AIM: To explore the roles of microRNA-let7 c(miR-let7 c) and transforming growth factor-β2(TGF-β2) and cellular signaling during epithelial-to-mesenchymal transition(EMT) of retinal pigment epithelial cells. METHODS...AIM: To explore the roles of microRNA-let7 c(miR-let7 c) and transforming growth factor-β2(TGF-β2) and cellular signaling during epithelial-to-mesenchymal transition(EMT) of retinal pigment epithelial cells. METHODS: Retinal pigment epithelial(ARPE-19) cells were cultured with no serum for 12 h, and then with recombinant human TGF-β2 for different lengths of time. ARPE-19 cells were transfected with 1×106 TU/mL miR-let7 c mimcs(miR-let7 cM), miR-let7 c mimcs negative control(miR-let7cMNC) and miR-let7 c inhibitor(miR-let7 cI) using the transfection reagent. The expression of keratin-18, vimentin, N-cadherin, IKB alpha, p65 were detected by Western blot, quantitative polymerase chain reaction and immunofluorescence. RESULTS: The expression of miR-let7c was dramatically reduced and the nuclear factor-kappa B(NF-κB) signaling pathway was activated after induction by TGF-β2(P<0.05). In turn, overexpressed miR-let7 c significantly inhibited TGF-β2-induced EMT(P<0.05). However, miR-let7 c was unable to inhibit TGF-β2-induced EMT when the NF-κB signaling pathway was inhibited by BAY11-7082(P<0.01). CONCLUSION: The miR-let7 c regulates TGF-β2-induced EMT through the NF-κB signaling pathway in ARPE-19 cells.展开更多
3背景 ·转移性乳腺癌（metastatic breast cancer，MBC）病人的一线治疗中，此前的3个Ⅲ期临床试验（E2100、AVADO和RIBBON-1）已经证实，贝伐单抗联合多种化疗药物，都可以提高患者的无进展生存率（progression-free survival，PF...3背景 ·转移性乳腺癌（metastatic breast cancer，MBC）病人的一线治疗中，此前的3个Ⅲ期临床试验（E2100、AVADO和RIBBON-1）已经证实，贝伐单抗联合多种化疗药物，都可以提高患者的无进展生存率（progression-free survival，PFS）。展开更多
AIM:To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2(HER2)antibodies in whole-tissue sections and tissue microarrays(TMAs)of a series of gastric tumors.METHODS:We...AIM:To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2(HER2)antibodies in whole-tissue sections and tissue microarrays(TMAs)of a series of gastric tumors.METHODS:We present a comparative analysis of three anti-HER2 antibodies(HercepTest,4B5 and SP3)using TMA and whole-tissue sections prepared from the same paraffin blocks of 199 gastric adenocarcinomas operated upon between January 2004 and December2008 at a Brazilian cancer hospital.The data on the patients’age,sex,the anatomical location of the tumor and the Lauren’s histological classification were collected from clinical and pathological records.The immunohistochemical(IHC)results were examined by two pathologists and the cases were classified as positive(3+),equivocal(2+)and negative(0 or 1+),according to the criteria of the IHC scoring system of gastric cancer.TMAs and whole-tissue sections were evaluated separately and independently.All cases yielding discordant IHC results and/or scored as 2+were subjected to dual-color in situ hybridization in order to determine the final HER2 status.Besides determining the sensitivity and predictive value for HER2-positive status,we measured the accuracy of each antibody by calculating the area under the receiver operating characteristic(ROC)curve.The agreement between the results obtained using the TMAs and those obtained using the whole-tissue sections was assessed by means of Kappa coefficient.RESULTS:Intratumoral heterogeneity of HER2 expression was observed with all antibodies.HER2-positive expression(3+)in the whole-tissue sections was observed in 23 cases(11.6%)using the 4B5 antibody,in 18 cases(9.1%)using the SP3 antibody and in 10 cases(5.1%)using the HercepTest antibody.In the TMAs,11 positive cases(5.6%)were identified using SP3 antibody,9(4.6%)using the 4B5 antibody and 6(3%)using the HercepTest antibody.The sensitivity using whole-tissue sections and TMA,respectively,was 95.2%and 42.9%with 4B5,90.5%and 66.7%with SP3 and 47.6%and42.9%with HercepTest.The accuracy,calculated from the area under the ROC curve,using whole-tissue sections and TMA,respectively,was 0.91 and 0.79 by 4B5,0.86 and 0.80 by SP3 and 0.73 and 0.71 by HercepTest.The concordance of the results obtained using wholetissue sections and TMA was 97.4%(Kappa 0.75)using HercepTest,85.6%(Kappa 0.56)using SP3 and 84.1%(Kappa 0.38)using 4B5.CONCLUSION:The use of the 4B5 antibody on wholetissue sections was the most accurate IHC method for evaluating HER2 expression in gastric adenocarcinoma.展开更多
