Name: pre-conditioning the airways of mice with bleomycin increases the efficiency of orthotopic lung cancer cell engraftment
Uploaded: 2018-06-28T12:30:00
Description: Watch this Scientific Journal Video about Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment at JoVE.com

Cette étude a été financée par des subventions de l’Institut National du Cancer (R01CA166376 et R01CA191489 à D.X. Nguyen) et le Department of Defense (W81XWH-16-1-0227 à D.X. Nguyen).

Toutes les expériences ont été effectuées conformément aux protocoles approuvés par l’animalier institutionnel et utilisation Comité (IACUC) à l’Université Yale.
1. mise en place / préparation des réactifs.
<ol><li>
Bléomycine ATTENTION : Basé sur le système général harmonisé (SGH) de Classification et d’étiquetage des produits chimiques, la bléomycine est classée comme un danger pour la santé GHS08.<ol>
<li>Préparer la bléomycine sous une ho...

<ol>
	<li>Siegel, R. L., Miller, K. D., Jemal, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cancer+statistics,+2015.">Cancer statistics, 2015.</a> CA-Cancer J Clin. 65, 5-29 (2015).</li><li>Gaspar, L. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Brain+metastases+in+lung+cancer.">Brain metastases in lung cancer.</a> Expert Rev Anticanc. 4, 259-270 (2004).</li><li>Hess, K. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Metastatic+patterns+in+adenocarcinoma.">Metastatic patterns in adenocarcinoma.</a> Cancer. 106, 1624-1633 (2006).</li><li>Hoffman, P. C., Mauer, A. M., Vokes, E. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lung+cancer.">Lung cancer.</a> Lancet. 355, 479-485 (2000).</li><li>Travis, W. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathology+of+lung+cancer.">Pathology of lung cancer.</a> Clin Chest Med. 23 (1), 65-81 (2002).</li><li>Chen, Z., Fillmore, C. M., Hammerman, P. S., Kim, C. F., Wong, K. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Non-small-cell+lung+cancers:+a+heterogeneous+set+of+diseases.">Non-small-cell lung cancers: a heterogeneous set of diseases.</a> Nat Rev Cancer. 14, 535-546 (2014).</li><li>Kim, C. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+models+of+human+non-small-cell+lung+cancer:+raising+the+bar.">Mouse models of human non-small-cell lung cancer: raising the bar.</a> Cold Spring Harb Sym. 70, 241-250 (2005).</li><li>Meuwissen, R., Berns, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+models+for+human+lung+cancer.">Mouse models for human lung cancer.</a> Gene Dev. 19, 643-664 (2005).</li><li>Junttila, M. R., de Sauvage, F. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+tumour+micro-environment+heterogeneity+on+therapeutic+response.">Influence of tumour micro-environment heterogeneity on therapeutic response.</a> Nature. 501, 346-354 (2013).</li><li>Nguyen, L. V., Vanner, R., Dirks, P., Eaves, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cancer+stem+cells:+an+evolving+concept.">Cancer stem cells: an evolving concept.</a> Nat Rev Cancer. 12, 133-143 (2012).</li><li>Minchinton, A. I., Tannock, I. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Drug+penetration+in+solid+tumours.">Drug penetration in solid tumours.</a> Nat Rev Cancer. 6, 583-592 (2006).</li><li>Leblond, A. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Developing+cell+therapy+techniques+for+respiratory+disease:+intratracheal+delivery+of+genetically+engineered+stem+cells+in+a+murine+model+of+airway+injury.">Developing cell therapy techniques for respiratory disease: intratracheal delivery of genetically engineered stem cells in a murine model of airway injury.</a> Hum Gene Ther. 20, 1329-1343 (2009).</li><li>Vaughan, A. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lineage-negative+progenitors+mobilize+to+regenerate+lung+epithelium+after+major+injury.">Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury.</a> Nature. 517, 621-625 (2015).</li><li>Zuo, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=p63(+)Krt5(+)+distal+airway+stem+cells+are+essential+for+lung+regeneration.">p63(+)Krt5(+) distal airway stem cells are essential for lung regeneration.</a> Nature. 517, 616-620 (2015).</li><li>Mahoney, J. E., Kim, C. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tracing+the+potential+of+lung+progenitors.">Tracing the potential of lung progenitors.</a> Nat Biotechnol. 33, 152-154 (2015).</li><li>Wang, D., Morales, J. E., Calame, D. G., Alcorn, J. L., Wetsel, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transplantation+of+human+embryonic+stem+cell-derived+alveolar+epithelial+type+II+cells+abrogates+acute+lung+injury+in+mice.">Transplantation of human embryonic stem cell-derived alveolar epithelial type II cells abrogates acute lung injury in mice.</a> Mol Ther. 18, 625-634 (2010).</li><li>Ortiz, L. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mesenchymal+stem+cell+engraftment+in+lung+is+enhanced+in+response+to+bleomycin+exposure+and+ameliorates+its+fibrotic+effects.">Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects.</a> Proc Natl Acad Sci USA. 100, 8407-8411 (2003).</li><li>Suzuki, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prognostic+significance+of+the+size+of+central+fibrosis+in+peripheral+adenocarcinoma+of+the+lung.">Prognostic significance of the size of central fibrosis in peripheral adenocarcinoma of the lung.</a> Ann Thorac Surg. 69, 893-897 (2000).</li><li>Cancer Genome Atlas Research, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comprehensive+molecular+profiling+of+lung+adenocarcinoma.">Comprehensive molecular profiling of lung adenocarcinoma.</a> Nature. 511, 543-550 (2014).</li><li>Scotton, C. J., Chambers, R. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bleomycin+revisited:+towards+a+more+representative+model+of+IPF?.">Bleomycin revisited: towards a more representative model of IPF?.</a> Am J Physiol-Lung C. 299, L439-L441 (2010).</li><li>Hay, J., Shahzeidi, S., Laurent, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanisms+of+bleomycin-induced+lung+damage.">Mechanisms of bleomycin-induced lung damage.</a> Arch Toxicol. 65, 81-94 (1991).</li><li>Vaccaro, C. A., Brody, J. S., Snider, G. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alveolar+wall+basement+membranes+in+bleomycin-induced+pulmonary+fibrosis.">Alveolar wall basement membranes in bleomycin-induced pulmonary fibrosis.</a> Am Rev Respir Dis. 132, 905-912 (1985).</li><li>Venkatesan, N., Ebihara, T., Roughley, P. J., Ludwig, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alterations+in+large+and+small+proteoglycans+in+bleomycin-induced+pulmonary+fibrosis+in+rats.">Alterations in large and small proteoglycans in bleomycin-induced pulmonary fibrosis in rats.</a> Am J Resp Crit Care. 161, 2066-2073 (2000).</li><li>Moore, B. B., Hogaboam, C. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Murine+models+of+pulmonary+fibrosis.">Murine models of pulmonary fibrosis.</a> Am J Physiol-Lung C. 294, L152-L160 (2008).