支持这项工作是由国家卫生和医学研究理事会，澳大利亚（1008865），澳大利亚研究理事会（LE110100125），美国国家癌症研究所（CA138687，01），埃里卡斯隆支持全国乳腺癌早期职业院士基金会，澳大利亚。支持科里纳金福克斯由从瑞士癌症联盟和HDR莫纳什药学研究所奖学金相交。 ELIANE AN​​GST是支持的由授出从伯尔尼癌症联赛。

该协议被证明是作者的机构的动物护理和使用委员会的指导和批准下进行。所有的实验都符合所有有关准则，法规和监管机构执行。 1。转导胰腺癌细胞株<ol><li>混合厚膜胰腺癌细胞表达荧光素酶的如前面所述。12,13 PANC-1和胰腺癌-1胰腺癌细胞株转导的萤火虫荧光素酶，是用在这里。 </li></ol> 注：也可用于海肾荧光素或细菌荧光素酶。 2。胰腺癌细胞制备<ol><li>文化导胰腺癌细胞，直到70％汇合。 </li><li>提起胰腺细胞和确保生存能力大于90％。 </li><li>在2×10 7个细胞/毫升的冷冻基质胶中的3:2混合物：磷酸盐缓冲液重悬萨尔INE（PBS）中。 </li><li>保持基底膜的细胞悬浮液在冰上之前注入胰腺。 </li></ol> 注意：为了确保基质胶的快速凝固，减少PBS将细胞沉淀的体积占体积。拉手基底膜在任何时候使用冰冷的仪器和注射器，注射前防止凝固。所建议的细胞数是一个指南，应根据经验来确定每种细胞系。 3。鼠标准备<ol><li>使用吸入2-3％的异氟醚麻醉鼠标。确定一个温柔的脚趾捏缺乏踏板反射麻醉深度。 </li><li>涂抹润滑剂的眼睛，以防止脱水。 </li><li>将鼠标放在其背部37℃加热垫，并轻轻转动鼠标提高的腹部左侧。 </li><li>准备腹部有10％的聚维酮碘溶液。 </li></ol> 注释：Injectab文件可以用来代替麻醉吸入麻醉。手术前禁食是没有必要的。 4。剖腹探查<ol><li>使用无菌手术器械做一个1.5厘米的切口，在皮肤约1厘米左外侧从中线。 </li><li>做一个1.5厘米的切口，在底层的腹部肌肉。 </li><li>找到脾脏，使用镊子轻轻取出脾脏从腹腔。沿着无菌棉花棒露出底层胰腺，脾脏固定。 </li><li>找到胰腺脾脏相邻的尾部。 </li><li>使用地下29 0.3毫升的胰岛素注射器，注入20μl的基底膜细胞悬液到胰腺。 </li><li>注射后，持注射器在胰腺，持续30-60秒，直到基底膜凝固。这一重要步骤，最大限度地减少细胞泄漏。 </li><li>检查注射部位的，以确保没有发生泄漏。 </li><li>返回到腹腔的脾脏和胰腺。 </li></ol> 注意：要小心，以避免穿刺胰腺背侧这可能是薄。 5。腹壁封闭<ol><li>采用连续缝合圆针编织4-0可吸收缝合关闭鼠标的腹部肌肉。 </li><li>关闭外部的皮肤，用6-0不可吸收的单丝用切割针的缝合线，使用一个连续的针迹。 </li><li>将鼠标从吸入麻醉和注射0.05-0.1毫克/公斤丁丙诺啡皮下。 </li><li>让鼠标在笼子放置在37℃的加热垫，免费获得食物和水恢复。如果老鼠证明疼痛的迹象，如拱起或行动不便，丁丙诺啡可能每12小时超过36小时期间。 </li><li>伤口愈合后（7-10天），麻醉鼠标和消除外部缝线。 </li></ol> 6。生物发光追踪胰腺CANCER进展<ol><li>使用吸入异氟醚麻醉鼠标。 </li><li>经尾静脉注射150毫克/千克的D-荧光素。 </li><li>鼠标放置在生物发光成像系统捕获白光和生物发光的图像，如前面所述。14,15 </li><li>取出鼠标吸入麻醉剂，并允许它来恢复在其家笼。 </li></ol> 注：生物发光成像的非侵入性的，可以定期进行，以探讨肿瘤的生长动力学。胰尾肿瘤图像，重要的是把鼠标放在左侧，所以肿瘤指向相机。我们想像每周一次的频率上升到每周三次的实验端点使用第二Lumina的成像系统（Perkin-Elmer公司，原卡尺生命科学版）运行生活成像4.3.1软件分级4，视场角12.5， F-STOP 1，曝光1 - 60秒（由最高地契osure不饱和像素）。

