Objective: To evaluate antitumor activities of Fritillaria imperialis and Eryngium caucasicum methanolic extracts on human hepatoma (HepG2) and colon cancer (HCT116) cell lines in comparison to human foreskin fibrobla...Objective: To evaluate antitumor activities of Fritillaria imperialis and Eryngium caucasicum methanolic extracts on human hepatoma (HepG2) and colon cancer (HCT116) cell lines in comparison to human foreskin fibroblasts as the normal cells. Methods: Methanolic extracts of Fritillaria imperialis and Eryngium caucasicum were prepared by the maceration method. The effect of the extracts at various concentrations (100, 200, 400, 600, and 800 μg/mL) on cell survival was evaluated using the MTT method. Besides, fluorescence staining was used to evaluate death patterns of the cells. Results: MTT assay showed that Fritillaria imperialis significantly decreased the viability of all cell lines after 24 and 48 hours of treatments. However, Eryngium caucasicum extract did not show any significant cytotoxicity effect on the cell lines. Fluorescence staining revealed that Fritillaria imperialis induced apoptosis of HCT116 cells at 550 μg/mL. Conclusions: Fritillaria imperialis extract has antiproliferative and cytotoxic effects on HCT116 and HepG2 cancer cells and therefore, may serve as an anticancer agent.展开更多
Objective: To study the potential role of cellular macrophage colony-stimulating factor (cM-CSF) and cellular macrophage colony-stimulating factor receptor (cM-CSF-R) with breast cancer and hepatoma and search the way...Objective: To study the potential role of cellular macrophage colony-stimulating factor (cM-CSF) and cellular macrophage colony-stimulating factor receptor (cM-CSF-R) with breast cancer and hepatoma and search the way for clinical application. Methods: Frozen surgical specimens from 48 breast cancer patients, including 29 cases of histological grade II and 19 eases of grade III, and 16 hepatoma patients were investigated by Avidin Biotin Complex (ABC) immunohistochemical assay with anti-M-CSF monoclonal antibody (Mab) and anti-M-CSF-R Mab. Pathohistological examination was performed as well. Results: cM-CSF and cM-CSF-R were detected in tested specimens. The expression levels of cM-CSF and cM-CSF-R in grade III group were higher than in grade II group and more higher than control group hyperplasia of breast. Hepatoma tissues also showed higher expression level of cM-CSF and cM-CSF-R than normal adult and fetal liver. Conclusion: Breast cancer and hepatoma tissues presented higher expression levels of cM-CSF and cM-CSF-R than control and expression level might be related with tumor’s process.展开更多
AIM:To assess the expression of nuclear hepatomaderived growth factor(HDGF)in benign and malignant gallbladder lesions and to determine its clinicopathological significance.METHODS:We studied 40 patients with gallblad...AIM:To assess the expression of nuclear hepatomaderived growth factor(HDGF)in benign and malignant gallbladder lesions and to determine its clinicopathological significance.METHODS:We studied 40 patients with gallbladder cancer(GBC)and a control group of 40 patients with cholelithiasis.All diagnoses of GBC and cholelithiasis were confirmed by histopathological examination after surgery.None of the patients received chemotherapy or radiotherapy before surgery.All tissue samples were fixed in 4%formalin immediately after removal and embedded in paraffin for immunohistochemical staining.The HDGF expression in the GBC and cholelithiasis specimens was examined by immunohistochemical staining.The relationship between the HDGF expression and the clinicopathological parameters of GBC was analyzed.RESULTS:Nuclear HDGF expression was significantly higher(77.5%)in GBC than in chronic cholelithiasis(21.5%,P<0.001).High nuclear HDGF levels were associated with histopathological subtype(P<0.05),clinical stage(P<0.01),and perineural invasion(P<0.01)but not with sex,age,history of gallstones,or lymph node metastasis.A univariate Kaplan-Meier analysis showed that positive nuclear HDGF expression was associated with decreased overall survival(P<0.01).Multivariate Cox regression analysis showed that nuclear HDGF expression and lymph node metastasis were independent risk factors for disease-free survival.CONCLUSION:The expression of nuclear HDGF might be closely related to the carcinogenesis,clinical biological behaviors,and prognosis of gallbladder adenocarcinoma.展开更多
