AIM: To investigate the effects of thalidomide on angiogenesis, tumor growth and metastasis of hepatocellular carcinoma in nude mice.METHODS: Twenty-four nude mice were randomly divided into therapy group and control ...AIM: To investigate the effects of thalidomide on angiogenesis, tumor growth and metastasis of hepatocellular carcinoma in nude mice.METHODS: Twenty-four nude mice were randomly divided into therapy group and control group, 12 mice in each group. Thalidomide dissolved in 0.5% sodium carboxyl methyl cellulose (CMC) suspension was administered intraperitoneally once a day at the dose of 200 mg/kg in therapy group, and an equivalent volume of 0.5% CMC in control group. Mice were sacrificed on the 30th d, tumor size and weight and metastases in liver and lungs were measured. CD34 and VEGF mRNA in tumor tissue were detected by immunohistochemistry and semi-quantitative RT-PCR respectively and microvessel density (MVD) was counted. Serum concentrations of TNF-α and ALT and AFP were also tested.RESULTS: MVD and VEGF mRNA in therapy group were less than those in control group (31.08±16.23 vessels/HP vs 80.00±26.27 vessels/HP, 0.0538±0.0165 vs 0.7373±0.1297,respectively, P＜0.05). No statistical difference was observed in tumor size and weight and metastases in liver and lungs.TNF-α was significantly lower in therapy group than in control group (28.64±4.64 ng/L vs42.69±6.99 ng/L, P＜0.05). No statistical difference in ALT and AFP was observed between groups.CONCLUSION: Thalidomide can significantly inhibitangiogenesis and metastasis of hepatocellular carcinoma.Italso has inhibitory effects on circulating TNF-α.展开更多
AIM： To evaluate the efficacy of thalidomide in com- bination with other therapies to treat patients with ad- vanced hepatocellular carcinoma （HCC）. METHODS： We performed a retrospective analysis of all patients w...AIM： To evaluate the efficacy of thalidomide in com- bination with other therapies to treat patients with ad- vanced hepatocellular carcinoma （HCC）. METHODS： We performed a retrospective analysis of all patients with HCC who were treated with thalido- mide for at least two months. The medical records of patients with HCC who were treated at our institution between April 2003 and March 2008 were reviewed. Image studies performed before and after treatment, tumor response, overall survival, and the decrease in o-fetoprotein （AFP） levels were evaluated. RESULTS： A total of 53 patients with HCC received either 100 or 200 mg/d of thalidomide. The patient population consisted of 9 women and 44 men with a median age of 61 years. Thirty patients （56.6%） were classified as Child-Pugh A, and 12 patients （22.6%） were classified as Child-Pugh B. Twenty-six patients had portal vein thrombosis （49.1%）, and 25 patients had extrahepatic metastasis （47.1%）. The median duration of thalidomide treatment was 6.0 mo. Six of the 53 patients achieved a confirmed response （11.3%）, one achieved a complete response （1.9%） and 5 achieved a partial response （9.4%）. The disease control rate （CR ＋ PR ＋ SD） was 28.3% （95% CI： 17.8-42.4）, and the median overall survival rate was 10.5 too. The 1- and 2-year survival rates were 45% and 20%, respectively. Only one complete response patient showed an im- proved overall survival rate of 66.8 mo. Sixteen patients （30.2%） showed more than a 50% decrease in their serum AFP levels from baseline, indicating a better re- sponse rate （31.3%）, disease control rate （43.8%）, and overall survival time （20.7 mo）. The therapy was well tolerated, and no significant toxicities were observed. CONCLUSION： Thalidomide was found to be safe for advanced HCC patients, demonstrating anti-tumor ac- tivity including response, survival, and AFP decreases of greater than 50% from baseline.展开更多
AIM: To evaluate which patients with hepatocellular carcinoma (HCC) are most likely to respond to thalidomide treatment. METHODS: From July 2002 to July 2004, patients with HCC who received thalidomide treatment, were...AIM: To evaluate which patients with hepatocellular carcinoma (HCC) are most likely to respond to thalidomide treatment. METHODS: From July 2002 to July 2004, patients with HCC who received thalidomide treatment, were enrolled. We extracted relevant data from the patients’ medical records, including history and type of hepatitis, comorbidity, serum α-fetoprotein (α-FP) level, volumetric changes in tumor, length of survival, and the dose, duration, side effects of thalidomide treatment. The tumor response was evaluated. On the basis of these data, the patients were divided into two groups: those with either partial response or stable disease (PR + SD group) and those with progressive disease (PD group). RESULTS: Two of 42 (5%) patients had a partial tumor response after treatment with thalidomide, 200 mg/d, and 9 (21%) had stable disease. Patients in the PR + SD group all had cirrhosis. Comparing patients with and without cirrhosis, the former were more likely to respond to thalidomide therapy (PR + SD: 100% vs PD: 64.5%, P = 0.041 < 0.05). Thalidomide was significantly more likely to be effective in tumors smaller than 5 cm (PR + SD: 63.6% vs PD: 25.8%, P = 0.034 < 0.05). Compared with patients with progressive disease (PD), patients in the PR + SD group had a higher total dose of thalidomide (13 669.4 ± 8446.0 mg vs 22 022.7 ± 11 461.4 mg, P = 0.023 < 0.05) and a longer survival (181.0 ± 107.1 d vs 304.4 ± 167.1 d, P = 0.047 < 0.05). Patients with comorbid disease had a significantly greater incidence of adverse reactions than those without (93.8% vs 60.0%, P = 0.021 < 0.05). The average number of adverse reactions in each person with a comorbid condition was twice as high as in those without other diseases (2.2 ± 1.3 vs 1.1 ± 1.2; P = 0.022 < 0.05). CONCLUSION: Thalidomide therapy is most likely to beeffective in patients with early stage small HCC, espe- cially in those with other underlying diseases. A low dose (200 mg/d) of thalidomide is recommended to continue the treatment long enough to make it展开更多
