Digital Commons Network^™

Investigation Of Quatitative Image Features From Pretreatment Ct And Fdg-Pet Scans In Stage Iii Nsclc Patients Undergoing Defintive Radiation Therapy, David Fried

Dissertations and Theses (Open Access)

The purpose of this work was to determine if quantitative image features (QIFs) extracted from computed tomography (CT) and flourodeoxyglucose (FDG) positron emission tomography (PET) could provide prognostic information to improve outcome models. Our goal for this work was to determine if it may one day be feasible to incorporate QIFs into personalized cancer care. QIFs were used to quantitatively characterize patient disease as seen on imaging. A leave-one-out cross-validation procedure was used to assess the prognostic ability of QIFs extracted from CT and PET in addition to conventional prognostic factors (CPFs). QIFs were found to improve model fit for …

Pamam Dendrimers As Promising Nanocarriers For Rnai Therapeutics, Prashant Kesharwani, Sanjeev Banerjee, Umesh Gupta, Mohd Cairul Iqbal Mohd Amin, Subhash Padhye, Fazlul H. Sarkar, Arun K. Iyer

Pharmaceutical Sciences Faculty Publications

Therapeutics based on RNA interference mechanisms are highly promising for the management of several diseases including multi-drug resistant cancers. However, effective delivery of siRNAs and oligonucleotides still remains challenging. In this regard, hyper-branched, PAMAM dendrimers having unique three-dimensional architecture and nanoscale size, with cationic surface charge can potentially serve as siRNA condensing agents as well as robust nano-vectors for targeted delivery. In addition, their surface functionality permits conjugation of drugs and genes or development of hybrid systems for combination therapy. Thus far, in vitro cellular testing of dendrimer-mediated siRNA delivery has revealed great potential, with reports on their in vivo …

The Environmental Profile Of A Community’S Health: A Cross-Sectional Study On Tobacco Marketing In 16 Countries., Emily Savell, Anna B. Gilmore, Michelle Sims, Prem K. Mony, Teo Koon, Khalid Yusoff, Scott A. Lear, Pamela Seron, Noorhassim Ismail, K Burcu Tumerdem Calik, Annik Rosengren, Ahmad Bahonar, Rajesh Kumar, Krishnapillai Vijayakumar, Annamarie Kruger, Hany Swidan, Rajeev Gupta, Ehimario Igumbor, Asad Ali Khan Afridi, Omar Rahman, Jephat Chifamba, Katarzyna Zatonska, V Mohan, Deepa Mohan, Patricio Lopez-Jaramillo, Alvaro Avezum, Paul Poirier, Andres Orlandini, Wei Li, Martin Mckee, Sumathy Rangarajan, Salim Yusuf, Clara K. Chow

Community Health Sciences

OBJECTIVE:

To examine and compare tobacco marketing in 16 countries while the Framework Convention on Tobacco Control requires parties to implement a comprehensive ban on such marketing.

METHODS:

Between 2009 and 2012, a kilometre-long walk was completed by trained investigators in 462 communities across 16 countries to collect data on tobacco marketing. We interviewed community members about their exposure to traditional and non-traditional marketing in the previous six months. To examine differences in marketing between urban and rural communities and between high-, middle- and low-income countries, we used multilevel regression models controlling for potential confounders.

FINDINGS:

Compared with high-income countries, …

Prevalence And Antimicrobial Susceptibility Pattern Of Coagulase-Negative Staphylococci (Cons) Isolated From Clinical Specimens In Northern Of Jordan, Ibrahim Ali Al Tayyar, Mazhar Salim Al-Zoubi, Emad Hussein, Salih Khudairat, Konrad Sarosiek

Department of Surgery Faculty Papers

No abstract provided.

Movement Disorders Care In Pakistan, Nadir A. Syed

Pakistan Journal of Neurological Sciences (PJNS)

Earlier discussions about a professional society relating to movement disorders took place about a decade ago and were felt to be a little premature. However PSN nominated Dr Nadir Ali Syed to promote movement disorders related activities. Dr Nadir worked with patients to form a patient centered body, the Pakistan Parkinson's Society which has been quite active in the last several years.

