OBJECTIVE:To evaluate the therapeutic effect of a selfformulated Traditional Chinese Medicine(TCM),Shugan Jieyu San(疏肝解郁散),on improvement of liver function and depression alleviation in the patients with triple n...OBJECTIVE:To evaluate the therapeutic effect of a selfformulated Traditional Chinese Medicine(TCM),Shugan Jieyu San(疏肝解郁散),on improvement of liver function and depression alleviation in the patients with triple negative breast cancer(TNBC).METHODS:A total of 60 patients diagnosed with TNBC and depression were enrolled and randomly assigned to either the control group(receiving routine tumor treatment and duloxetine)or the treatment group(receiving the TCM in addition to routine treatment).RESULTS:Both treatment and control groups showed a reduction in depressive symptoms and improved daily living abilities after treatment.However,the treatment group demonstrated significantly better outcomes compared to the control group.Furthermore,the levels of dopamine and serotonin in the serum increased in both groups after 8 weeks of treatment,while the treatment group exhibited superior results.CONCLUSIONS:This TCM showed promising results in reducing depressive symptoms and improving daily abilities in patients with TNBC and comorbid depression,which was verified by the increase in serum levels of dopamine and serotonin,suggesting the potential involvement of these neurotransmitters in the therapeutic effects of this TCM.展开更多
Background:Intratumoral flora and its metabolites play an important role in the occurrence,development and treatment of cancer,and are correlated with the genotype expression of breast cancer;However,the internal rela...Background:Intratumoral flora and its metabolites play an important role in the occurrence,development and treatment of cancer,and are correlated with the genotype expression of breast cancer;However,the internal relationship between intratumoral flora and triple negative breast cancer(TNBC)has not been elucidated.Methods:Fourteen patients with TNBC who met the criteria were included.The tumor tissues and adjacent tissues were respectively taken as the patient group and the control group.The 5R 16S sequencing technique was used to detect the abundance and distribution of the intratumoral flora between the two groups,and the differences between the groups were analyzed to find the bacteria with significant differences between groups(P<0.05).Results:The abundance of intratumoral microbiota in TNBC patients was significantly lower than that in adjacent tissues(P<0.05).The differential bacteria in TNBC tumors(P<0.05)included Acinetobacter,Renibacterium,Flavobacterium,Dechloromonas and others.The differential bacteria genera(P<0.05)in the adjacent tissues included Comamonas,Bacillus,Caulobacter,Afipia,Aerococcus,Roseomonas and so on.Conclusion:There is a significant difference in the flora structure between the tumor and normal tissues in TNBC patients.Proteobacteria plays an important role in the occurrence,development and treatment of TNBC.Among them,Acinetobacter may be the key reason for the metastasis of TNBC.展开更多
Triple-negative breast cancer(TNBC)is one of the most lethal diseases and lack of feasible therapeutic methods.Herein,we developed a bioactive covalent organic framework(COF)for adoptive cell therapy(ACT)of TNBC.In ou...Triple-negative breast cancer(TNBC)is one of the most lethal diseases and lack of feasible therapeutic methods.Herein,we developed a bioactive covalent organic framework(COF)for adoptive cell therapy(ACT)of TNBC.In our design,Mn^(2+)functionalized COF was employed as a bioactive CpG carrier,which could simultaneously engineer and polarize macrophages to the antitumor phenotype,via the synergistic interaction of CpG and Mn^(2+).In the in vitro experiments,the engineered macrophages were found to secret high levels of antitumor cytokines for efficient TNBC cell inhibition.In the in vivo antitumor model,bioactive COF-engineered macrophages were found to relieve the hypoxia tumor microenvironment,enabling prevention of immune cell depletion during ACT.Thus,we realized efficient TNBC therapy and metastasis inhibition with the engineered macrophages in a long-term therapy model.This work provides a promising strategy for metastatic TNBC treatment and highlights the importance of bioactive COF in biomedicine.展开更多
OBJECTIVE To discover a small molecule targeting ULK1-modulated cell death of triple negative breast cancer and exploreits potential mechanisms.METHODS ULK1 expression was analyzed by The Cancer Genome Atlas(TCGA)anal...OBJECTIVE To discover a small molecule targeting ULK1-modulated cell death of triple negative breast cancer and exploreits potential mechanisms.METHODS ULK1 expression was analyzed by The Cancer Genome Atlas(TCGA)analysis and tissue microarray(TMA)analysis.ULK1agonist was designed by using in silico screening,as well as modified by chemical synthesis and screened by kinase and anti-proliferative activities.The amino acid residues that key to the activation site of LYN-1604 were determined by site-directed mutagenesis,as well as in vitro kinase assay and ADP-Glo kinase assay.The mechanisms of LYN-1604 induced cell death were investigated by fluorescence microscope,western blotting,flow cytometry analysis,immunocytochemistry,as well as si RNA and GFP-m RFP-LC3 plasmid transfections.Potential ULK1 interactors were discovered by performing comparative microarray analysis and the therapeutic effect of LYN-1604 was assessed by xenograft breast cancer mouse model.RESULTS We found that ULK1 was remarkably downregulated in breast cancer tissue samples,especial y in triple negative breast cancer(TNBC).32 candidate smal molecules were synthesized,and we discovered a small molecule named LYN-1604 as the best candidate ULK1agonist.Additionally,we identified that three amino acid residues(LYS50,LEU53 and TYR89)were key to the activation site of LYN-1604 and ULK1.Subsequently,we demonstrated that LYN-1604 could induce autophagy-associated cell death via ULK complex(ULK1-m ATG13-FIP200-ATG101)in MDA-MB-231 cells.We also found that LYN-1604 induced cell death involved in ATF3,RAD21 and caspase 3,accompanied with autophagy and apoptosis.Moreover,we demonstrated that LYN-1604 had a good therapeutic potential on TNBC by targeting ULK1-modulated cell death in vivo.CONCLUSION We discovered a small molecule(LYN-1604)has therapeutic potential by targeting ULK1-modulated cell death associated with autophagy and apoptosis of TNBC in vitro and in vivo,which could be utilized as a new anti-TNBC drug candidate.展开更多
Triple negative breast cancer(TN BC)is a complex and malignant breast cancer subtype that lacks expression of the estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor 2(H ER2),ther...Triple negative breast cancer(TN BC)is a complex and malignant breast cancer subtype that lacks expression of the estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor 2(H ER2),thereby making therapeutic targeting difficult.TNBC is generally considered to have high malignancy and poor prognosis.However,patients diagnosed with certain rare histomorphologic subtypes of TNBC have better prognosis than those diagnosed with typical triple negative breast cancer.In addition,with the discovery and development of novel treatment targets such as the androgen receptor(AR),PI3K/AKT/mTOR and AMPK signaling pathways,as well as emerging immunotherapies,the therapeutic options for TNBC are increasing.In this paper,we review the literature on various histological types of TNBC and focus on newly developed therapeutic strategies that target and potentially affect molecular pathways or emerging oncogenes,thus providing a basis for future tailored therapies focused on the mutational aspects of TNBC.展开更多
Objective： A previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide（TC） regimen was inferior to docetaxel, anthracycline and cyclophosphamide（TAC） in neoadjuvant treatment o...Objective： A previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide（TC） regimen was inferior to docetaxel, anthracycline and cyclophosphamide（TAC） in neoadjuvant treatment of triple-negative breast cancer（TNBC） and human epidermal growth factor receptor-2-（HER2）-positive breast cancer in a short-term follow-up. Herein, long-term follow-up survival outcomes have been investigated.Methods： TNBC or HER2-positive patients were randomized to receive 6 cycles of TC or TAC neoadjuvant treatment. The primary endpoint was pathological complete remission（p CR）. Secondary endpoints included clinical response rate, event-free survival（EFS）, and overall survival（OS）.Results： A cohort of 96 patients consisted of 45 in TC and 51 in TAC arm. With a median follow-up period of53（range, 8-76） months, the patients achieving p CR post neoadjuvant chemotherapy exhibited superior EFS and OS than patients without p CR（P〈0.05）. TAC treatment resulted in consistently better EFS than TC treatment：the estimated 5-year EFS was 66.1% vs. 29.8%（P=0.002）. Moreover, the estimated 5-year OS was also in favor of TAC： 88.4% vs. 51.6%（P〈0.001）. Multivariable analysis demonstrated that the treatment regimen was an independent prognostic factor, and patients treated with TAC had a superior EFS [hazard ratio（HR）, 0.48; 95%confidence interval（95% CI）, 0.26-0.90; P=0.021] and OS（HR, 0.20; 95% CI, 0.08-0.60; P=0.003）.Conclusions： The updated long-term follow-up data demonstrated a sustained benefit in EFS and OS from anthracycline-containing TAC treatment, indicating that anthracycline is an essential and effective drug in this clinical trial.展开更多
