Name: a syngeneic mouse model of metastatic renal cell carcinoma for quantitative and longitudinal assessment of preclinical therapies
Uploaded: 2017-04-12T14:00:00
Description: Watch this Scientific Journal Video about A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies at JoVE.com

这项工作是由美国国家癌症研究所（R15CA173657到AW和R01CA109446到TSG），西蒙斯癌症研究所（至AW），以及Minnestoa大学助学金爬上4肾脏癌症基金会（TSG到）的支持。我们感谢克丽斯廷·安德森博士与免疫援助。

以下方案描述用于诱导和监测实验原位肾肿瘤和任何潜在自发转移的生长的实验程序。下面的所有程序都是按照有关人性化的使用实验动物的体制政策和批准的程序进行。 1.细胞系的维护<ol><li>维持鼠肾腺癌细胞系的Renca，在的Roswell Park Memorial研究所（RPMI）1640培养基补充有10％胎牛血清（FCS），1％青霉素 - 链霉素，和各1mM的非必需氨基酸，L-谷氨酰胺的和丙酮酸钠（简称完全RPMI）。培养细...

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我们提出了一个原位RCC小鼠模型的协议。小鼠肾腺癌肿瘤细胞植入小鼠肾脏提供海上救援协调中心临床相关模型。该模型导致在肺中，这两者都是晚期RCC的标志的肾脏和远处转移中的原发肿瘤。本文中所呈现的描述是具体的在免疫活性Balb / c小鼠的的Renca细胞系。使用这种原位模型，我们已经表明的Renca肿瘤响应免疫，表明治疗性测试<sup class="xref...

肾细胞癌（RCC）占全世界大多数恶性肾肿瘤的和约3％所有成年恶性肿瘤的1，2。由于缺乏症状，误诊，和不足的筛选工具，用于RCC，患者几乎30％将呈现与转移性RCC（MRCC）在诊断时，与患者进展至转移期2 20-30％的额外。这些情况导致每年〜13500人死亡1，3。虽然早期检测和治疗原发性RCC的有所改善，RCC相关的死亡的速率持续增加，这表明转移性疾病是死亡3的主要原因。治疗发展RCC已经发展了与发现并实施有针对性的治疗和免疫治疗的最后十年。不幸的是，无进展surviv人与晚期病例总生存率仍远低于2年，大多数患者4，5，6。这些统计数据为保证进一步研究的识别和对RCC有效的治疗方法发展的需要。为了充分促进治疗性干预在一项针对mRCC，首先需要疾病的翻译相关的临床前模型。 相关的和一致的模型的发展概括晚期RCC人的条件应解决几个关键问题：1）是模型解剖相关; 2）是否肿瘤进展类似于人体病理学; 3）执行转移从原发肿瘤出现;及4）可原发性和转移性肿瘤进展随时间监测？根据治疗的类型被调查，小鼠RCC肿瘤细胞系，人肾细胞癌的肿瘤细胞系，和人RCC患者来源xenog筏可在免疫活性或免疫缺陷的小鼠中。具有完整和功能性免疫系统中的主机需要这些研究评估免疫疗法的一些方面中，需要使用来自Balb / c小鼠7的自发肾腺癌导出的充分描述的Renca细胞系。大多数研究注入RENCA细胞皮下（sc），其形成一个易于度量局部肿瘤，或静脉内（IV）到Balb / c小鼠，以产生实验性肺“转移” 8，9，10，11，12。的SC-植入的Renca肿瘤模型人RCC的使用具有许多限制，包括脉管系统13的不准确的神经支配，在微环境14，15，和缺乏器官/肿瘤细胞COMMUNIC差异通货膨胀13,16。此外，许多皮下肿瘤（特别的Renca）不会转移到远端器官，抑制这是一种常见的临床特征17事件的研究。为了研究mRCC的，RENCA细胞可以静脉注射以建立在RCC患者转移肺-主要位置肿瘤负荷。发起转移性肿瘤的静脉内注射的方法，然而，不允许的侦查如何，何时，或为什么细胞已经从初级器官（ 即，肾）到远端部位迁移。与原发性和转移性疾病明显在相同的动物模型是研究晚期疾病的进展和治疗是至关重要的，尤其是考虑到转移通常在这些患者中的死亡率的原因。 我们的实验室已开发海上救援协调中心的鼠模型，结合了所有上述功能。要建立公关imary，原位肿瘤，的Renca细胞直接植入到动物的透过半透明腹膜肾。在左侧面一个小切口允许脾（如地标）和左肾的可视化。使用小规格针，的Renca肿瘤细胞通过腹膜用于原位移植直接注射到肾脏。相比植入肾囊18的下方的Renca细胞的其它方法中，注入的这个方法允许更高的吞吐量，因为它是相当的非侵入性的，并不需要缝合，是一种低疼痛类的，而且是时间有效时实践。 这充分表征的模型的结果在注射肾再现的原发性肿瘤负担（〜99％的接受率），以及转移性肿瘤负荷于肺部。这种模式的优点显著包括它的同源性质，允许免疫治疗调查;其自发转移，以研究疾病的先进适用的;其原位移植，来模拟对疾病进展和治疗解剖的影响。旨在针对RCC的治疗会从这个模型的临床前开发过程中的利用率大大受益。

