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Suély V Silva, Maíra A Lima, Nathalie Cella, Ruy G Jaeger, Vanessa M Freitas
Proteins secreted in the extracellular matrix microenvironment (ECM) by tumor cells are involved in cell adhesion, motility, intercellular communication and invasion. The tumor microenvironment is expansively modified and remodeled by proteases, resulting in important changes in both cell-cell and cell-ECM interactions and in the generation of new signals from the cell surface. Metalloproteinases belonging to the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family have been implicated in tissue remodeling events observed in cancer development, growth and progression...
2016: PloS One
Sarah L Maguire, Barrie Peck, Patty T Wai, James Campbell, Holly Barker, Aditi Gulati, Frances Daley, Simon Vyse, Paul Huang, Christopher J Lord, Gillian Farnie, Keith Brennan, Rachael Natrajan
The initiation and progression of breast cancer from the transformation of the normal epithelium to ductal carcinoma in situ (DCIS) and invasive disease is a complex process involving the acquisition of genetic alterations, changes in gene expression, alongside microenvironmental and recognised histological alterations. Here we sought to comprehensively characterise the genomic and transcriptomic features of the MCF10 isogenic model of breast cancer progression and to functionally validate potential driver alterations in 3-dimensional (3D) spheroids that may give insight into breast cancer progression and identify targetable alterations in conditions more similar to those encountered in vivo...
August 11, 2016: Journal of Pathology
Henna V Kuusisto, David A Jans
We previously reported that overexpression of members of the Importin (Imp) superfamily of nuclear transporters results in increased nuclear trafficking through conventional transport pathways in tumour cells. Here we show for the first time that the extent of overexpression of Impβ1 correlates with disease state in the MCF10 human breast tumour progression system. Excitingly, we find that targeting Impβ1 activity through siRNA is >30 times more efficient in decreasing the viability of malignant ductal carcinoma cells compared to isogenic non-transformed counterparts, and is highly potent and tumour selective at subnanomolar concentrations...
August 2015: Biochimica et Biophysica Acta
Eneritz Agirre, Nicolás Bellora, Mariano Alló, Amadís Pagès, Paola Bertucci, Alberto R Kornblihtt, Eduardo Eyras
BACKGROUND: Alternative splicing is primarily controlled by the activity of splicing factors and by the elongation of the RNA polymerase II (RNAPII). Recent experiments have suggested a new complex network of splicing regulation involving chromatin, transcription and multiple protein factors. In particular, the CCCTC-binding factor (CTCF), the Argonaute protein AGO1, and members of the heterochromatin protein 1 (HP1) family have been implicated in the regulation of splicing associated with chromatin and the elongation of RNAPII...
2015: BMC Biology
Reyhane Hoshyar, Zahra Mahboob, Asghar Zarban
In this study we evaluated the biological activity of alcoholic and aqueous extracts from the fruit of Berberis vulgaris. The total antioxidant capacity of Berberis was characterized by FRAP, DPPH, Folin-Ciocalteu while the anthocyanins content was measured by pH differential method. Cell viability and apoptotic property were determined by MTT and DNA fragmentation assays, respectively. Alcoholic extract of Berberis was richer in antioxidants and anthocyanins compared to aqueous extract. Although both extracts significantly inhibited proliferation of breast cancer cells (MCF-7); these changes were not observed in normal human breast epithelial cells (MCF10-A)...
August 2016: Cytotechnology
Francisco G Ortega, Martín A Fernández-Baldo, Jorge G Fernández, María J Serrano, María I Sanz, Juan J Diaz-Mochón, José A Lorente, Julio Raba
In the present article, we describe a study of antitumor activity in breast cell lines using silver nanoparticles (Ag NPs) synthesized by a microbiological method. These Ag NPs were tested for their antitumor activity against MCF7 and T47D cancer cells and MCF10-A normal breast cell line. We analyzed cell viability, apoptosis induction, and endocytosis activity of those cell lines and we observed that the effects of the biosynthesized Ag NPs were directly related with the endocytosis activity. Moreover, Ag NPs had higher inhibition efficacy in tumor lines than in normal lines of breast cells, which is due to the higher endocytic activity of tumor cells compared to normal cells...
2015: International Journal of Nanomedicine
K G Khusal, R R Tonelli, E C Mattos, C O Soares, B M Di Genova, M A Juliano, U Urias, W Colli, M J M Alves
Trypanosoma cruzi trypomastigotes invade a great variety of mammalian cells, with several molecules being implicated in this complex event. Herein, the sequence GGIALAG present in prokineticin-2 receptor (PKR2), selected by phage display technology, is described as a new T. cruzi receptor for the Tc85 group of glycoproteins belonging to the gp85/TS superfamily and involved in cellular invasion of mammalian hosts. This finding is confirmed by the inhibitory activity of MCF10-A (human mammary) cell invasion by T...
