Digital Commons Network^™

Molecular Docking And Inhibition Of Matrix Metalloproteinase-2 By Novel Difluorinatedbenzylidene Curcumin Analog, Aamir Ahmad, Afreen Sayed, Kevin R. Ginnebaugh, Vivek Sharma, Anita Suri, Arundhati Saraph, Subhash Padhye, Fazlul H. Sarkar

Department of Pathology

We recently described the synthesis and characterization of a novel difluorinatedbenzylidene analog of curcumin, commonly referred as CDF, which demonstrated significantly enhanced bioavailability and in vivo anticancer activity. CDF targets many factors similar to curcumin, albeit with more potency, as reported previously. To further highlight this differential behavior of CDF, we chose matrix metalloproteinase protein MMP-2 which is involved in the processes of invasion and metastasis of human tumors. Both curcumin and CDF were characterized for their binding characteristics using in silico docking studies; they were also evaluated via biological assays involving gelatin zymography, miRNA analysis, invasion assays and ELISA. …

The Effect Of Active Video Games On The Heart Rate Of Older Adults, Yeon Bai, Shahla M. Wunderlich, Diane M. Hanel

Department of Nutrition and Food Studies Scholarship and Creative Works

Background: Heart rate is used as a health biomarker. This aim of this study was to investigate the effects of playing active video games on the heart rate of older adults, in comparison to the heart rate after common table recreational activity.

Methods: An experimental study with 40 participants was conducted: a control group (n=20) participated in common Pokeno® card games; an experimental group (n=20) played WiiTM bowling. The participants’ pre- and post-activity heart rates were measured and compared between and within groups using t-tests.

Results: The findings signified an 11.9% increase (p

Conclusions: The inclusion of active video games …

Novel Actions Of Next-Generation Taxanes Benefit Advanced Stages Of Prostate Cancer., Renée De Leeuw, Lisa D. Berman-Booty, Matthew J. Schiewer, Stephen J Ciment, Robert Den, Adam P. Dicker, William Kelly, Edouard J. Trabulsi, Costas D. Lallas, Leonard G. Gomella, Karen E. Knudsen

Department of Cancer Biology Faculty Papers

PURPOSE: To improve the outcomes of patients with castration-resistant prostate cancer (CRPC), there is an urgent need for more effective therapies and approaches that individualize specific treatments for patients with CRPC. These studies compared the novel taxane cabazitaxel with the previous generation docetaxel, and aimed to determine which tumors are most likely to respond.

EXPERIMENTAL DESIGN: Cabazitaxel and docetaxel were compared via in vitro modeling to determine the molecular mechanism, biochemical and cell biologic impact, and cell proliferation, which was further assessed ex vivo in human tumor explants. Isogenic pairs of RB knockdown and control cells were interrogated in vitro …

Factors Affecting Ventriculoperitoneal Shunt Survival In Adult Patients, Farid Khan, Abdul Rehman, Muhammad Shahzad Shamim, Muhammad Ehsan Bari

Section of Neurosurgery

Background: Ventriculoperitoneal (VP) shunt insertion remains the mainstay of treatment for hydrocephalus despite a high rate of complications. The predictors of shunt malfunction have been studied mostly in pediatric patients. In this study, we report our 11-year experience with VP shunts in adult patients with hydrocephalus. We also assess the various factors affecting shunt survival in a developing country setting.
Methods: A retrospective chart analysis was conducted for all adult patients who had undergone shunt placement between the years 2001 and 2011. Kaplan-Meier curves were used to determine the duration from shunt placement to first malfunction and log-rank (Cox-Mantel) tests …

The Regulatory Function Of Sphingosine-1-Phosphate Signaling Axis On Regulatory T Cells In Colorectal Cancer, Andrew V. Nguyen, Yuan-Yuan Wu, Elaine Y. Lin

