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

Diese Studie wurde finanziert durch Zuschüsse aus dem National Cancer Institute (R01CA166376 und R01CA191489 zu D.X. Nguyen) und das Department of Defense (W81XWH-16-1-0227, D.X. Nguyen).

Alle Experimente wurden gemäß Protokollen genehmigt durch die institutionelle Animal Care und Nutzung Committee (IACUC) an der Yale University durchgeführt.
1. richten Sie / Vorbereitung der Reagenzien.
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Bleomycin Achtung: Basiert auf das Global Harmonisierte System (GHS) der Einstufung und Kennzeichnung von Chemikalien, wird Bleomycin als GHS08 gesundheitsschädlich eingestuft.<ol>
<li>Bleomycin in einer chemischen Kapuze vorbereiten. Aufschwemmen Sie 15 U in ...

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Markante klinische parallelen wurden zwischen Lungenkrebs und andere chronische Erkrankungen der Lunge36dokumentiert. Insbesondere Patienten mit idiopathischer Lungenfibrose (IPF) haben eine erhöhte Vorliebe für Lungenkrebs zu erkranken, und der Verein ist unabhängig vom Rauchen Geschichte37,38. IPF zeichnet sich durch die fortschreitende Zerstörung der Lunge Architektur und eingeschränkter Atemfunktion durch Ablagerung von ECM<sup cl...

