scholarly journals The Role of Hypoxia-Inducible Factor-1α, Glucose Transporter-1, (GLUT-1) and Carbon Anhydrase IX in Endometrial Cancer Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Pawel Sadlecki ◽  
Magdalena Bodnar ◽  
Marek Grabiec ◽  
Andrzej Marszalek ◽  
Pawel Walentowicz ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Patients ◽  
Glucose Transporter ◽  
Hypoxia Inducible Factor ◽  
Clinicopathological Features ◽  
Glucose Transporter 1 ◽  
Histologic Subtype ◽  
Risk Of Recurrence ◽  
Glut 1

Hypoxia-inducible factor-1α(HIF-1α), glucose transporter-1 (GLUT-1), and carbon anhydrase IX (CAIX) are important molecules that allow adaptation to hypoxic environments. The aim of our study was to investigate the correlation between HIF-1α, GLUT-1, and CAIX protein level with the clinicopathological features of endometrial cancer patients.Materials and Methods. 92 endometrial cancer patients, aged 37–84, were enrolled to our study. In all patients clinical stage, histologic grade, myometrial invasion, lymph node, and distant metastases were determined. Moreover, the survival time was assessed. Immunohistochemical analyses were performed on archive formalin fixed paraffin embedded tissue sections.Results. High significant differences(P=0.0115)were reported between HIF-1αexpression and the histologic subtype of cancer. Higher HIF-1αexpression was associated with the higher risk of recurrence(P=0.0434). The results of GLUT-1 and CAIX expression did not reveal any significant differences between the proteins expression in the primary tumor and the clinicopathological features.Conclusion. The important role of HIF-1αin the group of patients with the high risk of recurrence and the negative histologic subtype of the tumor suggest that the expression of this factor might be useful in the panel of accessory pathomorphological tests and could be helpful in establishing more accurate prognosis in endometrial cancer patients.

scholarly journals Glut-1 explains the evolutionary advantage of the loss of endogenous vitamin C-synthesis

2019 ◽  
Vol 2019 (1) ◽  
pp. 221-231
Author(s):  
Tabea C Hornung ◽  
Hans-Konrad Biesalski
Keyword(s):  
Vitamin C ◽  
Glucose Transporter ◽  
Dietary Vitamin ◽  
Glucose Transporter 1 ◽  
Glut 1 ◽  
Micronutrient Uptake ◽  
Evolutionary Advantage ◽  
Extracellular Substances ◽  
Human Rbcs

Abstract Introduction During evolution, some species including humans, monkeys and fruit bats lost the ability for ascorbic acid (AA) biosynthesis due to inactivation of the enzyme l-gulono-lactone oxidase (GLO) and subsequently became dependent on dietary vitamin C. There are four current hypotheses in relation to the benefit of vitamin C dependence in the context of adaptation and reproduction. Here we advance and test a new ‘electron transfer hypothesis’, which focusses on the role of the expression of glucose transporter 1 (Glut-1) in red blood cells (RBCs) in recycling vitamin C, thereby increasing the efficiency of micronutrient uptake. Methods To evaluate the benefit of Glut-1 expression, we determined vitamin C uptake into RBCs and potential release from two different species, humans with l-Gulono-lactone-oxidase (GLO-loss) and pigs with functional GLO. Results The oxidized form of vitamin C (dehydroascorbate, DHA) was transported into human RBCs via Glut-1. There was no transport of either the reduced (AA) or the oxidized vitamin in pig erythrocytes. Conclusion We propose that the transport of vitamin C increases an intracellular electron pool, which transfers electrons from intracellular ascorbate to extracellular substances like ascorbyl free radical or DHA, resulting in 100-fold smaller daily requirement of this essential redox sensitive micronutrient. This would be an advantage during seasonal changes of the availability from food and may be the key for the survival of individuals without vitamin C biosynthesis. Lay Summary 40 million years ago some individuals lost the ability to synthesize vitamin C. Why did they survive such as humans until now? Individuals with a specific glucose transporter Glut-1 on their erythrocytes which transports vitamin C need less and are protected from scarcity due to seasons and food competitors.

