Digital Commons Network^™

Head And Neck Manifestations Of Eosinophilic Granulomatosis With Polyangiitis: A Systematic Review., Jared M. Goldfarb, Mindy R. Rabinowitz, Shristi Basnyat, Gurston G. Nyquist, Marc R. Rosen

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVE: To conduct the first and only systematic review of the existing literature on head and neck manifestations of eosinophilic granulomatosis with polyangiitis to guide clinical decision making for the otolaryngologist.

DATA SOURCES: PubMed, Cochrane Library, Scopus, and LILACS.

REVIEW METHODS: A systematic review of the aforementioned sources was conducted per the PRISMA guidelines.

RESULTS: From an initial 574 studies, 28 trials and reports were included, accounting for a total of 1175 patients with eosinophilic granulomatosis with polyangiitis. Among clinical and cohort studies, 48.0% to 96.0% of all included patients presented with head and neck manifestations. In a distinct group …

Constitutively Activated Pi3k Accelerates Tumor Initiation And Modifies Histopathology Of Breast Cancer, M. R. Sheen, J. D. Marotti, M. J. Allegrezza, M. Rutkowski, J. R. Conejo-Garcia, S. Fiering

Dartmouth Scholarship

The gene encoding phosphatidylinositol 3-kinase catalytic subunit α-isoform (PIK3CA, p110α) is frequently activated by mutation in human cancers. Based on detection in some breast cancer precursors, PIK3CA mutations have been proposed to have a role in tumor initiation. To investigate this hypothesis, we generated a novel mouse model with a Cre-recombinase regulated allele of p110α (myristoylated-p110α, myr-p110α) along with p53fl/fl deletion and KrasG12D also regulated by Cre-recombinase. After instillation of adenovirus-expressing Cre-recombinase into mammary ducts, we found that myr-p110α accelerated breast tumor initiation in a copy number-dependent manner. Breast tumors induced by p53fl/fl;KrasG12D with no or one copy of myr-p110α …

P70s6k1 (S6k1)-Mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I Γ Degradation And Cell Invasion, Naser Jafari, Qiaodan Zheng, Liqing Li, Wei Li, Lei Qi, Jianyong Xiao, Tianyan Gao, Cai Huang

Markey Cancer Center Faculty Publications

Phosphatidylinositol 4-phosphate 5-kinase type I γ (PIPKIγ90) ubiquitination and subsequent degradation regulate focal adhesion assembly, cell migration, and invasion. However, it is unknown how upstream signals control PIPKIγ90 ubiquitination or degradation. Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKIγ90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKIγ90 phosphorylation is essential for cell migration and invasion. Moreover, PIPKIγ90 phosphorylation is required for the development of focal adhesions and invadopodia, key machineries for cell migration and invasion. Surprisingly, substitution of Thr-553 and Ser-555 …

A Proteogenomic Approach To Understanding Myc Function In Metastatic Medulloblastoma Tumors., Jerome A Staal, Yanxin Pei, Brian R. Rood

Pediatrics Faculty Publications

Brain tumors are the leading cause of cancer-related deaths in children, and medulloblastoma is the most prevalent malignant childhood/pediatric brain tumor. Providing effective treatment for these cancers, with minimal damage to the still-developing brain, remains one of the greatest challenges faced by clinicians. Understanding the diverse events driving tumor formation, maintenance, progression, and recurrence is necessary for identifying novel targeted therapeutics and improving survival of patients with this disease. Genomic copy number alteration data, together with clinical studies, identifies c-MYC amplification as an important risk factor associated with the most aggressive forms of medulloblastoma with marked metastatic potential. Yet despite …

Spyb, A Small Heme-Binding Protein, Affects The Composition Of The Cell Wall In Streptococcus Pyogenes, Rebecca J. Edgar, Jing Chen, Sashi Kant, Elena Rechkina, Jeffrey S. Rush, Lennart S. Forsberg, Bernhard Jaehrig, Parastoo Azadi, Veronika Tchesnokova, Evgeni V. Sokurenko, Haining Zhu, Konstantin V. Korotkov, Vijay Pancholi, Natalia Korotkova

