Oncology 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.

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, …

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 …

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.

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.

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.

Physiologically Based Pharmacokinetics Of Molecular Imaging Nanoparticles For Mrna Detection Determined In Tumor-Bearing Mice., Armin W Opitz, Eric Wickstrom, Mathew L Thakur, Norman J Wagner

Kimmel Cancer Center Faculty Papers

Disease detection and management might benefit from external imaging of disease gene mRNAs. Previously we designed molecular imaging nanoparticles (MINs) based on peptide nucleic acids complementary to cancer gene mRNAs. The MINs included contrast agents and analogs of insulin-like growth factor 1 (IGF-1). Analysis of MIN tumor uptake data showed stronger binding in tumors than in surrounding tissues. We hypothesized that MINs with an IGF-1 analog stay in circulation by binding to IGF-binding proteins. To test that hypothesis, we fit the tissue distribution results of several MINs in xenograft-bearing mice to a physiological pharmacokinetics model. Fitting experimental tissue distribution data …

Assessment Of Epidermal Growth Factor Receptor (Egfr) Expression In Human Meningioma., A Gabriella Wernicke, Adam P Dicker, Michal Whiton, Jana Ivanidze, Terry Hyslop, Elizabeth H Hammond, Arie Perry, David W Andrews, Lawrence Kenyon

Kimmel Cancer Center Faculty Papers

PURPOSE: This study explores whether meningioma expresses epidermal growth factor receptor (EGFR) and determines if there is a correlation between the WHO grade of this tumor and the degree of EGFR expression.

METHODS: Following institutional review board approval, 113 meningioma specimens from 89 patients were chosen. Of these, 85 were used for final analysis. After a blinded review, immunohistochemical stains for EGFR were performed. Staining intensity (SI) was scored on a scale 0-3 (from no staining to strong staining). Staining percentage of immunoreactive cells (SP) was scored 1-5 (from the least to the maximum percent of the specimen staining). Immunohistochemical …

Differential Impact Of Tumor Suppressor Pathways On Dna Damage Response And Therapy-Induced Transformation In A Mouse Primary Cell Model., A Kathleen Mcclendon, Jeffry L Dean, Adam Ertel, Erik S Knudsen

Department of Cancer Biology Faculty Papers

The RB and p53 tumor suppressors are mediators of DNA damage response, and compound inactivation of RB and p53 is a common occurrence in human cancers. Surprisingly, their cooperation in DNA damage signaling in relation to tumorigenesis and therapeutic response remains enigmatic. In the context of individuals with heritable retinoblastoma, there is a predilection for secondary tumor development, which has been associated with the use of radiation-therapy to treat the primary tumor. Furthermore, while germline mutations of the p53 gene are critical drivers for cancer predisposition syndromes, it is postulated that extrinsic stresses play a major role in promoting varying …