Human Hilar Cholangiocarcinoma In Nude Mice Transplantation Model Of Hepatic Portal And Cd, Hsv-tk, Double Suicide Gene Therapy Experiments

OBJECT To establish a xenograft model in porta hepatis of human hilar cholgangiocarcinoma in nude mice, and observe its biological characteeristics. METHOD The 90^th generation FRH cells(2 × 10⁶) were subcutaneously transplanted into the back of the hindlimbs of 6 Balb/c-nu/nu mice. When the tumors reached 8mm × 6mm in diameter two weeks late, the tumors were cut into 1mm³ pieces and retransplanted into porta hepatis of 32 new nude mice.The mice were observed every day. Each week the belly of two mice were laparotomize to observe the growth of xenograft tumor by measuring its diameter and volum, and the growth curves of the tumor were figured. The mice were killed when jaundice appeared and they were on the brink of death.They were laparotomized to exmine metastatic tumors in nearby and distants organs and pathologic examanition was made. Electron microscope was used to observe the ultrastructure. VEGF, bFGF, PCNA, bcl-2, Fas , P53, P21, MMP-9, TIMP-1, TIMP-2, CD34were examined with imrnunohistochemical methods. Microvessel density (MVD) was counted also to observe the expression of these tumor marks.RESULT 30 out of 32 nude mice xenograft model of human hilar cholangiocarcinoma were successfully established. The rate of tumor occurring was 94%.28 out of 30 nude mice had , The rate of jaundice occurring was 93%. About two weeks later, small nodes in porta hepatis were found; and about four weeks later, jaundice occurred. Dyscrasia appeared in six weeks or so. The xenograft tumor reached 1.8 to 2.8cm in major diameter.