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.

Transforming growth factor beta-1 upregulates glucose transporter 1 and glycolysis through canonical and noncanonical pathways in hepatic stellate cells

BACKGROUND Hepatic stellate cells(HSCs)are the key effector cells mediating the occurrence and development of liver fibrosis,while aerobic glycolysis is an important metabolic characteristic of HSC activation.Transforming growth factor-β1(TGF-β1)induces aerobic glycolysis and is a driving factor for metabolic reprogramming.The occurrence of glycolysis depends on a high glucose uptake level.Glucose transporter 1(GLUT1)is the most widely distributed glucose transporter in the body and mainly participates in the regulation of carbohydrate metabolism,thus affecting cell proliferation and growth.However,little is known about the relationship between TGF-β1 and GLUT1 in the process of liver fibrosis and the molecular mechanism underlying the promotion of aerobic glycolysis in HSCs.AIM To investigate the mechanisms of action of GLUT1,TGF-β1 and aerobic glycolysis in the process of HSC activation during liver fibrosis.METHODS Immunohistochemical staining and immunofluorescence assays were used to examine GLUT1 expression in fibrotic liver tissue.A Seahorse extracellular flux(XF)analyzer was used to examine changes in aerobic glycolytic flux,lactate production levels and glucose consumption levels in HSCs upon TGF-β1 stimulation.The mechanism by which TGF-β1 induces GLUT1 protein expression in HSCs was further explored by inhibiting/promoting the TGF-β1/mothersagainst-decapentaplegic-homolog 2/3(Smad2/3)signaling pathway and inhibiting the p38 and phosphoinositide 3-kinase(PI3K)/AKT signaling pathways.In addition,GLUT1 expression was silenced to observe changes in the growth and proliferation of HSCs.Finally,a GLUT1 inhibitor was used to verify the in vivo effects of GLUT1 on a mouse model of liver fibrosis.RESULTS GLUT1 protein expression was increased in both mouse and human fibrotic liver tissues.In addition,immunofluorescence staining revealed colocalization of GLUT1 and alpha-smooth muscle actin proteins,indicating that GLUT1 expression was related to the development of liver fibrosis.TGF-β1 caused an increase in aerobic glycolysis in HSCs and induced GLUT1 expression in HSCs by activating the Smad,p38 MAPK and P13K/AKT signaling pathways.The p38 MAPK and Smad pathways synergistically affected the induction of GLUT1 expression.GLUT1 inhibition eliminated the effect of TGF-β1 on HSC proliferation and migration.A GLUT1 inhibitor was administered in a mouse model of liver fibrosis,and GLUT1 inhibition reduced the degree of liver inflammation and liver fibrosis.CONCLUSION TGF-β1 induces GLUT1 expression in HSCs,a process related to liver fibrosis progression.In vitro experiments revealed that TGF-β1-induced GLUT1 expression might be one of the mechanisms mediating the metabolic reprogramming of HSCs.In addition,in vivo experiments also indicated that the GLUT1 protein promotes the occurrence and development of liver fibrosis.

Effects of suppressing glucose transporter-1 by an antisense oligodeoxynucleotide on the growth of human hepatocellular carcinoma cells

BACKGROUND:The glucose transporter-1(Glut-1),a key ratelimiting factor in the transport and metabolism of glucose in cancer cells,is over-expressed in many human cancer cells and this overexpression is correlated with poor biological behavior. The increased levels of Glut-1 expression in hepatocellular carcinoma(HCC)cells functionally affect tumorigenicity.This study was undertaken to investigate effects of suppressing Glut-1 by an antisense oligodeoxynucleotide(AS-ODN)on the growth of human hepatocellular carcinoma(HepG-2)cells. METHODS:We used AS-ODN targeting against the Glut-1 gene in a HepG-2 cell line.There were four experimental groups: empty pcDNA3.1 vector(mock transfection),pcDNA3.1-anti-Glut(+),pcDNA3.1-Glut(+),and non-transfected HepG-2 cells. The Glut-1 mRNA expression was detected by RT-PCR and the Glut-1 protein expression by Western blotting after cell culture, and the glucose uptake was detected after glucose stimulation in each group. RESULTS:Compared with non-transfected HepG-2 or Glut-1 pcDNA3.1,a down-regulation of Glut-1 mRNA in HepG-2 cells transfected with anti-Glut-1 pcDNA3.1 was noted(P<0.05).Glut-1 protein in HepG-2 cells transfected with Glut-1 AS-ODN was decreased compared with non-transfected HepG-2,Glut-1 pcDNA3.1,or empty vectors. Glucose uptake by the HepG-2 cells transfected with AS-ODN was decreased at 1 hour after glucose stimulation.CONCLUSIONS:The application of Glut-1 AS-ODN can down-regulate the expression of Glut-1 at mRNA and protein,and inhibit glucose uptake partially in HepG-2 cells.The Glut-1 gene maybe a potential therapeutic target for HCC.

