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

Undersøgelsen blev finansieret af tilskud fra National Cancer Institute (R01CA166376 og R01CA191489 til D.X. Nguyen) og Department of Defense (W81XWH-16-1-0227 til D.X. Nguyen).

Alle eksperimenter blev udført i overensstemmelse med protokoller godkendt af institutionelle Animal Care og brug udvalg (IACUC) ved Yale University.
1. sæt op / forberedelse af reagenser.
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Bleomycin Forsigtig: Baseret på den globalt harmoniserede System (GHS) af klassificering og mærkning af kemikalier, er bleomycin klassificeret som en GHS08-sundhedsfare.<ol>
<li>Forberede bleomycin i en kemisk hætte. Resuspend 15 U i 5 mL sterilt fosfatbufferet saltopløsn...

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Slående kliniske paralleller er blevet dokumenteret mellem lungekræft og andre kroniske sygdomme i lungerne36. I særdeleshed patienter med idiopatisk lungefibrose (IPF) har en større forkærlighed for udvikle lungekræft, og denne forening er uafhængig af rygning historie37,38. IPF er karakteriseret ved fremadskridende ødelæggelse af lungen arkitektur og nedsat respiratoriske funktion gennem aflejring af ECM39</sup...

Lungekræft er førende årsag til cancer relaterede dødsfald på verdensplan1. Patienter med lungekræft efterhånden bukke under fra metastaser til fjerntliggende organer, navnlig til centralnervesystemet, lever, binyrer og ben2,3,4. Thorax maligniteter har traditionelt været klassificeret som småcellet lungecancer (SCLC) eller ikke-småcellet lungekræft (NSCLC) kræft5. NSCLC er mest hyppigt diagnosticeret malignitet og kan opdeles i forskellige histologiske undertyper, herunder lunge adenocarcinom (LUAD) og lunge planocellulært karcinom (LUSC)6. Genomisk analyse af resektion menneskelige primære lungekræft har afsløret, at tumorer inden for en given histotype også kan udtrykke forskellige molekylære perturbationer, yderligere bidrager til deres divergerende klinisk progression og confounding patientens prognose. Den bemærkelsesværdige heterogenitet af lungekræft udgør en betydelig udfordring for rationelt design, præ-klinisk test og gennemførelsen af effektive terapeutiske strategier. Derfor er der behov for at udvide repertoiret af tractable eksperimentelle lung cancer modeller at studere forskellige cellulære oprindelse, molekylære undertyper og stadier af denne sygdom.
Forskellige tilgange ved hjælp af dyremodeller har været ansat til at studere lung cancer i vivo, hver med deres egne fordele og ulemper afhængigt af de biologiske spørgsmål af interesse. Gensplejsede musemodeller (GEMMs) kan målrette specifikke genetiske ændringer i en given stamfader celletype, hvilket resulterer i tumorer, fremskridt inden for en immunkompetente vært7. Mens ekstremt kraftfuld og klinisk relevante, kan den ventetid, variation og/eller lunge tumor sygelighed forbundet med GEMMs være uoverkommelige til visse kvantitative målinger og påvisning af sene fase metastase i fjerntliggende organer8. En supplerende strategi er brugen af allograft modeller, hvorved lunge kræftceller, fremstillet enten direkte fra en mus-svulsten eller afledt først som etablerede cellelinier i kultur, der genindsættes syngeneic værter. Analogt, er lung cancer xenografts nedsat fra menneskelige cellelinjer eller patient afledte tumor prøver. Humane celle linje xenografts eller patient afledte xenografts (PDXs) vedligeholdes normalt i immunkompromitterede mus og derfor udelukker fuldstændig immun-overvågning9. Trods denne ulempe giver de en avenue for at udbrede begrænse mængder af menneskelige biospecimens og studere grundlæggende i vivo egenskaber af menneskelige kræftceller, som koder for mere komplekse genomisk aberrationer end CLAUSS tumorer.
En nyttig egenskab af allografts og xenografts er at de er indstillet til traditionelle begrænsende celle fortynding assays, ansat til at kvantificere hyppigheden af tumor indlede celler (TICs) inden for en malign celle befolkning10. I disse eksperimenter, et defineret antal celler injiceres subkutant i flanke af dyr og hyppigheden af TICs kan skønnes baseret på tumor tage sats. Subkutane tumorer dog kan være mere hypoksiske11 og kan ikke model fysiologiske databasenøgler af lunge tumor mikromiljø. Intratrakeal levering af epitel stamceller eller stamceller i lungerne på mus er en metode til at studere pulmonal regenerering og luftvejene stamcelle biologi12. Engraftment sats fra denne teknik kan dog relativt lavt, medmindre lungerne udsættes først for fysiologiske former for skade, såsom virusinfektion13,14. Støtte fra inflammatoriske stromale celler og/eller afbrydelse af lunge basalmembranen kan forbedre fastholdelsen af transplanterede celler i relevante stamcelle nicher i distale airways15. Fibrose inducerende agenter kan også pre betingelse lungerne til at forbedre engraftment inducerede pluripotente celler16 og mesenkymale stamceller17. Om tilsvarende former for airway skade kan påvirke engraftment sats, har tumor igangsættende kapacitet og udvækst af lunge kræftceller endnu skal vurderes systematisk.
I denne undersøgelse beskriver vi en metode til at øge effektiviteten af orthotopic lunge kræft celle engraftment, ved forudgående konditionering lungerne på mus med skade. LUAD opstår i de distale airways med en væsentlig delmængde af disse kræftformer, udvikle en fibrotisk stroma18 der ofte korrelerer med dårlig prognose19. Bleomycin, en naturlig nonribosomal hybrid peptid-polyketide, har været flittigt udnyttet til at fremkalde pulmonal fibrose i mus20. Luftvejene instillation af bleomycin fremmer først epitelial nedslidning i alveolerne og rekruttering af inflammatoriske celler, herunder makrofager, neutrofile og monocytter21. Dette er efterfulgt af væv remodellering i distale airways, basalmembranen reorganisering22,23 og ekstracellulære matrix (ECM) deposition24. Virkningerne af en enkelt bleomycin injektion er forbigående, med fibrose løse efter 30 dage i de fleste undersøgelser25. Brug af både allograft og xenograft modeller, testet vi hvis forudgående konditionering luftvejene i mus med bleomycin kunne øge tage sats af LUAD celler i lungerne.

