Medicine and Health Sciences Commons^™

Dysregulated Methylation At Imprinted Genes In Prostate Tumor Tissue Detected By Methylation Microarray., Daniel I Jacobs, Yingying Mao, Alan Fu, William Kevin Kelly, Yong Zhu

Department of Medical Oncology Faculty Papers

BACKGROUND: Imprinting is an important epigenetic regulator of gene expression that is often disrupted in cancer. While loss of imprinting (LOI) has been reported for two genes in prostate cancer (IGF2 and TFPI2), disease-related changes in methylation across all imprinted gene regions has not been investigated.

METHODS: Using an Illumina Infinium Methylation Assay, we analyzed methylation of 396 CpG sites in the promoter regions of 56 genes in a pooled sample of 12 pairs of prostate tumor and adjacent normal tissue. Selected LOI identified from the array was validated using the Sequenom EpiTYPER assay for individual samples and further confirmed …

Ezh2 Knockdown Suppresses The Growth And Invasion Of Human Inflammatory Breast Cancer Cells., Zhaomei Mu, Hua Li, Sandra V Fernandez, Katherine R Alpaugh, Rugang Zhang, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

INTRODUCTION: Inflammatory breast cancer (IBC) is the most metastatic variant of breast cancer with the poorest survival in all types of breast cancer patients and presently therapeutic targets for IBC are very limited. Enhancer of zeste homolog 2 (EZH2) is frequently expressed in human IBC and its expression positively correlates with worse clinical outcome. However, the molecular basis for EZH2 promoting IBC has not been explored. Here, we investigated the functional role of EZH2 in IBC cells by examining the effects of its knockdown on the formation of tumor spheroids and invasion of these cells in vitro and in vivo …

Vascular Endothelial Growth Factor (Vegf) Expression In Locally Advanced Prostate Cancer: Secondary Analysis Of Radiation Therapy Oncology Group (Rtog) 8610., Larry Pan, Seunghee Baek, Pamela R Edmonds, Mack Roach, Harvey Wolkov, Satish Shah, Alan Pollack, M Elizabeth Hammond, Adam P Dicker

Department of Radiation Oncology Faculty Papers

BACKGROUND: Angiogenesis is a key element in solid-tumor growth, invasion, and metastasis. VEGF is among the most potent angiogenic factor thus far detected. The aim of the present study is to explore the potential of VEGF (also known as VEGF-A) as a prognostic and predictive biomarker among men with locally advanced prostate cancer.

METHODS: The analysis was performed using patients enrolled on RTOG 8610, a phase III randomized control trial of radiation therapy alone (Arm 1) versus short-term neoadjuvant and concurrent androgen deprivation and radiation therapy (Arm 2) in men with locally advanced prostate carcinoma. Tissue samples were obtained from …

Glutamine Supplementation Alleviates Vasculopathy And Corrects Metabolic Profile In An In Vivo Model Of Endothelial Cell Dysfunction., Francesco Addabbo, Qiuying Chen, Dhara P Patel, May Rabadi, Brian Ratliff, Frank Zhang, Jean-Francois Jasmin, Michael Wolin, Michael Lisanti, Steven S Gross, Michael S Goligorsky

Kimmel Cancer Center Faculty Papers

Endothelial Cell Dysfunction (ECD) is a recognized harbinger of a host of chronic cardiovascular diseases. Using a mouse model of ECD triggered by treatment with L-Nω-methylarginine (L-NMMA), we previously demonstrated that renal microvasculature displays a perturbed protein profile, including diminished expression of two key enzymes of the Krebs cycle associated with a Warburg-type suppression of mitochondrial metabolism. We hypothesized that supplementation with L-glutamine (GLN), that can enter the Krebs cycle downstream this enzymatic bottleneck, would normalize vascular function and alleviate mitochondrial dysfunction. To test this hypothesis, mice with chronic L-NMMA-induced ECD were co-treated with GLN at different concentrations for 2 …

A Phase 1b Study Of Humanized Ks-Interleukin-2 (Huks-Il2) Immunocytokine With Cyclophosphamide In Patients With Epcam-Positive Advanced Solid Tumors., Joseph P Connor, Mihaela C Cristea, Nancy L Lewis, Lionel D Lewis, Philip B Komarnitsky, Maria R Mattiacci, Mildred Felder, Sarah Stewart, Josephine Harter, Jean Henslee-Downey, Daniel Kramer, Roland Neugebauer, Roger Stupp

Kimmel Cancer Center Faculty Papers

BACKGROUND: Humanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent.

METHODS: Phase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300 mg/m2 on day 1), and escalating doses of huKS-IL2 (0.5-4.0 mg/m2 IV continuous infusion over 4 hours) on days 2, 3, and 4 of each 21-day cycle. Safety, pharmacokinetic profile, immunogenicity, anti-tumor and biologic activity were evaluated.

RESULTS: Twenty-seven patients were treated …