Objective: To analyze the role and influence of the GINS4 gene in breast cancer progression and to explore its expression in triple-negative and non-triple-negative breast cancer cell lines. Methods: Single-gene analy...Objective: To analyze the role and influence of the GINS4 gene in breast cancer progression and to explore its expression in triple-negative and non-triple-negative breast cancer cell lines. Methods: Single-gene analysis of GINS4 was performed by breast cancer RNA transcriptome data from The Cancer Genome Atlas (TCGA). Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression of GINS4 in triple-negative and non-triple-negative breast cancer cell lines. The knockdown effects of GINS4 in MDA-MB-231 and MCF-7 cell lines on the proliferation and invasion of breast cancer cells were examined by cell counting kit 8 (CCK8) and Transwell assays. Results: Bioinformatics analysis showed that the expression of GINS4 in breast cancer was significantly higher than that in normal breast tissues (P > 0.05). At the same time, cell experiments confirmed that GINS4 was highly expressed in human breast cancer cell lines with normal breast cells as reference and in MDA-MB-231 and MCF-7 cell lines as reference, where the ability of proliferation and invasion of MDA-MB-231 and MCF-7 cells decreased after GINS4 knockdown. Conclusion: GINS4 is a gene associated with breast cancer malignancy, which can act as a novel tumor marker and has the potential as a new therapeutic target for breast cancer.展开更多
The development of accessory breast tissue,which is found anywhere along the milk line,is attributed to the failure of milk line remnants to regress during embryogenesis.Primary tumors may arise from any ectopic breas...The development of accessory breast tissue,which is found anywhere along the milk line,is attributed to the failure of milk line remnants to regress during embryogenesis.Primary tumors may arise from any ectopic breast tissue.Accessory breast cancer occurring concurrently with primary invasive breast cancer is extremely rare.Two such cases were reported in this article.One was a 43-year-old Chinese female who exhibited bilateral breast cancer(invasive ductal carcinoma,not otherwise specified,IDC-NOS) and an accessory breast carcinoma(IDC-NOS) incidentally identified in her left axilla.The ectopic breast tissue in her right axilla presented with adenosis.The patient was surgically treated,followed by postoperative docetaxel epirubicin(TE) chemotherapy.The second case was a 53-year-old Chinese female with bilateral breast cancer(apocrine carcinoma) accompanied by an accessory breast carcinoma(IDC-NOS) in her right axilla that was also incidentally identified.The patient was surgically treated after three doses of cyclophosphamide epirubicin docetaxel(CET) neoadjuvant chemotherapy,followed by adjuvant chemotherapy of the same regimen.展开更多
Objectives: The invasive breast cancer is divided into four clinical subtypes: Luminal A-like, Luminal B-like, HER-2 positive, and triple-negative according to the expression status of estrogen receptor (ER), progeste...Objectives: The invasive breast cancer is divided into four clinical subtypes: Luminal A-like, Luminal B-like, HER-2 positive, and triple-negative according to the expression status of estrogen receptor (ER), progesterone receptor(PR), human epidermal growth factor receptor-2 (HER-2) and Ki-67. The prognosis and treatment strategy vary with subtypes. The current studies have reported the relation between lymphatic vessel invasion (LVI) and the expression status of ER, PR, HER-2, Ki-67 in invasive breast cancer, but the results were debatable. So the meta-analysis was conducted to confirm the relation between LVI and the four factors. Methods: Literature was searched by entering the terms: breast AND (neoplasm OR cancer OR carcinoma) AND (lymphovascular OR “lymph vessel” OR “lymphatic vessel” invasion OR carcinoma embolus) AND (ER OR estrogen receptor OR PR OR progesterone receptor OR HER-2 OR human epidermal growth factor receptor-2 OR Ki-67 OR clinicopathological) in Pubmed. The merged odds ratio (OR) and 95% confidence interval (CI) were estimated using fixed-effect model. Review Manager 5.2 was used to analysis the relation between LVI and the expression status of ER, PR, HER-2, Ki-67 in invasive breast cancer respectively. The fail-safe number was used to estimate publication bias. Results: The analysis included 5 studies, LVI positive rate was significant lower in ER positive, PR positive, HER-2 negative, low Ki-67 expression group statistically. The OR and 95% CI were 0.6(0.44 - 0.81), 0.64(0.43 - 0.95), 1.52(1.03 - 2.24), 5.29(1.53 - 18.35) respectively.Conclusions:?LVI was significantly correlated with the expression status of ER, PR, HER-2 and Ki-67 in invasive breast cancer. Furthermore, LVI was consistent with poor prognostic expression status of the four factors.展开更多
Objective: To study the correlation of MRI apparent diffusion coefficient (ADC value) of invasive breast cancer with tumor tissue growth and angiogenesis. Methods: Patients with breast mass who were treated in Wuhan N...Objective: To study the correlation of MRI apparent diffusion coefficient (ADC value) of invasive breast cancer with tumor tissue growth and angiogenesis. Methods: Patients with breast mass who were treated in Wuhan No. 6 Hospital between March 2014 and May 2017 were selected as the research subjects and divided into group A with invasive ductal carcinoma, group B with intraductal carcinoma and group C with benign lesion according to the biopsy results, magnetic resonance diffusion-weighted imaging was conducted to determine ADC values, and biopsy tissue was taken to determine the expression of proliferation genes and angiogenesis genes. Results: USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in lesions of group A and group B were significantly higher than those of group C while ADC value as well as ALEX1 and Bax protein expression levels were significantly lower than those of group C;USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in lesions of group A were significantly higher than those of group B while ADC value as well as ALEX1 and Bax protein expression levels was significantly lower than those of group B;USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in invasive breast cancer tissue with high ADC value were significantly lower than those in invasive breast cancer tissue with low ADC value while ALEX1 and Bax protein expression levels were significantly higher than those in invasive breast cancer tissue with low ADC value. Conclusion: The decrease of ADC value of invasive breast cancer is closely related to cancer cell proliferation and angiogenesis.展开更多
Circular RNA(circRNA),as a newly discovered non-coding RNA with important regulatory potential,is closely related to the occurrence and progression of various tumors.This study aimed to investigate has_circ_0000069 ex...Circular RNA(circRNA),as a newly discovered non-coding RNA with important regulatory potential,is closely related to the occurrence and progression of various tumors.This study aimed to investigate has_circ_0000069 expression in breast cancer and its influence on cellular activities.Using real-time quantitative polymerase chain reaction,has_circ_0000069 levels were measured in 137 pairs of tissue specimens,as well as cancer cell lines.The cellular activities of cell lines were determined by cell counting kit-8(CCK-8)and Transwell assays.The potential targeting miRNAs were predicted and verified using an online database and dual-luciferase reporter assay.Has_circ_0000069 was highly expressed in breast cancer tissues and cells.The expression of has_circ_0000069 was associated with the five-year overall survival of patients.After silencing has_circ_0000069 in breast cancer cells,its expression reduced,and the ability of cell proliferation,migration,and invasion decreased.MiR-432 was verified as a targeting miRNA of has_circ_0000069.Has_circ_0000069 expression increased in breast cancer and was negatively related to patient’s prognosis.Has_circ_0000069 may facilitate breast cancer tumor progression by sponging miR-432.These findings revealed that has_circ_0000069 may be a biomarker for predicting prognosis and a therapeutic target for treating patients with breast cancer.展开更多
