Predicting response to neoadjuvant therapy with glucose transporter-1 in breast cancer

SUMMARY OBJECTIVE: Glucose transporter-1 is a marker involved in energy transport in cancer cells. It has been shown to be a poor prognostic factor in many cancer types, including breast cancer. However, there is no satisfactory parameter predicting treatment in breast cancer patients receiving neoadjuvant therapy. This study investigated the effect of glucose transporter-1 in predicting the treatment response of patients receiving neoadjuvant therapy. METHODS: In this study, glucose transporter-1 immunohistochemistry was applied to tru-cut biopsy of patients who were diagnosed with breast cancer and received neoadjuvant therapy between 2010 and 2021. A built-in scoring system was used to evaluate both the pattern and intensity of glucose transporter-1 immunohistochemistry staining. The relationship between glucose transporter-1 immunohistochemistry staining and other clinicopathological parameters was examined. In addition, the relationship of glucose transporter-1 with response to treatment was investigated. RESULTS: A relationship was found between high glucose transporter-1 expression and other clinicopathological parameters (such as estrogen and progesterone receptor negativity, high Ki-67, triple-negative, and Her2 status). Cases with high glucose transporter-1 expression had either a complete or a partial pathologic response. The result was statistically significant. CONCLUSION: Glucose transporter-1 has the potential to be a biomarker that can be evaluated more objectively as an alternative to Ki-67 labeling index in evaluating the response to treatment in patients receiving neoadjuvant therapy.

Deficiencia del transportador de glucosa tipo 1: aspectos clínicos, diagnóstico y terapéutica / Glucose transporter type 1 deficiency syndrome: clinical aspects, diagnosis, and treatment

El síndrome de deficiencia del transportador de glucosa tipo 1 es una enfermedad de causa genética, que involucra el gen SLC2A1. En general, se presenta durante los primeros años de vida con retraso en la adquisición de pautas madurativas, epilepsia farmacorresistente y desórdenes del movimiento. La clínica y la disminución de glucosa en líquido cefalorraquídeo permiten sospechar el diagnóstico, el cual debe ser confirmado mediante el estudio molecular del gen SLC2A1. Debido a que se trata de una enfermedad poco frecuente y de expresión clínica variable, el diagnóstico precoz suele representar un desafío para los equipos de salud. Este es importante, ya que la implementación de la terapia cetogénica logra controlar las manifestaciones clínicas y mejora el pronóstico a largo plazo. Presentamos una revisión sobre el déficit del transportador de glucosa tipo 1, que abarca sus características clínicas, bioquímicas, moleculares y terapéuticas.

Glucose transporter type 1 deficiency with a typical onset is a genetic disorder associated with the SLC2A1 gene. Usually appears during the first years of life with severe developmental delay, drugresistant epilepsy, and movement disorders. Diagnosis is suspected based on clinical manifestations and a low glucose level in cerebrospinal fluid, and should be confirmed by the molecular genetic study of the SLC2A1 gene. As it is a rare disease with variable clinical expression, early diagnosis is often challenging for the healthcare team. Nevertheless, this is important because early implementation of ketogenic therapy will lead to control of the clinical manifestations and a better long-term prognosis. Here we review the glucose transporter type 1 deficiency syndrome focusing on its clinical, biochemical, molecular, and therapeutic characteristics.

Hemidistonía y hemicorea en un paciente pediátrico con déficit del transportador de glucosa de tipo 1 / Hemidystonia and hemichorea in a pediatric patient with glucose transporter type 1 deficiency

El síndrome de deficiencia del transportador de glucosa cerebral de tipo 1 es una enfermedad neurometabólica rara en pediatría. Existe un fenotípico clásico (85 %) y otro no clásico (15 %). Ambos fenotipos se asocian con hipoglucorraquia. Se identifican múltiples mutaciones en el gen SLC2A1. El tratamiento es la terapia cetogénica. Se presenta un varón que comenzó a los cuatro años con hemicorea y hemidistonía medicado con anticonvulsivantes sin respuesta clínica, por lo que consultó nuevamente a los seis años. Con sospecha diagnóstica de síndrome de déficit de glut-1 atípico se realizó punción lumbar; el diagnóstico se confirmó por la presencia de hipoglucorraquia. Inmediatamente después de iniciar la dieta cetogénica, el paciente no presentó más movimientos anormales durante los siguientes 8 años hasta la actualidad, ya cumplidos los 14 años.

