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.

OPMERKING: Patiënt weefselverkrijging werd geautoriseerd door institutioneel Review Board (IRB) -goedgekeurd Biospecimen en Klinische protocollen (protocol nummers 09-121 en 11-041, respectievelijk) in het Memorial Sloan Kettering Cancer Center. 1 Tissue Procurement <ol><li> Bij de aanschaf van de patiënt primaire tumor / metastasen LET OP: Tot op heden heeft dit protocol zijn uitgevoerd op operatief verwijderd alvleesklier, maag-en borstkanker tumor types, evenals, lymfoom metast...

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Kanker biologen worden geconfronteerd met grote uitdagingen bij een poging om effectieve therapeutische strategieën te ontwikkelen. Het testen van geneesmiddelen in ontwikkeling op gevestigde kanker cellijnen kan niet altijd volledig zijn in vivo respons en in vivo experimenten op PDX modellen zijn arbeidsintensief en zeer duur. Gezien het bovenstaande is de toepassing van ex vivo technieken van primaire tumoren van patiënten 14, 15 bevindt zich nu naast de moleculaire analyse van...

Het ontwikkelen van effectieve kanker geneeswijze heeft bewezen zeer uitdagend te zijn. Kanker cellijnen en tumor explantaten - evenals xenotransplantaties zijn gebruikt in het onderzoek naar kanker meer dan een halve eeuw 1,2,3. Tot op heden, de moleculaire analyse van drug gevoeligheid en weerstand in zowel gevestigde kanker cellijnen en-patiënt afgeleid xenograften (PDX) onontbeerlijk. Echter, testen van verbindingen gevestigde kankercellijnen niet vaak voorspellend in vivo werkzaamheid en overeenkomstige in vivo studies bij dieren, vooral in PDX modellen, is zeer duur en tijdrovend. De beperkingen van deze modelsystemen, namelijk het onvermogen te informeren over de invloed van de natieve micro bij tumorprogressie en reactie op therapeutische strategieën, heeft het veldonderzoek aanvullende methoden om deze analyses complimenteren ontwikkelen geleid. Recente, wordt versterkt aandacht naar ex vivo analyse van patiëntengegevens tumof explantaten 4, 5 door de grotere verstande dat kanker therapeutische respons is niet exclusief de inherente moleculaire samenstelling van kankercellen maar wordt sterk beïnvloed door de tumorcel micro 6, 7, een eigenschap die niet kan worden samengevat door traditionele kweekmethoden en / of PDX. Ex vivo analyse in deze context (dwz., invloed van aangrenzende omringende tumorcellen micro) houdt beoordeling van levensvatbare primaire tumor / metastase secties, in plaats van ex vivo analyse van de cellulaire isolaten 8, 9. Wij rapporteren hier over een ex vivo techniek (dwz., Precisie gesneden coupes vers) van zowel de patiënt als primaire tumoren en metastasen geassocieerd (dwz, lymfeklieren) dat trouw informeert over respons (IC50), off-target effecten en maakt het mogelijk voor de moleculaire analyse van de weerstand en feedback mechanismen. Daarnaast werd een correlatieve analyse van therapeTherapeutische gevoeligheid / weerstand versus biomarker en genexpressie-profiel kan worden uitgevoerd in een poging om patiënten meer kans om te reageren op de experimentele drug van belang vast te stellen (dwz., hoge drug respons overeenkomt patiënt met bepaalde biologische profiel). Toepassing van de ex vivo techniek en beoordeling in een multi-parameter mode is beweging naar selectie van patiënten en algehele verbetering van de klinische resultaten. Ex vivo behandeling respons analyse kan een standaard instrument in de preklinische en klinische ontwikkeling van geneesmiddelen tegen kanker worden en wordt voorgesteld als een stap naar een gepersonaliseerde geneeskunde aanpak in therapeutische strategieën.

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			<td style="width:167px;">Prepare 4% and 6% before use</td>
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			<td style="width:167px;">The media is prepared at Memorial Sloan Kettering Cancer Center&#160;</td>
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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.

Voor dit onderzoek werd de ex vivo techniek in een correlatieve analyse van therapeutische gevoeligheid / weerstand van een heat shock eiwit 90 inhibitor (Hsp90i). In een preklinische beoordeling van deze Hsp90i, borstkanker primaire tumor, een ER + invasief ductaal carcinoom (IDC) en bijbehorende lymfeklier werden ex vivo geanalyseerd op behandelingsrespons &#160; (Figuur 1). Multiple 200 urn serial secties werden behandeld met vehikel alleen en toenemende doses (0,25...

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

Opgericht kanker cellijnen en xenograften hebben de steunpilaar van het onderzoek naar kanker in de afgelopen paar decennia. Echter, recente gegevens blijkt dat de therapeutische respons sterk wordt beïnvloed door de tumorcel micromilieu. Daarom hebben wij een ex vivo analyse van de primaire tumor specimens geneesmiddelontwikkeling doeleinden ontwikkeld.

Ex vivo behandeling Reactie van primaire tumoren en / of geassocieerde Metastasen voor preklinische en klinische ontwikkeling van 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 ...

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Medicine

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

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