Name: analysis of lymph node volume by ultra-high-frequency ultrasound imaging in the braf/pten genetically engineered mouse model of melanoma
Uploaded: 2021-09-08T14:00:00
Description: Watch this Scientific Journal Video about Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma at JoVE.com

作者要感谢S. Burchielli（FTGM，比萨）在动物手术方面的帮助。这项工作得到了ISPRO-Istituto per lo Studio la Prevenzione e la Rete Oncologica机构对LP的资助;MFAG #17095由AIRC-Associazione Italiana Ricerca sul Cancro授予LP。

此处描述的所有方法均已获得意大利卫生部的批准（动物协议#754 / 2015-PR和#684 / 2018-PR）。
1. 黑色素瘤诱导
注意：六周龄的Tyr：：CreER+，BrafCA/+，Ptenlox/lox小鼠[B6.Cg-Braftm1Mmcm Ptentm1Hwu Tg（Tyr-cre/ERT2）13Bos/BosJ（Braf/Pten）]在本研究中使用（见材料表）。
<ol><li>如前所述，通过在上背部约1 cm2?...

<ol>
	<li>Schvartsman, G., 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=Management+of+metastatic+cutaneous+melanoma:+updates+in+clinical+practice.">Management of metastatic cutaneous melanoma: updates in clinical practice.</a> Therapeutic Advances in Medical Oncology. 11, 1758835919851663 (2019).</li><li>Blum, A., 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=Ultrasound+examination+of+regional+lymph+nodes+significantly+improves+early+detection+of+locoregional+metastases+during+the+follow-up+of+patients+with+cutaneous+melanoma+-+Results+of+a+prospective+study+of+1288+patients.">Ultrasound examination of regional lymph nodes significantly improves early detection of locoregional metastases during the follow-up of patients with cutaneous melanoma - Results of a prospective study of 1288 patients.</a> Cancer. 88 (11), 2534-2539 (2000).</li><li>Olmedo, D., 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=Use+of+lymph+node+ultrasound+prior+to+sentinel+lymph+node+biopsy+in+384+patients+with+melanoma:+a+cost-effectiveness+analysis.">Use of lymph node ultrasound prior to sentinel lymph node biopsy in 384 patients with melanoma: a cost-effectiveness analysis.</a> Actas Dermo-Sifiliograficas. 108 (10), 931-938 (2017).</li><li>Voit, C., 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=Ultrasound+morphology+criteria+predict+metastatic+disease+of+the+sentinel+nodes+in+patients+with+melanoma.">Ultrasound morphology criteria predict metastatic disease of the sentinel nodes in patients with melanoma.</a> Journal of Clinical Oncology. 28 (5), 847-852 (2010).</li><li>Hayes, A. J., 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=Prospective+cohort+study+of+ultrasound+surveillance+of+regional+lymph+nodes+in+patients+with+intermediate-risk+cutaneous+melanoma.">Prospective cohort study of ultrasound surveillance of regional lymph nodes in patients with intermediate-risk cutaneous melanoma.</a> British Journal of Surgery. 106 (6), 729-734 (2019).</li><li>Ipenburg, N. A., Thompson, J. F., Uren, R. F., Chung, D., Nieweg, O. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Focused+ultrasound+surveillance+of+lymph+nodes+following+lymphoscintigraphy+without+sentinel+node+biopsy:+a+useful+and+safe+strategy+in+elderly+or+frail+melanoma+patients.">Focused ultrasound surveillance of lymph nodes following lymphoscintigraphy without sentinel node biopsy: a useful and safe strategy in elderly or frail melanoma patients.</a> Annals of Surgical Oncology. 26 (9), 2855-2863 (2019).</li><li>Jayapal, N., 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=Differentiation+between+benign+and+metastatic+cervical+lymph+nodes+using+ultrasound.">Differentiation between benign and metastatic cervical lymph nodes using ultrasound.</a> Journal of Pharmacy and Bioallied Sciences. 11, 338-346 (2019).