Objective: To study the regulatory effects of miR-21 on breast cancer cell line proliferation and invasion as well as the downstream target genes. Methods: Breast cancer cell lines MCF-7 were cultured and transfected ...Objective: To study the regulatory effects of miR-21 on breast cancer cell line proliferation and invasion as well as the downstream target genes. Methods: Breast cancer cell lines MCF-7 were cultured and transfected with miR-21 mimics and the corresponding negative control mimics(NC mimics), and then MTS kits were used to detect cell viability. Transwell experiment was used to detect cell invasion ability, and fluorescence quantitative PCR was used to detect the expression of proliferation and invasion-related genes in cells. Results: 24 h after transfection of miR-21 mimics and NC mimics, cell OD value and the number of invasive cells of miR-21 group were significantly higher than those of NC group, and m RNA contents of PDCD-4, Fas L, PTEN, Rho B, Maspin, TIMP3 and RECK in cells were significantly lower than those of NC group. Conclusion: miR-21 can promote the proliferation and invasion of breast cancer cell lines, and its downstream target genes include PDCD-4, Fas L, PTEN, Rho B, Maspin, TIMP3 and RECK.展开更多
To characterize AXL receptor tyrosine kinase (AXL) expression in relationship to tumor protein P53 (TP53 gene, p53 protein) and its role in tumor invasion and response to therapy.METHODSWe used 14 cell lines, includin...To characterize AXL receptor tyrosine kinase (AXL) expression in relationship to tumor protein P53 (TP53 gene, p53 protein) and its role in tumor invasion and response to therapy.METHODSWe used 14 cell lines, including 3 isogenic pairs carrying mutant/knockout p53, to gain insight into the relationship between AXL and TP53. These included HCT116, HCT116.p53 mutant, RKO, and RKO.p53<sup>-/-</sup> lines (all from colon cancers) as well as breast cancer cell lines MCF7 and 1001 (MCF7-p53 mutant clone). HeLa cell line was used as a positive control for epithelial to mesenchymal transition (EMT). AXL expression was determined by Western blotting using rabbit monoclonal antibody clone C89E7. AXL siRNA silencing was performed and followed by collagen invasion assay. Cell viability analysis using the sulforhodamine B assay and the invasion assay were performed after exposure to chemotherapeutic agents (doxorubicin for breast cancer cells; 5FU or irinotecan for colon cancer cells).RESULTSWe showed that the introduction of p53 mutations or knockout increased expression levels of AXL in isogenic cells compared to the matching p53 wild-type parental cells. Overall, we found a trend for correlation between the potential EMT candidate AXL, p53 alterations, and EMT markers in colorectal and breast cancers. The expression of AXL in RKO cells, a rare colon cancer cell line with inactive Wnt signaling, suggests that the AXL oncogene might provide an alternative genetic pathway for colorectal carcinogenesis in the absence of Wnt signaling activation and TP53 mutation. AXL silencing in the TP53 mutant isogenic cell lines 1001, HCT116.p53 mutant and RKO.P53<sup>-/-</sup> was > 95% efficient and the silenced cells were less invasive compared to the parental TP53 wild-type cells. AXL silencing showed a subtle trend to restore colon cancer cell sensitivity to 5FU or irinotecan. Importantly, AXL expressing cells developed more invasive potential after exposure to chemotherapy compared to the AXL-silenced cells.CONCLUSIONAXL is influenced by p53 status and could cause the emergence of aggressive clones after exposure to chemotherapy. These findings could have applications in cancer management.展开更多
Objective: The aim of this study was to investigate the effects of plumbagin (PL), a naphthoquinone derived from the medicinal plant plumbago zeylanica, on the invasion and migration of human breast cancer cells. M...Objective: The aim of this study was to investigate the effects of plumbagin (PL), a naphthoquinone derived from the medicinal plant plumbago zeylanica, on the invasion and migration of human breast cancer cells. Methods: Human breast cancer MDA-MB-231SArfp cells were treated with different concentrations of plum- bagin for 24 h. The effects of plumbagin on the migration and invasion were observed by a transwell method. The expressions of IL-1α, IL-1β, IL-6, IL-8, TGF-β, TNFα, MMP-2 and MMP-9 mRNA in MDA-MB-231SArfp cells were detected using Real-Time PCR. MDA-MB-231SArfp cells were treated with plumbagin at different concentrations for 45 minutes. The activation of STAT3 was detected by western blot. Following this analysis, STAT3 in MDA-MB-231SArfp cells was knocked out using specific siRNA, mRNA levels of IL-1α, TGF-β, MMP-2 and MMP-9 were then detected. Consequently, MDA-MB-231SArfp cells were injected intracardially into BALB/c nude mice to construct a breast cancer bone metastatic model. The mice were injected intra- peritoneally with plumbagin. Non-invasive in vivo monitoring, X-ray imaging and histological staining were performed to investigate the effects of plumbagin on the invasion and migration of breast cancer cells in vivo. Results: The in vitro results showed that plumbagin could suppress the migration and invasion of breast cancer cells and down-regulate mRNA expressions of IL-1α TGF-β, MMP-2 and MMP-9. Western blotting demonstrated that plumbagin inhibited the activation of STAT3 signaling in MDA-MB-231SArfp cells. The inactivation of STAT3 was found to have an inhibitory effect on the expressions of IL-1α, TGF-β, MMP-2 and MMP-9. In vivo studies showed that plumbagin inhibited the metastasis of breast cancer cells and decreased osteolytic bone metastases, as well as the secretion of MMP-2 and MMP-9 by tumor cells at metastatic lesions. Conclusions: Plumbagin can suppress the invasion and migration of breast cancer cells via the inhibition of STAT3 signaling and by downregulation of IL-1α, TGF-β, MMP-2 and MMP-9.展开更多
Objective:To investigate the relationship between CYPIA1 genetic polymorphisms and the invasion and metastasis of breast cancer.Methods:The CYP1A1 gene polymorphism(an T-C transversion at nucleotide position 3801)was ...Objective:To investigate the relationship between CYPIA1 genetic polymorphisms and the invasion and metastasis of breast cancer.Methods:The CYP1A1 gene polymorphism(an T-C transversion at nucleotide position 3801)was detected by the polymerase chain reaction and restriction fragment length polymorphism in 80 cases with breast cancer and 60 samples of normal breast tissue.The difference in genotypic distribution frequency between the groups,the correlation between the genotypes and the factors related to prognosis were analyzed.Results:The incidence of homozygous and variant genotypes had no difference between the breast cancer group and controls group(P=0.746).The proportion of variant genotype increased as clinical stage(P=0.006)advanced,as well as with increased numbers of lymph node metastases(P=0.010).Conclusions:In patients with breast cancer there is a correlation between the CYP1A1 CC allele and some factors indicating poor prognosis,including more lymph node metastases as well as a more advanced clinical stage.展开更多