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作者宣称，他们有没有竞争经济利益。

在这里，我们描述了一个原位模型胰腺肿瘤发生和发展的纵向评估。原发肿瘤生长动力学重现性（ 图3），并且可以非侵入性地使用生物发光成像的荧光素酶标记的细胞， 如肿瘤反应的新型抗胰腺癌的治疗学的分析监测。该模型与人类疾病相一致，显示本地侵犯胰腺（ 图4A），允许调查肿瘤细胞的胰腺微环境的相互作用。荧光素酶标记的细胞株中允许使用频率，地...

胰腺癌是癌症相关死亡的第四大原因，与5年生存率为4-6％。1,2只有15％的患者及早诊断疾病获手术，肿瘤复发&gt; 80％，这些患者3,4吉西他滨用于治疗胰腺癌，但是，化疗是常见的药物往往有整体生存影响不大。我们亟需新的药理治疗胰腺癌的策略。他们的发展依赖于了解疾病进展的关键步骤，可能是敏感的干预治疗明显改善。 原位胰腺癌模型模拟人类疾病的关键环节，使他们的理想工具研究胰腺癌的生物学6-9相反在体外细胞检测胰腺癌细胞的行为。ð胰腺癌的体内模型，皮下原位模型允许调查肿瘤细胞胰腺微环境的相互作用。病情恶化的动力学在原位模型和高度重复性发生在很短的时间框架（周），这使得它们非常适合新型疗法的临床前试验。这是在发病发生在一个时间更长，更可变帧（个月至1年）10当用更积极的细胞株转基因模型，原位胰腺癌模型看到那些类似自发转移模式患者如萤火虫荧光素酶的生物发光报告基因的表达，有利于纵向监测肿瘤的生长，转移传播，复发和响应疗法6,11 在这里，我们描述了胰腺癌原位模型，利用MATR埃吉尔局部细胞传递， 在体内生物发光成像的非侵入性的监测肿瘤进展。胰腺癌原位模型允许非侵入性的疾病进展和治疗干预在同基因或异种移植模型分析。

<table border="1">
 <tbody>
 <tr>
 <td>Equipment</td>
 <td>Company</td>
 <td>Catalog Number</td>
 <td>Comments</td>
 </tr>
 <tr>
 <td>Clean Bench coat</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Heating pad</td>
 <td></td>
 <td></td>
 <td>Set to 37 &deg;C </td>
 </tr>
 <tr>
 <td>Ivis Lumina ll Bioluminescent imager</td>
 <td>Caliper </td>
 <td></td>
 <td>Alternative bioluminescent imaging systems include In vivo F PRO (Carestream) and Photon Imager (Biospace Lab)</td>
 </tr>
 <tr>
 <td>Dissecting scissors</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Iris forceps (serrated)</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Needle holder</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>27 G 0.3 ml insulin syringe</td>
 <td>Terumo</td>
 <td>T35525M2913</td>
 <td></td>
 </tr>
 </tbody>
</table>

bioluminescent orthotopic model of pancreatic cancer progression

<p class="jove_content"&gt;胰腺癌有一个非常可怜的5年生存率为4-6％。我们亟需新的治疗选择，依赖于改善胰腺癌生物学的理解。为了更好地了解癌症细胞具有胰腺微环境的相互作用，我们演示了一种胰脏癌，可以允许非侵入性的监测癌症进展原位模型。荧光素酶标记的胰腺癌细胞悬浮在基底膜，并交付到胰尾在剖腹手术。基底膜在体温下固化，在注射过程中的癌细胞，以防止泄漏。原发肿瘤的生长和转移到远处器官监测荧光素酶底物虫荧光素注射后，用<em&gt;在体内</em&gt;从癌细胞的生物发光发射成像。<em&gt;在体内</em&gt;摄像也可以被用来跟踪原发肿瘤切除后复发。这种原位模型适合于同源和异种移植模型，可用于临床前试验调查新颖的抗癌疗法对主胰腺肿瘤的生长和转移的影响。</p&gt;

这种方法介绍胰腺癌原位模型，采用外科手术，包括诱导麻醉，剖腹探查术，注射癌细胞在基底膜和腹部闭合（ 图1A）。注入的细胞形成一个气泡在胰腺的表面（ 图1B）。胰腺癌恶化可能非侵入性监测使用在体内生物发光成像跟踪癌细胞扩散和传播（ 图2）。肝转移手术切除过程中，通过观察在肝脏中的生物发光显示（ 图2）和组织学（ <st...

