Tumor cell membrane-coated continuous electrochemical sensor for GLUT1 inhibitor screening / 药物分析学报

Glucose transporter 1(GLUT1)overexpression in tumor cells is a potential target for drug therapy,but few studies have reported screening GLUT1 inhibitors from natural or synthetic compounds.With cur-rent analysis techniques,it is difficult to accurately monitor the GLUT1 inhibitory effect of drug molecules in real-time.We developed a cell membrane-based glucose sensor(CMGS)that integrated a hydrogel electrode with tumor cell membranes to monitor GLUT1 transmembrane transport and screen for GLUT1 inhibitors in traditional Chinese medicines(TCMs).CMGS is compatible with cell membranes of various origins,including different types of tumors and cell lines with GLUT1 expression knocked down by small interfering RNA or small molecules.Based on CMGS continuous monitoring technique,we inves-tigated the glucose transport kinetics of cell membranes with varying levels of GLUT1 expression.We used CMGS to determine the GLUT1-inhibitory effects of drug monomers with similar structures from Scutellaria baicalensis and catechins families.Results were consistent with those of the cellular glucose uptake test and molecular-docking simulation.CMGS could accurately screen drug molecules in TCMs that inhibit GLUT1,providing a new strategy for studying transmembrane protein-receptor interactions.

Research progress on T cell glycolytic metabolism in oral lichen planus / 口腔疾病防治

@#Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa. The pathogenesis of OLP is still unclear. Immune abnormalities mediated by T cells and related cytokines play a crucial role in the pathogenesis of OLP. In recent years, glycolytic metabolism-related transporters, enzymes and regulators, such as glucose transporter-1 (Glut1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase A (LDHA), mammalian target of rapamycin (mTOR) and hypoxia inducible factor-1α (HIF-1a), have attracted an increasing amount of attention in OLP by regulating the proliferation and differentiation of T cells and the secretion of inflammatory factors. It has been shown that 2-deoxy-D-glucose (2-DG) or rapamycin (RAPA) inhibits the glycolytic metabolism of T cells and then inhibits OLP. This article reviews the research progress of glycolytic metabolism-related transporters, enzymes and regulatory factors in OLP in recent years.

The diagnostic value of glucose transporter 1 level of erythrocyte membrane and glucose uptake rate of erythrocytes in glucose transporter type 1 deficiency syndrome / 中华实用儿科临床杂志

Objective:To explore new methods to assist the diagnosis of glucose transporter type 1 deficiency syndrome (GLUT1-DS).Methods:Sixteen children with epilepsy and/or movement disorder carrying the SLC2A1 mutation who admitted to Department of Pediatrics, the First Medical Center, Chinese People′s Liberation Army General Hospital and Department of Nutrition, Shanghai Deji Hospital from October 2019 to October 2020 were retrospectively analyzed.GLUT1-DS was diagnosed based on clinical phenotype, glucose level in CSF and/or genetic testing results.Forty-four healthy children who underwent physical examination in the First Medical Center, Chinese People′s Liberation Army General Hospital during the same period were selected as healthy control group.Glucose transporter 1 (GLUT1) level on the membrane surface of peripheral red blood cells and erythrocyte glucose uptake rate were measured by flow cytometry and glucose oxidase method, respectively.Their differences between groups were compared by the rank sum test.The receiver operating cha-racteristic (ROC) curve was plotted to assess their diagnostic value. Results:Sixteen children were diagnosed as GLUT1-DS.GLUT1 levels of 16 children with GLUT1-DS were significantly lower than those of healthy control group [17.96% (13.43%, 22.12%) vs.27.93% (24.76%, 34.30%), Z=5.249, P<0.001]. Area under curve (AUC) was 0.946, and weighted Kappa was 0.791 ( P<0.001). The erythrocyte glucose uptake was measured in 12 children with GLUT1-DS, which was significantly lower than that of healthy control group [23.14% (14.80%, 26.45%) vs.27.40% (24.61%, 32.82%), Z=2.366, P=0.018]. AUC and weighted Kappa were 0.724 and 0.344, respectively ( P<0.001), showing a poor consistency. Conclusions:GLUT1 level on the surface of human erythrocyte membrane measured by flow cytometry may be a new method to assist the diagnosis of GLUT1-DS.The erythrocyte glucose uptake rate test requires stricter experimental conditions and needs further investigation.

