Digital Commons Network^™

Signaling Mechanisms Of Vav3, A Guanine Nucleotide Exchange Factor And Androgen Receptor Coactivator, In Physiology And Prostate Cancer Progression, Leah S. Lyons, Kerry L. Burnstein

Faculty Books and Book Chapters

The Rho GTPase guanine nucleotide exchange factor (GEF) Vav3 is the third member of the Vavfamily of GEFS and is activated by tyrosine phosphorylation. Through stimulation of Rho GTPaseactivity, Vav3 promotes cell migration, invasion, and other cellular processes. Work from our laboratory first established that Vav3 is upregulated in models of castration-resistant prostate cancer progression and enhances androgen receptor as well as androgen receptor splice variant activity. Recent analysis of clinical specimens supports Vav3 as a potential biomarker of aggressive prostate cancer. Consistent with a role in promoting castration-­resistant disease, Vav3 is a versatile enhancer of androgen receptor …

Physical Mistreatment In Persons With Alzheimer’S Disease, Gregory Paveza, Carla Vandeweerd, Margaret Walsh, Jaime Corvin

Library Scholarship

Physical mistreatment has been estimated to affect 2 million older persons each year and dramatically affects health outcomes. While researchers have attempted to examine risk factors for specific forms of abuse, many have been able to focus on only victim or perpetrator characteristics, or a limited number of psychosocial variables at any one time. Additionally, data on risk factors for subgroups such as persons with Alzheimer’s disease who may have heightened and/or unique risk profiles has also been limited. This paper examines risk for physical violence in caregiver/patient dyads who participated in the Aggression and Violence in Community-Based Alzheimer’s Families …

Metabolic Causes Of Epileptic Encephalopathy, Joe Yuezhou Yu, Phillip L. Pearl

Neurology Faculty Publications

Epileptic encephalopathy can be induced by inborn metabolic defects that may be rare individually but in aggregate represent a substantial clinical portion of child neurology. These may present with various epilepsy phenotypes including refractory neonatal seizures, early myoclonic encephalopathy, early infantile epileptic encephalopathy, infantile spasms, and generalized epilepsies which in particular include myoclonic seizures. There are varying degrees of treatability, but the outcome if untreated can often be catastrophic. The importance of early recognition cannot be overemphasized. This paper provides an overview of inborn metabolic errors associated with persistent brain disturbances due to highly active clinical or electrographic ictal activity. …

Stereotactic Body Radiotherapy For Localized Prostate Cancer: Disease Control And Quality Of Life At 6 Years, A. J. Katz, M. Santoro, F. Diblasio, R. Ashley

Journal Articles

Background: Stereotactic body radiotherapy (SBRT) may yield disease control for prostate cancer in a brief, hypofractionated treatment regimen without increasing treatment toxicity. Our report presents a 6-year update from 304 low- (n = 211), intermediate- (n = 81), and high-risk (n = 12) prostate cancer patients who received CyberKnife SBRT. Methods: The median PSA at presentation was 5.8 ng/ml. Fifty-seven patients received neoadjuvant hormonal therapy for up to one year. The first 50 patients received a total dose of 35 Gy in 5 fractions of 7 Gy. The subsequent 254 patients received a total dose of 36.25 Gy in 5 …

Stereotactic Localization And Targeting Accuracy For Experimental Proton Radiosurgery, Yin Chen

Theses Digitization Project

The purpose of this study was to improve an existing experimental proton radiosurgery system at Loma Linda University Medical Center to reach sub-millimeter accuracy before proton radiosurgery with narrow beams can be used in a clinical trial. Protons, different from photons (i.e., x-rays or gamma rays), are charged with particles that slow down in matter and release a burst of energy near the end of their range (maximum depth of penetration), which is called the Bragg peak, named after the physicist William Henry Bragg who discovered it in 1903. Photon beams deliver most doses over a large area near the …

An Update On Braf Inhibitors And Other New Molecular Targets For The Treatment Of Malignant Melanoma Of The Skin, M. O. Faruk Khan, Carroll L. Ramos

