Name: an orthotopic resectional mouse model of pancreatic cancer
Uploaded: 2020-09-24T14:45:00
Description: Watch this Scientific Journal Video about An Orthotopic Resectional Mouse Model of Pancreatic Cancer at JoVE.com

Yazarlar Avner Pankreas Kanseri Vakfı'ndan destek aldılar.

Tüm prosedürler Yeni Güney Galler Üniversitesi Hayvan Bakım ve Etik Kurulu tarafından onaylandı (17/109A). Bu protokol için 8-10 haftalık 16-19 g ağırlığında dişi athymic Balb/c çıplak fareler kullanılmıştır. Fareler mikro izolatör kafeslerinde barındırıldı ve ticari olarak mevcut peletlenmiş yiyecek ve su ad libitumile beslendi.
1. Ortopedik pankreas kanseri implantasyonu
<ol><li>Hücreleri implantasyona hazırlayın. İlk olarak, prosedür için gerekli ...

<ol>
	<li>. SEER Cancer Statistics Review, 1975-2015, National Cancer Institute Available from: <a target="_blank" href="https://seer.cancer.gov/csr/1975_2015/">https://seer.cancer.gov/csr/1975_2015/</a> (2018)</li><li>Sugiura, 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=Margin+status,+recurrence+pattern,+and+prognosis+after+resection+of+pancreatic+cancer.">Margin status, recurrence pattern, and prognosis after resection of pancreatic cancer.</a> Surgery. 154 (5), 1078-1086 (2013).</li><li>Hishinuma, 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=Patterns+of+recurrence+after+curative+resection+of+pancreatic+cancer,+based+on+autopsy+findings.">Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings.</a> Journal of Gastrointestinal Surgery. 10 (4), 511-518 (2006).</li><li>NCCN Clinical Practice Guidelines in Oncology - Pancreatic Adenocarcinoma (Version 3.2019). National Comprehensive Cancer Network Available from: <a target="_blank" href="https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf">https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf</a> (2019)</li><li>Breslin, T. 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=Neoadjuvant+chemoradiotherapy+for+adenocarcinoma+of+the+pancreas:+treatment+variables+and+survival+duration.">Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration.</a> Annals of Surgical Oncology. 8 (2), 123-132 (2001).</li><li>Mokdad, A. 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=Neoadjuvant+Therapy+Followed+by+Resection+Versus+Upfront+Resection+for+Resectable+Pancreatic+Cancer:+A+Propensity+Score+Matched+Analysis.">Neoadjuvant Therapy Followed by Resection Versus Upfront Resection for Resectable Pancreatic Cancer: A Propensity Score Matched Analysis.</a> Journal of Clinical Oncology. 35 (5), 515-522 (2017).</li><li>Tachezy, 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=Sequential+neoadjuvant+chemoradiotherapy+(CRT)+followed+by+curative+surgery+vs.+primary+surgery+alone+for+resectable,+non-metastasized+pancreatic+adenocarcinoma:+NEOPA-+a+randomized+multicenter+phase+III+study+(NCT01900327,+DRKS00003893,+ISRCTN82191749).">Sequential neoadjuvant chemoradiotherapy (CRT) followed by curative surgery vs. primary surgery alone for resectable, non-metastasized pancreatic adenocarcinoma: NEOPA- a randomized multicenter phase III study (NCT01900327, DRKS00003893, ISRCTN82191749).</a> BMC Cancer. 14, 411 (2014).</li><li>Barbour, A. P., 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=The+AGITG+GAP+Study:+A+Phase+II+Study+of+Perioperative+Gemcitabine+and+Nab-Paclitaxel+for+Resectable+Pancreas+Cancer.">The AGITG GAP Study: A Phase II Study of Perioperative Gemcitabine and Nab-Paclitaxel for Resectable Pancreas Cancer.</a> Annals of Surgical Oncology. , (2020).