Name: ex vivo treatment response of primary tumors and/or associated metastases for preclinical and clinical development of therapeutics
Uploaded: 2014-10-02T15:00:00
Description: Watch this Scientific Journal Video about Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics at JoVE.com

The authors would like to thank the MSKCC Tissue Procurement Service Team (TPS), specifically, Maria Corazon Mariano, Priscilla McNeil, Anas Idelbi, Daniel Navarrete and Katrina Allen, in all of their efforts in the successful pursuit of this project and funding from the following sources: 5 R21 CA158609-02 and the Conquer Cancer Foundation and the Breast Cancer Research Foundation. In addition, the authors would like to thank Eric Cottington PhD, Vice President of the Office of Research and Project Administration, the Office of Technology Development, Research Outreach and Compliance and RTM Information Systems Support, in the support of the submission of this manuscript.

NOTA: la obtención de tejidos del paciente fue autorizada mediante junta de revisión institucional (IRB): aprobado muestras biológicas y Protocolos Clínicos (números 09-121 y 11-041 de Protocolo, respectivamente) en el Centro de Cáncer Memorial Sloan Kettering. Adquisiciones 1. Tissue <ol><li> Adquisición de paciente del tumor primario / metástasis NOTA: Hasta la fecha, este protocolo se ha realizado sobre tipos pancreáticos, gástricos y de tumor de mama extirpado quirúrg...

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Biólogos del cáncer se enfrentan a retos significativos al intentar desarrollar estrategias terapéuticas eficaces. Prueba de fármacos en desarrollo en las líneas celulares de cáncer establecidas no puede reflejar con precisión en la respuesta in vivo e in vivo en modelos PDX son mano de obra intensiva y muy caro. Teniendo en cuenta lo anterior, la aplicación de técnicas ex vivo de los tumores primarios del paciente 14, 15 se posiciona al lado del análisis molecular de lín...

El desarrollo de la terapéutica del cáncer eficaces ha demostrado ser extremadamente difícil. Líneas celulares de cáncer y explantes tumorales -, así como xenoinjertos se han utilizado en la investigación del cáncer durante más de medio siglo 1,2,3. Hasta la fecha, el análisis molecular de sensibilidad a los fármacos y la resistencia en las dos líneas celulares de cáncer establecidos y xenoinjertos derivados del paciente (PDX) es indispensable. Sin embargo, las pruebas de los compuestos en líneas celulares de cáncer establecidas a menudo no es predictivo de la eficacia in vivo, y los correspondientes estudios in vivo en animales, especialmente en los modelos de PDX, es muy caro y consume mucho tiempo. Las limitaciones de estos sistemas de modelo, a saber, la incapacidad para informar sobre la influencia del microambiente nativo en la progresión tumoral y la respuesta a estrategias terapéuticas, ha llevado al campo de la investigación para desarrollar métodos adicionales para complementar estos análisis. De reciente, se está prestando mayor atención a ex vivo análisis de tum pacienteo explantes 4, 5, debido a la mayor comprensión de que la respuesta terapéutica del cáncer no es exclusivo de la composición molecular inherente de las células cancerosas, sino que está fuertemente influenciado por el microambiente de las células tumorales 6, 7 una función que no puede ser recapitulado por métodos de cultivo tradicionales y / o PDX. análisis ex vivo en el contexto anterior (es decir., influencia de la célula tumoral adyacente microambiente circundante) implica la evaluación de secciones de tumor / metástasis primarias viables, en lugar de análisis ex vivo de los aislamientos celulares 8, 9. Se presenta aquí en una técnica ex vivo (es decir., Secciones de precisión en rodajas frescas de tejido) de los tumores primarios de pacientes y metástasis asociados (es decir, los ganglios linfáticos) que informa fielmente de la respuesta (IC50), fuera de objetivo efectos y permite molecular análisis de los mecanismos de resistencia y de retroalimentación. Además, un análisis correlativo de therapeUTIC sensibilidad / resistencia en función de biomarcadores y genes perfil de expresión se puede realizar en un esfuerzo por identificar a los pacientes más propensos a responder al fármaco experimental de interés (es decir., respuesta de alta drogas coincide paciente con especial perfil biológico). Aplicación de la técnica ex vivo y la evaluación de una manera multi-parámetro es movimiento hacia la selección de los pacientes y la mejora general de los resultados clínicos. Ex vivo análisis de la respuesta al tratamiento podría convertirse en una herramienta estándar en el desarrollo preclínico y clínico de la terapéutica del cáncer y está concebido como un paso hacia un enfoque de medicina personalizada en las estrategias de desarrollo terapéutico.

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ex vivo treatment response of primary tumors and/or associated metastases for preclinical and clinical development of therapeutics

The molecular analysis of established cancer cell lines has been the mainstay of cancer research for the past several decades. Cell culture provides both direct and rapid analysis of therapeutic sensitivity and resistance. However, recent evidence suggests that therapeutic response is not exclusive to the inherent molecular composition of cancer cells but rather is greatly influenced by the tumor cell microenvironment, a feature that cannot be recapitulated by traditional culturing methods. Even implementation of tumor xenografts, though providing a wealth of information on drug delivery/efficacy, cannot capture the tumor cell/microenvironment crosstalk (i.e., soluble factors) that occurs within human tumors and greatly impacts tumor response. To this extent, we have developed an ex vivo (fresh tissue sectioning) technique which allows for the direct assessment of treatment response for preclinical and clinical therapeutics development. This technique maintains tissue integrity and cellular architecture within the tumor cell/microenvironment context throughout treatment response providing a more precise means to assess drug efficacy.

Para este estudio, se utilizó la técnica ex vivo en un análisis correlativo de terapéutica de sensibilidad / resistencia de un inhibidor de la proteína de choque térmico 90 (Hsp90i). En una evaluación preclínica de este Hsp90i, el tumor primario del cáncer de mama, una ER + carcinoma ductal invasivo (IDC), y asociado metástasis en los ganglios linfáticos se analizaron ex vivo para la respuesta al tratamiento &#160; (Figura 1). Múltiples 200 m de serie de se...

Watch this Scientific Journal Video about Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics at JoVE.com

Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics

Establecido líneas celulares de cáncer y xenoinjertos han sido el pilar de la investigación del cáncer durante las últimas décadas. Sin embargo, la evidencia reciente sugiere que la respuesta terapéutica está fuertemente influenciado por el microambiente de las células tumorales. Por lo tanto, hemos desarrollado un análisis ex vivo de las muestras de tumor primario con fines de desarrollo de fármacos.

Ex Vivo respuesta al tratamiento de los tumores primarios y / o Asociados Metástasis de Preclínica y Desarrollo Clínico de Terapéutica

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