HIF / 中南大学学报(医学版)

OBJECTIVES@#To analyze the expressions and distributions of hypoxia-inducible factor-1α (HIF-1α), CD147, and glucose transporter 1 (GLUT1) in epidermis from psoriasis vulgaris and normal people, and to explore the associations among these proteins and their roles in hypoxic HaCaT cell line.@*METHODS@#The expression levels of HIF-1α, CD147, and GLUT1 were determined by immunohistochemistry staining in skin biopsies from 48 psoriasis vularis patients and 33 healthy subjects. Cobalt chloride (CoCl@*RESULTS@#HIF-1α, CD147, and GLUT1 were highly expressed and the glycolytic capacity was increased in lesions of psoriasis vulgaris; HIF-1α upregulated the expression of CD147 and GLUT1, increased the lactate production and decreased the ATP level in CoCl@*CONCLUSIONS@#Glycolytic capacity increases in the injured keratinocytes of psoriasis vulgaris, suggesting that HIF-1α, CD147, and GLUT1 are associated with glycolysis, which can be considered as the promising targets for psoriasis therapy.

Progress in the clinical application and correlation between glucose transporter-1 and / 生物医学工程学杂志

Because of the unobvious early symptoms and low 5-year survival rate, the early diagnosis and treatment is of great significance for patients with non-small cell lung cancer. Glucose transporter-1 is the most widely distributed glucose transporters in various tissue cells in the human body, whose expression in non-small cell lung cancer is closely related to the histological types, lymph node metastasis, degree of differentiation, progression and prognosis.

Effect of Sijunzi Decoction on regulation of Aβ-related proteins across blood-brain barrier / 中国中药杂志

According to traditional Chinese medicine, "spleen transport" is closely related to the metabolism of substance and energy. Studies have shown that Alzheimer's disease(AD) is a disease related to glucose and lipid metabolism and energy metabolism. The traditional Chinese medicine Jiangpi Recipe can improve the learning ability and memory of AD animal model. Sijunzi Decoction originated from Taiping Huimin Hefang Prescription is the basic prescription for strengthening and nourishing the spleen, with the effects of nourishing Qi and strengthening the spleen. In this experiment, human brain microvascular endothelial cells(HBMEC) and Sijunzi Decoction water extract(0.25, 0.5, 1 mg·L~(-1)) were pre-incubated for 2 h, and then Aβ_(25-35) oligomers(final concentration 40 μmol·L~(-1)) was added for co-culture for 22 hours. The effect of Sijunzi Decoction on the activity of Aβ_(25-35) oligomer injured cells and the expression of related proteins were investigated. Q-TOF-LC-MS was used first for principal component analysis of Sijunzi Decoction water extract. Then MTT assay was used to investigate the effect of Sijunzi Decoction water extract on the proliferation of HBMEC cells. Real-time fluorescence quantitative PCR(RT-qPCR) was employed to detect the mRNA expression of GLUT1, RAGE, and LRP1. The expression of Aβ-related proteins across blood-brain barrier(RAGE, LRP1) was detected by Western blot. The results showed that 40 μmol·L~(-1) Aβ_(25-35) oligomers could induce endothelial cell damage, reduce cell survival, increase expression of RAGE mRNA and RAGE protein, and reduce expression of GLUT1 mRNA, LRP1 mRNA, and LRP1 protein. Sijunzi Decoction water extract could reduce the Aβ_(25-35) oligomer-induced cytotoxicity of HBMEC, decrease the expression of RAGE mRNA and RAGE protein, and increase the expression of GLUT1 mRNA, LRP1 mRNA and LRP1 protein. The results indicated that Sijunzi Decoction could reduce the injury of HBMEC cells induced by Aβ_(25-35) oligomer, and regulate the transport-related proteins GLUT1, RAGE and LRP1, which might be the mechanism of regulating Aβ_(25-35) transport across the blood-brain barrier.

