Zuo Lian-fu

Establishment of intraperitoneal transplantation model of cisplatin-resistant ovarian carcinoma cell in scid mice

Objectiveto develop an intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP cell in severe combined immunodeficiency (SCID) mouse and to study its biologic characteristics.MethodsSixteen qualified C.B17/SCID mouse were divided into two groups randomly. Human ovarian carcinoma SKOV3 or SKOV3/CDDP cells were injected intraperitoneally into the SCID mouse at the amount of 1×107 cells (0.5 mL) per mouse. The behaviors of mice, tumor growth and morphology were analyzed. The expression of cancer antigen 125 (CA 125), GST-π and Topo-II were examined by immunohistochemical method.ResultsIn this experimental study, transplanted tumors are formed in 100% SCID mice in the two groups. The morphology, growth pattern and CA125 secretion of SKOV3/CDDP group were as same as those of SKOV3 group. It shows that the tumors of the two groups kept the characteristics of ovaries serosity papillary adenocarcinoma. Compared with SKOV3 group, the expression of GST-π and Topo-II gene in SKOV3/CDDP group were significantly higher (P<0.05).ConclusionAn intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP in SCID mice has been developed successfully. It may be an ideal animal model for biotherapy research of ovarian carcinoma as it can simulate the biological behavior of peritoneal metastasis of human ovarian carcinoma and the drug tolerance is maintained.

Significance of Skp2 expression in human gastric carcinoma and the relationship between Skp2, p27 and PTEN expression

Objective: S-phase kinase-associated protein 2 (Skp2) is a positive regulator of G1-S transition and promotes ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor p27. Its overexpression has been implicated in cell transformation and oncogenesis. In this study, we investigated significance of Skp2 expression in human gastric carcinoma and the relationship between Skp2, p27 and PTEN expression. Methods: Immunohistochemical analysis was performed on 138 surgical resected primary gastric carcinoma specimens, 102 paired metastasis carcinoma tissue specimens in lymph node from the same set of 138 surgical resected primary gastric carcinoma specimens, 30 dysplasia specimens, 30 intestinal metaplasia specimens, and 20 normal gastric mucosa specimens for Skp2 and performed on the same set of 138 surgical resected primary gastric carcinoma specimens for p27 and PTEN. Results: Skp2 labeling frequency % was increased dramatically in intestinal metaplasia, dysplasia, and primary gastric carcinoma compared with normal gastric mucosa (P=0.000, all the same). Skp2 labeling frequency % in metastasis gastric carcinoma in lymph node was significantly higher than primary gastric carcinoma (P=0.037). Skp2 labeling frequency % was positively associated with differentiated degree (rho=0.315, P=0.000), vessel invasion (rho=0.303, P=0.000) and lymph node metastasis (rho=0.254, P=0.000) respectively. An inverse correlation of Skp2 was observed with both its biochemical target p27 expression in gastric carcinoma (rho=−0.451, P=0.000) and with its putative negative regulator, the PTEN tumor suppressor protein (rho=−0.480, P=0.000). p27 expression had positive relationship with PTEN expression in gastric carcinoma (rho=0.642, P=0.000). Conclusion: Skp2 overexpression is correlated with carcinogenesis and progression of gastric carcinoma: elevated Skp2 expression is correlated with decreased p27 and PTEN in gastric carcinoma, and p27 expression is parallel with PTEN expression. These suggest that PTEN may regulate expression of p27 through the Skp2 pathway, and the effects of Skp2, p27 and PTEN together play an important role in carcinogenesis and progression of gastric carcinoma.

Correlative study on the expression of p53 and DNA ploidy in acute nonlymphocytic leukemia

SummaryWe used the flow cytometric immunoassay to study the correlation between the tumor-suppressor gene product p53− and the DNA ploidy in 30de novo cases of acute nonlymphocytic leukemia (ANLL). The results showed that 15 cases were negative and the other 15 cases were positive expression for p53. As compared with p53 negative (p53) cases, the patients with positive p53 (p53+) had higher percentage of bone marrow blasts and lower peripheral leukocyte and platelet counts, which had no influence on the complete remission rate. Before treatment, DNA diploidy was seen in 18 cases including 12 p53− cases, and DNA aneuploidy in 12 cases including 9 p53+. After therapy, aneuploidy could be transformed into diploidy. Patients with P53+ or having aneuploidy in complete remission were at risk for early relapse. We believe that p53 may be involved in the process of leukemogenesis and progression of ANLL.