Pharmacy and Pharmaceutical Sciences Commons^™

Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad

Dissertations, Theses, and Capstone Projects

The overexpression of HER2 accounts for 20-30% of breast cancer tumors and not only serves as a marker for poor predictive clinical outcomes but also as a target for treatment. Antibody-drug conjugates (ADCs) combine the selectivity of monoclonal antibodies (mAbs) with the efficacy of chemotherapeutic drugs to provide targeted treatment without toxicity to normal tissue. Most of the ADCs currently in the clinic for cancer chemotherapy are based on complex organic molecules. In contrast, the conjugation of metallodrugs to mAbs has been overlooked when there is enormous potential in this area with the resurgence of metal-based drugs as prospective cancer …

Characterization Of Epithelial Growth Factor Transcripts Identified In Crotalus Atrox Venom, Ivan Lopez, Ying Jia

Research Symposium

Epithelial Growth Factor (EGF) is the primary source in regeneration and stimulation of essential fibroblasts cells commonly found in epithelium. Studies have shown that snake venom components are becoming a growing factor in treating illnesses such as cancer, muscular dystrophy, chronic pain, blood pressure, blood clotting, etc. EGF in human cells contains a promising quaternary structure that can bind to snake venom metalloproteinases, proposing a means of activating biochemical responses through protein-protein interactions to regulate unwanted cellular functions. This supports promising research in achieving a greater understanding of regulation along cellular pathways through ligands, increasing the likelihood of targeting unwanted …

Assessment Of Adherence To National Comprehensive Cancer Network Guideline Recommended Anticoagulant Therapy In The Management Of Patients With Cancer-Associated Venous Thromboembolic Disease, Ghufran Hassoun Naeemah, Ayad Ali Hussein Ameen

Maaen Journal for Medical Sciences

Background: Venous thromboembolism (VTE), a vascular disorder, is a serious and sometimes fatal problem, ranking as the second-deadliest complication for people with cancer. VTE includes pulmonary embolism, superficial vein thrombosis, deep vein thromboembolism, and internal vein thrombosis. It is important to note that cancer patients have almost nine times higher odds of dying from this illness. Objective: The Najaf Cancer Center conducted a study to evaluate the effectiveness of oncologist strategies in the prevention and treatment of cancer-associated venous thromboembolism (VTE). The primary objective was to measure the adherence of VTE patients to anticoagulant therapy recommended by the NCCN guidelines. …

Isolation And Total Synthesis Of Sigma-2 Ligands From Marine Cyanobacteria, Andrea Hough

Electronic Theses and Dissertations

Cyanobacteria have been studied for over 50 years as a source of new antibiotics, antiviral, and anticancer drugs. The research described in this dissertation investigates marine cyanobacteria as a source of natural products with activity within the central nervous system and with cytotoxicity against breast cancer cells. Barbamide (1) is a known cyanobacterial metabolite that has been re-isolated from a variety of species and collection sites suggesting broad utility as a signaling molecule. Utilizing the psychoactive drug screening program, we screened barbamide for CNS activity and found that barbamide exhibited affinity for the kappa opioid receptor (KOR) and …

Modified Linear Peptides Effectively Silence Stat-3 In Breast Cancer And Ovarian Cancer Cell Lines, Dindyal Mandal, Sandeep Lohan, Muhammad Imran Sajid, Abdulelah Alhazza, Rakesh Kumar Tiwari, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

RNA interference (RNAi) has drawn enormous attention as a powerful tool because of its capability to interfere with mRNA and protein production. However, designing a safe and efficient delivery system in RNAi therapeutics remains challenging. Herein, we have designed and synthesized several linear peptides containing tryptophan (W) and arginine (R) residues separated by the β-alanine (βA) spacer and attached to a lipophilic fatty acyl chain, cholesterol, or PEG. The peptide backbone sequences were: Ac-C-βA-βA-W4-βA-βA-R4-CO-NH2 and Ac-K-βA-βA-W4-βA-βA-R4-CO-NH2, with only a difference in N-terminal amino acid. The cysteine side chain in the first sequence was used for the conjugation with PEG2000 and …

Investigation Of Folate-Poly(Glutamic Acid)/Polyethylenimine/Dna Complexes For In Vitro Gene Delivery, Caleb Akers

Theses and Dissertations--Pharmacy

Gene therapy is currently being studied as a treatment for a variety of indications, including cancer, infectious disease, and cardiovascular diseases, among others. While many of the early treatments in the field involved the use of viral delivery methods, various safety, ethical, and financial concerns limit the potential uses of this methodology. As such, more recent research has focused on developing non-viral delivery platforms to alleviate some of the issues inherent in viral delivery. Recently, the release of the COVID-19 vaccines from Pfizer and Moderna represents a promising use of non-viral delivery as both utilized a lipid-based delivery vector.

