AIM： To estimate whether S-TI571 inhibits the expression of vascular endothelial growth factor （VEGF） in the gastrointestinal stromal tumor （GIST） cells. METHODS： We used GIST cell line, GIST-T1. It has a hetero...AIM： To estimate whether S-TI571 inhibits the expression of vascular endothelial growth factor （VEGF） in the gastrointestinal stromal tumor （GIST） cells. METHODS： We used GIST cell line, GIST-T1. It has a heterogenic 57-bp deletion in exon 11 to produce a mutated c-KIT, which results in constitutive activation of c-KIT. Cells were treated with/without STI571 or stem cell factor （SCF）. Transcription and expression of VEGF were determined by RT-PCR and flow cytometry or Western blotting, respectively. Activated c-KIT was estimated by immunoprecipitation analysis. Cell viability was determined by PITT assay. RESULTS： Activation of c-KIT was inhibited by STI571 treatment. VEGF was suppressed at both the transcriptional and translational levels in a temporal and dose-dependent manner by STI571. SCF upregulated the expression of VEGF and it was inhibited by S-13571. STI571 also reduced the cell viability of the GIST-T1 cells, as determined by PTT assay. CONCLUSION： Activation of c-KIT in the GIST-T1 regulated the expression of VEGF and it was inhibited by ST571. STI571 has antitumor effects on the GIST cells with respect to not only the inhibition of cell growth, but also the suppression of VEGF expression.展开更多
Objective： To elucidate the clinical significance of serum vascular endothelial growth factor （VEGF） level in pa- tients with advanced cancer. Methods： Enzyme linked immunosorbent assay （ELISA） was used to deter...Objective： To elucidate the clinical significance of serum vascular endothelial growth factor （VEGF） level in pa- tients with advanced cancer. Methods： Enzyme linked immunosorbent assay （ELISA） was used to determine the serum VEGF concentration in 40 patients with advanced cancer [non-small cell rung cancer （NSCLC）, esophageal cancer （EC） and nasopharyngeal carcinoma （NPC）] before and after chemotherapy and 10 healthy volunteers as control group. Results： The serum VEGF concentrations in 40 cases of advanced cancer patients were significantly higher than those of 10 healthy control cases [（477.07 ± 374.10 ） pg/mL vs （139.09 ± 133.41 ） pg/mL; P = 0.016]. The serum VEGF concentrations in patients with NSCLC, EC and NPC were （518.53 _± 378.99） pg/mL, （399.21 ± 393.69） pg/mL and （500.68 ± 348.48） pg/mL, respectively. The differences were all statistically significant as compared with healthy control group （P values were 0.011,0.044 and 0.019, respectively）. The serum VEGF concentrations of the patients in response to chemotherapy was significantly lower than those of the same patients before they undergoing chemotherapy [（400.41 ± 332.84） pg/mL vs （777.10 ± 666.01） pg/mL; P = 0.034]. Conclusion： The serum VEGF level might be a novel and promising tumor marker of advanced malignancies and a predictor of disease progression, prognosis and therapeutic efficacy,展开更多
Objective: To reveal the mechanism and effect of SU5416 in the treatment of mouse Lewis cancer in vivo. Methods: Lewis cell was transplanted into groin of C57/B6 mouse by subcutaneous injection, then SU5416 was admini...Objective: To reveal the mechanism and effect of SU5416 in the treatment of mouse Lewis cancer in vivo. Methods: Lewis cell was transplanted into groin of C57/B6 mouse by subcutaneous injection, then SU5416 was administrated intraperitoneally to investigate the impact of SU5416 on tumor angiogenesis and growth in vivo. 32 mice were treated with SU5416 at two different doses every day until the end-point. As a control, 8 mice received no treatment and 8 mice were treated with vehicle (DMSO) only after implantation. Results: Median survival in the treated group was statistically longer compared to that in the control groups (P < 0.05) and no significant systemic adverse was observed. Histological analysis of the treated tumors showed an increase in necroses and reduced in angiogenesis compared to the control tumors. Furthermore, the percent of apoptotic cells increased in the treated tumors by FCM, the expressions of VEGF and KDR had no change after SU5416 administration by western blot. Conclusion: SU5416 may be useful therapeutics drug that specifically inhibits the enzymatic activity of KDR kinase and could down regulate the tumor angiogenesis.展开更多
