AIM：To investigate the effect and mechanism of action of erlotinib, an epidermal growth factor receptor （EGFR） small molecule tyrosine kinase inhibitor （TKI）, in the human pancreatic cancer cell line BxPC-3 both ...AIM：To investigate the effect and mechanism of action of erlotinib, an epidermal growth factor receptor （EGFR） small molecule tyrosine kinase inhibitor （TKI）, in the human pancreatic cancer cell line BxPC-3 both in vitro and in vivo.METHODS： In vitro, human pancreatic cancer cell line BxPC-3 was exposed to varying concentrations of ertotinib, and its effects on proliferation, cell cycle distribution, apoptosis and the expression of proand antiapoptotic factors such as bcl-2, bcl-xl, bax and bak, and the expression of vascular endothelial cell growth factor （VEGF） were measured with 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, flow cytometric analysis, terminal deoxynucleotidyl transferase-mediated nick end labeling assay （TUNEL）, and reverse transcriptionpolymerase chain reaction （RT-PCR）. Potential effect of erlotinib on angiogenesis was examined by tube formation assay. Tumor growth suppression was observed in xenografted nude mice with pancreatic cancer in vivo. Immunohistochemical （IHC） staining for EGFR and factor VII-related antigen was undertaken to detect the microvessel density and VEGF expression in tumor tissue in xenograft nude mice.RESULTS： Erlotinib, as a single agent, repressed BxPC-3 cell growth in a dose-dependent manner, triggered G1 arrest and induced cell apoptosis, and suppressed capillary formation of endothelium in vitro. Expressions of VEGF were significantly down-regulated at a high concentration of 200 μmol/L, however, the expressions of bcl-2 and bcl-xl were decreased at 50 μmol/L. In vivo, Erlotinib-treated mice demonstrated a reduced tumor volume, weight and microvessel density as compared to the control. IHC staining showed decreased expression of EGFR and RT-PCR had lower VEGF expression in treated mice.CONCLUSION： The in vitro and in vivo findings provide evidence that BxPC-3 cells are inhibited with erlotinib treatment. Inhibition of EGFR may be a promising adjuvant chemotherapy strategy in pancreatic cancer treatment.展开更多
Objective： To evaluate the functional outcome and complications of allograft replacement in management of bone tumors. Methods： Between March 1992 and September 2002, 164 patients underwent bone tumor resection and ...Objective： To evaluate the functional outcome and complications of allograft replacement in management of bone tumors. Methods： Between March 1992 and September 2002, 164 patients underwent bone tumor resection and massive allograft reconstruction of bone defects. The length of the resected part ranged from 5-35 cm. The resections were classified as marginal or wide resections of the tumor on the basis of the Musculoskeletal Tumor Society staging system. Fresh-frozen allografts were employed as osteoarticular grafts （n = 95）, hemi-condylar （n = 15）, massive （n = 23）, allograft-prosthesis composite （n = 12）, intercalary grafts （n = 15） or hemi-pelvic grafts （n = 4）. Most of the lesions were osteosarcoma and giant cell tumor of bone and located in proximal and distal femur, proximal tibia and humerus. Results： At a median follow-up of 47 months （range, 12 to 168 months） after the operation, 154 of the patients in the study were free of disease and 10 died of disease. Twenty-one （12.8%） patients had local recurrence and 38 （23.2%） nonunion. Late complications included 11 （6.7%） fractures of the allograft and 18 （11.0%） infections of the graft, instability of the joint in the form of subluxation was noted in 13 （7.9%） patients. Ten extremities were amputated due to local recurrence or severe infection. Conclusion： AIIografts can be used for reconstruction of bony defects after tumor resection. AIIograft has nearly similar shape, strength, osteo-inductivity and osteo-conductivity with host bone. AIIograft implantation is a high complication reconstruction method, and the dsk of recurrence increases when less surgical margin achieves.展开更多
AIM: To evaluate the anti-tumor effects and possible involvement of anti-tumor immunity of electrochemotherapy (ECT) employing electroporation and bleomycin in human colon cancer xenografts in nude mice, and to establ...AIM: To evaluate the anti-tumor effects and possible involvement of anti-tumor immunity of electrochemotherapy (ECT) employing electroporation and bleomycin in human colon cancer xenografts in nude mice, and to establish the experimental basis for clinical application of ECT. METHODS: Forty nude mice, inoculated subcutaneously human colon cancer cell line LoVo for 3 wk, were allocated randomly into four groups: B+E+ (ECT), B+E- (administration of bleomycin alone), B-E+ (administration of electric pulses alone), and B-E- (no treatment). Tumor volumes were measured daily. The animals were killed on the 7* d, the weights of xenografts were measured, and histologies of tumors were evaluated. Cytotoxicity of spleen natural killer (NK) and lymphokine-activated killer (LAK) cells was then assessed by lactic dehydrogenase release assay. RESULTS: The mean tumor volume of group B+E+ was statistically different from the other three groups after the treatment (F= 36.80, P<0.01). There was one case of complete response, seven cases of partial response (PR) in group B+E+, one case of PR in group B+E- and group B-E+ respectively, and no response was observed in group B-E-. The difference of response between group B+E+ and the other three groups was statistically significant (X2 = 25.67,P<0.01). Histologically, extensive necrosis of tumor cells with considerable vascular damage and inflammatory cells infiltration were observed in group B+E+. There was no statistical difference between the cytotoxicity of NK and LAK cells in the four treatment groups. CONCLUSION: ECT significantly enhances the chemosensitivity and effects of chemotherapy in human colon cancer xenografts in nude mice, and could be a kind of novel treatment modality for human colon cancer. The generation of T-cell-dependent, tumor-specific immunity might be involved in the process of ECT.展开更多