Molecular and Cellular Biochemistry Faculty Publications

Streptococcus pyogenes (Group A Streptococcus or GAS) is a hemolytic human pathogen associated with a wide variety of infections ranging from minor skin and throat infections to life-threatening invasive diseases. The cell wall of GAS consists of peptidoglycan sacculus decorated with a carbohydrate comprising a polyrhamnose backbone with immunodominant N-acetylglucosamine side-chains. All GAS genomes contain the spyBA operon, which encodes a 35-amino-acid membrane protein SpyB, and a membrane-bound C3-like ADP-ribosyltransferase SpyA. In this study, we addressed the function of SpyB in GAS. Phenotypic analysis of a spyB deletion mutant revealed increased bacterial aggregation, and reduced sensitivity to β-lactams of the …

Identification Of Putative Receptors For The Novel Adipokine Ctrp3 Using Ligand-Receptor Capture Technology, Ying Li, Tammy Ozment, Gary L. Wright, Jonathan M. Peterson

ETSU Faculty Works

C1q TNF Related Protein 3 (CTRP3) is a member of a family of secreted proteins that exert a multitude of biological effects. Our initial work identified CTRP3’s promise as an effective treatment for Nonalcoholic fatty liver disease (NAFLD). Specifically, we demonstrated that mice fed a high fat diet failed to develop NAFLD when treated with CTRP3. The purpose of this current project is to identify putative receptors which mediate the hepatic actions of CTRP3.

Methods

We used Ligand-receptor glycocapture technology with TriCEPS™-based ligand-receptor capture (LRC-TriCEPS; Dualsystems Biotech AG). The LRC-TriCEPS experiment with CTRP3-FLAG protein as ligand and insulin as a …

Inside Pediatrics Wins Emmy Award . . . Again!, Children's Mercy Hospital

Our Story Continues

'The Heart of Children's Mercy' garners hospital's second trophy for programming excellence.

Once again, Inside Pediatrics has been recognized with a prestigious Emmy award for outstanding programming by the National Academy of Television Arts and Sciences. At the awards event Saturday night, the fifth episode (titled “The Heart of Children’s Mercy”) of the show’s second season won for Best Public/Current/Community Affairs Program or Special.

Last year, Season 1 of Inside Pediatrics won an Emmy in the same category.

Sulfatase 2 Facilitates Lymphangiogenesis In Breast Cancer By Regulating Vegf-D., Chenfang Zhu, Xiaoliang Qi, Xin Zhou, Xin Nie, Yan Gu

Surgery Faculty Publications

In our previous studies, sulfatase 2 (Sulf2) was found to upregulate vascular endothelial growth factor-D (VEGF-D) expression in breast cancer. As VEGF-D plays an important role in lymphangiogenesis, we hypothesized that Sulf2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D. To evaluate the functions of Sulf2 on lymphangiogenesis in breast cancer, proliferation, apoptosis, cell cycle, cell mobility and tube-formation of lymphatic endothelial cells (LECs) were measured in vitro. Lymphangiogenesis in nude mouse ears and breast cancer xenografts were examined in vivo. Furthermore, the expression levels of related signaling pathway genes were screened and verified in LECs. We found that Sulf2 …

Fhf2 Gene Deletion Causes Temperature-Sensitive Cardiac Conduction Failure, David S. Park, Akshay Shekhar, Christopher Marra, Xianming Lin, Carolina Vasquez, Sergio Solinas, Kevin Kelley, Gregory Morley, Mitchell Goldfarb, Glenn I. Fishman

Publications and Research

Fever is a highly conserved systemic response to infection dating back over 600 million years. Although conferring a survival benefit, fever can negatively impact the function of excitable tissues, such as the heart, producing cardiac arrhythmias. Here we show that mice lacking fibroblast growth factor homologous factor 2 (FHF2) have normal cardiac rhythm at baseline, but increasing core body temperature by as little as 3 C causes coved-type STelevations and progressive conduction failure that is fully reversible upon return to normothermia. FHF2-deficient cardiomyocytes generate action potentials upon current injection at 25 C but are unexcitable at 40 C. The absence …

Distinct Cell Stress Responses Induced By Atp Restriction In Quiescent Human Fibroblasts., Nirupama Yalamanchili, Andres Kriete, David Alfego, Kelli M Danowski, Csaba Kari, Ulrich Rodeck

Department of Dermatology and Cutaneous Biology Faculty Papers

Quiescence is the prevailing state of many cell types under homeostatic conditions. Yet, surprisingly little is known about how quiescent cells respond to energetic and metabolic challenges. To better understand compensatory responses of quiescent cells to metabolic stress, we established, in human primary dermal fibroblasts, an experimental 'energy restriction' model. Quiescence was achieved by short-term culture in serum-deprived media and ATP supply restricted using a combination of glucose transport inhibitors and mitochondrial uncouplers. In aggregate, these measures led to markedly reduced intracellular ATP levels while not compromising cell viability over the observation period of 48 h. Analysis of the transcription …

A Survey Of Physician Receptivity To Molecular Diagnostic Testing And Readiness To Act On Results For Early-Stage Colon Cancer Patients., Ronald E. Myers, Thomas Wolf, Phillip Shwae, Sarah E. Hegarty, Stephen C. Peiper, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: We sought to assess physician interest in molecular prognosic testing for patients with early stage colon cancer, and identify factors associated with the likelihood of test adoption.