Objective: To investigate the clinical significance of the serum VEGF as a marker for monitoring the clinical course of tumor patients cured by surgery and radiotherapy. Methods: Enzyme linked immunosobent assay (ELIS...Objective: To investigate the clinical significance of the serum VEGF as a marker for monitoring the clinical course of tumor patients cured by surgery and radiotherapy. Methods: Enzyme linked immunosobent assay (ELISA) was used to detect serum levels of VEGF in the patients with carcinoma. Results: X-ray irradiation could induce the tumor cells to express and secret VEGF. Patients with elevated values of serum VEGF 60 days after radiotherapy had higher rate of tumor recurrence and metastasis. There was more chance of metastasis in lung cancer patients with higher level of VEGF after surgical resection (12/21). Less post-operation (3 months-4 years) patients without relapse or cancerometastasis showed elevated values of serum VEGF than those with relapse or cancerometastasis. There was negative correlation between the serum Hb and VEGF in the tumor patients (γ=?0.289, P<0.01). In the 28 patients with normal Hb levels at pre-operation, 17 patients with decreased Hb levels had more chance getting higher VEGF after operation than the others (P<0.05). Conclusion: clinical manifestation should be considered in the application of serum VEGF as a tumor marker, a prognostic factor, and a recurrence indicator of tumor. To determine the levels of serum VEGF and Hb, correct the low level of Hb and block the effect of VEGF by special means may be helpful for tumor patients.展开更多
Objective: The aim of this study was to investigate the effect of grape proanthocyanidins(GPC) on the growth and angiogenesis of hepatocellular carcinoma H22 cells xenograft in mice. Methods: The xenograft model was e...Objective: The aim of this study was to investigate the effect of grape proanthocyanidins(GPC) on the growth and angiogenesis of hepatocellular carcinoma H22 cells xenograft in mice. Methods: The xenograft model was established using injected subcutaneously H22 cells into the right axilla of the mice. Each group was treated with different doses of GPC and Endostar. All these treatments were maintained for 10 days, and mice were sacrificed. The xenograft tumors in mice were measured. The proliferation activity level of H22 cells was determined by MTT assay, and the levels of vascular endothelial growth factor(VEGF) protein were examined by immunohistochemistry. Results: When treated with 50, 100 and 200 mg/kg of GPC and Endostar, the tumor inhibition rates were 13.17%, 23.37%, 36.15% and 14.71%, respectively. The tumor weight of xenograft was significantly lighter in high GPC group than the control group(P < 0.05). The ODs in GPC groups were 0.835, 0.666 and 0.519, respectively. The absorbances in middle and high GPC groups were statistically significant, compared with control group(P < 0.01). Immunohistochemical technique showed the expression of VEGF of the GPC groups was downregulated significantly compared with the control group(P < 0.01). Conclusion: GPC can inhibit the growth of hepatocellular carcinoma H22 cell xenograft in mice. The inhibition of angiogenesis by the down-regulation of VEGF expression may play a key role in the anti-neoplastic effect of GPC.展开更多