Breast cancer,particularly Invasive Ductal Carcinoma(IDC),is a primary global health concern predominantly affecting women.Early and precise diagnosis is crucial for effective treatment planning.Several AI-based tech-...Breast cancer,particularly Invasive Ductal Carcinoma(IDC),is a primary global health concern predominantly affecting women.Early and precise diagnosis is crucial for effective treatment planning.Several AI-based tech-niques for IDC-level classification have been proposed in recent years.Processing speed,memory size,and accuracy can still be improved for better performance.Our study presents ECAM,an Enhanced Channel-Wise Attention Mechanism,using deep learning to analyze histopathological images of Breast Invasive Ductal Carcinoma(BIDC).The main objectives of our study are to enhance computational efficiency using a Separable CNN architecture,improve data representation through hierarchical feature aggregation,and increase accuracy and interpretability with channel-wise attention mechanisms.Utilizing publicly available datasets,DataBioX IDC and the BreakHis,we benchmarked the proposed ECAM model against existing state-of-the-art models:DenseNet121,VGG16,and AlexNet.In the IDC dataset,the model based on AlexNet achieved an accuracy rate of 86.81%and an F1 score of 86.94%.On the other hand,DenseNet121 outperformed with an accuracy of 95.60%and an F1 score of 95.75%.Meanwhile,the VGG16 model achieved an accuracy rate of 91.20%and an F1 score of 90%.Our proposed ECAM model outperformed the state-of-the-art,achieving an impressive F1 score of 96.65%and an accuracy rate of 96.70%.The BreakHis dataset,the AlexNet-based model,achieved an accuracy rate of 90.82%and an F1 score of 90.77%.DenseNet121 achieved a higher accuracy rate of 92.66%with an F1 score of 92.72%,while the VGG16 model achieved an accuracy of 92.60%and an F1 score of 91.31%.The proposed ECAM model again outperformed,achieving an F1 score of 96.37%and an accuracy rate of 96.33%.Our model is a significant advancement in breast cancer diagnosis,with high accuracy and potential as an automated grading,especially for IDC.展开更多
Low-grade invasive ductal carcinoma is almost diploid, and has frequent losses of chromosome 16q, which is shared by other precancerous lesions of the mammary gland such as flat epithelial atypia (FEA), atypical duc...Low-grade invasive ductal carcinoma is almost diploid, and has frequent losses of chromosome 16q, which is shared by other precancerous lesions of the mammary gland such as flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), and lownuclear grade ductal carcinoma in situ (DCIS). The genetic alterations accumulate in a stepwise fashion as the precancerous lesions progress to invasve ductal carcinoma. This supports the linear progression model of breast cancer from FEA, through ADH, to low- nuclear grade DCIS as non-obligate early events in low-grade IDC evolution. In contrast, high-grade carcinoma tends to aneuploidy with complex genetic alterations--most importantly, frequent gains at chromosome 16q. Frequent losses at chromosome 16q in low-grade IDC and gains in the same arm of the same chromosome in high-grade IDC imply that these lesions are two end outcomes of different disease processes and that they do not lie in the same continuum of a process. Therefore, low-grade and high-grade IDC are two distinct diseases with a divergent route of progression.展开更多
Objective: To explore the effects of Janus activated kinase (JAK) inhibitor AG490 on the phosphorylation of extracellular signal regulated protein kinase (ERK) in human breast cancer cells MDA-MB-231 and the role...Objective: To explore the effects of Janus activated kinase (JAK) inhibitor AG490 on the phosphorylation of extracellular signal regulated protein kinase (ERK) in human breast cancer cells MDA-MB-231 and the roles of JAK in the invasion and metastasis of the human breast cancer cells through ERK signaling transduction pathways. Methods: MDA-MB-231 cells were treated with 20 μmol/L, 40 μmol/L, 80 μmol/L Janus kinase inhibitor AG490 for 24, 48 and 72 h. Proliferation and adhesion of MDA-MB-231 cells to matrigel were measured with MTT assay. When treated with 40 μmol/L AG490 for 24 h, the expressions of P-ERK and MMP-9 of cells were detected by Western-blot and invasion and metastasis of MDA-MB-231 cells were evaluated with transwell chamber. Results: After being treated with 20 μmol/L, 40 μ/L, 80 μmol/L AG490 for 24, 48 and 72 h, the proliferation of MDA-MB-231 cells was inhibited in a dose-and time-dependent manner. MDA-MB-231 cells treated with 40 μmol/L AG490 for 30, 60, 90 and 120 rain resulted in the increasing adhesion of cells to Matrigel in a time-dependent manner. However, capacity of adhesion in the group treated with AG490 was significantly decreased in comparison with the control group (P〈0.01). The expression level of P-ERK and MMP-9 were decreased when treated with AG490. After treatment with 40 μmol/L AG490, in invasion assay, the number of cells in AG490 treated group to migrate to filter coated with Matrigel was reduced compared with control group (P〈0.05) Meanwhile, in migration assay, the number of cells in AG490 treated group to migrate to filter was also decreased compared with control group (P〈0.05). Conclusion: Our study indicates that JAK kinase could affect the activity of ERK signal transduction pathway through the phosphorylation of ERK. The inhibitory effects of JAK kinase on MMP-9 expression and invasion of breast cancer cells were associated with the down-regulation of the ERK signaling pathway.展开更多
Objective: To explore the effects of neuregulins on ErbB2 receptor signal transduction pathway activation, and invasion and metastasis of non-overexpression ErbB2 breast cancer cell MDA-MB-231. Methods: The express...Objective: To explore the effects of neuregulins on ErbB2 receptor signal transduction pathway activation, and invasion and metastasis of non-overexpression ErbB2 breast cancer cell MDA-MB-231. Methods: The expressions of neuregulin were detected by immunocytochemistry and Western blot. MDA-MB-231 cells were treated with ErbB2 kinase inhibitor AG825. Proliferations were measured with MTT assay. Invasion and metastasis of MDA-ME-231 cells were evaluated with transwell chamber. The enzyme activities of MMP-2 and MMP-9 were detected by gelatin zymography. The expressions of MMP-2 and HIF-1α were detected by Western blot. Results: MDA-MB-231 cells expressed a relatively higher level of neuregulin. In Western blot, the positive reaction band was found at 44KD which coincides with the molecular weight of NRG. When MDA-MB-231 cells were treated with AG825, the proliferation was inhibited in a time-dose-dependent manner (P〈0.01), invasion and metastasis were also depressed (P〈0.05). The enzyme activities of MMP-2 and MMP-9 were lower (P〈0.05). The expression levels of MMP-2 and HIF-lct were decreased (P〈0.05). Conclusion: Our study indicates that neuregulins are synthesized in MDA-MB-231 cells as transmembrane proteins, neuregulins could activate ErbB2 receptor signal transduction pathway by autocrine or paracrine secretion, and induce invasion and metastasis of MDA-MB-231 cells.展开更多
This study was aimed to explore the influence of breast cancer associated fibroblasts (CAFs) in migration and invasion of breast cancer cell line MCF-7,and investigate whether hepatocyte growth factor (HGF) is involve...This study was aimed to explore the influence of breast cancer associated fibroblasts (CAFs) in migration and invasion of breast cancer cell line MCF-7,and investigate whether hepatocyte growth factor (HGF) is involved in this process.Primary breast CAFs and their corresponding normal breast fi-broblasts (NFs) were obtained by collagenase digestion.On the basis of the co-culture,the migration and invasion capacity of MCF-7 cells was compared between CAFs and NFs by Transwell.The differ-ence in the HGF expression between them was detected by ELISA.The secretion of HGF was knocked down by using RNA interference technology in CAFs.Then the changes of migration and invasion ca-pacity of MCF-7 cells were investigated by Transwell.Eventually,we isolated high-purity CAFs and NFs,and the CAFs had a stronger ability in promoting MCF-7 migration and invasion than the NFs.ELISA results demonstrated that CAFs secreted higher HGF,and the capacity of MCF-7 migration and invasion was declined after knocking down the secretion of HGF in CAFs by RNA interference.It is suggested that CAFs can promote MCF-7 migration and invasion through HGF in vitro.展开更多
