Name: a preclinical murine model of hepatic metastases
Uploaded: 2014-09-27T13:00:00.000+00:00
Duration: 6 min 51 s
Description: Watch this Scientific Journal Video about A Preclinical Murine Model of Hepatic Metastases at JoVE.com

KF和KO是共同第一作者以及堪萨斯州 这项工作是由AHPBA奖学金（堪萨斯州），美国国立卫生研究院K23 CA148964-01（LZ），医学的约翰霍普金斯学院的临床科学家奖（LZ），Viragh基金会和跳过Viragh胰腺癌症中心的约翰霍普金斯大学（EMJ，部分支持LZ），全国胰腺基金会（LZ），在莱夫科夫斯基家族基金会（LZ），美国国立癌症研究所孢子在胃肠道癌症P50 CA062924（EMJ，LZ），在Lustgarten基金会（LZ）和索尔高盛胰腺癌中心补助（KS ，BHE，LZ）。

所有的动物实验符合美国约翰霍普金斯大学的动物护理和使用委员会的指导方针，与动物保持在按照协会的评估和实验室服务的认证（AAALAC）的指导方针。在无菌条件下在手术室中的经历至少每小时15空气交换进行的外科手术过程。所有的仪器是由高压灭菌之前的程序，并再次用70％乙醇中的每个小鼠的过程中，灭菌。预计无法生存的外科手术所有小鼠都CO 2条件下实施安乐死3分钟后颈椎脱位，同时仍然在麻醉状态下。 1，细胞的制备<ol><li>悬浮培养的PANC02细胞在磷酸盐缓冲盐水中以2×10 7个细胞/毫升，并保持在冰上。 </li></ol> 2，鼠标准备<ol><li>管理氯胺酮E（100毫克/千克），甲苯噻嗪（10毫克/千克）混合腹腔，以8-12周龄的C57BL / 6雌性小鼠，分次给药。 </li><li>请检查脚趾捏撤回反射被废除，以确保鼠标完全麻醉。 </li><li>施用额外剂量的氯胺酮（100毫克/千克）和赛拉嗪（10毫克/千克），为需要充分麻醉小鼠混合。 </li><li>申请Puralube兽医软膏对小鼠的眼中，以防止干燥时的小鼠是在麻醉状态下。 </li><li>剃鼠的手术区，以避免伤口污染。 </li><li>制备型切口，用70％乙醇中，然后碘的左肋下区域。 </li><li>放置在腹部外科手术铺巾，以保持无菌。 </li></ol> 3，剖腹<ol><li>让左肋下切口线与通过皮肤，并通过使用手术刀腹膜左耳。 </li><li>通过应用同步数字p表示通过切口脾沿切口的头部和尾部方面ressure。 </li><li>找到脾血管在脾脏的下结束。 </li><li>将两个豪华中型结扎夹在脾，请小心操作以免损坏脾血管的脾极的中心划分脾。 </li><li>将脾脏的上极放回腹腔，以避免污染。 </li></ol> 4，肿瘤注射液<ol><li>拟定150μL磷酸盐缓冲液成26国祥5/8"注射器。 </li><li>拟定100微升PANC02（2×10 6细胞）到相同的注射器的注射过程中保持在任何时候都将注射器在一个直立的位置。 </li><li>浸在70％的乙醇溶液中的针。针被浸在70％的乙醇，以确保无菌。 </li><li>慢慢注入的细胞进入暴露hemispleen是肯定的注射器保持直立在任何时候。该syrin的伞GE应该在任何时候都通过脾胶囊可以观察到，以避免脾下注入细胞。脾血管美白应在注射后观察。 </li><li>提高脾脏和应用脾下一个媒介地平线剪辑闭塞脾血管。 </li><li>将一个小的地平线剪辑胰腺和脾脏血管的最前端部分。 </li><li>通过削减上述地平线短片结扎从hemispleen胰腺和脾脏血管。 </li><li>放置在其&#39;侧的鼠标和灌溉的切口，用蒸馏水。 </li></ol> 5，关腹和麻醉恢复期<ol><li>关闭腹膜有4-0跑步针。 </li><li>适用于两到三个皮肤剪辑，关闭皮肤切口。 </li><li>管理0.1毫克/公斤丁丙诺啡或5-10毫克/千克卡洛芬皮下，以减轻手术后疼痛。 </li><li>把鼠标放在一个加热垫的REC安理，直到移动和鼠标演示了普通的呼吸方式。动物从外科手术完全恢复后只返回到其他动物的公司。 </li></ol> 6，剖检检查和肝脏的收获<ol><li>介于30至60天以下的手术，小鼠开始显示转移的临床症状和需要安乐死。转移性疾病的需要人道安乐死的症状包括腹部增大，腹水的发展。通过吸入CO 2安乐死的小鼠。 </li><li>下面吸入，进行颈椎脱位。 </li><li>后的动物已被确定为无响应，使一个切口穿过腹膜，露出用剪刀腹部。 </li><li>使用镊子和剪刀，轻轻地割肝出了腹部。 </li><li>放置在OCT化合物中的肝和闪光灯用液氮速冻。储存在肝脏-80℃。可替代地，实况r的在RT被固定在16％中性福尔马林缓冲液中24小时和石蜡包埋。 </li></ol>

