Glutamine metabolism is a key driver of tumor progression, yet the molecular basis and prognostic relevance of glutamine metabolism-related genes in breast cancer (BC) remain incompletely defined. In this study, integrated analysis of public datasets identified Actin-like protein 8 (ACTL8) as a key prognostic gene significantly upregulated in BC tissue and associated with poor patient survival. In vitro, shRNA knockdown of ACTL8 reduced MYC expression and its downstream targets SLC1A5 and GLS1, suppressing cell proliferation, migration and invasion. This disruption led to impaired redox homeostasis as evidenced by reduced GSH/GSSG and NADPH/NADP+ ratios. Mechanistically, MYC overexpression restored metabolic enzymes and phenotypes but failed to rescue p-AKT levels, confirming ACTL8 acts upstream of the PI3K/AKT/mTOR axis. Virtual screening identified Momordin Ic as a small molecule that directly interacts with ACTL8. Surface plasmon resonance (SPR) and Thermal shift assay (TSA) confirmed this high-affinity binding, which destabilized ACTL8 and promoted its ubiquitin-proteasome degradation. Moreover, ACTL8 knockdown significantly attenuated the sensitivity of BC cells to Momordin Ic treatment, confirming ACTL8 as the specific therapeutic target. In vivo, suppression of ACTL8 markedly reduced tumor growth. Together, these findings establish ACTL8 as a key oncogenic driver of BC progression. Targeting ACTL8 offers a novel strategy to disrupt glutamine-dependent metabolic reprogramming, and Momordin Ic represents a promising lead agent to combat ACTL8-driven BC.

Background: This study aims to evaluate the real-world efficacy and safety of dalpiciclib in patients with hormone receptor-positive (HR+) advanced breast cancer and explore the impact of different clinical characteristics on treatment outcomes. Methods: This was a two-center, retrospective cohort study involving 76 patients treated with dalpiciclib between January 2022 and June 2024 at two affiliated hospitals of Anhui Medical University in China. Data on progression-free survival (PFS), adverse events, and key clinical factors were collected and analyzed. Kaplan-Meier estimates were used for statistical analysis. Results: The median PFS (mPFS) for the entire cohort was 12.00 months (95% CI: 10.09-13.91 months). Patients receiving dalpiciclib as first-line therapy had significantly better outcomes (mPFS: 17.00 months, 95% CI: 9.19-24.81 months) than those receiving later-line therapy (p < 0.001). Patients with prior exposure to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and those with endocrine resistance had poorer outcomes. Multivariate Cox proportional hazards regression analysis confirmed that earlier treatment line (HR for second-line vs. first-line: 3.89, p = 0.015; HR for third-line or later vs. first-line: 5.56, p = 0.006) and prior CDK4/6i treatment (HR = 3.42, p = 0.040) were independent predictors of PFS. The most common adverse events were hematologic toxicities, including leukopenia (76.6%) and neutropenia (72.4%), mostly grade 1-2. No febrile neutropenia cases were reported, indicating a manageable safety profile. Conclusions: Dalpiciclib combined with endocrine therapy is associated with favorable efficacy and safety in real-world settings, with early-line treatment and lower tumor proliferative activity associated with better outcomes. While findings suggest potential for clinical application, further large-scale prospective studies are needed to validate its effectiveness in different patient subgroups and optimize treatment strategies.

DJ-1, also known as PARK7 (Parkinson's disease protein 7), which is involved in cell viability, apoptosis, transcriptional regulation, and oxidative stress adaptation, is also involved in the pathogenesis of various human diseases including carcinogenesis. Here, we aimed to determine the novel mechanism by which DJ-1 inhibition suppresses tumor growth. Our results showed that DJ-1 knockdown in cancer cells promoted the secretion of a significantly larger amount of mitochondrial transcription factor A (TFAM) into the cell culture medium. DJ-1 knockdown promotes p53 translocation to the mitochondria and stimulates the intrinsic mitochondrial apoptosis pathway, resulting in TFAM release. Moreover, DJ-1 knockdown induced the downregulation of sirtuin 3 (SIRT3), which increased the acetylation of TFAM and triggered its release. Furthermore, we found that extracellular TFAM played a critical role in antitumor activity by upregulating the expression of chemokine (CC motif) ligand 4 (CCL4) and chemokine (C-X-C motif) ligand 5 (CXCL5) in cancer cells, contributing to the promotion of M1 macrophage polarization in the tumor microenvironment (TME). Finally, we confirmed that the DJ-1 inhibitor suppressed tumor growth by increasing TFAM release from cancer cells and M1 macrophage polarization in vivo. These findings indicate that the depletion of DJ-1 stimulates apoptosis-dependent TFAM secretion that triggers M1 macrophage polarization, indicating a new therapeutic strategy by interfering with the DJ-1 function in cancer therapy.

