TNF-a gene

Newell CL, Deisseroth AB, Lopezberestein G. Interaction of nuclear proteins with an Ap-1 Cre-like promoter sequence in the human TNF-a gene. J Leukocyte Biol 1994 56 27-35. 

Staba MJ, Mauceri HJ, Kufe DW, et al. Adenoviral TNF-a gene therapy and radiation damage tumor vasculature in a human malignant glioma xenografts. Gene Ther 1998 5 293-300. 

Anti-arthritic effect. Oral administration of AJA, a cannabinoid acid devoid of psychoactivity, reduced joint tissue damage in rats with adjuvant arthritis. Peripheral blood monocytes (PBM) and synovial fluid monocytes (SFM) were isolated from healthy subjects and patients with inflammatory arthritis, respectively, treated with AJA (0-30 mM) in vitro, and then stimulated with lipopolysaccharide. Cells were harvested for messenger RNA (mRNA), and supernatants were collected for cytokine assay. Addition of AJA to PBM and SFM in vitro reduced both steady-state levels of interleukin-ly (IL-ly) mRNA and secretion of IL-ly in a concentration-dependent manner. Suppression was maximal (50.4%) at 10 mM AJA (p < 0.05 vs untreated controls, n = 7). AJA did not influence tumor necrosis factor-a (TNF-a) gene expression in or secretion from PBM . 

Hajeer AH, Hutchinson IV. Influence of TNF-a gene polymorphisms on TNF-a production and disease. Hum Immunol. 2001, 62 1191-1199. 

TNF promoter -308A>G May increase transcription of TNF-a gene Increased response to INF [93, 97]... 

In mouse splenocytes and human peripheral blood mononuclear cells treated with an extract of shiitake, the expression levels of IL-2 and TNF-a genes were augmented in both sets of cells. The production of IL-2 was augmented in the mouse splenocytes, and the production of TNF-a was augmented in murine peritoneal exudate macrophages. The production of IL-2 and TNF-a was augmented in the human mononuclear cells (Liu et al. 1998). 

Our results demonstrate that in vivo transfection of TNF-a genes using FL to the artery leading to tumors and tumor-vessels could efficiently... 

By using FL as the gene transfer vector, DNA was transferred only into the femoral artery and its downstream tissue, the site for S-180 solid tumors. FL mediate rapid and efficient gene transfer but are inactivated after entering the blood stream by the complement system. Thus, DNA would be introduced only into local tissues at the site of inoculation. No TNF-a was detected in the semm of mice injected with TNF-a gene. TNF-a would be produced only in local tissues. 

In summary, transfection of TNF-a gene into the endothelial cells located upstream of the tumors and the tumor tissues specifically enhanced the TNF-a concentration at the tumor sites and was found to be effective in tumor regression. This system using FL, which targets not only most tumor cells, but also tumor-endothelial cells, is a novel and effective approach to in vivo gene therapy of solid cancer. 

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