METHODS: We identified physicians who care for patients with early-stage (pN0) colon cancer patients, mailed them a survey, and analyzed survey responses to assess clinician receptivity to the use of a new molecular test (GUCY2C) that identifies patients at risk for recurrence, and clinician readiness to act on abnormal test results.

RESULTS: Of 104 eligible potential respondents, 41 completed and returned the survey. Among responding physicians, 56 % were receptive to using …

Epigenetics Of Lipid Phenotypes, Sergi Sayols-Baixeras, Marguerite R. Irvin, Donna K. Arnett, Roberto Elosua, Stella W. Aslibekyan

Epidemiology and Environmental Health Faculty Publications

Dyslipidemia is a well-established risk factor for cardiovascular disease, the main cause of death worldwide. Blood lipid profiles are patterned by both genetic and environmental factors. In recent years, epigenetics has emerged as a paradigm that unifies these influences. In this review, we have summarized the latest evidence implicating epigenetic mechanisms—DNA methylation, histone modification, and regulation by RNAs—in lipid homeostasis. Key findings have emerged in a number of novel epigenetic loci located in biologically plausible genes (eg, CPT1A, ABCG1, SREBF1, and others), as well as microRNA-33a/b. Evidence from animal and cell culture models suggests a complex interplay …

Lessons Learnt From The Cerca Project, A Multicomponent Intervention To Promote Adolescent Sexual And Reproductive Health In Three Latin America Countries: A Qualitative Post-Hoc Evaluation., Olena Ivanova, Kathya Cordova Pozo, Zoyla Esmeralda Segura, Bernardo Vega, Venkatraman Chandra-Mouli, Michelle J. Hindin, Marleen Temmerman, Peter Decat, Sara De Meyer, Kristien Michielsen

Obstetrics and Gynaecology, East Africa

The Community-Embedded Reproductive Health Care for Adolescents (CERCA) Project was implemented in Bolivia, Ecuador and Nicaragua (2011–2014) to test the effectiveness of interventions preventing teenage pregnancies. As the outcome evaluation showed limited impact, a post-hoc process evaluation was carried out to determine if and how CERCA’s design, implementation, monitoring and evaluation affected the results. We did a document analysis and conducted 18 in-depth interviews and 21 focus group discussions with stakeholders and beneficiaries. Transcripts were analyzed using directed content analysis.

Data showed that CERCA sensitized stakeholders and encouraged the discussion on this sensitive issue. In terms of design, a strong …

Practice Characteristics Of Emergency Department Extracorporeal Cardiopulmonary Resuscitation (Ecpr) Programs In The United States: The Current State Of The Art Of Emergency Department Extracorporeal Membrane Oxygenation (Ed Ecmo)., Joseph E. Tonna, Nicholas J. Johnson, John Greenwood, David F. Gaieski, Zachary Shinar, Joseph M. Bellezo, Lance Becker, Atman P. Shah, Scott T. Youngquist, Michael P. Mallin, James Franklin Fair, Kyle J. Gunnerson, Cindy Weng, Stephen Mckellar

Department of Emergency Medicine Faculty Papers

PURPOSE: To characterize the current scope and practices of centers performing extracorporeal cardiopulmonary resuscitation (eCPR) on the undifferentiated patient with cardiac arrest in the emergency department.

METHODS: We contacted all US centers in January 2016 that had submitted adult eCPR cases to the Extracorporeal Life Support Organization (ELSO) registry and surveyed them, querying for programs that had performed eCPR in the Emergency Department (ED ECMO). Our objective was to characterize the following domains of ED ECMO practice: program characteristics, patient selection, devices and techniques, and personnel.