BACKGROUND Gastrointestinal metastasis of breast cancer is rare,and clinicians may not have previously encountered this disease in clinical practice.CASE SUMMARY We report a patient with invasive lobular carcinoma of ...BACKGROUND Gastrointestinal metastasis of breast cancer is rare,and clinicians may not have previously encountered this disease in clinical practice.CASE SUMMARY We report a patient with invasive lobular carcinoma of the breast who developed gastrointestinal metastasis two years after modified radical surgery.Mild elevation of carbohydrate antigen 15-3 was observed in the patient at an early stage;however,diagnosis and treatment were delayed due to non-specific clinical manifestations and no identifiable metastasis observed on imaging.CONCLUSION Clinicians should pay attention to gastrointestinal metastasis of breast cancer,especially invasive lobular carcinoma of the breast.展开更多
BACKGROUND Invasive lobular carcinomas(ILC)form 5%-10%of breast cancer and rarely show overexpression of human epidermal growth factor receptor 2(HER2).AIM To describe the prevalence and prognostic factors of HER2 pos...BACKGROUND Invasive lobular carcinomas(ILC)form 5%-10%of breast cancer and rarely show overexpression of human epidermal growth factor receptor 2(HER2).AIM To describe the prevalence and prognostic factors of HER2 positive(HER2+)ILC in an Asian population.METHODS A retrospective review of patients with ILC seen between January 1985 and March 2018 at various SingHealth medical institutions was conducted.Demographic and clinical data were collected from medical records.We examined clinicopathological characteristics and survival in relation to HER2 status.RESULTS A total of 864 patients were included.Prevalence of HER2 positivity was 10.1%(87 patients).Compared with HER2 negative(HER2-)ILC,HER2+ILC was associated with a higher proportion of estrogen receptor negative(24.4%vs 5.9%,P<0.001),progesterone receptor negative(PR-)(40.2%vs 24%,P=0.002)and grade 3 tumours(Grade 3,29.0%vs 10.2%,P<0.001).Overall survival rate was poorer in patients with HER2+compared to HER2-ILC(56.7%vs 72.9%alive at 10 years;hazard ratio 1.87,95%confidence interval:1.21-2.90,P=0.004).Based on multivariate analysis,negative prognostic factors for overall survival included HER2 positivity,PR negativity,older age,Indian ethnicity and higher tumour stage.CONCLUSION Prevalence of HER2+ILC was 10.1%.HER2+ILC was more likely to have poorer prognostic features such as estrogen receptor negative,PR-and higher tumour grade,and have a poorer survival.展开更多
Objective:To investigate the effects of exosomes derived from tumor-associated macrophages(TAMs)on migration and invasion of MDA-MB-231 cells in triple negative breast cancer.Methods:The MDA-MB-231 cells,a human breas...Objective:To investigate the effects of exosomes derived from tumor-associated macrophages(TAMs)on migration and invasion of MDA-MB-231 cells in triple negative breast cancer.Methods:The MDA-MB-231 cells,a human breast cancer cell line,were divided into the experimental group and the blank control group.The exosomes were isolated from the supernatant of human peripheral blood mononuclear cells(THP-1)by a multi-step ultracentrifugal procedure.The effects of exosomes on migration and invasion of MDAMB-231 cells were studied by endocytosis assay of exosomes,Transwell migration assay and Celigo scratch assay.Results:Exosomes were ingested and endocytosed by MDAMB-231 cells,brought into the cytoplasm at 3h and enriched significantly at 6h.Compared with the blank control group,the number of metastatic cells in the Transwell compartment(241±3.35)and its variation relative to normal cells(144±2.33)in the experimental group were significantly increased(P<0.05).The 24 h migration rate of MDA-MB-231 cells treated with exosomes in the scratch assay showed similar results(39.86±3.47 in the experimental group vs.24.48±2.97 in the control group,P<0.05).Conclusion:TAM-derived exosomes can be ingested and endocytosed by MDA-MB-231 cells,and promote their migration and invasion in vitro.展开更多
Objective:To study the dynamic contrast-enhanced MRI (DCE-MRI) parameters of breast cancer tissue and their correlation with cancer cell proliferation and invasion.Methods: A total of 92 patients with breast mass who ...Objective:To study the dynamic contrast-enhanced MRI (DCE-MRI) parameters of breast cancer tissue and their correlation with cancer cell proliferation and invasion.Methods: A total of 92 patients with breast mass who underwent surgical treatment in our hospital between July 2012 and June 2016 were collected as research subjects. According to the results of pathological examination, the patients were divided into breast adenoma group (n=52) and breast cancer group (n=40). DCE-MRI parameter levels of breast mass were analyzed between two groups of patients, and the mRNA expression of proliferation and invasion genes in tumor samples were compared. Pearson test was used to further evaluate the relationship between the DCE-MRI parameter levels of breast cancer tissue and the malignant degree of tumor.Results:The DCE-MRI parameter TTP level in breast cancer group was lower than that in breast adenoma group while EER and SLOPE levels were higher than those in breast adenoma group. Proliferation genes C6orf106, HMGB2, ETS-1 and BRG1 mRNA expression in tumor tissue of breast cancer group were higher than those of breast adenoma group, and invasion genes ADAM9, Ezrin and Nanog mRNA expression were higher than those of breast adenoma group while CRM197 and EBP50 mRNA expression were lower than those of breast adenoma group. The Pearson test showed that the DCE-MRI parameter levels of breast cancer tissues were directly correlated with the mRNA expression of proliferation and invasion genes.Conclusion:DCE-MRI parameter levels are abnormal in breast cancer tissues, and the abnormal degree is directly correlated with the malignant biological behavior of tumor cells.展开更多
<span style="font-family:Verdana;">Breast conservation surgery (BCS) and nipple-areola-sparing (NAS) mastectomy have been recognized as two milestones in this period. This study included 60 Egyptian fe...<span style="font-family:Verdana;">Breast conservation surgery (BCS) and nipple-areola-sparing (NAS) mastectomy have been recognized as two milestones in this period. This study included 60 Egyptian female patients with breast cancer, all of them were subjected to modified radical mastectomy operation. Methods: This study included female patients > 18 years old who have breast cancer with healthy looking non invaded skin of nipple and areola and excluded patients < 18 years old, patients unfit for surger, patients previously subjected to chemo or radiotherapy for breast cancer. We peformed clinical examination of 60 patients with breast cancer. We studied the relevant factors that affect NAC invasion such as patient’s age, menstrual state, family history, tumor size, tumor location (central vs peripheral), tumor to nipple distance, lymphovascular invasion of NAC, lymph node metastasis, histological tumor type, tumor stage, multifocal/multicentric tumors and (ER, PR, HER2) status. Result: In our study, we have shown that NAC invasion is strongly associated with: 1) Nipple retraction as a patient’s complaint;2) Tumor site;3) Tumor-nipple-distance ≤ 4 cm;4) Multifocal/multicentric tumor;5) Tumor grade (grade III tumors);6) Positive lymph node invasion;7) ER and PR receptors negativity;8) HER2 positivity. This helps in preoperative planning for selecting patients for NAS mastectomy. Conclusion: The ideal patients for NAS mastectomy are with these criteria: 1) Clinically normal nipple areola complex;2) Distance from the tumor to the nipple is >4 cm;3) No multifocal/multicentric tumor;4) Absence of lymph node invasion;5) Tumor grade (grade I, II);6) Peripheral not central tumor;7) No sub-areolar lymphovascular invasion (LVI);8) ER receptor positive;9) PR receptor positive;10) HER2 negative.</span>展开更多
