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1.
Science ; 369(6499)2020 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-32345712

RESUMEN

Cancer treatments are often more successful when the disease is detected early. We evaluated the feasibility and safety of multicancer blood testing coupled with positron emission tomography-computed tomography (PET-CT) imaging to detect cancer in a prospective, interventional study of 10,006 women not previously known to have cancer. Positive blood tests were independently confirmed by a diagnostic PET-CT, which also localized the cancer. Twenty-six cancers were detected by blood testing. Of these, 15 underwent PET-CT imaging and nine (60%) were surgically excised. Twenty-four additional cancers were detected by standard-of-care screening and 46 by neither approach. One percent of participants underwent PET-CT imaging based on false-positive blood tests, and 0.22% underwent a futile invasive diagnostic procedure. These data demonstrate that multicancer blood testing combined with PET-CT can be safely incorporated into routine clinical care, in some cases leading to surgery with intent to cure.


Asunto(s)
Detección Precoz del Cáncer/métodos , Pruebas Hematológicas , Tamizaje Masivo/métodos , Neoplasias/sangre , Neoplasias/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Anciano , Estudios de Cohortes , Femenino , Humanos
2.
Nat Chem Biol ; 9(2): 81-3, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23222886

RESUMEN

Engineering functional protein scaffolds capable of carrying out chemical catalysis is a major challenge in enzyme design. Starting from a noncatalytic protein scaffold, we recently generated a new RNA ligase by in vitro directed evolution. This artificial enzyme lost its original fold and adopted an entirely new structure with substantially enhanced conformational dynamics, demonstrating that a primordial fold with suitable flexibility is sufficient to carry out enzymatic function.


Asunto(s)
Catálisis , Ingeniería de Proteínas/métodos , ARN Ligasa (ATP)/química , Alanina/química , Secuencia de Aminoácidos , Dominio Catalítico , Evolución Molecular Dirigida/métodos , Enzimas/química , Humanos , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Metales/química , Modelos Moleculares , Datos de Secuencia Molecular , Mutación , Conformación Proteica , Pliegue de Proteína
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