Name: the influence of liver resection on intrahepatic tumor growth
Uploaded: 2016-04-09T14:00:00
Description: Watch this Scientific Journal Video about The Influence of Liver Resection on Intrahepatic Tumor Growth at JoVE.com

特别致谢去本杰明博士天牛他在技术问题援助。作者也想感谢马库斯Forschner博士和伯克穆勒为自己的多媒体支持，埃里卡Magelky她编辑的专业知识和丽莎霍农，罗兰Jurgons博士和斯蒂芬·冯·Hörsten教授（均来自弗朗兹 - Penzoldt中心，大学埃尔兰根），他们在动物处理和护理专业精神。我们感谢在临床化学研究所，德国海德堡大学医学院曼海姆迈克尔Neumaier教授提供MC38肿瘤细胞。 目前的工作是在用于获得程度的要求履行执行“MED博士”。在弗里德里希 - 亚历山大大学埃尔兰根 - 纽伦堡（FAU）。

中弗兰肯在德国巴伐利亚州政府授予描述的过程的权限。任何类似的实验，需要由有关当局事先批准。 注：以下手册可以通过在A，B组被排除在外有相应标志C.步骤可用于前面所讨论的A组。 1.准备<ol><li>戴上手套，放置在显微镜下的聚苯乙烯垫，并且透镜集中于垫稍稍上方的区域。 </li><li>拆分无菌纸和地方一半以上的聚苯乙烯板，另一半只是在它旁边。 </li><li>消毒手术器械，将它们?...

<ol>
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表演在啮齿类动物外科手术之前的实验已经能够确定某些变量，可以作为来源的偏见。为了获得可靠和有效的结果，请考虑以下注意事项。 常规操作前禁食可导致肝脂肪变性12，其可以抑制肝再生13,14。因此，不建议使用。肝细胞的有丝分裂最高活性在整个15天发生变化。如果可能的话，在白天所有组在一定的时间进行的程序。鼠肝再生是最有效的动?...

结直肠癌（CRC）占近9％的恶性肿瘤。它是第三大常见癌症，无论是在美国和世界各地。从30万CRC全球范围内的死亡率为50多万，每年1。患者的百分之二十在他们的大肠肿瘤的发现从肝转移苦。可切除的转移是由部分肝切除2,3通常的方式处理。改进的外科技术，新的多策略和可切除转移新的定义呈现部分肝切除可能越来越多的患者4的疗法。 继发性恶性肿瘤复发，但是，在现代胃肠外科具有挑战性的临床后遗症。 CRC患者谁接受肝转移灶切除术在其剩余肝5开发一种新的肿瘤的30〜50％的机会。因此，有必要对在进一步的研究参与肝转移复发的机制。 约70％的肝切除通常是由剩余的肝组织在几周内补偿。该再生涉及多个机制，包括象白细胞介素-6（IL-6），肿瘤坏死因子α（TNF-α），肝细胞生长因子（HGF）的细胞因子，转化生长因子β（TGF-β），血管内皮生长因子（VEGF ），基质金属蛋白酶（MMP-2和MMP-9）和CXC趋化因子6-11。这些物质支持肝再生，并且还可以通过诱导的小肿瘤细胞沉积物，其中不是由常规临床成像检测到的剩余的肝生长负责初级和次级肝恶性肿瘤的复发率较高。这种因果关系尚未迄今证实。 建立了如下假设。部分肝切除之后，增殖因子，负责活ř肥大也可能诱导以前未发现的肿瘤细胞在肝脏的生长。小鼠模型的设计相结合肝切除和肿瘤诱导的技术。第三无胸腺裸-foxn1nu / nu小鼠分为三组，每组10只动物。他们每个人都用无论是单独的剖腹手术（A组）治疗，30％的肝切除（B组）或70％肝切除术（C组）。在所有组中的动物随后收到一个肿瘤细胞注射到肝脏的定义剩余部分​​，​​以模拟休眠肿瘤细胞。其中，两个星期观察，然后动物评价肿瘤生长和肝脏肥大。 的目标是创建可用于搜索可能发挥肝切除后肿瘤形成的作用的分子和致病因素的模型。这种方法可以是在评估帮助：参与肝再生内分泌因子的来源;肝内TUM责任机制或肝切除术后的增长;和必要的肝内肿瘤生长诱导肝切除量。只是对动物，因为它们承诺向的基本生物学原理的理解，并可以预期受益通过​​改进的治疗选择人类知识的发展已经执行了下面的方法。由于涉及在这些问题的机制，它在体内被检查，如体外方法可能无法提供人类病理学的一个真实的表现。 这些调查可能导致的有关目标的发现为用于降低肿瘤复发的预防性治疗方案。

