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Heterogeneity breast metastasis

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https://www.readbyqxmd.com/read/28442559/impact-of-27-hydroxylase-cyp27a1-and-27-hydroxycholesterol-in-breast-cancer
#1
Siker Kimbung, Chingyi Chang, Pär-Ola Bendahl, Laura Dubois, Will J Thompson, Donald P McDonnell, Signe Borgquist
The impact of systemic 27-hydroxycholesterol (27HC) and intra-tumoral CYP27A1 expression on pathobiology and clinical response to statins in breast cancer needs clarification. 27HC is an oxysterol produced from cholesterol by the monooxygenase CYP27A1, which regulates intracellular cholesterol homeostasis. 27HC also acts as an endogenous selective estrogen receptor (ER) modulator capable of increasing breast cancer growth and metastasis. 27HC levels can be modulated by statins or direct inhibition of CYP27A1, thereby attenuating its pro-tumorigenic activities...
April 25, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28430642/immunocompetent-mouse-allograft-models-for-development-of-therapies-to-target-breast-cancer-metastasis
#2
Yuan Yang, Howard H Yang, Ying Hu, Peter H Watson, Huaitian Liu, Thomas R Geiger, Miriam R Anver, Diana C Haines, Philip Martin, Jeffrey E Green, Maxwell P Lee, Kent W Hunter, Lalage M Wakefield
Effective drug development to combat metastatic disease in breast cancer would be aided by the availability of well-characterized preclinical animal models that (a) metastasize with high efficiency, (b) metastasize in a reasonable time-frame, (c) have an intact immune system, and (d) capture some of the heterogeneity of the human disease. To address these issues, we have assembled a panel of twelve mouse mammary cancer cell lines that can metastasize efficiently on implantation into syngeneic immunocompetent hosts...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429735/phylogenetic-analysis-of-metastatic-progression-in-breast-cancer-using-somatic-mutations-and-copy-number-aberrations
#3
David Brown, Dominiek Smeets, Borbála Székely, Denis Larsimont, A Marcell Szász, Pierre-Yves Adnet, Françoise Rothé, Ghizlane Rouas, Zsófia I Nagy, Zsófia Faragó, Anna-Mária Tőkés, Magdolna Dank, Gyöngyvér Szentmártoni, Nóra Udvarhelyi, Gabriele Zoppoli, Lajos Pusztai, Martine Piccart, Janina Kulka, Diether Lambrechts, Christos Sotiriou, Christine Desmedt
Several studies using genome-wide molecular techniques have reported various degrees of genetic heterogeneity between primary tumours and their distant metastases. However, it has been difficult to discern patterns of dissemination owing to the limited number of patients and available metastases. Here, we use phylogenetic techniques on data generated using whole-exome sequencing and copy number profiling of primary and multiple-matched metastatic tumours from ten autopsied patients to infer the evolutionary history of breast cancer progression...
April 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28428107/clinicopathologic-factors-associated-with-survival-in-patients-with-breast-cancer-brain-metastasis
#4
Rong Li, Kui Zhang, Gene P Siegal, Shi Wei
Brain metastasis from breast cancer generally represents a catastrophic event yet demonstrates substantial biological heterogeneity. There have been limited studies solely focusing on the prognosis of patients with such metastasis. In this study, we carried out a comprehensive analysis in 108 consecutive patients with breast cancer brain metastases between 1997 and 2012 to further define clinicopathologic factors associated with early onset of brain metastasis and survival outcomes after development of them...
April 17, 2017: Human Pathology
https://www.readbyqxmd.com/read/28425064/a-pathway-to-personalizing-therapy-for-metastases-using-liver-on-a-chip-platforms
#5
A S Khazali, A M Clark, A Wells
Metastasis accounts for most cancer-related deaths. The majority of solid cancers, including those of the breast, colorectum, prostate and skin, metastasize at significant levels to the liver due to its hemodynamic as well as tumor permissive microenvironmental properties. As this occurs prior to detection and treatment of the primary tumor, we need to target liver metastases to improve patients' outcomes. Animal models, while proven to be useful in mechanistic studies, do not represent the heterogeneity of human population especially in drug metabolism lack proper human cell-cell interactions, and this gap between animals and humans results in costly and inefficient drug discovery...