Publications and Research

In tumors associated with inflammation such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), high numbers of regulatory T cells (Tregs) are associated with both favorable and poor prognoses. The functions of Tregs in CRC remain elusive and have yet to be clearly defined. With new evidence supporting many subsets of Tregs, the research on the development and functions of these cells has begun to come to fruition. The sphingosine 1 phosphate (S1P) pathway was recently reported to regulate the development and function of regulatory T cells. This pathway may shine new light into the pleiotropic nature of these …

Prostate Cancer And Li-Fraumeni Syndrome: Implications For Screening And Therapy., Colleen K Spees, Kelly J Kelleher, Ronney Abaza, Steven K Clinton

Oncology Articles

Li-Fraumeni Syndrome (LFS) is an autosomal dominant genetic disorder associated with mutations in the TP53 gene and characterized by a propensity to develop a variety of malignancies resulting in a shortened lifespan. We report a case of prostate cancer in a 50 year old male with LFS. Experimental studies suggest that TP53 mutations in prostate cancer are associated with therapeutic resistance to radiation, chemotherapy, and anti-androgens, implying that LFS men may experience more aggressive cancer biology with implications for therapeutic decisions. The potential of prostate cancer to develop earlier in LFS favors institution of screening at earlier ages.

Tsc2/Mtorc1 Signaling Controls Paneth And Goblet Cell Differentiation In The Intestinal Epithelium, Y. Zhou, Piotr G. Rychahou, Q. Wang, Heidi L. Weiss, B. Mark Evers

Markey Cancer Center Faculty Publications

The intestinal mucosa undergoes a continual process of proliferation, differentiation and apoptosis, which is regulated by multiple signaling pathways. Notch signaling is critical for the control of intestinal stem cell maintenance and differentiation. However, the precise mechanisms involved in the regulation of differentiation are not fully understood. Previously, we have shown that tuberous sclerosis 2 (TSC2) positively regulates the expression of the goblet cell differentiation marker, MUC2, in intestinal cells. Using transgenic mice constitutively expressing a dominant negative TSC2 allele, we observed that TSC2 inactivation increased mTORC1 and Notch activities, and altered differentiation throughout the intestinal epithelium, with a marked …

Department Of Surgery Update, February 2015, Wright State University Department Of Surgery

Department of Surgery Updates

A four page newsletter created by the Department of Surgery documenting changes to the department. This issue contains note about Margaret M. Dunn, M.D., being appointed dean of the Boonshoft School of medicine, a message from the chair, a list of important dates, a call for abstracts, scholarly activity and more.

Active Brain Regions During Sleep Using Electroencephalography-Functional Magnetic Resonance Imaging, Grace Duan '15, Sameeksha Malhotra '15, Todd B. Parrish

Student Publications & Research

Purpose: To determine the differences in functional connectivity among brain regions during the different stages of the human sleep cycle.

Cytometric Characterization Of Circulating Tumor Cells Captured By Microfiltration And Their Correlation To The Cellsearch(®) Ctc Test., Daniel L Adams, Steingrimur Stefansson, Christian Haudenschild, Stuart S Martin, Monica Charpentier, Saranya Chumsri, Massimo Cristofanilli, Cha-Mei Tang, R Katherine Alpaugh

Pathology Faculty Publications

Recent studies reporting hundreds, to thousands, of circulating tumor cells (CTCs) in the blood of cancer patients have raised questions regarding the prevalence of CTCs, as enumerated by the CellSearch(®) CTC Test. Although CellSearch has been shown to consistently detect clinically relevant CTCs; the ability to only capture EpCAM positive cells has led to speculation that it captures limited subsets of CTCs. In contrast, alternative approaches to CTC isolation are often cited as capturing large numbers of CTCs from patient blood. Not surprisingly the number of cells isolated by alternative approaches show poor correlations when compared to CellSearch, even when …

The Artificial Divide Between Biomedical Sciences And Clinical Medicine In Undergraduate Medical Education, Abdul Rehman, Noor Ul-Ain Baloch, Muhammad Awais

Department of Biological & Biomedical Sciences

No abstract provided.