</li><li>Fu, X., Guadagni, F., Hoffman, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+metastatic+nude-mouse+model+of+human+pancreatic+cancer+constructed+orthotopically+with+histologically+intact+patient+specimens.">A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically with histologically intact patient specimens.</a> Proceedings of the National Academy of Sciences of the United States of America. 89 (12), 5645-5649 (1992).</li><li>Marincola, F., Taylor-Edwards, C., Drucker, B., Holder, 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=Orthotopic+and+heterotopic+xenotransplantation+of+human+pancreatic+cancer+in+nude+mice.">Orthotopic and heterotopic xenotransplantation of human pancreatic cancer in nude mice.</a> Current Surgery. 44 (4), 294-297 (1987).</li><li>Vonlaufen, 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=Pancreatic+stellate+cells:+partners+in+crime+with+pancreatic+cancer+cells.">Pancreatic stellate cells: partners in crime with pancreatic cancer cells.</a> Cancer Research. 68 (7), 2085-2093 (2008).</li><li>Xu, Z., 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=Role+of+pancreatic+stellate+cells+in+pancreatic+cancer+metastasis.">Role of pancreatic stellate cells in pancreatic cancer metastasis.</a> American Journal of Pathology. 177 (5), 2585-2596 (2010).</li><li>Tepel, 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=Adjuvant+treatment+of+pancreatic+carcinoma+in+a+clinically+adapted+mouse+resection+model.">Adjuvant treatment of pancreatic carcinoma in a clinically adapted mouse resection model.</a> Pancreatology. 6 (3), 240-247 (2006).</li><li>Torgenson, M. 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=Natural+history+of+pancreatic+cancer+recurrence+following+"curative"+resection+in+athymic+mice.">Natural history of pancreatic cancer recurrence following "curative" resection in athymic mice.</a> Journal Surgical Research. 149 (1), 57-61 (2008).</li><li>Metildi, C. 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=Fluorescence-guided+surgery+allows+for+more+complete+resection+of+pancreatic+cancer,+resulting+in+longer+disease-free+survival+compared+with+standard+surgery+in+orthotopic+mouse+models.">Fluorescence-guided surgery allows for more complete resection of pancreatic cancer, resulting in longer disease-free survival compared with standard surgery in orthotopic mouse models.</a> Journal of the American College of Surgeons. 215 (1), 126-135 (2012).</li><li>Ni, X., Yang, J., Li, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Imaging-guided+curative+surgical+resection+of+pancreatic+cancer+in+a+xenograft+mouse+model.">Imaging-guided curative surgical resection of pancreatic cancer in a xenograft mouse model.</a> Cancer Letters. 324 (2), 179-185 (2012).</li><li>Hiroshima, 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=Hand-held+high-resolution+fluorescence+imaging+system+for+fluorescence-guided+surgery+of+patient+and+cell-line+pancreatic+tumors+growing+orthotopically+in+nude+mice.">Hand-held high-resolution fluorescence imaging system for fluorescence-guided surgery of patient and cell-line pancreatic tumors growing orthotopically in nude mice.</a> Journal of Surgical Research. 187 (2), 510-517 (2014).</li><li>Hiroshima, 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=Metastatic+recurrence+in+a+pancreatic+cancer+patient+derived+orthotopic+xenograft+(PDOX)+nude+mouse+model+is+inhibited+by+neoadjuvant+chemotherapy+in+combination+with+fluorescence-guided+surgery+with+an+anti-CA+19-9-conjugated+fluorophore.">Metastatic recurrence in a pancreatic cancer patient derived orthotopic xenograft (PDOX) nude mouse model is inhibited by neoadjuvant chemotherapy in combination with fluorescence-guided surgery with an anti-CA 19-9-conjugated fluorophore.</a> PLoS One. 9 (12), 114310 (2014).