The authors have no acknowledgements.

EBUS-안내 시스플라틴으로 치료 모든 환자에 대한 자료를 검토 하였다. 플로리다 대학의 제도적 검토위원회는이 연구 (# IRB201400823)를 승인했다. 모든 데이터는 전향 적으로 수집하여 후 향적으로 분석 하였다. 다음의 등록 기준을 사용합니다. 1. 환자 선택 <ol><li> 조직 검사에서 확인 된 비 - 소세포 폐암 (NSCLC) 또는 비소 세포 폐암 (SCLC)를 가지며, 조직 학적 확인 된 재발이 18에서 80 세 사이의 선택 환자. 6 개월 이상에 대한 폐문 및 종격동 구조 방사선의 적어도 50 GY을받은 환자를 등록. EBUS 및 원격 전이를 통해 액세스 할 수있는 폐문, 종격동 제한 재발 환자 및 주변 기관지 구조 (림프절, 결절 및 질량)를 포함한다. </li><li> 멀티 징계 흉부 종양학 종양 보드에 이러한 모든 환자를 제시하고의 진행에 합의를 얻기다른 국소 치료 옵션의 부족으로 인해 tratumoral 시스플라틴. EBUS-안내 ITC 진행하기로 한 결정은 기관 흉부 종양학 종양 보드의 공동 추천해야한다. </li></ol> 2. 기관지 초음파 (EBUS)는 시스플라틴 주입을 -guided <ol><li> ITC에 대한 폐문, 종격동 및 주변 기관지 구조의 유연한 지경에 초음파 프로브에 내장 할 수 있습니다 실시간 시각화가 볼록 프로브 EBUS를 사용합니다. </li><li> 환자는 절차 이전에 적어도 6 시간 동안 경구 음식과 액체 절제 있는지 확인합니다. </li><li> 이전에 공개 된 문헌 9, 10에 기초하여, 세션 당 40 밀리그램의 최대 투여 량으로 1 ㎎ / ㎖의 농도로 수성 시스플라틴 용액을 만든다. 사용 직전 0.9 % NaCl 용액에서 동결 건조 시스플라틴 분말을 녹인다. </li><li> 정맥 시작에서 덱사메타손 10 mg의 및 온단세트론 8 mg을 보내기절차의 닝은 메스꺼움을 방지합니다. </li><li> 정맥 미다 졸람과 펜타닐을 사용하여 수면 마취와 절차를 수행 (IV). 절차 이전에 4 % 리도카인 분무 5 ㎖의 형태로 국소 마취를 사용한다. </li><li> 미다 졸람의 2 밀리그램과 펜타닐 50 μg의의 IV 주입 함께 시작합니다. 환자마다 1-2 분을 재평가하고 달성 수면 마취를 유지하기 위해 추가 1 밀리그램 미다 졸람, 25 μg의 펜타닐 루스 줄 (최소한 눌려 의식을 환자에게 지속적이고 독립적 특허기도를 유지할 수 있도록 보호 반사 유지, 언어 적 명령 및 물리적 자극)에 응답 남아있다. 각각 펜타닐과 미다 졸람, 200 μg의 10 밀리그램의 최대 허용 용량을 초과하지 마십시오. </li><li> 상기 심장 박동을 모니터링 연속 3 리드 심전도, 연속 맥박 산소 측정기, 호흡 속도 측정을 포함, 표준 모니터링을 사용합니다. 지역 ANEST를 제공합니다hesia 필요에 따라 보조 O 2. </li><li> 기도의 성대를 통해 범위를 사전. 확인 대상 병변을 찾습니다. </li><li> EBUS 프로세서를 켜고 생리 식염수 1-2 mL로 사용하여 범위의 끝에서 풍선을 팽창. 기도 벽에서 범위를 Flex와 병변을 찾습니다. 병변의 위치는 CT / PET 결과에 달려 있지만, 일반적인 위치의 일부 중 subcarinal 영역 좌우 paratracheal 영역과 좌우의 폐문 영역을 포함한다. </li><li> 범위의 작업 채널을 통해 칼집에 수납 된 22 G EBUS 바늘을 배포하고 위치에 고정. 주 : 주사 부위에 대한 정확한 수술 좌표가 없지만, 일반적으로 처리 된 부위의 일부는 (내측 좌우 주 기관지의 교차점에서) 중 subcarinal 측 방향 우측 주 기관지의 오른쪽 paratracheal를 (포함 , 왼쪽 paratracheal) 오른쪽 상단 로브 구멍 위에서 (, (오른쪽 상단 로브 구멍 아래 측면 근위 기관지의 intermedius는에서) 오른쪽 폐문 및 좌측 폐문 (말초 기관의 접합과 대동맥의 아치와 왼쪽 폐동맥 사이의 왼쪽 주에서) 좌측 상엽의 교차점과 좌하 엽 기관지). </li><li> 실시간 초음파 유도 하에서, 기관지 벽에 구멍을 대상 병변에 바늘을 배치합니다. 니들 내에서 탐침을 제거하고 시간에 환부 10 ㎖ (1 밀리그램 / 시스플라틴 mL)에 시스플라틴을 주입. 시트 내의 바늘을 철회. </li><li> 전반에 걸쳐 약물의 주입을 용이하게하기 위해 다른 위치에서 세션 당 네 개의 천공 각 병변을 치료. 펑크 당 시스플라틴 10 mg을 주입한다. </li><li> 세션 당 두 개의 병변을 치료. 이상의 병변 세션 당 처리되는 경우, 40 mg를 초과하지 세션 당 총 투여 량과 시스플라틴 20mg을 각각 주입 사이트. </li><li> 가공용에서 바늘을 제거범위의 NG 채널. </li><li> 말초기도에서 추가 약물을 흡입하고, 기관 지경을 제거합니다. </li><li> 환자가 병원 프로토콜에 따라 복구하고 같은 날에 그들을 배출 할 수 있습니다. </li><li> 4 주 총 일주일에 한 번 (2.7-2.13 단계)에 시스플라틴 주입을 반복 (일 1, 8, 15, 22). 참고 : 처리되면, 특정 병변이 이후의 만남에 ITC와 재치료 고려해서는 안됩니다. </li></ol> 3. 포스트 분사 <ol><li> 후속 흉부 컴퓨터 단층 촬영 (CT)이나 양전자 방출 단층 촬영 (PET / CT)에 의해 응답을 평가하는 8-12주 마지막 치료 세션 후 스캔. 치료의 사이트에서 재발과 종격동, 폐문의 재발, 또는 쇄골 포사과 지역 재발과 국소 재발을 정의합니다. </li></ol>