Pharmaceutical Science and Research

Malignant melanoma of the skin originates from mutations in melanocytes and can be lethal if unrecognized or untreated in its earlier stages. Deaths from melanoma are increasing in the United States and around the world every year. The available treatments produce low rates of response with modest survival impact. Among potential molecular targets under investigation, which are mostly in the tyrosine kinase pathway, the BRAF (V-raf murine sarcoma viral oncogene homolog B1) gene is the best studied and most frequently reported mutation in melanoma. The molecular targets for melanoma treatment, promising drugs for future melanoma treatment as well as the …

Effect Of Budesonide On Fibroblast-Mediated Collagen Gel Contraction And Degradation, Qiuhong Fang, Nancy A. Schulte, Huijung Kim, Tetsu Kobayashi, Xingqi Wang, Anna Miller-Larsson, Elisabet Wieslander, Myron L. Toews, Xiangde Liu, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: The balance between production and degradation of extracellular matrix is crucial in maintaining normal tissue structure. This study was designed to investigate the effect of budesonide on fibroblast-mediated tissue repair and remodeling.

METHODS: Using human fetal lung fibroblasts in a three-dimensional collagen gel culture system, we investigated the effect of budesonide (1-1000 nM) on collagen gel contraction and degradation in the presence or absence of Inflammatory cytokines (interleukin-1β and tumor necrosis factor α; 5 ng/mL each) and, in order to activate latent proteases, serine protease trypsin 0.25 μg/mL. The effects of budesonide on metalloproteinase production and activation were also …

Hydraphiles: A Rigorously Studied Class Of Synthetic Channel Compounds With In Vivo Activity, Saeedeh Negin, Bryan Smith, Alexandra Unger, W. Leevy, George Gokel

Chemistry & Biochemistry Faculty Works

No abstract provided.

On An Ensemble Algorithm For Clustering Cancer Patient Data, Ran Qi, Dengyuan Wu, Li Sheng, Donald E. Henson, Arnold M. Schwartz, Eric Xu, Kai Xing, Dechang Chen

Pathology Faculty Publications

Background

The TNM staging system is based on three anatomic prognostic factors: Tumor, Lymph Node and Metastasis. However, cancer is no longer considered an anatomic disease. Therefore, the TNM should be expanded to accommodate new prognostic factors in order to increase the accuracy of estimating cancer patient outcome. The ensemble algorithm for clustering cancer data (EACCD) by Chen et al. reflects an effort to expand the TNM without changing its basic definitions. Though results on using EACCD have been reported, there has been no study on the analysis of the algorithm. In this report, we examine various aspects of …

Graduate Medical Education 2012-2013 Annual Report, Children's Mercy Hospital

GME Annual Reports

Annual report of the Children's Mercy Hospital Graduate Medical Education department, including pediatric residency, internal medicine/pediatrics residency, fellowship programs, medical students, continuing medical education, and library services.

Pge 2 Desensitizes Β -Agonist Effect On Human Lung Fibroblast-Mediated Collagen Gel Contraction Through Opregulating Pde4, Qiuhong Fang, Yingmin Ma, Jing Wang, Joel Michalski, Stephen I. Rennard, Xiangde Liu

Journal Articles: Pulmonary & Critical Care Med

In the current study, we investigated the effect of a long-acting β -agonist (salmeterol) and a phosphodiesterase 4 (PDE4) inhibitor (cilomilast) on human lung fibroblast-mediated collagen gel contraction. Higher concentrations of salmeterol (10(-7) and 10(-6) M) inhibited fibroblast-mediated collagen gel contraction. No effect was observed with cilomilast alone (up to 10(-5) M). In the presence of 10(-8) M salmeterol, however, cilomilast could significantly inhibit fibroblast-mediated collagen gel contraction in a concentration-dependent manner (10(-7) ~10(-5) M). Blockade of endogenous PGE2 by indomethacin further potentiated the inhibitory effect of salmeterol on fibroblast-mediated collagen gel contraction, but it did not affect cilomilast's effect. …

Com Outlook Winter 2013, College Of Osteopathic Medicine

COM Outlook

No abstract provided.