</li><li>Izbicki, G., Segel, M. J., Christensen, T. G., Conner, M. W., Breuer, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Time+course+of+bleomycin-induced+lung+fibrosis.">Time course of bleomycin-induced lung fibrosis.</a> Int J Exp Pathol. 83, 111-119 (2002).</li><li>Schrier, D. J., Phan, S. H., McGarry, B. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effects+of+the+nude+(nu/nu)+mutation+on+bleomycin-induced+pulmonary+fibrosis.+A+biochemical+evaluation.">The effects of the nude (nu/nu) mutation on bleomycin-induced pulmonary fibrosis. A biochemical evaluation.</a> Am Rev Respir Dis. 127, 614-617 (1983).</li><li>Ponomarev, V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+triple-modality+reporter+gene+for+whole-body+fluorescent,+bioluminescent,+and+nuclear+noninvasive+imaging.">A novel triple-modality reporter gene for whole-body fluorescent, bioluminescent, and nuclear noninvasive imaging.</a> Eur J Nucl Med Mol I. 31, 740-751 (2004).</li><li>Morten, B. C., Scott, R. J., Avery-Kiejda, K. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+Three+Different+Methods+for+Determining+Cell+Proliferation+in+Breast+Cancer+Cell.">Comparison of Three Different Methods for Determining Cell Proliferation in Breast Cancer Cell.</a> J. Vis. Exp. , (2016).</li><li>Tseng, J. C., Kung, A. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+bioluminescence+imaging+of+mouse+tumor+models.">Quantitative bioluminescence imaging of mouse tumor models.</a> Cold Spring Harbor protocols. , (2015).</li><li>Byrne, F. L., McCarroll, J. A., Kavallaris, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Analyses+of+Tumor+Burden+In+Vivo+and+Metastasis+Ex+Vivo+Using+Luciferase-Expressing+Cancer+Cells+in+an+Orthotopic+Mouse+Model+of+Neuroblastoma.">Analyses of Tumor Burden In Vivo and Metastasis Ex Vivo Using Luciferase-Expressing Cancer Cells in an Orthotopic Mouse Model of Neuroblastoma.</a> Methods Mol Biol. 1372, 61-77 (2016).</li><li>Parkinson, C. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnostic+necropsy+and+selected+tissue+and+sample+collection+in+rats+and+mice.">Diagnostic necropsy and selected tissue and sample collection in rats and mice.</a> J. Vis. Exp. , (2011).</li><li>Tammela, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Wnt-producing+niche+drives+proliferative+potential+and+progression+in+lung+adenocarcinoma.">A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma.</a> Nature. 545, 355-359 (2017).</li><li>DuPage, M., Dooley, A. L., Jacks, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conditional+mouse+lung+cancer+models+using+adenoviral+or+lentiviral+delivery+of+Cre+recombinase.">Conditional mouse lung cancer models using adenoviral or lentiviral delivery of Cre recombinase.</a> Nat Protoc. 4, 1064-1072 (2009).</li><li>Byrne, A. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interrogating+open+issues+in+cancer+precision+medicine+with+patient-derived+xenografts.">Interrogating open issues in cancer precision medicine with patient-derived xenografts.</a> Nat Rev Cancer. 17, 254-268 (2017).</li><li>Nguyen, D. X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=WNT/TCF+signaling+through+LEF1+and+HOXB9+mediates+lung+adenocarcinoma+metastasis.">WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis.</a> Cell. 138, 51-62 (2009).</li><li>Raghu, G., Nyberg, F., Morgan, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+epidemiology+of+interstitial+lung+disease+and+its+association+with+lung+cancer.">The epidemiology of interstitial lung disease and its association with lung cancer.</a> Brit J Cancer. 91, S3-S10 (2004).</li><li>Hubbard, R., Venn, A., Lewis, S., Britton, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lung+cancer+and+cryptogenic+fibrosing+alveolitis.+A+population-based+cohort+study.">Lung cancer and cryptogenic fibrosing alveolitis. A population-based cohort study.</a> Am J Resp Crit Care. 161, 5-8 (2000).</li><li>Nagai, A., Chiyotani, A., Nakadate, T., Konno, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lung+cancer+in+patients+with+idiopathic+pulmonary+fibrosis.">Lung cancer in patients with idiopathic pulmonary fibrosis.</a> Tohoku J Exp Med. 167, 231-237 (1992).</li><li>Rock, J. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multiple+stromal+populations+contribute+to+pulmonary+fibrosis+without+evidence+for+epithelial+to+mesenchymal+transition.">Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition.</a> Proc Natl Acad Sci USA. 108, E1475-E1483 (2011).</li><li>Saito, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Survival+after+surgery+for+pathologic+stage+IA+non-small+cell+lung+cancer+associated+with+idiopathic+pulmonary+fibrosis.">Survival after surgery for pathologic stage IA non-small cell lung cancer associated with idiopathic pulmonary fibrosis.</a> Ann Thorac Surg. 92, 1812-1817 (2011).</li><li>Stevens, L. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Extracellular+Matrix+Receptor+Expression+in+Subtypes+of+Lung+Adenocarcinoma+Potentiates+Outgrowth+of+Micrometastases.">Extracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of Micrometastases.</a> Cancer Res. 77, 1905-1917 (2017).</li><li>Harrison, J. H., Lazo, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High+dose+continuous+infusion+of+bleomycin+in+mice:+a+new+model+for+drug-induced+pulmonary+fibrosis.">High dose continuous infusion of bleomycin in mice: a new model for drug-induced pulmonary fibrosis.</a> J Pharmacol Exp Ther. 243, 1185-1194 (1987).</li><li>Shcherbo, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bright+far-red+fluorescent+protein+for+whole-body+imaging.">Bright far-red fluorescent protein for whole-body imaging.</a> Nature Methods. 4, 741-746 (2007).</li><li>Aso, Y., Yoneda, K., Kikkawa, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Morphologic+and+biochemical+study+of+pulmonary+changes+induced+by+bleomycin+in+mice.">Morphologic and biochemical study of pulmonary changes induced by bleomycin in mice.</a> Lab Invest. 35, 558-568 (1976).</li><li>Kim, C. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identification+of+bronchioalveolar+stem+cells+in+normal+lung+and+lung.">Identification of bronchioalveolar stem cells in normal lung and lung.</a> Cell. 121, 823-835 (2005).</li><li>Fichtner, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Establishment+of+patient-derived+non-small+cell+lung+cancer+xenografts+as+models+for+the+identification+of+predictive+biomarkers.">Establishment of patient-derived non-small cell lung cancer xenografts as models for the identification of predictive biomarkers.</a> Clin Cancer Res. 14, 6456-6468 (2008).</li><li>Zhang, X. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Establishment+of+patient-derived+non-small+cell+lung+cancer+xenograft+models+with+genetic+aberrations+within+EGFR,+KRAS+and+FGFR1:+useful+tools+for+preclinical+studies+of+targeted+therapies.">Establishment of patient-derived non-small cell lung cancer xenograft models with genetic aberrations within EGFR, KRAS and FGFR1: useful tools for preclinical studies of targeted therapies.</a> J Transl Med. 11, 168 (2013).</li></ol>