<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

Lungekræft er en dødelig behandling refraktær sygdom, der er biologisk heterogene. For at forstå og effektivt at behandle den fuldstændige klinisk spektrum af thorax maligniteter, der er behov for yderligere dyremodeller, der kan sammenfatte forskellige menneskelige lung cancer undertyper og faser. Allograft eller xenograft modeller er alsidig og aktiverer kvantificering af tumorfremkaldende kapacitet i vivo, ved hjælp af maligne celler af enten murine eller menneskelig oprindelse. Imidlertid har tidligere beskrevet metoder af lunge kræft celle engraftment udført i ikke-fysiologisk steder, såsom flanke af mus, på grund af ineffektiviteten af orthotopic transplantation af celler ind i lungerne. I denne undersøgelse beskriver vi en metode til at forbedre orthotopic lunge kræft celle engraftment ved forudgående konditionering luftvejene i mus med fibrose inducerende agent bleomycin. Som en proof-of-concept eksperiment, vi har anvendt denne fremgangsmåde for at indpode tumorceller af undertypen lunge adenocarcinom, fremstillet af enten musen eller menneskelige kilder, til forskellige stammer af mus. Vi demonstrere, at beskadige luftvejene med bleomycin før tumor celle indsprøjtning øger engraftment af tumorceller fra 0-17% til 71-100%. Denne metode forbedret betydeligt, lunge tumor forekomsten og efterfølgende udvækst ved hjælp af forskellige modeller og mus stammer. Derudover formidle aflægger lung cancerceller fra lungerne til relevante fjerntliggende organer. Dermed, vi leverer en protokol, der kan bruges til at etablere og vedligeholde nye orthotopic modeller af lungekræft med begrænse mængder af celler eller biospecimen og kvantitativt vurdere tumorfremkaldende kapaciteten af lunge kræftceller i fysiologisk relevante indstillinger .

For at øge effektiviteten af LUAD kræft celle engraftment i lungerne på mus, udviklet vi en protokol, der først pre betingelser luftvejene ved hjælp af bleomycin efterfulgt af orthotopic tumor celle indsprøjtning (figur 1). Vi bekræftede, at selv når det gives til immunkompromitterede athymiske mus, bleomycin induceret forbigående fibrose af dag 14 som det fremgår af tab af luftvejene arkitektur og øget kollagen deposition (fig...

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

Vi beskriver en metode til at forbedre betydeligt orthotopic engraftment lunge kræft celler i murine lungerne af forudgående konditionering airways med skade. Denne tilgang kan også anvendes til at studere stromale interaktioner i lunge mikromiljø, metastatisk spredning, lung cancer co-morbiditet, og for at mere effektivt generere patienten afledt xenografts.

Forudgående konditionering luftvejene i mus med Bleomycin øger effektiviteten af Orthotopic lunge kræft celle 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.

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Hjertekateterisation i mus til at måle trykket Volume Forholdet: Undersøgelse af 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

En &quot;Patient-Like&quot; ortotopisk Syngene musemodel af hepatocellulært carcinom Metastase

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 ...