The authors have no acknowledgements.

与EBUS引导顺铂治疗所有患者的数据进行了审查。在佛罗里达大学的机构审查委员会批准了这项研究（＃IRB201400823）。所有数据收集前瞻性和回顾性分析。使用下面的入选标准。 1.病人选择<ol><li>谁拥有活检证实的非小细胞肺癌（NSCLC）或小细胞肺癌（SCLC），并有病理确诊复发的18和80岁之间的患者选择。报名谁收到至少50 GY辐射到肺门和纵隔结构为6个月或更长的患者。包括复发患者仅限于肺门，纵膈，支气管周围和结构（淋巴结肿大，结节，群众）通过EBUS和远处转移访问。 </li><li>目前所有此类病人多学科胸部肿瘤肿瘤委员会以及与在继续取得共识tratumoral顺铂由于缺乏其它局部治疗选择。着手EBUS引导ITC的决定应该是制度性胸腔肿瘤肿瘤委员会的联合推荐。 </li></ol> 2.支气管超声（EBUS）引导下顺铂注射液<ol><li>使用凸探针EBUS，其具有肺门，纵隔和ITC支气管周围结构的一个内置的超声波探头上的柔性支气管镜，使实时可视化。 </li><li>确保患者口腔的食物和液体弃权事先的程序至少6小时。 </li><li>创建在1毫克/毫升的带的每个会话40毫克最大剂量的浓度的含水氯氨铂溶液，根据先前发表的文献9,10。刚好在使用前溶解在0.9％NaCl溶液冻干氯氨铂细粉。 </li><li>给予地塞米松10mg和8毫克的恩丹西酮静脉注射的开始程序的宁以防止恶心。 </li><li>使用咪唑安定和静脉注射芬太尼进行清醒镇静的程序（IV）。在5mL之前的步骤4％利多卡因雾化的形式使用局部麻醉。 </li><li>与2毫克咪达唑仑和芬太尼50微克的静脉注射开始了。重新评估患者每1-2分钟，并得到额外的1毫克咪达唑仑和25微克芬太尼以实现和保持清醒镇静（一个最小压下意识使得患者能够连续地和独立地保持气道通畅，保留保护性反射，并保持响应口头命令和物理刺激）。不要超过最大允许剂量的芬太尼和咪达唑仑，200微克和10毫克，分别。 </li><li>使用标准的监测，包括连续3导联心电图监测心脏率，连续脉搏血氧饱和度，呼吸频率测量。提供本地ANESThesia并根据需要补充氧气 。 </li><li>通过在呼吸道声带前进的范围。识别和定位靶病变。 </li><li>打开EBUS处理器上，并在使用1-2毫升生理盐水的范围的末端充气气球。弯曲整个气道壁的范围和定位病灶。病变的位置将取决于CT / PET表现，但一些常见的部位的包括隆突区域，右侧和左侧气管区域，和左，右肺门区域。 </li><li>部署容纳在鞘通过范围的工作通道的22克EBUS针和在适当的位置锁定。 注意:虽然有对注射部位没有精确外科坐标，一些常用处理的部位的包括隆突（内侧在左和右主支气管的交界处），在右气管（横向在右主支气管，只是上面的右肺上叶口），左侧气管旁（在远端气管的接合处和主动脉弓和左肺动脉之间的左主），右肺门（横向在近端支气管中间型，右上叶开口下方），和左肺门（在左上叶交界处和左下叶支气管）。 </li><li>下实时超声引导，穿刺气管支气管壁和放置针在靶病变。针内移除管心针和注射顺铂进入病灶10毫升（1毫克/顺铂毫升）一次。缩回片内的针。 </li><li>对待每第四讲刺在不同的位置每个病变，以促进整个药物注射。注射10毫克每穿刺顺铂。 </li><li>治疗一到每个会话两支病变。如果一个以上的病变每个会话处理，注入每个站点与20mg顺铂，每会话不超过40毫克总剂量。 </li><li>从worki取出针范围的纳克通道。 </li><li>吸力从远端气道的任何其他药物并取出支气管镜。 </li><li>允许患者以恢复按照医院的协议和放电它们在同一天。 </li><li>重复顺铂注射（步骤2.7-2.13），每周一次，共4周（在天1，8，15，和22）。 注:一旦治疗，特定的损害不应该被视为在随后的遭遇与ITC复治。 </li></ol> 3.后喷射<ol><li>评估由后续胸部计算机断层扫描（CT）或正电子发射断层扫描（PET / CT）的响应中的最后一个疗程后8-12周进行扫描。定义局部复发于治疗部位复发和局部复发如纵隔，肺门复发，或锁骨上窝。 </li></ol>