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作者没有利益冲突的相关披露。

胰腺癌转移这个临床前鼠模型中，以通过一个hemispleen注射技术肝脏是反映了许多的转移性疾病患者的肝的临床和免疫学条件描述的第一模型。这种模式提供了比其他小鼠模型中的几个优点。首先，与胰腺癌的转基因模型中，只有30％的小鼠发生转移至肝脏和转移瘤的形成时机是相当的变量，该模型提供始终如一获得转移的优势，肝脏中的小鼠100％以统一的时间，使研究人员能够研究转移性疾病在?...

胰腺导管腺癌（PDA）是癌症相关死亡的美国1的第四大死因。的5年生存率为治疗转移性PDA是2-12％1。虽然辅助和新辅助化疗对胰腺癌的效果更明显今天比以往任何时候都仍然是一个迫切需要新的治疗方法。 新颖的治疗学的发展就必须可靠的临床前动物模型。虽然皮下肿瘤模型是直接使用，缺点包括这些肿瘤无法转移和模仿肿瘤进展和微环境见于人类癌症。基因工程化的模型，如遗传工程小鼠含有的Kras和p53敲除中的致癌基因突变（保护团模型）2与KPC模型与YFP谱系示踪（在PKCY模型）3允许在immunocompete天然存在的肿瘤的研究NT小鼠。此外，在肿瘤微环境是不变的和更类似于见于人类肿瘤进展。不幸的是，肿瘤发展的时间是这些模型中，这使得它难以研究实验性疗法中的变量。此外，这些小鼠回交需要显著大量的时间和资金承诺，这并不总是可行的。最后，异种移植小鼠的PDA机型必要免疫功能低下小鼠，改变或缺失的肿瘤微环境。其结果是，在这些临床前模型中显示出实验性疗法的功效通常是在人类临床试验4不能再现。 这hemisplenectomy小鼠模型利用PANC02肿瘤细胞，这是一种高度致瘤性，甲基胆蒽诱导的胰腺肿瘤细胞的C57BL / 6小鼠5,6衍生线。此外，其他的PDA小鼠细胞系从KPC麦克风衍生E可在该模型中使用。 Schulick 等人以前开发的hemisplenectomy技术，创造了结肠癌转移7同系小鼠模型。这hemisplenectomy模型（ 图1），提供一致和平等的肿瘤接种在免疫小鼠贷款本身的新的治疗药物7-10调查。

