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Heterogeneity breast metastasis

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https://www.readbyqxmd.com/read/27933405/current-challenges-of-metastatic-breast-cancer
#1
Bora Lim, Gabriel N Hortobagyi
Metastasis is one of the most characteristic yet problematic behaviors of cancer cells. Stage IV breast cancer accounts for a large portion of breast cancer-related morbidity and mortality. Despite early detection and improvement in survival owing to advancements in biomedical research and overall improvement of the health system, 6-10% of patients present with stage IV disease in the developed world, with a higher incidence noted elsewhere. Despite advances in biomedical research into cancer, up to 70-80% of patients with stage IV breast cancer die of cancer in 5 years, a disproportionally higher mortality compared with non-metastatic breast cancer...
December 8, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27931250/tracing-the-origin-of-disseminated-tumor-cells-in-breast-cancer-using-single-cell-sequencing
#2
Jonas Demeulemeester, Parveen Kumar, Elen K Møller, Silje Nord, David C Wedge, April Peterson, Randi R Mathiesen, Renathe Fjelldal, Masoud Zamani Esteki, Koen Theunis, Elia Fernandez Gallardo, A Jason Grundstad, Elin Borgen, Lars O Baumbusch, Anne-Lise Børresen-Dale, Kevin P White, Vessela N Kristensen, Peter Van Loo, Thierry Voet, Bjørn Naume
BACKGROUND: Single-cell micro-metastases of solid tumors often occur in the bone marrow. These disseminated tumor cells (DTCs) may resist therapy and lay dormant or progress to cause overt bone and visceral metastases. The molecular nature of DTCs remains elusive, as well as when and from where in the tumor they originate. Here, we apply single-cell sequencing to identify and trace the origin of DTCs in breast cancer. RESULTS: We sequence the genomes of 63 single cells isolated from six non-metastatic breast cancer patients...
December 9, 2016: Genome Biology
https://www.readbyqxmd.com/read/27929464/labeling-of-breast-cancer-patient-derived-xenografts-with-traceable-reporters-for-tumor-growth-and-metastasis-studies
#3
Colton Hanna, Letty Kwok, Jessica Finlay-Schultz, Carol A Sartorius, Diana M Cittelly
The use of preclinical models to study tumor biology and response to treatment is central to cancer research. Long-established human cell lines, and many transgenic mouse models, often fail to recapitulate the key aspects of human malignancies. Thus, alternative models that better represent the heterogeneity of patients' tumors and their metastases are being developed. Patient-derived xenograft (PDX) models in which surgically resected tumor samples are engrafted into immunocompromised mice have become an attractive alternative as they can be transplanted through multiple generations,and more efficiently reflect tumor heterogeneity than xenografts derived from human cancer cell lines...
November 30, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27925648/sonographic-evaluation-of-intrathyroid-metastases
#4
J Matthew Debnam, Michael Kwon, Bruno D Fornage, Savitri Krishnamurthy, Gary L Clayman, Beth S Edeiken-Monroe
OBJECTIVES: Intrathyroid metastases from extrathyroid primary tumors are rare. Clinical findings may be subtle, but detection of intrathyroid metastases has improved with sonography. The objective of this study was to evaluate the sonographic appearance of intrathyroid metastases. METHODS: Patients with thyroid masses with cytopathologic features matching those of an extrathyroid primary tumor were retrospectively identified. The appearances of intrathyroid metastases on sonography were reviewed for the following features: size, margin regularity, echogenicity, echotexture, vascularity on power or color Doppler ultrasonography, and the presence or absence of any associated cervical adenopathy...
