The Role of Tocilizumab in the Treatment of Rheumatoid Arthritis

Hirabayashi, Yasuhiko

doi:10.5772/25752

Cited by 2 publications

(3 citation statements)

References 52 publications

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“…Definitions of and are provided in the following section. We note that when IL-6 binds to IL-6R, it subsequently recruits a GP130 molecule to form a ternary complex (IL-6/IL-6R/GP130) [ 15 ]. However, we do not model GP130 explicitly here, instead, we indirectly account for its role in the binding parameters and recycling parameters.…”

Section: Methodsmentioning

confidence: 99%

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A mathematical model for IL-6-mediated, stem cell driven tumor growth and targeted treatment

Nazari¹,

Pearson²,

Jackson³

2018

PLoS Comput Biol

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Targeting key regulators of the cancer stem cell phenotype to overcome their critical influence on tumor growth is a promising new strategy for cancer treatment. Here we present a modeling framework that operates at both the cellular and molecular levels, for investigating IL-6 mediated, cancer stem cell driven tumor growth and targeted treatment with anti-IL6 antibodies. Our immediate goal is to quantify the influence of IL-6 on cancer stem cell self-renewal and survival, and to characterize the subsequent impact on tumor growth dynamics. By including the molecular details of IL-6 binding, we are able to quantify the temporal changes in fractional occupancies of bound receptors and their influence on tumor volume. There is a strong correlation between the model output and experimental data for primary tumor xenografts. We also used the model to predict tumor response to administration of the humanized IL-6R monoclonal antibody, tocilizumab (TCZ), and we found that as little as 1mg/kg of TCZ administered weekly for 7 weeks is sufficient to result in tumor reduction and a sustained deceleration of tumor growth.

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Section: Methodsmentioning

confidence: 99%

“…IL-6 is a pleiotropic cytokine, secreted by a variety of cell types, that is a key player in number of cellular processes including proliferation, survival, differentiation, migration and invasion [ 14 ]. It is also commonly overexpressed in most cancer types including HNSCC [ 8 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

A mathematical model for IL-6-mediated, stem cell driven tumor growth and targeted treatment

Nazari¹,

Pearson²,

Jackson³

2018

PLoS Comput Biol

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show abstract

“…Although biologics has improved the clinical outcomes of RA, radiographic repair of bone erosions is still limited [ 1 ]. Tocilizumab (TCZ), an anti-interleukin-6-receptor antibody, has been shown to be highly efficacious in the treatment of RA, regardless of the age of patients, and to inhibit progression of joint damage [ 2–4 ]. Here we present the case of a very elderly patient with RA who showed dramatic radiographic repair by TCZ.…”

mentioning

confidence: 99%