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Walter bodmer

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https://www.readbyqxmd.com/read/27543333/stromal-uptake-and-transmission-of-acid-is-a-pathway-for-venting-cancer-cell-generated-acid
#1
Alzbeta Hulikova, Nicholas Black, Lin-Ting Hsia, Jennifer Wilding, Walter F Bodmer, Pawel Swietach
Proliferation and invasion of cancer cells require favorable pH, yet potentially toxic quantities of acid are produced metabolically. Membrane-bound transporters extrude acid from cancer cells, but little is known about the mechanisms that handle acid once it is released into the poorly perfused extracellular space. Here, we studied acid handling by myofibroblasts (colon cancer-derived Hs675.T, intestinal InMyoFib, embryonic colon-derived CCD-112-CoN), skin fibroblasts (NHDF-Ad), and colorectal cancer (CRC) cells (HCT116, HT29) grown in monoculture or coculture...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27101942/paul-ichiro-terasaki-1929-2016-inventor-of-the-microcytotoxicity-assay-and-pioneer-tissue-typer
#2
Walter F Bodmer
No abstract text is available yet for this article.
May 2016: HLA
https://www.readbyqxmd.com/read/27036009/myofibroblasts-are-distinguished-from-activated-skin-fibroblasts-by-the-expression-of-aoc3-and-other-associated-markers
#3
Lin-Ting Hsia, Neil Ashley, Djamila Ouaret, Lai Mun Wang, Jennifer Wilding, Walter F Bodmer
Pericryptal myofibroblasts in the colon and rectum play an important role in regulating the normal colorectal stem cell niche and facilitating tumor progression. Myofibroblasts previously have been distinguished from normal fibroblasts mostly by the expression of α smooth muscle actin (αSMA). We now have identified AOC3 (amine oxidase, copper containing 3), a surface monoamine oxidase, as a new marker of myofibroblasts by showing that it is the target protein of the myofibroblast-reacting mAb PR2D3. The normal and tumor tissue distribution and the cell line reactivity of AOC3 match that expected for myofibroblasts...
April 12, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26861458/a-novel-carcinoembryonic-antigen-t-cell-bispecific-antibody-cea-tcb-for-the-treatment-of-solid-tumors
#4
Marina Bacac, Tanja Fauti, Johannes Sam, Sara Colombetti, Tina Weinzierl, Djamila Ouaret, Walter Bodmer, Steffi Lehmann, Thomas Hofer, Ralf J Hosse, Ekkehard Moessner, Oliver Ast, Peter Bruenker, Sandra Grau-Richards, Teilo Schaller, Annette Seidl, Christian Gerdes, Mario Perro, Valeria Nicolini, Nathalie Steinhoff, Sherri Dudal, Sebastian Neumann, Thomas von Hirschheydt, Christiane Jaeger, Jose Saro, Vaios Karanikas, Christian Klein, Pablo Umaña
PURPOSE: CEA TCB is a novel IgG-based T-cell bispecific (TCB) antibody for the treatment of CEA-expressing solid tumors currently in phase I clinical trials (NCT02324257). Its format incorporates bivalent binding to CEA, a head-to-tail fusion of CEA- and CD3e-binding Fab domains and an engineered Fc region with completely abolished binding to FcγRs and C1q. The study provides novel mechanistic insights into the activity and mode of action of CEA TCB. EXPERIMENTAL DESIGN: CEA TCB activity was characterized on 110 cell lines in vitro and in xenograft tumor models in vivo using NOG mice engrafted with human peripheral blood mononuclear cells...
July 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26510401/separation-of-cancer-cells-from-white-blood-cells-by-pinched-flow-fractionation
#5
Marie Pødenphant, Neil Ashley, Kamila Koprowska, Kalim U Mir, Maksim Zalkovskij, Brian Bilenberg, Walter Bodmer, Anders Kristensen, Rodolphe Marie
In this paper, the microfluidic size-separation technique pinched flow fractionation (PFF) is used to separate cancer cells from white blood cells (WBCs). The cells are separated at efficiencies above 90% for both cell types. Circulating tumor cells (CTCs) are found in the blood of cancer patients and can form new tumors. CTCs are rare cells in blood, but they are important for the understanding of metastasis. There is therefore a high interest in developing a method for the enrichment of CTCs from blood samples, which also enables further analysis of the separated cells...