Objective: To study the effect of trastuzumab combined with paclitaxel neoadjuvant chemotherapy on the cell proliferation and invasion in human epidermal growth factor receptor-2 (HER-2)-positive breast cancer lesions...Objective: To study the effect of trastuzumab combined with paclitaxel neoadjuvant chemotherapy on the cell proliferation and invasion in human epidermal growth factor receptor-2 (HER-2)-positive breast cancer lesions. Methods: Patients who were diagnosed with HER-2-positive breast cancer in the Central Hospital of Enshi Autonomous Prefecture Hubei Province between April 2015 and January 2017 were selected and randomly divided into two groups, the combined group received trastuzumab combined with paclitaxel chemotherapy, and the control group accepted paclitaxel chemotherapy. The surgically removed breast cancer lesions were collected to determine the expression of cell proliferation genes, cell invasion genes and angiogenesis molecules. Results: USP39, EphA2, NUAK1, Gab2, Raptor, ICAM-1, HIF-1α, VEGF, ANGPLT-2 and ANGPLT-4 mRNA expression in tumor lesion of combined group were significantly lower than those of control group while CCN5, ALEX1, ATG2B, ATG4D, E-cadherin and EBP50 mRNA expression were significantly higher than those of control group. Conclusion: Trastuzumab combined with paclitaxel neoadjuvant chemotherapy can inhibit the cell proliferation and invasion and decrease the angiogenesis in HER-2-positive breast cancer lesions.展开更多
文摘Objective: To analyze the role and influence of the GINS4 gene in breast cancer progression and to explore its expression in triple-negative and non-triple-negative breast cancer cell lines. Methods: Single-gene analysis of GINS4 was performed by breast cancer RNA transcriptome data from The Cancer Genome Atlas (TCGA). Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression of GINS4 in triple-negative and non-triple-negative breast cancer cell lines. The knockdown effects of GINS4 in MDA-MB-231 and MCF-7 cell lines on the proliferation and invasion of breast cancer cells were examined by cell counting kit 8 (CCK8) and Transwell assays. Results: Bioinformatics analysis showed that the expression of GINS4 in breast cancer was significantly higher than that in normal breast tissues (P > 0.05). At the same time, cell experiments confirmed that GINS4 was highly expressed in human breast cancer cell lines with normal breast cells as reference and in MDA-MB-231 and MCF-7 cell lines as reference, where the ability of proliferation and invasion of MDA-MB-231 and MCF-7 cells decreased after GINS4 knockdown. Conclusion: GINS4 is a gene associated with breast cancer malignancy, which can act as a novel tumor marker and has the potential as a new therapeutic target for breast cancer.
基金supported by the National Natural Science Foundation of China(No.30930038)National"973"Program of China(No.2009CB521700+1 种基金2009CB918903)Program for Changjiang Scholars and Innovative Research Team in University(No.IRT0743)
文摘The development of accessory breast tissue,which is found anywhere along the milk line,is attributed to the failure of milk line remnants to regress during embryogenesis.Primary tumors may arise from any ectopic breast tissue.Accessory breast cancer occurring concurrently with primary invasive breast cancer is extremely rare.Two such cases were reported in this article.One was a 43-year-old Chinese female who exhibited bilateral breast cancer(invasive ductal carcinoma,not otherwise specified,IDC-NOS) and an accessory breast carcinoma(IDC-NOS) incidentally identified in her left axilla.The ectopic breast tissue in her right axilla presented with adenosis.The patient was surgically treated,followed by postoperative docetaxel epirubicin(TE) chemotherapy.The second case was a 53-year-old Chinese female with bilateral breast cancer(apocrine carcinoma) accompanied by an accessory breast carcinoma(IDC-NOS) in her right axilla that was also incidentally identified.The patient was surgically treated after three doses of cyclophosphamide epirubicin docetaxel(CET) neoadjuvant chemotherapy,followed by adjuvant chemotherapy of the same regimen.
文摘Objectives: The invasive breast cancer is divided into four clinical subtypes: Luminal A-like, Luminal B-like, HER-2 positive, and triple-negative according to the expression status of estrogen receptor (ER), progesterone receptor(PR), human epidermal growth factor receptor-2 (HER-2) and Ki-67. The prognosis and treatment strategy vary with subtypes. The current studies have reported the relation between lymphatic vessel invasion (LVI) and the expression status of ER, PR, HER-2, Ki-67 in invasive breast cancer, but the results were debatable. So the meta-analysis was conducted to confirm the relation between LVI and the four factors. Methods: Literature was searched by entering the terms: breast AND (neoplasm OR cancer OR carcinoma) AND (lymphovascular OR “lymph vessel” OR “lymphatic vessel” invasion OR carcinoma embolus) AND (ER OR estrogen receptor OR PR OR progesterone receptor OR HER-2 OR human epidermal growth factor receptor-2 OR Ki-67 OR clinicopathological) in Pubmed. The merged odds ratio (OR) and 95% confidence interval (CI) were estimated using fixed-effect model. Review Manager 5.2 was used to analysis the relation between LVI and the expression status of ER, PR, HER-2, Ki-67 in invasive breast cancer respectively. The fail-safe number was used to estimate publication bias. Results: The analysis included 5 studies, LVI positive rate was significant lower in ER positive, PR positive, HER-2 negative, low Ki-67 expression group statistically. The OR and 95% CI were 0.6(0.44 - 0.81), 0.64(0.43 - 0.95), 1.52(1.03 - 2.24), 5.29(1.53 - 18.35) respectively.Conclusions:?LVI was significantly correlated with the expression status of ER, PR, HER-2 and Ki-67 in invasive breast cancer. Furthermore, LVI was consistent with poor prognostic expression status of the four factors.
文摘Objective: To study the correlation of MRI apparent diffusion coefficient (ADC value) of invasive breast cancer with tumor tissue growth and angiogenesis. Methods: Patients with breast mass who were treated in Wuhan No. 6 Hospital between March 2014 and May 2017 were selected as the research subjects and divided into group A with invasive ductal carcinoma, group B with intraductal carcinoma and group C with benign lesion according to the biopsy results, magnetic resonance diffusion-weighted imaging was conducted to determine ADC values, and biopsy tissue was taken to determine the expression of proliferation genes and angiogenesis genes. Results: USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in lesions of group A and group B were significantly higher than those of group C while ADC value as well as ALEX1 and Bax protein expression levels were significantly lower than those of group C;USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in lesions of group A were significantly higher than those of group B while ADC value as well as ALEX1 and Bax protein expression levels was significantly lower than those of group B;USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in invasive breast cancer tissue with high ADC value were significantly lower than those in invasive breast cancer tissue with low ADC value while ALEX1 and Bax protein expression levels were significantly higher than those in invasive breast cancer tissue with low ADC value. Conclusion: The decrease of ADC value of invasive breast cancer is closely related to cancer cell proliferation and angiogenesis.
