27 results on '"Rancourt R"'
Search Results
2. Nitro-oleic Acid Mitigates Chlorine-induced Lung Injury in Mice by Inhibiting Pro-inflammatory Macrophage Activation
- Author
-
Malaviya, R., primary, Gow, A., additional, Freeman, B., additional, Rancourt, R., additional, Abramova, E., additional, Vayas, K., additional, Laskin, J., additional, and Laskin, D.L., additional
- Published
- 2024
- Full Text
- View/download PDF
3. The influence of migration on women’s satisfaction during pregnancy and birth: results of a comparative prospective study with the Migrant Friendly Maternity Care Questionnaire (MFMCQ)
- Author
-
Gürbüz, B., Großkreutz, C., Vortel, M., Borde, T., Rancourt, R. C., Stepan, H., Sauzet, O., Henrich, W., David, M., and Seidel, V.
- Published
- 2019
- Full Text
- View/download PDF
4. Reliability of a novel approach for reference-based cell type estimation in human placental DNA methylation studies
- Author
-
Dieckmann, L. (Linda), Cruceanu, C. (Cristiana), Lahti-Pulkkinen, M. (Marius), Lahti, J. (Jari), Kvist, T. (Tuomas), Laivuori, H. (Hannele), Sammallahti, S. (Sara), Villa, P. M. (Pia M.), Suomalainen-König, S. (Sanna), Rancourt, R. C. (Rebecca C.), Plagemann, A. (Andreas), Henrich, W. (Wolfgang), Eriksson, J. G. (Johan G.), Kajantie, E. (Eero), Entringer, S. (Sonja), Braun, T. (Thorsten), Räikkönen, K. (Katri), Binder, E. B. (Elisabeth B.), Czamara, D. (Darina), Dieckmann, L. (Linda), Cruceanu, C. (Cristiana), Lahti-Pulkkinen, M. (Marius), Lahti, J. (Jari), Kvist, T. (Tuomas), Laivuori, H. (Hannele), Sammallahti, S. (Sara), Villa, P. M. (Pia M.), Suomalainen-König, S. (Sanna), Rancourt, R. C. (Rebecca C.), Plagemann, A. (Andreas), Henrich, W. (Wolfgang), Eriksson, J. G. (Johan G.), Kajantie, E. (Eero), Entringer, S. (Sonja), Braun, T. (Thorsten), Räikkönen, K. (Katri), Binder, E. B. (Elisabeth B.), and Czamara, D. (Darina)
- Abstract
The placenta is a central organ during early development, influencing trajectories of health and disease. DNA methylation (DNAm) studies of human placenta improve our understanding of how its function relates to disease risk. However, DNAm studies can be biased by cell type heterogeneity, so it is essential to control for this in order to reduce confounding and increase precision. Computational cell type deconvolution approaches have proven to be very useful for this purpose. For human placenta, however, an assessment of the performance of these estimation methods is still lacking. Here, we examine the performance of a newly available reference-based cell type estimation approach and compare it to an often-used reference-free cell type estimation approach, namely RefFreeEWAS, in placental genome-wide DNAm samples taken at birth and from chorionic villus biopsies early in pregnancy using three independent studies comprising over 1000 samples. We found both reference-free and reference-based estimated cell type proportions to have predictive value for DNAm, however, reference-based cell type estimation outperformed reference-free estimation for the majority of data sets. Reference-based cell type estimations mirror previous histological knowledge on changes in cell type proportions through gestation. Further, CpGs whose variation in DNAm was largely explained by reference-based estimated cell type proportions were in the proximity of genes that are highly tissue-specific for placenta. This was not the case for reference-free estimated cell type proportions. We provide a list of these CpGs as a resource to help researchers to interpret results of existing studies and improve future DNAm studies of human placenta.