Transcriptional activation of glucose transporter 1 in orthodontic tooth movement-associated mechanical response

The interplay between mechanoresponses and a broad range of fundamental biological processes, such as cell cycle progression,growth and differentiation, has been extensively investigated. However, metabolic regulation in mechanobiology remains largely unexplored. Here, we identified glucose transporter 1(GLUT1)—the primary glucose transporter in various cells—as a novel mechanosensitive gene in orthodontic tooth movement(OTM). Using an in vivo rat OTM model, we demonstrated the specific induction of Glut1 proteins on the compressive side of a physically strained periodontal ligament. This transcriptional activation could be recapitulated in in vitro cultured human periodontal ligament cells(PDLCs), showing a time-and dose-dependent mechanoresponse. Importantly, application of GLUT1 specific inhibitor WZB117 greatly suppressed the efficiency of orthodontic tooth movement in a mouse OTM model, and this reduction was associated with a decline in osteoclastic activities. A mechanistic study suggested that GLUT1 inhibition affected the receptor activator for nuclear factor-κ B Ligand(RANKL)/osteoprotegerin(OPG)system by impairing compressive force-mediated RANKL upregulation. Consistently, pretreatment of PDLCs with WZB117 severely impeded the osteoclastic differentiation of co-cultured RAW264.7 cells. Further biochemical analysis indicated mutual regulation between GLUT1 and the MEK/ERK cascade to relay potential communication between glucose uptake and mechanical stress response. Together, these cross-species experiments revealed the transcriptional activation of GLUT1 as a novel and conserved linkage between metabolism and bone remodelling.

Constructing recombinant replication-defective adenoviral vectors that express glucose transporter-1 through in vitro ligation

BACKGROUND： We constructed a homologous recombination bacterial method based on the pAdEasy system, a widely used system, for generating recombinant adenoviral vectors that express glucose transporter- 1 （GLUT 1） in rats, OBJECTIVE： This study was designed to investigate the feasibility of generating recombinant replication-defective adenoviral vectors that express GLUT1 in rats by in vitro ligation based on the Adeno-X^TM system. DESIGN： An in vitro cell-based experiment. SETTING： This study was performed at the Linbaixin Medical Research Center of the Second Hospital Affiliated to Sun Yat-sen University and Central Laboratory for Prevention and Treatment of Tumor, Sun Yat-sen University between January and August 2004. MATERIALS： Male, adult, Sprague Dawley rats were used to extract total RNA from brain tissue. E. coli DH5 a and human embryonic kidney 293 cells （HEK293 cells） used in the present study were cryo-preserved by the Second Hospital Affiliated to Sun Yat-sen University. Rabbit anti-rat GLUT1 polyclonal antibody （Chemicon, U.S.A.） and primers （Shanghai Boya Bioengineering Co., Ltd） were also used. METHODS： E1/E3-deleted replication-defective adenoviral vectors were used. Using in vitro ligation, the target gene was first sub-cloned into a shuttle vector plasmid to obtain the fragment containing target gene expression cassettes by enzyme digestion. Subsequently, the fragment was co-transformed with linearized adenoviral backbone vector into the E. coli strain. The recombinant adenoviral plasmid was transfected into HEK293 cells to assembly recombinant adenoviral vectors with replication capabilities. The procedure was repeated several times for recombinant adenoviral vectors amplification. MAIN OUTCOME MEASURES： Efficiency of recombinant adenoviral vectors to express the target gene was measured by gene and protein expression through polymerase chain reaction and Western Blot assays, respectively. RESULTS： Results demonstrated that recombinant adenoviral vectors successfully expressed GLUT1 protein, with a relative molecular mass of 55000 in HEK293 cells. These results suggest that recombinant adenoviral vectors obtained by homologous bacterial recombination feature high efficiency, rapidness, and simplicity. CONCLUSION： We successfully amplified the rat GLUT1 gene and constructed replication-defective adenoviral vectors expressing GLUT1. The replication-defective adenoviral vectors proved to successfully express the target gene in HEK293 cells.

