이 연구는 사례 종합 암 센터 (P30 CA43703)에 의해 지원되었다.

1. Stereotactic Radiosurgery Cyber​​knife 상담 <ol><li> Cyberknife의 radiosurgery 치료를 설명해주십시오. Cyberknife radiosurgery이 자동차를 만들기 위해 사용되는 기계와 유사한 산업용 로봇 팔에 장착된 선형 가속기의 사용을 포함한다. 그것이 빔 전송을위한 여러 치료를 &#39;중지&#39;를 통해 진행됨에 따라 로봇 팔이 환자 주위를 3 차원 공간에서 선형 가속기를 이동합니다. 엑스레이는 환자를 확인하기 위해 치료 도중에 획득되는 크로스 비행기는 올바른 치료 위치에 있습니다. 치료 빔 전송은 2 차원 평면에 국한되지 않고 있기 때문에,이 시스템은 더욱 중요한 피부와 내장 기관의 구조에 방사선 선량을 최소화하면서 암을 대상으로 집중 방사선 접종을 전달하는 능력을 향상시킵니다. </li><li> Cyberknife의 radiosurgery 위험을 의논하십시오. Cyberknife radiosurgery 가능 피부, 피로, 메스꺼움이나 드문 diarrh에게의 선탠과 붉어지는 것을 초래할 수EA, 희귀 내장 장기 손상, 근육, 신경 및 뼈 부상, 둘째 암의 아주 작은 위험. </li></ol> 2. Stereotactic Radiosurgery Cyber​​knife Fiducial 배정 <ol><li> fiducial 위치를 설명해주십시오. 영구 또는 재발성 gynecologic의 암 치료를 받고 여성은 암 표적 내에서 혹은 가까운 적어도 세 싱글 1.6 × 3 밀리미터 황금 연조직 fiducials (쌀알 크기)의 요원이나 CT-가이드 배정을 받고있다. 이전 수술 시에 배치 외과 클립 radiosurgical의 fiducials로 사용될 수있는 충분한 밀도 없습니다. 외과 클립 radiosurgical 때문에 밀도 불일치 타겟팅을 방해하지 않습니다. </li><li> radiosurgical 대상에 상대 fiducial 위치를 나타냅니다. Fiducials는 radiosurgical 대상 주위 조직 깊이를 변화에 배치되며 이cm 이상으로 구분해야합니다. Fiducials는 전술 4~6센티미터 내에 위치하고 있습니다arget. </li></ol> 3. Stereotactic Radiosurgery Cyber​​knife 처리 계획 <ol><li> radiosurgical 치료 계획을 의논하십시오. fiducial 배치 후 적어도 하나의 주 (즉, 그래서 치유가 발생했으며 fiducial 움직임이 최소화), 환자는 CT-가이드 SBRT 치료 시뮬레이션을 받고있다. 저희 프로그램에서 두 개의 핀화된 대피 진공 백 골반 고정이 사용됩니다. </li><li> . 여성은 Cyberknife의 radiosurgical 플랫 탁상에 나태한 치료 위치에서 처리되는 치료 테이블에 환자 위치를 나타냅니다. </li><li> 대상 및 환자 고정 의논하십시오. 환자가 방사선 선량 전달하는 동안 intrafraction 모션을 줄이기위한 대피 진공 백 부동화를 받게됩니다. 일단 고정화, 여성 받아야 비 대비 연속 축 중부 표준시 고해상도 이미징을 (1-1 피치, 1.0 밀리미터 슬라이스 두께, 전압 120 kVp, 450 가구). </li><li> 고급의 사용을 토론대상 지방화를위한 이미징. 중부 표준시 이미징 후, 여성은 같은 SBRT 처리 위치에 선호 종래의 18 F-FDG PET / 중부 표준시 이미징을 받고있다. 또한, 여성들은 전통적인 대조 골반 자기 공명 영상을 받다 수 있습니다. </li><li> 이미지 radiosurgical 치료 계획을위한 공동 등록을 설명해주십시오. 고해상도 중부 표준시 18 F-FDG PET / 중부 표준시에서 이미지 MultiPlan 3.5.2 치료 계획 시스템 (Accuray)에 반비례 방사선 치료 계획에 대해 가져옵니다. </li><li> radiosurgical 치료 계획에 팀 접근 방식을 기술합니다. 치료 계획, 방사선 종양학 의사 모두와 gynecologic 종양학 의사 윤곽 암 대상 임상 대상 볼륨 (CTVs) 때문이다. 기타 질병의 위험에 처한 조직은 contoured되고 CTVs에 포함되어 있습니다. 그러한 작은 창자, 직장, 방광, 간, 신장, 폐, 양자 근위 대퇴골, 질, 그리고 성례의 신경 뿌리와 같은 주변 정상 조직 구조에 의해 contoured됩니다방사선 종양학 의사. </li><li> 방사선 선량 처방을 설명합니다. 3 방사선 처방 선량 × 800 cGy = 2,400 cGy가 (일반적으로 70 % isodose 라인까지) 선택되었습니다. 