Name: ex vivo treatment response of primary tumors and/or associated metastases for preclinical and clinical development of therapeutics
Uploaded: 2014-10-02T15:00:00
Description: Watch this Scientific Journal Video about Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics at JoVE.com

The authors would like to thank the MSKCC Tissue Procurement Service Team (TPS), specifically, Maria Corazon Mariano, Priscilla McNeil, Anas Idelbi, Daniel Navarrete and Katrina Allen, in all of their efforts in the successful pursuit of this project and funding from the following sources: 5 R21 CA158609-02 and the Conquer Cancer Foundation and the Breast Cancer Research Foundation. In addition, the authors would like to thank Eric Cottington PhD, Vice President of the Office of Research and Project Administration, the Office of Technology Development, Research Outreach and Compliance and RTM Information Systems Support, in the support of the submission of this manuscript.

참고 : 환자 조직 조달이 제도적 검토위원회 (IRB)를 통해 권한이 부여 된 기념 슬로안 케터링 암 센터에서 Biospecimen 및 임상 프로토콜 (프로토콜 번호는 각각 09-121 및 11-041을) -approved. 1 조직 조달 <ol><li> 환자의 기본 종양 / 전이 조달 참고 : 현재까지,이 프로토콜은 수술로 제거 췌장, 위 및 유방 종양 유형뿐만 아니라, 같은 림프종 전이에 수행되었습니다. <ol><li> 멸균 유...

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효과적인 치료 전략을 개발하려고 할 때 암 생물 학자들은 상당한 도전에 직면하고 있습니다. 확립 암 세포주에서 약물 개발을 테스트하는 것은 정확하게 생체 반응과 PDX 모델에서 생체 내 실험은 노동 집약적이고 비용이 매우 다를 수있다. 상기를 감안 기본 환자의 생체 기술의 애플리케이션 (15)은 현재 설정된 암 세포주와 환자 유래의 이종 이식 (PDX)의 분자량 분석 ...

효과적인 암 치료제를 개발하는 것이 매우 어려운 것으로 입증되었습니다. 암 세포주와 종양 이식편 -뿐만 아니라 이종 절반 위에 세기 1,2,3 대한 암 연구에서 사용되어왔다. 현재까지, 약물 감수성 및 내성 둘 확립 암 세포주 및 이종 이식 환자 유래의 분자량 분석 (PDX)이 필수적이다. 그러나, 확립 암 세포주에서의 시험 화합물들은 생체 내 효능을 예측할 수없고, 특히 PDX 모델에서, 동물의 생체 내 연구에 대응하는, 매우 많은 비용과 시간이 소요된다. 이 모델 시스템, 종양 진행 및 치료 전략에 응답하여 네이티브 미세의 영향에 알리는 즉 무능력의 한계는 이러한 분석을 보완하기위한 추가 방법을 개발하는 연구 분야를 주도하고있다. 최근의, 높아진 관심은 환자 다치의 생체 분석으로 지급되는암 치료 반응은 암세포의 내재적 분자 조성물 단독이 아니라 오히려 크게 기존 배양 방법에 의해 효과적으로 요약 할 수없는 종양 세포 미세 환경 (6, 7) 기능에 의해 영향을 받는다는 인해 큰 이해 또는 이식편 4, 5 / 또는 PDX. 상기 컨텍스트의 생체 외 분석 (예. 인접한 주위 종양 세포 미세 환경의 영향)보다는 셀룰러 균주 8, 9의 생체 외 분석을보다 실용적 일차 종양 / 전이 섹션의 평가를 의미한다. 우리는 모두 환자의 기본 종양 (정밀 분리 된 신선한 조직 섹션 즉.) 및 관련 전이 (즉, 림프절)을 충실하게 응답에 알립니다 (IC50), 오프 대상 효과 생체 기술에 여기에보고하고 분자 수 있습니다 저항과 피드백 메커니즘의 분석. 치료 적 레이저 각막 절제의 또한, 상관 관계 분석바이오 마커 및 유전자 발현 프로파일 대 utic 감도 / 저항 (즉. 높은 약물 반응이 특히 생물학적 프로필을 가진 환자와 일치) 관심 실험 약물에 반응 할 가능성 환자를 확인하기 위해 수행 될 수있다. 다중 매개 변수 방식으로 생체 기술과 평가의 적용은 환자의 선택과 임상 결과의 전반적인 개선을 향한 움직임이다. 생체 내 치료 반응 분석은 암 치료제의 전임상 및 임상 개발의 표준 도구가 될 수 있고, 치료 개발 전략에 맞춤 의학의 접근 방식으로 단계로 구상된다.