- Published
- 2022
5. Betamethasone administration during pregnancy is associated with placental epigenetic changes with implications for inflammation
- Author
-
Czamara, D. (Darina), Dieckmann, L. (Linda), Röh, S. (Simone), Kraemer, S. (Sarah), Rancourt, R. C. (Rebecca C.), Sammallahti, S. (Sara), Kajantie, E. (Eero), Laivuori, H. (Hannele), Eriksson, J. G. (Johan G.), Räikkönen, K. (Katri), Henrich, W. (Wolfgang), Plagemann, A. (Andreas), Binder, E. B. (Elisabeth B.), Braun, T. (Thorsten), Entringer, S. (Sonja), Czamara, D. (Darina), Dieckmann, L. (Linda), Röh, S. (Simone), Kraemer, S. (Sarah), Rancourt, R. C. (Rebecca C.), Sammallahti, S. (Sara), Kajantie, E. (Eero), Laivuori, H. (Hannele), Eriksson, J. G. (Johan G.), Räikkönen, K. (Katri), Henrich, W. (Wolfgang), Plagemann, A. (Andreas), Binder, E. B. (Elisabeth B.), Braun, T. (Thorsten), and Entringer, S. (Sonja)
- Abstract
Background: Glucocorticoids (GCs) play a pivotal role in fetal programming. Antenatal treatment with synthetic GCs (sGCs) in individuals in danger of preterm labor is common practice. Adverse short- and long-term effects of antenatal sGCs have been reported, but their effects on placental epigenetic characteristics have never been systematically studied in humans. Results: We tested the association between exposure to the sGC betamethasone (BET) and placental DNA methylation (DNAm) in 52 exposed cases and 84 gestational-age-matched controls. We fine-mapped associated loci using targeted bisulfite sequencing. The association of placental DNAm with gene expression and co-expression analysis on implicated genes was performed in an independent cohort including 494 placentas. Exposure to BET was significantly associated with lower placenta DNAm at an enhancer of FKBP5. FKBP5 (FK506-binding protein 51) is a co-chaperone that modulates glucocorticoid receptor activity. Lower DNAm at this enhancer site was associated with higher expression of FKBP5 and a co-expressed gene module. This module is enriched for genes associated with preeclampsia and involved in inflammation and immune response. Conclusions: Our findings suggest that BET exposure during pregnancy associates with few but lasting changes in placental DNAm and may promote a gene expression profile associated with placental dysfunction and increased inflammation. This may represent a pathway mediating GC-associated negative long-term consequences and health outcomes in offspring.
- Published
- 2021
6. Formation documentaire (la)
- Author
-
Bonnelly, C., Laverdière, R., J.-P., Devroey, Rancourt, R., Bujold, N., Coulon, A., Bourquin, Y., Panijel, C., Pocher, B., Verreault, L., Série, H., Caron, G., M.-G., Bodart, Bretelle-Desmazières, D., Xhoffer-Wolf, D., Côté J.-P., Jean-Pierre, J.P., Denis, Dandjinou, P., Ducasse, R., Greene, R., M.-D., Heusse, Thirion, P., and Deggis, Gilles
- Subjects
francophonie ,documentaliste ,technologies de l'information ,bibliothèque ,[SHS.INFO] Humanities and Social Sciences/Library and information sciences - Abstract
Après l'ENSSIB à Villeurbanne en 1990, l'Université de Dakar en 1993, ce fut au tour de l'Université Laval d'accueillir en 1995 à Québec les troisièmes Colloque et Assemblée générale de l'ABCDEF. Le comité scientifique a retenu "la formation documentaire des utilisateurs" comme thème d'échanges et de discussions. En cette fin de siècle où les technologies de l'information viennent transformer le fonctionnement des services documentaires, ce thème revêt certes une importance capitale. Centrant leur réflexion sur les moyens de faciliter l'autonomie documentaire des usagers, il ramène en effet les bibliothèques à leur mission fondamentale : celle de bien soutenir les professeurs, chercheurs et étudiants, dans un monde où la maîtrise de l'information est devenue un facteur incontournable de réussite, de performance et de compétitivité.
- Published
- 1999
7. Formation documentaire (la): Actes du colloque de l'ABCDEF, Université Laval, Québec, 23-25 octobre 1995
- Author
-
Bonnelly, C., Laverdière, R., J.-P., Devroey, Rancourt, R., Bujold, N., Coulon, A., Bourquin, Y., Panijel, C., Pocher, B., Verreault, L., Série, H., Caron, G., M.-G., Bodart, Bretelle-Desmazières, D., Xhoffer-Wolf, D., Côté J.-P., Jean-Pierre, J.P., Denis, Dandjinou, P., Ducasse, R., Greene, R., M.-D., Heusse, Thirion, P., and Agence Universitaire de la Francophonie (AUF)
- Subjects
francophonie ,documentaliste ,[SHS.INFO]Humanities and Social Sciences/Library and information sciences ,technologies de l'information ,bibliothèque - Abstract
Après l'ENSSIB à Villeurbanne en 1990, l'Université de Dakar en 1993, ce fut au tour de l'Université Laval d'accueillir en 1995 à Québec les troisièmes Colloque et Assemblée générale de l'ABCDEF. Le comité scientifique a retenu "la formation documentaire des utilisateurs" comme thème d'échanges et de discussions. En cette fin de siècle où les technologies de l'information viennent transformer le fonctionnement des services documentaires, ce thème revêt certes une importance capitale. Centrant leur réflexion sur les moyens de faciliter l'autonomie documentaire des usagers, il ramène en effet les bibliothèques à leur mission fondamentale : celle de bien soutenir les professeurs, chercheurs et étudiants, dans un monde où la maîtrise de l'information est devenue un facteur incontournable de réussite, de performance et de compétitivité.
