Yazarlar cömertçe fare fenotipleme yöntemleri onun uzmanlık paylaşımı için ve onun sürekli teknik yardım için Ulusal Sağlık Enstitüleri Ulusal Kalp, Akciğer ve Kan Enstitüsü (NHLBI) (NIH) Michele Allen teşekkür yanı gibi istiyorum bize koruyucu cihaz geliştirmek yardımcı olmak için NHLBI Timothy Hunt. Bu çalışma, Hemşirelik NIH Araştırma ve doğrulama deneme parçası Ulusal Enstitüsü İntramural Araştırma Bölümü tarafından desteklenen Toplum Vakfı&#39;na Hemşireliği Onkoloji bir hibe ile desteklenmektedir.

Etik Beyanı: Bu çalışma Ulusal Sağlık Enstitüleri (NIH) Hayvan Bakımı ve Kullanımı Komitesi tarafından onaylandı. hayvan taşıma ve çalışma sonuçlarının ölçülmesi katılan tüm araştırmacılar düzgün Hayvan Bakım ve Kullanım NIH Ofisi ve Ulusal Kalp, Akciğer ve Kan Enstitüsü Fare Fenotiplendirme Core eğitilmiştir. Hayvanlar üzerinde test, konut ve bu çalışmada kullanılan çevre koşullarının tüm yönleri Laboratuar Hayvanlarının 11 Bakım Kılavuzu ile uyumlu ve kullanımı vardı. 1. Konut ve Deney Hayvanları NOT: tek tek deney boyunca yiyecek ve su ad libitum erişim sağlamak (girişte yaklaşık beş haftalık) Ev erkek C57BL / 6 fare. Tüm kafesleri hafif faz 6 pm 6 am ve karanlık faz başlayarak ile 12:12 saat aydınlık-karanlık döngüsünde tutulur. <ol><li> fareler tanımlamak ve bireysel standart ventilate atamakd fare kafesleri. 24 saatlik bir geri kazanım için tanımlama işlem sonrası izin verin. NOT: Kuyruk dövme kulak etiketi çalışan bir tekerlek yakalanmak olabilir olasılığını ortadan kaldırmak için bir kimlik aracı olarak tavsiye edilir. farenin kafesine yazılı numarayı eşleşen kuyruk numarası ile, her fare kuyruk bir dizi dövme. </li><li> günde üç dakikalık bir süre boyunca yavaşça her fare taşıma fareler en az üç gün daha kafeslerine gelmesini izin verir. </li></ol> Tekerlek Acclimation ve Baseline Koşu 2. <ol><li> Bireysel VWRA kafesleri, sürekli kaydı için bir elektronik sayaç bağlı bir tekerlek ile donatılmıştır fareler tanıtılması. NOT: Tüm tekerlek sayaçları tek bir USB arayüzü aracılığıyla bir bilgisayara bağlanmak (Malzeme Listesine bakınız). bilgisayar programı mesafesi belirtilen toplam duratio her belirlenmiş zaman aralığında gitti ve ortalama hız, tekerlek dönüş sayısını hesaplarn. Kayıt durduğunda, verileri otomatik metin olarak ve elektronik tablo gibi hem kaydedilir. </li><li> bilgisayar programı arabirimi aracılığıyla VWRA kayıt başlatın. En az beş gün bir saat aralıkları ve süresi kayıt ayarlayın. en az beş gün süreyle VWRA kayıt devam edin. Not: Aşama 2.2 sonunda, bütün fareler, günlük tekerlek döndürme aktivitesi nispeten tutarlı bir miktarda sağlamalıdır. Değilse, daha sonra tanımlamak ve herhangi bir outliers dahil değildir. </li><li> VWRA