【Abstract】ObjectiveTo investigate the effects of As2O3 on expression of NF-κB p65, survivin and caspase-3 in human breast infiltrating duct carcinoma xenograft model on nude mice. Methods A human breast infiltrating duct carcinoma model on nude mice was established and the nude mice were divided randomly into three groups: control group, DDP group and As2O3 group （1.5 and 3.0 mg/kg concentrations）. The expression of survivin mRNA was detected with the method of in situ hybridization and the expressions of NF-κB p65, survivin and caspase-3 protein were measured with immunohistochemistry. ResultsThe positive rates of NF-κB p65 and survivin expression were higher in the control group than those in the DDP group and the As2O3 groups, but that of caspase-3 was on the opposite way (P＜0.01). The positive rates of NF-κB p65 and survivin in As2O3 group were negatively related with the concentrations of As2O3 (P＜0.01), but that of caspase-3 was on the opposite way (P＜0.01). The expressions of NF-κB p65 and survivin protein were positively correlated with that of survivin mRNA, but any of them was negatively correlated with the expression of caspase-3 protein. ConclusionAs2O3 inhibites survivin probably by inhibiting the activity of NFκB p65 and subsequently activates caspase-3, which induces apoptosis of human breast infiltrating duct carcinoma cells and is in a dose-dependent manner.
Objective To investigate the effect of steroid receptor coactivator family in initiation, development, treatment and prognosis of breast cancer. Methods The literatures in recent years which have related to the effect of steroid receptor coactivators in breast cancer are reviewed. Results Steroid receptor coactivators are essential for several kinds of steroid hormones binding to steroid receptors, so they are important accessory factors that induce the initiation, development and recurrence of breast cancer, and predictive factors that estimate the prognosis of breast cancer. Conclusion Inhibition of the expression and signaling pathway of steroid receptor coactivators may be effective for breast cancer prevention and treatment.
【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.
Objective To study the effects of hepatocyte growth factor (HGF) and receptor c-met on the development of primary breast carcinoma, and the relationship between it and prognosis. Methods The study of HGF and c-met related to breast carcinoma was reviewed by history document and experimental study in recent years. Results HGF is a growth factor which has mitogenic, migrating, invasive and angiogenic activities in breast carcinoma cells. The carcinogenic mechanism of breast carcinoma was more clear with the discovery of the relationship between HGF and its receptor c-met. Conclusion The HGF/c-met plays an important role in the generation and progress of breast carcinoma. Studying the effects of HGF/cmet on breast carcinoma is significant in guiding clinical treatment.
Objective To study the expression and significance of CCR chemokine receptor-7 (CCR7) protein and vascular endothelial growth factor-D (VEGF-D) protein in the progression of breast cancer, including normal breast tissue, slight and moderate atypical hyperplasia, severe atypical hyperplasia and intraductal carcinoma in situ, as well as invasive ductal carcinoma. Methods Immunohistochemistry was used to detect the expression of CCR7 and VEGF-D protein in the nomal breast tissue (n=20), slight and moderate ductal atypical hyperplasia tissue (n=20), severe atypical hyperplasia and intraductal carcinoma in situ tissue, as well as invasive ductal breast carcinoma tissue (n=73). In addition, the D2-40 staining was also used to determine lymphatic microvessel density (LMVD). Meanwhile, the relationship between the expression of the two kinds of protein and clinicopathological factors/LMVD was analyzed by statistical analysis in breast cancer, and the correlation between expression of CCR7 protein and expression of VEGF-D protein was analyzed too. Results ①The positive rates of CCR7 protein (χ 2 =23.905，P<0.050) and VEGF-D protein (χ 2 =22.349，P<0.050) were gradually increased in the normal breast tissue group 〔CCR7 protein: 0 (0/20), VEGF-D protein: 5.0% (1/20)〕, slight and moderate atypical hyperplasia group 〔CCR7 protein: 5.0% (1/20), VEGF-D protein: 20.0% (4/20)〕, severe atypical hyperplasia and intraductal carcinoma in situ group 〔CCR7 protein: 30.0% (6/20), VEGF-D protein: 40.0% (8/20)〕, and invasive ductal carcinoma group 〔CCR7 protein: 47.9% (35/73), VEGF-D protein: 57.5% (42/73)〕. ②The LMVD value gradually increased in normal breast tissue group (2.00±1.02), slight and moderate atypical hyperplasia group (6.70± 3.48), severe atypical hyperplasia and intraductal carcinoma in situ group (9.01±2.13), as well as invasive ductal carcinoma group (16.32±4.07), there was significant difference between any 2 groups (P<0.050). ③The expressions of CCR7 protein and VEGF-D protein were correlated with clinical staging, histological grading, lymph node metastasis, and expression of human epidermal growth factor receptor-2 (HER-2) protein in patients with breast cancer (P<0.050), the higher positive rates of CCR7 and VEGF-D protein occurred in patients with higher histological grading, later clinical staging of Ⅲ+Ⅳ (compared with staging of Ⅰ+Ⅱ), lymph node metastasis (compared with no lymph node metastasis), and positive expression of HER-2 protein (compared with negative expression of HER-2 protein). The result indicated that LMVD value was related with expression of VEGF-D protein (r=0.623, P<0.010) in patients with breast cancer, but there was no correlation with expression of CCR7 protein (r=-0.303, P>0.050). Furthermore, there was weak positive correlation between expression of CCR7 protein and expression of VEGF-D protein in breast cancer (r=0.112, P<0.050). Conclusion The results strongly suggest that the expression levels of the VEGF-D protein and CCR7 protein indicate the potential of translation some extent, and they play an important role in the progression of breast cancer.
Objective To investigate expression of p16 protein in breast cancer and its clinical significance. Methods Using immunohistochemical techniques (LSAB) the expression of p16 protein in 107 breast carcinomas was examined. Results The positive rate of p16 protein expression was 40.19% (43/107). The p16 protein over expression of the cases surviving ≤5 years and surviving ≥10 years were 8.00% and 75.68% respectively. Conclusion Expression of p16 protein might play an important role in the prognosis of breast cancer.
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 evaluate the effectiveness of exercise and rehabilitation program in improving shoulder function and quality of life for breast cancer patients after mastectomy. Method We searched the Cochrane Database of Systematic Reviews, JBI Database of Systematic Reviews, MEDLINE (1966 to 2008), EMbase (1989 to 2007), CINAHL (Cumulative Index to Nursing and Allied Health literature), CBMdisc (1978 to 2008), and CNKI (1994 to 2008) to collect randomized controlled trials (RCTs). The quality of RCTs was critically appraised and data were extracted by 3 reviewers independently. Meta-analyses were conducted for the eligible RCTs. Result Nineteen RCTs were included. Stepwise upper extremity exercise and body exercise were reported in the rehabilitation program. Nine studies indicated that the rehabilitation program significantly improved the shoulder function of breast cancer patients after mastectomy. Four studies demonstrated its effect on cardiopulmonary function and body endurance. Six RCTs proved the effect of rehabilitation program on health-related quality of life and fatigue alleviation. Conclusion Rehabilitation program consisting of stepwise upper extremity exercise and full-body exercise is effective in improving the shoulder function and enhancing the quality of life of breast cancer patients after mastectomy. It also has a positive effect in reducing fatigue for those undergoing chemotherapy or radiotherapy.
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.
Objective To review the recent studies on the multidrug resistance of breast cancer. Methods The literatures of recent years on the studies of multidrug resistance, multidrug resistance protein and breast cancer resistance protein were reviewed. Results Multidrug resistance resulted from multiple factors. How to identify the sensibility of chemotherapy drugs and select individual therapeutic regime early were important to improve the survival rate and life quality of breast cancer patients. Conclusion These studies on multidrug resistance of breast cancer are helpful to predicting the effect and outcome of chemotherapy and overcoming the barrier of drug resistance.