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The authors have nothing to disclose.

<html> 우리의 원고는 더 많은 방사선이 옵션을 선택하지 않습니다 누구에 환자의 폐암의 고립 된 종격동 및 폐문 재발의 관리에 초점을 맞추고있다. IMHR의 발생 빈도는 약 9 % (11)이다. 다른 치료 방법은 고식적 항암 화학 요법, 더 많은 외부 빔 방사선 치료, 또는지지 요법 및 감시를 포함하여, 이러한 환자에서 시도되고있다. 우리 기관에서, 우리는 기관지 내시경에 의해 유도 종양...

폐암은 모든 암 관련 사망의 5 일에 대한 남성과 여성 모두와 계정에서 전 세계적으로 가장 널리 퍼진 암이다. 그것은 0.87 1, 2의 경우 치사율이 있습니다. 초기 치료 후 재발 폐암 환자에서 대부분의 사망자를 차지한다. 재발 성 폐암에 대한 치료 옵션이 제한됩니다. 재발 성 폐암은 더 개입 (3)에 수용과 관용의 가능성을 감소 모두의 삶의 질에 상당한 교사 단선에 상당한 손상에 이르게 추가지지 요법이 필요합니다. 비소 세포 폐암 환자의 약 30 %는 방사선 사 후 국소 재발이있다. 이들 환자에 대한 치료 옵션은 제한적이며 10 % (5), (6)의 대물 응답 속도가 전신 화학 요법을 포함한다.반복 흉부 방사선이 가능하지만, 그 목적 완화 및 증상 완화 주로 연구되었다 질병 관해 3에 사용되지 않았다. 우리 기관에서, 기관지 내시경을 통해 액세스 격리 된 종격동 및 폐문 재발 (IMHR) 모든 환자는 시스플라틴의 기관지 종양 내 주사 (ITC)를 -guided 기관지 초음파 (EBUS)로 처리 하였다. 전신 화학 요법 및 / 또는 외부 빔 방사선 요법 (EBRT)와 동시 치료는 치료 종양 &#39;재량권에 따라시켰다. 이 원고는 안전성, 유효성, 타당성, 그리고 우리의 기관에서 사용되는 프로토콜에 대한 자세한 방법을 강조한다.