Glucose transporter type 1 deficiency syndrome is a rare pediatric neurometabolic disorder. There are two phenotypes: the classical phenotype (85%) and the non-classic (15%). Both phenotypes are associated with hypoglycorrhachia. Multiple mutations are described in the SCL2A1 gene. The treatment is the ketogenic diet. We report a case of a four-year-old male patient who started with hemichorea and hemidystonia and was medicated with drugs for seizures without clinical response, that's why his parents made another pediatric consultation at his six-year-old. With the suggestive clinical findings of glucose transporter type 1 deficiency syndrome the lumbar puncture was made confirming the diagnosis. Immediately after starting the ketogenic diet the patient stopped making abnormal movements up to the moment when he is fourteen years old, eight years after.

Effects of resveratrol on the activity of infantile hemangioma-derived endothelial cells / 中华皮肤科杂志

Objective:To investigate the effect of the glucose transporter 1 (Glut-1) inhibitor resveratrol on the activity of infantile hemangioma (IH) -derived endothelial cells (HemEC) .Methods:IH tissues were collected from 4 cases of proliferating IH and 4 cases of involuting IH, and immunohistochemical study was performed to determine the Glut-1 expression. Primary HemEC were extracted from 4 proliferating IH tissues, real-time fluorescence-based quantitative PCR (qPCR) and Western blot analysis were performed to determine the mRNA and protein expression of Glut-1 in HemEC and human umbilical vein endothelial cells (HUVEC) , respectively. HemEC were cultured in vitro and treated with 0 (control group) , 50, 100, 200, 400 and 800 μmol/L resveratrol for 24 hours, respectively. Cell counting kit-8 (CCK8) assay was performed to evaluate the proliferative ability of HemEC in the above groups, and the 50% inhibitory concentration (IC50) was calculated. The migratory ability and apoptosis level of HemEC were assessed by Transwell assay and flow cytometry, respectively. Intergroup comparisons were performed using t test or analysis of variance, and multiple comparisons were performed using least significant difference- t test. Results:Immunohistochemical study showed that Glut-1 was expressed in vascular endothelial cells derived from both proliferating and involuting IH tissues, and the Glut-1 expression was abundant in the proliferating IH but markedly decreased in the involuting IH tissues. The mRNA and protein expression levels of Glut-1 were significantly higher in HemEC (1.793 ± 0.041, 1.959 ± 0.144, respectively) than in HUVEC (0.820 ± 0.073, 0.648 ± 0.046, t = 16.35, 12.28, respectively, both P < 0.001) . After the treatment with Glut-1 inhibitor resveratrol at different concentrations, the proliferative ability of HemEC significantly differed among the control group, 50-, 100-, 200-, 400- and 800-μmol/L resveratrol groups ( F = 1 043.00, P < 0.001) , and was significantly lower in all the resveratrol groups than in the control group (all P < 0.05) . The IC50 of resveratrol was calculated to be 150 μmol/L by using GraphPad Prism 8 software. Transwell assay and flow cytometry showed significantly decreased number of migratory HemEC but significantly increased apoptosis rate respectively in the 150 μmol/L resveratrol group (61 ± 5, 13.01% ± 0.45%, respectively) compared with the control group (150 ± 6, 3.93% ± 0.68%, t = 15.11, 19.34, respectively, both P < 0.001) . Conclusion:The key glycolytic enzyme Glut-1 was highly expressed in proliferating IH tissues and HemEC, and resveratrol could inhibit the proliferation and migration of HemEC, but promote their apoptosis.