April 19, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28361862/circulating-tumor-cells-in-breast-cancer-functional-heterogeneity-pathogenetic-and-clinical-aspects
#6
N V Cherdyntseva, N V Litviakov, E V Denisov, P A Gervas, E S Cherdyntsev
Each patient has a unique history of cancer ecosystem development, resulting in intratumor heterogeneity. In order to effectively kill the tumor cells by chemotherapy, dynamic monitoring of driver molecular alterations is necessary to detect the markers for acquired drug resistance and find the new therapeutic targets. To perform the therapeutic monitoring, frequent tumor biopsy is needed, but it is not always possible due to small tumor size or its regression during the therapy or tumor inaccessibility in advanced cancer patients...
March 2017: Experimental Oncology
https://www.readbyqxmd.com/read/28359244/potential-therapeutic-targets-in-energy-metabolism-pathways-of-breast-cancer
#7
Rowshan Ara Islam, Sazzad Hossain, Ezharul Hoque Chowdhury
Mutations in proto-oncogenes and tumor suppressor genes make cancer cells proliferate indefinitely. As they possess almost all mechanisms for cell proliferation and survival like healthy cells, it is difficult to specifically target cancer cells in the body. Current treatments in most of the cases are harmful to healthy cells as well. Thus, it would be of great prudence to target specific characters of cancer cells. Since cancer cells avidly use glucose and glutamine to survive and proliferate by upregulating the relevant enzymes and their specific isoforms having important regulatory roles, it has been of great interest recently to target the energy-related metabolic pathways as part of the therapeutic interventions...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28351929/genetic-heterogeneity-in-therapy-na%C3%A3-ve-synchronous-primary-breast-cancers-and-their-metastases
#8
François-Clément Bidard, Charlotte K Y Ng, Salvatore Piscuoglio, Felipe C Geyer, Reymond Lim, Ino De Bruijn, Ronglai Shen, Fresia Pareja, Samuel Berman, Lu Wang, Jean-Yves Pierga, Anne Vincent-Salomon, Agnes Viale, Larry Norton, Brigitte Sigal, Britta Weigelt, Paul Cotu, Jorge S Reis-Filho
PURPOSE: Paired primary breast cancers and metachronous metastases after adjuvant treatment differed in their clonal composition and genetic alterations, but it is unclear whether the differences stem from the selective pressures of the metastatic process, the systemic therapies or both. We sought to define the repertoire of genetic alterations in breast cancer patients with de novo metastatic disease who had not received local or systemic therapy. EXPERIMENTAL DESIGN: Up to two anatomically distinct core biopsies of primary breast cancers and synchronous distant metastases from nine patients who presented with metastatic disease were subjected to high-depth whole-exome sequencing...
March 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28336365/breast-cancer-cells-focus-on-the-consequences-of-epithelial-to-mesenchymal-transition
#9
Alice H L Bong, Gregory R Monteith
Breast cancers are highly heterogeneous and successful treatment of those subtypes with a high frequency of metastases and resistance to clinically available therapies remains a challenge. An understanding of mechanisms which may contribute to this heterogeneity and generation of more resilient cancer cells is therefore essential. Epithelial-to-mesenchymal transition (EMT) is a dynamic two-way process that occurs during embryonic development and wound healing whereby epithelial cells can gain plasticity and switch to a mesenchymal-like phenotype...
