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

Denne studien ble finansiert av tilskudd fra National Cancer Institute (R01CA166376 og R01CA191489 å D.X. Nguyen) og Department of Defense (W81XWH-16-1-0227 til D.X. Nguyen).

Alle eksperimentene ble utført i henhold til protokoller godkjent av institusjonelle Animal Care og bruk Committee (IACUC) ved Yale University.
1. Sett opp / forberedelse av reagenser.
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Bleomycin Forsiktig: Basert på den globalt harmoniserte System (GHS) for klassifisering og merking av kjemikalier, er bleomycin klassifisert som helsefarlig GHS08.<ol>
<li>Forberede bleomycin i kjemisk hette. Resuspend 15 U i 5 mL steril fosfat bufret saltoppløsning (PBS).</li>
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Slående klinisk paralleller dokumentert mellom lungekreft og andre kroniske sykdommer i lungene36. Spesielt pasienter med idiopatisk lungefibrose (IPF) har en økt forkjærlighet for utvikle lungekreft, og denne tilknytningen er uavhengig av røyking historie37,38. IPF er preget av progressiv ødeleggelse av lunge arkitektur og svekket lungefunksjon gjennom deponering av ECM39. Også etter kirurgisk resection har t...

Lungekreft er ledende årsak til kreft relaterte dødsfall verden1. Pasienter med lungekreft bukke til slutt fra metastase å fjerne organer, særlig i det sentrale nervesystemet, lever, binyrene og bein2,3,4. Thorax malignitet er tradisjonelt klassifisert som småcellet lungekreft (SCLC) eller ikke-småcellet lungekreft kreft (NSCLC)5. NSCLC er mest vanlige diagnosen kreft og kan deles inn i ulike histologiske subtyper, inkludert lunge adenocarcinoma (LUAD) og lunge squamous celle carcinoma (LUSC)6. Genomic analyse av resected menneskelige primære lunge kreft har avdekket at svulster i en gitt histotype kan også uttrykke ulike molekylær forstyrrelser, ytterligere bidrar til deres forskjellige kliniske progresjon og forvirrer pasienten prognose. Den bemerkelsesverdige heterogeniteten av lunge kreft representerer en betydelig utfordring for rasjonell design, pre-klinisk testing og gjennomføring av effektive strategier. Derfor er det behov for å utvide repertoaret medgjørlig eksperimentelle lunge kreft modeller å studere ulike mobilnettet opprinnelse, molekylær subtyper, og stadier av denne sykdommen.
Ulike tilnærminger med dyr modeller har vært ansatt å studere lunge kreft i vivo, hver med sine egne fordeler og ulemper avhengig av på biologiske spørsmålene rundt. Genmodifiserte musen modeller (GEMMs) kan målrette bestemte genetiske endringer i en gitt stamfar celle type, som fører til svulster at fremgangen innen en immunkompetente vert7. Mens svært kraftig og klinisk relevante, være ventetid, variasjon eller lunge svulst sykelighet knyttet GEMMs uoverkommelige visse kvantitative mål og gjenkjenning av sent stadium metastasering i fjerne organer8. En utfyllende tilnærming er bruk av allograft modeller, der lunge kreftceller, hentes direkte fra en mus svulst eller avledet først som etablerte cellelinjer i kultur, er re-introdusert i syngeneic verter. Analogt, opprettes lunge kreft xenografts fra humane cellelinjer eller pasienten avledede svulst prøver. Human celle linje xenografts eller pasienten avledede xenografts (PDXs) er vanligvis opprettholdt i immunsupprimerte mus og derfor utelukke fullstendig immun-overvåking9. Til tross for denne ulempen gir de en avenue overføres begrense mengder av menneskelig biospecimens og studere grunnleggende i vivo egenskapene for menneskelig kreftceller, som kode for mer komplekse genomisk avvik enn GEMM svulster.
En nyttig egenskap av allografts og xenografts er at de er mottakelig for tradisjonelle begrensende celle fortynning analyser, ansatt å kvantifisere frekvensen av svulst starte celler (TICs) innenfor en ondartet celle befolkningen10. I disse eksperimentene, et definert antall celler er subcutaneously injiseres i flanken av dyr og hyppigheten av TICs kan beregnes basert på svulst ta rate. Subkutan svulster men kan være mer hypoxic11 og kan ikke modell fysiologiske begrensninger av lunge svulst microenvironment. Intratracheal levering av epitelial stammen eller progenitor celler inn i lungene of mus er en lunge regenerasjon og luftveier stamcelleforskningen biologi12. Men kan engraftment prisen fra denne teknikken være relativt lav, med mindre lungene er første utsatt for fysiologiske former for skader, virusinfeksjon13,14. Støtte fra stromal betennelsesceller og/eller avbrudd i lunge kjelleren membranen kan forbedre oppbevaring av transplantert celler i relevante stamcelleforskningen nisjer i distale airways15. Fibrose inducing agenter kan også pre tilstand lungene å forbedre engraftment av indusert pluripotent celler16 og mesenchymal stamceller17. Om lignende typer airway skade kan påvirke engraftment prisen, ennå svulst initiering kapasitet og utvekst av lungekreft cellene vurderes systematisk.
I denne studien beskriver vi en metode for å øke effektiviteten i orthotopic lunge kreft celle engraftment, ved pre condition lungene mus med skade. LUAD oppstår i distale luftveiene med en stor undergruppe av disse kreft utvikle en fibrotiske stroma18 som ofte samsvarer med dårlig prognose19. Bleomycin, en naturlig polypeptid hybrid peptid-polyketide, har blitt mye utnyttet for å indusere lungefibrose i mus20. Airway instillasjon av bleomycin fremmer først epithelial slitasje i alveoler og rekruttering av inflammatoriske celler, inkludert makrofager, nøytrofile og monocytter21. Dette etterfølges av vev remodeling i distale airways, kjelleren membran omorganisering22,23 og ekstracellulær matrix (EFM) deponering24. Effektene av en enkelt bleomycin injeksjon er forbigående, med fibrose løse etter 30 dager i de fleste studier25. Bruker både allograft og xenograft modeller, testet vi hvis pre condition luftveiene mus med bleomycin kan øke betydelig ta frekvensen av LUAD celler i lungene.