December 21, 2015: Lab on a Chip
https://www.readbyqxmd.com/read/25939053/a-mathematician-s-odyssey
#6
Walter Bodmer
In this overview of my research, I have aimed to give the background as to how I came to be involved in my various areas of interest, with an emphasis on the early phases of my career, which largely determined my future directions. I had the enormous good fortune to have worked under two of the most outstanding scientists of the twentieth century, R.A. Fisher and Joshua Lederberg. From mathematics and statistics, I went to population genetics and the early use of computers for modeling and simulation. Molecular biology took me into the laboratory and eventually to somatic cell genetics and human gene mapping...
2015: Annual Review of Genomics and Human Genetics
https://www.readbyqxmd.com/read/25788095/the-fine-scale-genetic-structure-of-the-british-population
#7
Stephen Leslie, Bruce Winney, Garrett Hellenthal, Dan Davison, Abdelhamid Boumertit, Tammy Day, Katarzyna Hutnik, Ellen C Royrvik, Barry Cunliffe, Daniel J Lawson, Daniel Falush, Colin Freeman, Matti Pirinen, Simon Myers, Mark Robinson, Peter Donnelly, Walter Bodmer
Fine-scale genetic variation between human populations is interesting as a signature of historical demographic events and because of its potential for confounding disease studies. We use haplotype-based statistical methods to analyse genome-wide single nucleotide polymorphism (SNP) data from a carefully chosen geographically diverse sample of 2,039 individuals from the United Kingdom. This reveals a rich and detailed pattern of genetic differentiation with remarkable concordance between genetic clusters and geography...
March 19, 2015: Nature
https://www.readbyqxmd.com/read/25775580/the-cdx1-microrna-215-axis-regulates-colorectal-cancer-stem-cell-differentiation
#8
Matthew F Jones, Toshifumi Hara, Princy Francis, Xiao Ling Li, Sven Bilke, Yuelin Zhu, Marbin Pineda, Murugan Subramanian, Walter F Bodmer, Ashish Lal
The transcription factor caudal-type homeobox 1 (CDX1) is a key regulator of differentiation in the normal colon and in colorectal cancer (CRC). CDX1 activates the expression of enterocyte genes, but it is not clear how the concomitant silencing of stem cell genes is achieved. MicroRNAs (miRNAs) are important mediators of gene repression and have been implicated in tumor suppression and carcinogenesis, but the roles of miRNAs in differentiation, particularly in CRC, remain poorly understood. Here, we identified microRNA-215 (miR-215) as a direct transcriptional target of CDX1 by using high-throughput small RNA sequencing to profile miRNA expression in two pairs of CRC cell lines: CDX1-low HCT116 and HCT116 with stable CDX1 overexpression, and CDX1-high LS174T and LS174T with stable CDX1 knockdown...
March 31, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/25657345/genetic-characterization-of-human-populations-from-abo-to-a-genetic-map-of-the-british-people
#9
REVIEW
Walter Bodmer
From 1900, when Landsteiner first described the ABO blood groups, to the present, the methods used to characterize the genetics of human populations have undergone a remarkable development. Concomitantly, our understanding of the history and spread of human populations across the earth has become much more detailed. As has often been said, a better understanding of the genetic relationships among the peoples of the world is one of the best antidotes to racial prejudices. Such an understanding provides us with a fascinating, improved insight into our origins as well as with valuable information about population differences that are of medical relevance...
February 2015: Genetics
https://www.readbyqxmd.com/read/25290318/histocompatibility-1984
#10
J Bodmer, W Bodmer
It is twenty years and nine workshops on from the first international gathering of tissue typers in Durham, North Carolina. The size and range of the series of meetings centred on this year's workshop show the success achieved by the unique collaboration of workers in the HLA field. The main workshop meeting in Munich, organized by Ekkehard Albert and Wolfgang Mayr, was preceded by the third H-2 and HLA cloning meeting, organized by Jean Dausset in Strasbourg and by a biochemistry workshop in Munich organized by Julia and Walter Bodmer and Michael Crumpton...
September 1984: Immunology Today
https://www.readbyqxmd.com/read/25168481/dsh-homolog-dvl3-mediates-resistance-to-igfir-inhibition-by-regulating-igf-ras-signaling
#11
Shan Gao, Ilirjana Bajrami, Clare Verrill, Asha Kigozi, Djamila Ouaret, Tamara Aleksic, Ruth Asher, Cheng Han, Paul Allen, Deborah Bailey, Stephan Feller, Takeshi Kashima, Nicholas Athanasou, Jean-Yves Blay, Sandra Schmitz, Jean-Pascal Machiels, Nav Upile, Terry M Jones, George Thalmann, Shazad Q Ashraf, Jennifer L Wilding, Walter F Bodmer, Mark R Middleton, Alan Ashworth, Christopher J Lord, Valentine M Macaulay
Drugs that inhibit insulin-like growth factor 1 (IGFI) receptor IGFIR were encouraging in early trials, but predictive biomarkers were lacking and the drugs provided insufficient benefit in unselected patients. In this study, we used genetic screening and downstream validation to identify the WNT pathway element DVL3 as a mediator of resistance to IGFIR inhibition. Sensitivity to IGFIR inhibition was enhanced specifically in vitro and in vivo by genetic or pharmacologic blockade of DVL3. In breast and prostate cancer cells, sensitization tracked with enhanced MEK-ERK activation and relied upon MEK activity and DVL3 expression...
