Abstract. As 2 O 3 has been reported to induce apoptosis and inhibit the proliferation of various human cancer cells. We evaluated the ability of a novel arsenic compound, As 4 O 6 , along with As 2 O 3 in vitro and in vivo. To examine the levels of apoptosis of HPV 16-positive SiHa cervical cancer cell, flow cytometry and Western blotting were employed at various time intervals after two arsenic compound treatments. Ingenuity Pathway Analysis (IPA) was applied to investigate the differential cell death pathway of As 4 O 6 and As 2 O 3 . The results showed that As 4 O 6 was more effective in suppressing SiHa cell growth in vitro and in vivo compared to As 2 O 3 . In addition, the cell cycle was arrested at the sub-G 1 phase by As 4 O 6 . Western blot analysis showed that the proliferating cell nuclear antigen (PCNA) and Bcl-X L with sequence homology to Bcl-2 were significantly suppressed by As 4 O 6 . However, the apoptosis-related proteins such as p21 and Bax were overexpressed by As 4 O 6 . IPA suggested that there is a significant difference between As 2 O 3 -and As 4 O 6 -induced cell death pathways. Taken together, As 4 O 6 has a specific cell death pathway and possesses more potent anti-tumor effects on human cervical cancer cells in vitro and in vivo.

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Objective: To investigate the immunoregulatory effects of allogeneic mixed chimerism induced by T-cell depleted, nonmyeloablative bone marrow transplantation (TCD-NMT) on chronic inflammatory arthritis and autoimmunity developed in interleukin-1 receptor antagonist-deficient (IL-1Ra−/ −) mice. Methods: IL-1Ra−/ − mice (H-2kd) were treated with anti-asialoGM1 Ab, TBI 500 cGy, and TCD-NMT from C57BL/6 mice (H-2kb). Engraftment and chimerism were evaluated on peripheral blood (PB), lymph node, and spleen by multi-color flow cytometry. The severity of arthritis was evaluated by clinical score and histopathology. IgG1 and IgG2a subtype of anti-type II collagen (CII) were measured in PB samples. After T cells were stimulated with CII, ovalbumin, and phytohemagglutinin, T-cell proliferation response and cytokines production (INF-g, TNF-a, IL-10, and IL-17) in culture supernatant were assayed. Results: All the transplanted IL-1Ra mice showed marked improvement of arthritis within 3 weeks after transplantation as well as successful induction of mixed chimerism. Mice in mixed chimerism showed higher level of anti-CII IgG1 and lower level of anti-CII IgG2a and weaker T cell proliferative response than in control groups, such as no-treatment and conditioning only without BM rescue. In mixed chimera, INF-g, TNF-a and IL-17 production from CII-stimulated T cells was significantly suppressed and IL-10 production was significantly increased as compared to the control groups. Conclusion: These observations indicate that the introduction of allogeneic mixed chimerism has a strong immunoregulatroy potential to correct established chronic inflammatory arthritis and autoimmunity originating from dysregulated proinflammatory cytokine network.