</li><li>Dankort, D., 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=Braf(V600E)+cooperates+with+Pten+loss+to+induce+metastatic+melanoma.">Braf(V600E) cooperates with Pten loss to induce metastatic melanoma.</a> Nature Genetics. 41 (5), 544-552 (2009).</li><li>Damsky, W. E., 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=&#946;-catenin+signaling+controls+metastasis+in+Braf-activated+Pten-deficient+melanomas.">&#946;-catenin signaling controls metastasis in Braf-activated Pten-deficient melanomas.</a> Cancer Cell. 20 (6), 741-754 (2011).</li><li>Xie, X., Koh, J. Y., Price, S., White, E., Mehnert, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Atg7+overcomes+senescence+and+promotes+growth+of+BrafV600E-driven+melanoma.">Atg7 overcomes senescence and promotes growth of BrafV600E-driven melanoma.</a> Cancer Discovery. 5 (4), 410-423 (2015).</li><li>Kohler, C., 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=Mouse+cutaneous+melanoma+induced+by+mutant+BRaf+arises+from+expansion+and+dedifferentiation+of+mature+pigmented+melanocytes.">Mouse cutaneous melanoma induced by mutant BRaf arises from expansion and dedifferentiation of mature pigmented melanocytes.</a> Cell Stem Cell. 21 (5), 679-693 (2017).</li><li>Yuan, 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=Phenformin+enhances+the+therapeutic+benefit+of+BRAF(V600E)+inhibition+in+melanoma.">Phenformin enhances the therapeutic benefit of BRAF(V600E) inhibition in melanoma.</a> Proceedings of the National Academy of Sciences of the United States of America. 110 (45), 18226-18231 (2013).</li><li>Marsh Durban, V., Deuker, M. M., Bosenberg, M. W., Phillips, W., McMahon, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+AKT+dependency+displayed+by+mouse+models+of+BRAFV600E-initiated+melanoma.">Differential AKT dependency displayed by mouse models of BRAFV600E-initiated melanoma.</a> Journal of Clinical Investigation. 123 (12), 5104-5118 (2013).</li><li>Hooijkaas, A. I., Gadiot, J., vander Valk, M., Mooi, W. J., Blank, C. U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Targeting+BRAFV600E+in+an+inducible+murine+model+of+melanoma.">Targeting BRAFV600E in an inducible murine model of melanoma.</a> American Journal of Pathology. 181 (3), 785-794 (2012).</li><li>Steinberg, S. M., 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=BRAF+inhibition+alleviates+immune+suppression+in+murine+autochthonous+melanoma.">BRAF inhibition alleviates immune suppression in murine autochthonous melanoma.</a> Cancer Immunology Research. 2 (11), 1044-1050 (2014).</li><li>Vitiello, M., 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=Antitumoral+effects+of+attenuated+Listeria+monocytogenes+in+a+genetically+engineered+mouse+model+of+melanoma.">Antitumoral effects of attenuated Listeria monocytogenes in a genetically engineered mouse model of melanoma.</a> Oncogene. 38 (19), 3756-3762 (2019).</li><li>Moon, 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=Melanocyte+stem+cell+activation+and+translocation+initiate+cutaneous+melanoma+in+response+to+UV+exposure.">Melanocyte stem cell activation and translocation initiate cutaneous melanoma in response to UV exposure.</a> Cell Stem Cell. 21 (5), 665-678 (2017).</li><li>Zhao, L., Zhan, Y. T., Rutkowski, J. L., Feuerstein, G. Z., Wang, X. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Correlation+between+2-and+3-dimensional+assessment+of+tumor+volume+and+vascular+density+by+ultrasonography+in+a+transgenic+mouse+model+of+mammary+carcinoma.">Correlation between 2-and 3-dimensional assessment of tumor volume and vascular density by ultrasonography in a transgenic mouse model of mammary carcinoma.</a> Journal of Ultrasound in Medicine. 29 (4), 587-595 (2010).</li></ol>

