Breast Cancer : Targets and Therapy最新文献

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Identification and Validation of circDOCK1/miR-138-5p/GRB7 Axis for Promoting Breast Cancer Progression.
IF 3.3 4区 医学
Breast Cancer : Targets and Therapy Pub Date : 2024-11-26 eCollection Date: 2024-01-01 DOI: 10.2147/BCTT.S495517
Yan Zhang, Mei Yang, Yiping Wang, Junhao Zhao, Pei Yao Lee, Yuhua Ma, Shaohua Qu
{"title":"Identification and Validation of circDOCK1/miR-138-5p/GRB7 Axis for Promoting Breast Cancer Progression.","authors":"Yan Zhang, Mei Yang, Yiping Wang, Junhao Zhao, Pei Yao Lee, Yuhua Ma, Shaohua Qu","doi":"10.2147/BCTT.S495517","DOIUrl":"10.2147/BCTT.S495517","url":null,"abstract":"<p><strong>Background: </strong>Non-coding RNAs have received increasing attention in human tumors, with RNA interaction networks playing important roles in breast cancer. This study aims to explore novel circular RNAs and their mechanisms of biological function in breast cancer.</p><p><strong>Methods: </strong>Six HER2-positive breast cancer tissues and paired normal tissues were obtained for the whole transcriptome RNA sequencing. Differentially expressed (DE) circRNAs, miRNAs and mRNAs were identified and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DERNAs were performed. DECircRNAs- DEmiRNAs- DEmRNAs networks were constructed and further verified by bioinformatics database analyses, luciferase assays and RIP assays. The expression level of circDOCK1 in breast cancer specimens was measured using qRT-PCR. Functional rescue experiments were conducted to explore the role of circDOCK1/miR-138-5p/GRB7 axis in breast cancer cells. The correlation of circDOCK1 expression and clinicopathologic features of 102 HER2 positive breast cancer patients was analyzed.</p><p><strong>Results: </strong>A total of 6960 DEmRNAs, 133 DE miRNAs and 1691 DE circRNAs were identified from HER2-positive breast cancer tissues and paracancerous tissues. Enrichment Analysis showed that the differential mRNAs were associated with cell division in biological processes and cell cycle and signaling pathways. GO and KEGG analysis demonstrated that DE circRNAs were mainly enriched in double-strand break repair, positive regulation of transcription by RNA polymerase II, nucleoplasma, nucleus, chromatin binding and protein binding. Forty networks of competing endogenous RNAs (ceRNAs) were constructed and circDOCK1/miR-138-5p/GRB7 axis was verified. Functional experiments revealed that the axis promotes migration and invasion of breast cancer cells. CircDOCK1 expression was elevated in breast cancer patients and correlated with adverse clinicopathologic parameters. Patients with high circDOCK1 level had poor outcomes.</p><p><strong>Conclusion: </strong>A novel circDOCK1/miR-138-5p/GRB7 axis promotes HER2 positive breast cancer metastasis and progression, providing a potential therapeutic target in the treatment of breast cancer.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"16 ","pages":"795-810"},"PeriodicalIF":3.3,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11611708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unfavorable Prognostic Impact of HER2 2+/FISH-Negativity in Older Patients with HER2-Negative and High-Risk Breast Cancer. HER2 阴性和高危乳腺癌老年患者 HER2 2+/FISH 阴性的不利预后影响
IF 3.3 4区 医学
Breast Cancer : Targets and Therapy Pub Date : 2024-11-19 eCollection Date: 2024-01-01 DOI: 10.2147/BCTT.S495183
Hao Wang, Miao Yu, Meihua Chen, Hui Li, Shiwei Liu
{"title":"Unfavorable Prognostic Impact of HER2 2+/FISH-Negativity in Older Patients with HER2-Negative and High-Risk Breast Cancer.","authors":"Hao Wang, Miao Yu, Meihua Chen, Hui Li, Shiwei Liu","doi":"10.2147/BCTT.S495183","DOIUrl":"10.2147/BCTT.S495183","url":null,"abstract":"<p><strong>Purpose: </strong>Human epidermal growth factor receptor 2 (HER2)-low breast cancer, consisted of carcinomas with HER2 protein 1+ or 2+ without gene amplification, has been considered a biologically heterogeneous disease. Limited research separately investigated the prognostic significance of HER2 2+ without gene amplification, and no evidence can be identified in older patients. In this dedicated cohort of older patients with HER2-negative and high-risk breast cancer, we analyzed the real-world prognosis after standard adjuvant chemotherapy, and investigated the associations of survival with HER2 2+ without gene amplification.