Pre-Operative Treatment For Disc Herniation: A Case Study Of Chronic Pain, Catherine Bixby, Ellesse Credaroli, Morgan Mitchell, Samantha Shepard, Ernie Merritt, Edward Bilsky

Osteopathic Medicine Student Research Posters

Introduction: Chronic back pain is a prevalent condition that is a leading cause of disability and a major financial obligation for both patients and the healthcare system. Disc herniation contributes to the growing number of back pain cases and determining the best course of care can present a challenge. Surgical intervention carries risks including a complication termed Failed Back Syndrome. This case study provides further investigation into the impact of pain, a sensation that is debilitating and chronic for many. It will provide insight into both surgical and non-surgical interventions that will allow us to provide the highest quality of …

Analysis Of Multiple Cytokine Polymorphisms In Individuals With Untreated Deep Carious Lesions Reveals Il1b (Rs1143643) As A Susceptibility Factor For Periapical Lesions Development, Alisa Dill, Ariadne Letra, Letıcia Chaves De Souza, Mamatha Yadlapati, Cláudia Cristina Biguetti, Gustavo P. Garlet, Alexandre R. Vieira, Renato Menezes Silva

School of Podiatric Medicine Publications

Introduction

It has been proposed that individual genetic predisposition may contribute to persistent apical periodontitis. Cytokines are associated with levels of inflammation and are involved in caries, pulpal, and periapical tissue destruction. We hypothesized that polymorphisms in cytokine genes may contribute to an individual’s increased susceptibility to apical tissue destruction in response to deep carious lesions.

Methods

Subjects with deep carious lesions, with or without periapical lesions (≥ 3 mm) were recruited at the University of Pittsburgh and the University of Texas at Houston. Genomic DNA samples of 316 patients were sorted into 2 groups: 136 cases with deep carious …

Tcr Alpha Lcr And Non-Lcr Cis-Elements Contributing To Tissue Specific Expression Of The Tcr Alpha Gene In Thymic And Peripheral T Cells, Martina Kucerova-Levisohn

Dissertations, Theses, and Capstone Projects

Orchestrated expression of multiple genes residing in the complex TCRα/δ/Dad1 locus requires tight control from multiple cis-acting elements. The TCRα locus control region (LCR), is positioned between TCRα and Dad1 gene, and has been implicated in the differential expression of both genes. In this study, we focus our work on the hypersensitive site (HS)1 prime (HS1'), located 3' of the classical Eα enhancer, within the TCRα LCR. We investigated its non- redundant role in TCRα expression in thymic and peripheral T cells as assayed by in vivo and in vitro studies. Furthermore, formation of HS1' in both lymphoid and …

On Voxel-By-Voxel Accumulated Dose For Prostate Radiation Therapy Using Deformable Image Registration., Jialu Yu, Nicholas Hardcastle, Kyoungkeun Jeong, Edward T. Bender, Mark A. Ritter, Wolfgang A. Tomé

Department of Radiation Oncology Faculty Papers

Since delivered dose is rarely the same with planned, we calculated the delivered total dose to ten prostate radiotherapy patients treated with rectal balloons using deformable dose accumulation (DDA) and compared it with the planned dose. The patients were treated with TomoTherapy using two rectal balloon designs: five patients had the Radiadyne balloon (balloon A), and five patients had the EZ-EM balloon (balloon B). Prostate and rectal wall contours were outlined on each pre-treatment MVCT for all patients. Delivered fractional doses were calculated using the MVCT taken immediately prior to delivery. Dose grids were accumulated to the last MVCT using …

Study Protocol: Asymptomatic Intracranial Atherosclerotic Disease In Pakistanis., Ayeesha Kamran Kamal, Farzin Majeed,, Omrana Pasha, Muhammad Islam, Iqbal Azam Syed, Muhammad Saleem Ilyas, Munawar Hussain, Kamran Masood, Bilal Ahmed, Sumaira Nazir,, Zafar Sajjad, Scott E. . Kasner

Department of Medicine

Background : Intracranial atherosclerotic disease (ICAD) is the most frequent subtype of ischemic stroke globally. It is important to describe the determinants of early ICAD as a strategy to prevent strokes from clinically evident and progressive ICAD. Our objective is to report the determinants of asymptomatic ICAD by linking the presence or absence of ICAD on magnetic resonance angiogram (MRA) with detailed risk assessment in asymptomatic adults.

