Clinical Implications of High-mobility Group Box-1 (HMGB1) and the Receptor for Advanced Glycation End-products (RAGE) in Cutaneous Malignancy: A Systematic Review

Nguyen, Austin Huy; Detty, Shannon Q.; Agrawal, Devendra K.

doi:10.21873/anticanres.11282

Cited by 42 publications

(28 citation statements)

References 32 publications

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“…This result indicated that intracellularly formed AGE, rather than O‐GlcNAc modification, may further modify transcription factors including Hif1α and AP‐1, leading to the synergistic enhancement of MTM‐induced VEGF expression. Interestingly, VEGF was not induced by AGE, but its constitutive level was downregulated by Ager siRNA in PDL cells, implying that other agonistic ligands such as S100 and HMGB1 may also work for Ager in PDL cells . These suggestions may need to be further investigated and validated.…”

Section: Discussionmentioning

confidence: 97%

Synergistic alveolar bone resorption by diabetic advanced glycation end products and mechanical forces

Moon

Lee

Kim

et al. 2019

Journal of Periodontology

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Background The association between diabetes mellitus (DM) and bone diseases is acknowledged. However, the mechanistic pathways leading to the alveolar bone (AB) destruction remain unclear. This study aims to elucidate the mechanical forces (MF)‐induced AB destruction in DM and its underlying mechanism. Methods In vivo periodontal tissue responses to MF were evaluated in rats with diabetes. In vitro human periodontal ligament (PDL) cells were either treated with advanced glycation end products (AGEs) alone or with AGEs and MF. Results In vivo, the transcription of VEGF‐A, colony stimulating factor‐1 (CSF‐1), and Ager was upregulated in diabetes, whereas changes in DDOST and Glo1 mRNAs were negligible. DM induced VEGF‐A protein in the vascular cells of the PDL and subsequent angiogenesis, but DM itself did not induce osteoclastogenesis. MF‐induced AB resorption was augmented in DM, and such augmentation was morphologically substantiated by the occasional undermining resorption as well as the frontal resorption of the AB by osteoclasts. The mRNA levels of CSF‐1 and vascular endothelial growth factor (VEGF) during MF application were highly elevated in diabetes, compared with those of the normal counterparts. In vitro, AGEs treatment elevated Glut‐1 and CSF‐1 mRNA levels via the p38 and JNK pathways, whereas OGT and VEGF levels remained unchanged. Compressive MF especially caused upregulation of VEGF, CSF‐1, and Glut‐1 levels, and such upregulation was further enhanced by AGEs treatment. Conclusions Overloaded MF and AGEs metabolites may synergistically aggravate AB destruction by upregulating CSF‐1 and VEGF. Therefore, regulating the compressive overloading of teeth, as well as the levels of diabetic AGEs, may prove to be an effective therapeutic modality for managing DM‐induced AB destruction.

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Section: Discussionmentioning

confidence: 97%

Synergistic alveolar bone resorption by diabetic advanced glycation end products and mechanical forces

Moon

Lee

Kim

et al. 2019

Journal of Periodontology

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“…In the experimental setting, inhibition of HMGB1 release diminish ATP production and retard tumor growth [10]. Overexpression of HMGB1 in tumor tissue and increased HMGB1 serum level are near-universal in virtually every examined type of cancer, including colon carcinoma [11–13], hepatoma [14,15], breast cancer (BC) [16], pancreatic cancer [11], melanoma [17], ovarian cancer [18], and mesothelioma [19,20], indicating a carcinogenic role of HMGB1.…”

Section: Introductionmentioning

confidence: 99%

No association between HMGB1 polymorphisms and cancer risk: evidence from a meta-analysis

Liang

Yang

et al. 2018

Bioscience Reports

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The aim of the present study was to determine whether High mobility group box 1 (HMGB1) polymorphism was associated with cancer susceptibility. PubMed, Embase, and ISI Web of Science were extensively searched without language restriction. Data were extracted using a standardized data collection sheet after two reviewers scanned studies independently. The association between HMGB1 polymorphism and cancer risks was indicated as odds ratio (OR) along with its related 95% confidence interval (95%CI). Meta-analysis was conducted via RevMan 5.3 software. A total of ten studies comprising 4530 cases and 5167 controls were included in our study. Meta-analysis revealed no statistical association between rs1045411, rs1360485, rs1412125, or rs2249825 polymorphisms in HMGB1 gene and risk of cancer, either did subgroup analysis of rs1045411 stratified by cancer types and ethnic groups. Our results revealed no statistical association between current four polymorphism loci and cancer risks, suggesting that the attempt of applying HMGB1 variants as a therapeutic target or a prognosis predictor might still require a second thought. However, HMGB1 is deemed to play pleiotropic roles in cancers, we strongly call for large-scale studies with high evidence level to uncover the exact relationship between HMGB1 gene variants and cancer progression.

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“…The use of decoys may not be restricted to S100A8/A9 since each receptor's extracellular region is capable of interacting with several ligands that are related to cancer progression. For example, RAGE interacts with AGEs, HMGB1 and most S100 family proteins; MCAM interacts with galectin‐3 and Wnt5a; and EMMPRIN interacts with cyclophilin A . Thus, interactions with these factors may provide additional decoy‐mediated suppressive effects.…”

Section: Resultsmentioning

confidence: 99%

exSSSRs (extracellular S100 soil sensor receptors)‐Fc fusion proteins work as prominent decoys to S100A8/A9‐induced lung tropic cancer metastasis

Kinoshita

Sato

Yamauchi

et al. 2018

Intl Journal of Cancer

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Within the “seed and soil” theory of organ tropic cancer metastasis is a growing compilation of evidence that S100A8/A9 functions as a soil signal that attracts cancer cells to certain organs, which prove beneficial to their growth. S100A8/A9‐sensing receptors including Toll‐like receptor 4 (TLR4), advanced glycation end products (RAGE), and also important receptors we recently succeeded in identifying (EMMPRIN, NPTNβ, MCAM, and ALCAM) have the potential to become promising therapeutic targets. In our study, we prepared extracellular regions of these novel molecules and fused them to human IgG2‐Fc to extend half‐life expectancy, and we evaluated the anti‐metastatic effects of the purified decoy proteins on metastatic cancer cells. The purified proteins markedly suppressed S100A8/A9‐mediated lung tropic cancer metastasis. We hence expect that our novel biologics may become a prominent medicine to prevent cancer metastasis in clinical settings through cutting the linkage between “seed and soil”.

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Clinical Implications of High-mobility Group Box-1 (HMGB1) and the Receptor for Advanced Glycation End-products (RAGE) in Cutaneous Malignancy: A Systematic Review

Abstract: Abstract. Inflammation and the immune system play a role in the development and progression of melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC

Cited by 42 publications

References 32 publications

Synergistic alveolar bone resorption by diabetic advanced glycation end products and mechanical forces

Synergistic alveolar bone resorption by diabetic advanced glycation end products and mechanical forces

No association between HMGB1 polymorphisms and cancer risk: evidence from a meta-analysis

exSSSRs (extracellular S100 soil sensor receptors)‐Fc fusion proteins work as prominent decoys to S100A8/A9‐induced lung tropic cancer metastasis

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