January 2015: Parasitology Research
Ekkehard Weber, Elena Barbulescu, Rita Medek, Thomas Reinheckel, Mansoureh Sameni, Arulselvi Anbalagan, Kamiar Moin, Bonnie F Sloane
Cathepsin B has been demonstrated to be involved in several proteolytic processes that support tumor progression and metastasis and neurodegeneration. To further clarify its role, defined monoclonal antibodies are needed. As the primary structure of human cathepsin B is almost identical to that of the mouse, cathepsin B-deficient mice were used in a novel approach for generating such antibodies, providing the chance of an increased immune response to the antigen, human cathepsin B. Thirty clones were found to produce cathepsin B-specific antibodies...
March 2015: Biological Chemistry
Karen T Liby
Synthetic oleanane triterpenoids are multifunctional drugs being developed for the prevention and treatment of a variety of chronic diseases driven by inflammation and oxidative stress. Low nanomolar concentrations of triterpenoids inhibit the induction of inflammatory cytokines, and these drugs are potent activators of the Nrf2 cytoprotective pathway. In contrast, low micromolar concentrations of triterpenoids increased the production of ROS and induced apoptosis in a dose-dependent manner in malignant MCF10 CA1a breast cancer cells...
January 2014: Dose-response: a Publication of International Hormesis Society
Jae Young So, Hong Jin Lee, Pavel Kramata, Audrey Minden, Nanjoo Suh
Breast cancer is a heterogeneous disease that develops through a multistep process whose molecular basis remains poorly understood. The molecular mechanisms of breast cancer progression have been extensively studied using the MCF10 model. We summarized recent results on differential expression of proteins in the MCF10 cell series - MCF10A, MCF10AT1, and MCF10CA1a - and compared the ability of the latter 3 lines to form tumors in immunodeficient mice. In addition, we also investigated expression of several key signaling proteins in the MCF10 cell series corresponding to different stages of breast cancer progression...
January 1, 2012: Molecular and Cellular Pharmacology
Malathi Banda, Cecilia L Speyer, Sara N Semma, Kingsley O Osuala, Nicole Kounalakis, Keila E Torres Torres, Nicola J Barnard, Hyunjin J Kim, Bonnie F Sloane, Fred R Miller, James S Goydos, David H Gorski
TNBC is an aggressive breast cancer subtype that does not express hormone receptors (estrogen and progesterone receptors, ER and PR) or amplified human epidermal growth factor receptor type 2 (HER2), and there currently exist no targeted therapies effective against it. Consequently, finding new molecular targets in triple negative breast cancer (TNBC) is critical to improving patient outcomes. Previously, we have detected the expression of metabotropic glutamate receptor-1 (gene: GRM1; protein: mGluR1) in TNBC and observed that targeting glutamatergic signaling inhibits TNBC growth both in vitro and in vivo...
2014: PloS One
Nur P Damayanti, Ana Paula Craig, Joseph Irudayaraj
We report a label-free fluorescence lifetime profiling strategy to classify breast cancer cells, MCF10CA1h (malignant), MCF10A (nonmalignant), and MCF10AneoT (premalignant) in different stages of malignancy. Fluorescence Lifetime Imaging Microscopy (FLIM) was used to record the lifetime of autofluorescence of endogenous flavin in MCF10 cells in different stages of malignancy. Predominant differences in lifetimes ascertained by multi-exponential fitting curves can be attributed to the different forms of flavin protein; flavin mononucleotide (FMN), free flavin adenine dinucleotide (FAD), semiquinone, and bound FAD...
December 7, 2013: Analyst
Sara Crocetti, Christian Beyer, Grit Schade, Marcel Egli, Jürg Fröhlich, Alfredo Franco-Obregón
INTRODUCTION: A common drawback of many anticancer therapies is non-specificity in action of killing. We investigated the potential of ultra-low intensity and frequency pulsed electromagnetic fields (PEMFs) to kill breast cancer cells. Our criteria to accept this technology as a potentially valid therapeutic approach were: 1) cytotoxicity to breast cancer cells and; 2) that the designed fields proved innocuous to healthy cell classes that would be exposed to the PEMFs during clinical treatment...
2013: PloS One
Patricia Casbas-Hernandez, Monica D'Arcy, Erick Roman-Perez, Heather Ann Brauer, Kirk McNaughton, Samantha M Miller, Raghav K Chhetri, Amy L Oldenburg, Jodie M Fleming, Keith D Amos, Liza Makowski, Melissa A Troester
INTRODUCTION: Basal-like and luminal breast cancers have distinct stromal-epithelial interactions, which play a role in progression to invasive cancer. However, little is known about how stromal-epithelial interactions evolve in benign and pre-invasive lesions. METHODS: To study epithelial-stromal interactions in basal-like breast cancer progression, we cocultured reduction mammoplasty fibroblasts with the isogenic MCF10 series of cell lines (representing benign/normal, atypical hyperplasia, and ductal carcinoma in situ)...
