Digital Commons Network^™

Epigenetic Modulation In Braf Mutated Metastatic Colorectal Cancer, Van Morris

Dissertations and Theses (Open Access)

Introduction: BRAF V600E mutations are associated with poor clinical outcomes for patients with metastatic colorectal cancer (mCRC). Unlike other tumors with the same mutation, BRAF inhibitors are ineffective as monotherapy. CRC tumors with BRAF V600E mutations are associated with global hypermethylation, which may turn off tumor suppressor gene expression. We studied demethylation in BRAF V600E mCRC to restore sensitivity to BRAF inhibitors.

Methods: Tumor databanks were investigated for genes differentially expressed according to BRAF mutation status to identify genes which may be particularly susceptible to epigenetic influence. Mouse xenograft models of BRAFV600E mCRC were treated with vemurafenib or azacitidine, alone …

The Immune Microenvironment Of Microsatellite Instable Endometrial Cancer, Janelle B. Pakish

Dissertations and Theses (Open Access)

Limited treatment options are available for patients with advanced and recurrent endometrial cancer (EC) should standard chemotherapy fail. Recent studies in other tumor types have shown that tumors with high microsatellite instability (MSI-H) have increased immunogenicity and response to immunotherapy treatments compared to microsatellite stable (MSS) tumors. Patients with MSI-H EC may also benefit from these therapies; however, the tumor immune microenvironment in MSI-H EC has not yet been well described.

In order to evaluate the immune microenvironment of MSI-H EC, multiple approaches were used, including analysis of large publically available datasets and detailed characterization of patient tumor samples. Uterine …

Dissemination And Spread Of New Delhi Metallo-Beta-Lactamase-1 Superbugs In Hospital Settings, Erum Khan, Seema Irfan, Binish Arif Sultan, Amna Nasir, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objective:
To find out frequency of isolation of carbapenem-resistant enterobacteriaceae and the predominantly responsible metallo-beta-lactamasegene in a hospital setting.
Methods:
The descriptive, cross-sectional study was conducted from May 2009 to June 2012 at the Aga Khan University Hospital, Karachi, and comprised non-duplicate clinical carbapenem-resistant enterobacteriaceae isolates obtained from different collection units across Pakistan. Kirby-Bauer disk diffusion screening of carbapenem-resistant enterobacteriaceae was confirmed by minimum inhibitory concentration using E-test. Polymerase chain reaction assay was performed to detect blaKPC, blaNDM-1, blaIMP, and blaVIM genes. In addition variable number tandem repeat typing was performed on selected cluster of New Delhi metallo-beta-lactamase-1- positive …

Three Siblings With Familial Non-Medullary Thyroid Carcinoma: A Case Series, Muhammad Owais Rashid, Naeemul Haq, Saad Farooq, Zareen Kiran,, Sabeehuddin Siddique, Shahid Pervez, Najmul Islam

Department of Pathology and Laboratory Medicine

Background: In 2015, thyroid carcinoma affected approximately 63,000 people in the USA, yet it remains one of the most treatable cancers. It is mainly classified into medullary and non-medullary types. Conventionally, medullary carcinoma was associated with heritability but increasing reports have now begun to associate non-medullary thyroid carcinoma with a genetic predisposition as well. It is important to identify a possible familial association in patients diagnosed with non-medullary thyroid carcinoma because these cancers behave more destructively than would otherwise be expected. Therefore, it is important to aggressively manage such patients and screening of close relatives might be justified. Our case …

Investigation Of Cnt-Induced Escherichia Coli Lysis And Protein Release, Abdollah Mosleh

Graduate Theses and Dissertations

This research investigated the use of carbon nanotubes (CNTs) as a treatment to increase the permeability of a bacterial cell wall. Recombinant Escherichia coli BL21 (DE3) containing a plasmid that expressed Green Fluorescent Protein (GFP) and -lactamase were exposed to CNTs under various levels of agitation for different times. Fluorescence assay for GFP, optical absorbance for -lactamase activity, and Transmission Electron Microscopy (TEM) were used to determine the amount of released protein, and visually examine the permeability enhancement of the cells, respectively. It was found that more -lactamase was present in the culture fluid after treatment with CNTs in a …