</p><p><strong>Patients and methods: </strong>From January 2016 to December 2021, older patients (≥65 years) with breast cancer were reviewed, and HER2-negative/high-risk disease receiving standard adjuvant chemotherapy was included. HER2-negativity was defined as immunohistochemistry (IHC) score 0, 1+ or 2+ without gene amplification by fluorescent in situ hybridization (FISH). Cox proportional hazards regression analyses were performed to assess the associations of HER2 2+/FISH-negativity with disease-free survival (DFS), which was estimated by the Kaplan-Meier method and compared by the Log rank test.</p><p><strong>Results: </strong>This cohort consisted of 121 consecutive older patients. With a median follow-up of 46 months, 12 patients had a DFS event. By univariate and multivariate analyses, HER2 2+/FISH-negativity was the only independent predictor for worse DFS (hazard ratio 5.56; <i>P</i>=0.046). Patients with HER2 2+/FISH-negativity had significantly poorer DFS compared with those with HER2 0 or 1+ (Log rank test, <i>P</i>=0.029). In both hormone receptor (HR)-positive (Log rank test, <i>P</i>=0.052) and HR-negative (Log rank test, <i>P</i>=0.125) subgroups, HER2 2+/FISH-negativity showed a marginally significant adverse influence on DFS.</p><p><strong>Conclusion: </strong>In older patients with HER2-negative/high-risk breast cancer undergoing standard adjuvant chemotherapy, our findings suggest that HER2 2+/FISH-negativity has an independent negative impact on prognosis.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"16 ","pages":"785-793"},"PeriodicalIF":3.3,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neuron-Specific Gene Family Member 1 is a Potential New Therapeutic Target Associated with Immune Cell Infiltration for Breast Cancer. 神经元特异性基因家族成员 1 是与乳腺癌免疫细胞浸润相关的潜在新治疗靶点
IF 3.3 4区 医学
Breast Cancer : Targets and Therapy Pub Date : 2024-11-15 eCollection Date: 2024-01-01 DOI: 10.2147/BCTT.S483757
Haoyun Zhang, Ying Li, Ran Wang, Xindan Hu, Zai Wang
{"title":"Neuron-Specific Gene Family Member 1 is a Potential New Therapeutic Target Associated with Immune Cell Infiltration for Breast Cancer.","authors":"Haoyun Zhang, Ying Li, Ran Wang, Xindan Hu, Zai Wang","doi":"10.2147/BCTT.S483757","DOIUrl":"10.2147/BCTT.S483757","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) is the most common cancer and is highly morphologically and molecularly heterogeneous. Neuron-specific gene family member 1 (NSG1) is a small single-channel transmembrane protein that consists of 185 amino acids and has been reported in a variety of tumours in recent years. However, the role of NSG1 in BC is unclear.</p><p><strong>Objective: </strong>This study aimed to explore the role of NSG1 in the pathogenesis and development of BC and its potential as a prognostic marker for BC.</p><p><strong>Methods: </strong>This study analysed data from The Cancer Genome Atlas database and the Gene Expression Omnibus database to determine the expression level and prognostic value of NSG1 messenger ribonucleic acid in BC. Using this data, we constructed a clinical risk model. Immunohistochemistry was performed in combination with a clinical cohort of 192 patients with BC to explore the NSG1 protein expression in BC. Enrichment analysis was used to predict the biological function of NSG1 in BC. To analyse the correlation between NSG1 and the BC immune microenvironment, a single-cell analysis of NSG1 expression and cells in BC was performed. Kaplan‒Meier curves and Cox regression analysis were utilised to identify the relationship between the expression of NSG1 protein and clinicopathological features and prognosis.