AIM: To examine the association of hepatoma-derived growth factor(HDGF) expression with the prognosis of patients with cervical cancer of the uterus(CC). METHODS: HDGF is a unique nuclear growth factor, and it may pla...AIM: To examine the association of hepatoma-derived growth factor(HDGF) expression with the prognosis of patients with cervical cancer of the uterus(CC). METHODS: HDGF is a unique nuclear growth factor, and it may play an important role in the development and progression of carcinoma. HDGF expression in 88 CC patients aged 23 to 76 years(median, 54 years) was analyzed by immunohistochemistry. A rabbit polyclonal antibody against the C-terminal amino acids(aa 231-240) of the human HDGF sequence was used as primary antibody at a dilution of 1:5000. This specific anti-HDGF antibody was purified using C-terminal peptide-conjugated Sepharose columns. Staining of endothelial cells in the noncancerous areas of each specimen was used as an internal positive control. Samples with more than 80% of tumor cells showing positive immunoreactivity in both the nucleus and cytoplasm were regarded as HDGF index level 2, more than 80% positive immunoreactivity in either the nucleus or cytoplasm as level 1, and less than 80% in both the nucleus and cytoplasm as level 0. The chisquare test and Fisher's exact probability test were used to examine the relationship between HDGF expression and clinicopathologic parameters, and statistical significance was examined by the log-rank test. Multivariate analysis of factors related to survival was performed using Cox's proportional hazards regression model. Statistical significance was set at P < 0.05. RESULTS: The five-year overall survival rate was 82.9%. Fourteen patients died due to tumors, nine of whom had tumor recurrence at 2-21 mo(median, 10 mo) after surgery. Tumor recurrence in five patients was determined at the time of the patients' deaths. Nineteen cases were regarded as HDGF index level 0, 11 as level 1, and 58 as level 2. Patients with level 2 expression showed higher rates of histological classification of keratinized squamous cell carcinomaand adenosquamous carcinoma(44.8% of level 2 patients and 13.3% in levels 0 and 1), deep invasion(p T2-4 in 65.5% of level 2 patients, and 30.0% in levels 0 and 1), the presence of lymphatic invasion(50.0% in level 2, and 20.0% in levels 0 and 1), and the presence of lymph node metastasis(37.9% in level 2, and 6.7% in levels 0 and 1). Patients with an HDGF index of level 2 CC showed poorer 5-year overall survival rates than those with level 0 or 1 CC(74.0% and 100%, respectively, P = 0.0036). Univariate analysis revealed that histological classification(P = 0.04), depth of tumor invasion(P = 0.0001), vascular invasion(P = 0.004), and lymph node metastasis(P = 0.0001) were significant factors affecting overall survival in addition to HDGF expression. Multivariate analysis revealed HDGF expression level and lymph node metastasis as independent prognostic factors for overall survival(P = 0.0148 and P = 0.0197, respectively). The prognostic significance of HDGF was further analyzed in p T1 and p T2-4 patient groups, respectively. Among patients with p T1 CC, one the 39 analyzed patients died during the study, and no difference was observed among patients with HDGF index level 0, 1, or 2 CC. However, prognostic significance of the HDGF index was observed in the p T2-4 patient group, in which the mortality rates of patients with HDGF index level 2 CC and those with level 0 or 1 CC significantly differed(P = 0.0463). CONCLUSION: The HDGF expression level is of prognostic significance in CC.展开更多
Ever since its discovery two decades ago,the erythro- poietin-producing hepatoma (EPH)-EPHRIN system has been shown to play multifaceted roles in human gastroenterological cancer as well as neurodevelopment.Overexpres...Ever since its discovery two decades ago,the erythro- poietin-producing hepatoma (EPH)-EPHRIN system has been shown to play multifaceted roles in human gastroenterological cancer as well as neurodevelopment.Overexpression,amplif ication and point mutations have been found in many human cancers and many investigators have shown correlations between these up-regulationsand tumor angiogenesis.Thus,the genes in this family are considered to be potential targets of cancer therapy.On the other hand,the down-regulation of some members as a result of epigenetic changes has also been reported in some cancers.Furthermore,the correlation between altered expressions and clinical prognosis seems to be inconclusive.A huge amount of protein-protein interaction studies on the EPH-EPHRIN system have provided a basic scheme for signal transductions,especially bi-directional signaling involving EPH-ERPHRIN molecules at the cell membrane.This information also provides a manipulative strategy for harnessing the actions of these molecules.In this review,we summarize the known alterations of EPH-EPHRIN genes in human tumors of the esophagus,stomach,colorectum,liver and pancreas and present the perspective that the EPH-EPHRIN system could be a potential target of cancer therapy.展开更多
