Medicine and Health Sciences Commons^™

Feasibility Of Improving Cone Beam Ct Number Consistency With A Scatter-Correction Algorithm, J. Li, W. Yao, Y. Xiao, Y. Yu

Bodine Journal

Purpose: To explore the feasibility of improving Elekta cone beam CT (CBCT) number consistency using a scatter-correction algorithm, with the aim of using CBCT images for treatment planning with heterogeneity correction.

American Association of Physicists in Medicine (AAPM) 52nd Annual Meeting July 18-22, Philadelphia, PA

Acute Neurological Toxicity (Nt) And Long-Term Outcomes In High-Grade Glioma Rtog Trials, Y. R. Lawrence, M. Wang, A. P. Dicker, D. W. Andrews, W. J. Curran, J. M. Michalski, L. Souhami, W. A. Yung, M. Mehta

Bodine Journal

Background: Treatment of high-grade glioma consists of fractionated radiation therapy (RT) ± chemotherapy. The incidence/significance of neurological toxicity (NT) in this disease is not known. We evaluated the relationship between acute and chronic NT, and ultimate outcome, as well as risk factors for NT from the RTOG database.

American Society of Clinical Oncology (ASCO) 46th Annual Meeting June 4-8, Chicago, IL.

Potential For Thermal Enhancement By Quercetin Mediated Mechanisms Targeting P53 Antagonists In Human Melanoma Cells, T. Thangasamy, K. Limesand, D. B. Leeper, R. Burd

Bodine Journal

Introduction: Recently Temozolomide (TMZ) has become the more commonly used analog of DTIC-related oral agents. Although the response rates achieved by TMZ alone are less than satisfactory, there is great interest in identifying compounds that could be used in combination therapy. We have previously demonstrated that the bioflavonoid quercetin (Qct) promotes a p53-mediated response in melanoma and sensitizes melanoma to DTIC. Here we demonstrate that Qct also sensitizes cells to TMZ by a mechanism that involves the modulation of a truncated p53 family member, ΔNp73.

Society for Thermal Medicine Annual Meeting April 23-26, Clearwater Beach, FL.

Control Of Glycolytic Flux By Ampk And P53-Mediated Signaling Pathways In Tumor Cells Adapted To Grow At Low Ph, E. E. Mendoza, J. Caro, D. B. Leeper, R. Burd

Bodine Journal

Introduction: Tumor cells grow in nutrient and oxygen deprived microenvironments and adapt to the suboptimal growth conditions by altering metabolic pathways. This adaptation process characteristically results in a tumor phenotype that displays anaerobic glycolysis, chronic acidification and aggressive tumor characteristics. Understanding the tumor cell reaction to the microenvironment is a critical factor in predicting the tumor response to hyperthermia. The glucose regulatory molecule, 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase Isoform-3 (PFKFB3), is a bifunctional enzyme central to glycolytic flux and downstream of the metabolic stress sensor AMP-activated protein kinase (AMPK), which has been shown to activate an isoform of Phosphofructokinase (PFK-2).

Society for Thermal Medicine …

Functional Antagonism Between Vorinostat And Temozolomide When Combined With Ionizing Radiation (Ir) In Glioblastoma, Y. R. Lawrence, Y. Liu, B. Andersen, X. Xia, A. P. Dicker, P. Wachsberger

Bodine Journal

Background: Glioblastoma is the most common primary adult brain tumor. Surgery followed by radiation therapy in combination with temozolomide (Tmz) produces a median survival of 14.6 months. Tmz is a DNA akylating agent that leads to the mispairing of guanine residues with thymine. An intact mismatch-repair mechanism (MMR) converts the mispaired thymine into a lethal double-strand DNA break. Vorinostat (SAHA), an HDAC inhibitor, has been shown to act as a radiosensitizer, possibly through inhibition of DNA repair. SAHA has successfully been combined with a number of cytotoxic agents. We hypothesized that SAHA would further potentiate the radiosensitizing properties of Tmz …

Effects Of Egfr Expression On Anti-Tumor Efficacy Of Vandetanib Or Cediranib Combined With Radiotherapy (Rt) In U87 Human Glioblastoma (Gbm) Xenografts, P. Wachsberger, Y. R. Lawrence, Y. Liu, A. P. Dicker

Bodine Journal

Introduction: Vandetanib is a receptor tyrosine kinase inhibitor (RTKI) with activity against vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR). Cediranib is a highly potent VEGF RTKI that inhibits all three VEGF receptors. In this study we investigated the effect of exogenous overexpression of EGFR on sensitivity of human GBM U87 xenografts to vandetanib or cediranib, alone or in combination with RT.