Objective： To investigate the effect of direct moxibustion at Ganshu （BL18） on the serum concentrations of tumor specific growth factor （TSGF） and tumor necrosis factor a （TNF-a） in a rat model with precancerou...Objective： To investigate the effect of direct moxibustion at Ganshu （BL18） on the serum concentrations of tumor specific growth factor （TSGF） and tumor necrosis factor a （TNF-a） in a rat model with precancerous lesion of primary hepatocellular carcinoma （HCC）, so as to explore the mechanism of moxibustion underlying improvement of HCC. Methods： Sixty male Wistar rats were randomly divided into control group （n=10）, model group （n=20）, prevention group 1 （n=15） and prevention group 2 （n=15）. The normal rats were injected with physiological saline as blank control. At the same time, the rats of other three groups were injected with diethylnitrosamine to establish the HCC model. Direct moxibusUon with grain-sized moxa was applied to bilateral Ganshu acupoint of the rats in the prevention group 1 （1 treatment course, 20 days） and prevention group 2 （2 treatment courses, 40 days）, 5 doses for each acupoint, 0.5 mg/dose, once every other day. At each time point （before model establishment, the end of 1st course prevention, the end of 2rid course prevention and the end of model establishment）, serum levels of TSGF and TNF-eL were detected using enzyme-linked immunosorbent assay. Results： Compared with the control group, there was a remarkably increase of serum TSGF and TNF-eL contents in the model group at the end of the experiment （P〈0.05）. At the end of the 1st course of direct moxibustion, the contents of serum TSGF and TNF- a of rats in the prevention group 1 were significantly increased compared with that of the model group （P〈0.05）. At the end of the 2nd course of direct moxibustion, serum TSGF and TNF-a levels of rats in the model group were higher than the normal group with significantly difference （P〈0.05）, and the levels of TSGF and TNF-a in the prevention group 2 were significantly reduced in comparison with the model group （P〈0.05）. Conclusion： It was possible that direct moxibustion could inhibit precancerous lesion and postpone hepatocarcinogenesis, and the therapeutic effect of two courses were better than one course.展开更多
[目的]通过应用马血清、激素作用新西兰兔,诱导激素性股骨头坏死动物模型,分析TNFα、VEGF在激素性股骨头坏死中的作用。[方法]将20只健康新西兰兔随机分成2组,每组10只。A组为模型组,每只用马血清10 m l/kg,经兔耳缘静脉注射,间隔2周,...[目的]通过应用马血清、激素作用新西兰兔,诱导激素性股骨头坏死动物模型,分析TNFα、VEGF在激素性股骨头坏死中的作用。[方法]将20只健康新西兰兔随机分成2组,每组10只。A组为模型组,每只用马血清10 m l/kg,经兔耳缘静脉注射,间隔2周,按5 m l/kg剂量连续2 d注射马血清各1次,间隔2周后,注射醋酸泼尼松龙,按7.5 mg/kg腹腔注射3次。B组:正常对照组。动物注射激素5周后,采血,应用ELISA法测血清中TNF-α浓度。处死模型组,标本进行常规组织病理学检查,免疫组化分析股骨头VEGF的表达。[结果]模型组兔血清TNF-α浓度明显高于正常组(P<0.01)。组织病理学检查显示:部分血管栓塞,骨髓腔内造血组织明显减少,免疫组化结果显示:骨细胞及骨髓组织VEGF表达明显减少。[结论]血清中TNF-α浓度升高及股骨头骨髓组织VEGF表达减少可能是激素性股骨头坏死发生的重要因素。展开更多
文摘AIM： To estimate whether S-TI571 inhibits the expression of vascular endothelial growth factor （VEGF） in the gastrointestinal stromal tumor （GIST） cells. METHODS： We used GIST cell line, GIST-T1. It has a heterogenic 57-bp deletion in exon 11 to produce a mutated c-KIT, which results in constitutive activation of c-KIT. Cells were treated with/without STI571 or stem cell factor （SCF）. Transcription and expression of VEGF were determined by RT-PCR and flow cytometry or Western blotting, respectively. Activated c-KIT was estimated by immunoprecipitation analysis. Cell viability was determined by PITT assay. RESULTS： Activation of c-KIT was inhibited by STI571 treatment. VEGF was suppressed at both the transcriptional and translational levels in a temporal and dose-dependent manner by STI571. SCF upregulated the expression of VEGF and it was inhibited by S-13571. STI571 also reduced the cell viability of the GIST-T1 cells, as determined by PTT assay. CONCLUSION： Activation of c-KIT in the GIST-T1 regulated the expression of VEGF and it was inhibited by ST571. STI571 has antitumor effects on the GIST cells with respect to not only the inhibition of cell growth, but also the suppression of VEGF expression.
