Name: carotid artery infusions for pharmacokinetic and pharmacodynamic analysis of taxanes in mice
Uploaded: 2014-10-27T14:00:00.000+00:00
Duration: 8 min 41 s
Description: Watch this Scientific Journal Video about Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice at JoVE.com

我々は、このプロジェクトでのサポートのためにFCCC実験動物施設を承認したいと思います。私たちは、血漿および組織中のパクリタキセル濃度を分析する上で彼らの支援のためにウォルフ·ラボラトリーズ社に感謝します。この作品は、国立衛生研究所EHBにK01CA120091を付与し、フォックスチェイスがんセンターへCA06927によってサポートされていました。

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H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Normal+Viability+and+Altered+Pharmacokinetics+in+Mice+Lacking+mdr1-type+(drug-transporting)+P-glycoproteins.">Normal Viability and Altered Pharmacokinetics in Mice Lacking mdr1-type (drug-transporting) P-glycoproteins.</a> Proc. Nat. Acad. Sci. USA. 94, 4028-4033 (1997).</li><li>Fraser, I. J., Dear, G. J., Plumb, R., L&#8217;Affineur, M., Fraser, D., Skippen, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Use+of+Capillary+High+Performance+Liquid+Chromatography+with+Electrospray+Mass+Spectrometry+for+the+Analysis+of+Small+Volume+Blood+Samples+from+Serially+Bled+Mice+to+Determine+the+Pharmacokinetics+of+Early+Discovery+Compounds.">The Use of Capillary High Performance Liquid Chromatography with Electrospray Mass Spectrometry for the Analysis of Small Volume Blood Samples from Serially Bled Mice to Determine the Pharmacokinetics of Early Discovery Compounds.</a> Rapid Communications in Mass Spectrometry. 13 (23), 2366-2375 (1999).</li><li>Bateman, K. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reduction+of+Animal+Usage+by+Serial+Bleeding+of+Mice+for+Pharmacokinetic+Studies:+Application+of+Robotic+Sample+Preparation+and+Fast+Liquid+Chromatography+&#8211;+Mass+Spectrometry.">Reduction of Animal Usage by Serial Bleeding of Mice for Pharmacokinetic Studies: Application of Robotic Sample Preparation and Fast Liquid Chromatography &#8211; Mass Spectrometry.</a> Journal of Chromatography B: Biomedical Sciences and Applications. 754 (1), 245-251 (2001).</li><li>Berndt, K., Vogel, J., Buehler, C., Vogt, P., Born, W., Fuchs, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+method+for+repeated+drug+infusion+into+the+femoral+artery+of+mice.">A new method for repeated drug infusion into the femoral artery of mice.</a> J. Am. Assoc. Lab Animal Sci. 51 (6), 825-831 (2012).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Squibb+&amp;+Sons,+L.L.C..">Squibb &amp; Sons, L.L.C..</a> Drug Information for TAXOL (Paclitaxel) Injection. , (2011).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Abraxis+BioScience+L.L.C.">Abraxis BioScience L.L.C.</a> Full Prescribing Information ABRAXANE for Injectable suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound). , (2013).</li><li>Fergusson, G., Ethier, M., Zarrouki, B., Font&#233;s, G., Poitout, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Model+of+Chronic+Nutrient+Infusion+in+the+Rat.">A Model of Chronic Nutrient Infusion in the Rat.</a> J. Vis. 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著者らは、開示することは何もない。

頸動脈内注入は、パクリタキセルの薬物動態のこの研究で重要なテクニックです。頸動脈内注入は迅速に循環系14を通して薬物を分配するための方法である。 3時間の注入は、ボーラス注射よりタキサンのような薬物の臨床的管理の近い模倣である。手術は確実に一人の個人によって実行することができ、手術時間が比較的短く、成功率は&gt; 75％である。サンプルが収集された後、そ...