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			<td colspan="2" height="20" style="height:20px;width:261px;">Bronchoscope</td>
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			<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

폐암 환자의 격리 된 폐문 및 외부 빔 방사선 요법 (EBRT) 다음 종격동 재발 (IMHR)이 일반적이다. 이 환자들은 많은 치료 옵션이없는 일반적으로 고식적 항암 화학 요법 또는 최선의지지 요법을 제공됩니다. 기관지 초음파 (EBUS)는 시스플라틴의 종양 내 주입을 -guided (ITC)는 이러한 환자에 대한 새로운 접근 방식이다. 절차는 수면 마취 하에서 수행된다. 병변은 EBUS를 사용하여 기관지에 위치되고, 22 게이지 바늘 EBUS 범위의 워킹 채널을 통해 전진 위치에 고정된다. 초음파 안내 하에서, 기관지 벽의 천공 바늘은 표적 병변에 이동된다. 니들 탐침이어서 제거되고 시스플라틴은 (40 밀리그램 / 40 mL)을 환부에 주입된다. 한 두 사이트는 세션 당 처리됩니다. 절차의 세부 사항은 용지의 프로토콜 섹션에 설명되어 있습니다. 우리 센터에서 50 사이트는 36 명에서 치료를 받았다(19 남성, 17 여성). 우리의 코호트의 평균 연령은 61.9 ± 8.5 세였다. 우리는 35 명, 41 사이트에 최종 분석을 수행 하였다. 35분의 11 (31 %)이 안정 또는 진행성 질환 (비 대응)을 가지고, 반면 35분의 24 (69 %)은 전체 또는 부분 반응 (대응)를 가지고 있었다. 전반적으로, 우리 그룹의 생존하지 않았다 것보다 훨씬 더 나은 생존을 갖는 반응했다 환자 8 개월 (6-11개월의 95 % CI)이었다.

응답은 8~12주 치료 후 후속 촬상하여 측정 하였다. 반응은 완전 관해 (CR), 부분 관해 (PR), 안정한 질환 (SD), 진행성 질환 (PD), 또는 8 RECIST 1.1 기준에 기초하여 응답을 평가할 수없는 것으로 분류 하였다. CR과 PR 환자는 조치로 간주하고, 나머지는 비 반응 군으로 분류 하였다. 이차 결과는 종양의 조직 학적, 재발의 크기, 동시 전신 요법에 따라 응답을 포함. ...

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.

기관지 폐암의 고립 된 종격동 재발의 치료에 시스플라틴의 종양 내 주입을 초음파 유도

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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Research

JoVE Journal

Cancer Research

10.3K 조회수.  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. 

비디오: 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.

개와 고양이 종양의 치료에 대한 Electrochemotherapy의 운영 절차

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

연구

암 연구학

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.

순환 종양 세포 시각화 폐 조직에 대 한 폐 식민 분석 결과의 설립

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.

초음파의 이용 가이드 생물학 관련 전이성 종양 Xenografts의 설립을 위한 세포 이식 조직 감독

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.

간 전이 치료를 위한 초음파 장치 타당성, 안전, 그리고 자가 고 강도의 정확도의 평가 초점을 맞춘

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 위암 조직의 파라핀 내장 슬라이드에 탄성 염색

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.

뮤린 췌장 연성 선암의 초음파 유도 정형 외 이식

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.

종양 연고학을 위한 마우스 폐의 관류 및 인플레이션

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.

종양 세포의 측면 꼬리 정맥 주입 다음 폐 전이의 병리학 적 분석

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.

두개 내 주입 및 자기 공명 이미징을 통해 뇌 전이를 모델링

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.

염증성 유방암 세포의 꼬리 정맥 주입을 통한 뇌 전이 모델링

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 ...