- Published
- 1999
8. Reduced thioredoxin increases proinflammatory cytokines and neutrophil influx in rat airways: Modulation by airway mucus☆
- Author
-
RANCOURT, R, primary, LEE, R, additional, ONEILL, H, additional, ACCURSO, F, additional, and WHITE, C, additional
- Published
- 2007
- Full Text
- View/download PDF
9. Administration and intradisciplinary conflict within nursing.
- Author
-
Noble KA and Rancourt R
- Published
- 1991
10. An analysis of the epistemic orientation of first- and third-year students in a physiotherapy program.
- Author
-
Rancourt R and Ballantine C
- Published
- 1990
11. Antimutagenicity, cytotoxicity and composition of chlorophyllin copper complex
- Author
-
Chernomorsky, S., Rancourt, R., Virdi, K., Segelman, A., and Poretz, R. D.
- Published
- 1997
- Full Text
- View/download PDF
12. Embryonic 'over'-nutrition and metabolic malprogramming in the avian primary brain area for control of energy balance, feed intake and body weight.
- Author
-
Tzschentke, B., Bogatyrev, S., Yakimova, K. S., Rancourt, R. C., Schellong, K., and Plagemann, A.
- Subjects
BIOENERGETICS & poultry ,BIRDS ,BIRD weight ,ANIMAL health - Abstract
During critical prenatal periods nutrient supply programs central control of energy balance, feed intake and body weight. In mammals as well in birds, prenatal glucose oversupply, for instance, may increases the offspring risk for metabolic disorders and related diseases throughout life. We investigated the long-lasting influence of temporary inovo hyperglycemia in chickens on neuronal mechanisms of the nucleus infundibuli hypothalami (NI), the 'critical' centre regulation metabolism, feed intake and body weight as well as on related peripheral parameters. Experiments were carried out in Lohmann White Leghorn chickens starting in embryos in three experimental groups: one untreated control group, one in-ovo injection control (daily single injection of 0.5 ml NaCl-solution) and one group prenatally experienced with temporary hyperglycemia by daily single injection of 0.5 ml glucose solution (30 mmol/l) from days 14 to 17 of incubation. After three weeks post-hatching in the untreated control group for the first time the avian neuronal glucose and leptin sensitivity was investigated using extracellular recordings in brain slices. Human recombinant leptin was also tested in combination with GABAB-receptor agonist and antagonist. The longlasting effect of temporary in-ovo hyperglycemia was examined on neuronal glucose sensitivity, the glucose transporter GLUT1 and 3, the leptin and insulin receptor expression as well as on the total body fat and blood glucose level. Additional, in male and female chickens the body weight development was recorded in all experimental groups during the total 3-weeks growing period. Results can be summarized as follows (RANCOURT et al., 2015; TZSCHENTKE et al., 2015; BOGATYREV et al., 2017): 1) NI-neurons show mammalian-like responsiveness after acute glucose, leptin and GABA application. GABA
B -mechanisms involved in GABA release play a likely important role in the leptin mediated effects on NI neurons via functional leptin receptors. 4) Temporary late prenatal hyperglycemia induces lasting hypothalamic 'glucose-resistance' via strongly decreased neuronal glucose sensitivity as well glucose transporter, insulin- and leptin receptor expression. 3) After 3 weeks post-hatching the strong changes in the neuronal mechanisms were not accompanied by changes in related peripheral metabolic parameters as well in the body weight in male and female chickens. In conclusion, although in 3 weeks old chickens no changes in peripheral metabolic parameters and body weight development could be observed, just temporary hyperglycemia during the second half of incubation, may leading to persistent malprogramming in central control of energy balance, feed intake and body weight as predisposition for the development of metabolic disorders. It shows a risk of in-ovo feeding. Further, the chicken embryo provides a valuable new model for investigating early central nervous origins of 'diabesity' and related diseases. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
13. Effect of cell cycle growth arrest on global DNA methylation status in human lung epithelial-like (A549) cells
- Author
-
Panayiotidis, M. I., Rancourt, R. C., Aglaia Pappa, and White, C. W.
14. Ways of Knowing of First-Year Engineering Students in the English and French Language Programmed at the University of Ottawa
- Author
-
Gibbons, D.T., primary and Rancourt, R., additional
- Full Text
- View/download PDF
15. Ways of Knowing of First-Year Engineering Students in the English and French Language Programmed at the University of Ottawa.