頸動脈を介して薬物注入機器および技術を最適化することにより、確実かつ再現可能に行うことができる。それは細部への微調整と注意を必要としないものの、手順は、複雑ではありません。優れたケアおよび器用さは頸動脈を分離し、一般的に実践を通して取得することができるカテーテルを挿入するために必要とされる。経験豊富な技術者による手術は1時間を超えないようにしてください。 （マウスが実際の薬物注入に反応するかもしれないが）手術の成功の後、マウスは、正常で健康な表示され、そして薬物は制御され、均一な連続用量で投与してもよい。血液サンプルを頸動脈以外の部位から採取されなければならない。後眼窩採血を収集しやすく、薬物濃度の分析のための十分な証明した。 最適なサイズと形状のカテーテルは、成功した注入11を行う際の貴重な資産である。私たちは、カテーテル使用可能commerciallを見つけたyはしばしば大きすぎるおよび/またはマウスの頚動脈への便利なアクセスを可能にするには柔軟である。これは、注入シリンジにマウスを接続するために使用されるポリエチレン管からファッションカテーテルよりも好ましいが判明した。したがって、すべてのチューブ、コネクタ、針は、注入アセンブリを簡略化し一貫性のある寸法は、であった。この技術を使用して、それがまだ表示されている点を越えて動脈内にカテーテルの先端をプッシュする必要がなく、頚動脈への血流が、カテーテルが最初に固定された後まで復元されない。これは、動脈を穿刺するか、血流の高い圧力によって押し出されたカテーテルを有することの危険を低減する。カテーテルのデザインは、ここに所定の位置に保持するために「バンプ」、そう縫合糸およびサージカルテープとよくカテーテルの確保が優先されるが組み込まれていない。 注入は、臨床投与のよりよい模倣として、一般的な静脈内ボーラス注射に好ましいかもしれないタキサン3、12、13などの薬物。ここに記載の技術は、もともと頸静脈または大腿静脈へのアクセスが乳腺腫瘍の成長および/ ​​または挿入領域の過剰な血管新生によって除外されたことを特徴マウスモデルへの注入を可能にするために開発された。この方法は、多くの場合であっても無腫瘍マウスでは適切かもしれない：頸静脈壁の傾向は以上の失敗の挿入が完了する故障が生じリッピングするための単離および頸動脈をcatheterizingものの、わずかにより侵襲的な、我々は、それが望ましい頸静脈に発見された3時間のタイムコース。 ここに示された結果は、C57BL / 6Jからですが（社内で飼育）マウス、我々が正常にトランスジェニック的に操作マウスモデルにおける薬物動態に従うことを、FVBおよびミックスド株を含むマウスのいくつかの株の中にパクリタキセルを注入するためにこのテクニックを使用している細胞のトランスポーターの機能をダウンレギュレートする。採取した血液および組織サンプルはpaclitaxの予想レベルを示したエル、頚静脈点滴1後に見られるレベルの範囲内である。この技術は、他のマウスモデルおよび他の注入溶液と同様に機能することが期待されてもよい。

