AIM: To investigate the effect of CpG-containing oligodeoxynucleotides (CpG ODN) alone or in combination with the chemotherapeutic agent 5-fluorouracil (5-FU) on tumor growth and whether CpG ODN can reverse the immuno...AIM: To investigate the effect of CpG-containing oligodeoxynucleotides (CpG ODN) alone or in combination with the chemotherapeutic agent 5-fluorouracil (5-FU) on tumor growth and whether CpG ODN can reverse the immunosuppression caused by the chemotherapy with 5-FU in murine hepatoma model. METHODS: Hepatoma model was established by subcutaneous inoculation with hepatoma-22 (H22) cells into the right flank of BALB/c mice. Mice with tumor were treated by peritumoral injection of CpG ODN alone or in combination with subcutaneous injection of 5-FU. Tumor size was quantified regularly. Serum levels of IL-12 and IFN-γ in mice were assayed by enzyme-linked immunosorbent assay (ELISA). The lytic capacity of splenic NK cells was tested by lactate dehydrogenase release assay. RESULTS: Peritumoral injection of CpG ODN alone or in combination with subcutaneous injection of 5-FU, and the treatment with 5-FU alone all led to significant inhibition of hepatoma growth. The mean tumor volumes fell by 46.66% in mice injected with CpG ODN, 68.34% in the 5-FU treated mice, and 70.23% in mice treated with the combination of CpG ODN and 5-FU than in controls. There was no significant difference in tumor size between 5-FU-treated mice and mice treated with the combination of 5-FU and CpG ODN (P>0.05). The serum levels of IL-12 and IFN-γ of mice treated with CpG ODN alone (IL-12: 464.50±24.37 pg/mL; IFN-γ: 134.20?5.76 pg/mL) or with the co-administration of CpG ODN and 5-FU (IL-12: 335.83±28.74 pg/mL; IFN-γ: 111.00±5.33 pg/mL) were significantly higher than that of controls (IL-12: 237.50±45.31 pg/mL; IFN-γ: 56.75±8.22 pg/mL). The production of IL-12 and IFN-γ was suppressed moderately in 5-FU-treated mice (IL-12: 166.67±53.22 pg/mL; 53.33±16.98 pg/mL) compared to control mice (P>0.05), whereas the combination of CpG ODN and 5-FU significantly increased the serum levels of IL-12 and IFN-γ compared to 5-FU alone (P<0.05). The NK cell killing activity in CpG ODN-treated mice (44.04±1.38%) or the mice treated with CpG ODN combined with 5-FU (30.67±1.28%) was significantly potentiated compared to controls (19.22±0.95%, P<0.05). The co-administration of CpG ODN and 5-FU also significantly enhanced the lytic activity of NK cells when compared with the treatment with 5-FU alone (12.03±1.42%, P<0.05). CONCLUSION: The present data suggests that CpG ODN used as single therapeutic agent triggers anti-tumor immune response to inhibit the growth of implanted hepatoma and reverses the immunosuppression caused by the chemotherapy with 5-FU.展开更多
AIM:To study the anti-hepatocarcinoma effects of 5-fluorouracil (5-Fu) encapsulated by galactosylceramide liposomes (5-Fu-GCL) in vivo and in vitro. METHODS: Tumor-bearing animal model and HepA cell line were respecti...AIM:To study the anti-hepatocarcinoma effects of 5-fluorouracil (5-Fu) encapsulated by galactosylceramide liposomes (5-Fu-GCL) in vivo and in vitro. METHODS: Tumor-bearing animal model and HepA cell line were respectively adopted to evaluate the anti-tumor effects of 5-Fu-GCL in vivo and in vitro. Tumor cell growth inhibition effects of 5-Fu-GCL in vitro were assessed by cell viability assay and MTT assay. In vivo experiment, the inhibitory effects on tumor growth were evaluated by tumor inhibition rate and animal survival days. High performance liquid chromatography was used to detect the concentration-time course of 5-Fu-GCL in intracellular fluid in vitro and the distribution of 5-Fu-GCL in liver tumor tissues in vivo. Apoptosis and cell cycle of tumor cells were demonstrated by flow cytometry. RESULTS: In vitro experiment, 5-Fu-GCL (6.25-100 μmol/L) and free 5-Fu significantly inhibited HepA cell growth. Furthermore, IC50 of 5-Fu-GCL (34.5 μmol/L) was lower than that of free 5-Fu (51.2 μmol/L). In vivo experiment, 5-Fu-GCL (20, 40, 80 mg/kg) significantly suppressed the tumor growth in HepA bearing mice model. Compared with free 5-Fu, the area under curve of 5-Fu-GCL in intracellular fluid increased 2.6 times. Similarly, the distribution of 5-Fu-GCL in liver tumor tissues was significantly higher than that of free 5-Fu. After being treated with 5-Fu-GCL, the apoptotic rate and the proportion of HepA cells in the S phase increased, while the proportion in the G0/G1 and G2/M phases decreased. CONCLUSION: 5-Fu-GCL appears to have anti-hepatocarcinoma effects and its drug action is better than free 5-Fu. Its mechanism is partly related to increased drug concentrations in intracellular fluid and liver tumor tissues, enhanced tumor cell apoptotic rate and arrest of cell cycle in S phase.展开更多