scholarly journals VHL inactivation is an important pathway for the development of malignant sporadic pancreatic endocrine tumors

2009 ◽  
Vol 16 (4) ◽  
pp. 1219-1227 ◽  
Author(s):  
A M Schmitt ◽  
S Schmid ◽  
T Rudolph ◽  
M Anlauf ◽  
C Prinz ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Adverse Outcome ◽  
Hypoxia Inducible Factor ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Small Subset ◽  
Endocrine Tumors ◽  
Glucose Transporter 1 ◽  
Glut 1 ◽  
Pancreatic Endocrine Tumors

A small subset of familial pancreatic endocrine tumors (PET) arises in patients with von Hippel–Lindau syndrome and these tumors may have an adverse outcome compared to other familial PET. Sporadic PET rarely harbors somatic VHL mutations, but the chromosomal location of the VHL gene is frequently deleted in sporadic PET. A subset of sporadic PET shows active hypoxia signals on mRNA and protein level. To identify the frequency of functionally relevant VHL inactivation in sporadic PET and to examine a possible prognostic significance we correlated epigenetic and genetic VHL alterations with hypoxia signals. VHL mutations were absent in all 37 PETs examined. In 2 out of 35 informative PET (6%) methylation of the VHL promoter region was detected and VHL deletion by fluorescence in situ hybridization was found in 14 out of 79 PET (18%). Hypoxia inducible factor 1α (HIF1-α), carbonic anhydrase 9 (CA-9), and glucose transporter 1 (GLUT-1) protein was expressed in 19, 27, and 30% of the 152 PETs examined. Protein expression of the HIF1-α downstream target CA-9 correlated significantly with the expression of CA-9 RNA (P<0.001), VHL RNA (P<0.05), and VHL deletion (P<0.001) as well as with HIF1-α (P<0.005) and GLUT-1 immunohistochemistry (P<0.001). These PET with VHL alterations and signs of hypoxia signalling were characterized by a significantly shortened disease-free survival. We conclude that VHL gene impairment by promoter methylation and VHL deletion in nearly 25% of PET leads to the activation of the HIF-pathway. Our data suggest that VHL inactivation and consecutive hypoxia signals may be a mechanism for the development of sporadic PET with an adverse outcome.

scholarly journals Glucose Transporter 1 and Hypoxia-Inducible Factor 1α is Indicators of Head and Neck Squamous Cell Carcinoma Aggressiveness and Poor Prognosis: A Case Control Study

2020 ◽  
Author(s):  
Jia Liu ◽  
Qiong Xu ◽  
Yun-Zhen Luo ◽  
Hong-Tian Yao ◽  
Shui-Hong Zhou
Keyword(s):  
Squamous Cell Carcinoma ◽  
Poor Prognosis ◽  
Glucose Transporter ◽  
Clinical Stage ◽  
Hypoxia Inducible Factor ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Glucose Transporter 1 ◽  
Glut 1 ◽  
Node Metastasis