<table><tbody><tr><td>Polyethylene tubing 0.024&amp;rdquo; OD X 0.011&amp;rdquo; ID&amp;nbsp;</td><td>Braintree Scientific, Inc.</td><td>PE10</td><td></td></tr><tr><td>3 Blunted needles (30 gauge)</td><td>Braintree Scientific, Inc.</td><td>NB-30</td><td></td></tr><tr><td>Stainless steel port plug (28 gauge)</td><td>Braintree Scientific, Inc.</td><td>PP-28</td><td>Slightly larger than PE tubing ID, to fit snugly and keep a tight seal.</td></tr><tr><td>2 Stainless steel connector plugs (30 gauge)</td><td>Braintree Scientific, Inc.</td><td>C-30</td><td></td></tr><tr><td>Three 1 cc syringes</td><td>Becton, Dickinson and Co.</td><td>309659</td><td></td></tr><tr><td>Sterile 0.9% Saline solution</td><td>Hospira</td><td>0409-7984-37</td><td></td></tr><tr><td>Cath-Loc HGS Heparin/Glycerol Solution&amp;nbsp;</td><td>Braintree Scientific, Inc.</td><td>HGS</td><td></td></tr><tr><td>Silk suture</td><td>Braintree Scientific, Inc.</td><td>SUT-S&amp;nbsp;113</td><td></td></tr><tr><td>Vanna Scissors (micro-scissors)</td><td>World Precision Instruments</td><td>14122</td><td>This model has a curved tip, but straight-tip scissors work as well.</td></tr><tr><td>Hartman Mesquito Hemostatic Forceps</td><td>World Precision Instruments</td><td>501705</td><td></td></tr><tr><td>Betadine Swabsticks</td><td>Perdue Products L.P.</td><td>BSWS1S</td><td></td></tr><tr><td>Bupivacaine</td><td>Hospira</td><td>0409-1160-01</td><td>May be replaced with Lidocaine, or similar local anesthesia.</td></tr><tr><td>Paclitaxel</td><td>LC Laboratories</td><td>P-9600</td><td></td></tr><tr><td>Methanol</td><td>Sigma-Aldrich</td><td>32213</td><td></td></tr><tr><td>Micro-Hematocrit Capillary Tubes, Heparinized</td><td>Fisher Scientific</td><td>22-362-566</td><td></td></tr><tr><td>Micro Capillary Tube Sealant&amp;nbsp;</td><td>Fisher Scientific</td><td>02-678</td><td></td></tr><tr><td>C57BL/6J mice</td><td>Fox Chase Cancer Center, Laboratory Animal Facility in-house-bred</td><td></td><td></td></tr><tr><td>API 4000 Q-Trap mass spetrometer</td><td>Applied Biosystems</td><td></td><td></td></tr></tbody></table>

carotid artery infusions for pharmacokinetic and pharmacodynamic analysis of taxanes in mice

新規システムへの薬物、薬剤の組み合わせ、または薬物送達の使用を提案する場合、人は研究モデルにおける薬物の薬物動態を評価しなければならない。マウスモデルの使用は、しばしば、前臨床創薬および薬剤開発1-8に重要なステップであるので、均一な、再現可能な方法でマウスに薬剤を導入するためのシステムを設計する必要がある。理想的には、システムは、設定時間経過にわたって定期的に血液サンプルの収集を可能にするはずである。質量分析による薬物濃度を測定する能力は、10、9、研究者は、個々のマウス1の経時的血漿薬物レベルの変化に追従することを可能にした。本研究では、パクリタキセルは、3つを超える連続動脈注入としてトランスジェニックマウスに導入した時間に、血液サンプルを同時に設定した時点で後眼窩採血によって採取した。頸動脈注入は頸静脈注入への潜在的な代替案、要因などである乳腺腫瘍やその他の障害物が頸静輸液は非現実的。この技術を使用して、血漿及び組織中のパクリタキセル濃度は、頸静脈内注入と比較して同様のレベルを達成した。このチュートリアルでは、当時通ってカテーテルの端をスレッド、マウス頸動脈にカテーテルを挿入し、保護する方法を示して、成功裏に個々のマウスモデル用に最適化されたカテーテルを調製することにより、頸動脈カテーテルを挿入する方法を紹介しますマウスの首の、薬物流入の制御された速度を提供するためにポンプにマウスをフック。複数の低容量眼窩採血を経時的に血漿中薬物濃度の分析を可能にする。

<html>パクリタキセルの分布は165分の低速注入に続いて、15​​分間高速注入の3時間投与レジメン中に予測可能なパターンに従う。 図1は、頚静脈注入血漿パクリタキセル濃度及び頸動脈、注入の比較を示す。パクリタキセル濃度は、初期の高容量注入後の最初の15分で急速に低下した後、次の150分間にわたって横ばい。比較することによって、貧しい点滴中?...

