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Objective: To investigate the stimulated effect of liver regeneration on colon cancer cells in remnant liver in rats., Methods: Rat models with liver metastases or retro-peritoneal metastases of colon cancer were established: animals underwent 37% or 70% liver resection and were compared with a sham laparotomy (15, 25, 15 cases, respectively). Metastases were performed two weeks before resection. Rats were killed 3 weeks after the resection. Total body weight, liver and tumor weights were recorded. The human colon adenocarcinoma cell line Lovo was cultured in the presence of portal serum withdrawn 24 hours and 14 days after partial hepatectomy (PH). DNA synthesis was assessed by flow cytometry analysis for 5-Bromodeoxyuridine (5-BrdU) incorporation., Results: The tumor growth was accelerated in the remnant liver in 70% PH group, but the tumors in 37% PH group and retro-peritoneal site were not influenced by PH. Compared with the control group, after cultured 72 hours with portal serum withdrawn 24 h after PH, a higher 5-BrdU incorporation was found in the Lovo cell lines (P < 0.05), and it reached the peak after 120 hours of culture (P < 0.05). No difference was found between the groups when cultured with the portal serum withdrawn 14 d after PH (P > 0.05)., Conclusions: PH may accelerate the growth of residual microscopic tumor in the liver which contributes to local recurrence. It has no systemic effect and effects on the cancer cell lines in extrahepatic sites. The excision extension is related to the stimulating effects on the cancer cell line, and subtotal hepatectomy is presumably a major determinant.

Objective: To investigate the effect of chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 on liver metastasis of human colon cancer., Methods: Expression of CXCR4 in different colon cancer cell lines and SDF-1 in different tissues were detected by using Western-blot technique. Effect of SDF-1 and anti-CXCR4 monoclonal antibody (McAb) on proliferation and migration of HT-29 cells were measured using MTT methods. Model mimicking liver metastasis of human colon cancer was established by injecting HT-29 cells intrasplenically into BALB/C nude mice. Mice were randomly divided into AMD3100 treated group and control group. Liver metastatic rate and tumor foci were measured 7 weeks after., Results: HT-29 cells expressed higher level of CXCR4 protein, and liver tissue expressed higher level of SDF-1 protein. Compared with the control, SDF-1 could significantly induced the proliferation and migration of the HT-29 cells, and anti-CXCR4 McAb could inhibited both functions of SDF-1. The liver metastasis rate in the control group was 100%, and it was 40% in the AMD3100 treating group (P < 0.05). The mean liver metastasis number also significantly decreased by AMD3100 (7.8 +/- 2.6 vs 22.4 +/- 8.6, P < 0.05)., Conclusions: SDF-1/CXCR4 biological axis play an important role in liver metastasis of human colon cancer. Arrest of CXCR4 can inhibit liver metastasis of colon cancer through blocking cell proliferation and migration induced by SDF-1.

Objective: To provide ideal animal models for exploring pathogenesis and experimental therapy of primary malignant melanoma of the small intestine., Methods: The histologically intact primary and liver metastatic fragments derived from surgical specimens of one patient with metastatic malignant melanoma of the small intestine were orthotopically implanted in the small intestinal mucous layer of nude mice. The take rate, invasion and liver metastasis were observed. Morphology (light microscopy, electron microscopy), immunophenotype analysis, flow cytometry and karyotype analysis were applied for the original human tumors and the transplanted tumors., Results: The primary and liver metastatic fragments of malignant melanoma of the small intestine were successfully implanted in nude mice. After continuous passages in nude mice,an orthotopic model of human primary malignant melanoma of the small intestine(from the primary focus)in nude mice (termed HSIM-0501) and a liver metastatic model of human primary malignant melanoma of the small intestine (from the liver metastatic focus) in nude mice (termed HSIM-0502) were established. Histological examination of transplanted tumors revealed high-grade melanoma. S-100 protein and HMB45 were positive. Massive melanin granules and melanin complex were seen in cytoplasm of tumor cells.Chromosomal modal number was between 55 and 59. DNA index (DI) was 1.49-1.61, representing heteroploid. HSIM-0501 and HSIM-0502 were maintained for 25 and 27 passages in nude mice respectively. Three hundred and seventeen nude mice were used for transplantation. Both the take rate after transplantation and resuscitation rate of liquid nitrogen cryopreservation were 100%. HSIM-0501 exhibited 46.2% liver metastasis and 36.7% lymph node metastases. In HSIM-0502, both liver and lymph node metastases were 100%.The transplanted tumors autonomically and invasively grew in the small intestines of nude mice and hematogenous metastasis, lymph node metastasis and celiac planting metastasis occurred., Conclusion: Two nude mice liver metastatic models of human primary malignant melanoma of the small intestine are successfully established, which provide ideal animal models for the research of pathogenesis,metastasis biology and anti-metastatic experimental therapy of primary malignant melanoma of the small intestine.