Watch this Scientific Journal Video about Bioluminescent Orthotopic Model of Pancreatic Cancer Progression at JoVE.com

Bioluminescent Orthotopic Model of Pancreatic Cancer Progression

改进胰腺癌生物学的理解是迫切需要的，以便更好的治疗选择治疗胰腺癌的发展。为了满足这一需求，我们展示了胰脏癌，原位模型允许非侵入性的监测癌症进展<em&gt;在体内</em&gt;生物发光成像。

生物荧光原位模型胰腺癌进展

Pancreatic cancer has an extremely poor five-year survival rate of 4-6%.  New therapeutic options are critically needed and depend on improved ...

bioluminescent-orthotopic-model-of-pancreatic-cancer-progression

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Medicine

26.7K 次观看.  Monash University. 改进胰腺癌生物学的理解是迫切需要的，以便更好的治疗选择治疗胰腺癌的发展。为了满足这一需求，我们展示了胰脏癌，原位模型允许非侵入性的监测癌症进展在体内生物发光成像。

视频: Bioluminescent Orthotopic Model of Pancreatic Cancer Progression

Murine Bioluminescent Hepatic Tumour Model

This video describes the establishment of liver metastases in a mouse model that can be subsequently analysed by bioluminescent imaging. Tumour cells are administered specifically to the liver to induce a localised liver tumour, via mobilisation of the spleen and splitting into two, leaving intact the vascular pedicle for each half of the spleen. Lewis lung carcinoma cells that constitutively express the firefly luciferase gene (luc1) are inoculated into one hemi-spleen which is then resected 10 minutes later. The other hemi-spleen is left intact and returned to the abdomen. Liver tumour growth can be monitored by bioluminescence imaging using the IVIS whole body imaging system. Quantitative imaging of tumour growth using IVIS provides precise quantitation of viable tumour cells. Tumour cell death and necrosis due to drug treatment is indicated early by a reduction in the bioluminescent signal. This mouse model allows for investigating the mechanisms underlying metastatic tumour-cell survival and growth and can be used for the evaluation of therapeutics of liver metastasis. 

This article describes a procedure for the induction of orthotopic bioluminescent liver tumours in mice, and subsequent analysis of tumour growth confined to the liver using live whole body luminescence imaging.

发光法小鼠肝肿瘤模型

This video describes the establishment of liver metastases in a mouse model that can be subsequently analysed by bioluminescent imaging. Tumour cells are ...

科研

医学

An Orthotopic Model of Murine Bladder Cancer

In this straightforward procedure, bladder tumors are established in female C57 mice through the use of catheterization, local cauterization, and subsequent cell adhesion. After their bladders are transurethrally catheterized and drained, animals are again catheterized to permit insertion of a platinum wire into bladders without damaging the urethra or bladder. The catheters are made of Teflon to serve as an insulator for the wire, which will conduct electrical current into the bladder to create a burn injury. An electrocautery unit is used to deliver 2.5W to the exposed end of the wire, burning away extracellular layers and providing attachment sites for carcinoma cells that are delivered in suspension to the bladder through a subsequent catheterization. Cells remain in the bladder for 90 minutes, after which the catheters are removed and the bladders allowed to drain naturally. The development of tumor is monitored via ultrasound. Specific attention is paid to the catheterization technique in the accompanying video.

Bladder tumors are established in female mice in a minimally invasive fashion through catheterization, local cauterization, and subsequent adhesion of carcinoma cells to the burn sites.

一个小鼠膀胱癌原位模型

In this straightforward procedure, bladder tumors are established in female C57 mice through the use of catheterization, local cauterization, and ...

Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma

Loco-regional invasion of head and neck cancer is linked to metastatic risk and presents a difficult challenge in designing and implementing patient management strategies. Orthotopic mouse models of oral cancer have been developed to facilitate the study of factors that impact invasion and serve as model system for evaluating anti-tumor therapeutics. In these systems, visualization of disseminated tumor cells within oral cavity tissues has typically been conducted by either conventional histology or with in vivo bioluminescent methods. A primary drawback of these techniques is the inherent inability to accurately visualize and quantify early tumor cell invasion arising from the primary site in three dimensions. Here we describe a protocol that combines an established model for squamous cell carcinoma of the tongue (SCOT) with two-photon imaging to allow multi-vectorial visualization of lingual tumor spread. The OSC-19 head and neck tumor cell line was stably engineered to express the F-actin binding peptide LifeAct fused to the mCherry fluorescent protein (LifeAct-mCherry). Fox1nu/nu mice injected with these cells reliably form tumors that allow the tongue to be visualized by ex-vivo application of two-photon microscopy. This technique allows for the orthotopic visualization of the tumor mass and locally invading cells in excised tongues without disruption of the regional tumor microenvironment. In addition, this system allows for the quantification of tumor cell invasion by calculating distances that invaded cells move from the primary tumor site. Overall this procedure provides an enhanced model system for analyzing factors that contribute to SCOT invasion and therapeutic treatments tailored to prevent local invasion and distant metastatic spread. This method also has the potential to be ultimately combined with other imaging modalities in an in vivo setting.

A comprehensive overview of the techniques involved in generating a mouse model of oral cancer and quantitative monitoring of tumor invasion within the tongue through multi-photon microscopy of labeled cells is presented. This system can serve as a useful platform for the molecular assessment and drug efficacy of anti-invasive compounds.

多光子成像在口腔鳞状细胞癌原位小鼠模型的肿瘤细胞的侵袭

Loco-regional invasion of head and neck cancer is linked to metastatic risk and presents a difficult challenge in designing and implementing patient ...

In vivo Dual Substrate Bioluminescent Imaging

Our understanding of how and when breast cancer cells transit from established primary tumors to metastatic sites has increased at an exceptional rate since the advent of in vivo bioluminescent imaging technologies 1-3. Indeed, the ability to locate and quantify tumor growth longitudinally in a single cohort of animals to completion of the study as opposed to sacrificing individual groups of animals at specific assay times has revolutionized how researchers investigate breast cancer metastasis. Unfortunately, current methodologies preclude the real-time assessment of critical changes that transpire in cell signaling systems as breast cancer cells (i) evolve within primary tumors, (ii) disseminate throughout the body, and (iii) reinitiate proliferative programs at sites of a metastatic lesion. However, recent advancements in bioluminescent imaging now make it possible to simultaneously quantify specific spatiotemporal changes in gene expression as a function of tumor development and metastatic progression via the use of dual substrate luminescence reactions. To do so, researchers take advantage for two light-producing luciferase enzymes isolated from the firefly (Photinus pyralis) and sea pansy (Renilla reniformis), both of which react to mutually exclusive substrates that previously facilitated their wide-spread use in in vitro cell-based reporter gene assays 4. Here we demonstrate the in vivo utility of these two enzymes such that one luminescence reaction specifically marks the size and location of a developing tumor, while the second luminescent reaction serves as a means to visualize the activation status of specific signaling systems during distinct stages of tumor and metastasis development. Thus, the objectives of this study are two-fold. First, we will describe the steps necessary to construct dual bioluminescent reporter cell lines, as well as those needed to facilitate their use in visualizing the spatiotemporal regulation of gene expression during specific steps of the metastatic cascade. Using the 4T1 model of breast cancer metastasis, we show that the in vivo activity of a synthetic Smad Binding Element (SBE) promoter was decreased dramatically in pulmonary metastasis as compared to that measured in the primary tumor 4-6. Recently, breast cancer metastasis was shown to be regulated by changes within the primary tumor microenvironment and reactive stroma, including those occurring in fibroblasts and infiltrating immune cells 7-9. Thus, our second objective will be to demonstrate the utility of dual bioluminescent techniques in monitoring the growth and localization of two unique cell populations harbored within a single animal during breast cancer growth and metastasis.

In vivo Dual Substrate Bioluminescent Imaging

Herein we describe the methods to construct, visualize, and quantify the bioluminescent reactions of both firefly and renilla luciferase enzymes expressed in metastatic breast cancer cells during their growth and metastasis in vivo.

在体内的双基体生物光学成像

Our understanding of how and when breast cancer cells transit from established primary tumors to metastatic sites has increased at an exceptional rate ...