<ol>
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The authors have nothing to disclose.

<html>我们的手稿集中在肺癌纵隔孤立和肺门复发的管理病人谁更辐射是不是一种选择。 IMHR的发病率约为9％11。不同的治疗方案已经尝试在这些患者中，包括姑息性化疗，更多的外照射放疗，或支持治疗和监测。在我们的机构，我们将这些患者经纤支镜引导下肿瘤内顺铂。 出现了在肿瘤内化疗和免疫过去几年越来越感兴趣。之一的注入化疗剂进入肿瘤块的潜...

肺癌是所有癌症相关死亡的5男女双方，占全球1最常见的癌症。它有0.87 1，2病死率。初次治疗后复发占患者死亡人数最多肺癌。复发性肺癌的治疗选择是有限的。复发性肺癌也导致显著损害生活质量和护理人员显著倦怠并且需要额外的支持治疗，从而会降低接受和容忍的可能性进一步干预3。 NSCLC患者近30％有辐射4后局部复发。对这些患者的治疗选择是有限的，包括全身化疗，其具有仅10％的5，6的客观响应率。虽然重复胸部放疗是可行的，它已被主要研究姑息目的，缓解症状，并没有被用于疾病缓解3。 在我们的机构，孤立纵隔及肺门复发（IMHR）通过支气管镜访问的所有患者均与支气管内超声（EBUS）引导下治疗顺铂支气管内注射（ITC）。全身化疗和/或体外放射治疗（EBRT）并行处理被允许按照所述处理肿瘤学家"酌情。这份手稿突出了安全性，有效性，可行性，并在我们的机构所使用的协议的详细方法。

<table border="0" cellpadding="0" cellspacing="0" width="261">
	<tbody>
		<tr height="20">
			<td colspan="2" height="20" style="height:20px;width:261px;">Bronchoscope</td>
		</tr>
		<tr height="20">
			<td colspan="2" height="20" style="height:20px;">22 Guage olympus EBUS needle</td>
		</tr>
		<tr height="20">
			<td colspan="2" height="20" style="height:20px;">40 g of cisplatin in 40 mls of normal saline</td>
		</tr>
	</tbody>
</table>

endobronchial ultrasound-guided intratumoral injection of cisplatin for the treatment of isolated mediastinal recurrence of lung cancer

患者孤立肺门以下体外放射治疗（EBRT）纵隔复发（IMHR）肺癌是常见的。这些患者没有太多的治疗方案，并且通常提供姑息性化疗或最佳支持治疗。支气管内超声（EBUS）引导下顺铂瘤内注射（ITC）是这些患者的新方法。该过程下清醒镇静进行。病变位于使用EBUS支气管镜，和22号针头EBUS通过范围的工作通道先进，锁定到位。在超声引导下，气管支气管树的壁被刺穿并且针移入目标病变。然后将针管心针被移除，顺铂（40毫克/ 40毫升）注射到病灶。一到两个站点每个会话处理。该过程的细节将在纸的协议部分中描述。在我们中心，50个站点中36例患者接受治疗（男性19例，女性17例）。我们的队列的平均年龄为61.9±8.5年。我们对35例患者和41位点进行最终的分析。 24/35（69％）有完全或部分响应（应答），而11/35（31％）具有稳定或进行性疾病（无应答）。总体而言，生存在我们组为8个月（6-11个月95％CI），与谁回答具有比谁没有的那些显著更好地生存的病人。

该反应是由后续成像治疗后8-12周进行测量。响应被列为完全缓解（CR），部分缓解（PR），稳定疾病（SD），进展性疾病（PD）或不能根据RECIST 1.1标准8来评估响应。与CR和PR患者被认为反应，和其他人被列为无反应。次要结果基于肿瘤组织学，复发的大小，和并发的全身治疗包括响应。也分析了协议的副作用和可行性。 <p class="jove_content" fo:keep-together.wit...