</p><p><strong>Results: </strong>Neuron-specific gene family member 1 is highly expressed in patients with early BC, and its expression suggests a good prognosis for patients with BC. Neuron-specific gene family member 1 is involved in the T-cell receptor complex in BC and is associated with CD8 T cells in the BC immune microenvironment and may induce M1 polarisation of macrophages.</p><p><strong>Conclusion: </strong>Neuron-specific gene family member 1 is a biomarker of good prognosis in BC. It is associated with the immune microenvironment of BC and may be a potential therapeutic target.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"16 ","pages":"769-783"},"PeriodicalIF":3.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Aneuploid Circulating Endothelial Cells with Prognostic Value in Locally Advanced Breast Cancer Patients After Neoadjuvant Chemotherapy. 新辅助化疗后局部晚期乳腺癌患者中具有预后价值的非整倍体循环内皮细胞
IF 3.3 4区 医学
Breast Cancer : Targets and Therapy Pub Date : 2024-11-12 eCollection Date: 2024-01-01 DOI: 10.2147/BCTT.S487336
Minghui Li, Yuelin Liu, Xu Han, Tao Li, Zhizheng Zhang, Ningyi Xue, Mengdi Liang, Ge Ma, Tiansong Xia
{"title":"Aneuploid Circulating Endothelial Cells with Prognostic Value in Locally Advanced Breast Cancer Patients After Neoadjuvant Chemotherapy.","authors":"Minghui Li, Yuelin Liu, Xu Han, Tao Li, Zhizheng Zhang, Ningyi Xue, Mengdi Liang, Ge Ma, Tiansong Xia","doi":"10.2147/BCTT.S487336","DOIUrl":"10.2147/BCTT.S487336","url":null,"abstract":"<p><strong>Background: </strong>Aneuploid circulating endothelial cells (CECs) are an indicator in breast cancer (BC). Significant changes of aneuploid CECs occurred during neoadjuvant chemotherapy (NCT). This study aimed to explore the predictive and prognostic values of aneuploid CECs in locally advanced breast cancer (LABC) patients with different NCT responses.</p><p><strong>Methods: </strong>Breast cancer patients received an EC4-T4 NCT regimen. A novel subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) strategy was applied for the detection of CECs (CD45-/CD31+/DAPI+). Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of aneuploid CEC counts in distinguishing NCT-resistant patients from sensitive ones. All patients were observed for progression-free survival (PFS) and overall survival (OS).</p><p><strong>Results: </strong>The CEC counts at any time point did not show the ability to predict the efficacy of NCT. The difference in the CECs between post-chemotherapy levels and baseline could be sufficient to distinguish chemotherapy-resistant cases from other cases in Hormone+Her-2-/+ (HR+) BC patients. Patients with reduction of CECs after all courses of NCT were associated with higher probability of PFS.</p><p><strong>Conclusion: </strong>Variations in aneuploid CECs during NCT may predict chemotherapy response in patients with HR+ breast cancer. The decrease in the number of aneuploid CECs after all courses of NCT indicates better treatment outcomes in patients with LABC.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"16 ","pages":"761-768"},"PeriodicalIF":3.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of the Effects of Different Chemotherapy Methods on Blood Lipid Levels in Breast Cancer Patients. 不同化疗方法对乳腺癌患者血脂水平的影响分析
IF 3.3 4区 医学
Breast Cancer : Targets and Therapy Pub Date : 2024-11-11 eCollection Date: 2024-01-01 DOI: 10.2147/BCTT.S456422
Jiaqi Mu, Mai Zhou, GangJun Jiao
{"title":"Analysis of the Effects of Different Chemotherapy Methods on Blood Lipid Levels in Breast Cancer Patients.","authors":"Jiaqi Mu, Mai Zhou, GangJun Jiao","doi":"10.2147/BCTT.S456422","DOIUrl":"10.2147/BCTT.S456422","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;To analyze the impacts of distinct chemotherapy methods on blood lipid levels in breast cancer patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Three hundred breast cancer patients were selected as the research subjects. The inclusion time limit was from January 2021 to January 2023, and all received treatment in our hospital. Based on the therapy plan, the patients were divided into group A (epirubicin + cyclophosphamide followed by paclitaxel regimen, 103 premenopausal cases + 61 postmenopausal cases), group B (docetaxel + cyclophosphamide regimen, 41 premenopausal instances + 37 