이 연구는 국립 암 연구소 (R01CA166376 및 D.X. 구 엔에 R01CA191489)와 국방부 (W81XWH-16-1-0227 D.X. 구 엔 하)에서 교부 금에 의해 투자 되었다.

<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>

저자 아무 경쟁 금융 관심사를 선언합니다.

눈에 띄는 임상 유사물 폐암 및 폐36의 다른 만성 질환 사이 문서화 되었습니다. 특히, 환자 특 발성 폐 섬유 증 (IPF) 개발 폐암에 대 한 증가 취향이 있고이 협회는 독립적인 역사37,38흡연의. IPF 폐 건축과 ECM39의 증 착을 통해 장애인된 호흡 기능의 진보적인 파괴에 의해 특징입니다. 또한, 외과 절제술 다음 초기 단계 N...

폐암은 주요 원인의 암 관련 사망 세계1. 폐암 환자 결국 굴복 하는 전이에서 먼 장기에, 특히 중앙 신경 조직, 간, 부 신 분 비, 및 뼈2,,34. 흉부 악성 작은 세포 폐 암 (SCLC) 또는 비 작은 세포 폐 암 (NSCLC)5전통적으로 분류 되어 있다. NSCLC 이며 가장 자주 암 진단 폐 선 암 (LUAD)와 폐 편평 상피 세포 암 (LUSC)6을 포함 하 여 다른 조직학 하위로 세분화 될 수 있습니다. 절제 인간의 기본 폐 암의 게놈 분석 주어진된 histotype 내 종양 또한 다양 한 분자 섭, 더 그들의 분기 임상 진행에 기여 하 고 환자의 예 후를 혼동을 표현할 수 있는 공개 했다. 폐 암의 놀라운이 합리적인 디자인, 전 임상 테스트 및 효과적인 치료 전략의 구현에 중요 한 도전을 나타냅니다. 따라서, 다양 한 세포 기원, 분자 하위,이 질병의 단계를 공부 하 고 온순한 실험 폐 암 모델의 레 퍼 토리를 확장 하는 필요가 있다.
동물 모델을 사용 하 여 다양 한 접근 폐 암에서 공부 vivo에서, 각각의 생물 학적 질문에 따라 그들의 자신의 장단점을 고용 했습니다. 유전자 조작된 마우스 모델 (GEMMs) 주어진된 조상 세포 유형, 종양 immunocompetent 호스트7그 진행 결과에 특정 유전 변경 대상 수 있습니다. 매우 강력 하 고 임상 관련, 대기 시간, 변화, 및 폐 종양 사망률 GEMMs와 관련 된 특정 양적 측정 및 먼 장기8에 늦게 단계 전이의 탐지 금지 될 수 있습니다. 상호 보완적인 접근 이식 모델, 폐 암 세포, 마우스 종양에서 직접 하거나 문화, 설립된 셀 라인으로 먼저 파생 된 syngeneic 호스트에 다시 도입 이다 그것에 의하여의 사용 이다. 비슷하게, 폐 암 xenografts 인간 세포 선 또는 환자 파생된 종양 샘플에서 설정 됩니다. 인간 세포 선 xenografts 또는 환자 파생된 xenografts (PDXs)는 일반적으로 immunocompromised 쥐에서 하 고 따라서 완전 한 면역 감시9배제. 이 결점에도 불구 하 고 그들은 인간 biospecimens 연구 기본적인 vivo에서 속성과 GEMM 종양 보다 더 복잡 한 게놈 착오에 대 한 인코딩 인간 암 세포의 양의 제한 전파 하는 수단을 제공 합니다.
이식 및 xenografts 하나의 유용한 속성은 전통적인 제한 셀 희석 분석 실험, 종양 세포 (TICs)을 시작 하는 악성 세포 인구10의 주파수 척도를 고용 의무가 다는 것. 이 실험에서 셀의 정의 수는 동물의 측면으로 피하 주입 하 고 TICs의 주파수를 종양 걸릴 속도에 따라 예상할 수 있는. 그러나 피하 종양은 더 hypoxic11 수 있으며 폐 종양 microenvironment의 주요 생리 적인 제약을 모델링 하지 않을 수 있습니다. 쥐의 폐에 상피 줄기 또는 조상 세포의 Intratracheal 배달 폐 중생과 기도 줄기 세포 생물학12공부 하는 방법입니다. 그러나,이 기술은에서 engraftment 속도 폐 손상, 바이러스 감염13,14등의 생리 적 형태를 먼저 받게 됩니다 않는 한 상대적으로 낮은 수 있습니다. 자극적인 stromal 세포에서 지원 및 폐 지하실 막의 장애 원심 항공15벽 감 관련 줄기 세포로 이식된 세포의 보존을 높일 수 있습니다. 에이전트를 유도 하는 섬유 증 폐 engraftment 유도 만능 세포16 및17중간 엽 줄기 세포 강화에 사전 조건 또한 수 있습니다. 비슷한 형태의 기도 부상 engraftment 속도 영향을 미칠 수 있습니다, 여부를 종양 시작 용량 및 폐 암 세포의 파생물은 아직 체계적으로 평가 한다.
이 연구에서 우리는 사전 조건 부상으로 쥐의 폐에 의해 orthotopic 폐 암 세포 engraftment의 효율성을 증가 하는 방법을 설명 합니다. LUAD는 수시로 빈약한 예 지19와 상관 관계가 거리 기질18 개발이 암의 중요 한 하위 집합으로 원심 항공에서 발생 한다. Bleomycin polyketide-자연 nonribosomal 하이브리드 펩 티 드은 쥐20에 폐 섬유 증을 유도 하기 위해 광범위 하 게 이용 되어. Bleomycin의 기도 점 먼저 상피 마찰을 포에 염증 세포, 대 식 세포, 호 중구, monocytes21등의 채용을 승진 시킨다. 이것은 원심 항공, 지하실 멤브레인 개편22,23 , 세포 외 기질 (ECM) 증 착24에 개장 하는 조직에 의해 선행 된다. 대부분 연구25에서 30 일 후 해결 하는 섬유 증과 단일 bleomycin 주입의 효과 일시적 이며, 이식 및이 종이 식 모델을 사용 하 여, 사전 조건 bleomycin와 쥐의 기도 폐에서 LUAD 셀의 포획 률 증가 크게 수 테스트.

