• Title/Summary/Keyword: 2-deoxy-D-glucose

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18F-2-Deoxy-2-Fluoro-D-Glucose Positron Emission Tomography: Computed Tomography for Preoperative Staging in Gastric Cancer Patients

  • Youn, Seok Hwa;Seo, Kyung Won;Lee, Sang Ho;Shin, Yeon Myung;Yoon, Ki Young
    • Journal of Gastric Cancer
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    • v.12 no.3
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    • pp.179-186
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    • 2012
  • Purpose: The use of 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography-computed tomography as a routine preoperative modality is increasing for gastric cancer despite controversy with its usefulness in preoperative staging. In this study we aimed to determine the usefulness of preoperative positron emission tomography-computed tomography scans for staging of gastric cancer. Materials and Methods: We retrospectively analyzed 396 patients' positron emission tomography-computed tomography scans acquired for preoperative staging from January to December 2009. Results: The sensitivity of positron emission tomography-computed tomography for detecting early gastric cancer was 20.7% and it was 74.2% for advanced gastric cancer. The size of the primary tumor was correlated with sensitivity, and there was a positive correlation between T stage and sensitivity. For regional lymph node metastasis, the sensitivity and specificity of the positron emission tomography-computed tomography were 30.7% and 94.7%, respectively. There was no correlation between T stage and maximum standardized uptake value or between tumor markers and maximum standardized uptake value. Fluorodeoxyglucose uptake was detected by positron emission tomography-computed tomography in 24 lesions other than the primary tumors. Among them, nine cases were found to be malignant, including double primary cancers and metastatic cancers. Only two cases were detected purely by positron emission tomography-computed tomography. Conclusions: Positron emission tomography-computed tomography could be useful in detecting metastasis or another primary cancer for preoperative staging in gastric cancer patients, but not for T or N staging. More prospective studies are needed to determine whether positron emission tomography-computed tomography scans should be considered a routine preoperative imaging modality.

4-Acetoxyscirpendiol of Paecilomyces tenuipes Inhibits Na+/D-Glucose Cotransporter Expressed in Xenopus laevis Oocytes

  • Yoo, Oc-Ki;Son, Joo-Hiuk;Lee, Dong-Hee
    • BMB Reports
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    • v.38 no.2
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    • pp.211-217
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    • 2005
  • Cordyceps, an entomopathogenic fungus, contains many health-promoting ingredients. Recent reports indicate that the consumption of cordyceps helps reduce blood-sugar content in diabetics. However, the mechanism underlying this reduction in circulatory sugar content is not fully understood. Methanolic extracts were prepared from the fruiting bodies of Paecilomyces tenuipes, and 4-beta acetoxyscirpendiol (4-ASD) was eventually isolated and purified. $Na^+$/Glucose transporter-1 (SGLT-1) was expressed in Xenopus oocytes, and the effect of 4-ASD on SGLT-1 was analyzed utilizing a voltage clamp and by performing 2-deoxy-D-glucose (2-DOG) uptake studies. 4-ASD was shown to significantly inhibit SGLT-1 activity compared to the non-treated control in a dose-dependent manner. In the presence of the derivatives of 4-ASD (diacetoxyscirpenol or 15-acetoxyscirpendiol), SGLT-1 activity was greatly inhibited in an 4-ASD-like manner. Of these derivatives, 15-acetoxyscirepenol inhibited SGLT-1 as well as 4-ASD, whereas diacetoxyscirpenol was slightly less effective. Taken together, these results strongly indicate that 4-ASD in P. tenuipes may lower blood sugar levels in the circulatory system. We conclude that 4-ASD and its derivatives are effective SGLT-1 inhibitors.

Bioactivity Guided Phytochemical Study of Clematis hirsuta Growing in Saudi Arabia

  • Abdel-Kader, Maged S.;Al-Taweel, Areej M.;El-Deeb, Kadriya S.
    • Natural Product Sciences
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    • v.14 no.1
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    • pp.56-61
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    • 2008
  • Bioactivity guided phytochemical study of the petroleum ether and butanol extracts of Clematis hirsuta resulted in the isolation of 12 compounds. Rat paw edema as a model of acute inflammation was used to evaluate the anti-inflammatory activity of the extracts and the chromatographic fractions. Five known sterols and triterpenes namely: ${\beta}-amyrin$ (1), lupeol (2), ${\beta}-sitosterol$ (3), oleanolic acid (4) and stigmasterol glycoside (5) were isolated from the petroleum ether extract. The n-butanol extract afforded two compounds reported for the first time from natural source: (S)-(+)-dihydro-5-(hydroxymethyl)-2(3H)-furanone (7) and (s)-(-)-5-hydroxymethyl-2(5H)-furanone (8). In addition, anemonin (6), dihydro-4-hydroxy-5-(hydroxymethyl)-2(3H)-furanone (2-deoxy-D-ribono-1,4-lactone) (9), biophenol (cimidahurin) (10), glucose (11) and sucrose (12) were also identified. The structures were determined from spectroscopic data including 1D- and 2D-NMR experiments.

Clinical Application of PET in Abdominal Cancers (소화기 암에서 PET의 임상적 의의)

  • Choi, Chang-Woon
    • The Korean Journal of Nuclear Medicine
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    • v.36 no.1
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    • pp.39-45
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    • 2002
  • Clinical application of positron emission tomography (PET) is rapidly increasing for the defection and staging of cancer at whole-body studios performed with the glucose analogue tracer 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG). Although FDG PET cannot match the anatomic resolution of conventional imaging techniques in the liver and the other abdominal organs, it is particularly useful for identification and characterization of the entire body simultaneously. FDG PET can show foci of metastatic disease that may not be apparent at conventional anatomic imaging and can aid in the characterizing of indeterminate soft-tissue masses. Most abdominal cancer requires surgical management. FDG PET can improve the selection of patients for surgical treatment and thereby reduce the morbidity and mortality associated with inappropriate surgery. FDG PET is also useful for the early detection of recurrence and the monitoring of therapeutic effect. The abdominal cancers, such as gastroesophageal cancer, colorectal cancer, liver cancer and pancreatic cancer, are common malignancies in Korea, and PET is one of the most promising and useful methodologies for the management of abdominal cancers.

2-Deoxy-D-glucose Regulates Dedifferentiation but not Cyclooxygenase-2 Expression through Reorganization of Actin Cytoskeletal Architecture in Rabbit Articular Chondrocytes

  • Yu, Seon-Mi;Kim, Song-Ja
    • Biomedical Science Letters
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    • v.15 no.2
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    • pp.113-118
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    • 2009
  • Actin cytoskeletal architecture is believed to be a crucially important modulator of chondrocyte phenotype. 2DG(2-Dexoy-D-glucose) induces reorganization of actin cytoskeletal architecture in chondrocytes. In this study, we have investigated the effects of 2DG on dedifferentiation and inflammation via reorganization of cytoskeletal architecture in rabbit articular chondrocytes, with a focus on p38 kinase pathway. Treatment of 2DG alone reduced type II collagen and COX-2 expression in chondrocytes. But, 2DG reduced type II collagen was recovered by CD, disruptor of actin cytoskeletal architecture, whereas did not affect on COX-2 expression and production of $PGE_2$ compared with 2DG alone treated cells. Treatment of 2DG with JAS, inducer of cytoskeletal architecture polymerization, accelerated reduction of type II collagen expression and synthesis of proteoglycan but did not affect on COX-2 expression and production of $PGE_2$. Also, 2DG stimulated activation of p38 kinase. This result showed that 2DG regulates type II collagen but not cyclooxygenase-2 expression through reorganization of cytoskeletal architecture via p38 kinase pathway in rabbit articular chondrocytes.

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A Study on the Production of Aromatic Amino Acids by Escherichia coli. (Escherichia coli에 의한 방향족 아미노산 생산에 관한 연구)

  • Park, Young-Jin
    • Microbiology and Biotechnology Letters
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    • v.13 no.2
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    • pp.119-127
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    • 1985
  • A series of Escherichia coli mutants were exmined for ability to convert glucose and ammonium salts into phenylalanine. This enabled the biochemical changes having major. effects on phenylaianine yield, and interactions between mutations, to be identified. Changes to the common pathway of aromatic biosynthesis having a major effects include desensitization of the first enzyme (3-deoxy-D-arabinoheptulosonate synthase) to end-product inhibition, and removal of repression of enzyme synthesis. It is suggested that the 3-deoxy-D-arabino-heptulosonate synthase Phe isoenzyme has a more important effect on yield. Similarly, removal of repression and end-product inhibition on the phenylalanine terminal pathway increased yield, and changes to both common and branch pathways were synergistic. Blockage of the typrosine and tryptophan pathways had minor effects on phenylalanine yield, and a mutation affecting aramatic amino acid transport (aroP) decreased yield. With multiple-mutation strains hish specific rates of product formation (ie 0.1-0.17g phenylalanine/g cells/h) were obtained.

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Effects of Cadmium on Glucose Transport in L6 Myocytes (L6 근육세포에서 포도당 수송능에 미치는 $CdCl_2$의 영향)

  • Kang Donghee;Khil Lee-Yong;park Kwangsik;Lee Byung-Hoon;Moon Chang-Kiu
    • Environmental Analysis Health and Toxicology
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    • v.20 no.1
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    • pp.75-85
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    • 2005
  • This study was aimed to know the effect of cadmium chloride (CdCl₂) on glucose transport in L6 myotube and its action mechanism. CdCl₂ increased the 2-deoxy- (l-3H)-D-glucose (2-DOG) uptake 1.9 and 2.4 fold at 10 and 25 μM respectively. To investigate the stimulating-mechanism of glucose transport induced by CdCl₂, the wortmannin and PD98059 were used as PI3K (phosphatidylinositol 3-kinase) inhibitor and MAPK inhibitor respectively, which did not affect 2-DOG uptake. This fact suggests that CdCl₂ induced 2-DOG uptake may not be concerned to the insulin signalling pathway. Whereas nifedipine, a calcium channel blocker, and trifluoperazine, a calmodulin inhibitor, were found to inhibit the 2-DOG uptake stimulted by CdCl₂. In addition, we also measured the ROS (reactive oxygen species) production and GSH level in L6 myotube to investigate the correlation between the glucose uptake and ROS. CdCl₂(25 μM) increased ROS generation approximately 1.5 fold and changed the cellular GSH level, but GSSG/GSH ratio remained unchanged. CdCl₂ stimulated 2-DOG uptake and ROS generation were inhibited by N-acetylcystein. And BSO pretreatment, a potent inhibitor of γ-GCS, resulted in the dramatic decrease of 2-DOG uptake and also the increase of the sensitivity to cadmium cytotoxicity. The obtained results suggest that CdCl₂-stimulated glucose uptake might be based on the activation of HMP shunt as an antioxidant defense mechanism of the cells.

Effect of Glucose, Its Analogs and Some Amino Acids on Pre-steady State Kinetics of ATP Hydrolysis by PM-ATPase of Pathogenic Yeast (Candida albicans)

  • Bushra, Rashid;Nikhat, Manzoor;M., Amin;Luqman A., Khan
    • Animal cells and systems
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    • v.8 no.4
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    • pp.307-312
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    • 2004
  • Fast kinetics of transient pH changes and difference spectrum formation have been investigated following mixing of ADP/ATP with partially purified plasma membrane PM-ATPase of the pathogenic yeast Candida albicans in the presence of five nutrients: glucose, glutamic acid, proline, lysine, and arginine and two analogs of glucose: 2-deoxy D-glucose and xylose. Average $H^+$- absorption to release ratio, indicative of population of ATPase undergoing complete hydrolytic cycle, was found to be 0.27 for control. This ratio varied between 0.25 (proline) to 0.36 (arginine) for all other compounds tested, except for glucose. In the presence of glucose, $H^+$- absorption to release ratio was exceptionally high (0.92). While no UV difference spectrum was observed with ADP, mixing of ATP with ATPase led to a large conformational change. Exposure to different nutrients restricted the magnitude of the conformational change; the analogs of glucose were found to be ineffective. This suppression was maximal in the case of glucose (80%); with other nutrients, the magnitude of suppression ranged from 40-50%. Rate of $H^+$- absorption, which is indicative of E~P complex dissociation, showed positive correlation with suppression of conformational change only in the case of glucose and no other nutrient/analog. Mode of interaction of glucose with plasma membrane $H^+$-ATPase thus appears to be strikingly distinct compared to that of other nutrients/analogs tested. The results obtained lead us to propose a model for explaining glucose stimulation of plasma membrane $H^+$-ATPase activity.

Characterization of Acetoxyscirpendiol of Paecilomyces tenuipes as Inhibitor of Sodium Glucose Co-transporters Expressed in Xenopus laevis Oocytes

  • Park, Il-Woon;Hwang, Gwi-Seo;Kim, Ha-Won;Lee, Dong-Hee
    • Biomolecules & Therapeutics
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    • v.12 no.4
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    • pp.250-256
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    • 2004
  • Cordyceps possesses numerous health-promoting ingredients including hypoglycemic agents. The mechanism for the reduction of circulatory sugar content, however, is still not fully understand. In this study, 4-beta acetoxyscirpendiol (ASD) was purified from the methanolic extracts from fruiting bodies of Paecilomyces tenuipes. Na+/Glucose transporter-1 (SGLT-1) was expressed in the Xenopus oocytes. The effect of ASD on the oocyte expressed SGLT-1 was analyzed utilizing the voltage clamp and 2-deoxy-D-glucose (2-DOG) uptake studies. ASD was shown to significantly inhibit SGLT-1 activity compared to the non-treated control in a dose- dependent manner. In the presense of its two derivatives (diacetoxyscirpenol or 15-acetoxyscirpendiol), SGLT-1 activity was greatly inhibited similarly as ASD. Between ASD derivatives, 15-acetoxyscirepenol showed inhibition equivalent to that of ASD while diacetoxyscirpenol did less degree of inhibition. Insummary , these results strongly indicate that ASD in P. tenuipes may serve as a functional substance in lowering blood sugar in the circulatory system. ASD and its derivatives can be utilized as inhibitors of SGLT-1.

2-deoxy-D-Glucose Synergizes with Doxorubicin or L-Buthionine Sulfoximine to Reduce Adhesion and Migration of Breast Cancer Cells

  • Mustafa, Ebtihal H;Mahmoud, Huda T;Al-Hudhud, Mariam Y;Abdalla, Maher Y;Ahmad, Iman M;Yasin, Salem R;Elkarmi, Ali Z;Tahtamouni, Lubna H
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3213-3222
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    • 2015
  • Background: Cancer metastasis depends on cell motility which is driven by cycles of actin polymerization and depolymerization. Reactive oxygen species (ROS) and metabolic oxidative stress have long been associated with cancer. ROS play a vital role in regulating actin dynamics that are sensitive to oxidative modification. The current work aimed at studying the effects of sub-lethal metabolic oxidative stress on actin cytoskeleton, focal adhesion and cell migration. Materials and Methods: T47D human breast cancer cells were treated with 2-deoxy-D-glucose (2DG), L-buthionine sulfoximine (BSO), or doxorubicin (DOX), individually or in combination, and changes in intracellular total glutathione and malondialdehyde (MDA) levels were measured. The expression of three major antioxidant enzymes was studied by immunoblotting, and cells were stained with fluorescent-phalloidin to evaluate changes in F-actin organization. In addition, cell adhesion and degradation ability were measured. Cell migration was studied using wound healing and transwell migration assays. Results: Our results show that treating T47D human breast cancer cells with drug combinations (2DG/BSO, 2DG/DOX, or BSO/DOX) decreased intracellular total glutathione and increased oxidized glutathione, lipid peroxidation, and cytotoxicity. In addition, the drug combinations caused a reduction in cell area and mitotic index, prophase arrest and a decreased ability to form invadopodia. The formation of F-actin aggregates was increased in treated T47D cells. Moreover, combination therapy reduced cell adhesion and the rate of cell migration. Conclusions: Our results suggest that exposure of T47D breast cancer cells to combination therapy reduces cell migration via effects on metabolic oxidative stress.