Characterization of gastric cancer models from different cell lines orthotopically constructed using improved implantation techniques.

AIM: To develop orthotopic gastric cancer mouse models from different cell lines and characterize the tumor features to assist further in preclinical trials and clinical treatment strategies. METHODS: Human gastric cancer SGC-7901 and BGC-823 cell suspensions were injected subcutaneously into nude mice to develop solid tumors, and tumor tissue pieces were then implanted under the serous coat of the stomach. An autopsy was performed on all animals of the SGC-7901 and BGC-823 models to observe the primary tumor growth and metastases using pathological and immunohistochemical methods. RESULTS: Both models showed large tumors in situ resulting in pressure and infiltration of the adjacent organs. The gastric cavity became smaller, along with stenosis of the cardia or pylorus. There were biological and statistical differences between the two models. The metastasis rate in involved organs (lymph nodes, kidney, spleen, testis) was significantly higher in the BGC-823 model compared to the SGC-7901 model (P < 0.05 or P < 0.01). The median survival of the BGC-823 model was shorter than that of SGC-7901 (23 d vs 84 d, P < 0.05). Histopathologically, the primary tumor and metastatic lesions of the two models showed obvious atypia and mucus in the cytoplasm. Compared with the SGC-7901 model, BGC-823 appeared more poorly differentiated (absence of adenoid structure), had a smaller volume, and richer capillary structure. Immunohistochemical staining revealed cytokeratin 20 and epithelial membrane antigen expression was positive in the SGC-7901 tumors, while negative in BGC-823 ones. CONCLUSION: Models using the SGC-7901 and BGC-823 cell lines were established which could function in gastric cancer research on carcinogenesis mechanism and drug discovery. The two models showed different tumor behavior and the latter was more malignant than the former.

Serial observations on an orthotopic gastric cancer model constructed using improved implantation technique.

AIM: To establish a gastric cancer nude-mouse model with improved orthotopic implantation and investigate its biological characteristics at different time points. METHODS: Human gastric cancer SGC-7901 cell suspensions were injected subcutaneously into a nude mouse to develop solid tumors, and the tumor tissue pieces were implanted under the serous coat. The nude mice were then euthanized in group every two weeks to observe the primary tumor growth and metastases. RESULTS: Within 2-4 wk, there were no obvious changes about the primary tumor in stomach. At the sixth week, the primary tumor began to grow fast, resulting in incrassation of the gastric wall and stenosis of the gastric cavity, and metastases into the liver and lymph nodes were detected. The tumor, which compressed the adjacent organs, gradually became bigger and bigger followed by stenosis or vanishment of the gastric cavity from 8 to 12 wk. There were massive metastases, and the rate of metastasis was 58% in lymph nodes, 78% in liver, 39% in kidney, and 81% in peritoneum or septum. CONCLUSION: A gastric cancer model is established, which can simulate the clinical tumor behavior and provide experimental carrier for clinical trials of gastric cancer treatment.

Prognostic value of hedgehog signal component expressions in hepatoblastoma patients.

OBJECTIVE: Activation of hedgehog (Hh) pathway has been implicated in the development of human malignancies. Hh as well as related downstream target genes has been extensively studied in many kinds of malignant tumours for clinical diagnostic or prognostic utilities. This study aimed at investigating whether Hh molecules provides a molecular marker of hepatoblastoma malignancy. METHODS: We obtained tissue sections from 32 patients with hepatoblastoma as well as cholestasis and normal control. Immunohistochemical analysis were performed to determine Hh signal components in human hepatoblastoma. The prognostic significance of single expression of Hh signal components were evaluated using Cox proportional hazards regression models and Kaplan-Meier survival analysis for statistical analysis. RESULTS: Expression of Hh signal components showed an increase in hepatoblastoma compared with cholestasis and normal tissues. There was a positive correlation between Smo or Gli1 expression and tumor clinicopathological features, such as histological type, tumor grade, tumor size and clinical stage. Both Smo or Gli1 protein high expression was significantly associated with poor prognosis by univariate analyses and multivariate analyses. CONCLUSIONS: Abnormal Hh signaling activation plays important roles in the malignant potential of hepatoblastoma. Gli1 expression is an independent prognostic marker.