October 15, 2014: Cancer Research
https://www.readbyqxmd.com/read/24797403/rapidly-derived-colorectal-cancer-cultures-recapitulate-parental-cancer-characteristics-and-enable-personalized-therapeutic-assays
#12
Neil Ashley, Matthew Jones, Djamila Ouaret, Jenny Wilding, Walter F Bodmer
We have developed a simple procedure for deriving pure cultures of growing cancer cells from colorectal cancers, including material refrigerated overnight, for pathological characterization and cytotoxicity assays. Forty-six cancers were processed and cultures set up under varying culture conditions. Use of a Rho kinase (ROCK1) inhibitor markedly increased culture survival, resulting in 80% of samples growing in culture for at least 1 month and beyond. Overnight refrigeration of samples before culture initiation had little effect on success rates, paving the way for cultures to be established for samples collected over wide geographical areas, such as those for clinical trials...
September 2014: Journal of Pathology
https://www.readbyqxmd.com/read/24755471/colorectal-cancer-cell-lines-are-representative-models-of-the-main-molecular-subtypes-of-primary-cancer
#13
Dmitri Mouradov, Clare Sloggett, Robert N Jorissen, Christopher G Love, Shan Li, Antony W Burgess, Diego Arango, Robert L Strausberg, Daniel Buchanan, Samuel Wormald, Liam O'Connor, Jennifer L Wilding, David Bicknell, Ian P M Tomlinson, Walter F Bodmer, John M Mariadason, Oliver M Sieber
Human colorectal cancer cell lines are used widely to investigate tumor biology, experimental therapy, and biomarkers. However, to what extent these established cell lines represent and maintain the genetic diversity of primary cancers is uncertain. In this study, we profiled 70 colorectal cancer cell lines for mutations and DNA copy number by whole-exome sequencing and SNP microarray analyses, respectively. Gene expression was defined using RNA-Seq. Cell line data were compared with those published for primary colorectal cancers in The Cancer Genome Atlas...
June 15, 2014: Cancer Research
https://www.readbyqxmd.com/read/24717177/cancer-cell-lines-for-drug-discovery-and-development
#14
REVIEW
Jennifer L Wilding, Walter F Bodmer
Despite the millions of dollars spent on target validation and drug optimization in preclinical models, most therapies still fail in phase III clinical trials. Our current model systems, or the way we interpret data from them, clearly do not have sufficient clinical predictive power. Current opinion suggests that this is because the cell lines and xenografts that are commonly used are inadequate models that do not effectively mimic and predict human responses. This has become such a widespread belief that it approaches dogma in the field of drug discovery and optimization and has spurred a surge in studies devoted to the development of more sophisticated animal models such as orthotopic patient-derived xenografts in an attempt to obtain more accurate estimates of whether particular cancers will respond to given treatments...
May 1, 2014: Cancer Research
https://www.readbyqxmd.com/read/23867471/stem-cell-differentiation-and-lumen-formation-in-colorectal-cancer-cell-lines-and-primary-tumors
#15
Neil Ashley, Trevor M Yeung, Walter F Bodmer
Single cancer stem-like cells (CSC) from colorectal cancers can be functionally identified by their ability to form large lumen-containing colonies in three-dimensional Matrigel cultures. These colonies contain the three types of differentiated colorectal epithelial cells, and single cells obtained from them can reproduce themselves and form tumors efficiently in immunodeficient mice. In this study, we show how hypoxia affects these CSC-derived lumens to control differentiation of stem-like cells and enterocytes via the homeobox gene CDX1...
September 15, 2013: Cancer Research
https://www.readbyqxmd.com/read/23213241/direct-and-immune-mediated-antibody-targeting-of-erbb-receptors-in-a-colorectal-cancer-cell-line-panel
#16
Shazad Q Ashraf, Angela M Nicholls, Jennifer L Wilding, Triantafyllia G Ntouroupi, Neil J Mortensen, Walter F Bodmer
A significant proportion of colorectal cancer (CRC) patients are resistant to anti-ERBB1 [avian erythroblastic leukemia viral (v-erb-b) oncogene homolog, receptor for EGF] monoclonal antibodies (Mabs). We evaluated both immune and nonimmune effects of cetuximab (anti-ERBB1 Mab), trastuzumab (anti-ERBB2 Mab), pertuzumab (anti-ERBB2 Mab), and lapatinib (dual ERBB1 and ERBB2 tyrosine kinase inhibitor) in a large well-characterized panel of 64 CRC cell lines to find response predictive tumor characteristics. There was a significant correlation between the direct effects of cetuximab and lapatinib...
