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Author |
Vicente-Duenas, C.; Abollo-Jimenez, F.; Ruiz-Roca, L.; Alonso-Escudero, E.; Jimenez, R.; Cenador, M.B.G.; Criado, F.J.G.; Cobaleda, C.; Sanchez-Garcia, I. |
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Title |
The age of the target cell affects B-cell leukaemia malignancy |
Type |
Journal Article |
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Year |
2010 |
Publication |
Aging |
Abbreviated Journal |
Aging (Albany NY) |
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Volume |
2 |
Issue |
12 |
Pages |
908-913 |
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Keywords |
Age Factors; Animals; Bone Marrow Transplantation; *Cell Aging; Cell Line; Cell Survival; Fusion Proteins, bcr-abl/genetics/metabolism; Genes, abl; Humans; Leukemia, B-Cell/genetics/metabolism/*pathology; Leukemia, Experimental/genetics/metabolism/*pathology; Mice; Mice, Transgenic; Neoplasm Invasiveness; Neoplastic Stem Cells/metabolism/*pathology |
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Abstract |
The incidence, malignancy and treatment resistance of many types of human B-cell leukaemias (B-ALL) are directly related to patient age. A major obstacle to elucidate the contribution of age to the development and evolution of leukaemias is the lack of appropriate mouse models where precise control of the timing of oncogene expression is possible. Here we present proof-of-principle experiments showing how a conditional transgenic mouse model of BCR-ABLp190-driven B-ALL offers the opportunity to test the hypothesis that the age of the leukemic cells-of-origin of B-ALL influences B-ALL malignancy. B-ALLs generated from 12- and 20-month-old progenitors gave rise to a more invasive B-ALL than the one developed from 4-month old precursors. This was evidenced by survival analysis revealing the increased malignancy of B-ALLs generated from 20 or 12-month-old transformed progenitors compared with the 4-month equivalents (median survival of 88 days versus 50.5 and 33 days, respectively). Our study shows that the age of target cells at the time of transformation affects B-ALL malignancy. |
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Address |
Experimental Therapeutics and Translational Oncology Program, Instituto de Biologia Molecular y Celular del Cancer, CSIC/ Universidad de Salamanca, Campus M. de Unamuno s/n, 37007- Salamanca, Spain. cvd@usal.es; isg@usal.es |
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English |
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ISSN |
1945-4589 |
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Area |
WP6 In vivo |
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Notes |
PMID:21164221 |
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Call Number |
CBM.UAM @ ccobaleda @ |
Serial |
50 |
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Author |
Vicente-Duenas, C.; Cobaleda, C.; Perez-Losada, J.; Sanchez-Garcia, I. |
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Title |
The evolution of cancer modeling: the shadow of stem cells |
Type |
Journal Article |
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Year |
2010 |
Publication |
Disease Models & Mechanisms |
Abbreviated Journal |
Dis Model Mech |
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Volume |
3 |
Issue |
3-4 |
Pages |
149-155 |
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Keywords |
Animals; *Disease Models, Animal; Embryonic Stem Cells/metabolism; Gene Knock-In Techniques; Humans; Mice; Mutation/genetics; Neoplasms/*pathology; Neoplastic Stem Cells/*pathology; Oncogenes/genetics |
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Abstract |
Cancer is a complex and highly dynamic process. Genetically engineered mouse models (GEMs) that develop cancer are essential systems for dissecting the processes that lead to human cancer. These animal models provide a means to determine the causes of malignancy and to develop new treatments, thus representing a resource of immense potential for medical oncology. The sophistication of modeling cancer in mice has increased to the extent that now we can induce, study and manipulate the cancer disease process in a manner that is impossible to perform in human patients. However, all GEMs described so far have diverse shortcomings in mimicking the hierarchical structure of human cancer tissues. In recent years, a more detailed picture of the cellular and molecular mechanisms determining the formation of cancer has emerged. This Commentary addresses new experimental approaches toward a better understanding of carcinogenesis and discusses the impact of new animal models. |
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Address |
Experimental Therapeutics and Translational Oncology Program, Instituto de Biologia Molecular y Celular del Cancer, CSIC/Universidad de Salamanca, Campus M. Unamuno s/n, 37007-Salamanca, Spain |
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ISSN |
1754-8403 |
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Area |
WP6 In vivo |
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Notes |
PMID:20212083 |
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Call Number |
CBM.UAM @ ccobaleda @ |
Serial |
51 |
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Author |
Roosli, M.; Jenni, D.; Kheifets, L.; Mezei, G. |
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Title |
Extremely low frequency magnetic field measurements in buildings with transformer stations in Switzerland |
Type |
Journal Article |
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Year |
2011 |
Publication |
The Science of the Total Environment |
Abbreviated Journal |
Sci Total Environ |
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Volume |
409 |
Issue |
18 |
Pages |
3364-3369 |
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Keywords |
*Electrical Equipment and Supplies; *Electromagnetic Fields; Environmental Exposure/*analysis/statistics & numerical data; Housing; Humans; Switzerland |
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Abstract |
The aim of this study was to evaluate an exposure assessment method that classifies apartments in three exposure categories of extremely low frequency magnetic fields (ELF-MF) based on the location of the apartment relative to the transformer room. We completed measurements in 39 apartments in 18 buildings. In each room of the apartments ELF-MF was concurrently measured with 5 to 6 EMDEX II meters for 10 min. Measured arithmetic mean ELF-MF was 0.59 muT in 8 apartments that were fully adjacent to a transformer room, either directly above the transformer or touching the transformer room wall-to-wall. In apartments that only partly touched the transformer room at corners or edges, average ELF-MF level was 0.14 muT. Average exposure in the remaining apartments was 0.10 muT. Kappa coefficient for exposure classification was 0.64 (95%-CI: 0.45-0.82) if only fully adjacent apartments were considered as highly exposed (>0.4 muT). We found a distinct ELF-MF exposure gradient in buildings with transformer. Exposure classification based on the location of the apartment relative to the transformer room appears feasible. Such an approach considerably reduces effort for exposure assessment and may be used to eliminate selection bias in future epidemiologic studies. |