Metastatic triple negative breast cancer(TNBC)has an aggressive phenotype with a predilection for visceral organs and brain.Best responses to chemotherapy are predominately in the first line.Recent studies have demons...Metastatic triple negative breast cancer(TNBC)has an aggressive phenotype with a predilection for visceral organs and brain.Best responses to chemotherapy are predominately in the first line.Recent studies have demonstrated improved progression free survival with the combination of atezolizumab/pembrolizumab and chemotherapy in programmed death-ligand 1 positive metastatic TNBC.However,a recent trial in a similar population showed no benefit for atezolizumab and paclitaxel which led to a Food and Drug Administration alert.Two phase III trials(OLYMPIAD and BROCADE3)demonstrated a benefit in progression free survival(PFS)but not overall survival in patients with BRCAassociated metastatic TNBC treated with Olaparib or Talazoparib respectively.For those treated with Talazoparib,the time to deterioration in health related-quality of life was also longer compared to chemotherapy.The BROCADE3 trial demonstrated that the combination of a platinum and veliparib increased PFS in first-line metastatic TNBC but at the cost of increased toxicity.There are no headto-head comparisons of a poly(adenosine diphosphate-ribose)polymerase inhibitors(PARPi)and platinums.There are unanswered questions regarding the role of PARPi maintenance after platinum therapy as is standard of care in BRCAassociated ovarian cancer.Other areas of therapeutic interest include targeting aberrations in the phosphoinositide 3-kinase pathway,protein kinase B,mammalian target of rapamycin or utilising antibody drug conjugates.This review focusses on recent and emerging therapeutic options in metastatic TNBC.We searched PubMed,clinicaltrials.gov and recent international meetings from American Society of Clinical Oncology,San Antonio Breast Cancer Conference and the European Society of Medical Oncology.展开更多
Triple negative breast cancer(TNBC) is an aggressive subtype of breast cancer that currently lacks effective biomarkers and therapeutic targets required to investigate the diagnosis and treatment of TNBC. Here we perf...Triple negative breast cancer(TNBC) is an aggressive subtype of breast cancer that currently lacks effective biomarkers and therapeutic targets required to investigate the diagnosis and treatment of TNBC. Here we performed a comprehensive differential analysis of 165 TNBC samples by integrating RNA-seq data of breast tumor tissues and adjacent normal tissues from both our cohort and The Cancer Genome Atlas(TCGA). Pathway enrichment analysis was conducted to evaluate the biological function of TNBC-specific expressed genes. Further multivariate Cox proportional hazard regression was performed to evaluate the effect of these genes on TNBC prognosis. In this report, we identified a total of 148 TNBC-specific expressed genes that were primarily enriched in mammary gland morphogenesis and hormone levels related pathways, suggesting that mammary gland morphogenesis might play a unique role in TNBC patients differing from other breast cancer types. Further survival analysis revealed that nine genes(FSIP1, ADCY5, FSD1, HMSD, CMTM5, AFF3, CYP2 A7, ATP1 A2,and C11 orf86) were significantly associated with the prognosis of TNBC patients, while three of them(ADCY5,CYP2 A7, and ATP1 A2) were involved in the hormone-related pathways. These findings indicated the vital role of the hormone-related genes in TNBC tumorigenesis and may provide some independent prognostic markers as well as novel therapeutic targets for TNBC.展开更多
OBJECTIVE:To investigate the efficacy of Biejia(Carapax Trionycis)and Ezhu(Rhizoma Curcumae Phaeocaulis)couplet medicine on epithelial-mesenchymal transition(EMT),invasion and migration of MDA-MB-231 triple negative b...OBJECTIVE:To investigate the efficacy of Biejia(Carapax Trionycis)and Ezhu(Rhizoma Curcumae Phaeocaulis)couplet medicine on epithelial-mesenchymal transition(EMT),invasion and migration of MDA-MB-231 triple negative breast cancer(TNBC)cells based on PI3K/Akt/mTOR signaling pathway.METHODS:MDA-MB-231 cells were treated with different medicated serum as Biejia-,Ezhu-,Biejia-Ezhu(BJ-,EZ-,BJ-EZ-)groups,intervened with no drug rat serum and paclitaxel with final concentration of 33 nM(IC50)as negative and positive control(NC and PC)groups.CCK-8 assay,scratch test,and Transwell assay were used to examine cell proliferation,invasion,and migration.The expression of E-cadherin,N-cadherin,Vimentin,MMP-2,MMP-9,PI3K,Akt,p-Akt,mTOR,and p-mTOR was determined by Western blot,and the m RNA expression of PI3K,Akt and mTOR was determined by real-time polymerase chain reaction.RESULTS:BJ-EZ group inhibited proliferation after 24,48,and 72 h compared with the NC group(P<0.05,<0.01 or<0.001)and reduced the invasion and migration of MDA-MB-231 cells(P<0.01 or<0.001).In addition,BJ-EZ group upregulated the expression of E-cadherin,downregulated the expression of N-cadherin,Vimentin,MMP-2,and MMP-9(P<0.05,P<0.01 or P<0.001),and inhibited the m RNA and protein expression of PI3K,Akt(p-Akt),mTOR(p-mTOR)(P<0.05,<0.01 or<0.001).CONCLUSION:Biejia(Carapax Trionycis)and Ezhu(Rhizoma Curcumae Phaeocaulis)couplet medicine can inhibit the proliferation,invasion,migration and EMT of MDA-MB-231 cells through PI3K/Akt/mTOR signaling pathway,and the effect is better than that of Biejia(Carapax Trionycis)or Ezhu(Rhizoma Curcumae Phaeocaulis)alone.展开更多
OBJECTIVE: To evaluate the effects of tetrandrine plus arsenic trioxide on HCC1937 cells, a triple negative breast cancer cell line, and to explore possible mechanisms.METHODS: The 3-(4,5-Dimethylthiazol-2-yl)-2, 5-di...OBJECTIVE: To evaluate the effects of tetrandrine plus arsenic trioxide on HCC1937 cells, a triple negative breast cancer cell line, and to explore possible mechanisms.METHODS: The 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide method was used to compare the antiproliferative effects of tetrandrine,arsenic trioxide alone and tetrandrine plus arsenic trioxide on HCC1937 cells. The median-effect principle(Chou-Talalay combination index method) was used to examine the interaction between the two drugs. Flow cytometry was used to evaluate effects of treatment with tetrandrine, arsenic trioxide or the combination of both on HCC1937 cell apoptosis. Real-time polymerase chain reaction and western blotting were performed to evaluate changes in apoptosis-related gene expression and protein levels.RESULTS: Tetrandrine and arsenic trioxide each in-hibited HCC1937 cell proliferation in a dose-dependent manner. The cell inhibition rate of HCC1937 cells treated with a combination of tetrandrine and arsenic trioxide was significantly higher than with either compound alone. The two drugs produced a synergistic effect when the inhibition rate was20%-40%. Flow cytometry results showed that treatment with the two drugs increased the proportion of apoptotic cells. In the combination treated group, caspase-3 activation and PARP cleavage were significantly higher than in the other groups.Moreover, Bcl-2 and survivin expression were decreased, whereas that of both Bid and Bax was increased.CONCLUSION: These findings demonstrated that tetrandrine plus arsenic trioxide had synergistic efficacy on induction of apoptosis in HCC1937 cells.展开更多