RESULTS: Among 99 centers queried, 70 responded. Among these, 36 centers performed ED ECMO. …

Development Of Holographic Sensors For Monitoring Relative Humidity And Temperature, Tatsiana Mikulchyk

Doctoral

Photonic structures capable of responding to an analyte with an easily identifiable change in their optical properties have generated wide interest due to their possible application as holographic sensors. Holographic sensors are considered a low-cost, lightweight and disposable technology, and have potential for application in different areas ranging from medical diagnostics to environmental sensing including the monitoring of environmental temperature and relative humidity. In spite of the existing wide range of temperature and humidity sensors, holographic sensors are of special interest as they can provide fast, real-time, reversible or irreversible, visual colorimetric or electronic readouts. The main objective of this …

Emergency Medical Services And Public Policy In Durban, Kwazulu-Natal, John Buyske

Independent Study Project (ISP) Collection

This project seeks to explore the realities of the emergency medical system in the Durban area, particularly relative to government policy. It contextualizes its findings within the literature on public policy. Data for the project was collected via nine in-depth interviews with various professionals working in the field of emergency medical services, as well as a survey of fourteen citizens conducted in the peri-urban township of Cato Manor. This data was analyzed using qualitative methods. While every participant had different views and a different perspective on emergency services, some recurring themes and trends became evident, allowing for conclusions to be …

Access Is Not Enough: Family Planning In Dar Es Salaam, Claire Burrus

Independent Study Project (ISP) Collection

Population growth is a large problem, both globally and at local levels. The global population is growing at an unsustainable rate, particularly in developing nations. Tanzania, as a developing nation, is one of the fastest growing countries in the world, and as a result, faces many hardships related to high population. The Tanzanian government, non-governmental organizations, and private institutions have made attempts to address these concerns by encouraging family planning. Even so, the national population continues to rise. Many social and cultural factors have contributed to this phenomenon. This study was performed in the Women’s Clinic at Sanitas Hospital in …

Frequency Of Sensorineural Hearing Loss In Chronic Suppurative Otitis Media, Syed Sajjad Ali Zaidi, Hamdan Ahmed Pasha,, Anwar Suhail,, Talha Ahmed Qureshi

Department of Surgery Docs

Abstract Chronic suppurative otitis media (CSOM) is defined as chronic otorrhea (i.e., lasting > 6-12 weeks) through a perforated tympanic membrane. It is generally associated with some degree of conductive hearing loss. However, recurrent ear infections due to perforated eardrum result in absorption of toxins and macromolecules into the cochlea leading to sensorineural hearing loss (SNHL). We planned to determine the frequency of sensorineural hearing loss in chronic suppurative otitis media. A descriptive cross-sectional study was conducted at Aga Kgan University Hospital, Karachi, from October 2013 to March 2014. Average threshold of speech frequencies was calculated via pure tone audiogram for …

Nutritional Status And Physical Abuse Among The Children Involved In Domestic Labour In Karachi Pakistan: A Cross-Sectional Survey., Saima Zainab, Muhammad Masood Kadir

Community Health Sciences

OBJECTIVE:

To determine the prevalence of physical abuse among domestic child labours and to assess the nutritional status by calculating the Body Mass Index of children involved in domestic labour in Karachi.

METHODS:

A cross sectional study was conducted in the squatter settlements of Karachi. Questionnaire based interviews were conducted to capture physical abuse with 385 children who worked as domestic labour in the household of their employer. The ages of the children were between 10 to 14 years belonging to both genders. The children were enrolled in study by snow-ball sampling technique.

RESULTS:

The overall prevalence of physical abuse …

Frequency And Predictors Of Recurrence Of Bladder Tumour On First Check Cystoscopy - A Tertiary Care Hospital Experience, Muhammad Farhan, Nazim Syed Muhammad, Jibran Ahmed, Hammad Ather

Department of Surgery Docs

Abstract

OBJECTIVE:

To determine the frequency and predictors of non-muscle invasive bladder tumour recurrence on first-check cystoscopy after transurethral resection of bladder tumour.

METHODS:

This cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from April to November 2014, and comprised patients with a suspected newly-diagnosed urothelial cancer. Patients with non-muscle invasive disease with complete resection of all visible lesions along with deep biopsy from the tumour base were included. Patients received standard adjuvant intravesical therapy according to their risk stratification and underwent a white-light check cystoscopy at 3 months to look for tumour recurrence. Association between clinico-pathological …

Recent Strategies To Improve Community Case Management Of Diarrhea Among Children Under Five In Developing Countries, Fauziah Rabbani, Aysha Zahidie

Community Health Sciences

No abstract provided.

The Role Of Hydration And N-Acetyl Cysteine Combination In 48hours Contrast-Induced Nephropaty After Percutaneous Coronaryintervention In Stage Three Chronic Kidney Disease Patients, Lydia D. Simatupang, Endang Susalit, Ika Prasetya Wijaya

Jurnal Penyakit Dalam Indonesia

Introduction. Contrast Induced Nephropathy (CIN) after percutaneous coronary intervention (PCI) is common in stage 3 chronic kidney disease (CKD) patients. While there is no cure for CIN and some cases are fatal for the kidney or even life, it is preventable. Eventhough controversial, hydration and N-Acetyl Cysteine (NAC) are modalities to prevent CIN. Not having a certain guideline to prevent CIN in Integrated Cardiac Services (ICS) Cipto Mangunkusumo Hospital for PCI patients generates interest to study it. Methods. A prospective cohort is conducted to evaluate plasma creatinine before and 48 hours after PCI, meanwhile recording whom is given combined hydration …

The Difference Of C-Reactive Protein Levels In Acute Fever Causedby Dengue And Typhoid Infections, Adeputri Tanesha Idhayu, Lie Khie Chen, Suhendro Suhendro

Jurnal Penyakit Dalam Indonesia

Introduction. Dengue infection and typhoid fever are endemic disease in Indonesia. But in the early days of onset sometimes it is difficult to distinguish them. A simple modality test is needed to support the diagnosis. C-Reactive Protein (CRP) is an affordable, fast and relatively less expensive diagnostic tool to diagnose the causes of acute fever. This study was aimed to determine the differences of CRP level in the acute febrile caused by dengue infection or typhoid fever. Methods. A cross sectional study has been conducted among acute febrile patients with diagnosis of dengue fever/ dengue hemorrhagic fever or typhoid fever …

Glycemic Variability Predicts Inflammation In Adolescents With Type 1 Diabetes, Robert P. Hoffman, Amanda S. Dye, Hong Huang, John A. Bauer

Pediatrics Faculty Publications

Background: Adolescents with type 1 diabetes (T1D) have increased risk of cardiovascular disease as well as elevations in biomarkers of systemic inflammation, plasma protein oxidation and vascular endothelial injury. It is unclear whether hyperglycemia itself, or variations in blood glucose are predictors of these abnormalities.

Methods: This study was designed to determine the relationship of inflammatory (C-reactive protein, CRP), oxidative (total anti-oxidative capacity, TAOC) and endothelial injury (soluble intracellular adhesion molecule 1, sICAM1) markers to glycemic control measures from 3 days of continuous glucose monitoring (CGM) and to hemoglobin A_1c (HbA_1c), and HbA_1c×duration area under …

Extracellular Vesicle-Associated Aβ Mediates Trans-Neuronal Bioenergetic And Ca2+-Handling Deficits In Alzheimer's Disease Models, Erez Eitan, Emmette R. Hutchison, Krisztina Marosi, James Comotto, Maja Mustapic, Saket M. Nigam, Caitlin Suire, Chinmoyee Maharana, Gregory A. Jicha, Dong Liu, Vasiliki Machairaki, Kenneth W. Witwer, Dimitrios Kapogiannis, Mark P. Mattson

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which aggregation-prone neurotoxic amyloid β-peptide (Aβ) accumulates in the brain. Extracellular vesicles (EVs), including exosomes, are small 50–150 nm membrane vesicles that have recently been implicated in the prion-like spread of self-aggregating proteins. Here we report that EVs isolated from AD patient cerebrospinal fluid and plasma, from the plasma of two AD mouse models, and from the medium of neural cells expressing familial AD presenilin 1 mutations, destabilize neuronal Ca²⁺ homeostasis, impair mitochondrial function, and sensitize neurons to excitotoxicity. EVs contain a relatively low amount of Aβ but have an …

Impact Of Hur Inhibition By The Small Molecule Ms-444 On Colorectal Cancer Cell Tumorigenesis., Fernando F. Blanco, Ranjan Preet, Andrea Aguado, Vikalp Vishwakarma, Laura E. Stevens, Alok Vyas, Subhash Padhye, Liang Xu, Scott J. Weir, Shrikant Anant, Nicole Meisner-Kober, Jonathan R. Brody, Dan A. Dixon