Improved Sensitivity To Fluorescence For Cancer Detection In Wide-Field Image-Guided Neurosurgery, Michael Jermyn, Yoann Gosselin, Pablo A. Valdes, Mira Sibai, Kolbein Kolste

Dartmouth Scholarship

In glioma surgery, Protoporphyrin IX (PpIX) fluorescence may identify residual tumor that could be resected while minimizing damage to normal brain. We demonstrate that improved sensitivity for wide-field spectroscopic fluorescence imaging is achieved with minimal disruption to the neurosurgical workflow using an electron-multiplying charge-coupled device (EMCCD) relative to a state-of-the-art CMOS system. In phantom experiments the EMCCD system can detect at least two orders-of-magnitude lower PpIX. Ex vivo tissue imaging on a rat glioma model demonstrates improved fluorescence contrast compared with neurosurgical fluorescence microscope technology, and the fluorescence detection is confirmed with measurements from a clinically-validated spectroscopic probe. Greater PpIX …

Epithelial Neoplasia Coincides With Exacerbated Injury And Fibrotic Response In The Lungs Of Gprc5a-Knockout Mice Following Silica Exposure, Xiaofei Wang, Dongliang Xu, Yueling Liao, Shuangshuang Zhong, Hongyong Song, Beibei Sun, Binhua P. Zhou, Jiong Deng, Baohui Han

Markey Cancer Center Faculty Publications

Exposure to crystalline silica is suggested to increase the risk for a variety of lung diseases, including fibrosis and lung cancer. However, epidemiological evidences for the exposure-risk relationship are ambiguous and conflicting, and experimental study from a reliable animal model to explore the relationship is lacking. We reasoned that a mouse model that is sensitive to both lung injury and tumorigenesis would be appropriate to evaluate the exposure-risk relationship. Previously, we showed that, Gprc5a^-/- mice are susceptible to both lung tumorigenesis and endotoxin-induced acute lung injury. In this study, we investigated the biological consequences in Gprc5a^-/- mouse model …

In Vitro Growth Suppression Of Renal Carcinoma Cells By Curcumin, Santhi D. Konduri, Madhavi Latha Yadav Bangaru, Phu Thanh Do, Shenglin Chen, Jeffrey Woodliff, Sanjay Kansra

Journal of Patient-Centered Research and Reviews

Purpose

Malignant clear cell renal carcinoma (ccRCC) is an aggressive tumor highly resistant to chemotherapy and radiation. Current therapeutic approaches to management of ccRCC have not significantly improved patient survival, therefore novel therapies are needed. Activated NFκB and STAT3 expression is associated with ccRCC pathogenesis. The dietary polyphenol curcumin is a well-documented antitumor agent and a known inhibitor of NFκB and STAT3 activation. Given the lack of effective therapies that block ccRCC progression, our objective was to examine whether curcumin could suppress the growth and migration of ccRCC cells, and whether this suppression was mediated via inhibition of NFκB and …

Lipoproteins And Health Outcomes: Cognitive And Physical Function In Older Adults, Marianne Chanti-Ketterl

USF Tampa Graduate Theses and Dissertations

Cardiovascular health is a major determinant of quality of life and mortality, especially in older adulthood. With the world’s oldest population increasing at expedited rates, challenges from cardiovascular conditions and its implications are spawning. Although it is well known that dyslipidemia may lead to cardiac events, less is known about the effects on cognitive and physical function in older adults. Epidemiological studies show that optimizing current preventive strategies even at older ages may reduce the incidence of cardiovascular comorbidity (e.g. hypertension, stroke) and increase quality of life. Determining the association between lipoproteins and cognitive and functional performance in older adults …

A Disease-Based Approach To The Vertical And Horizontal Integration Of A Medical Curriculum, Charles A. Gullo Phd, Brian R. Dzwonek, Bobby L. Miller

