Pharmacy and Pharmaceutical Sciences Commons^™

Post-Discharge Telephone Intervention With A Clinical Pharmacy Specialist For Gastrointestinal Medical Oncology Patients, Jane E. Rogers, Michael Leung, Amanda Sirisaengtaksin, Jennifer Zadlo, Van Nguyen, Morgan Mace, Wendy Covert, Makenna Smack, Stacy Diao, Zhou Fang, Andrea Landgraf, Mariela Blum Murphy

Advances in Cancer Education and Quality Improvement

Background: Oncology patients are a vulnerable population with medication-related problems spanning across care settings. Gastrointestinal medical oncology (GIMO) patients often have unique medication challenges due to extensive treatment history. High-quality medication reconciliation aids in preventing medication discrepancies and potential adverse events during transitions of care. We conducted a pilot post-hospital discharge intervention with clinical pharmacy specialists for GIMO patients.

Objective: The primary objective was to identify the frequency of medication discrepancies.

Methods: GIMO patients discharged from our hospital were identified and called within 7 days of discharge. Clinical pharmacy specialist telephone encounters occurred between December 2021 and February 2022.

Results: …

Immune-Related Adverse Events Associated With Pembrolizumab In Dmmr/Msi-H Colorectal Cancer: A Single Arm Safety Meta-Analysis, Joshi Simran, Saman Javid, Gaurav Sharma, Corinne Caissie, Armando Dominguez-Diaz

Posters

Pembrolizumab, a PD-1 checkpoint inhibitor, enhances immune response and has proven effective against various cancers, including melanoma, non-small cell lung cancer, and head and neck squamous cell carcinoma.

Clinical trials have also shown its efficacy in treating various types of cancers with different mismatch-repair statuses. However, the spectrum and frequency of immune-related adverse events (irAEs) in the dMMR (deficient mismatch repair) / MSI-H (microsatellite instability-high) colorectal cancer remain underexplored.

Therefore, this meta-analysis aims to evaluate pembrolizumab's safety profile in this colorectal cancer subset.

1st Place Contest Entry: Effectiveness Of Intravesical Bcg In The Treatment Of Nonmuscle Invasive Bladder Cancer: An Umbrella Review, Gerald Obinna Ozota

Eric M. Scandrett Graduate Library Research Prize

This is Gerald Obinna Ozota's submission for the 2025 Eric M. Scandrett Graduate Research Prize, which won first place. It contains their essay on using library resources, their bibliography, and a summary of their research project on conducting a systematic literature search to identify all relevant systematic reviews and meta-analyses investigating the effectiveness of intravesical Bacillus Calmette-Guerin (BCG) on Non-muscle-invasive Bladder Cancer (NIMBC).

Gerald is a student in the Ph.D. in Pharmaceutical Sciences program at Chapman University. Their faculty mentor is Dr. Lawrence Brown.

Short-Course Subcutaneous Alemtuzumab Induces Clinical Responses In Relapsed T-Cell Large Granular Leukemia, Miguel Ruiz, Zachary Braunstein, Eric Mclaughlin, Anjali Mishra, Pierluigi Porcu, Jonathan E. Brammer

Department of Medical Oncology Faculty Papers

No abstract provided.

Crosstalk Between Nnos/No And Cox-2 Enhances Interferon-Gamma-Stimulated Melanoma Progression, Anika Patel, Shirley Tong, Moom R. Roosan, Basir Syed, Amardeep Awasthi, Richard B. Silverman, Sun Yang

Pharmacy Faculty Articles and Research

Background/Objectives: Interferon gamma (IFN-γ) in the melanoma tumor microenvironment plays opposing roles, orchestrating both pro-tumorigenic activity and anticancer immune responses. Our previous studies demonstrated the role of neuronal nitric oxide synthase (nNOS) in IFN-γ-stimulated melanoma progression. However, the underlying mechanism has not been well defined. This study determined whether the nNOS/NO and COX-2/PGE2 signaling pathways crosstalk and augment the pro-tumorigenic effects of IFN-γ in melanoma. Methods: Bioinformatic analysis of patient and cellular proteomic data was conducted to identify proteins of interest associated with IFN-γ treatment in melanoma. Changes in protein expression were determined using various analytical techniques including …