American Association for Cancer Research (AACR) 101st Annual Meeting April 17-21, Washington, DC.

Bodine Journal, Table Of Contents, Volume 3, Issue 1, Fall 2010

Bodine Journal

Table of Contents for Fall 2010 issue of Bodine Journal.

Is The Quality Of Neurosurgical Literature Improving?, James Harrop, Md, Mitchell Maltenfort, Phd

JHN Journal

Introduction:

The advent of evidence-based medicine has resulted in higher quality journal manuscripts in numerous medical disciplines. However, the impact in the neurosurgical literature has not been reported.

Objective:

To quantify the impact of evidence-based medicine on the quality of articles published in the Neurosurgery literature.

Methods:

Articles published in the journal Neurosurgery (founded in 1977) were reviewed for 1978, 1988, 1998, and 2008. Each decade’s sample was classified as therapeutic, diagnostic and prognostic based on a published system for determining level of evidence.

Results:

438 articles were reviewed. Articles not considered included any published under the heading “Case Report” …

Acetate Causes Alcohol Hangover Headache In Rats., Christina R Maxwell, Rebecca Jay Spangenberg, Jan B Hoek, Stephen D Silberstein, Michael L Oshinsky

Department of Neurology Faculty Papers

BACKGROUND: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache.

METHODS: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats.

RESULTS: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate …

Biological Rationale For The Use Of Dna Methyltransferase Inhibitors As New Strategy For Modulation Of Tumor Response To Chemotherapy And Radiation., Giovanni L Gravina, Claudio Festuccia, Francesco Marampon, Vladimir M Popov, Richard G Pestell, Bianca M Zani, Vincenzo Tombolini

Kimmel Cancer Center Faculty Papers

Epigenetic modifications play a key role in the patho-physiology of many tumors and the current use of agents targeting epigenetic changes has become a topic of intense interest in cancer research. DNA methyltransferase (DNMT) inhibitors represent a promising class of epigenetic modulators. Research performed yielded promising anti-tumorigenic activity for these agents in vitro and in vivo against a variety of hematologic and solid tumors. These epigenetic modulators cause cell cycle and growth arrest, differentiation and apoptosis. Rationale for combining these agents with cytotoxic therapy or radiation is straightforward since the use of DNMT inhibitor offers greatly improved access for cytotoxic …

Pp32 (Anp32a) Expression Inhibits Pancreatic Cancer Cell Growth And Induces Gemcitabine Resistance By Disrupting Hur Binding To Mrnas., Timothy K Williams, Christina L Costantino, Nikolai A Bildzukewicz, Nathan G Richards, David W Rittenhouse, Lisa Einstein, Joseph A Cozzitorto, Judith C Keen, Abhijit Dasgupta, Myriam Gorospe, Gregory E Gonye, Charles J Yeo, Agnieszka K Witkiewicz, Jonathan R Brody

Department of Surgery Faculty Papers

The expression of protein phosphatase 32 (PP32, ANP32A) is low in poorly differentiated pancreatic cancers and is linked to the levels of HuR (ELAV1), a predictive marker for gemcitabine response. In pancreatic cancer cells, exogenous overexpression of pp32 inhibited cell growth, supporting its long-recognized role as a tumor suppressor in pancreatic cancer. In chemotherapeutic sensitivity screening assays, cells overexpressing pp32 were selectively resistant to the nucleoside analogs gemcitabine and cytarabine (ARA-C), but were sensitized to 5-fluorouracil; conversely, silencing pp32 in pancreatic cancer cells enhanced gemcitabine sensitivity. The cytoplasmic levels of pp32 increased after cancer cells are treated with certain stressors, …

Ms4a4b, A Cd20 Homologue In T Cells, Inhibits T Cell Propagation By Modulation Of Cell Cycle., Hui Xu, Yaping Yan, Mark S Williams, Gregory B Carey, Jingxian Yang, Hongmei Li, Guang-Xian Zhang, Abdolmohamad Rostami

Department of Neurology Faculty Papers

MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural …

A New Frontier For Headache., Stephen Silberstein

Department of Jefferson Headache Center papers and presentations

No abstract provided.

Those Who Give: The Kristen Olewine Milke Breast Cancer Research Fund

Jefferson Surgical Solutions

No abstract provided.

