Abstract
Introduction.Approaches based on the principles of a targeted therapy are considered a promising strategy that is capable to improve the effectiveness of treatment for bladder cancer (BC) patients.The purposeof the study was to establish an orthotopic xenograft model of human BC in mice and to prove its suitability for experimental examination of drugs targeting the epidermal growth factor receptor (EGFR).Materials and methods.The objects of the study were ectopic subcutaneous and orthotopic human BC xenografts established using EJ and 5637 human BC cell lines. The growth of orthotopic xenografts in vivo was assessed by magnetic resonance imaging. Tumor tissues were investigated using histological and immunohistochemical techniques.Results.It was shown that EJ and 5637 xenografts exhibit a good reproducibility, a sufficient blood supply of the tumor tissues, a high level of EGFR expression, and different pattern of a subcellular receptor localization. Implantation and subsequent proliferation of human EJ or 5637 cells in the murine bladder mucosa presumably results in muscle-non-invasive tumor formation.Conclusions.The EJ and 5637 xenograft models can be useful for investigation of the efficacy of EGFR-targeted biotherapeutic treatments.
Highlights
Approaches based on the principles of a targeted therapy are considered a promising strategy that is capable to improve the effectiveness of treatment for bladder cancer (BC) patients
The growth of orthotopic xenografts in vivo was assessed by magnetic resonance imaging
It was shown that EJ and 5637 xenografts exhibit a good reproducibility, a sufficient blood supply of the tumor tissues, a high level of epidermal growth factor receptor (EGFR) expression, and different pattern of a subcellular receptor localization
Summary
МОДЕЛИ ПОДКОЖНОГО И ОРТОТОПИЧЕСКОГО КСЕНОГРАФТОВ РАКА МОЧЕВОГО ПУЗЫРЯ ЧЕЛОВЕКА У МЫШЕЙ NUDE ДЛЯ ИССЛЕДОВАНИЯ ВОЗДЕЙСТВИЙ, НАЦЕЛЕННЫХ НА РЕЦЕПТОР ЭПИДЕРМАЛЬНОГО ФАКТОРА РОСТА. Цель исследования – получение ортотопической модели РМП человека у мышей линии nude и обоснование ее пригодности для экспериментального изучения таргетных препаратов, нацеленных на рецептор эпидермального фактора роста (РЭФР). Объектом исследования служили эктопические подкожные и ортотопические ксенографты РМП человека, полученные с использованием культивируемых клеток линий EJ и 5637. Для исследования тканей опухолей использованы методы гистологического и иммуногистохимического анализа. Пролиферация клеток EJ и 5637 в слизистой оболочке мочевого пузыря мышей при их внутрипузырной имплантации преимущественно приводит к образованию мышечно-неивазивной формы опухоли. Ксенографты EJ и 5637 у иммунодефицитных мышей могут быть использованы в качестве моделей РМП человека для изучения эффективности биотерапевтических воздействий, использующих в качестве мишени РЭФР. Ключевые слова: рак мочевого пузыря, ксенографт опухоли, мыши nude, рецептор эпидермального фактора роста. Pirogov Russian National Research Medical University, Ministry of Health of Russia; 1 Ostrovitianovа st., Moscow 117997, Russia; 3 National University of Science and Technology “MISiS”; 4 Leniskiy Prospekt, Moscow 119094, Russia
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