Watch this Scientific Journal Video about Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer at JoVE.com

Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer

The management of isolated recurrent lung cancer in a previously-irradiated field is challenging. Here, we describe an endobronchial ultrasound (EBUS)-guided cisplatin injection for the management of patients with localized lung cancer recurrence in a previously-radiated field.

支气管内超声引导下顺铂瘤内注射对肺癌纵隔孤立复发的治疗

Isolated hilar and mediastinal recurrence (IMHR) following external beam radiation therapy (EBRT) in patients with lung cancer is common. These patients ...

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Cancer Research

10.4K 次观看.  University of Florida College of Medicine. The management of isolated recurrent lung cancer in a previously-irradiated field is challenging. Here, we describe an endobronchial ultrasound (EBUS)-guided cisplatin injection for the management of patients with localized lung cancer recurrence in a previously-radiated field. 

视频: Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer

Operating Procedures of the Electrochemotherapy for Treatment of Tumor in Dogs and Cats

Electrochemotherapy (ECT) is a local approach which is used for treating solid tumors of different histologies. Its mechanism is based on cell membrane permeabilization by means of &#34;electroporation&#34;. To achieve the &#34;electroporation&#34; of the cells, electric pulses are generated by a generator and delivered to the target tissue by the use of electrodes. Electroporation is a physical method which is used to introduce molecules, like cytostatic drugs, into the cells that could not pass the cell membrane on their own. In electrochemotherapy, currently, cisplatin and bleomycin are clinically used. Electrochemotherapy antitumor effectiveness is high, for example up to 100% complete response of canine mast cell tumors smaller than 2 cm3 was achieved. Additionally, electrochemotherapy can be used for the treatment of inoperable tumors. One of the important characteristics of electrochemotherapy is that it can be effective as a one-time treatment only. However, in the case of failure or partial tumor response it can be repeated several times with equal or improved effectiveness. Electrochemotherapy is already a standard treatment for cutaneous and subcutaneous tumors of various histologies in human and veterinary oncology. Furthermore, several clinical studies exploiting electrochemotherapy for deep-seated tumors are on-going.

Electrochemotherapy is the local treatment of solid tumors. The main mechanism is electroporation-mediated permeabilization of the tumor cells' membrane which enables increased internalization of cytostatics like bleomycin and cisplatin. Thus, antitumor effectiveness is potentiated at the site of the application of electric pulses to the tumors.

在电化学疗法的操作程序在肿瘤治疗中的狗和猫

Electrochemotherapy (ECT) is a local approach which is used for treating solid tumors of different histologies. Its mechanism is based on cell membrane ...

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癌症研究

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues

Metastasis is the major cause of cancer death. The role of circulating tumor cells (CTCs) in promoting cancer metastasis, in which lung colonization by CTCs critically contributes to early lung metastatic processes, has been vigorously investigated. As such, animal models are the only approach that captures the full systemic process of metastasis. Given that problems occur in previous experimental designs for examining the contributions of CTCs to blood vessel extravasation, we established an in vivo lung colonization assay in which a long-term-fluorescence cell-tracer, carboxyfluorescein succinimidyl ester (CFSE), was used to label suspended tumor cells and lung perfusion was performed to clear non-specifically trapped CTCs prior to lung removal, confocal imaging, and quantification. Polymeric fibronectin (polyFN) assembled on CTC surfaces has been found to mediate lung colonization in the final establishment of metastatic tumor tissues. Here, to specifically test the requirement of polyFN assembly on CTCs for lung colonization and extravasation, we performed short term lung colonization assays in which suspended Lewis lung carcinoma cells (LLCs) stably expressing FN-shRNA (shFN) or scramble-shRNA (shScr) and pre-labeled with 20 &#956;M of CFSE were intravenously inoculated into C57BL/6 mice. We successfully demonstrated that the abilities of shFN LLC cells to colonize the mouse lungs were significantly diminished in comparison to shScr LLC cells. Therefore, this short-term methodology may be widely applied to specifically demonstrate the ability of CTCs within the circulation to colonize the lungs.

