Mechanical unloading aggravates bone destruction and tumor expansion in myeloma

Tanimoto, Kotaro; Hiasa, Masahiro; Tenshin, Hirofumi; Teramachi, Jumpei; Oda, Asuka; Harada, Takeshi; Higa, Yoshiki; Sogabe, Kimiko; Oura, Masahiro; Sumitani, Ryohei; Hara, Tomoyo; Endo, Itsuro; Matsumoto, Toshio; Tanaka, Eiji; Abe, Masahiro

doi:10.3324/haematol.2021.278295

Cited by 2 publications

(3 citation statements)

References 16 publications

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“…Treatment with 5Z-7 at 20 mg/kg twice a week has been reported to reduce MM growth enhancement in immobilized hind legs [ 6 ]. 5Z-7 at 20 mg/kg every other day for 14 days has been shown in vivo to suppress MM tumour growth, serum IgG2b levels, and bone destruction.…”

Section: Discussionmentioning

confidence: 99%

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TAK1-inhibitors did not reduce disease burden in a Vκ*MYC model of multiple myeloma

Håland¹,

Moen

Vandsemb³

et al. 2022

BMC Res Notes

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Objective Multiple myeloma is a haematological malignancy characterized by proliferation of monoclonal plasma cells in the bone marrow. Development of resistance and minimal residual disease remain challenging in the treatment of multiple myeloma. Transforming growth factor-β activated kinase 1 (TAK1) has recently gained attention as a potential drug target in multiple myeloma. This study aimed at determining the in vivo effects of TAK1-inhibitors in a Vκ*MYC multiple myeloma mouse model. Results We treated mice carrying Vκ*MYC multiple myeloma cells with the TAK1-inhibitors 5Z-7-oxozeaenol and NG25. There were tendencies towards increased survival for both inhibitors, but only NG25 prolonged survival significantly. However, this effect was limited, and no differences in disease burden were observed for any of the treatments. In conclusion, although TAK1-inhibitors might prolong survival somewhat, they do not prevent disease in the Vκ*MYC mouse model of multiple myeloma.

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Section: Discussionmentioning

confidence: 99%

“…NF-κB is of critical importance in the pathogenesis of MM [ 5 ]. Targeting TAK1 has recently gained attention as a possible antimyeloma strategy [ 6 – 8 ]. We have previously shown that TAK1-inhibitors are cytotoxic to human myeloma cell lines patient cells [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

TAK1-inhibitors did not reduce disease burden in a Vκ*MYC model of multiple myeloma

Håland¹,

Moen

Vandsemb³

et al. 2022

BMC Res Notes

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“…Notably, MM tumor growth was suppressed in mice that underwent mechanical loading compared with control mice. We conducted an experiment with mechanical unloading in MM-bearing mice [ 65 ]. Right hind legs of mice were immobilized and exposed to mechanical unloading by sciatic denervation or casting with an adhesive bandage.…”

Section: Mutual Interaction Between MM Cells and Bone Microenvironmentmentioning

confidence: 99%

Myeloma bone disease: pathogenesis and management in the era of new anti-myeloma agents

et al. 2023

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Introduction Multiple myeloma (MM) is a malignancy of plasma cells with characteristic bone disease. Despite recent great strides achieved in MM treatment owing to the implementation of new anti-MM agents, MM is still incurable and bone destruction remains a serious unmet issue in patients with MM. Approach In this review, we will summarize and discuss the mechanisms of the formation of bone disease in MM and the available preclinical and clinical evidence on the treatment for MM bone disease. Conclusions MM cells produce a variety of cytokines to stimulate receptor activator of nuclear factor-κB ligand-mediated osteoclastogenesis and suppress osteoblastic differentiation from bone marrow stromal cells, leading to extensive bone destruction with rapid loss of bone. MM cells alter the microenvironment through bone destruction where they colonize, which in turn favors tumor growth and survival, thereby forming a vicious cycle between tumor progression and bone destruction. Denosumab or zoledronic acid is currently recommended to be administered at the start of treatment in newly diagnosed patients with MM with bone disease. Proteasome inhibitors and the anti-CD38 monoclonal antibody daratumumab have been demonstrated to exert bone-modifying activity in responders. Besides their anti-tumor activity, the effects of new anti-MM agents on bone metabolism should be more precisely analyzed in patients with MM. Because prognosis in patients with MM has been significantly improved owing to the implementation of new agents, the therapeutic impact of bone-modifying agents should be re-estimated in the era of these new agents.

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Mechanical unloading aggravates bone destruction and tumor expansion in myeloma

Abstract: Not available.

Cited by 2 publications

References 16 publications

TAK1-inhibitors did not reduce disease burden in a Vκ*MYC model of multiple myeloma

TAK1-inhibitors did not reduce disease burden in a Vκ*MYC model of multiple myeloma

Myeloma bone disease: pathogenesis and management in the era of new anti-myeloma agents

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