Department of Surgery Faculty Papers

Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related mortality. Observed during CRC tumorigenesis is loss of post-transcriptional regulation of tumor-promoting genes such as COX-2, TNFα and VEGF. Overexpression of the RNA-binding protein HuR (ELAVL1) occurs during colon tumorigenesis and is abnormally present within the cytoplasm, where it post-transcriptionally regulates genes through its interaction with 3'UTR AU-rich elements (AREs). Here, we examine the therapeutic potential of targeting HuR using MS-444, a small molecule HuR inhibitor. Treatment of CRC cells with MS-444 resulted in growth inhibition and increased apoptotic gene expression, while similar treatment doses …

Cellular And Morphological Alterations In The Vastus Lateralis Muscle As The Result Of Acl Injury And Reconstruction, Brian W. Noehren, Anders H. Andersen, Peter A. Hardy, Darren L. Johnson, Mary Lloyd Ireland, Katherine L. Thompson, Bruce Damon

Physical Therapy Faculty Publications

Background: Individuals who have had an anterior cruciate ligament (ACL) tear and reconstruction continue to experience substantial knee extensor strength loss despite months of physical therapy. Identification of the alterations in muscle morphology and cellular composition are needed to understand potential mechanisms of muscle strength loss, initially as the result of the injury and subsequently from surgery and rehabilitation.

Methods: We performed diffusion tensor imaging-magnetic resonance imaging and analyzed muscle biopsies from the vastus lateralis of both the affected and unaffected limbs before surgery and again from the reconstructed limb following the completion of rehabilitation. Immunohistochemistry was done to determine …

Molecular Characterization Of Staphylococcus Aureus Isolates From Various Healthcare Institutions In Nairobi, Kenya: A Cross Sectional Study, Geoffrey Omuse, Kristien Nel Van Zyl, Kim Hoek, Shima Abdulgader, Samuel Kariuki, Andrew Whitelaw, Gunturu Revathi

Pathology, East Africa

Background: Staphylococcus aureus (S. aureus) has established itself over the years as a major cause of morbidity and mortality both within the community and in healthcare settings. Methicillin resistant S. aureus (MRSA) in particular has been a major cause of nosocomial infections resulting in significant increase in healthcare costs. In Africa, the MRSA prevalence has been shown to vary across different countries. In order to better understand the epidemiology of MRSA in a setting, it is important to define its population structure using molecular tools as different clones have been found to predominate in certain geographical locations.

Methods: We carried …

Aging-Associated Changes In Microrna Expression Profile Of Internal Anal Sphincter Smooth Muscle: Role Of Microrna-133a., Jagmohan Singh, Boopathi Ettickan, Sankar Addya, Benjamin Philllips, Isidore Rigoutsos, Raymond B. Penn, Phd, Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

A comprehensive -omic, computational, and physiological approach was employed to examine the (previously unexplored) role of microRNAs (miRNAs) as regulators of IAS smooth muscle contractile phenotype and basal tone. MicroRNA profiling, genome wide expression, validation and network analyses were employed to assess changes in mRNA and miRNA expression in IAS smooth muscles from young vs. aging rats. Multiple miRNAs, including rno-miR-1, rno-miR-340-5p, rno-miR-185, rno-miR-199a-3p, rno-miR-200c, rno-miR-200b, rno-miR-31, rno-miR-133a and rno-miR-206 were found to be up-regulated in aging IAS. qRT-PCR confirmed the up-regulated expression of these miRNAs and down regulation of multiple, predicted targets (Eln, Col3a1, Col1a1, Zeb2, Myocd, SRF, Smad1, …

A Microrna/Runx1/Runx2 Network Regulates Prostate Tumor Progression From Onset To Adenocarcinoma In Tramp Mice., Nicholas H Farina, Areg Zingiryan, Jacqueline A Akech, Cody J Callahan, Huimin Lu, Janet L Stein, Lucia R Languino, Gary S Stein, Jane B Lian

Department of Cancer Biology Faculty Papers

While decades of research have identified molecular pathways inducing and promoting stages of prostate cancer malignancy, studies addressing dynamic changes of cancer-related regulatory factors in a prostate tumor progression model are limited. Using the TRAMP mouse model of human prostate cancer, we address mechanisms of deregulation for the cancer-associated transcription factors, Runx1 and Runx2 by identifying microRNAs with reciprocal expression changes at six time points during 33 weeks of tumorigenesis. We molecularly define transition stages from PIN lesions to hyperplasia/neoplasia and progression to adenocarcinoma by temporal changes in expression of human prostate cancer markers, including the androgen receptor and tumor …