Gender Differences In The Development Of Uremic Cardiomyopathy Following Partial Nephrectomy: Role Of Progesterone, Christopher A. Drummond, George Buddny, Steven T. Haller, Jiang Liu, Yanling Yan, Zijian Xie, Deepak Malhotra, Joseph I. Shapiro Md, Jiang Tian

Biochemistry and Microbiology

Gender difference has been suggested as a risk factor for developing cardiovascular and renal diseases in humans and experimental animals. As a major sex hormone, progesterone was reported to compete with cardiotonic steroid binding to Na/K-ATPase. Our previous publication demonstrated that cardiotonic steroids (e.g., marinobufagenin) play an important role in the development of experimental uremic cardiomyopathy. We also observed that the putative mineralocorticoid antagonists, spironolactone and its major metabolite canrenone, antagonize binding of cardiotonic steroids to Na/K-ATPase in a competitive manner and also ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy. In the following studies, we noted that progesterone displayed …

Diet And Nutrition In Cancer Survivorship And Palliative Care., Anthony J Bazzan, Andrew B Newberg, William C Cho, Daniel A Monti

Marcus Institute of Integrative Health Faculty Papers

The primary goal of palliative cancer care is typically to relieve suffering and improve quality of life. Most approaches to diet in this setting have focused only on eating as many calories as possible to avoid cachexia. However, as the concept of palliative care has evolved to include all aspects of cancer survivorship and not just end of life care, there is an increasing need to thoughtfully consider diet and nutrition approaches that can impact not only quality of life but overall health outcomes and perhaps even positively affect cancer recurrence and progression. In this regard, there has been a …

Linking Environmental Toxicant Exposure To Diabetes Susceptibility, Jannifer Beth Tyrrell

Wayne State University Dissertations

An important and unresolved question in the environmental health field is whether exposure to common environmental toxicants, such as dioxin and heavy metals like Pb, increase the risk of developing diabetes, especially in combination with other common metabolic stressors such as obesity.

Previous studies suggested that dioxin exposure increased peripheral insulin resistance but did not appear to cause fasting hyperglycemia or elevated hepatic glucose output. In concordance with those findings we observed that dioxin treatment caused a strong suppression of the expression of the key hepatic gluconeogenic genes PEPCK and G6Pase. However, this suppression was not solely mediated by the …

Children's Mercy Hospital Annual Report 2012, Children's Mercy Hospital

Children's Mercy Annual Reports

Annual report for The Children's Mercy Hospital in Kansas City MO, a pediatric medical center.

Bone-Targeted Therapies In Metastatic Castration-Resistant Prostate Cancer: Evolving Paradigms, Joelle El-Amm, Ashley Freeman, Nihar Patel, Jeanny B. Aragon-Ching

Medicine Faculty Publications

Majority of patients with metastatic castrate resistant prostate cancer (mCRPC) develop bone metastases which results in significant morbidity and mortality as a result of skeletal-related events (SREs). Several bone-targeted agents are either in clinical use or in development for prevention of SREs. Bisphosphonates were the first class of drugs investigated for prevention of SREs and zoledronic acid is the only bisphosphonate that is FDA-approved for this indication. Another bone-targeted agent is denosumab which is a fully humanized monoclonal antibody that binds to the RANK-L thereby inhibiting RANK-L mediated bone resorption. While several radiopharmaceuticals were approved for pain palliation in mCRPC …

Biclonal Gammopathy In A Patient Taking Efalizumab For The Treatment Of Psoriasis, Antonia Fthenakis, Kurt S. Wenk, Alison Ehrlich, Jeanny B. Aragon-Ching

Dermatology Faculty Publications

We report a patient who developed biclonal gammopathy of undetermined significance during treatment with
efalizumab for psoriasis. This plasma cell disorder was found during the evaluation of the patient’s complaint of mild lower extremity paresthesia. The gammopathy spontaneously remitted following cessation of therapy and has not recurred to date. Given the increasing use and development of biological agents for the treatment of psoriasis and other disorders, this finding and the mechanisms by which it may have occurred is of clinical significance.

Middle Ear Myoclonus: Two Informative Cases And A Systematic Discussion Of Myogenic Tinnitus, Aviva Ellenstein, Nadia Yusuf, Mark Hallett

Neurology Faculty Publications

Background: The term middle ear myoclonus (MEM) has been invoked to explain symptoms of tinnitus presumably caused by the dysfunctional movement of either of the two muscles that insert in the middle ear: tensor tympani and stapedius. MEM has been characterized through heterogeneous case reports in the otolaryngology literature, where clinical presentation is variable, phenomenology is scarcely described, the pathogenic muscle is usually not specified, natural history is unknown, and the presumptive definitive treatment, tensor tympani or stapedius tendon lysis, is inconsistently effective. It is not surprising that no unique acoustogenic mechanism or pathophysiologic process has been identified to explain …

Alloreactivity-Based Medical Conditions, Stanislav Vukmanovic, Margaret G. Petroff, Anne M. Stevens, Daniel Rukavina

Pediatrics Faculty Publications

No abstract provided.