Despite …

Identifying Unexpected Inflammation Resulting From Drug-Drug Interactions, Keegan Jolly

All Master's Theses

Adverse drug events result in nearly 1.3 million emergency room visits per year in the United States of America. As much as 30% of these adverse events are a result of drug-drug interactions (DDI’s). There is a gap in knowledge concerning these DDI outcomes especially when it comes to inflammation. Inflammation is linked to a variety of chronic health conditions and non-infectious diseases such as cancer. Purpose: The goal of this study was to examine how many active drug ingredients from FDA’s Adverse Event Reporting System (FAERS), when combined (in groups of two or more), elicit an inflammatory response …

Nurse-Led Education On Oral Chemotherapy Medications, Carmen Lucia Glick Alonso

Master's Projects and Capstones

Problem: Breast cancer is one of the leading causes of cancer death among women in the United States. Annually, around 264,000 breast cancer cases are diagnosed in women and 2,400 in men (Centers for Disease Control and Prevention, 2022). According to the American Cancer Society, the risk of a woman in the United States being diagnosed with breast cancer in their life is around 13% (2022).

Context: Along with a cancer diagnosis comes the need to introduce patient education about new oral chemotherapy treatments. As a treatment team member, the oncology nurse plays a vital role in this …

Abstracts From The 2022 Health Care Systems Research Network (Hcsrn) Annual Conference

Journal of Patient-Centered Research and Reviews

The Health Care Systems Research Network (HCSRN) is comprised of 20 health systems with embedded research units. The network’s annual conference serves as a forum for research teams from member institutions to disseminate scientific findings, explore new collaborations, and share insights about conducting research in real-world care delivery settings. Abstracts accepted for presentation at HCSRN 2022 are published in this supplement of Journal of Patient-Centered Research and Reviews, the official journal of HCSRN’s annual conference proceedings.

Identification Of Translesion Synthesis Inhibitors That Target Rev7/Rev3 Protein-Protein Interactions, Seema Patel

Honors Scholar Theses

Translesion synthesis (TLS) is a cellular mechanism utilized by cancer cells to tolerate DNA damage caused by chemotherapeutics, like cisplatin, by replicating past unrepaired lesions. This increases the rate of mutations, which leads to the emergence of drug-resistant cancer cells. Preliminary studies have shown that disrupting the protein-protein interactions (PPI) in the TLS heteroprotein complex increases cells’ sensitivity to first-line genotoxic chemotherapy, illustrating how inhibiting TLS assembly and function can significantly increase cancer cell death. These results underscore the therapeutic potential of targeting TLS PPI. Our current work in this area is focusing on inhibitors capable of disrupting the Rev7/Rev3 …

The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez

Thinking Matters Symposium

In a clinical setting, some patients are exposed to an anti-cancer chemotherapy agent, paclitaxel. Cancerous cells undergo rapid, continuous cell division without control. Chemotherapy treatments try to slow and stop the uncontrollable cell division cycles and eliminate cancerous cells in the process. Paclitaxel serves as a treatment for some types of cancers, including lung, melanoma, bladder, and esophageal. Because it targets the cytoskeleton, paclitaxel can also influence cell migration. This project utilizes a cellular migration assay and an immunohistochemistry assay to analyze the effects of paclitaxel on the movement of cells and on the cytoskeleton of neuroglia rat cells with …

Editorial: Anticancer Potential Of Artemisia Annua, Jill M. Kolesar, Peter H. Seeberger

Pharmacy Practice and Science Faculty Publications

No abstract provided.

Design And Synthesis Of Curcumin Analogs For Anticancer Activity And Discovery Of Novel Hit Molecules Targeting Cxcr4., Maryam Sadat Hosseini Zare

Dissertations (2016-Present)

Curcumin as a natural compound is made of various components including protein, carbohydrate, and curcuminoid. Curcuminoid is made of curcumin, desmethoxycurcumin and bis desmethoxycurcumin. Curcumin is used for the treatment of cancer and inflammatory disorders, but it has some therapeutic problems like poor bioavailability, poor efficacy, and chemical instability. To overcome these problems, the objective of this study is (1) synthesis of pyrazole curcumin analogs, (2) synthesis of triazole curcumin analogs, and (3) in-vitro study of the anticancer activity of these curcumin analogs on head & neck, breast, pancreatic and glioblastoma cancer cells. During this part of my Ph.D. project, …