<table><tbody><tr><td>Cell culture media and components</td><td></td><td></td><td>will vary depending on cell line</td></tr><tr><td>Phosphate Buffered Saline</td><td>Gibco by Life Technologies</td><td>10010-023</td><td></td></tr><tr><td>15 ml centrifuge tubes</td><td>Corning</td><td>430052</td><td></td></tr><tr><td>Curved Operating Scissor</td><td>Roboz Surgical Store</td><td>RS-6835</td><td></td></tr><tr><td>Micro Dissecting Graefe Forceps</td><td>Roboz Surgical Store</td><td>RS-5130</td><td></td></tr><tr><td>Needle holder (regular)</td><td>World Precision Instruments, Inc</td><td></td><td></td></tr><tr><td>3-0 or 4-0 suture</td><td></td><td></td><td>courtesy of dept of surgery, Johns Hopkins</td></tr><tr><td>Weck Horizon Open Ligating Clip Applier, small, angled</td><td>Teleflex</td><td>137085</td><td></td></tr><tr><td>Weck Horizon Open Ligating Clip Applier, medium, angled</td><td>Teleflex</td><td>237115</td><td></td></tr><tr><td>Weck Horizon medium ligating clips</td><td>Teleflex</td><td>002200</td><td></td></tr><tr><td>Weck Horizon small ligating clips</td><td>Teleflex</td><td>001200</td><td></td></tr><tr><td>Syringe, 1 cc, tb syringe, 3/8&quot; slip tip</td><td>Becton Dickinson</td><td>309625</td><td></td></tr><tr><td>Syringe, 1 cc, tb syringe, 5/8&quot; slip tip</td><td>Becton Dickinson</td><td>309597</td><td></td></tr><tr><td>9 mm Autoclip Applier</td><td>Mikron</td><td>427630</td><td></td></tr><tr><td>9 mm Autoclip</td><td>Becton Dickinson</td><td>427631</td><td></td></tr><tr><td>Heating pad</td><td>Sunbeam</td><td>CAT93</td><td></td></tr><tr><td>70% Ethanol</td><td></td><td></td><td>sold by numerous vendors</td></tr><tr><td>Ketamine Hydrochloride&amp;nbsp;</td><td>Hospira</td><td>22395DD</td><td></td></tr><tr><td>Xylazine hydrochloride</td><td>Sigma</td><td>X1251</td><td></td></tr></tbody></table>

a preclinical murine model of hepatic metastases

许多小鼠模型已经被开发，研究人类癌症和推进癌症治疗和发展的理解。在这里，临床前，鼠胰腺肿瘤肝转移通过hemispleen注入同系小鼠胰腺肿瘤细胞的模型描述。此模型模拟了许多在转移性疾病患者的肝的临床情况。小鼠持续开发在肝脏允许调查的转移过程中，实验性治疗试验和肿瘤免疫学研究转移。

PANC02肿瘤细胞注射到hemispleen（ 图1）在小鼠的100％形式肝转移，而如果正确地进行技术肺和腹膜转移都没有观察到。这种技术已在一百多个，独立的实验中使用PANC02细胞的小鼠被执行，并重复地，所有未治疗的小鼠死于与以下的hemisplenectomy过程（ 图2）30到60天之间的肝转移。要获取未处理和处理组之间的统计学意义，还需要每组10只。但是，这个数字将相对于所使用的细...

Watch this Scientific Journal Video about A Preclinical Murine Model of Hepatic Metastases at JoVE.com

A Preclinical Murine Model of Hepatic Metastases

通过hemispleen注射技术进行肝转移的临床前，小鼠模型。

肝转移的临床前小鼠模型

Numerous murine models have been developed to study human cancers and advance the understanding of cancer treatment and development. Here, a preclinical, ...

a-preclinical-murine-model-of-hepatic-metastases

Research

JoVE Journal

Medicine

28.5K 次观看.  The Johns Hopkins University School of Medicine. 通过hemispleen注射技术进行肝转移的临床前，小鼠模型。 

视频: A Preclinical Murine Model of Hepatic Metastases

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

Advanced Animal Model of Colorectal Metastasis in Liver: Imaging Techniques and Properties of Metastatic Clones