Effect of Zhenxin Shengshui Yizhi Fang on Damage of Human Brain Microvascular Endothelial Cells Induced by Aβ25-35 / 中国实验方剂学杂志

Objective::To observe the neuroprotective effect and potential mechanism of Zhenxin Shengshui Yizhi Fang(XSF) aqueous extract on human brain microvascular endothelial cells (HBMEC) injury induced by amyloid-β protein(Aβ)25-35. Method::HBMEC cells damage induced by Aβ25-35 was used as Alzheimer' s disease(AD) cell model. The study included control group, Aβ25-35 group, and low, medium and high-dose XSF aqueous extract groups (125, 250, 500 mg·L-1). After treatment, the cytotoxicity of different concentrations of drugs and Aβ25-35 was determined by methyl thiazolyl tetrazolium(MTT) colorimetry. Apoptosis was observed by Hoechst-33258 staining. The activity of Caspase-3 was detected by colorimetry. Western blot was used to detect the expression levels of the receptor of advanced glycation end products (RAGE) and low-density lipoprotein receptor-related protein (LRP1). Result::Compared with the control group, the cell viability of Aβ25-35 group was significantly decreased (P<0.01). Hoechst-33258 staining showed bright blue fluorescence, chromatin condensation, dense staining or fragmentation dense staining, whitening in color, and significant increase of the percentage of apoptotic cells (P<0.01). Caspase-3 activity increased significantly (P<0.01). Western blot showed that RAGE protein expression increased significantly (P<0.01), while low-density lipoprotein receptor-related protein(LRP1), glucose transporter 1(GLUT1) and GLUT3 protein expressions decreased significantly (P<0.01). Compared with the Aβ25-35 group, the cell viability of XSF aqueous extract groups was significantly increased in a dose-dependent manner. The XSF aqueous extract had a more significant protective effect of than the other groups (P<0.05). The XSF aqueous extract group (500 mg·L-1) significantly inhibited the number of apoptotic cells (P<0.01), but significantly reduced the Caspase-3 activity (P<0.01). RAGE protein expression was not significantly decreased in XSF aqueous extract group (125 mg·L-1), but significantly decreased in XSF aqueous extract group (250, 500 mg·L-1, P<0.01), while LRP1, GLUT1 and GLUT3 protein expression significantly increased (P<0.05, P<0.01) in a dose-dependent manner. Conclusion::XSF aqueous extract can attenuate the cytotoxicity of HBMEC induced by Aβ25-35 oligomer, inhibit apoptosis, decrease caspase-3 activity and RAGE protein expression, increase LRP1, GLUT1 and GLUT3 protein expressions, and reduce the abnormal accumulation and deposition of Aβ in the brain, which may be its mechanisms for prevention and treatment of AD.

Effect of Zhenxin Xingshui Yizhi Fang and Its Essential Oil Extract on Ability of Learning and Memory in Alzheimer's Disease Model Mice / 中国实验方剂学杂志

Objective: The present study was designed to investigate the modulating effect of Zhenxin Xingshui Yizhi Fang and its essential oil extract on cognitive deficits in mice.Method: For the purpose of this study 5 months old APP/PS1 double transgenic mice and wild-type C57BL/6JNju were selected as experimental animals.Then APP/PS1 double transgenic mice were randomly divided into model group,essential oil low and high-dose groups (12.13,48.50 mg·L-1),Zhenxin Xingshui Yizhi Fang group (0.46 g·kg-1).Meanwhile,wild-type C57BL/6JNju mice were used as a normal group.APP/PS1 double transgenic mice were treated with Zhenxin Xingshui Yizhi Fang and its essential oil extract for 22 consecutive days.Mice were subjected to a Morris water maze test and a platform test in order to determine their cognitive effect.Nissl's staining was used to observe pathological changes in brain tissue.Meanwhile,senile plaques (SP) were observed by employing Thioflavin-S staining.The expression of glucose transporter 1(GLUT1) and insulin receptor substrate-1(IRS-1) were analyzed using immunohistochemistry techniques.The levels of neurotransmitters such as acetylcholine (ACH),glutamate (GLU) and γ-aminobutyric acid (GABA) in the hippocampus were quantified by enzyme-linked immunosorbent assay (ELISA).Result: The memory function was significantly reduced in model group,and severe brain injury and neuronal apoptosis were also observed in comparison to normal group (PPPPPPPConclusion: These results indicate that Zhenxin Xingshui Yizhi Fang and its essential oil extract could ameliorate cognitive deficits and GLUT1 and IRS-1 could be a possible therapeutic target for AD.It may be an interesting approach to the treatment of Alzheimer's disease.