yazılım arayüzü üzerinden Kaydı durdur, ve (tekerlekler çalıştırmadan kafesleri) adım 1.1 tarif standart kafeslerine fareler dönün. </li><li> sahte ışınlanmış kontrolü veya ışınlanmış gruplara ya içine fareler Rastgele. </li></ol> 3. Işınlama Not: ardışık üç gün boyunca günde bir kez, her iki grupta da tüm fareler için aşağıdaki adımları gerçekleştirin. her gün aynı sırayla fareler davranın. <ol><li> intraperitoneal enjeksiyonu ile, her fare anestezisiketamin (100 mg / kg) ve ksilazin (10 mg / kg) karışımı ile gerçekleştirilmektedir. </li><li> Bir ayak tutam anestezi onaylayın ve anestezi altında iken kuruluğunu önlemek için gözleri merhem kullanın. </li><li> bir kurşun koruyucu cihazın içine anestezi fare aktarın. Sadece alt karın / pelvik bölge açıkta kalacak şekilde koruyucu fare düzenleyin. NOT: Koruyucu o fare küçük, hedeflenen bölgeye radyasyona maruz veriyor arasında dar bir açık alan ile &quot;, kutular&quot; iki kurşun oluşmaktadır (Şekil 1). </li><li> koruyucu içindeki pozisyonda fare kuyruğunun tabanını korumak için tıbbi bant kullanın. NOT: Adım 3.4 isteğe bağlıdır, ancak bunu yaparken farenin konumu aşağıdaki adımı sırasında değişmez sağlamaya yardımcı olabilir. </li><li> koruyucu içindeki hayvan pozisyonu muhafaza edilmesini sağlamak, irradiator içine koruyucu cihazı taşıyın. </li><li> Fare ışınlama grubunda ise, dos 800 cGy teslimyaklaşık 110 cGy / dak e oranı. Fare sahte-ışınlama kontrol grubunda ise, eşdeğer bir süre için etkin ışınlayıcıdaki fareyi bırakın. NOT: Optimal ışınlayıcı ayarları belirli bir cihazda bağlıdır. Bir 137 Sezyum kaynağından teslim 110 cGy / dk doz oranı Burada kullanılan irradiator merkezi doz oranıdır. Pozlama süresi 800 cGy istenen toplam doz ulaşmak için ayarlandı. </li><li> irradiator ve koruyucu fareyi çıkarın ve daha sonra adım 1.1 belirtilen özgün, standart kafes iade. </li><li> sternal yatma korumak için yeterli kendine geldi kadar sürekli fare monitör. </li></ol> 4. Radyasyona bağlı Yorulma Ölçümü <ol><li> Işınlama birbirini takip eden üç gün tamamlandıktan sonra günde, aşama 2.1&#39;de tanımlanan bireysel VWRA kafeslerine fareler aktarın. </li><li> Tutanak VWRA, burada kayıt ayarı dışında adım 2.2 &#39;de açıklandığı gibi15&#39;den fazla gün süresi. 15 gün sonunda, elle yazılım arayüzü üzerinden kayıt VWRA durdurun. NOT: Her bir kayıt dönemi verileri otomatik olarak kayıt süresi boyunca tüm hayvanlarda (sütunlar) ve tüm aralıkları (satırlar) için rotasyon, mesafe ve hız ölçümleri içeren her biri elektronik tablolar, olarak kaydedilir. ışınlama öncesi VWRA için bir ve radyasyon sonrası VWRA için bir: Deneyin sonunda, kayıt yazılımı tarafından üretilen iki-tablo vardır. </li></ol>