Chlorogenic Acid Maintains Glucose Homeostasis through Modulating the Expression of SGLT-1,GLUT-2,and PLG in Different Intestinal Segments of Sprague-Dawley Rats Fed a High-Fat Diet

Objective To reveal the effects and related mechanisms of chlorogenic acid(CGA)on intestinal glucose homeostasis.Methods Forty male Sprague-Dawley rats were randomly and equally divided into four groups:normal chow(NC),high-fat diet(HFD),HFD with low-dose CGA(20 mg/kg,HFD-LC),and HFD with high-dose CGA(90 mg/kg,HFD-HC).The oral glucose tolerance test was performed,and fast serum insulin(FSI)was detected using an enzyme-linked immunosorbent assay.The m RNA expression levels of glucose transporters(Sglt-1 and Glut-2)and proglucagon(Plg)in different intestinal segments(the duodenum,jejunum,ileum,and colon)were analyzed using quantitative real-time polymerase chain reaction.SGLT-1 protein and the morphology of epithelial cells in the duodenum and jejunum was localized by using immunofluorescence.Results At both doses,CGA ameliorated the HFD-induced body weight gain,maintained FSI,and increased postprandial 30-min glucagon-like peptide 1 secretion.High-dose CGA inhibited the HFD-induced elevation in Sglt-1 expression.Both CGA doses normalized the HFD-induced downregulation of Glut-2 and elevated the expression of Plg in all four intestinal segments.Conclusion An HFD can cause a glucose metabolism disorder in the rat intestine and affect body glucose homeostasis.CGA can modify intestinal glucose metabolism by regulating the expression of intestinal glucose transporters and Plg,thereby controlling the levels of blood glucose and insulin to maintain glucose homeostasis.

BcSDR1 is involved in regulation of glucose transport and cAMP and MAPK signaling pathways in Botrytis cinerea

Botrytis cinerea is a typical necrotrophic pathogenic fungus that causes severe diseases in a wide range of plant species, leading to significant economic losses. Our previous study showed that BcSDR1 positively regulates growth,development, and pathogenicity of B. cinerea. However, the regulation mechanism of BcSDR1 and the relationship between BcSDR1 and cAMP and MAPK signaling pathways are not well understood. In this study, transcriptome data showed that BcSDR1 is involved in glucose transmembrane transport, signal transduction, secondary metabolism, and other biological processes. BcSDR1 mutant(BCt41) showed remarkably weak sensitivity to cAMP and MAPK signaling pathways specific inhibitors, SQ22536 and U0126, and significantly decreased cAMP content. The key genes of cAMP and MAPK signaling pathways, BcGB1, BcBTP1, BcBOS1, BcRAS1, and BcBMP3 were significantly upregulated,whereas BcPLC1, BcBCG1, BcCDC4, BcSAK1, BcATF1, and BcBAP1 were significantly downregulated(P<0.05).BcSDR1 was obviously upregulated in BcBCG2, BcBCG3, BcPKA1, and BcPKAR RNA interference(RNAi) mutants, but significantly downregulated in BcPKA2, BcBMP1, and BcBMP3 RNAi mutants. Thus, BcBCG2, BcBCG3, BcPKA1, and BcPKAR negatively regulate BcSDR1 expression, whereas BcPKA2, BcBMP1, and BcBMP3 positively regulate BcSDR1expression.