基金supported by deputy of Research and Technology,Mazandaran University of Medical Sciences
文摘Objective: To evaluate antitumor activities of Fritillaria imperialis and Eryngium caucasicum methanolic extracts on human hepatoma (HepG2) and colon cancer (HCT116) cell lines in comparison to human foreskin fibroblasts as the normal cells. Methods: Methanolic extracts of Fritillaria imperialis and Eryngium caucasicum were prepared by the maceration method. The effect of the extracts at various concentrations (100, 200, 400, 600, and 800 μg/mL) on cell survival was evaluated using the MTT method. Besides, fluorescence staining was used to evaluate death patterns of the cells. Results: MTT assay showed that Fritillaria imperialis significantly decreased the viability of all cell lines after 24 and 48 hours of treatments. However, Eryngium caucasicum extract did not show any significant cytotoxicity effect on the cell lines. Fluorescence staining revealed that Fritillaria imperialis induced apoptosis of HCT116 cells at 550 μg/mL. Conclusions: Fritillaria imperialis extract has antiproliferative and cytotoxic effects on HCT116 and HepG2 cancer cells and therefore, may serve as an anticancer agent.
基金Foundation item: This work was supported by '863' High Technology Grant of China (No. 102-11-01-03).
文摘Objective: To study the potential role of cellular macrophage colony-stimulating factor (cM-CSF) and cellular macrophage colony-stimulating factor receptor (cM-CSF-R) with breast cancer and hepatoma and search the way for clinical application. Methods: Frozen surgical specimens from 48 breast cancer patients, including 29 cases of histological grade II and 19 eases of grade III, and 16 hepatoma patients were investigated by Avidin Biotin Complex (ABC) immunohistochemical assay with anti-M-CSF monoclonal antibody (Mab) and anti-M-CSF-R Mab. Pathohistological examination was performed as well. Results: cM-CSF and cM-CSF-R were detected in tested specimens. The expression levels of cM-CSF and cM-CSF-R in grade III group were higher than in grade II group and more higher than control group hyperplasia of breast. Hepatoma tissues also showed higher expression level of cM-CSF and cM-CSF-R than normal adult and fetal liver. Conclusion: Breast cancer and hepatoma tissues presented higher expression levels of cM-CSF and cM-CSF-R than control and expression level might be related with tumor’s process.
文摘AIM:To assess the expression of nuclear hepatomaderived growth factor(HDGF)in benign and malignant gallbladder lesions and to determine its clinicopathological significance.METHODS:We studied 40 patients with gallbladder cancer(GBC)and a control group of 40 patients with cholelithiasis.All diagnoses of GBC and cholelithiasis were confirmed by histopathological examination after surgery.None of the patients received chemotherapy or radiotherapy before surgery.All tissue samples were fixed in 4%formalin immediately after removal and embedded in paraffin for immunohistochemical staining.The HDGF expression in the GBC and cholelithiasis specimens was examined by immunohistochemical staining.The relationship between the HDGF expression and the clinicopathological parameters of GBC was analyzed.RESULTS:Nuclear HDGF expression was significantly higher(77.5%)in GBC than in chronic cholelithiasis(21.5%,P<0.001).High nuclear HDGF levels were associated with histopathological subtype(P<0.05),clinical stage(P<0.01),and perineural invasion(P<0.01)but not with sex,age,history of gallstones,or lymph node metastasis.A univariate Kaplan-Meier analysis showed that positive nuclear HDGF expression was associated with decreased overall survival(P<0.01).Multivariate Cox regression analysis showed that nuclear HDGF expression and lymph node metastasis were independent risk factors for disease-free survival.CONCLUSION:The expression of nuclear HDGF might be closely related to the carcinogenesis,clinical biological behaviors,and prognosis of gallbladder adenocarcinoma.