Effect of different glucose concentrations on the uptake of 18F-FDG in non-small cell lung cancer / 中华核医学与分子影像杂志

Objective:To explore the effect of different glucose concentrations on the uptake of 18F-FDG and the expression of glucose transport protein(Glut)-1 and Glut-3 in non-small cell lung cancer (NSCLC). Methods:NSCLC cell line A549 cells were cultured in DMEM medium with glucose concentrations of 3.9, 5.0, 6.1, 8.3 and 11.1 mmol/L respectively for 24 h. Then 3.7×10 4 Bq 18F-FDG was added into each group and γ counter was used to measure the radioactivity count 1 h later. Western blot was used to examine the expression of Glut-1 and Glut-3. One-way analysis of variance and Bonferroni test were used for data analysis. The correlation was analyzed by Pearson correlation analysis. Results:The 18F-FDG uptake rates in 3.9, 5.0, 6.1, 8.3 and 11.1 mmol/L groups were (4.89±0.83)%, (4.07±0.23)%, (3.66±0.29)%, (3.34±0.16)% and (3.29±0.24)%, respectively ( F=7.05, P=0.006). Compared with 3.9 mmol/L group, the 18F-FDG uptake rates in 8.3 and 11.1 mmol/L groups were reduced and differences were statistically significant ( P values: 0.013, 0.010), while there were no statistical differences between the other groups ( P values: 0.057-0.999). The relative expressions of Glut-1 and Glut-3 in each group were 1.17±0.10, 1.00±0.00, 0.84±0.07, 0.70±0.18, 0.61±0.16, and 1.14±0.05, 1.00±0.00, 0.86±0.12, 0.71±0.05, 0.40±0.06, respectively ( F values: 10.26 and 51.94, P values: 0.001, <0.001). Moreover, the 18F-FDG uptake rates were positively correlated with the expression of Glut-1 and Glut-3 ( r values: 0.775 and 0.744, both P=0.001). Conclusions:When the glucose concentration fluctuates within 3.9-11.1 mmol/L, the change of glucose will affect the 18F-FDG uptake rate and the expression of Glut-1 and Glut-3 in A549 cells. Moreover, the 18F-FDG uptake rate is related to the expressions of Glut-1 and Glut-3.

Effects of glycemic control on placental glucose transporters in women with hyperglycemia in pregnancy / 中华围产医学杂志

Objective:To investigate the expression of placental glucose transport protein (GLUT)1 and 4 in women with hyperglycemia in pregnancy.Methods:A total of 48 full-term singleton pregnant women who underwent elective cesarean section at Peking University First Hospital from January 2017 to December 2019 were included retrospectively, and were divided into pregestational diabetes mellitus (PGDM) group, gestational diabetes mellitus (GDM) group, and normal glucose tolerance (NGT) group (16 women in each). According to the blood glucose level after control during pregnancy, the PGDM and GDM groups were further divided into PGDM-, GDM-well controlled subgroups (both n=10), and PGDM-, GDM-uncontrolled subgroups (both n=6). The expression of GLUT1 and GLUT4 proteins, detected by Western blot, between different groups were compared and the correlation between GLUT1 and GLUT4 protein expression and the pre-pregnancy body mass index (BMI), pre-delivery weight,gestational weight gain (GWG), and neonatal birth weight were analyzed using two independent samples t-test, one-way analysis of variance, Kruskal-Wallis H-test, Chi-square test, and Pearson correlation analysis. Results:(1) The pre-pregnanct BMI and insulin treatment ratio in PGDM group were higher than those in GDM group and NGT group [27.0 kg/m 2 (22.1-29.9 kg/m 2) vs 22.9 kg/m 2 (20.5-25.7 kg/m 2) and 21.7 kg/m 2 (20.5-24.3 kg/m 2); 13/16 vs 1/16 and 0/16; all P<0.05]. In the PGDM group, fasting blood glucose at the second trimester and mean glycosylated hemoglobin during the second and the third trimester were higher than those in the GDM group [(6.1±1.2) vs (5.0±0.4) mmol/L; (5.9±0.5)% vs (5.2±0.3)%; both P<0.05]. (2) GLUT1 protein level was the highest in the PGDM group, followed by the GDM and NGT group (1.251±0.354 vs 1.004±0.368 vs 0.733±0.216, both P<0.05). And all the subgroups had higher protein level than NGT group [PGDM-good (1.270±0.417); PGDM-uncontrolled (1.218±0.245), GDM-well controlled (0.900±0.424); GDM-uncontrolled (1.177±0.158); LSD test,all P<0.05]. The variation of GLUT4 protein level was consistent with GLUT1. There was no significant difference in GLUT1 and GLUT4 expression between PGDM-uncontrolled and PGDM-well controlled subgroups, neither between GDM-uncontrolled and GDM-well controlled subgroups (all P>0.05). (3) GLUT1 and GLUT4 in the PGDM-well controlled subgroup, as well as GLUT1 in the GDM-uncontrolled subgroup, had a positive correlation with GWG ( r=0.635, 0.810, and 0.833, all P<0.05). Conclusions:The increased expression of placental GLUT1 and GLUT4 were associated with different types of gestational hyperglycemia and GWG. However, glucose control has little effect on placental GLUT expression.

