المؤلفون: Ganesan, Kumar, Xu, Cong, Wu, Jianming, Du, Bing, Liu, Qingqing, Sui, Yue, Song, Cailu, Zhang, Jinhui, Tang, Hailin^{Aff4, IDs1142702324992_cor9}, Chen, Jianping^{Aff1, IDs1142702324992_cor10}

المصدر: Science China Life Sciences. :1-18

المؤلفون: Li, Lei^{Aff1, Aff2}, Zhou, Xinglu^{Aff3, Aff4}, Cui, Wenju^{Aff1, Aff2}, Li, Yingci, Liu, Tianyi, Yuan, Gang^{Aff1, Aff2, IDs00432023053292_cor6}, Peng, Yunsong^{Aff6, IDs00432023053292_cor7}, Zheng, Jian^{Aff1, Aff2}

المصدر: Journal of Cancer Research and Clinical Oncology. 149(17):15469-15478

المؤلفون: Liu Y, Tang J, Qiu X, Teng LA, Sriwastva MK, Han X, Li Z, Liu M, Liu S, Da D, Zhen L, Ren Y

المصدر: Breast Cancer: Targets and Therapy, Vol Volume 15, Pp 403-419 (2023)

مصطلحات موضوعية: extracellular vehicles, exosomes, breast cancer lung metastasis, mir-200c, rab1a, mirna sorting, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Yuting Liu,1,* Jie Tang,1,* Xiaolan Qiu,1,* Lucy A Teng,2 Mukesh K Sriwastva,2 Xuedong Han,1 Zhi Li,1 Minmin Liu,1 Shuangyue Liu,1 Dongzhu Da,1 Zhi Li,1 Linlin Zhen,1 Yi Ren1 1Department of Breast and Thyroid Surgery, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China; 2Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, Louisville, KY, USA*These authors contributed equally to this workCorrespondence: Yi Ren; Linlin Zhen, Department of Breast and Thyroid Surgery, The Affiliated Huai’an No. 1 People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China, Email only_renyi@163.com; simu1027@sina.comBackground: Recent therapeutic approaches have improved survival rate for women with breast cancer, but the survival rate for metastatic breast cancer is still low. Exosomes released by various cells are involved in all steps of breast cancer development.Methods: We established the multimodal imaging report expression in breast cancer cells with lentivirus vectors pGluc and pBirA to investigate the secreted exosomes. Comparative microRNA (miRNA) analysis was performed with miRNA qPCR array in mice with breast cancer lung metastasis. The co-immunoprecipitation and chromatin immunoprecipitation assays were used to identify the mechanism of miRNA sorting to exosomes. The potential therapeutic strategy using an anti-sorting antibody was used to investigate breast cancer lung metastasis.Results: We identified 26 high- and 32 low-expression level miRNAs in exosomes from metastasis compared to those from primary tumors and normal tissues. The tumor suppressors, including miR-200c and let-7a, were reduced in tumor tissues and metastasis but increased in the respective exosomes compared to normal tissues. Furthermore, the Ras-related protein (Rab1A) facilitated miR-200c sorting to exosomes circumventing the influence of tumor suppressor miR-200c on tumor cells, while the metastatic exosome cargo miR-200c inhibited F4/80+ macrophage immune response. Administration of anti-Rab1A antibody significantly repressed the trafficking of miR-200c to exosomes and breast cancer lung metastasis.Conclusion: Our study has identified a novel molecular mechanism for breast cancer lung metastasis mediated by exosome cargo miRNAs and provided a new therapeutic strategy for cancer immunotherapy.Graphical Abstract: Keywords: extracellular vehicles, exosomes, breast cancer lung metastasis, miR-200c, Rab1A, miRNA sorting

وصف الملف: electronic resource

Relation: https://www.dovepress.com/rab1a-mediated-exosomal-sorting-of-mir-200c-enhances-breast-cancer-lun-peer-reviewed-fulltext-article-BCTT; https://doaj.org/toc/1179-1314

URL الوصول: https://doaj.org/article/9f0fc7d103c443f2bf77a107df832592

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المؤلفون: WenYi Wang, JiaJing Liu, YuQiu Chen, XiaoFan Xu, LiQun Huo, XuLin Wang, Jun Gu