<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

폐 암은 생물학적으로 이기종은 치명적인 치료 내 화 질병입니다. 이해 하 고 효과적으로 치료 흉부 악성의 전체 임상 스펙트럼, 다양 한 인간의 폐 암 하위 유형 및 단계 정리 수 추가적인 동물 모델 필요 합니다. 이식 또는 종이 식 모델 다재 다능 하 고 tumorigenic 용량에 vivo에서, murine 또는 인간 기원의 악성 세포를 사용 하 여의 정량화를 활성화. 그러나, 폐 암 세포 engraftment의 앞에서 설명한 방법 orthotopic 이식 세포는 폐로의 비 효율으로 인해 마우스의 측면 등 생리 적 비 사이트에서 수행 되었습니다. 이 연구에서 우리가 미리 섬유 증 유도 에이전트 bleomycin와 쥐의 기도 조절 하 여 orthotopic 폐 암 세포 engraftment를 강화 하는 방법을 설명 합니다. 개념 증명 실험으로 우리 쥐의 다양 한 긴장으로 마우스 또는 인간의 소스에서 얻은 폐 선 암 하위의 종양 세포를 engraft에이 접근을 적용. 우리는 0-17에서 종양 세포의 engraftment 증가 종양 세포 주입 전에 bleomycin과 항공 부상 입증 71-100% %. 상당히,이 방법은 폐 종양 발생과 이후의 파생물을 다른 모델 및 마우스 긴장을 사용 하 여 향상. 또한, engrafted 폐 암 세포 관련 먼 장기로는 폐에서 보급. 따라서, 설정 하 고 셀 또는 biospecimen의 양의 제한 폐암의 새로운 orthotopic 모델을 유지 하 고 양적 폐 암 세포 생리학 관련 설정에서의 tumorigenic 용량을 평가 하기 위해 사용할 수 있는 프로토콜 제공 .

