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Аннотация
Тимидинфосфорилаза является ключевым ферментом метаболизма тимидина и фактором ангиогенеза – PD/ECGF. Фермент одновременно катализирует как фосфоролиз тимидина до тимина и рибозо-1-фосфата, так и обратный перенос фосфопентозы на тимин. Установлена высокая активность ТФ в опухолевых тканях. Выявлено участие фермента в пролиферативных процессах при целом ряде хронических воспалительных заболеваний. Возрастание экспрессии ТФ при злокачественном росте характеризует агрессивное течение заболевания и негативный прогноз. Высокая активность ТФ взаимосвязана с прорастанием сосудов и метастазированием.
С другой стороны, фермент ингибирует процессы апоптоза, индуцируемые гипоксией, стимулирует продукцию воспалительных цитокинов и интерферонов. Эти свойства легли в основу принципа использования ингибиторов ТФ в качестве лекарственных препаратов при химиотерапии. Кроме того, PD/ECGF принимает участие в летальном синтезе 5-фторурацила из капецитабина и других предшественников. Такая особенность указала на возможность использования фермента в качестве биомаркера при лечении онкологических больных. Определение активности ТФ в сыворотке крови пациентов с злокачественными новообразованиями дает возможность прогнозировать, как течение заболевания, так и ответ опухоли на химиотерапию.
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