本研究获得的数据证明了超声成像监测转移性黑色素瘤Braf / Pten小鼠模型腹股沟淋巴结转移性受累的能力。如前所述16，该技术对于评估药物治疗的疗效特别有用。这是因为它允许通过比较在t1和 t2收集的测量值与在t0处收集的测量值来监测同一动物中淋巴结体积随时间的变化。反过来，这有助于增加所获得结果的稳健性，因为小鼠间变异性和其?...

黑色素瘤是一种侵袭性皮肤癌，通常扩散到其他皮肤部位（皮下转移），以及淋巴结、肺、肝脏、脑和骨骼1。在过去十年中，新药已被引入临床实践，并有助于提高转移性黑色素瘤患者的预期寿命。然而，局限性仍然存在，包括不同的反应时间和程度，严重的副作用以及获得性耐药性的激增1。因此，在早期阶段检测转移扩散至关重要，即当它到达局部淋巴结时。
通常进行局部淋巴结（前哨淋巴结）的活检以检查黑色素瘤细胞的存在。然而，超声成像作为检测转移性受累的非侵入性方法正在发挥作用，因为它优于临床评估，并且可以帮助避免不必要的活检2，3，4。此外，超声影像学检查似乎适用于淋巴结监测，特别是在高龄和/或合并症的情况下5，6。通过超声分析检测并允许区分正常和转移性淋巴结的特征包括增加大小（体积），形状从椭圆形变为圆形，不规则边缘，回声模式改变和血管形成改变（增加）7。
Tyr：：CreER+，BrafCA/+，Ptenlox/lox基因工程小鼠（Braf/Pten小鼠）最近已作为转移性黑色素瘤的组织特异性诱导模型8提供给科学界。在这种动物模型中，原发性肿瘤发展得非常快：在诱导从野生型（wt）布拉夫到布拉夫600E的转换以及Pten的损失后2-3周内，它们在2-3周内变得可见，而它们在4周内达到50-100 mm3的体积。在接下来的2周内，原发性肿瘤的生长伴随着其他皮肤部位，淋巴结和肺部转移负担的逐渐增加。
Braf / Pten小鼠已被广泛用于多种目的，包括解剖参与黑色素瘤发生的信号通路9，10，鉴定起源的黑色素瘤细胞11，12，13，以及根据靶向治疗和免疫疗法测试新的治疗方案8，14，15，16.具体来说，我们使用Braf / Pten小鼠来证明减毒 单核细胞增多性李斯特菌 （Lmat）作为抗黑色素瘤疫苗有效。当在治疗环境中全身给药时，Lmat与整体毒性无关，因为它选择性地积聚在肿瘤部位。此外，它导致原发性黑色素瘤肿块显着减少，淋巴结和肺部转移负担减少。在分子水平上，Lmat引起黑色素瘤细胞的凋亡性杀伤，这至少部分是由于非细胞自主活动（CD4 +和CD8 + T淋巴细胞现场募集）16。
当Braf / Pten小鼠用于黑色素瘤建模时，可以通过卡尺测量来监测原发性肿瘤和皮下转移的生长。然而，淋巴结和肺部的受累需要使用替代技术进行调查，可能是一种非侵入性的技术，允许研究人员随着时间的推移跟踪同一动物。本文描述了使用超声成像（图1），加上随后获得的数据的3D体积分析，用于腹股沟淋巴结大小（体积）增加的纵向监测。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>4-hydroxytamoxifen</td>
			<td>Merck</td>
			<td>H6278</td>
			<td>drug used for tumor induction</td>
		</tr>
		<tr>
			<td>B6.Cg-Braftm1Mmcm Ptentm1Hwu Tg(Tyr-cre/ERT2)13Bos/BosJ (Braf/Pten) mice</td>
			<td>The Jackson Laboratory</td>
			<td>013590</td>
			<td></td>
		</tr>
		<tr>
			<td>Blu gel</td>
			<td>Sooft Ialia</td>
			<td></td>
			<td>ophthalmic solution gel</td>
		</tr>
		<tr>
			<td>BRAFV600E antibody</td>
			<td>Spring Bioscience Corporation</td>
			<td>E19290</td>
			<td></td>
		</tr>
		<tr>
			<td>IsoFlo (isoflorane)</td>
			<td>Zoetis</td>
			<td></td>
			<td>liquid for gaseous anaesthesia</td>
		</tr>
		<tr>
			<td>MLANA antibody</td>
			<td>Thermo Fisher Scientific</td>
			<td>M2-7C10</td>
			<td></td>
		</tr>
		<tr>
			<td>Sigma gel</td>
			<td>Parker</td>
			<td></td>
			<td>electrode gel</td>
		</tr>
		<tr>
			<td>Transonic gel clear</td>
			<td>Telic SAU</td>
			<td></td>
			<td>ultrasound gel</td>
		</tr>
		<tr>
			<td>Veet</td>
			<td>Reckitt Benckiser IT</td>
			<td></td>
			<td>depilatory cream</td>
		</tr>
		<tr>
			<td>Compact Dual Anesthesia System</td>
			<td>Fujifilm, Visualsonics Inc.</td>
			<td></td>
			<td>Isoflurane-based anesthesia system equipped with nose cone and induction chamber</td>
		</tr>
		<tr>
			<td>MX550S</td>
			<td>Fujifilm, Visualsonics Inc.</td>
			<td></td>
			<td>UHFUS linear probe</td>
		</tr>
		<tr>
			<td>Vevo 3100</td>
			<td>Fujifilm, Visualsonics Inc.</td>
			<td></td>
			<td>UHFUS system</td>
		</tr>
		<tr>
			<td>Vevo Imaging Station</td>
			<td>Fujifilm, Visualsonics Inc.</td>
			<td></td>
			<td>UHFUS imaging station and Advancing Physiological Monitoring Unit endowed with heated board</td>
		</tr>
		<tr>
			<td>Vevo Lab</td>
			<td>Fujifilm, Visualsonics Inc.</td>
			<td></td>
			<td>software platform for ultrasound image post-processing</td>
		</tr>
	</tbody>
</table>

analysis of lymph node volume by ultra-high-frequency ultrasound imaging in the braf/pten genetically engineered mouse model of melanoma

