Recently, a series of gold(III) meso-tetraarylporphyrins that are stable against demetallation in physiological conditions have been synthesized. In the present study, the antitumor effects of one of these compounds, gold(III) meso-tetraarylporphyrin 1a (gold-1a) was investigated in an orthotopic rat hepatocellular carcinoma (HCC) model as well as using a HCC cell line. The rat HCC model was induced by injection of rat hepatoma cells, McA-RH7777, into the left lobe of the liver. Seven days after tumor cell inoculation, gold-1a was injected directly into the tumor nodule at different doses, followed by the same doses via intraperitoneal injection twice a week. Gold-1a administration significantly prolonged the survival of HCC-bearing rats. Importantly, gold-1a induced necrosis as well as apoptosis in the tumor tissues, but not in the normal liver tissues. Furthermore, gold-1a treatment neither caused significant drop in body weight of the rats nor affected plasma aspartate aminotransferase level. In the in vitro studies, we observed that gold-1a treatment inhibited the proliferation of McA-RH7777 cells. Gold-1a upregulated genes that increase apoptosis, stabilize p53, decrease proliferation and downregulated genes playing roles in angiogenesis, invasion, and metabolism, as demonstrated by microarray. In particular, the compound upregulated 2 members of the growth arrest and DNA damage (Gadd) inducible gene family, Gadd34 and Gadd153. Suppression of Gadd34 and Gadd153 in McA-RH7777 cells by small hairpin RNA reduced the gold-1a-induced apoptosis and growth inhibition, indicating that gold-1a mediated its effects via upregulation of Gadd34 and Gadd153. Results from our study demonstrated that gold-1a might be a novel promising chemocytotoxic agent for treating HCC. ' 2005 Wiley-Liss, Inc.Key words: gold(III) compound; chemocytotoxic; hepatocellular carcinoma; apoptosis; growth arrest and DNA damage (Gadd) inducible genes Hepatocellular carcinoma (HCC) ranks fifth in frequency worldwide among all malignancies and causes 1 million deaths annually. 1,2 Over 500,000 new cases are currently diagnosed every year. 3 Hepatic resection and liver transplantation are the only 2 approaches that may cure HCC, but the majority of patients present with an advanced stage beyond surgical treatment. Chemotherapy is widely employed to treat unresectable HCC, 4,5 but the efficacy is not satisfactory because of the resistance of tumor cells to the chemocytotoxic agents.The inorganic complex cis-diamminedichloroplatinum(II) (cisplatin), which possesses potent antitumor activity, 6 has been extensively used to treat various human solid carcinomas. 7 Although cisplatin was effective in treating metastatic nasopharyngeal carcinoma 8,9 and prolonged survival in advanced and metastatic non-small cell lung cancer, 10 its overall response rates in HCC patients were low, and thus it failed to prolong patient survival. 11 Therefore, novel and nontoxic therapeutic agents are urgently needed to treat HCC.Gold compounds have long been shown to pose...

CONCLUSION:We established and characterized a colorectal cancer cell line, LST-R1 and LST-R1 has an obvious malignant tendency, which maybe partially attributed to the changes of the expression of some adhesion molecules, such as E-cadherin. It is also a versatile tool for exploring the original and progressive mechanisms of laterally spreading tumor and the early colon cancer genesis. INTRODUCTIONTwo routes have been described that can lead to colon carcinogenesis: one is the adenoma-carcinoma model, which is the main carcinogenetic pathway of prudent colorectal tumor and has been widely accepted in the west. However, an increasing number of superficial or flat colorectal tumors have been reported, particular in Japan [1,2] . The superficial tumors are considered to have a distinct clinicopathologic, genetic feature and behave a different carcinogenetic pathway, called de novo pathway [3][4][5][6] . Laterally spreading tumor (LST) is a unique subtype of superficial colorectal tumor, which was first reported by Kudo S in 1993 [7,8] and many names such as granular cluster type, nodule-aggregating tumor, creeping tumor, superficial spreading (epithelial) tumor, flower-bed-like lesion had been used. In 1998, it was defined as tumors originated from the colorectal mucous membranes and mainly extends laterally rather than vertically with its diameter greater than 1 cm ( Figure 1A) [9][10][11][12] . It has a tendency to affect the rectum, sigmoid colon, and caecum. In some studies, it has been reported that the carcinogenesis rate of LST is 8.64%-52.5% [13][14][15] . Abstract AIM: To study the molecular mechanism of laterally spreading tumor (LST), a cell line [Laterally Spreading Tumor-Rectum 1 (LST-R1)] was derived and the characteristics of this cell line were investigated. BASIC RESEARCH METHODS:A new cell line (LST-R1) originated from laterally spreading tumor was established. Properties of the cell line were characterized using scanning and transmission electron microscopy, immunohistochemistry method, cytogenetic analysis and nude mice xenograft experiments. In vitro invasion assay, cDNA microarray and Western blotting were used to compare the difference between the LST-R1 and other colorectal cancer cell lines derived from prudent colon cancer. RESULTS:Our study demonstrated that both epithelial special antigen (ESA) and cytokeratin-20 (CK20) were expressed in LST-R1. The cells presented microvilli and tight junction with large nuclei. The karyotypic analysis showed hyperdiploid features with structural chromosome aberrations. The in vivo tumorigenicity was also demonstrated in nude mice xenograft experiments. The invasion assay suggested this cell line has a higher invasive ability. cDNA microarray and Western blotting show the loss of the expression of E-cadherin in LST-R1 cells.