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https://www.readbyqxmd.com/read/27926867/genomic-instability-is-induced-by-persistent-proliferation-of-cells-undergoing-epithelial-to-mesenchymal-transition
#1
Valentine Comaills, Lilian Kabeche, Robert Morris, Rémi Buisson, Min Yu, Marissa Wells Madden, Joseph A LiCausi, Myriam Boukhali, Ken Tajima, Shiwei Pan, Nicola Aceto, Srinjoy Sil, Yu Zheng, Tilak Sundaresan, Toshifumi Yae, Nicole Vincent Jordan, David T Miyamoto, David T Ting, Sridhar Ramaswamy, Wilhelm Haas, Lee Zou, Daniel A Haber, Shyamala Maheswaran
TGF-β secreted by tumor stroma induces epithelial-to-mesenchymal transition (EMT) in cancer cells, a reversible phenotype linked to cancer progression and drug resistance. However, exposure to stromal signals may also lead to heritable changes in cancer cells, which are poorly understood. We show that epithelial cells failing to undergo proliferation arrest during TGF-β-induced EMT sustain mitotic abnormalities due to failed cytokinesis, resulting in aneuploidy. This genomic instability is associated with the suppression of multiple nuclear envelope proteins implicated in mitotic regulation and is phenocopied by modulating the expression of LaminB1...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27903155/obesity-and-cancer-mechanisms-tumor-microenvironment-and-inflammation
#2
Neil M Iyengar, Ayca Gucalp, Andrew J Dannenberg, Clifford A Hudis
Purpose There is growing evidence that inflammation is a central and reversible mechanism through which obesity promotes cancer risk and progression. Methods We review recent findings regarding obesity-associated alterations in the microenvironment and the local and systemic mechanisms through which these changes support tumor growth. Results Locally, hyperadiposity is associated with altered adipose tissue function, adipocyte death, and chronic low-grade inflammation. Most individuals who are obese harbor inflamed adipose tissue, which resembles chronically injured tissue, with immune cell infiltration and remodeling...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27895501/a-fish-based-method-for-assessment-of-her-2-amplification-status-in-breast-cancer-circulating-tumor-cells-following-cellsearch-isolation
#3
Henrik Frithiof, Kristina Aaltonen, Lisa Rydén
INTRODUCTION: Amplification of the HER-2/neu (HER-2) proto-oncogene occurs in 10%-15% of primary breast cancer, leading to an activated HER-2 receptor, augmenting growth of cancer cells. Tumor classification is determined in primary tumor tissue and metastatic biopsies. However, malignant cells tend to alter their phenotype during disease progression. Circulating tumor cell (CTC) analysis may serve as an alternative to repeated biopsies. The Food and Drug Administration-approved CellSearch system allows determination of the HER-2 protein, but not of the HER-2 gene...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27889762/evaluation-of-isolation-methods-for-circulating-tumor-cells-ctcs
#4
Galatea Kallergi, Eleni Politaki, Saad Alkahtani, Christos Stournaras, Vassilis Georgoulias
BACKGROUND: Detection of CTCs is a poor prognostic factor for many cancer types; however, their very low frequency represents an obstacle for their detection. The objective of the current study was to compare the performance of commonly used methods for CTCs isolation. METHODS: The evaluated methods using spiking experiments of MCF7, SKBR3 and MDA MB-231 breast cancer cell lines were (i) ficoll density gradient separation (DGS), (ii) red blood cell lysis (Erythrolysis) isolation, (iii) positive immunomagnetic selection (EpCAM Dynal beads), (iv) two different negative immunomagnetic separation systems (Dynal vs Miltenyi CD45 beads) as well as (v) the Cell Search platform and (vi) the ISET system...
November 25, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27886589/esr1-mutations-moving-towards-guiding-treatment-decision-making-in-metastatic-breast-cancer-patients
#5
REVIEW
Lindsay Angus, Nick Beije, Agnes Jager, John W M Martens, Stefan Sleijfer
Mutations in the gene coding for the estrogen receptor (ER), ESR1, have been associated with acquired endocrine resistance in patients with ER-positive metastatic breast cancer (MBC). Functional studies revealed that these ESR1 mutations lead to constitutive activity of the ER, meaning that the receptor is active in absence of its ligand estrogen, conferring resistance against several endocrine agents. While recent clinical studies reported that the occurrence of ESR1 mutations is rare in primary breast cancer tumors, these mutations are more frequently observed in metastatic tissue and circulating cell-free DNA of MBC patients pretreated with endocrine therapy...