An animal model is needed to decipher the role of circulating tumor cells (CTCs) in promoting lung colonization during cancer metastasis. Here, we established and successfully performed an in vivo assay to specifically test the requirement of polymeric fibronectin (polyFN) assembly on CTCs for lung colonization.

肺定植法在肺部组织循环肿瘤细胞可视化中的建立

Metastasis is the major cause of cancer death. The role of circulating tumor cells (CTCs) in promoting cancer metastasis, in which lung colonization by ...

Utilization of Ultrasound Guided Tissue-directed Cellular Implantation for the Establishment of Biologically Relevant Metastatic Tumor Xenografts

Preclinical testing of anticancer therapies relies on relevant xenograft models that mimic the innate tendencies of cancer. Advantages of standard subcutaneous flank models include procedural ease and the ability to monitor tumor progression and response without invasive imaging. Such models are often inconsistent in translational clinical trials and have limited biologically relevant characteristics with low proclivity to produce metastasis, as there is a lack of a native microenvironment. In comparison, orthotopic xenograft models at native tumor sites have been shown to mimic the tumor microenvironment and replicate important disease characteristics such as distant metastatic spread. These models often require tedious surgical procedures with prolonged anesthetic time and recovery periods. To address this, cancer researchers have recently utilized ultrasound-guided injection techniques to establish cancer xenograft models for preclinical experiments, which allows for rapid and reliable establishment of tissue-directed murine models. Ultrasound visualization also provides a noninvasive method for longitudinal assessment of tumor engraftment and growth. Here, we describe the method for ultrasound-guided injection of cancer cells, utilizing the adrenal gland for NB and renal sub capsule for ES. This minimally invasive approach overcomes tedious open surgery implantation of cancer cells in tissue-specific locations for growth and metastasis, and abates morbid recovery periods. We describe the utilization of both established cell lines and patient derived cell lines for orthotopic injection. Pre-made commercial kits are available for tumor dissociation and luciferase tagging of cells. Injection of cell suspension using image-guidance provides a minimally invasive and reproducible platform for the creation of preclinical models. This method is utilized to create reliable preclinical models for other cancers such as bladder, liver and pancreas exemplifying its untapped potential for numerous cancer models.

Here, we present a protocol to utilize ultrasound-guided injection of neuroblastoma (NB) and Ewing's sarcoma (ES) cells (established cell lines and patient-derived tumor cells) at biologically relevant sites to create reliable preclinical models for cancer research.

超声引导组织定向细胞植入术在生物学相关转移性肿瘤移植中的应用

Preclinical testing of anticancer therapies relies on relevant xenograft models that mimic the innate tendencies of cancer. Advantages of standard ...

Evaluation of the Feasibility, Safety, and Accuracy of an Intraoperative High-intensity Focused Ultrasound Device for Treating Liver Metastases

