Publicado

2023-07-01

Human gastric adenocarcinoma explant culture: a model for the evaluation of the oncolytic activity of rotavirus Wt1-5

Cultivo de explantes de adenocarcinoma gástrico humano: modelo para la evaluación de la actividad oncolítica del rotavirus Wt1-5

Palabras clave:

Rotavirus, Oncolytic Virotherapy, Gastric Cancer, Immunohistochemistry (en)
Rotavirus, Viroterapia oncolítica, Cáncer gástrico, Inmunohistoquímica (es)

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Autores/as

  • Henry Sossa-Rojas Universidad Nacional de Colombia - Sede Bogotá - Facultad de Odontología - Departamento de Ciencias Básicas y Medicina Oral - Bogotá D.C. - Colombia. https://orcid.org/0000-0003-2379-3691
  • Pedro Gabriel Franco-Maz Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Morfología - Bogotá D.C. - Colombia. | Hospital Universitario La Samaritana - Servicio de Patología - Bogotá https://orcid.org/0000-0001-7854-0689
  • Carlos Manuel Zapata-Acevedo Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Cirugía - Bogotá D.C. - Colombia. | Hospital Universitario La Samaritana - Servicio de Cirugía General - Bogotá D.C. - Colombia. https://orcid.org/0000-0002-8493-1528
  • Carlos Arturo Guerrero-Fonseca Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Ciencias Fisiológicas - Bogotá D.C. - Colombia. https://orcid.org/0000-0003-2863-6345

Introduction: Gastric cancer is the fifth most frequently diagnosed type of cancer and the fourth leading cause of cancer mortality worldwide. Oncolytic viruses are a potential agent for cancer treatment.

Objective: To evaluate the penetration capacity, selectivity, and oncolytic efficiency of rotavirus Wt1-5 using an ex vivo infection model in tumor samples obtained from patients diagnosed with gastric adenocarcinoma.

Materials and methods: Experimental laboratory study performed on explants of diffuse and intestinal-
subtype gastric adenocarcinomas collected at the Hospital Universitario de La Samaritana (Bogotá D.C., Colombia). These explants were infected with rotavirus Wt1-5, and immunocytochemistry tests were used to assess its penetration and diffusion capacity through the tumor microenvironment, as well as its potential as an oncolytic virus. Data are described using means and standard deviations. In addition, a bivariate analysis was performed using the Mann-Whitney U test to determine differences between the data from the evaluated assays and the control used in each assay. A statistical significance level of p<0.05 was considered.

Results: At 12 hours post infection (h.p.i), rotavirus Wt1-5 had disseminated in all tumor layers, promoting the infection of tumor cells and resulting in necrosis of tumor tissue after 48 h.p.i. On the other hand, adjacent non-tumor tissues showed no evidence of infection with this rotavirus or tissue lysis (p<0.05).

Conclusions: Explant culture is a useful model for studying and predicting ex vivo infectious behavior. Rotavirus Wt1-5 selectively and efficiently infects tumor cells in gastric adenocarcinoma explants, both diffuse and intestinal.

Introducción. A nivel mundial, el cáncer gástrico es el quinto cáncer más comúnmente diagnosticado y la cuarta causa de mortalidad por cáncer. Los virus oncolíticos son un agente terapéutico potencial para el cáncer.

Objetivo. Evaluar la capacidad de penetración, la selectividad y la eficiencia oncolítica del rotavirus Wt1-5 mediante un modelo de infección ex vivo en muestras tumorales obtenidas de pacientes con diagnóstico de adenocarcinoma gástrico.

Materiales y métodos. Estudio experimental de laboratorio realizado en explantes de adenocarcinoma gástricos de subtipo difuso e intestinal recolectados en el Hospital Universitario de La Samaritana (Bogotá D.C., Colombia). Estos explantes se infectaron con el rotavirus Wt1-5 y, mediante pruebas inmunohistoquímicas, se evaluó su capacidad de penetración y difusión a través del microambiente tumoral, así como su potencial como virus oncolítico. Los datos se describen usando medias y desviaciones estándar. Además, se realizó un análisis bivariado mediante la prueba de U de Mann-Whitney para determinar las diferencias entre los datos de los ensayos evaluados y el control empleado en cada uno. Se consideró un nivel de significancia estadística de p<0.05.

Resultados. A las 12 horas post infección (h.p.i) se observó que el rotavirus Wt1-5 se había diseminado en todas las capas del tumor, lo cual favoreció la infección de las células tumorales y generó necrosis del tejido tumoral a partir de las 48 h.p.i. Por otro lado, los tejidos no tumorales adyacentes no mostraron evidencia de infección con este rotavirus, ni lisis tisular (p<0.05).

Conclusiones. El cultivo de explantes es un modelo útil para estudiar y predecir el comportamiento infeccioso ex vivo. El rotavirus Wt1-5 infecta de manera selectiva y eficiente las células tumorales en explantes de adenocarcinoma gástrico, tanto del subtipo difuso como del subtipo intestinal.

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