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Bu araştırma İntramural Araştırma, Hemşirelik Araştırma Ulusal Enstitüsü, Ulusal Sağlık Enstitüleri Bölümü tarafından desteklenmiştir.

Biz morbidite ve mortalite karıştırıcı olmadan farelerde VWRA bir azalma ikna etmek için hedeflenen çevre radyasyon kullanarak bir protokol tanımlanmıştır. Önemlisi, basit bir koruyucu cihaz pelvik kanserli hastalarda tarafından alınan radyasyon tedavileri taklit, sürekli bir arzu bölgeyi hedeflemek için bu protokolde ışınlama sağlar. Beyin veya total vücut ışınlaması 8, 9 içeren mevcut CRF modellerinin tersine, bu model bir periferik ...

Kansere bağlı yorgunluk (CRF) sık sık kanser tedavileri 1 alıcı hastaları etkileyen üzücü ve masraflı bir durumdur. Yorgunluk son etkinliği ile orantılı ne de geri kalanı tarafından azaltılabilir ne olduğunu ve ruh, motivasyon, dikkat ile ilgili rahatsızlıkların geniş bir yelpazede ile ilişkilidir ve biliş 2.. Hemoglobin düzeyleri ve hormon sistemleri fonksiyonu ile, bazı durumlarda, aynı zamanda, enflamasyon ve sitokin seviyeleri ile ilişkili olduğu birçok durumda gösterilmiştir da CRF biyolojik nedenleri bilinmemektedir (bakınız Saligan ve ark., 3, biyolojik bir inceleme için CRF çalışmaları). hayvan modelleri kullanılarak kontrollü çalışmalar bu kompleks durumla ilişkili davranış ve biyolojisini anlamak için gereklidir. Tümör-ile ilgili 4 veya kemoterapi ile ilişkili 5, 6 yağ daigue kemirgen modellerinde incelenmiştir, CRF etyolojisi işleme özgü olabilir. Radyasyon tedavisi ile ilgili CRF araştırmak için, bizim grup son ışınlama kaynaklı yorgunluk 7 bir fare modeli geliştirmiştir. Beyin veya total vücut ışınlaması 8, 9 içeren mevcut CRF modellerinin tersine, bu model, merkezi odaklı davranış değişikliği, yorgunluk gibi, bir periferik hedefli ışınlama işlemi ile tetiklenebilir nasıl araştırıyor. Burada açıklanan prosedür ışınlama ile alt karın / pelvik bölgeyi hedef kurşun kalkan kullanarak, pelvik kanserli hastalarda uygulanan radyasyon tedavisi modellemek için tasarlanmıştır. Ancak, kurşun kalkan veya deney hayvanları kendi yerleşim göreceli değiştirerek, bu işlem vücudun diğer kısımlarının radyasyon modellemek için adapte edilebilir. Gönüllü tekerlek çalışan aktivite (VWRA) yorgunluk gibi behavio ölçmek için kullanılırR; Bir gönüllü ve normal bir davranış 10 çünkü, diğer davranışsal ve biyolojik testler eşzamanlı kullanımına izin gerekir. Periferal ışınlama aşikar morbidite 7 neden olmadan farede VWRA düşürmek için yeterli olduğunu bulmuşlardır. Bu model ile, gelecek deneylerde, bağışıklık ve diğer biyolojik sinyali periferik ışınlama, hem de CRF ile ilişkili defisitlerine, merkezi sinir sistemindeki alt değişikliklerin etkisini ortaya çıkarmaya yardımcı olabilir.

<table border="0" cellpadding="0" cellspacing="0" width="1098">
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:255px;">C57BL/6 Mice</td>
			<td style="width:135px;">Charles River</td>
			<td style="width:119px;"></td>
			<td style="width:591px;">Strain code 027 (http://www.criver.com/products-services/basic-research/find-a-model/c57bl-6n-mouse)</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Ketamine HCl</td>
			<td style="width:135px;">Putney</td>
			<td style="width:119px;"></td>
			<td style="width:591px;">100 mg/ml stock solution</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Xylazine HCl</td>
			<td style="width:135px;">Lloyd Laboratories</td>
			<td></td>
			<td style="width:591px;">100 mg/ml stock solution</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Rodent Tattoo System</td>
			<td style="width:135px;">AIMS</td>
			<td style="width:119px;">ATS-3</td>
			<td>http://animalid.com/lab-animal-identification-systems/ats-3-general-rodent-tattoo-system</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:255px;">Lead Shielding Apparatus</td>
			<td style="width:135px;">(custom made)</td>
			<td style="width:119px;"></td>
			<td style="width:591px;">One-inch thick lead shielding arranged as two boxes with a one-inch thick gap between them for targeted irradiation</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:255px;">Plexiglass shielding container</td>
			<td style="width:135px;">(custom made)</td>
			<td style="width:119px;"></td>
			<td style="width:591px;">Plexiglass container filled with styrofoam. Styrofoam cutouts hold the lead shielding in place.</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">GammaCell 40 Exactor</td>
			<td style="width:135px;">Best Theratronics</td>
			<td style="width:119px;"></td>
			<td>http://www.theratronics.ca/product_gamma40.html</td>
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		<tr height="21">
			<td height="21" style="height:21px;width:255px;">RAD Disk Ultra</td>
			<td style="width:135px;">Best Theratronics</td>
			<td style="width:119px;"></td>
			<td>http://www.theratronics.ca/product_rad.html</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;">Mouse Single Activity Wheel Chamber</td>
			<td style="width:135px;">Lafayette Instrument Company</td>
			<td style="width:119px;">#80820</td>
			<td>http://www.lafayetteneuroscience.com/product_detail.asp?itemid=980</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:255px;">Activity Wheel Counter for Computer Monitoring</td>
			<td style="width:135px;">Lafayette Instrument Company</td>
			<td style="width:119px;">#86061</td>
			<td>http://www.lafayetteneuroscience.com/product_detail.asp?itemid=1052</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:255px;">Modular Cable for Wheel Counters</td>
			<td style="width:135px;">Lafayette Instrument Company</td>
			<td style="width:119px;">#86051-7</td>
			<td>http://www.lafayetteneuroscience.com/product_detail.asp?itemid=1046</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:255px;">USB Computer Interface for Activity Wheel Counters</td>
			<td style="width:135px;">Lafayette Instrument Company</td>
			<td style="width:119px;">#86056A</td>
			<td>http://www.lafayetteneuroscience.com/product_detail.asp?itemid=1047</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:255px;">Activity Wheel Monitor Software</td>
			<td style="width:135px;">Lafayette Instrument Company</td>
			<td style="width:119px;">#86065</td>
			<td>http://www.lafayetteneuroscience.com/product_detail.asp?itemid=1053</td>
		</tr>
	</tbody>
</table>