Periodontitis In Chronic Heart Failure, Hanna Fröhlich, Kristina Herrmann, Jennifer Franke, Alamara Karimi, Tobias Täger, Rita Cebola, Hugo A Katus, Christian Zugck, Lutz Frankenstein

The Texas Heart Institute Journal

Periodontal disease has been associated with an increased risk of cardiovascular events. The purpose of our study was to investigate whether a correlation between periodontitis and chronic heart failure exists, as well as the nature of the underlying cause.

We enrolled 71 patients (mean age, 54 ± 13 yr; 56 men) who had stable chronic heart failure; all underwent complete cardiologic and dental evaluations. The periodontal screening index was used to quantify the degree of periodontal disease. We compared the findings to those in the general population with use of data from the 4th German Dental Health Survey.

Gingivitis, moderate …

Moderation Analysis Of Bowel Function Among Nutrients And Physical Function Or Depression, As Well As Whether Bowel Function Is Related To Cognition In Older Adults, Jessie Alwerdt

USF Tampa Graduate Theses and Dissertations

As we age, the risk for gut issues, such as smooth muscle tone, may be an underlying indirect or direct cause or risk factor for many age-related issues, such as frailty. Consequences of decreased motility and depleted epithelial barrier may result in nutrient deficiencies that may increase the risk for malnutrition (Brownie, 2006). Further, there is increasing evidence that there is a gut-brain-axis relationship that may influence cognition and mental health issues, such as depression and anxiety. While there are relationships established, the interconnections of these factors have yet to be fully understood.

This dissertation examined several relationships specific to …

Samarium-153-Edtmp (Quadramet®) With Or Without Vaccine In Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase 2 Trial, Christopher R. Heery, Ravi A. Madan, Mark N. Stein, Walter M. Stadler, Robert S. Dipaola, Myrna Rauckhorst, Seth M. Steinberg, Jennifer L. Marté, Clara C. Chen, Italia Grenga, Renee N. Donahue, Caroline Jochems, William L. Dahut, Jeffrey Schlom, James L. Gulley

Internal Medicine Faculty Publications

PSA-TRICOM is a therapeutic vaccine in late stage clinical testing in metastatic castration-resistant prostate cancer (mCRPC). Samarium-153-ethylene diamine tetramethylene phosphonate (Sm-153-EDTMP; Quadramet^®), a radiopharmaceutical, binds osteoblastic bone lesions and emits beta particles causing local tumor cell destruction. Preclinically, Sm-153-EDTMP alters tumor cell phenotype facilitating immune-mediated killing. This phase 2 multi-center trial randomized patients to Sm-153-EDTMP alone or with PSA-TRICOM vaccine. Eligibility required mCRPC, bone metastases, prior docetaxel and no visceral disease. The primary endpoint was the proportion of patients without radiographic disease progression at 4 months. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and immune responses. …

Mechanisms Of Progranulin Action And Regulation In Genitourinary Cancers., Ryuta Tanimoto, Kuojung G Lu, Shi-Qiong Xu, Simone Buraschi, Antonino Belfiore, Renato V. Iozzo, Andrea Morrione

Department of Urology Faculty Papers

The growth factor progranulin has emerged in recent years as a critical regulator of transformation in several cancer models, including breast cancer, glioblastomas, leukemias, and hepatocellular carcinomas. Several laboratories, including ours, have also demonstrated an important role of progranulin in several genitourinary cancers, including ovarian, endometrial, cervical, prostate, and bladder tumors, where progranulin acts as an autocrine growth factor thereby modulating motility and invasion of transformed cells. In this review, we will focus on the mechanisms of action and regulation of progranulin signaling in genitourinary cancers with a special emphasis on prostate and bladder tumors.