<table border="0" cellpadding="0" cellspacing="0" width="844">
	<tbody>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Equipment</td>
			<td style="width:217px;"></td>
			<td style="width:143px;"></td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Operation Microscope</td>
			<td style="width:217px;">Zeiss</td>
			<td style="width:143px;">OPMI-1 FC S21</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Induction Cage (Plexiglas Box)</td>
			<td style="width:217px;">UNO BV, Netherlands</td>
			<td style="width:143px;">180000132</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Flowmeter + Connection Kit</td>
			<td style="width:217px;">UNO BV, Netherlands</td>
			<td style="width:143px;">180000008</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">UNO Vaporizer Sigma Delta</td>
			<td style="width:217px;">UNO BV, Netherlands</td>
			<td style="width:143px;">180000002</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Key Filler for Anesthetic</td>
			<td style="width:217px;">UNO BV, Netherlands</td>
			<td style="width:143px;">180000010</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Activated Charcoal Filter Adsorber</td>
			<td style="width:217px;">UNO BV, Netherlands</td>
			<td style="width:143px;">180000140</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Gas Exhaust Unit</td>
			<td style="width:217px;">UNO BV, Netherlands</td>
			<td style="width:143px;">180000118</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Face Mask for mouse</td>
			<td style="width:217px;">UNO BV, Netherlands</td>
			<td style="width:143px;">180000065</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Vaporizer Stand</td>
			<td style="width:217px;">UNO BV, Netherlands</td>
			<td style="width:143px;">180000006</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Heat lamp</td>
			<td style="width:217px;">Physitemp Instruments</td>
			<td style="width:143px;">HL-1</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Styrofoam Pad</td>
			<td style="width:217px;">RAYHER</td>
			<td style="width:143px;">30074000&#160;</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Third Hand Tool</td>
			<td style="width:217px;">TOOLCRAFT&#160;</td>
			<td style="width:143px;">ZD-10F</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Precision Scales</td>
			<td style="width:217px;">Kern</td>
			<td style="width:143px;">EW 220-3NM</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Scales&#160;</td>
			<td style="width:217px;">Kern</td>
			<td style="width:143px;">EMB 500-1</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Sliding Caliper</td>
			<td style="width:217px;">MIB</td>
			<td style="width:143px;">MIB 82026100</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Microdissection forceps</td>
			<td style="width:217px;">Braun/Aesculap</td>
			<td style="width:143px;">BD195R</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Microdissection scissors</td>
			<td style="width:217px;">Braun/Aesculap</td>
			<td style="width:143px;">FD100R</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Microdissection needle holder</td>
			<td style="width:217px;">Braun/Aesculap</td>
			<td>BM563R</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Retractor</td>
			<td style="width:217px;">Fine Science Tools (F.S.T.)</td>
			<td style="width:143px;">No. 17001-0</td>
			<td>Type: Bowmann</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Clamp</td>
			<td style="width:217px;">Braun/Aesculap</td>
			<td style="width:143px;">BJ002R</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Name</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Expendable Items</td>
			<td style="width:217px;"></td>
			<td style="width:143px;"></td>
			<td></td>
		</tr>
		<tr height="20">
			<td colspan="4" height="20" style="height:20px;width:845px;">(NOTE: Quantities are per animal and procedure)</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Foliodrape sterile cover (45x75cm)</td>
			<td style="width:217px;">Hartmann</td>
			<td style="width:143px;">2775001</td>
			<td></td>
		</tr>
		<tr height="20">
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			<td style="width:143px;">3570310</td>
			<td>PZN=04454809</td>
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			<td height="20" style="height:20px;width:319px;">30G canula (Sterican)&#160; - for Tumor injection</td>
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			<td>4656300</td>
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			<td height="20" style="height:20px;width:319px;">Metamizole (=Novaminsulfon)</td>
			<td style="width:217px;">Ratiopharm</td>
			<td style="width:143px;">16543.00.00</td>
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			<td height="20" style="height:20px;width:319px;">4-0 Vicryl suture</td>
			<td style="width:217px;">Ethicon</td>
			<td style="width:143px;">J835G</td>
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			<td height="20" style="height:20px;width:319px;">5-0 Prolene suture</td>
			<td style="width:217px;">Ethicon</td>
			<td style="width:143px;">8618G</td>
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		<tr height="20">
			<td height="20" style="height:20px;">SafeLock Flex-Tube 1.5mL</td>
			<td style="width:217px;">Eppendorf&#160;</td>
			<td style="width:143px;">22363778</td>
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		<tr height="20">
			<td height="20" style="height:20px;width:319px;">4x4 Gauze Sponge</td>
			<td style="width:217px;">Kendall/Covidien&#160;</td>
			<td style="width:143px;">UPC: 728795135355&#160;</td>
			<td>ASIN: B005BFQTWM&#160;</td>
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		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Large paperclip</td>
			<td style="width:217px;">ACCO</td>
			<td style="width:143px;">A7072510G</td>
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		<tr height="20">
			<td height="20" style="height:20px;">Name</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments</td>
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			<td height="20" style="height:20px;width:319px;">Animals</td>
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		<tr height="20">
			<td height="20" style="height:20px;width:319px;">Female athymic nude-foxn1nu/nu</td>
			<td style="width:217px;">Harlan Laboratories B.V.</td>
			<td style="width:143px;">Code 069</td>
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the influence of liver resection on intrahepatic tumor growth