</li><li>Hiroshima, 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=Fluorescence-guided+surgery+in+combination+with+UVC+irradiation+cures+metastatic+human+pancreatic+cancer+in+orthotopic+mouse+models.">Fluorescence-guided surgery in combination with UVC irradiation cures metastatic human pancreatic cancer in orthotopic mouse models.</a> PLoS One. 9 (6), 99977 (2014).</li><li>Metildi, C. 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=Ratiometric+activatable+cell-penetrating+peptides+label+pancreatic+cancer,+enabling+fluorescence-guided+surgery,+which+reduces+metastases+and+recurrence+in+orthotopic+mouse+models.">Ratiometric activatable cell-penetrating peptides label pancreatic cancer, enabling fluorescence-guided surgery, which reduces metastases and recurrence in orthotopic mouse models.</a> Annals of Surgical Oncology. 22 (6), 2082-2087 (2015).</li><li>Metildi, C. 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=Fluorescence-guided+surgery+with+a+fluorophore-conjugated+antibody+to+carcinoembryonic+antigen+(CEA),+that+highlights+the+tumor,+improves+surgical+resection+and+increases+survival+in+orthotopic+mouse+models+of+human+pancreatic+cancer.">Fluorescence-guided surgery with a fluorophore-conjugated antibody to carcinoembryonic antigen (CEA), that highlights the tumor, improves surgical resection and increases survival in orthotopic mouse models of human pancreatic cancer.</a> Annals of Surgical Oncology. 21 (4), 1405-1411 (2014).</li><li>NCCN Guidelines: Pancreatic Adenocarcinoma. National Comprehensive Cancer Network Available from: <a target="_blank" href="https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf">https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf</a> (2019)</li><li>Maithel, S. K., Allen, P. J., Jarnagin, W. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Blumgart's Surgery of the Liver, Biliary Tract and Pancreas, 2-Volume Set (Sixth Edition). , 1007-1023 (2017).</li><li>Egberts, J. 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=Dexamethasone+reduces+tumor+recurrence+and+metastasis+after+pancreatic+tumor+resection+in+SCID+mice.">Dexamethasone reduces tumor recurrence and metastasis after pancreatic tumor resection in SCID mice.</a> Cancer Biology &amp; Therapy. 7 (7), 1044-1050 (2008).</li><li>Xu, Z. 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=Targeting+the+HGF/c-MET+pathway+in+advanced+pancreatic+cancer:+a+key+element+of+treatment+that+limits+primary+tumor+growth+and+eliminates+metastasis.">Targeting the HGF/c-MET pathway in advanced pancreatic cancer: a key element of treatment that limits primary tumor growth and eliminates metastasis.</a> British Journal of Cancer. , (2020).</li><li>Pothula, S. P., 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=Targeting+the+HGF/c-MET+pathway:+stromal+remodelling+in+pancreatic+cancer.">Targeting the HGF/c-MET pathway: stromal remodelling in pancreatic cancer.</a> Oncotarget. 8 (44), 76722-76739 (2017).</li><li>Pothula, S. P., 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=Hepatocyte+growth+factor+inhibition:+a+novel+therapeutic+approach+in+pancreatic+cancer.">Hepatocyte growth factor inhibition: a novel therapeutic approach in pancreatic cancer.</a> British Journal of Cancer. 114 (3), 269-280 (2016).</li><li>Giri, B., 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=An+Immunocompetent+Model+of+Pancreatic+Cancer+Resection+and+Recurrence.">An Immunocompetent Model of Pancreatic Cancer Resection and Recurrence.</a> Journal of Gastrointestinal Surgery. , (2020).</li><li>Allen, V. B., Gurusamy, K. S., Takwoingi, Y., Kalia, A., Davidson, B. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnostic+accuracy+of+laparoscopy+following+computed+tomography+(CT)+scanning+for+assessing+the+resectability+with+curative+intent+in+pancreatic+and+periampullary+cancer.">Diagnostic accuracy of laparoscopy following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer.</a> Cochrane Database of Systematic Reviews. (11), 009323 (2013).</li><li>Vaillant, F., Lindeman, G. J., Visvader, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Jekyll+or+Hyde:+does+Matrigel+provide+a+more+or+less+physiological+environment+in+mammary+repopulating+assays.">Jekyll or Hyde: does Matrigel provide a more or less physiological environment in mammary repopulating assays.</a> Breast Cancer Research. 13 (3), 108 (2011).</li><li>Jesnowski, 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=Immortalization+of+pancreatic+stellate+cells+as+an+in+vitro+model+of+pancreatic+fibrosis:+deactivation+is+induced+by+matrigel+and+N-acetylcysteine.">Immortalization of pancreatic stellate cells as an in vitro model of pancreatic fibrosis: deactivation is induced by matrigel and N-acetylcysteine.</a> Laboratory Investigation. 85 (10), 1276-1291 (2005).</li><li>Phillips, P. 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Pankreas kanserinin rezeksiyonlu ortotopik fare modeli önemlidir, çünkü adjuvan ve neoadjuvan tedavilerin testine izin verir. Bu özellikle cerrahinin en etkili tedavi olmaya devam ettiği ancak yüksek nüks riski ile ilişkili olduğu pankreas kanserinde önemlidir. Bu makalede, neoadjuvan / adjuvan tedavinin gerekli olduğu klinik senaryoyu çoğaltarak, rezeksiyonla tedavi edilebilen pankreas kanserini güvenilir bir şekilde üretecek bir yöntem açıklanmaktadır.
Mevcut yö...

Pankreas düktal adenokarsinom (pankreas kanseri [PC]) zayıf bir prognoz ile ilişkilidir1. Cerrahi rezeksiyon PC için potansiyel olarak iyileştirici tek tedavi olmaya devam etmektedir ve erken evre hastalığı olan hastalar için düşünülmelidir. Ne yazık ki, R0 rezeksiyonu (yani tümör içermeyen rezeksiyon marjları) ile bile, tekrarlama oranı (lokal veya tespit edilmemiş metastatik hastalıktan) yüksektir2,3. Bu nedenle, rezeksiyon uygulanan hemen hemen tüm hastalarda sistemik adjuvan tedavi endikedir4. Ayrıca, neoadjuvan tedavi artık sadece borderline-rezeke edilebilir kanserler için tavsiye edilirken, endikasyonları rutin kullanımı çok klinik araştırmaların odak noktası olacak şekilde genişliyor5,6,7,8. PC için rezeksiyon içeren yeni terapötik yaklaşımlar geliştirmek için, bu yaklaşımların öncelikle klinik ayarları doğru bir şekilde yeniden deneyen klinik öncesi modellerde değerlendirilmesi gerekir.
PC'nin ortotopik fare modelleri geçmişte ilaç tedavilerini test etmek için sıklıkla kullanılmıştır9,10. Bunların çoğu, kanser hücrelerinin tek başına fare pankreasına enjekte ederek üretildi ve PC'nin karakteristik özelliği olan belirgin stromadan yoksun tümörlerle sonuçlandı. Daha yakın zamanda, ilk olarak insan PC ve insan pankreas yıldız hücrelerinin bir karışımını enjekte ederek geliştirdiğimiz gibi ortak enjeksiyon ortotopik modeller (PC'deki kollajenöz stromanın birincil üreticileri olan PSC'ler) düzenli olarak kullanıma girdi11,12. Kanser ve stromal hücrelerin bu tür ko-enjeksiyonu ile üretilen tümörler (i) hem kanser elementlerini hem de PC'nin karakteristik stromal (desmoplastik) bileşenini ve (ii) gelişmiş kanser hücresi çoğalması ve metastazını sergiler11. Bu nedenle, bu model insan PC'ye çok benziyor. Ortotopik PC'nin bir dizi rezeksiyon modeli tanımlanmış olsa da13,14,15,16, hiçbiri insanlarda pankreas rezeksiyonunun klinik gerçeklerini bu model kadar doğru yansıtmamıştır ve bu nedenle adjuvan veya neoadjuvan tedavileri test etmek için suboptimal olmuştur.