LUAD 암 세포 engraftment 쥐의 폐에의 효율성 증가, 우리는 먼저 사전 조건 항공 bleomycin orthotopic 종양 세포 주입 (그림 1) 다음을 사용 하 여 프로토콜 개발. 우리는 immunocompromised athymic 마우스에 투여 하는 경우에 bleomycin 과도 섬유 증에 의해 유도 된 하루 14 기도 건축과 증가 교원 질 공 술 서 (그림 2)의 손실에 의해 입증으로 확인 했...

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

상해 항공을 미리 조절 하 여 murine 폐에 폐 암 세포의 orthotopic engraftment를 크게 향상 하는 방법을 설명 합니다. 이 방법은 또한 폐 microenvironment, 전이성 보급, 폐 암 공동 morbidities stromal 상호 작용 연구에 적용 될 수 있습니다 그리고 파생 xenografts 환자를 보다 효율적으로 생성 하.

Orthotopic 폐 암 세포 Engraftment의 효율성 증가 사전 조건 Bleomycin와 쥐의 기도

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

pre-conditioning-airways-mice-with-bleomycin-increases-efficiency

Universidad de Cartagena UDEC

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JoVE Journal

Medicine

13.5K 조회수.  Yale University School of Medicine. 상해 항공을 미리 조절 하 여 murine 폐에 폐 암 세포의 orthotopic engraftment를 크게 향상 하는 방법을 설명 합니다. 이 방법은 또한 폐 microenvironment, 전이성 보급, 폐 암 공동 morbidities stromal 상호 작용 연구에 적용 될 수 있습니다 그리고 파생 xenografts 환자를 보다 효율적으로 생성 하.

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

Bronchial Thermoplasty:  A Novel Therapeutic Approach to Severe Asthma

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled manner to reduce excessive airway smooth muscle. Reducing airway smooth muscle decreases the ability of the airways to constrict, thereby reducing the frequency of asthma attacks. Bronchial thermoplasty is delivered by the Alair System and is performed in three outpatient procedure visits, each scheduled approximately three weeks apart. The first procedure treats the airways of the right lower lobe, the second treats the airways of the left lower lobe and the third and final procedure treats the airways in both upper lobes. After all three procedures are performed the bronchial thermoplasty treatment is complete.
Bronchial thermoplasty is performed during bronchoscopy with the patient under moderate sedation. All accessible airways distal to the mainstem bronchi between 3 and 10 mm in diameter, with the exception of the right middle lobe, are treated under bronchoscopic visualization. Contiguous and non-overlapping activations of the device are used, moving from distal to proximal along the length of the airway, and systematically from airway to airway as described previously. Although conceptually straightforward, the actual execution of bronchial thermoplasty is quite intricate and procedural duration for the treatment of a single lobe is often substantially longer than encountered during routine bronchoscopy. As such, bronchial thermoplasty should be considered a complex interventional bronchoscopy and is intended for the experienced bronchoscopist. Optimal patient management is critical in any such complex and longer duration bronchoscopic procedure. This article discusses the importance of careful patient selection, patient preparation, patient management, procedure duration, postoperative care and follow-up to ensure that bronchial thermoplasty is performed safely.
Bronchial thermoplasty is expected to complement asthma maintenance medications by providing long-lasting asthma control and improving asthma-related quality of life of patients with severe asthma. In addition, bronchial thermoplasty has been demonstrated to reduce severe exacerbations (asthma attacks) emergency rooms visits for respiratory symptoms, and time lost from work, school and other daily activities due to asthma.

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled manner to reduce excessive airway smooth muscle. Reducing airway smooth muscle decreases the ability of the airways to constrict, thereby reducing the frequency of asthma attacks.