December 7, 2016: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
https://www.readbyqxmd.com/read/27923045/tumor-evolution-in-two-patients-with-basal-like-breast-cancer-a-retrospective-genomics-study-of-multiple-metastases
#5
Katherine A Hoadley, Marni B Siegel, Krishna L Kanchi, Christopher A Miller, Li Ding, Wei Zhao, Xiaping He, Joel S Parker, Michael C Wendl, Robert S Fulton, Ryan T Demeter, Richard K Wilson, Lisa A Carey, Charles M Perou, Elaine R Mardis
BACKGROUND: Metastasis is the main cause of cancer patient deaths and remains a poorly characterized process. It is still unclear when in tumor progression the ability to metastasize arises and whether this ability is inherent to the primary tumor or is acquired well after primary tumor formation. Next-generation sequencing and analytical methods to define clonal heterogeneity provide a means for identifying genetic events and the temporal relationships between these events in the primary and metastatic tumors within an individual...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27916281/intratumoral-heterogeneity-of-macrophages-and-fibroblasts-in-breast-cancer-is-associated-with-the-morphological-diversity-of-tumor-cells-and-contributes-to-lymph-node-metastasis
#6
Lubov A Tashireva, Evgeny V Denisov, Tatiana S Gerashchenko, Daria N Pautova, Mikhail A Buldakov, Marina V Zavyalova, Julia Kzhyshkowska, Nadezhda V Cherdyntseva, Vladimir M Perelmuter
Recent studies have highlighted the heterogeneity of the tumor microenvironment (ME) and the importance of its analysis to the understanding of its impact on clinical outcomes. In this study, we aimed to analyze the intratumoral distribution of macrophages and fibroblasts in breast cancer (BC) based on the morphological diversity of tumor cells (tubular, alveolar, solid, trabecular and discrete structures) and the clinicopathological parameters of the disease. Thirty-six patients with invasive breast carcinoma of no special type were included in the study...
November 27, 2016: Immunobiology
https://www.readbyqxmd.com/read/27906044/high-mammographic-breast-density-predicts-locoregional-recurrence-after-modified-radical-mastectomy-for-invasive-breast-cancer-a-case-control-study
#7
Yu-Sen Huang, Jenny Ling-Yu Chen, Chiun-Sheng Huang, Sung-Hsin Kuo, Fu-Shan Jaw, Yao-Hui Tseng, Wei-Chun Ko, Yeun-Chung Chang
BACKGROUND: We aimed to evaluate the influence of mammographic breast density at diagnosis on the risk of cancer recurrence and survival outcomes in patients with invasive breast cancer after modified radical mastectomy. METHODS: This case-control study included 121 case-control pairs of women diagnosed with invasive breast cancer between 2004 and 2009, and who had undergone modified radical mastectomy and had mammographic breast density measured before or at diagnosis...
December 1, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27885435/comparison-of-immunophenotypes-of-primary-breast-carcinomas-and-multiple-corresponding-distant-metastases-an-autopsy-study-of-25-patients
#8
B Szekely, Zs I Nagy, Zs Farago, O Kiss, G Lotz, K A Kovacs, L Madaras, N Udvarhelyi, M Dank, Gy Szentmartoni, Zs Baranyai, L Harsanyi, A M Tőkés, Jozsef Timar, A M Szasz, J Kulka
Phenotypical change in metastatic breast carcinoma has widely been accepted as an inherent biological feature rather than technical fault. We analyzed the immunohistochemical phenotype and histopathological features of 25 primary breast carcinomas and 90 corresponding distant metastases in 23 organs retrospectively. Histological slides were reviewed for prognostic and predictive factors. Overall, metastases were more similar to each other and often differed from the primary tumor. We created a 3-step grouping system based on the localization of metastases...
November 24, 2016: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/27880891/a-novel-3d-in%C3%A2-vitro-metastasis-model-elucidates-differential-invasive-strategies-during-and-after-breaching-basement-membrane
#9
Asja Guzman, Víctor Sánchez Alemany, Yen Nguyen, Catherine Ruiqi Zhang, Laura J Kaufman
Invasive breast cancer and other tumors of epithelial origin must breach a layer of basement membrane (BM) that surrounds the primary tumor before invading into the adjacent extracellular matrix. To analyze invasive strategies of breast cancer cells during BM breaching and subsequent invasion into a collagen I-rich extracellular matrix (ECM), we developed a physiologically relevant 3D in vitro model that recreates the architecture of a solid tumor with an intact, degradable, cell-assembled BM layer embedded in a collagen I environment...
January 2017: Biomaterials
https://www.readbyqxmd.com/read/27858305/one-microenvironment-does-not-fit-all-heterogeneity-beyond-cancer-cells
#10
Ik Sun Kim, Xiang H-F Zhang
Human cancers exhibit formidable molecular heterogeneity, to a large extent accounting for the incomplete and transitory efficacy of current anti-cancer therapies. However, neoplastic cells alone do not manifest the disease, but conscript a battery of non-tumor cells to enable and sustain hallmark capabilities of cancer. Escaping immunosurveillance is one of such capabilities. Tumors evolve immunosuppressive microenvironment to subvert anti-tumor immunity. In this review, we will focus on tumor-associated myeloid cells, which constitute an essential part of the immune microenvironment and reciprocally interact with cancer cells to establish malignancy toward metastasis...