We report a case of hepatocellular carcinoma （HCC） treated successfully by transarterial chemoembolization （TACE） followed by combination therapy of 5-fluorouracil （5-FU） and pegylated interferon-α （PEG-IFN-α...We report a case of hepatocellular carcinoma （HCC） treated successfully by transarterial chemoembolization （TACE） followed by combination therapy of 5-fluorouracil （5-FU） and pegylated interferon-α （PEG-IFN-α）. In the present case, the patient had massive and advanced HCC with a diameter of over 8 cm located in segment 7 （S7） of the liver. Furthermore, the tumor invaded into the major branch of the portal vein （Vp3）. After TACE, combined administration of 5-FU and PEG-IFN-α was performed for 5 too. HCC was totally eradicated and the serum levels of tumor markers were markedly decreased by the treatment. Although it has been reported that the combined use of conventional IFN-α and 5-FU showed striking effects on HCC in some cases, this case may suggest the more promising effect of PEG-IFN-α with a long-lasting effect, in the combined use with 5-FU for the treatment of massive advanced HCC.展开更多
OBJECTIVE To examine the therapeutic effects and toxicity of high-dose-folinic acid plus a 5-fluorouracil(5-FU)bolus and continuous infusion with 5-FU combined with locally produced oxaliplatin(L-HOP)in treating advan...OBJECTIVE To examine the therapeutic effects and toxicity of high-dose-folinic acid plus a 5-fluorouracil(5-FU)bolus and continuous infusion with 5-FU combined with locally produced oxaliplatin(L-HOP)in treating advanced gastric carcinoma patients. METHODS Sixty-five patients with advanced gastric carcinoma were treated with high-dose-folinic acid plus a 5-FU bolus and a 48-h continuous infusion of 5-FU combined with oxaliplatin.The effects of treatment and toxicity were observed. RESULTS There were 4 complete responses,26 partial responses, 30 with no change and 5 with progressive disease.The overall effective response rate was 46.2%(30/65).The median duration was 7 months,with the main side effects including nausea and vomiting,peripheral phlebitis,alopecia,leukopenia,dental ulcers, peripheral neuritis and diarrhea.All the side effects were tolerated and minimal. CONCLUSION The results showed that high-dose folinic acid plus a 5-FU bolus and continuous infusion of 5-FU combined with oxaliplatin appears to be a safe and effective therapy for patients with advanced gastric carcinoma.This therapeutic regimen is of value for these patients.展开更多
基金Supported by the Natural Science Foundation of Hubei Province, No. 2000J006
文摘AIM: To investigate the effect of CpG-containing oligodeoxynucleotides (CpG ODN) alone or in combination with the chemotherapeutic agent 5-fluorouracil (5-FU) on tumor growth and whether CpG ODN can reverse the immunosuppression caused by the chemotherapy with 5-FU in murine hepatoma model. METHODS: Hepatoma model was established by subcutaneous inoculation with hepatoma-22 (H22) cells into the right flank of BALB/c mice. Mice with tumor were treated by peritumoral injection of CpG ODN alone or in combination with subcutaneous injection of 5-FU. Tumor size was quantified regularly. Serum levels of IL-12 and IFN-γ in mice were assayed by enzyme-linked immunosorbent assay (ELISA). The lytic capacity of splenic NK cells was tested by lactate dehydrogenase release assay. RESULTS: Peritumoral injection of CpG ODN alone or in combination with subcutaneous injection of 5-FU, and the treatment with 5-FU alone all led to significant inhibition of hepatoma growth. The mean tumor volumes fell by 46.66% in mice injected with CpG ODN, 68.34% in the 5-FU treated mice, and 70.23% in mice treated with the combination of CpG ODN and 5-FU than in controls. There was no significant difference in tumor size between 5-FU-treated mice and mice treated with the combination of 5-FU and CpG ODN (P>0.05). The serum levels of IL-12 and IFN-γ of mice treated with CpG ODN alone (IL-12: 464.50±24.37 pg/mL; IFN-γ: 134.20?5.76 pg/mL) or with the co-administration of CpG ODN and 5-FU (IL-12: 335.83±28.74 pg/mL; IFN-γ: 111.00±5.33 pg/mL) were significantly higher than that of controls (IL-12: 237.50±45.31 pg/mL; IFN-γ: 56.75±8.22 pg/mL). The production of IL-12 and IFN-γ was suppressed moderately in 5-FU-treated mice (IL-12: 166.67±53.22 pg/mL; 53.33±16.98 pg/mL) compared to control mice (P>0.05), whereas the combination of CpG ODN and 5-FU significantly increased the serum levels of IL-12 and IFN-γ compared to 5-FU alone (P<0.05). The NK cell killing activity in CpG ODN-treated mice (44.04±1.38%) or the mice treated with CpG ODN combined with 5-FU (30.67±1.28%) was significantly potentiated compared to controls (19.22±0.95%, P<0.05). The co-administration of CpG ODN and 5-FU also significantly enhanced the lytic activity of NK cells when compared with the treatment with 5-FU alone (12.03±1.42%, P<0.05). CONCLUSION: The present data suggests that CpG ODN used as single therapeutic agent triggers anti-tumor immune response to inhibit the growth of implanted hepatoma and reverses the immunosuppression caused by the chemotherapy with 5-FU.