기관지 Thermoplasty : 심한 천식에 소설 치료 접근

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

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An Orthotopic Model of Murine Bladder Cancer

In this straightforward procedure, bladder tumors are established in female C57 mice through the use of catheterization, local cauterization, and subsequent cell adhesion. After their bladders are transurethrally catheterized and drained, animals are again catheterized to permit insertion of a platinum wire into bladders without damaging the urethra or bladder. The catheters are made of Teflon to serve as an insulator for the wire, which will conduct electrical current into the bladder to create a burn injury. An electrocautery unit is used to deliver 2.5W to the exposed end of the wire, burning away extracellular layers and providing attachment sites for carcinoma cells that are delivered in suspension to the bladder through a subsequent catheterization. Cells remain in the bladder for 90 minutes, after which the catheters are removed and the bladders allowed to drain naturally. The development of tumor is monitored via ultrasound. Specific attention is paid to the catheterization technique in the accompanying video.

Bladder tumors are established in female mice in a minimally invasive fashion through catheterization, local cauterization, and subsequent adhesion of carcinoma cells to the burn sites.

Murine 방광 암의 Orthotopic 모델

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

Loco-regional invasion of head and neck cancer is linked to metastatic risk and presents a difficult challenge in designing and implementing patient management strategies. Orthotopic mouse models of oral cancer have been developed to facilitate the study of factors that impact invasion and serve as model system for evaluating anti-tumor therapeutics. In these systems, visualization of disseminated tumor cells within oral cavity tissues has typically been conducted by either conventional histology or with in vivo bioluminescent methods. A primary drawback of these techniques is the inherent inability to accurately visualize and quantify early tumor cell invasion arising from the primary site in three dimensions. Here we describe a protocol that combines an established model for squamous cell carcinoma of the tongue (SCOT) with two-photon imaging to allow multi-vectorial visualization of lingual tumor spread. The OSC-19 head and neck tumor cell line was stably engineered to express the F-actin binding peptide LifeAct fused to the mCherry fluorescent protein (LifeAct-mCherry). Fox1nu/nu mice injected with these cells reliably form tumors that allow the tongue to be visualized by ex-vivo application of two-photon microscopy. This technique allows for the orthotopic visualization of the tumor mass and locally invading cells in excised tongues without disruption of the regional tumor microenvironment. In addition, this system allows for the quantification of tumor cell invasion by calculating distances that invaded cells move from the primary tumor site. Overall this procedure provides an enhanced model system for analyzing factors that contribute to SCOT invasion and therapeutic treatments tailored to prevent local invasion and distant metastatic spread. This method also has the potential to be ultimately combined with other imaging modalities in an in vivo setting.

A comprehensive overview of the techniques involved in generating a mouse model of oral cancer and quantitative monitoring of tumor invasion within the tongue through multi-photon microscopy of labeled cells is presented. This system can serve as a useful platform for the molecular assessment and drug efficacy of anti-invasive compounds.

구강 편평 세포 암종의 Orthotopic 마우스 모델에서 종양 세포 침략의 다중 광자 이미징

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

We present a novel method for treating bladder cancer with intravesically delivered small activating RNA (saRNA) in an orthotopic xenograft mouse bladder tumor model. The mouse model is established by urethral catheterization under inhaled general anesthetic. Chemical burn is then introduced to the bladder mucosa using intravesical silver nitrate solution to disrupt the bladder glycosaminoglycan layer and allows cells to attach. Following several washes with sterile water, human bladder cancer KU-7-luc2-GFP cells are instilled through the catheter into the bladder to dwell for 2 hours. Subsequent growth of bladder tumors is confirmed and monitored by in vivo bladder ultrasound and bioluminescent imaging. The tumors are then treated intravesically with saRNA formulated in lipid nanoparticles (LNPs). Tumor growth is monitored with ultrasound and bioluminescence. All steps of this procedure are demonstrated in the accompanying video.

Establishing an orthotopic bladder tumor model to evaluate antitumor effects of intravesically delivered saRNA and monitoring tumor growth by ultrasound and bioluminescent imaging.