March 20, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28327601/bcip-a-gene-centered-platform-for-identifying-potential-regulatory-genes-in-breast-cancer
#10
Jiaqi Wu, Shuofeng Hu, Yaowen Chen, Zongcheng Li, Jian Zhang, Hanyu Yuan, Qiang Shi, Ningsheng Shao, Xiaomin Ying
Breast cancer is a disease with high heterogeneity. Many issues on tumorigenesis and progression are still elusive. It is critical to identify genes that play important roles in the progression of tumors, especially for tumors with poor prognosis such as basal-like breast cancer and tumors in very young women. To facilitate the identification of potential regulatory or driver genes, we present the Breast Cancer Integrative Platform (BCIP, http://omics.bmi.ac.cn/bcancer/). BCIP maintains multi-omics data selected with strict quality control and processed with uniform normalization methods, including gene expression profiles from 9,005 tumor and 376 normal tissue samples, copy number variation information from 3,035 tumor samples, microRNA-target interactions, co-expressed genes, KEGG pathways, and mammary tissue-specific gene functional networks...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28300837/a-cd44v-subpopulation-of-breast-cancer-stem-like-cells-with-enhanced-lung-metastasis-capacity
#11
Jing Hu, Gang Li, Peiyuan Zhang, Xueqian Zhuang, Guohong Hu
Cancer stem-like cells (CSCs) are a subpopulation of cancer cells responsible for tumor growth, and recent evidence suggests that CSCs also contribute to cancer metastasis. However, the heterogeneity of CSCs in metastasis capacities is still unclear in breast cancer. Here we show that among the CD24(-)/CD44(+) breast CSCs, a subset expressing the variant isoform of CD44 (CD44v) displays significantly higher capacity of lung metastasis than that expressing the standard CD44 isoform CD44s. Increasing or reducing the CD44v/CD44s ratio of breast cancer cells by regulating the expression of epithelial splicing regulatory protein 1 (ESRP1) leads to promotion or suppression of lung metastasis without influencing cancer cell stemness...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28294120/down-regulation-of-adam33-as-a-predictive-biomarker-of-aggressive-breast-cancer
#12
Graciele C M Manica, Caroline F Ribeiro, Marco A S de Oliveira, Isabela T Pereira, Andressa Chequin, Edneia A S Ramos, Liliane M B Klassen, Ana Paula M Sebastião, Larissa M Alvarenga, Silvio M Zanata, Lucia De Noronha, Iris Rabinovich, Fabricio F Costa, Emanuel M Souza, Giseli Klassen
Breast cancer is a heterogeneous disease with differences in its clinical, molecular and biological features. Traditionally, immunohistochemical markers together with clinicopathologic parameters are used to classify breast cancer and to predict disease outcome. Triple-negative breast cancer (TNBC) is a particular type of breast cancer that is defined by a lack of expression of hormonal receptors and the HER2 gene. Most cases of TNBC also have a basal-like phenotype (BLBC) with expression of cytokeratin 5/6 and/or EGFR...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28280388/alternative-therapies-for-metastatic-breast-cancer-multimodal-approach-targeting-tumor-cell-heterogeneity
#13
REVIEW
Manpreet Sambi, Sabah Haq, Vanessa Samuel, Bessi Qorri, Fiona Haxho, Kelli Hill, William Harless, Myron R Szewczuk
One of the primary challenges in developing effective therapies for malignant tumors is the specific targeting of a heterogeneous cancer cell population within the tumor. The cancerous tumor is made up of a variety of distinct cells with specialized receptors and proteins that could potentially be viable targets for drugs. In addition, the diverse signals from the local microenvironment may also contribute to the induction of tumor growth and metastasis. Collectively, these factors must be strategically studied and targeted in order to develop an effective treatment protocol...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28271309/mutational-studies-on-single-circulating-tumor-cells-isolated-from-the-blood-of-inflammatory-breast-cancer-patients
#14
Catherine Bingham, Sandra V Fernandez, Patricia Fittipaldi, Paul W Dempsey, Karen J Ruth, Massimo Cristofanilli, R Katherine Alpaugh
PURPOSE: The molecular characterization of circulating tumor cells (CTCs) is critical to identify the key drivers of cancer metastasis and devising therapeutic approaches, particularly for inflammatory breast cancer (IBC) which is usually diagnosed at advance stages and progresses rapidly. METHODS: Genomic alterations in tumor tissue samples were studied using Foundation One™. Single CTCs were isolated using CellSearch followed by single-cell isolation by DEPArray™...
March 7, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28250928/location-of-tumor-affects-local-and-distant-immune-cell-type-and-number
#15
Jonathan A Hensel, Vinayak Khattar, Reading Ashton, Carnellia Lee, Gene P Siegal, Selvarangan Ponnazhagan
INTRODUCTION: Tumors comprise heterogeneous populations of cells, including immune infiltrates that polarize during growth and metastasis. Our preclinical studies on breast cancer (BCa) identified functional differences in myeloid-derived suppressor cells based on tumor microenvironment (TME), prompting variations in host immune response to tumor growth, and dissemination based on tissue type. METHODS: In order to understand if such variations existed among other immune cells, and if such alteration occurs in response to tumor growth at the primary site or due to bone dissemination, we characterized immune cells, examining localized growth and in the tibia...