- Author
-
Gibbons, D.T. and Rancourt, R.
- Published
- 1992
- Full Text
- View/download PDF
16. Getting ready for the European Health Data Space (EHDS): IDERHA's plan to align with the latest EHDS requirements for the secondary use of health data.
- Author
-
Hussein R, Balaur I, Burmann A, Ćwiek-Kupczyńska H, Gadiya Y, Ghosh S, Jayathissa P, Katsch F, Kremer A, Lähteenmäki J, Meng Z, Morasek K, C Rancourt R, Satagopam V, Sauermann S, Scheider S, Stamm T, Muehlendyck C, and Gribbon P
- Abstract
Objective: The European Health Data Space (EHDS) shapes the digital transformation of healthcare in Europe. The EHDS regulation will also accelerate the use of health data for research, innovation, policy-making, and regulatory activities for secondary use of data (known as EHDS2). The Integration of heterogeneous Data and Evidence towards Regulatory and HTA Acceptance (IDERHA) project builds one of the first pan-European health data spaces in alignment with the EHDS2 requirements, addressing lung cancer as a pilot., Methods: In this study, we conducted a comprehensive review of the EHDS regulation, technical requirements for EHDS2, and related projects. We also explored the results of the Joint Action Towards the European Health Data Space (TEHDAS) to identify the framework of IDERHA's alignment with EHDS2. We also conducted an internal webinar and an external workshop with EHDS experts to share expertise on the EHDS requirements and challenges., Results: We identified the lessons learned from the existing projects and the minimum-set of requirements for aligning IDERHA infrastructure with EHDS2, including user journey, concepts, terminologies, and standards. The IDERHA framework (i.e., platform architecture, standardization approaches, documentation, etc.) is being developed accordingly., Discussion: The IDERHA's alignment plan with EHDS2 necessitates the implementation of three categories of standardization for: data discoverability: Data Catalog Vocabulary (DCAT-AP), enabling semantics interoperability: Observational Medical Outcomes Partnership (OMOP), and health data exchange (DICOM and FHIR). The main challenge is that some standards are still being refined, e.g., the extension of the DCAT-AP (HealthDCAT-AP). Additionally, extensions to the Observational Health Data Sciences and Informatics (OHDSI) OMOP Common Data Model (CDM) to represent the patient-generated health data are still needed. Finally, proper mapping between standards (FHIR/OMOP) is a prerequisite for proper data exchange., Conclusions: The IDERHA's plan and our collaboration with other EHDS initiatives/projects are critical in advancing the implementation of EHDS2., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Hussein R et al.)
- Published
- 2024
- Full Text
- View/download PDF
17. Optimized RNA isolation of FFPE uterine scar tissues for RNA expression analyses delineated by laser microdissection.
- Author
-
Paping A, Basler C, C Rancourt R, Ehrlich L, Melchior K, Henrich W, and Braun T
- Subjects
- Formaldehyde, Humans, Laser Capture Microdissection, Lasers, Paraffin Embedding methods, Tissue Fixation methods, Cicatrix genetics, RNA genetics
- Abstract
Samples for histological analyses are often formalin-fixed paraffin-embedded (FFPE) and slide-mounted, which complicates RNA extraction for many downstream molecular applications. Furthermore, when the region of interest is extremely small due to isolation with laser microdissection (LMD), extracting RNA of adequate quality and quantity is difficult. We describe an optimized protocol for maximizing RNA output from FFPE tissue devised to identify and analyze gene expression of human maternal uterine scar tissue obtained from uterotomy scars resulting from prior cesarean deliveries. Gomori trichrome staining allowed for region identification for LMD. Successful RNA isolation, reverse transcription and, importantly, quantitative real-time PCR (qRT-PCR) were performed. This report provides an optimized step-by-step protocol yielding sufficient RNA for qRT-PCR analyses from challenging tissue/LMD-FFPE samples.