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Address |
Swiss Tropical and Public Health Institute, Basel, Switzerland. martin.roosli@unibas.ch |
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English |
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ISSN |
0048-9697 |
ISBN |
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Area |
WP2 Exposure measurements |
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Notes |
PMID:21684576 |
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Call Number |
CBM.UAM @ ccobaleda @ |
Serial |
54 |
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Author |
Ahlbom, A.; Day, N.; Feychting, M.; Roman, E.; Skinner, J.; Dockerty, J.; Linet, M.; McBride, M.; Michaelis, J.; Olsen, J.H.; Tynes, T.; Verkasalo, P.K. |
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Title |
A pooled analysis of magnetic fields and childhood leukaemia |
Type |
Journal Article |
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Year |
2000 |
Publication |
British Journal of Cancer |
Abbreviated Journal |
Br J Cancer |
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Volume |
83 |
Issue |
5 |
Pages |
692-698 |
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Keywords |
Adolescent; Bias (Epidemiology); Case-Control Studies; Child; Child, Preschool; Electromagnetic Fields/*adverse effects; Humans; Infant; Infant, Newborn; Leukemia/*etiology; Regression Analysis; Risk |
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Abstract |
Previous studies have suggested an association between exposure to 50-60 Hz magnetic fields (EMF) and childhood leukaemia. We conducted a pooled analysis based on individual records from nine studies, including the most recent ones. Studies with 24/48-hour magnetic field measurements or calculated magnetic fields were included. We specified which data analyses we planned to do and how to do them before we commenced the work. The use of individual records allowed us to use the same exposure definitions, and the large numbers of subjects enabled more precise estimation of risks at high exposure levels. For the 3203 children with leukaemia and 10 338 control children with estimated residential magnetic field exposures levels < 0.4 microT, we observed risk estimates near the no effect level, while for the 44 children with leukaemia and 62 control children with estimated residential magnetic field exposures >/= 0.4 microT the estimated summary relative risk was 2.00 (1.27-3.13), P value = 0.002). Adjustment for potential confounding variables did not appreciably change the results. For North American subjects whose residences were in the highest wire code category, the estimated summary relative risk was 1.24 (0.82-1.87). Thus, we found no evidence in the combined data for the existence of the so-called wire-code paradox. In summary, the 99.2% of children residing in homes with exposure levels < 0.4 microT had estimates compatible with no increased risk, while the 0.8% of children with exposures >/= 0.4 microT had a relative risk estimate of approximately 2, which is unlikely to be due to random variability. The explanation for the elevated risk is unknown, but selection bias may have accounted for some of the increase. |
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Address |
Division of Epidemiology, National Institute of Environmental Medicine, Karolinska Institute, Sweden |
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English |
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ISSN |
0007-0920 |
ISBN |
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Area |
WP2 Exposure measurements & WP9 Epidemiology |
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Notes |
PMID:10944614 |
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Call Number |
CBM.UAM @ ccobaleda @ |
Serial |
55 |
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Author |
Greenland, S.; Sheppard, A.R.; Kaune, W.T.; Poole, C.; Kelsh, M.A. |
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Title |
A pooled analysis of magnetic fields, wire codes, and childhood leukemia. Childhood Leukemia-EMF Study Group |
Type |
Journal Article |
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Year |
2000 |
Publication |
Epidemiology (Cambridge, Mass.) |
Abbreviated Journal |
Epidemiology |
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Volume |
11 |
Issue |
6 |
Pages |
624-634 |
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Keywords |
Child; *Electric Wiring; Electromagnetic Fields/*adverse effects; Environmental Exposure/*adverse effects; Humans; Leukemia/*etiology |
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Abstract |
We obtained original individual data from 15 studies of magnetic fields or wire codes and childhood leukemia, and we estimated magnetic field exposure for subjects with sufficient data to do so. Summary estimates from 12 studies that supplied magnetic field measures exhibited little or no association of magnetic fields with leukemia when comparing 0.1-0.2 and 0.2-0.3 microtesla (microT) categories with the 0-0.1 microT category, but the Mantel-Haenszel summary odds ratio comparing >0.3 microT to 0-0.1 microT was 1.7 (95% confidence limits = 1.2, 2.3). Similar results were obtained using covariate adjustment and spline regression. The study-specific relations appeared consistent despite the numerous methodologic differences among the studies. The association of wire codes with leukemia varied considerably across studies, with odds ratio estimates for very high current vs low current configurations ranging from 0.7 to 3.0 (homogeneity P = 0.005). Based on a survey of household magnetic fields, an estimate of the U.S. population attributable fraction of childhood leukemia associated with residential exposure is 3% (95% confidence limits = -2%, 8%). Our results contradict the idea that the magnetic field association with leukemia is less consistent than the wire code association with leukemia, although analysis of the four studies with both measures indicates that the wire code association is not explained by measured fields. The results also suggest that appreciable magnetic field effects, if any, may be concentrated among relatively high and uncommon exposures, and that studies of highly exposed populations would be needed to clarify the relation of magnetic fields to childhood leukemia. |
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Address |
Department of Epidemiology, UCLA School of Public Health, Los Angeles, CA, USA |
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English |
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ISSN |
1044-3983 |
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WP2 Exposure measurements & WP9 Epidemiology |
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Notes |
PMID:11055621 |
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Call Number |
CBM.UAM @ ccobaleda @ |
Serial |
56 |
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