GLUT-1在三阴性乳腺癌中的表达及其与临床病理特征和预后的关系研究

目的分析三阴性乳腺癌(TNBC)中葡萄糖转运蛋白1(GLUT-1)的表达水平,并探讨其与患者临床病理特征和预后的关系。方法回顾性选取2019年1月至2021年1月在嘉兴市第一医院行乳腺癌根治术的TNBC患者79例(TNBC组),另择同期本院乳腺良性疾病(包括乳腺炎、乳腺纤维瘤等)患者40例为对照(对照组)。留取TNBC组患者的肿瘤组织与癌旁组织,对照组患者乳腺活检组织。采用qRT-PCR法检测组织标本GLUT-1 mRNA表达情况。收集TNBC组患者的临床病理资料,术后每3个月随访1次,随访时间截至2023年12月,其中随访1年时出现死亡、肿瘤复发进展、出现严重并发症(恶病质)等定义为预后不良。比较TNBC组肿瘤组织、癌旁组织与对照组乳腺活检组织GLUT-1 mRNA表达水平;比较不同临床病理特征的TNBC组患者肿瘤组织GLUT-1 mRNA表达水平;分析不同临床病理特征对TNBC患者术后1年预后不良的预测效能、TNBC患者死亡的危险因素及不同GLUT-1 mRNA表达水平TNBC患者生存情况。结果TNBC组肿瘤组织GLUT-1 mRNA表达水平高于癌旁组织、对照组乳腺活检组织(均P<0.05),而TNBC组癌旁组织与对照组乳腺活检组织GLUT-1 mRNA表达水平比较差异无统计学意义(P>0.05)。低分化、肿瘤直径≥5 cm、Ki-67指数≥70%、有神经脉管浸润、有淋巴结转移、有远处转移及TNM分期Ⅲ期的TNBC组患者肿瘤组织GLUT-1 mRNA表达水平分别高于中-高分化、肿瘤直径<5 cm、Ki-67指数<70%、无神经脉管浸润、无淋巴结转移、无远处转移及TNM分期Ⅰ~Ⅱ期的患者(均P<0.05)。肿瘤组织GLUT-1 mRNA表达水平预测TNBC患者术后1年预后不良的灵敏度、特异度及AUC分别为0.845、0.812、0.842,最佳截断值为0.83,有较高的预测效能(P<0.05)。多因素Cox回归分析显示,GLUT-1 mRNA表达水平≥0.83是TNBC患者死亡的独立危险因素(P<0.05)。肿瘤组织GLUT-1 mRNA表达水平≥0.83的TNBC患者生存期低于<0.83的患者[(27.9±4.6)个月比(36.5±5.8)个月,P<0.05]。结论TNBC患者肿瘤组织GLUT-1表达上调,其与临床病理特征及预后存在密切关系,或可作为TNBC病情及预后评估的标志物。

Effects of electroacupuncture on microcirculatory blood flow and glucose transporter function in the hippocampus

Nerve cell metabolism in post brain ischemia depends on increased microcirculation perfusion and transport function of microvascular endothelial cells. In the present study, a rat model of middle cerebral artery occlusion was established to investigate the influence of electroacupuncture （EA） on hippocampal CA1 cerebral blood flow and glucose transporter 1 （GLUT1） expression in the microvascular endothelial cells. Following EA at Neiguan （PC 6）, the cerebral blood flow in the ischemic hippocampal CA1 region was significantly elevated, the number and microvascular integrated absorbance of the GLUTl-positive cells were significantly increased, nerve cell damage was ameliorated, and GLUT1 protein expression in the ischemic hippocampus was significantly increased. Results demonstrate that EA increased the cerebral blood flow of the hippocampal CA1 region and improved the glucose transport function, thereby attenuating neuronal injuries.

Icariin ameliorates learning and memory function via improving cerebral glucose metabolism disorder in APP/PS1/Tau triple transgenic Alzheimer disease mice

OBJECTIVE To investigate the protective effect of icariin(ICA) on learning and memory function in APP/PS1/Tau triple transgenic Alzheimer disease mice(3×Tg-AD mice),and then to explore whether its mechanism is related to the improvement of brain glucose metabolism disorder.METHODS Three-month-old male 3 ×Tg-AD mice were randomly divided into three groups(n=10):3×Tg group,3×Tg+ICA low-dose group(30 mg·kg-1) and 3×Tg + ICA high-dose group(60 mg·kg-1).Age-matched male wild type(WT) mice were randomly divided into two groups(n=10):WT control group and WT+ICA60 mg·kg-1 group.ICA in vehicle(0.5% Tween-80 in distilled water) was given orally once a day for five months in the 3×Tg+ICA groups.3×Tg and WT control group were given an equal volume vehicle.Morris water maze was used to detect the learning and memory function of mice.Brain glucose metabolism in 3×Tg mice was observed by 18 F-FDG microPET imaging technique.Nissl staining and HE staining were used to evaluate the survival neurons in hippocampus of mice.Glucose oxidase assay was used to detect glucose contents in cortex of mice.The protein expression of APP,Aβ1-40,Aβ1-42 and glucose transporter 1(GLUT1),and the phosphorylation level of tau protein at multiple sites in hippocampus were detected by Western blotting.RESULTS Behavioral examination revealed a profound decrease learning and memory function,accompanied by a decrease in number of neuronal cells in 3×Tg-AD mice.Moreover,the cerebral18 F-FDG uptake rate per gram tissue was reduced and the glucose contents in the cortex were increased in 3×Tg-AD mice.In addition,Western blotting analysis showed that the expression of APP,Aβ1-40,Aβ1-42 proteins and the levels of tau protein phosphorylation at Ser199/202 and PHF-1(Ser396/404) sites were increased significantly,followed by a decrease of GLUT1 expression in hippocampus of 3×Tg-AD mice.All of these changes in behavioral functions,neuronal loss and related protein expression were reversed when mice were treated with ICA.CONCLUSION ICA can improve the learning and memory ability of AD model mice,the mechanism may be related to the improvement of cerebral glucose metabolism dysfunction by increasing the expression of GLUT1.