Sunulan fare modelinin amacı şu şekildeydi: (i) yanlışlıkla periton yayılımını en aza indirirken ortotopik pankreas kanserinin başarılı bir şekilde implante edildiğini ve (ii) daha sonra kanserin tamamen resect olduğunu göstermekti. Makale, bu tekniğin ipuçlarını ve potansiyel tuzaklarını vurgulamaktadır.

<table>
	<tbody>
		<tr>
			<td>Animals, Materials and Equipment for Implantation Procedure</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>AsPC-1 human pancreatic cancer cell line, luciferase tagged (luc+ gene from Promega PGL3 Basic plasmid)</td>
			<td>American Type Culture Collection, Manassas, VA, USA</td>
			<td></td>
			<td>supplied by Professor Takashi Murakami, Saitama Medical University, Saitama, Japan</td>
		</tr>
		<tr>
			<td>Autoclip wound clips, 9 mm</td>
			<td>Becton Dickson Pty Ltd, North Ryde, NSW, Australia</td>
			<td>500346</td>
			<td></td>
		</tr>
		<tr>
			<td>Basic Dressing Pack</td>
			<td>Multigate Medical Products Pty Ltd, Villawood, NSW, Australia</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Cancer associated human pancreatic stellate cells</td>
			<td>Pancreatic Research Group cell bank</td>
			<td></td>
			<td>In house cell bank</td>
		</tr>
		<tr>
			<td>Cryogenic tubes, 1.0 mL</td>
			<td>Thermo Fisher Scientific Australia Pty Ltd, Scoresby, VIC, Australia</td>
			<td>366656</td>
			<td></td>
		</tr>
		<tr>
			<td>Disposable stainless-steel scalpel blade with handle, size 15</td>
			<td>Livingstone International, Mascot, NSW,</td>
			<td>SCP15</td>
			<td></td>
		</tr>
		<tr>
			<td>Foetal bovine serum (FBS)</td>
			<td>Life Technologies Corporation, Tullamarine, VIC, Australia</td>
			<td>16000044</td>
			<td></td>
		</tr>
		<tr>
			<td>Gilles fine tooth forceps 12 cm</td>
			<td></td>
			<td></td>
			<td>Generic stainless steel microsurgical instrument set</td>
		</tr>
		<tr>
			<td>Heated mats to maintain body temperature during surgery and postoperative recovery</td>
			<td>Generic</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Homozygous athymic nude mice: Strain BALB/c-Fox1nu/Ausb, female</td>
			<td>Australian Bioresources, Moss Vale, NSW, Australia</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Iscove&#39;s modified Dulbecco&#39;s medium (IMDM) with 4mM L-glutamine and no phenol red</td>
			<td>Life Technologies Corporation, Tullamarine, VIC, Australia</td>
			<td>21056023</td>
			<td></td>
		</tr>
		<tr>
			<td>Jewellers forceps 11.5 cm</td>
			<td></td>
			<td></td>
			<td>Generic stainless steel microsurgical instrument set</td>
		</tr>
		<tr>
			<td>Micro needle holder (round handle) 15 cm straight</td>
			<td></td>
			<td></td>
			<td>Generic stainless steel microsurgical instrument set</td>
		</tr>
		<tr>
			<td>Micro scissors (round handle) 15 cm straight</td>
			<td></td>
			<td></td>
			<td>Generic stainless steel microsurgical instrument set</td>
		</tr>
		<tr>
			<td>Penicillin 10,000 U/mL, streptomycin 10,000 &#956;g/mL</td>
			<td>Life Technologies Corporation, Tullamarine, VIC, Australia</td>
			<td>15140122</td>
			<td></td>
		</tr>
		<tr>
			<td>Polyglycolic acid suture, size USP 5/0 on 13mm half-circle round-bodied needle</td>
			<td>Braun Australia Pty Ltd, Bella Vista, NSW, Australia</td>
			<td>C1049407</td>
			<td></td>
		</tr>
		<tr>
			<td>Portable weighing scale</td>