a mouse model of fatigue induced by peripheral irradiation

Kansere bağlı yorgunluk (CRF) sık sık radyasyon tedavisi dahil kanser tedavileri, alıcı hastaları etkileyen üzücü ve masraflı bir durumdur. Burada farelerde yorgunluk benzeri bir davranış ikna etmek için hedeflenen çevre radyasyon kullanarak bir yöntem açıklanmaktadır. Uygun koruma ile, ışınlama pelvik kanserler bireyler tarafından alınan radyasyon tedavisi modellemek için bir çaba, beyin tutumlu, fare alt karın / pelvik bölgeyi hedefliyor. Bu belirgin morbidite neden olmadan, isteğe bağlı tekerlek çalışan aktivitesi (VWRA) ile ölçülen farelerde, yorgunluk benzeri bir davranış uyarılması için yeterli olan bir radyasyon dozu sağlar. Tekerlek çalışan farelerde normal, gönüllü davranış olduğundan, kullanımı diğer davranış testleri veya biyolojik önlemler hakkında çok az karıştırıcı etkiye sahip olmalıdır. Bu nedenle, tekerlek döndürme yorgunluk davranışsal ve biyolojik ilişkilere anlama uygun bir sonuç ölçütü olarak kullanılabilir. KBY sık işbirliği ile karmaşık bir durumdurbüyük olasılıkla morbidite ve kanser ve çeşitli tedaviler hem ilgili nedenleri vardır. Bu yazıda anlatılan yöntemleri yorgunluk gibi periferik tetiklenen ama merkezi odaklı davranış gelişimini ve sebat açıklayabilir biyolojik ağlar keşfetmek için, CRF gelişmesine ve daha genel katkıda radyasyona bağlı değişiklikleri araştırmak için yararlıdır .

fareler üç partisi, yukarıda tarif edilen protokol ile gerçekleştirilmiştir. 16 sham ve ışınlanmış 20 (2400 cGy, 3 x 800 cGy / gün) fareler toplam vardı. Işınlama üst üste üç gün sonra, ışınlanmış grup anlamlı sham göre VWRA azalma görülmüştür (karışık tekrarlayan ölçümler ANOVA: ışınlama tedavisi, F 1,13 = 19,233, p &lt;0.001 ana etkisi). Etkisi düşük ortalama VWRA mesafe radyasyon (Şekil 2A) sonra üçüncü gün ...

Watch this Scientific Journal Video about A Mouse Model of Fatigue Induced by Peripheral Irradiation at JoVE.com

A Mouse Model of Fatigue Induced by Peripheral Irradiation

Biz farelerde yorgunluk benzeri bir davranış ikna etmek için hedeflenen çevre radyasyon kullanarak bir yöntem açıklanmaktadır. Seçilen öldürücü olmayan ışınlama dozu gönüllü tekerlek çalışan aktivitesinde bir hafta süren azalmaya yol açar.