200 cGy 생물 학적 등가 선량 계산에서 약 6,170 cGy이 처방은 종양에 대한 10의 &quot;β / α&quot;비율을 가정으로 배달됩니다. SBRT 선형 가속기로부터 방출되는 방사선은 12 고정된 텅스텐 원형 collimators 중 하나를 (5-60밀리미터)을 사용하여 혹은 텅스텐 - 구리 합금 세그먼트 육각 홍채 콜리 메 이터를 사용하여 중 collimated됩니다. 14 정상 장기의 방사선 내성을 가지고 있으며 사용을 용융 stereotactic radiosurgery의 동안 정상적인 조직 제약 조건에 대한 선량 - 볼륨 히스토그램 매개 변수는 표 1에 나열되어 있습니다. </li></ol> 4. Stereotactic Radiosurgery Cyber​​knife 처리 배달 <ol><li> 교차 평면 이미지 검증을 수행합니다. Cyberknife SBRT 동안, 살짝 fiducials(또는 어떤 경우에는 같은 intracranial 병변과 척추 병변에 대한 척추의 두개골과 같은 단단한 해부 학적 경계표)가 교차 비행기 radiographic 영상에서 추적하고 대상 현지화 시스​​템 (TLS) 서브 시스템에 의해 예상되는 대상 위치에 있어야 확인하고 있습니다. </li><li> 대상 위치를 확인하십시오. Fiducials은 자유, 셋, 최대 6 도까지 (즉, X, Y, Z, 피치, 롤, 그리고 편주)에서 추적됩니다. TLS에 의해 생성된 이미지는 자동으로 등록되고 CT 촬영을 계획 초기 치료에서 생성된 디지털 복원 radiographs (DRRs)과 비교된다. </li><li> 대상 위치를 확인하십시오. 자동 등록 결과 fiducials 자유의 여섯 학위 (X, Y, Z, 피치, 롤, 그리고 편주) 중 하나에 정의된 허용 오차 이상으로 이동하셨습니다 경우, 치료가 자동적으로 일시 중지됩니다. 환자 위치 조정 후 발생합니다. </li><li> 대상 모션을 고려하십시오. 목표를 호흡 운동과 움직임 TR 것을Synchrony의 호흡기 추적 서브 시스템 (Synchrony)를 이용 eated. 카메라의 사용이 치료 방에 탑재로 시스템은 지속적으로 환자의 흉부 주위 조끼에 부착된 발광 다이오드 (LED가)의 사용으로 환자의 호흡 패턴 (즉, 외부 위치 데이터를 얻기)를 추적합니다. 함께 10 교차 비행기 엑스레이에서 얻은 fiducial 위치 정보 (내부 위치 데이터)와 함께 Synchrony 시스템은 외부 데이터 및 내부 데이터와 상관 관계 모델을 만듭니다. 이 상관 관계 모델은 로봇 팔이 어떤의 전달 및 모든 치료 광선 동안 동안 대상의 모든 호흡기 유도된 운동을 따르 수 있습니다. </li><li> 치료는 로봇 팔 100-150 deliverable 치료 위치를 수반 있습니다. 트리 트먼트는 30 90 분 지속될 수 있습니다. </li></ol> 5. 대표 결과 Stereotactic 바디 방사선 치료 (SBRT)은 많은 개별 방사능 광선이 포함되어 있습니다 (<html> 그림 1A와 같이 파란색 벡터)는 모두 하나 또는 여러 개의 밀접하게 관련된 임상 방사선 표적을 수렴. 대표 좋은 radiosurgical 계획 결과는 높은 방사선 선량 암 대상 볼륨 범위와 암 대상 conformality있는 deliverable SBRT 트리 트먼트를 제공합니다. 그림 1B-D 쇼 131 대들보가 42분 이상 chemorefractory 난소암 대상의 골반 재발을 치료하는 데 사용되었다. 80 % isodose 라인에 처방 SBRT 세 일일 800 cGy의 분수에 2,400 cGy의 총 복용량을위한 1.94의 conformality 지수 100 % 임상 대상 볼륨 범위를 렌더링. 임상 대상 (적색)과 직장 (갈색), 방광 (노란색)의 중요한 구조의 선량 - 볼륨 histograms은 작은 창자이 (하늘색) 성례의 신경 (황갈색)와 엉덩이 (오렌지) 그림 2에 표시됩니다. <img alt="그림 1" src="/files/ftp_upload/3793/3793fig1.jpg" /> 1 그림.TP :/ / www.jove.com/files/ftp_upload/3793/3793fig1large.jpg &quot;대상 =&quot;_blank &quot;&gt; 큰 그림을 보려면 여기를 클릭하십시오. <img alt="그림 2" src="/files/ftp_upload/3793/3793fig2.jpg" /> 그림 2. 임상 대상 (적색)과 직장 (갈색), 방광 (노란색)의 중요한 구조의 선량 - 볼륨 histograms, 작은 창자 (하늘색) 성례의 신경 (황갈색)와 엉덩이 (오렌지).