Methods : This is an observational cross-sectional analytical study. We plan to recruit 200 adult participants from the radiology departments of two tertiary care centers of Karachi, Pakistan. The participants will first be …

Breast Cancer Screening: Early Detection Is Not Enough, Judy A. Tjoe

Journal of Patient-Centered Research and Reviews

N/A

Ketones Prevent Oxidative Impairment Of Hippocampal Synaptic Integrity Through KAtp Channels, Do Young Kim, Mohammed G. Abdelwahab, Soo Han Lee, Derek O'Neill, Roger J. Thompson, Henry J. Duff, Patrick G. Sullivan, Jong M. Rho

Spinal Cord and Brain Injury Research Center Faculty Publications

Dietary and metabolic therapies are increasingly being considered for a variety of neurological disorders, based in part on growing evidence for the neuroprotective properties of the ketogenic diet (KD) and ketones. Earlier, we demonstrated that ketones afford hippocampal synaptic protection against exogenous oxidative stress, but the mechanisms underlying these actions remain unclear. Recent studies have shown that ketones may modulate neuronal firing through interactions with ATP-sensitive potassium (K_ATP) channels. Here, we used a combination of electrophysiological, pharmacological, and biochemical assays to determine whether hippocampal synaptic protection by ketones is a consequence of K_ATP channel activation. Ketones dose-dependently …

Targeting Cell Cycle Proteins In Breast Cancer Cells With Sirna By Using Lipid-Substituted Polyethylenimines, Manoj Parmar, Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Cezary Kucharski, Robert Maranchuk, Judith C. Hugh, Hasan Uludag

Pharmacy Faculty Articles and Research

The cell cycle proteins are key regulators of cell cycle progression whose de-regulation is one of the causes of breast cancer. RNA interference (RNAi) is an endogenous mechanism to regulate gene expression and it could serve as the basis of regulating aberrant proteins including cell cycle proteins. Since the delivery of small interfering RNA (siRNA) is a main barrier for implementation of RNAi therapy, we explored the potential of a non-viral delivery system, 2.0 kDa polyethylenimines substituted with linoleic acid and caprylic acid, for this purpose. Using a library of siRNAs against cell cycle proteins, we identified cell division cycle …

A Standardized Autopsy Procurement Allows For The Comprehensive Study Of Dipg Biology., Madhuri Kambhampati, Jennifer P. Perez, Sridevi Yadavilli, Amanda M. Saratsis, D. Ashley Hill, Cheng-Ying Ho, Eshini Panditharatna, Melissa Markel, Roger J. Packer, Javad Nazarian

Pathology Faculty Publications

Diffuse intrinsic pontine glioma (DIPG) is one of the least understood and most deadly childhood cancers. Historically, there has been a paucity of DIPG specimens for molecular analysis. However, due to the generous participation of DIPG families in programs for postmortem specimen donation, there has been a recent surge in molecular analysis of newly available tumor specimens. Collaborative efforts to share data and tumor specimens have resulted in rapid discoveries in other pediatric brain tumors, such as medulloblastoma, and therefore have the potential to shed light on the biology of DIPG. Given the generous gift of postmortem tissue donation from …

2015 Founders' Day, Philadelphia College Of Osteopathic Medicine

Founders Day Programs

The 2015 Founders Day OJ Snyder Memorial Medal recipients were Oliver Bullock DO '78 and Joseph Dieterle DO '70. The Philadelphia Campus Mason W Pressly Memorial Medal Recipient was Valerie Moore (DO '15). The Georgia campus Mason W Pressly Memorial Medal Recipient was Lauren Smith, (DO '16)

