Objective: To investigate the correlation between c-erbB-2 and multidrug resistance (MDR) and its clinical significance, Methods: Immunohistochemistry stain was used to examine the expression of c-erbB-2 and flow ...Objective: To investigate the correlation between c-erbB-2 and multidrug resistance (MDR) and its clinical significance, Methods: Immunohistochemistry stain was used to examine the expression of c-erbB-2 and flow cytometry was used to detect the expression of P-glycoprotein (P-gp) in samples from 46 patients with esophageal carcinoma. Results: The positive expression rate of c-erbB-2 was 26.1% (12/46) in the 46 cases of esophageal carcinoma, of which 4 cases being low expression and 8 cases mediumhigh expression. The positive expression rate of P-gp was 60.9% (28/46) in the 46 cases of esophageal carcinoma, of which 6 cases being low expression, 13 cases medium expression and 9 cases high expression. Comparing c-erbB-2 with P-gp expression in different lymph node metastasis statuses showed that there was significant difference (P〈0.01) between P-gp expressions with lymph node metastasis (31.09%±5.33%) and without lymph node metastasis (8.04%±3.03%) when c-erbB-2 expression was positive. Comparing c-erbB-2 with P-gp expression in different TNM stages of esophageal carcinoma showed that there was significant difference (P〈0.01) between P-gp expressions in HI Ⅳ stage (33.68%±5.51%)and in Ⅱ stage patients (9.30%±2.78%) when c-erbB-2 expression was positive. The tumor's size and differentiation degree were not related to c-erbB-2 and P-gp expression. Conclusion: The high level of P-gp expression was related to the positive expression of c-erbB-2 with the lymph node metastasis in clinical Ⅲ-Ⅳ stage patients of esophageal carcinoma, suggesting that the double positive might lead to a poor prognosis. However, when the c-erbB-2 expression was negative, the lymph node metastasis and clinical staging were not related to the P-gp expression in esophageal carcinoma patients.展开更多
Objective: To investigate the relationship between the expression of survivin and mutant p53, C-erbB-2 proteins in breast cancer to explore the possible molecular mechanisms. Methods: The expression of survivin, mut...Objective: To investigate the relationship between the expression of survivin and mutant p53, C-erbB-2 proteins in breast cancer to explore the possible molecular mechanisms. Methods: The expression of survivin, mutant p53, and C-erbB-2 was detected in 62 specimens of breast carcinoma by using streptavidin-peroxidase (SP) immunocytochemical assay. Results: Among the 62 cases of breast carcinoma, the positive rate of survivin was 67.7%; 35.5% of the tumors were positive for p53; and 37.1% for C-erbB-2 overexpression. Survivin expression was independent on patient's menopausal status, tumor histology, clinical stage, tumor size, lymph node metastasis, and estrogen receptor level. Although survivin expression was not correlated with p53 mutations, the positive expression of survivin was associated with C-erbB-2 overexpression (87.0% vs 56.4%, P〈0.05). Conclusion: The positive expression of survivin was independent on p53 mutation, but dependent on the overexpression of C-erbB-2. C-erbB-2 might up-regulate the expression of survivin.展开更多
The c-erbB-2 proto-oncogene encodes a 185kDa protein p!85, which belongs to epidermal growth factor receptor family. Amplification of this gene has been shown to correlate with poor clinical prognosis for certain canc...The c-erbB-2 proto-oncogene encodes a 185kDa protein p!85, which belongs to epidermal growth factor receptor family. Amplification of this gene has been shown to correlate with poor clinical prognosis for certain cancer patients. The monoclonal antibody A21 which directed against p185 specifically inhibits proliferation of tumor cells overexpressing p185, hence allows it to be a candidate for targeted therapy. In order to overcome several drawbacks of murine MAb, we cloned its VH and VL genes and constructed the single-chain Fv (scFv) through a peptide linker. The recombinant scFvA21 was expressed in Escherichia coli and purified by the affinity column. Subsequently it was characterized by ELISA, Western blot, cell immunohistochemistry and FACS. All these assays showed the binding activity to extracellular domain (ECD) of p!85. Based on those properties of scFvA21, we further constructed the scFv-Fc fusion molecule with a homodimer form and the recombinant product was expressed in mammalian cells. In a series of subsequent analysis this fusion protein showed identical antigen binding site and activity with the parent antibody. These anti-p185 engineered antibodies have promised to be further modified as a tumor targeting drugs, with a view of application in the diagnosis and treatment of human breast cancer.展开更多