肿瘤复发转移切除肝脏病变后的高发病率仍然是一个未解决的问题。小的肿瘤细胞沉积物，这是不通过常规临床成像可检测的，可通过肝切除后的肝再生因子来刺激。这是不完全清楚，但是，哪些因素是肿瘤复发的关键。 所提出的小鼠模型可能是有用的，以探索肝切除后发挥复发性恶性病变的发展中的作用的机制。该模型结合了规定量的小鼠肝组织切除，肿瘤诱导（注射）中的易于执行和可重复的技术。动物用一个单剖腹手术，30％的肝切除，或70％的肝切除术。所有动物随后收到一个肿瘤细胞注射到剩余的肝组织。两周的观察后，将肝脏和肿瘤大小和重量，并进行了评价免疫组化检查。 一个70％的肝切除后，肿瘤的体积和重量比单独一个剖腹（P &lt;0.05）均显著增加。此外，免疫组织化学（Ki67的）显示切除组中增加的肿瘤增殖率（P &lt;0.05）。 这些结果表明，对肝内肿瘤生长肝再生机制的影响。像组织后处理，或RNA分析相结合的方法，所描述的小鼠模型可以作为参与肝脏内肿瘤的生长和转移复发的疾病不同因素密切审查的基础。相当多的像的术后观察的长度的变量，用于注射或注射和肝切除的时刻的细胞系探索肝切除后的转移的情况下的一个具体问题时提供多种角度。此过程的局限性是互惠thorization执行对动物的过程中，获得适当的动物试验设施，并购置某些设备。

在我们具体的实验中，我们包括30个裸鼠-foxn1nu / nu小鼠。他们接到位数剖腹500,000 MC38肿瘤细胞（溶于50μl生理盐水）的肿瘤细胞的注射，并随后用任一个70％肝切除，30％肝切除，或没有进一步的介入治疗。 后14天，剩余的肝的几乎完全再生以下30％或70％肝切除（30％肝切除组肝脏肥大指数为1.06与0.8从70％肝切除组）中观察到。...