The Tmao-Generating Enzyme Flavin Monooxygenase 3 Is A Central Regulator Of Cholesterol Balance, Manya Warrier, Diana M. Shih, Amy C. Burrows, Daniel Ferguson, Anthony D. Gromovsky, Amanda L. Brown, Stephanie Marshall, Allison Mcdaniel, Rebecca C. Schugar, Zeneng Wang, Jessica Sacks, Xin Rong, Thomas De Aguiar Vallim, Jeff Chou, Pavlina T. Ivanova, David S. Myers, H. Alex Brown, Richard G. Lee, Rosanne M. Crooke, Mark J. Graham, Xiuli Liu, Paolo Parini, Peter Tontonoz, Aldon J. Lusis, Stanley L. Hazen, Ryan E. Temel, J. Mark Brown

Saha Cardiovascular Research Center Faculty Publications

Circulating levels of the gut microbe-derived metabolite trimethylamine-N-oxide (TMAO) have recently been linked to cardiovascular disease (CVD) risk. Here, we performed transcriptional profiling in mouse models of altered reverse cholesterol transport (RCT) and serendipitously identified the TMAO-generating enzyme flavin monooxygenase 3 (FMO3) as a powerful modifier of cholesterol metabolism and RCT. Knockdown of FMO3 in cholesterol-fed mice alters biliary lipid secretion, blunts intestinal cholesterol absorption, and limits the production of hepatic oxysterols and cholesteryl esters. Furthermore, FMO3 knockdown stimulates basal and liver X receptor (LXR)-stimulated macrophage RCT, thereby improving cholesterol balance. Conversely, FMO3 knockdown exacerbates hepatic endoplasmic reticulum (ER) stress …

Pyruvate Carboxylase Is Critical For Non-Small-Cell Lung Cancer Proliferation, Katherine Sellers, Matthew P. Fox, Michael Bousamra Ii, Stephen P. Slone, Richard M. Higashi, Donald M. Miller, Yali Wang, Jun Yan, Mariia O. Yuneva, Rahul Deshpande, Andrew N. Lane, Teresa W-M Fan

Toxicology and Cancer Biology Faculty Publications

Anabolic biosynthesis requires precursors supplied by the Krebs cycle, which in turn requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the activity of pyruvate carboxylase (PC) and glutaminase 1 (GLS1), respectively. Due to their rapid proliferation, cancer cells have increased anabolic and energy demands; however, different cancer cell types exhibit differential requirements for PC- and GLS-mediated pathways for anaplerosis and cell proliferation. Here, we infused patients with early-stage non-small-cell lung cancer (NSCLC) with uniformly 13C-labeled glucose before tissue resection and determined that the cancerous tissues in these patients had enhanced PC activity. …

Effects Of (R)-(-)-5-Methyl-1-Nicotinoyl-2-Pyrazoline On Glutamate Transporter 1 And Cysteine/Glutamate Exchanger As Well As Ethanol Drinking Behavior In Male, Alcohol-Preferring Rats, Munaf Aal-Aaboda, Hasan Alhaddad, Francis Osowik, Surya M. Nauli, Youssef Sari

Pharmacy Faculty Articles and Research

Alcohol consumption is largely associated with alterations in the extracellular glutamate concentrations in several brain reward regions. We recently showed that glutamate transporter 1 (GLT-1) is downregulated following chronic exposure to ethanol for 5 weeks in alcohol-preferring (P) rats and that upregulation of the GLT-1 levels in nucleus accumbens and prefrontal cortex results, in part, in attenuating ethanol consumption. Cystine glutamate antiporter (xCT) is also downregulated after chronic ethanol exposure in P rats, and its upregulation could be valuable in attenuating ethanol drinking. This study examines the effect of a synthetic compound, (R)-(−)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), on ethanol drinking and expressions of …

Understanding Early Organogenesis Using A Simplified In Situ Hybridization Protocol In Xenopus, Steven J. Deimling, Rami R. Halabi, Stephanie A. Grover, Jean H. Wang, Thomas A. Drysdale

