Sublethal heat stress-induced O-GlcNAcylation coordinates the Warburg effect to promote hepatocellular carcinoma recurrence and metastasis after thermal ablation

Chen, Ye; Bei, Jiaxin; Liu, Mingyu; Huang, Jingjun; Xie, Lulu; Huang, Wensou; Cai, Mingyue; Guo, Yongjian; Li, Lin; Zhu, Kangshun

doi:10.1016/j.canlet.2021.06.001

Cited by 37 publications

(40 citation statements)

References 56 publications

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“…reported that moderate heat stress may result in insufficient ablation and stimulate HCC growth, with the mechanism partly mediated by the growth factor dependent PI3K/mTOR/AKT signaling pathway ( 9 ). Moreover, Sublethal heat stress-induced O-GlcNAcylation coordinates the Warburg effect to promote tumor progression by providing anabolic substrates to meet the high energy demand of rapid cell division ( 16 ). Several previous studies have also demonstrated insufficient thermal ablation accelerates the residual tumor progression by promoting Epithelial-Mesenchymal Transition (EMT), increasing tumor-infiltrating myeloid-derived suppressor cells (MDSCs) and reducing T-Cell-Mediated anti-tumor immune responses ( 17 , 18 ).…”

Section: Discussionmentioning

confidence: 99%

Initial Incomplete Thermal Ablation Is Associated With a High Risk of Tumor Progression in Patients With Hepatocellular Carcinoma

et al. 2021

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PurposeTo investigate whether incomplete thermal ablation is associated with a high risk of tumor progression in patients with hepatocellular carcinoma (HCC), and to compare the efficacy of repeated thermal ablation and transarterial chemoembolization (TACE) for residual tumor after incomplete ablation.MethodsThis retrospective study included 284 patients with unresectable HCC who underwent thermal ablation from June 2014 to September 2020. The response of the initially attempted ablation was classified into complete (n=236) and incomplete (n=48). The progression-free survival (PFS) and overall survival (OS) were compared between patients with complete and incomplete responses, before and after a one-to-one propensity score-matching (PSM), and between patients in whom repeated ablation or TACE was performed after a first attempt incomplete ablation.ResultsAfter PSM of the 284 patients, 46 pairs of patients were matched. The PFS was significantly higher in the complete response group than in the incomplete response group (P<0.001). No difference in OS was noted between two groups (P=0.181). After a first attempt incomplete ablation, 29 and 19 patients underwent repeated ablation and TACE, respectively. There were no significant differences in PFS (P=0.424) and OS (P=0.178) between patients who underwent repeated ablation and TACE. In multivariate Cox regression analysis, incomplete response (P<0.001) and Child-Pugh class B (P=0.017) were independent risk factors for tumor progression, while higher AFP level (P=0.011) and Child-Pugh class B (P=0.026) were independent risk factors for poor OS.ConclusionAlthough patients with incomplete ablation are associated with tumor progression compared with those with complete ablation, their OS is not affected by incomplete ablation. When patients present with residual tumors, TACE may be an alternative if repeated ablation is infeasible.

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Section: Discussionmentioning

confidence: 99%

Initial Incomplete Thermal Ablation Is Associated With a High Risk of Tumor Progression in Patients With Hepatocellular Carcinoma

et al. 2021

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“…8–10 Moreover, insufficient thermal ablation could induce angiogenesis and aggravate hypoxia in tumors, resulting in increased local recurrence and distance metastasis. Accumulating evidence has shown that high expressions of VEGF and CD31 and elevation of HIFs were observed after insufficient MW ablation 11–13 and insufficient radiofrequency ablation (RFA). 14–19 Inhibition of tumor recurrence following MW ablation remains a challenge in clinic, as evidenced by three-year clinical postablation recurrence data, 20 which threatened the prognosis and lifetime of patients with cancer.…”

Section: Introductionmentioning

confidence: 99%

Graphene-containing metal–organic framework nanocomposites for enhanced microwave ablation of salivary adenoid cystic carcinoma

Tian

Zhu

et al. 2022

Nanoscale Adv.

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“…Despite the current progress of hepatocellular carcinoma (HCC)-related research, the overall prognosis of advanced HCC is still poor (1,2). Increasing evidence has indicated that aberrant glucose metabolism (aerobic glycolysis/Warburg effect) is a hallmark of HCC and is active in the tumor microenvironment, tumor proliferation, drug-resistance, or epithelial-mesenchymal transition (EMT) (3)(4)(5). The liver is a pivotal organ responsible for the body's energy metabolism and the excessive uptake of glucose by HCC cells is the key to abnormal metabolism, a mechanism which is mediated by glucose transporters (GLUT) (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma

et al. 2021

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BAY-876 is an effective antagonist of the Glucose transporter type 1 (GLUT1) receptor, a mediator of aerobic glycolysis, a biological process considered a hallmark of hepatocellular carcinoma (HCC) together with cell proliferation, drug-resistance, and metastasis. However, the clinical application of BAY-876 has faced many challenges. In the presence study, we describe the formulation of a novel microcrystalline BAY-876 formulation. A series of HCC tumor models were established to determine not only the sustained release of microcrystalline BAY-876, but also its long-acting antitumor activity. The clinical role of BAY-876 was confirmed by the increased expression of GLUT1, which was associated with the worse prognosis among advanced HCC patients. A single dose of injection of microcrystalline BAY-876 directly in the HCC tissue achieved sustained localized levels of Bay-876. Moreover, the single injection of microcrystalline BAY-876 in HCC tissues not only inhibited glucose uptake and prolonged proliferation of HCC cells, but also inhibited the expression of epithelial-mesenchymal transition (EMT)-related factors. Thus, the microcrystalline BAY-876 described in this study can directly achieve promising localized effects, given its limited diffusion to other tissues, thereby reducing the occurrence of potential side effects, and providing an additional option for advanced HCC treatment.

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Sublethal heat stress-induced O-GlcNAcylation coordinates the Warburg effect to promote hepatocellular carcinoma recurrence and metastasis after thermal ablation

Cited by 37 publications

References 56 publications

Initial Incomplete Thermal Ablation Is Associated With a High Risk of Tumor Progression in Patients With Hepatocellular Carcinoma

Initial Incomplete Thermal Ablation Is Associated With a High Risk of Tumor Progression in Patients With Hepatocellular Carcinoma

Graphene-containing metal–organic framework nanocomposites for enhanced microwave ablation of salivary adenoid cystic carcinoma

A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma

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