Periferik Radyasyonla Bağlı Yorgunluk A Fare Modeli

Cancer-related fatigue (CRF) is a distressing and costly condition that often affects patients receiving cancer treatments, including radiation therapy. ...

a-mouse-model-of-fatigue-induced-by-peripheral-irradiation

Research

JoVE Journal

Cancer Research

7.8K Görüntüleme.  National Institutes of Health.  Biz farelerde yorgunluk benzeri bir davranış ikna etmek için hedeflenen çevre radyasyon kullanarak bir yöntem açıklanmaktadır. Seçilen öldürücü olmayan ışınlama dozu gönüllü tekerlek çalışan aktivitesinde bir hafta süren azalmaya yol açar. 

Video: A Mouse Model of Fatigue Induced by Peripheral Irradiation

Fluorescent Orthotopic Mouse Model of Pancreatic Cancer

Pancreatic cancer remains one of the cancers for which survival has not improved substantially in the last few decades. Only 7% of diagnosed patients will survive longer than five years. In order to understand and mimic the microenvironment of pancreatic tumors, we utilized a murine orthotopic model of pancreatic cancer that allows non-invasive imaging of tumor progression in real time. Pancreatic cancer cells expressing green fluorescent protein (PANC-1 GFP) were suspended in basement membrane matrix, high concentration, (e.g., Matrigel HC) with serum-free media and then injected into the tail of the pancreas via laparotomy. The cell suspension in the high concentration basement membrane matrix becomes a gel-like substance once it reaches room temperature; therefore, it gels when it comes in contact with the pancreas, creating a seal at the injection site and preventing any cell leakage. Tumor growth and metastasis to other organs are monitored in live animals by using fluorescence. It is critical to use the appropriate filters for excitation and emission of GFP. The steps for the orthotopic implantation are detailed in this article so researchers can easily replicate the procedure in nude mice. The main steps of this protocol are preparation of the cell suspension, surgical implantation, and whole body fluorescent in vivo imaging. This orthotopic model is designed to investigate the efficacy of novel therapeutics on primary and metastatic tumors.

A procedure to implant green fluorescent protein-expressing pancreatic cancer cells (PANC-1 GFP) orthotopically into the pancreas of Balb-c Ola Hsd-Fox1nu mice to assess tumor progression and metastasis is presented here.

Pankreas Kanseri Floresan Ortotopik Fare Modeli

Pancreatic cancer remains one of the cancers for which survival has not improved substantially in the last few decades. Only 7% of diagnosed patients will ...

Kanser Araştırmaları

Transduction-Transplantation Mouse Model of Myeloproliferative Neoplasm

Transduction-transplantation is a quick and efficient way to model human hematologic malignancies in mice. This technique results in expression of the gene of interest in hematopoietic cells and can be used to study the gene's role in normal and/or malignant hematopoiesis. This protocol provides a detailed description on how to perform transduction-transplantation using calreticulin (CALR) mutations recently identified in myeloproliferative neoplasm (MPN) as an example. In this protocol whole bone marrow cells from 5-flurouracil (5-FU) treated donor mice are transduced with a retrovirus encoding mutant CALR and transplanted into lethally irradiated syngeneic hosts. Donor cells expressing mutant CALR are marked with green fluorescent protein (GFP). Transplanted mice develop an MPN phenotype including elevated platelets in the peripheral blood, expansion of megakaryocytes in the bone marrow, and bone marrow fibrosis. We provide a step-by-step account of how to generate retrovirus, calculate viral titer, transduce whole bone marrow cells, and transplant into irradiated recipient mice.

This manuscript provides a description of the methodology used to establish transduction-transplantation mouse models. A detailed account is given of technical errors to avoid when performing bone marrow transplants. A clear understanding should be gained of the importance of high viral titer, transfection/transduction, and irradiation.

Myeloproliferatif tümörün İletimi-Transplantasyon Fare Modeli

Transduction-transplantation is a quick and efficient way to model human hematologic malignancies in mice. This technique results in expression of the ...

Isolation of Circulating Tumor Cells in an Orthotopic Mouse Model of Colorectal Cancer

Despite the advantages of easy applicability and cost-effectiveness, subcutaneous mouse models have severe limitations and do not accurately simulate tumor biology and tumor cell dissemination. Orthotopic mouse models have been introduced to overcome these limitations; however, such models are technically demanding, especially in hollow organs such as the large bowel. In order to produce uniform tumors which reliably grow and metastasize, standardized techniques of tumor cell preparation and injection are critical. 
We have developed an orthotopic mouse model of colorectal cancer (CRC) which develops highly uniform tumors and can be used for tumor biology studies as well as therapeutic trials. Tumor cells from either primary tumors, 2-dimensional (2D) cell lines or 3-dimensional (3D) organoids are injected into the cecum and, depending on the metastatic potential of the injected tumor cells, form highly metastatic tumors. In addition, CTCs can be found regularly. We here describe the technique of tumor cell preparation from both 2D cell lines and 3D organoids as well as primary tumor tissue, the surgical and injection techniques as well as the isolation of CTCs from the tumor-bearing mice, and present tips for troubleshooting.