postmenopausal instances), group C (docetaxel + carboplatin regimen, 61 premenopausal instances + 24 postmenopausal instances), comparing the changes in blood lipid levels of patients in each group at pre-therapy and post-therapy, and the abnormality frequency of blood lipids in every group of patients after therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;After treatment, the triglyceride (TG) levels of the three groups of patients were clearly greater than those at pre-therapy, and the high-density lipoprotein cholesterol (HDL-C) levels were clearly less than before therapy. The levels of low-density lipoprotein cholesterol (LDL-C) in group B and C patients were clearly greater than those before therapy in the same one, while the LDL-C levels in group A were clearly less than those before therapy in the same one; after therapy, the TG levels of patients in group A were clearly less than those in group B, and LDL-C, total Cholesterol (TC) levels were clearly less than that in group B and C (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). The proportion of dyslipidemia in patients in the group A after therapy was clearly less than in group B (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). After treatment, the HDL-C levels of premenopausal patients in the three groups were clearly less than those at pre-therapy. The TG, TC, and LDL-C levels of premenopausal patients in groups B and C were clearly greater than those at pre-therapy. The TG levels of premenopausal patients in group A were clearly less than those before therapy. After treatment, the TG and TC levels of premenopausal patients in group A were clearly less than those in group C, and the LDL-C levels were clearly less than those in group B and C (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). The proportion of dyslipidemia in premenopausal patients in the group A and C after therapy was clearly less than the group B (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). After therapy, the TG levels of postmenopausal patients in the three groups were clearly greater than those at pre-therapy, and the HDL-C levels were clearly less than those at pre-therapy. The LDL-C levels of postmenopausal patients in group B and C were clearly greater than those at pre-therapy. The TC and LDL-C levels of postmenopausal patients in group A were clearly less than those at pre-therapy; after therapy, the LDL-C and TC levels of postmenopausal patients in group A were clearly less than those in group B and C (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). It had no s","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"16 ","pages":"745-760"},"PeriodicalIF":3.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Serum Direct Bilirubin as a Biomarker for Breast Cancer. 作为乳腺癌生物标志物的血清直接胆红素
IF 3.3 4区 医学
Breast Cancer : Targets and Therapy Pub Date : 2024-11-07 eCollection Date: 2024-01-01 DOI: 10.2147/BCTT.S491523
Jinxi Hu, Yangjun Cai, Yijun Chen, Xiaoli Zhu
{"title":"Serum Direct Bilirubin as a Biomarker for Breast Cancer.","authors":"Jinxi Hu, Yangjun Cai, Yijun Chen, Xiaoli Zhu","doi":"10.2147/BCTT.S491523","DOIUrl":"https://doi.org/10.2147/BCTT.S491523","url":null,"abstract":"<p><strong>Background: </strong>The role of serum total bilirubin (TB) in cancer has been a subject of controversy, as has the role of its subtypes, particularly serum direct bilirubin (DB). The aim of the present study was to investigate the association between serum DB levels and breast cancer, as well as to assess the diagnostic utility of serum DB in breast cancer.</p><p><strong>Methods: </strong>A total of 5299 patients diagnosed with breast cancer for the first time at Taizhou Hospital of Zhejiang Province were included in the study, and 10028 healthy physical examination subjects were included as healthy controls. Logistics regression was used to investigate the relationship between serum DB and breast cancer, and the value of serum DB in the diagnosis of breast cancer was assessed by means of receiver operator characteristic (ROC) curve analysis.