AIM: We examined quantitative mRNA expression of growth factor receptors (c-erbB-1, c-erbB-2) and the anti-apoptosis gene survivin known to be regulated in pancreatic adenocarcinomas and compared the expression pat...AIM: We examined quantitative mRNA expression of growth factor receptors (c-erbB-1, c-erbB-2) and the anti-apoptosis gene survivin known to be regulated in pancreatic adenocarcinomas and compared the expression pattern with that in carcinomas of the papilla of Vater. METHODS: Quantitative real-time reverse transcriptase- PCR (QRT-PCR, Taqman^TM) was performed to analyze mRNA expression levels of c-erbB-1, c-erbB-2 and survivin in normal and corresponding tumor samples of 31 pancreatic adenocarcinomas and 8 cancers of the papilla of Vater. RESULTS: The overall median mRNA expression of survivin was significantly increased in both adenocarcinoma of the pancreas (P〈0.01) and papilla of Vater (P〈0.008) compared with uninvolved normal control tissue. In pancreatic cancer, expression of c-erbB-1 was significantly decreased compared with the normal pancreatic tissue (P〈0.03), whereas in the cancer of the papilla of Vater expression of c-erbB-2 was significantly downregulated (P〈0.05) compared with the paired normal samples. Gene expression was not associated with tumor stage, differentiation or prognosis. CONCLUSION: The common anti-apoptosis gene survivin is overexpressed both in the cancer of the papilla of Vater and pancreas. In contrast, the growth factor receptor genes c-erbB-1 and c-erbB-2 are differentially regulated in both tumor entities adding further evidence that pancreatic cancer is biologically different from the cancer of papilla of Vater.展开更多
基金This work was supported by a grant from Zhejiang Medical and Health Research Foundation (No. 2000A017).
文摘Objective: To investigate the correlation between c-erbB-2 and multidrug resistance (MDR) and its clinical significance, Methods: Immunohistochemistry stain was used to examine the expression of c-erbB-2 and flow cytometry was used to detect the expression of P-glycoprotein (P-gp) in samples from 46 patients with esophageal carcinoma. Results: The positive expression rate of c-erbB-2 was 26.1% (12/46) in the 46 cases of esophageal carcinoma, of which 4 cases being low expression and 8 cases mediumhigh expression. The positive expression rate of P-gp was 60.9% (28/46) in the 46 cases of esophageal carcinoma, of which 6 cases being low expression, 13 cases medium expression and 9 cases high expression. Comparing c-erbB-2 with P-gp expression in different lymph node metastasis statuses showed that there was significant difference (P〈0.01) between P-gp expressions with lymph node metastasis (31.09%±5.33%) and without lymph node metastasis (8.04%±3.03%) when c-erbB-2 expression was positive. Comparing c-erbB-2 with P-gp expression in different TNM stages of esophageal carcinoma showed that there was significant difference (P〈0.01) between P-gp expressions in HI Ⅳ stage (33.68%±5.51%)and in Ⅱ stage patients (9.30%±2.78%) when c-erbB-2 expression was positive. The tumor's size and differentiation degree were not related to c-erbB-2 and P-gp expression. Conclusion: The high level of P-gp expression was related to the positive expression of c-erbB-2 with the lymph node metastasis in clinical Ⅲ-Ⅳ stage patients of esophageal carcinoma, suggesting that the double positive might lead to a poor prognosis. However, when the c-erbB-2 expression was negative, the lymph node metastasis and clinical staging were not related to the P-gp expression in esophageal carcinoma patients.