Watch this Scientific Journal Video about Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice at JoVE.com

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

この方法は、マウスモデルにおける新規薬物の薬物動態を評価するために、頸動脈を介して安定した薬液を送達することを目標に開発された。

マウスにおけるタキサンの薬物動態学的および薬力学的分析のための頸動脈煎茶

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study ...

carotid-artery-infusions-for-pharmacokinetic-pharmacodynamic-analysis

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Pharmacokinetics and Pharmacodynamics

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Unit 1

Pharmacokinetic Models

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22.9K ビュー.  Fox Chase Cancer Center. この方法は、マウスモデルにおける新規薬物の薬物動態を評価するために、頸動脈を介して安定した薬液を送達することを目標に開発された。 

ビデオ: Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

A Model of Disturbed Flow-Induced Atherosclerosis in Mouse Carotid Artery by Partial Ligation and a Simple Method of RNA Isolation from Carotid Endothelium

Despite the well-known close association, direct evidence linking disturbed flow to atherogenesis has been lacking. We have recently used a modified version of carotid partial ligation methods [1,2] to show that it acutely induces low and oscillatory flow conditions, two key characteristics of disturbed flow, in the mouse common carotid artery. Using this model, we have provided direct evidence that disturbed flow indeed leads to rapid and robust atherosclerosis development in Apolipoprotein E knockout mouse [3]. We also developed a method of endothelial RNA preparation with high purity from the mouse carotid intima [3]. Using this mouse model and method, we found that partial ligation causes endothelial dysfunction in a week, followed by robust and rapid atheroma formation in two weeks in a hyperlipidemic mouse model along with features of complex lesion formation such as intraplaque neovascularization by four weeks. This rapid in vivo model and the endothelial RNA preparation method could be used to determine molecular mechanisms underlying flow-dependent regulation of vascular biology and diseases. Also, it could be used to test various therapeutic interventions targeting endothelial dysfunction and atherosclerosis in considerably reduced study duration.

This describes a partial carotid ligation surgery, which causes disturbed flow conditions and subsequent atherosclerosis development (in two weeks) with intraplaque neo-vascularization (in four weeks) in the mouse common carotid artery. We also describe a novel method of RNA isolation from the carotid intima, providing high purity endothelial RNA.

部分的ライゲーションによるマウス頸動脈における乱流誘発アテローム性動脈硬化症と頸動脈内皮からのRNA単離の方法における簡便な方法のモデル

Despite the well-known close association, direct evidence linking disturbed flow to atherogenesis has been lacking. We have recently used a modified ...

医学

Intracarotid Cancer Cell Injection to Produce Mouse Models of Brain Metastasis

Metastasis, the spread and growth of malignant cells at secondary sites within a patient&#39;s body, accounts for &#62; 90% of cancer-related mortality. Recently, impressive advances in novel therapies have dramatically prolonged survival and improved quality of life for many cancer patients. Sadly, incidence of brain metastatic recurrences is fast rising, and all current therapies are merely palliative. Hence, good experimental animal models are urgently needed to facilitate in-depth studies of the disease biology and to assess novel therapeutic regimens for preclinical evaluation. However, the standard in vivo metastasis assay via tail vein injection of cancer cells produces predominantly lung metastatic lesions; animals usually succumb to the lung tumor burden before any meaningful outgrowth of brain metastasis. Intracardiac injection of tumor cells produces metastatic lesions to multiple organ sites including the brain; however, the variability of tumor growth produced with this model is large, dampening its utility in evaluating therapeutic efficacy. To generate reliable and consistent animal models for brain metastasis study, here we describe a procedure for producing experimental brain metastasis in the house mouse (Mus musculus) via intracarotid injection of tumor cells. This approach allows one to produce large number of brain metastasis-bearing mice with similar growth and mortality characteristics, thus facilitating research efforts to study basic biological mechanisms and to assess novel therapeutic agents.

Brain metastasis has become an urgent unmet medical need as its incidence has increased while therapeutic options have remained palliative. Creating experimental animal models of brain metastasis via intracarotid arterial injection of cancer cells facilitates mechanistic studies of the disease biology and evaluation of novel intervention regimens.

脳転移のマウスモデルを生成するために頸動脈内癌細胞注入

Metastasis, the spread and growth of malignant cells at secondary sites within a patient&#39;s body, accounts for &#62; 90% of cancer-related mortality. ...