Objective： The triple negative （TN） metastatic breast cancer （MBC） patients are known to have worse prognosis, shorter progressive free survival （PFS）, and overall survival （OS）, that mandates using aggressiv...Objective： The triple negative （TN） metastatic breast cancer （MBC） patients are known to have worse prognosis, shorter progressive free survival （PFS）, and overall survival （OS）, that mandates using aggressive chemotherapy regimens. This phase II study aimed at investigating the efficacy and safety of using cisplatin and docetaxel in patients with triple negative metastatic breast cancer, and the possibility of using breast cancer susceptibility genel （BRCA1） expression as a predictive marker of chemotherapy response, and epidermal growth factor receptor （EGFR） as prognostic marker. Method： Between January 2006 and March 2009, 40 eligible patients with TN MBC were included in the study. We examined BRCA1 expression and EGFR protein in their specimens using immunohistochemistry. The patients were treated with cisplatin 75 mg/m2 and docetaxel 75 mg/m2 every 3 weeks, TN measurable MBC patients previously treated with anthracycline in their adjuvant or neo adjuvant settings were included in the study. Results： The median age of the treated patients was 43.5 years. Nearly half of the patients had an ECOG performance status of 0 or 1, and about third of them had one metastatic site. These metastatic sites were predominantly visceral in 80% of the patients. Fifty-five percent of TNMBC stained positive for BRCA1 and sixty-five percent for EGFR. Positivity for both markers was significantly associated with grade III tumors （P = 0.004）, OS, and PFS （P = 0.001 and 0.009） respectively. Overall, the regimen was well tolerated as Gill vomiting and neurological side effects were observed in 20% of the patients. Other toxiciUes were generally mild and medically manageable; with no treatment mortality was recorded. The overall disease control rate （ODCR） was 60%; the median PFS was 8 months, with a median overall OS of 17.5 months; while the median OS among responders was 23 months （95% CI 21.35 to 25.32）. The patients with negative EGFR had a significantly better OR, PFS, and OS than EGFR positive cases. There was no significant difference concerning OR, PFS, and OS, between positive and negative BRCA1 cases, which could be attributed to the better efficacy of cisplatin in the positive BRCA1 cases. Conclusion： This chemotherapy regimen is effective with tolerable toxicity profile, our results point out the importance of BRCA1 expression as predictive marker of chemotherapy response, and EGFR as prognostic marker, which could identify a certain group of patients with more aggressive disease who might benefit from using anti EGFR targeted therapy plus cisplatin.展开更多
The triple-negative subtype of breast cancer(TNBC)has the bleakest prognosis,owing to its lack of either hormone receptor as well as human epidermal growth factor receptor 2.Henceforth,immunotherapy has emerged as the...The triple-negative subtype of breast cancer(TNBC)has the bleakest prognosis,owing to its lack of either hormone receptor as well as human epidermal growth factor receptor 2.Henceforth,immunotherapy has emerged as the front-runner for TNBC treatment,which avoids potentially damaging chemotherapeutics.However,despite its documented association with aggressive side effects and developed resistance,immune checkpoint blockade continues to dominate the TNBC immunotherapy scene.These immune checkpoint blockade drawbacks necessitate the exploration of other immunotherapeutic methods that would expand options for TNBC patients.One such method is the exploitation and recruitment of natural killer cells,which by harnessing the innate rather than adaptive immune system could potentially circumvent the downsides of immune checkpoint blockade.In this review,the authors will elucidate the advantageousness of natural killer cell-based immuno-oncology in TNBC as well as demonstrate the need to more extensively research such therapies in the future.展开更多
Objective： The aim of the study was to investigate the long-term therapeutic effects of triple negative breast cancers （TNBCs） and find a standardized treatment. Methods： The clinical data and survival status of 6...Objective： The aim of the study was to investigate the long-term therapeutic effects of triple negative breast cancers （TNBCs） and find a standardized treatment. Methods： The clinical data and survival status of 69 patients with TNBC were collected, who were treated from 2003 to 2007 at Chongqing Cancer Institute, China. Results： Median observation for 61 months showed the local recurrence rate was 13.0% （9/69）, the overall survival （OS） rate was 76.8% （53/69） and the disease free survival （DFS） rate was 59.4% （41169）. Log-rank univariate survival analysis showed the OS and DFS rates of TNBCs with axillary lymph node metastasis were 38.1% and 23.8%, respectively, and the OS and DFS rates of triple negative breast cancer with axillary lymph node non-metastasis were 93.6% and 75.0%, respectively. There were significant differences comparing with two groups. Indictor analysis of age, menstruation status, tumor size, TNM stage, histological type, neoadjuvant chemotherapy and p53 did not show any prognostic influence. Conclusion： The axillary nodes metastasis is associated with DFS and OS in triple negative breast cancers. Cisplatin-based chemotherapy may be good choice for triple negative breast cancers with metastasis or local recurrence, who received Anthracycline and Taxane-based chemotherapy. Targeted therapies strategies such as EGFR-targeted therapy may be necessary.展开更多
Vibration isolation for low frequency excitation and the power supply for low power monitoring sensors are important issues in bridge engineering.The main problem is how to effectively combine the vibration isolator w...Vibration isolation for low frequency excitation and the power supply for low power monitoring sensors are important issues in bridge engineering.The main problem is how to effectively combine the vibration isolator with the energy harvester to form a multi-functional structure.In this paper,a system called quasi-zero stiffness energy harvesting isolator(QZS-EHI)with triple negative stiffness(TNS)is proposed.The TNS structure consists of linear springs,rigid links,sliders,and ring permanent magnets.Newton’s second law and Kirchhoff’s law construct dynamic equations of the QZS-EHI,and a comparison is made to contrast it with other QZS and linear isolators.The comparison field includes the QZS range,amplitude-frequency relationship,force transmissibility,and energy harvested power.The isolator can be applied to many engineering fields such as bridges,automobiles,and railway transportation.This paper selects bridge engineering as the main field for the dynamic analysis of this system.Considering the multi-span beam bridge,this paper compares different situations including the bridge with QZS-EHI support,with linear stiffness isolator support,and with single beam support.All results show that the QZS-EHI is not only better than the traditional isolator with linear stiffness under both harmonic and stochastic excitation,but also better than some QZS isolators with double or single negative stiffness in bridge vibration isolation and energy harvesting.Theoretical analysis is verified to correspond to the simulation analysis,which means the proposed QZS-EHI has practical application value.展开更多
Objective： To study the clinicopathological characters Methods： A total of 629 patients with breast cancer of triple negative breast cancer （TNBC）. were reviewed, who were treated from 2003 to 2007 in Chongqing Ca...Objective： To study the clinicopathological characters Methods： A total of 629 patients with breast cancer of triple negative breast cancer （TNBC）. were reviewed, who were treated from 2003 to 2007 in Chongqing Cancer Institute. The comparison of clinicopathological features including TNM classification, histological type, tumor location, axillary lymphonodes status and neoadjuvant chemotherapy between TNBC and nontriple negative breast cancer （NTNBC） was performed. The overall response was evaluated by whether the patients achieve complete remission （CR） and partial remission （PR） after chemotherapy. Results： There were 69 TNBCs in the 629 patients with breast cancer. The premenopausal patients, which was found in 49/69 of TNBCs, was more than NTNBCs. The average diameter of tumor in TNBC group was 4.1 cm, lager than NTNBC group. TNBC with axillary nodes metastasis occurred in 21 cases, and the axillary nodes metastasis rate was lower than NTNBC. The positive expression rate of p53 in TNBC was 44.9%, and the overall response （CR＋PR） was 72.2%. No statistical differences were found regarding the positive expression rate of p53 and the overall response between TNBC and NTNBC. Conclusion： TNBC were a group of primary breast cancers with triple negative, tending to occur in premenopausal women, with larger tumors, lower axillary nodes metastasis rate. TNBC had worse clinical prognosis and currently lacked effective targeted therapies.展开更多
BACKGROUND Forkhead box P3(FOXP3)is a specific marker for immunosuppressive regulatory T(T-reg)cells.T-regs and an immunosuppressive enzyme,indoleamine 2,3-dioxygenase(IDO),are associated with advanced disease in canc...BACKGROUND Forkhead box P3(FOXP3)is a specific marker for immunosuppressive regulatory T(T-reg)cells.T-regs and an immunosuppressive enzyme,indoleamine 2,3-dioxygenase(IDO),are associated with advanced disease in cancer.AIM To evaluate the co-expression of FOXP3 and IDO in triple negative breast cancer(TNBC)with respect to hormone-positive breast cancer patients from Pakistan.METHODS Immunohistochemistry was performed to analyze the expression of FOXP3,IDO,estrogen receptor,progesterone receptor,and human epidermal growth factor receptor on tissues of breast cancer patients(n=100):Hormone-positive breast cancer(n=51)and TNBC(n=49).A total of 100 patients were characterized as FOXP3 negative vs positive and further categorized based on low,medium,and high IDO expression score.Univariate and multivariate logistic regression models were used.RESULTS Out of 100 breast tumors,25%expressed FOXP3 positive T-regs.A significant coexpression of FOXP3 and IDO was observed among patients with TNBC(P=0.01)compared to those with hormone-positive breast cancer.Two variables were identified as significant independent risk factors for FOXP3 positive:IDO expression high(adjusted odds ratio(AOR)5.90;95%confidence interval(CI):1.22-28.64;P=0.03)and TNBC(AOR 2.80;95%CI:0.96-7.95;P=0.05).CONCLUSION Our data showed that FOXP3 positive cells might be associated with high expression of IDO in TNBC patients.FOXP3 and IDO co-expression may also suggest its involvement in disease,and evaluation of FOXP3 and IDO expression in TNBC patients may offer a new therapeutic option.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
