Name: chemotherapy-induced vascular toxicity - real-time in vivo imaging of vessel impairment
Uploaded: 2015-01-07T13:00:00
Description: Watch this Scientific Journal Video about Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment at JoVE.com

Etik erklæring: Alle forsøg blev godkendt af Institutional Animal Care og brug Udvalg. Animal pleje var efter fastlagte retningslinier. ICR hunmus (7-8 uger gammel, 25-30 g) blev anbragt i aircondition, lys kontrolleret dyrefaciliteter af Sackler medicinske fakultet i Tel-Aviv University. På sigt blev dyr aflivet med anæstesi overdosis. 1. fibred Konfokal Fluorescens mikroskopi (FCFM) Kalibrering <ol><li> Tænd enheden. </li><li> Slut mikrosonde (mini0 / 30). </li><li>...

<ol>
	<li>Chow, A. 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=Anthracyclines+cause+endothelial+injury+in+pediatric+cancer+patients:+a+pilot+study.">Anthracyclines cause endothelial injury in pediatric cancer patients: a pilot study.</a> J Clin Oncol. 24 (6), 925-928 (2006).</li><li>Nuver, J., 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=Acute+chemotherapy-induced+cardiovascular+changes+in+patients+with+testicular+cancer.">Acute chemotherapy-induced cardiovascular changes in patients with testicular cancer.</a> J Clin Oncol. 23 (36), 9130-9137 (2005).</li><li>Vos, F. 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=Endothelial+cell+effects+of+cytotoxics:+balance+between+desired+and+unwanted+effects.">Endothelial cell effects of cytotoxics: balance between desired and unwanted effects.</a> Cancer Treat Rev. 30 (6), 495-513 (2004).</li><li>Kerbel, R. S., 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='Accidental'+anti-angiogenic+drugs.+anti-oncogene+directed+signal+transduction+inhibitors+and+conventional+chemotherapeutic+agents+as+examples.Eur.">'Accidental' anti-angiogenic drugs. anti-oncogene directed signal transduction inhibitors and conventional chemotherapeutic agents as examples.Eur.</a> J Cancer. 36 (10), 1248-1257 (2000).</li><li>Soultati, 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=Endothelial+vascular+toxicity+from+chemotherapeutic+agents:+preclinical+evidence+and+clinical+implications.">Endothelial vascular toxicity from chemotherapeutic agents: preclinical evidence and clinical implications.</a> Cancer Treat Rev. 38 (5), 473-483 (2012).</li><li>Tempelhoff, G. 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=Blood+coagulation+during+adjuvant+epirubicin/cyclophosphamide+chemotherapy+in+patients+with+primary+operable+breast+cancer.">Blood coagulation during adjuvant epirubicin/cyclophosphamide chemotherapy in patients with primary operable breast cancer.</a> J Clin Oncol. 14 (9), 2560-2568 (1996).</li><li>Ben Aharon, 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=Doxorubicin-induced+vascular+toxicity--targeting+potential+pathways+may+reduce+procoagulant+activity.">Doxorubicin-induced vascular toxicity--targeting potential pathways may reduce procoagulant activity.</a> PLoS One. 8 (9), e7515 (2013).</li><li>Laemmel, 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=Fibered+confocal+fluorescence+microscopy+(Cell-viZio)+facilitates+extended+imaging+in+the+field+of+microcirculation.+A+comparison+with+intravital+microscopy.">Fibered confocal fluorescence microscopy (Cell-viZio) facilitates extended imaging in the field of microcirculation. A comparison with intravital microscopy.</a> J Vasc Res. 41 (5), 400-411 (2004).</li><li>Al-Gubory, K. H., Houdebine, L. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+imaging+of+green+fluorescent+protein-expressing+cells+in+transgenic+animals+using+fibred+confocal+fluorescence+microscopy.">In vivo imaging of green fluorescent protein-expressing cells in transgenic animals using fibred confocal fluorescence microscopy.</a> Eur J Cell Biol. 85 (8), 837-845 (2006).</li><li>Bar-Joseph, H., 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=In+vivo+bioimaging+as+a+novel+strategy+to+detect+doxorubicin-induced+damage+to+gonadal+blood+vessels.">In vivo bioimaging as a novel strategy to detect doxorubicin-induced damage to gonadal blood vessels.</a> PLoS One. 6 (9), e23492 (2011).</li><li>Kaushal, V., Kaushal, G. P., Mehta, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+toxicity+of+anthracyclines+on+cultured+endothelial+cells.">Differential toxicity of anthracyclines on cultured endothelial cells.</a> Endothelium. 11 (5-6), 253-258 (2004).</li><li>Kim, E. J., 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=Doxorubicin-induced+platelet+cytotoxicity:+a+new+contributory+factor+for+doxorubicin-mediated+thrombocytopenia.">Doxorubicin-induced platelet cytotoxicity: a new contributory factor for doxorubicin-mediated thrombocytopenia.</a> J Thromb Haemost. 7 (7), 1172-1183 (2009).</li><li>Walsh, J., Wheeler, H. R., Geczy, C. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulation+of+tissue+factor+on+human+monocytes+by+cisplatin+and+adriamycin.">Modulation of tissue factor on human monocytes by cisplatin and adriamycin.</a> Br J Haematol. 81 (4), 480-488 (1992).</li><li>Kotamraju, S., 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=Doxorubicin-induced+apoptosis+in+endothelial+cells+and+cardiomyocytes+is+ameliorated+by+nitrone+spin+traps+and+ebselen.+Role+of+reactive+oxygen+and+nitrogen+species.">Doxorubicin-induced apoptosis in endothelial cells and cardiomyocytes is ameliorated by nitrone spin traps and ebselen. Role of reactive oxygen and nitrogen species.</a> J Biol Chem. 275 (43), 33585-33592 (2000).</li><li>Vasquez-Vivar, J., 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=Endothelial+nitric+oxide+synthase-dependent+superoxide+generation+from+adriamycin.">Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin.</a> Biochemistry. 36 (38), 11293-11297 (1997).</li></ol>