Frappant de parallels cliniques ont été recensées entre le cancer du poumon et autres maladies chroniques du poumon36. En particulier, les patients atteints de fibrose pulmonaire idiopathique (IPF) ont une prédilection accrue pour développer un cancer du poumon, et cette association est indépendante du tabagisme histoire37,38. IPF est caractérisée par une destruction progressive de l’architecture de poumon et fonction respiratoir...

Cancer du poumon est la principale cause de cancer liée décès dans le monde1. Patients atteints de cancer du poumon a finit par succombent de métastases à des organes éloignés, notamment pour le système nerveux central, foie, glandes surrénales et OS2,3,4. Tumeurs thoraciques ont été traditionnellement classées comme le cancer du poumon à petites cellules (CPPC) ou non-small cell lung cancer (NSCLC)5. NSCLC est le plus fréquemment diagnostiqué une tumeur maligne et peuvent être subdivisés en différents sous-types histologiques, y compris l’adénocarcinome pulmonaire (LUAD) et poumon épidermoïde (ULEMC)6. L’analyse génomique des cancers du poumon primaires humaines réséqués a révélé que les tumeurs au sein d’un histotype donné peuvent également exprimer diverses perturbations moléculaires, outre contribuant à leur progression clinique divergente et déconcertants pronostic patient. L’hétérogénéité remarquable des cancers du poumon représente un défi important à la conception rationnelle, les essais précliniques et mise en œuvre de stratégies thérapeutiques efficaces. Par conséquent, il y a lieu d’élargir le répertoire des modèles de cancer du poumon expérimental tractable pour étudier les diverses origines cellulaires et moléculaires sous-types stades de cette maladie.
Diverses approches à l’aide de modèles animaux ont été utilisés pour étudier lung cancer in vivo, chacun avec leurs propres avantages et inconvénients selon l’ou les questions d’intérêt biologiques. Modèles de souris génétiquement modifiées (edged) peuvent cibler des altérations génétiques spécifiques à un type de cellules progénitrices donnée, résultant dans les tumeurs que les progrès dans un hôte immunocompétent7. Bien qu’extrêmement puissant et cliniquement pertinents, la morbidité de tumeur de latence, variabilité, et/ou du poumon associée à Gregory peut être prohibitif pour certaines des mesures quantitatives et la détection des métastases de stade tardif dans des organes éloignés,8. Une approche complémentaire est l’utilisation de modèles d’allogreffe, par lequel cellules de cancer pulmonaire, obtenue directement auprès d’une tumeur de souris ou de dérivés d’abord comme les lignées cellulaires établies dans la culture, sont réintroduites en hôtes syngéniques. Par analogie, xénogreffes de cancer du poumon sont établies à partir des lignées cellulaires humaines ou des échantillons de patient tumeur dérivée. Xénogreffes de ligne de cellules humaines ou patients xénogreffes dérivés (PDXs) sont généralement conservées dans des souris immunodéprimées et interdit donc de surveillance immunitaire complète9. Malgré cet inconvénient, ils fournissent une avenue pour propager la limitation des quantités d’humains échantillons biologiques et l’étude fondamentale en vivo propriétés des cellules cancéreuses humaines, qui codent pour des aberrations génomiques plus complexes que les tumeurs GEMM.
Une propriété utile des allogreffes et xénogreffes, c’est qu’ils sont prêtent à des traditionnels essais de dilution cellules limitant, utilisés pour quantifier la fréquence de tumeur initiant des cellules (TICs) au sein d’une population de cellules malignes10. Dans ces expériences, un nombre défini de cellules est injecté par voie sous-cutanée dans le flanc des animaux et la fréquence des TICs peut être estimée selon le taux d’abonnement de tumeur. Tumeurs sous-cutanées cependant peuvent être plus hypoxique11 et ne peuvent pas modéliser principales contraintes physiologiques du microenvironnement tumoral de poumon. Livraison par voie intratrachéale de souches épithéliales ou cellules progénitrices dans les poumons des souris est une méthode pour étudier la régénération pulmonaire et bronchique stem cell biology12. Toutefois, le taux de prise de greffe de cette technique peut être relativement faible, à moins que les poumons sont d’abord soumis à des formes physiologiques de blessure, comme une infection virale13,14. Soutien de cellules stromales inflammatoires et/ou la rupture de la membrane basale de poumon peut améliorer la rétention des cellules transplantées dans les niches des cellules souches dans les voies respiratoires distales15. Fibrose induisant des agents peut également pré-conditionner les poumons afin d’améliorer la prise de greffe de cellules pluripotentes induites16 des cellules souches mésenchymateuses17. Si des formes similaires de lésion des voies aériennes peuvent influer sur le taux de prise de greffe, capacité initiatrice de la tumeur et la croissance des cellules cancéreuses du poumon doit encore être systématiquement évalués.
Dans cette étude, nous décrivons une méthode pour accroître l’efficacité de l’orthotopic lung cancer cellule prise de greffe, de préconditionner les poumons des souris atteintes de blessures. LUAD apparaît dans les voies aériennes distales avec un sous-ensemble important de ces cancers développant un stroma fibreux18 souvent corrélé avec le pronostic19. Bléomycine, un naturel synthases hybrides peptide-polykétide, a été largement utilisée pour induire une fibrose pulmonaire dans la souris20. L’instillation des voies aériennes de bléomycine favorise tout d’abord épithéliale attrition dans les alvéoles et le recrutement des cellules inflammatoires, y compris les macrophages, les neutrophiles et les monocytes21. Elle est suivie de tissu transformant en voies respiratoires distales, membrane basale réorganisation22,23 et matrice extracellulaire (ECM) dépôts24. Les effets d’une injection de bléomycine unique sont transitoires, fibro-résoudre après 30 jours dans la plupart des études25. À l’aide de modèles des allogreffes et xénogreffes, nous avons testé si préconditionner les voies respiratoires des souris à la bléomycine pourrait augmenter significativement le taux de cellules LUAD dans les poumons.