<table border="0" cellpadding="0" cellspacing="0" width="598">
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			<td height="43" style="height:43px;width:216px;">Name of Material/ Equipment</td>
			<td style="width:96px;">Company</td>
			<td style="width:119px;">Catalog Number</td>
			<td style="width:167px;">Comments/Description</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Vibratome Leica VT1000s</td>
			<td style="width:96px;">Leica</td>
			<td style="width:119px;">14047235613</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">UltraPure agarose</td>
			<td style="width:96px;">Invitrogen</td>
			<td style="width:119px;">16500500</td>
			<td style="width:167px;">Prepare 4% and 6% before use</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Injector blade</td>
			<td style="width:96px;">Ted Pella</td>
			<td style="width:119px;">121-4</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">MEM with Penicillin&#160; + Streptomycin</td>
			<td style="width:96px;">Media Core Facilities (MSKCC)</td>
			<td style="width:119px;"></td>
			<td style="width:167px;">The media is prepared at Memorial Sloan Kettering Cancer Center&#160;</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Scalpel no. 10</td>
			<td style="width:96px;">Thermo Scientific</td>
			<td style="width:119px;">31-200-32</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Disposable forceps</td>
			<td style="width:96px;">Cole-Parmer</td>
			<td style="width:119px;">84011182</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Embedding mold</td>
			<td style="width:96px;">Electron Microscopy Science</td>
			<td style="width:119px;">70181</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">FBS (heat inactivated)</td>
			<td style="width:96px;">Gemini</td>
			<td style="width:119px;">100106</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">24 well plates</td>
			<td style="width:96px;">Corning</td>
			<td style="width:119px;">3524</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Formalin (10%)</td>
			<td style="width:96px;">Sigma Diagnostics</td>
			<td style="width:119px;">SDHT501128&#160;</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">16% Formaldehyde solution</td>
			<td style="width:96px;">Thermo Scientific</td>
			<td style="width:119px;">28908</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Embedding microsettes</td>
			<td style="width:96px;">Simport</td>
			<td style="width:119px;">M503-2</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Ethanol (70%)</td>
			<td style="width:96px;">Fisher Scientific</td>
			<td style="width:119px;">A405P-4</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Waterbath</td>
			<td style="width:96px;">Fisher Scientific</td>
			<td style="width:119px;">15-462-2SQ</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Microwave</td>
			<td style="width:96px;">General Electric</td>
			<td style="width:119px;">ModelJES2051DNBB</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Adhesive (Ethyl Cyanoacrylate)</td>
			<td style="width:96px;">Sigma-Aldrich</td>
			<td style="width:119px;">E1505-5G</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">10mm dishes</td>
			<td style="width:96px;">BD Falcon</td>
			<td style="width:119px;">353003</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:216px;">15ml tubes</td>
			<td style="width:96px;">BD Falcon</td>
			<td style="width:119px;">352096</td>
			<td style="width:167px;"></td>
		</tr>
	</tbody>
</table>

ex vivo treatment response of primary tumors and/or associated metastases for preclinical and clinical development of therapeutics

The molecular analysis of established cancer cell lines has been the mainstay of cancer research for the past several decades. Cell culture provides both direct and rapid analysis of therapeutic sensitivity and resistance. However, recent evidence suggests that therapeutic response is not exclusive to the inherent molecular composition of cancer cells but rather is greatly influenced by the tumor cell microenvironment, a feature that cannot be recapitulated by traditional culturing methods. Even implementation of tumor xenografts, though providing a wealth of information on drug delivery/efficacy, cannot capture the tumor cell/microenvironment crosstalk (i.e., soluble factors) that occurs within human tumors and greatly impacts tumor response. To this extent, we have developed an ex vivo (fresh tissue sectioning) technique which allows for the direct assessment of treatment response for preclinical and clinical therapeutics development. This technique maintains tissue integrity and cellular architecture within the tumor cell/microenvironment context throughout treatment response providing a more precise means to assess drug efficacy.