基金a grant from the Administration of Chinese Traditional Medicine of Guangdong Province(No.1040101)
文摘Objective： To elucidate the clinical significance of serum vascular endothelial growth factor （VEGF） level in pa- tients with advanced cancer. Methods： Enzyme linked immunosorbent assay （ELISA） was used to determine the serum VEGF concentration in 40 patients with advanced cancer [non-small cell rung cancer （NSCLC）, esophageal cancer （EC） and nasopharyngeal carcinoma （NPC）] before and after chemotherapy and 10 healthy volunteers as control group. Results： The serum VEGF concentrations in 40 cases of advanced cancer patients were significantly higher than those of 10 healthy control cases [（477.07 ± 374.10 ） pg/mL vs （139.09 ± 133.41 ） pg/mL; P = 0.016]. The serum VEGF concentrations in patients with NSCLC, EC and NPC were （518.53 _± 378.99） pg/mL, （399.21 ± 393.69） pg/mL and （500.68 ± 348.48） pg/mL, respectively. The differences were all statistically significant as compared with healthy control group （P values were 0.011,0.044 and 0.019, respectively）. The serum VEGF concentrations of the patients in response to chemotherapy was significantly lower than those of the same patients before they undergoing chemotherapy [（400.41 ± 332.84） pg/mL vs （777.10 ± 666.01） pg/mL; P = 0.034]. Conclusion： The serum VEGF level might be a novel and promising tumor marker of advanced malignancies and a predictor of disease progression, prognosis and therapeutic efficacy,
基金a grant from the National Key Project of Scientific and Technical Supporting Programs funded by Ministry of Science & Technology of China (No. 2006BAI02A05).
文摘Objective: To reveal the mechanism and effect of SU5416 in the treatment of mouse Lewis cancer in vivo. Methods: Lewis cell was transplanted into groin of C57/B6 mouse by subcutaneous injection, then SU5416 was administrated intraperitoneally to investigate the impact of SU5416 on tumor angiogenesis and growth in vivo. 32 mice were treated with SU5416 at two different doses every day until the end-point. As a control, 8 mice received no treatment and 8 mice were treated with vehicle (DMSO) only after implantation. Results: Median survival in the treated group was statistically longer compared to that in the control groups (P < 0.05) and no significant systemic adverse was observed. Histological analysis of the treated tumors showed an increase in necroses and reduced in angiogenesis compared to the control tumors. Furthermore, the percent of apoptotic cells increased in the treated tumors by FCM, the expressions of VEGF and KDR had no change after SU5416 administration by western blot. Conclusion: SU5416 may be useful therapeutics drug that specifically inhibits the enzymatic activity of KDR kinase and could down regulate the tumor angiogenesis.
基金This work was supported by a grant from the Natural Science Foundation of Liaoning Province of China (No. 002032).
文摘Objective: To investigate the clinical significance of the serum VEGF as a marker for monitoring the clinical course of tumor patients cured by surgery and radiotherapy. Methods: Enzyme linked immunosobent assay (ELISA) was used to detect serum levels of VEGF in the patients with carcinoma. Results: X-ray irradiation could induce the tumor cells to express and secret VEGF. Patients with elevated values of serum VEGF 60 days after radiotherapy had higher rate of tumor recurrence and metastasis. There was more chance of metastasis in lung cancer patients with higher level of VEGF after surgical resection (12/21). Less post-operation (3 months-4 years) patients without relapse or cancerometastasis showed elevated values of serum VEGF than those with relapse or cancerometastasis. There was negative correlation between the serum Hb and VEGF in the tumor patients (γ=?0.289, P<0.01). In the 28 patients with normal Hb levels at pre-operation, 17 patients with decreased Hb levels had more chance getting higher VEGF after operation than the others (P<0.05). Conclusion: clinical manifestation should be considered in the application of serum VEGF as a tumor marker, a prognostic factor, and a recurrence indicator of tumor. To determine the levels of serum VEGF and Hb, correct the low level of Hb and block the effect of VEGF by special means may be helpful for tumor patients.
