【Abstract】Objective Stromal cell-derived factor-1(SDF-1, CXCL12) is a member of the CXC subfamily of chemokines which, through its cognate receptor (CXCR4), plays an important role in tumor invasion and metastasis. This study analyzed quantitatively the expression of SDF-1 and its relation with clinicopathologic feature and clinical outcome in human breast cancer.Methods Expression of SDF-1 mRNA in 8 breast cancer cell lines, an endothelial cell line HECV and a fibroblast cell MRC5 was studied by using RT-PCR. In addition, the expression of SDF-1 was investigated at both protein (immunohistochemistry) and mRNA(real-time PCR) levels in a group of human normal mammary(n=32) and tumour tissues(n=120). Results SDF-1 expression was identified in MRC5, MDA-MB435s, MDA-MB436, MCF7 cell lines, breast tumour and normal tissues. Significantly higher level of SDF-1 was seen in lymph node positive than in lymph node negative tumours (399.00±210.00 vs 0.89±0.47), P=0.048. The level of SDF-1 expression in patients who developed local recurrence or metastasis, or patients who died of breast cancer was higher than in patients who were disease free as well, (670.00±346.00 vs 0.83±0.35), P=0.01. It was most notable that level of SDF-1 was significantly correlated with over survival (P=0.01) and incidence free survival (P=0.035, by Cox proportion analysis).Conclusion SDF-1 is a factor that is expressed in both stromal cells and some breast cancer cells. Its level are correlated with lymph node involvement, prognosis and survival in patients with breast cancer. SDF-1 may therefore have a potential prognostic value in breast cancer.
目的 评价凋亡相关基因bcl-2、p53的表达与乳腺癌新辅助化学疗法（化疗）疗效的关系。 方法 计算机检索Cochrane、Pubmed、Embase、中国知网、万方、维普等数据库，2003年4月－2013年4月bcl-2、p53蛋白与乳腺癌新辅助化疗的病例对照研究，应用RevMan 4.2统计软件进行定量分析。 结果 共纳入15篇病例对照研究，bcl-2与乳腺癌新辅助化疗6篇，治疗有效279例，其中bcl-2表达阳性159例；治疗无效115例，其中bcl-2表达阳性57例。p53与乳腺癌新辅助化疗13篇，治疗有效679例，其中p53表达阳性249例；治疗无效341例，其中p53表达阳性195例。Meta分析结果显示，bcl-2表达的阳性率与乳腺癌新辅助化疗疗效无统计学意义[OR=1.40，95%CI（0.89，2.18），P=0.14]，而p53表达的阳性率与乳腺癌新辅助化疗疗效有统计学意义[OR=0.46，95%CI（0.26，0.80），P=0.007]。 结论 p53可以作为乳腺癌新辅助化疗疗效敏感性的一个指标，对乳腺癌新辅助化疗有提示作用。
ObjectiveTo study the apoptotic induction effect of Thapsigargin on estrogen receptor positive human breast cancer cell lines MCF7. MethodsCells were treated with Thapsigargin and 5FU in vitro. The rate of cell apoptosis and distribution of cell cycle were detected on flow cytometry. The cell viability was measured by MTT assay and ultrastructural changes in apoptotic cells were confirmed by transmission electron microscopy.ResultsThapsigargin could increase the rates both of cell apoptosis and growth supression of MCF7 cells induced by 5FU and alter the distribution of cell cycle. Under electron microscope, apoptotic bodies in MCF7 cells considerably increased.ConclusionThapsigargin apparently enhances the effect of apoptotic induction of 5FU on MCF7 cells, it is worthy of being further studied.