We describe the establishment of orthotopic colorectal tumors via injection of tumor cells or organoids into the cecum of mice and the subsequent isolation of circulating tumor cells (CTCs) from this model.

Kolorektal kanserli bir Ortotopik Fare Modelinde Dolaşan Tümör Hücrelerinin İzolasyonu

Despite the advantages of easy applicability and cost-effectiveness, subcutaneous mouse models have severe limitations and do not accurately simulate ...

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer

Despite the advantages of easy applicability and cost-effectiveness, colorectal cancer mouse models based on tumor cell injection have severe limitations and do not accurately simulate tumor biology and tumor cell dissemination. Genetically engineered mouse models have been introduced to overcome these limitations; however, such models are technically demanding, especially in large organs such as the colon in which only a single tumor is desired.
As a result, an immunocompetent, genetically engineered mouse model of colorectal cancer was developed which develops highly uniform tumors and can be used for tumor biology studies as well as therapeutic trials. Tumor development is initiated by surgical, segmental infection of the distal colon with adeno-cre virus in compound conditionally mutant mice. The tumors can be easily detected and monitored via colonoscopy. We here describe the surgical technique of segmental adeno-cre infection of the colon, the surveillance of the tumor via high-resolution colonoscopy and present the resulting colorectal tumors.

A protocol for the establishment of a genetically engineered mouse model of colorectal cancer by segmental adeno-cre infection and its surveillance via high-resolution colonoscopy is presented.

Sporadik Kolorektal Kanserin Genetik Olarak Geliştirilmiş Fare Modeli

Despite the advantages of easy applicability and cost-effectiveness, colorectal cancer mouse models based on tumor cell injection have severe limitations ...

Tumor Engraftment in a Xenograft Mouse Model of Human Mantle Cell Lymphoma

B lymphocytes are key players in immune cell circulation and they mainly home to and reside in lymphoid organs. While normal B cells only proliferate when stimulated by T lymphocytes, oncogenic B cells survive and expand autonomously in undefined organ niches. Mantle cell lymphoma (MCL) is one such B cell disorder, where the median survival rate of patients is 4 - 5 years. This calls for the need of effective mechanisms by which the homing and engraftment of these cells are blocked in order to increase the survival and longevity of patients. Therefore, the effort to develop a xenograft mouse model to study the efficacy of MCL therapeutics by blocking the homing mechanism in vivo is of utmost importance. Development of animal recipients for human cell xenotransplantation to test early stage drugs have long been pursued, as relevant preclinical mouse models are crucial to screen new therapeutic agents. This animal model is developed to avoid human graft rejection and to establish a model for human diseases, and it may be an extremely useful tool to study disease progression of different lymphoma types and to perform preclinical testing of candidate drugs for hematologic malignancies, like MCL. We established a xenograft mouse model that will serve as an excellent resource to study and develop novel therapeutic approaches for MCL.

Mantle cell lymphoma (MCL) is a difficult to treat B cell disorder and it is equally difficult to establish a xenograft mouse model of primary MCL to study and develop therapeutics. Here, we describe the successful establishment of MCL xenografts in mice to help understand its underlying biology.

Tümör Engraftment insan Mantle hücreli lenfoma, Xenograft fare modeli

B lymphocytes are key players in immune cell circulation and they mainly home to and reside in lymphoid organs. While normal B cells only proliferate when ...

Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines

The crosstalk between tumor cells and bone cells in the bone microenvironment is crucial to understanding the mechanism of bone metastasis formation. We developed an in vitro fully human preclinical model of a co-culture of breast cancer cells and monocytes undergoing differentiation towards osteoclasts. We optimized a model of osteoclastogenesis starting from a sample of peripheral blood collected from healthy donors. Peripheral blood mononuclear cells (PBMCs) were first separated by density gradient centrifugation, seeded at a high density and induced to differentiate by adding two growth factors (GFs): receptor activator of nuclear factor-&#954;B ligand (RANKL) and macrophage colony-stimulating factor (MCSF). The cells were left in culture for 14 days and then fixed and analyzed by downstream analysis. In osteolytic bone metastases, one of the effects of cancer cell arrival in bone is the induction of osteoclastogenesis. We thus challenged our model with co-cultures of breast cancer cells to study the differentiation power of cancer cells with respect to GFs. A straightforward way of studying cancer cell-osteoclast interaction is to perform indirect co-cultures based on the use of conditioned medium collected from breast cancer cell cultures and mixed with fresh medium. This mixture is then used to induce osteoclast differentiation. We also optimized a method of direct co-culture in which cancer cells and monocytes undergoing differentiation share the medium and exchange secreted factors. This is a significant improvement over the original indirect co-culture method as researchers can observe the reciprocal interactions of the two cell types and perform downstream analyses for both cancer cells and osteoclasts. This method enables us to study the effect of drugs on the metastatic bone microenvironment and to seed cell lines other than those derived from breast cancer. The model can also be used to study other diseases such as osteoporosis or other bone conditions.

This protocol describes development of an in vitro human preclinical model of osteoclastogenesis from peripheral blood monocytes cultured with breast cancer cell lines to mimic the cancer cell-osteoclast interaction. The model could be used to further our understanding of bone metastasis formation and improve therapeutic options.

Osteoclastogenesis periferik kan monosit kültürlü meme kanseri hücre hatları ile birlikte gelen bir insan preklinik modelinin geliştirilmesi

The crosstalk between tumor cells and bone cells in the bone microenvironment is crucial to understanding the mechanism of bone metastasis formation. We ...

PET and MRI Guided Irradiation of a Glioblastoma Rat Model Using a Micro-irradiator

For decades, small animal radiation research was mostly performed using fairly crude experimental setups applying simple single-beam techniques without the ability to target a specific or well-delineated tumor volume. The delivery of radiation was achieved using fixed radiation sources or linear accelerators producing megavoltage (MV) X-rays. These devices are unable to achieve sub-millimeter precision required for small animals. Furthermore, the high doses delivered to healthy surrounding tissue hamper response assessment. To increase the translation between small animal studies and humans, our goal was to mimic the treatment of human glioblastoma in a rat model. To enable a more accurate irradiation in a preclinical setting, recently, precision image-guided small animal radiation research platforms were developed. Similar to human planning systems, treatment planning on these micro-irradiators is based on computed tomography (CT). However, low soft-tissue contrast on CT makes it very challenging to localize targets in certain tissues, such as the brain. Therefore, incorporating magnetic resonance imaging (MRI), which has excellent soft-tissue contrast compared to CT, would enable a more precise delineation of the target for irradiation. In the last decade also biological imaging techniques, such as positron emission tomography (PET) gained interest for radiation therapy treatment guidance. PET enables the visualization of e.g., glucose consumption, amino-acid transport, or hypoxia, present in the tumor. Targeting those highly proliferative or radio-resistant parts of the tumor with a higher dose could give a survival benefit. This hypothesis led to the introduction of the biological tumor volume (BTV), besides the conventional gross target volume (GTV), clinical target volume (CTV), and planned target volume (PTV).
At the preclinical imaging lab of Ghent University, a micro-irradiator, a small animal PET, and a 7 T small animal MRI are available. The goal was to incorporate MRI-guided irradiation and PET-guided sub-volume boosting in a glioblastoma rat model.

In the past, small animal irradiation was usually performed without the ability to target a well-delineated tumor volume. The goal was to mimic the treatment of human glioblastoma in rats. Using a small animal irradiation platform, we performed MRI-guided 3D conformal irradiation with PET-based sub-volume boosting in a preclinical setting.

Bir mikro-irradiator kullanarak Glioblastoma fare modeli ışınlama güdümlü evde beslenen hayvan ve MRI

For decades, small animal radiation research was mostly performed using fairly crude experimental setups applying simple single-beam techniques without ...