The glucose transporter type 1 deficiency syndrome / 中华神经科杂志

Glucose transporter type 1 deficiency syndrome is a rare neurometabolic disorder caused by mutations of the solute carrier family 2 facilitated glucose transporter member 1 (SLC2A1) gene, characterized by complex manifestations including early onset epilepsy, motor and mental retardation, and movement disorders and so on. Ketogenic-diet is most suitable therapy and should be commenced as early as possible because timing the initiation of the diet may prevent seizure, movement disorder, and cognitive impairment. This review aims to improve the clinicians′ understanding of glucose transporter type 1 deficiency syndrome to ensure the diagnosis as early as possible.

The glucose transporter type 1 deficiency syndrome / 中华神经科杂志

Glucose transporter type 1 deficiency syndrome is a rare neurometabolic disorder caused by mutations of the solute carrier family 2 facilitated glucose transporter member 1 (SLC2A1) gene,characterized by complex manifestations including early onset epilepsy,motor and mental retardation,and movement disorders and so on.Ketogenic-diet is most suitable therapy and should be commenced as early as possible because timing the initiation of the diet may prevent seizure,movement disorder,and cognitive impairment.This review aims to improve the clinicians' understanding of glucose transporter type 1 deficiency syndrome to ensure the diagnosis as early as possible.

Clinical features and genetic characteristics of myoclonic-atonic epilepsy caused by SLC6A1 gene mutation / 中国医师杂志

Objective@#To explore the clinical features and genetic characteristics of myoclonic-atonic epilepsy (MAE) caused by SLC6A1 gene mutation.@*Methods@#The clinical data of a patient with SLC6A1 gene mutation from Xiangya Hospital of Central South University was collected. The related literatures were reviewed from Wanfang Data, China National Knowledge Infrastructure, PubMed (until July 2019) by using keywords " SLC6A1" and " myoclonic-atonic epilepsy" . The characteristics of SLC6A1 gene mutation and the clinical phenotype of children with myoclonic-atonic epilepsy were summarized.@*Results@#A 8 year and 8 months old girl was enrolled in the study. Her first attack happened at the age of 19 months, and multiple seizure types including myoclonic-atonic, atonic and absence were observed. The seizures were well controlled by valproate (VPA), but she has mild-moderate intellectual disability. Whole exome-sequencing study identified a de novo nonsense variant of c. 46G>T(p.Glu16*)in SLC6A1 gene. A total of 27 cases including the present case with SLC6A1 gene mutation were analyzed. 22 mutations were identified, including 11 missense mutations, 5 nonsense mutations, 3 frameshift mutations, 2 splicing mutation and 1 with chromosome microdeletion. Among them 26 patients had more one type of seizures, 20 cases had absence seizures, 17 cases had atonic seizures, 14 cases had myoclonic seizures, 11 cases had myoclonic-atonic seizures, 4 cases had generalized tonic-clonic seizures, 3 cases had eyelid myoclonias, 2 cases had nonconvulsive status epilepticus and 2 cases had tonic seizure. 24 patients had described intelligence assessment. Among them, 18 had developmental delay before epilepsy onset, 11 had developmental regression after onset. There were 9 cases with autistic features, 4 cases with attention deficit hyperactivity disorder and 3 cases with ataxia. The seizures of 17 cases were controlled, 4 cases had partial seizure control, 3 cases had no significant improvement, and other 3 cases were unclear.@*Conclusions@#The main clinical feature of MAE patients with SLC6A1 gene mutations is absence and atonic seizures, cognition before epilepsy onset can be impaired, and some patients had behavioral problems, such as autistic features or attention deficit hyperactivity disorders. VPA is recommend as first-line treatment.