Breast invasive carcinoma (BRCA) is the most common type of cancer affecting women worldwide. Biomarkers such as estrogen receptor, progesterone receptor and HER2 are currently utilized in clinical practice for breast cancer diagnosis; yet their sensitivity and specificity remain limited. However, Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1), an RNA-binding protein, has been implicated in tumor progression in various cancers, yet its clinical relevance and mechanistic role in BRCA still remain unclear. The present study integrated multi-omics data analysis and experimental validation to address this. G3BP1 mRNA and protein expression levels in BRCA were analyzed using The Cancer Genome Atlas, Tumor Immune Estimation Resource (TIMER) and Clinical Proteomic Tumor Analysis Consortium databases. Kaplan-Meier survival analysis and Cox regression were employed to evaluate the prognostic value of G3BP1. Gene set enrichment analysis (GSEA) was performed to identify associated signaling pathways and immune cell infiltration correlations were assessed using CIBERSORT and TIMER. Additionally, 38 samples of BRCA and adjacent normal tissue were collected for immunohistochemical (IHC) validation and diagnostic efficacy was evaluated using receiver operating characteristic (ROC) curves. G3BP1 was significantly upregulated in BRCA tissues at both mRNA and protein levels (P<0.05). High G3BP1 expression was associated with the advanced cancer lymph node stage (P=0.005) and a poor prognosis [overall survival, disease-free survival (DFS), distant metastasis-free survival and post-progression survival; all P<0.05]. Differential gene analysis identified 67 upregulated and 9 downregulated genes. GSEA revealed G3BP1 enrichment in key pathways such as PI3K/AKT/mTOR signaling and ubiquitin-mediated proteolysis. Immune analysis showed a significant positive association between G3BP1 and M2 macrophage infiltration (P<0.05) and a significant negative association between G3BP1 and CD8+ T cells (P<0.05). IHC confirmed higher G3BP1 expression in BRCA compared with normal tissues (P<0.001), with an area under the ROC curve (AUC) of 0.777 and a 5-year DFS prediction AUC of 0.730. The present findings indicate that G3BP1 is a potential independent prognostic biomarker for BRCA. Its upregulation promotes tumor progression by activating the PI3K/AKT/mTOR signaling pathway and modulating the tumor immune microenvironment. These findings provide a theoretical foundation for targeting G3BP1 in BRCA diagnosis and immunotherapy.

Zr-based metal–organic frameworks (MOFs) using thiazolothiazole as an organic ligand exhibit excellent two-photon excited fluorescence performance, particularly in the generation of reactive oxygen species. In this study, a ZrTc nanoMOF was designed and modified with hyaluronic acid (HA) to provide good biocompatibility and cancer cell-specific targeting. In triple negative breast cancer (TNBC), the optimized composite ZrTc@HA exhibited considerable two-photon activity and excellent light-triggered O2·− generation ability at an excitation wavelength of 780 nm. ZrTc@HA can be used as a diagnostic probe for fluorescence imaging and as a therapeutic agent for photodynamic therapy (PDT) with no remarkable toxicity in vitro or in a subcutaneous tumor model in vivo. In summary, we developed a promising two-photon-activated ZrTc@HA for PDT in TNBC, with immense potential for advancements in monotherapy and synergistic phototherapy.