<strong>Background:</strong><span><span><span style="font-family:""><span style="font-family:Verdana;"> In India approximately 20% of the patients with brea...<strong>Background:</strong><span><span><span style="font-family:""><span style="font-family:Verdana;"> In India approximately 20% of the patients with breast cancer are triple receptor negative. Owing to the aggressive nature and shorter disease-free survival judicious follow up and identification of failure pattern will benefit the patient. Similar studies have been conducted among non-Hispanic population and in China. This study aims to identify failure pattern in radically treated breast cancer patients who are triple receptor negative among Indian population. </span><b><span style="font-family:Verdana;">Methods</span></b><span style="font-family:Verdana;">: This prospective observational study was conducted in the Department of Radiation Oncology, a tertiary cancer centre in Kerala, India. The objective was to record the pattern of recurrence among triple negative breast cancer patients who completed their planned radical treatment. 171 patients with triple negative breast cancer were included in the study. Patients who completed the planned radical treatment were kept under regular follow up. Details of clinical examination and investigations during the follow up were recorded periodically. </span><b><span style="font-family:Verdana;">Results</span></b><span style="font-family:Verdana;">: Out of 171 patients 30 patients had </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">a </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">recurrence of disease. Median age of the population was 53 years. Among the 30 patients who had </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">a </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">recurrence, 16 patients (53%) had systemic relapse and 14 patients (47%) had locoregional relapse. Lung was found to be the most common site of distant metastasis (37%). Ipsilateral chest wall was found to be the most common site of locoregional relapse (50%). 6 months disease free survival was found to be 91.8%</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">and 1-year disease free survival was found to be 70.2%. </span><b><span style="font-family:Verdana;">Conclusion</span></b><span style="font-family:Verdana;">: Among radically treated triple negative breast cancers relapses, systemic recurrence was more than locoregional recurrences.</span></span></span></span>展开更多
<strong>Objective:</strong><span><span><span style="font-family:""><span style="font-family:Verdana;"> Describe the epidemiological, diagnostic, therapeutic...<strong>Objective:</strong><span><span><span style="font-family:""><span style="font-family:Verdana;"> Describe the epidemiological, diagnostic, therapeutic and evolutionary profile of triple negative breast cancer at the Dakar Cancer Institute in Senegal. </span><b><span style="font-family:Verdana;">Patients and Methods:</span></b><span style="font-family:Verdana;"> This was a retrospective study between January 1, 2011 and December 31, 2014. All patients with a triple negative molecular profile were included. The data were collected from the medical records of the patients. The data were entered and analyzed with SPSS edition 16 software under Windows 7</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">.</span></span></span><span><span><span style="font-family:""> <b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">Two hundred and twenty-five patients were selected. The mean age was 47.9 ± 12.5 years with extremes of 25 and 90 years. The main reason for consultation was dominated by the finding of a breast lump. The mean clinical tumor size was 8</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">, </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">54 cm with a large majority of T3-T4 tumors 26% and 63% respectively, lymph node involvement in one hundred and seventy-two cases (76.4%);twenty eight patients (12.4%) were metastatic from the outset. Non-specific invasive carcinoma was the most common histologic type (78.2%), and more than half of the patients (53.3%) had an aggressive tumor (Scarff-Bloom-Richardson grading III). Neoadjuvant chemotherapy was performed in 65.78% of cases. We noted 27.7% total response and 41.7% partial response in patients who have received this neoadjuvant chemotherapy. The surgery was radical in 77% of cases, conservative in 14% and cleanliness surgery for palliative purposes in 9% of cases. Adjuvant radiotherapy is performed in 58.6% of operated patients. The mean time to follow-up was 20.63 months with extremes of 1 and 53 months. Overall survival was 69.8% at one year, 41.6% at two years and 25.6% at three years. </span><b><span style="font-family:Verdana;">Conclusion: </span></b><span style="font-family:Verdana;">The descriptive analysis of these results confirms the high frequency of triple-negative breast cancer in Senegal and its poor prognosis.</span></span></span></span>展开更多
A retrospective, serial analysis of 181 triple negative breast cancer (TNBC) patients was undertaken at a regional cancer centre in Canada. The primary focus of the analysis was to investigate the effect of presenting...A retrospective, serial analysis of 181 triple negative breast cancer (TNBC) patients was undertaken at a regional cancer centre in Canada. The primary focus of the analysis was to investigate the effect of presenting stage in patients with TNBC on progression free and overall survival. We were able to demonstrate that patients presenting with an earlier stage breast cancer had a significantly superior progression free and overall survival when compared to more advanced stage. The adjusted multivariate cox-regression analyses for the overall and progression free survival suggest that the hazard of death was significantly lower for patients with stages I (HR = 0.09;95% CI 0.03 - 0.24) and II (HR = 0.29;95% CI 0.16 - 0.54) than for patients with stage III. The only other predictor of progression free survival besides stage, was receipt of radiotherapy (HR = 0.39;95% CI 0.22 - 0.69) in the adjusted cox regression analysis. Less than 2% of patients presented with stage IV disease. The small numbers presenting with stage IV disease may have impact on the development of clinical and translational trials. Certainly there may be stage migration if staging included more standardized or more sensitive investigations such as PET scans, and this might an important consideration in developing clinical trials. Twenty-five percent of patients presented with stage I disease. It is important for patients with TNBC presenting with earlier stages of disease that they are aware that they will have a better prognosis than their counterparts with more advanced disease. It is important that we are aware of this patient population, as their treatment recommendations are unclear and a source of a fair amount of controversy currently.展开更多
文摘OBJECTIVE:To evaluate the therapeutic effect of a selfformulated Traditional Chinese Medicine(TCM),Shugan Jieyu San(疏肝解郁散),on improvement of liver function and depression alleviation in the patients with triple negative breast cancer(TNBC).METHODS:A total of 60 patients diagnosed with TNBC and depression were enrolled and randomly assigned to either the control group(receiving routine tumor treatment and duloxetine)or the treatment group(receiving the TCM in addition to routine treatment).RESULTS:Both treatment and control groups showed a reduction in depressive symptoms and improved daily living abilities after treatment.However,the treatment group demonstrated significantly better outcomes compared to the control group.Furthermore,the levels of dopamine and serotonin in the serum increased in both groups after 8 weeks of treatment,while the treatment group exhibited superior results.CONCLUSIONS:This TCM showed promising results in reducing depressive symptoms and improving daily abilities in patients with TNBC and comorbid depression,which was verified by the increase in serum levels of dopamine and serotonin,suggesting the potential involvement of these neurotransmitters in the therapeutic effects of this TCM.