Dr. Adam Berger Heads New Section Of Surgical Oncology

Jefferson Surgical Solutions

No abstract provided.

Meet Our Surgical Interns

Jefferson Surgical Solutions

No abstract provided.

Vascular Center Offers Leading- Edge, Integrated Care

Jefferson Surgical Solutions

No abstract provided.

Overview: Charles J. Yeo, Md

Jefferson Surgical Solutions

No abstract provided.

About The Surgeon

Jefferson Surgical Solutions

No abstract provided.

What Makes A Surgeon Of Choice: Dr. John Maxwell

Jefferson Surgical Solutions

No abstract provided.

Differential Regulation Of P53 Function By The N-Terminal Δnp53 And Δ113p53 Isoforms In Zebrafish Embryos., William R Davidson, Csaba Kari, Qing Ren, Borbala Daroczi, Adam P Dicker, Ulrich Rodeck

Department of Radiation Oncology Faculty Papers

BACKGROUND: The p53 protein family coordinates stress responses of cells and organisms. Alternative promoter usage and/or splicing of p53 mRNA gives rise to at least nine mammalian p53 proteins with distinct N- and C-termini which are differentially expressed in normal and malignant cells. The human N-terminal p53 variants contain either the full-length (FL), or a truncated (ΔN/Δ40) or no transactivation domain (Δ133) altogether. The functional consequences of coexpression of the different p53 isoforms are poorly defined. Here we investigated functional aspects of the zebrafish ΔNp53 ortholog in the context of FLp53 and the zebrafish Δ133p53 ortholog (Δ113p53) coexpressed in the …

High Inspired Co2 Capnograph Reading Due To Misplaced End Tidal Co2 Sampling Port, Andrew Ng, Md, Elia Elia, Md, Lisa Luyun, Md

Department of Anesthesiology Faculty Papers

In conclusion, if abnormal capnography is seen where the baseline inspiratory CO2 is higher than usual, inspect the circuit for rebreathing and consider examining the position of ETCO2 sampling port. We recommend confirming ETCO2 sampling port is connected immediately distal to Y-piece before starting a case for accurate CO2 measurement.

Clinical And Diagnostic Features Of Patients With Compound Heterozygous A467t/W748s Polg1 Mutations: A Case Report And Review Of Previous Cases, David Roshal, D.O., Andro Zangaladze, Md, Phd

Department of Neurology Faculty Papers

Introduction

Mutations in the POLG1 gene are considered to be the most common gene defect identified in autosomal recessive mitochondrial DNA depletion disorders. POLG1 is a gene encoding the 195kDa catalytic (alpha) subunit of the mitochondrial (gamma) DNA polymerase, located on chromosome 15q25 and is responsible for mtDNA replication. Mutations in POLG1 are associated with chronic progressive external ophthalmoplegia (CPEO). Other genes that have been implicated in causing syndromic and non-syndromic mitochondrial disorders have been found on both mtDNA (3243A>G, 8344A>G, 8993T>G, and 11778A>G) and nDNA (SURF1, POLG1, TWINKLE, and ANT1).

We report a patient with …

Factors Influencing The One- And Two-Year Growth Response In Children Treated With Growth Hormone: Analysis From An Observational Study., Judith Ross, Peter A Lee, Robert Gut, John Germak

Department of Pediatrics Faculty Papers

To assess gender-, pubertal-, age-related differences in change from baseline height standard deviation score (ΔHSDS), data from 5,797 growth hormone (GH) naïve pediatric patients (<18 >years) with growth hormone deficiency (GHD), multiple pituitary hormone deficiency (MPHD), Turner syndrome (TS), small for gestational age (SGA), Noonan syndrome (NS), and idiopathic short stature (ISS) were obtained from the ANSWER (American Norditropin Studies: Web-enabled Research) Program registry. For patients with SGA, ΔHSDS at year 1 was significantly greater for males versus females (P = .016), but no other gender differences were observed. For patients with GHD, ΔHSDS was greater in prepubertal than in …

Using Hospital Discharge Abstract Data To Identify Incident Breast Cancer Cases And Assess Quality Of Care, Elaine J. Yuen, Daniel Z. Louis, Carol Rabinowitz, Vittorio Maio, L. Cisbani, R. Depalma, R. Grilli

College of Population Health Faculty Papers

No abstract provided.