Evaluating the Role of Mitochondrial Function in Cancer-related Fatigue

Fatigue is a common and debilitating condition that affects most cancer patients. To date, fatigue remains poorly characterized with no diagnostic test to objectively measure the severity of this condition. Here we describe an optimized method for assessing mitochondrial function of PBMCs collected from fatigued cancer patients. Using a compact extracellular flux system and sequential injection of respiratory inhibitors, we examined PBMC mitochondrial functional status by measuring basal mitochondrial respiration, spare respiratory capacity, and energy phenotype, which describes the preferred energy pathway to respond to stress. Fresh PBMCs are readily available in the clinical setting using standard phlebotomy. The entire assay described in this protocol can be completed in less than 4 hours without the involvement of complex biochemical techniques. Additionally, we describe a normalization method that is necessary for obtaining reproducible data. The simple procedure and normalization methods presented allow for repeated sample collection from the same patient and generation of reproducible data that can be compared between time points to evaluate potential treatment effects.

Our goal was to develop a practical protocol to evaluate mitochondrial dysfunction associated with fatigue in cancer patients. This innovative protocol is optimized for clinical use involving only standard phlebotomy and basic laboratory procedures.

Kanserle ilgili yorgunluk mitokondriyal işlev rolünün değerlendirilmesi

Fatigue is a common and debilitating condition that affects most cancer patients. To date, fatigue remains poorly characterized with no diagnostic test to ...

Important Endpoints and Proliferative Markers to Assess Small Intestinal Injury and Adaptation using a Mouse Model of Chemotherapy-Induced Mucositis

Intestinal adaptation is the natural compensatory mechanism that occurs when the bowel is lost due to trauma. The adaptive responses, such as crypt cell proliferation and increased nutrient absorption, are critical in recovery, yet poorly understood. Understanding the molecular mechanism behind the adaptive responses is crucial to facilitate the identification of nutrients or drugs to enhance adaptation. Different approaches and models have been described throughout the literature, but a detailed descriptive way to essentially perform the procedures is needed to obtain reproducible data. Here, we describe a method to estimate important endpoints and proliferative markers of small intestinal injury and compensatory hyperproliferation using a model of chemotherapy-induced mucositis in mice. We demonstrate the detection of proliferating cells using a cell cycle specific marker, as well as using small intestinal weight, crypt depth, and villus height as endpoints. Some of the critical steps within the described method are the removal and weighing of the small intestine and the rather complex software system suggested for the measurement of this technique. These methods have the advantages that they are not time-consuming, and that they are cost-effective and easy to carry out and measure.

Here, we present a protocol to establish important endpoints and proliferative markers of small intestinal injury and compensatory hyperproliferation using a model of chemotherapy-induced mucositis. We demonstrate the detection of proliferating cells using a cell cycle specific marker and using small intestinal weight, crypt depth, and villus height as endpoints.

Kemoterapiye bağlı Mukozinin fare modelini kullanarak küçük bağırsak yaralanmasını ve uyarlamasını değerlendirmek için önemli uç noktalar ve proliferatif Işaretçiler

Intestinal adaptation is the natural compensatory mechanism that occurs when the bowel is lost due to trauma. The adaptive responses, such as crypt cell ...

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

The absence of a clinically relevant animal model addressing the typical immune characteristics of hepatocellular cancer (HCC) has significantly impeded elucidation of the underlying mechanisms and development of innovative immunotherapeutic strategies. To develop an ideal animal model recapitulating human HCC, immunocompetent male C57BL/6J mice first receive a carbon tetrachloride (CCl4) injection to induce liver fibrosis, then receive histologically-normal oncogenic hepatocytes from young male SV40 T antigen (TAg)-transgenic mice (MTD2) by intra-splenic (ISPL) inoculation. Androgen generated in recipient male mice at puberty initiates TAg expression under control of a liver-specific promoter. As a result, the transferred hepatocytes become cancer cells and form tumor masses in the setting of liver fibrosis/cirrhosis. This novel model mimics human HCC initiation and progression in the context of liver fibrosis/cirrhosis and reflects the most typical features of human HCC including immune dysfunction.

Here, we describe the development of a clinically relevant murine model of liver cancer recapitulating the typical immune features of hepatocellular cancer (HCC).

Hepatik İnflamasyon ve Fibrozis Ortamında Ortaya Çıkan Hepatosellüler Kanserin Onkojenik Hepatositkaynaklı Ortotopik Fare Modeli

The absence of a clinically relevant animal model addressing the typical immune characteristics of hepatocellular cancer (HCC) has significantly impeded ...