文摘Circular RNA(circRNA),as a newly discovered non-coding RNA with important regulatory potential,is closely related to the occurrence and progression of various tumors.This study aimed to investigate has_circ_0000069 expression in breast cancer and its influence on cellular activities.Using real-time quantitative polymerase chain reaction,has_circ_0000069 levels were measured in 137 pairs of tissue specimens,as well as cancer cell lines.The cellular activities of cell lines were determined by cell counting kit-8(CCK-8)and Transwell assays.The potential targeting miRNAs were predicted and verified using an online database and dual-luciferase reporter assay.Has_circ_0000069 was highly expressed in breast cancer tissues and cells.The expression of has_circ_0000069 was associated with the five-year overall survival of patients.After silencing has_circ_0000069 in breast cancer cells,its expression reduced,and the ability of cell proliferation,migration,and invasion decreased.MiR-432 was verified as a targeting miRNA of has_circ_0000069.Has_circ_0000069 expression increased in breast cancer and was negatively related to patient’s prognosis.Has_circ_0000069 may facilitate breast cancer tumor progression by sponging miR-432.These findings revealed that has_circ_0000069 may be a biomarker for predicting prognosis and a therapeutic target for treating patients with breast cancer.
基金supported by National Natural Science Foundation of China(Grant No.:81560269)
文摘Objective: To study the regulatory effects of miR-21 on breast cancer cell line proliferation and invasion as well as the downstream target genes. Methods: Breast cancer cell lines MCF-7 were cultured and transfected with miR-21 mimics and the corresponding negative control mimics(NC mimics), and then MTS kits were used to detect cell viability. Transwell experiment was used to detect cell invasion ability, and fluorescence quantitative PCR was used to detect the expression of proliferation and invasion-related genes in cells. Results: 24 h after transfection of miR-21 mimics and NC mimics, cell OD value and the number of invasive cells of miR-21 group were significantly higher than those of NC group, and m RNA contents of PDCD-4, Fas L, PTEN, Rho B, Maspin, TIMP3 and RECK in cells were significantly lower than those of NC group. Conclusion: miR-21 can promote the proliferation and invasion of breast cancer cell lines, and its downstream target genes include PDCD-4, Fas L, PTEN, Rho B, Maspin, TIMP3 and RECK.
基金Supported by Terry Fox Foundation for Cancer Research
文摘To characterize AXL receptor tyrosine kinase (AXL) expression in relationship to tumor protein P53 (TP53 gene, p53 protein) and its role in tumor invasion and response to therapy.METHODSWe used 14 cell lines, including 3 isogenic pairs carrying mutant/knockout p53, to gain insight into the relationship between AXL and TP53. These included HCT116, HCT116.p53 mutant, RKO, and RKO.p53<sup>-/-</sup> lines (all from colon cancers) as well as breast cancer cell lines MCF7 and 1001 (MCF7-p53 mutant clone). HeLa cell line was used as a positive control for epithelial to mesenchymal transition (EMT). AXL expression was determined by Western blotting using rabbit monoclonal antibody clone C89E7. AXL siRNA silencing was performed and followed by collagen invasion assay. Cell viability analysis using the sulforhodamine B assay and the invasion assay were performed after exposure to chemotherapeutic agents (doxorubicin for breast cancer cells; 5FU or irinotecan for colon cancer cells).RESULTSWe showed that the introduction of p53 mutations or knockout increased expression levels of AXL in isogenic cells compared to the matching p53 wild-type parental cells. Overall, we found a trend for correlation between the potential EMT candidate AXL, p53 alterations, and EMT markers in colorectal and breast cancers. The expression of AXL in RKO cells, a rare colon cancer cell line with inactive Wnt signaling, suggests that the AXL oncogene might provide an alternative genetic pathway for colorectal carcinogenesis in the absence of Wnt signaling activation and TP53 mutation. AXL silencing in the TP53 mutant isogenic cell lines 1001, HCT116.p53 mutant and RKO.P53<sup>-/-</sup> was > 95% efficient and the silenced cells were less invasive compared to the parental TP53 wild-type cells. AXL silencing showed a subtle trend to restore colon cancer cell sensitivity to 5FU or irinotecan. Importantly, AXL expressing cells developed more invasive potential after exposure to chemotherapy compared to the AXL-silenced cells.CONCLUSIONAXL is influenced by p53 status and could cause the emergence of aggressive clones after exposure to chemotherapy. These findings could have applications in cancer management.
基金supported by grants from the National Natural Science Foundation of China(No.81172549)the Shanghai Science and Technology Development Fund(No.11XD1403300)the Opening Project of Shanghai Key Laboratory of Orthopaedic Implant(KFKT2011003)
文摘Objective: The aim of this study was to investigate the effects of plumbagin (PL), a naphthoquinone derived from the medicinal plant plumbago zeylanica, on the invasion and migration of human breast cancer cells. Methods: Human breast cancer MDA-MB-231SArfp cells were treated with different concentrations of plum- bagin for 24 h. The effects of plumbagin on the migration and invasion were observed by a transwell method. The expressions of IL-1α, IL-1β, IL-6, IL-8, TGF-β, TNFα, MMP-2 and MMP-9 mRNA in MDA-MB-231SArfp cells were detected using Real-Time PCR. MDA-MB-231SArfp cells were treated with plumbagin at different concentrations for 45 minutes. The activation of STAT3 was detected by western blot. Following this analysis, STAT3 in MDA-MB-231SArfp cells was knocked out using specific siRNA, mRNA levels of IL-1α, TGF-β, MMP-2 and MMP-9 were then detected. Consequently, MDA-MB-231SArfp cells were injected intracardially into BALB/c nude mice to construct a breast cancer bone metastatic model. The mice were injected intra- peritoneally with plumbagin. Non-invasive in vivo monitoring, X-ray imaging and histological staining were performed to investigate the effects of plumbagin on the invasion and migration of breast cancer cells in vivo. Results: The in vitro results showed that plumbagin could suppress the migration and invasion of breast cancer cells and down-regulate mRNA expressions of IL-1α TGF-β, MMP-2 and MMP-9. Western blotting demonstrated that plumbagin inhibited the activation of STAT3 signaling in MDA-MB-231SArfp cells. The inactivation of STAT3 was found to have an inhibitory effect on the expressions of IL-1α, TGF-β, MMP-2 and MMP-9. In vivo studies showed that plumbagin inhibited the metastasis of breast cancer cells and decreased osteolytic bone metastases, as well as the secretion of MMP-2 and MMP-9 by tumor cells at metastatic lesions. Conclusions: Plumbagin can suppress the invasion and migration of breast cancer cells via the inhibition of STAT3 signaling and by downregulation of IL-1α, TGF-β, MMP-2 and MMP-9.
基金supported by Guangzhou Municipal Science and Technology Support Program(No:10A32060573)
文摘Objective:To investigate the relationship between CYPIA1 genetic polymorphisms and the invasion and metastasis of breast cancer.Methods:The CYP1A1 gene polymorphism(an T-C transversion at nucleotide position 3801)was detected by the polymerase chain reaction and restriction fragment length polymorphism in 80 cases with breast cancer and 60 samples of normal breast tissue.The difference in genotypic distribution frequency between the groups,the correlation between the genotypes and the factors related to prognosis were analyzed.Results:The incidence of homozygous and variant genotypes had no difference between the breast cancer group and controls group(P=0.746).The proportion of variant genotype increased as clinical stage(P=0.006)advanced,as well as with increased numbers of lymph node metastases(P=0.010).Conclusions:In patients with breast cancer there is a correlation between the CYP1A1 CC allele and some factors indicating poor prognosis,including more lymph node metastases as well as a more advanced clinical stage.