Cell Therapy Must Be Regulated As Medicine, Zihai Li, Delong Liu

NYMC Faculty Publications

Background

The current standard of care for relapsed and refractory acute lymphoblastic leukemia (ALL) is combination chemotherapy.

Case presentation

We report a case of highly refractory ALL who was treated with blinatumomab. The ALL in this patient relapsed within a month after completion of hyperCVAD regimen and was refractory to high dose mitoxantrone/cytarabine and CLAG regimens.

Conclusion This highly refractory pre-B Ph− ALL was induced to complete remission after one course of single agent blinatumomab.

Sarcoidosis Activates Diverse Transcriptional Programs In Bronchoalveolar Lavage Cells., Sina A. Gharib, Anagha Malur, Isham Huizar, Barbara P. Barna, Mani S. Kavuru, Lynn M. Schnapp, Mary Jane Thomassen

Division of Pulmonary, Allergy, and Critical Care Medicine Presentations and Grand Rounds

BACKGROUND: Sarcoidosis is a multisystem immuno-inflammatory disorder of unknown etiology that most commonly involves the lungs. We hypothesized that an unbiased approach to identify pathways activated in bronchoalveolar lavage (BAL) cells can shed light on the pathogenesis of this complex disease.

METHODS: We recruited 15 patients with various stages of sarcoidosis and 12 healthy controls. All subjects underwent bronchoscopy with lavage. For each subject, total RNA was extracted from BAL cells and hybridized to an Affymetrix U133A microarray. Rigorous statistical methods were applied to identify differential gene expression between subjects with sarcoidosis vs.

CONTROLS: To better elucidate pathways differentially activated …

Maternal Age Of Menarche And Blood Pressure In Adolescence: Evidence From Hong Kong’S “Children Of 1997” Birth Cohort, Tsz Chun Lai, Gabriel Matthew Leung, C Mary Schooling

Publications and Research

Background Age of puberty has declined substantially in developed settings and is now declining in the rest of the world with economic development. Early age of puberty is associated with noncommunicable diseases in adulthood, and may be a long-term driver of population health with effects over generations. In a non-Western setting, we examined the association of maternal age of menarche with blood pressure in late childhood/adolescence.

Methods We used generalised estimating equations to estimate the adjusted association of maternal age of menarche with age-, sex- and height-adjusted blood pressure z-score from 10 to 16 years in Hong Kong’s population-representative birth …

What's New In Musculoskeletal Infection: Update On Biofilms., Arvind Nana, Sandra B Nelson, Alex Mclaren, Antonia F. Chen, Md, Mba

Rothman Institute Papers

No abstract provided.

Tricurin, A Novel Formulation Of Curcumin, Epicatechin Gallate, And Resveratrol, Inhibits The Tumorigenicity Of Human Papillomaviruspositive Head And Neck Squamous Cell Carcinoma, Longzhu Piao, Sumit Mukherjee, Qing Chang, Xiujie Xie, Hong Li, Mario R. Castellanos, Probal Banerjee, Hassan Iqbal, Ryan Ivancic, Xueqian Wang, Theodoros N. Teknos, Quintin Pan

Publications and Research

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. The incidence of human papillomavirus-positive head and neck squamous cell carcinoma (HPV-positive HNSCC) has rapidly increased over the past 30 years prompting the suggestion that an epidemic may be on the horizon. Therefore, there is a clinical need to develop alternate therapeutic strategies to manage the growing number of HPV-positive HNSCC patients. TriCurin is a composition of three food-derived polyphenols in unique stoichiometric proportions consisting of curcumin from the spice turmeric, resveratrol from red grapes, and …

Effects Of Quercetin On Blood Pressure: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Maria-Corina Serban, Alberto Zanchetti, George Howard, Diana Antal, Wilbert S. Aronow, Lipid And Blood Pressure Meta-Analysis Collaboration (Lbpmc) Group

NYMC Faculty Publications

BACKGROUND: Quercetin, the most abundant dietary flavonol, has antioxidant effects in cardiovascular disease, but the evidence regarding its effects on blood pressure (BP) has not been conclusive. We assessed the impact of quercetin on BP through a systematic review and meta-analysis of available randomized controlled trials.