November 10, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27873491/detection-of-circulating-tumor-cells-in-breast-cancer-patients-using-cytokeratin-19-real-time-rt-pcr
#6
Hyung Seok Park, Hyun Ju Han, Soohyeon Lee, Gun Min Kim, Seho Park, Yeon A Choi, Jeong Dong Lee, Gi Moon Kim, Joohyuk Sohn, Seung Il Kim
PURPOSE: The roles of circulating tumor cells (CTCs) as predictive and prognostic factors, as well as key mediators in the metastatic cascade, have been investigated. This study aimed to validate a method to quantify CTCs in peripheral blood using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay for cytokeratin (CK)-19 and to evaluate the utility of this assay in detecting CTCs in breast cancer patients. MATERIALS AND METHODS: Real-time monitoring PCR of fluorescently labeled specific hybridization probes for CK-19 mRNA was established...
January 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/27870562/monitoring-of-serum-dna-methylation-as-an-early-independent-marker-of-response-and-survival-in-metastatic-breast-cancer-tbcrc-005-prospective-biomarker-study
#7
Kala Visvanathan, MaryJo S Fackler, Zhe Zhang, Zoila A Lopez-Bujanda, Stacie C Jeter, Lori J Sokoll, Elizabeth Garrett-Mayer, Leslie M Cope, Christopher B Umbricht, David M Euhus, Andres Forero, Anna M Storniolo, Rita Nanda, Nancy U Lin, Lisa A Carey, James N Ingle, Saraswati Sukumar, Antonio C Wolff
Purpose Epigenetic alterations measured in blood may help guide breast cancer treatment. The multisite prospective study TBCRC 005 was conducted to examine the ability of a novel panel of cell-free DNA methylation markers to predict survival outcomes in metastatic breast cancer (MBC) using a new quantitative multiplex assay (cMethDNA). Patients and Methods Ten genes were tested in duplicate serum samples from 141 women at baseline, at week 4, and at first restaging. A cumulative methylation index (CMI) was generated on the basis of six of the 10 genes tested...
November 21, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27868036/the-state-of-the-art-in-prediction-of-breast-cancer-relapse-using-cell-free-circulating-tumor-dna-liquid-biopsies
#8
COMMENT
Niklas Loman, Lao H Saal
No abstract text is available yet for this article.
October 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27858503/high-throughput-sequencing-of-two-populations-of-extracellular-vesicles-provides-an-mrna-signature-that-can-be-detected-in-the-circulation-of-breast-cancer-patients
#9
Andrew Conley, Valentina R Minciacchi, Dhong Hyun Lee, Beatrice S Knudsen, Beth Y Karlan, Luigi Citrigno, Giuseppe Viglietto, Muneesh Tewari, Michael R Freeman, Francesca Demichelis, Dolores Di Vizio
Extracellular vesicles (EVs) contain a wide range of RNA types with a reported prevalence of non-coding RNA. To date a comprehensive characterization of the protein coding transcripts in EVs is still lacking. We performed RNA-Sequencing (RNA-Seq) of two EV populations and identified a small fraction of transcripts that were expressed at significantly different levels in large oncosomes and exosomes, suggesting they may mediate specialized functions. However, these two EV populations exhibited a common mRNA signature that, in comparison to their donor cells, was significantly enriched in mRNAs encoding E2F transcriptional targets and histone proteins...
November 18, 2016: RNA Biology
https://www.readbyqxmd.com/read/27842518/mir-199a-5p-confers-tumor-suppressive-role-in-triple-negative-breast-cancer
#10
Jiawei Chen, Vivian Y Shin, Man T Siu, John C W Ho, Isabella Cheuk, Ava Kwong
BACKGROUND: Triple-negative breast cancer (TNBC) remains a poor prognostic factor for breast cancer since no effective targeted therapy is readily available. Our previous studies confirmed miR-199a-5p is a TNBC-specific circulating biomarker, however, its functional roles in breast cancer is largely unknown. Thus, we investigated the functional implication of miR-199a-5p in TNBC and its potential underlying mechanisms. METHODS: MTT assay was performed to investigate the cell proliferation after transient transfection of miR-199a-5p in MDA-MB-231 cell line, followed by cell cycle analysis...