Objective： To investigate the clinical significance of COX-2 （Cyclooxygenase-2） expression in HCC （Primary hepatocellular carcinoma） and clarify whether COX-2 is correlated with hypoxia-inducible factor-1α （HI...Objective： To investigate the clinical significance of COX-2 （Cyclooxygenase-2） expression in HCC （Primary hepatocellular carcinoma） and clarify whether COX-2 is correlated with hypoxia-inducible factor-1α （HIF-1α） in the development of HCC. Methods： Tumor tissues were obtained from 53 patients with HCC. COX-2 and HIF-1α were determined by immunohistochemistry. All 53 patients were regularly followed up and the data were collected prospectively. Results： Immunostaining showed the expression of COX-2 （ n = 33, 62.3 % ） and HIF-1α （ n = 36, 67.9% ） in most tumor cells. The level of COX-2 was correlated with HIF-1α levels（ r = 0.4413, P 〈0.01 ）. There were significant correlation between clinicopathological features and higher tumor cytosolic COX-2 level was in the presence of multiple tumors （ P = 0.01）, venous invasion （ P = 0.03）, advanced tumor stage （ P = 0.01）, and well-different tumor grade （P =0.03）. High-tumor cytosolic COX-2 level was correlated with patient＇s worse prognosis （P = 0.0085）. Conclusion： Elevated tumor COX-2 level is correlated with elevated HIF-1α levels and invasiveness in HCC, suggesting COX-2 plays an important role in the progression of HCC, and may be an important therapeutic target in HCC.展开更多
Background： Current understanding of tumor biology suggests that breast cancer is a group of diseases with different intrinsic molecular subtypes. Anatomic staging system alone is insufficient to provide future outco...Background： Current understanding of tumor biology suggests that breast cancer is a group of diseases with different intrinsic molecular subtypes. Anatomic staging system alone is insufficient to provide future outcome information. The American Joint Committee on Cancer （AJCC） expert panel updated the 8th edition of the staging manual with prognostic stage groups by incorporating biomarkers into the anatomic stage groups. In this study, we retrospectively analyzed the data from our center in China using the anatomic and prognostic staging system based on the AJCC 8th edition staging manual. Methods： We reviewed the data from January 2008 to December 2014 for cases with Luminal B Human Epidermal Growth Factor Receptor 2 （HER2）-negative breast cancer in our center. All cases were restaged using the AJCC 8th edition anatomic and prognostic staging system. The Kaplan-Meier method and log-rank test were used to compare the survival differences between different subgroups. SPSS software version 19.0 （IBM Corp., Armonk, NY, USA） was used for the statistical analyses. Results： This study consisted of 796 patients with Luminal B HER-negative breast cancer. The 5-year disease-free survival （DFS） of 769 Stage I-III patients was 89.7%, and the 5-year overall survival （OS） of all 796 patients was 91.7%. Both 5-year DFS and 5-year OS were significantly different in the different anatomic and prognostic stage groups, There were 372 cases （46.7%） assigned to a different group. The prognostic Stage II and III patients restaged from anatomic Stage III had significant differences in 5-year DFS （v2 = 11.319; P = 0.001） and 5-year OS （χ2 = 5.225, P = 0.022）. In addition, cases restaged as prognostic Stage I, II, or III from the anatomic Stage II group had statistically significant differences in 5-year DFS （χ2 = 6.510, P = 0.039） but no significant differences in 5-year OS （χ2 = 5.087, P = 0.079）. However, the restaged prognostic Stage I and II cases from anatomic Stage I had no statistically significant differences in either 5-year DFS （χ2 = 0.440, P = 0.507） or 5-year OS （χ2= 1.530, P = 0.216）. Conclusions： The prognostic staging system proposed in the AJCC 8th edition refines the anatomic stage group in Luminal B HER2-negative breast cancer and will lead to a more personalized approach to breast cancer treatment.展开更多