Microenvironment Generated During Egfr Targeted Killing Of Pancreatic Tumor Cells By Atc Inhibits Myeloid-Derived Suppressor Cells Through Cox2 And Pge2 Dependent Pathway, Archana Thakur, Dana Schalk, Elyse Tomaszewski, Sri Kondadasula, Hiroshi Yano, Fazlul H. Sarkar, Lawrence G. Lum

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Myeloid-derived suppressor cells (MDSCs) are one of the major components of the immune-suppressive network, play key roles in tumor progression and limit therapeutic responses. Recently, we reported that tumor spheres formed by breast cancer cell lines were visibly smaller in a Th₁ enriched microenvironment with significantly reduced differentiation of MDSC populations in 3D culture. In this study, we investigated the mechanism(s) of bispecific antibody armed ATC mediated inhibition of MDSC in the presence or absence of Th₁ microenvironment.

Methods

We used 3D co-culture model of peripheral blood mononuclear cells (PBMC) with pancreatic cancer cells MiaPaCa-2 [MiaE] …

Inhibition Of Hedgehog Signaling Sensitizes Nsclc Cells To Standard Therapies Through Modulation Of Emt-Regulating Mirnas, Aamir Ahmad, Ma'in Y. Maitah, Kevin R. Ginnebaugh, Yiwei Li, Bin Bao, Shirish M. Gadgeel, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Epidermal growth factor receptor- tyrosine kinase inhibitors (EGFR-TKIs) benefit Non-small cell lung cancer (NSCLC) patients, and an EGFR-TKIi erlotinib, is approved for patients with recurrent NSCLC. However, resistance to erlotinib is a major clinical problem. Earlier we have demonstrated the role of Hedgehog (Hh) signaling in Epithelial-to-Mesenchymal transition (EMT) of NSCLC cells, leading to increased proliferation and invasion. Here, we investigated the role of Hh signaling in erlotinib resistance of TGF-β1-induced NSCLC cells that are reminiscent of EMT cells.

Methods

Hh signaling was inhibited by specific siRNA and by GDC-0449, a small molecule antagonist of G protein coupled …

Complex Biological Reconstruction After Wide Excision Of Osteogenic Sarcoma In Lower Extremities, Kashif Abbas, Masood Umer, Haroon Ur Rashid

Section of Orthopaedic Surgery

Wide margin resection of extremity tumor sometimes leaves a huge soft tissue and bony defects in limb salvage surgery. Adequate management of these defects is an absolute requirement when aiming for functional limb. Multidisciplinary management in such cases is an answer when complex biologic reconstruction is desired. We aim to present cases of osteogenic sarcoma of lower extremity requiring combined surgical approach to achieve effective musculoskeletal reconstruction. Patients and Methods. From 2006 to 2010 ten patients were operated on for osteogenic sarcoma of lower extremity requiring complex musculoskeletal reconstruction. Results. Six patients had pathology around knee joint, whereas one each …

Autoclaved Tumor Bone For Skeletal Reconstruction In Paediatric Patients: A Low Cost Alternative In Developing Countries, Masood Umer, Hafiz Muhammad Umer, Irfan Qadir, Haroon Rashid, Rabia Awan, Raza Askari, Shamvil Ashraf

Section of Orthopaedic Surgery

We reviewed in this series forty patients of pediatric age who underwent resection for malignant tumors of musculoskeletal system followed by biological reconstruction. Our surgical procedure for reconstruction included (1) wide en bloc resection of the tumor; (2) curettage of tumor from the resected bone; (3) autoclaving for 8 minutes (4) bone grafting from the fibula (both vascularized and nonvascularized fibular grafts used); (5) reimplantation of the autoclaved bone into the host bone defect and fixation with plates. Functional evaluation was done using MSTS scoring system. At final followup of at least 18 months (mean 29.2 months), 31 patients had …

Risk Of Childhood Asthma In A Tropical African Urban Setting: A Case - Control Study At The Aga Khan Hospital, Dar-Es-Salaam, Tanzania, Lynda C. Koech

