There is no known underlying genetic defect predisposing patients ? to develop primary intraocular lymphoma (PIOL). Discovery of genetic ? factors predisposing to the development of PIOL would be of benefit for ? early diagnosis, prognostic staging, and development of novel treatments ? for PIOL. Until recently, genetic approaches to investigate the etiology ? of cancer have relied upon methods utilizing linkage based on traditional ? Mendelian inheritance patterns. It is probable that many diseases are a ? consequence of multiple genetic factors, and are therefore less amenable ? to study using traditional methods of linkage analysis and positional ? cloning to isolate single genes. Single nucleotide polymorphisms (SNPs) ? are the most common sources of variation in the human genome. SNPs are ? single-base differences in the DNA sequence that can be observed among ? individuals in a population. A SNP is defined on the basis of a frequency ? of at least 1% prevalence in one or more populations. SNPs are present ? throughout the genome at an average frequency of 1/1000 base pairs. We ? propose to analyze the frequency of SNPs specifically within the coding ? frames of biologically plausible genes responsible for function of the ? innate immune system. The interleukins are a specific pathway of interest ? because previous research has demonstrated derangements in the ratios of ? interleukins 10 and 6 in the vitreous humor and spinal fluid of patients ? with PIOL, leading to the hypothesis that altered function or expression ? of these or other interleukins could permit the development of this rare ? malignancy. Samples continue to be collected, but as no results have yet ? been obtained. We hosted a workshop on this subject at the NIH this past ? fiscal year with the results recently published. Since recruitment for ? this study was very slow we have made the decision to suspend this study. ? However, we received a Bench to Bedside award to begin to investigate the use of a ? CD-22/pseudomonas construct in order to kill intraocular tumor. Initial ? studies have been promising with our plan to carry these further in animal ? studies and ultimately to the treatment of patients.? From 2005 to 2007, we have made substantial progress in establishing a ? murine model to mimic human PIOL as well as searching for novel and ? effective therapy for this disease. We have established a mouse model that ? resembles human PIOL at the level of histopathology and molecular ? pathogenesis. We demonstrated that the model shares several hall mark ? characteristics of human PIOL and is ideal for further studying the ? molecular mechanisms of human PIOL. Furthermore, in collaboration with ? NCI, we found that a recently developed immunotoxin (HA22) can eradicate ? the tumor with minimal toxicity and is potentially a novel therapeutic ? agent for treating human PIOL. Currently, we are investigating the toxicity of HA22 ? to ocular tissues using a rabbit model.
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