AIM:To evaluate the clinical benefit of thalidomide in patients with advanced hepatocellular carcinoma (hepatoma).METHODS:From March 2000 to July 2002, patients who had advanced hepatocellular carcinoma and failed to ...AIM:To evaluate the clinical benefit of thalidomide in patients with advanced hepatocellular carcinoma (hepatoma).METHODS:From March 2000 to July 2002, patients who had advanced hepatocellular carcinoma and failed to or were unsuited for aggressive treatment, were enrolled and took thalidomide 150 to 300mg/d. All cases were followed till April 2003. Data collection included viral hepatitis, grade of cirrhosis, total dosage of thalidomide, side effect, stage of hepatoma by Okuda and CLIP classification, and prognosis.The subjects were divided into A and B groups, depending on 5000 mg dosage of thalidomide. Survival time of all cases and in the two subgroups was evaluated.RESULTS:Ninety-nine patients with hepatoma were enrolled,81 men and 18 females with median age 58±14.1 years.Eighty-six percent had viral hepatitis and one case was alcoholism. Hepatoma was diagnosed with histology, alpha-fetoprotein (aFP) >400ng/mL, or image examination, there were 30,33 and 36 cases respectively. At the time of thalidomide therapy, more than 81% had cirrhotic status.Twenty-two patients were in group A (<5 000 rag) with median survival time about 25 days, for 77 cases in group B(≥5000mg) the median survival time was about 109 days.Six subjects had partial response. Most adverse effects were skin rush, neuropathy, somnolence, and constipation.CONCLUSION: Several patients responded to thalidomide therapy. As a single drug therapy, thalidomide might not have good therapeutic effect for all cases, but a small ratio of patients had exciting response, the resistance or tumor escape would develop after long-term use. Up to now, no defined facts could be used to predict response. The effect of thalidomide on hepatoma might be associated with the dosage. As salvage therapy, thalidomide has its value.Combination or adjuvant therapy will be the next trial.展开更多
OBJECTIVE DNA methylation has been regarded as an important epige-netic signature reflecting the transcription state of DNA in cells. This study was to conducted to assess the relationship between human alpha-feto-pro...OBJECTIVE DNA methylation has been regarded as an important epige-netic signature reflecting the transcription state of DNA in cells. This study was to conducted to assess the relationship between human alpha-feto-protein (AFP) gene expression and the DNA methylation status of the promoter region in three different cells, namely two human hepatocellular carcinoma (HCC) cell lines and normal human fibroblasts. METHODS Transcription of the AFP gene was verified by RT-PCR. After bisulphate treatment of DNA, the methods of MSP and BSP were used to analyze the methylation density and status within single DNA strands of two closely spaced CpG dinucleotides of the promoter region in the different cells. RESULTS RT-PCR analysis indicated that the expression of the AFP gene in HepG2 cells was significantly higher than in SMMC-7721 cells, and that the AFP gene was not expressed in normal human fibroblasts. By MSP and BSP we observed that the promoter region was demethylat-ed in the AFP-high-expressing cell lines, and that the sites of -2,494 bp and -2,431 bp in the AFP genomic sequence can be used as detection sites for early tumorous diagnosis. CONCLUSION These results indicate that the DNA methylation state of the promoter region has a negative correlation with AFP gene expression.展开更多
文摘AIM:To evaluate the clinical benefit of thalidomide in patients with advanced hepatocellular carcinoma (hepatoma).METHODS:From March 2000 to July 2002, patients who had advanced hepatocellular carcinoma and failed to or were unsuited for aggressive treatment, were enrolled and took thalidomide 150 to 300mg/d. All cases were followed till April 2003. Data collection included viral hepatitis, grade of cirrhosis, total dosage of thalidomide, side effect, stage of hepatoma by Okuda and CLIP classification, and prognosis.The subjects were divided into A and B groups, depending on 5000 mg dosage of thalidomide. Survival time of all cases and in the two subgroups was evaluated.RESULTS:Ninety-nine patients with hepatoma were enrolled,81 men and 18 females with median age 58±14.1 years.Eighty-six percent had viral hepatitis and one case was alcoholism. Hepatoma was diagnosed with histology, alpha-fetoprotein (aFP) >400ng/mL, or image examination, there were 30,33 and 36 cases respectively. At the time of thalidomide therapy, more than 81% had cirrhotic status.Twenty-two patients were in group A (<5 000 rag) with median survival time about 25 days, for 77 cases in group B(≥5000mg) the median survival time was about 109 days.Six subjects had partial response. Most adverse effects were skin rush, neuropathy, somnolence, and constipation.CONCLUSION: Several patients responded to thalidomide therapy. As a single drug therapy, thalidomide might not have good therapeutic effect for all cases, but a small ratio of patients had exciting response, the resistance or tumor escape would develop after long-term use. Up to now, no defined facts could be used to predict response. The effect of thalidomide on hepatoma might be associated with the dosage. As salvage therapy, thalidomide has its value.Combination or adjuvant therapy will be the next trial.
基金This work was supported by the Tianjin Municipal Science and Technology Commission (No.05YFJMJC08100).
文摘OBJECTIVE DNA methylation has been regarded as an important epige-netic signature reflecting the transcription state of DNA in cells. This study was to conducted to assess the relationship between human alpha-feto-protein (AFP) gene expression and the DNA methylation status of the promoter region in three different cells, namely two human hepatocellular carcinoma (HCC) cell lines and normal human fibroblasts. METHODS Transcription of the AFP gene was verified by RT-PCR. After bisulphate treatment of DNA, the methods of MSP and BSP were used to analyze the methylation density and status within single DNA strands of two closely spaced CpG dinucleotides of the promoter region in the different cells. RESULTS RT-PCR analysis indicated that the expression of the AFP gene in HepG2 cells was significantly higher than in SMMC-7721 cells, and that the AFP gene was not expressed in normal human fibroblasts. By MSP and BSP we observed that the promoter region was demethylat-ed in the AFP-high-expressing cell lines, and that the sites of -2,494 bp and -2,431 bp in the AFP genomic sequence can be used as detection sites for early tumorous diagnosis. CONCLUSION These results indicate that the DNA methylation state of the promoter region has a negative correlation with AFP gene expression.