Cellular senescence is characterized by a tumor-suppressive program as well as a pro-inflammatory secretome. Neutrophils constitute significant compositions of malignancies and play key roles in tumor development. However, the role of senescent neutrophils in cancer progression is presently unexplored. Here, we demonstrate that neutrophils display enhanced senescence in breast cancer patients receiving chemotherapy. The senescent neutrophils produce increased number of exosomes, which confer drug resistance to tumor cells in vitro and in vivo. Mechanistically, senescent neutrophils-derived exosomal piRNA-17560 enhances the expression of fat mass and obesity-associated protein (FTO) in breast cancer cells. The upregulation of FTO further strengthens ZEB1 transcripts stability and expression by decreasing N6-methyladenosine (m6A) RNA methylation, leading to chemoresistance and epithelial-mesenchymal transition (EMT) of tumor cells. Clinically, the level of exosomal piR-17560 correlates with poor chemotherapy response in patients with breast cancer. In addition, YTHDF2 is essential for the posttranscriptional regulation of ZEB1 by piRNA-17560/FTO signaling. Senescent neutrophils secret exosomal piR-17560 in a STAT3-dependent manner. Altogether, this study suggests that senescent neutrophils-derived exosomal piR-17560 confers chemoresistance to tumor cells and senescent neutrophils may serve as a potential therapeutic target in breast cancer.

目的 探讨激素受体阳性的乳腺癌患者新辅助化疗(NACT)效果影响因素及临床病理特征变化.方法 选取安徽医科大学第一附属医院自2016年1月至2019年12月收治的接受新辅助化疗激素受体阳性的163例乳腺癌患者为研究对象.对新辅助疗效进行评估、分析NACT前后标本激素受体(HR)、人类表皮生长因子受体2(HR-2)、细胞增殖抗原(Ki-67)蛋白染色情况.采用单因素分析与多因素Logistic回归分析确定激素受体阳性的乳腺癌患者NACT效果影响因素.结果 雌激素受体(ER)、孕激素受体(PR)激素受体的染色比率与染色强度均呈正相关性(r=0.448、0.488,P<0.05).NACT后,ER、PR、Ki-67的表达率均低于NACT前,差异均有统计学意义(P<0.05).结论 未绝经、腋窝淋巴结阳性、组织学分级高、Ki-67高表达均可作为激素受体阳性乳腺癌患者NACT有效预测因素.

Neutrophils are significant compositions of solid tumors and exert distinct functions in different types of tumors. However, the precise role of neutrophils in the progression of breast cancer (BC) is presently unclear. In this study, by investigating the single-cell RNA sequencing data, we identify a new neutrophil subset, C5aR1-positive neutrophils, that correlates with tumor progression and poor survival for BC patients. Furthermore, it is discovered that C5aR1-positive neutrophils enhance BC cell glycolysis via upregulating ENO1 expression. Mechanically, C5aR1-positive neutrophil-secreted IL1β and TNFα cooperatively activate ERK1/2 signaling, which phosphorylates WTAP at serine341 and thereby stabilizes WTAP protein. The stabilization of WTAP further promotes RNA m6A methylation of ENO1, impacting the glycolytic activity of BC cells. Importantly, C5aR1-positive neutrophils also promote breast cancer growth in vivo, and this effect is abolished by WTAP silencing. In clinical BC samples, increased C5aR1-positive neutrophils correlate with elevated IL1β, TNFα, and ENO1 expression. A high co-expression of C5aR1-positive neutrophil gene signature and ENO1 predicts worse prognosis of BC patients compared with a low co-expression. Collectively, our study reveals a novel subset of C5aR1-positive neutrophils that induces breast cancer glycolysis via increasing ERK1/2-WTAP-dependent m6A methylation of ENO1. These findings support the potential for exploration of C5aR1-positive neutrophils as a therapeutic target in breast cancer.