Pediatric Ophthalmology And Strabismus: Something For Everyone., Alex V. Levin

Wills Eye Hospital Papers

This issue of Current Opinion in Ophthalmology highlights the uniquely broad range of pediatric ophthalmology and strabismus. Perhaps, unlike any other area of ophthalmology, our specialty covers virtually every part of the eye and a multitude of systemic disorders. Pediatric ophthalmology offers the practitioner the opportunity to impact a patient’s visual life for many decades giving them a lifetime of good vision. This issue of the journal highlights the many ways that this is so.

One Year Survival With Poorly Differentiated Metastatic Pancreatic Carcinoma Following Chemoembolization With Gemcitabine And Cisplatin., Daniel B Brown, Carin F Gonsalves, Charles J Yeo, Agnes K Witkiewicz, Brian I Carr

Department of Radiology Faculty Papers

While hepatic arterial chemoembolization is efficacious for a number of malignancies, there is scant data regarding treatment of pancreatic adenocarcinoma. We report a complete radiographic response at one year from diagnosis of metastatic pancreatic carcinoma. Gemcitabine/cisplatin based chemoembolization may be of potential benefit for patients with liver-dominant metastases from pancreatic carcinoma. Given the typical survival of 6 months or less in this patient group with standard therapies, further research is warranted.

Relationship Between Maternal Methadone Dose At Delivery And Neonatal Abstinence Syndrome., Neil S., Seligman, Christopher V. Almario, Edward J. Hayes, Kevin C. Dysart, Vincenzo Berghella, Jason K. Baxter

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: To estimate the relationship between maternal methadone dose and the incidence of neonatal abstinence syndrome (NAS).

STUDY DESIGN: We performed a retrospective cohort study of pregnant women treated with methadone for opiate addiction who delivered live-born neonates between 1996 and 2006. Four dose groups, on the basis of total daily methadone dose, were compared (160 mg/d). The primary outcome was treatment for NAS. Symptoms of NAS were objectively measured with the Finnegan scoring system, and treatment was initiated for a score>24 during the prior 24 hours.

RESULTS: A total of 330 women treated with methadone and their 388 …

Survival Associated Pathway Identification With Group Lp Penalized Global Auc Maximization., Zhenqiu Liu, Laurence S Magder, Terry Hyslop, Li Mao

Department of Pharmacology and Experimental Therapeutics Faculty Papers

It has been demonstrated that genes in a cell do not act independently. They interact with one another to complete certain biological processes or to implement certain molecular functions. How to incorporate biological pathways or functional groups into the model and identify survival associated gene pathways is still a challenging problem. In this paper, we propose a novel iterative gradient based method for survival analysis with group Lp penalized global AUC summary maximization. Unlike LASSO, Lp (p < 1) (with its special implementation entitled adaptive LASSO) is asymptotic unbiased and has oracle properties 1. We first extend Lp for individual gene identification to group Lp penalty for pathway selection, and then develop a novel iterative gradient algorithm for penalized global AUC summary maximization (IGGAUCS). This method incorporates the genetic pathways into global AUC summary maximization and identifies survival associated pathways instead of individual genes. The tuning parameters are determined using 10-fold cross validation with training data only. The prediction performance is evaluated using test data. We apply the proposed method to survival outcome analysis with gene expression profile and identify multiple pathways simultaneously. Experimental results with simulation and gene expression data demonstrate that the proposed procedures can be used for identifying important biological pathways that are related to survival phenotype and for building a parsimonious model for predicting the survival times.

Gsk-3alpha Directly Regulates Beta-Adrenergic Signaling And The Response Of The Heart To Hemodynamic Stress In Mice., Jibin Zhou, Hind Lal, Xiongwen Chen, Xiying Shang, Jianliang Song, Yingxin Li, Risto Kerkela, Bradley W Doble, Katrina Macaulay, Morgan Decaul, Walter J Koch, John Farber, James Woodgett, Erhe Gao, Thomas Force

Center for Translational Medicine Faculty Papers

The glycogen synthase kinase-3 (GSK-3) family of serine/threonine kinases consists of 2 highly related isoforms, alpha and beta. Although GSK-3beta has an important role in cardiac development, much remains unknown about the function of either GSK-3 isoform in the postnatal heart. Herein, we present what we believe to be the first studies defining the role of GSK-3alpha in the mouse heart using gene targeting. Gsk3a(-/-) mice over 2 months of age developed progressive cardiomyocyte and cardiac hypertrophy and contractile dysfunction. Following thoracic aortic constriction in young mice, we observed enhanced hypertrophy that rapidly transitioned to ventricular dilatation and contractile dysfunction. …