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Diagnostic Technologies and Molecular and Cellular Profiling: Biomarkers in Early Detection and Diagnosis |
Self employed, Salt Lake City, UT
Abstract
A20
Pancreatic cancer is a deadly disease with over 31,000 new cases in the United States each year and over 30,000 deaths. This cancer has metastasized or spread from the pancreas in more than 85% of the patients by the time the diagnosis is made with the present imaging and other diagnostic tests. Earlier and accurate diagnosis of this fatal disease is needed. (1,2)The tumor starts in the lining cells of the pancreatic duct as a hyperplasia of these cells, progressing to a papillary hyperplasia, dysplasia, cancer and finally an invasive ductal pancreatic adenocarcinoma. Early in its development the dendritic cells recognize a change in the cells of the growth and convey altered proteins to the lymphocyte system. The lymphocytes are programmed against these altered proteins and send TIL cells or 'tumor infiltrating lymphocytes' to fight the abnormal cells of the developing tumor. In doing this the lymphocytes change their patterns of gene expression. Microarray analysis of the gene expression patterns of the peripheral blood mononuclear cells, consisting of 80% to 95% lymphocytes, allows the specific significant diagnosis of this developing tumor. (3-8)In this preliminary study a method was developed in which 16ml of intravenous peripheral blood was drawn from patients with ductal pancreatic adenocarcinoma. The mononuclear cells were analyzed with microarray gene analysis and compared to similarly processed specimens drawn from age and gender approximated controls without pancreatic disease. Statistically significant specific genes displayed over expression and suppression in the specimens of patients with pancreatic cancer as compared to the controls. These specific genes were consistently identified by different statistical methods across different specimens. The noted genes appear to identify the specific ductal pancreatic adenocarcinoma which constitutes most of the pancreatic cancers, as distinct from other pancreatic diseases and tumors and were not the genes noted in other cancers and diseases.This increasingly accepted concept of utilizing the peripheral blood mononuclear cells and lymphocytes for the diagnosis of disease and measurement of therapeutic response, when combined with a developing microfluidic device, could allow the earlier, easily obtained diagnosis of this dreaded disease and better treatment design. (9-12)1. Jemal A. CA Cancer J Clin 2005 Jan-Feb; 55(1):10-302. Ros PR. JBR-BTR 2001; 84(6):239-2493. Fujii H. Am J Pathol 1997 Nov; 151(5):1447-544. Rosty C. Hematol Oncol Clin North Am 2002 Feb; 16(1):37-525. Baxevanis CN J Immunol 2000 April; 164(7) 3902-126. Zeng G. J Immunother 2001 May; 23(3): 195-2047. Pages F. NEJM 2005 Dec; 353(25):2654-668. Parmiani G. NEJM 2005 Dec; 353(25) 2640-419. Burczynski ME. J Mol Diag 2006 Feb; 8(1): 51-6110. Satoh J. J Neuroimmunol 2006; 174: 108-11811. Potti A. Blood 2006 Feb 15; 107(4): 1391-612. Tang Y. J Cereb Blood Flow Metab 2006 Jan; 4: 1-14
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