基金Supported by the Key Teacher Foundation of Ministry of Education of China, No. 1869 Young Teacher Foundation of Department of Education of Anhui Province, No. 2000jp112
文摘AIM:To study the anti-hepatocarcinoma effects of 5-fluorouracil (5-Fu) encapsulated by galactosylceramide liposomes (5-Fu-GCL) in vivo and in vitro. METHODS: Tumor-bearing animal model and HepA cell line were respectively adopted to evaluate the anti-tumor effects of 5-Fu-GCL in vivo and in vitro. Tumor cell growth inhibition effects of 5-Fu-GCL in vitro were assessed by cell viability assay and MTT assay. In vivo experiment, the inhibitory effects on tumor growth were evaluated by tumor inhibition rate and animal survival days. High performance liquid chromatography was used to detect the concentration-time course of 5-Fu-GCL in intracellular fluid in vitro and the distribution of 5-Fu-GCL in liver tumor tissues in vivo. Apoptosis and cell cycle of tumor cells were demonstrated by flow cytometry. RESULTS: In vitro experiment, 5-Fu-GCL (6.25-100 μmol/L) and free 5-Fu significantly inhibited HepA cell growth. Furthermore, IC50 of 5-Fu-GCL (34.5 μmol/L) was lower than that of free 5-Fu (51.2 μmol/L). In vivo experiment, 5-Fu-GCL (20, 40, 80 mg/kg) significantly suppressed the tumor growth in HepA bearing mice model. Compared with free 5-Fu, the area under curve of 5-Fu-GCL in intracellular fluid increased 2.6 times. Similarly, the distribution of 5-Fu-GCL in liver tumor tissues was significantly higher than that of free 5-Fu. After being treated with 5-Fu-GCL, the apoptotic rate and the proportion of HepA cells in the S phase increased, while the proportion in the G0/G1 and G2/M phases decreased. CONCLUSION: 5-Fu-GCL appears to have anti-hepatocarcinoma effects and its drug action is better than free 5-Fu. Its mechanism is partly related to increased drug concentrations in intracellular fluid and liver tumor tissues, enhanced tumor cell apoptotic rate and arrest of cell cycle in S phase.
文摘We report a case of hepatocellular carcinoma （HCC） treated successfully by transarterial chemoembolization （TACE） followed by combination therapy of 5-fluorouracil （5-FU） and pegylated interferon-α （PEG-IFN-α）. In the present case, the patient had massive and advanced HCC with a diameter of over 8 cm located in segment 7 （S7） of the liver. Furthermore, the tumor invaded into the major branch of the portal vein （Vp3）. After TACE, combined administration of 5-FU and PEG-IFN-α was performed for 5 too. HCC was totally eradicated and the serum levels of tumor markers were markedly decreased by the treatment. Although it has been reported that the combined use of conventional IFN-α and 5-FU showed striking effects on HCC in some cases, this case may suggest the more promising effect of PEG-IFN-α with a long-lasting effect, in the combined use with 5-FU for the treatment of massive advanced HCC.
文摘OBJECTIVE To examine the therapeutic effects and toxicity of high-dose-folinic acid plus a 5-fluorouracil(5-FU)bolus and continuous infusion with 5-FU combined with locally produced oxaliplatin(L-HOP)in treating advanced gastric carcinoma patients. METHODS Sixty-five patients with advanced gastric carcinoma were treated with high-dose-folinic acid plus a 5-FU bolus and a 48-h continuous infusion of 5-FU combined with oxaliplatin.The effects of treatment and toxicity were observed. RESULTS There were 4 complete responses,26 partial responses, 30 with no change and 5 with progressive disease.The overall effective response rate was 46.2%(30/65).The median duration was 7 months,with the main side effects including nausea and vomiting,peripheral phlebitis,alopecia,leukopenia,dental ulcers, peripheral neuritis and diarrhea.All the side effects were tolerated and minimal. CONCLUSION The results showed that high-dose folinic acid plus a 5-FU bolus and continuous infusion of 5-FU combined with oxaliplatin appears to be a safe and effective therapy for patients with advanced gastric carcinoma.This therapeutic regimen is of value for these patients.