- Published
- 2022
- Full Text
- View/download PDF
18. Lung injury, oxidative stress and fibrosis in mice following exposure to nitrogen mustard.
- Author
-
Sunil VR, Vayas KN, Abramova EV, Rancourt R, Cervelli JA, Malaviya R, Goedken M, Venosa A, Gow AJ, Laskin JD, and Laskin DL
- Subjects
- Acute Lung Injury immunology, Acute Lung Injury pathology, Animals, Disease Models, Animal, Feasibility Studies, Female, Fibrosis, Humans, Lung drug effects, Macrophages drug effects, Macrophages immunology, Male, Mice, Oxidative Stress drug effects, Acute Lung Injury chemically induced, Chemical Warfare Agents toxicity, Lung pathology, Mechlorethamine toxicity
- Abstract
Nitrogen mustard (NM) is a cytotoxic vesicant known to cause acute lung injury which progresses to fibrosis. Herein, we developed a murine model of NM-induced pulmonary toxicity with the goal of assessing inflammatory mechanisms of injury. C57BL/6J mice were euthanized 1-28 d following intratracheal exposure to NM (0.08 mg/kg) or PBS control. NM caused progressive alveolar epithelial thickening, perivascular inflammation, bronchiolar epithelial hyperplasia, interstitial fibroplasia and fibrosis, peaking 14 d post exposure. Enlarged foamy macrophages were also observed in the lung 14 d post NM, along with increased numbers of microparticles in bronchoalveolar lavage fluid (BAL). Following NM exposure, rapid and prolonged increases in BAL cells, protein, total phospholipids and surfactant protein (SP)-D were also detected. Flow cytometric analysis showed that CD11b
+ Ly6G- F4/80+ Ly6Chi proinflammatory macrophages accumulated in the lung after NM, peaking at 3 d. This was associated with macrophage expression of HMGB1 and TNFα in histologic sections. CD11b+ Ly6G- F4/80+ Ly6Clo anti-inflammatory/pro-fibrotic macrophages also increased in the lung after NM peaking at 14 d, a time coordinate with increases in TGFβ expression and fibrosis. NM exposure also resulted in alterations in pulmonary mechanics including increases in tissue elastance and decreases in compliance and static compliance, most prominently at 14 d. These findings demonstrate that NM induces structural and inflammatory changes in the lung that correlate with aberrations in pulmonary function. This mouse model will be useful for mechanistic studies of mustard lung injury and for assessing potential countermeasures., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)- Published
- 2020
- Full Text
- View/download PDF
19. Methylation levels at imprinting control regions are not altered with ovulation induction or in vitro fertilization in a birth cohort.
- Author
-
Rancourt RC, Harris HR, and Michels KB
- Subjects
- Adult, Alleles, Cohort Studies, Epigenesis, Genetic, Female, Humans, Infant, Newborn, Infertility therapy, Male, Reproductive Techniques, Assisted adverse effects, Transcription, Genetic, DNA Methylation, Fertilization in Vitro adverse effects, Genomic Imprinting, Ovulation Induction adverse effects
- Abstract
Study Question: Do fertility treatments, including ovulation induction (OI), alter epigenetic mechanisms such as DNA methylation at imprinted loci?, Summary Answer: We observed small but statistically significant differences in certain imprinting control regions (ICRs) based on the method of conception, however, these small changes in methylation did not correlate to the overall transcriptional levels of the genes adjacent to the ICRs (such as KCNQ1 and SNRPN)., What Is Known and What This Paper Adds: Assisted reproductive technology (ART) has been associated with an increase in the risk of rare childhood disorders caused by loss of imprinting (LOI). This study provides novel epigenetic analyses on infants conceived by OI and examines how methylation levels correlate with gene expression., Design: Data and biospecimens used in this study were from 147 participants of the Epigenetic Birth Cohort comprising 1941 mother-child dyads recruited between June 2007 and June 2009 at the Department of Obstetrics, Gynecology and Reproductive Biology at Brigham and Women's Hospital (BWH) in Boston, MA, USA. Wilcoxon rank-sum tests were used to examine the differences in median percent methylation at each differentially methylated region (DMR) between the spontaneous conception control group and the fertility treatment groups (OI and IVF)., Participants and Setting: For each woman who reported IVF we selected a woman who conceived spontaneously matched on age (± 2 years). To increase efficiency, we matched the same controls from the spontaneously conceived group to participants who reported OI. If an appropriate control was not identified that had been previously matched to an IVF participant, a new control was selected. The final analytic sample consisted of 61 spontaneous, 59 IVF and 27 OI conceptions., Main Results and the Role of Chance: No functionally relevant differences in methylation levels were observed across five (out of six) imprinted DMRs in either the placenta or cord blood of infants conceived with OI or IVF compared with infants conceived spontaneously. While KCNQ1, SNRPN and H19 DMRs demonstrated small but statistically significant differences in methylation based on the method of conception, expression levels of the genes related to these control regions only correlated with the methylation levels of H19., Bias, Confounding and Other Reasons for Caution: Limitations of our study include the limited sample size, lack of information on OI medication used and culture medium for the IVF procedures and underlying reasons for infertility among OI and IVF patients. We did not perform allele-specific expression analyses and therefore cannot make any inferences about LOI., Generalizability to Other Populations: These results are likely to be generalizable to non-Hispanic white individuals in populations with similar ART and fertility treatments.