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			<td height="52" style="height:52px;width:88px;">Artificial tears ophthalmic ointment</td>
			<td style="width:88px;">Akorn</td>
			<td style="width:156px;">NDC 17478-162-35</td>
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		<tr height="52">
			<td height="52" style="height:52px;width:88px;">Vetbond Tissue Adhesive</td>
			<td style="width:88px;">3M</td>
			<td style="width:156px;">CBGBIW011019</td>
			<td></td>
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		<tr height="69">
			<td height="69" style="height:69px;width:88px;">Betadine Solution (Povidone-iodine, 5%)</td>
			<td style="width:88px;">Purdue Products, L.P.</td>
			<td style="width:156px;">NDC 67618-155-32</td>
			<td></td>
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			<td height="69" style="height:69px;width:88px;">0.25% Marcaine (bupivavaine HCL injection)</td>
			<td style="width:88px;">Hospira</td>
			<td style="width:156px;">0409-1587-50&#160;</td>
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			<td height="22" style="height:22px;width:88px;">Heating pad</td>
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			<td height="22" style="height:22px;width:88px;">Syringes</td>
			<td style="width:88px;">BD</td>
			<td style="width:156px;">309659</td>
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			<td height="22" style="height:22px;width:88px;">Gauze</td>
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			<td style="width:156px;">908291</td>
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			<td height="51" rowspan="2" style="height:51px;width:88px;">Ketamine</td>
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			<td rowspan="2" style="width:156px;">NDC 57319-609-02</td>
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			<td height="22" style="height:22px;width:88px;">Xylazine&#160;</td>
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			<td height="52" style="height:52px;width:88px;">Hank&#8217;s Balanced Salts</td>
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			<td height="22" style="height:22px;width:88px;">IVIS</td>
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			<td height="52" style="height:52px;width:88px;">D-Luciferin, Potassium Salt</td>
			<td style="width:88px;">GoldBio</td>
			<td style="width:156px;">LUCK-1G</td>
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			<td height="22" style="height:22px;width:88px;">India Ink</td>
			<td style="width:88px;">Chartpak Inc</td>
			<td style="width:156px;">44201</td>
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			<td height="22" style="height:22px;width:88px;">Scissors</td>
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			<td height="22" style="height:22px;width:88px;">Forceps</td>
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			<td height="69" style="height:69px;width:88px;">Sleeping Beauty (SB) transposon system</td>
			<td style="width:88px;">Neuromics</td>
			<td style="width:156px;">SBT0200</td>
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			<td height="22" style="height:22px;width:88px;">Renca</td>
			<td style="width:88px;">ATCC</td>
			<td style="width:156px;">CRL-2947</td>
			<td></td>
		</tr>
	</tbody>
</table>

a syngeneic mouse model of metastatic renal cell carcinoma for quantitative and longitudinal assessment of preclinical therapies