文摘AIM：To investigate the effect and mechanism of action of erlotinib, an epidermal growth factor receptor （EGFR） small molecule tyrosine kinase inhibitor （TKI）, in the human pancreatic cancer cell line BxPC-3 both in vitro and in vivo.METHODS： In vitro, human pancreatic cancer cell line BxPC-3 was exposed to varying concentrations of ertotinib, and its effects on proliferation, cell cycle distribution, apoptosis and the expression of proand antiapoptotic factors such as bcl-2, bcl-xl, bax and bak, and the expression of vascular endothelial cell growth factor （VEGF） were measured with 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, flow cytometric analysis, terminal deoxynucleotidyl transferase-mediated nick end labeling assay （TUNEL）, and reverse transcriptionpolymerase chain reaction （RT-PCR）. Potential effect of erlotinib on angiogenesis was examined by tube formation assay. Tumor growth suppression was observed in xenografted nude mice with pancreatic cancer in vivo. Immunohistochemical （IHC） staining for EGFR and factor VII-related antigen was undertaken to detect the microvessel density and VEGF expression in tumor tissue in xenograft nude mice.RESULTS： Erlotinib, as a single agent, repressed BxPC-3 cell growth in a dose-dependent manner, triggered G1 arrest and induced cell apoptosis, and suppressed capillary formation of endothelium in vitro. Expressions of VEGF were significantly down-regulated at a high concentration of 200 μmol/L, however, the expressions of bcl-2 and bcl-xl were decreased at 50 μmol/L. In vivo, Erlotinib-treated mice demonstrated a reduced tumor volume, weight and microvessel density as compared to the control. IHC staining showed decreased expression of EGFR and RT-PCR had lower VEGF expression in treated mice.CONCLUSION： The in vitro and in vivo findings provide evidence that BxPC-3 cells are inhibited with erlotinib treatment. Inhibition of EGFR may be a promising adjuvant chemotherapy strategy in pancreatic cancer treatment.
文摘Objective： To evaluate the functional outcome and complications of allograft replacement in management of bone tumors. Methods： Between March 1992 and September 2002, 164 patients underwent bone tumor resection and massive allograft reconstruction of bone defects. The length of the resected part ranged from 5-35 cm. The resections were classified as marginal or wide resections of the tumor on the basis of the Musculoskeletal Tumor Society staging system. Fresh-frozen allografts were employed as osteoarticular grafts （n = 95）, hemi-condylar （n = 15）, massive （n = 23）, allograft-prosthesis composite （n = 12）, intercalary grafts （n = 15） or hemi-pelvic grafts （n = 4）. Most of the lesions were osteosarcoma and giant cell tumor of bone and located in proximal and distal femur, proximal tibia and humerus. Results： At a median follow-up of 47 months （range, 12 to 168 months） after the operation, 154 of the patients in the study were free of disease and 10 died of disease. Twenty-one （12.8%） patients had local recurrence and 38 （23.2%） nonunion. Late complications included 11 （6.7%） fractures of the allograft and 18 （11.0%） infections of the graft, instability of the joint in the form of subluxation was noted in 13 （7.9%） patients. Ten extremities were amputated due to local recurrence or severe infection. Conclusion： AIIografts can be used for reconstruction of bony defects after tumor resection. AIIograft has nearly similar shape, strength, osteo-inductivity and osteo-conductivity with host bone. AIIograft implantation is a high complication reconstruction method, and the dsk of recurrence increases when less surgical margin achieves.
基金Supported by the Grant from Science and Technology Development of Shanghai, No. 00440
文摘AIM: To evaluate the anti-tumor effects and possible involvement of anti-tumor immunity of electrochemotherapy (ECT) employing electroporation and bleomycin in human colon cancer xenografts in nude mice, and to establish the experimental basis for clinical application of ECT. METHODS: Forty nude mice, inoculated subcutaneously human colon cancer cell line LoVo for 3 wk, were allocated randomly into four groups: B+E+ (ECT), B+E- (administration of bleomycin alone), B-E+ (administration of electric pulses alone), and B-E- (no treatment). Tumor volumes were measured daily. The animals were killed on the 7* d, the weights of xenografts were measured, and histologies of tumors were evaluated. Cytotoxicity of spleen natural killer (NK) and lymphokine-activated killer (LAK) cells was then assessed by lactic dehydrogenase release assay. RESULTS: The mean tumor volume of group B+E+ was statistically different from the other three groups after the treatment (F= 36.80, P<0.01). There was one case of complete response, seven cases of partial response (PR) in group B+E+, one case of PR in group B+E- and group B-E+ respectively, and no response was observed in group B-E-. The difference of response between group B+E+ and the other three groups was statistically significant (X2 = 25.67,P<0.01). Histologically, extensive necrosis of tumor cells with considerable vascular damage and inflammatory cells infiltration were observed in group B+E+. There was no statistical difference between the cytotoxicity of NK and LAK cells in the four treatment groups. CONCLUSION: ECT significantly enhances the chemosensitivity and effects of chemotherapy in human colon cancer xenografts in nude mice, and could be a kind of novel treatment modality for human colon cancer. The generation of T-cell-dependent, tumor-specific immunity might be involved in the process of ECT.