Biochemistry and Microbiology

As medical disciplines have become increasingly interdisciplinary and evidenced-based medicine is widely practiced, there is a need for curricula that reflect these changes. The newly revised LCME standards 1.1 Strategic Planning and Continuous Quality Improvement and 8.3 Curricular Design, Review, Revision/Content Monitoring require ongoing curricular review to assure accreditation compliancy. We have completed a comprehensive review of our curriculum and have moved from a discipline-based curriculum to that of one that focuses on a systems/disease-based model. The approach allows for a more horizontally integrated curriculum in the preclinical years, while the use of 115 distinct disease and eight themes creates …

Microrna Molecular Profiling From Matched Tumor And Bio-Fluids In Bladder Cancer, David A. Armstrong, Benjamin B. Green, John D. Seigne, Alan R. Schned, Carmen Marsit

Dartmouth Scholarship

MicroRNAs have been identified as potential cancer biomarkers due to their presence and stability in many body fluids including urine and plasma, but the relationship of the pattern of expression of these messengers across various biological media has not been addressed and could provide important information in order to translate these biomarkers for epidemiologic or clinical use. We analyzed microRNA of matched FFPE-tumor tissue, plasma, urine exosomes (n = 16) and WBCs (n = 11) from patients with bladder cancer, using Nanostring miRNA assays and droplet digital PCR for validation. Pearson correlations were used to compare expression between …

Mice Deficient In Endothelial Α5 Integrin Are Profoundly Resistant To Experimental Ischemic Stroke, Jill Roberts, Leon De Hoog, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

Stroke is a disease in dire need of better therapies. We have previously shown that a fragment of the extracellular matrix proteoglycan, perlecan, has beneficial effects following cerebral ischemia via the α5β1 integrin receptor. We now report that endothelial cell selective α5 integrin deficient mice (α5 KO) are profoundly resistant to ischemic infarct after transient middle cerebral artery occlusion. Specifically, α5 KOs had little to no infarct 2–3 days post-stroke, whereas controls had an increase in mean infarct volume over the same time period as expected. Functional outcome is also improved in the α5 KOs compared with controls. Importantly, no …

Sh2 Ligand-Like Effects Of Second Cytosolic Domain Of Na/K-Atpase Α1 Subunit On Src Kinase, Moumita Banerjee, Qiming Duan, Zijian Xie

Pharmaceutical Science and Research

Our previous studies have suggested that the α1 Na/K-ATPase interacts with Src to form a receptor complex. In vitro binding assays indicate an interaction between second cytosolic domain (CD2) of Na/K-ATPase α1 subunit and Src SH2 domain. Since SH2 domain targets Src to specific signaling complexes, we expressed CD2 as a cytosolic protein and studied whether it could act as a Src SH2 ligand in LLC-PK1 cells. Co-immunoprecipitation analyses indicated a direct binding of CD2 to Src, consistent with the in vitro binding data. Functionally, CD2 expression increased basal Src activity, suggesting a Src SH2 ligand-like property of CD2. Consistently, …

Introduction To Dermoscopy, Deborah Bren Do

Department of Family Medicine

No abstract provided.

Integrin Α6Β4 Promotes Autocrine Epidermal Growth Factor Receptor (Egfr) Signaling To Stimulate Migration And Invasion Toward Hepatocyte Growth Factor (Hgf), Brittany L. Carpenter, Min Chen, Teresa Knifley, Kelley A. Davis, Susan M.W. Harrison, Rachel L. Stewart, Kathleen O'Connor

Markey Cancer Center Faculty Publications

Integrin α6β4 is up-regulated in pancreatic adenocarcinomas where it contributes to carcinoma cell invasion by altering the transcriptome. In this study, we found that integrin α6β4 up-regulates several genes in the epidermal growth factor receptor (EGFR) pathway, including amphiregulin (AREG), epiregulin (EREG), and ectodomain cleavage protease MMP1, which is mediated by promoter demethylation and NFAT5. The correlation of these genes with integrin α6β4 was confirmed in The Cancer Genome Atlas Pancreatic Cancer Database. Based on previous observations that integrin α6β4 cooperates with c-Met in pancreatic cancers, we examined the impact of EGFR signaling on hepatocyte growth factor (HGF)-stimulated migration and …