METHODS AND RESULTS: We searched PUBMED, Cochrane Library, Scopus, and EMBASE up to January 31, 2015 to identify placebo-controlled randomized controlled trials investigating the effect of quercetin on BP. Meta-analysis was performed using either a fixed-effects or random-effect model according to I(2) statistic. Effect size was expressed as weighted mean difference (WMD) and 95% …

The Genetic Landscape Of Dural Marginal Zone Lymphomas, Karthik A. Ganapathi, Vaidehi Jobanputra, Fabio Iwamoto, Pallavi Khattar, Elaine S. Jaffe, Mahesh M. Mansukhani, Govind Bhagat

NYMC Faculty Publications

The dura is a rare site of involvement by marginal zone lymphoma (MZL) and the biology of dural MZL is not well understood. We performed genome-wide DNA copy number and targeted mutational analysis of 14 dural MZL to determine the genetic landscape of this entity. Monoallelic and biallelic inactivation of TNFAIP3 by mutation (n=5) or loss (n=1) was observed in 6/9 (67%) dural MZL exhibiting plasmacytic differentiation, including 3 IgG4+ cases. In contrast, activating NOTCH2 mutations were detected in 4/5 (80%) dural MZL displaying variable monocytoid morphology. Inactivating TBL1XR1 mutations were identified in all NOTCH2 mutated cases. Recurrent mutations in …

High Crlf2 Expression Associates With Ikzf1 Dysfunction In Adult Acute Lymphoblastic Leukemia Without Crlf2 Rearrangement., Zheng Ge, Yan Gu, Gang Zhao, Jianyong Li, Baoan Chen, Qi Han, Xing Guo, Juan Liu, Hui Li, Michael D. Yu, Justin Olson, Sadie Steffens, Kimberly J. Payne, Chunhua Song, Sinisa Dovat

Student Papers, Posters & Projects

Overexpression of cytokine receptor-like factor 2 (CRLF2) due to chromosomal rearrangement has been observed in acute lymphoblastic leukemia (ALL) and reported to contribute to oncogenesis and unfavorable outcome in ALL. We studied B-ALL and T-ALL patients without CRLF2 rearrangement and observed that CRLF2 is significantly increased in a subset of these patients. Our study shows that high CRLF2expression correlates with high-risk ALL markers, as well as poor survival. We found that the IKZF1-encoded protein, Ikaros, directly binds to the CRLF2 promoter and regulates CRLF2 expression in leukemia cells. CK2 inhibitor, which can increase Ikaros activity, significantly increases Ikaros binding in …

Dasatinib-Loaded Albumin Nanoparticles Possess Diminished Endothelial Cell Barrier Disruption And Retain Potent Anti-Leukemia Cell Activity, Chunling Dong, Bo Li, Zhenyu Li, Sreerama Shetty, Jian Fu

Internal Medicine Faculty Publications

Dasatinib (DAS), a second-generation tyrosine kinase inhibitor, is highly effective in treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. However, its clinical use is limited due to serious adverse effects. DAS can disrupt endothelial barrier integrity and increase endothelial permeability which may cause peripheral edema and pleural effusion. Albumin nanoparticles (NPs) as a drug carrier may serve as a useful tool for cell-selective drug delivery to reduce DAS-induced endothelial hyperpermeability and maintain endothelial barrier integrity. In this study, we reported that DAS-loaded NPs exhibited potent anti-leukemia efficacy as DAS alone. Importantly, albumin NPs as a drug carrier markedly …