<table>
	<tbody>
		<tr>
			<td>Bleomycin</td>
			<td>Sigma</td>
			<td>B5507-15UN</td>
			<td>CAUTION Health hazard GHS08</td>
		</tr>
		<tr>
			<td>Exel Catheter 24G</td>
			<td>Fisher</td>
			<td>1484121</td>
			<td>Remove needle. For intratracheal injection</td>
		</tr>
		<tr>
			<td>Ketamine (Ketaset inl 100 mg/mL C3N 10 mL)</td>
			<td>Butler Schein</td>
			<td>56344</td>
			<td>To anesthetize mice</td>
		</tr>
		<tr>
			<td>Xylazine</td>
			<td>Butler Schein</td>
			<td>33198</td>
			<td>To anesthetize mice</td>
		</tr>
		<tr>
			<td>Ketoprofen, 5,000 mg</td>
			<td>Cayman Chemical</td>
			<td>10006661</td>
			<td>Analgesic</td>
		</tr>
		<tr>
			<td>Puralube Veterinary Ophthalmic Ointment</td>
			<td>BUTLER ANIMAL HEALTH COMPANY LLC</td>
			<td>8897</td>
			<td>To prevent eye dryness while under anesthesia</td>
		</tr>
		<tr>
			<td>D-Luciferin powder</td>
			<td>Perkin Elmer Health Sciences Inc</td>
			<td>122799</td>
			<td>For luminescent imaging. Reconstitute powder with PBS for a working concentration of 15mg/mL. Protect from Light</td>
		</tr>
		<tr>
			<td>Rodent Intubation stand</td>
			<td>Braintree Scientific</td>
			<td>RIS-100</td>
			<td>Recommended stand for intratracheal injection</td>
		</tr>
		<tr>
			<td>MI-150 ILLUMINATOR 150W MI-150</td>
			<td>DOLAN-JENNER INDUSTRIES</td>
			<td>MI-150 / EEG2823M</td>
			<td>To illuminate and visualize trachea</td>
		</tr>
		<tr>
			<td>Graefe Forceps, 2.75 (7 cm) long serrat</td>
			<td>Roboz</td>
			<td>RS-5111</td>
			<td>For intratracheal injection</td>
		</tr>
		<tr>
			<td>Syringe Luer-Lok Sterile 5ml</td>
			<td>BD / Fisher</td>
			<td>309646</td>
			<td></td>
		</tr>
		<tr>
			<td>Satiny Smooth by Conair Dual Foil Wet/Dry Rechargeable Shaver</td>
			<td>Conair</td>
			<td>-</td>
			<td>To shave mice</td>
		</tr>
		<tr>
			<td>Bonn Scissors, 3.5&#34; straight 15 mm sharp/sharp sure cut blades</td>
			<td>Roboz</td>
			<td>RS-5840SC</td>
			<td></td>
		</tr>
		<tr>
			<td>15 mL conical tube</td>
			<td>BD / Fisher</td>
			<td>352097</td>
			<td></td>
		</tr>
		<tr>
			<td>1.5 mL centrifuge tubes</td>
			<td>USA SCIENTIFIC INC</td>
			<td>1615-5500</td>
			<td></td>
		</tr>
		<tr>
			<td>Vial Scintillation 7 mL Borosilicate Glass GPI</td>
			<td>Fisher</td>
			<td>701350</td>
			<td></td>
		</tr>
		<tr>
			<td>Filter pipette tips (200 &#956;L)</td>
			<td>USA SCIENTIFIC INC</td>
			<td>1120-8710</td>
			<td></td>
		</tr>
		<tr>
			<td>Phosphate Buffered Saline</td>
			<td>Life Technologies</td>
			<td>14190-144</td>
			<td></td>
		</tr>
		<tr>
			<td>0.25% Trypsin-EDTA</td>
			<td>Life Technologies</td>
			<td>25200-056</td>
			<td></td>
		</tr>
		<tr>
			<td>DMEM high glucose</td>
			<td>Life Technologies</td>
			<td>11965-092</td>
			<td></td>
		</tr>
		<tr>
			<td>RPMI Medium 1640</td>
			<td>Life Technologies</td>
			<td>11875-093</td>
			<td></td>
		</tr>
		<tr>
			<td>Fetal bovine serum USDA</td>
			<td>Life Technologies</td>
			<td>10437-028</td>
			<td></td>
		</tr>
		<tr>
			<td>Penicillin-Streptomycin</td>
			<td>Life Technologies</td>
			<td>15140-122</td>
			<td></td>
		</tr>
		<tr>
			<td>Amphotericin B</td>
			<td>Sigma</td>
			<td>A2942-20ML</td>
			<td></td>
		</tr>
		<tr>
			<td>Trypan Blue Stain 0.4%</td>
			<td>Life Technologies</td>
			<td>15250-061</td>
			<td></td>
		</tr>
		<tr>
			<td>Countess Automated Cell Counter</td>
			<td>Life Technologies</td>
			<td>AMQAX1000</td>
			<td></td>
		</tr>
		<tr>
			<td>Flask T/C 75cm sq canted neck, blue cap</td>
			<td>Fisher / Corning</td>
			<td>353135</td>