Exosomes And Encapsulated Exomirs In Breast Cancer: Theragnostic Applications And Clinical Implications, Muhammad Imran Sajid, Shafia Bukhari, Hamid Ilyas, Rubina Malik, Minahil Fatima, Rakesh Kumar Tiwari, Surya M. Nauli, Khawaja Husnain Haider

Pharmacy Faculty Books and Book Chapters

Exosomes, released by cells, are small vesicles that have emerged as critical theranostic tools in breast cancer due to their unique ability to transport diverse biomolecules such as proteins, lipids, and RNAs, including microRNAs (ExomiRs). These vesicles are critical in modulating the tumor microenvironment, driving processes like cancer proliferation, invasion, metastasis, and drug resistance. Exosomal microRNAs such as ExomiR-21, ExomiR-1246, and ExomiR-155, with their profound influence on the gene expressions in the recipient cells, are the unsung heroes in tumor progression and immune modulation. This chapter delves into exosome's dual diagnostic and therapeutic potential in breast cancer. It highlights their …

Magnetic And Ph-Sensitive Dual Actuation Of Biohybrid Microswimmer Of Targeted Drug Release Suitable For Cancer Cell Microenvironment, Richa Chaturvedi, Yumin Kang, Yunji Eom, Sri Ramulu Torati, Cheolgi Kim

Center for Bioelectronics Publications

The chemotherapeutic agents most frequently used in cancer treatment often have limited effectiveness because of their low specificity for tumors and poor therapeutic performance. In addition to the aforementioned therapeutic challenges the drug delivery carriers conjugated with the drug encounter early detection and elimination from the immune system before arriving at the affected area continues to be a significant research focus among researchers. To address this prevalent issue, an effective approach has been developed that leverages the physiological differences between normal and tumor tissue to enhance the efficacy of anticancer drugs. This drug delivery system is designed based on pH-sensitive …

Using Hyperactive Shp-2 Mutants, A Phosphatase, To Identify Interactions With The Rna Helicase Ddx3, Devin Montgomery

Theses and Dissertations--Pharmacy

Protein-protein interactions are critical in cellular signaling pathways. This project investigates binding interactions between SHP-2, a tyrosine phosphatase, and DDX3, an RNA helicase. There is a specific focus on the impact that gain-of-function SHP-2 mutations may impact binding to DDX3 via conformational change. Using immunoprecipitation protocols as well as western blotting we were able to provide insights into SHP-2 molecular mechanisms and subsequent binding to DDX3.

Novel Micro-And Nanoformulations Of Paclitaxel For Targeting Metastatic Breast, Non-Small Cell Lung, And Pancreatic Cancers, Lobat Tayebi, Mehran Alavi

Electrical & Computer Engineering Faculty Publications

Nonlinear pharmacokinetics resulting from high lipophilic and low oral bioavailability, and hypersensitivity reactions and hyperlipidemia caused by formulation by Cremophor EL have limited clinical effectiveness of paclitaxel (Taxol). In this way, there is the critical necessity of innovative drug delivery systems (DDSs) to mitigate severe side effects and overcome clinical limitations of paclitaxel. In recent years, various micro- and nanoformulations, specifically polymeric nanoparticles (NPs) and lipid NPs, have been presented and approved by the Food and Drug Administration (FDA). In addition, other nanoformulations, such as polymeric nanoparticles (NPs), micelles, liposomes, and mesoporous silica nanoparticles, have shown promising results in vitro …

Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells, Ashley V. Huang, Yali Kong, Kan Wang, Milton L. Brown, David Mu

Department of Biomedical and Translational Sciences Faculty Publications

Breast cancer is one of the most common cancers globally. Unfortunately, many patients with breast cancer develop resistance to chemotherapy and tumor recurrence, which is primarily driven by breast cancer stem cells (BCSCs). BCSCs behave like stem cells and can self-renew and differentiate into mature tumor cells, enabling the cancer to regrow and metastasize. Key markers like CD44 and aldehyde dehydrogenase-1 (ALDH1), along with pathways like Wingless-related integration site (Wnt), Notch, and Hedgehog, are critical to regulating this stem-like behavior of BCSCs and, thus, are being investigated as targets for various new therapies. This review summarizes marker-dependent strategies for targeting …

A Novel D-Peptide Modulates Dclk1 Gelsolin Interactions, Reducing Pdac Tumor Growth, Landon L. Moore, Dongfeng Qu, Parthasarathy Chandrekesan, Kamille Pitts, Randal May, Byron E. Anderson, Milton L. Brown, Courtney W. Houchen