Optimization Of The Structure Of Ttr Ligands For Half-Life Extension (Tlhe), Guanming Jiang

University of the Pacific Theses and Dissertations

Many potential therapeutic agents face challenges for their clinical development due to short circulation half-life. As a result, prolonging the half-life of therapeutic drugs in circulation while preserving their hydrophilicity and small size will be a key step toward more effective and safe pharmacological molecules. Our lab developed a new approach for enhancing the safety and efficacy of therapeutic agents. By endowing therapeutic agents with a hydrophilic small molecule (a derivative of the clinical candidate, AG10) which reversibly binds to the serum protein transthyretin (TTR), the half-life of the therapeutic agent should be extended by binding to the TTR in …

The Global Burden Of Adolescent And Young Adult Cancer In 2019: A Systematic Analysis For The Global Burden Of Disease Study 2019, Elysia M. Alvarez, Lisa M. Force, Rixing Xu, Kelly Compton, Dan Lu, Ismaeel Yunusa Ph. D., Et Al.

Faculty Publications

Background

Methods

Conference Proceedings: Select Abstracts Presented At 2021 Advocate Aurora Health Scientific Day

Journal of Patient-Centered Research and Reviews

Abstracts published within this supplement were presented at the 47th annual Advocate Aurora Health Scientific Day, held virtually on May 26, 2021. This research symposium provides a forum for disseminating results from studies conducted by faculty, fellows, residents, and other allied health professionals associated with Midwest-based health system Advocate Aurora Health, which publishes the Journal of Patient-Centered Research and Reviews.

Design And Application Of Hybrid Cyclic-Linear Peptide-Doxorubicin Conjugates As A Strategy To Overcome Doxorubicin Resistance And Toxicity, Saghar Mozaffari, David Salehi, Parvin Mahdipoor, Richard Beuttler, Rakesh Tiwari, Hamidreza Montazeri Aliabadi, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is used for breast cancer, leukemia, and lymphoma treatment as an effective chemotherapeutic agent. However, Dox use is restricted due to inherent and acquired resistance and an 8-fold increase in the risk of potentially fatal cardiotoxicity. Hybrid cyclic-linear peptide [R5K]W7A and linear peptide R5KW7A were conjugated with Dox through a glutarate linker to afford [R5K]W7A-Dox and R5KW7A-Dox conjugates to generate Dox derivatives. Alternatively, [R5K]W7C was conjugated with Dox via a disulfide linker to generate [R5K]W7C–S–S-Dox conjugate, where S–S is a disulfide bond. Comparative antiproliferative assays between conjugates [R5K]W7A-Dox, [R5K]W7C–S–S-Dox, linear R5KW7A-Dox, the corresponding physical mixtures of the peptides, …

Real-World Evaluation Of Universal Germline Screening For Cancer Treatment-Relevant Pharmacogenes, Megan L. Hutchcraft, Nan Lin, Shulin Zhang, Catherine Sears, Kyle Zacholski, Elizabeth A. Belcher, Eric B. Durbin, John L. Villano, Michael J. Cavnar, Susanne M. Arnold, Frederick R. Ueland, Jill M. Kolesar

Pathology and Laboratory Medicine Faculty Publications

The purpose of this study was to determine the frequency of clinically actionable treatment-relevant germline pharmacogenomic variants in patients with cancer and assess the real-world clinical utility of universal screening using whole-exome sequencing in this population. Cancer patients underwent research-grade germline whole-exome sequencing as a component of sequencing for somatic variants. Analysis in a clinical bioinformatics pipeline identified clinically actionable pharmacogenomic variants. Clinical Pharmacogenetics Implementation Consortium guidelines defined clinical actionability. We assessed clinical utility by reviewing electronic health records to determine the frequency of patients receiving pharmacogenomically actionable anti-cancer agents and associated outcomes. This observational study evaluated 291 patients with …

Clinical Correlations Of Polycomb Repressive Complex 2 In Different Tumor Types, Maksim Erokhin, Olga Chetverina, Balázs Győrffy, Victor V. Tatarskiy, Vladic Mogila, Alexander A. Shtil, Igor Roninson, Jerome Moreaux, Pavel Georgiev, Giacomo Cavalli, Darya Chetverina