			<td></td>
		</tr>
		<tr>
			<td>IVIS Spectrum Xenogen Bioluminiscence</td>
			<td>Perkin Elmer Health Sciences Inc</td>
			<td>124262</td>
			<td>For in vivo bioluminescence imaging</td>
		</tr>
		<tr>
			<td>Living image software</td>
			<td>Perkin Elmer Health Sciences Inc</td>
			<td>128113</td>
			<td>For in vivo bioluminescence analysis</td>
		</tr>
		<tr>
			<td>XGI-8 Gas Anesthesia System</td>
			<td>Perkin Elmer Health Sciences Inc</td>
			<td>118918</td>
			<td>For Isoflurane anesthesia</td>
		</tr>
		<tr>
			<td>BD Ultra-Fine II Short Needle Insulin Syringe 1 cc. 31 G x 8 mm (5/16 in)</td>
			<td>BD / Fisher</td>
			<td>BD328418</td>
			<td>For retro-orbital luciferin injection</td>
		</tr>
		<tr>
			<td>Syringe 1ml</td>
			<td>BD / Fisher</td>
			<td>14-823-434</td>
			<td>For intraperitoneal injections</td>
		</tr>
		<tr>
			<td>26 G x 1/2 in. needle</td>
			<td>BD / Fisher</td>
			<td>305111</td>
			<td>For intraperitoneal injections</td>
		</tr>
		<tr>
			<td>4% Paraformaldehyde</td>
			<td>VWR</td>
			<td>43368-9M</td>
			<td>CAUTION Health hazard GHS07, GHS08. For fixing tissue</td>
		</tr>
		<tr>
			<td>Pipet-Lite Pipette, Unv. SL-200XLS+</td>
			<td>METTLER-TOLEDO INTERNATIONAL</td>
			<td>17014411</td>
			<td></td>
		</tr>
		<tr>
			<td>Mayer&#39;s Hematoxylin</td>
			<td>ELECTRON MICROSCOPY SCIENCES</td>
			<td>517-28-2</td>
			<td></td>
		</tr>
		<tr>
			<td>Eosin Y stain 0.25% (w/v) in 57%</td>
			<td>Fisher</td>
			<td>67-63-0</td>
			<td></td>
		</tr>
		<tr>
			<td>Masson Trichrome Stain Kit</td>
			<td>IMEB Inc</td>
			<td>K7228</td>
			<td>For masson trichrome stain to visualize collagen</td>
		</tr>
		<tr>
			<td>Superfrost plus glass slides</td>
			<td>Fisher</td>
			<td>1255015</td>
			<td></td>
		</tr>
		<tr>
			<td>6 well plate</td>
			<td>Corning</td>
			<td>C3516</td>
			<td></td>
		</tr>
		<tr>
			<td>Universal Mycoplasma Detection Kit</td>
			<td>ATCC</td>
			<td>30-1012K</td>
			<td></td>
		</tr>
		<tr>
			<td>OCT Embedding compound</td>
			<td>ELECTRON MICROSCOPY SCIENCES</td>
			<td>62550-12</td>
			<td>For embedding tissue for frozen sections</td>
		</tr>
		<tr>
			<td>Leica CM3050 S Research Cryostat</td>
			<td>Leica</td>
			<td>CM3050 S</td>
			<td>To section tissue for staining analysis</td>
		</tr>
		<tr>
			<td>Keyence All-in One Fluorescence Microscope</td>
			<td>Keyence</td>
			<td>BZ-X700</td>
			<td></td>
		</tr>
		<tr>
			<td>ImageJ</td>
			<td>US National Institutes of Health</td>
			<td>IJ1.46</td>
			<td>http://rsbweb.nih.gov/ij/ download.html</td>
		</tr>
		<tr>
			<td>Prism 7.0 for Mac OS X</td>
			<td>GraphPad Software, Inc.</td>
			<td>-</td>
			<td></td>
		</tr>
		<tr>
			<td>Athymic (Crl:NU(NCr)-Foxn1nu) mice</td>
			<td>Charles River</td>
			<td>NIH-553</td>
			<td></td>
		</tr>
		<tr>
			<td>NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice</td>
			<td>Jackson Laboratories</td>
			<td>5557</td>
			<td></td>
		</tr>
		<tr>
			<td>B6129SF1/J mice</td>
			<td>Jackson Laboratories</td>
			<td>101043</td>
			<td></td>
		</tr>
		<tr>
			<td>NIH-H2030 cells</td>
			<td>ATCC</td>
			<td>CRL-5914</td>
			<td></td>
		</tr>
		<tr>
			<td>368T1</td>
			<td>generously provided by Monte Winslow (Standford University)</td>
			<td>-</td>
			<td></td>
		</tr>
		<tr>
			<td>PC9 cells</td>
			<td>Nguyen DX et al. Cell. 2009;138:51&#8211;62</td>
			<td>-</td>
			<td></td>
		</tr>
		<tr>
			<td>H2030 BrM3 cells</td>
			<td>Nguyen DX et al. Cell. 2009;138:51&#8211;62</td>
			<td>-</td>
			<td></td>
		</tr>
	</tbody>
</table>