Glucose transporter expression in the human colon

AIM To investigate by immunostaining glucose transporter expression in human colorectal mucosa in controls and patients with inflammatory bowel disease(IBD). METHODS Colorectal samples were obtained from patients undergoing lower endoscopic colonoscopy or rectosigmoidoscopy. Patients diagnosed with ulcerativecolitis(n = 18) or Crohn's disease(n = 10) and scheduled for diagnostic colonoscopy were enrolled. Patients who underwent colonoscopy for prevention screening of colorectal cancer or were followed-up after polypectomy or had a history of lower gastrointestinal symptoms were designated as the control group(CTRL, n = 16). Inflammatory status of the mucosa at the sampling site was evaluated histologically and/or endoscopically. A total of 147 biopsies of colorectal mucosa were collected and processed for immunohistochemistry analysis. The expression of GLUT2, SGLT1, and GLUT5 glucose transporters was investigated using immunoperoxidase labeling. To compare immunoreactivity of GLUT5 and LYVE-1, which is a marker for lymphatic vessel endothelium, doublelabeled confocal microscopy was used. RESULTS Immunohistochemical analysis revealed that GLUT2, SGLT1, and GLUT5 were expressed only in short epithelial portions of the large intestinal mucosa. No important differences were observed in glucose transporter expression between the samples obtained from the different portions of the colorectal tract and between the different patient groups. Unexpectedly, GLUT5 expression was also identified in vessels, mainly concentrated in specific areas where the vessels were clustered. Immunostaining with LYVE-1 and GLUT5 antibodies revealed that GLUT5-immunoreactive(-IR) clusters of vessels were concentrated in areas internal to those that were LYVE-1 positive. GLUT5 and LYVE-1 did not appear to be colocalized but rather showed a close topographical relationship on the endothelium. Based on their LYVE-1 expression, GLUT5-IR vessels were identified as lymphatic. Both inflamed and noninflamed mucosal colorectal tissue biopsies from the IBD and CTRL patients showed GLUT5-IR clusters of lymphatic vessels. CONCLUSION Glucose transporter immunoreactivity is present in colorectal mucosa in controls and IBD patients. GLUT5 expression is also associated with lymphatic vessels. This novel finding aids in the characterization of lymphatic vasculature in IBD patients.

Photoactivation of GLUT4 translocation promotes glucose uptake via PI3-K/Akt2 signaling in 3T3-L1 adipocytes

Insulin resistance is a hallmark of the metabolic syndrome and type 2 diabetes.Dysfunction of PI-3K/Akt signaling was involved in insulin resistance.Glucose transporter 4(GLUT4)is a keyfactor for glucose uptake in muscle and adipose tissues,which is closely regulated by Pi-3K/Aktsignaling in response to insulin treatment.Low-power laser irradiation(LPLI)has been shown toregulate various physiological processes and induce the synthesis or release of multiple moleculessuch as growth factors,which(especially red and near infrared light)is mainly through theactivation of mitochondrial respiratory chain and the initiation of intracellular signaling path-ways.Nevertheless,it is unclear whether LPLI could promote glucose uptake through activationof PI-3K/Akt/GLUT4 signaling in 3T3L-1 adipocytes.In this study,we investigated how LPLIpromoted glucose uptake through activation of PI-3K/Akt/GLUT4 signaling path way.Here,we showed that GLUT4 was localized to the Golgi apparatus and translocated from cytoplasm tocytomembrane upon LPLI treatment in 3T3L-1 adipocytes,which enhanced glucose uptake.Moreover,we found that glucose uptake was mediated by the PI3-K/Akt2 signaling,but notAkt1 upon LPLI treatment with Akt isoforms gene silence and PI3-K/Akt inhibitors.Collec-tively,our results indicate that PI3-K/Akt2/GLUT4 signaling act as the key regulators forimprovement of glucose uptake under LPLI treatment in 3T3L-i adipocytes.More importantly,our findings suggest that activation of PI3-K/Akt2/GLUT4 signaling by LPLI may provideguidance in practical applications for promotion of glucose uptake in insulin-resistant adiposetissue.