Lungenkrebs ist die führende Ursache von Krebs im Zusammenhang mit Todesfällen weltweit1. Patienten mit Lungenkrebs erliegen schließlich von Metastasen in entfernten Organen, vor allem auf das zentrale Nervensystem, Leber, Nebennieren und Knochen2,3,4. Thorakale Tumoren wurden traditionell als kleinzelligem Lungenkrebs (SCLC) oder nicht-kleinzelligem Lungenkrebs (NSCLC) Krebs5eingestuft. NSCLC ist die am häufigsten malignen Erkrankungen diagnostiziert und können unterteilt werden in verschiedene histologische Subtypen, einschließlich Lungenkrebs Adenokarzinom (LUAD) und Lunge Plattenepithel-Karzinom (LUSC)6. Genomische Analyse des resezierten menschlichen primären Lungenkrebs hat ergeben, dass Tumoren innerhalb einer gegebenen Histotype auch unterschiedliche Molekulare Störungen, weiter einen Beitrag zu ihrer divergente klinische Progression und verwirrende Patienten Prognose zum Ausdruck bringen können. Die bemerkenswerte Heterogenität der Fälle von Lungenkrebs stellt eine große Herausforderung dar, der rationales Design, prä-klinischen Erprobung und Umsetzung von wirksamen Therapiestrategien. Infolgedessen gibt es eine Notwendigkeit, das Repertoire der gefügig experimentelle Lunge Krebs Modelle zur Untersuchung der verschiedenen zellulären Ursprung, molekularen Subtypen und Stadien der Erkrankung zu erweitern.
Verschiedene Ansätze mit Tiermodellen sind eingesetzt worden, um Lungenkrebs Krebs in Vivo, jede mit ihren eigenen vor- und Nachteile je nach den biologischen Frage(n) von Interesse zu studieren. Gentechnisch veränderte Mausmodelle (GEMMs) können bestimmte genetische Veränderungen in einem bestimmten Vorläuferzellen Zelltyp, was zu Tumoren, dass Fortschritte innerhalb einer immunkompetenten Wirt7ausrichten. Während extrem leistungsstark und klinisch relevante, kann die Latenz, Variabilität und/oder Lunge Tumor Morbidität verbunden mit GEMMs bestimmte quantitativen Messungen und die Aufdeckung von späten Stadium Metastasen in entfernten Organen8unerschwinglich sein. Ein ergänzenden Ansatz ist die Verwendung von Allograft-Modelle, wobei Lungenkrebszellen, entweder direkt von einem Maus-Tumor oder zunächst als etablierte Zelllinien in der Kultur abgeleitet in Phänomen Gastgeber wieder eingeführt werden. Analog, sind Lungenkrebs Krebs Xenotransplantate aus humanen Zelllinien oder Patienten abgeleiteten tumorproben gegründet. Menschliche Zelle Zeile Xenotransplantate oder Patienten abgeleiteten Xenotransplantate (PDXs) bestehen in der Regel bei immungeschwächten Mäusen und daher komplett immun-Überwachung9entgegen. Trotz dieses Nachteils bieten sie eine Allee zu propagieren, Begrenzung der Mengen an menschliche bioproben und Studium grundlegende in Vivo Eigenschaften von menschlichen Krebszellen, die komplexere genomische Aberrationen als GEMM Tumoren zu codieren.
Eine nützliche Eigenschaft von Allografts und Xenografts ist, dass sie zu traditionellen begrenzende Zelle Verdünnung Assays eingesetzt, um die Häufigkeit der Tumor Zellen (TICs) innerhalb einer malignen Zelle Bevölkerung10Einleitung zu quantifizieren. In diesen Experimenten eine definierte Anzahl von Zellen werden in die Flanke der Tiere subkutan injiziert und die Häufigkeit der TICs basierend auf Tumor nehmen Rate geschätzt werden kann. Subkutane Tumoren können jedoch mehr hypoxischen11 und können nicht physiologischen Einschränkungen der Lunge Tumor Mikroumgebung modellieren. Intratrachealen Lieferung von epithelialen Stammzellen und Vorläuferzellen in der Lunge von Mäusen ist eine Methode, pulmonale Regeneration und Atemwege Stammzell-Biologie12zu studieren. Die Engraftment Rate von dieser Technik kann relativ gering, jedoch, wenn die Lunge physiologischen Formen der Verletzung, wie virale Infektion13,14zunächst ausgesetzt sind. Unterstützung von Stromazellen Entzündungszellen und/oder die Unterbrechung der Basalmembran der Lunge kann Beibehaltung der transplantierten Zellen in relevanten Stammzell-Nischen in den distalen Atemwege15verbessern. Fibrose induzieren Agenten kann auch die Lungen Engraftment induzierten pluripotenten Zellen16 und mesenchymalen Stammzellen17verbessern Pre-Zustand. Ob ähnliche Formen der Atemwege Verletzungen die Engraftment Rate beeinflussen können, ist Tumor auslösende Kapazität und Auswuchs der Lungenkrebszellen noch nicht systematisch untersucht werden.
In dieser Studie beschreiben wir eine Methode zur Steigerung der Effizienz des orthotopen Lunge Krebs Zelle Engraftment durch Vorklimatisierung der Lunge von Mäusen mit Verletzungen. LUAD entsteht in den distalen Atemwegen eine bedeutende Teilmenge dieser Krebsarten entwickeln eine fibrotische Stroma18 , die oft mit schlechter Prognose19korreliert. Bleomycin, eine natürliche Nonribosomal Hybrid Peptid-Polyketid, wurde ausgiebig genutzt, Lungenfibrose in Mäusen20induzieren. Atemwege Instillation von Bleomycin fördert zuerst epithelialen Fluktuation in den Alveolen und Rekrutierung von Entzündungszellen, einschließlich Makrophagen, Neutrophilen und Monozyten21. Dies wird gefolgt von Gewebe Umbau in der distalen Atemwegen, Basalmembran Reorganisation22,23 und extrazelluläre Matrix (ECM) Ablagerung24. Die Auswirkungen einer einzigen Bleomycin Einspritzung sind vergänglich, mit Fibrose nach 30 Tagen in den meisten Studien25zu lösen. Mit Allograft und Xenograft Modellen, haben wir getestet, wenn die Atemwege von Mäusen mit Bleomycin Vorklimatisierung Take-Rate von LUAD Zellen in der Lunge erheblich steigern könnte.