</p><p><strong>Results: </strong>The serum DB concentration in the breast cancer group was significantly higher than the healthy controls (<i>P</i> < 0.001). Multivariate logistic regression results show that serum DB was an independent risk factor for breast cancer (odds ratio [OR]=4.504, 95% confidence interval [CI]: 4.200-4.831). Subjects with a serum DB concentration in the fourth quartile had a higher risk of breast cancer occurrence compared to those in the first quartile after adjusting for age (OR = 7.155, 95%CI: 6.474-7.907). The optimal cut-off value of serum DB for diagnosing breast cancer was determined to be 2.75 μmol/L, with an area under the curve (AUC) of 0.712 (95% CI: 0.703-0.722). This value exhibited good specificity (77.0%) and negative predictive value (77.8%).</p><p><strong>Conclusion: </strong>Serum DB was identified as a risk factor for breast cancer, demonstrating good diagnostic potential for the disease. These findings suggest that serum DB could serve as a promising serum molecular marker for breast cancer.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"16 ","pages":"735-743"},"PeriodicalIF":3.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting erbB Pathways in Breast Cancer: Dual Kinase Inhibition for Brain Metastasis and Prevention of p185HER2/Neu Tumor Development. 靶向乳腺癌中的 erbB 通路:双重激酶抑制脑转移和预防 p185HER2/Neu 肿瘤发展。
IF 3.3 4区 医学
Breast Cancer : Targets and Therapy Pub Date : 2024-10-30 eCollection Date: 2024-01-01 DOI: 10.2147/BCTT.S490904
Peeyush N Goel, Makoto Katsumata, Wei Qian, Sunil Mathur, Mei Q Ji, Arabinda Samanta, Payal Grover, George Sgouros, Jenny C Chang, Mark I Greene
{"title":"Targeting erbB Pathways in Breast Cancer: Dual Kinase Inhibition for Brain Metastasis and Prevention of p185HER2/Neu Tumor Development.","authors":"Peeyush N Goel, Makoto Katsumata, Wei Qian, Sunil Mathur, Mei Q Ji, Arabinda Samanta, Payal Grover, George Sgouros, Jenny C Chang, Mark I Greene","doi":"10.2147/BCTT.S490904","DOIUrl":"10.2147/BCTT.S490904","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer predominantly affects women and poses challenges in the treatment of both local and advanced diseases. In a previous study, we reported the effectiveness of ER121, a structurally resolved small compound specifically designed to target human cancers expressing or overexpressing mutant EGFR and HER2.</p><p><strong>Purpose: </strong>The objective of this study is to assess the efficacy and toxicity of ER121 in metastatic and triple negative breast cancer (TNBC, HER2+) cells and tumor models. The Herceptin-resistant breast cancer cell line JIMT-1 was used in an in vivo tumor model, and MMTV-erbB2 (Fo5) transgenic mice models were used to evaluate the efficacy and safety of ER121 as neoadjuvant.</p><p><strong>Methods: </strong>ER121 treatment focusing on experimental brain metastasis in TNBC, HER2+ model, was quantified by total flux employing the In Vivo Imaging System (IVIS). We also compared the brain tissue from the treated and the controls groups. Additionally, ER121 was evaluated in JIMT-1, a Herceptin-resistant breast cancer cell line, both in vitro and in vivo tumor model. We also administered ER121 orally in neoadjuvant model with the MMTV-erbB2 (Fo5) transgenic mice, the survival rates were compared with the control group. Tumor-free survival of multiple treated groups were analyzed by Kaplan-Meier analysis employing the log-rank test with the Bonferroni correction using R Statistical Software.</p><p><strong>Results: </strong>In this study, we present findings indicating that ER121 treatment significantly attenuated breast tumor growth using a TNBC, HER2+ model, focusing on experimental brain metastasis, as quantified by total flux employing IVIS. These observations were further corroborated by analysis of brain tissue from the treatment group compared to controls. Data is presented as Mean ± S.D. statistical significance was calculated using Student <i>t</i> test (*<i>p</i> < 0.05). Additionally, ER121 significantly inhibited JIMT-1, a Herceptin-resistant breast cancer cell line was used in vivo xenograft model. Additionally, we used a neoadjuvant model with the MMTV-erbB2 (Fo5) transgenics and the tumor-free survival rates exhibited a remarkable difference between the control and treated groups when ER121 was administered orally. We found statistically significant p values of 0.048 employing log-rank test with Bonferroni Correction for comparing ER121 high, ER121 Low, Herceptin and PBS groups. All analyses were performed using R Statistical Software.