Faculty Publications

PRC2 (Polycomb repressive complex 2) is an evolutionarily conserved protein complex required to maintain transcriptional repression. The core PRC2 complex includes EZH2, SUZ12, and EED proteins and methylates histone H3K27. PRC2 is known to contribute to carcinogenesis and several small molecule inhibitors targeting PRC2 have been developed. The present study aimed to identify the cancer types in which PRC2 targeting drugs could be beneficial. We queried genomic and transcriptomic (cBioPortal, KMplot) database portals of clinical tumor samples to evaluate clinical correlations of PRC2 subunit genes. EZH2, SUZ12, and EED gene amplification was most frequently found in prostate cancer, whereas lymphoid …

Ethiopian Medicinal Plants Traditionally Used For The Treatment Of Cancer; Part 3: Selective Cytotoxic Activity Of 22 Plants Against Human Cancer Cell Lines, Solomon Tesfaye, Hannah Braun, Kaleab Asres, Ephrem Engidawork

Faculty and Student Publications

Medicinal plants have been traditionally used to treat cancer in Ethiopia. However, very few studies have reported the in vitro anticancer activities of medicinal plants that are collected from different agro‐ecological zones of Ethiopia. Hence, the main aim of this study was to screen the cytotoxic activities of 80% methanol extracts of 22 plants against human peripheral blood mononuclear cells (PBMCs), as well as human breast (MCF‐7), lung (A427), bladder (RT‐4), and cervical (SiSo) cancer cell lines. Active extracts were further screened against human large cell lung carcinoma (LCLC‐103H), pancreatic cancer (DAN‐G), ovarian cancer (A2780), and squamous cell carcinoma of …

Design And Synthesis Of Macrocyclic Peptide Braf-Wt Dimerization Inhibitors For The Treatment Of Metastatic Melanoma, Chad Mulloy Beneker

Theses and Dissertations

In cases of metastatic melanoma, BRAF is frequently mutated to the V600E oncoprotein causing uncontrolled cell proliferation driven by the MAPK-ERK pathway. There are several BRAF inhibitors, such as vemurafenib, which are FDA approved, but patients treated with these Type-I kinase inhibitors frequently observe relapse under mutant RAS and BRAF-wt conditions due to paradoxical activation. The mechanism of this resistance occurs through binding of the inhibitor to BRAF-wt initiating conformational changes which leads to BRAF dimerization. Once in the dimerized state, the inhibited monomer induces allosteric transactivation of the second monomer. This drug-induced activation of BRAF in cells with mutant …

[(Wr)8Wkβa]-Doxorubicin Conjugate: A Delivery System To Overcome Multi-Drug Resistance Against Doxorubicin, Khalid Zoghebi, Hamidreza Montazeri Aliabadi, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is an anthracycline chemotherapeutic agent used to treat breast, leukemia, and lymphoma malignancies. However, cardiotoxicity and inherent acquired resistance are major drawbacks, limiting its clinical application. We have previously shown that cyclic peptide [WR]₉ containing alternate tryptophan (W) and arginine (R) residues acts as an efficient molecular transporter. An amphiphilic cyclic peptide containing a lysine (K) residue and alternative W and R was conjugated through a free side chain amino group with Dox via a glutarate linker to afford [(WR)₈WKβA]-Dox conjugate. Antiproliferative assays were performed in different cancer cell lines using the conjugate and the …

A Global Review On Short Peptides: Frontiers And Perspectives, Vasso Apostolopoulos, Joanna Bojarska, Tsun-Thai Chai, Sherif Elnagdy, Krzysztof Kaczmarek, John Matsoukas, Roger New, Keykavous Parang, Octavio Paredes Lopez, Hamideh Parhiz, Conrad O. Perera, Monica Pickholz, Milan Remko, Michele Saviano, Mariusz Skwarczynski, Yefeng Tang, Wojciech M. Wolf, Taku Yoshiya, Janusz Zabrocki, Piotr Zielenkiewicz, Maha Alkhazindar, Vanessa Barriga, Konstantinos Kelaidonis, Elham Mousavinezhad Sarasia, Istvan Toth

Pharmacy Faculty Articles and Research

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. …

Rasburicase Utilization After Protocol Implementation Focused On Fixed Dosing By Limiting Use Of Weight-Based Dosing To Oncology Providers, Dakota Smith Bs, Jamie Gaul Pharmd, Bcps, Liam Dadey Pharmd, Bcps

Parkview Pharmacy Department

Dec 2021 ASHP Midyear Clinical Meeting / Poster

Objective: Evaluate the change in rasburicase use pre- and post-implementation of dosing restriction protocol.