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우리는 (CAK, JMB, R &amp; D) 공개 게 없다.

유도 초기 SBRT의 성과가 지속 또는 재발 부인과 암의 치료에 radiosurgery의 임상 조사. 7, 8를 자극했습니다 15 데이터 radiobiological 효과와 SBRT로 인한 세포 사망의 모드 문제를 제기하고 있습니다. 소규모 임상 연구 SBRT에서 제공 절제 방사선 양이 90 %를 초과하는 대상 질병 제어 속도를 생산하는 것으로 나타났습니다. 기존의 방사선와는 달리, 그것은 radiosensitizing 및 cytostatic / 세포 독성 chemotherapies로 SBRT을 결합하는 데 도전했습니다. 증가 계획 처리 볼륨 확장을 통해 18 F-FDG PET / 중부 표준시 이미지의 포함을 통한 타겟팅 암치료법은 임상 결과를 향상되었습니다. 그것은 높은 정밀도와 선량 - 에스컬레이션된 방사선을 전달하는 다른 방법에 대해 조사하는 필수적이지만, 그것은 SBRT은 낮은 근접 치료 선량 속도 높이 동등한 치료 효과를 제공할 수 있는지 여부 미정 남아있다. 사실, 근접 치료는 더 많이하고 vali입니다gynecologic의 암 표적에 방사선 선량 상승을 달성하기위한 기술 일자. 따라서, 열정과 신중함 모두 gynecologic의 암 치료에 사용할 수 SBRT 데이터를 읽기에 적합합니다.

<table border="1"><tbody><tr><td> 장치의 이름 </td><td> 회사 </td><td> 카탈로그 번호 </td><td> 댓글 </td></tr><tr><td> Cyber​​knife 시스템 </td><td> Accuray (서니 베일, 캘리포니아) </td><td></td><td></td></tr></tbody></table>

stereotactic radiosurgery for gynecologic cancer

Stereotactic 바디 방사선 치료 (SBRT)은 더 호흡 운동에 대한 까다로운 환자 고정, 회계, 복잡한 치료 계획, 온 - 보드 영상, 그리고 암으로 절제 방사선 접종의 감소 수를 일반적으로 화학 요법과 종래의 방사선에 대한 내화물 목표를 necessitating하여 자신을 구별. 가파른 SBRT의 방사선 선량은 드롭 오프 허가 좁은 &#39;연필 빔&#39;치료 분야는 1-3 트리 트먼트를 응축 절제 방사선 치료에 사용될 수 있습니다. 의사들을 처리하면 해당 SBRT 지리적 종양의 양 정상 조직 손상과 기회의 더 큰 위험에 온다 주셔서 감사합니다. 모두 암 표적의 부동화 의해 고정밀 치료 납품가 달려드는해야합니다. 암 대상 부동화는 환자 독립적인 복부 압축과 인덱스 맞춤 스티로폼 기초가, 대피 콩 봉지, 또는 체형 수정 금형을 사용하여 달성되었습니다. 암 targe 중 1-3 Intrafraction 운동은호흡에 의한 TS는 이제 환자 반응 숨을 보류 기법, 4 환자 떠벌이 활성 호흡 조정, 5 호흡 - 상호 계산된 tomography, 6, 움직이는 종양 내에 그리고 주변에 심어 fiducials의 이미지 가이드 추적에 의해 감소될 수있다. 7-9는 Cyber​​knife 시스템 (Accuray [서니 베일, 캘리포니아])는 정확하게 카메라 추적 환자에 장착 조끼에 임신 발광 다이오드 (LED)로 설정하여 환자의 호흡 운동을 다음과 산업용 로봇 팔에 장착된 방사선 선형 가속기를 활용합니다. 방사선 요법 마진 10 실질적인 감소는 궁극적으로 submillimeter 정확하게 반구하고 작은 계획 대상 볼륨 렌더링, 모션 추적에 의해 달성될 수있다. 11-13 SBRT로 치료 암 목표 수렴, 긴밀하게 collimated 광선에 의해 반구됩니다. 암 대상 볼륨 histograms에 대한 결과 방사선 선량은 더 대명사가높은 비율의 대상 범위 및 소형 높은 선량 방사선 나타내는 ced 방사선 &quot;어깨&quot; &quot;꼬리.&quot; 따라서 증가 대상 conformality은 SBRT 암 표적의 감소 선량 균일성의 비용으로 온다. 이것은 SBRT 대상에서 후속 종양 제어 및 위험 장기의 정상적인 조직 내성 모두에게 의미가있을 수 있습니다. 암 표적이 완전히 인식되지 않으며 불충 분한 SBRT 선량 마진이 적용되면 SBRT의 날카로운 선량 falloff으로 인해 절제 방사선 선량을 탈출할 초자연 질병의 가능성이 발생합니다. 큰 계획 대상 볼륨 (PTV)의 결과로 0.5 cm에 의한 임상 대상 볼륨 (CTV) 확장은, 부당한 정상 조직 손상없이 증가 대상 컨트롤과 연결됩니다. 지리적 미스의 확률에 7,8 추가 감축이 정관에 의해 달성될 수있다 중 2 - [18 F] 플루오로 -2 - 데옥시-D-글루코오스 (18 F-FDG) 양전자 방출 tomography (PET) SBRT treatme 18 F-FDG PET / 중부 표준시 8 사용.NT 계획은 gynecologic의 암 새로운 영상 표적 분자 서명을 발견하려는 시도의 시작일뿐입니다.