المصدر: Frontiers in Surgery, Vol 9 (2023)

مصطلحات موضوعية: breast cancer lung metastasis, nomogram, prognosis, SEER, survival, Surgery, RD1-811

الوصف: Background & objectivesAn effective tool for forecasting the survival of BCLM is lacking. This study aims to construct nomograms to predict overall survival (OS) and breast cancer-specific survival (BCSS) in breast cancer patients with de novo lung metastasis, and to help clinicians develop appropriate treatment regimens for breast cancer lung metastasis (BCLM) individuals.MethodsWe gathered clinical data of 2,537 patients with BCLM between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Cox regression analysis was employed to identify independent prognostic parameters for BCLM, which were integrated to establish nomograms by R software. The discriminative ability and predictive accuracy of the nomograms were assessed using the concordance index (C-index), receiver operating characteristic (ROC) curves, and calibration plots. Kaplan–Meier analyses were applied to evaluate the clinical utility of the risk stratification system and investigate the survival benefit of primary site surgery, chemotherapy, and radiotherapy for BCLM patients.ResultsTwo nomograms shared common prognostic indicators including age, marital status, race, laterality, grade, AJCC T stage, subtype, bone metastasis, brain metastasis, liver metastasis, surgery, and chemotherapy. The results of the C-index, ROC curves, and calibration curves demonstrated that the nomograms exhibited an outstanding performance in predicting the prognosis of BCLM patients. Significant differences in the Kaplan–Meier curves of various risk groups corroborated the nomograms' excellent stratification. Primary site surgery and chemotherapy remarkably improved OS and BCSS of BCLM patients whether the patients were at low-risk or high-risk, but radiotherapy did not.ConclusionsWe successfully developed prognostic stratification nomograms to forecast prognosis in BCLM patients, which provide important information for indicating prognosis and facilitating individualized treatment regimens for BCLM patients.

وصف الملف: electronic resource

Relation: https://www.frontiersin.org/articles/10.3389/fsurg.2022.939132/full; https://doaj.org/toc/2296-875X

URL الوصول: https://doaj.org/article/a7516d1e65494bdca0b92d0e9c9b0dbc

المؤلفون: Ying Yang, Tao Lu, Xiaowei Jia, Yan Gao

المصدر: Diagnostics, Vol 13, Iss 10, p 1724 (2023)

مصطلحات موضوعية: triple-negative breast cancer, breast cancer lung metastasis, follistatin-like 1 (FSTL1), tumor microenvironment, M2-like tumor-associated macrophages, Medicine (General), R5-920

الوصف: Immune cell infiltration into the tumor microenvironment is associated with cancer prognosis. Tumor-associated macrophages play essential roles in tumor initiation, progression, and metastasis. Follistatin-like protein 1 (FSTL1), a widely expressed glycoprotein in human and mouse tissues, is a tumor suppressor in various cancers and a regulator of macrophage polarization. However, the mechanism by which FSTL1 affects crosstalk between breast cancer cells and macrophages remains unclear. By analyzing public data, we found that FSTL1 expression was significantly low in breast cancer tissues compared to normal breast tissues, and high expression of FSTL1 in patients indicated prolonged survival. Using flow cytometry, we found that total and M2-like macrophages dramatically increased in the metastatic lung tissues during breast cancer lung metastasis in Fstl1+/− mice. Transwell assay in vitro and q-PCR experimental results showed that FSTL1 inhibited macrophage migration toward 4T1 cells by decreasing CSF1, VEGF-α, and TGF-β secretion in 4T1 cells. We demonstrated that FSTL1 inhibited M2-like tumor-associated macrophage recruitment toward the lungs by suppressing CSF1, VEGF-α, and TGF-β secretion in 4T1 cells. Therefore, we identified a potential therapeutic strategy for triple-negative breast cancer.

