【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.
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.
The authors studied retrospectively clinical data of seventy cases with breast cancer during pregnancy and lactation.They were treated and diagnosed by operation and pathology.Primary factors influencing prognosis were analyzed.It was demonstrated that 5year survival rate of the patients were significantly influenced by clinical stage , month of pregnancy and lactation, time of symptoms, type of operation, type of pathology, histological grade of malignancy, recurrence and metastasis, and estrogen receptor status (Ｐ＜0.05).Age and termination of pregnancy had no beneficial effect on survival (Ｐ＞0.05).The prognosis of pregnant and lactating breast cancer was poorer than ordinary breast cancer.Their 5year survival rate were 55.7% and 74.3%, respectively. After they were matched for stage and for age, no difference in survival was found.Early diagnosis and radical operation combined with radiotherapy, chemotherapy and hormonal therapy have better prognosis.The method can shorten time of treatment and improve survival rate.Termination of pregnancy has not been shown to improve survival and shall not be advised routinely.Future pregnancy may be detrimental and shall be discouraged.
Objective To determine the value of 99m Tc-MIBI scintimmmography in diagnosing primary breast cancer and axillary lymph node metastases.Methods Independent, prospective, blinded studies were selected from the Cochrane Library, MEDLINE, Springer, Elsevier and China National Knowledge Infrastructure, Sensitivity, specificity, and accuracy of scintimammography were estimated by comparison with the results of biopsy. Subsequently, the characteristics of included articles such as sensitivity, specificity of 99m
ObjectiveTo investigate the regulatory mechanism of thioredoxin binding protein (TXNIP)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) pathway in the occurrence and development of breast cancer.MethodsThe resected 15 cases of breast cancer tissues and their adjacent tissues in our hospital from September 2019 to June 2020 were selected, and the immunohistochemistry was used to detect the expression levels of TXNIP and NLRP3 in breast cancer and its adjacent tissues. Three kinds of breast cancer cell lines (MDA-MB231, MCF-7 and SKBR3) and normal breast epithelial cell line (HMEC) were collected. Western blot was used to detect the relative expression levels of TXNIP and NLRP3 in three kinds of breast cancer cell lines and HMEC cell line. MDA-MB231 cancer cells were divided into blank control group (normal culture without any treatment), TXNIP overexpression group (Ad-TXNIP group, transfected with adenovirus vector carrying TXNIP overexpression sequence), Ad-TXNIP negative control group (Ad-eGFP1 group, transfected of empty adenovirus vector without TXNIP overexpression sequence), NLRP3 overexpression group (Ad-NLRP3 group, transfected with adenovirus vector containing NLRP3 overexpression sequence), TXNIP and NLRP3 overexpression co-transfection group (Ad-TXNIP+Ad-NLRP3 group, co-transfection of adenovirus vector carrying TXNIP and NLRP3 overexpression sequence), TXNIP overexpression and Ad-NLRP3 negative control (Ad-eGFP2) co-transfection group (Ad-TXNIP+Ad-eGFP2 group,co-transfection of adenovirus vector carrying TXNIP overexpression sequence and empty adenovirus without NLRP3 overexpression sequence). After 24 hours of transfection and culture, CCK-8 method was used to detect the MDA-MB231 cells proliferation. Transwell chamber method was used to detect MDA-MB231 cells migration and invasion. Nude mice tumorigenicity test was used to detect the tumorigenicity of the MDA-MB231 cells in vivo. Western blot was used to detect the expressions of TXNIP, NLRP3, proliferation marker protein (Ki-67), caspase-1, vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-18 and caspase-1 precursor protein (pro-caspase-1) in the MDA-MB231 cells.ResultsCompared with the adjacent tissues, the relative expression level of TXNIP decreased (P<0.05) and the relative expression level of NLRP3 increased (P<0.05) in breast cancer tissues. Compared with normal breast epithelial cell line (HMEC cell line), the relative expression levels of TXNIP in MDA-MB231, MCF-7 and SKBR3 breast cancer cell lines were decreased (P<0.05), and the relative expression levels of NLRP3 were increased (P<0.05). Compared with the blank control group, the relative expression levels of TXNIP, NLRP3, IL-1β, IL-18, pro-caspase-1 and caspase-1 were increased (P<0.05), the relative expression levels of Ki-67 and VEGF, the proliferation activity, invasion and migration ability of MDA-MB231 cells and tumor weight were decreased (P<0.05) in the Ad-TXNIP group and the Ad-NLRP3 group. Compared with the Ad-TXNIP group and the Ad-NLRP3 group, the relative expression levels of TXNIP, NLRP3, IL-1β, IL-18, pro-caspase-1 and caspase-1 were further increased (P<0.05), the relative expression levels of Ki-67 and VEGF, the proliferation activity, invasion and migration ability of MDA-MB231 cells and tumor weight were further decreased (P<0.05) in the Ad-TXNIP+Ad-NLRP3 group.ConclusionsIn breast cancer tissues and breast cancer cell lines, TXNIP is low expression and NLRP3 is high expression. They can interact with each other to promote pyroptosis and inhibit the proliferation, invasion and migration of breast cancer cells.
ObjectiveTo review the progress of treatment and prevention of breast cancer related lymphedema. MethodsThe recent literature concerning treatment and prevention of breast cancer related lymphedema was extensively consulted and reviewed. ResultsThe treatment of lymphedema is now based on complete decongestive therapy, supplemented with medicine and surgery. Those procedures have been proved to be safe and effective. Sentinel lymph node biopsy, axillary reverse mapping, and lymphaticovenous anastomoses have been used to decrease the incidence of lymphedema. They show promising effectiveness in short term, but the long-term effectiveness needs further tests. ConclusionIn clinical practice, many treatment methods are used to decrease lymphedema, and lymphedema prevention is playing an increasingly important role. Lymphaticovenous anastomoses shows a promising effectiveness in reducing lymphedema.