Watch this Scientific Journal Video about Stereotactic Radiosurgery for Gynecologic Cancer at JoVE.com

Stereotactic Radiosurgery for Gynecologic Cancer

암을 전달 Stereotactic 바디 방사선 치료 (SBRT)가 관련된 이미지를 유도, 절제 방사선 화학 요법이나 기존의 방사선 치료에 대한 내화 대상으로하고 있습니다. 정교한 대상 지방화를 사용하여 로봇-무장한 Cyber​​knife SBRT 시스템, 암 목표를 살균 능력 hypofractionated 방사선 접종을 제공합니다. 이 문서는 부인과 암에 대한 SBRT의 새로운 치료 역할을 고려할 것입니다.

Gynecologic 암에 대한 Stereotactic Radiosurgery의

Stereotactic body radiotherapy (SBRT) distinguishes itself by necessitating more rigid patient immobilization, accounting for respiratory motion, ...

stereotactic-radiosurgery-for-gynecologic-cancer

Research

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Medicine

17.6K 조회수.  University Hospitals Case Medical Center and Case Western Reserve University School of Medicine. 암을 전달 Stereotactic 바디 방사선 치료 (SBRT)가 관련된 이미지를 유도, 절제 방사선 화학 요법이나 기존의 방사선 치료에 대한 내화 대상으로하고 있습니다. 정교한 대상 지방화를 사용하여 로봇-무장한 Cyber​​knife SBRT 시스템, 암 목표를 살균 능력 hypofractionated 방사선 접종을 제공합니다. 이 문서는 부인과 암에 대한 SBRT의 새로운 치료 역할을 고려할 것입니다...

비디오: Stereotactic Radiosurgery for Gynecologic Cancer

Multispectral Real-time Fluorescence Imaging for Intraoperative Detection of the Sentinel Lymph Node in Gynecologic Oncology

The prognosis in virtually all solid tumors depends on the presence or absence of lymph node metastases.1-3 Surgical treatment most often combines radical excision of the tumor with a full lymphadenectomy in the drainage area of the tumor. However, removal of lymph nodes is associated with increased morbidity due to infection, wound breakdown and lymphedema.4,5 As an alternative, the sentinel lymph node procedure (SLN) was developed several decades ago to detect the first draining lymph node from the tumor.6 In case of lymphogenic dissemination, the SLN is the first lymph node that is affected (Figure 1). Hence, if the SLN does not contain metastases, downstream lymph nodes will also be free from tumor metastases and need not to be removed. The SLN procedure is part of the treatment for many tumor types, like breast cancer and melanoma, but also for cancer of the vulva and cervix.7 The current standard methodology for SLN-detection is by peritumoral injection of radiocolloid one day prior to surgery, and a colored dye intraoperatively. Disadvantages of the procedure in cervical and vulvar cancer are multiple injections in the genital area, leading to increased psychological distress for the patient, and the use of radioactive colloid.
Multispectral fluorescence imaging is an emerging imaging modality that can be applied intraoperatively without the need for injection of radiocolloid. For intraoperative fluorescence imaging, two components are needed: a fluorescent agent and a quantitative optical system for intraoperative imaging. As a fluorophore we have used indocyanine green (ICG). ICG has been used for many decades to assess cardiac function, cerebral perfusion and liver perfusion.8 It is an inert drug with a safe pharmaco-biological profile. When excited at around 750 nm, it emits light in the near-infrared spectrum around 800 nm. A custom-made multispectral fluorescence imaging camera system was used.9.
The aim of this video article is to demonstrate the detection of the SLN using intraoperative fluorescence imaging in patients with cervical and vulvar cancer. Fluorescence imaging is used in conjunction with the standard procedure, consisting of radiocolloid and a blue dye. In the future, intraoperative fluorescence imaging might replace the current method and is also easily transferable to other indications like breast cancer and melanoma.