Abcc9/Sur2 In The Brain: Implications For Hippocampal Sclerosis Of Aging And A Potential Therapeutic Target, Peter T. Nelson, Gregory A. Jicha, Wang-Xia Wang, Eseosa T. Ighodaro, Sergey C. Artiushin, Colin G. Nichols, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“K _ATP ”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The K _ATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is …

Enos Transfection Of Adipose-Derived Stem Cells Yields Bioactive Nitric Oxide Production And Improved Results In Vascular Tissue Engineering., Stephen Mcilhenny, Ping Zhang, Thomas Tulenko, Jason Comeau, Sarah Fernandez, Aleksandra Policha, Matthew Ferroni, Elizabeth J Faul, Gabor Bagameri, Irving Shapiro, Paul J. Dimuzio

Department of Surgery Faculty Papers

This study evaluates the durability of a novel tissue engineered blood vessel (TEBV) created by seeding a natural vascular tissue scaffold (decellularized human saphenous vein allograft) with autologous adipose-derived stem cells (ASC) differentiated into endothelial-like cells. Previous work with this model revealed the graft to be thrombogenic, likely due to inadequate endothelial differentiation as evidenced by minimal production of nitric oxide (NO). To evaluate the importance of NO expression by the seeded cells, we created TEBV using autologous ASC transfected with the endothelial nitric oxide synthase (eNOS) gene to produce NO. We found that transfected ASC produced NO at levels …

Bomb Blast Injuries: Tertiary Care Hospital In-Patient Experience Over The Last 20 Years, Naveed A. Pasha, Raja Samir Khan, Shahryar Noordin

Department of Surgery Docs

Abstract

OBJECTIVE:

To examine the distribution and nature of limb injuries in young bomb blast victimsand their management in a tertiary healthcare setting.

METHODS:

The retrospective study was conducted at the Aga Khan University Hospital, Karachi and data was searched using the University Medical Record Database with International Classification of Diseases-Ninth Revision-Clinical Modification codes for injuries and terrorism between 1990 and 2012. Data regarding injuries, including admission time, hospital stay duration, interventions and mortality, was collected and classified as per the New Injury Severity Score.

RESULTS:

There were 22 patients in the study; 19(86.3%) males and 3(13.7%) females. The mean …

Residual Barriers For Utilization Of Maternal And Child Health Services: Community Perceptions From Rural Pakistan., Zahid Memon, Shehla Zaidi, Atif Riaz

Community Health Sciences

Low utilization of maternal and child care services in rural areas has constrained Pakistan from meeting targets of Millennium Development Goals (MDGs) 4 and 5. This study explores community barriers in accessing Maternal and Child Health (MCH) services in ten remote rural districts of Pakistan. It further presents how the barriers differ across a range of MCH services, and also whether the presence of Community Health Workers (CHWs) reduces client barriers. Qualitative methods were used involving altogether sixty focus group discussions with mothers, their spouses and community health workers. Low awareness, formidable distances, expense, and poorly functional services were the …

Deletion Of Cyclophilin D Impairs Β-Oxidation And Promotes Glucose Metabolism., Michele Tavecchio, Sofia Lisanti, Michael J Bennett, Lucia R Languino, Dario C Altieri

Department of Cancer Biology Faculty Papers

Cyclophilin D (CypD) is a mitochondrial matrix protein implicated in cell death, but a potential role in bioenergetics is not understood. Here, we show that loss or depletion of CypD in cell lines and mice induces defects in mitochondrial bioenergetics due to impaired fatty acid β-oxidation. In turn, CypD loss triggers a global compensatory shift towards glycolysis, with transcriptional upregulation of effectors of glucose metabolism, increased glucose consumption and higher ATP production. In vivo, the glycolytic shift secondary to CypD deletion is associated with expansion of insulin-producing β-cells, mild hyperinsulinemia, improved glucose tolerance, and resistance to high fat diet-induced liver …

Loss Of Glycosaminoglycan Receptor Binding After Mosquito Cell Passage Reduces Chikungunya Virus Infectivity, Amber M. Paul, Dhiraj Acharya, John F. Anderson, Faqing Huang, Fengwei Bai