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is a common and aggressive malignancy with a high morbidity and mortality profile. Increased levels of expression of the tumor hypoxia markers, hypoxia-inducible factor 1α (HIF-1α) and glucose transporter 1 (GLUT-1), are indicators of poor prognosis in carcinoma.Materials and methods: This study involved detection of HIF-1α and GLUT-1 expression with a mean follow-up period of 10 years in 69 cases of HNSCC (23 cases of hypopharyngeal carcinoma and 46 of laryngeal carcinoma) and 30 controls (15 cases of vocal cord polyps and 15 of leukoplakia). The χ2 test, Fisher’s exact probability method, Pearson’s test, Kaplan–Meier method, Cox proportional hazards regression model of SPSS version 22.0 was used. In all analyses, P < 0.05 was taken to indicate statistical significance.Results: Compared with inflammatory and precancerous lesion tissues, the levels of GLUT-1 and HIF-1α expression were significantly increased in HNSCC (P < 0.001). There was a positive correlation between HIF-1α and GLUT-1 (r = 0.338, P = 0.004). GLUT-1 expression was significantly associated with primary tumor site (P = 0.032), clinical stage (P = 0.036), lymph node metastasis (P = 0.032), and distant metastasis (P = 0.002). HIF-1α expression was significantly related to recurrence (P = 0.013), distant metastasis (P = 0.044), second primary cancer (P = 0.040), and overall survival (OS) (P = 0.029). The OS of the 69 patients with HNSCC was significantly associated with the primary tumor site (P = 0.024), clinical stage (P = 0.041), and lymph node metastasis (P = 0.039). Conclusion: The increased levels of GLUT-1 and HIF-1α expression may serve as molecular markers for diagnosis of HNSCC. High GLUT-1 and HIF-1α expression, especially HIF-1α expression, may be indicators of HNSCC aggressiveness and poor prognosis.

scholarly journals LAT-1 and GLUT-1 Carrier Expression and Its Prognostic Value in Gastroenteropancreatic Neuroendocrine Tumors

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2968
Author(s):  
Miguel Sampedro-Núñez ◽  
Antonio Bouthelier ◽  
Ana Serrano-Somavilla ◽  
Rebeca Martínez-Hernández ◽  
Magdalena Adrados ◽  
...  
Keyword(s):  
Nutrient Uptake ◽  
Neuroendocrine Tumors ◽  
Glucose Transporter ◽  
Tumor Tissue ◽  
Hypoxia Inducible Factor ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Tissue Samples ◽  
Glucose Transporter 1 ◽  
Von Hippel Lindau ◽  
Glut 1

Cancer cells develop mechanisms that increase nutrient uptake, including key nutrient carriers, such as amino acid transporter 1 (LAT-1) and glucose transporter 1 (GLUT-1), regulated by the oxygen-sensing Von Hippel Lindau-hypoxia-inducible factor (VHL-HIF) transcriptional pathway. We aimed to analyze these metabolic players in gastroenteropancreatic neuroendocrine tumors (GEP-NET) and correlate them with tumor malignancy and progression. LAT-1, GLUT-1, and pVHL expression was analyzed in 116 GEP-NETs and 48 peritumoral tissue samples by immunohistochemistry. LAT-1 was stably silenced using specific shRNA in the human NET BON cell line. LAT-1 expression was significantly increased in tumor tissue compared to non-tumor tissue in both gastrointestinal (67% vs. 44%) and pancreatic NETs (54% vs. 31%). Similarly, GLUT-1 was substantially elevated in gastrointestinal (74% vs. 19%) and pancreatic (58% vs. 4%) NETs. In contrast, pVHL expression was decreased (85% vs. 58%) in pancreatic NETs. Tumors with metastases at diagnosis displayed increased LAT-1 and GLUT-1 and decreased pVHL expression (p < 0.001). In accordance with these data, silencing LAT-1 curtailed cell proliferation in BON cells. These findings suggest that specific mechanisms that increase nutrient uptake, such as LAT-1 and GLUT-1, are increased in GEP-NETs, whereas pVHL is decreased. These markers might be related to the proliferation and metastatic capacity of these tumors.

scholarly journals Induction of Hypoxia-Inducible Factor-1, Erythropoietin, Vascular Endothelial Growth Factor, and Glucose Transporter-1 by Hypoxia: Evidence Against a Regulatory Role for Src Kinase

Blood ◽  
1997 ◽  
Vol 89 (2) ◽  
pp. 503-509 ◽  
Author(s):  
Jonathan M. Gleadle ◽  
Peter J. Ratcliffe
Keyword(s):  
Glucose Transporter ◽  
Hypoxia Inducible Factor ◽  
Src Kinase ◽  
Severe Hypoxia ◽  
Vascular Endothelial ◽  
Glucose Transporter 1 ◽  
Glut 1 ◽  
Hypoxia Inducible Factor 1 ◽  
Hypoxic Induction ◽  
Endothelial Growth Factor