基金Supported by National Natural Science Foundation of China(No.81600754)。
文摘AIM: To explore the roles of microRNA-let7 c(miR-let7 c) and transforming growth factor-β2(TGF-β2) and cellular signaling during epithelial-to-mesenchymal transition(EMT) of retinal pigment epithelial cells. METHODS: Retinal pigment epithelial(ARPE-19) cells were cultured with no serum for 12 h, and then with recombinant human TGF-β2 for different lengths of time. ARPE-19 cells were transfected with 1×106 TU/mL miR-let7 c mimcs(miR-let7 cM), miR-let7 c mimcs negative control(miR-let7cMNC) and miR-let7 c inhibitor(miR-let7 cI) using the transfection reagent. The expression of keratin-18, vimentin, N-cadherin, IKB alpha, p65 were detected by Western blot, quantitative polymerase chain reaction and immunofluorescence. RESULTS: The expression of miR-let7c was dramatically reduced and the nuclear factor-kappa B(NF-κB) signaling pathway was activated after induction by TGF-β2(P<0.05). In turn, overexpressed miR-let7 c significantly inhibited TGF-β2-induced EMT(P<0.05). However, miR-let7 c was unable to inhibit TGF-β2-induced EMT when the NF-κB signaling pathway was inhibited by BAY11-7082(P<0.01). CONCLUSION: The miR-let7 c regulates TGF-β2-induced EMT through the NF-κB signaling pathway in ARPE-19 cells.
文摘AIM:To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2(HER2)antibodies in whole-tissue sections and tissue microarrays(TMAs)of a series of gastric tumors.METHODS:We present a comparative analysis of three anti-HER2 antibodies(HercepTest,4B5 and SP3)using TMA and whole-tissue sections prepared from the same paraffin blocks of 199 gastric adenocarcinomas operated upon between January 2004 and December2008 at a Brazilian cancer hospital.The data on the patients’age,sex,the anatomical location of the tumor and the Lauren’s histological classification were collected from clinical and pathological records.The immunohistochemical(IHC)results were examined by two pathologists and the cases were classified as positive(3+),equivocal(2+)and negative(0 or 1+),according to the criteria of the IHC scoring system of gastric cancer.TMAs and whole-tissue sections were evaluated separately and independently.All cases yielding discordant IHC results and/or scored as 2+were subjected to dual-color in situ hybridization in order to determine the final HER2 status.Besides determining the sensitivity and predictive value for HER2-positive status,we measured the accuracy of each antibody by calculating the area under the receiver operating characteristic(ROC)curve.The agreement between the results obtained using the TMAs and those obtained using the whole-tissue sections was assessed by means of Kappa coefficient.RESULTS:Intratumoral heterogeneity of HER2 expression was observed with all antibodies.HER2-positive expression(3+)in the whole-tissue sections was observed in 23 cases(11.6%)using the 4B5 antibody,in 18 cases(9.1%)using the SP3 antibody and in 10 cases(5.1%)using the HercepTest antibody.In the TMAs,11 positive cases(5.6%)were identified using SP3 antibody,9(4.6%)using the 4B5 antibody and 6(3%)using the HercepTest antibody.The sensitivity using whole-tissue sections and TMA,respectively,was 95.2%and 42.9%with 4B5,90.5%and 66.7%with SP3 and 47.6%and42.9%with HercepTest.The accuracy,calculated from the area under the ROC curve,using whole-tissue sections and TMA,respectively,was 0.91 and 0.79 by 4B5,0.86 and 0.80 by SP3 and 0.73 and 0.71 by HercepTest.The concordance of the results obtained using wholetissue sections and TMA was 97.4%(Kappa 0.75)using HercepTest,85.6%(Kappa 0.56)using SP3 and 84.1%(Kappa 0.38)using 4B5.CONCLUSION:The use of the 4B5 antibody on wholetissue sections was the most accurate IHC method for evaluating HER2 expression in gastric adenocarcinoma.