がん研究

Implantation of a Carotid Cuff for Triggering Shear-stress Induced Atherosclerosis in Mice

It is widely accepted that alterations in vascular shear stress trigger the expression of inflammatory genes in endothelial cells and thereby induce atherosclerosis (reviewed in 1 and 2). The role of shear stress has been extensively studied in vitro investigating the influence of flow dynamics on cultured endothelial cells 1,3,4 and in vivo in larger animals and humans 1,5,6,7,8. However, highly reproducible small animal models allowing systematic investigation of the influence of shear stress on plaque development are rare. Recently, Nam et al. 9 introduced a mouse model in which the ligation of branches of the carotid artery creates a region of low and oscillatory flow. Although this model causes endothelial dysfunction and rapid formation of atherosclerotic lesions in hyperlipidemic mice, it cannot be excluded that the observed inflammatory response is, at least in part, a consequence of endothelial and/or vessel damage due to ligation.
In order to avoid such limitations, a shear stress modifying cuff has been developed based upon calculated fluid dynamics, whose cone shaped inner lumen was selected to create defined regions of low, high and oscillatory shear stress within the common carotid artery 10. By applying this model in Apolipoprotein E (ApoE) knockout mice fed a high cholesterol western type diet, vascular lesions develop upstream and downstream from the cuff. Their phenotype is correlated with the regional flow dynamics 11 as confirmed by in vivo Magnetic Resonance Imaging (MRI) 12: Low and laminar shear stress upstream of the cuff causes the formation of extensive plaques of a more vulnerable phenotype, whereas oscillatory shear stress downstream of the cuff induces stable atherosclerotic lesions 11. In those regions of high shear stress and high laminar flow within the cuff, typically no atherosclerotic plaques are observed.
 
In conclusion, the shear stress-modifying cuff procedure is a reliable surgical approach to produce phenotypically different atherosclerotic lesions in ApoE-deficient mice.

The constricting cuff presented in this article is designed to induce atherosclerosis in the murine common carotid artery. Due to the conical shape of its inner lumen the implanted cuff generates well-defined regions of low, high and oscillatory shear stress triggering the development of atherosclerotic lesions of different inflammatory phenotypes.

マウスでのせん断応力誘発アテローム性動脈硬化症をトリガするための頸動脈カフの注入

It is widely accepted that alterations in vascular shear stress trigger the expression of inflammatory genes in endothelial cells and thereby induce ...

Modeling Brain Metastasis by Internal Carotid Artery Injection of Cancer Cells

Brain metastasis is a cause of severe morbidity and mortality in cancer patients. Critical aspects of metastatic diseases, such as the complex neural microenvironment and stromal cell interaction, cannot be entirely replicated with in vitro assays; thus, animal models are critical for investigating and understanding the effects of therapeutic intervention. However, most brain tumor xenografting methods do not produce brain metastases consistently in terms of the time frame and tumor burden. Brain metastasis models generated by intracardiac injection of cancer cells can result in unintended extracranial tumor burden and lead to non-brain metastatic morbidity and mortality. Although intracranial injection of cancer cells can limit extracranial tumor formation, it has several caveats, such as the injected cells frequently form a singular tumor mass at the injection site, high leptomeningeal involvement, and damage to brain vasculature during needle penetration. This protocol describes a mouse model of brain metastasis generated by internal carotid artery injection. This method produces intracranial tumors consistently without the involvement of other organs, enabling the evaluation of therapeutic agents for brain metastasis.

Brain metastasis is a cause of severe morbidity and mortality in cancer patients. Most brain metastasis mouse models are complicated by systemic metastases confounding analysis of mortality and therapeutic intervention outcomes. Presented here is a protocol for internal carotid injection of cancer cells that produces consistent intracranial tumors with minimal systemic tumors.

がん細胞の内頸動脈注射による脳転移のモデル化

Brain metastasis is a cause of severe morbidity and mortality in cancer patients. Critical aspects of metastatic diseases, such as the complex neural ...