文摘Breast cancer,particularly Invasive Ductal Carcinoma(IDC),is a primary global health concern predominantly affecting women.Early and precise diagnosis is crucial for effective treatment planning.Several AI-based tech-niques for IDC-level classification have been proposed in recent years.Processing speed,memory size,and accuracy can still be improved for better performance.Our study presents ECAM,an Enhanced Channel-Wise Attention Mechanism,using deep learning to analyze histopathological images of Breast Invasive Ductal Carcinoma(BIDC).The main objectives of our study are to enhance computational efficiency using a Separable CNN architecture,improve data representation through hierarchical feature aggregation,and increase accuracy and interpretability with channel-wise attention mechanisms.Utilizing publicly available datasets,DataBioX IDC and the BreakHis,we benchmarked the proposed ECAM model against existing state-of-the-art models:DenseNet121,VGG16,and AlexNet.In the IDC dataset,the model based on AlexNet achieved an accuracy rate of 86.81%and an F1 score of 86.94%.On the other hand,DenseNet121 outperformed with an accuracy of 95.60%and an F1 score of 95.75%.Meanwhile,the VGG16 model achieved an accuracy rate of 91.20%and an F1 score of 90%.Our proposed ECAM model outperformed the state-of-the-art,achieving an impressive F1 score of 96.65%and an accuracy rate of 96.70%.The BreakHis dataset,the AlexNet-based model,achieved an accuracy rate of 90.82%and an F1 score of 90.77%.DenseNet121 achieved a higher accuracy rate of 92.66%with an F1 score of 92.72%,while the VGG16 model achieved an accuracy of 92.60%and an F1 score of 91.31%.The proposed ECAM model again outperformed,achieving an F1 score of 96.37%and an accuracy rate of 96.33%.Our model is a significant advancement in breast cancer diagnosis,with high accuracy and potential as an automated grading,especially for IDC.
文摘Low-grade invasive ductal carcinoma is almost diploid, and has frequent losses of chromosome 16q, which is shared by other precancerous lesions of the mammary gland such as flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), and lownuclear grade ductal carcinoma in situ (DCIS). The genetic alterations accumulate in a stepwise fashion as the precancerous lesions progress to invasve ductal carcinoma. This supports the linear progression model of breast cancer from FEA, through ADH, to low- nuclear grade DCIS as non-obligate early events in low-grade IDC evolution. In contrast, high-grade carcinoma tends to aneuploidy with complex genetic alterations--most importantly, frequent gains at chromosome 16q. Frequent losses at chromosome 16q in low-grade IDC and gains in the same arm of the same chromosome in high-grade IDC imply that these lesions are two end outcomes of different disease processes and that they do not lie in the same continuum of a process. Therefore, low-grade and high-grade IDC are two distinct diseases with a divergent route of progression.
基金supported by the Scientific Research Foundation of Chonging Medical University (No. XBYB2007089).
文摘Objective: To explore the effects of Janus activated kinase (JAK) inhibitor AG490 on the phosphorylation of extracellular signal regulated protein kinase (ERK) in human breast cancer cells MDA-MB-231 and the roles of JAK in the invasion and metastasis of the human breast cancer cells through ERK signaling transduction pathways. Methods: MDA-MB-231 cells were treated with 20 μmol/L, 40 μmol/L, 80 μmol/L Janus kinase inhibitor AG490 for 24, 48 and 72 h. Proliferation and adhesion of MDA-MB-231 cells to matrigel were measured with MTT assay. When treated with 40 μmol/L AG490 for 24 h, the expressions of P-ERK and MMP-9 of cells were detected by Western-blot and invasion and metastasis of MDA-MB-231 cells were evaluated with transwell chamber. Results: After being treated with 20 μmol/L, 40 μ/L, 80 μmol/L AG490 for 24, 48 and 72 h, the proliferation of MDA-MB-231 cells was inhibited in a dose-and time-dependent manner. MDA-MB-231 cells treated with 40 μmol/L AG490 for 30, 60, 90 and 120 rain resulted in the increasing adhesion of cells to Matrigel in a time-dependent manner. However, capacity of adhesion in the group treated with AG490 was significantly decreased in comparison with the control group (P〈0.01). The expression level of P-ERK and MMP-9 were decreased when treated with AG490. After treatment with 40 μmol/L AG490, in invasion assay, the number of cells in AG490 treated group to migrate to filter coated with Matrigel was reduced compared with control group (P〈0.05) Meanwhile, in migration assay, the number of cells in AG490 treated group to migrate to filter was also decreased compared with control group (P〈0.05). Conclusion: Our study indicates that JAK kinase could affect the activity of ERK signal transduction pathway through the phosphorylation of ERK. The inhibitory effects of JAK kinase on MMP-9 expression and invasion of breast cancer cells were associated with the down-regulation of the ERK signaling pathway.
文摘Objective: To explore the effects of neuregulins on ErbB2 receptor signal transduction pathway activation, and invasion and metastasis of non-overexpression ErbB2 breast cancer cell MDA-MB-231. Methods: The expressions of neuregulin were detected by immunocytochemistry and Western blot. MDA-MB-231 cells were treated with ErbB2 kinase inhibitor AG825. Proliferations were measured with MTT assay. Invasion and metastasis of MDA-ME-231 cells were evaluated with transwell chamber. The enzyme activities of MMP-2 and MMP-9 were detected by gelatin zymography. The expressions of MMP-2 and HIF-1α were detected by Western blot. Results: MDA-MB-231 cells expressed a relatively higher level of neuregulin. In Western blot, the positive reaction band was found at 44KD which coincides with the molecular weight of NRG. When MDA-MB-231 cells were treated with AG825, the proliferation was inhibited in a time-dose-dependent manner (P〈0.01), invasion and metastasis were also depressed (P〈0.05). The enzyme activities of MMP-2 and MMP-9 were lower (P〈0.05). The expression levels of MMP-2 and HIF-lct were decreased (P〈0.05). Conclusion: Our study indicates that neuregulins are synthesized in MDA-MB-231 cells as transmembrane proteins, neuregulins could activate ErbB2 receptor signal transduction pathway by autocrine or paracrine secretion, and induce invasion and metastasis of MDA-MB-231 cells.
基金supported by grants from the National Natural Science Foundation of China (No. 81000979No. 30901584+1 种基金No. 30801224)the National Key Basic Research Program Foundation of China (Program 973) (No. 2009CB521800)
文摘This study was aimed to explore the influence of breast cancer associated fibroblasts (CAFs) in migration and invasion of breast cancer cell line MCF-7,and investigate whether hepatocyte growth factor (HGF) is involved in this process.Primary breast CAFs and their corresponding normal breast fi-broblasts (NFs) were obtained by collagenase digestion.On the basis of the co-culture,the migration and invasion capacity of MCF-7 cells was compared between CAFs and NFs by Transwell.The differ-ence in the HGF expression between them was detected by ELISA.The secretion of HGF was knocked down by using RNA interference technology in CAFs.Then the changes of migration and invasion ca-pacity of MCF-7 cells were investigated by Transwell.Eventually,we isolated high-purity CAFs and NFs,and the CAFs had a stronger ability in promoting MCF-7 migration and invasion than the NFs.ELISA results demonstrated that CAFs secreted higher HGF,and the capacity of MCF-7 migration and invasion was declined after knocking down the secretion of HGF in CAFs by RNA interference.It is suggested that CAFs can promote MCF-7 migration and invasion through HGF in vitro.
文摘BACKGROUND Gastrointestinal metastasis of breast cancer is rare,and clinicians may not have previously encountered this disease in clinical practice.CASE SUMMARY We report a patient with invasive lobular carcinoma of the breast who developed gastrointestinal metastasis two years after modified radical surgery.Mild elevation of carbohydrate antigen 15-3 was observed in the patient at an early stage;however,diagnosis and treatment were delayed due to non-specific clinical manifestations and no identifiable metastasis observed on imaging.CONCLUSION Clinicians should pay attention to gastrointestinal metastasis of breast cancer,especially invasive lobular carcinoma of the breast.