基金Supported by The Japan Society for the Promotion of Science,No.21590412The Osaka Foundation for the Prevention of Cancer and Cardiovascular Diseases
文摘AIM: To examine the association of hepatoma-derived growth factor(HDGF) expression with the prognosis of patients with cervical cancer of the uterus(CC). METHODS: HDGF is a unique nuclear growth factor, and it may play an important role in the development and progression of carcinoma. HDGF expression in 88 CC patients aged 23 to 76 years(median, 54 years) was analyzed by immunohistochemistry. A rabbit polyclonal antibody against the C-terminal amino acids(aa 231-240) of the human HDGF sequence was used as primary antibody at a dilution of 1:5000. This specific anti-HDGF antibody was purified using C-terminal peptide-conjugated Sepharose columns. Staining of endothelial cells in the noncancerous areas of each specimen was used as an internal positive control. Samples with more than 80% of tumor cells showing positive immunoreactivity in both the nucleus and cytoplasm were regarded as HDGF index level 2, more than 80% positive immunoreactivity in either the nucleus or cytoplasm as level 1, and less than 80% in both the nucleus and cytoplasm as level 0. The chisquare test and Fisher's exact probability test were used to examine the relationship between HDGF expression and clinicopathologic parameters, and statistical significance was examined by the log-rank test. Multivariate analysis of factors related to survival was performed using Cox's proportional hazards regression model. Statistical significance was set at P < 0.05. RESULTS: The five-year overall survival rate was 82.9%. Fourteen patients died due to tumors, nine of whom had tumor recurrence at 2-21 mo(median, 10 mo) after surgery. Tumor recurrence in five patients was determined at the time of the patients' deaths. Nineteen cases were regarded as HDGF index level 0, 11 as level 1, and 58 as level 2. Patients with level 2 expression showed higher rates of histological classification of keratinized squamous cell carcinomaand adenosquamous carcinoma(44.8% of level 2 patients and 13.3% in levels 0 and 1), deep invasion(p T2-4 in 65.5% of level 2 patients, and 30.0% in levels 0 and 1), the presence of lymphatic invasion(50.0% in level 2, and 20.0% in levels 0 and 1), and the presence of lymph node metastasis(37.9% in level 2, and 6.7% in levels 0 and 1). Patients with an HDGF index of level 2 CC showed poorer 5-year overall survival rates than those with level 0 or 1 CC(74.0% and 100%, respectively, P = 0.0036). Univariate analysis revealed that histological classification(P = 0.04), depth of tumor invasion(P = 0.0001), vascular invasion(P = 0.004), and lymph node metastasis(P = 0.0001) were significant factors affecting overall survival in addition to HDGF expression. Multivariate analysis revealed HDGF expression level and lymph node metastasis as independent prognostic factors for overall survival(P = 0.0148 and P = 0.0197, respectively). The prognostic significance of HDGF was further analyzed in p T1 and p T2-4 patient groups, respectively. Among patients with p T1 CC, one the 39 analyzed patients died during the study, and no difference was observed among patients with HDGF index level 0, 1, or 2 CC. However, prognostic significance of the HDGF index was observed in the p T2-4 patient group, in which the mortality rates of patients with HDGF index level 2 CC and those with level 0 or 1 CC significantly differed(P = 0.0463). CONCLUSION: The HDGF expression level is of prognostic significance in CC.
基金Supported by A Grant in Aid for Scientific Research (2001407, 22659072, 22590356, 22790378, 221S0001) from the Ministry of Education, Culture, Sports, Science and Technology of Japana Grant in Aid for the 3rd anti-Cancer from the Ministry of Health, Labour and Welfare (H22-017) and from the Smoking Research Foundation
文摘Ever since its discovery two decades ago,the erythro- poietin-producing hepatoma (EPH)-EPHRIN system has been shown to play multifaceted roles in human gastroenterological cancer as well as neurodevelopment.Overexpression,amplif ication and point mutations have been found in many human cancers and many investigators have shown correlations between these up-regulationsand tumor angiogenesis.Thus,the genes in this family are considered to be potential targets of cancer therapy.On the other hand,the down-regulation of some members as a result of epigenetic changes has also been reported in some cancers.Furthermore,the correlation between altered expressions and clinical prognosis seems to be inconclusive.A huge amount of protein-protein interaction studies on the EPH-EPHRIN system have provided a basic scheme for signal transductions,especially bi-directional signaling involving EPH-ERPHRIN molecules at the cell membrane.This information also provides a manipulative strategy for harnessing the actions of these molecules.In this review,we summarize the known alterations of EPH-EPHRIN genes in human tumors of the esophagus,stomach,colorectum,liver and pancreas and present the perspective that the EPH-EPHRIN system could be a potential target of cancer therapy.
