The authors have no acknowledgements.

EBUSガイド下シスプラチンで処理された全ての患者のデータを検討しました。フロリダ大学の施設内倫理委員会は、この研究（＃IRB201400823）を承認しました。すべてのデータは、プロスペクティブに収集し、遡及的に分析しました。下記の登録基準を使用してください。 1.患者の選択<ol><li>生検で確認された非小細胞肺癌（NSCLC）、または小細胞肺癌（SCLC）を有しており、病理学的に確認された再発を有する18から80歳の間で選択した患者。 6ヶ月以上肺門および縦隔構造に放射線の少なくとも50 GYを受けた患者を登録します。 EBUSおよび遠隔転移を介してアクセス可能な肺門、縦隔に限定再発した患者、および気管支周囲の構造（リンパ節、結節、および大衆）が挙げられます。 </li><li>学際的な胸部腫瘍学腫瘍ボードにすべてのそのような患者を提示し、中を進める上でのコンセンサスを得ますローカライズされた他の治療法の選択肢が不足しているためtratumoralシスプラチン。 EBUSガイド下ITCを続行するという決定は、機関胸部腫瘍学腫瘍ボードの共同勧告すべきです。 </li></ol> 2.気管支内超音波（EBUS）はシスプラチン注射を-guided <ol><li>柔軟な気管支鏡に超音波プローブを内蔵し、肺門、縦隔、およびITCのための気管支周囲構造のリアルタイム可視化を可能にした凸プローブEBUSを、使用してください。 </li><li>患者は手順の前に、少なくとも6時間、経口食品や流体控えることを確認してください。 </li><li>以前に発表された文献9、10に基づいて、セッションごとに40mgの最大用量での1mg / mLの濃度で水性シスプラチンソリューションを作成します。使用直前に、0.9％NaCl溶液中で凍結乾燥されたシスプラチン粉末を溶解します。 </li><li>開始で静脈内デキサメタゾンを10mgおよびオンダンセトロンの8 mgを得吐き気を防止するための手順の寧。 </li><li>静脈内ミダゾラムとフェンタニル（IV）を使用して、意識下鎮静を使用して手順を実行します。手続きの前に4％のリドカイン噴霧の5ミリリットルの形で局所麻酔を使用してください。 </li><li>ミダゾラム2mgのフェンタニル50μgののIV注射から始めます。 、患者ごとに1〜2分を再評価し、追加1mgのミダゾラムと意識下鎮静を達成し、維持するために、25μgのフェンタニルボーラス（患者が継続的かつ独立して特許気道を維持することができるように、最小限に落ち込ん意識を与え、保護反射を保持そして、口頭コマンドや物理的刺激）に応答残ります。それぞれ、フェンタニルおよびミダゾラム、200μgのおよび10mgの最大許容用量を超えないようにしてください。 </li><li>心拍数を監視し、連続3誘導心電図、連続パルスオキシメトリー、および呼吸数の測定を含む、標準的な監視を使用してください。ローカルANESTを提供hesia、必要に応じて補足O 2。 </li><li>気道における声帯を通ってスコープを進めます。特定し、標的病変を見つけます。 </li><li> EBUSプロセッサの電源をオンにし、通常の生理食塩水の1-2ミリリットルを使用してスコープの先端にバルーンを膨らませます。気道壁全体に範囲をFlexおよび病変を見つけます。病変の位置は、CT / PET所見に依存するが、一般的なサイトのいくつかはsubcarinalエリア、左右の傍気管エリア、左右の肺門領域を含みます。 </li><li>スコープの作業チャネルを通ってシース内に収容されている22 G EBUS針を配備し、所定の位置にロックします。 注：注射部位には正確な外科的座標はありませんが、一般的に処理されたサイトのいくつかは、単にsubcarinal（内側左右の主気管支の接合部で）、（横方向に右主気管支に右傍気管を含み、右上葉オリフィス上記）、左傍気管、（大動脈弓と左肺動脈間の遠位気管と左主の接合部で）（横方向近位気管支intermediusので、右上葉の開口部の下）、右肺門、左肺門（で左上葉の接合部と左下葉気管支）。 </li><li>リアルタイム超音波ガイド下では、気管支壁を穿刺し、標的病変に針を配置します。針内にスタイレットを取り外し、一度に病変10ミリリットル（シスプラチンのを1mg / mL）にシスプラチンを注入します。シート内針を撤回。 </li><li>全体で薬の注入を容易にするために、異なる場所でのセッションごとに4つのパンクで各病変を治療します。穿刺あたりシスプラチン10mgを注入します。 </li><li>セッションごとに2つの病変に1を扱います。複数の病変はセッションごとに処理されている場合は、セッション当たりの総投与量は40ミリグラムを超えないと、シスプラチン20mgので各サイトを注入します。 </li><li> workiから針を外しますスコープのngのチャンネル。 </li><li>遠位気道からの追加の薬物を吸引し、気管支鏡を削除します。 </li><li>患者が病院のプロトコルどおりに回復し、同じ日にそれらを排出することができます。 </li><li> 4週間（1日目に、8、15、および22）の合計のために週に一度（2.7から2.13ステップ）シスプラチン注射を繰り返します。 注：処理された後は、特定の病変は、その後の出会いにITCでの再治療のために考慮すべきではありません。 </li></ol> 3.ポスト噴射<ol><li>フォローアップ胸部コンピュータ断層撮影法（CT）やポジトロン放出断層撮影（PET / CT）の応答を評価するには、8-12週間最後の治療セッションの後のスキャン。治療部位の再発および縦隔、肺門で再発、または鎖骨上窩などの局所再発として局所再発を定義します。 </li></ol>

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The authors have nothing to disclose.