Objective:To explore the correlation among supportive care needs, psychological resilience and quality of life in breast cancer patients undergoing postoperative chemotherapy.Methods:A total of 140 female breast cancer patients who received postoperative chemotherapy in the daycare ward of the First Affiliated Hospital of Anhui Medical University from July to December 2019 were selected as subjects for a cross-sectional investigation. The Chinese version of Supportive Care Need Survey (SCNS)-SF34, Chinese version of Connor-Davidson Resilience Scale (CD-RISC), Chinese version of Function Assessment of Cancer Therapy-Breast (FACT-B) were used for evaluation. The t test or one-factor variance analysis was used to compare the SCNS-SF34, CD-RISC and FACT-B scores among breast cancer patients with different clinical characteristics, and Pearson correlation analysis was used to explore the correlation among the scores of three scales. The influence of SCNS-SF34 and CD-RISC dimensions on FACT-B score was analyzed by multiple linear regression.Results:A total of 140 questionnaires were distributed, 138 were recovered, and 4 incomplete questionnaires were excluded. There were 134 valid questionnaires, with an effective rate of 95.7%. SCNS-SF34 score of 134 patients was 140.3±11.3, CD-RISC score was 59.6±8.0, FACT-B score was 88.8±13.7. There were significant differences in SCNS-SF34, CD-RISC and FACT-B scores among patients with different educational level, family monthly income, medical insurance type, clinical stage of tumor, chemotherapy course and surgical method (SCNS-SF34 score: F=7.161, 4.780, 7.413, 3.505, 8.996, t=3.750, all P<0.050; CD-RISC score: F=6.628, 5.059, 7.292, 4.533, 9.105, t=-2.822, all P<0.050; FACT-B score: F=6.350, 5.152, 6.771, 3.955, 8.180, t=-2.373, all P<0.050), and there was a significant difference in CD-RISC score among patients with different marital status (F=3.144, P=0.046). SCNS-SF34 score was negatively correlated with CD-RISC score and FACT-B score (r=-0.947, -0.918, both P<0.001), and CD-RISC score was positively correlated with FACT-B score (r=0.963, P<0.001). Tenacity and self-reliance were the influencing factors of FACT-B score (B=4.235, 95%CI: 3.873-4.596, t=23.157, P<0.001; B=0.417, 95%CI: 0.059-0.775, t=2.304, P=0.023).Conclusions:Breast cancer patients undergoing postoperative chemotherapy have different supportive care needs and low psychological resilience and quality of life scores. Patients with low levels of psychological resilience have a high need for supportive care. Tenacity and self-reliance can predict patients’ quality of life. Nursing staff can give different nursing interventions according to patients’ supportive care needs and psychological resilience.

目的 分析年轻女性乳腺癌患者的临床特征及死亡的影响因素.方法 回顾性分析2008年1月至2013年12月安徽医科大学第一附属医院和安徽省立医院乳腺外科收治的年轻(年龄≤35岁)女性乳腺癌患者130例的临床资料,统计患者临床特征(肿瘤大小、位置、病理类型、临床分期、淋巴结转移数目、雌孕激素受体表达等);依据患者5年生存与否,将患者分为生存组92例与死亡组17例,采用单因素分析患者临床特点与死亡的相关性,通过logistic回归分析患者死亡的影响因素.结果 130例患者中,肿瘤位置发生在外上象限占62.3％,浸润性导管癌占84.6％.单因素分析显示,淋巴结转移数目和雌孕激素受体表达等因素组间差异有统计学意义(P<0.05);logistic分析显示,淋巴结转移数目是患者死亡的独立影响因素(P=0.001).结论 年轻女性乳腺癌患者肿瘤主要位于外上象限且以浸润性导管癌多见,淋巴结转移数目是影响年轻女性乳腺癌患者死亡的独立影响因素.

Purpose: To investigate the differential diagnosis and diagnostic values of the elasticity score, strain rate ratio, and area ratio methods in ultrasonic elastography for benign and malignant breast lesions. Methods: We retrospectively analyzed the medical records of 165 patients with breast cancer and assessed and compared the diagnostic values of the elasticity score, strain rate ratio, and area ratio methods. Results: The elasticity score, strain rate ratio, and area ratio methods showed differences in mean diagnostic values for benign and malignant breast tumors (P<0.05; sensitivities, 80.6%, 74.5%, and 50.3%, respectively; and specificities, 85.5%, 95.2%, and 97.6%, respectively). The accuracies of the elasticity score and strain rate ratio methods were higher than those of the area ratio method (P<0.05). The specificity of the elasticity score method for the diagnosis of breast lesions was lower than that of the strain rate ratio and area ratio methods (P<0.05). The areas under the receiver operating curve for the diagnosis of breast lesions were 0.903, 0.858, and 0.744 for the strain rate ratio, elasticity score, and area ratio methods, respectively. Conclusion: The differential diagnostic value of the strain rate ratio method in ultrasonic elastography was high for benign and malignant breast tumors.