The influence of OCT1 gene polymorphisms on the metformin response in Uygur patients with glucose metabolism disorder

Objective To determine the effects of genetic variation in the organic cation transporter 1(OCT1)on the short-term responses of the antidiabetic drug,metformin.Method A total of 22 patients recruited with type 2 diabetes or IFG were treated with metformin(2 000 mg/day)for 1 week.The patients were screened from Second Jikun hospital and Kashidonglu community medicine service,Urumqi,China and their surrounding districts.To examine the effects of metformin on plasma glucose,total cholesterol,low-density lipoprotein-cholesterol,high-density lipoprotein-cholesterol and triglyceride in relation with R61C,G465R and 420 del variants of OCT1(gene encoding organic cation transporter 1,mainly locating in liver,which is metformin's major target)in subjects.In all,R61C,G465R and 420del of OCT1 gene were examined using DNA extracted from whole blood and PCR-RFLP.Data concerning with gene and metformin treatment were handled by t-test.Result After metformin treatment,there were increases both in FPG and LDL(P=0.011and P=0.013 respectively).To divide all participants into mutant and wild groups,according to the polymorphisms of R61C,G465R and 420 del respectively,as well as carriers with one of the mutant genotypes at least and carriers with none of the mutant sites.Analysis was made to compared FPG,Chol,TG,and LDL and HDL between carriers of wild genotypes and carriers of other genotypes showed no statistic significance both before the metformin treatment and after the treatment.The same is the case with changes of FPG,Chol,TG,and LDL and HDL of wild genotype carriers and variant genotype carriers,except of LDL changes(P=0.05)in patients grouped by G465R polymorphisms and TG changes(P=0.03)in subjects differed by 420del genotypes.Conclusion In this study,it is suggested that OCT1 gene polymorphisms have little contribution to the clinical efficacy of blood glucose control by metformin among Uygur people with type 2 diabetes or IFG,but it may have possible relationship with the clinical efficacy on fat metabolism by metformin.

HIF-1α和GLUT-1在鼻咽癌中的表达及其临床意义

背景与目的:在鼻咽癌患者肿瘤组织中普遍存在乏氧诱导因子的过表达,且其表达与鼻咽癌的发生、发展及疗效密切相关。本研究旨在探讨乏氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)和葡萄糖转运蛋白-1(glucose transporter-1,GLUT-1)在鼻咽癌组织中的表达及其在鼻咽癌疗效判断及预后预测中的作用。方法:采用免疫组化方法检测92例鼻咽癌组织和20例鼻咽慢性炎性组织中HIF-1α和GLUT-1蛋白表达,分析其表达状况与鼻咽癌患者临床病理特征及预后的关系。结果:鼻咽癌组织HIF-1α和GLUT-1蛋白阳性表达率明显高于鼻咽慢性炎性组织(P<0.01)。HIF-1α蛋白阳性表达与患者年龄、有无颈淋巴结转移和临床分期明显相关(P<0.01),而与患者性别、T分期无明显相关性(P>0.05)。GLUT-1蛋白阳性表达与患者性别、年龄、T分期、有无颈淋巴结转移和临床分期均无明显相关性(P>0.05)。HIF-1α和GLUT-1蛋白阳性表达均与患者较差的4年无进展生存率明显相关(P<0.05);HIF-1α蛋白阳性表达患者的4年总生存率有低于阴性表达者的趋势(P=0.059),而GLUT-1蛋白阳性表达与患者4年总生存率无明显相关性(P>0.05)。鼻咽癌组织中HIF-1α和GLUT-1蛋白的阳性表达间无明显相关性(r=0.107,P>0.05)。结论:检测鼻咽癌组织中HIF-1α和GLUT-1蛋白的表达在鼻咽癌患者的疗效判断和预后预测中有一定的临床价值。