Publications

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that can cause fever and chronic arthritis in humans. CHIKV that is generated in mosquito or mammalian cells differs in glycosylation patterns of viral proteins, which may affect its replication and virulence. Herein, we compare replication, pathogenicity, and receptor binding of CHIKV generated in Vero cells (mammal) or C6/36 cells (mosquito) through a single passage. We demonstrate that mosquito cell derived CHIKV (CHIKVmos) has slower replication than mammalian cell derived CHIKV (CHIKVvero), when tested in both human and murine cell lines. Consistent with this, CHIKVmos infection in both cell lines produce less cytopathic …

The Role Of Quality Health Services And Discussion About Birth Spacing In Postpartum Contraceptive Use In Sindh, Pakistan: A Multilevel Analysis, Hannah Tappis, Anis Kazi, Waqas Hameed, Zaib Dahar, Anayat Ali, Sohail Agha

Community Health Sciences

Introduction: Rapid population growth, stagnant contraceptive prevalence, and high unmet need for family planning present significant challenges for meeting Pakistan's national and international development goals. Although health behaviors are shaped by multiple social and environmental factors, research on contraceptive uptake in Pakistan has focused on individual and household determinants, and little attention has been given to community characteristics that may affect access to services and reproductive behavior.
Methods: Individual and community determinants of contraceptive use were identified using multivariable multilevel logistic regression to analyze data from a 2014 cross-sectional survey of 6,200 mothers in 503 communities in Sindh, Pakistan.
Results: …

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md

Biochemistry and Microbiology

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice fed …

Mitochondrial Mass, A New Metabolic Biomarker For Stem-Like Cancer Cells: Understanding Wnt/Fgf-Driven Anabolic Signaling., Rebecca Lamb, Gloria Bonuccelli, Béla Ozsvári, Maria Peiris-Pagès, Marco Fiorillo, Duncan L Smith, Generoso Bevilacqua, Chiara Maria Mazzanti, Liam A Mcdonnell, Antonio Giuseppe Naccarato, Maybo Chiu, Luke Wynne, Ubaldo E Martinez-Outschoorn, Federica Sotgia, Michael P. Lisanti

Kimmel Cancer Center Faculty Papers

Here, we developed an isogenic cell model of "stemness" to facilitate protein biomarker discovery in breast cancer. For this purpose, we used knowledge gained previously from the study of the mouse mammary tumor virus (MMTV). MMTV initiates mammary tumorigenesis in mice by promoter insertion adjacent to two main integration sites, namely Int-1 (Wnt1) and Int-2 (Fgf3), which ultimately activates Wnt/β-catenin signaling, driving the propagation of mammary cancer stem cells (CSCs). Thus, to develop a humanized model of MMTV signaling, we over-expressed WNT1 and FGF3 in MCF7 cells, an ER(+) human breast cancer cell line. We then validated that MCF7 cells …

Plant-Derived Sac Domain Of Par-4 (Prostate Apoptosis Response 4) Exhibits Growth Inhibitory Effects In Prostate Cancer Cells, Shayan Sarkar, Sumeet Jain, Vineeta Rai, Dipak K. Sahoo, Sumita Raha, Sujit Suklabaidya, Shantibhusan Senapati, Vivek M. Rangnekar, Indu B. Maiti, Nrisingha Dey

Radiation Medicine Faculty Publications

The gene Par-4 (Prostate Apoptosis Response 4) was originally identified in prostate cancer cells undergoing apoptosis and its product Par-4 showed cancer specific pro-apoptotic activity. Particularly, the SAC domain of Par-4 (SAC-Par-4) selectively kills cancer cells leaving normal cells unaffected. The therapeutic significance of bioactive SAC-Par-4 is enormous in cancer biology; however, its large scale production is still a matter of concern. Here we report the production of SAC-Par-4-GFP fusion protein coupled to translational enhancer sequence (5′ AMV) and apoplast signal peptide (aTP) in transgenic Nicotiana tabacum cv. Samsun NN plants under the control of a unique recombinant promoter M24. …