肾细胞癌（RCC）每年影响&gt; 60000人在美国，和RCC〜30％的患者在诊断时多发转移。转移性肾细胞癌（MRCC）是不治之症，与只有18个月的中位生存时间。基于免疫的干预（ 例如，干扰素（IFN）和白细胞介素（IL）-2）诱导的mRCC患者的一小部分持续反应，和多激酶抑制剂（ 例如，舒尼替尼或索拉非尼）或抗VEGF受体的单克隆抗体（单抗）是主要是治标不治本，因为完全缓解是罕见的。在目前的治疗对于患者mRCC的这些缺点提供的新颖的治疗方案的开发的理由。在新的疗法用于mRCC的临床前检测的关键部件是一个合适的动物模型。重演人的条件有益特征包括原发性肾肿瘤，肾肿瘤转移，和一个完整的免疫系统，以调查任何治疗驱动的免疫效：ř反应和肿瘤诱导的免疫抑制因子的形成。这份报告描述了具有所有这些特征的原位mRCC的小鼠模型。我们描述使用鼠标肾腺癌细胞系的Renca一个肾内注入技术，随后在肾（原发部位）肿瘤生长和肺（转移部位）的评估。

<html> RENCA细胞的成功植入会导致肿瘤的发展在肾脏和转移到小鼠肺。荷瘤和对侧肾脏切除后，湿组织重量（克）进行测定，以证实基于增加的重量（ 图1）的肿瘤负荷。 RENCA肿瘤可以通过免疫组化通过细胞角蛋白8和18染色（ 图2）来识别。对于纵向研究中，荧光素酶表达的Renca细胞系植入。使用体内成像系统（IVIS）来跟踪肿瘤负荷和对治疗?...

Watch this Scientific Journal Video about A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies at JoVE.com

A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies

在免疫活性小鼠肾细胞癌的原位模型的实现，得到研究者通过初级肾肿瘤和肺转移瘤的在相同的动物的存在所定义的临床相关系统。该系统可用于临床前测试各种体内治疗。

转移性的型号同源小鼠肾细胞癌的临床前疗法的定量和纵向评估

Renal cell carcinoma (RCC) affects &#62; 60,000 people in the United States annually, and ~ 30% of RCC patients have multiple metastases at the time of ...

Research

JoVE Journal

Cancer Research

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

开发和维护的临床前患者来源的肿瘤异种移植模型为新的抗癌疗法的调查

Patient derived tumor xenograft (PDTX) models provide a necessary platform in facilitating anti-cancer drug development prior to human trials. Human tumor ...

科研

癌症研究

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

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

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 ...

The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia

结肠-26癌荷瘤小鼠为癌症恶病质的研究模型

Cancer cachexia is the progressive loss of skeletal muscle mass and adipose tissue, negative nitrogen balance, anorexia, fatigue, inflammation, and ...

A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma

在头颈部鳞状细胞癌的神经浸润模型

Perineural invasion (PNI) is found in approximately 40% of head and neck squamous cell carcinomas (HNSCC). Despite multimodal treatment with surgery, ...

Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma

基于球形的头颈部鳞状细胞癌3D 细胞培养模型的治疗试验

Current treatment options for advanced and recurrent head and neck squamous cell carcinoma (HNSCC) enclose radiation and chemo-radiation approaches with ...

A Syngeneic Pancreatic Cancer Mouse Model to Study the Effects of Irreversible Electroporation

自体胰腺癌小鼠模型研究不可逆电穿孔的影响

Pancreatic cancer (PC), a disease which kills approximately 40,000 patients each year in the US, has successfully evaded several therapeutic approaches ...

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

雄激素依赖性和去势抗性前列腺癌的荧光自体小鼠模型

Orthotopic tumor modeling is a valuable tool for pre-clinical prostate cancer research, as it has multiple advantages over both subcutaneous and ...

A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells

同源小鼠 B 细胞淋巴瘤模型对 CD19 轿车 T 细胞的临床前评价

The astonishing clinical success of CD19 chimeric antigen receptor (CAR) T-cell therapy has led to the approval of two second generation chimeric antigen ...

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment

小鼠鳞状细胞细胞的肿瘤免疫分析及治疗反应评价

Head and neck squamous cell carcinoma (HNSCC) is a debilitating and deadly disease with a high prevalence of recurrence and treatment failure. To develop ...

Micromanipulation of Circulating Tumor Cells for Downstream Molecular Analysis and Metastatic Potential Assessment

循环肿瘤细胞的微操作, 用于下游分子分析和转移电位评估

Blood-borne metastasis accounts for&#160;most cancer-related deaths and involves circulating tumor cells (CTCs) that are successful in establishing new ...