<html>私たちの原稿は、より多くの放射線がオプションではありません人の患者のための肺癌の孤立した縦隔および肺門再発の管理に焦点を当てています。 IMHRの発生率は約9〜11％です。別の治療法の選択肢は緩和的化学療法、より多くの外部ビーム放射線療法、または支持療法および監視を含め、これらの患者に試みられてきました。当院では、我々は気管支鏡検査によっ?...

肺癌は、男性と女性の両方で世界的に最も一般的な癌であり、すべての癌関連死の5で1を占めています。それは0.87 1、2の場合の致死率を持っています。初期治療後の再発は肺癌患者の中で最も死亡を占めます。再発性肺癌の治療の選択肢は限られています。再発肺癌はまた、生活の質に有意な介護者のバーンアウトに重大な障害につながり、さらなる介入3に受け入れと寛容の可能性を減少させるそのすべてが、追加の支持療法を必要とします。 NSCLC患者の約30％は、放射線4の後に局所領域での再発を持っています。これらの患者のための治療の選択肢は限られており、わずか10％5、6の客観的な応答速度を有する全身化学療法が含まれます。繰り返し胸部放射が実現可能であるが、緩和を目的と症状緩和のために主に研究されており、疾患の寛解3のために使用されていません。 当院では、気管支鏡を介してアクセス可能な気管支内超音波（EBUS）で処理した孤立した縦隔および肺門再発（IMHR）を持つすべての患者は、シスプラチンの経気管支腫瘍内注射（ITC）を-guided。全身化学療法および/または外部ビーム放射線療法（EBRT）との併用療法は、治療専門医「裁量に従ってせました。本稿では、安全性、有効性、実現可能性、および当社の機関で使用されるプロトコルの詳細な方法を強調しています。

<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

肺癌患者における外照射療法（EBRT）以下の単離された肺門および縦隔再発（IMHR）が一般的です。これらの患者は、多くの治療の選択肢を持っていないと、通常は緩和的化学療法や対症療法を提供しています。気管支内超音波（EBUS）シスプラチンの腫瘍内注射を-guided（ITC）は、これらの患者のための新規なアプローチです。手順は、意識鎮静下で行われます。病変は、EBUSを使用して気管支鏡検査で配置され、22ゲージのEBUS針は、スコープの作業チャネルを通って前進し、位置にロックされます。超音波ガイド下では、気管気管支樹の壁が穿刺されると、針が標的病変に移動されます。針スタイレットを除去するとシスプラチン（40ミリグラム/ 40 mL）を病変部に注入されます。 1〜2サイトは、セッションごとに処理されます。手順の詳細は、紙のプロトコルの項に記載されています。当センターでは、50サイトが36人の患者に治療を受けました（19人の男性、17人の女性）。私たちのコホートの平均年齢は61.9±8.5歳でした。私たちは、35人の患者と41のサイト上で、最終的な分析を行いました。 11/35（31％）が安定または進行性疾患（非応答者）を有していたのに対し、24/35（69％）は、完全または部分的なレスポンス（応答）を有していました。全体的に、私たちのグループの生存率はしませんでしたものよりも有意に良好な生存率を持つ回答患者と8ヶ月（6-11カ月の95％CI）でした。

応答は、8-12週間治療後のフォローアップイメージングによって測定しました。応答は、完全寛解（CR）、部分寛解（PR）、安定な疾患（SD）、進行性疾患（PD）、またはRECIST 1.1基準8に基づいて応答を評価することができないとして分類されました。 CRとPRを有する患者はレスポンダーとみなされ、他は非応答者として分類しました。副次的転帰は、腫...

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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.

肺癌の単離された縦隔再発の治療のためのシスプラチンの気管支内超音波ガイド下腫瘍内注射

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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10.4K ビュー.  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. 

ビデオ: 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.

犬と猫における腫瘍の治療のための電気化学の操作手順

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

がん研究

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.

肺組織に腫瘍のセルの視覚化を循環させるため肺植民地化アッセイの確立

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.

超音波の利用ガイド生物学的関連性の転移性腫瘍の異種移植片の確立のため組織指示細胞注入

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.

肝転移の治療に超音波装置が可能性、安全性、術中の高輝度の精度の評価に焦点を当ててください。

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胃癌組織のパラフィン埋め込みスライド上の弾性染色

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.

マウス膵管腺癌の超音波誘導矯正着移植

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.

腫瘍組織学におけるマウス肺の多灌流とインフレーション

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.

腫瘍細胞の横尾静脈注入後の肺転移の病理学的解析

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.

頭蓋内注射と磁気共鳴画像による脳転移のモデル化

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.

炎症性乳癌細胞の尾静脈注射による脳転移のモデル化

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 ...