Bibliography Of Secondary Sources On The History Of Dermatology Ii. Obituaries And Biographies In English Supplemented Through 2015, Sarah Brenner, Md (Editor), Lawrence Parish, Md, Michael J. Lavery, Mb Bch Bao; Mrcp, Andrzej Grzybowski, Md, Phd, Jennifer L. Parish, Md, Daniel H. Parish, Md, Jd

Department of Dermatology and Cutaneous Biology Faculty Papers

Introduction

A bibliographic record on the history of dermatology has been a project that started over 4 decades ago. It is a collection of all forms of history, ranging from dermatologic conditions, to famous dermatologists and physicians who have advanced the field of both dermatology and medicine, to the different countries that promoted the development of scientists, researchers and physicians alike.

It was decided that the bibliographic record would encompass journals, books and a compilation of obituaries. A pertinent question is whether a manually created bibliographic project is still warranted in the 21^st century. In short, yes. While Index …

Bibliography Of Secondary Sources On The History Of Dermatology, Sarah Brenner, Md (Editor), Lawrence Parish, Md, Michael J. Lavery, Mb Bch Bao; Mrcp, Andrzej Grzybowski, Md, Phd, Jennifer L. Parish, Md, Daniel H. Parish, Md, Jd

Department of Dermatology and Cutaneous Biology Faculty Papers

Introduction

A bibliographic record on the history of dermatology has been a project that started over 4 decades ago. It is a collection of all forms of history, ranging from dermatologic conditions, to famous dermatologists and physicians who have advanced the field of both dermatology and medicine, to the different countries that promoted the development of scientists, researchers and physicians alike.

It was decided that the bibliographic record would encompass journals, books and a compilation of obituaries. A pertinent question is whether a manually created bibliographic project is still warranted in the 21^st century. In short, yes. While Index …

Bibliography Of Secondary Sources On The History Of Dermatology Iii. Books, Monographs, And Chapters In English Supplemented Through 2015, Sarah Brenner, Md (Editor), Lawrence Parish, Md, Michael J. Lavery, Mb Bch Bao; Mrcp (Uk, Andrzej Grzybowski, Md, Phd, Jennifer L. Parish, Md, Daniel H. Parish, Md, Jd

Department of Dermatology and Cutaneous Biology Faculty Papers

Introduction

A bibliographic record on the history of dermatology has been a project that started over 4 decades ago. It is a collection of all forms of history, ranging from dermatologic conditions, to famous dermatologists and physicians who have advanced the field of both dermatology and medicine, to the different countries that promoted the development of scientists, researchers and physicians alike.

It was decided that the bibliographic record would encompass journals, books and a compilation of obituaries. A pertinent question is whether a manually created bibliographic project is still warranted in the 21^st century. In short, yes. While Index …

The Cutting Edge Summer 2016, Wright State University Department Of Surgery

The Cutting Edge Newsletter

A twelve page newsletter created by the Department of Surgery documenting current affairs of the department. This issue contains features such as faculty news, information on general surgery residencies, a list of scholarly activity, special lectures, and more.

Global Assessment Of Schistosomiasis Control Over The Past Century Shows Targeting The Snail Intermediate Host Works Best., Susanne H Sokolow, Chelsea L Wood, Isabel J Jones, Scott J Swartz, Melina Lopez, Michael H. Hsieh, Kevin D Lafferty, Armand M Kuris, Chloe Rickards, Giulio A De Leo

Urology Faculty Publications

BACKGROUND: Despite control efforts, human schistosomiasis remains prevalent throughout Africa, Asia, and South America. The global schistosomiasis burden has changed little since the new anthelmintic drug, praziquantel, promised widespread control.

METHODOLOGY: We evaluated large-scale schistosomiasis control attempts over the past century and across the globe by identifying factors that predict control program success: snail control (e.g., molluscicides or biological control), mass drug administrations (MDA) with praziquantel, or a combined strategy using both. For data, we compiled historical information on control tactics and their quantitative outcomes for all 83 countries and territories in which: (i) schistosomiasis was allegedly endemic during the …

Com Outlook Summer-Fall 2016, College Of Osteopathic Medicine

COM Outlook

No abstract provided.