Department of Medicine Faculty Publications

What drives inflammation-associated tumorigenesis and progression in pancreatic ductal adenocarcinoma (PDAC)? Doublecortin-like kinase 1 (DCLK1) is a central driver of inflammation-associated tumorigenesis, with elevated expression linked to worse clinical outcomes. Two isoforms of DCLK1 possess a unique extracellular domain (ECD). DCLK1 isoform 2 contains two microtubule-binding domains, while isoform 4, lacks the microtubule-binding domains but, plays a pivotal role in tumor progression. We identified novel D-peptides that selectively target this ECD, significantly suppressing PDAC cell proliferation in vitro and tumor growth in xenograft models without inducing cell death. In silico modeling and binding assays revealed DCLK1 isoform 4 interacts with …

Dual Inhibitor Of Mdm2 And Nfat1 For Experimental Therapy Of Breast Cancer: In Vitro And In Vivo Anticancer Activities And Newly Discovered Effects On Cancer Metabolic Pathways, Wei Wang, Marlene Aguilar, Sayantap Datta, Abigail Alley, Meheret Tadesse, Xinshi Wang, Xia Gao, Ruiwen Zhang

Faculty, Staff and Students Publications

INTRODUCTION: The oncogene MDM2 has garnered attention not only for its role in cancer as a negative regulator of the tumor suppressor p53 but also for its p53-independent oncogenic activities. MDM2 also involves metabolic reprogramming, such as serine metabolism, respiration, mitochondrial functions, the folate cycle, and redox balance. Traditional MDM2 inhibitors blocking the protein-protein binding between MDM2 and p53 have shown limited clinical success in various stages of clinical trials, most likely due to low efficacy, drug toxicity, and drug resistance, highlighting the need for a novel, p53-independent strategy to inhibit MDM2. The present study investigated the antitumor effects of …

The Significance Of Aldehyde Dehydrogenase 1 In Cancers, Anh L. Nguyen, Caroline O. B. Facey, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The goal of this paper is to discuss the role of ALDH isozymes in different cancers, review advances in ALDH1-targeting cancer therapies, and explore a mechanism that explains how ALDH expression becomes elevated during cancer development. ALDH is often overexpressed in cancer, and each isoform has a unique expression pattern and a distinct role in different cancers. The abnormal expression of ALDHs in different cancer types (breast, colorectal, lung, gastric, cervical, melanoma, prostate, and renal) is presented and correlated with patient prognosis. ALDH plays a significant role in various cellular functions, such as metabolism, oxidative stress response, detoxification, and cellular …

Specifically Targeting Muc16 For Fluorescence-Guided Surgery Of Pancreatic Ductal Adenocarcinoma, Kathryn M. Muilenburg

Theses & Dissertations

Pancreatic cancer is a lethal disease with a low 5-year survival rate and a high rate of resection recurrence. However, surgery remains the only treatment with curative potential for pancreatic cancer. Many factors such as high desmoplasia, a lack of intraoperative imaging, and micrometastatic disease contribute to the high rate of incomplete resections in pancreatic cancer. Fluorescence-guided surgery (FGS) is a potential intraoperative tool for application in surgical resection. FGS works through passive or active targeting of a free dye or dye-containing moiety (e.g. antibody, peptide, and nanoparticles) to specifically fluoresce the tumor compared to the surrounding normal, fibrotic, and …

Effectiveness Of Pharmacist-Managed Oncology Ambulatory Care For Patients With Non–Small Cell Lung Cancer In Taiwan, Ding-Cheng Liu, Chuan-Lun Hung, Yi-Wen Chen, Li-Na Kuo, Yen-Chun Hsin, Chun-Nan Kuo

Journal of Food and Drug Analysis

Non-small cell lung cancer (NSCLC) is commonly treated with tyrosine kinase inhibitors (TKIs). However, adverseevents from such treatment can lead to treatment discontinuation and additional medical expenditures. Ambulatory carefrom oncology pharmacists in patient education and symptom management can benefit patients with NSCLC. In thisstudy, we evaluated the effectiveness of an oncology pharmacy service at a medical center in Taiwan. We retrospectivelyenrolled 137 patients with NSCLC who initiated treatment with afatinib, gefitinib, or erlotinib between January 2017 andDecember 2021; 40 of them utilized the oncology pharmacy service (intervention group), and the remaining 97 did not(nonintervention group). To determine the effectiveness of …