- Published
- 2012
- Full Text
- View/download PDF
20. DNA methylation of stress-related genes and LINE-1 repetitive elements across the healthy human placenta.
- Author
-
Non AL, Binder AM, Barault L, Rancourt RC, Kubzansky LD, and Michels KB
- Subjects
- Adult, Cohort Studies, Female, Gestational Age, Health, Humans, Male, Models, Biological, Placentation genetics, Placentation physiology, Pregnancy, Tissue Distribution, DNA Methylation physiology, Long Interspersed Nucleotide Elements genetics, Placenta metabolism, Stress, Physiological genetics
- Abstract
Objectives: DNA methylation is known to play a critical role in regulating development of placental morphology and physiology. The methylation of genes mediated by glucocorticoid hormones may be particularly vulnerable to intrauterine stress in the placenta. However little is known about DNA methylation of stress-related genes within a healthy placenta, and particularly whether methylation occurs uniformly across different regions of the placenta, which is a critical question for researchers seeking to analyze methylation patterns. We examined DNA methylation across four regions of the placenta to evaluate methylation levels of stress-related genes within a healthy placenta, and to evaluate whether methylation patterns vary by sampling location., Study Design: We evaluated levels of DNA methylation of three stress-related genes: NR3C1, BDNF, and 11B-HSD2 and of the repetitive element, LINE-1, in four different sample locations of 20 healthy placentas., Main Outcome Measures: Pyrosequencing was used to quantify levels of methylation at CpG sites within the promoter regions of each of the three stress-related genes, and global methylation of LINE-1., Results: Very low levels of methylation were found across all three stress-related genes; no gene showed a median methylation level greater than 4.20% across placental regions. Variation in methylation between placental regions for stress-related genes and for LINE-1 was minimal., Conclusions: Our data suggest that these frequently studied stress-related genes have low levels of methylation in healthy placenta tissue. Minimal variation between sites suggests that sampling location does not affect DNA methylation analyses of these genes or of LINE-1 repetitive elements., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
21. Chimeric mouse tumor models reveal differences in pathway activation between ERBB family- and KRAS-dependent lung adenocarcinomas.
- Author
-
Zhou Y, Rideout WM 3rd, Zi T, Bressel A, Reddypalli S, Rancourt R, Woo JK, Horner JW, Chin L, Chiu MI, Bosenberg M, Jacks T, Clark SC, Depinho RA, Robinson MO, and Heyer J
- Subjects
- Adenocarcinoma pathology, Animals, Disease Models, Animal, Embryonic Stem Cells drug effects, Embryonic Stem Cells metabolism, Mice, Mice, Transgenic, Mutation genetics, Phenotype, Piperazines pharmacology, Quinazolines pharmacology, Respiratory Insufficiency metabolism, Respiratory Insufficiency pathology, Adenocarcinoma metabolism, Chimera metabolism, ErbB Receptors metabolism, Lung Neoplasms metabolism, Lung Neoplasms pathology, Proto-Oncogene Proteins p21(ras) metabolism, Signal Transduction drug effects
- Abstract
To recapitulate the stochastic nature of human cancer development, we have devised a strategy for generating mouse tumor models that involves stepwise genetic manipulation of embryonic stem (ES) cells and chimera generation. Tumors in the chimeric animals develop from engineered cells in the context of normal tissue. Adenocarcinomas arising in an allelic series of lung cancer models containing HER2 (also known as ERBB2), KRAS or EGFR oncogenes exhibit features of advanced malignancies. Treatment of EGFR(L858R) and KRAS(G12V) chimeric models with an EGFR inhibitor resulted in near complete tumor regression and no response to the treatment, respectively, accurately reflecting previous clinical observations. Transcriptome and immunohistochemical analyses reveal that PI3K pathway activation is unique to ERBB family tumors whereas KRAS-driven tumors show activation of the JNK/SAP pathway, suggesting points of therapeutic intervention for this difficult-to-treat tumor category.
- Published
- 2010
- Full Text
- View/download PDF
22. p53-dependent induction of p21(Cip1/WAF1/Sdi1) protects against oxygen-induced toxicity.