Watch this Scientific Journal Video about The Influence of Liver Resection on Intrahepatic Tumor Growth at JoVE.com

The Influence of Liver Resection on Intrahepatic Tumor Growth

A high incidence of tumor recurrence after resection of liver metastases remains an unsolved problem. The illustrated mouse model may be useful to investigate the reasons for such recurrences. It combines a liver resection model with intrahepatic tumor cell injection for the first time.

肝切除肝内肿瘤生长的影响

The high incidence of tumor recurrence after resection of metastatic liver lesions remains an unsolved problem. Small tumor cell deposits, which are not ...

The recurrence of primary and secondary liver malignoma after partial liver resection remains a common, yet unsolved, problem. The exact mechanisms of tumor formation in the remaining parts of the liver are not understood so far. The following mouse model studied the proliferation of secondary liver malignoma after partial liver resection.In mice, a liver resection of about 70%is normally compensated by liver hypertrophy of the remaining parts of the liver within two to three weeks. The endocrine factors, which play a role in the liver's regeneration, may also induce the growth of liver malignoma. This video introduces a method which can be used to investigate the relationship between liver hypertrophy after resection and tumor growth.The experiment tried to prove that a partial liver resection accelerates the growth of liver malignoma. The shown illustration outlines the murine liver anatomy. To achieve a liver volume reduction of 65 to 70%resection of the median and left lateral lobe is necessary.To induce a liver tumor, a predefined volume of cancerous cells is injected into the inferior right lobe. A Plexiglas box is used for anesthetic induction. The mouse is then positioned and the abdomen disinfected.To provide adequate analgesia, five milligrams per kilogram body weight of Carprofen are administered. The skin incision is made along the median line of the abdomen, from the area above the xiphoid down to the lower abdomen. The xiphoid is carefully dissected from the surrounding tissue, and the abdominal fascia opened, along the linea alba.A stay suture then fixes the now exposed xiphoid bone to a retainer above the animal's head, in order to expose the different liver parts. The retractor is introduced to spread the abdominal wall apart, and gain better access to the abdominal organs. A saline soaked cotton swab is used to shift the median lobe downward.The now exposed falciform ligament is dissected. Median lobe and left lateral lobe are shifted upward against the diaphragm, in order to dissect the thin membrane between the left lateral lobe and the caudate lobe. A size 4.0 ligature is placed at the base of the left lateral lobe, which is subsequently returned to its original position using only the saline soaked cotton swab.It is now tied up using multiple knots. A gradual change of the lobe's superficial color to a more cyanotic tone is a sign of adequately interrupted blood supply. After trimming the ligature threads, the left lateral lobe is resected by cutting along the slightly diagonal line along its base.Now a new ligature is put in place at the median lobe's base. The lobe is likewise repositioned by applying gentle pressure from above with a cotton swab. The median lobe is similarly tied up with multiple knots.With the previously described color change, again indicating effective disruption of blood flow. The ligature threads are trimmed, and the lobe is removed. Because the inferior vena cava runs through the dorsal portion of the lobe, it is prone to damage by the ligature, which may lead to liver necrosis.This part of the lobe must therefore remain in situ. The inferior right lobe is demonstrated by moving the intestinal loops to the left. A 13 gauge syringe containing the tumor cell suspension is carefully introduced into the lobe until the syringe's tip is approximately in the lobe's center part.Inject the tumor cells by slowly applying gentle pressure to the plunger over a period of about 30 to 45 seconds. Afterwards, the penetrated area must be compressed for at least three minutes to control bleeding. Retractor and stay suture are removed, and a single button suture is performed to close the fascia.It is highly recommended to use two lines of sutures, as some animals may try to remove the sutures and reopen the laparotomy after the procedure. The skin is therefore separately adapted with single button knots. To provide adequate recovery and analgesia, the mouse is placed into a warm environment and the animal's drinking water is mixed with 500 milligrams per kilogram body weight of Metamizole.In the experiment, 30 animals were divided into three groups. All groups were injected with tumor cells. Group A was treated only with a laparotomy.Animals in groups B and C underwent liver resection of 30 and 70%of the original liver volume, respectively. It was then found that a liver resection of 70%correlated significantly positive with a greater tumor volume and tumor weight. Immunohistochemistry also showed a greater proliferation rate of tumor cells in animals from the liver resection groups, when comparing them with tumor cells from the laparotomy group.This correlation confirms clinical observations, although further examinations are required in the human system.

