• IMMUNE NETWORK
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• v.4 no.1
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• pp.44-52
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• 2004

Background: As a potent antigen presenting cell and a powerful inducer of antigen specific immunity, dendritic cells (DCs) are being considered as a promising anti-tumor therapeutic module. The expected therapeutic effect of DCs in renal cell carcinoma was tested in the mouse model. Established late-stage tumor therapeutic (E-T) and minimal residual disease (MRD) model was considered in the in vivo experiments. Methods: Syngeneic renal cell carcinoma cells (RENCA) were inoculated either subcutaneously (E-T) or intravenously (MRD) into the Balb/c mouse. Tumor cell lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started 3 week (E-T model) or one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, the tumor growth and the systemic immunity were observed. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with RENCA cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor growth (E-T model) or formation (MRD model) was suppressed in pulsed-DC treated group. RENCA specific lymphocyte proliferation was observed in the RENCA tumor-bearing mice treated with pulsed-DCs. Primary cytotoxic T cell activity against RENCA cells was increased in pulsed-DC treated group. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs in established or minimal residual disease/metastasis state of renal cell carcinoma. Systemic tumor specific immunity including cytotoxic T cell activity was modulated also in pulsed-DC treated group.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.86-86
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• 2004

• Biomolecules & Therapeutics
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• v.16 no.2
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• pp.87-94
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• 2008

In view of obtaining potential anticancer compounds, we studied the inhibitory activity and the cytotoxic effects of a candidate compound in cancer cells. The cytotoxic effects of cannabidiol (CBD) in vitro were evaluated in NIH3T3 fibroblasts, B16 melanoma cells, A549 lung cancer cells, MDA-MB-231 breast cancer cells, Lenca kidney cells and SNU-C4 colon cancer cells. The cells were cultured in various concentrations of CBD for 48 h and 25 ${\mu}$M of CBD for 6-36 h. The cells were observed to exhibit inhibitory effects of the cell viability in their growth, and then cytotoxicity was estimated. The inhibitory activity of CBD was increased in all cancer cells and showed especially strong increment in breast cancer cells. The cytotoxicity of CBD increased in a dose- and time-dependent manner with growth inhibition in all cancer cell lines. Also, to assess the membrane toxicity induced by CBD, we investigated lactate dehydrogenase (LDH) release. After treatment with various concentrations of CBD, LDH release rate of cancer cells was accelerated. On the other hand, in the induction of cell death, caspase-3, -8 and -9 activations were detected in cancer cells after treatment with various concentrations of CBD, and CBD effectively induced activity of caspase-3, -8 and -9 in A549 lung cancer cells, MDAMB-231 breast cancer cells and Renca kidney cells. Therefore these results suggest that CBD has a possibility of anticancer agents and anticancer effects against cancer cells by modulation of apoptotic pathway in the range of 5-80 ${\mu}$M concentration.

• YAKHAK HOEJI
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• v.48 no.6
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• pp.335-344
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• 2004

Interleukin-2 (IL-2), a glycoprotein mainly secreted by CD4+ T helper Iymphocytes, has been developed to use recombinant cytokine to augment the immune response against cancer since IL-2 not only stimulates T Iymphocytes but also enhances natural killer (NK) cell activity. In order to evaluate the immunological safety of recombinant mouse IL-2 (rmIL-2) in cancer therapy, renal cell carcinoma was established in the flank by s.c. injection of renca cell line. Tumor-bearing BALB/c mice were treated with I.p. injections with $2{\times}10^5$ Lu rmIL-2. Even though the tumor size was diminished, there were not significant recovery of body and relative lymphoid organ weights including thymic atrophy in rmIL-2 immunotherapy. Distribution ratios of T cell subsets in thymus were analysed using flow cytometry. Without regard to dosage of rmIL-2, the ratio of CD3+CD4-CD8- T cells was increased in accordance with survival of solid tumor but that of CD4+CD8+ T cells was decreased dramatically. Emergence of autoantibodies (ANA, anti-dsDNA, and anti-histone) in blood was measured after rmIL-2 treatment. The results showed that the levels of ANA and anti-dsDNA did not significantly changed, but the level of anti-histone was increased significantly owing to rmIL-2 therapy. These results indicate rmIL-2 immunotherapy is to induce the autoimmune potential, and the anti-histone measurement as a biomarker of autoimmunity is useful in cancer immunotherapy.