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Original Article
Thyroid
Prognostic Roles of Inflammatory Biomarkers in Radioiodine-Refractory Thyroid Cancer Treated with Lenvatinib
Chae A Kim, Mijin Kim, Meihua Jin, Hee Kyung Kim, Min Ji Jeon, Dong Jun Lim, Bo Hyun Kim, Ho-Cheol Kang, Won Bae Kim, Dong Yeob Shin, Won Gu Kim
Endocrinol Metab. 2024;39(2):334-343.   Published online April 4, 2024
DOI: https://doi.org/10.3803/EnM.2023.1854
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  • 36 Download
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), serve as valuable prognostic indicators in various cancers. This multicenter, retrospective cohort study assessed the treatment outcomes of lenvatinib in 71 patients with radioactive iodine (RAI)-refractory thyroid cancer, considering the baseline inflammatory biomarkers.
Methods
This study retrospectively included patients from five tertiary hospitals in Korea whose complete blood counts were available before lenvatinib treatment. Progression-free survival (PFS) and overall survival (OS) were evaluated based on the median value of inflammatory biomarkers.
Results
No significant differences in baseline characteristics were observed among patients grouped according to the inflammatory biomarkers, except for older patients with a higher-than-median NLR (≥2) compared to their counterparts with a lower NLR (P= 0.01). Patients with a higher-than-median NLR had significantly shorter PFS (P=0.02) and OS (P=0.017) than those with a lower NLR. In multivariate analysis, a higher-than-median NLR was significantly associated with poor OS (hazard ratio, 3.0; 95% confidence interval, 1.24 to 7.29; P=0.015). However, neither the LMR nor the PLR was associated with PFS. A higher-than-median LMR (≥3.9) was significantly associated with prolonged OS compared to a lower LMR (P=0.036). In contrast, a higher-than-median PLR (≥142.1) was associated with shorter OS compared to a lower PLR (P=0.039).
Conclusion
Baseline inflammatory biomarkers can serve as predictive indicators of PFS and OS in patients with RAI-refractory thyroid cancer treated with lenvatinib.
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Review Article
Calcium & bone metabolism
Nuclear Factor-Kappa B Regulation of Osteoclastogenesis and Osteoblastogenesis
Brendan F. Boyce, Jinbo Li, Zhenqiang Yao, Lianping Xing
Endocrinol Metab. 2023;38(5):504-521.   Published online September 26, 2023
DOI: https://doi.org/10.3803/EnM.2023.501
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  • 104 Download
  • 4 Web of Science
  • 6 Crossref
AbstractAbstract PDFPubReader   ePub   
Maintenance of skeletal integrity requires the coordinated activity of multinucleated bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoclasts form resorption lacunae on bone surfaces in response to cytokines by fusion of precursor cells. Osteoblasts are derived from mesenchymal precursors and lay down new bone in resorption lacunae during bone remodeling. Nuclear factorkappa B (NF-κB) signaling regulates osteoclast and osteoblast formation and is activated in osteoclast precursors in response to the essential osteoclastogenic cytokine, receptor activator of NF-κB ligand (RANKL), which can also control osteoblast formation through RANK-RANKL reverse signaling in osteoblast precursors. RANKL and some pro-inflammatory cytokines, including tumor necrosis factor (TNF), activate NF-κB signaling to positively regulate osteoclast formation and functions. However, these cytokines also limit osteoclast and osteoblast formation through NF-κB signaling molecules, including TNF receptor-associated factors (TRAFs). TRAF6 mediates RANKL-induced osteoclast formation through canonical NF-κB signaling. In contrast, TRAF3 limits RANKL- and TNF-induced osteoclast formation, and it restricts transforming growth factor β (TGFβ)-induced inhibition of osteoblast formation in young and adult mice. During aging, neutrophils expressing TGFβ and C-C chemokine receptor type 5 (CCR5) increase in bone marrow of mice in response to increased NF-κB-induced CC motif chemokine ligand 5 (CCL5) expression by mesenchymal progenitor cells and injection of these neutrophils into young mice decreased bone mass. TGFβ causes degradation of TRAF3, resulting in decreased glycogen synthase kinase-3β/β-catenin-mediated osteoblast formation and age-related osteoporosis in mice. The CCR5 inhibitor, maraviroc, prevented accumulation of TGFβ+/CCR5+ neutrophils in bone marrow and increased bone mass by inhibiting bone resorption and increasing bone formation in aged mice. This paper updates current understanding of how NF-κB signaling is involved in the positive and negative regulation of cytokine-mediated osteoclast and osteoblast formation and activation with a focus on the role of TRAF3 signaling, which can be targeted therapeutically to enhance bone mass.

Citations

Citations to this article as recorded by  
  • The Role of Rosavin in the Pathophysiology of Bone Metabolism
    Piotr Wojdasiewicz, Paweł Turczyn, Anna Lach-Gruba, Łukasz A. Poniatowski, Daryush Purrahman, Mohammad-Reza Mahmoudian-Sani, Dariusz Szukiewicz
    International Journal of Molecular Sciences.2024; 25(4): 2117.     CrossRef
  • The role of monocyte/macrophage chemokines in pathogenesis of osteoarthritis: A review
    Hao Luo, Linfeng Li, Song Han, Tao Liu
    International Journal of Immunogenetics.2024; 51(3): 130.     CrossRef
  • The effect of low-level laser therapy on osteoclast differentiation: Clinical implications for tooth movement and bone density
    Chun-Yi Huang, Huynh Hoai Thuong Le, Hsiao-Chi Tsai, Chih-Hsin Tang, Jian-Hong Yu
    Journal of Dental Sciences.2024;[Epub]     CrossRef
  • Anti-arthritic and immunomodulatory efficacy of Micromeria biflora Benth extract and its fractions in rats by restoring oxidative stress, metalloproteinases, pro-inflammatory and anti-inflammatory cytokines network
    Fakhria A. Al-Joufi, Ambreen Malik Uttra, Sumera Qasim, Urooj Iqbal, Nabeela Tabassum Sial, Noura M. Alhumaid
    Inflammopharmacology.2024;[Epub]     CrossRef
  • Evaluation of Immunohistochemical Biomarkers in Diabetic Wistar Rats with Periodontal Disease
    Ioana Scrobota, Ioan Andrei Tig, Andrea Olivia Marcu, Georgiana Ioana Potra Cicalau, Liliana Sachelarie, Gilda Iova
    Journal of Personalized Medicine.2024; 14(5): 527.     CrossRef
  • Genetic Deficiency of the Long Pentraxin 3 Affects Osteogenesis and Osteoclastogenesis in Homeostatic and Inflammatory Conditions
    Valentina Granata, Dario Strina, Maria Lucia Schiavone, Barbara Bottazzi, Alberto Mantovani, Antonio Inforzato, Cristina Sobacchi
    International Journal of Molecular Sciences.2023; 24(23): 16648.     CrossRef
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