Wednesday, August 27, 2014

 

 



Soy un nuevo usuario

Olvidé mi contraseña

Entrada usuarios

Lógica Matemáticas Astronomía y Astrofísica Física Química Ciencias de la Vida
Ciencias de la Tierra y Espacio Ciencias Agrarias Ciencias Médicas Ciencias Tecnológicas Antropología Demografía
Ciencias Económicas Geografía Historia Ciencias Jurídicas y Derecho Lingüística Pedagogía
Ciencia Política Psicología Artes y Letras Sociología Ética Filosofía


Metabolic Targeting of Lactate Efflux by Malignant Glioma Inhibits Invasiveness and Induces Necrosis: An In Vivo Study1

1) La descarga del recurso depende de la página de origen
2) Para poder descargar el recurso, es necesario ser usuario
    registrado en Universia

  Descargar recurso

Detalles del recurso

Pertenece a: PubMed Central (PMC3 - NLM DTD)  

Descripción: Glioblastoma multiforme (GBM) are the most malignant among brain tumors. They are frequently refractory to chemotherapy and radiotherapy with mean patient survival of approximately 6 months, despite surgical intervention. The highly glycolytic nature of glioblastomas describes their propensity to metabolize glucose to lactic acid at an elevated rate. To survive, GBMs efflux lactic acid to the tumor microenvironment through transmembrane transporters denoted monocarboxylate transporters (MCTs). We hypothesized that inhibition of MCT function would impair the glycolytic metabolism and affect both glioma invasiveness and survival. We examined the effect on invasiveness with α-cyano-4-hydroxy-cinnamic acid (ACCA, 4CIN, CHCA), a small-molecule inhibitor of lactate transport, through Matrigel-based and organotypic (brain) slice culture invasive assays using U87-MG and U251-MG glioma cells. We then conducted studies in immunodeficient rats by stereotaxic intracranial implantation of the glioma cells followed by programmed orthotopic application of ACCA through osmotic pumps. Effect on the implanted tumor was monitored by small-animal magnetic resonance imaging. Our assays indicated that glioma invasion was markedly impaired when lactate efflux was inhibited. Convection-enhanced delivery of inhibitor to the tumor bed caused tumor necrosis, with 50% of the animals surviving beyond the experimental end points (3 months after inhibitor exhaustion). Most importantly, control animals did not display any adverse neurologic effects during orthotopic administration of ACCA to brain through programmed delivery. These results indicate the clinical potential of targeting lactate efflux in glioma through delivery of small-molecule inhibitors of MCTs either to the tumor bed or to the postsurgical resection cavity.

Autor(es): Colen, Chaim B -  Shen, Yimin -  Ghoddoussi, Farhad -  Yu, Pingyang -  Francis, Todd B -  Koch, Brandon J -  Monterey, Michael D -  Galloway, Matthew P -  Sloan, Andrew E -  Mathupala, Saroj P - 

Id.: 54060132

Idioma: English  - 

Versión: 1.0

Estado: Final

Palabras claveResearch Article - 

Tipo de recurso: Text  - 

Tipo de Interactividad: Expositivo

Nivel de Interactividad: muy bajo

Audiencia: Estudiante  -  Profesor  -  Autor  - 

Estructura: Atomic

Coste: no

Copyright: sí

Requerimientos técnicos:  Browser: Any - 

Fecha de contribución: 01-ago-2011

Contacto:

Localización:


Otros recursos del mismo autor(es)

  1. Inhibition of the fracture healing process in smokers: deregulation of cellular and molecular milieu in tibial fracture micro-environment Introduction: Tobacco smoking has been shown to have a detrimental impact on fracture healing and is...
  2. Brain Tumor Initiating Cells Adapt to Restricted Nutrition through Preferential Glucose Uptake Like all cancers, brain tumors require a continuous source of energy and molecular resources for new...
  3. Risk of subsequent cancer following a primary CNS tumor Improvements in survival among central nervous system (CNS) tumor patients has made the risk of deve...
  4. Glioblastoma Stem Cells Generate Vascular Pericytes to Support Vessel Function and Tumor Growth
  5. Single prolonged stress enhances hippocampal glucocorticoid receptor and phosphorylated protein kinase B levels Animal models of posttraumatic stress disorder (PTSD) can explore neurobiological mechanisms by whic...

Otros recursos de la misma colección

  1. Amino Acid Deprivation Promotes Tumor Angiogenesis through the GCN2/ATF4 Pathway1 As tumors continue to grow and exceed their blood supply, nutrients become limited leading to defici...
  2. The N550K/H Mutations in FGFR2 Confer Differential Resistance to PD173074, Dovitinib, and Ponatinib ATP-Competitive Inhibitors12 We sought to identify fibroblast growth factor receptor 2 (FGFR2) kinase domain mutations that confe...
  3. p53-stabilizing Agent CP-31398 Prevents Growth and Invasion of Urothelial Cancer of the Bladder in Transgenic UPII-SV40T Mice12 The high prevalence of bladder cancer and its recurrence make it an important target for chemopreven...
  4. A Novel PTEN/Mutant p53/c-Myc/Bcl-XL Axis Mediates Context-Dependent Oncogenic Effects of PTEN with Implications for Cancer Prognosis and Therapy12 Phosphatase and tensin homolog located on chromosome 10 (PTEN) is one of the most frequently mutated...
  5. Flavopiridol Synergizes with Sorafenib to Induce Cytotoxicity and Potentiate Antitumorigenic Activity in EGFR/HER-2 and Mutant RAS/RAF Breast Cancer Model Systems12 Oncogenic receptor tyrosine kinase (RTK) signaling through the Ras-Raf-Mek-Erk (Ras-MAPK) pathway is...

Valoración de los usuarios

No hay ninguna valoración para este recurso.Sea el primero en valorar este recurso.
 

Busque un recurso