وصف الملف: electronic resource

Relation: https://www.mdpi.com/2075-4418/13/10/1724; https://doaj.org/toc/2075-4418

URL الوصول: https://doaj.org/article/30e58d0478f04f04a360851b933af51a

المؤلفون: Kangtao Wang, Yuqiang Li, Dan Wang, Zhongyi Zhou

المصدر: Journal of Personalized Medicine, Vol 13, Iss 1, p 43 (2022)

مصطلحات موضوعية: breast cancer lung metastasis (BCLM), estrogen receptor (ER), web-based dynamic nomogram, SEER database, overall survival (OS), Medicine

الوصف: Background: 60–70% of patients who die from breast cancer have lung metastases. However, there is a lack of readily available tools for accurate risk stratification in patients with breast cancer lung metastases (BCLM). Therefore, a web-based dynamic nomogram was developed for BCLM to quickly, accurately, and intuitively assess overall and cancer-specific survival rates. Methods: Patients diagnosed with BCLM between 2004 and 2016 were extracted from the Surveillance, Epidemiology, and Final Results (SEER) database. After excluding incomplete data, all patients were randomly assigned to training and validation cohorts (2:1). Patients’ basic clinical information, detailed pathological staging and treatment information, and sociological information were included in further analysis. Nomograms were constructed following the evaluations of the Cox regression model and verified using the concordance index (C-index), calibration curves, time-dependent receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Web-based dynamic nomograms were published online. Results: 3916 breast cancer patients with lung metastases were identified from the SEER database. Based on multivariate Cox regression analysis, overall survival (OS) and cancer-specific survival (CSS) are significantly correlated with 13 variables: age, marital status, race, grade, T stage, surgery, chemotherapy, bone metastatic, brain metastatic, liver metastatic, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). These are included in the construction of the nomogram of OS and CSS. The time-dependent receiver operating characteristic curve, decision curve analysis, consistency index, and calibration curve prove the distinct advantages of the nomogram. Conclusions: Our web-based dynamic nomogram effectively integrates patient molecular subtype and sociodemographic characteristics with clinical characteristics and guidance and can be easily used. ER-Negative should receive attention in diagnosing and treating BCLM.

وصف الملف: electronic resource

Relation: https://www.mdpi.com/2075-4426/13/1/43; https://doaj.org/toc/2075-4426

URL الوصول: https://doaj.org/article/fbc29a39f11b41989c49a2d097058704

المؤلفون: Shao, Wei, Li, Shasha, Li, Lu, Lin, Kequan, Liu, Xinhong, Wang, Haiyan, Wang, Huili, Wang, Dong^{Aff1, Aff2, Aff3}

المصدر: Protein & Cell. 10(3):161-177

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المؤلفون: Wei Shao, Shasha Li, Lu Li, Kequan Lin, Xinhong Liu, Haiyan Wang, Huili Wang, Dong Wang

المصدر: Protein & Cell, Vol 10, Iss 3, Pp 161-177 (2018)

مصطلحات موضوعية: anti-metastatic drug discovery, gene expression signature, high-throughput sequencing-based high-throughput screening, Ponatinib, breast cancer lung metastasis, c-Jun, Cytology, QH573-671, Animal biochemistry, QP501-801

الوصف: Abstract Metastasis is the leading cause of human cancer deaths. Unfortunately, no approved drugs are available for anti-metastatic treatment. In our study, high-throughput sequencing-based high-throughput screening (HTS2) and a breast cancer lung metastasis (BCLM)-associated gene signature were combined to discover anti-metastatic drugs. After screening of thousands of compounds, we identified Ponatinib as a BCLM inhibitor. Ponatinib significantly inhibited the migration and mammosphere formation of breast cancer cells in vitro and blocked BCLM in multiple mouse models. Mechanistically, Ponatinib represses the expression of BCLM-associated genes mainly through the ERK/c-Jun signaling pathway by inhibiting the transcription of JUN and accelerating the degradation of c-Jun protein. Notably, JUN expression levels were positively correlated with BCLM-associated gene expression and lung metastases in breast cancer patients. Collectively, we established a novel approach for the discovery of anti-metastatic drugs, identified Ponatinib as a new drug to inhibit BCLM and revealed c-Jun as a crucial factor and potential drug target for BCLM. Our study may facilitate the therapeutic treatment of BCLM as well as other metastases.

وصف الملف: electronic resource

Relation: http://link.springer.com/article/10.1007/s13238-018-0533-8; https://doaj.org/toc/1674-800X; https://doaj.org/toc/1674-8018

URL الوصول: https://doaj.org/article/315f7f43904f476088fa9fbc75b66233