Value of glucose transport protein 1 expression in detecting lymph node metastasis in patients with colorectal cancer

BACKGROUND There are limited data on the use of glucose transport protein 1(GLUT-1)expre-ssion as a biomarker for predicting lymph node metastasis in patients with colorectal cancer.GLUT-1 and GLUT-3,hexokinase(HK)-II,and hypoxia-induced factor(HIF)-1 expressions may be useful biomarkers for detecting primary tumors and lymph node metastasis when combined with fluorodeoxyglucose(FDG)uptake on positron emission tomography/computed tomography(PET/CT).AIM To evaluate GLUT-1,GLUT-3,HK-II,and HIF-1 expressions as biomarkers for detecting primary tumors and lymph node metastasis with 18F-FDG-PET/CT.METHODS This retrospective study included 169 patients with colorectal cancer who underwent colectomy and preoperative 18F-FDG-PET/CT at Chungbuk National University Hospital between January 2009 and May 2012.Two tissue cores from the central and peripheral areas of the tumors were obtained and were examined by a dedicated pathologist,and the expressions of GLUT-1,GLUT-3,HK-II,and HIF-1 were determined using immunohisto-chemical staining.We analyzed the correlations among their expressions,various clinicopathological factors,and the maximum standardized uptake value(SUVmax)of PET/CT.RESULTS GLUT-1 was found at the center or periphery of the tumors in 109(64.5%)of the 169 patients.GLUT-1 positivity was significantly correlated with the SUVmax of the primary tumor and lymph nodes,regardless of the biopsy site(tumor center,P<0.001 and P=0.012;tumor periphery,P=0.030 and P=0.010,respectively).GLUT-1 positivity and negativity were associated with higher and lower sensitivities of PET/CT,respectively,for the detection of lymph node metastasis,regardless of the biopsy site.GLUT3,HK-II,and HIF-1 expressions were not significantly correlated with the SUVmax of the primary tumor and lymph nodes.CONCLUSION GLUT-1 expression was significantly correlated with the SUVmax of 18F-FDG-PET/CT for primary tumors and lymph nodes.Clinicians should consider GLUT-1 expression in preoperative endoscopic biopsy in interpreting PET/CT findings.

Arginine ADP-ribosyltransferase 1 Regulates Glycolysis in Colorectal Cancer via the PI3K/AKT/HIF1αPathway

Objective:Arginine ADP-ribosyltransferase 1(ART1)is involved in the regulation of a diverse array of pathophysiological processes,including proliferation,invasion,apoptosis,autophagy and angiogenesis of colorectal cancer(CRC)cells.However,how ART1 regulates glycolysis in CRC remains elusive.Methods:To elucidate the role of ART1 in glycolysis in CRC,we assessed the protein level of ART1,hypoxia-inducible factor 1α(HIF1α),and glucose transporter type 1(GLUT1)in 61 CRC tumor tissue specimens obtained from patients with different 2-[^(18)F]fluoro-2-deoxy-D-glucose(^(18)F-FDG)uptake as analyzed by PET/CT before surgery.Colon adenocarcinoma CT26 cells with ART1 knockdown and overexpression were established,respectively,and the molecular mechanism underlying the effect of ART1 on glycolysis in CRC was determined both in vivo and in vitro.Results:The expression of ART1 and GLUT1 was significantly associated with FDG uptake(P=0.037 and P=0.022,respectively)in CRC tissues.Furthermore,the expression of hexokinase 2(HK2)and lactate dehydrogenase(LDH)was upregulated in ART1-overexpressed CT26 cells,but was downregulated in ART1-knockdown CT26 cells.The volume and weight of subcutaneously transplanted tumors were markedly increased in the ART1-overexpressed BALB/c mice group and decreased in the ART1-knockdown group.In CT26 cells,the overexpression of ART1 promoted the expression levels of HK2 and LDH,and knockdown of ART1 suppressed them in the CT26 tumors.In both normal and hypoxic conditions,ART1 expression was associated with the protein level of phospho-serine/threonine kinase(p-AKT),HIF1α,and GLUT1 but not with that of AKT in CT26 cells and subcutaneous transplanted tumors.Conclusion:ART1 plays a crucial role in the elevation of glucose consumption in CT26 cells and may regulate GLUT1-dependent glycolysis in CRC via the PI3K/AKT/HIF1αpathway.

Ketogenic diet therapy in children with epilepsy caused by SLC2A1 mutations:a single-center single-arm retrospective study

Background This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency syndrome.Methods Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome sequencing.We analyzed the patients’convulsions and treatment with antiepileptic drugs.The patients were followed up at different time periods after ketogenic diet therapies.Results Six patients with SLC2A1 mutations were included in this study.The patients had seizures of different types and frequencies,and they took antiepileptic drugs to relieve their symptoms.They were then treated with a ketogenic diet for at least four months.We analyzed epilepsy control rates at 1,2,3,6,and 12 months after ketogenic diet treatment.All patients were seizure-free within a month of receiving the diet therapy.All patients were followed up for six months,three were followed up for 12 months after the treatment,and there was no recurrence of epilepsy during this period.After antiepileptic drug withdrawal,none of the patients experienced seizure relapse when receiving ketogenic diet treatment alone.No severe adverse events occurred during the therapy.Conclusions Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 mutations.Therefore,patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible.