238 results match your criteria glut targeting

Targeting of GLUT5 for Transporter-Mediated Drug-Delivery Is Contingent upon Substrate Hydrophilicity.

Int J Mol Sci 2021 May 11;22(10). Epub 2021 May 11.

Chemistry Department, Michigan Technological University, Houghton, MI 49931, USA.

Specific link between high fructose uptake and cancer development and progression highlighted fructose transporters as potential means to achieve GLUT-mediated discrimination between normal and cancer cells. The gained expression of fructose-specific transporter GLUT5 in various cancers offers a possibility for developing cancer-specific imaging and bioactive agents. Herein, we explore the feasibility of delivering a bioactive agent through cancer-relevant fructose-specific transporter GLUT5. Read More

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Surgically Induced Ischemia has no Impact on Protein Expression Levels of HIF-1α and Related Biomarkers in Renal Cell Carcinoma.

APMIS 2021 May 4. Epub 2021 May 4.

Department of Pathology, Odense University Hospital, Odense, Denmark.

Background And Purpose: The increasing demands for personalized targeted therapy directed against Renal Cell Carcinoma has driven a search for predictive markers. Novel therapies targeting HIF-1α in Renal Cell Carcinoma have been developed and HIF-1α has been suggested as a novel predictive marker of response to therapy. The surgical resection of a kidney tumor induces tissue ischemia and HIF-1α is an oxygen-sensitive transcription factor, which is known to be up-regulated during hypoxia. Read More

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Targeting Colorectal Cancer with Conjugates of a Glucose Transporter Inhibitor and 5-Fluorouracil.

J Med Chem 2021 04 5;64(8):4450-4461. Epub 2021 Apr 5.

School of Pharmacy, College of Medicine, National Taiwan University, Taipei 100, Taiwan.

Overexpression of glucose transporters (GLUTs) in colorectal cancer cells is associated with 5-fluorouracil (, 5-FU) resistance and poor clinical outcomes. We designed and synthesized a novel GLUT-targeting drug conjugate, triggered by glutathione in the tumor microenvironment, that releases 5-FU and GLUTs inhibitor (phlorizin () and phloretin ()). Using an orthotopic colorectal cancer mice model, we showed that the conjugate exhibited better antitumor efficacy than 5-FU, with much lower exposure of 5-FU during treatment and without significant side effects. Read More

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Regulation of Glycolysis in Head and Neck Cancer.

Adv Exp Med Biol 2021 ;1280:219-230

Amity Institute of Molecular Medicine & Stem Cell Research, Amity University, Noida, Uttar Pradesh, India.

Head and neck squamous cell carcinoma (HNSCC) glycolysis is an important factor for the advancement of the disease and metastasis. Upregulation of glycolysis leads to decreased sensitivity to chemotherapy and radiation. HNSCC cells maintain constitutive glycolytic flux generating metabolic intermediates for the synthesis of amino acids, nucleotides, and fats for cell survival and disease progression. Read More

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A small-molecule pan-class I glucose transporter inhibitor reduces cancer cell proliferation in vitro and tumor growth in vivo by targeting glucose-based metabolism.

Cancer Metab 2021 Mar 26;9(1):14. Epub 2021 Mar 26.

Department of Biological Sciences, Ohio University, Athens, OH, 45701, USA.

Background: Cancer cells drastically increase the uptake of glucose and glucose metabolism by overexpressing class I glucose transporters (GLUT1-4) to meet their energy and biomass synthesis needs and are very sensitive and vulnerable to glucose deprivation. Although targeting glucose uptake via GLUTs has been an attractive anticancer strategy, the relative anticancer efficacy of multi-GLUT targeting or single GLUT targeting is unclear. Here, we report DRB18, a synthetic small molecule, is a potent anticancer compound whose pan-class I GLUT inhibition is superior to single GLUT targeting. Read More

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In silico design and pharmacological evaluation of conjugates of atenolol with modified saccharide for cardiovascular targeting.