Curcumin reduces the invasion and migration abilities of papillary thyroid carcinoma TPC1 cells / 医学研究生学报

Objective Comparatively few studies are reported on the invasion and migration of papillary thyroid carcinoma (PTC) TPC1 cells. This study was to investigate the effects of curcumin on the invasion and migration abilities of TPC1 cells and its possible action mechanisms.MethodsWe treated TPC1 single cell suspension with curcumin at the concentrations of 0 (DMSO solvent), 10, 20, 40, 60, 80 and 100 μmol/L. At 24 and 48 hours after exposure, we examined the inhibitory effect of curcumin on the cells by CCK8 assays, detected the migration and invasion abilities of the TPC1 cells by Transwell and wound healing assay, and determined the gene and protein expressions Glut1 and MT1MMP by RTPCR and Western blot, respectively.ResultsThere were statistically significant differences in the cell viability among different groups of the TPC1 cells (P<0.05) as well as in the cell migration ability at 24 hours between any two groups of the cells treated with curcumin at 0 μmol/L (\[0.842±0.096\] mm), 10 μmol/L (\[0.911±0.049\] mm), 20 μmol/L (\[0.926±0.107\] mm) and 40 μmol/L (\[1.076±0.093\] mm) (P<0.05) and at 48 hours (P<0.05). Statistically significant differences were also observed between any two of the 0, 10, 20 and 40 μmol/L groups in the number of migrated cells (196, 142, 57, and 17/100x visual field) (P<0.05) as well in the protein expression of Glut1 (0.786±0.112, 0.518±0.106, 0.359±0.121, and 0.266±0.087) (P<0.05) and the mRNA and protein expressions of MT1MMP (P<0.05).ConclusionCurcumin can inhibit the invasion and migration of thyroid papillary carcinoma TPC1 cells, which may be associated with the decreased expressions of Glut1 and MT1MMP.

Matrix stiffness impacts the morphology and the levels of glucose transporter proteins in human renal tubular epithelial cells / 药学学报

As the common pathway of chronic renal diseases leading to end-stage renal failure, renal tubulointerstitial fibrosis is characterized by the deposition of extracellular matrix and scar hardening. Our study aimed to construct an in vitro cell culture platform to explore the impact of matrix stiffness on cell morphology and function of renal tubular epithelial cells. Photopolymerized polyacrylamide gels (PAA gel) with varying stiffnesses as model substrates was selected to simulate the matrix stiffness of normal and fibrotic renal tissues with elastic moduli ranging from 1 to 40 kPa. The human renal tubular epithelial cells (HK-2) were seeded on the surface of PAA gels. The impact of matrix stiffness on the morphology of HK-2 were investigated via immunofluorescence staining and confocal microscopy. The expression levels of glucose transporter 1 (GLUT1), glucose transporter 2 (GLUT2), glucose transporter 5 (GLUT5) were semi-quantitatively analyzed. With increasing matrix stiffness, both the levels of GLUT1 and GLUT5 in HK-2 cells were significantly decreased, whereas the expression level and the distribution pattern of GLUT2 in HK-2 remained unchanged with stiffness variation.

Expression of HIF-1α ,GLUT-1 and LDH-5 in gastric cancer tissues and their correlation with pathological features / 国际检验医学杂志

Objective To investigate the expression of hypoxia inducible factor 1α (HIF-1α) ,glucose trans-porter-1 (GLUT-1) and lactate dehydrogenase-5 (LDH-5) in gastric cancer tissues and their correlation with pathological features.Methods From June 2015 to June 2017 ,93 cases of gastric cancer resection were select-ed as the observation group ,and the cancer adjacent tissues were taken as the control group.Immunohisto-chemical staining was used to detect the expression of HIF-1α ,GLUT-1 and LDH-5.The gastric cancer tissues from 93 patients with gastric cancer who underwent gastrectomy in the hospital were taken as the observation group ,and the adjacent tissues were taken as the control group.The expressions of HIF-1α ,GLUT-1 and LDH-5 in two groups were determined by Immunohistochemical MaxVision Ⅲ method.The positive expres-sions of HIF-1α ,GLUT-1 and LDH-5 in two groups were compared ,and the correlation between HIF-1α , GLUT-1 and LDH-5 in gastric cancer tissues ,and the expressions of HIF-1α ,GLUT-1 and LDH-5 in different sex ,age ,clinical stage and differentiation degree were compared.Results The positive expression rates of HIF-1α ,GLUT-1 and LDH-5 in the observation group were higher than those in the control group ,and the differences were statistically significant (P＜ 0.05) ;HIF-1α ,GLUT-1 and LDH-5 were positively correlated with each other ;there were no significant differences of HIF-1α ,GLU T-1 and LDH-5 levels in different gender group and different age group (P＞0.05) ;the positive expression rates of HIF-1α ,GLU T-1 and LDH-5 at Ⅲ and Ⅳ stages were higher than those at Ⅰ and Ⅱ stages ,the positive expression rates of HIF-1α ,GLUT-1 and LDH-5 of low differentiation were higher than those of high and middle differentiation and the differences were statistically significant (P＜ 0.05).Conclusion The high expressions of HIF-1α ,GLUT-1 and LDH-5 were observed in gastric cancer tissue.HIF-1α ,GLUT-1 and LDH-5 were linearly and positively correlated with each other ,and had a significant correlation with the clinicopathological features.With the increase of clinical stage and the degree of differentiation ,the expression of HIF-1 a ,GLUT-1 and LDH-5 were higher.