Today, the only potentially curative option in patients with colorectal liver metastases is surgery. However, liver resection is feasible in less than 20% of patients. Surgery has been widely used in association with radiofrequency, cryotherapy, or microwaves to expand the number of treatments performed with a curative intent. Nevertheless, several limitations have been documented when using these techniques (i.e., a traumatic puncture of the parenchyma, a limited size of lesions, and an inability to monitor the treatment in real-time).High-intensity focused ultrasound (HIFU) technology can achieve precise ablations of biological tissues without incisions or radiation. Current HIFU devices are based on an extracorporeal approach with limited access to the liver. We have developed a HIFU device designed for intraoperative use. The use of a toroidal transducer enables an ablation rate (10 cm3&#183;min-1) higher than any other treatment and is independent of perfusion.
The feasibility, safety, and accuracy of intraoperative HIFU ablation were evaluated during an ablate-and-resect prospective study. This clinical phase I and IIa study was performed in patients undergoing hepatectomy for liver metastases. The HIFU treatment was performed on healthy tissue scheduled for resection.Liver metastases measuring less than 20 mm will be targeted during phase IIb (currently ongoing). This set-up allows the real-time evaluation of HIFU ablation while protecting participating patients from any adverse effects related to this new technique.
Fifteen patients were included in phase I&#8211;IIa and 30 HIFU ablations were safely created within 40 s and with a precision of 1&#8211;2 mm. The average dimensions of the HIFU ablations were 27.5 x 21.0 mm2, corresponding to a volume of approximately 7.5 cm3. The aim of the ongoing phase IIb is to ablate metastases of less than 20 mm in diameter with a 5 mm margin.

Here, we present an ablate-and-resect prospective study to evaluate the feasibility, safety, and accuracy of intraoperative high-intensity focused ultrasound ablation in patients undergoing hepatectomy for liver metastases.

术中高强度聚焦超声装置治疗肝转移的可行性、安全性和准确性评价

Today, the only potentially curative option in patients with colorectal liver metastases is surgery. However, liver resection is feasible in less than 20% ...

Elastic Staining on Paraffin-embedded Slides of pT3N0M0 Gastric Cancer Tissue

The elastic lamina, which is usually located in the sub-mesothelial layer, adjacent to the peritoneum mesothelial cells, is amphiphilic on hematoxylin and eosin (H&amp;E) staining but can be visualized through elastic staining. One of the important benefits of elastic staining is that it makes it easy to determine whether tumor cells have invaded beyond the elastic lamina. This helps in examining the extent of peritoneal surface invasion, thereby distinguishing the pT3 and pT4 stages in gastrointestinal cancer. In this study, we present a protocol to identify elastic fibers in the formalin-fixed, paraffin-embedded pT3N0M0 gastric cancer tissue sections. We prepare 5-&#181;m paraffin sections fixed on slides, and then all the slides are deparaffinated and rehydrated during the staining procedure. Subsequently, all the sections are oxidized by potassium permanganate, bleached by oxalic acid, stained by elastic staining, and counterstained by Van Gieson's. Finally, we examine the effect of staining; elastic lamina is stained blue-black and collagen fibers are stained red, while the cancer cells are stained in varying shades of yellow. We also describe in detail the methods used for determining the positional relationship between cancer cells and elastic lamina. This method is simple, low-cost, and widely applicable in the identification of peritoneal surface invasion in gastrointestinal cancer because of its outstanding selectivity for elastic fibers and authentic results.

Here, we present a protocol of elastic staining to identify elastic fibers in pT3N0M0 gastric cancer tissues on formalin-fixed, paraffin-embedded sections. Subsequently, we describe a method to determine whether tumor cells invade beyond the elastic lamina.

pT3N0M0 胃癌组织石蜡嵌入幻灯片上的弹性染色

The elastic lamina, which is usually located in the sub-mesothelial layer, adjacent to the peritoneum mesothelial cells, is amphiphilic on hematoxylin and ...

Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma

The recent success of immune checkpoint blockade in melanoma and lung adenocarcinoma has galvanized the field of immuno-oncology as well as revealed the limitations of current treatments, as the majority of patients do not respond to immunotherapy. Development of accurate preclinical models to quickly identify novel and effective therapeutic combinations are critical to address this unmet clinical need. Pancreatic ductal adenocarcinoma (PDA) is a canonical example of an immune checkpoint blockade resistant tumor with only 2% of patients responding to immunotherapy. The genetically engineered KrasG12D+/-;Trp53R172H+/-;Pdx-1 Cre (KPC) mouse model of PDA recapitulates human disease and is a valuable tool for assessing therapies for immunotherapy resistant in the preclinical setting, but time to tumor onset is highly variable. Surgical orthotopic tumor implantation models of PDA maintain the immunobiological hallmarks of the KPC tissue-specific tumor microenvironment (TME) but require a time-intensive procedure and introduce aberrant inflammation. Here, we use an ultrasound-guided orthotopic tumor implantation model (UG-OTIM) to non-invasively inject KPC-derived PDA cell lines directly into the mouse pancreas. UG-OTIM tumors grow in the endogenous tissue site, faithfully recapitulate histological features of the PDA TME, and reach enrollment-sized tumors for preclinical studies by four weeks after injection with minimal seeding on the peritoneal wall. The UG-OTIM system described here is a rapid and reproducible tumor model that may allow for high throughput analysis of novel therapeutic combinations in the murine PDA TME.

We describe a protocol for the ultrasound guided implantation of murine-derived pancreatic ductal adenocarcinoma cell lines directly into the native tumor site. This approach resulted in pancreatic tumors detectable by ultrasound scanning within 2-4 weeks of injection, and significantly reduced the proportion tumor cell seeding on the peritoneal wall as compared to surgical orthotopic implantation.

毛尿胰腺腺腺腺癌超声引导正射植入

The recent success of immune checkpoint blockade in melanoma and lung adenocarcinoma has galvanized the field of immuno-oncology as well as revealed the ...

Perfusion and Inflation of the Mouse Lung for Tumor Histology

The ability to evaluate lung histology is critical for the fields of lung cancer research and cancer metastasis. It is equally important to perform necropsies rapidly and efficiently from studies without sacrificing the quality of the tissues procured. The goal of this protocol is to present a method to rapidly perfuse, inflate, and fix mouse lungs for downstream histological analysis. This method does not standardize lung inflation; thus, it does not require any special procedures or equipment and instead simply instills fixative directly through the trachea following perfusion through the heart. This allows for sufficient estimation of tumor size, histology, and scoring. This also allows for the collection of frozen tissue prior to lung tissue fixation. This method is limited in that it does not allow for later morphometric quantification of the lung; however, it is more than sufficient for lung tumor analysis from genetically engineered mouse models (GEMMs), syngeneic models, as well as xenograft tumor and metastasis studies.

The purpose of this method is to present a simple and efficient method for the perfusion, inflation, and fixation of mouse lungs for the examination of lung tumor pathology and evaluation of metastases to the lung.

肿瘤病理学鼠肺的灌注和膨胀

The ability to evaluate lung histology is critical for the fields of lung cancer research and cancer metastasis. It is equally important to perform ...

Pathological Analysis of Lung Metastasis Following Lateral Tail-Vein Injection of Tumor Cells

Metastasis, the primary cause of morbidity and mortality for most cancer patients, can be challenging to model preclinically in mice. Few spontaneous metastasis models are available. Thus, the experimental metastasis model involving tail-vein injection of suitable cell lines is a mainstay of metastasis research. When cancer cells are injected into the lateral tail-vein, the lung is their preferred site of colonization. A potential limitation of this technique is the accurate quantification of the metastatic lung tumor burden. While some investigators count macrometastases of a pre-defined size and/or include micrometastases following sectioning of tissue, others determine the area of metastatic lesions relative to normal tissue area. Both of these quantification methods can be exceedingly difficult when the metastatic burden is high. Herein, we demonstrate an intravenous injection model of lung metastasis followed by an advanced method for quantifying metastatic tumor burden using image analysis software. This process allows for investigation of multiple end-point parameters, including average metastasis size, total number of metastases, and total metastasis area, to provide a comprehensive analysis. Furthermore, this method has been reviewed by a veterinary pathologist board-certified by the American College of Veterinary Pathologists (SEK) to ensure accuracy.

