Hypoxia-induced modulation of glucose transporter expression impacts 18F-fluorodeoxyglucose PET-CT imaging in hepatocellular carcinoma

Xia, Hongping; Chen, Jianxiang; Gao, Hengjun; Kong, Shik Nie; Deivasigamani, Amudha; Shi, Ming; Xie, Tian; Hui, Kam M.

doi:10.1007/s00259-019-04638-4

Cited by 29 publications

(30 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GLUT1/3 and HK2 are prognostic markers in HCC patients. Clinically, overexpression of GLUT1/3 and HK2 was associated with poor clinical outcomes, including more advanced tumor stage, greater tumor burden, higher rate of recurrence and poor survival in HCC patients [19,32,36]. Pyruvate is then converted to acetyl coenzyme A (acetyl-CoA), which fuels the TCA cycle for maximum adenosine triphosphate (ATP) production with ample oxygen (O 2 ) supply.…”

Section: Hif-mediated Induction Of Glucose Metabolism Under Hypoxiamentioning

confidence: 99%

“…PET-CT imaging found that uptake of fluorodeoxyglucose (FDG), a glucose analog, increased with decreasing O 2 availability in cancer cells [ 31 ]. Human HCC with high FDG uptake had significantly higher expression of GLUT1 and GLUT3, and these patients had shorter overall survival [ 32 ]. Most glycolytic genes, including hexokinase ( HK ), phosphofructokinase, liver type ( PFKL ), aldolase ( ALD ), triosephosphate isomerase 1 ( TPI ), glyceraldehyde-3-phosphate dehydrogenase ( GAPDH ), phosphoglycerate kinase ( PGK ), enolase 1 ( ENO1 ) and pyruvate kinase M1/2 ( PKM ), were induced by hypoxia and/or HIF-1 ( Table 1 ) [ 30 ].…”

Section: Hif-induced Metabolic Reprogramming Under Hypoxia and Drug Resistance In Hccmentioning

confidence: 99%

See 1 more Smart Citation

Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer

Bao

Wong

2021

Cells

178

121

View full text Add to dashboard Cite

Hypoxia, low oxygen (O2) level, is a hallmark of solid cancers, especially hepatocellular carcinoma (HCC), one of the most common and fatal cancers worldwide. Hypoxia contributes to drug resistance in cancer through various molecular mechanisms. In this review, we particularly focus on the roles of hypoxia-inducible factor (HIF)-mediated metabolic reprogramming in drug resistance in HCC. Combination therapies targeting hypoxia-induced metabolic enzymes to overcome drug resistance will also be summarized. Acquisition of drug resistance is the major cause of unsatisfactory clinical outcomes of existing HCC treatments. Extra efforts to identify novel mechanisms to combat refractory hypoxic HCC are warranted for the development of more effective treatment regimens for HCC patients.

show abstract

Section: Hif-mediated Induction Of Glucose Metabolism Under Hypoxiamentioning

confidence: 99%

Section: Hif-induced Metabolic Reprogramming Under Hypoxia and Drug Resistance In Hccmentioning

confidence: 99%

Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer

Bao

Wong

2021

Cells

178

121

View full text Add to dashboard Cite

show abstract

“…In RCCs, alterations in leucine and tryptophan transport by large amino acid transporters have been reported [ 4 , 38 ]. Since MET shares the same transporter system with leucine or tryptophan [ 39 ], C-11 MET PET/CT is a potential candidate for evaluating amino acid metabolism in RCCs. In this study, we found variable C-11 MET uptake in RCCs, in which increased C-11 MET uptake was correlated with high grade (AUC of 0.726 with MET SUV max cut-off > 4.3).…”

Section: Discussionmentioning

confidence: 99%

Glycolysis on F-18 FDG PET/CT Is Superior to Amino Acid Metabolism on C-11 Methionine PET/CT in Identifying Advanced Renal Cell Carcinoma at Staging