基金supported by Department of Oncology, the Affiliated Hospital of Qingdao University, China
文摘Objective: The aim of this study was to investigate the effect of grape proanthocyanidins(GPC) on the growth and angiogenesis of hepatocellular carcinoma H22 cells xenograft in mice. Methods: The xenograft model was established using injected subcutaneously H22 cells into the right axilla of the mice. Each group was treated with different doses of GPC and Endostar. All these treatments were maintained for 10 days, and mice were sacrificed. The xenograft tumors in mice were measured. The proliferation activity level of H22 cells was determined by MTT assay, and the levels of vascular endothelial growth factor(VEGF) protein were examined by immunohistochemistry. Results: When treated with 50, 100 and 200 mg/kg of GPC and Endostar, the tumor inhibition rates were 13.17%, 23.37%, 36.15% and 14.71%, respectively. The tumor weight of xenograft was significantly lighter in high GPC group than the control group(P < 0.05). The ODs in GPC groups were 0.835, 0.666 and 0.519, respectively. The absorbances in middle and high GPC groups were statistically significant, compared with control group(P < 0.01). Immunohistochemical technique showed the expression of VEGF of the GPC groups was downregulated significantly compared with the control group(P < 0.01). Conclusion: GPC can inhibit the growth of hepatocellular carcinoma H22 cell xenograft in mice. The inhibition of angiogenesis by the down-regulation of VEGF expression may play a key role in the anti-neoplastic effect of GPC.
基金Supported by the National Natural Science Foundation of China(No.81202760)the Doctoral Program of Higher Educition of Ministry Education of China(No.20100013120014)
文摘Objective： To investigate the effect of direct moxibustion at Ganshu （BL18） on the serum concentrations of tumor specific growth factor （TSGF） and tumor necrosis factor a （TNF-a） in a rat model with precancerous lesion of primary hepatocellular carcinoma （HCC）, so as to explore the mechanism of moxibustion underlying improvement of HCC. Methods： Sixty male Wistar rats were randomly divided into control group （n=10）, model group （n=20）, prevention group 1 （n=15） and prevention group 2 （n=15）. The normal rats were injected with physiological saline as blank control. At the same time, the rats of other three groups were injected with diethylnitrosamine to establish the HCC model. Direct moxibusUon with grain-sized moxa was applied to bilateral Ganshu acupoint of the rats in the prevention group 1 （1 treatment course, 20 days） and prevention group 2 （2 treatment courses, 40 days）, 5 doses for each acupoint, 0.5 mg/dose, once every other day. At each time point （before model establishment, the end of 1st course prevention, the end of 2rid course prevention and the end of model establishment）, serum levels of TSGF and TNF-eL were detected using enzyme-linked immunosorbent assay. Results： Compared with the control group, there was a remarkably increase of serum TSGF and TNF-eL contents in the model group at the end of the experiment （P〈0.05）. At the end of the 1st course of direct moxibustion, the contents of serum TSGF and TNF- a of rats in the prevention group 1 were significantly increased compared with that of the model group （P〈0.05）. At the end of the 2nd course of direct moxibustion, serum TSGF and TNF-a levels of rats in the model group were higher than the normal group with significantly difference （P〈0.05）, and the levels of TSGF and TNF-a in the prevention group 2 were significantly reduced in comparison with the model group （P〈0.05）. Conclusion： It was possible that direct moxibustion could inhibit precancerous lesion and postpone hepatocarcinogenesis, and the therapeutic effect of two courses were better than one course.
文摘[目的]通过应用马血清、激素作用新西兰兔,诱导激素性股骨头坏死动物模型,分析TNFα、VEGF在激素性股骨头坏死中的作用。[方法]将20只健康新西兰兔随机分成2组,每组10只。A组为模型组,每只用马血清10 m l/kg,经兔耳缘静脉注射,间隔2周,按5 m l/kg剂量连续2 d注射马血清各1次,间隔2周后,注射醋酸泼尼松龙,按7.5 mg/kg腹腔注射3次。B组:正常对照组。动物注射激素5周后,采血,应用ELISA法测血清中TNF-α浓度。处死模型组,标本进行常规组织病理学检查,免疫组化分析股骨头VEGF的表达。[结果]模型组兔血清TNF-α浓度明显高于正常组(P<0.01)。组织病理学检查显示:部分血管栓塞,骨髓腔内造血组织明显减少,免疫组化结果显示:骨细胞及骨髓组织VEGF表达明显减少。[结论]血清中TNF-α浓度升高及股骨头骨髓组织VEGF表达减少可能是激素性股骨头坏死发生的重要因素。