Combination Radiotherapy in an Orthotopic Mouse Brain Tumor Model

Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors1. In recent years there has been substantial progress in the understanding of the mechanics of tumor invasion, and direct intracerebral inoculation of tumor provides the opportunity of observing the invasive process in a physiologically appropriate environment2. As far as human brain tumors are concerned, the orthotopic models currently available are established either by stereotaxic injection of cell suspensions or implantation of a solid piece of tumor through a complicated craniotomy procedure3. In our technique we harvest cells from tissue culture to create a cell suspension used to implant directly into the brain. The duration of the surgery is approximately 30 minutes, and as the mouse needs to be in a constant surgical plane, an injectable anesthetic is used. The mouse is placed in a stereotaxic jig made by Stoetling (figure 1). After the surgical area is cleaned and prepared, an incision is made; and the bregma is located to determine the location of the craniotomy. The location of the craniotomy is 2 mm to the right and 1 mm rostral to the bregma. The depth is 3 mm from the surface of the skull, and cells are injected at a rate of 2 &mu;l every 2 minutes. The skin is sutured with 5-0 PDS, and the mouse is allowed to wake up on a heating pad. From our experience, depending on the cell line, treatment can take place from 7-10 days after surgery. Drug delivery is dependent on the drug composition. For radiation treatment the mice are anesthetized, and put into a custom made jig. Lead covers the mouse's body and exposes only the brain of the mouse. The study of tumorigenesis and the evaluation of new therapies for GBM require accurate and reproducible brain tumor animal models. Thus we use this orthotopic brain model to study the interaction of the microenvironment of the brain and the tumor, to test the effectiveness of different therapeutic agents with and without radiation.

The purpose of this article is to describe the use of an orthotopic glioblastoma model for chemoradiation studies. This article will go though cell processing, implanting, and radiotherapy of the mouse using an intracranial model.

在原位小鼠脑肿瘤模型结合放疗

Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors1. In recent years there has been substantial progress in the ...

An Orthotopic Bladder Tumor Model and the Evaluation of Intravesical saRNA Treatment

We present a novel method for treating bladder cancer with intravesically delivered small activating RNA (saRNA) in an orthotopic xenograft mouse bladder tumor model. The mouse model is established by urethral catheterization under inhaled general anesthetic. Chemical burn is then introduced to the bladder mucosa using intravesical silver nitrate solution to disrupt the bladder glycosaminoglycan layer and allows cells to attach. Following several washes with sterile water, human bladder cancer KU-7-luc2-GFP cells are instilled through the catheter into the bladder to dwell for 2 hours. Subsequent growth of bladder tumors is confirmed and monitored by in vivo bladder ultrasound and bioluminescent imaging. The tumors are then treated intravesically with saRNA formulated in lipid nanoparticles (LNPs). Tumor growth is monitored with ultrasound and bioluminescence. All steps of this procedure are demonstrated in the accompanying video.

Establishing an orthotopic bladder tumor model to evaluate antitumor effects of intravesically delivered saRNA and monitoring tumor growth by ultrasound and bioluminescent imaging.

原位膀胱肿瘤模型和评价治疗膀胱萨纳

We present a novel method for treating bladder cancer with intravesically delivered small activating RNA (saRNA) in an orthotopic xenograft mouse bladder ...

Surgical Procedures for a Rat Model of Partial Orthotopic Liver Transplantation with Hepatic Arterial Reconstruction

Orthotopic liver transplantation (OLT) in rats using a whole or partial graft is an indispensable experimental model for transplantation research, such as studies on graft preservation and ischemia-reperfusion injury 1,2, immunological responses 3,4, hemodynamics 5,6, and small-for-size syndrome 7. The rat OLT is among the most difficult animal models in experimental surgery and demands advanced microsurgical skills that take a long time to learn. Consequently, the use of this model has been limited. Since the reliability and reproducibility of results are key components of the experiments in which such complex animal models are used, it is essential for surgeons who are involved in rat OLT to be trained in well-standardized and sophisticated procedures for this model.
While various techniques and modifications of OLT in rats have been reported 8 since the first model was described by Lee et al. 9 in 1973, the elimination of the hepatic arterial reconstruction 10 and the introduction of the cuff anastomosis technique by Kamada et al. 11 were a major advancement in this model, because they simplified the reconstruction procedures to a great degree. In the model by Kamada et al., the hepatic rearterialization was also eliminated. Since rats could survive without hepatic arterial flow after liver transplantation, there was considerable controversy over the value of hepatic arterialization. However, the physiological superiority of the arterialized model has been increasingly acknowledged, especially in terms of preserving the bile duct system 8,12 and the liver integrity 8,13,14.
In this article, we present detailed surgical procedures for a rat model of OLT with hepatic arterial reconstruction using a 50% partial graft after ex vivo liver resection. The reconstruction procedures for each vessel and the bile duct are performed by the following methods: a 7-0 polypropylene continuous suture for the supra- and infrahepatic vena cava; a cuff technique for the portal vein; and a stent technique for the hepatic artery and the bile duct.