Clinical features and genetic characteristics of myoclonic-atonic epilepsy caused by SLC6A1 gene mutation / 中国医师杂志

Objective To explore the clinical features and genetic characteristics of myoclonic-atonic epilepsy (MAE) caused by SLC6A1 gene mutation.Methods The clinical data of a patient with SLC6A1 gene mutation from Xiangya Hospital of Central South University was collected.The related literatures were reviewed from Wanfang Data,China National Knowledge Infrastructure,PubMed (until July 2019) by using keywords "SLC6A1" and "myoclonic-atonic epilepsy".The characteristics of SLC6A1 gene mutation and the clinical phenotype of children with myoclonic-atonic epilepsy were summarized.Results A 8 year and 8 months old girl was enrolled in the study.Her first attack happened at the age of 19 months,and multiple seizure types including myoclonic-atonic,atonic and absence were observed.The seizures were well controlled by valproate (VPA),but she has mild-moderate intellectual disability.Whole exome-sequencing study identified a de novo nonsense variant of c.46G ＞ T(p.Glu16 *)in SLC6A1 gene.A total of 27 cases including the present case with SLC6A1 gene mutation were analyzed.22 mutations were identified,including 11 missense mutations,5 nonsense mutations,3 frameshift mutations,2 splicing mutation and 1 with chromosome microdeletion.Among them 26 patients had more one type of seizures,20 cases had absence seizures,17 cases had atonic seizures,14 cases had myoclonic seizures,11 cases had myoclonic-atonic seizures,4 cases had generalized tonic-clonic seizures,3 cases had eyelid myoclonias,2 cases had nonconvulsive status epilepticus and 2 cases had tonic seizure.24 patients had described intelligence assessment.Among them,18 had developmental delay before epilepsy onset,11 had developmental regression after onset.There were 9 cases with autistic features,4 cases with attention deficit hyperactivity disorder and 3 cases with ataxia.The seizures of 17 cases were controlled,4 cases had partial seizure control,3 cases had no significant improvement,and other 3 cases were unclear.Conclusions The main clinical feature of MAE patients with SLC6A1 gene mutations is absence and atonic seizures,cognition before epilepsy onset can be impaired,and some patients had behavioral problems,such as autistic features or attention deficit hyperactivity disorders.VPA is recommend as first-line treatment.

Expression of hypoxia inducible factor 1αand glucose transporter 1 in lung adenocarcinoma and their clinical significances / 肿瘤研究与临床

Objective To investigate the expression of hypoxia inducible factor 1α (HIF-1α) and glucose transporter 1 (GLUT1) in lung adenocarcinoma and its correlation with tumor metastasis. Methods SP immunohistochemistry was used to detect GLUT1 and HIF-1α protein expression in 125 lung adenocarcinoma, including 41 cases without metastasis, 38 cases with lymphatic metastasis and 46 cases with brain metastasis. The correlation of GLUT1 and HIF-1α in lung adenocarcinoma metastasis was analyzed by using x 2 test and Pearson correlation analysis. Results Most lung adenocarcinoma were histologically heterogeneous, which contained more than one adenocarcinoma type. 73.2 % (30/41) cases were acinar predominant adenocarcinoma in lung adenocarcinoma without metastasis; 53.6 % (15/38) cases were acinar predominant adenocarcinoma and 26.3 % (10/38) cases were solid predominant adenocarcinoma in lung adenocarcinoma with lymphatic metastasis; 47.8 % (22/46) cases were papillary predominant adenocarcinoma and 34.8 % (16/46) cases were solid predominant adenocarcinoma in lung adenocarcinoma with brain metastases. The expression level of GLUT1 and HIF-1α in lung adenocarcinoma with lymphatic metastasis group was higher than that of the group without tumor metastasis (P< 0.05); the expression of GLUT1 and HIF-1α were positively correlated (r=0.407, P=0.000). Conclusions Papillary adenocarcinoma is the most histological type in lung adenocarcinoma with brain metastasis, suggesting that papillary adenocarcinoma is more prone to brain metastasis. The expression of GLUT1 and HIF-1α play an important role in lymph node metastasis and brain metastasis of lung adenocarcinoma.