Abstract The induction by hypoxia of genes such as erythropoietin, vascular endothelial growth factor (VEGF ), and glucose transporter-1 (Glut-1) is mediated in part by a transcriptional complex termed hypoxia-inducible factor-1 (HIF-1). Several lines of evidence have implicated protein phosphorylation in the mechanism of activation of HIF-1 by hypoxia. Recent reports have described the activation of the tyrosine kinase src by severe hypoxia, and a role in the induction of VEGF by severe hypoxia has been proposed. This led us to examine whether src and related kinases operated more widely in the hypoxic induction of HIF-1 and HIF-1–dependent genes regulated by hypoxia. Measurements of src kinase activity in cells exposed to varying severities of hypoxia showed activation by severe hypoxia (0.1% oxygen or catalyst induced anoxia), but not 1% oxygen. This contrasted with the marked induction of HIF-1 by exposure to 1% oxygen. Manipulations of src activity were produced by transient and stable transfection of Hep3B cells. Despite substantial changes in src activity, no alteration was seen in the normoxic or hypoxic expression of erythropoietin, VEGF, or Glut-1, or in the regulation of HIF-1–dependent reporter genes inducible by hypoxia. Similarly, we found that the expression of these genes in src- or c-src kinase-deficient cells did not differ from wild-type cells at either 1% oxygen or more severe hypoxia. These results indicate that src is not critical for the hypoxic induction of HIF-1, erythropoietin, VEGF, or Glut-1.

Abstract 522: Cd163 Macrophage Content and Glucose Transporter-1 Expression in Aspirated Deep Vein Thrombus Are Associated With the Time After Onset

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Atsushi Yamashita ◽  
Eiji Furukoji ◽  
Sayaka Moriguchi-Goto ◽  
Mio Kojima ◽  
Chihiro Sugita ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Smooth Muscle Actin ◽  
Hypoxia Inducible Factor ◽  
Glycophorin A ◽  
Glucose Transporter 1 ◽  
Glut 1 ◽  
Vein Thrombosis ◽  
Metabolic Marker ◽  
The Times ◽  
Deep Vein

Background: Leukocytes involve resolution of deep vein thrombosis (DVT) and glucose uptake may reflect acute phase of DVT. Macrophages in M2-like phenotype are related to the tissue repair. However, markers reflecting thrombus age have not been established. The aims of this study were to identify a cellular or metabolic marker that reflects the time after onset in human aspirated DVT. Methods: We histologically and immunohistochemically analyzed 17 aspirated thrombi. The times from onset to aspiration ranged from 5 to 60 days. Paraffin sections were stained with hematoxylin and eosin and antibodies for fibrin, glycophorin A, integrin α2bβ3, CD68, M2-markers (CD163, CD206), CD34, smooth muscle actin (SMA), glucose transporter (Glut)-1, and hypoxia inducible factor (HIF)-1α (a metabolic regulator). Results: All thrombi were immunopositive for glycophorin A, fibrin, and integrin α2bβ3, CD68, CD163, CD206 and Glut-1, and contained granulocytes without lytic change. Almost all of the thrombi had small foci of CD34 or SMA immunopositive areas. The CD163- but not CD206-positive cells existed predominantly among the macrophage population. Glut-1 was exclusively expressed on the erythrocytes. There were a few HIF-1α immunopositive nuclei. The values of the immunopositive areas for glycophorin A and Glut-1 were negatively correlated and those of CD68 and CD163 were positively correlated with the time after the onset. The CD163-positive macrophages were associated with glycophorin A, CD34, or SMA positive cell-rich areas. Conclusions: These findings suggest that CD163 and Glut-1 expression could be markers for the evaluations of thrombus age in DVT and CD163 macrophages might play a role in the organization of DVT.

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