			<td>Precision balances, Bradford, MA, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Reflex clip applier and clip remover</td>
			<td>World Precision Instruments, Sarasota, FL, USA</td>
			<td>500345</td>
			<td></td>
		</tr>
		<tr>
			<td>Roswell Park Memorial Institute (RPMI) 1640 with phenol red and 300 mg/L Lglutamine</td>
			<td>Life Technologies Corporation, Tullamarine, VIC, Australia</td>
			<td>11875085</td>
			<td></td>
		</tr>
		<tr>
			<td>Round bodied vessel dilator 15 cm, 0.1 mm tip</td>
			<td></td>
			<td></td>
			<td>Generic stainless steel microsurgical instrument set</td>
		</tr>
		<tr>
			<td>Trypsin 0.05%, EDTA 0.02%</td>
			<td>Life Technologies Corporation, Tullamarine, VIC, Australia</td>
			<td>25300054</td>
			<td>For pancreatic stellate cells</td>
		</tr>
		<tr>
			<td>Trypsin 0.25%, EDTA 0.02%</td>
			<td>Life Technologies Corporation, Tullamarine, VIC, Australia</td>
			<td>25200056</td>
			<td>For ASPC-1 cells</td>
		</tr>
		<tr>
			<td>U-100 insulin syringes, 0.5 mL with 29 G (0.33 mm) &#215; 13 mm needle</td>
			<td>Terumo Medical Corporation, Elkton, MD, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Equipment for Resection Procedure</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Alm self-retaining retractor</td>
			<td></td>
			<td></td>
			<td>Generic stainless steel microsurgical instrument set</td>
		</tr>
		<tr>
			<td>Autoclip wound clips 9 mm</td>
			<td>Becton Dickson Pty Ltd, North Ryde, NSW</td>
			<td>500346</td>
			<td></td>
		</tr>
		<tr>
			<td>Basic Dressing Pack</td>
			<td>Multigate Medical Products Pty Ltd, Villawood, NSW, Australia</td>
			<td>08-559NP</td>
			<td></td>
		</tr>
		<tr>
			<td>Disposable stainless-steel scalpel blade with handle, size 15</td>
			<td>Livingstone International, Mascot, NSW,</td>
			<td>SCP15</td>
			<td></td>
		</tr>
		<tr>
			<td>Gilles fine tooth forceps 12 cm</td>
			<td></td>
			<td></td>
			<td>Generic stainless steel microsurgical instrument set</td>
		</tr>
		<tr>
			<td>Hand-held high temperature fine tip cautery</td>
			<td>Bovie Medical Corporation, Melville, NY, USA</td>
			<td>AA01</td>
			<td></td>
		</tr>
		<tr>
			<td>Heated mats to maintain body temperature during surgery and postoperative recovery</td>
			<td>Generic</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>IVIS Lumina II Bioluminescent Imaging Device</td>
			<td>Caliper Life Sciences, Hopkinton, MA, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Jewellers forceps 11.5 cm</td>
			<td></td>
			<td></td>
			<td>Generic stainless steel microsurgical instrument set</td>
		</tr>
		<tr>
			<td>Micro needle holder (round handle) 15 cm straight</td>
			<td></td>
			<td></td>
			<td>Generic stainless steel microsurgical instrument set</td>
		</tr>
		<tr>
			<td>Micro scissors (round handle) 15 cm straight</td>
			<td></td>
			<td></td>
			<td>Generic stainless steel microsurgical instrument set</td>
		</tr>
		<tr>
			<td>Polyglycolic acid suture, size USP 5/0 on 13mm half-circle round-bodied needle</td>
			<td>Braun Australia Pty Ltd, Bella Vista, NSW, Australia</td>
			<td>C1049407</td>
			<td></td>
		</tr>
		<tr>
			<td>Portable weighing scale</td>
			<td>Precision balances, Bradford, MA, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Reflex wound clip applier and clip remover</td>
			<td>World Precision Instruments, Sarasota, FL, USA</td>
			<td>500345</td>
			<td></td>