March 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28248929/rnai-screens-for-rho-gtpase-regulators-of-cell-shape-and-yap-taz-localisation-in-triple-negative-breast-cancer
#16
Patricia Pascual-Vargas, Samuel Cooper, Julia Sero, Vicky Bousgouni, Mar Arias-Garcia, Chris Bakal
In order to metastasise, triple negative breast cancer (TNBC) must make dynamic changes in cell shape. The shape of all eukaryotic cells is regulated by Rho Guanine Nucleotide Exchange Factors (RhoGEFs), which activate Rho-family GTPases in response to mechanical and informational cues. In contrast, Rho GTPase-activating proteins (RhoGAPs) inhibit Rho GTPases. However, which RhoGEFs and RhoGAPS couple TNBC cell shape to changes in their environment is very poorly understood. Moreover, whether the activity of particular RhoGEFs and RhoGAPs become dysregulated as cells evolve the ability to metastasise is not clear...
March 1, 2017: Scientific Data
https://www.readbyqxmd.com/read/28230773/programmed-death-ligand-1-pd-l1-tumor-expression-is-associated-with-a-better-prognosis-and-diabetic-disease-in-triple-negative-breast-cancer-patients
#17
Gerardo Botti, Francesca Collina, Giosuè Scognamiglio, Federica Rao, Valentina Peluso, Rossella De Cecio, Michela Piezzo, Gabriella Landi, Michelino De Laurentiis, Monica Cantile, Maurizio Di Bonito
Triple Negative Breast Cancers (TNBC) subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1) is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28195880/pd-l1-expression-and-intratumoral-heterogeneity-across-breast-cancer-subtypes-and-stages-an-assessment-of-245-primary-and-40-metastatic-tumors
#18
Erik A Dill, Alejandro A Gru, Kristen A Atkins, Lisa A Friedman, Margaret E Moore, Timothy N Bullock, Janet V Cross, Patrick M Dillon, Anne M Mills
Tumor expression of programmed cell death ligand 1 (PD-L1) is associated with immune evasion in a variety of malignancies, including a subset of triple-negative breast carcinomas, and may mark cancers as susceptible to PD-1/PD-L1 inhibitor therapies. We herein characterize PD-L1 expression in breast cancers across the full range of histomorphologies and investigate its intratumoral heterogeneity and fidelity across primaries and metastases. A total of 245 primary and 40 metastatic (20 nodal, 20 distant) breast carcinomas were evaluated with PD-L1 immunohistochemistry on tissue microarray...
March 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28191804/does-alternative-and-traditional-wasam-local-cautery-therapy-facilitate-an-early-and-more-extensive-locoregional-metastasis-of-breast-cancer
#19
(no author information available yet)
INTRODUCTION: A large heterogeneous group of unproven remedies exist to treat cancer in both developed and developing countries. Some of these remedies often do more harm than good to the patients. The traditional medicine is the sum total of the knowledge, skills, and practices based on the theories, beliefs, and experiences indigenous to different cultures. The traditional medicine in Oman is based on herbal treatment and skin treatment (massage, Cupping and skin burn "cautery" treatment-known as Wasam or Kaiy)...
September 2016: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/28185146/mr-imaging-features-associated-with-distant-metastasis-free-survival-of-patients-with-invasive-breast-cancer-a-case-control-study
#20
Sung Eun Song, Sung Ui Shin, Hyeong-Gon Moon, Han Suk Ryu, Kwangsoo Kim, Woo Kyung Moon
PURPOSE: Preoperative breast magnetic resonance (MR) imaging features of primary breast cancers may have the potential to act as prognostic biomarkers by providing morphologic and kinetic features representing inter- or intra-tumor heterogeneity. Recent radiogenomic studies reveal that several radiologist-annotated image features are associated with genes or signal pathways involved in tumor progression, treatment resistance, and distant metastasis (DM). We investigate whether preoperative breast MR imaging features are associated with worse DM-free survival in patients with invasive breast cancer...
February 9, 2017: Breast Cancer Research and Treatment
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