Lee

Park

Kim

et al. 2021

Cancers

View full text Add to dashboard Cite

We evaluated the value of F-18 fluorodeoxyglucose (FDG) and C-11 methionine positron emission tomography/computed tomography (PET/CT) to predict high-Fuhrman grade and advanced-stage tumours in patients with renal cell carcinoma (RCC). Forty patients with RCC underwent F-18 FDG and C-11 methionine PET/CT between September 2016 and September 2018. They were classified into limited (stages I and II, n = 15) or advanced stages (stages III and IV, n = 25) according to pathological staging. Logistic regressions were used to predict the advanced stage using various parameters, including maximum standardised uptake value (SUVmax) and metabolic tumour volume (MTV). Receiver operating characteristic analyses were performed to predict high-grade tumours (Fuhrman 3 and 4). On univariate analysis, tumour size, SUVmax and MTV of F-18 FDG and C-11 methionine, and Fuhrman grades were significant predictors for the advanced stage. On multivariate analysis, F-18 FDG MTV > 21.3 cm3 was the most significant predictor (p < 0.001). The area under the curve for predicting high-grade tumours was 0.830 for F-18 FDG (p < 0.001) and 0.726 for C-11 methionine PET/CT (p = 0.014). In conclusion, glycolysis on F-18 FDG PET/CT and amino acid metabolism on C-11 methionine PET/CT were variable but increased in high-grade RCCs. Increased MTV on F-18 FDG PET/CT is a powerful predictor of advanced-stage tumours.

show abstract

“…HCC cell metabolism ( Figure 1 ) is shifted to an increased glucose uptake through the glucose transporter 1 (GLUT1) channel [ 13 , 14 , 15 ]. GLUT1 expression is significantly associated with HCC tumorigenicity, tumor invasiveness, and growth.…”

Section: Hcc and Glucose Metabolismmentioning

confidence: 99%

“…GLUT1 expression is significantly associated with HCC tumorigenicity, tumor invasiveness, and growth. GLUT1 protein expression is increased in HCC cancer tissues and is associated with an increase in 18 F-FDG PET-CT (glucose analogue) uptake [ 13 , 14 , 15 ]. Once inside the HCC cells, glucose is converted into glucose-6-phosphate (G6P) by the activity of proteins belonging to the hexokinase (HK) protein family.…”

Section: Hcc and Glucose Metabolismmentioning

confidence: 99%

Glucose Metabolism and Oxidative Stress in Hepatocellular Carcinoma: Role and Possible Implications in Novel Therapeutic Strategies

Mossenta

Busato

et al. 2020

Cancers

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) metabolism is redirected to glycolysis to enhance the production of metabolic compounds employed by cancer cells to produce proteins, lipids, and nucleotides in order to maintain a high proliferative rate. This mechanism drives towards uncontrolled growth and causes a further increase in reactive oxygen species (ROS), which could lead to cell death. HCC overcomes the problem generated by ROS increase by increasing the antioxidant machinery, in which key mechanisms involve glutathione, nuclear factor erythroid 2-related factor 2 (Nrf2), and hypoxia-inducible transcription factor (HIF-1α). These mechanisms could represent optimal targets for innovative therapies. The tumor microenvironment (TME) exerts a key role in HCC pathogenesis and progression. Various metabolic machineries modulate the activity of immune cells in the TME. The deregulated metabolic activity of tumor cells could impair antitumor response. Lactic acid–lactate, derived from the anaerobic glycolytic rate of tumor cells, as well as adenosine, derived from the catabolism of ATP, have an immunosuppressive activity. Metabolic reprogramming of the TME via targeted therapies could enhance the treatment efficacy of anti-cancer immunotherapy. This review describes the metabolic pathways mainly involved in the HCC pathogenesis and progression. The potential targets for HCC treatment involved in these pathways are also discussed.

show abstract

Hypoxia-induced modulation of glucose transporter expression impacts 18F-fluorodeoxyglucose PET-CT imaging in hepatocellular carcinoma

Cited by 29 publications

References 31 publications

Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer

Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer

Glycolysis on F-18 FDG PET/CT Is Superior to Amino Acid Metabolism on C-11 Methionine PET/CT in Identifying Advanced Renal Cell Carcinoma at Staging

Glucose Metabolism and Oxidative Stress in Hepatocellular Carcinoma: Role and Possible Implications in Novel Therapeutic Strategies

Contact Info

Product

Resources

About