		</tr>
		<tr>
			<td>Round bodied vessel dilator 15 cm, 0.1 mm tip</td>
			<td></td>
			<td></td>
			<td>Generic stainless steel microsurgical instrument set</td>
		</tr>
		<tr>
			<td>Titanium &#8220;Weck style&#8221; Ligaclip, small</td>
			<td>HZMIM, Hangzhou, China</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Titanium Ligaclip applier for open surgery, small</td>
			<td>HZMIM, Hangzhou, China</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Volatile anaesthetic machine, including vapouriser and induction chamber</td>
			<td>Generic</td>
			<td></td>
			<td>Generic vapouriser and induction chamber</td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Drugs for Procedures</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>70% w/w ethanol solution</td>
			<td>Sigma-Aldrich Pty Ltd, Castle Hill, NSW, Australia</td>
			<td></td>
			<td>Applied topically as surgical skin preparation</td>
		</tr>
		<tr>
			<td>Buprenorphine 0.3 mg/mL</td>
			<td>Troy Laboratories Pty Ltd, Glendenning, NSW, Australia</td>
			<td></td>
			<td>Dose: 0.05 mg/kg s.c.</td>
		</tr>
		<tr>
			<td>D-Luciferin (1 U/g)</td>
			<td>PerkinElmer, Inc., Waltham, MA, USA</td>
			<td>122799</td>
			<td>diluted in PBS to 15 mg/mL. Dose: 150 mg/kg i.p</td>
		</tr>
		<tr>
			<td>Enrofloxacin 50 mg/mL</td>
			<td>Troy Laboratories Pty Ltd, Glendenning, NSW, Australia</td>
			<td></td>
			<td>Dose: 5 mg/kg s.c.</td>
		</tr>
		<tr>
			<td>Flunixin 50 mg/mL</td>
			<td>Norbrook Laboratories Australia, Tullamarine, VIC, Australia</td>
			<td></td>
			<td>Dose: 2.5 mg/kg s.c.</td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>Zoetis Australia Pty Ltd., Rhodes, NSW, Australia</td>
			<td></td>
			<td>Dose (vapourised with oxygen): 4% induction, 3% maintenance</td>
		</tr>
		<tr>
			<td>Ketamine 100 mg/mL</td>
			<td>Maylab, Slacks Creek, QLD, Australia</td>
			<td></td>
			<td>Dose: 80 mg/kg i.p.</td>
		</tr>
		<tr>
			<td>Povidone-Iodine 10% w/v solution</td>
			<td>Perrigo Australia, Balcatta, WA, Australia</td>
			<td>RIO00802F</td>
			<td>Applied topically to the anterior abdomen as surgical skin preparation</td>
		</tr>
		<tr>
			<td>Refresh eye ointment (liquid paraffin 42.5% w/w, soft white paraffin 57.3% w/w)</td>
			<td>Allergan Australia Pty Ltd, Gordon, NSW, Australia</td>
			<td></td>
			<td>Applied to both eyes</td>
		</tr>
		<tr>
			<td>Sodium chloride 0.9% w/v</td>
			<td>Braun Australia Pty Ltd, Bella Vista, NSW, Australia</td>
			<td>9481P</td>
			<td>Dose: 900 &#956;L s.c.</td>
		</tr>
		<tr>
			<td>Water for injections BP</td>
			<td>Pfizer Australia, Sydney, NSW, Australia</td>
			<td></td>
			<td>For dilution of drugs</td>
		</tr>
		<tr>
			<td>Xylazine 20 mg/mL</td>
			<td>Troy Laboratories Pty Ltd, Glendenning, NSW, Australia</td>
			<td></td>
			<td>Dose: 10 mg/kg i.p.</td>
		</tr>
	</tbody>
</table>

an orthotopic resectional mouse model of pancreatic cancer

Pankreas kanseri (PC) cerrahisi için düşünülen hastalarda adjuvan ve/veya neoadjuvan tedaviyi incelemek için tatmin edici hayvan modellerinin eksikliği vardır. Bu eksikliği gidermek için, PC'nin ortotopik implantasyonunu ve ardından distal pankreastomi ve splenektomi içeren bir fare modelini tarif ediyoruz. Modelin, adjuvan ve neo adjuvan ortamlarda çeşitli terapötik yaklaşımların incelenmesi için güvenli ve uygun şekilde esnek olduğu gösterilmiştir.