Tyr：：CreER+，BrafCA/+，Ptenlox/lox基因工程小鼠（Braf/Pten小鼠）被广泛用作转移性黑色素瘤的体内模型。一旦原发性肿瘤被他莫昔芬治疗诱导，诱导后4-6周内观察到转移负担增加。本文展示了如何利用超高频超声（UHFUS）成像通过测量腹股沟淋巴结体积的增加来监测腹股沟淋巴结转移性受累的增加。
UHFUS系统用于使用UHFUS线性探针（22-55 MHz，轴向分辨率40μm）扫描麻醉小鼠。从腹股沟淋巴结（左侧和右侧）的B模式图像以短轴视图获取，将动物定位在背卧位。超声波记录是在电动机械臂上使用44μm步长获取的。之后，将二维（2D）B模式采集导入软件平台进行超声图像后处理，并在获取的横截面2D图像中识别和半自动分割腹股沟淋巴结。最后，随着淋巴结体积的渲染，自动获得三维（3D）体积的总重建，这也表示为绝对测量值。
这种非侵入性体内技术具有非常好的耐受性，并允许 在 2周内对同一实验动物安排多次成像会话。因此，评估药物治疗对转移性疾病的影响是理想的选择。

在 对Tyr：：CreER+，BrafCA/+，Ptenlox/lox小鼠进行4-HT的皮肤涂漆后，诱导Cre活性，因此在基因组水平上从wt Braf 切换到BrafV600E，而Pten丢失（图3A）。在2-3周内，小鼠发生100%外显率的现场原发性肿瘤。从4-HT治疗（t0）四周后，原发性肿瘤达到50-100 mm3的体积，并且可以通过卡尺再测量2周（（t1 和t2; 图3B</...

Watch this Scientific Journal Video about Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma at JoVE.com

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma

黑色素瘤是一种非常具有侵袭性的疾病，可迅速扩散到其他器官。该协议描述了超高频超声成像的应用，结合3D渲染，以监测转移性黑色素瘤Braf / Pten小鼠模型中腹股沟淋巴结的体积。

超高频超声成像分析黑色素瘤Braf/Pten基因工程小鼠模型中的淋巴结体积

Tyr::CreER+,BrafCA/+,Ptenlox/lox&#160;genetically engineered mice (Braf/Pten mice) are widely used as an in vivo model of metastatic melanoma. Once a ...