이 연구를 위해 생체 외 기술은 열 충격 단백질 90 저해제 (Hsp90i)의 치료 감수성 / 내성 상관 분석에 사용 하였다. 이 Hsp90i, 유방암 일차 종양, ER + 침윤성 암종 (IDC), 및 관련된 림프절 전이의 임상 평가에 치료 반응을위한 생체 외 분석 하였다 &#160; (그림 1). 여러 200 μm의 시리얼 섹션 Hsp90i의 차량 만 증가 복용량 (0.25, 0.50, 1.0 및 2.5 μM)로 처리 하였다. 그?...

Watch this Scientific Journal Video about Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics at JoVE.com

Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics

설립 암 세포주 및 이종 이식편은 지난 수십 년간 암 연구의 주류이었다. 그러나, 최근의 증거는 치료 반응이 크게 종양 세포 미세 환경에 의해 영향을 받는다는 의미한다. 따라서, 우리는 약물 개발을 목적으로 일차 종양 시료의 생체 외 분석을 개발 하였다.

기본 종양 및 / 또는 전임상에 대한 관련 전이 및 치료제의 임상 개발의 전 생체 치료 응답

The molecular analysis of established cancer cell lines has been the mainstay of cancer research for the past several decades. Cell culture provides both ...

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Medicine

Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics

Thermal Ablation for the Treatment of Abdominal Tumors

복부 종양의 치료를위한 열 절제

Percutaneous thermal ablation is an emerging treatment option for many tumors of the abdomen not amenable to conventional treatments. During a thermal ...

연구

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In vitro Organoid Culture of Primary Mouse Colon Tumors

In vitro Organoid Culture of Primary Mouse Colon Tumors

기본 마우스 대장 종양의 체외 Organoid의 문화

Several  human and murine colon cancer cell lines have been established, physiologic  integrity of colon tumors such as multiple cell layers, basal-apical ...

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

소설 고해상도<em&gt; 생체 내</em종양의 성장과 치료학에 두개 내 구조물의 동적 응답을 공부하기&gt; 이미징 기술

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

Adaptation of Semiautomated Circulating Tumor Cell (CTC) Assays for Clinical and Preclinical Research Applications

Adaptation of Semiautomated Circulating Tumor Cell CTC Assays for Clinical and Preclinical Research Applications

임상 및 전임상 연구 응용 프로그램에 대한 종양 세포 (CTC) 분석 실험을 순환 반자동의 적응

The majority of cancer-related deaths occur subsequent to the development of metastatic disease. This highly lethal disease stage is associated with the ...

A Preclinical Murine Model of Hepatic Metastases

간 전이의 전임상 쥐과 모델

Numerous murine models have been developed to study human cancers and advance the understanding of cancer treatment and development. Here, a preclinical, ...

Isolated Hepatic Perfusion as a Treatment for Liver Metastases of Uveal Melanoma

포도막 흑색 종의 간전이에 대한 치료로 고립 간 관류

Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic ...

Generation of Microtumors Using 3D Human Biogel Culture System and Patient-derived Glioblastoma Cells for Kinomic Profiling and Drug Response Testing

Kinomic 프로파일 의약품 응답 테스트를위한 3D 인간의를 Biogel 문화 시스템을 사용 Microtumors 및 환자 유래 아교 모세포종 세포의 생성

The use of patient-derived xenografts for modeling cancers has provided important insight into cancer biology and drug responsiveness. However, they are ...

Assessment of Spontaneous Alternation, Novel Object Recognition and Limb Clasping in Transgenic Mouse Models of Amyloid-&#946; and Tau Neuropathology

아밀로이드 -β 및 타우 신경 병증의 유전자 변형 마우스 모델에서 자발적 교대, 새로운 대상 인식 및 사지 걸림의 평가

Here we describe a staged, behavioral testing approach that can be used to screen for compounds that exhibit in vivo efficacy on cognitive and functional ...

Treatment of Liver Metastases Using an Internal Target Volume Method for Stereotactic Body Radiotherapy

몸 정위 적 방사선 치료에 대 한 내부 대상 볼륨 메서드를 사용 하 여 간 전이의 치료

The prognosis of patients with metastatic cancers has improved in the past decades due to effective chemotherapy and oligometastatic surgery. For ...

Contractions of Human-iPSC-derived Cardiomyocyte Syncytia Measured with a Ca-sensitive Fluorescent Dye in Temperature-controlled 384-well Plates

Spontaneously contracting syncytia of cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CM) are a useful model of human cardiac ...