Bu modelde, pankreas tümörü ilk olarak balb/c athymic çıplak farelerin distal pankreasına insan pankreas kanseri hücrelerinin (luciferaz etiketli AsPC-1) ve insan kanseri ilişkili pankreas yıldız hücrelerinin bir karışımının yerleştirilmesiyle üretilir. Üç hafta sonra, kanser yeniden laparotomi, distal pankreastomi ve splenektomi ile resected edilir. Bu modelde biyolüminesans görüntüleme, kanser gelişiminin ilerlemesini ve rezeksiyon/tedavilerin etkilerini takip etmek için kullanılabilir. Rezeksiyondan sonra adjuvan tedavi verilebilir. Alternatif olarak, rezeksiyondan önce neoadjuvan tedavi verilebilir.
45 fareden temsili veriler sunulmaktadır. Tüm farelere hemostaz sorunu olmayan başarılı distal pankreastomi / splenektomi uygulandı. 43'te 5 mm'den büyük makroskopik proksimal pankreas marjı elde edildi (%96) Fare. Pankreas rezeksiyonunun teknik başarı oranı %100, erken mortalite ve morbiditesi %0 idi. Rezeksiyondan sonraki hafta boyunca hayvanların hiçbiri ölmedi.
Özetle, klinik senaryoyu taklit eden farelerde pankreas kanserinin cerrahi rezeksiyon modeli için sağlam ve tekrarlanabilir bir teknik tanımlıyoruz. Model hem adjuvan hem de neoadjuvan tedavilerin test edilmesi için yararlı olabilir.

Ardışık 59 fare implantasyon ameliyatı geçirdi. Brüt sızıntı sekizde meydana geldi (%14) Fare. Enjeksiyon anında sızıntı derecesi, protokol bölümünde yukarıda açıklandığı gibi tahmin edilmektedir. Bu implante tümörlerin büyümesine izin vermek için üç hafta sonra, rezeksiyon öncesi biyolüminesans görüntülemesi, rezeksiyondan önce brüt metastatik hastalığı olan fareleri dışlamak için yapıldı. Kırk beş (%76) farelere cerrahi rezeksiyon uygulandı.
Hep...

Watch this Scientific Journal Video about An Orthotopic Resectional Mouse Model of Pancreatic Cancer at JoVE.com 

An Orthotopic Resectional Mouse Model of Pancreatic Cancer (Video) | JoVE 

Klinik bağlamda lokalize pankreas kanseri olan hastalar pankreastektomi ve ardından adjuvan tedavi görecektir. Burada bildirilen bu protokol, pankreas kanserinin ortotopik implantasyonu ve ardından distal pankreasektomi ve splenektomi yoluyla çıplak farelerde bu klinik senaryoyu modellemek için güvenli ve etkili bir yöntem oluşturmayı amaçlamaktadır.

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