我们的方法可以通过测量腹股沟淋巴结体积的增加来监测腹股沟淋巴结转移性受累的增加。这种非侵入性方法的耐受性非常好，因此，可以在两周内对同一实验动物安排多次成像。该方法非常适合评估药物治疗对转移性疾病的影响。我们将这种方法应用于Braf / Pten黑色素瘤模型，但原则上，它可以用于评估各种药物在转移性癌症的各种临床前小鼠模型中的疗效。演示该程序的将是我实验室的博士后Marianna Vitiello博士和IFC-CNR研究员Claudia Kusmic博士。对于黑色素瘤诱导，连续三天在上背部约一平方厘米的剃须皮肤上涂抹三微升五毫摩尔4-羟基他莫昔芬。皮肤涂漆六周后，使用卡尺测量原发性肿瘤的体积，并最终测量皮下转移的体积。然后，使用超声成像来测量腹股沟淋巴结的体积。通过目视检查分析原发肿瘤和淋巴结后，切除它们以进行组织学研究。确认麻醉后，将动物转移到超高频超声成像站的加热板上，将动物保持在仰卧位置。使用用凡士林润滑的直肠探头调节板温度，将小鼠的体温保持在生理范围内。用导电膏涂覆前爪和后爪，并用胶带将其贴在嵌入板中的ECG板电极上。检查生理参数是否正确获取和显示。通过施用脱毛剂去除腹股沟区域的毛发，并用声耦合介质涂覆它们。然后，将超高频超声线性探头夹在嵌入成像站中的专用3D电机中，允许探头的自动和逐步移动。正确定位并调整超声探头的位置，以获得腹股沟淋巴结的短通图像，并将感兴趣区域置于焦点区域。将扫描距离设置为 2 到 5 毫米，步长设置为 44 微米，结果每个淋巴结切片 46 到 114 个扫描步长，每只动物的采集时间为 1 到 3 分钟。扫描腹股沟淋巴结的整个体积作为2D B模式图像序列，通过以微米级阶梯大小的换能器的线性运动来获取多个级别的图像，以生成呼吸和心脏门控电影回路方面的3D数据。成像后，以原始格式以数字方式存储采集的图像，以便进一步离线分析。对于超声图像的后处理，打开3D腹股沟淋巴结图像的数据集，选择多切片方法并按“开始”按钮，以可视化当前帧以及与3D采集期间捕获的每个图像相对应的所有帧的缩略图。选择淋巴结明显的第一帧的缩略图，以将其加载到轮廓视图中。在轮廓视图中，左键单击鼠标以沿淋巴结边界放置点。设置所需点数后，右键单击以完成轮廓。完成第一个轮廓后，使用缩略图视图选择要轮廓的下一个图像。如果需要，请在轮廓之间跳过多个图像，以减少每个 3D 体积所需的手动迹线数。重复此过程，直到整个卷被勾勒出来，然后单击“完成”。在 3D 模式窗口工作区中，单击图像显示区域下方的体积测量图标以可视化淋巴结体积的数值，并通过淋巴结体积的 3D 渲染激活表面视图。用4-羟基他莫昔芬治疗小鼠诱导CreER酶活性，导致基因组水平从野生型Braf到突变的Braf V600E的转换，而Pten则丢失。4-羟基他莫昔芬治疗后四周，原发性肿瘤达到50至100立方毫米的体积，并且可以通过卡尺再测量两周的生长，从而显示腹股沟淋巴结中观察到的色素沉着逐渐增加。黑色素沉积总是由于转移的黑色素瘤细胞的存在，正如黑色素瘤抗原黑色素A和Braf V600E的免疫组织化学染色所证实的那样。在分割阶段结束时，所有部分都显示了淋巴结外部轮廓的叠加。这里显示了在4-HT治疗后4周，5周和6周分析的右腹股沟淋巴结的3D渲染图。同一动物的左腹股沟和右腹股沟淋巴结体积随时间推移的增加也被量化。建议将超声成像与适当的免疫组织化学染色相结合，以便在分子水平上确认癌细胞的存在。除淋巴结外，还可以使用超声成像随时间监测皮下转移的体积。如果两周的时间范围太短而无法理解所研究药物的作用，请选择更外周的诱导位点或不太容易发生肿瘤的基因型。

Research

JoVE Journal

Cancer Research

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer

遗传工程小鼠模型的散发性结肠直肠癌

Despite the advantages of easy applicability and cost-effectiveness, colorectal cancer mouse models based on tumor cell injection have severe limitations ...

科研

癌症研究

Utilizing High Resolution Ultrasound to Monitor Tumor Onset and Growth in Genetically Engineered Pancreatic Cancer Models

应用高分辨率超声监测基因工程胰腺癌的肿瘤发病和生长

The LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre (KPC) mouse model represents an established and frequently used transgenic model to evaluate novel ...

In Vitro Establishment of a Genetically Engineered Murine Head and Neck Cancer Cell Line using an Adeno-Associated Virus-Cas9 System

使用腺相关病毒-Cas9系统在Vitro建立基因工程的毛因头和颈部癌细胞系

The use of primary normal epithelial cells makes it possible to reproducibly induce genomic alterations required for cellular transformation by ...

Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma

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 ...

Quantification of Tumor Cell Adhesion in Lymph Node Cryosections

淋巴结冷冻科肿瘤细胞粘附的定量

Tumor-draining lymph nodes (LNs) are not merely filters of tumor-produced waste. They are one of the most common regional sites of provisional residence ...

Detection of Lung Tumor Progression in Mice by Ultrasound Imaging

超声成像对小鼠肺肿瘤进展的检测

With ~1.6 million victims per year, lung cancer contributes tremendously to the worldwide burden of cancer. Lung cancer is partly driven by genetic ...

Sentinel Lymph Node Mapping and Biopsy for Endometrial Cancer at Early Stage with Laparoscopy

腹腔镜检查早期子宫内膜癌的前哨淋巴结定位和活检

Sentinel lymph node (SLN) mapping and biopsy is a promising technique for visualizing and evaluating lymph node status in cancer. This approach has been ...

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis

用于鉴定黑色素瘤转移新介质的强大发现平台

Metastasis is a complex process, requiring cells to overcome barriers that are only incompletely modeled by in vitro assays. A systematic workflow was ...

Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor

分子和免疫技术在胃肠道间质瘤基因工程小鼠模型中

Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and is typically driven by a single mutation in the KIT receptor. Across tumor ...

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

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 ...