Expression of hypoxia-inducible factor 1α, glucose transporter 1 and lactate dehydrogenase 5 in colorectal cancer and clinicopathologic significance / 中华病理学杂志

Objective@#To investigate the expression and clinicopathological significance of hypoxia-inducible factor 1 alpha (HIF-1α), glucose transporter 1(GLUT-1) and lactate dehydrogenase(LDH)-5 in colorectal cancer.@*Methods@#The expression levels of HIF-1α, GLUT-1 and LDH-5 were detected by immunohistochemical staining in 142 specimens of human carcinoma in comparison with adjacent normal tissues.@*Results@#The expression levels of HIF-1α(78.2%, 111/142), GLUT-1(75.4%, 107/142) and LDH-5(68.3%, 97/142) were higher in tumor tissues than in adjacent normal tissues(14.8%, 21/142; 11.3%, 16/142; 7.0%, 10/142; P<0.01 for all three proteins), and such over-expression was significantly associated with lymphovascular invasion, tumor grade and pathological stages(all P<0.01). Additional studies showed that HIF-1α, GLUT-1 and LDH-5 were positively associated with each other(r<0.3, P<0.05 for all three proteins).@*Conclusion@#The data suggest that HIF-1α, GLUT-1 and LDH-5 expression may serve as prognostic indicators for colorectal cancer patients.

Negative regulation of glucose transport alleviates microvasculature pathological changes of retinopathy in diabetic mice / 第二军医大学学报

Objective To investigate the effect of glucose transporter-1 (GLUT1) suppression on microvasculature pathological changes in diabetic mice. Methods Thirty-six 8-week-old C57BL/6 mice were randomly divided into normal control, diabetic control and GLUT1siRNA treatment groups. Diabetic model was established by intraperitoneal injection of streptozotocin. GLUT1siRNA treatment group received intravitreal injection of siRNA-mediated GLUT1, and the other two groups received equal amount of non-specific siRNA. Twenty-one weeks after diabetic induction, immunoblotting was conducted to examine the expression of GLUT1 and two inflammation factors; ICAM-1 and TNF-α. We also calculated the retinal glucose concentration. Leukostasis assay and vascular leakage assay were utilized to compare the microvasculature pathological changes between the two groups. Results The expression of GLUT1 was significantly down-regulated in GLUT1siRNA treatment group compared with the other two groups (P

A Case Report of Glucose Transporter 1 Deficiency Syndrome with a Novel Splice Site Mutation (SLC2A1: c.680-2delA)

Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is caused by impaired glucose transport across the blood-brain barrier (BBB) and characterized by infantile seizures, developmental delay, acquired microcephaly, spasticity, ataxia, and a low cerebrospinal glucose concentration (hypoglycorrhachia). A diagnosis of GLUT1-DS is biochemically established in neurologically impaired patients with hypoglycorrhachia in the normoglycemia. GLUT1-DS can be confirmed by mutation analysis of the solute carrier family 2 (facilitated glucose transporter), member 1 (SLC2A1) gene or reduced 3-O-methyl-D-glucose uptake into erythrocytes. The patient was a 12-year-old boy born at term. He had experienced seizures from 4 months of age. Electroencephalography (EEG) did not show epileptiform activity. Brain magnetic resonance imaging (MRI) revealed mild diffuse cortical atrophy and ventricular dilatation. Furthermore, he showed developmental delay, mental retardation, and ataxia, which all became more apparent with age progression. For 7 years, he had experienced paroxysmal episodes of atonic behavioral changes that were aggravated before meals or when he became tired. When he was 12 years old, cerebrospinal fluid (CSF) analysis revealed a low glucose concentration in the normal serum glucose and lactate levels. Under the impression of GLUT1-DS, mutation analysis of the SLC2A1 gene by direct sequencing was performed using white blood cells, and c.680-2delA of intron 5 was found. We describe a GLUT1-DS patient with a typical natural history of GLUT1-DS through a long term follow-up visits, with a novel splice site mutation (SLC2A1: c.6802delA).