文摘BACKGROUND Invasive lobular carcinomas(ILC)form 5%-10%of breast cancer and rarely show overexpression of human epidermal growth factor receptor 2(HER2).AIM To describe the prevalence and prognostic factors of HER2 positive(HER2+)ILC in an Asian population.METHODS A retrospective review of patients with ILC seen between January 1985 and March 2018 at various SingHealth medical institutions was conducted.Demographic and clinical data were collected from medical records.We examined clinicopathological characteristics and survival in relation to HER2 status.RESULTS A total of 864 patients were included.Prevalence of HER2 positivity was 10.1%(87 patients).Compared with HER2 negative(HER2-)ILC,HER2+ILC was associated with a higher proportion of estrogen receptor negative(24.4%vs 5.9%,P<0.001),progesterone receptor negative(PR-)(40.2%vs 24%,P=0.002)and grade 3 tumours(Grade 3,29.0%vs 10.2%,P<0.001).Overall survival rate was poorer in patients with HER2+compared to HER2-ILC(56.7%vs 72.9%alive at 10 years;hazard ratio 1.87,95%confidence interval:1.21-2.90,P=0.004).Based on multivariate analysis,negative prognostic factors for overall survival included HER2 positivity,PR negativity,older age,Indian ethnicity and higher tumour stage.CONCLUSION Prevalence of HER2+ILC was 10.1%.HER2+ILC was more likely to have poorer prognostic features such as estrogen receptor negative,PR-and higher tumour grade,and have a poorer survival.
基金Key research and development project of Hainan provincial department of science and technology(No.ZDYF2018158)。
文摘Objective:To investigate the effects of exosomes derived from tumor-associated macrophages(TAMs)on migration and invasion of MDA-MB-231 cells in triple negative breast cancer.Methods:The MDA-MB-231 cells,a human breast cancer cell line,were divided into the experimental group and the blank control group.The exosomes were isolated from the supernatant of human peripheral blood mononuclear cells(THP-1)by a multi-step ultracentrifugal procedure.The effects of exosomes on migration and invasion of MDAMB-231 cells were studied by endocytosis assay of exosomes,Transwell migration assay and Celigo scratch assay.Results:Exosomes were ingested and endocytosed by MDAMB-231 cells,brought into the cytoplasm at 3h and enriched significantly at 6h.Compared with the blank control group,the number of metastatic cells in the Transwell compartment(241±3.35)and its variation relative to normal cells(144±2.33)in the experimental group were significantly increased(P<0.05).The 24 h migration rate of MDA-MB-231 cells treated with exosomes in the scratch assay showed similar results(39.86±3.47 in the experimental group vs.24.48±2.97 in the control group,P<0.05).Conclusion:TAM-derived exosomes can be ingested and endocytosed by MDA-MB-231 cells,and promote their migration and invasion in vitro.
文摘Objective:To study the dynamic contrast-enhanced MRI (DCE-MRI) parameters of breast cancer tissue and their correlation with cancer cell proliferation and invasion.Methods: A total of 92 patients with breast mass who underwent surgical treatment in our hospital between July 2012 and June 2016 were collected as research subjects. According to the results of pathological examination, the patients were divided into breast adenoma group (n=52) and breast cancer group (n=40). DCE-MRI parameter levels of breast mass were analyzed between two groups of patients, and the mRNA expression of proliferation and invasion genes in tumor samples were compared. Pearson test was used to further evaluate the relationship between the DCE-MRI parameter levels of breast cancer tissue and the malignant degree of tumor.Results:The DCE-MRI parameter TTP level in breast cancer group was lower than that in breast adenoma group while EER and SLOPE levels were higher than those in breast adenoma group. Proliferation genes C6orf106, HMGB2, ETS-1 and BRG1 mRNA expression in tumor tissue of breast cancer group were higher than those of breast adenoma group, and invasion genes ADAM9, Ezrin and Nanog mRNA expression were higher than those of breast adenoma group while CRM197 and EBP50 mRNA expression were lower than those of breast adenoma group. The Pearson test showed that the DCE-MRI parameter levels of breast cancer tissues were directly correlated with the mRNA expression of proliferation and invasion genes.Conclusion:DCE-MRI parameter levels are abnormal in breast cancer tissues, and the abnormal degree is directly correlated with the malignant biological behavior of tumor cells.
文摘<span style="font-family:Verdana;">Breast conservation surgery (BCS) and nipple-areola-sparing (NAS) mastectomy have been recognized as two milestones in this period. This study included 60 Egyptian female patients with breast cancer, all of them were subjected to modified radical mastectomy operation. Methods: This study included female patients > 18 years old who have breast cancer with healthy looking non invaded skin of nipple and areola and excluded patients < 18 years old, patients unfit for surger, patients previously subjected to chemo or radiotherapy for breast cancer. We peformed clinical examination of 60 patients with breast cancer. We studied the relevant factors that affect NAC invasion such as patient’s age, menstrual state, family history, tumor size, tumor location (central vs peripheral), tumor to nipple distance, lymphovascular invasion of NAC, lymph node metastasis, histological tumor type, tumor stage, multifocal/multicentric tumors and (ER, PR, HER2) status. Result: In our study, we have shown that NAC invasion is strongly associated with: 1) Nipple retraction as a patient’s complaint;2) Tumor site;3) Tumor-nipple-distance ≤ 4 cm;4) Multifocal/multicentric tumor;5) Tumor grade (grade III tumors);6) Positive lymph node invasion;7) ER and PR receptors negativity;8) HER2 positivity. This helps in preoperative planning for selecting patients for NAS mastectomy. Conclusion: The ideal patients for NAS mastectomy are with these criteria: 1) Clinically normal nipple areola complex;2) Distance from the tumor to the nipple is >4 cm;3) No multifocal/multicentric tumor;4) Absence of lymph node invasion;5) Tumor grade (grade I, II);6) Peripheral not central tumor;7) No sub-areolar lymphovascular invasion (LVI);8) ER receptor positive;9) PR receptor positive;10) HER2 negative.</span>
文摘Objective: To study the effect of trastuzumab combined with paclitaxel neoadjuvant chemotherapy on the cell proliferation and invasion in human epidermal growth factor receptor-2 (HER-2)-positive breast cancer lesions. Methods: Patients who were diagnosed with HER-2-positive breast cancer in the Central Hospital of Enshi Autonomous Prefecture Hubei Province between April 2015 and January 2017 were selected and randomly divided into two groups, the combined group received trastuzumab combined with paclitaxel chemotherapy, and the control group accepted paclitaxel chemotherapy. The surgically removed breast cancer lesions were collected to determine the expression of cell proliferation genes, cell invasion genes and angiogenesis molecules. Results: USP39, EphA2, NUAK1, Gab2, Raptor, ICAM-1, HIF-1α, VEGF, ANGPLT-2 and ANGPLT-4 mRNA expression in tumor lesion of combined group were significantly lower than those of control group while CCN5, ALEX1, ATG2B, ATG4D, E-cadherin and EBP50 mRNA expression were significantly higher than those of control group. Conclusion: Trastuzumab combined with paclitaxel neoadjuvant chemotherapy can inhibit the cell proliferation and invasion and decrease the angiogenesis in HER-2-positive breast cancer lesions.