基金Administration of Traditional Chinese Medicine of Zhejiang Province and Young Talents Fund Project of Zhejiang Province Traditional Chinese Medicine Scienese and Technology Project(2022ZQ015).
文摘Background:Intratumoral flora and its metabolites play an important role in the occurrence,development and treatment of cancer,and are correlated with the genotype expression of breast cancer;However,the internal relationship between intratumoral flora and triple negative breast cancer(TNBC)has not been elucidated.Methods:Fourteen patients with TNBC who met the criteria were included.The tumor tissues and adjacent tissues were respectively taken as the patient group and the control group.The 5R 16S sequencing technique was used to detect the abundance and distribution of the intratumoral flora between the two groups,and the differences between the groups were analyzed to find the bacteria with significant differences between groups(P<0.05).Results:The abundance of intratumoral microbiota in TNBC patients was significantly lower than that in adjacent tissues(P<0.05).The differential bacteria in TNBC tumors(P<0.05)included Acinetobacter,Renibacterium,Flavobacterium,Dechloromonas and others.The differential bacteria genera(P<0.05)in the adjacent tissues included Comamonas,Bacillus,Caulobacter,Afipia,Aerococcus,Roseomonas and so on.Conclusion:There is a significant difference in the flora structure between the tumor and normal tissues in TNBC patients.Proteobacteria plays an important role in the occurrence,development and treatment of TNBC.Among them,Acinetobacter may be the key reason for the metastasis of TNBC.
基金supported by the National Natural Science Foundation of China(No.22304073)the Dongguan Science and Technology of Social Development Program(No.20231800935782)。
文摘Triple-negative breast cancer(TNBC)is one of the most lethal diseases and lack of feasible therapeutic methods.Herein,we developed a bioactive covalent organic framework(COF)for adoptive cell therapy(ACT)of TNBC.In our design,Mn^(2+)functionalized COF was employed as a bioactive CpG carrier,which could simultaneously engineer and polarize macrophages to the antitumor phenotype,via the synergistic interaction of CpG and Mn^(2+).In the in vitro experiments,the engineered macrophages were found to secret high levels of antitumor cytokines for efficient TNBC cell inhibition.In the in vivo antitumor model,bioactive COF-engineered macrophages were found to relieve the hypoxia tumor microenvironment,enabling prevention of immune cell depletion during ACT.Thus,we realized efficient TNBC therapy and metastasis inhibition with the engineered macrophages in a long-term therapy model.This work provides a promising strategy for metastatic TNBC treatment and highlights the importance of bioactive COF in biomedicine.
基金supported by National Natural Science Foundation of China(81402496,81673455and 81602627)China Postdoctoral Special Science Foundation(2017T100704)China Postdoctoral Science Foundation(2015M580794)
文摘OBJECTIVE To discover a small molecule targeting ULK1-modulated cell death of triple negative breast cancer and exploreits potential mechanisms.METHODS ULK1 expression was analyzed by The Cancer Genome Atlas(TCGA)analysis and tissue microarray(TMA)analysis.ULK1agonist was designed by using in silico screening,as well as modified by chemical synthesis and screened by kinase and anti-proliferative activities.The amino acid residues that key to the activation site of LYN-1604 were determined by site-directed mutagenesis,as well as in vitro kinase assay and ADP-Glo kinase assay.The mechanisms of LYN-1604 induced cell death were investigated by fluorescence microscope,western blotting,flow cytometry analysis,immunocytochemistry,as well as si RNA and GFP-m RFP-LC3 plasmid transfections.Potential ULK1 interactors were discovered by performing comparative microarray analysis and the therapeutic effect of LYN-1604 was assessed by xenograft breast cancer mouse model.RESULTS We found that ULK1 was remarkably downregulated in breast cancer tissue samples,especial y in triple negative breast cancer(TNBC).32 candidate smal molecules were synthesized,and we discovered a small molecule named LYN-1604 as the best candidate ULK1agonist.Additionally,we identified that three amino acid residues(LYS50,LEU53 and TYR89)were key to the activation site of LYN-1604 and ULK1.Subsequently,we demonstrated that LYN-1604 could induce autophagy-associated cell death via ULK complex(ULK1-m ATG13-FIP200-ATG101)in MDA-MB-231 cells.We also found that LYN-1604 induced cell death involved in ATF3,RAD21 and caspase 3,accompanied with autophagy and apoptosis.Moreover,we demonstrated that LYN-1604 had a good therapeutic potential on TNBC by targeting ULK1-modulated cell death in vivo.CONCLUSION We discovered a small molecule(LYN-1604)has therapeutic potential by targeting ULK1-modulated cell death associated with autophagy and apoptosis of TNBC in vitro and in vivo,which could be utilized as a new anti-TNBC drug candidate.
基金the National Natural Science Foundation of China(Grant No.81172532).
文摘Triple negative breast cancer(TN BC)is a complex and malignant breast cancer subtype that lacks expression of the estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor 2(H ER2),thereby making therapeutic targeting difficult.TNBC is generally considered to have high malignancy and poor prognosis.However,patients diagnosed with certain rare histomorphologic subtypes of TNBC have better prognosis than those diagnosed with typical triple negative breast cancer.In addition,with the discovery and development of novel treatment targets such as the androgen receptor(AR),PI3K/AKT/mTOR and AMPK signaling pathways,as well as emerging immunotherapies,the therapeutic options for TNBC are increasing.In this paper,we review the literature on various histological types of TNBC and focus on newly developed therapeutic strategies that target and potentially affect molecular pathways or emerging oncogenes,thus providing a basis for future tailored therapies focused on the mutational aspects of TNBC.