Effects of polysaccharides from Ginkgo biloba on proliferation of 4T1 breast cancer cells and expression of GLUT family genes / 中国药理学通报

Aim To investigate the effects of polysac-charides from Ginkgo biloba on the proliferation, apop-tosis of mouse 4T1 breast cancer cells and the possible mechanism. Methods 4T1 cells in logarithmic growth phase were treated with polysaccharides from Ginkgo biloba of different concentrations. The effect of poly-saccharides from Ginkgo biloba on inhibition of prolif-eration and cytotoxicity of 4T1 cells was determined by MTT assay and trypan blue exclusion assay respective-ly. The apoptotic effect of polysaccharides from Ginkgo biloba on 4T1 cells was detected by DAPI staining. qRT-PCR experiments were carried out for the detec-tion of gene expressions of the glucose transporter fami-ly upon the treatment with the polysaccharides from Ginkgo biloba. Results Polysaccharides from either Ginkgo biloba leaf or Ginkgo biloba exocarp significant-ly inhibited the proliferation of 4T1 cells in a dose-and time-dependent manner. Moreover, with the increasing doses of polysaccharides, cell viability decreased, ac-companied by the increased cell cytotoxicity and apop-tosis. qRT-PCR results showed that polysaccharides from Ginkgo biloba significantly reduced glucose trans-porter 1 gene expression. Conclusions Polysaccha-rides from Ginkgo biloba can both inhibit 4T1 cell pro-liferation and induce cell apoptosis, and by regulating glucose transporter family gene expression, it interfered with cell energy metabolism, which infers that the effects of cell proliferation inhibition as well the apopto-sis induction might be due to the regulation of glucose transporter family gene expression.

Glucose transporter-1 promotes migration of osteosarcoma MG63 cells via the Wnt/β-catenin pathway / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To explore the mechanism of glucose transport protein-1(Glut-1) promoting the migration of osteosarcoma MG63 cells through Wnt/β-catenin pathway. Methods: RNA interference recombinant adenovirus targeting Glut-1 gene (Ad-Glut-siRNA) and control recombinant adenovirus (Ad-GFP) were constructed and transfected into MG63 cells to silence Glut-1 gene expression. The cell migration ability of Blank group, Ad-AFP group, Ad-Glut-siRNA group and AZD2858 (inhibitor of GSK-3) group were detected by Transwell chamber migration assay. Immunofluorescence assay was used to detect the expression of E-cadherin and vimentin in each group and the nuclear translocation of β-catenin. The expression of MMP-2 and MMP-9 in each group and FZD7, β-catenin, Dsh protein in Blank group, Ad-AFP group, Ad-Glut-siRNA group were detected by Western blotting assay. Results: The migration ability of MG63 cells was significantly decreased (P<0.05) after Glut-1 gene silencing, which was restored afterAZD2858 treatment (P <0.05). Compared with Blank group and Ad-GFP group, the E-cadherin level in MG63 cells in Ad-Glut-siRNA group was significantly increased (P<0.05), while the expressions of vimentin, MMP-2, MMP-9, FZD7, β-catenin and Dsh protein were significantly reduced (all P<0.05). Compared with Ad-Glut-siRNA group, E-cadherin expression of AZD2858 group was significantly reduced, while the expressions of vimentin, MMP-2, MMP-9 were significantly up-regulated (P<0.05). Conclusion: The high expression of Glut-1 gene is closely related to the invasion and metastasis of MG63 cells. The possible mechanism is that the high expression of Glut-1 leads to the activation of Wnt/β-catenin pathway, which leads to the decrease of EMT-related protein E-cadherin, and the increase of vimentin and MMP-2, MMP-9, and further promotes the migration of MG63 cells.