HIF-1α和GLUT-1在卵巢癌中的表达及临床意义

目的:探讨缺氧诱导因子-1α(hypoxia-inducible factor-1alpha,HIF-1α)和葡萄糖转运蛋白1(glucose transporter-1,GLUT-1)在卵巢癌中的表达及其与临床病理特征间的相互关系和临床意义。方法:用免疫组化法检测卵巢上皮性癌30例、卵巢上皮性交界性肿瘤10例、卵巢上皮性良性肿瘤10例中HIF-1α和GLUT-1的表达。结果:HIF-lα和GLUT-1在卵巢上皮性良性肿瘤中均呈阴性表达,在交界性及癌组织中均有表达,三者比较有显著性差异(均为P<0.05);HIF-1α和GLUT-1的表达在卵巢癌各临床分期、患者年龄间比较,差异均无显著性(P>0.05),而在病理分级间有显著性差异(P<0.05),其表达强度随病理分级的增高而加强;HIF-1α蛋白的表达在不同组织类型的卵巢癌中有显著性差异(P<0.05),而GLUT-1蛋白的表达差异无显著性(P>0.05)。HIF-1α蛋白与GLUT-1的表达呈正相关。结论:HIF-lα和GLUT-1在卵巢肿瘤中的不同表达,提示二者在卵巢癌的进展中可能起着重要作用,且二者的过度表达可能与卵巢癌的发生和发展有关。

卵巢癌组织中GLUT-1及MMP-2的表达和临床意义

目的:研究葡萄糖转运蛋白-1(GLUT-1)和基质金属蛋白酶-2(MMP-2)在卵巢肿瘤组织中的表达,探讨其与恶性卵巢肿瘤临床分期、组织学分级、组织学分类、转移及预后的关系。方法:应用免疫组织化学法(SP法)对30例卵巢癌、8例交界性卵巢肿瘤、12例良性卵巢肿瘤组织中的GLUT-1和MMP-2进行检测。结果:GLUT-1和MMP-2在恶性卵巢肿瘤组织中的阳性表达率明显高于良性卵巢肿瘤组织,差异有显著性(P<0.01);GLUT-1及MMP-2的阳性表达与患者的临床分期有关,临床期别越高,阳性表达率越高;与组织学分类及组织学分级无关。GLUT-1及MMP-2在发生转移的恶性卵巢肿瘤组织中的表达明显增加,两者在卵巢恶性肿瘤组织中的阳性表达呈正相关(相关系数rs=0.646,P<0.01)。结论:GLUT-1和MMP-2在卵巢癌的发生发展过程中可能起重要作用。

GLUT-1和DNA-PKcs在卵巢浆液性肿瘤组织中的表达及其意义

背景与目的:已知肿瘤细胞生长所需能量是通过葡萄糖转运体蛋白1(glucose transporter protein1,GLUT-1)完成的葡萄糖代谢来提供的。另外,参与基因损伤修复的催化亚单位——DNA蛋白激酶(DNA-dependent protein kinase catalytic subunit,DNA-PKcs)在肿瘤形成中也起着非常重要的作用。本研究旨在探讨GLUT-1和DNA-PKcs在卵巢浆液性肿瘤组织中的表达及其与肿瘤生物学行为的关系和意义。方法:免疫组化方法检测80例卵巢浆液性肿瘤组织中GLUT-1、DNA-PKcs的表达,分析其异常表达与临床病理参数之间的相关性,以正常卵巢组织20例为对照。结果:正常卵巢组织GLUT-1表达全阴性,DNA-PKcs表达全阳性。GLUT-1在良性、交界性、恶性卵巢浆液性肿瘤中的表达呈增高的趋势,与卵巢浆液性肿瘤的发生发展呈正相关(rs=0.943,P<0.01);