Fluorescence imaging is a promising innovative modality for image-guided surgery in surgical oncology. In this video we describe the technical procedure for detection of the sentinel lymph node using fluorescence imaging as showcased in gynecologic oncologicy. A multispectral fluorescence camera system, together with the fluorescent agent indocyanine green, is applied.

Gynecologic 종양학의 센티널 림프절의 Intraoperative 감지 Multispectral 실시간 형광 이미징

The prognosis in virtually all solid tumors depends on the presence or absence of lymph node metastases.1-3 Surgical treatment most often combines radical ...

연구

의학

Stereotactic Intracranial Implantation and In vivo Bioluminescent Imaging of Tumor Xenografts in a Mouse Model System of Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is a high-grade primary brain cancer with a median survival of only 14.6 months in humans despite standard tri-modality treatment consisting of surgical resection, post-operative radiation therapy and temozolomide chemotherapy 1. New therapeutic approaches are clearly needed to improve patient survival and quality of life. The development of more effective treatment strategies would be aided by animal models of GBM that recapitulate human disease yet allow serial imaging to monitor tumor growth and treatment response. In this paper, we describe our technique for the precise stereotactic implantation of bio-imageable GBM cancer cells into the brains of nude mice resulting in tumor xenografts that recapitulate key clinical features of GBM 2. This method yields tumors that are reproducible and are located in precise anatomic locations while allowing in vivo bioluminescent imaging to serially monitor intracranial xenograft growth and response to treatments 3-5. This method is also well-tolerated by the animals with low perioperative morbidity and mortality.

Stereotactic Intracranial Implantation and In vivo Bioluminescent Imaging of Tumor Xenografts in a Mouse Model System of Glioblastoma Multiforme

We describe an integrated method for the precise, stereotactic implantation of human glioblastoma multiforme cells into the brains of nude mice and subsequent serial in vivo imaging to monitor growth and response to treatment of the resultant xenografts.

Stereotactic Intracranial 주입 및<em&gt; 생체에</emGlioblastoma의 Multiforme의 마우스 모델 시스템에서 종양 Xenografts의&gt; 발광 생물 이미징

Glioblastoma multiforme (GBM) is a high-grade primary brain cancer with a median survival of only 14.6 months in humans despite standard tri-modality ...

Cerenkov Luminescence Imaging (CLI) for Cancer Therapy Monitoring

In molecular imaging, positron emission tomography (PET) and optical imaging (OI) are two of the most important and thus most widely used modalities1-3. PET is characterized by its excellent sensitivity and quantification ability while OI is notable for non-radiation, relative low cost, short scanning time, high throughput, and wide availability to basic researchers. However, both modalities have their shortcomings as well. PET suffers from poor spatial resolution and high cost, while OI is mostly limited to preclinical applications because of its limited tissue penetration along with prominent scattering optical signals through the thickness of living tissues.
 Recently a bridge between PET and OI has emerged with the discovery of Cerenkov Luminescence Imaging (CLI)4-6. CLI is a new imaging modality that harnesses Cerenkov Radiation (CR) to image radionuclides with OI instruments. Russian Nobel laureate Alekseyevich Cerenkov and his colleagues originally discovered CR in 1934. It is a form of electromagnetic radiation emitted when a charged particle travels at a superluminal speed in a dielectric medium7,8. The charged particle, whether positron or electron, perturbs the electromagnetic field of the medium by displacing the electrons in its atoms. After passing of the disruption photons are emitted as the displaced electrons return to the ground state. For instance, one 18F decay was estimated to produce an average of 3 photons in water5. 
 Since its emergence, CLI has been investigated for its use in a variety of preclinical applications including in vivo tumor imaging, reporter gene imaging, radiotracer development, multimodality imaging, among others4,5,9,10,11. The most important reason why CLI has enjoyed much success so far is that this new technology takes advantage of the low cost and wide availability of OI to image radionuclides, which used to be imaged only by more expensive and less available nuclear imaging modalities such as PET.
 Here, we present the method of using CLI to monitor cancer drug therapy. Our group has recently investigated this new application and validated its feasibility by a proof-of-concept study12. We demonstrated that CLI and PET exhibited excellent correlations across different tumor xenografts and imaging probes. This is consistent with the overarching principle of CR that CLI essentially visualizes the same radionuclides as PET. We selected Bevacizumab (Avastin; Genentech/Roche) as our therapeutic agent because it is a well-known angiogenesis inhibitor13,14. Maturation of this technology in the near future can be envisioned to have a significant impact on preclinical drug development, screening, as well as therapy monitoring of patients receiving treatments.