December 18, 2012: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/22875147/role-of-rare-variants-in-undetermined-multiple-adenomatous-polyposis-and-early-onset-colorectal-cancer
#17
Jérémie H Lefevre, Carolina Bonilla, Chrystelle Colas, Bruce Winney, Elaine Johnstone, Susan Tonks, Tammy Day, Katarzyna Hutnik, Abdelhamid Boumertit, Florent Soubrier, Rachel Midgley, David Kerr, Yann Parc, Walter F Bodmer
Some 15-20% of multiple adenomatous polyposis have no genetic explanation and 20-30% of colorectal cancer (CRC) cases are thought to be due to inherited multifactorial causes. Accumulation of deleterious effects of low-frequency dominant and independently acting variants may be a partial explanation for such patients. The aim of this study was to type a selection of rare and low-frequency variants (<5%) to elucidate their role in CRC susceptibility. A total of 1181 subjects were included (866 controls; 315 cases)...
November 26, 2012: Journal of Human Genetics
https://www.readbyqxmd.com/read/21865258/the-peopling-of-europe-and-the-cautionary-tale-of-y-chromosome-lineage-r-m269
#18
George B J Busby, Francesca Brisighelli, Paula Sánchez-Diz, Eva Ramos-Luis, Conrado Martinez-Cadenas, Mark G Thomas, Daniel G Bradley, Leonor Gusmão, Bruce Winney, Walter Bodmer, Marielle Vennemann, Valentina Coia, Francesca Scarnicci, Sergio Tofanelli, Giuseppe Vona, Rafal Ploski, Carla Vecchiotti, Tatijana Zemunik, Igor Rudan, Sena Karachanak, Draga Toncheva, Paolo Anagnostou, Gianmarco Ferri, Cesare Rapone, Tor Hervig, Torolf Moen, James F Wilson, Cristian Capelli
Recently, the debate on the origins of the major European Y chromosome haplogroup R1b1b2-M269 has reignited, and opinion has moved away from Palaeolithic origins to the notion of a younger Neolithic spread of these chromosomes from the Near East. Here, we address this debate by investigating frequency patterns and diversity in the largest collection of R1b1b2-M269 chromosomes yet assembled. Our analysis reveals no geographical trends in diversity, in contradiction to expectation under the Neolithic hypothesis, and suggests an alternative explanation for the apparent cline in diversity recently described...
March 7, 2012: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/21829225/people-of-the-british-isles-preliminary-analysis-of-genotypes-and-surnames-in-a-uk-control-population
#19
Bruce Winney, Abdelhamid Boumertit, Tammy Day, Dan Davison, Chikodi Echeta, Irina Evseeva, Katarzyna Hutnik, Stephen Leslie, Kristin Nicodemus, Ellen C Royrvik, Susan Tonks, Xiaofeng Yang, James Cheshire, Paul Longley, Pablo Mateos, Alexandra Groom, Caroline Relton, D Tim Bishop, Kathryn Black, Emma Northwood, Louise Parkinson, Timothy M Frayling, Anna Steele, Julian R Sampson, Turi King, Ron Dixon, Derek Middleton, Barbara Jennings, Rory Bowden, Peter Donnelly, Walter Bodmer
There is a great deal of interest in a fine-scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to have a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved...
February 2012: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/21368208/hypoxia-and-lineage-specification-of-cell-line-derived-colorectal-cancer-stem-cells
#20
Trevor M Yeung, Shaan C Gandhi, Walter F Bodmer
Hypoxia is an important regulator of normal and cancer stem cell (CSC) differentiation. Colorectal CSCs from SW1222, LS180, and CCK81 colorectal cancer-derived cell lines are able to differentiate into complex 3D lumen-containing structures in normoxia, whereas in hypoxia, they form undifferentiated dense colonies that have reduced expression of the enterocyte differentiation marker CDX1, lack goblet cell formation, and have increased expression of BMI1 and activated Notch1. Hypoxia increases the clonogenicity of CSCs, which is cumulative as each round of hypoxia enriches for more CSCs...
March 15, 2011: Proceedings of the National Academy of Sciences of the United States of America
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