Patients with a limited number of hepatic metastases and slow rates of progression can be successfully treated with local treatment approaches1,2. However, little is known about the heterogeneity of liver metastases, and animal models capable of evaluating the development of individual metastatic colonies are needed. Here, we present an advanced model of hepatic metastases that provides the ability to quantitatively visualize the development of individual tumor clones in the liver and estimate their growth kinetics and colonization efficiency. We generated a panel of monoclonal derivatives of HCT116 human colorectal cancer cells stably labeled with luciferase and tdTomato and possessing different growth properties. With a splenic injection followed by a splenectomy, the majority of these clones are able to generate hepatic metastases, but with different frequencies of colonization and varying growth rates. Using the In Vivo&#160;Imaging System (IVIS), it is possible to visualize and quantify metastasis development with in vivo luminescent and ex vivo fluorescent imaging. In addition, Diffuse Luminescent Imaging Tomography (DLIT) provides a 3D distribution of liver metastases in vivo. Ex vivo fluorescent imaging of harvested livers provides quantitative measurements of individual hepatic metastatic colonies, allowing for the evaluation of the frequency of liver colonization and the growth kinetics of metastases. Since the model is similar to clinically observed liver metastases, it can serve as a modality for detecting genes associated with liver metastasis and for testing potential ablative or adjuvant treatments for liver metastatic disease.

The ability of metastatic clones to colonize distant sites depends on their proliferation capacity and/or their ability to survive in the host microenvironment without significant proliferation. Here, we present an animal model that allows quantitative visualization of both types of liver colonization by metastatic clones.

肝大肠癌转移的高级动物模型:成像技术和转移性克隆性质

Patients with a limited number of hepatic metastases and slow rates of progression can be successfully treated with local treatment approaches1,2. ...

癌症研究

Surgical Procedures and Methodology for a Preclinical Murine Model of De Novo Mammary Cancer Metastasis

A rate-limiting aspect of transgenic mouse models of mammary adenocarcinoma is that primary tumor burden in mammary tissue typically defines study end-points. Thus, studies focused on elucidating mechanisms of late-stage de novo metastasis are compromised, as are studies examining efficacy of anti-cancer therapies targeting mediators of metastasis in the adjuvant setting. Numerous murine mammary cancer models have been developed via targeted expression of dominant oncoproteins to mammary epithelial cells yielding models variably mimicking histopathologic and transcriptome-defined breast cancer subtypes common in women1. While much has been learned regarding the biology of mammary carcinogenesis with these models, their utility in identifying molecules regulating growth of late-stage metastasis are compromised as mice are typically euthanized at earlier time points due to significant primary tumor burden. Moreover, since a significant percentage of women diagnosed with breast cancer receive adjuvant therapy after surgical resection of primary tumors and prior to presence of detectable metastatic disease, preclinical models of de novo metastasis are urgently needed as platforms to evaluate new therapies aimed at targeting metastatic foci. To address these deficiencies, we developed a murine model of de novo mammary cancer metastasis, wherein primary mammary tumors are surgically resected, and metastatic foci subsequently develop over a 115 day post-surgical period. This long latency provides a tractable model to identify functionally significant regulators of metastatic progression in mice lacking primary tumor, as well as a model to evaluate preclinical therapeutic efficacy of agents aimed at blocking functionally significant molecules aiding metastatic tumor survival and growth.

Surgical Procedures and Methodology for a Preclinical Murine Model of De Novo Mammary Cancer Metastasis

Pre-clinical models evaluating adjuvant therapy targeting breast cancer metastasis are lacking. To address this, we developed a murine model of de novo pulmonary mammary adenocarcinoma metastasis, wherein therapies administered in the adjuvant setting (post surgical resection of primary tumors) can be evaluated for efficacy in impacting previously seeded pulmonary metastases.

临床前小鼠模型的外科手术和方法<em&gt; De Novo</em&gt;乳腺癌转移

A rate-limiting aspect of transgenic mouse models of mammary adenocarcinoma is that primary tumor burden in mammary tissue typically defines study ...