Orthotopic 방광 종양 모델 및 Intravesical saRNA 트리 트먼트의 평가

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

Vascular procedures involving anastomoses in the mouse are generally thought to be difficult and highly dependent on the skill of the individual surgeon. This is largely true, but there are a number of important principles that can reduce the difficulty of these procedures and enhance reproducibility. Orthotopic aortic transplantation is an excellent procedure in which to learn these principles because it involves only two end-to-end anastomoses, but requires good suturing technique and handling of the vessels for consistent success. This procedure begins with the procurement of a length of abdominal aorta from a donor animal, followed by division of the native aorta in the recipient. The procured aorta is then placed between the divided ends of the recipient aorta and sutured into place using end-to-end anastomoses. To accomplish this objective successfully requires a high degree of concentration, good tools, a steady hand, and an appreciation of how easily the vasculature of a mouse can be damaged, resulting in thrombosis. Learning these important principles is what occupies most of the beginner's time when learning microsurgery in small rodents. Throughout this protocol, we refer to these important points. This model can be used to study vascular disease in a variety of different experimental systems1-8. In the context shown here, it is most often used for the study of post-transplant vascular disease, a common long-term complication of solid organ transplantation in which intimal hyperplasia occurs within the allograft. The primary advantage of the model is that it facilitates quantitative morphometric analyses and the transplanted vessel lies contiguous to the endogenous vessel, which can serve as an additional control9. The technique shown here is most often used for mice weighing 18-25 grams. We have accumulated most of our experience using the C57BL/6J, BALB/cJ, and C3H/HeJ strains.

We describe a technique in which a section of the abdominal aorta from a mouse is transplanted orthotopically to just below the renal arteries in an allogeneic or syngeneic recipient. This technique can be useful in studies in which transplantation of large arteries of uniform size is deemed advantageous.

혈관 질병의 연구에 대한 마우스의 Orthotopic 대동맥 이식

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

Bioluminescent Orthotopic Model of Pancreatic Cancer Progression

Pancreatic cancer has an extremely poor five-year survival rate of 4-6%. New therapeutic options are critically needed and depend on improved understanding of pancreatic cancer biology. To better understand the interaction of cancer cells with the pancreatic microenvironment, we demonstrate an orthotopic model of pancreatic cancer that permits non-invasive monitoring of cancer progression. Luciferase-tagged pancreatic cancer cells are resuspended in Matrigel and delivered into the pancreatic tail during laparotomy. Matrigel solidifies at body temperature to prevent leakage of cancer cells during injection. Primary tumor growth and metastasis to distant organs are monitored following injection of the luciferase substrate luciferin, using in vivo imaging of bioluminescence emission from the cancer cells. In vivo imaging also may be used to track primary tumor recurrence after resection. This orthotopic model is suited to both syngeneic and xenograft models and may be used in pre-clinical trials to investigate the impact of novel anti-cancer therapeutics on the growth of the primary pancreatic tumor and metastasis.

Improved understanding of pancreatic cancer biology is critically needed to enable the development of better therapeutic options to treat pancreatic cancer. To address this need, we demonstrate an orthotopic model of pancreatic cancer that permits non-invasive monitoring of cancer progression using in vivo bioluminescence imaging.

췌장암의 진행 발광 동소 모델

Pancreatic cancer has an extremely poor five-year survival rate of 4-6%.  New therapeutic options are critically needed and depend on improved ...

Noninvasive Intratracheal Intubation to Study the Pathology and Physiology of Mouse Lung

The use of a model that mimics the condition of lung diseases in humans is critical for studying the pathophysiology and/or etiology of a particular disease and for developing therapeutic intervention. With the increasing availability of knockout and transgenic derivatives, together with a vast amount of genetic information, mice provide one of the best models to study the molecular mechanisms underlying the pathology and physiology of lung diseases. Inhalation, intranasal instillation, intratracheal instillation, and intratracheal intubation are the most widely used techniques by a number of investigators to administer materials of interest to mouse lungs. There are pros and cons for each technique depending on the goals of a study. Here a noninvasive intratracheal intubation method that can directly deliver exogenous materials to mouse lungs is presented. This technique was applied to administer bleomycin to mouse lungs as a model to study pulmonary fibrosis.

The use of a model that mimics the condition of lung diseases in humans is critical for studying the pathophysiology and/or etiology of a particular disease and for developing therapeutic intervention. Here a noninvasive intratracheal intubation method that can directly deliver exogenous materials to mouse lungs is presented.