Evaluering kemoterapi-induceret vaskulær toksicitet er udfordrende på grund af vanskeligheden ved at visualisere dynamikken i vaskulatur som reaktion på en stimuli i realtid. Talrige kliniske undersøgelser har impliceret, at flere kemoterapi forårsager direkte vaskulær skade, men mekanismen og karakteristika denne toksicitet er endnu ikke klarlagt. Vi har etableret en real-time, in vivo molekylær billeddannelse platform til vurdering af potentialet vaskulær toksicitet kemoterapi i mus bestående af fibe...

Klinisk evidens for, at flere klasser af kemoterapi fremkalde forskellige vaskulære patologier manifesteret ved Raynaud fænomen, hypertension, myocardialinfarction, cerebrovaskulær angreb, og hepatisk veno-occlusivedisease 1,2. &quot;» Utilsigtet &quot;anti-angiogenese lægemidler&quot; er en forholdsvis nyt begreb, som beskriver konventionelle kemoterapeutiske midler, der virker som mulige angiogeneseinhibitorer, selv om de ikke oprindeligt udviklet til dette formål 3-5, men designet til at fjerne tumorceller ved at pålægge så lidt &quot;sikkerhed skade &quot;på normale celler som muligt 3. Flere kemoterapier er underforstået som vasculo-giftstoffer som observeret i kliniske undersøgelser af serum biomarkører. Blandt disse er alkyleringsmidler (såsom cyclophosphamid), platinforbindelser (såsom cisplatin) og anthracycliner 1,2,5-7. Akutte kardiovaskulære komplikationer kan opstå som result vaskulær toksicitet induceret af kemoterapi. De kan udvikle sig til kroniske lidelser som åreforkalkning og redegøre for øget risiko for sen vaskulær sygelighed. Men på trods af stigende klinisk bevis, der er en mangel på udpegede undersøgelser med vægt mekanismen af ​​vaskulær toksicitet og derfor er yderligere belysning af den nøjagtige patogenese de påfører berettiget. En stor udfordring i at afsløre mekanismen for kemoterapi-induceret vaskulær toksicitet stammer fra kompleksiteten i at undersøge vaskulær funktion in vivo. Vi beskriver heri en platform af høj opløsning in vivo molekylær billeddannelse i mus, der gør det muligt at fange blodgennemstrømning og fartøjernes karakteristika. Denne platform letter påvisning af direkte behandling inducerede vaskulære virkninger: i realtid, samt efter dem over en periode inden for de samme individer.