Effects of Different Degrees of Intermittent Hypoxia on Inflammatory Cytokines and Adipokines in 3T3-L1 Adipocytes / 天津医药

Objective To study the effect of different degrees of intermittent hypoxia (IH) on inflammatory cytokines and adipokines in 3T3-L1 adipocytes. Methods An intermittent hypoxia/reoxygenation (IH/ROX) from obstructive sleep apnea (OSA) adipocyte model was established. 3T3-L1 adipocytes were divided into five groups, three IH groups (5% O2, 7.5%O2 and 10%O2, referred to as IH-1, IH-2 and IH-3), sustained hypoxia group (10%O2, CH) and the normal oxygen control group (21%O2, IN). ELISA method was used to detect values of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), leptin and adiponectin in cell supernatant. Western blot analysis was used to detect levels of hypoxia-inducible fac-tor-1α(HIF-1α) and glucose transporter-1 (Glut-1). RT-PCR assay was used to analyze HIF-1α, Glut-1, TNF-α, IL-6, leptin and adiponectin mRNA expression levels in adipocytes. Results The expression levels of TNF-α, IL-6 and leptin were significantly higher in IH and CH groups than those of IN group (P<0.05). The expression levels of TNF-α, IL-6 and leptin protein and leptin mRNA were significantly higher in IH-1 group than those of IH-2 and IH-3 groups (P<0.05). The adiponectin and its mRNA levels were significantly lower in IH and CH groups than those of IN group (P<0.05). The adipo-nectin level was significantly lower in IH-1 group than that of IH-2 and IH-3 groups (P<0.05). Conclusion These results demonstrate that IH is related to the extensive changes in the expression and release of inflammation-related adipokines in cultured adipocytes. IH from OSA may underlie the development of the inflammatory response in adipocytes, which is in-volved in insulin resistance in patients with OSA.

Effect of mild hypothermia on the expression of hypoxia-inducible factor-1a and glucose transporter-1 in a rat model of chronic cerebral ischemia-reperfusion / 中华麻醉学杂志

Objective To investigate the effect of mild hypothermia on the expression of hypoxia-inducible factor-1α (HIF-1α) and glucose transporter-1 (GLUT-1) in a rat model of chronic cerebral ischemia-reperfusion.Methods Thirty-six female SD rats weighing 170-210 g were randomly divided into 3 groups (n = 12 each):sham operation group (group S), normal body temperature group (group NT ) and mild hypothermia group (group MH). Arterio-venous fistula was established by end-to-end anastomosis between the right common carotid artery and right external jugular vein for 6 weeks followed by reperfusion. In group MH, mild hypothermia was induced at the initiation of reperfusion and the rectal temperature was reduced to 31.5-32.5 ℃. In group S and NT, the rectal temperature was maintained at 37-38 ℃. Six rats in each group were sacrificed at 3 and 48 h of reperfusion. The brains were immediately removed for determination of the expression of HIF-1α, GLUT-1, HIF-1α mRNA and GLUT-1 mRNA and microscopic examination. Results Compared with group S, the expression of HIF-1α and HIF-1α mRNA at 3 and 48 h of reperfusion and GLUT-1 mRNA at 3 h of reperfusion was up-regulated, while the expression of GLUT-1 and GLUT-1 mRNA at 48 h of reperfusion was down-regulated in group NT (P ＜ 0.05).Compared with group NT, the expression of HIF-1α and HIF-1α mRNA at 48 h of reperfusion and HIF-1α mRNA and GLUT-1 mRNA at 3 h of reperfusion was down-regulated, while the expression of GLUT-1 and GLUT-1 mRNA at 48 h of reperfusion was up-regulated in group MH (P ＜ 0.05).Microscopic examination showed that the injury to the ultrastructure of blood-brain barrier was significantly attenuated in group MH compared with group NT. Conclusion Mild hypothermia can attenuate chronic ischemia-reperfusion injury by down-regulating the expression of HIF-1α and up-regulating the expression of GLUT-1.

Expressions of hypoxia-inducible factor 1α and glucose transporter type 1 in psoriatic lesions / 中华皮肤科杂志

Objective To investigate the expression of glucose transporter type 1(GLUT-1)and hypoxia-inducible factor 1 (HIF-1)α in psoriatic lesions,and to explore their correlations with keratinocyte proliferation.Methods Biopsy specimens were obtained from 30 patients with psoriasis and 20 normal human controls.Immunohistochemistry and Western blotting were used to examine the protein expression of GLUT-1 and HIF-1α in these specimens.Results GLUT-1 and HIF-1α were mainly expressed in the basal layer of the control skin,but throughout the whole epidermis of psoriatic lesions.A significant increase was observed in the expression of GLUT-1 and HIF-1α in psoriatic lesions compared with that in the control skin (botb P＜0.01).In the case of psoriatic lesions,both the expression of GLUT-1 and HIF-1α was positively correlated with that of Ki-67(r=0.70,0.81 respectively,both P＜0.01),and positive correlation was also found between the expression of GLUT-1 and HIF-1α(r=0.85.P＜0.01).Conclusion Our data suggest that uprcgulation Of GLUT-1 and HIF-1α expression in psoriatic lesions might contribute to the proliferation of keratinocytes and psoriasis development.