文摘Objective： To investigate the clinical significance of COX-2 （Cyclooxygenase-2） expression in HCC （Primary hepatocellular carcinoma） and clarify whether COX-2 is correlated with hypoxia-inducible factor-1α （HIF-1α） in the development of HCC. Methods： Tumor tissues were obtained from 53 patients with HCC. COX-2 and HIF-1α were determined by immunohistochemistry. All 53 patients were regularly followed up and the data were collected prospectively. Results： Immunostaining showed the expression of COX-2 （ n = 33, 62.3 % ） and HIF-1α （ n = 36, 67.9% ） in most tumor cells. The level of COX-2 was correlated with HIF-1α levels（ r = 0.4413, P 〈0.01 ）. There were significant correlation between clinicopathological features and higher tumor cytosolic COX-2 level was in the presence of multiple tumors （ P = 0.01）, venous invasion （ P = 0.03）, advanced tumor stage （ P = 0.01）, and well-different tumor grade （P =0.03）. High-tumor cytosolic COX-2 level was correlated with patient＇s worse prognosis （P = 0.0085）. Conclusion： Elevated tumor COX-2 level is correlated with elevated HIF-1α levels and invasiveness in HCC, suggesting COX-2 plays an important role in the progression of HCC, and may be an important therapeutic target in HCC.
文摘Background： Current understanding of tumor biology suggests that breast cancer is a group of diseases with different intrinsic molecular subtypes. Anatomic staging system alone is insufficient to provide future outcome information. The American Joint Committee on Cancer （AJCC） expert panel updated the 8th edition of the staging manual with prognostic stage groups by incorporating biomarkers into the anatomic stage groups. In this study, we retrospectively analyzed the data from our center in China using the anatomic and prognostic staging system based on the AJCC 8th edition staging manual. Methods： We reviewed the data from January 2008 to December 2014 for cases with Luminal B Human Epidermal Growth Factor Receptor 2 （HER2）-negative breast cancer in our center. All cases were restaged using the AJCC 8th edition anatomic and prognostic staging system. The Kaplan-Meier method and log-rank test were used to compare the survival differences between different subgroups. SPSS software version 19.0 （IBM Corp., Armonk, NY, USA） was used for the statistical analyses. Results： This study consisted of 796 patients with Luminal B HER-negative breast cancer. The 5-year disease-free survival （DFS） of 769 Stage I-III patients was 89.7%, and the 5-year overall survival （OS） of all 796 patients was 91.7%. Both 5-year DFS and 5-year OS were significantly different in the different anatomic and prognostic stage groups, There were 372 cases （46.7%） assigned to a different group. The prognostic Stage II and III patients restaged from anatomic Stage III had significant differences in 5-year DFS （v2 = 11.319; P = 0.001） and 5-year OS （χ2 = 5.225, P = 0.022）. In addition, cases restaged as prognostic Stage I, II, or III from the anatomic Stage II group had statistically significant differences in 5-year DFS （χ2 = 6.510, P = 0.039） but no significant differences in 5-year OS （χ2 = 5.087, P = 0.079）. However, the restaged prognostic Stage I and II cases from anatomic Stage I had no statistically significant differences in either 5-year DFS （χ2 = 0.440, P = 0.507） or 5-year OS （χ2= 1.530, P = 0.216）. Conclusions： The prognostic staging system proposed in the AJCC 8th edition refines the anatomic stage group in Luminal B HER2-negative breast cancer and will lead to a more personalized approach to breast cancer treatment.