Cerenkov Luminescence Imaging CLI for Cancer Therapy Monitoring

Use of Cerenkov Luminescence Imaging (CLI) for monitoring preclinical cancer treatment is described here. This method takes advantage of Cerenkov Radiation (CR) and optical imaging (OI) to visualize radiolabeled probes and thus provides an alternative to PET in preclinical therapeutic monitoring and drug screening.

암 치료 모니터링을위한 Cerenkov 발광 이미징 (CLI)

In  molecular imaging, positron emission tomography (PET) and optical imaging (OI)  are two of the most important and thus most widely used modalities1-3. ...

Bioluminescent Orthotopic Model of Pancreatic Cancer Progression

Pancreatic cancer has an extremely poor five-year survival rate of 4-6%. New therapeutic options are critically needed and depend on improved understanding of pancreatic cancer biology. To better understand the interaction of cancer cells with the pancreatic microenvironment, we demonstrate an orthotopic model of pancreatic cancer that permits non-invasive monitoring of cancer progression. Luciferase-tagged pancreatic cancer cells are resuspended in Matrigel and delivered into the pancreatic tail during laparotomy. Matrigel solidifies at body temperature to prevent leakage of cancer cells during injection. Primary tumor growth and metastasis to distant organs are monitored following injection of the luciferase substrate luciferin, using in vivo imaging of bioluminescence emission from the cancer cells. In vivo imaging also may be used to track primary tumor recurrence after resection. This orthotopic model is suited to both syngeneic and xenograft models and may be used in pre-clinical trials to investigate the impact of novel anti-cancer therapeutics on the growth of the primary pancreatic tumor and metastasis.

Improved understanding of pancreatic cancer biology is critically needed to enable the development of better therapeutic options to treat pancreatic cancer. To address this need, we demonstrate an orthotopic model of pancreatic cancer that permits non-invasive monitoring of cancer progression using in vivo bioluminescence imaging.

췌장암의 진행 발광 동소 모델

Pancreatic cancer has an extremely poor five-year survival rate of 4-6%.  New therapeutic options are critically needed and depend on improved ...

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

Estrogen plays vital roles in mammary gland development and breast cancer progression. It mediates its function by binding to and activating the estrogen receptors (ERs), ER&#945;, and ER&#946;. ER&#945; is frequently upregulated in breast cancer and drives the proliferation of breast cancer cells. The ERs function as transcription factors and regulate gene expression. Whereas ER&#945;&#39;s regulation of protein-coding genes is well established, its regulation of noncoding microRNA (miRNA) is less explored. miRNAs play a major role in the post-transcriptional regulation of genes, inhibiting their translation or degrading their mRNA. miRNAs can function as oncogenes or tumor suppressors&#160;and are also promising biomarkers. Among the miRNA assays available, microarray and quantitative real-time polymerase chain reaction (qPCR) have been extensively used to detect and quantify miRNA levels. To identify miRNAs regulated by estrogen signaling in breast cancer, their expression in ER&#945;-positive breast cancer cell lines were compared before and after estrogen-activation using both the &#181;Paraflo-microfluidic microarrays and Dual Labeled Probes-low density arrays. Results were validated using specific qPCR assays, applying both Cyanine dye-based and Dual Labeled Probes-based chemistry. Furthermore, a time-point assay was used to identify regulations over time. Advantages of the miRNA assay approach used in this study is that it enables a fast screening of mature miRNA regulations in numerous samples, even with limited sample amounts. The layout, including the specific conditions for cell culture and estrogen treatment, biological and technical replicates, and large-scale screening followed by in-depth confirmations using separate techniques, ensures a robust detection of miRNA regulations,&#160;and eliminates false positives and other artifacts. However, mutated or unknown miRNAs, or regulations at the primary and precursor transcript level, will not be detected. The method presented here represents a thorough investigation of estrogen-mediated miRNA regulation.

Molecular signaling through both estrogen and microRNAs are critical in breast cancer development and growth. Estrogen activates the estrogen receptors, which are transcription factors. Many transcription factors can regulate the expression of microRNAs, and estrogen-regulated microRNAs can be profiled using different large-scale techniques.

유방암 세포에서 에스트로겐 조절 마이크로 RNA의 프로파일

Estrogen plays vital roles in mammary gland development and breast cancer progression. It mediates its function by binding to and activating the estrogen ...