Intravenous injection of cancer cells is often used in metastasis research, but the metastatic tumor burden can be difficult to analyze. Herein, we demonstrate a tail-vein injection model of metastasis and include a novel approach to analyze the resulting metastatic lung tumor burden.

肿瘤细胞外侧尾静脉注射后肺转移的病理分析

Metastasis, the primary cause of morbidity and mortality for most cancer patients, can be challenging to model preclinically in mice. Few spontaneous ...

Modeling Brain Metastases Through Intracranial Injection and Magnetic Resonance Imaging

Metastatic spread of cancer is an unfortunate consequence of disease progression, aggressive cancer subtypes, and/or late diagnosis. Brain metastases are particularly devastating, difficult to treat, and confer a poor prognosis. While the precise incidence of brain metastases in the United States remains hard to estimate, it is likely to increase as extracranial therapies continue to become more efficacious in treating cancer. Thus, it is necessary to identify and develop novel therapeutic approaches to treat metastasis at this site. To this end, intracranial injection of cancer cells has become a well-established method in which to model brain metastasis. Previously, the inability to directly measure tumor growth has been a technical hindrance to this model; however, increasing availability and quality of small animal imaging modalities, such as magnetic resonance imaging (MRI), are vastly improving the ability to monitor tumor growth over time and infer changes within the brain during the experimental period. Herein, intracranial injection of murine mammary tumor cells into immunocompetent mice followed by MRI is demonstrated. The presented injection approach utilizes isoflurane anesthesia and a stereotactic setup with a digitally controlled, automated drill and needle injection to enhance precision, and reduce technical error. MRI is measured over time using a 9.4 Tesla instrument in The Ohio State University James Comprehensive Cancer Center Small Animal Imaging Shared Resource. Tumor volume measurements are demonstrated at each time point through use of ImageJ. Overall, this intracranial injection approach allows for precise injection, day-to-day monitoring, and accurate tumor volume measurements, which combined greatly enhance the utility of this model system to test novel hypotheses on the drivers of brain metastases.

Intracranial brain metastasis modeling is complicated by an inability to monitor tumor size and response to treatment with precise and timely methods. The presented methodology couples intracranial tumor injection with magnetic resonance imaging analysis, which when combined, cultivates precise and consistent injections, enhanced animal monitoring, and accurate tumor volume measurements.

通过颅内注射和磁共振成像对大脑转移进行建模

Metastatic spread of cancer is an unfortunate consequence of disease progression, aggressive cancer subtypes, and/or late diagnosis. Brain metastases are ...

Modeling Brain Metastasis Via Tail-Vein Injection of Inflammatory Breast Cancer Cells

Metastatic spread to the brain is a common and devastating manifestation of many types of cancer. In the United States alone, about 200,000 patients are diagnosed with brain metastases each year. Significant progress has been made in improving survival outcomes for patients with primary breast cancer and systemic malignancies; however, the dismal prognosis for patients with clinical brain metastases highlights the urgent need to develop novel therapeutic agents and strategies against this deadly disease. The lack of suitable experimental models has been one of the major hurdles impeding advancement of our understanding of brain metastasis biology and treatment. Herein, we describe a xenograft mouse model of brain metastasis generated via tail-vein injection of an endogenously HER2-amplified cell line derived from inflammatory breast cancer (IBC), a rare and aggressive form of breast cancer. Cells were labeled with firefly luciferase and green fluorescence protein to monitor brain metastasis, and quantified metastatic burden by bioluminescence imaging, fluorescent stereomicroscopy, and histologic evaluation. Mice robustly and consistently develop brain metastases, allowing investigation of key mediators in the metastatic process and the development of preclinical testing of new treatment strategies.

We describe a xenograft mouse model of breast cancer brain metastasis generated via tail-vein injection of an endogenously HER2-amplified inflammatory breast cancer cell line.

通过炎症性乳腺癌细胞的尾静脉注射模拟脑转移

Metastatic spread to the brain is a common and devastating manifestation of many types of cancer. In the United States alone, about 200,000 patients are ...