<table border="0" cellpadding="0" cellspacing="0" width="1395">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:579px;">Name of Material/ Equipment</td>
			<td style="width:423px;">Company</td>
			<td style="width:213px;">Catalog Number</td>
			<td style="width:183px;">Comments/Description</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">general anesthesia (100mg/kg ketaset and 6mg/kg XYL-M2).&#160;</td>
			<td>Fort Dodge Animal Health, IA, USA and Biove Laboratories, France</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">a depilatory cream (Veet)</td>
			<td>&#160;ReckittBenckiser, Bristol, UK</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">A 30-gauge, 1/2-inch needle attached to 1 ml syringe&#160;</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">FITC dextran at a volume of 100 &#181;l (10 mg/ml; FD2000S, MW 2000000 Dalton)&#160;</td>
			<td>Sigma</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Doxorubicin (8 mg/kg, Adriamycin)</td>
			<td>Teva, Israel</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">paclitaxel (1.2 mg/kg, Medexel)&#160;</td>
			<td>Taro, Israel</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Saline</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

chemotherapy-induced vascular toxicity - real-time in vivo imaging of vessel impairment

Visse klasser af kemoterapi kan udøve akutte vaskulære ændringer, der kan udvikle sig til langvarige forhold, som kan prædisponerer patienten for en øget risiko for vaskulær sygelighed. Men selv montere kliniske beviser, der er en mangel på klare studier af vaskulær toksicitet og derfor ætiologien af ​​en heterogen gruppe af vaskulære / kardiovaskulære lidelser stadig at blive belyst. Endvidere kan den mekanisme, der kan ligge til grund for vaskulær toksicitet er fuldstændig forskellig fra principperne for kemoterapi-induceret kardiotoksicitet, som er relateret til direkte myocyt skade. Vi har etableret en real-time, in vivo molekylær billeddannelse platform til at vurdere den potentielle akutte vaskulære toksicitet af anti-cancer behandlinger. Vi har oprettet en platform af in vivo, høj opløsning molekylær billeddannelse i mus, som er egnet til at visualisere kar indenfor snævre organer og reference- blood fartøjer i de samme personer, mens hver enkelt tjener som sin egen kontrol. Blodkarrenes vægge blev forringet, efter doxorubicin administration, der repræsenterer en unik mekanisme af vaskulær toksicitet, som kan være den tidlige begivenhed i slutningen-orgel skade. Heri er metoden til fibered konfokal fluorescensmikroskopi (FCFM) baseret imaging beskrevet, hvilket giver en innovativ indstilling for at forstå fysiologiske fænomener på cellulært og sub-cellulære niveauer i animalske fag.

In vivo kontinuerlig billeddannelse på real-time Den billeddannende apparat bruges her er en high definition, fibered konfokalt mikroskop, er udstyret med en sonde, der muliggør visualisering af kar og dens reaktion på forskellige stimuli som kemoterapi. Denne metode er minimalt invasiv, idet selv om det kan lette billeddannelse af dybe kar eller organ, kræver et lille snit for sonden. De probe bundter består af titusinder af fibre, mikroskop optik og en proprietær præcision sti...

Watch this Scientific Journal Video about Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment at JoVE.com

Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment

We herein describe the method of fibered confocal fluorescent microscopy (FCFM) based imaging, which provides an innovative mode to understand physiological phenomena at the cellular and sub-cellular levels in animal subjects.

Kemoterapi-induceret vaskulær toksicitet - Real-time<em&gt; In vivo</em&gt; Imaging af Vessel Nedskrivninger

Certain classes of chemotherapies may exert acute vascular changes that may progress into long-term conditions that may predispose the patient to an ...

