Medicine and Health Sciences Commons^™

Precise Method To Identify Kinase Drug Targets In Complex Diseases: The First Step Towards Sustainable And Effective Treatment, Hasbanny Irisson, Marzieh Ayati

Research Symposium

Background: Kinases are enzymes that have proven to be important drug targets due to their role in critical biological mechanisms such as phosphorylation. Phosphorylation happens when a kinase catalyzes the transfer of a phosphate group to a protein in a phosphorylated site, which then becomes known as the substrate of the kinase. Any dysregulation of protein phosphorylation causes a wide range of complex diseases including cancer. Thus, discovering the links between kinases and their substrates (i.e. predicting kinase-substrate associations (KSAs)) is crucial in developing effective and sustainable treatments. Presently, less than 5% of phosphorylated sites have an associated kinase, and …

Identification And Characterization Of Anticancer Potential Of A Novel Small Molecule, Mortaparibmild, Hazna Noor Meidinna, Anissa Nofita Sari, Sunil C. Kaul, Renu Wadhwa

Research Symposium

Background: The development of new anticancer drugs and treatment modalities form a priority research field. The tumor suppressor protein p53 is frequently mutated or functionally inactivated in a large variety of cancers. Its inactivation by mortalin, a member of the heat shock 70 protein family, has been shown to contribute to carcinogenesis. The small molecule inhibitors of mortalin-p53 interactions have been shown to reactivate p53 yielding apoptosis/growth arrest in cancer cells. Therefore, abrogators of mortalin-p53 interaction have emerged as possible new therapeutic anticancer reagents.

Methods: We performed chemical library screening based on the imaging of mortalin-p53 interaction, leading to the …

Mortaparibplus- A Novel Anticancer Small Molecule Abrogating Mortalin-P53 Interaction In Cancer Cells, Anissa N. Sari, Ahmed Elwakeel, Jaspreet K. Dhanjal, Vipul Kumar, Durai Sundar, Sunil C. Kaul, Renu Wadhwa

Research Symposium

Background. The cessation of tumor cell growth through cell cycle arrest and apoptosis is determined by p53, a tumor suppressor protein. However, the interaction between mortalin-p53 within cytoplasm/nucleus leads to the inactivation of p53 transcriptional activation function. The disruption of mortalin-p53 complex has been suggested as an approach for developing a potential anticancer drug.

Methods. A screening of a high-content chemical library was performed to determine a molecule with mortalin-p53-interaction disrupting characteristics. After four-rounds of visual assays, we discovered a triazole derivative (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole, named Mortaparib^Plus) with a potential ability of disrupting mortalin-p53-complex. In this study, we recruited …

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 …

Quantitative Analysis Of Cadaveric Pelvic Lymph Nodes, Brandon Y. Boeur, Matthew P. Kayal, Jade Johnson, Yuhyun Kang, Kelsey Rice, Alicia Schmidt, Shelley Dicecco

Research Day

Introduction: Lymphedema commonly develops as a result of cancer treatments, including surgical removal of lymph nodes (LN). Research suggests there are 500-800 (LN) throughout the body. Deciding how many LN to remove and predicting possible severity of damage can become problematic when the range of LN in one area can vary by 30 LN.

Objective: The purpose of this study was to investigate more precise ranges of pelvic LN within cadaver samples.

Methods: Quantification of LN for number occurred on cadavers simultaneous with DO, PT, and PA students’ dissections. Demographics of the cadavers were 27 female, 16 male, 39 Caucasian, …

Temporal Resolution Of Cell Death Signaling Events Induced By Cold Atmospheric Plasma And Electroporation In Human Cancer Cells, Danielle M. Krug, Prasoon K. Diwakar, Ahmed Hassanein

The Summer Undergraduate Research Fellowship (SURF) Symposium

Cancer treatment resistance and their invasive and expensive nature is propelling research towards developing alternate approaches to eradicate cancer in patients. Non-thermal, i.e., cold atmospheric plasma (CAP) and electroporation (EP) applied to the surface of cancerous tissue are new methods that are minimally invasive, safe, and selective. These approaches, both independently and synergistically, have been shown to deplete cancer cell populations, but the signaling mechanisms of death and their timelines of action are still widely unknown. To better understand the timeframe of signaling events occurring upon treatment, human cancer cell lines were treated with CAP, EP, and combined CAP with …

Mutations In Braf Are Associated With Higher Levels Of Immune Infiltrates In Microsatellite-Stable Colon Cancer, Jake Rubin, Eduard Porta Parto

GW Research Days 2016 - 2020

While BRAF is among the most well-established oncogenes in human cancers, more recently it has garnered attention for its role in suppressing antitumor immunity, especially in melanoma. Because tumor-infiltrating lymphocyte (TIL) density is strongly prognostic in colorectal cancer (CRC)⁷, we decided to investigate the connection between TIL density and the BRAF-activating V600E mutation in CRC.

We used ESTIMATE to quantify immune infiltrate in samples from the TCGA colon adenocarcinoma (COAD) dataset (n = 216). This is an algorithm that uses the gene-expression signature of 141 immune-related genes to infer the presence of immune cells in the tumor infiltrate. …

Nanobubbles Provide Theranostic Relief To Cancer Hypoxia, Christopher M. Long, Pushpak N. Bhandari, Joseph Irudayaraj

The Summer Undergraduate Research Fellowship (SURF) Symposium

Hypoxia is a common motif among tumors, contributing to metastasis, angiogenesis, cellular epigenetic abnormality, and resistance to cancer therapy. Hypoxia also plays a pivotal role in oncological studies, where it can be used as a principal target for new anti-cancer therapeutic methods. Oxygen nanobubbles were designed in an effort to target the hypoxic tumor regions, thus interrupting the hypoxia-inducible factor-1α (HIF-1α) regulatory pathway and inhibiting tumor progression. At less than 100nm, oxygen nanobubbles act as a vehicle for site-specific oxygen delivery, while also serving as an ultrasound contrast agent for advanced imaging purposes. Through in vitro and in vivo studies, …

Cellular Uptake Mechanism Of Paclitaxel Nanocrystals, Iris K. Archer, Zhaohui Wang, Tonglei Li

The Summer Undergraduate Research Fellowship (SURF) Symposium

Therapeutic options for metastasized human cancer in current practice remain limited and, sadly, there is no cure for metastatic cancer. The typical approach, chemotherapy, has both low efficacy due to poor drug solubility, and cytotoxic side effects to healthy tissue when delivered indiscriminately. To address both of these issues, we are pursuing the use of nanocrystal formulations of current chemotherapeutic agents as delivery platforms. Herein, we have studied cellular uptake mechanisms in cancer cells of nanocrystals of a chemotherapeutic agent, paclitaxel. Our goal in this study is to determine whether the nanocrystals can be taken up via endocytosis, especially when …