Mechanisms Of Apoptosis Induced By Actinomycin D In Aerodigestive Tract Cancers, Adeoluwa Ayodeji Adeluola

Theses, Dissertations and Capstones

Upper aerodigestive tract cancers including cancers of the oral cavity, pharynx, larynx, esophagus, and lungs are the most prevalent cancers and leading causes of cancer-related deaths. Collectively, over 300,000 new cases and 146,500 deaths are projected within the US in the year 2021. Drug-associated toxicities, as well as resistance to therapy (intrinsic and acquired), are big challenges for successfully treating these cancers. Recent studies have shown that combining low-dose actinomycin D with existing therapies is a promising strategy to reduce toxicity (cyclotherapy) and to overcome resistance. The development of these treatment strategies however requires an understanding of the molecular mechanisms …

Association Of Incident Cancer To Low-Value Care And Healthcare Cost Burden Among Elderly Medicare Beneficiaries, Chibuzo Iloabuchi

Graduate Theses, Dissertations, and Problem Reports

In the United States (US), 25% of healthcare spending is considered wasteful because it is spent reimbursing low-value care. Low-value care is the utilization of healthcare services, medical tests, and procedures that have unclear or no clinical benefit to patients but still exposes them to risk. World-wide, low-value care imposes a significant economic burden on patients, payers, governments, and society. Cancer care among older adults > 65 years is one of the biggest drivers of healthcare expenditure in the US and accounts for nearly 40% of all spending, and low-value care among cancer patients is prevalent and contributes to the financial …

Redox-Sensitive Nanocomplex For Targeted Delivery Of Melittin, Bei Cheng, Peisheng Xu

Faculty Publications

Although peptide therapeutics have been explored for decades, the successful delivery of potent peptides in vitro and in vivo remains challenging due to the poor stability, low cell permeability, and off-target effects. We developed a redox sensitive polymer-based nanocomplex which can efficiently and stably deliver the peptide drug melittin for cancer therapy. The nanocomplex selectively targets cancer cells through lactobionic acid mediated endocytosis and releases melittin intracellularly upon the trigger of elevated redox potential. In vivo study proved that the targeted nanocomplex shows excellent potency in inhibiting tumor growth in a xenograft colon cancer mouse model. Thus, the polymer/melittin nanocomplexes …

Cancer-Targeting Immunostimulatory Peptides As An Immunotherapeutic Approach To Cancer, Rachel Montel

Seton Hall University Dissertations and Theses (ETDs)

This dissertation reports the synthesis and biological applications of bifunctional trimeric peptides with B7H6-derived NKp30 binding motifs that serve to activate an immunocytotoxic response in natural killer cells and a GRP78-binding motif that can target tumors that express surface GRP78. In this manner the cancer-targeting immunostimulatory peptides are anticipated to directly bind and activate effector NK92-MI cells while also recognizing and binding to target A549 tumor cells to facilitate NK cell-dependent immunocytotoxicity of the targeted tumors. The NKp30 binding peptide motifs are derived from the tumor associated B7H6 antigen that is often downregulated or shed from the surface of tumors …

Ligand-Installed Polymeric Nanocarriers For Combination Chemotherapy, Xinyuan Xi

Theses & Dissertations

Combination chemotherapy remains the mainstay of cancer treatment because such strategy targets different cell signaling pathways to decrease the likelihood of developing protective mechanisms by cancer cells, thereby delaying the onset of recurrence and prolonging the survival. The co-delivery of binary drug combination via a single nanocarrier provides benefits in reducing dose-limiting toxicities, improving the pharmacokinetic properties of the cargo, spatial-temporal synchronization of drug exposure, and synergistic therapeutic effects. Rational design of such regimen is crucial for maximizing the therapeutic effects since only certain drug ratios exposed to the target might be synergistic while other ratios exert additive or even …

The Apoptotic Effect Of Gsk-3 Inhibitors: Bio And Chir 98014 On H1975 Lung Cancer Cells Through Ros Generation And Mitochondrial Dysfunction., Theodore Lemuel Mathuram, Thiagarajan Venkatesan, Jayanta Das, Umamaheswari Natarajan, Appu Rathinavelu

HPD Articles

OBJECTIVE: GSK-3 has been reported to be upregulated in malignant diseases, including lung cancers, thus suggesting it to be a valid target for cancer treatment. The study elucidates the possible mechanism involved in the ability of GSK-3 inhibitors: BIO and CHIR 98014 to regulate proteins involved in cell death of H1975 lung cancer cells.

RESULTS: BIO and CHIR 98014 successfully induced apoptosis at lower concentrations in H1975 cells but not in H460 lung cancer cells. Moreover, increased ROS generation and depolarization of mitochondrial membrane potential were observed in both treatments. Cleavage of caspase-3 was observed in both BIO and CHIR …