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Telomere dysfunction-induced loss of genome integrity and its associated DNA damage signaling and checkpoint responses are well-established drivers that cause tissue degeneration during ageing. Cancer, with incidence rates greatly increasing with age, is characterized by short telomere lengths and high telomerase activity. To study the roles of telomere dysfunction and telomerase reactivation in ageing and cancer, the protocol shows how to generate two murine inducible telomerase knock-in alleles 4-Hydroxytamoxifen (4-OHT)-inducible TERT-Estrogen Receptor (mTERT-ER) and Lox-Stopper-LoxTERT (LSL-mTERT). The protocol describes the procedures to induce telomere dysfunction and reactivate telomerase activity in mTERT-ER and LSL-mTERT mice in vivo. The representative data show that reactivation of telomerase activity can ameliorate the tissue degenerative phenotypes induced by telomere dysfunction. In order to determine the impact of telomerase reactivation on tumorigenesis, we generated prostate tumor model G4 PB-Cre4 PtenL/L p53L/L LSL-mTERTL/L and thymic T-cell lymphoma model G4 Atm-/- mTERTER/ER. The representative data show that telomerase reactivation in the backdrop of genomic instability induced by telomere dysfunction can greatly enhance tumorigenesis. The protocol also describes the procedures used to isolate neural stem cells (NSCs) from mTERT-ER and LSL-mTERT mice and reactivate telomerase activity in NSCs in vitro. The representative data show that reactivation of telomerase can enhance the self-renewal capability and neurogenesis in vitro. Finally, the protocol describes the procedures for performing telomere FISH (Fluorescence In Situ Hybridization) on both mouse FFPE (Formalin Fixed and Paraffin Embedded) brain tissues and metaphase chromosomes of cultured cells.

Telomere and telomerase play essential roles in ageing and tumorigenesis. The goal of this protocol is to show how to generate two murine inducible telomerase knock-in alleles and how to utilize them in the studies of tissue degeneration/regeneration and cancer.

조직의 변성 / 재생 및 암의 연구에서 설치류 유도 성 텔로 머라 대립 유전자를 활용

Telomere dysfunction-induced loss of genome integrity and its associated DNA damage signaling and checkpoint responses are well-established drivers that ...

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies

Pancreatic ductal adenocarcinoma (PDAC) contains a subset of exclusively tumorigenic cancer stem cells (CSCs) which have been shown to drive tumor initiation, metastasis and resistance to radio- and chemotherapy. Here we describe a specific methodology for culturing primary human pancreatic CSCs as tumor spheres in anchorage-independent conditions. Cells are grown in serum-free, non-adherent conditions in order to enrich for CSCs while their more differentiated progenies do not survive and proliferate during the initial phase following seeding of single cells. This assay can be used to estimate the percentage of CSCs present in a population of tumor cells. Both size (which can range from 35 to 250 micrometers) and number of tumor spheres formed represents CSC activity harbored in either bulk populations of cultured cancer cells or freshly harvested and digested tumors 1,2. Using this assay, we recently found that metformin selectively ablates pancreatic CSCs; a finding that was subsequently further corroborated by demonstrating diminished expression of pluripotency-associated genes/surface markers and reduced in vivo tumorigenicity of metformin-treated cells. As the final step for preclinical development we treated mice bearing established tumors with metformin and found significantly prolonged survival. Clinical studies testing the use of metformin in patients with PDAC are currently underway (e.g., NCT01210911, NCT01167738, and NCT01488552). Mechanistically, we found that metformin induces a fatal energy crisis in CSCs by enhancing reactive oxygen species (ROS) production and reducing mitochondrial transmembrane potential. In contrast, non-CSCs were not eliminated by metformin treatment, but rather underwent reversible cell cycle arrest. Therefore, our study serves as a successful example for the potential of in vitro sphere formation as a screening tool to identify compounds that potentially target CSCs, but this technique will require further in vitro and in vivo validation to eliminate false discoveries.

Pancreatic cancer stem cells (CSCs) can be expanded in vitro using the anchorage-independent sphere culture technique, which represents a powerful tool to study CSC biology and can serve as the first step to develop novel CSC-targeting therapies. Here the methodology for expanding, analyzing and targeting of pancreatic CSCs is provided.

췌장암 새로운 치료 전략을 개발하기위한 전지 특성 줄기 공부

Pancreatic ductal adenocarcinoma (PDAC) contains a subset of exclusively tumorigenic cancer stem cells (CSCs) which have been shown to drive tumor ...