Neonatal Pain Management: Still In Search For The Holy Grail., Karel Allegaert, John N. Van Den Anker

Pediatrics Faculty Publications

Inadequate pain management but also inappropriate use of analgesics in early infancy has negative effects on neurodevelopmental outcome. As a consequence, neonatal pain management is still in search for the Holy Grail. At best, effective pain management is based on prevention, assessment, and treatment followed by a re-assessment of the pain to determine if additional treatment is still necessary. Unfortunately, epidemiological observations suggest that neonates are undergoing painful procedures very frequently, unveiling the need for effective preventive, non-pharmacological strategies. In addition, assessment is still based on validated, multimodal, but subjective pain assessment tools. Finally, in neonatal intensive care units, there …

G Protein-Coupled Receptor Kinases: Crucial Regulators Of Blood Pressure, J. Yang, V. Villar, Ines Armando, Pedro A. Jose, C. Zeng

Medicine Faculty Publications

No abstract provided.

Adgrl3 (Lphn3) Variants Are Associated With A Refined Phenotype Of Adhd In The Mta Study, Maria T. Acosta, James Swanson, Annamarie Stehli, Brooke Molina, The Mta Team

Neurology Faculty Publications

Background

ADHD is the most common neuropsychiatric condition affecting individuals of all ages. Long-term outcomes of affected individuals and association with severe comorbidities as SUD or conduct disorders are the main concern. Genetic associations have been extensively described. Multiple studies show that intronic variants harbored in the ADGRL3 (LPHN3) gene are associated with ADHD, especially associated with poor outcomes.

Methods

In this study, we evaluated this association in the Multimodal Treatment Study of children with ADHD (MTA), initiated as a 14-month randomized clinical trial of 579 children diagnosed with DSM-IV ADHD-Combined Type (ADHD-C), that transitioned to a 16-year prospective observational …

Reduction Of Friction By Recombinant Human Proteoglycan 4 In Il-1Α Stimulated Bovine Cartilage Explants, Katherine M. Larson, Ling Zhang, Khaled A. Elsaid, Tannin A. Schmidt, Braden C. Fleming, Gary J. Badger, Gregory D. Jay

Pharmacy Faculty Articles and Research

A boundary lubricant attaches and protects sliding bearing surfaces by preventing interlocking asperity-asperity contact. Proteoglycan-4 (PRG4) is a boundary lubricant found in the synovial fluid that provides chondroprotection to articular surfaces. Inflammation of the diarthrodial joint modulates local PRG4 concentration. Thus, we measured the effects of inflammation, with Interkeukin-1α (IL-1α) incubation, upon boundary lubrication and PRG4 expression in bovine cartilage explants. We further aimed to determine whether the addition of exogenous human recombinant PRG4 (rhPRG4) could mitigate the effects of inflammation on boundary lubrication and PRG4 expression in vitro.

Cartilage explants, following a 7-day incubation with IL-1α, were tested …

Three-Dimensional Printing And Nanotechnology For Enhanced Implantable Materials, Karthik Kumar Tappa

Doctoral Dissertations

Orthopedic and oro-maxillofacial implants have revolutionized treatment of bone diseases and fractures. Currently available metallic implants have been in clinical use for more than 40 years and have proved medically efficacious. However, several drawbacks remain, such as excessive stiffness, accumulation of metal ions in surrounding tissue, growth restriction, required removal/revision surgery, inability to carry drugs, and susceptibility to infection. The need for additional revision surgery increases financial costs and prolongs recovery time for patients. These metallic implants are bulk manufactured and often do not meet patient's requirements. A surgeon must machine (cut, weld, trim or drill holes) them in order …

Precision Medicine Informatics, Lewis J Frey, Elmer V Bernstam, Joshua C Denny

Faculty, Staff and Student Publications

No abstract provided.