Objective: To investigate the anti-tumor effect of intraportal administration of Adv-p53 in the treatment of the liver metastasis in mice., Methods: 2 x 10(5) of MCA-205 cells were injected into the mouse portal vein to establish a murine liver metastasis model. The spleen was transpositioned subcutaneously to enable the administration of Adv-p53 continually into the portal system. Different doses of Adv-p53 were injected intraportally, while HBSS and Adv-CMV were injected intraportaly in the control group. Tumors in the liver were examined on day 21 after Adv-p53 administration., Results: The liver weight in the Adv-p53 treated mice on day 0 group (1.20 +/- 0.34 g) was significantly less than that in the Adv-CMV group (2.59 +/- 0.48 g, P < 0.05). The number of metastatic nodules in the Adv-p53 treated mice on day 0 group (9.0 +/- 9.9) was significantly less than that in the Adv-CMV group (57.1 +/- 11.3, P < 0.05), indicating that intraportal administration of Adv-p53 inhibited the formation of liver metastasis. This anti-tumor effect was in a dose-dependent manner. After the liver metastasis was formed, Adv-p53 was administered intraportally. The liver weight in the Adv-p53 treated mice on day 5 group (1.22 +/- 0.09 g) was significantly less than that in the Adv-CMV group (3.98 +/- 1.01 g , P < 0.05). The number of metastatic nodules in the Adv-p53 treaed mice on day 5 group (5.5 +/- 3.5) was significantly less than that in the Adv-CMV group (113.2 +/- 5.8, P < 0.05). Repeatedly intraportal administration of Adv-p53 could enhance this anti-tumor effect., Conclusion: Local administration of Adv-p53 into the portal system would be a useful strategy for the liver metastasis treatment.

Objective: To isolate a subclone from human colorectal cancer cell line SW480 with unique metastatic potential in the liver., Methods: Human colorectal cancer cells SW480 were implanted into BALB/c nude mice, and the hepatic metastatic lesions were harvested, and the tumor tissue blocks were re-implantated into nude mice for a second round of in vivo selection. The same procedure was repeated 5 times until a new cell subline, designated as SW480/M5, was established, whose biological behaviors was investigated both in vivo and in vitro., Results: After orthotopic implantation of the tumor tissue into the colon of nude mouse for 28 days, widespread loco-regional and distant metastases occurred in mice inoculated with SW480 tissue, and those inoculated with SW480/M5 tissue had hepatic metastasis only. Compared with the parental cells, SW480/M5 cells were characterized by greater clonality, reproductive activity, motor ability, invasiveness, and weaker adhesive capacity to fibronectin., Conclusion: A human colorectal cancer cell subline with unique liver metastatic potential has been established by in vivo selection to serve as a new model for study ing colorectal cancer metastasis.

Objective: To establish a hepatic metastatic subline of nasopharyngeal carcinoma (NPC) cell line., Methods: NPC cells metastatic to the liver were isolated from nude mice and the invasion and metastatic ability of the cells was observed in vivo and in vitro., Results and Conclusion: The invasion and metastasis activity of 5-8F-H3B-EGFP (an in vivo isolate with enhanced liver metastatic behaviors) were enhanced obviously in comparison with the parent cell line 5-8F-EGFP. This subline may be useful for cloning genes related to liver metastasis of NPC.

Objective: To observe the correlation between serum level of TXB2, 6-Keto-PGF1alpha and liver metastasis., Methods: The metastatic model was made by injection of W256 carcinosarcoma. Rats were randomly divided into two groups: rats with blood stasis group and control group. Rats in control group were given normal saline via abdominal cavity once a day. Rats in blood stasis group were injected adrenalin in the fourteenth day. Tumor size and liver metastasis were observed. Serum TXB2 and 6-Keto-PGF1alpha were tested by radioimmunoassay., Results: Tumor size in rats with blood stasis was significantly smaller than that of the control group (P<0.01). Occurrence of liver metastasis in rats with blood stasis was significantly lower than that of the control group (P<0.01). The values of 6-Keto-PGF1alpha, TXB2, and TXB2/6-Keto-PGF1alpha were higher in the group with blood stasis., Conclusion: In the status of blood stasis, W256 carcinosarcoma grows slowly, and liver metastasis increases insignificantly, with the elevations of 6-Keto-PGF1alpha, TXB2 and TXB2/6-Keto-PGF1alpha.

Objective: To explore the influence of scatter factor/hepatocyte growth factor (SF/HGF) on the growth and transmission of hepatocarcinoma SMMC 7721 cells by SF/HGF cDNA transfection., Methods: Gene transfection was operated by lipofectin method. In vitro, SF/HGF and c-met expression was tested by ELISA and Western blot. Cell proliferation and motility were compared by growth curves and wound healing assays. In vivo, cells before and after transfection were implanted subcutaneously into nude mice respectively to observe tumor growth and metastasis., Results: After transfection, the expression of SF/HGF reached 694 pg/ml, compared with 0.26 pg/ml before transfection; however the expression of c-met protein did not change obviously. Growth curves showed that cells after transfection proliferated more rapidly than those before transfection and had an increased capability of motility together with enlarged morphological changes. In vivo experiment, tumors originated from SF/HGF(+) cells grew faster than those from SF/HGF(-) cells and had embolism formed inside and metastasis in the corresponding lung tissues, whereas no such findings in SF/HGF(-) cell originated tumors., Conclusions: High expression of SF/HGF can stimulate tumor cell proliferation and metastasis in hepatocellular carcinoma