Real-Time Detection Of Breast Cancer Cells Using Peptidefunctionalized Microcantilever Arrays, Hashem Etayash, Keren Jiang, Sarfuddin Azmi, Thomas Thundat, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Ligand-directed targeting and capturing of cancer cells is a new approach for detecting circulating tumor cells (CTCs). Ligands such as antibodies have been successfully used for capturing cancer cells and an antibody based system (CellSearch®) is currently used clinically to enumerate CTCs. Here we report the use of a peptide moiety in conjunction with a microcantilever array system to selectively detect CTCs resulting from cancer, specifically breast cancer. A sensing microcantilever, functionalized with a breast cancer specific peptide 18-4 (WxEAAYQrFL), showed significant deflection on cancer cell (MCF7 and MDA-MB-231) binding compared to when exposed to noncancerous (MCF10A and HUVEC) cells. …

Standards Of Evidence For Efficacy, Effectiveness, And Scale-Up Research In Prevention Science: Next Generation., Denise C. Gottfredson, Thomas D. Cook, Frances E.M. Gardner, Deborah Gorman-Smith, George W. Howe, Irwin N. Sandler, Kathryn M. Zafft

Psychiatry and Behavioral Sciences Faculty Publications

A decade ago, the Society of Prevention Research (SPR) endorsed a set of standards for evidence related to research on prevention interventions. These standards (Flay et al., Prevention Science 6:151-175, 2005) were intended in part to increase consistency in reviews of prevention research that often generated disparate lists of effective interventions due to the application of different standards for what was considered to be necessary to demonstrate effectiveness. In 2013, SPR's Board of Directors decided that the field has progressed sufficiently to warrant a review and, if necessary, publication of "the next generation" of standards of evidence. The Board convened …

The P53 Tumor Suppressor Protein Protects Against Chemotherapeutic Stress And Apoptosis In Human Medulloblastoma Cells., Sarah Waye, Aisha Naeem, Muhammad Umer Choudhry, Erika Parasido, Lucas Tricoli, Brian R. Rood, +6 Additional Authors

Pediatrics Faculty Publications

Medulloblastoma (MB), a primitive neuroectodermal tumor, is the most common malignant childhood brain tumor and remains incurable in about a third of patients. Currently, survivors carry a significant burden of late treatment effects. The p53 tumor suppressor protein plays a crucial role in influencing cell survival in response to cellular stress and while the p53 pathway is considered a key determinant of anti-tumor responses in many tumors, its role in cell survival in MB is much less well defined. Herein, we report that the experimental drug VMY-1-103 acts through induction of a partial DNA damage-like response as well induction of …

Women With Disabilities: Reproductive Care And Women’S Health, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

Children, adolescents, and women with disabilities experience the same sexual development, pubertal changes, concerns, and desire to reproduce as their typically developing counterparts. However, society has tended to stigmatize women with disabilities as “asexual” and ignore this aspect of their health care. These women are less likely to receive gynecological exams, contraception, and evaluation of sexual dysfunction. Unfortunately, having a disability places women at risk for sexual exploitation and abuse as well as sexually transmitted infections. Therefore, reproductive health care for these women is imperative. A number of barriers to receiving reproductive care exist. However, with proper education and knowledge …

Increased Expression Of Napdh Oxidase 4 In Systemic Sclerosis Dermal Fibroblasts: Regulation By Transforming Growth Factor Β., Sonsoles Piera-Velazquez, Alma Makul, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: Systemic sclerosis (SSc) is characterized by severe and often progressive fibrosis of the skin and multiple internal organs. The mechanisms responsible for these alterations remain obscure, although excessive reactive oxygen species (ROS)-mediated oxidative stress has been implicated. NOX-4 is 1 of 7 isoforms of NADPH oxidase responsible for the generation of ROS. The purpose of this study was to examine NOX-4 expression in skin and cultured dermal fibroblasts from SSc patients and to examine its regulation by transforming growth factor β1 (TGFβ1).

METHODS: NOX-4 was assessed in normal and SSc skin by immunohistologic analysis and in normal and SSc …