pre-conditioning the airways of mice with bleomycin increases the efficiency of orthotopic lung cancer cell engraftment

Cancer du poumon est une maladie réfractaire de traitement mortelle qui est biologiquement hétérogène. Pour comprendre et traiter efficacement le spectre clinique complète de malignités thoraciques, des modèles animaux supplémentaires qui peuvent récapituler les étapes et les sous-types de cancer de poumon humain diverses sont nécessaires. Une allogreffe ou xénogreffe modèles sont polyvalents et permettent la quantification des capacité tumorigènes in vivo, en utilisant des cellules malignes d’origine murine ou humaine. Cependant, les méthodes décrites précédemment de greffe de cellule pour le cancer du poumon ont été effectuées dans des sites non physiologiques, tels que le flanc de la souris, en raison de l’inefficacité de l’orthotopic transplantation de cellules dans les poumons. Dans cette étude, nous décrivons une méthode pour améliorer la prise de greffe orthotopique lung cancer cell en préconditionner les voies respiratoires des souris avec la bléomycine agent inducteur de la fibrose. Comme une expérience de validation, nous avons appliqué cette approche pour greffer des cellules tumorales du sous-type adénocarcinome pulmonaire, provenant de souris ou de sources humaines, dans diverses souches de souris. Nous démontrons que blessant les voies respiratoires à la bléomycine avant l’injection de cellules de tumeur augmente la prise de greffe de cellules tumorales de 0 à 17 % de 71 à 100 %. Significativement, cette méthode améliorée incidence des tumeurs pulmonaires et une excroissance ultérieure à l’aide de différents modèles et les souches de souris. En outre, les cellules cancéreuses du poumon implantée diffusent des poumons dans des organes éloignés. Ainsi, nous fournissons un protocole qui peut être utilisé pour établir et maintenir de nouveaux modèles orthotopique du cancer du poumon avec la limitation des quantités de cellules ou recueillis et à évaluer de façon quantitative la capacité tumorigène des cellules cancéreuses du poumon dans les paramètres physiologiquement pertinents .