Case report of congenital glucose-galactose malabsorption in China and literature review / 中国新生儿科杂志

Objective To study the clinical features of congenital glucose-galactose malabsorption (CGGM),and to improve the understanding of CGGM.Method Clinical manifestations and treatment process of one patient with CGGM in our hospital were retrospectively analyzed.From 1966 to 2016 May,Chinese medical database and PUBMED were searched using Malabsorption syndrome,dehydration,hypernatremia , diarrhea , newborn , carbohydrate metabolism ,andglucose/galactose malabsorption as key words.The clinical features of CGGM reported in literatures were summarized.Result The patient in our hospital was a full-term female infant naturally delivered.The onset of the disease was on the 9th day after birth,and the clinical manifestations included severe diarrhea,severe dehydration,hypernatremia,metabolic acidosis and malnutrition.After intravenous infusion and symptomatic treatment,dehydration,hypernatremia and metabolic acidosis were corrected.However,there was no improvement of diarrhea characterized with watery and acidic stools,and neither was weight gain.Glucose loading test was negative,and fructose loading test was positive.Diarrhea was improved markedly using diagnostic carbohydrate-free formula,so CGGM was diagnosed clinically.SLC5A1 homozygous IVS7-2 A ＞ G mutation was detected which confirmed the diagnosis of CGGM.With carbohydrate-free formula feeding,the body weight of the infant was increased.Followed up for 2 months now,her body length and body weight were at P25 and P22 on growth curve respectively,and no obvious neurological sequela was observed.Our literature review revealed 7 reports including 48 cases of CGGM children.Literature review showed that:most children with CGGM (79.2％) had the onset within 7 days of life;main clinical features included diarrhea (100％),dehydration (100％),and malnutrition (54.2％);22.9％ of patients with carbohydrate-free formula and 27.1％ with fructose matrix formula were fed well;no death was detected,77.1％ had normal weight gain,and 91.7％ had normal development of the nervous system.Conclusion CGGM is rare.The symptoms include severe watery and acidic stools with onset during neonatal period.CGGM is associated with severe complications such as hypertonic dehydration and hypernatremia.The diagnosis is established based upon typical clinical manifestations,sugar loading test and SLC5A1 gene detection.Carbohydrate-free formula feeding is effective.

The clinical feature of glucose transporter 1 deficiency syndrome and literature review / 中国小儿急救医学

Objective To investigate the clinical features of glucose transporter 1 deficiency syndrome(GLUT1-DS) and summarize the characteristics of GLUT1-DS through reviewing related references.Methods The clinical data including manifestation,cerebrospinal fluid (CSF) glucose,electroencephalogram,MRI and gene mutation of a patient with GLUT1-DS was collected and the related literatures were reviewed.Results The patient was a 6 years old boy.The patient,whose seizures occurred at the age of 9 month-old and prolonged to 6 year-old,attacked before breakfast.Physical examination showed microcephaly with head circumference 47.5 cm.Laboratory tests showed that CSF glucose decreased (1.87 mmol/L) and CSF-serum ratio was 0.36.And meantime the MRI was normal and electroencephalogram showed general spike and slow wave complex paroxysm.Mutation of SLC2A1 gene,c.350_385del,was found in the patient.There were 219 cases with GLUT1-DS had been reported and the age of onset was 15.69 months.In 219 patients,159 cases (72％) suffered seizures,105 cases (47％) had motor abnormalities,61 cases (27％) suffered intellectual disability.The CSF glucose values were (1.92±0.31) mmol/L,CSF-serum ratio was 0.36±0.07.SLC2A1 gene mutations were detected in 183 patients(96％)in which missense mutation was the most mutation.Conclusion A wide range of phenotypes of GLUT1-DS include seizures,motor abnormalities,mental retardation.The diagnosis is confirmed when CSF glucose and CSF-serum ratio are continuously decreased which in the absence of meningitis.The SLC2A1 gene should be detected in suspicion of GLUTI-DS patients.Early diagnosis and treatment may improve the prognosis of those GLUTI-DS patients.