A Conjugate Of An Egfr-Binding Peptide And Doxorubicin Shows Selective Toxicity To Triple-Negative Breast Cancer Cells, Phi-Phung Than, Shih-Jing Yao, Emad Althagafi, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Selective targeting of cancer cells via overexpressed cell-surface receptors is a promising strategy to enhance chemotherapy efficacy and minimize off-target side effects. In this study, we designed peptide 31 (YHWYGYTPERVI) to target the overexpressed epidermal growth factor receptor (EGFR) in triple-negative breast cancer (TNBC) cells. Peptide 31 is internalized by TNBC cells through EGFR-mediated endocytosis and shares sequence and structural similarities with human EGF (hEGF), a natural EGFR ligand. Unlike hEGF, peptide 31 does not induce cell migration in TNBC cells. A novel conjugate of peptide 31 with doxorubicin (Dox) retains selectivity for TNBC cells and exhibits significant toxicity comparable …

Physicochemical Property Effects On Immune Modulating Polymeric Nanoparticles: Potential Applications In Spinal Cord Injury, Daniel J. Kolpek, Jaechang Kim, Hisham Mohammed, John C. Gensel, Jonghyuck Park

Markey Cancer Center Faculty Publications

Nanoparticles (NPs) offer promising potential as therapeutic agents for inflammation-related diseases, owing to their capabilities in drug delivery and immune modulation. In preclinical studies focusing on spinal cord injury (SCI), polymeric NPs have demonstrated the ability to reprogram innate immune cells. This reprogramming results in redirecting immune cells away from the injury site, downregulating pro-inflammatory signaling, and promoting a regenerative environment post-injury. However, to fully understand the mechanisms driving these effects and maximize therapeutic efficacy, it is crucial to assess NP interactions with innate immune cells. This review examines how the physicochemical properties of polymeric NPs influence their modulation of …

Evaluating Tirzepatide's Therapeutic Potential In Mitigating Obesity-Associated Comorbidities, Zaneh Kahook, Talaya Jones, Carina Bryan, Mayur Parmar

HCA-NSU MD Research Day

Objective: The study aims to explore the therapeutic potential of dual GIP/GLP-1 agonist tirzepatide in managing obesity and its associated manifestations, including obstructive sleep apnea (OSA), hidradenitis suppurativa (HS), and obesity-associated cancer (OAC) risks. Background: OSA and HS are the associated comorbidities noted in persons with obesity. Obesity has been associated with an increased risk of cancers, such as breast cancer. Reducing obesity could improve these conditions. Tirzepatide has demonstrated efficacy in reducing body weight, but its benefits in obesity-related conditions and cancer risk need further investigation. Methods: Data was synthesized from peer-reviewed literature on tirzepatide. Additional sources were identified …

Predicting And Monitoring Immune Checkpoint Inhibitor Therapy Using Artificial Intelligence In Pancreatic Cancer, Guangbo Yu, Zigeng Zhang, Aydin Eresen, Qiaoming Hou, Farideh Amirrad, Sha Webster, Surya M. Nauli, Vahid Yaghmai, Zhuoli Zhang

Pharmacy Faculty Articles and Research

Pancreatic cancer remains one of the most lethal cancers, primarily due to its late diagnosis and limited treatment options. This review examines the challenges and potential of using immunotherapy to treat pancreatic cancer, highlighting the role of artificial intelligence (AI) as a promising tool to enhance early detection and monitor the effectiveness of these therapies. By synthesizing recent advancements and identifying gaps in the current research, this review aims to provide a comprehensive overview of how AI and immunotherapy can be integrated to develop more personalized and effective treatment strategies. The insights from this review may guide future research efforts …

Hepatotoxicity Induced By Immune Checkpoint Inhibitors, Flaviu Muresan, Olga Hilda Orasan, Angela Cozma, Madalina Daiana Bancos, Lorena Ciumarnean, Mircea Vasile Milaciu, Tinca Codruta Pocol, Nicoleta Valentina Leach, Teodora Gabriela Alexescu, Ovidiu Vasile Fabian, George Ciulei, Mirela Georgiana Perne