Pour augmenter l’efficacité de la greffe de cellules de cancer LUAD dans les poumons des souris, nous avons développé un protocole qui tout d’abord les conditions préalablement les voies respiratoires à l’aide de bléomycine suivie d’injection de cellules de tumeur orthotopique (Figure 1). Nous avons confirmé que même lorsqu’il est administré à des souris athymiques immunodéprimés, bléomycine transitoire fibrose induite par jour 14 comme...

Watch this Scientific Journal Video about Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment at JoVE.com

Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment

Les auteurs décrivent une méthode pour améliorer significativement la greffe orthotopique de cellules de cancer du poumon dans les poumons murines en préconditionner les voies respiratoires avec des blessures. Cette approche peut également être appliquée pour étudier les interactions stroma dans le microenvironnement de poumon, la diffusion métastatique, la comorbidité de cancer du poumon, et pour produire plus efficacement les patients issus des xénogreffes.

Pré conditionnement les voies respiratoires des souris à la bléomycine augmente l’efficacité de la prise de greffe orthotopique Lung Cancer Cell

Lung cancer is a deadly treatment refractory disease that is biologically heterogeneous. To understand and effectively treat the full clinical spectrum of ...

The overall goal of this procedure is to increase the efficiency of transplanting tumor-initiating lung cancer cells into the airways of mice. This method can help establish new preclinical models in order to answer key questions in cancer biology, including the causes of drug resistance and relationship between fibrosis and lung cancer. The main advantage of this technique is that it increase the transplantation efficiency of tumor-initiating cells into the lungs of a variety of mouse strains.The implications of this technique extend toward therapy, because it enables us to model a greater variety of human lung cancer subtypes, known to have different clinical responses to treatment. For this protocol, the mice must first be injected with bleomycin. Then, after 14 days, the tumor cells are injected.The procedure for both injections is very similar and described here. Two hours prior to the injection, thaw the bleomycin stock on ice and dilute it to the working concentration. Keep it on ice.For a cell bolus, have a cell suspension prepared as described in the text protocol. The procedure time for each mouse is about 10 minutes all together. Be certain to confirm proper anesthesia using a toe pinch, and apply vet ointment to the eyes.At this time, if the mouse has dark hair, then shave the entire rib area both ventrally and dorsally so it can be imaged correctly. Then, place the mouse on the intubation platform by securing it by its front teeth with it's back against the platform. If a cell bolus is to be injected, resuspend it now with gentle trituration.Now illuminate the upper-chest region, open the mouth, and gently pull out the tongue using flat forceps. Prepare an IV catheter for the trachea by removing the needle, then position it over the tracheal opening. Next, insert the catheter into the trachea until the top of the catheter is near the front teeth and illuminate the interior of the catheter to confirm its placement.Then, dispense the 50 microliters of freshly made bleomycin, or cell suspension, directly into the catheter. Wait a few seconds for the entire volume to travel down the catheter. Then, remove the catheter and dispose of it in 10%bleach.If the mouse is not inhaling the liquid, carefully monitor its breathing and adjust the catheter position. If the mouse stops breathing, immediately remove the catheter and allow the mouse to breath before you reinsert the catheter in. After removing the catheter, continue performing the procedure to have five treated mice, still anesthetized, and ready to image.For recovery, place the mouse supine on an IACUC approved heating pad in a recovery cage and monitor it until it has fully recovered. Two or three minutes after injecting the cells, inject 100 microliters of luciferin retro-orbitally, using an insulin needle. Alternate the eye used for injection every imaging session.After waiting at lest two minutes, position up to five mice in an animal bioluminescence imager, in the sternal recumbency position and acquire a dorsal picture using luminescence settings. Under the control panel, adjust the resolution and sensitivity settings, to measure the luminescence of the cells. For most applications, start with three minutes, set the binning to medium, set the f/stop to one, set the field of view to d, and set the subject height to 1.5.If the injection was successful, a signal is detected in the upper chest area in one lung or both lungs. If cells are clustered at the entrance of the trachea, the injection was unsuccessful. After taking the dorsal image, flip the mice and acquire a ventral image and adjust the setting as needed.After imaging, proceed with postoperative care as described in the text protocol. Then, repeat this imaging protocol three days post-engraftment and weekly thereafter. To analyze the images, use a bioluminescence analysis software.First, load all the appropriate images in the series. This section is detailed to one software package. Next, for each mouse, in the first image of the series, create a square region of interest and position it over the upper chest area covering the entire lung region.Then, using a right click, access the copy all regions of interest function, and use this tool to apply the same regions of interest to each image in the group. Then, within each image, tweak the positions of the squares to cover the upper chest of each mouse. Do this for both the ventral and dorsal views.Now, in the upper left corner of the image window, select the photons function. Then select the measure option. The data from the regions of interest is then displayed in an output table as total flux.Analyze this data as needed. When immune compromised, athymic mice were treated with bleomycin. Prior to cell-bolus engraftment, transient fibrosis was observed by day 14 in bleomycin-treated mice, but not vehicle-treated mice.Next, cells from the established human lung cancer cell line, H2030, were delivered intratracheally into the lungs of these mice. After 35 days, bleomycin-treated mice had a high lung-tumor burden. However, in vehicle treated animals, no tumors were detected.The lung-tumor burden was confirmed using histology. Lungs pretreated with vehicle had no evidence of tumor nodules, whereas bleomycin pretreated lungs had large tumor nodules. After transplanting a metastatic H2030 BrM 3 cell line, by 39 to 57 days, bioluminescence was too intense for imaging, so metastasis was analyzed in distant organs ex vivo.Small lesions could be detected in various tissues, suggesting that this method holds promise, to study spontaneously disseminated disease. Once mastered, this technique can be done in 10 minutes per cage of five mice without imaging and 20 minutes per cage when also imaging the mice. While attempting this procedure, it is important to remember to ensure proper insertion of the catheter and to monitor the animal's breathing.Following this procedure, other methods like pharmacological studies or aminoacetic chemistry of harvested tissue can be performed in order to answer additional questions, like how engrafted tumors respond to drugs or characterizing tumor stromal interactions specific to the lungs. After its development, this technique can be applied to different mouse strains and tumor models, including patient-derived xenografts in a physiologically relevant setting. Don't forgot that working with bleomycin can be extremely hazardous and precautions such as manipulation in a biohazard hood and proper disposal should always be taken while performing this procedure.

