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Nghiên cứu tiền lâm sàng về PAI2 gắn nhãn 213Bi trong việc kiểm soát ung thư tụy vi di căn
Tóm tắt
Mục đích: Urokinase plasminogen activator (uPA) và thụ thể của nó (uPAR) được biểu hiện bởi các tế bào ung thư tụy và có thể được nhắm tới bởi plasminogen activator inhibitor type 2 (PAI2). Chúng tôi đã gắn nhãn PAI2 bằng 213Bi để tạo thành chế phẩm liên hợp alpha (AC), và đã nghiên cứu độc tính tế bào in vitro và hiệu quả in vivo của nó. Phương pháp và tài liệu: Sự biểu hiện của uPA/uPAR trên các dòng tế bào tụy, mô ung thư tụy người, di căn hạch lympho và xenograft trên chuột đã được phát hiện bằng phương pháp nhuộm miễn dịch, kính hiển vi quang học đồng phát và phân tích tế bào dòng chảy. Độc tính tế bào được đánh giá qua xét nghiệm MTS và TUNEL. Hai ngày sau khi tiêm tế bào ung thư dưới da, chuột được tiêm AC qua tiêm tại chỗ hoặc tiêm toàn thân. Kết quả: uPA/uPAR được biểu hiện mạnh mẽ trên các dòng tế bào ung thư tụy và mô ung thư. AC có thể nhắm tới và tiêu diệt tế bào ung thư in vitro theo cách phụ thuộc nồng độ. Khoảng 90% tế bào dương tính với TUNEL được tìm thấy sau khi ủ với 1.2 MBq/ml AC. Một lần tiêm tại chỗ ~222 MBq/kg 2 ngày sau khi tiêm tế bào có thể hoàn toàn ức chế sự phát triển của khối u trong 12 tuần, và một lần tiêm trong khoang bụng 111 MBq/kg gây ra sự chậm phát triển khối u đáng kể. Kết luận: 213Bi-PAI2 có thể nhắm mục tiêu một cách đặc hiệu tới các tế bào ung thư tụy in vitro và ức chế sự phát triển khối u in vivo. 213Bi-PAI2 có thể là một tác nhân hữu ích cho việc điều trị bệnh nhân ung thư tụy sau phẫu thuật với bệnh lý tối thiểu còn lại.
Từ khóa
#213Bi #PAI2 #ung thư tụy #độc tính tế bào #ức chế sự phát triển khối uTài liệu tham khảo
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