A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer

Breast cancer is the leading cause of cancer-related mortality in women worldwide. Liver metastasis is involved in upwards of 30% of cases with breast cancer metastasis, and results in poor outcomes with median survival rates of only 4.8 - 15 months. Current rodent models of breast cancer metastasis, including primary tumor cell xenograft and spontaneous tumor models, rarely metastasize to the liver. Intracardiac and intrasplenic injection models do result in liver metastases, however these models can be confounded by concomitant secondary-site metastasis, or by compromised immunity due to removal of the spleen to avoid tumor growth at the injection site. To address the need for improved liver metastasis models, a murine portal vein injection method that delivers tumor cells firstly and directly to the liver was developed. This model delivers tumor cells to the liver without complications of concurrent metastases in other organs or removal of the spleen. The optimized portal vein protocol employs small injection volumes of 5 - 10 &#956;l, &#8805; 32 gauge needles, and hemostatic gauze at the injection site to control for blood loss. The portal vein injection approach in Balb/c female mice using three syngeneic mammary tumor lines of varying metastatic potential was tested; high-metastatic 4T1 cells, moderate-metastatic D2A1 cells, and low-metastatic D2.OR cells. Concentrations of &#8804; 10,000 cells/injection results in a latency of ~ 20 - 40 days for development of liver metastases with the higher metastatic 4T1 and D2A1 lines, and &#62; 55 days for the less aggressive D2.OR line. This model represents an important tool to study breast cancer metastasis to the liver, and may be applicable to other cancers that frequently metastasize to the liver including colorectal and pancreatic adenocarcinomas.

A surgical procedure was developed to deliver mammary tumor cells to the murine liver via portal vein injection. This model permits investigation of late stages of liver metastasis in a fully immune competent host, including tumor cell extravasation, seeding, survival, and metastatic outgrowth in the liver.

门静脉注射模型来研究肝转移乳腺癌

Breast cancer is the leading cause of cancer-related mortality in women worldwide. Liver metastasis is involved in upwards of 30% of cases with breast ...

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).

在肝炎症和纤维化环境中产生的肝细胞癌的致癌肝细胞诱导正交小鼠模型

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

Murine Model of Metastatic Liver Tumors in the Setting of Ischemia Reperfusion Injury

Liver ischemia and reperfusion (I/R) injury, a common clinical challenge, remains an inevitable pathophysiological process that has been shown to induce multiple tissue and organ damage. Despite recent advances and therapeutic approaches, the overall morbidity has remained unsatisfactory especially in patients with underlying parenchymal abnormalities. In the context of aggressive cancer growth and metastasis, surgical I/R is suspected to be the promoter regulating tumor recurrence. This article aims to describe a clinically relevant murine model of liver I/R and colorectal liver metastasis. In doing so, we aim to assist other investigators in establishing and perfecting this model for their routine research practice to better understand the effects of liver I/R on promoting liver metastases.

We describe in detail a clinically relevant colorectal cancer liver metastases (CRLM) tumor model and the influence of liver ischemia reperfusion (I/R) in tumor growth and metastasis. This model can help to better understand the mechanisms underlying surgery-induced promotion of liver metastatic growth.

缺血再灌注损伤中转移性肝肿瘤的模样

Liver ischemia and reperfusion (I/R) injury, a common clinical challenge, remains an inevitable pathophysiological process that has been shown to induce ...

Portal Vein Injection of Colorectal Cancer Organoids to Study the Liver Metastasis Stroma

Hepatic metastasis of colorectal cancer (CRC) is a leading cause of cancer-related death. Cancer-associated fibroblasts (CAFs), a major component of the tumor microenvironment, play a crucial role in metastatic CRC progression and predict poor patient prognosis. However, there is a lack of satisfactory mouse models to study the crosstalk between metastatic cancer cells and CAFs. Here, we present a method to investigate how liver metastasis progression is regulated by the metastatic niche and possibly could be restrained by stroma-directed therapy. Portal vein injection of CRC organoids generated a desmoplastic reaction, which faithfully recapitulated the fibroblast-rich histology of human CRC liver metastases. This model was tissue-specific with a higher tumor burden in the liver when compared to an intra-splenic injection model, simplifying mouse survival analyses. By injecting luciferase-expressing tumor organoids, tumor growth kinetics could be monitored by in vivo imaging. Moreover, this preclinical model provides a useful platform to assess the efficacy of therapeutics targeting the tumor mesenchyme. We describe methods to examine whether adeno-associated virus-mediated delivery of a tumor-inhibiting stromal gene to hepatocytes could remodel the tumor microenvironment and improve mouse survival. This approach enables the development and assessment of novel therapeutic strategies to inhibit hepatic metastasis of CRC.