Research progress on relationship between glucose transporter 1 and tumor energy metabolism / 中国药理学通报

The study on tumor metabolism has been gradually be-come a hot spot in recent years .A lot of proteins involved in the regulation of tumor metabolism especially the glucose transporter protein 1(GLUT1).As a key regulatory factor mediating energy metabolism within tumor cells , GLUT1 can regulate the glucose intake and maintain the basic level of metabolism in tumor cells . More importantly, the abnormal expression of GLUT1 was asso-ciated with many kinds of tumors , of which GLUT1 was used to meet the energy requirement for the fast growth of tumor .Thus GLUT1 also played a crucial role in growth , differentiation and metastasis of tumor cells and prognosis of tumors .Meanwhile , as three-dimensional crystal structure of GLUT 1 was determined , it is possible to design the small molecular inhibitors of GLUT 1, which can realize “starve to death” tumor cells.GLUT1 can be a particularly attractive target for tumor treatment and interfer-ence.The relationship between abnormal expression of GLUT 1 protein and tumor metabolism was reviewed . Moreover , the mechanism of tumor metabolism regulated by GLUT 1 protein ex-pression and treatment of cancers were discussed , which may provide references for future research and clinical treatment .

Extranodal Nasal NK/T-Cell Lymphoma: A Rare Oral Presentation and FASN, CD44 and GLUT-1 Expression

Extranodal natural killer (NK)/T-cell lymphoma is an aggressive malignant tumor with distinctive clinicopathological features, characterized by vascular invasion and destruction, prominent necrosis, cytotoxic lymphocyte phenotype and a strong association with Epstein-Barr virus. Here is reported an extranodal nasal NK/T-cell lymphoma case, involving the maxillary sinus, floor of the orbit, and interestingly extending to the oral cavity through the alveolar bone and buccal mucosa, preserving the palate, leading to a primary misdiagnosis of aggressive periodontal disease. Moreover, this work investigated for the first time the immunohistochemical expression of fatty acid synthase (FASN) and glucose transporter 1 (GLUT-1) proteins in this neoplasia. FASN showed strong cytoplasmatic expression in the neoplastic cells, whereas GLUT-1 and CD44 were negative. These findings suggest that the expression of FASN and the loss of CD44 might be involved in the pathogenesis of the extranodal nasal NK/T-cell lymphoma, and that GLUT-1 may not participate in the survival adaptation of the tumor cells to the hypoxic environment. Further studies with larger series are required to confirm these initial results.

O linfoma de células natural killers (NK)/T extranodal é um tumor maligno agressivo com características clinicopatológicas distintas, caracterizadas por invasão e destruição vasculares, necrose proeminente, fenótipo linfocítico citotóxico e uma forte associação com o vírus Epstein-Barr. Relatamos aqui um caso de linfoma de células NK/T nasal extranodal, envolvendo o seio maxilar, assoalho de órbita, e interessantemente estendendo-se para a cavidade oral através do osso alveolar e mucosa vestibular, preservando o palato, levando a um diagnóstico inicial equivocado de doença periodontal agressiva. Ainda, nós investigamos pela primeira vez a expressão imunoistoquímica das proteínas Fatty acid sinthase (FASN) e glucose transporter 1 (GLUT-1) nesta neoplasia. FASN revelou uma forte expressão citoplasmática nas células neoplásicas, enquanto GLUT-1 e CD44 foram negativas. Estes achados sugerem que a expressão de FASN e a perda de CD44 podem estar envolvidas na patogênese do linfoma de células NK/T nasal extranodal, e que GLUT-1 não deve participar da adaptação das células tumorais ao ambiente de hipóxia. Estudos adicionais com séries maiores são necessários para confirmar nossos resultados iniciais.