Intracranial Cannula Implantation for Serial Locoregional Chimeric Antigen Receptor (CAR) T Cell Infusions in Mice

Pediatric CNS tumors are responsible for the majority of cancer-related deaths in children and have poor prognoses, despite advancements in chemotherapy and radiotherapy. As many tumors lack efficacious treatments, there is a crucial need to develop more promising therapeutic options, such as immunotherapies; the use of chimeric antigen receptor (CAR) T cell therapy&#160;directed against CNS tumors is of particular interest. Cell surface targets such as B7-H3, IL13RA2, and the disialoganglioside GD2 are highly expressed on the surface of several pediatric and adult CNS tumors,&#160;raising the opportunity to use CAR T cell therapy against these and other surface targets. To evaluate the repeated locoregional delivery of CAR T cells in preclinical murine models, an indwelling catheter system that recapitulates indwelling catheters currently being used in human clinical trials was established. Unlike stereotactic delivery, the indwelling catheter system allows for repeated dosing without the use of multiple surgeries. This protocol describes the intratumoral placement of a fixed guide cannula that has been used to successfully test serial CAR T cell infusions in orthotopic murine models of pediatric brain tumors. Following orthotopic injection and engraftment of the tumor cells in mice, intratumoral placement of a fixed guide cannula is completed on a stereotactic apparatus and secured with screws and acrylic resin. Treatment cannulas are then inserted through the fixed guide cannula for repeated CAR T cell delivery. Stereotactic placement of the guide cannula can be adjusted to deliver CAR T cells directly into the lateral ventricle or other locations in the brain. This platform offers a reliable mechanism for the preclinical testing of repeated intracranial infusions of CAR T cells and other novel therapeutics for these devastating pediatric tumors.

Intracranial Cannula Implantation for Serial Locoregional Chimeric Antigen Receptor CAR T Cell Infusions in Mice

Central nervous system (CNS) tumors are the leading cause of cancer-related death in children, and locoregional immune-based therapies are increasingly being tested for patients in clinical trials. This protocol describes methods for locoregional cannula implantation in mice for the preclinical evaluation of immunotherapeutic infusions targeting CNS tumors.

マウスにおける連続局所キメラ抗原受容体(CAR)T細胞注入のための頭蓋内カニューレ移植

Pediatric CNS tumors are responsible for the majority of cancer-related deaths in children and have poor prognoses, despite advancements in chemotherapy ...

Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment

Certain classes of chemotherapies may exert acute vascular changes that may progress into long-term conditions that may predispose the patient to an increased risk of vascular morbidity.&#160;Yet, albeit&#160;the mounting clinical evidence, there is a paucity of clear studies of vascular toxicity and therefore the etiology of a heterogeneous group of vascular/cardiovascular disorders remains to be elucidated. Moreover, the mechanism that may underlie vascular toxicity can completely differ from the principles of chemotherapy-induced cardiotoxicity, which is related to direct myocyte injury. We have established a real-time, in vivo molecular imaging platform&#160;to evaluate&#160;the potential&#160;acute&#160;vascular toxicity of anti-cancer therapies.
We have set up a platform of in vivo, high-resolution molecular imaging&#160;in mice,&#160;suitable for visualizing vasculature within confined organs and reference blood vessels within the same individuals whereas each individual serve as its own control. Blood vessel walls were impaired after doxorubicin administration, representing a unique mechanism of vascular toxicity that may be the early event in end-organ injury. Herein, the method of fibered confocal fluorescent microscopy (FCFM) based imaging is described, which provides an innovative mode to understand physiological phenomena at the cellular and sub-cellular levels in animal subjects.

Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment

We herein describe the method of fibered confocal fluorescent microscopy (FCFM) based imaging, which provides an innovative mode to understand physiological phenomena at the cellular and sub-cellular levels in animal subjects.

化学療法誘発性血管毒性 - リアルタイム<em&gt;インビボ</em船舶減損の&gt;イメージング

Certain classes of chemotherapies may exert acute vascular changes that may progress into long-term conditions that may predispose the patient to an ...

