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Regulation of Angiogenesis and Blood Supply01:24

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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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In Vivo Model for Testing Effect of Hypoxia on Tumor Metastasis
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Hipoxia sistémica suprime el crecimiento de tumores sólidos

Ayush D Midha, Brandon T L Chew, Benedict M H Choi

    bioRxiv : the preprint server for biology
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    PubMed
    Resumen
    Este resumen es generado por máquina.

    La hipoxia sistémica, a diferencia de la hipoxia tumoral localizada, inhibe el crecimiento del cáncer al suprimir la síntesis de purinas. Este novedoso enfoque, lograble con HypoxyStat, ofrece una estrategia terapéutica potencial contra tumores sólidos.

    Palabras clave:
    hipoxia sistémicacrecimiento tumoralsíntesis de purinasterapia contra el cáncer

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    Área de la Ciencia:

    • Oncología
    • Vías metabólicas
    • Biología del cáncer

    Sus antecedentes:

    • La hipoxia local es un factor pronóstico negativo conocido en el cáncer.
    • El papel de la hipoxia sistémica en la progresión tumoral ha sido menos comprendido.

    Objetivo del estudio:

    • Investigar el efecto de la hipoxia sistémica en el crecimiento tumoral.
    • Elucidar los mecanismos subyacentes del impacto de la hipoxia sistémica en el cáncer.
    • Explorar el potencial terapéutico de la hipoxia sistémica.

    Principales métodos:

    • Estudios in vivo en múltiples tipos de cáncer y modelos preclínicos.
    • Perfilado de metabolitos de tumores y fluido intersticial.
    • Trazado de isótopos estables para seguir las vías metabólicas.
    • Inducción farmacológica de hipoxia sistémica utilizando HypoxyStat.

    Principales resultados:

    • La hipoxia sistémica disminuyó significativamente el crecimiento tumoral en varios tipos de cáncer.
    • La reducción del crecimiento tumoral se relacionó con la supresión de la síntesis de purinas de novo, no con hipoglucemia o activación de HIF.
    • Los tumores no desarrollaron resistencia a la hipoxia sistémica.
    • La terapia combinada con quimioterapia o inmunoterapia mejoró la supresión tumoral.

    Conclusiones:

    • La hipoxia sistémica representa una nueva estrategia terapéutica para tumores sólidos, desafiando la visión tradicional de la hipoxia.
    • La supresión de la síntesis de purinas es un mecanismo clave por el cual la hipoxia sistémica inhibe el crecimiento del cáncer.
    • La inducción farmacológica de la hipoxia sistémica ofrece una vía prometedora para el tratamiento del cáncer.