Master of Medicine in Family Medicine

Objective: To determine the modifiable and non-modifiable risk factors for childhood asthma in children aged between two and 15years in a tropical urban East-African setting. Methods: Hospital based case-control study matched for age + two months and sex. Data were obtained from parents of cases and controls using a structured interviewer-administered questionnaire. The study sample consisted of 226 cases of two to 15years old, with physician-confirmed asthma, who met a set of defined clinical criteria and 226 controls with no previous diagnosis or symptoms of asthma matched by sex and age (+two months). The Risk Factors included in this study …

Perception Of Final Year Undergraduate Medical Students Towards Family Medicine In Dar Es Salaam, Tanzania, Eric Luggar Aghan

Master of Medicine in Family Medicine

Primary health care was identified as the ideal model of health care delivery during the Alma Atta conference in USSR in 1978. The World Health Organization urged member countries to adopt it as a model of health care service delivery to their people. Since then many countries have adopted a primary health care model including Tanzania. In countries such as Cuba and Costa Rica where primary health care has successfully been implemented, access to affordable and quality health care service to all has resulted in lowered morbidity, mortality, improved quality and longevity of life. The success story behind primary health …

Gut Modulator Effects Of Conyza Bonariensis Explain Its Traditional Use In Constipation And Diarrhea, I A. Bukhari, A J. Shah, R A. Khan, S A. Meo, A Khan, A H. Gilani

Department of Biological & Biomedical Sciences

BACKGROUND AND OBJECTIVES:

The current investigation was carried out to explore the pharmacological basis of the crude extract of Conyza bonariensis (Cb.Cr) for its use in constipation and diarrhea.

MATERIALS AND METHODS:

The plant extract of Conyza bonariensis (C. bonariensis) was prepared, isolated guinea-pig ileum and rabbit jejunum preparations were used to evaluate its gut modulator effects.

RESULTS:

The Cb.Cr (0.3-10 mg/mL) exhibited spasmogenic effect in isolated guinea-pig ileum preparation, which was about 19-84% of the acetylcholine maximum. Pretreatment of the tissues with atropine (0.1 µM) abolished the contractile effect, similar to acetylcholine. Among the fractions, only the butanol fraction …

Systems Analysis Reveals A Transcriptional Reversal Of The Mesenchymal Phenotype Induced By Snail-Inhibitor Gn-25, Asfar S. Azmi, Aliccia Bollig-Fischer, Bin Bao, Bum-Joon Park, Sun-Hye Lee, Gyu Yong-Song, Gregory Dyson, Chandan K. Reddy, Fazlul H. Sarkar, Ramzi M. Mohammad

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

HMLEs (HMLE-SNAIL and Kras-HMLE, Kras-HMLE-SNAIL pairs) serve as excellent model system to interrogate the effect of SNAIL targeted agents that reverse epithelial-to-mesenchymal transition (EMT). We had earlier developed a SNAIL-p53 interaction inhibitor (GN-25) that was shown to suppress SNAIL function. In this report, using systems biology and pathway network analysis, we show that GN-25 could cause reversal of EMT leading to mesenchymal-to-epithelial transition (MET) in a well-recognized HMLE-SNAIL and Kras-HMLE-SNAIL models.

Results

GN-25 induced MET was found to be consistent with growth inhibition, suppression of spheroid forming capacity and induction of apoptosis. Pathway network analysis of mRNA expression …

Astrue V. Capato: Forcing A Shoe That Doesn't Fit, Courtney Hannon

Journal of Health Care Law and Policy

No abstract provided.

Factors Associated Within 28 Days In-Hospital Mortality Of Patients With Acute Respiratory Distress Syndrome, Nadia Sharif, Muhammad Irfan, Javaid Hussain, Javaid Khan

Section of Pulmonary & Critical Care

Objective. To determine the factors leading to in-hospital mortality within 28 days in hospitalized patients with ARDS. It was a prospective observational cohort study conducted in Intensive Care Unit of Aga Khan University Hospital Karachi from March to August 2011. Methodology. Data was collected from patients admitted in the intensive care unit on the basis of inclusion and exclusion criteria. The patients were followed daily for 28 days to record any in-hospital complications and the outcome of patients. Results. Total of 46 patients were included during this period out of which 56% (26) were males and 43% (20) were females. …