Glycoconj J 2021 Apr 9;38(2):261-271. Epub 2021 Mar 9.

Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, India.

Amongst a wide range of biological macromolecules, saccharides exhibit the potential to be specifically recognized by cell-surface receptors and hence can be utilized as ligands in targeted drug delivery. The current study aims to use saccharides viz. Galactose, Pectin and Chitosan to improve targeting of Atenolol by oxalyl chloride mediated grafting. Read More

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Functional Expression of the Human Glucose Transporters GLUT2 and GLUT3 in Yeast Offers Novel Screening Systems for GLUT-Targeting Drugs.

Front Mol Biosci 2020 18;7:598419. Epub 2021 Feb 18.

Institute of Molecular Biosciences, Faculty of Biological Sciences, Goethe University Frankfurt, Frankfurt am Main, Germany.

Human GLUT2 and GLUT3, members of the GLUT/SLC2 gene family, facilitate glucose transport in specific tissues. Their malfunction or misregulation is associated with serious diseases, including diabetes, metabolic syndrome, and cancer. Despite being promising drug targets, GLUTs have only a few specific inhibitors. Read More

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February 2021

Vitamin C activates pyruvate dehydrogenase (PDH) targeting the mitochondrial tricarboxylic acid (TCA) cycle in hypoxic mutant colon cancer.

Theranostics 2021 25;11(8):3595-3606. Epub 2021 Jan 25.

Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz-UAM (Madrid), Spain.

In hypoxic tumors, positive feedback between oncogenic KRAS and HIF-1α involves impressive metabolic changes correlating with drug resistance and poor prognosis in colorectal cancer. Up to date, designed KRAS-targeting molecules do not show clear benefits in patient overall survival (POS) so pharmacological modulation of aberrant tricarboxylic acid (TCA) cycle in hypoxic cancer has been proposed as a metabolic vulnerability of KRAS-driven tumors. Annexin V-FITC and cell viability assays were carried out in order to verify vitamin C citotoxicity in KRAS mutant SW480 and DLD1 as well as in Immortalized Human Colonic Epithelial Cells (HCEC). Read More

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January 2021

Unraveling GLUT-mediated transcytosis pathway of glycosylated nanodisks.

Asian J Pharm Sci 2021 Jan 27;16(1):120-128. Epub 2020 Jul 27.

Department of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200032, China.

Glucose transporter (GLUT)-mediated transcytosis has been validated as an efficient method to cross the blood-brain barrier and enhance brain transport of nanomedicines. However, the transcytosis process remains elusive. Glycopeptide-modified nanodisks (Gly-A7R-NDs), which demonstrated high capacity of brain targeting via GLUT-mediated transcytosis in our previous reports, were utilized to better understand the whole transcytosis process. Read More

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January 2021

Glycosylated Nanoparticles for Cancer-Targeted Drug Delivery.

Front Oncol 2020 30;10:605037. Epub 2020 Nov 30.

Laboratorio de Citopatología Ambiental, Departamento de Morfología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Zacatenco, Mexico City, Mexico.

Nanoparticles (NPs) are novel platforms that can carry both cancer-targeting molecules and drugs to avoid severe side effects due to nonspecific drug delivery in standard chemotherapy treatments. Cancer cells are characterized by abnormal membranes, metabolic changes, the presence of lectin receptors, glucose transporters (GLUT) overexpression, and glycosylation of immune receptors of programmed death on cell surfaces. These characteristics have led to the development of several strategies for cancer therapy, including a large number of carbohydrate-modified NPs, which have become desirable for use in cell-selective drug delivery systems because they increase nanoparticle-cell interactions and uptake of carried drugs. Read More

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November 2020

The Safe Soluble Compound Dehydroascorbic Acid Inhibits Various Upstream and Downstream Effectors of PI3K and KRAS Signaling Pathways in Undruggable -Mutant Colorectal Cancer Stem-Like Cells.

Nutr Cancer 2020 Dec 7:1-16. Epub 2020 Dec 7.

Department of Cellular and Molecular Biotechnology, Institute of Biotechnology, Urmia University, Urmia, Iran.

Efforts to develop effective drugs targeting PI3K and KRAS signaling pathways in -mutant colorectal cancer stem cells (CRCSCs) remain challenging. Finding safe compounds that can easily enter CRCSCs with the ability to target metastasis-driver gene and pluripotency network genes as key upstream and downstream effectors of both PI3K and KRAS signaling pathways may provide promising results. -mutant CRCSCs display high expression of glucose transporters (GLUTs) on their cell membrane and a glycolytic phenotype providing an opportunity to deliver antiglycolytic compounds into these cells via the GLUTs. Read More

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December 2020

Targeting metabolic plasticity in glioma stem cells in vitro and in vivo through specific inhibition of c-Src by TAT-Cx43.

EBioMedicine 2020 Dec 27;62:103134. Epub 2020 Nov 27.

Instituto de Neurociencias de Castilla y León (INCYL), Universidad de Salamanca, Calle Pintor Fernando Gallego 1, Salamanca 37007, Spain; Departamento de Bioquímica y Biología Celular, Universidad de Salamanca, Edificio Departamental, Campus Miguel de Unamuno, Salamanca 37007, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Virgen de la Vega, 10ª planta, Paseo de San Vicente, 58-182, Salamanca 37007, Spain. Electronic address:

Background: Glioblastoma is the most aggressive primary brain tumour and has a very poor prognosis. Inhibition of c-Src activity in glioblastoma stem cells (GSCs, responsible for glioblastoma lethality) and primary glioblastoma cells by the peptide TAT-Cx43 reduces tumorigenicity, and boosts survival in preclinical models. Because c-Src can modulate cell metabolism and several reports revealed poor clinical efficacy of various antitumoral drugs due to metabolic rewiring in cancer cells, here we explored the inhibition of advantageous GSC metabolic plasticity by the c-Src inhibitor TAT-Cx43. Read More

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December 2020

SGLT2 Inhibition by Intraperitoneal Dapagliflozin Mitigates Peritoneal Fibrosis and Ultrafiltration Failure in a Mouse Model of Chronic Peritoneal Exposure to High-Glucose Dialysate.

Biomolecules 2020 11 19;10(11). Epub 2020 Nov 19.

Department of Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, Germany.

Peritoneal dialysis (PD) is limited by glucose-mediated peritoneal membrane (PM) fibrosis, angiogenesis, and ultrafiltration failure. Influencing PM integrity by pharmacologically targeting sodium-dependent glucose transporter (SGLT)-mediated glucose uptake has not been studied. In this study, wildtype C57Bl/6N mice were treated with high-glucose dialysate via an intraperitoneal catheter, with or without addition of selective SGLT2 inhibitor dapagliflozin. Read More

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November 2020

Small Molecular Prodrug Amphiphile Self-Assembled AIE Dots for Cancer Theranostics.

Front Bioeng Biotechnol 2020 2;8:903. Epub 2020 Oct 2.

Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab for Biomaterials, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

A simple and facile one-step method was developed to construct a small molecular prodrug amphiphile self-assembled organic dots CPPG with aggregation-induced emission (AIE) characteristics. Diphenylalanine peptide (FF), which is the essential moiety of the self-assembling peptide-drug conjugate and as its core recognition motifs for molecular self-assembly. In addition, the D-glucose transported protein (GLUT), which is one of the important nutrient transporters and is overexpressed in cancer cells. Read More

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October 2020

Power of two: combination of therapeutic approaches involving glucose transporter (GLUT) inhibitors to combat cancer.

Biochim Biophys Acta Rev Cancer 2020 12 21;1874(2):188457. Epub 2020 Oct 21.

Department of Pharmaceutical Chemistry, Bharati Vidyapeeth's College of Pharmacy, Navi Mumbai, Maharashtra, India. Electronic address:

Cancer research of the Warburg effect, a hallmark metabolic alteration in tumors, focused attention on glucose metabolism whose targeting uncovered several agents with promising anticancer effects at the preclinical level. These agents' monotherapy points to their potential as adjuvant combination therapy to existing standard chemotherapy in human trials. Accordingly, several studies on combining glucose transporter (GLUT) inhibitors with chemotherapeutic agents, such as doxorubicin, paclitaxel, and cytarabine, showed synergistic or additive anticancer effects, reduced chemo-, radio-, and immuno-resistance, and reduced toxicity due to lowering the therapeutic doses required for desired chemotherapeutic effects, as compared with monotherapy. Read More

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December 2020

Simultaneous Combination of the CDK4/6 Inhibitor Palbociclib With Regorafenib Induces Enhanced Anti-tumor Effects in Hepatocarcinoma Cell Lines.

Front Oncol 2020 23;10:563249. Epub 2020 Sep 23.

Department of Medicine and Surgery, University of Parma, Parma, Italy.

Advanced hepatocarcinoma (HCC) is an aggressive malignancy with poor prognosis and limited treatment options. Alterations of the cyclin D-CDK4/6-Rb pathway occur frequently in HCC, providing the rationale for its targeting at least in a molecular subset of HCC. In a panel of HCC cell lines, we investigated whether the CDK4/6 inhibitor palbociclib might improve the efficacy of regorafenib, a powerful multi-kinase inhibitor approved as second-line treatment for advanced HCC after sorafenib failure and currently under clinical investigation as first-line therapy in combination with immunotherapy. Read More

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September 2020

SLC2A3 promotes macrophage infiltration by glycolysis reprogramming in gastric cancer.

Cancer Cell Int 2020 12;20:503. Epub 2020 Oct 12.

Department of General Surgery, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong China.

Background: Tumors display a high rate of glucose metabolism and the SLC2A (also known as GLUT) gene family may be central regulators of cellular glucose uptake. However, roles of SLC2A family in mechanism of metabolite communication with immunity in gastric cancer remains unknown.

Methods: Bioinformatics analysis and IHC staining were used to reveal the expression of SLC2A3 in gastric cancer and the correlation with survival prognosis. Read More

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October 2020

Labelled micelles for the delivery of cytotoxic Cu(II) and Ru(III) compounds in the treatment of aggressive orphan cancers: Design and biological in vitro data.

J Inorg Biochem 2020 12 2;213:111259. Epub 2020 Oct 2.

Department of Chemical Sciences, University of Padova, Via F. Marzolo 1, 35131 Padova, Italy. Electronic address:

A recent study on our metal-dithiocarbamato complexes pointed out the antiproliferative properties and the druglikeness of some new patented derivatives. In this work, the best compounds have been encapsulated in micellar nanocarriers, being also carbohydrate-functionalized on their hydrophilic surface to investigate the possibility of a cancer-selective delivery. In particular, the nonionic block copolymer Pluronic® F127 (PF127) has been chemically modified with sugars and the derivatives characterized by means of NMR spectroscopy and FT-IR spectrophotometry. Read More

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December 2020

Clinical significance and in vitro cellular regulation of hypoxia mimicry on HIF-1α and downstream genes in canine appendicular osteosarcoma.

Vet J 2020 Oct 9;264:105538. Epub 2020 Sep 9.

Department of Veterinary Science, University of Turin, Grugliasco (TO), Italy. Electronic address:

Cellular adaptation to a hypoxic microenvironment is essential for tumour progression and is largely mediated by HIF-1α and hypoxia-regulated factors, including CXCR4, VEGF-A and GLUT-1. In human osteosarcoma, hypoxia is associated with resistance to chemotherapy as well as with metastasis and poor survival, whereas little is known about its role in canine osteosarcoma (cOSA). This study aimed primarily to evaluate the prognostic value of several known hypoxic markers in cOSA. Read More

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October 2020

Influences of galactose ligand on the uptake of TADF liposomes by HepG cells.

Photodiagnosis Photodyn Ther 2020 Dec 18;32:102014. Epub 2020 Sep 18.

Daqing Campus of Harbin Medical University, 1 Xinyang Rd Daqing, 163319, China. Electronic address:

Glucose is the main energy substance to drive the physiological events of the cell.. Malignant cells exhibit a much higher rate of glycolysis than healthy cells to relieve the increased needs of energy. Read More

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December 2020

Let-7a-5p inhibits triple-negative breast tumor growth and metastasis through GLUT12-mediated warburg effect.

Cancer Lett 2020 12 15;495:53-65. Epub 2020 Sep 15.

Medical School of Guizhou University, Guiyang, 550025, China; Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, 100850, China. Electronic address:

Triple-negative breast cancer (TNBC) is known for its aggressive phenotype with limited treatment modalities and poor prognosis. The Warburg effect (aerobic glycolysis) is a hallmark of cancer that serves as a promising target for diagnosis and therapy. However, how aerobic glycolysis regulates TNBC remains largely unknown. Read More

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December 2020

Melittin ameliorates inflammation in mouse acute liver failure via inhibition of PKM2-mediated Warburg effect.

Acta Pharmacol Sin 2020 Sep 16. Epub 2020 Sep 16.

Viral hepatitis of Hunan Key Laboratory and Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, 410008, China.

Acute liver failure (ALF) is a fatal clinical syndrome with no special drug. Recent evidence shows that modulation of macrophage to inhibit inflammation may be a promising strategy for ALF treatment. In this study we investigated the potential therapeutic effects of melittin, a major peptide component of bee venom both in mice model of ALF and in LPS-stimulated macrophages in vitro, and elucidated the underlying mechanisms. Read More

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September 2020

Enforced C-Src Activation Causes Compartmental Dysregulation of PI3K and PTEN Molecules in Lipid Rafts of Tongue Squamous Carcinoma Cells by Attenuating Rac1-Akt-GLUT-1-Mediated Sphingolipid Synthesis.

Int J Mol Sci 2020 Aug 13;21(16). Epub 2020 Aug 13.

Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung 406053, Taiwan.

Pharmacologic intervention to affect the membrane lipid homeostasis of lipid rafts is a potent therapeutic strategy for cancer. Here we showed that gallic acid (GA) caused the complex formation of inactive Ras-related C3 botulinum toxin substrate 1 (Rac1)-phospho (p)-casein kinase 2 α (CK2α) (Tyr 255) in human tongue squamous carcinoma (TSC) cells, which disturbed the lipid raft membrane-targeting of phosphatidylinositol 3-kinase (PI3K)-Rac1-protein kinase B (Akt) signal molecules by inducing the association of p110α-free p85α with unphosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN) in lipid rafts. The effects on induction of inactive Rac1-p-CK2α (Tyr 255) complex formation and attenuation of p-Akt (Ser 473), GTP-Rac1, glucose transporter-1 (GLUT-1) lipid raft membrane-targeting, and cell invasive activity by GA were counteracted either by CK2α short hairpin RNA or cellular-Src (c-Src) inhibitor PP1. Read More

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Glucose transporters in cardiovascular system in health and disease.

Pflugers Arch 2020 09 18;472(9):1385-1399. Epub 2020 Aug 18.

Institut de Recherche Expérimentale et Clinique, Pole of Cardiovascular Research, Université catholique de Louvain, Avenue Hippocrate 55, B1.55.05, B-1200, Brussels, Belgium.

Glucose transporters are essential for the heart to sustain its function. Due to its nature as a high energy-consuming organ, the heart needs to catabolize a huge quantity of metabolic substrates. For optimized energy production, the healthy heart constantly switches between various metabolites in accordance with substrate availability and hormonal status. Read More

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September 2020

Design and Validation of Liposomal ApoE2 Gene Delivery System to Evade Blood-Brain Barrier for Effective Treatment of Alzheimer's Disease.

Mol Pharm 2021 02 16;18(2):714-725. Epub 2020 Sep 16.

Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, 58105 North Dakota, United States.

Targeting gene-based therapeutics to the brain is a strategy actively sought to treat Alzheimer's disease (AD). Recent findings discovered the role of apolipoprotein E (ApoE) isoforms in the clearance of toxic amyloid beta proteins from the brain. ApoE2 isoform is beneficial for preventing AD development, whereas ApoE4 is a major contributing factor to the disease. Read More

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February 2021

Pyruvate kinase M2 in lung APCs regulates Alternaria-induced airway inflammation.

Immunobiology 2020 07 30;225(4):151956. Epub 2020 May 30.

Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, United States. Electronic address:

Sensitivity to allergenic fungi (Alternaria alternata) is associated with acute, severe asthma attacks. Antigen presenting cells (APCs) in the lung sense environmental perturbations that induce cellular stress and metabolic changes and are critical for allergic airway inflammation. However, the mechanisms underlying such environmental sensing by APCs in the lung remains unclear. Read More

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LncRNA DBH-AS1 facilitates the tumorigenesis of melanoma by targeting miR-233-3p via IGF-1R/Akt signaling.

Eur Rev Med Pharmacol Sci 2020 07;24(14):7698-7708

Department of Dermatology, Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China.

Objective: While Long Noncoding RNAs (LncRNAs) are well-known to modulate human cancer progression, the specific function of DBH-AS1 in melanoma remains to be fully established. The study will investigate the role of DBH-AS1 in melanoma cell.

Patients And Methods: The expression profiles of DBH-AS1, miR-223-3p, and IGF-1R in melanoma tissues and cell lines were determined by RT-qPCR analysis. Read More

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Dual Inhibition of CDK4/6 and PI3K/AKT/mTOR Signaling Impairs Energy Metabolism in MPM Cancer Cells.

Int J Mol Sci 2020 Jul 21;21(14). Epub 2020 Jul 21.

Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.

: Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated to asbestos exposure. One of the most frequent genetic alteration in MPM patients is loss, leading to aberrant activation of the Rb pathway. In MPM cells, we previously demonstrated the therapeutic efficacy of targeting this signaling with the CDK4/6 inhibitor palbociclib in combination with PI3K/mTOR inhibitors. Read More

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Visualization of GLUT1 Trafficking in Live Cancer Cells by the Use of a Dual-Fluorescence Reporter.

ACS Omega 2020 Jul 23;5(26):15911-15921. Epub 2020 Jun 23.

Institute of Orthopedic Diseases and Department of Bone and Joint Surgery, the First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, China.

Glucose metabolism is an essential process for energy production and cell survival for both normal and abnormal cellular metabolism. Several glucose transporter/solute carrier 2A (GLUT/SLC2A) superfamily members, including glucose transporter 1 (GLUT1), have been shown to mediate the cellular uptake of glucose in diverse cell types. GLUT1-mediated glucose uptake is a transient and rapid process; thus, the real-time monitoring of GLUT1 trafficking is pivotal for a better understanding of GLUT1 expression and GLUT1-dependent glucose uptake. Read More

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Targeting hepatocyte carbohydrate transport to mimic fasting and calorie restriction.

FEBS J 2020 Jul 12. Epub 2020 Jul 12.

Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.

The pervasion of three daily meals and snacks is a relatively new introduction to our shared experience and is coincident with an epidemic rise in obesity and cardiometabolic disorders of overnutrition. The past two decades have yielded convincing evidence regarding the adaptive, protective effects of calorie restriction (CR) and intermittent fasting (IF) against cardiometabolic, neurodegenerative, proteostatic, and inflammatory diseases. Yet, durable adherence to intensive lifestyle changes is rarely attainable. Read More

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