</p><p><strong>Conclusion: </strong>ER121 is a non-toxic small-molecule erbB kinase inhibitor and holds promise as an oral and systemic therapeutic agent for treating progressive erbB-driven tumors in therapeutic settings. Moreover, ER121 shows potential as a preventive therapy in neoadjuvant settings for erbB2-associated tumors and when administered systemically can dramatically limit erbB2 brain metastases in animal models.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"16 ","pages":"725-733"},"PeriodicalIF":3.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transcription Factor Forkhead Box Protein 3 (FOXP3) as a Prognostic Indicator for Postoperative Outcomes in Patients with Breast Cancer: Establishment of a Prognostic Nomogram. 转录因子叉头盒蛋白 3 (FOXP3) 作为乳腺癌患者术后结果的预后指标:建立预后提名图。
IF 3.3 4区 医学
Breast Cancer : Targets and Therapy Pub Date : 2024-10-21 eCollection Date: 2024-01-01 DOI: 10.2147/BCTT.S484055
Chunlei Tan, Jinling Xu, Shiyuan Zhang, Shuqiang Liu, Xiaotian Yang, Danping Wu, Boqian Yu, Yuanxi Huang
{"title":"Transcription Factor Forkhead Box Protein 3 (FOXP3) as a Prognostic Indicator for Postoperative Outcomes in Patients with Breast Cancer: Establishment of a Prognostic Nomogram.","authors":"Chunlei Tan, Jinling Xu, Shiyuan Zhang, Shuqiang Liu, Xiaotian Yang, Danping Wu, Boqian Yu, Yuanxi Huang","doi":"10.2147/BCTT.S484055","DOIUrl":"10.2147/BCTT.S484055","url":null,"abstract":"<p><strong>Purpose: </strong>The current investigation is to assess FOXP3 expression in breast cancer patients and evaluate the predictive significance of FOXP3.</p><p><strong>Patients and methods: </strong>A cohort of 313 cases between January 2015 and November 2015 were enrolled this research. Immunohistochemistry (IHC) assay was utilized to detect the expression levels of FOXP3 in primary breast carcinoma specimens. These patients were separated into two groups by semiquantitative scoring approach. Chi-square test and Fisher's exact test were conducted to investigate the correlations between FOXP3 expression in tumors and clinicopathological variables. Kaplan-Meier method and Log rank test were utilized to generate survival curves for disease-free survival (DFS) and overall survival (OS). The independent factors were examined using Cox regression analysis. Nomogram models were created for assessing DFS and OS rates.</p><p><strong>Results: </strong>Depending on the levels of FOXP3 expression in tumors, these patients were categorized into two groups: low FOXP3 expression (174 cases) and high FOXP3 expression (139 cases). The patients exhibiting low levels of FOXP3 expression in tumors demonstrated a longer survival duration contrasted with those with high expression (DFS: 88.75 vs 65.87 months, χ<sup>2</sup>=36.1100, P<0.0001; OS: 89.70 vs 78.37 months, χ<sup>2</sup>=32.4900, P<0.0001). Multivariate analysis revealed that FOXP3 was a significant prognostic factor [DFS: hazard ratio (HR): 2.822, 95% CI: 1.595-4.992, P<0.0001; OS: HR: 3.232, 95% CI: 1.812-5.763, P<0.0001]. The good predictive clinical utility of FOXP3-based nomograms within the threshold probability range for different survival rates was demonstrated by calibration curve and decision curve analyses.</p><p><strong>Conclusion: </strong>FOXP3 expression serves as a crucial prognostic indicator in breast cancer patients, and may aid preoperative evaluation in clinical practice.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"16 ","pages":"705-723"},"PeriodicalIF":3.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intermediate Filaments in Breast Cancer Progression, and Potential Biomarker for Cancer Therapy: A Narrative Review. 乳腺癌进展过程中的中间丝及癌症治疗的潜在生物标记物:叙述性综述。
IF 3.3 4区 医学