<meta charset="utf8"></head><body>マウスモデルでの注射後の総頸動脈修復

Facilitating Repeat Intracarotid Injections in Mouse Models by a Novel Injection Site Repair Technique

Given recent advances in the delivery of novel antitumor therapeutics using endovascular selective intraarterial delivery methods in neuro-oncology, there is an urgent need to develop methods for intracarotid injections in mouse models, including methods to repair the carotid artery in mice after injection to allow for subsequent injections. We developed a method of intracarotid injection in a mouse model to deliver therapeutics into the internal carotid artery (ICA) with two alternative procedures. 
During injection, the needle is inserted into the common carotid artery (CCA) after tying a suture around the external carotid artery (ECA) and injected therapeutics are delivered into the ICA. Following injection, the common carotid artery (CCA) can be ligated, which limits the number of intracarotid injections to one. The alternative procedure described in this article includes a modification where intracarotid artery injection is followed by injection site repair of the CCA, which restores blood flow within the CCA and avoids the complication of cerebral ischemia seen in some mouse models. 
We also compared the delivery of bone marrow-derived human mesenchymal stem cells (BM-hMSCs) to intracranial tumors when delivered through intracarotid injection with and without injection site repair following the injection. Delivery of BM-hMSCs does not differ significantly between the methods. Our results demonstrate that injection site repair of the CCA allows for repeat injections through the same artery and does not impair the delivery and distribution of injected material, thus providing a model with greater flexibility that more closely emulates intracarotid injection in humans.

<meta charset="utf8"></head><body>著者スポットライト:腫瘍溶解性ウイルスとマイクロRNAの動脈内送達戦略による膠芽腫治療の進歩

Repair of the intracarotid artery in a mouse model after injection returns blood flow to the artery without negatively impacting the distribution of the injected material. Injection site repair facilitates subsequent injections through the same artery and prevents cerebral ischemia in mouse strains that lack a complete Circle of Willis.

新しい注射部位修復技術によるマウスモデルにおける反復頸動脈内注射の促進

Given recent advances in the delivery of novel antitumor therapeutics using endovascular selective intraarterial delivery methods in neuro-oncology, there ...

Mouse Microsurgery Infusion Technique for Targeted Substance Delivery into the CNS via the Internal Carotid Artery

Animal models of central nervous system (CNS) diseases and, consequently, blood-brain barrier disruption diseases, require the delivery of exogenous substances into the brain. These exogenous substances may induce injurious impact or constitute therapeutic strategy. The most common delivery methods of exogenous substances into the brain are based on systemic deliveries, such as subcutaneous or intravenous routes. Although commonly used, these approaches have several limitations, including low delivery efficacy into the brain. In contrast, surgical methods that locally deliver substances into the CNS are more specific and prevent the uptake of the exogenous substances by other organs. Several surgical methods for CNS delivery are available; however, they tend to be very traumatic. Here, we describe a mouse infusion microsurgery technique, which effectively delivers substances into the brain via the internal carotid artery, with minimal trauma and no interference with normal CNS functionality.

Mouse Microsurgery Infusion Technique for Targeted Substance Delivery into the CNS via the Internal Carotid Artery

The present protocol describes a mouse microsurgery infusion technique, which effectively delivers substances directly into the brain via the internal carotid artery.

CNSへの標的化物質送達のためのマウス顕微注入法<i&gt;経由で</i&gt;内頸動脈

Animal models of central nervous system (CNS) diseases and, consequently, blood-brain barrier disruption diseases, require the delivery of exogenous ...

マウスにおけるタキサンの薬物動態学的および薬力学的分析のための頸動脈煎茶

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部分的ライゲーションによるマウス頸動脈における乱流誘発アテローム性動脈硬化症と頸動脈内皮からのRNA単離の方法における簡便な方法のモデル

脳転移のマウスモデルを生成するために頸動脈内癌細胞注入

マウスでのせん断応力誘発アテローム性動脈硬化症をトリガするための頸動脈カフの注入

がん細胞の内頸動脈注射による脳転移のモデル化

マウスにおける連続局所キメラ抗原受容体(CAR)T細胞注入のための頭蓋内カニューレ移植

化学療法誘発性血管毒性 - リアルタイム

新しい注射部位修復技術によるマウスモデルにおける反復頸動脈内注射の促進

新しい注射部位修復技術によるマウスモデルにおける反復頸動脈内注射の促進

新しい注射部位修復技術によるマウスモデルにおける反復頸動脈内注射の促進

CNSへの標的化物質送達のためのマウス顕微注入法