Bu araştırma Olgu Kapsamlı Kanser Merkezi (P30 CA43703) tarafından desteklenmiştir.

1. Stereotaktik Cyberknife Radyocerrahi Danışma <ol><li> CyberKnife radyocerrahi tedavisi anlatınız. CyberKnife radyocerrahi otomobil yapmak için kullanılan makinelere benzer bir endüstriyel robot kol üzerine monte edilmiş bir lineer hızlandırıcı kullanımını gerektirir. Bu ışın teslimat için birden fazla tedavi &#39;durak&#39; aracılığıyla ilerledikçe robotik kol hastanın etrafında üç boyutlu uzayda lineer hızlandırıcı taşır. X-ışınları hastanın doğrulamak için tedavi sırasında elde edilen çapraz düzlemine doğru bir tedaviye pozisyondadır. Tedavisi ışın dağıtım iki boyutlu bir düzlem ile sınırlı olmadığından, bu sistemi daha da kritik deri ve iç organ yapıları radyasyon dozunu en aza indirerek kansere hedeflere konsantre radyasyon dozları teslim yeteneğini artırır. </li><li> CyberKnife radyocerrahi riskleri tartışın. CyberKnife radyocerrahi olası deri, yorgunluk, sık mide bulantısı ya da diarrh bronzlaşma ve kızarmasına neden olabilirea, nadir organ yaralanma, kas, sinir ve kemik hasarı, ve ikinci kanser riski çok küçük. </li></ol> 2. Stereotaktik Cyberknife Radyocerrahi ölçü noktası Yerleştirme <ol><li> Yanlılık yerleştirme anlatınız. Kalıcı veya tekrarlayan jinekolojik kanserlerin tedavisi gören kadınlar kanser hedef içinde veya yakınında en az üç tek 1,6 x 3 mm altın yumuşak doku fiducials (bir pirinç tanesi büyüklüğünde) operatif veya BT eşliğinde yerleştirme uğrarlar. Önceden cerrahisi sırasında yerleştirilen cerrahi klipler radyocerrahi fiducials olarak kullanılmak üzere yeterli yoğunluktaki değildir. Cerrahi klipleri radyocerrahi nedeniyle yoğunluk farklılığı hedef karışmaz. </li><li> Radyocerrahi Hedefe göre yanlılık konumlandırma belirtiniz. Fiducials radyocerrahi hedef etrafında doku derinliklerinde değişen yerleştirilir ve iki santimetre ya da daha fazla ayrılmalıdır. Fiducials t 4-6 cm içinde konumlandırılırarget. </li></ol> 3. Stereotaktik Cyberknife Radyocerrahi Tedavi Planlaması <ol><li> Radyocerrahi tedavi planlaması tartışın. Yanlılık yerleştirildikten sonra en az bir hafta (yani, böylece iyileşme oluştu ve yanlılık hareketi minimize edilir), hastalarda BT eşliğinde SBRT tedavi simülasyon uğrarlar. Program, iki-pin lokalize tahliye vakum torbası pelvik immobilizasyon kullanılır. </li><li> . Kadınlar CyberKnife radyocerrahi düz bir masa üzerine supin Tedavi pozisyonunda tedavi edilir tedavi masasında hasta konumlandırma belirtiniz. </li><li> Hedef ve yaralı tespit tartışın. Hasta radyasyon dozu doğum sırasında intrafraction hareketi azaltmak için tahliye vakum torbası immobilizasyon geçirebilir. Bir kez immobilize, kadınların tabi olmayan bitişik kontrastlı aksiyel BT yüksek çözünürlüklü görüntüleme (1 ile 1 aralığı, 1.0 mm kesit kalınlığı, voltaj 120 kVp, 450 mAs). </li><li> Gelişmiş kullanımını tartışmakhedef lokalizasyonu için görüntüleme. CT görüntüleme sonra, kadınların aynı SBRT Tedavi pozisyonunda tercihen geleneksel 18F-FDG PET / BT görüntüleme uğrarlar. Alternatif olarak, kadınların geleneksel kontrastlı pelvik manyetik rezonans görüntüleme olabilir. </li><li> Görüntü radyocerrahi tedavi planlaması için ortak kayıt anlatınız. Yüksek çözünürlüklü BT ve 18F-FDG PET / BT Görüntüler Multiplan 3.5.2 Tedavi Planlama Sistemi (Accuray) üzerinde ters radyasyon tedavi planlaması için ithal edilmektedir. </li><li> Radyocerrahi tedavi planlaması ekip yaklaşımı anlatınız. Tedavi planlaması, bir radyasyon onkoloğu hem jinekolojik onkolog kontur kanseri hedef klinik hedef hacim (CTVs) için. Diğer hastalığı risk altındaki doku konturlu ve CTVs dahildir. Bu tür ince barsak, rektum, mesane, karaciğer, böbrekler, akciğerler, bilateral proksimal femur, vajina ve sakral sinir kökleri gibi Yakındaki normal doku yapıları tarafından kıvrımlıdırradyasyon onkolojisi. </li><li> Radyasyon dozu reçete açıklayınız. 