Open Access Journals at IU Indianapolis
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Feature: Visual Art, Justin Yu
Get PDFJustin Yu, MS1 showcases his artwork. Works include:
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Enzyme Assay Development for Hormonally Up-regulated Neu-associated Kinase (HUNK) Protein: A Target in EGFR+ (HER2+/ErbB2+) Breast Cancers
Get PDFBackground: Breast cancer is the second leading cause of cancer death among women in the United States, with about 264,000 cases of breast cancer diagnoses and 42,000 deaths per year. For many drug-resistant metastatic breast cancers, epidermal growth factor receptor (EGFR) is highly expressed with a conferred resistance to HER2/ErbB2 inhibitors. Hormonally up-regulated protein kinase (HUNK) is a protein kinase that has been evidenced as a target in EGFR+ (HER2+/ErbB2+) breast cancers, presenting a potential for targeted treatment.
Methods: To determine its efficacy as a target, we implemented ADP enzyme assays to test the amount of phosphorylation of HUNK, both alone and in the presence of various HUNK inhibitors.
Results: The activity of specific drug inhibitors was found to be inconclusive. However, HUNK does demonstrate affinity to EGFR when combined with additional DTT, suggesting its potential for further study as a target for drug-resistant breast cancer therapy
Importance of Per2 in Cardiac Mitochondrial Function during Stress
Get PDFBackground/Objective: Ischemic heart disease is the worldwide leading cause of death. Cardiac cellular damage from ischemia is mainly inflicted in the form of mitochondrial dysfunction by inflammatory cytokines and reactive oxidative species (ROS). Mitochondria are critical for metabolic function to maintain cardiac activity. Interventions against inflammatory cytokines and ROS are therefore cardioprotective during ischemic damage. Period Circadian Regulator 2 (Per2) is a circadian rhythm protein involved in metabolic regulation as a time-responsive gene in cardiomyocytes during ischemic damage. Overexpression of Per2 has been shown to decrease infarct size following myocardial infarction. In this study, we hypothesize that Per2 protein plays a regulatory role in the mitochondrial response to inflammatory cytokine TNFα and oxidative stressor H2O2 in human cardiomyocytes.
Methods: AC16 Human Cardiomyocytes (HCM) transfected with Per2 or control siRNA were subjected to stress treatment of 100ng/mL TNFa or 100μM H2O2. RT-PCR and Western blot were used to detect Per2 expression. After two hours of treatment, mitochondrial membrane potential (ΔψM) was detected using JC1 fluorescence probe and mitochondrial respiration capacity was evaluated via Seahorse Mito Stress Test. After four hours of treatment, cell death was measured using Annexin V and propidium iodide (PI) apoptosis kit via flow cytometry.
Results: Per2 siRNA significantly reduced Per2 mRNA and protein levels in HCM. Increased cell death and decreased ΔψM were observed in HCM treated with TNFa or H2O2. Knockdown of Per2 potentiated TNFa-induced cell death, TNFa- or H2O2 -disrupted ΔψM, and TNFa- or H2O2- impaired mitochondrial maximal respiration.
Conclusion/Implication: Per2 knockdown increases apoptotic susceptibility and mitochondrial dysfunction in human cardiomyocytes exposed to TNFa or H2O2. Delivery of Per2 may serve as a promising therapeutic strategy to protect cardiomyocyte mitochondrial function during periods of stress, such as myocardial infarction, organ transplantation, and cardiac surgery
Comparison of Visual Field Fluctuation Between Myopic and Emmetropic Glaucoma Patients
Get PDFBackground: Conflicting epidemiologic studies suggest that myopia may both increase and decrease the risk of glaucomatous visual field loss. To provide appropriate treatment to glaucoma patients, it is important to detect meaningful changes in the visual field, which requires distinguishing between visual field fluctuation and progression. Visual field fluctuation is defined as the variability between two visual field tests performed on separate days or months on the same eye that cannot be attributed to a pathologic change. We hypothesize that glaucoma patients with myopia will demonstrate more visual field fluctuation compared to emmetropic patients.
Methods: Four or more 24-2 or 30-2 Humphrey visual field tests over several visits will be analyzed per patient. Data including the VFI plot, mean deviation, and threshold sensitivity on the glaucoma progression analysis will be collected to measure fluctuation. The sample is divided into two groups: 1. emmetropic glaucoma patients with a spherical equivalent refraction between +2 to -2 diopters and 2. high myopic glaucoma patients with a spherical equivalent refraction over -5 diopters. Bland-Altman plots, Mann-Whitney U tests, Root Mean Square Error (RMSE), intraclass correlation coefficients, and generalized estimating equation models for ordinal data will be used to analyze the collected data.
Results: Thus far, 2,979 charts have been reviewed with data collected from 27 emmetropes and myopes who met the inclusion criteria. The recruitment goal is 78 per group and 156 total. Preliminary results for RMSE found a statistically significant p-value for mean deviation (0.0320), and no statistically significant difference for threshold sensitivity (0.5179) and VFI (0.0904).
Conclusion and Potential Impact: This ongoing study will help establish if glaucoma patients with high myopia demonstrate greater visual field fluctuation. It is important for clinicians to have this information so that these patients can be examined carefully to prevent misdiagnoses or delayed glaucoma treatment
Effect of Oxygen Tension on Glioblastoma Cell Growth
Get PDFBackground and Hypothesis:Glioblastoma (GBM) is an aggressive primary malignancy of the CNS with a dismal prognosis (~15-20 months) despite standard of care therapies. The poor prognosis of GBM despite ongoing research may be due to inaccuracies in preclinical models of the disease. Cell lines typically used to study GBM are exposed to ambient air containing 21% oxygen (normoxia compared to physiologic oxygen tension, physoxia, ~5%). In extracranial tumors, exposure to the oxygen in ambient air triggers epigenetic changes that alter cell growth, metabolism, and treatment responsiveness. The aim of this study is to obtain preliminary data on the impact ofphysiologic oxygen tensions on primary glioma cell growth in vitro.
Experimental Design:Growth of primary glioma cell lines (GB43, GB10, GB001) and one immortalized cell line (293T HEK) was assessed in normoxia and physoxia. All cell lines were plated at 10,000 cells per well. Cells were harvested and counted in triplicate on days 2, 4, 6, 8, 10, 12. On each day the cells were counted, the media in the remaining wells was changed. This experiment was repeated three times. Wound healing assays with all cell lines were also performed at normoxia and physoxia.
Results:Cells line growth curves were plotted and showed consistent exponential growth after counting on day two. From these graphs, the cell doubling time was calculated over a period of four days during which the cells were undergoing exponential growth.
Conclusions:Current results indicated that primary glioblastoma cell lines grow at different rates at differing oxygen tensions. In ongoing studies, we are exploring the effect of low oxygen tensions on functional assays such as wound-healing. Future work will assess rates of growth and functional consequence of physoxia in tumor samples never exposed to ambient air to most accurately recapitulate the in-situ environment