November 14, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27798883/influence-of-circulating-tumour-cells-on-production-of-il-1%C3%AE-il-1%C3%AE-and-il-12-in-sera-of-patients-with-primary-diagnosis-of-breast-cancer-before-treatment
#11
Theresa Vilsmaier, Brigitte Rack, Alexander König, Klaus Friese, Wolfgang Janni, Udo Jeschke, Tobias Weissenbacher
BACKGROUND: Circulating tumour cells (CTCs) have been found to be a prognostic marker for reduced disease-free survival (DFS), distant DFS, breast cancer-specific survival, and overall survival (OS) before the start of systemic treatment. Determination of CTCs with the CellSearch System (Veridex, Raritan, NJ, USA) is a valuable but time-consuming and costly method. Therefore, the aim of this study was to evaluate cytokine profiles as a marker for CTC involvement. PATIENTS AND METHODS: Patients chosen for this study were defined as women with breast cancer who agreed to participate in the phase I SUCCESS study...
October 2016: Anticancer Research
https://www.readbyqxmd.com/read/27794222/neovasculature-and-circulating-tumor-cells-dual-targeting-nanoparticles-for-the-treatment-of-the-highly-invasive-breast-cancer
#12
Jianhui Yao, Jingxian Feng, Xiaoling Gao, Dan Wei, Ting Kang, Qianqian Zhu, Tianze Jiang, Xunbin Wei, Jun Chen
Antiangiogenesis therapy has been served as a potent cancer treatment strategy for decades, yet disrupting neovasculature would provoke tumor cells into invasive growth and result in distal metastasis. The basic cause of cancer metastasis can be traced down to the presence of circulating tumor cells (CTCs) which detach from primary tumor site and act as 'seeds'. Epithelial cell adhesion molecule (EpCAM) is a potential biomarker for selective capture of epithelium-derived CTCs. Here, we integrated tumor neovessles-targetable ligands K237 peptide with Ep23 aptamer against EpCAM into a single drug-loaded nanoplatform using paclitaxel (PTX) as the model drug, aiming at damaging the primary tumor and neutralizing CTCs simultaneously to achieve a synergistic anti-tumor therapeutic effect...
October 22, 2016: Biomaterials
https://www.readbyqxmd.com/read/27783057/dissecting-the-heterogeneity-of-circulating-tumor-cells-in-metastatic-breast-cancer-going-far-beyond-the-needle-in-the-haystack
#13
REVIEW
Michela Bulfoni, Matteo Turetta, Fabio Del Ben, Carla Di Loreto, Antonio Paolo Beltrami, Daniela Cesselli
Although the enumeration of circulating tumor cells (CTC) defined as expressing both epithelial cell adhesion molecule and cytokeratins (EpCAM⁺/CK⁺) can predict prognosis and response to therapy in metastatic breast, colon and prostate cancer, its clinical utility (i.e., the ability to improve patient outcome by guiding therapy) has not yet been proven in clinical trials. Therefore, scientists are now focusing on the molecular characterization of CTC as a way to explore its possible use as a "surrogate" of tumor tissues to non-invasively assess the genomic landscape of the cancer and its evolution during treatment...
October 24, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27776431/safflower-yellow-prevents-pulmonary-metastasis-of-breast-cancer-by-inhibiting-tumor-cell-invadopodia
#14
Huiying Fu, Renjie Wu, Yuanyuan Li, Lizong Zhang, Xiaofang Tang, Jue Tu, Weimin Zhou, Jianchao Wang, Qiyang Shou
Carthamus tinctorius L. is a traditional Chinese medicine that activates blood circulation and dissipates blood stasis, and has been extensively used as antitumor treatment in a clinical setting in single or in compound preparation form. However, empirical evidence and a better understanding of the possible mechanisms involved are still required. Here, we investigated the role of safflower yellow (SY), the active ingredient of C. tinctorius, in the pulmonary metastasis of breast cancer, and the underlying mechanism of action...
October 25, 2016: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/27771841/longitudinally-collected-ctcs-and-ctc-clusters-and-clinical-outcomes-of-metastatic-breast-cancer
#15
Chun Wang, Zhaomei Mu, Inna Chervoneva, Laura Austin, Zhong Ye, Giovanna Rossi, Juan P Palazzo, Carl Sun, Maysa Abu-Khalaf, Ronald E Myers, Zhu Zhu, Yanna Ba, Bingshan Li, Lifang Hou, Massimo Cristofanilli, Hushan Yang
PURPOSE: Circulating tumor cell (CTC) is a well-established prognosis predictor for metastatic breast cancer (MBC), and CTC-cluster exhibits significantly higher metastasis-promoting capability than individual CTCs. Because measurement of CTCs and CTC-clusters at a single time point may underestimate their prognostic values, we aimed to analyze longitudinally collected CTCs and CTC-clusters in MBC prognostication. METHODS: CTCs and CTC-clusters were enumerated in 370 longitudinally collected blood samples from 128 MBC patients...
