In Dendritic Cells For Cancer Immunotherapy, 2022 Virginia Commonwealth University
Modified Ysk12-Mend-Sirna In Dendritic Cells For Cancer Immunotherapy, Syed S. Alam
Undergraduate Research 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 ...
Steroid-Refractory Lichenoid Eruption Associated With Pembrolizumab In A Patient With Non-Small Cell Lung Cancer, 2021 HCA Healthcare/USF Morsani College of Medicine (St. Petersburg General Hospital)
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 (PparaFatKO) 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 PparaFatKO animals had significantly more adiposity in the inguinal white adipose tissue ...
Assessing The Role Of Arsenic Exposure And Mirna-186 In Skin Tumorigenesis And Chromosomal Instability., 2021 University of Louisville
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., 2021 George Washington University
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, 2021 Thomas Jefferson University
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, 2021 University of Louisville
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, 2021 Michigan State University College of Osteopathic Medicine
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
Gestational Diabetes Triggers Postpartum Cardiac Hypertrophy Via Activation Of Calcineurin/Nfat Signaling, 2021 University of Kentucky
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, 2021 Wayne State University
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.