基金supported in part by the grants from the National Natural Science Foundation of China (Grant No. 81472462)Medical Guidance Foundation of Shanghai Municipal Science and Technology Commission (Grant No. 15411966400)Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission (Grant No. 14411950200, 14411950201) and Sanofi
文摘Objective： A previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide（TC） regimen was inferior to docetaxel, anthracycline and cyclophosphamide（TAC） in neoadjuvant treatment of triple-negative breast cancer（TNBC） and human epidermal growth factor receptor-2-（HER2）-positive breast cancer in a short-term follow-up. Herein, long-term follow-up survival outcomes have been investigated.Methods： TNBC or HER2-positive patients were randomized to receive 6 cycles of TC or TAC neoadjuvant treatment. The primary endpoint was pathological complete remission（p CR）. Secondary endpoints included clinical response rate, event-free survival（EFS）, and overall survival（OS）.Results： A cohort of 96 patients consisted of 45 in TC and 51 in TAC arm. With a median follow-up period of53（range, 8-76） months, the patients achieving p CR post neoadjuvant chemotherapy exhibited superior EFS and OS than patients without p CR（P〈0.05）. TAC treatment resulted in consistently better EFS than TC treatment：the estimated 5-year EFS was 66.1% vs. 29.8%（P=0.002）. Moreover, the estimated 5-year OS was also in favor of TAC： 88.4% vs. 51.6%（P〈0.001）. Multivariable analysis demonstrated that the treatment regimen was an independent prognostic factor, and patients treated with TAC had a superior EFS [hazard ratio（HR）, 0.48; 95%confidence interval（95% CI）, 0.26-0.90; P=0.021] and OS（HR, 0.20; 95% CI, 0.08-0.60; P=0.003）.Conclusions： The updated long-term follow-up data demonstrated a sustained benefit in EFS and OS from anthracycline-containing TAC treatment, indicating that anthracycline is an essential and effective drug in this clinical trial.
文摘Metastatic triple negative breast cancer(TNBC)has an aggressive phenotype with a predilection for visceral organs and brain.Best responses to chemotherapy are predominately in the first line.Recent studies have demonstrated improved progression free survival with the combination of atezolizumab/pembrolizumab and chemotherapy in programmed death-ligand 1 positive metastatic TNBC.However,a recent trial in a similar population showed no benefit for atezolizumab and paclitaxel which led to a Food and Drug Administration alert.Two phase III trials(OLYMPIAD and BROCADE3)demonstrated a benefit in progression free survival(PFS)but not overall survival in patients with BRCAassociated metastatic TNBC treated with Olaparib or Talazoparib respectively.For those treated with Talazoparib,the time to deterioration in health related-quality of life was also longer compared to chemotherapy.The BROCADE3 trial demonstrated that the combination of a platinum and veliparib increased PFS in first-line metastatic TNBC but at the cost of increased toxicity.There are no headto-head comparisons of a poly(adenosine diphosphate-ribose)polymerase inhibitors(PARPi)and platinums.There are unanswered questions regarding the role of PARPi maintenance after platinum therapy as is standard of care in BRCAassociated ovarian cancer.Other areas of therapeutic interest include targeting aberrations in the phosphoinositide 3-kinase pathway,protein kinase B,mammalian target of rapamycin or utilising antibody drug conjugates.This review focusses on recent and emerging therapeutic options in metastatic TNBC.We searched PubMed,clinicaltrials.gov and recent international meetings from American Society of Clinical Oncology,San Antonio Breast Cancer Conference and the European Society of Medical Oncology.
基金supported by the Nanjing Medical Science and Technique Development Foundation(ZKX17041)the Natural Science Foundation of Jiangsu Province(BK20161120)+2 种基金the Maternal and child health research project of Jiangsu Province(F201628)the Priority Academic Program Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine)Top-notch Academic Programs Project of Jiangsu Higher Education Institutions(PPZY2015A067)。
文摘Triple negative breast cancer(TNBC) is an aggressive subtype of breast cancer that currently lacks effective biomarkers and therapeutic targets required to investigate the diagnosis and treatment of TNBC. Here we performed a comprehensive differential analysis of 165 TNBC samples by integrating RNA-seq data of breast tumor tissues and adjacent normal tissues from both our cohort and The Cancer Genome Atlas(TCGA). Pathway enrichment analysis was conducted to evaluate the biological function of TNBC-specific expressed genes. Further multivariate Cox proportional hazard regression was performed to evaluate the effect of these genes on TNBC prognosis. In this report, we identified a total of 148 TNBC-specific expressed genes that were primarily enriched in mammary gland morphogenesis and hormone levels related pathways, suggesting that mammary gland morphogenesis might play a unique role in TNBC patients differing from other breast cancer types. Further survival analysis revealed that nine genes(FSIP1, ADCY5, FSD1, HMSD, CMTM5, AFF3, CYP2 A7, ATP1 A2,and C11 orf86) were significantly associated with the prognosis of TNBC patients, while three of them(ADCY5,CYP2 A7, and ATP1 A2) were involved in the hormone-related pathways. These findings indicated the vital role of the hormone-related genes in TNBC tumorigenesis and may provide some independent prognostic markers as well as novel therapeutic targets for TNBC.
基金Supported by the National Natural Science Foundation of China:Based on the"Hu-Chang"Theory,the Mechanism of Shuyu Pill on the Effect of Epithelial-mesenchymal Transition to Inhibit the Metastasis of Triple-negative Breast Cancer by P13K/Akt/mTOR Pathway(No.81960834)。
文摘OBJECTIVE:To investigate the efficacy of Biejia(Carapax Trionycis)and Ezhu(Rhizoma Curcumae Phaeocaulis)couplet medicine on epithelial-mesenchymal transition(EMT),invasion and migration of MDA-MB-231 triple negative breast cancer(TNBC)cells based on PI3K/Akt/mTOR signaling pathway.METHODS:MDA-MB-231 cells were treated with different medicated serum as Biejia-,Ezhu-,Biejia-Ezhu(BJ-,EZ-,BJ-EZ-)groups,intervened with no drug rat serum and paclitaxel with final concentration of 33 nM(IC50)as negative and positive control(NC and PC)groups.CCK-8 assay,scratch test,and Transwell assay were used to examine cell proliferation,invasion,and migration.The expression of E-cadherin,N-cadherin,Vimentin,MMP-2,MMP-9,PI3K,Akt,p-Akt,mTOR,and p-mTOR was determined by Western blot,and the m RNA expression of PI3K,Akt and mTOR was determined by real-time polymerase chain reaction.RESULTS:BJ-EZ group inhibited proliferation after 24,48,and 72 h compared with the NC group(P<0.05,<0.01 or<0.001)and reduced the invasion and migration of MDA-MB-231 cells(P<0.01 or<0.001).In addition,BJ-EZ group upregulated the expression of E-cadherin,downregulated the expression of N-cadherin,Vimentin,MMP-2,and MMP-9(P<0.05,P<0.01 or P<0.001),and inhibited the m RNA and protein expression of PI3K,Akt(p-Akt),mTOR(p-mTOR)(P<0.05,<0.01 or<0.001).CONCLUSION:Biejia(Carapax Trionycis)and Ezhu(Rhizoma Curcumae Phaeocaulis)couplet medicine can inhibit the proliferation,invasion,migration and EMT of MDA-MB-231 cells through PI3K/Akt/mTOR signaling pathway,and the effect is better than that of Biejia(Carapax Trionycis)or Ezhu(Rhizoma Curcumae Phaeocaulis)alone.