October 22, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27764697/prognostic-impact-of-her2-and-er-status-of-circulating-tumor-cells-in-metastatic-breast-cancer-patients-with-a-her2-negative-primary-tumor
#16
Nick Beije, Wendy Onstenk, Jaco Kraan, Anieta M Sieuwerts, Paul Hamberg, Luc Y Dirix, Anja Brouwer, Felix E de Jongh, Agnes Jager, Caroline M Seynaeve, Ngoc M Van, John A Foekens, John W M Martens, Stefan Sleijfer
BACKGROUND: Preclinical and clinical studies have reported that human epidermal growth factor receptor 2 (HER2) overexpression yields resistance to endocrine therapies. Here the prevalence and prognostic impact of HER2-positive circulating tumor cells (CTCs) were investigated retrospectively in metastatic breast cancer (MBC) patients with a HER2-negative primary tumor receiving endocrine therapy. Additionally, the prevalence and prognostic significance of HER2-positive CTCs were explored in a chemotherapy cohort, as well as the prognostic impact of the estrogen receptor (ER) CTC status in both cohorts...
October 17, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27761678/circulating-tumor-cells-in-breast-cancer-applications-in-personalized-medicine
#17
Jin Sun Lee, Mark Jesus M Magbanua, John W Park
Recent technological advancements in rare cell analysis have facilitated the detection of circulating tumor cells (CTCs) in the blood of patients diagnosed with breast and other types of cancers. Numerous clinical studies involving the enumeration of CTCs in breast cancer patients have unequivocally demonstrated the prognostic value of these cells. Evidence from recent molecular studies indicates that CTCs may be potential surrogate markers for systemic disease. As such, real-time assessment of therapeutic biomarkers in breast CTCs, such as the estrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER2), may have a tremendous impact in guiding-targeted cancer therapy...
October 19, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27761367/the-role-of-micrornas-in-bone-metastasis
#18
Eugenio Zoni, Gabri van der Pluijm
The skeleton represents a common site of metastases for osteotropic cancers such as prostate and breast tumors and novel therapeutic targets and new markers for the monitoring of bone lesions are urgently needed. The formation of bone metastases is a complex process that starts at the level of the confined tumor and that is characterized by a dynamic crosstalk between the primary cancer and the future metastatic site, the bone. Factors released by the primary tumor contribute to prepare a fertile "soil", where a "pre-metastatic niche" is established prior to future colonization by cancer cells...
September 2016: Journal of Bone Oncology
https://www.readbyqxmd.com/read/27760227/reproducibility-of-digital-pcr-assays-for-circulating-tumor-dna-analysis-in-advanced-breast-cancer
#19
Sarah Hrebien, Ben O'Leary, Matthew Beaney, Gaia Schiavon, Charlotte Fribbens, Amarjit Bhambra, Richard Johnson, Isaac Garcia-Murillas, Nicholas Turner
Circulating tumor DNA (ctDNA) analysis has the potential to allow non-invasive analysis of tumor mutations in advanced cancer. In this study we assessed the reproducibility of digital PCR (dPCR) assays of circulating tumor DNA in a cohort of patients with advanced breast cancer and assessed delayed plasma processing using cell free DNA preservative tubes. We recruited a cohort of 96 paired samples from 71 women with advanced breast cancer who had paired blood samples processed either immediately or delayed in preservative tubes with processing 48-72 hours after collection...
2016: PloS One
https://www.readbyqxmd.com/read/27753034/protein-content-of-circulating-nucleoprotein-complexes
#20
Svetlana N Tamkovich, Oleg S Tutanov, Danil S Serdukov, Maxim S Belenikin, Anatoliy G Shlikht, Natalia A Kirushina, Vladimir E Voytsitskiy, Yuri P Tsentalovich, Vsevolod A Tkachuk, Pavel P Laktionov
In the current study we have investigated the protein content of blood plasma deoxyribonucleoprotein complexes. The complexes were isolated using affinity chromatography with immobilized polyclonal anti-histone antibodies. Proteins were separated by SDS PAAGE and identified by MALDI-TOF mass-spectrometry. 111 and 56 proteins (excluding histones), respectively, were identified with a good score in deoxyribonucleoprotein complexes of healthy females and breast cancer patients. However, only four of these proteins were found in 30 % of all samples...
2016: Advances in Experimental Medicine and Biology
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