Expression of Stat 3, GluT-1 and PCNA in condylomata acuminata / 中华皮肤科杂志

Objective To explore the expression and significance of signal transducer and activator of transcription 3 (Stat 3), glucose transporter protein 1 (GluT-1) and proliferation cell nuclear antigen (PC NA) in lesions of condylomata acuminata (CA). Methods SP immunohistochemistry method was used to measure the expression of Stat 3, GluT-1 and PCNA in tissue samples from 40 cases of CA and 20 normal skin controls. Results The positivity rates of Stat 3, GluT-1 and PCNA were 85.0% (34/40), 87.5% (35/40) and 85.0%(34/40), respectively in CA tissue, 35.0% (7/20), 30.0% (6/20)and 55.0% (11/20),respectively in the control tissue; statistical difference was observed in these rates between the two groups (all P ＜ 0.05). The expression intensity of Stat 3, GluT-1 and PCNA was also higher in CA tissue than that in the controls. In addition, the expression intensity of PCNA was correlated with that of Stat 3 and GluT-1in CA tissue (both P＜ 0.05). Conclusions There is an overexpression of Star 3, GluT-1 and PCNA in CA tissue, and the overexpression of Stat 3 and GluT-1 may be associated with the over-proliferation of CA tissue.

The effect of diabetes on expression of the glucose transporter-1 in blood brain barrier endothelial cell of diabetic rats at different time points / 中华神经科杂志

Objective To investigate the effect of diabetes on the expression of the glucose transporter (GLUT-1) in blood brain barrier (BBB) endothelial cell at different time points. Methods Forty male SD rats were randomly divided into normal control and diabetic group. Diabetic model of SD rats was established by intravenous streptozotocin(50 mg/kg) injection. Ten rats in each group were sacrificed on the 2nd month and 10th month respectively. The rat' s prefrontal cortex was removed to observe the expression of GLUT-1 in BBB EC with immunohistochemical(IHC) staining. Results By IHC method, the number of GLUT-1 positive microvessels was significantly decreased in diabetic group in the 2nd month (4. 3 ± 0. 9) compared with that of control group (6.4 ± 1.7, t = 7. 586, P < 0. 01 ) ; the number of GLUT-1 positive microvessels was significantly increased in the diabetic group in the 10th month (8.4 ± 1.4) compared with that of control group (5. 8 ± 1.7, t = 15.922,P < 0. 01 ). Conclusions Short-term diabetes GLUT-1 expression in BBB EC is downregulated in early stage, while it is upregulated in advanced stage.

Expressions of HIF-1α, GLUT1, MRP1, and GST-π in NSCLC tissues and their significance / 肿瘤

Objective: To investigate the expressions of hypoxia-inducible factor-1α (HIF-1α), glucose transporter 1 (GLUT1), multidrug resistance associated protein (MRP1), and glutathione-S-transferases (GST-π) in non-small cell lung cancer (NSCLC) tissues and their relationship with the biological features of lung cancer. Methods: The expressions of HIF-1α, GLUT1, MRP1, and GST-π mRNA in 36 samples of NSCLC tissues and 12 samples of corresponding adjacent tissues were detected by RT-PCR and semiquantitative agarose gel electrophoresis. Their expression in various TNM staging cancer tissues was analyzed by SAS8.0 statistic software. Results: The expressions of the four genes significantly increased in NSCLC tissues than in the corresponding adjacent tissues (P 0.05). Conclusion: HIF-1α, GLUT1, MRP1, and GST-π were over-expressed in NSCLC tissues, which were associated with lymph node and distant metastasis. Expressions of HIF-1α and GLUT1 were elevated with the increase in the TNM staging but expressions of MRP1 and GST-π did not correlate with TNM staging. HIF-1α mRNA expression was positively related with the expression of GLUT1 mRNA (P 0.05). The over-expressions of the four genes may be useful markers indicating the carcinogenesis, Progression, and deterioration of NSCLC.