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J. Teramachi et al.
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Figure 6. TAK1 inhibition suppresses multiple myeloma tumor growth and bone destruction in vivo. The mice with intra-tibial inoculation of luciferase-transfected 5TGM1 were treated with LLZ at 20 mg/kg or saline intraperitoneally every other day from days 6 to 21. (A) Tumor sizes were assessed at day 21 via in vivo biolu- minescence measurement using the IVIS Imaging System. For the luciferase detection imaging, 100 μL of 15 mg/mL D-luciferin in phosphate-buffered saline was injected intraperitoneally before taking images. (B) Serum levels of mouse IgG2b were measured over time. (C) The tibiae with the tumor or control ones were extract- ed, and analyzed using soft X-ray (left) and m-computed tomography (right) imaging. (D) Immunohistochemical detection of cathepsin K in the tibia from a mouse inoculated with 5TGM1 multiple myeloma (MM) cells. (E) The tibiae were taken out at day 21 and analyzed histomorphometrically. The ratios of the bone volume to total volume (BV/TV), trabecular thickness (Tb.Th), trabecular numbers (Tb.N), trabecular separation (Tb.Sp), number of osteoclasts to bone surface (N.Oc/BS), num- ber of osteoblasts to bone surface (N.Ob/BS) osteoid surface to bone surface (OS/BS), and bone formation rate to bone surface (BFR/BS) were analyzed using sec- tions from three mice in each study arm. Data are expressed as mean ± standard deviation. *P<0.05.
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