비 침습적 기관 내 삽관 마우스 폐의 병리학 및 생리학을 연구하는

The use of a model that mimics the condition of lung diseases in humans is critical for studying the pathophysiology and/or etiology of a particular ...

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

Acute or chronic myocardial infarction (MI) are cardiovascular events resulting in high morbidity and mortality. Establishing the pathological mechanisms at work during MI and developing effective therapeutic approaches requires methodology to reproducibly simulate the clinical incidence and reflect the pathophysiological changes associated with MI. Here, we describe a surgical method to induce MI in mouse models that can be used for short-term ischemia-reperfusion (I/R) injury as well as permanent ligation. The major advantage of this method is to facilitate location of the left anterior descending artery (LAD) to allow for accurate ligation of this artery to induce ischemia in the left ventricle of the mouse heart. Accurate positioning of the ligature on the LAD increases reproducibility of infarct size and thus produces more reliable results. Greater precision in placement of the ligature will improve the standard surgical approaches to simulate MI in mice, thus reducing the number of experimental animals necessary for statistically relevant studies and improving our understanding of the mechanisms producing cardiac dysfunction following MI. This mouse model of MI is also useful for the preclinical testing of treatments targeting myocardial damage following MI.

We introduce a surgical method to induce experimental ischemia/reperfusion (I/R) injury to simulate myocardial infarction (MI) in mouse models that allows for more clarity in positioning of the ligation on the left anterior descending artery (LAD) to increase the reproducibility of MI experiments in mice.

왼쪽 앞쪽에 내림차순 동맥의 결찰을 통해 심근 허혈 - 재관류 손상의 생쥐 모델

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.

Breast cancer growth can be studied in mice using a plethora of models. Genetic manipulation of breast cancer cells may provide insights into the functions of proteins involved in oncogenic progression or help to discover new tumor suppressors. In addition, injecting cancer cells into mice with different genotypes might provide a better understanding of the importance of the stromal compartment. Many models may be useful to investigate certain aspects of disease progression but do not recapitulate the entire cancerous process. In contrast, breast cancer cells engraftment to the mammary fat pad of mice better recapitulates the location of the disease and presence of the proper stromal compartment and therefore better mimics human cancerous disease. In this article, we describe how to implant breast cancer cells into mice orthotopically and explain how to collect tissues to analyse the tumor milieu and metastasis to distant organs. Using this model, many aspects (growth, angiogenesis, and metastasis) of cancer can be investigated simply by providing a proper environment for tumor cells to grow.

Cancer is a complex disease that is influenced by the tissue surrounding the tumor as well as local pro- and anti-inflammatory mediators. Therefore, orthotropic injection models, rather than subcutaneous models may be useful to study cancer progression in a manner that better mimics human pathology.

마우스의 유방 지방 패드에 유방암 세포의 소성 주입은 종양의 성장을 연구한다.

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

Animal models of inflammatory bowel disease (IBD) and colorectal cancer (CRC) have provided significant insight into the cell intrinsic and extrinsic mechanisms that contribute to the onset and progression of intestinal diseases. The identification of new molecules that promote these pathologies has led to a flurry of activity focused on the development of potential new therapies to inhibit their function. As a result, various pre-clinical mouse models with an intact immune system and stromal microenvironment are now heavily used. Here we describe three experimental protocols to test the efficacy of new therapeutics in pre-clinical models of (1) acute mucosal damage, (2) chronic colitis and/or colitis-associated colon cancer, and (3) sporadic colorectal cancer. We also outline procedures for serial endoscopic examination that can be used to document the therapeutic response of an individual tumor and to monitor the health of individual mice. These protocols provide complementary experimental platforms to test the effectiveness of therapeutic compounds shown to be well tolerated by mice.

We describe methods for longitudinal monitoring of the efficacy of therapeutics for the treatment of colonic pathologies in mice using a rigid endoscope. This protocol can be readily used for the characterization of the therapeutic response of an individual tumor in live mice and also for monitoring potential disease relapse.

라이브 마우스의 직렬 내시경 이미징을 사용하여 소장 병변에 대한 새로운 치료제의 효능의 비 침습적 평가

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