文摘AIM: To investigate the effects of thalidomide on angiogenesis, tumor growth and metastasis of hepatocellular carcinoma in nude mice.METHODS: Twenty-four nude mice were randomly divided into therapy group and control group, 12 mice in each group. Thalidomide dissolved in 0.5% sodium carboxyl methyl cellulose (CMC) suspension was administered intraperitoneally once a day at the dose of 200 mg/kg in therapy group, and an equivalent volume of 0.5% CMC in control group. Mice were sacrificed on the 30th d, tumor size and weight and metastases in liver and lungs were measured. CD34 and VEGF mRNA in tumor tissue were detected by immunohistochemistry and semi-quantitative RT-PCR respectively and microvessel density (MVD) was counted. Serum concentrations of TNF-α and ALT and AFP were also tested.RESULTS: MVD and VEGF mRNA in therapy group were less than those in control group (31.08±16.23 vessels/HP vs 80.00±26.27 vessels/HP, 0.0538±0.0165 vs 0.7373±0.1297,respectively, P＜0.05). No statistical difference was observed in tumor size and weight and metastases in liver and lungs.TNF-α was significantly lower in therapy group than in control group (28.64±4.64 ng/L vs42.69±6.99 ng/L, P＜0.05). No statistical difference in ALT and AFP was observed between groups.CONCLUSION: Thalidomide can significantly inhibitangiogenesis and metastasis of hepatocellular carcinoma.Italso has inhibitory effects on circulating TNF-α.
文摘AIM： To evaluate the efficacy of thalidomide in com- bination with other therapies to treat patients with ad- vanced hepatocellular carcinoma （HCC）. METHODS： We performed a retrospective analysis of all patients with HCC who were treated with thalido- mide for at least two months. The medical records of patients with HCC who were treated at our institution between April 2003 and March 2008 were reviewed. Image studies performed before and after treatment, tumor response, overall survival, and the decrease in o-fetoprotein （AFP） levels were evaluated. RESULTS： A total of 53 patients with HCC received either 100 or 200 mg/d of thalidomide. The patient population consisted of 9 women and 44 men with a median age of 61 years. Thirty patients （56.6%） were classified as Child-Pugh A, and 12 patients （22.6%） were classified as Child-Pugh B. Twenty-six patients had portal vein thrombosis （49.1%）, and 25 patients had extrahepatic metastasis （47.1%）. The median duration of thalidomide treatment was 6.0 mo. Six of the 53 patients achieved a confirmed response （11.3%）, one achieved a complete response （1.9%） and 5 achieved a partial response （9.4%）. The disease control rate （CR ＋ PR ＋ SD） was 28.3% （95% CI： 17.8-42.4）, and the median overall survival rate was 10.5 too. The 1- and 2-year survival rates were 45% and 20%, respectively. Only one complete response patient showed an im- proved overall survival rate of 66.8 mo. Sixteen patients （30.2%） showed more than a 50% decrease in their serum AFP levels from baseline, indicating a better re- sponse rate （31.3%）, disease control rate （43.8%）, and overall survival time （20.7 mo）. The therapy was well tolerated, and no significant toxicities were observed. CONCLUSION： Thalidomide was found to be safe for advanced HCC patients, demonstrating anti-tumor ac- tivity including response, survival, and AFP decreases of greater than 50% from baseline.
文摘AIM: To evaluate which patients with hepatocellular carcinoma (HCC) are most likely to respond to thalidomide treatment. METHODS: From July 2002 to July 2004, patients with HCC who received thalidomide treatment, were enrolled. We extracted relevant data from the patients’ medical records, including history and type of hepatitis, comorbidity, serum α-fetoprotein (α-FP) level, volumetric changes in tumor, length of survival, and the dose, duration, side effects of thalidomide treatment. The tumor response was evaluated. On the basis of these data, the patients were divided into two groups: those with either partial response or stable disease (PR + SD group) and those with progressive disease (PD group). RESULTS: Two of 42 (5%) patients had a partial tumor response after treatment with thalidomide, 200 mg/d, and 9 (21%) had stable disease. Patients in the PR + SD group all had cirrhosis. Comparing patients with and without cirrhosis, the former were more likely to respond to thalidomide therapy (PR + SD: 100% vs PD: 64.5%, P = 0.041 < 0.05). Thalidomide was significantly more likely to be effective in tumors smaller than 5 cm (PR + SD: 63.6% vs PD: 25.8%, P = 0.034 < 0.05). Compared with patients with progressive disease (PD), patients in the PR + SD group had a higher total dose of thalidomide (13 669.4 ± 8446.0 mg vs 22 022.7 ± 11 461.4 mg, P = 0.023 < 0.05) and a longer survival (181.0 ± 107.1 d vs 304.4 ± 167.1 d, P = 0.047 < 0.05). Patients with comorbid disease had a significantly greater incidence of adverse reactions than those without (93.8% vs 60.0%, P = 0.021 < 0.05). The average number of adverse reactions in each person with a comorbid condition was twice as high as in those without other diseases (2.2 ± 1.3 vs 1.1 ± 1.2; P = 0.022 < 0.05). CONCLUSION: Thalidomide therapy is most likely to beeffective in patients with early stage small HCC, espe- cially in those with other underlying diseases. A low dose (200 mg/d) of thalidomide is recommended to continue the treatment long enough to make it