3 bir radyasyon dozu reçete × 800 cGy = 2400 cGy (genellikle% 70 izodoz hattına) seçilmiştir. 200 cGy biyolojik eşdeğer doz hesabında, yaklaşık 6170 cGy Bu reçete tümör için 10 olan bir &quot;β / α&quot; oranı varsayarak ile birlikte teslim edilir. Bir SBRT lineer hızlandırıcı yayılan radyasyonun 12 sabit tungsten dairesel kolimatörler biri (5 ila 60 mm) kullanarak veya bir tungsten-bakır alaşımlı parçalı altıgen IRIS kolimatör kullanılarak ya collimated. 14 Normal organların radyasyon tolerans var ve kullanımı ablatif stereotaktik radyocerrahi sırasında normal doku sınırlaması için doz-hacim histogramı parametreleri Tablo 1&#39;de verilmiştir. </li></ol> 4. Stereotaktik Cyberknife Radyocerrahi Tedavi Teslimat <ol><li> Çapraz-düzlem resim doğrulama gerçekleştirin. Cyberknife SBRT sırasında, yumuşak doku fiducials(Ya da bazı durumlarda bu intrakranyal lezyonlar ve omurga lezyonlar için omurga için kafatası gibi sert anatomik) çapraz-düzlem radyolojik görüntüleme ile izlenir ve hedef yerelleştirme sistemi (TLS) alt sistemi tarafından beklenen hedef konumda olarak onaylanır. </li><li> Hedef konumlandırma doğrulayın. Fiducials özgürlük, üç ve altı derece (yani x, y, z, pitch, roll ve yaw) izlenir. TLS tarafından oluşturulan görüntüler otomatik olarak kayıtlı ve BT planlama ilk tedavi üretilen dijital olarak yeniden grafileri (DRRs) ile karşılaştırılmıştır. </li><li> Hedef konumlandırma doğrulayın. Otomatik kayıt sonuçları fiducials özgürlüğü altı derece (x, y, z, pitch, roll ve yaw) herhangi birinde önceden toleranslar ötesine kaymıştır olduğunu gösteriyorsa, tedavi otomatik olarak durdurulur. Hasta konumlandırılması sonra oluşur. </li><li> Hedef hareket düşünün. Hedefler solunum hareketi ile hareket tr olduğunuSynchrony Solunum İzleme alt sistemi (Synchrony) kullanan eated. Bir kamera kullanımının tedavi odasında monte edilen sistem sürekli olarak hastanın göğüs etrafında bir yelek yapıştırılmış ışık yayan diyot (LED) kullanımı ile hastanın solunum paterni (yani, dış pozisyon verileri elde) izler. Birlikte 10 çapraz düzlemi X-ışınları ile elde edilen indirgeme konum bilgileri (iç konumda verileri) ile, Synchrony sistemi ve bir dış veri iç veri içeren bir korelasyon modeli oluşturur. Bu korelasyon modeli robotik kol herhangi birinin tedavisinde ve tüm doğum kirişler sırasında ise hedef herhangi solunum yolu ile endüklenen hareket takip sağlar. </li><li> Tedavi robot kolu 100-150 teslim tedavi pozisyonları gerektirebilir. Tedaviler 30 ile 90 dakika sürebilir. </li></ol> 5.. Temsilcisi Sonuçlar Stereotaktik vücut radyasyon tedavisi (SBRT) birçok bireysel ışınlar içerebilir (<html> Şekil 1A gösterildiği gibi mavi vektörler) bütün, tek veya çok yakından ilişkili klinik radyasyon hedeflere yakınsama. Bir temsilci iyi radyocerrahi planlama sonucu yüksek radyasyon dozu kanser hedef hacim kapsama ve kanser hedef konformluk ile teslim SBRT tedavi sağlar. Şekil 1B-D gösterisi 131 kirişler 42 dakika içinde bir chemorefractory yumurtalık kanseri hedefin pelvik nüks üzerine tedavi etmek için kullanılmıştır. % 80 izodoz hattına reçete SBRT üç günlük 800 cGy fraksiyon 2400 cGy toplam doz için 1.94 bir konformluk indeksi ile% 100 klinik hedef hacim kapsama işlenir. Klinik hedef (kırmızı) ve rektum (kahverengi), mesane (sarı) kritik yapılar için doz-volüm histogramları, ince barsak (açık mavi) sakral sinirlerin (tan) ve kalça (turuncu) Şekil 2&#39;de gösterilmiştir. <img alt="Şekil 1" src="/files/ftp_upload/3793/3793fig1.jpg" /> Şekil 1..tp :/ / www.jove.com/files/ftp_upload/3793/3793fig1large.jpg &quot;target =&quot; _blank &quot;&gt; büyük rakamı görmek için buraya tıklayın. <img alt="Şekil 2" src="/files/ftp_upload/3793/3793fig2.jpg" /> Şekil 2. Klinik hedef (kırmızı) ve rektum (kahverengi), mesane (sarı) kritik yapılar için doz-hacim histogramları, ince barsak (açık mavi) sakral sinirlerin (tan) ve kalça (turuncu).