Paediatrics Publications

Organogenesis is the study of how organs are specified and then acquire their specific shape and functions during development. The Xenopuslaevis embryo is very useful for studying organogenesis because their large size makes them very suitable for identifying organs at the earliest steps in organogenesis. At this time, the primary method used for identifying a specific organ or primordium is whole mount in situ hybridization with labeled antisense RNA probes specific to a gene that is expressed in the organ of interest. In addition, it is relatively easy to manipulate genes or signaling pathways in Xenopus and in situ hybridization …

The Cell's Antenna And Bending With The Flow, Surya M. Nauli, Kimberly F. Atkinson, Sarmed H. Kathem

Pharmacy Faculty Articles and Research

Polycystic kidney disease (PKD) is the most common life-threatening genetic disease worldwide – affecting about 12.5 million people. Patients with the condition have multiple fluid-filled cysts in their kidneys that lead to a massive enlargement of the organ and gradual worsening of its function, as well as complete failure in many cases. The lack of available treatment means patients may eventually require regular dialysis or a kidney transplant.

Morphine For The Treatment Of Pain In Sickle Cell Disease., Mihir Gupta, Lilian Msambichaka, Samir K. Ballas, Kalpna Gupta

Cardeza Foundation for Hematologic Research

Pain is a hallmark of sickle cell disease (SCD) and its treatment remains challenging. Opioids are the major family of analgesics that are commonly used for treating severe pain. However, these are not always effective and are associated with the liabilities of their own. The pharmacology and multiorgan side effects of opioids are rapidly emerging areas of investigation, but there remains a scarcity of clinical studies. Due to opioid-induced endothelial-, mast cell-, renal mesangial-, and epithelial-cell-specific effects and proinflammatory as well as growth influencing signaling, it is likely that when used for analgesia, opioids may have organ specific pathological effects. …

Biological Reasons For The Neurotoxic Effects Of Mdma (‘Ecstasy’) On The Developing Fetus, Leah Schneeweiss

The Science Journal of the Lander College of Arts and Sciences

MDMA (3, 4-methylenedioxymethamphetamine) is an illicit, recreational drug known by many individuals as ‘Ecstasy.’ MDMA has gained popularity over the past decade and has become a drug of choice at dance parties and clubs because of the stimulating and hallucinogenic effects that it has on the central nervous system. Scientists have determined that MDMA causes neurotoxic damage to adults by harming the serotonergic system in the adult brain. Researchers discovered that embryos exposed to MDMA while in utero also suffer neurotoxic deficits, although not due to impairments in the embryos’ serotonergic systems. These deficits arise because of the cortisol increase …

Oncology Providers’ Opinions On Preventative Recommendations For Patients With Brca1 Or Brca2 Breast Cancer Mutations, Rebecca L. Crissman, Kathleen Dunsmore

All Electronic Theses and Dissertations

BRCA1 and BRCA2 gene mutations have been identified as increasing an individual’s risk for developing breast cancer. Genetic testing for these genes has become increasingly more common. However, once genetic testing has established that an individual has either a BRCA1 or BRCA2 mutation, there is no set guideline for preventative measures. The purpose of this study is to gain the opinions of oncology healthcare providers on their recommendation for preventative treatment in women who have been diagnosed with the mutation at varying ages. A web-based survey was emailed to oncology healthcare providers from Minnesota Oncology in Minnesota and Allegheny Health …

Chemically Self-Assembled Antibody Nanorings: A Novel Approach To Bispecific Design For Cancer Therapeutics, Kari A. Gabrielse

All Electronic Theses and Dissertations

Targeted antibody therapeutics are currently being developed for treatment of a wide variety of cancers. By extending the scope of targeted antibody therapeutics into a bispecific design, it has been shown that simultaneous targeting of the CD3 T cell receptor and cancer cell receptors is possible. While great success has been achieved with the use of bispecific agents, many of these agents are genetically fused antibody fragments that can only target one type of cancerous receptor. Here we describe a simple and straightforward method of spontaneously assembling bispecific antibody therapeutics. Using fusion proteins consisting of two dihydrofolate reductase proteins and …