<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

Lungekreft er en dødelig behandling ildfaste sykdom som er biologisk heterogene. For å forstå og effektivt behandle full klinisk spekteret av thorax malignitet, kreves det flere dyr modeller som kan recapitulate ulike menneskelige lunge kreft subtyper og stadier. Allograft eller xenograft modeller er allsidig og aktiverer kvantifiseringen tumorigenic kapasitet i vivo, bruke ondartede celler murine eller menneskelige opprinnelse. Imidlertid har beskrevet tidligere metoder for lunge kreft celle engraftment utført i ikke-fysiologiske steder som flanken av mus, på grunn av ineffektiviteten i orthotopic transplantasjon av celler i lungene. I denne studien beskriver vi en metode for å forbedre orthotopic lunge kreft celle engraftment ved pre condition luftveiene mus med fibrose inducing agent bleomycin. Som et proof-of-concept eksperiment brukt vi denne tilnærmingen å engraft kreftceller av lunge adenocarcinoma undertypen, innhentet fra musen eller menneskelig kilder, i ulike stammer mus. Vi viser at skadet luftveiene med bleomycin før svulst celle injeksjon øker engraftment av kreftceller fra 0-17% til 71-100%. Betydelig, denne metoden forbedret lunge svulst forekomsten og senere utvekst bruker ulike modeller og musen stammer. I tillegg spre engrafted lungekreft cellene fra lungene til relevante fjerne organer. Derfor gir vi en protokoll som kan brukes til å opprette og vedlikeholde nye orthotopic modeller av lungekreft med begrense mengder celler eller biospecimen og kvantitativt vurdere tumorigenic kapasitet av lunge kreftceller i fysiologisk relevante innstillinger .

For å øke effektiviteten i LUAD kreft celle engraftment inn i lungene mus, utviklet vi en protokoll som først pre forhold luftveiene med bleomycin etterfulgt av orthotopic svulst celle injeksjon (figur 1). Vi bekreftet at selv når det gis i immunsupprimerte athymic mus, bleomycin indusert forbigående fibrose dag 14 som gjenspeiles av tap av luftveiene arkitektur og økt kollagen avsetning (figur 2). Brutto fibrosis disse mus...

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 for å betydelig forbedre orthotopic engraftment av lungekreft cellene inn i murine lungene ved pre condition luftveiene med skade. Denne tilnærmingen kan også brukes for å studere stromal interaksjoner i lunge microenvironment, metastatisk formidling, lunge kreft Co-morbidities, og for å generere mer effektivt pasienten avledet xenografts.

Pre condition luftveiene mus med Bleomycin øker effektiviteten av Orthotopic lunge kreft cellen 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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Acute or chronic myocardial infarction (MI) are cardiovascular events resulting in high morbidity and mortality. Establishing the pathological mechanisms ...

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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 ...

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Non-invasiv Vurdering av effekt av New Therapeutics for Intestinal Patologier Bruke Serial Endoskopisk Imaging av levende mus

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Hjertekateterisering i Mus for å måle trykket Volume Forholdet: Gransker Bowditch Effect

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

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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 ...