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Biz (CAK, JMB, RD) ifşa etmek yoktur.

Teşvik erken SBRT sonuçları sürekli veya tekrarlayan jinekolojik kanser tedavisinde radyocerrahi klinik araştırma. 7, 8 körükleyen var, 15 Veri radiobiological efektleri ve SBRT kaynaklanan hücre ölümü modu sorguluyorum. Küçük klinik çalışmalar SBRT tarafından sağlanan ablatif radyasyon dozları% 90 aşan hedeflenen hastalık kontrol oranları üretmek olduğunu göstermiştir. Konvansiyonel radyasyon aksine, radyasyona ve sitostatik / sitotoksik kemoterapi ile SBRT birleştirmek için teşvik ediyor. Artan planlama tedavi volümü açılımları ile ve 18 F-FDG PET / BT görüntülerinin eklenmesi ile hedef daha iyi kanser klinik sonuçlar alınmasını sağlamıştır. Yüksek hassasiyet ile doz-yükseltilmiş radyasyonu sağlama diğer yöntemlerle içine bakmak şart iken, SBRT düşük ve brakiterapi doz oranı yüksek olarak eşdeğer terapötik etkinliği sağlayabilir mi kararsız kalır. Gerçekten de, brakiterapi daha yaygın ve vali olduğujinekolojik kanser hedefleri radyasyon doz artırımı ulaşmak için teknik tarihli. Bunun gibi, coşku ve basiret hem jinekolojik kanserlerin tedavisi için kullanılabilir SBRT veri okuma uygundur.

<table border="1"><tbody><tr><td> Cihazının adı </td><td> Şirket </td><td> Katalog numarası </td><td> Yorumlar </td></tr><tr><td> CyberKnife sistemi </td><td> Accuray (Sunnyvale, CA) </td><td></td><td></td></tr></tbody></table>

