Objective This study aimed to evaluate serum and nipple discharge levels of carcinoembryonic antigen(CEA) and cancer antigen 153(CA153) and tissue cyclooxygenase-2(COX-2) expression in breast cancer cases and associat...Objective This study aimed to evaluate serum and nipple discharge levels of carcinoembryonic antigen(CEA) and cancer antigen 153(CA153) and tissue cyclooxygenase-2(COX-2) expression in breast cancer cases and associations of these proteins with breast cancer metastasis.Methods The immunohistochemical Ultra Sensitive^(TM) S-P method was used to detect COX-2 expression in 77 cases of invasive breast carcinoma. Of these cases, 52 exhibited CEA and CA153 in both serum and nipple discharge(electrochemiluminescence method), and associations of these biomarkers with breast cancer prognosis were studied. Sixty cases of benign breast lesion were selected as a control group. Overall survival of breast carcinoma patients was evaluated. COX-2 expression was evaluated relative to clinicopathological features and CEA and CA153 levels, and its role in invasiveness was investigated.Results Among cases of invasive breast cancer, 72.7%(56/77) were COX-2 immunopositive, compared to 16.7% of benign lesions(χ2 = 66.745, P = 0.000) percentage of positive cells. COX-2 overexpression in breast cancer correlated positively with histological grade(II vs III; χ2 = 4.064, P = 0.043), lymph node metastasis(χ2 = 9.135, P = 0.003), and distant metastasis(χ2 = 8.021, P = 0.003). However, COX-2 expression did not correlate with age(≤ 50 vs 50 years) or tumor size(≤ 5 vs > 5 cm)(χ2 = 0.081, P = 0.776 and χ2 = 3.702, P = 0.054, respectively). Among breast cancer patients, COX-2 overexpression in tumors also correlated with shorter overall survival(P < 0.05). In brief, increased COX-2 expression correlates with worse prognosis and shorter overall survival. Malignant lesions were associated with significantly higher serum and nipple discharge levels of biomarkers, relative to benign lesions(P < 0.05). These biomarkers were present at significantly higher levels in nipple discharge than in serum(P < 0.05). Furthermore, significantly higher nipple discharge levels of CEA and CA153 were observed in COX-2-positive breast carcinoma patients, compared to COX-2-negative patients(P <0.05). Shorter overall survival in cancer patients group related to COX-2 overexpression in tumors(P < 0.05).Conclusion The study suggests that COX-2 overexpression correlates with poor clinicopathological parameters in breast cancers and might be an important biological marker of invasion and metastasis. The findings of the present study suggest that combined detection of COX-2 tissue expression and CEA and CA153 in serum and nipple discharge could facilitate clinical monitoring and diagnosis of metastasis in patients with breast cancer.展开更多
Background Gene therapy by adenovirus-mediated wild-type p53 gene transfer has been shown to inhibit lung cancer growth in vitro,in animal models,and in human clinical trials.The antitumor effect of selective cyclooxy...Background Gene therapy by adenovirus-mediated wild-type p53 gene transfer has been shown to inhibit lung cancer growth in vitro,in animal models,and in human clinical trials.The antitumor effect of selective cyclooxygenase(COX)-2 inhibitors has been demonstrated in preclinical studies.However,no information is available on the effects of p53 gene therapy combined with selective COX-2 inhibitor on COX-2 gene expression and growth inhibition of human lung cancer cells.Methods We evaluated the effects of recombinant adenovirus-p53(Ad-p53) gene therapy combined with selective COX-2 inhibitor on the proliferation,apoptosis,cell cycle arrest of human lung adenocarcinoma A549 cell line,and the effects of tumor suppressor exogenous wild type p53 on COX-2 gene expression.ResultsAd-p53 gene therapy combined with selective COX-2 inhibitor celecoxib shows significant synergistic inhibition effects on the growth of human lung adenocarcinoma A549 cell line. Exogenous p53 gene can suppress COX-2 gene expression.ConclusionsSignificant synergistic inhibition effects of A549 cell line by the combined Ad-p53 and selective COX-2 inhibitor celecoxib may be achieved by enhancement of growth inhibition,apoptosis induction and suppression of COX-2 gene expression.This study provides first evidence that the administration of p53 gene therapy in combination with COX-2 inhibitors might be a new clinical strategy for the treatment or prevention of NSCLC.展开更多
目的:研究蝎毒多肽提取物(peptide extract from scorpion venom,PESV)对雄激素非依赖性人前列腺癌细胞株DU-145COX-2和MMP-9表达的影响,进一步探讨其抗血管生成的分子机制,为抗前列腺癌骨转移提供有效的治疗手段。方法:采用免疫组只化...目的:研究蝎毒多肽提取物(peptide extract from scorpion venom,PESV)对雄激素非依赖性人前列腺癌细胞株DU-145COX-2和MMP-9表达的影响,进一步探讨其抗血管生成的分子机制,为抗前列腺癌骨转移提供有效的治疗手段。方法:采用免疫组只化学方法检测PESV对COX-2、MMP-9蛋白表达的影响,应用RT-PCR检测PESV对MMP-9在mRNA水平表达的影响。结果:蝎毒多肽提取物(40μg/mL)作用于前列腺癌细胞后,COX-2、MMP-9蛋白表达水平明显下调(P<0.05),进一步检测发现MMP-9在mRNA水平亦明显下降(P<0.05)。结论:蝎毒多肽提取物(PESV)通过抑制前列腺癌细胞血管生成因子COX-2的表达而发挥其抗血管生成作用,具有临床应用价值。展开更多