Background: FAS cell surface death receptor (FAS) gene has 2 common single nucleotide polymorphisms (SNPs) in its promoter, FAS-1377> A (rs2234767) and FAS-670A > G (rs1800682). Several studies have investigated the role of these 2 polymorphisms in etiology of breast cancer in Asian population while the outcomes are inconsistent. To derive a more precise assessment of the association between breast cancer susceptibility with FAS gene promoter SNPs, a meta-analysis of published studies was performed. Material and methods: We systematically searched PubMed, Embase, Web of Science, and the Chinese biomedical database (CBM) for papers published until November 1, 2018. Odds ratio (OR) with 95% confidential interval (95%CI) was conducted to evaluate the associations. Statistical analysis was conducted using Stata 13.0 software. A total of 8 studies covering 2564 cases and 2633 controls were included. Results: The integrated results suggest the following: For the FAS-1377G/A polymorphism, we only found significant associations for allele G vs allele A (OR=1.100, 95%CI=1.004-1.206, P=.040). After stratification by ethnicity, a significant association was observed only for the AA+GA vs GG genotype in East Asian populations (OR=1.177, 95% CI=1.010-1.371, P=.037). The association was not found in West Asian populations. For the FAS -670A/G polymorphism, no association with cancer risk was found in any comparison model. Sensitivity analysis suggests that the meta-analysis results obtained after excluding any single study were similar to the original ones, suggesting that the meta-analysis results were not significantly affected by any single study. Conclusion: These results indicated that FAS-1377G/A polymorphism may contribute to the increased breast cancer susceptibility and could be a promising target for cancer risk prediction. Further studies are needed to determine if the FAS gene confers a risk of breast cancer in other ethnic groups, such as Africans and Latin Americans.

Hedgehog (Hh) pathway hyperactivation has been observed in various tumors, including breast cancer, and Hh pathway inhibitors have demonstrated antitumor activity in breast cancer. The tumor microenvironment (TME) has been shown to play an important role in modulating cancer cell drug sensitivity, but the TME response to Hh pathway inhibitors is unclear. In the current study, we observed increased TME infiltration of macrophages in breast cancer tissue, and specifically, M2 polarized macrophages after neoadjuvant chemotherapy. Furthermore, we observed an enhanced tolerance to Hh pathway inhibitors in MDA-MB-231 cells after co-culturing with M2 macrophages. In addition, we demonstrated that Hh pathway inhibition significantly induced IL6 expression, and validated that the tolerance to Hh pathway inhibitors was IL6-dependent. This study demonstrates a role of macrophages in Hh pathway inhibition resistance and a role of macrophage-derived IL6 in this resistance of breast cancer cells to Hh inhibition. These data indicate that antagonizing IL6 together with Hh pathway inhibitors may be a novel therapeutic strategy for breast cancer.

目的 大肿块乳腺癌患者往往合并有远处转移,预后差.本研究前瞻性观察紫杉醇联合卡铂周方案序贯卡培他滨一线治疗晚期大肿块乳腺癌的有效性与安全性.方法 2015-01-01-2018-04-30就诊安徽医科大学第一附属医院的初诊Ⅳ期大肿块乳腺癌患者16例,乳腺原发肿块分期T3～T4,且合并远处器官转移,给予紫杉醇75 mg/m2联合卡铂AUC=2方案,每7d重复,用药≤12周,客观疗效评价达到完全缓解(complete remission,CR)、部分缓解(partial response,PR)患者序贯卡培他滨单药2 000mg/m2,口服,2次/d,d1～d14,21d为1个周期.近期客观疗效评价采用RECIST 1.1标准,不良反应评价采用NCI-CTCAE 4.0标准.结果 可评价疗效16例患者,使用紫杉醇卡铂周方案化疗达CR 1例(6.3％),PR 13例(81.3％),稳定(stable disease,SD)2例(12.5％),CR+PR患者共14例进入卡培他滨序贯治疗,1例患者达到CR,中位无进展生存时间(progression free survival time,PFS)达到9.8个月,中位总生存时间尚未达到,1年生存率93.7％.Ⅲ～Ⅳ度不良反应为白细胞下降11例(78.6％),血小板下降2例(14.3％),恶心2例(14.3％),转氨酶升高1例(7.1％).结论 紫杉醇联合卡铂周方案序贯卡培他滨一线治疗晚期大肿块乳腺癌起效快,疗效好,不良反应可控.