Portal vein injection of colorectal cancer (CRC) organoids generates stroma-rich liver metastasis. This mouse model of CRC hepatic metastasis represents a useful tool to study tumor-stroma interactions and develop novel stroma-directed therapeutics such as adeno-associated virus-mediated gene therapies.

门静脉注射结直肠癌类器官研究肝转移基质

Hepatic metastasis of colorectal cancer (CRC) is a leading cause of cancer-related death. Cancer-associated fibroblasts (CAFs), a major component of the ...

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  ...

Non-Invasive PET/MR Imaging in an Orthotopic Mouse Model of Hepatocellular Carcinoma

Preclinical experimental models of hepatocellular carcinoma (HCC) that recapitulate human disease represent an important tool to study tumorigenesis and evaluate novel therapeutic approaches. Non-invasive whole-body imaging using positron emission tomography (PET) provides critical insights into the in vivo characteristics of tissues at the molecular level in real-time. We present here a protocol for orthotopic HCC xenograft creation with and without hepatic artery ligation (HAL) to induce tumor hypoxia and the assessment of their tumor metabolism in vivo using [18F]Fluoromisonidazole ([18F]FMISO) and [18F]Fluorodeoxyglucose ([18F]FDG) PET/magnetic resonance (MR) imaging. Tumor hypoxia could be readily visualized using the hypoxia marker [18F]FMISO, and it was found that the [18F]FMISO uptake was higher in HCC mice that underwent HAL than in the non-HAL group, whereas [18F]FDG could not distinguish tumor hypoxia between the two groups. HAL tumors also displayed a higher level of hypoxia-inducible factor (HIF)-1&#945; expression in response to hypoxia. Quantification of HAL tumors showed a 2.3-fold increase in [18F]FMISO uptake based on the standardized value uptake (SUV) approach.

Here, we present a protocol to create orthotopic hepatocellular carcinoma xenografts with and without hepatic artery ligation and perform non-invasive positron emission tomography (PET) imaging of tumor hypoxia using [18F]Fluoromisonidazole ([18F]FMISO) and [18F]Fluorodeoxyglucose ([18F]FDG).

肝细胞癌原位小鼠模型中的无创PET/MR成像

Preclinical experimental models of hepatocellular carcinoma (HCC) that recapitulate human disease represent an important tool to study tumorigenesis and ...

A "Patient-Like" Orthotopic Syngeneic Mouse Model of Hepatocellular Carcinoma Metastasis

The majority of cancer-related deaths are caused by the metastasis of the cancer rather than the primary tumor itself. Yet, the underlying mechanisms of cancer metastasis are still unclear. Animal models are essential for elucidating the mechanisms and for evaluating novel strategies for the treatment of metastatic cancers. Here, an in-depth description of a &#8220;patient-like&#8221; orthotopic syngeneic mouse model for exploring the mechanisms of metastasis of solid organ tumors is provided. The survival surgical implantation of BNL 1ME A.7R.1 mouse hepatocellular carcinoma cells directly into the liver (the organ of origin) of the inbred wild-type immune competent laboratory mouse strain, BALB/c is described. The success and reproducibility of this methodology recommends it for widespread use in elucidating the biological mechanisms of solid organ cancer metastasis.

The metastatic spread of cancer is the major cause of cancer-related deaths. We provide an in-depth description of our survival surgery methodology for establishing a &#8220;patient-like&#8221; orthotopic syngeneic mouse model system for studying the mechanisms of metastasis in solid organ tumors.

"以病人为像"肝癌原位同源小鼠模型的癌转移

The majority of cancer-related deaths are caused by the metastasis of the cancer rather than the primary tumor itself. Yet, the underlying mechanisms of ...