基金Supported by grants from the Medicine and Health Care Science and Technology Development Plan Projects Foundation of Shandong Province(No.2014WS0282,2014WSA11003)Application Technology Research and Development Project Foundation in Rizhao City(No.2014SZSH02)+1 种基金Science and technology innovation project of medical workers in Shandong Province(No.201515)the Scientific Research Projects of Jining Medical College(No.JY2013KJ051)
文摘Objective This study aimed to evaluate serum and nipple discharge levels of carcinoembryonic antigen(CEA) and cancer antigen 153(CA153) and tissue cyclooxygenase-2(COX-2) expression in breast cancer cases and associations of these proteins with breast cancer metastasis.Methods The immunohistochemical Ultra Sensitive^(TM) S-P method was used to detect COX-2 expression in 77 cases of invasive breast carcinoma. Of these cases, 52 exhibited CEA and CA153 in both serum and nipple discharge(electrochemiluminescence method), and associations of these biomarkers with breast cancer prognosis were studied. Sixty cases of benign breast lesion were selected as a control group. Overall survival of breast carcinoma patients was evaluated. COX-2 expression was evaluated relative to clinicopathological features and CEA and CA153 levels, and its role in invasiveness was investigated.Results Among cases of invasive breast cancer, 72.7%(56/77) were COX-2 immunopositive, compared to 16.7% of benign lesions(χ2 = 66.745, P = 0.000) percentage of positive cells. COX-2 overexpression in breast cancer correlated positively with histological grade(II vs III; χ2 = 4.064, P = 0.043), lymph node metastasis(χ2 = 9.135, P = 0.003), and distant metastasis(χ2 = 8.021, P = 0.003). However, COX-2 expression did not correlate with age(≤ 50 vs 50 years) or tumor size(≤ 5 vs > 5 cm)(χ2 = 0.081, P = 0.776 and χ2 = 3.702, P = 0.054, respectively). Among breast cancer patients, COX-2 overexpression in tumors also correlated with shorter overall survival(P < 0.05). In brief, increased COX-2 expression correlates with worse prognosis and shorter overall survival. Malignant lesions were associated with significantly higher serum and nipple discharge levels of biomarkers, relative to benign lesions(P < 0.05). These biomarkers were present at significantly higher levels in nipple discharge than in serum(P < 0.05). Furthermore, significantly higher nipple discharge levels of CEA and CA153 were observed in COX-2-positive breast carcinoma patients, compared to COX-2-negative patients(P <0.05). Shorter overall survival in cancer patients group related to COX-2 overexpression in tumors(P < 0.05).Conclusion The study suggests that COX-2 overexpression correlates with poor clinicopathological parameters in breast cancers and might be an important biological marker of invasion and metastasis. The findings of the present study suggest that combined detection of COX-2 tissue expression and CEA and CA153 in serum and nipple discharge could facilitate clinical monitoring and diagnosis of metastasis in patients with breast cancer.
文摘Background Gene therapy by adenovirus-mediated wild-type p53 gene transfer has been shown to inhibit lung cancer growth in vitro,in animal models,and in human clinical trials.The antitumor effect of selective cyclooxygenase(COX)-2 inhibitors has been demonstrated in preclinical studies.However,no information is available on the effects of p53 gene therapy combined with selective COX-2 inhibitor on COX-2 gene expression and growth inhibition of human lung cancer cells.Methods We evaluated the effects of recombinant adenovirus-p53(Ad-p53) gene therapy combined with selective COX-2 inhibitor on the proliferation,apoptosis,cell cycle arrest of human lung adenocarcinoma A549 cell line,and the effects of tumor suppressor exogenous wild type p53 on COX-2 gene expression.ResultsAd-p53 gene therapy combined with selective COX-2 inhibitor celecoxib shows significant synergistic inhibition effects on the growth of human lung adenocarcinoma A549 cell line. Exogenous p53 gene can suppress COX-2 gene expression.ConclusionsSignificant synergistic inhibition effects of A549 cell line by the combined Ad-p53 and selective COX-2 inhibitor celecoxib may be achieved by enhancement of growth inhibition,apoptosis induction and suppression of COX-2 gene expression.This study provides first evidence that the administration of p53 gene therapy in combination with COX-2 inhibitors might be a new clinical strategy for the treatment or prevention of NSCLC.
文摘目的:研究蝎毒多肽提取物(peptide extract from scorpion venom,PESV)对雄激素非依赖性人前列腺癌细胞株DU-145COX-2和MMP-9表达的影响,进一步探讨其抗血管生成的分子机制,为抗前列腺癌骨转移提供有效的治疗手段。方法:采用免疫组只化学方法检测PESV对COX-2、MMP-9蛋白表达的影响,应用RT-PCR检测PESV对MMP-9在mRNA水平表达的影响。结果:蝎毒多肽提取物(40μg/mL)作用于前列腺癌细胞后,COX-2、MMP-9蛋白表达水平明显下调(P<0.05),进一步检测发现MMP-9在mRNA水平亦明显下降(P<0.05)。结论:蝎毒多肽提取物(PESV)通过抑制前列腺癌细胞血管生成因子COX-2的表达而发挥其抗血管生成作用,具有临床应用价值。