曲线美是女性得天独厚的宝贵资源.然而,乳腺疾病一直是影响女性健与美的问题之一.如何防患于未然,让乳房保持健康、美丽?坚持定期自我检查乳房健康状况,不失为一种很好的保健方法.长期自我检查,便于早期发现乳房异常.月经正常的女性,自我检查乳房的最佳时间可以选在月经来潮后的第9-11天.

Rationale and Objectives Chemotherapy has many side effects on breast cancer patients, including cognition and other brain functions impairment, which can be studied using functional magnetic resonance imaging (fMRI). Our study aimed at investigating the executive function alternations of breast cancer patients after chemotherapy using resting-state fMRI. Materials and Methods This study included 32 breast cancer patients (BC group) and 24 control subjects (HC group). The functional connectivity of the dorsolateral prefrontal cortex (DLPFC) of the two groups was calculated from the resting-state fMRI data, and the correlation between the strength of the right DLPFC's connectivity and the behavior performance was analyzed with two-tailed Pearson correlative analysis. Results Evaluation of the capability of processing various complex cognition events showed that the executive function of the BC group was impaired after chemotherapy in comparison with the HC group. The functional connectivities of the right DLPFC with the right inferior frontal gyrus, right medial frontal gyrus, and left superior temporal gyrus in the BC group were significantly decreased in comparison with those in the HC group, respectively. The executive deficits were found correlated with the functional connectivity between the right DLPFC and the right inferior frontal gyrus. Meantime, the functional connectivity from the right DLPFC to the right middle temporal gyrus and the precuneus was compensatorily increased in the BC group, respectively. Conclusions These findings suggest that breast cancer patients after chemotherapy demonstrate executive control impairment, and provide evidence that the observed defects are correlated with alternations in the executive network of the brain. Chemotherapy has many side effects on breast cancer patients, including cognition and other brain functions impairment, which can be studied using functional magnetic resonance imaging (fMRI). Our study aimed at investigating the executive function alternations of breast cancer patients after chemotherapy using resting-state fMRI. This study included 32 breast cancer patients (BC group) and 24 control subjects (HC group). The functional connectivity of the dorsolateral prefrontal cortex (DLPFC) of the two groups was calculated from the resting-state fMRI data, and the correlation between the strength of the right DLPFC's connectivity and the behavior performance was analyzed with two-tailed Pearson correlative analysis. Evaluation of the capability of processing various complex cognition events showed that the executive function of the BC group was impaired after chemotherapy in comparison with the HC group. The functional connectivities of the right DLPFC with the right inferior frontal gyrus, right medial frontal gyrus, and left superior temporal gyrus in the BC group were significantly decreased in comparison with those in the HC group, respectively. The executive deficits were found correlated with the functional connectivity between the right DLPFC and the right inferior frontal gyrus. Meantime, the functional connectivity from the right DLPFC to the right middle temporal gyrus and the precuneus was compensatorily increased in the BC group, respectively. These findings suggest that breast cancer patients after chemotherapy demonstrate executive control impairment, and provide evidence that the observed defects are correlated with alternations in the executive network of the brain.

RATIONALE AND OBJECTIVES:Chemotherapy has many side effects on breast cancer patients, including cognition and other brain functions impairment, which can be studied using functional magnetic resonance imaging (fMRI). Our study aimed at investigating the executive function alternations of breast cancer patients after chemotherapy using resting-state fMRI.MATERIALS AND METHODS:This study included 32 breast cancer patients (BC group) and 24 control subjects (HC group). The functional connectivity of the dorsolateral prefrontal cortex (DLPFC) of the two groups was calculated from the resting-state fMRI data, and the correlation between the strength of the right DLPFC's connectivity and the behavior performance was analyzed with two-tailed Pearson correlative analysis.RESULTS:Evaluation of the capability of processing various complex cognition events showed that the executive function of the BC group was impaired after chemotherapy in comparison with the HC group. The functional connectivities of the right DLPFC with the right inferior frontal gyrus, right medial frontal gyrus, and left superior temporal gyrus in the BC group were significantly decreased in comparison with those in the HC group, respectively. The executive deficits were found correlated with the functional connectivity between the right DLPFC and the right inferior frontal gyrus. Meantime, the functional connectivity from the right DLPFC to the right middle temporal gyrus and the precuneus was compensatorily increased in the BC group, respectively.CONCLUSIONS:These findings suggest that breast cancer patients after chemotherapy demonstrate executive control impairment, and provide evidence that the observed defects are correlated with alternations in the executive network of the brain.