HIF-1α Glut-1表达与乳腺癌分化程度及分子亚型的关系

目的:探讨缺氧诱导因素-1α(HIF-1α)、葡萄糖转运蛋白1(Glut-1)表达与乳腺癌分化程度及分子亚型的关系。方法:采用免疫组化方法检测102例乳腺癌及60例癌旁正常组织的中HIF-1α、Glut-1蛋白表达情况,比较不同分化程度、分子分型乳腺癌组织中HIF-1α、Glut-1阳性表达率。结果:乳腺癌组织中HIF-1α、Glut-1蛋白阳性表达率分别为62.75%、68.63%高于癌旁正常组织的11.67%、16.67%,差异有统计学意义(P<0.05);高分化乳腺癌组织HIF-1α、Glut-1蛋白阳性表达率分别为34.78%、40.91%低于中分化的60.0%、68.88%和低分化的85.29%、88.24%(P<0.025),中分化低于低分化,差异有统计学意义(P<0.025);Luminal A型HIF-1α、Glut-1蛋白阳性表达率分别为46.67%、51.11%,与Luminal B型的54.55%、63.64%比较,差异无统计学意义(P>0.017),但Luminal A型、Luminal B型均低于HER-2过表达型的85.71%、92.86%和三阴型的90.48%、95.24%,差异有统计学意义(P<0.017),HER-2过表达型、三阴型比较,差异无统计学意义(P>0.017)。结论:乳腺癌患者HIF-1α、Glut-1呈高阳性表达,且不同分化程度、分子亚型的乳腺癌HIF-1α、Glut-1阳性表达存在差异。

胶质瘤中GLUT-1与GLUT-3表达的实验研究

目的探讨葡萄糖转运蛋白-1(GLUT-1)和葡萄糖转运蛋白-3(GLUT-3)在人脑胶质瘤中的表达及与病理分级的关系。方法用W estern b lot和逆转录-聚合酶链反应(RT-PCR)的方法检测80例胶质瘤中GLUT-1和GLUT-3的表达情况。结果 GLUT-1蛋白在Ⅰ、Ⅱ、Ⅲ、Ⅳ级胶质瘤中的表达分别为0.09±0.02、0.20±0.02、0.41±0.09和0.63±0.07;GLUT-3蛋白在Ⅰ、Ⅱ、Ⅲ、Ⅳ级胶质瘤中的表达分别为0.10±0.02、0.23±0.07、0.62±0.05和0.88±0.06。各组间有显著差异(P<0.01)。GLUT-1mRNA在Ⅰ、Ⅱ、Ⅲ、Ⅳ级胶质瘤中的表达分别为0.08±0.03、0.19±0.02、0.41±0.06和0.66±0.08;GLUT-3 mRNA在Ⅰ、Ⅱ、Ⅲ、Ⅳ级胶质瘤中的表达分别为0.17±0.01、0.36±0.09、0.64±0.09和0.89±0.11。各组间有显著差异(P<0.01)。结论胶质瘤中GLUT-1和GLUT-3表达随病理级别增高而增加,提示GLUT-1和GLUT-3在胶质瘤的发生过程中起重要作用。

低氧状态下芹黄素通过抑制HIF-1α下调卵巢癌SKOV3细胞GluT-1表达的实验研究

目的研究在低氧状态下芹黄素能否通过抑制HIF-1α下调卵巢癌SKOV3细胞GluT-1表达。方法将卵巢癌SKOV3细胞分为常氧组、低氧组和低氧+芹黄素组。在低氧状态下对卵巢癌SKOV3细胞使用终浓度为50μM的芹黄素进行干预,在不同时间点(0h、24h和72h)使用MTT法对SKOV3细胞活性进行检测;同时在干预24h后,分别使用qPCR法和western blot法对卵巢癌SKOV3细胞GluT-1和HIF-1αmRNA和蛋白表达水平进行检测。结果低氧环境下SKOV3细胞活性呈时间依赖性下降,差异均有显著统计学意义(P均<0.05);且在各时间点低氧+芹黄素组活性较低氧组下降更加明显,差异均有显著统计学意义(P均<0.05)。同时,在干预24h后卵巢癌SKOV3细胞GluT-1和HIF-1αmRNA和蛋白的表达水平较非干预组细胞明显降低,差异均有显著统计学意义(P均<0.05)。结论在低氧状态下,芹黄素可以通过抑制HIF-1α的合成下调卵巢癌SKOV3细胞GluT-1的表达,从而抑制肿瘤细胞的增殖。该基础研究为芹黄素应用于卵巢癌等恶性肿瘤的治疗奠定了一定的理论基础。