- Author
-
Helt CE, Rancourt RC, Staversky RJ, and O'Reilly MA
- Subjects
- Blotting, Western, Cell Survival, Clone Cells, Cyclin-Dependent Kinase Inhibitor p21, Cyclins genetics, Flow Cytometry, G1 Phase drug effects, Gene Expression Regulation, Neoplastic drug effects, Humans, Oxidative Stress physiology, Phosphorylation, RNA, Messenger genetics, Reactive Oxygen Species metabolism, Time Factors, Tumor Cells, Cultured, Tumor Suppressor Protein p53 genetics, Cyclins metabolism, Hyperoxia metabolism, Oxygen toxicity, Tumor Suppressor Protein p53 metabolism
- Abstract
The beneficial effects of supplemental oxygen delivered to patients suffering from acute respiratory distress is offset by its reduction to genotoxic reactive oxygen species (ROS) that inhibit proliferation and kill pulmonary cells. Cells respond to oxygen-induced damage by expressing the tumor suppressor p53 and the cyclin-dependent kinase inhibitor p21(Cip1/WAF1/Sdi1) (p21), which limits proliferation by blocking entry into S phase. Since preventing DNA synthesis during genotoxic stress may enhance survival, the current study examines whether hyperoxia induces p21 through a p53-dependent pathway and whether p21 protects cells from the toxic effects of oxygen. HCT116 colon carcinoma cells and clonal lines lacking p53 or p21were used in this study because they allow direct cytotoxic comparisons between isogenic cells, without complications arising from unknown genetic differences between nonhomologous cell lines. Hyperoxia (95% O2, 5% CO2) increased p53 abundance, phosphorylation of p53 on serine 15, and p21 mRNA and protein in parental HCT116 cells that ceased proliferation. In contrast, p21 was not detected in either p53- or p21-deficient HCT116 cells, which exited the G1 compartment and were arrested in S and G2/M phases during hyperoxia. Trypan blue-dye exclusion revealed that induction of p21 markedly enhanced survival during exposure and colony survival assays showed that p21 enhanced the ability to resume proliferation during recovery in room air. The observation that p53-dependent induction of p21 prevents exit from G1 and promotes survival during hyperoxia is consistent with the importance of limiting DNA replication during genotoxic stress caused by oxygen exposure.
- Published
- 2001
- Full Text
- View/download PDF
23. The role of p21(CIP1/WAF1) in growth of epithelial cells exposed to hyperoxia.
- Author
-
Rancourt RC, Keng PC, Helt CE, and O'Reilly MA
- Subjects
- Adenosine Triphosphate metabolism, Cell Division physiology, Cyclin-Dependent Kinase Inhibitor p21, Cyclins metabolism, DNA genetics, Epithelial Cells metabolism, Epithelial Cells pathology, Epithelial Cells physiology, G1 Phase physiology, G1 Phase radiation effects, Gamma Rays, Hyperoxia genetics, Hyperoxia metabolism, Phosphorylation, Transcription, Genetic, Tumor Cells, Cultured, Tumor Suppressor Protein p53 metabolism, Cyclins physiology, Hyperoxia pathology, Hyperoxia physiopathology
- Abstract
Previous studies have shown that hyperoxia inhibits proliferation and increases the expression of the tumor suppressor p53 and its downstream target, the cyclin-dependent kinase inhibitor p21(CIP1/WAF1), which inhibits proliferation in the G1 phase of the cell cycle. To determine whether growth arrest was mediated through activation of the p21-dependent G1 checkpoint, the kinetics of cell cycle movement during exposure to 95% O2 were assessed in the Mv1Lu and A549 pulmonary adenocarcinoma cell lines. Cell counts, 5-bromo-2'-deoxyuridine incorporation, and cell cycle analyses revealed that growth arrest of both cell lines occurred in S phase, with A549 cells also showing evidence of a G1 arrest. Hyperoxia increased p21 in A549 but not in Mv1Lu cells, consistent with the activation of the p21-dependent G1 checkpoint. The ability of p21 to exert the G1 arrest was confirmed by showing that hyperoxia inhibited proliferation of HCT 116 colon carcinoma cells predominantly in G1, whereas an isogenic line lacking p21 arrested in S phase. The cell cycle arrest in S phase appears to be a p21-independent process caused by a gradual reduction in the rate of DNA strand elongation. Our data reveal that hyperoxia inhibits proliferation in G1 and S phase and demonstrate that p53 and p21 retain their ability to affect G1 checkpoint control during exposure to elevated O2 levels.