Journal of Mind and Medical Sciences

Immune checkpoint inhibitors (ICIs) are an effective immunotherapeutic approach for cancers affecting the lung, skin, kidney, mammary gland, or certain hematologic malignancies. Regarding the prognosis of these oncological conditions, treatments with ICIs open new therapeutic perspectives with benefits for both patients and healthcare providers. A drawback of immune checkpoint inhibition is the occurrence of immune-related adverse events that can involve a wide range of organs, such as the liver. Given widespread usage of immunotherapy, the number of patients who suffer from this unwanted condition has increased. Hepatopathy induced by ICIs can be severe and can even lead to death. Detecting …

Identification Of New Leads Against Ubiquitin Specific Protease-7 (Usp7): A Step Towards The Potential Treatment Of Cancers, Sumaira Javaid, Seema Zadi, Muhammad Awais, Atai-Tul Wahab, Humaira Zafar, Innokentiy Maslennikov, M. Iqbal Choudhary

Pharmacy Faculty Articles and Research

Ubiquitin-specific protease-7 (USP7) is an important drug target as it regulates multiple proteins and genes (such as MDM2 and p53) with roles in cancer progression. Its inhibition can hinder the function of oncogenes, increase tumor suppression, and enhance immune response. The current study was designed to express USP7 in a prokaryotic system, followed by screening of small molecules against it using biophysical methods, primarily STD-NMR technique. Among them, 12 compounds showed interaction with USP7 as inferred from NMR-based screening. These compounds further caused destabilization of USP7 by reducing its melting temperature (T_m) up to 6 °C in …

The Impact Of Pdcd4, A Translation Inhibitor, On Drug Resistance, Qing Wang, Hsin-Sheng Yang

Markey Cancer Center Faculty Publications

Programmed cell death 4 (Pdcd4) is a tumor suppressor, which has been demonstrated to efficiently suppress tumorigenesis. Biochemically, Pdcd4 binds with translation initiation factor 4A and represses protein translation. Beyond its role in tumor suppression, growing evidence suggests that Pdcd4 enhances the chemosensitivity of several anticancer drugs. To date, numerous translational targets of Pdcd4 have been identified. These targets govern important signal transduction pathways, and their attenuation may improve chemosensitivity or overcome drug resistance. This review will discuss the signal transduction pathways regulated by Pdcd4 and the potential mechanisms through which Pdcd4 enhances chemosensitivity or counteracts drug resistance.

Molecular Targets For Breast Cancer Therapy, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

"Breast cancer is by far the most common cancer in women, and for a while, it surpassed lung cancer as the most diagnosed cancer, regardless of gender, in 2020 [1]. Chemotherapy and hormone therapy are still the first line of treatment, despite extensive research in molecularly targeted drugs. Therefore, triple negative breast cancer (TNBC) is still known as the most challenging type for treatment due to the limited identified targets. Inherent and acquired resistance are still major hurdles in breast cancer therapy, which further highlights the importance of identifying new molecular targets in this battle. The inherent resistance of unresponsive …

Targeting Ribosome Biogenesis Is A Novel Approach For The Management Of Pancreatic Cancer, Mudassier Ahmad, Haider Ahsan, Carlos Perez, Muhammad Bangash, Andrew Massey, Emmanuel Anning, Manish Tripathi, Dae Kim, Subhash C. Chauhan, Bilal Bin Hafeez

Research Colloquium

Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related deaths in the United States with limited therapeutic options available. Gemcitabine, a deoxycytidine nucleoside analog is currently considered the most effective therapy for PanCa. However, it shows only a marginal survival benefit of six months. Aberrant ribosome biogenesis occurs in most tumor types. We observed that PanCa cells are addicted to ribosome biogenesis, which supports their highly aggressive metastatic phenotypes. Thus, strategically targeting ribosome biogenesis process could be one of the ideal strategies for the prevention and treatment of PanCa. In this study, we elucidated the molecular mechanisms of POLR1A …

Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank Shekhar Rai, Muhammad Imran Sajid, Jonathan Moreno, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum …

Antitumor Activity Of A Pyrrolobenzodiazepine Antibody-Drug Conjugate Targeting Lgr5 In Preclinical Models Of Neuroblastoma, Jianghua Tu, Yukimatsu Toh, Adela M Aldana, Jake J Wen, Ling Wu, Joan Jacob, Li Li, Sheng Pan, Kendra S Carmon, Qingyun J Liu