Objective To investigate the trend of breast cancer treatment and prognosis in 30 years. Methods Total 1 092 patients with breast cancer treated in the Peking Union Medical College Hospital between 1975 and 2006 were reviewed in six time phases for therapy, metastasis, and survival rate. Six time phases were 1975-1980 years, 1985-1986 years, 1990-1991 years, 1995-1996 years, 2000-2001 years and 2005-2006 years. Results Radical operation was the major treatment (68.9%， 91/132) of breast cancer in 1975-1980 and then became less popular until it was totally abandoned after 2001. The number of modified radical operation begun to rise from 1980 and reached its peak in 1995-1996 (94.9%， 146/154). The number of lumpectomy had been increasing since 2000, and that of chemotherapy had been rising since 1985-1986. But there was no apparent change of the percentage of radiotherapy treatment. In 1975-1980, only 0.8% （1/126） patients received endocrine therapy, but in 1990-1991, the ratio was 66.0% （33/50）. The metastasis and recurrence ratio was declining gradually in the 6 time phases (P＜0.05). The 5-year and 10-year disease free survival rates in the groups of 1990-1991, 1995-1996, 2000-2001, and 2005-2006 were apparently higher than those in two earlier groups of 1975-1980 and 1985-1986 (P＜0.05). Conclusion The conclusions of laboratory experiments and clinical trials on breast cancer are critical for improving prognosis.
ObjectiveTo detect the expression of Krüppel like factor 8 (KLF8) in breast cancer tissues and cells and to explore the clinical significance of KLF8.Methods① The Oncomine database was used to analyze the differential expression of KLF8 mRNA in the breast cancer tissues. The Kaplan-Meier Plotter database was used to analyze the relationship between KLF8 mRNA expression and prognosis (relapse free survival, overall survival, post-progression survival, and distant metastasis-free survival) of patients with breast cancer. ② The quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the KLF8 expression levels in the 16 clinical patients with breast cancer and 7 breast cancer cell lines (MDA-MB-231, MCF-12A, Hs-578T, MCF-7, BT-474, MDA-MB-453, ZR-75-30) and normal breast epithelial cell lines MCF-10A, and the immunofluorescence was used to further detect the localization of KLF8 expression in the 2 breast cancer cell lines with higher KLF8 expression level. ③ The immunohistochemistry was used to detect the expression of KLF8 protein in 135 cases of breast cancer tissue microarrays, and the relationships between KLF8 protein expression and clinicopathologic characteristics or overall survival were analyzed.Results① The Oncomine database showed that KLF8 mRNA expression in the breast cancer tissues was higher than that in the normal breast tissues (P<0.001). The median KLF8 mRNA expression level was taken as the cut-off point for high or low KLF8 expression. The results of Kaplan-Meier Plotter data analysis showed that the prognosis (relapse free survival, overall survival, postprogression survival, and distant metastasis-free survival) of patients with low KLF8 mRNA expression were better than those of patients with high KLF8 mRNA expression (P<0.05). ② The results of qRT-PCR and Western blot all showed that the KLF8 mRNA and protein expression levels in the breast cancer tissues were higher than those in the adjacent normal tissues (P=0.002, P<0.001). In addition, the Western blot results showed that the expression of KLF8 protein in the 7 breast cancer cell lines was higher than that in the normal breast epithelial cell lines MCF-10A respectively, and KLF8 protein mainly expressed in the cytoplasm of breast cancer cells and highly expressed in the nuclear of a few cells. ③ There were 63 cases of high KLF8 expression and 72 cases of low KLF8 expression by the immunohistochemical analysis of 135 patients with breast cancer tissue microarray (the H-score of the immunohistochemical test results was 75 as the cut-off point, H-score >75 was the high KLF8 expression and H-score ≤75 was the low KLF8 expression), the differences of statuses of estrogen receptor (ER) and progesterone receptor (PR) between the patient with high KLF8 expression and low KLF8 expression were significant (P<0.05). The Kaplan-Meier survival curve analysis showed that the prognosis of patients with high KLF8 expression was worse than that of patients with low KLF8 expression (P=0.002). The univariate analysis showed that the TNM stage, statuses of ER and PR, and KLF8 expression were related to the prognosis of patients with breast cancer (P<0.05), further multivariate Cox proportional hazards regression analysis indicated that the later stage of TNM and high KLF8 expression were the independent risk factors (P<0.05).ConclusionsThe results of this study suggest that KLF8 highly expresses in both breast cancer tissues and breast cancer cells, which is related to the statuses of ER and PR and prognosis of patients with breast cancer. KLF8 might be involved in the progression of breast cancer as an oncogenic gene, or it might provide a new direction for prognosis judgment and molecular targeted therapy of breast cancer.