Research

JoVE Journal

Medicine

Bronchial Thermoplasty:  A Novel Therapeutic Approach to Severe Asthma

Thermoplastie bronchique: une nouvelle approche thérapeutique pour l&#39;asthme sévère

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled ...

Recherche

Médecine

An Orthotopic Model of Murine Bladder Cancer

Un modèle orthotopique de cancer de la vessie murin

In this straightforward procedure, bladder tumors are established in female C57 mice through the use of catheterization, local cauterization, and ...

Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma

Multi-photon imagerie de l&#39;invasion des cellules tumorales dans un modèle de souris orthotopique du carcinome épidermoïde oral

Loco-regional invasion of head and neck cancer is linked to metastatic risk and presents a difficult challenge in designing and implementing patient ...

An Orthotopic Bladder Tumor Model and the Evaluation of Intravesical saRNA Treatment

Un modèle de la vessie orthotopique tumorale et l&#39;évaluation de Sarna traitement intravésicale

We present a novel method for treating bladder cancer with intravesically delivered small activating RNA (saRNA) in an orthotopic xenograft mouse bladder ...

Orthotopic Aortic Transplantation in Mice for the Study of Vascular Disease

Transplantation orthotopique aortique chez la souris pour l&#39;étude des maladies vasculaires

Vascular procedures involving anastomoses in the mouse are generally thought to be difficult and highly dependent on the skill of the individual surgeon. ...

A Murine Model of Myocardial Ischemia-reperfusion Injury through Ligation of the Left Anterior Descending Artery

Un modèle murin d&#39;ischémie myocardique-reperfusion par ligature de l&#39;artère interventriculaire antérieure

Acute or chronic myocardial infarction (MI) are cardiovascular events resulting in high morbidity and mortality. Establishing the pathological mechanisms ...

Orthotopic Injection of Breast Cancer Cells into the Mammary Fat Pad of Mice to Study Tumor Growth.

Injection Orthotopique des cellules du cancer du sein dans le Fat Pad mammaire de souris pour étudier la croissance de la tumeur.

Breast cancer growth can be studied in mice using a plethora of models. Genetic manipulation of breast cancer cells may provide insights into the ...

Non-invasive Assessment of the Efficacy of New Therapeutics for Intestinal Pathologies Using Serial Endoscopic Imaging of Live Mice

Évaluation non invasive de l&#39;efficacité de nouveaux traitements pour les pathologies intestinales en utilisant l&#39;imagerie endoscopique de série de souris vivantes

Animal models of inflammatory bowel disease (IBD) and colorectal cancer (CRC) have provided significant insight into the cell intrinsic and extrinsic ...

Cardiac Catheterization in Mice to Measure the Pressure Volume Relationship: Investigating the Bowditch Effect

Cathétérisme cardiaque chez la souris pour mesurer le volume de pression Relation: Étudier les effets Bowditch

Animal models that mimic human cardiac disorders have been created to test potential therapeutic strategies. A key component to evaluating these ...

A "Patient-Like" Orthotopic Syngeneic Mouse Model of Hepatocellular Carcinoma Metastasis

Un «Patient-Like&quot; Orthotopique Syngénique modèle de souris de carcinome hépatocellulaire Métastases

The majority of cancer-related deaths are caused by the metastasis of the cancer rather than the primary tumor itself. Yet, the underlying mechanisms of ...