文摘Objective: To investigate the relationship between the expression of survivin and mutant p53, C-erbB-2 proteins in breast cancer to explore the possible molecular mechanisms. Methods: The expression of survivin, mutant p53, and C-erbB-2 was detected in 62 specimens of breast carcinoma by using streptavidin-peroxidase (SP) immunocytochemical assay. Results: Among the 62 cases of breast carcinoma, the positive rate of survivin was 67.7%; 35.5% of the tumors were positive for p53; and 37.1% for C-erbB-2 overexpression. Survivin expression was independent on patient's menopausal status, tumor histology, clinical stage, tumor size, lymph node metastasis, and estrogen receptor level. Although survivin expression was not correlated with p53 mutations, the positive expression of survivin was associated with C-erbB-2 overexpression (87.0% vs 56.4%, P〈0.05). Conclusion: The positive expression of survivin was independent on p53 mutation, but dependent on the overexpression of C-erbB-2. C-erbB-2 might up-regulate the expression of survivin.
基金This work was supported by funds of Natural Science of Scientific Committee and Educational Committee of AN-HUI Province respectively, and Hi-tech Research and Development Program ("863" Program).
文摘The c-erbB-2 proto-oncogene encodes a 185kDa protein p!85, which belongs to epidermal growth factor receptor family. Amplification of this gene has been shown to correlate with poor clinical prognosis for certain cancer patients. The monoclonal antibody A21 which directed against p185 specifically inhibits proliferation of tumor cells overexpressing p185, hence allows it to be a candidate for targeted therapy. In order to overcome several drawbacks of murine MAb, we cloned its VH and VL genes and constructed the single-chain Fv (scFv) through a peptide linker. The recombinant scFvA21 was expressed in Escherichia coli and purified by the affinity column. Subsequently it was characterized by ELISA, Western blot, cell immunohistochemistry and FACS. All these assays showed the binding activity to extracellular domain (ECD) of p!85. Based on those properties of scFvA21, we further constructed the scFv-Fc fusion molecule with a homodimer form and the recombinant product was expressed in mammalian cells. In a series of subsequent analysis this fusion protein showed identical antigen binding site and activity with the parent antibody. These anti-p185 engineered antibodies have promised to be further modified as a tumor targeting drugs, with a view of application in the diagnosis and treatment of human breast cancer.
文摘AIM: We examined quantitative mRNA expression of growth factor receptors (c-erbB-1, c-erbB-2) and the anti-apoptosis gene survivin known to be regulated in pancreatic adenocarcinomas and compared the expression pattern with that in carcinomas of the papilla of Vater. METHODS: Quantitative real-time reverse transcriptase- PCR (QRT-PCR, Taqman^TM) was performed to analyze mRNA expression levels of c-erbB-1, c-erbB-2 and survivin in normal and corresponding tumor samples of 31 pancreatic adenocarcinomas and 8 cancers of the papilla of Vater. RESULTS: The overall median mRNA expression of survivin was significantly increased in both adenocarcinoma of the pancreas (P〈0.01) and papilla of Vater (P〈0.008) compared with uninvolved normal control tissue. In pancreatic cancer, expression of c-erbB-1 was significantly decreased compared with the normal pancreatic tissue (P〈0.03), whereas in the cancer of the papilla of Vater expression of c-erbB-2 was significantly downregulated (P〈0.05) compared with the paired normal samples. Gene expression was not associated with tumor stage, differentiation or prognosis. CONCLUSION: The common anti-apoptosis gene survivin is overexpressed both in the cancer of the papilla of Vater and pancreas. In contrast, the growth factor receptor genes c-erbB-1 and c-erbB-2 are differentially regulated in both tumor entities adding further evidence that pancreatic cancer is biologically different from the cancer of papilla of Vater.