【摘要】目的探讨早期乳腺癌保乳术中电子线放射治疗(intraoperative radiotherapy with electron,ELIOT)的可行性,评价术后并发症和术后乳房外观。方法2007年6月2009年6月期间,共有26例早期乳腺癌(肿瘤直径不超过25 cm)患者接受乳腺癌保乳手术及ELIOT,放疗剂量为21 Gy(分割照射58～60 Gy)。术后1年内第1、2、3个月,第6、9、12个月,1年后每6个月评估一次,主要评估切口愈合状况、并发症、乳房外观及肿瘤复发情况。结果术后切口愈合时间14～22 d,平均17 d。随访2～25个月,平均12个月,有2例切口脂肪液化,11例切口水肿伴引流液较多,全组无切口感染或血肿。随访期间内,未发现局部复发、远处转移或对侧乳腺癌。手术切口愈合后、术后6个月,1、2年对乳房外观评价结果:优秀者分别依次为577%、667%、727%及100%;好者分别依次为346%、222%、182%及0;一般者分别依次为77%、111%、91%及0。结论乳腺癌保乳术后行ELIOT 疗效确切、安全,对早期乳腺癌患者是一种方法简便,疗效确切、安全的选择。
ObjectiveTo evaluate the efficacy and toxicity of TEC and CEF regimen in preoperative chemotherapy for patients with breast cancer. MethodsA total of one hundred breast cancer patients undergoing preoperative chemotherapy were divided into TEC group (n=50) and CEF group (n=50) by the pairgroup method and received surgical therapy after three courses of chemotherapy. The efficacy and toxicity of preoperative chemotherapy of patients in two groups were analyzed. ResultsFour patients with stage ⅢB breast cancer quit from CEF group after two courses of treatment because of the worse satisfaction. Clinical complete remission (cCR) was 7 cases, clinic partial remission (cPR) was 34 cases, stable disease (SD) was 9 cases, therefore, the remission rate (RR) was 82.0% (41/50), and reduction rate of tumor was 64.0% (32/50) in TEC group. cCR was 2 cases, cPR was 32 cases, SD was 12 cases, thus the RR was 680% (34/50), and reduction rate of tumor was 40.0% (20/50) in CEF group. The clinical efficacy and reduction rate of tumor of patients in TEC group were significantly superior than those in CEF group (Plt;0.05). The negative conversion ratio of lymph nodes were 54.1% (20/37) and 57.1% (20/35) in TEC group and CEF group, which was not statistically different (Plt;0.05). The occurrence of hair loss and leukopenia of patients in TEC group were significantly higher than those in CEF group (Plt;0.05), while the differences in thrombocytopenia, low concentration of hemoglobin, nausea, vomiting, diarrhea, cardiac toxicity, and neurotoxicity were not significant (Pgt;0.05). ConclusionTEC regimen is better than CEF regimen in the efficacy and safety of neo-adjuant therapy for patients with breast cancer, and well tolerated.
ObjectiveTo test the expressions of human mammary gland globin (hMAM) mRNA in the peripheral blood of breast cancer and breast benign lesions patients, try to provide the theory basis for the choice of breast cancer molecular marker. MethodsPolymerase chain reaction (PCR) technology was used to detect the expressions of hMAM mRNA in peripheral blood of 78 cases of breast cancer patients, 15 cases of hyperplasia of mammary gland, and 15 cases of breast fibroadenoma. The relationship between the expressions of hMAM-mRNA in peripheral blood of breast cancer patients with patient's age, tumor size, pathological type, tumor stage, axillary lymph node metastasis, and the ER, PR and HER-2 status were analyzed. ResultsThe expressions of hMAM-mRNA in peripheral blood were not detected in breast hyperplasia and breast fibroadenoma patients, but the peripheral blood hMAM-mRNA expression rate in breast cancer patients was 48.72% (38/78), the difference was statistically significant (χ2=12.357, P=0.000). The expression of peripheral blood hMAM mRNA was not related to the patient's age, tumor size, pathological type, and ER, PR and HER-2 status (P > 0.05), but the expression of peripheral blood hMAM mRNA was related to the clinical staging of tumor (Z=-2.214, P=0.027) and lymph node metastasis status (Z=-2.754, P=0.006). ConclusionPeripheral blood hMAM-mRNA detected is a sign of breast cancer, further research is needed to confirm whether hMAM mRNA detection in peripheral blood correlates with poor prognosis of breast cancer patients.