BACKGROUND:Radiotherapy is of critical importance in the treatment of breast cancer. However, not all patients derive therapeutic benefit and some breast cancers are resistant to the treatment, and are thus evidenced with prospective distant metastatic spread and local recurrence. In this study, we investigated the potential therapeutic effects of all-trans retinoic acid (ATRA) on radiation-resistant breast cancer cells and the associated invasiveness.METHODS:The MCF7/C6 cells with gained radiation resistance after a long term treatment with fractionated ionizing radiation were derived from human breast cancer MCF7 cell line, and are enriched with cells expressing putative breast cancer stem cell biomarker CD44(+)/CD24(-/low)/ALDH(+). The enhanced invasiveness and the acquired resistances to chemotherapeutic treatments of MCF7/C6 cells were measured, and potential effects of all-trans retinoic acid (ATRA) on the induction of differentiation, invasion and migration, and on the sensitivities to chemotherapies in MCF7/C6 cells were investigated.RESULTS:MCF7/C6 cells are with enrichment of cancer stem-cell like cells with positive staining of CD44(+)/CD24(-/low), OCT3/4 and NANOG. MCF7/C6 cells showed an increased tumoregensis potential and enhanced aggressiveness of invasion and migration. Treatment with ATRA induces the differentiation in MCF7/C6 cells, resulting in reduced invasiveness and migration, and increased sensitivity to Epirubincin treatment.CONCLUSION:Our study suggests a potential clinic impact for ATRA as a chemotherapeutic agent for treatment of therapy-resistant breast cancer especially for the metastatic lesions. The study also provides a rationale for ATRA as a sensitizer of Epirubincin, a first-line treatment option for breast cancer patients.

目的 研究内皮细胞特异性分子-1(ESM-1)作为敏感的分子标志物对乳腺癌预后的预测及复发的判断.方法 选取133例乳腺癌患者石蜡标本,进行癌组织和癌旁组织切片,采用免疫组化法研究ESM-1蛋白的表达,分析ESM-1与肿瘤生物学行为及患者预后之间的关系.结果 ESM-1的表达在乳腺癌组织中弱,而在癌旁组织中强;在分期早的肿瘤中表达高于分期晚的肿瘤.ESM-1和乳腺癌的预后有着密切的关系,在腋窝转移阳性患者中ESM-1表达低于腋窝阴性患者且差异有统计学意义(P＜0.05),人类表皮生长因子受体2(HER-2)过表达患者中ESM-1的表达低于HER-2无扩增患者,差异有统计学意义(P＜0.05),其他相关因素差异无统计学意义.结论 ESM-1可以成为判断乳腺癌患者预后的一个分子标志物,ESM-1在组织中的高表达往往预示着该患者有较好的预后和长期的生存.

Introduction Complaint about attention disorders is common among breast cancer patients who have undergone chemotherapy, which may be associated with the default mode network (DMN). To validate this hypothesis, we investigated the DMN functional connectivity (FC) change and its relationship with the attention function in breast cancer patients (BC) using resting-state functional magnetic resonance imaging (rs-fMRI). Methods Twenty-two BC treated with chemotherapy and 22 healthy controls (HC) were recruited into this study. The FC between the DMN’s hubs and regions of the dorsal medial prefrontal cortex (dMPFC) and medial temporal lobe (MTL) subsystems was respectively calculated for each participant. Results The statistical result showed significantly lower connectivity in dMPFC and MTL subsystems in the BC group. In addition, the partial correlation analysis result indicated that the low connectivity of some brain regions in MTL subsystem was correlated with attention dysfunction following BC chemotherapy. Conclusion These results suggest that the functional disconnection in MTL subsystem of the DMN may have association with attention function of BC after chemotherapy.