Breast Cancer : Targets and Therapy Pub Date : 2024-10-14 eCollection Date: 2024-01-01 DOI: 10.2147/BCTT.S489953
Widad Aghnia Shalannandia, Yoan Chou, Muhammad Hasan Bashari, Astrid Feinisa Khairani
{"title":"Intermediate Filaments in Breast Cancer Progression, and Potential Biomarker for Cancer Therapy: A Narrative Review.","authors":"Widad Aghnia Shalannandia, Yoan Chou, Muhammad Hasan Bashari, Astrid Feinisa Khairani","doi":"10.2147/BCTT.S489953","DOIUrl":"10.2147/BCTT.S489953","url":null,"abstract":"<p><p>Intermediate filaments are one of the three components of the cytoskeletons, along with actin and microtubules. The intermediate filaments consist of extensive variations of structurally related proteins with specific expression patterns in cell types. The expression pattern alteration of intermediate filaments is frequently correlated with cancer progression, specifically with the epithelial-to-mesenchymal transition process closely related to increasing cellular migration and invasion. This review will discuss the involvement of cytoplasmic intermediate filaments, specifically vimentin, nestin, and cytokeratin (CK5/CK6, CK7, CK8/CK18, CK17, CK19, CK20, CSK1), in breast cancer progression and as prognostic or diagnostic biomarkers. The potential for drug development targeting intermediate filaments in cancer will be reviewed.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"16 ","pages":"689-704"},"PeriodicalIF":3.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Potential Role of SNRPD1 Stabilized by IGF2BP2 in the Progression of Triple-Negative Breast Cancer. 被 IGF2BP2 稳定的 SNRPD1 在三阴性乳腺癌进展中的潜在作用
IF 3.3 4区 医学
Breast Cancer : Targets and Therapy Pub Date : 2024-10-11 eCollection Date: 2024-01-01 DOI: 10.2147/BCTT.S481549
Siqi Liu, Xin Sun, Na Liu, Fangcai Lin
{"title":"The Potential Role of SNRPD1 Stabilized by IGF2BP2 in the Progression of Triple-Negative Breast Cancer.","authors":"Siqi Liu, Xin Sun, Na Liu, Fangcai Lin","doi":"10.2147/BCTT.S481549","DOIUrl":"https://doi.org/10.2147/BCTT.S481549","url":null,"abstract":"<p><strong>Background: </strong>Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an RNA-binding protein with N6-methyladenosine (m6A) reader function, is associated with the poor prognosis of various tumors, including triple-negative breast cancer (TNBC). Small nuclear ribonucleoprotein D1 polypeptide (SNRPD1), a spliceosome member, exerts diagnostic and therapeutic functions in breast cancer by regulating the cell cycle and is a potential therapeutic target. However, the interaction between IGF2BP2 and SNRPD1 in the progression of TNBC remain unclear.</p><p><strong>Objective: </strong>This study aimed to investigate the interaction between IGF2BP2 and SNRPD1 in TNBC and elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression levels of SNRPD1 and IGF2BP2 in human normal breast cells (MCF10A) and TNBC cells (MDA-MB-231). MDA-MB-231 cells were transfected with SNRPD1 interference or overexpression vectors, or co-transfected with SNRPD1 interference and IGF2BP2 overexpression vectors simultaneously. Cell viability, apoptosis, and invasion were assessed using MTT, flow cytometry, and Transwell assays. RNA stability, m6A levels, and the interaction between SNRPD1 and IGF2BP2 were evaluated using qRT-PCR, methylated RNA immunoprecipitation, and RIP assays.</p><p><strong>Results: </strong>SNRPD1 was significantly up-regulated in TNBC cells, promoting cell viability and invasion while inhibiting apoptosis. IGF2BP2 was also up-regulated in TNBC cells and enhanced SNRPD1 mRNA stability via m6A modification. Furthermore, IGF2BP2 overexpression reversed the anti-tumor effect of SNRPD1 knockdown.</p><p><strong>Conclusion: </strong>IGF2BP2 and SNRPD1 were significantly highly expressed in TNBC cells. IGF2BP2 might enhance the stability and protein expression of SNRPD1 through m6A-dependent mechanisms, potentially contributing to the progression of TNBC.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"16 ","pages":"679-688"},"PeriodicalIF":3.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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