基金Supported by the National Natural Science Foundation of China(Experimental Study on Tumor Microenvironment and Intervention of Lung Metastatic Breast Cancer with the Synergistic Effect of Arsenic Trioxide,No.81256203)
文摘OBJECTIVE: To evaluate the effects of tetrandrine plus arsenic trioxide on HCC1937 cells, a triple negative breast cancer cell line, and to explore possible mechanisms.METHODS: The 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide method was used to compare the antiproliferative effects of tetrandrine,arsenic trioxide alone and tetrandrine plus arsenic trioxide on HCC1937 cells. The median-effect principle(Chou-Talalay combination index method) was used to examine the interaction between the two drugs. Flow cytometry was used to evaluate effects of treatment with tetrandrine, arsenic trioxide or the combination of both on HCC1937 cell apoptosis. Real-time polymerase chain reaction and western blotting were performed to evaluate changes in apoptosis-related gene expression and protein levels.RESULTS: Tetrandrine and arsenic trioxide each in-hibited HCC1937 cell proliferation in a dose-dependent manner. The cell inhibition rate of HCC1937 cells treated with a combination of tetrandrine and arsenic trioxide was significantly higher than with either compound alone. The two drugs produced a synergistic effect when the inhibition rate was20%-40%. Flow cytometry results showed that treatment with the two drugs increased the proportion of apoptotic cells. In the combination treated group, caspase-3 activation and PARP cleavage were significantly higher than in the other groups.Moreover, Bcl-2 and survivin expression were decreased, whereas that of both Bid and Bax was increased.CONCLUSION: These findings demonstrated that tetrandrine plus arsenic trioxide had synergistic efficacy on induction of apoptosis in HCC1937 cells.
文摘Objective： The triple negative （TN） metastatic breast cancer （MBC） patients are known to have worse prognosis, shorter progressive free survival （PFS）, and overall survival （OS）, that mandates using aggressive chemotherapy regimens. This phase II study aimed at investigating the efficacy and safety of using cisplatin and docetaxel in patients with triple negative metastatic breast cancer, and the possibility of using breast cancer susceptibility genel （BRCA1） expression as a predictive marker of chemotherapy response, and epidermal growth factor receptor （EGFR） as prognostic marker. Method： Between January 2006 and March 2009, 40 eligible patients with TN MBC were included in the study. We examined BRCA1 expression and EGFR protein in their specimens using immunohistochemistry. The patients were treated with cisplatin 75 mg/m2 and docetaxel 75 mg/m2 every 3 weeks, TN measurable MBC patients previously treated with anthracycline in their adjuvant or neo adjuvant settings were included in the study. Results： The median age of the treated patients was 43.5 years. Nearly half of the patients had an ECOG performance status of 0 or 1, and about third of them had one metastatic site. These metastatic sites were predominantly visceral in 80% of the patients. Fifty-five percent of TNMBC stained positive for BRCA1 and sixty-five percent for EGFR. Positivity for both markers was significantly associated with grade III tumors （P = 0.004）, OS, and PFS （P = 0.001 and 0.009） respectively. Overall, the regimen was well tolerated as Gill vomiting and neurological side effects were observed in 20% of the patients. Other toxiciUes were generally mild and medically manageable; with no treatment mortality was recorded. The overall disease control rate （ODCR） was 60%; the median PFS was 8 months, with a median overall OS of 17.5 months; while the median OS among responders was 23 months （95% CI 21.35 to 25.32）. The patients with negative EGFR had a significantly better OR, PFS, and OS than EGFR positive cases. There was no significant difference concerning OR, PFS, and OS, between positive and negative BRCA1 cases, which could be attributed to the better efficacy of cisplatin in the positive BRCA1 cases. Conclusion： This chemotherapy regimen is effective with tolerable toxicity profile, our results point out the importance of BRCA1 expression as predictive marker of chemotherapy response, and EGFR as prognostic marker, which could identify a certain group of patients with more aggressive disease who might benefit from using anti EGFR targeted therapy plus cisplatin.
文摘The triple-negative subtype of breast cancer(TNBC)has the bleakest prognosis,owing to its lack of either hormone receptor as well as human epidermal growth factor receptor 2.Henceforth,immunotherapy has emerged as the front-runner for TNBC treatment,which avoids potentially damaging chemotherapeutics.However,despite its documented association with aggressive side effects and developed resistance,immune checkpoint blockade continues to dominate the TNBC immunotherapy scene.These immune checkpoint blockade drawbacks necessitate the exploration of other immunotherapeutic methods that would expand options for TNBC patients.One such method is the exploitation and recruitment of natural killer cells,which by harnessing the innate rather than adaptive immune system could potentially circumvent the downsides of immune checkpoint blockade.In this review,the authors will elucidate the advantageousness of natural killer cell-based immuno-oncology in TNBC as well as demonstrate the need to more extensively research such therapies in the future.
文摘Objective： The aim of the study was to investigate the long-term therapeutic effects of triple negative breast cancers （TNBCs） and find a standardized treatment. Methods： The clinical data and survival status of 69 patients with TNBC were collected, who were treated from 2003 to 2007 at Chongqing Cancer Institute, China. Results： Median observation for 61 months showed the local recurrence rate was 13.0% （9/69）, the overall survival （OS） rate was 76.8% （53/69） and the disease free survival （DFS） rate was 59.4% （41169）. Log-rank univariate survival analysis showed the OS and DFS rates of TNBCs with axillary lymph node metastasis were 38.1% and 23.8%, respectively, and the OS and DFS rates of triple negative breast cancer with axillary lymph node non-metastasis were 93.6% and 75.0%, respectively. There were significant differences comparing with two groups. Indictor analysis of age, menstruation status, tumor size, TNM stage, histological type, neoadjuvant chemotherapy and p53 did not show any prognostic influence. Conclusion： The axillary nodes metastasis is associated with DFS and OS in triple negative breast cancers. Cisplatin-based chemotherapy may be good choice for triple negative breast cancers with metastasis or local recurrence, who received Anthracycline and Taxane-based chemotherapy. Targeted therapies strategies such as EGFR-targeted therapy may be necessary.
基金supported by the National Natural Science Foundation of China(Grant No.12272293)Guangdong Basic and Applied Basic Research Foundation(Grant Nos.2022A1515010967 and 2023A1515012821).
文摘Vibration isolation for low frequency excitation and the power supply for low power monitoring sensors are important issues in bridge engineering.The main problem is how to effectively combine the vibration isolator with the energy harvester to form a multi-functional structure.In this paper,a system called quasi-zero stiffness energy harvesting isolator(QZS-EHI)with triple negative stiffness(TNS)is proposed.The TNS structure consists of linear springs,rigid links,sliders,and ring permanent magnets.Newton’s second law and Kirchhoff’s law construct dynamic equations of the QZS-EHI,and a comparison is made to contrast it with other QZS and linear isolators.The comparison field includes the QZS range,amplitude-frequency relationship,force transmissibility,and energy harvested power.The isolator can be applied to many engineering fields such as bridges,automobiles,and railway transportation.This paper selects bridge engineering as the main field for the dynamic analysis of this system.Considering the multi-span beam bridge,this paper compares different situations including the bridge with QZS-EHI support,with linear stiffness isolator support,and with single beam support.All results show that the QZS-EHI is not only better than the traditional isolator with linear stiffness under both harmonic and stochastic excitation,but also better than some QZS isolators with double or single negative stiffness in bridge vibration isolation and energy harvesting.Theoretical analysis is verified to correspond to the simulation analysis,which means the proposed QZS-EHI has practical application value.