November 18, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27835577/a-functional-variant-rs4442975-modulating-foxa1-binding-affinity-does-not-influence-the-risk-or-progression-of-breast-cancer-in-chinese-han-population
#11
Yi Zhang, Yan Li, Shaojie Jiang, Wei Chen, Jiao Lou, Juntao Ke, Jiaoyuan Li, Ying Zhu, Yajie Gong, Yang Yang, Jianbo Tian, Xiating Peng, Danyi Zou, Jing Gong, Jiang Chang, Xiaoping Miao, Rong Zhong
The DNA-binding protein FOXA1 has been shown to regulate nearly all estrogen receptor-chromatin interactions, thereby influencing target gene expression levels in breast cancer (BC) cells. Recently, the rs4442975 T-allele, which disrupts the recruitment of FOXA1 and interacts with the IGFBP5 promoter, was associated to BC susceptibility in a European population. We conducted a hospital-based case-control study that included 1227 cases and 1285 controls to explore the potential association between rs4442975 and BC risk in Chinese Han population, and the effect of this SNP on BC progression was also observed in cases...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27817751/novel-insight-into-triple-negative-breast-cancers-the-emerging-role-of-angiogenesis-and-antiangiogenic-therapy
#12
Cornelia Braicu, Roxana Chiorean, Alexandru Irimie, Sergiu Chira, Ciprian Tomuleasa, Emilian Neagoe, Angelo Paradiso, Patriciu Achimas-Cadariu, Vladimir Lazar, Ioana Berindan-Neagoe
Triple-negative breast cancer (TNBC) is a heterogeneous group of tumours characterised by lack of expression of oestrogen-, progesterone- and human epidermal growth factor receptors. TNBC, which represents approximately 15% of all mammary tumours, has a poor prognosis because of an aggressive behaviour and the lack of specific treatment. Accordingly, TNBC has become a major focus of research into breast cancer and is now classified into several molecular subtypes, each with a different prognosis. Pathological angiogenesis occurs at a late stage in the proliferation of TNBC and is associated with invasion and metastasis; there is an association with metabolic syndrome...
November 7, 2016: Expert Reviews in Molecular Medicine
https://www.readbyqxmd.com/read/27791011/data-driven-identification-of-prognostic-tumor-subpopulations-using-spatially-mapped-t-sne-of-mass-spectrometry-imaging-data
#13
Walid M Abdelmoula, Benjamin Balluff, Sonja Englert, Jouke Dijkstra, Marcel J T Reinders, Axel Walch, Liam A McDonnell, Boudewijn P F Lelieveldt
The identification of tumor subpopulations that adversely affect patient outcomes is essential for a more targeted investigation into how tumors develop detrimental phenotypes, as well as for personalized therapy. Mass spectrometry imaging has demonstrated the ability to uncover molecular intratumor heterogeneity. The challenge has been to conduct an objective analysis of the resulting data to identify those tumor subpopulations that affect patient outcome. Here we introduce spatially mapped t-distributed stochastic neighbor embedding (t-SNE), a nonlinear visualization of the data that is able to better resolve the biomolecular intratumor heterogeneity...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27773784/treatment-of-brain-metastases-in-the-modern-genomic-era
#14
Ibiayi Dagogo-Jack, Corey M Gill, Daniel P Cahill, Sandro Santagata, Priscilla K Brastianos
Development of brain metastasis (BM) portends a dismal prognosis for patients with cancer. Melanomas and carcinomas of the lung, breast, and kidney are the most common malignancies to metastasize to the brain. Recent advances in molecular genetics have enabled the identification of actionable, clinically relevant genetic alterations within primary tumors and their corresponding metastases. Adoption of genotype-guided treatment strategies in the management of systemic malignancy has resulted in dramatic and durable responses...
October 20, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27768598/chemotherapy-enriches-for-an-invasive-triple-negative-breast-tumor-cell-subpopulation-expressing-a-precursor-form-of-n-cadherin-on-the-cell-surface
#15
Erik R Nelson, Shenduo Li, Margaret Kennedy, Sturgis Payne, Kelly Kilibarda, Jeffrey Groth, Michelle Bowie, Edgardo Parilla-Castellar, Gustaaf de Ridder, Paul Kelly Marcom, Matthew Lyes, Bercedis L Peterson, Michael Cook, Salvatore V Pizzo, Donald P McDonnell, Robin E Bachelder
BACKGROUND: Although most triple-negative breast cancer (TNBC) patients initially respond to chemotherapy, residual tumor cells frequently persist and drive recurrent tumor growth. Previous studies from our laboratory and others' indicate that TNBC is heterogeneous, being composed of chemo-sensitive and chemo-resistant tumor cell subpopulations. In the current work, we studied the invasive behaviors of chemo-resistant TNBC, and sought to identify markers of invasion in chemo-residual TNBC...