stereotactic radiosurgery for gynecologic cancer

Stereotaktik vücut radyoterapi (SBRT) daha fazla solunum hareketi için sert hasta immobilizasyon, muhasebe, karmaşık tedavi planlaması, on-board görüntüleme ve kansere ablatif radyasyon dozlarının sayısı azaltılmış genellikle kemoterapi ve konvansiyonel radyasyona dirençli hedefliyor gerektiren tarafından ayrılıyor. Dik SBRT radyasyon dozunun düşmesi-off izinleri dar &#39;kalem ışın&#39; tedavi alanları 1 ile 3 tedavileri yoğunlaşmış ablatif radyasyon tedavisi için kullanılacak. Doktorlar tedavisi olduğunu SBRT coğrafi tümör özlemeye normal doku hasarı ve şans büyük bir tehlike geliyor takdir etmelidirler. Her iki kanser hedeflerin immobilizasyonu ve yüksek hassasiyetli tedavi teslim tarafından ele alınmalıdır. Kanser hedef immobilizasyon hasta bağımsız karın sıkıştırma endeksli özelleştirilmiş Strafor atmalarını, tahliye fasulye torbaları, ya da vücut-fix kalıp kullanılarak elde edilmiştir. Kanser targe 1-3 Intrafraction hareketsolunum nedeniyle ts şimdi hasta duyarlı nefes tutma teknikleri, 4 hasta ağızlık aktif nefes koordinasyonu, 5 solunum korele bilgisayarlı tomografi, 6 ya da hareketli bir tümör içindeki ve etrafındaki implante fiducials görüntü eşliğinde takip ile azaltılabilir. 7-9 CyberKnife sistemi (Accuray [Sunnyvale]) doğru bir kamera-izlenen bir hastaya takılan bir yelek üzerine emdirilmiş ışık yayan diyotlar (LED) tarafından belirlenen hasta solunum hareketini takip eden bir endüstriyel robot kol üzerine monte edilmiş bir radyasyon lineer hızlandırıcı kullanır. radyasyon tedavisi marjlarının 10 Ölçüde azalma sonuçta milimetreden doğruluğu ışınlandı daha küçük bir planlama hedef hacim veren, hareket izleme ile elde edilebilir. 11-13 SBRT tarafından tedavi Kanser hedeflere yakınsama, sıkı kolime kirişler tarafından aydınlatılan edilir. Kanser hedef hacim histogramlarına Sonuç radyasyon dozu daha zamir varYüksek oranda hedef kapsama alanı ve küçük bir yüksek doz radyasyon belirten CED radyasyon &quot;omuz&quot; &quot;kuyruk&quot;. Böylece, artan hedef konformluk SBRT kanser hedef azaldı doz tekdüzelik pahasına geliyor. Bu SBRT hedef sonradan tümör kontrolü ve risk altındaki organların normal doku toleransı hem de etkili olabilir. Kanser hedefler tam takdir edilir ve yetersiz SBRT doz kenar uygulandığında SBRT keskin doz azalma nedeniyle, ablatif radyasyon dozu kaçmasını gizli hastalığı olasılığını ortaya çıkar. Daha büyük bir planlama hedef hacim (PTV) sonuçlanan 0.5 cm Klinik hedef hacim (CTV) genişleme, aşırı normal doku hasarı olmadan artan hedef kontrolü ile ilişkilidir. Coğrafi özlemeye olasılık 7,8 Diğer redüksiyon dahil edilmesi ile elde edilebilir 2 - [18F] floro-2-deoksi-D-glikoz (18F-FDG) pozitron emisyon tomografisi (PET) SBRT treatme 18 F-FDG PET / BT 8 Kullanımı.nt planlama jinekolojik kanserler için yeni görüntüleme hedef molekül imzaları keşfetme girişimleri sadece başlangıcıdır.

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

Stereotactic Radiosurgery for Gynecologic Cancer

Kanser teslim Stereotaktik vücut radyoterapi (SBRT) içerir görüntü kılavuzluğunda, ablatif radyasyon kemoterapi veya radyasyon konvansiyonel tedaviye dirençli hedefliyor. Gelişmiş hedef lokalizasyon kullanarak robotik kollu Cyberknife SBRT kanser, hedefleri sterilizasyon yeteneğine hipofraksiyone radyasyon dozları sunar. Bu makale, jinekolojik kanserler için SBRT yeni tedavi rolleri dikkate alacaktır.

Jinekolojik Kanserler için Stereotaktik Radyocerrahi

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

stereotactic-radiosurgery-for-gynecologic-cancer

Research

JoVE Journal

Medicine

17.5K Görüntüleme.  University Hospitals Case Medical Center and Case Western Reserve University School of Medicine. Kanser teslim Stereotaktik vücut radyoterapi (SBRT) içerir görüntü kılavuzluğunda, ablatif radyasyon kemoterapi veya radyasyon konvansiyonel tedaviye dirençli hedefliyor. Gelişmiş hedef lokalizasyon kullanarak robotik kollu Cyberknife SBRT kanser, hedefleri sterilizasyon yeteneğine hipofraksiyone radyasyon dozları sunar. Bu makale, jinekolojik kanserler için SBRT yeni tedavi rolleri dikkate alacaktır.

Video: 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.

Jinekolojik Onkoloji Sentinel lenf nodu intraoperatif Algılama için Multispektral Gerçek zamanlı Floresans Görüntüleme

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 ...

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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.

Stereotaktik intrakranial implantasyon ve<em&gt; In vivo</emGlioblastoma Multiforme bir Mouse Model Sistemde Tümör Xenografts arasında&gt; Bioluminescent Görüntüleme

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.

Kanser Tedavisi İzleme Cerenkov Lüminesans Görüntüleme (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.

Pankreas Kanseri İlerleme Bioluminescent Ortotopik Model

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.

Meme Kanseri Hücrelerinde östrojen düzenlenmiş microRNA profil

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.

Doku Dejenerasyonu / Yenilenme ve Kanser Araştırmaları Murin İndüklenebilir Telomeraz allelleri kullanılması

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.

Pankreas Kanseri Yeni Tedavi Stratejileri Geliştirme Hücre Özellikleri Kök incelenmesi

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.

Stereotaktik Ablatif Vücut Radyasyon Tedavisi için Dinamik Akciğer Tümör Takibi

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.

Translational Kanser Araştırma İnsan Doku ile Çalışma

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.

İnsan periton boşluğuna bir Organotipik Kültür Yumurtalık Kanseri Yaygınlaştırılması Erken Adımlar Modelleme

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