The analysis and expression of human epidermal growth factor-2,ventricular endothelial growth factor,glucose transporter-1 in breast cancer with lymph metastasis / 中国医师进修杂志

Objective To analyze the expression of human epidermal growth factor (HER)-2,ventricular endothelial growth factor (VEGF),glucose transporter (GLUT)-1 in breast cancer with lymph metastasis.Methods Eighty cases with breast cancer were selected,and 46 cases without lymph metastasis (non-lymph metastasis group),34 cases with lymph metastasis (lymph metastasis group).Immunohistochemical staining SP was used to detect the expression of HER-2,VEGF,GLUT-1.The level of HER-2,VEGF,GLUT-1 in different grade was analyzed.Results The positive expression of HER-2,VEGF,GLUT -1 was 13.0％(6/46),45.7％(21/46),17.4％(8/46) in non-lymph metastasis group,and 88.2％(30/34),88.2％ (30/34),88.2％ (30/34) in lymph metastasis group.There was significant difference between two groups(P ＜ 0.01 or ＜ 0.05).There was significant difference in the expression of HER-2,VEGF,GLUT-1 in grade Ⅰ,Ⅱ,Ⅲ between two groups (P＜0.01).Conclusion HER-2,GLUT-1 and VEGF in breast cancer with lymph metastasis for high expression,different tumor classification expresses different.

The Glycolytic Phenotype is Correlated with Aggressiveness and Poor Prognosis in Invasive Ductal Carcinomas / 한국유방암학회지

PURPOSE: Glucose uptake and glycolytic metabolism are enhanced in cancer cells, and increased expression of glucose transporter 1 (GLUT1) has also been reported. The aim of this study was to investigate GLUT1 expression in human breast tissues and invasive ductal carcinomas. METHODS: We used tissue microarrays consisting of normal breast tissue, ductal hyperplasia, ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastases. We examined GLUT1 expression in the microarrays by immunohistochemistry, reviewed the medical records and performed a clinicopathological analysis. RESULTS: Membranous GLUT1 expression was observed in normal and tumor cells. GLUT1 expression was higher in ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastasis than in normal tissue and ductal hyperplasia (p=0.002). Of 276 invasive ductal carcinomas, 106 (38.4%) showed GLUT1 expression. GLUT1 expression was correlated with higher histologic grade (p<0.001), larger tumor size (p=0.025), absence of estrogen receptor (p<0.001), absence of progesterone receptor (p<0.001), and triple-negative phenotype (p<0.001). In univariate survival analysis, patients with GLUT1 expression had poorer overall survival and disease-free survival (p=0.017 and p=0.021, respectively, log-rank test). In multivariate survival analysis with the Cox proportional hazards model, GLUT1 expression was an independent prognostic factor of poorer overall survival and disease-free survival (p=0.017 and p=0.019, respectively). CONCLUSION: GLUT1 expression seems to play an important role in malignant transformation, and the glycolytic phenotype in invasive ductal carcinoma may indicate aggressive biological behavior and a worse prognosis.

Correlation between glucose transporter type-1 expression and 18F-FDG uptake on PET in oral cancer

OBJECTIVES: Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) is a non-invasive diagnostic tool for many human cancers wherein glucose uptake transporter-1 (GLUT-1) acts as a main transporter in the uptake of 18F-FDG in cancer cells. Increased expression of glucose transporter-1 has been reported in many human cancers. In this study, we investigated the correlation between 18F-FDG accumulation and expression of GLUT-1 in oral cancer. MATERIALS AND METHODS: We evaluated 42 patients diagnosed with oral squamous cell carcinoma (OSCC) and malignant salivary gland tumor as confirmed by histology. 42 patients underwent pre-operative 18F-FDG PET, with the maximum standardized uptake value (SUVmax) measured in each case. Immunohistochemical staining was done for each histological specimen, and results were evaluated post-operatively according to the percentage (%) of positive area, intensity, and staining score. RESULTS: For OSCC, SUVmax significantly increased as T stage of tumor classification increased. For malignant salivary gland tumor, SUVmax significantly increased as T stage of tumor classification increased. For OSCC, GLUT-1 was expressed in all 36 cases. GLUT-1 staining score (GSS) increased as T stage of tumor classification increased, with the difference statistically significant. For malignant salivary gland tumor, GLUT-1 expression was observed in all 6 cases; average GSS was significantly higher in patients with cervical lymph node metastasis than that in patients without cervical lymph node metastasis. Average GSS was higher in OSCC (11.11+/-1.75) than in malignant salivary gland tumor (5.33+/-3.50). No statistically significant correlation between GSS and SUVmax was observed in OSCC or in malignant salivary gland tumor. CONCLUSION: We found no statistically significant correlation between GSS and SUVmax in OSCC or in malignant salivary gland tumor. Studies on the various uses of GLUT during 18F-FDG uptake and SUV and GLUT as tumor prognosis factor need to be conducted through further investigation with large samples.