October 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27753656/expression-patterns-of-biomarkers-in-primary-tumors-and-corresponding-metastases-in-breast-cancer
#16
Iben Kümler, Eva Balslev, Ann S Knop, Nils Brünner, Tobias W Klausen, Sofie S Jespersen, Signe L Nielsen, Dorte L Nielsen
Tumor heterogeneity has been shown for several cancers including breast cancer (BC). Despite the fact that expression of tumor markers may change throughout the metastatic process, rebiopsies at the time of recurrence are still not performed routinely at all institutions. The aims of the study were to evaluate changes in biomarker profiles during the metastatic process and to investigate whether previous anthracycline or endocrine therapy given in the adjuvant setting could affect the biomarker profile in metastatic lesions...
October 7, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/27752289/mechanical-properties-of-the-tumor-stromal-microenvironment-probed-in-vitro-and-ex-vivo-by-in-situ-calibrated-optical-trap-based-active-microrheology
#17
Jack R Staunton, Wilfred Vieira, King Leung Fung, Ross Lake, Alexus Devine, Kandice Tanner
One of the hallmarks of the malignant transformation of epithelial tissue is the modulation of stromal components of the microenvironment. In particular, aberrant extracellular matrix (ECM) remodeling and stiffening enhances tumor growth and survival and promotes metastasis. Type I collagen is one of the major ECM components. It serves as a scaffold protein in the stroma contributing to the tissue's mechanical properties, imparting tensile strength and rigidity to tissues such as those of the skin, tendons, and lungs...
September 2016: Cellular and Molecular Bioengineering
https://www.readbyqxmd.com/read/27729970/improving-systemic-breast-cancer-therapy-time-to-look-beyond-the-primary-tumour
#18
E Vandendriessche, G Van De Putte, R Van Den Broecke, Etm De Jonge
AIM: Intra and inter tumour heterogeneity is a known feature in cancer because tumour cells undergo changes at genetic and epigenetic level as they spread from their primary tumour site. Adjuvant treatment protocols in breast cancer are currently based on the biological characteristics of the primary tumour, which in most cases has been removed surgically. Considering tumour heterogeneity in metastases we examined the present status of knowledge regarding measurable differences in tumour profiling between the primary breast tumour and its synchronous axillary lymph node metastases (ALNM) and if so whether adjuvant therapy directed towards the tumour characteristics of the ALNM instead of those of the primary tumour is more effective...
December 28, 2015: Facts, Views & Vision in ObGyn
https://www.readbyqxmd.com/read/27713152/detection-of-cellular-senescence-within-human-invasive-breast-carcinomas-distinguishes-different-breast-tumor-subtypes
#19
Cristina L Cotarelo, Arno Schad, Charles James Kirkpatrick, Jonathan P Sleeman, Erik Springer, Marcus Schmidt, Sonja Thaler
Oncogene-induced senescence is thought to act as a barrier to tumorigenesis by arresting cells at risk of malignant transformation. Nevertheless, numerous findings suggest that senescent cells may conversely promote tumor progression through the development of the senescence-associated secretome they produce. It is likely that the composition and the physiological consequences mediated by the senescence secretome are dependent on the oncogenes that trigger the senescence program. Breast cancer represents a heterogenous disease that can be divided into breast cancer subtypes due to different subsets of genetic and epigenetic abnormalities...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27694895/identification-of-a-cancer-stem-cell-specific-function-for-the-histone-deacetylases-hdac1-and-hdac7-in-breast-and-ovarian-cancer
#20
A E Witt, C-W Lee, T I Lee, D J Azzam, B Wang, C Caslini, F Petrocca, J Grosso, M Jones, E B Cohick, A B Gropper, C Wahlestedt, A L Richardson, R Shiekhattar, R A Young, T A Ince
Tumours are comprised of a highly heterogeneous population of cells, of which only a small subset of stem-like cells possess the ability to regenerate tumours in vivo. These cancer stem cells (CSCs) represent a significant clinical challenge as they are resistant to conventional cancer therapies and play essential roles in metastasis and tumour relapse. Despite this realization and great interest in CSCs, it has been difficult to develop CSC-targeted treatments due to our limited understanding of CSC biology...
October 3, 2016: Oncogene
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