The family of NADPH oxidase (NOX) genes produces reactive oxygen species (ROS) pivotal for both cell signalling and host defense. To investigate whether NOX and NOX accessory gene expression might be a factor common to specific human tumour types, this study measured the expression levels of NOX genes 1-5, dual oxidase 1 and 2, as well as those of NOX accessory genes NoxO1, NoxA1, p47 phox , p67 phox and p22 phox in human cancer cell lines and in tumour and adjacent normal tissue pairs by quantitative, real-time RT-PCR. The results demonstrate tumour-specific patterns of NOX gene expression that will inform further studies of the role of NOX activity in tumour cell invasion, growth factor response and proliferative potential.
IntroductionInvestigators have focused on developing transgenic (Tg) mice containing human leukocyte antigen (HLA) alleles such as A*0201 (A2.1) in the class I system or DR1 in the class II system to address the problem of selection of epitopes that bind to major histocompatibility complex (MHC) molecules in an experimental model system. 1,2 Cellular immune responses to vaccines can then be studied in an easily manipulated vertebrate system with immunologic similarities to humans. We and others have characterized a repertoire of cytotoxic T-lymphocyte (CTL) epitopes specific for the immunodominant protein, cytomegalovirus (CMV)-pp65. 3,4 The choice of using CTL epitopes derived from CMV was based upon the absence of a Food and Drug Administration-approved vaccine modality against this significant opportunistic infection of solid organ and hematopoietic cell transplantation (HCT) recipients or its congenital manifestations. [5][6][7] The utility of using HLArestricted CTL epitopes is derived from the fact that HCT recipients are HLA typed and can be selected to be potential responders to the epitope-based vaccine. Reactivation of CMV and viremia are closely monitored during the first several months after HCT, representing a unique opportunity to investigate the properties of a therapeutic vaccine. [8][9][10] CMV-infected cells express pp65 both early and late after infection, making it an appropriate vaccine target. 11,12 Vaccines incorporating them would provide a strategy to immunize against CMV infection in the clinical setting. Since CMV-pp65 contains an HLA A2.1-specific epitope that is recognized by T cells from humans and from mice of the H-2 b background containing an HLA A2.1 or chimeric (human/mouse) A2.1/K b transgene, it has been chosen as a model class I epitope for these studies. 3,13,14 To circumvent allele specificity for the required T-helper (T H ) epitope, a series of T H sequences that promiscuously bind to either human or murine class II MHC alleles have been evaluated in combination with the CMV-pp65 HLA A*0201-restricted epitope. 13,15 In the last decade, investigators have studied the optimal means of delivering peptides corresponding to either CTL or T H epitopes as experimental vaccines. Peptides have been emulsified in adjuvants, complexed to alum, or suspended in liposomes, to name a few of the delivery strategies. [16][17][18] Successful epitope vaccine strategies against viruses, bacteria, and tumor antigens have been developed in mice using these delivery vehicles. 19,20 In addition, The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 U.S.C. section 1734. modification of the primary structure of peptides by incorporating lipids also has been extensively studied in both experimental animals and in man. 21,22 Lipopeptides (lipidated peptides) specific for hepatitis B (HBV), HIV, and tumor antigens have been studied clinically in phase 1 and...
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