Okayama Igakkai Zasshi (Journal of Okayama Medical Association)

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The efficacy and toxicity of adenoviral vectors that express Herpes Simplex Virus-thymidine kinase (HSV-tk) gene under the transcriptional control of caveolin-1 promoter (cav.-1-tk) was compared to Cytomegalovirus (CMV) promoter or Rous sarcoma virus (RSV) promoter HSV-tk for prostate cancer. The cav.-1-tk demonstrated the strong cytotoxicity in vitro for mouse human prostate cancer cell line (178BMA) and human prostate cancer cell line (PC-3), which overxpress caveolin-1 levels. On the other hand, the cytotoxicity was weak for mouse (178PA) and human (LNCaP) prostate cancer cell line, which express low caveolin-1 levels. The antitumor efficacy was observed in each vector in vivo orthotopic model using 178BMA prostate cancer cell line. The immunohistochemical analysis results indicated that not only cancer cells but also tumor vasculature were destroyed by cav.-1-tk. The serum AST levels of cav.-1-tk was minimal change following intravenous injection.
Taken together, adenovirus-mediated HSV-tk in situ gene therapy under the transcriptional control of caveolin-1 promoter may be effective and safe for prostate cancer compared to CMV or RSV promoter HSV-tk adenoviral vectors.

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β2-Glycoprotein I (β2-GPI) is a major antigen for anticardiolipin antibodies (aCL) appeared in patients with antiphospholipid syndrome (APS). We recently reported that β2-GPI specifically binds to oxidized low-density lipoprotein (oxLDL) and that on of the β2-GPI's major ligands derived from oxLDL, oxLig-1, is 9-(7-ketocholest-5-en-3β-yloxy)-9-oxononanoic acid (J. Lipid Res. 42, 697, 2001). In the present study, it was demonstrated that carboxylated variants of cholesteryl linoleate have a critical role for β2-GPI binding. In vitro experiments indicate that oxLDL was uptaken by macrophages via an interaction among the ligand such as oxLig-1, β2-GPI, and anti-β2-GPI autoantibodies. The uptake was not occurred by cholesterol or its ester without a free carboxyl residue, i.e., cholesteryl lenoleate, by cholesterol, or by 7-ketocholesterol alone, even in the presence of β2-GPI and anti-β2-GPI antibodies. Thus, carboxyl variants of cholesteryl ester specific for β2-GPI may mediate anti-β2-GPI Ab-dependent uptake of oxLDL by macrophages and autoimmune atherogenesis developed in APS.

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