Dynamic Lung Tumor Tracking for Stereotactic Ablative Body Radiation Therapy

Physicians considering stereotactic ablative body radiation therapy (SBRT) for the treatment of extracranial cancer targets must be aware of the sizeable risks for normal tissue injury and the hazards of physical tumor miss. A first-of-its-kind SBRT platform achieves high-precision ablative radiation treatment through a combination of versatile real-time imaging solutions and sophisticated tumor tracking capabilities. It uses dual-diagnostic kV x-ray units for stereoscopic open-loop feedback of cancer target intrafraction movement occurring as a consequence of respiratory motions and heartbeat. Image-guided feedback drives a gimbaled radiation accelerator (maximum 15 x 15 cm field size) capable of real-time &#177;4 cm pan-and-tilt action. Robot-driven &#177;60&#176; pivots of an integrated &#177;185&#176; rotational gantry allow for coplanar and non-coplanar accelerator beam set-up angles, ultimately permitting unique treatment degrees of freedom. State-of-the-art software aids real-time six dimensional positioning, ensuring irradiation of cancer targets with sub-millimeter accuracy (0.4 mm at isocenter). Use of these features enables treating physicians to steer radiation dose to cancer tumor targets while simultaneously reducing radiation dose to normal tissues. By adding respiration correlated computed tomography (CT) and 2-[18F] fluoro-2-deoxy-&#7429;-glucose (18F-FDG) positron emission tomography (PET) images into the planning system for enhanced tumor target contouring, the likelihood of physical tumor miss becomes substantially less1. In this article, we describe new radiation plans for the treatment of moving lung tumors.

Stereotactic ablative body radiation therapy (SBRT) involves the precise delivery of high-dose radiation to cancer tumor targets. A novel SBRT platform offers a first-of-its-kind gimbaled radiation accelerator mounted within a pivoting O-ring gantry capable of dynamic image-guided tumor tracking. Here, we describe dynamic tumor tracking for lung targets.

정위 절제 바디 방사선 치료에 대한 동적 폐 종양 추적

Physicians considering stereotactic ablative body radiation therapy (SBRT) for the treatment of extracranial cancer targets must be aware of the sizeable ...

Working with Human Tissues for Translational Cancer Research

Medical research for human benefit is greatly impeded by the necessity for human tissues and subjects. However, upon obtaining consent for human specimens, precious samples must be handled with the greatest care in order to ensure integrity of organs, tissues, and cells to the highest degree. Unfortunately, tissue processing by definition requires extraction of tissues from the host, a change which can cause great cellular stress and have major repercussions on subsequent analyses. These stresses could result in the specimen being no longer representative of the site from which it was retrieved. Therefore, a strict protocol must be adhered to while processing these specimens to ensure representativeness. The desired assay(s) must also be taken into consideration in order to ensure that an optimal technique is used for sample processing. Outlined here is a protocol for tissue retrieval, processing and various analyses which may be performed on processed tissue in order to maximize downstream production from limited tissue samples.

Translational cancer research is dependent on extraction of human tissues. Much work has gone into optimizing extraction methods for ex vivo analysis. Here, we describe tissue processing methods allowing for maximal data output from limited samples.

번역 상 암 연구를위한 인체 조직에 대한 작업

Medical research for human benefit is greatly impeded by the necessity for human tissues and subjects. However, upon obtaining consent for human ...

Modeling the Early Steps of Ovarian Cancer Dissemination in an Organotypic Culture of the Human Peritoneal Cavity

The pattern of ovarian cancer metastasis is markedly different from that of most other epithelial tumors, because it rarely spreads hematogenously. Instead, ovarian cancer cells exfoliated from the primary tumor are carried by peritoneal fluid to metastatic sites within the peritoneal cavity. These sites, most notably the abdominal peritoneum and omentum, are organs covered by a mesothelium-lined surface. To investigate the processes of ovarian cancer dissemination, we assembled a complex three-dimensional culture system that reconstructs the lining of the peritoneal cavity in vitro. Primary human fibroblasts and mesothelial cells were isolated from human omentum. The fibroblasts were then mixed with extracellular matrix and covered with a layer of the primary human mesothelial cells to mimic the peritoneal and omental surfaces encountered by metastasizing ovarian cancer cells. The resulting organotypic model is, as shown, used to examine the early steps of ovarian cancer dissemination, including cancer cell adhesion, invasion, and proliferation. This model has been used in a number of studies to investigate the role of the microenvironment (cellular and acellular) in early ovarian cancer dissemination. It has also been successfully adapted to high throughput screening and used to identify and test inhibitors of ovarian cancer metastasis.

Here, we present a protocol to construct a three-dimensional in vitro model of the lining of the peritoneal cavity, composed of primary human mesothelial cells and fibroblasts layered with extracellular matrix, as a tool to investigate ovarian cancer cell adhesion, invasion, and proliferation.

인간의 복강의의 Organotypic 문화 난소 암 보급의 초기 단계 모델링

The pattern of ovarian cancer metastasis is markedly different from that of most other epithelial tumors, because it rarely spreads hematogenously. ...