文摘Objective： To study the clinicopathological characters Methods： A total of 629 patients with breast cancer of triple negative breast cancer （TNBC）. were reviewed, who were treated from 2003 to 2007 in Chongqing Cancer Institute. The comparison of clinicopathological features including TNM classification, histological type, tumor location, axillary lymphonodes status and neoadjuvant chemotherapy between TNBC and nontriple negative breast cancer （NTNBC） was performed. The overall response was evaluated by whether the patients achieve complete remission （CR） and partial remission （PR） after chemotherapy. Results： There were 69 TNBCs in the 629 patients with breast cancer. The premenopausal patients, which was found in 49/69 of TNBCs, was more than NTNBCs. The average diameter of tumor in TNBC group was 4.1 cm, lager than NTNBC group. TNBC with axillary nodes metastasis occurred in 21 cases, and the axillary nodes metastasis rate was lower than NTNBC. The positive expression rate of p53 in TNBC was 44.9%, and the overall response （CR＋PR） was 72.2%. No statistical differences were found regarding the positive expression rate of p53 and the overall response between TNBC and NTNBC. Conclusion： TNBC were a group of primary breast cancers with triple negative, tending to occur in premenopausal women, with larger tumors, lower axillary nodes metastasis rate. TNBC had worse clinical prognosis and currently lacked effective targeted therapies.
文摘BACKGROUND Forkhead box P3(FOXP3)is a specific marker for immunosuppressive regulatory T(T-reg)cells.T-regs and an immunosuppressive enzyme,indoleamine 2,3-dioxygenase(IDO),are associated with advanced disease in cancer.AIM To evaluate the co-expression of FOXP3 and IDO in triple negative breast cancer(TNBC)with respect to hormone-positive breast cancer patients from Pakistan.METHODS Immunohistochemistry was performed to analyze the expression of FOXP3,IDO,estrogen receptor,progesterone receptor,and human epidermal growth factor receptor on tissues of breast cancer patients(n=100):Hormone-positive breast cancer(n=51)and TNBC(n=49).A total of 100 patients were characterized as FOXP3 negative vs positive and further categorized based on low,medium,and high IDO expression score.Univariate and multivariate logistic regression models were used.RESULTS Out of 100 breast tumors,25%expressed FOXP3 positive T-regs.A significant coexpression of FOXP3 and IDO was observed among patients with TNBC(P=0.01)compared to those with hormone-positive breast cancer.Two variables were identified as significant independent risk factors for FOXP3 positive:IDO expression high(adjusted odds ratio(AOR)5.90;95%confidence interval(CI):1.22-28.64;P=0.03)and TNBC(AOR 2.80;95%CI:0.96-7.95;P=0.05).CONCLUSION Our data showed that FOXP3 positive cells might be associated with high expression of IDO in TNBC patients.FOXP3 and IDO co-expression may also suggest its involvement in disease,and evaluation of FOXP3 and IDO expression in TNBC patients may offer a new therapeutic option.
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<strong>Background:</strong><span><span><span style="font-family:""><span style="font-family:Verdana;"> In India approximately 20% of the patients with breast cancer are triple receptor negative. Owing to the aggressive nature and shorter disease-free survival judicious follow up and identification of failure pattern will benefit the patient. Similar studies have been conducted among non-Hispanic population and in China. This study aims to identify failure pattern in radically treated breast cancer patients who are triple receptor negative among Indian population. </span><b><span style="font-family:Verdana;">Methods</span></b><span style="font-family:Verdana;">: This prospective observational study was conducted in the Department of Radiation Oncology, a tertiary cancer centre in Kerala, India. The objective was to record the pattern of recurrence among triple negative breast cancer patients who completed their planned radical treatment. 171 patients with triple negative breast cancer were included in the study. Patients who completed the planned radical treatment were kept under regular follow up. Details of clinical examination and investigations during the follow up were recorded periodically. </span><b><span style="font-family:Verdana;">Results</span></b><span style="font-family:Verdana;">: Out of 171 patients 30 patients had </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">a </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">recurrence of disease. Median age of the population was 53 years. Among the 30 patients who had </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">a </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">recurrence, 16 patients (53%) had systemic relapse and 14 patients (47%) had locoregional relapse. Lung was found to be the most common site of distant metastasis (37%). Ipsilateral chest wall was found to be the most common site of locoregional relapse (50%). 6 months disease free survival was found to be 91.8%</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">and 1-year disease free survival was found to be 70.2%. </span><b><span style="font-family:Verdana;">Conclusion</span></b><span style="font-family:Verdana;">: Among radically treated triple negative breast cancers relapses, systemic recurrence was more than locoregional recurrences.</span></span></span></span>
文摘<strong>Objective:</strong><span><span><span style="font-family:""><span style="font-family:Verdana;"> Describe the epidemiological, diagnostic, therapeutic and evolutionary profile of triple negative breast cancer at the Dakar Cancer Institute in Senegal. </span><b><span style="font-family:Verdana;">Patients and Methods:</span></b><span style="font-family:Verdana;"> This was a retrospective study between January 1, 2011 and December 31, 2014. All patients with a triple negative molecular profile were included. The data were collected from the medical records of the patients. The data were entered and analyzed with SPSS edition 16 software under Windows 7</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">.</span></span></span><span><span><span style="font-family:""> <b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">Two hundred and twenty-five patients were selected. The mean age was 47.9 ± 12.5 years with extremes of 25 and 90 years. The main reason for consultation was dominated by the finding of a breast lump. The mean clinical tumor size was 8</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">, </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">54 cm with a large majority of T3-T4 tumors 26% and 63% respectively, lymph node involvement in one hundred and seventy-two cases (76.4%);twenty eight patients (12.4%) were metastatic from the outset. Non-specific invasive carcinoma was the most common histologic type (78.2%), and more than half of the patients (53.3%) had an aggressive tumor (Scarff-Bloom-Richardson grading III). Neoadjuvant chemotherapy was performed in 65.78% of cases. We noted 27.7% total response and 41.7% partial response in patients who have received this neoadjuvant chemotherapy. The surgery was radical in 77% of cases, conservative in 14% and cleanliness surgery for palliative purposes in 9% of cases. Adjuvant radiotherapy is performed in 58.6% of operated patients. The mean time to follow-up was 20.63 months with extremes of 1 and 53 months. Overall survival was 69.8% at one year, 41.6% at two years and 25.6% at three years. </span><b><span style="font-family:Verdana;">Conclusion: </span></b><span style="font-family:Verdana;">The descriptive analysis of these results confirms the high frequency of triple-negative breast cancer in Senegal and its poor prognosis.</span></span></span></span>
文摘A retrospective, serial analysis of 181 triple negative breast cancer (TNBC) patients was undertaken at a regional cancer centre in Canada. The primary focus of the analysis was to investigate the effect of presenting stage in patients with TNBC on progression free and overall survival. We were able to demonstrate that patients presenting with an earlier stage breast cancer had a significantly superior progression free and overall survival when compared to more advanced stage. The adjusted multivariate cox-regression analyses for the overall and progression free survival suggest that the hazard of death was significantly lower for patients with stages I (HR = 0.09;95% CI 0.03 - 0.24) and II (HR = 0.29;95% CI 0.16 - 0.54) than for patients with stage III. The only other predictor of progression free survival besides stage, was receipt of radiotherapy (HR = 0.39;95% CI 0.22 - 0.69) in the adjusted cox regression analysis. Less than 2% of patients presented with stage IV disease. The small numbers presenting with stage IV disease may have impact on the development of clinical and translational trials. Certainly there may be stage migration if staging included more standardized or more sensitive investigations such as PET scans, and this might an important consideration in developing clinical trials. Twenty-five percent of patients presented with stage I disease. It is important for patients with TNBC presenting with earlier stages of disease that they are aware that they will have a better prognosis than their counterparts with more advanced disease. It is important that we are aware of this patient population, as their treatment recommendations are unclear and a source of a fair amount of controversy currently.