<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

Lungenkrebs ist eine tödliche Behandlung refraktärer Krankheit, die biologisch heterogen ist. Um zu verstehen und effektiv die volle klinische Spektrum der thorakalen Tumoren zu behandeln, werden zusätzliche Tiermodellen, die vielfältigen menschlichen Lunge-Krebs-Subtypen und Stufen rekapitulieren können benötigt. Allograft oder Xenograft-Modelle sind vielfältig und erlauben die Quantifizierung der tumorigenic Kapazität in Vivo, mit malignen Zellen murinen oder menschlichen Ursprungs. Jedoch wurden zuvor beschriebene Methoden der Lunge Krebs Zelle Engraftment unphysiologischen Websites, z. B. die Flanke von Mäusen, aufgrund der Ineffizienz des orthotopen Transplantation von Zellen in der Lunge durchgeführt. In dieser Studie beschreiben wir eine Methode zur orthotopen Lunge Krebs Zelle Engraftment verbessern, indem die Atemwege von Mäusen mit Fibrose induzieren Agent Bleomycin Vorklimatisierung. Als ein Proof-of-Concept-Experiment haben wir diesen Ansatz um Tumorzellen von der Lunge Adenokarzinom Untertyp, gewonnen aus menschlichen Quellen oder Maus in verschiedene Stämme von Mäusen weiterhin angewandt. Wir zeigen, dass verletzte die Atemwege mit Bleomycin vor der Tumor Zelle Injektion das Engraftment von Tumorzellen von 0-17 erhöht % und 71-100 %. Diese Methode verbessert deutlich, Lungen-Tumor-Inzidenz und anschließende Auswuchs mit verschiedenen Modellen und Mausstämme. Darüber hinaus verbreiten eingepflanzt Lungenkrebszellen aus der Lunge in relevanten entfernten Organen. So bieten wir ein Protokoll, das verwendet werden kann, zur Schaffung und Aufrechterhaltung orthotopen Modellneuheiten an Lungenkrebs zu erkranken mit der Begrenzung der Mengen von Zellen oder ibbl und quantitativ bewerten die tumorigenic Kapazität der Lungenkrebszellen in physiologisch relevanten Einstellungen .

Um die Effizienz der LUAD Krebs Zelle Engraftment in die Lunge von Mäusen zu erhöhen, haben wir eine Protokoll, die zuerst die Atemwege mit Bleomycin, gefolgt von orthotopen Tumor Zelle Injektion (Abbildung 1) Voraussetzungen entwickelt. Wir bestätigen, dass selbst wenn in immungeschwächten Athymic Mäuse verabreicht, Bleomycin transiente Fibrose 14.Tag ausweislich Verlust der Atemwege Architektur und erhöhte Kollagen Deposition (Abb...

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

Wir beschreiben eine Methode zur orthotopen Engraftment der Lungenkrebszellen in murinen Lungen deutlich zu verbessern, indem Vorklimatisierung die Atemwege mit Verletzungen. Dieser Ansatz kann auch angewendet werden, um die Stromale Interaktionen innerhalb der Lunge Mikroumgebung, metastasierendem Verbreitung, Lunge Krebs Komorbiditäten zu untersuchen und um effizienter Patient erzeugen Xenotransplantate abgeleitet.

Die Atemwege von Mäusen mit Bleomycin Vorklimatisierung erhöht die Effizienz der Orthotopen Lung Cancer Cell Engraftment

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

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

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

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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

Nicht-invasive Beurteilung der Wirksamkeit neuer Therapeutika für Darmpathologien Verwenden der seriellen endoskopische Bildgebung von lebenden Mäusen

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

Herzkatheter in Mäuse, um den Druck Volumen Relationship Maßnahme: Untersuchung der Bowditch Effect

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

Ein &quot;Patient-Like&quot; Orthotope Syngene Maus-Modell der Leberzellkarzinom Metastasen

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 ...