Faculty, Staff and Student Publications

Neuroblastoma (NB) is a cancer of the peripheral nervous system found in children under 15 years of age. It is the most frequently diagnosed cancer during infancy, accounting for ~12% of all cancer-related deaths in children. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a membrane receptor that is associated with the primary tumor formation and metastasis of cancers in the gastrointestinal system. Remarkably, high levels of LGR5 are found in NB tumor cells, and high LGR5 expression is strongly correlated with poor survival. Antibody-drug conjugates (ADCs) are monoclonal antibodies that are covalently linked to cell-killing cytotoxins to deliver the payloads …

Cgmp Compliant One-Step, One-Pot Automated [18f]Fbntp Production For Clinical Imaging Of Mitochondrial Activity, Mai Lin, Cong-Dat Pham, Robert T Ta, H Charles Manning

Faculty, Staff and Student Publications

Background

4-[18F]fluorobenzyl-triphenylphosphonium ([18F]FBnTP) is a lipophilic cation PET tracer. The cellular uptake of [18F]FBnTP is correlated with oxidative phosphorylation by mitochondria, which has been associated with multiple critical diseases. To date, [18F]FBnTP has been successfully applied for imaging myocardial perfusion, assessment of severity of coronary artery stenosis, delineation of the ischemic area after transient coronary occlusion, and detection/quantification of apoptosis in various animal models. Recent preclinical and clinical studies have also expanded the possibilities of using [18F]FBnTP in oncological diagnosis and therapeutic monitoring. However, [18F]FBnTP is typically prepared through a tediously lengthy four-step, three-pot reaction and required multiple synthesizer modules; …

Combination Treatment Of Biochanin A And Atorvastatin Alters Mitochondrial Bioenergetics, Modulating Cell Metabolism And Inducing Cell Cycle Arrest In Pancreatic Cancer Cells, Vilas Desai, Satya Murthy Tadinada, Hoora Shaghaghi, Ross Summer, James C.K. Lai, Alok Bhushan

College of Pharmacy Faculty Papers

Background/Aim: Pancreatic cancer is an aggressive type of cancer, with a dismally low survival rate of <5%. FDA-approved drugs like gemcitabine have shown little therapeutic success, prolonging survival by a mere six months. Isoflavones, such as biochanin A and daidzein, are known to exhibit anti-cancer activity, whereas statins reportedly have anti-proliferative effects. This study investigated the effects of combination treatment of biochanin A and atorvastatin on pancreatic cancer cells.

Materials and Methods: Pancreatic cancer cells AsPC-1, PANC-1, and MIA PaCa-2 were procured from ATCC. The cell viability studies were carried out using MTT & cell count assays. Flow cytometry was used to study cell apoptosis whereas cell metabolism studies were carried out using the Seahorse Mito stress test and XF-PMP assay. The effects of treatment on cell signaling pathways & cell cycle associated proteins were investigated using western blot whereas invasiveness of cancer cells was evaluated using gelatin zymography.

Results: The combination treatment …

Selective And Brain-Penetrant Acss2 Inhibitors Target Breast Cancer Brain Metastatic Cells, Emily Esquea, Lorela Ciraku, Riley Young, Jessica Merzy, Alexandra Talarico, Nusaiba Ahmed, Mangalam Karuppiah, Anna Ramesh, Adam Chatoff, Claudia Crispim, Adel Rashad, Simon Cocklin, Nathaniel Snyder, Joris Beld, Nicole Simone, Mauricio Reginato, Alexej Dick

Kimmel Cancer Center Faculty Papers

Breast cancer brain metastasis (BCBM) typically results in an end-stage diagnosis and is hindered by a lack of brain-penetrant drugs. Tumors in the brain rely on the conversion of acetate to acetyl-CoA by the enzyme acetyl-CoA synthetase 2 (ACSS2), a key regulator of fatty acid synthesis and protein acetylation. Here, we used a computational pipeline to identify novel brain-penetrant ACSS2 inhibitors combining pharmacophore-based shape screen methodology with absorption, distribution, metabolism, and excretion (ADME) property predictions. We identified compounds AD-5584 and AD-8007 that were validated for specific binding affinity to ACSS2. Treatment of BCBM cells with AD-5584 and AD-8007 leads to …

Ael Transformed From Post-Et Myelofibrosis With A Sinusoidal Pattern, Jak2 Mutation, And Biallelic Tp53 Inactivation, Qing Wei, M James You

Faculty, Staff and Student Publications

No abstract provided.