Orthotopic liver transplantation in rats is an indispensable experimental model for biomedical research. Here we present our surgical procedures for orthotopic rat liver transplantation with hepatic arterial reconstruction using a 50% partial graft.

部分原位肝移植大鼠模型的肝动脉重建的外科手术

Orthotopic liver transplantation (OLT) in rats using a whole or partial graft is an indispensable experimental model for transplantation research, such as ...

An Orthotopic Bladder Cancer Model for Gene Delivery Studies

Bladder cancer is the second most common cancer of the urogenital tract and novel therapeutic approaches that can reduce recurrence and progression are needed. The tumor microenvironment can significantly influence tumor development and therapy response. It is therefore often desirable to grow tumor cells in the organ from which they originated. This protocol describes an orthotopic model of bladder cancer, in which MB49 murine bladder carcinoma cells are instilled into the bladder via catheterization. Successful tumor cell implantation in this model requires disruption of the protective glycosaminoglycan layer, which can be accomplished by physical or chemical means. In our protocol the bladder is treated with trypsin prior to cell instillation. Catheterization of the bladder can also be used to deliver therapeutics once the tumors are established. This protocol describes the delivery of an adenoviral construct that expresses a luciferase reporter gene. While our protocol has been optimized for short-term studies and focuses on gene delivery, the methodology of mouse bladder catheterization has broad applications.

Implantation of cancer cells into the organ of origin can serve as a useful preclinical model to evaluate novel therapies. MB49 bladder carcinoma cells can be grown within the bladder following intravesical instillation. This protocol demonstrates catheterization of the mouse bladder for the purpose of tumor implantation and adenoviral delivery.

原位膀胱癌模型的基因传递研究

Bladder cancer is the second most common cancer of the urogenital tract and novel therapeutic approaches that can reduce recurrence and progression are ...

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Our laboratory has developed a novel orthotopic implantation model of human prostate cancer (PCa). As PCa death is not due to the primary tumor, but rather the formation of distinct metastasis, the ability to effectively model this progression pre-clinically is of high value. In this model, cells are directly implanted into the ventral lobe of the prostate in Balb/c athymic mice, and allowed to progress for 4-6 weeks. At experiment termination, several distinct endpoints can be measured, such as size and molecular characterization of the primary tumor, the presence and quantification of circulating tumor cells in the blood and bone marrow, and formation of metastasis to the lung. In addition to a variety of endpoints, this model provides a picture of a cells ability to invade and escape the primary organ, enter and survive in the circulatory system, and implant and grow in a secondary site. This model has been used effectively to measure metastatic response to both changes in protein expression as well as to response to small molecule therapeutics, in a short turnaround time.

This orthotopic model of human prostate cancer allows for quantification of tumor size, circulating tumor cells, and formation of distinct metastasis to the lung. As cells must escape the primary organ, enter the blood stream, and implant into a secondary site, this model effectively recapitulates the scenario in humans.

人类前列腺癌转移的原位小鼠模型

Our laboratory has developed a novel orthotopic implantation model of  human prostate cancer (PCa). As PCa death is not due to the primary tumor, but  ...

Dynamic Contrast Enhanced Magnetic Resonance Imaging of an Orthotopic Pancreatic Cancer Mouse Model

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has been limitedly used for orthotopic pancreatic tumor xenografts due to severe respiratory motion artifact in the abdominal area. Orthotopic tumor models offer advantages over subcutaneous ones, because those can reflect the primary tumor microenvironment affecting blood supply, neovascularization, and tumor cell invasion. We have recently established a protocol of DCE-MRI of orthotopic pancreatic tumor xenografts in mouse models by securing tumors with an orthogonally bent plastic board to prevent motion transfer from the chest region during imaging. The pressure by this board was localized on the abdominal area, and has not resulted in respiratory difficulty of the animals. This article demonstrates the detailed procedure of orthotopic pancreatic tumor modeling using small animals and DCE-MRI of the tumor xenografts. Quantification method of pharmacokinetic parameters in DCE-MRI is also introduced. The procedure described in this article will assist investigators to apply DCE-MRI for orthotopic gastrointestinal cancer mouse models.

The goal of this protocol is to apply dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) for orthotopic pancreatic tumor xenografts in mice. DCE-MRI is a non-invasive method to analyze microvasculature in a target tissue, and useful to assess vascular response in a tumor following a novel therapy.