Research

JoVE Journal

Medicine

Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment

Multispectral Real-time Fluorescence Imaging for Intraoperative Detection of the Sentinel Lymph Node in Gynecologic Oncology

The prognosis in virtually all solid tumors depends on the presence or absence of lymph node metastases.1-3 Surgical treatment most often combines radical ...

Evaluation of Nanoparticle Uptake in Tumors in Real Time Using Intravital Imaging

Current technologies for tumor imaging, such as ultrasound, MRI, PET and CT, are unable to yield high-resolution images for the assessment of nanoparticle ...

Real-time Digital Imaging of Leukocyte-endothelial Interaction in Ischemia-reperfusion Injury (IRI) of the Rat Cremaster Muscle

Real-time Digital Imaging of Leukocyte-endothelial Interaction in Ischemia-reperfusion Injury IRI of the Rat Cremaster Muscle

Realtid Digital Imaging af leukocyt-endotel Interaktion med iskæmi-reperfusionsskade (IRI) af rotte Cremaster Muscle

Ischemia-reperfusion injury (IRI) has been implicated in a large array of pathological conditions such as cerebral stroke, myocardial infarction, ...

An in vivo Assay to Test Blood Vessel Permeability

An in vivo Assay to Test Blood Vessel Permeability

En<em&gt; In vivo</em&gt; Assay til Test Blood Vessel Permeabilitet

This method is based on the intravenous injection of Evans Blue in mice as the test animal model. Evans blue is a dye that binds albumin. Under ...

Transplantation into the Anterior Chamber of the Eye for Longitudinal, Non-invasive In vivo Imaging with Single-cell Resolution in Real-time

Transplantation into the Anterior Chamber of the Eye for Longitudinal, Non-invasive In vivo Imaging with Single-cell Resolution in Real-time

Transplantation ind i det forreste kammer i øjet til langsgående, ikke-invasiv<em&gt; In vivo</em&gt; Imaging med Single-celle Opløsning i realtid

Intravital imaging has emerged as an indispensable tool in biological research.  In the process, many imaging techniques have been developed to study ...

Real-time X-ray Imaging of Lung Fluid Volumes in Neonatal Mouse Lung

Real-time X-ray Imaging af Lung Fluid Mængder i Neonatal Mouse Lung

At birth, the lung undergoes a profound phenotypic switch from secretion to absorption, which allows for adaptation to breathing independently. Promoting ...

Rose Bengal Photothrombosis by Confocal Optical Imaging In Vivo: A Model of Single Vessel Stroke

Rose Bengal Photothrombosis by Confocal Optical Imaging In Vivo:  A Model of Single Vessel Stroke

Rose Bengal Photothrombosis ved Konfokal Optical Imaging<em&gt; In vivo</em&gt;: En model af Single Vessel Stroke

In vivo imaging techniques have increased in utilization due to recent advances in imaging dyes and optical technologies, allowing for the ability to ...

Ferric Chloride-induced Thrombosis Mouse Model on Carotid Artery and Mesentery Vessel

Ferric Chloride-induceret Trombose Mouse Model på Arteria carotis og mesenterium Vessel

Severe thrombosis and its ischemic consequences such as myocardial infarction, pulmonary embolism and stroke are major worldwide health issues. The ferric ...

Extended Time-lapse Intravital Imaging of Real-time Multicellular Dynamics in the Tumor Microenvironment

Udvidet Time-lapse Intravital Imaging af Real-time flercellede Dynamics i Tumor mikromiljø

In the tumor microenvironment, host stromal cells interact with tumor cells to promote tumor progression, angiogenesis, tumor cell dissemination and ...

Real-time Pressure-volume Analysis of Acute Myocardial Infarction in Mice

Real-time pres-binds analyse af akut myokardieinfarkt i mus

Acute myocardial infarction can lead to acute heart failure and cardiogenic shock. The evaluation of hemodynamics is critical for the evaluation of any ...