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- Liu, Hua, et al.
(författare)
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Low dose Zebularine treatment enhances immunogenicity of tumor cells
- 2007
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Ingår i: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 257:1, s. 107-115
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Tidskriftsartikel (refereegranskat)abstract
- Strategy: We have investigated how alterations in gene expression induced by the demethylating drug Zebularine affect the immune response tumor cells elicit. The rational has been to treat syngeneic rat colon cancer cells with Zebularine at different concentrations and then use these cells to study gene expression of different genes involved in cancer immunogenicity. Gene expressions were monitored by semi-quantitative PCR and real-time PCR. Results: Intriguingly there was a large increase in the production of indoleamine 2,3-dioxygenase (IDO) after treatment with 100 mu M Zebularine as compared with untreated tumor cells, whereas treatment with 20 mu M Zebularine caused a significant decrease of the IDO production. After immunization with syngeneic tumor cells, spleen cells were isolated and restimulated in vitro with irradiated tumor cells. Immune reactivity was measured by proliferation, and production of interferon gamma and interleukinl0. The immunogenicity of tumor cells treated in vitro with a low dose of Zebularine increased, whereas it decreased after high dose exposure. The inhibition of immunogenicity by 100 mu M Zebularine was shown to be counteracted by the IDO inhibitor I methyl-tryptophan (1MT), confirming that this effect of Zebularine is mainly caused by IDO induction. Differences using Zebularine-treated or non-treated cells for in vitro restimulation were marginal. Conclusion: Low dose treatment with Zebularine (20 mu M) decreases the production of the immunosuppressive IDO from rat colon cancer cells and enhances their immunogenicity, whereas high dose Zebularine treatment (100 mu M) enhances the IDO production from the cancer cells and suppresses their immunogenicity. This immunosuppression should be considered when cancer is treated with Zebularine or drugs acting in a similar way. (C) 2007 Published by Elsevier Ireland Ltd.
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| 2. |
- Mårtensson, Linda, et al.
(författare)
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Improved tumor targeting and decreased normal tissue accumulation through extracorporeal affinity adsorption in a two-step pretargeting strategy
- 2007
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 13:18, s. 5572-5576
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Evaluation of the possibilities of reducing the accumulation of radiolabeled streptavidin in radiosensitive organs by extracorporeal affinity adsorption (ECAT). Experimental Design: Rats were injected with biotinylated antibody and subjected to removal of the antibodies from the circulation by ECAT 24 h after injection (avidin column). Animals were then injected with In-111-1,4,7,10-tetra-azacylododecane N,N',N '',N'''-tetraacetic acid (DOTA) streptavidin. In a third step, animals were subjected to a second ECAT 8 h after injection to remove the DOTA-streptavidin from the circulation (biotin column). Biodistribution and tumor targeting of DOTA-streptavidin 24 h after injection was determined. Results: Elimination of biotinylated antibody by ECAT before injection of DOTA-streptavidin increased the tumor targeting by 50%. In addition, the levels of DOTA-streptavidin in liver and lymph nodes were reduced by 60%, which implied a 4.3- and 3.8-fold increase of tumor-to-liver and tumor-to-lymph node ratios, respectively. By doing a second ECAT to remove DOTA-streptavidin from the circulation, accumulation in normal tissues was reduced. However, this latter ECAT also reduced tumor accumulation by 25% (mostly corresponding to radioactivity in the circulation). Conclusions: ECAT was efficient as a means of removing biotinylated antibodies and would probably also be efficient for the clearance of streptavidin-conjugated antibodies. Conversely, the use of ECAT for removal of radiolabeled streptavidin seems not to offer any advantage.
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