Therapeutic effects and prognostic factors in three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma

AIM: To evaluate the therapeutic efficacy of threedimensional conformal radiotherapy (3D-CRT) combined with transcatheter arterial chernoembolization (TACE) on the patients with hepatocellular carcinoma (HCC).METHODS: Between 1998 and 2001, 94 patients with HCC received 3D-CRT combined with TACE. A total 63 patients had a Okuda stage Ⅰ lesion and 31 patients had stage Ⅱ. The median tumor size was 10.7 cm (range 3.0-18 cm), and liver drrhosis was present in all the patients. There were 43 cases of class A and 51 dass B. TACE was performed using lipiodol,5-fluorouracil, cisplatin, doxorubicin hydrochloride and mitomycin, followed by gelatin sponge cubes. Fifty-nine patients received TACE only one time, while the others 2 to 3 times. 3D-CRT was started 3-4 wk after TACE. All patients were irradiated with a stereotactic body frame and received 4-8 Gy single high-dose radiation for 8-12 times at the isocenter during a period of 17-26 d (median 22 d).RESULTS: The median follow-up was 37 mo (range 10-48 mo) after diagnosis. The response rate was 90.5%. The overallsurvival rate at 1-, 2-, and 3- year was 93.6%, 53.8% and 26.0% respectively, with the median survival of 25 too. On univariate analysis, age (P=-0.026), Child-Pugh classification for cirrhosis of liver (P=0.010), Okuda stage (P=-0.026),tumor size (P=0.000), tumor type (P=0.029), albuminemia (P=0.035), and radiation dose (P=0.000) proved to be significant factors for survival. On multivariate analysis,age (P=-0.024), radiation dose(P=-0.001), and tumor size (P=0.000) were the significant factors.CONCLUSION: 3D-CRT combined with TACE is an effective and feasible approach for HCC. Age, radiation dose and tumor size were found to be significant prognostic factors for survival of patients with HCC treated by 3D-CRT combined with TACE. Further study for HCC is needed to improve the treatment efficacy.

KAI1 gene expression in colonic carcinoma and its clinical significances

AIM: To investigate KAI1 gene expression in the progression of human colonic carcinoma and its clinical significances.METHODS: KAI1 expression was detected by in situ hybridization and immunohistochemistry in the 4 established cell lines of colorectal carcinoma with different metastatic potentials, and in 80 specimens of colonic carcinoma, 21 colonic carcinoma specimens with lymphatic metastasis and 20 controls of normal colonic mucosa.RESULTS: The expressions of KAI1 in HT29 and SW480 cell lines were higher than those in LoVo and SW620. Theexpression of KAI1 gene was significantly higher in colorectal carcinoma compared with normal colonic mucosa andlymphatic metastasis (X^2=46.838, P<0.01). The expression of KAI1 gene had no relationship with histological grade.The KAI1 expressions in Dukes A and B carcinoma were higher at both mRNA and protein levels compared to Dukes C carcinoma (72=16.061, P<0.05). The expression of KAI1 in colonic carcinoma specimens with lymphatic metastasis was almost lost. The results of in situ hybridization were in concordance with immunohistochemistry.CONCLUSION: KAI1 is highly related to the metastasis of colonic carcinoma and may be a useful indicator of metastasis in colonic carcinoma.

Tiaml gene expression and its significance in colorectal carcinoma

AIM: To explore the expression of Tiam1 gene in colorectal carcinoma and its correlation with tumor metastasis. METHODS: Expressions of Tiaml gene in 8 colorectal carcinoma cell lines were detected by reverse transcriptase-polymerase chain reaction. In vitro invasiveness was determined by means of Matrigel invasion assay. The correlation of Tiaml expression with the invasive ability was also analyzed. RESULTS: Tiaml gene was highly expressed in LoVo and SW620, which were established from metastatic colorectal carcinomas in comparison with LS174T, SW480, HCT116, LST, HRT-18 and Hee8693, which were established from primary colorectal carcinomas. In vitro cell invasivion demonstrated that LoVo and SW620 had a higher invasive ability than LS174T, SW480, HCT116, LST, HRT-18 and Hee8693. The expression of Tiaml gene was highly related to the metastatic potential of colorectal carcinoma cells. CONCLUSION: Tiaml gene may play an important role in invasion and metastasis of colorectal carcinoma and is a metastasis-related gene.

Effects of KAI1/CD82 on biological behavior of human colorectal carcinoma cell line

AIM: To investigate the effects of KAI1/CD82 on biological behavior of colorectal carcinoma cells. METHODS: KAI1 cDNA was transfected into highly malignant colorectal carcinoma cell line, LoVo, which had low level of endogenous KAI1 expression, and established stable transfectant clones with high KAI1/CD82 expression.The cell-cell adhesion, cell aggregation, cell-matrix adhesion and cell invasion assay were performed to determine whether KAI1 transfectant could have an effect on proliferation,adhesion and tumor metastasis in comparison with the control transfectant cells. RESULTS: KAI1 expression did not alter in vitro cell proliferation. But the KAI1 transfectant cells exhibited significantly increased homotypic cell-cell adhesion and cell aggregation in comparison with the control transfectant cells (P＜0.05). Furthermore, KAI1 expression significantly suppressed the cell adhesion to extracellular matrix components and in vitro cell invasion in KAI1-transfected LoVo cells. The data indicated that KAI1 expression significantly suppressed the metastatic potential of KAI1-transfected LoVo cells. CONCLUSION: Our results suggest that KAI1 might function as a negative regulator of colorectal carcinoma metastasis.

Antitumor effects and radiosensitization of cytosine deaminase and thymidine kinase fusion suicide gene on colorectal carcinoma cells

AIM: To investigate the killing effect and radiosensitization of double suicide gene mediated by adenovirus on colorectal carcinoma cells. METHODS: Colorectal carcinoma cell line SW480 was transfected with adenovirus expression vector containing cytosine deaminase (CD) and thymidine kinase (TK) fusion gene. The expression of CD-TK fusion gene was detected by reverse transcriptase-polymerase chain reaction. The toxic effect of ganciclovir (GCV) and 5-fluorocytosine (5-FC) on infected cells was determined by MTT assay. The radiosensitization of double suicide gene was evaluated by clonogenic assay. RESULTS: After prodrugs were used, the survival rate of colorectal carcinoma cells was markedly decreased. When GCV and 5-FC were used in combination, the cytotoxicity and bystander effect were markedly superior to a single prodrug (X2 = 30.371, P<0.01). Both GCV and 5-FC could sensitize colorectal carcinoma cells to the toxic effect of radiation, and greater radiosensitization was achieved when both prodrug were used in combination. CONCLUSION: CD-TK double suicide gene can kill and radiosensitize colorectal carcinoma cells.