- Published
- 2001
- Full Text
- View/download PDF
24. Faculty ways of knowing: the crux of nursing curricula.
- Author
-
Rancourt R, Guimond-Papai P, and Prud'homme-Brisson D
- Subjects
- Empathy, Empiricism, Health Knowledge, Attitudes, Practice, Health Services Needs and Demand, Humanism, Humans, Intuition, Logic, Models, Educational, Models, Nursing, Narration, Nurse's Role psychology, Nursing Methodology Research, Problem Solving, Program Development, Thinking, Attitude of Health Personnel, Curriculum, Education, Nursing, Baccalaureate organization & administration, Faculty, Nursing organization & administration, Knowledge, Philosophy, Nursing
- Abstract
The authors, using the narrative form, examine three epistemological structures that are found in nursing curricula. Those fundamentally different approaches of knowledge acquisition are portrayed and discussed by the director and three staff members from a fictitious nursing school. Although faculty members naturally tend to adhere to their own embedded view of the way one learns, the authors stress the need for judicious blend of the three epistemic orientations when developing nursing curricula.
- Published
- 2000
- Full Text
- View/download PDF
25. Hyperoxia inhibits proliferation of Mv1Lu epithelial cells independent of TGF-beta signaling.
- Author
-
Rancourt RC, Staversky RJ, Keng PC, and O'Reilly MA
- Subjects
- Adenocarcinoma, Animals, Cell Division drug effects, Cell Division physiology, Epithelial Cells drug effects, Flow Cytometry, G1 Phase drug effects, Gene Expression drug effects, Genes, Reporter, Luciferases genetics, Lung Neoplasms, Mink, S Phase drug effects, S Phase physiology, Transcription, Genetic drug effects, Tumor Cells, Cultured, Epithelial Cells cytology, Lung cytology, Oxygen pharmacology, Signal Transduction physiology, Transforming Growth Factor beta physiology
- Abstract
High concentrations of O(2) inhibit epithelial cell proliferation that resumes on recovery in room air. To determine whether growth arrest is mediated by transforming growth factor-beta (TGF-beta), changes in cell proliferation during exposure to hyperoxia were assessed in the mink lung epithelial cell line Mv1Lu and the clonal variant R1B, which is deficient for the type I TGF-beta receptor. Mv1Lu cells treated with TGF-beta accumulated in the G(1) phase of the cell cycle as determined by propidium iodide staining, whereas proliferation of R1B cells was unaffected by TGF-beta. In contrast, hyperoxia inhibited proliferation of both cell lines within 24 h of exposure through an accumulation in the S phase. Mv1Lu cells treated with TGF-beta and exposed to hyperoxia accumulated in the G(1) phase, suggesting that TGF-beta can inhibit the S phase accumulation observed with hyperoxia alone. Cyclin A was detected in cultures exposed to room air or growth arrested by hyperoxia while decreasing in cells growth arrested in the G(1) phase by TGF-beta. Finally, hyperoxia failed to activate a TGF-beta-dependent transcriptional reporter in both Mv1Lu and R1B cells. These findings reveal that simple growth arrest by hyperoxia involves a defect in S phase progression that is independent of TGF-beta signaling.
- Published
- 1999
- Full Text
- View/download PDF
26. What knowledge-accessing modes tell administrators about interdisciplinary crises and conflicts.
- Author
-
Noble KA and Rancourt R
- Subjects
- Canada, Health Facility Environment, Humans, Models, Psychological, Sampling Studies, Attitude of Health Personnel, Conflict, Psychological, Health Facility Administrators psychology, Hospital Administrators psychology, Interprofessional Relations, Medical Staff, Hospital psychology, Nursing Staff, Hospital psychology, Social Perception
- Abstract
In hospitals administrators work with two major groups of medical professionals: physicians and nurses. Together, these three groups of professionals are primarily responsible for the care of patients. The quality of the service they provide is dependent on the working relationships among these disciplines. Potentially, the more harmony among administrators, physicians, and nurses, the better care patients can receive. The research reported in this article addresses the issue of interdisciplinary misunderstanding among these groups of professionals. The research was premised on the assumption that hospital administrators, physicians, and nurses differ in the way they access knowledge. That is, administrators, physicians, and nurses access knowledge in dissimilar ways and, by doing so, set the stage for crises and conflicts. Using a standardized instrument to assess knowledge-accessing modes, data were collected from samples of health administration, medical, and nursing students. The data indicated that the three groups did differ in the way they accessed knowledge. The individual discipline profiles generated from the data also revealed a finding common to the three disciplines, a finding may help resolve a very real problem for hospital patients. Based on the research results, the article discusses ways that administrators may be able to prevent crises and conflicts and enhance harmonious relations among the three disciplines, and thereby improve patient care. Avenues for further research are also suggested.
- Published
- 1987
27. Homosexuality among women.
- Author
-
Rancourt R and Limoges T
- Subjects
- Female, Humans, Women, Homosexuality
- Published
- 1967
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.