Research

JoVE Journal

Medicine

An In Vitro System to Study Tumor Dormancy and the Switch to Metastatic Growth

An In Vitro System to Study Tumor Dormancy and the Switch to Metastatic Growth

一个<em在体外系统来研究肿瘤休眠和转移性增长

Recurrence of breast cancer often follows a long latent period in which there are no signs of cancer, and metastases may not become clinically apparent ...

科研

医学

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics

一种新型的高分辨率<em&gt;在体内</em&gt;成像技术研究肿瘤生长及治疗颅内结构的动态响应

We have successfully integrated previously established Intracranial window (ICW) technology 1-4 with intravital 2-photon confocal microscopy to develop a ...

Orthotopic Injection of Breast Cancer Cells into the Mammary Fat Pad of Mice to Study Tumor Growth.

注射原位乳腺癌细胞到小鼠乳腺脂肪垫来研究肿瘤的生长。

Breast cancer growth can be studied in mice using a plethora of models. Genetic manipulation of breast cancer cells may provide insights into the ...

Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis

建立一个人类多发性骨髓瘤异种移植模型中的鸡，研究肿瘤的生长，侵袭和血管生成

Multiple myeloma (MM), a malignant plasma cell disease, remains incurable and novel drugs are required to improve the prognosis of patients. Due to the ...

Measuring the Effect of Chemicals on the Growth and Reproduction of Caenorhabditis elegans

Measuring the Effect of Chemicals on the Growth and Reproduction of Caenorhabditis elegans

测定化学物质对线虫线虫生长和繁殖的影响

Toxicological evaluation is crucial for understanding the effects of chemicals on living organisms in basic and applied biological science fields. A ...

Transaxillary First Rib Resection for Treatment of the Thoracic Outlet Syndrome

经腋窝第一肋骨切除术治疗胸廓出口综合征

Thoracic outlet syndrome (TOS) is a common disorder that causes a significant loss of productivity. The transaxillary first rib resection (TFRR) protocol ...

Minimizing Post-Infusion Portal Vein Bleeding during Intrahepatic Islet Transplantation in Mice

尽量减少小鼠肝内胰岛移植期间输注后门静脉出血

Although the liver is currently accepted as the primary transplantation site for human islets in clinical settings, islets are transplanted under the ...

Modified Posterior Vertebral Column Resection for Patients with Thoracolumbar Kyphotic Deformity

胸腰椎后凸畸形患者改良后椎柱切除术

Old compression vertebrae fracture or congenital kyphoscoliosis with abnormal vertebral body development and other diseases that invade the spine may ...

An Apical Resection Model in the Adult Xenopus tropicalis Heart

An Apical Resection Model in the Adult Xenopus tropicalis Heart

热带非洲爪蟾成人心脏的根尖切除模型

It is known that in adult mammals, the heart has lost its regenerative capacity, making heart failure one of the leading causes of death worldwide. ...

Microscopic Cyst Resection for the Treatment of Patients Diagnosed with Epididymal Cyst

显微镜囊肿切除术治疗诊断为附睾囊肿的患者

Epididymal cysts mostly occur in men aged 20-40 years old. Previous reports have covered concerns about postoperative complexes, including postoperative ...