2013: Breast Cancer Research: BCR
Adilson Kleber Ferreira, Renato Meneguelo, Alexandre Pereira, Otaviano Mendonça R Filho, Gilberto Orivaldo Chierice, Durvanei Augusto Maria
Phosphoethanolamine (Pho-s) is a compound involved in phospholipid turnover, acting as a substrate for many phospholipids of the cell membranes. In a recent study, we showed that Pho-s has antitumor effect in the several tumor cells. In this study we evaluated the antitumor activity of synthetic Pho-s on MCF-7 breast cancer cells. Here we demonstrate that Pho-s is cytotoxic to MCF-7 cells in a dose-dependent manner, while it is cytotoxic to MCF10 only at higher concentrations. In addition, Pho-s induces a disruption in mitochondrial membrane potential (Δψm)...
July 2013: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
T P Molitor, P Traktman
The vaccinia-related kinases (VRKs) comprise a branch of the casein kinase family. VRK1, a ser/thr kinase with a nuclear localization, is the most well-studied paralog and has been described as a proproliferative protein. In lower eukaryotes, a loss of VRK1 activity is associated with severe mitotic and meiotic defects. Mice that are hypomorphic for VRK1 expression are infertile, and depletion of VRK1 in tissue culture cells can impair cell proliferation and alter several signaling pathways. VRK1 has been implicated as part of a 'gene-expression signature' whose overexpression correlates with poor clinical outcome in breast cancer patients...
2013: Oncogenesis
Stefanie R Mullins, Mansoureth Sameni, Galia Blum, Matthew Bogyo, Bonnie F Sloane, Kamiar Moin
The expression of the cysteine protease cathepsin B is increased in early stages of human breast cancer.To assess the potential role of cathepsin B in premalignant progression of breast epithelial cells, we employed a 3D reconstituted basement membrane overlay culture model of MCF10A human breast epithelial cells and isogenic variants that replicate the in vivo phenotypes of hyper plasia(MCF10AneoT) and atypical hyperplasia (MCF10AT1). MCF10A cells developed into polarized acinar structures with central lumens...
December 2012: Biological Chemistry
José Manuel Calderón-Montaño, Andrés Madrona, Estefanía Burgos-Morón, Manuel Luis Orta, Santiago Mateos, José Luis Espartero, Miguel López-Lázaro
Recent data suggest that hydroxytyrosol, a phenolic compound of virgin olive oils, has anticancer activity. This communication reports the synthesis of decyl and hexadecyl hydroxytyrosyl ethers, as well as the cytotoxic activity of hydroxytyrosol and a series of seven hydroxytyrosol alkyl ether derivatives against A549 lung cancer cells and MRC5 non-malignant lung fibroblasts. Hydroxytyrosyl dodecyl ether (HTDE) showed the highest selective cytotoxicity, and possible mechanisms of action were investigated; results suggest that HTDE can moderately inhibit glycolysis, induce oxidative stress, and cause DNA damage in A549 cells...
May 29, 2013: Journal of Agricultural and Food Chemistry
R Lei, J Tang, X Zhuang, R Deng, G Li, J Yu, Y Liang, J Xiao, H-Y Wang, Q Yang, G Hu
Breast cancer is the most common type of cancer among women worldwide, and metastasis represents the most devastating stage of the disease. Recent studies have revealed that microRNAs (miRNA) have critical roles to regulate cancer cell invasion and metastasis. Here we present evidence to show the role of miR-182 in breast cancer metastasis. miR-182 is upregulated in the malignant cell line variants of both human MCF10 and mouse 4T1 series. Ectopic expression of miR-182 enhanced breast cancer cell motility and invasiveness, whereas miR-182 inhibition resulted in opposite changes...
March 6, 2014: Oncogene
Alessio Papi, Gianluca Storci, Tiziana Guarnieri, Sabrina De Carolis, Sara Bertoni, Nicola Avenia, Alessandro Sanguinetti, Angelo Sidoni, Donatella Santini, Claudio Ceccarelli, Mario Taffurelli, Marina Orlandi, Massimiliano Bonafé
AIMS: Cancer stem cell biology is tightly connected to the regulation of the pro-inflammatory cytokine network. The concept of cancer stem cells "inflammatory addiction" leads to envisage the potential role of anti-inflammatory molecules as new anti-cancer targets. Here we report on the relationship between nuclear receptors activity and the modulation of the pro-inflammatory phenotype in breast cancer stem cells. METHODS: Breast cancer stem cells were expanded as mammospheres from normal and tumor human breast tissues and from tumorigenic (MCF7) and non tumorigenic (MCF10) human breast cell lines...
2013: PloS One
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