| Source DB | nl |
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| Institution | UGent |
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| Code | 898151c3-fa2b-4438-9344-690ea932fa89 |
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| Unit | 85720305-a223-4aad-b6b6-5422ac5c0867
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| Begin | 11/1/2020 |
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| End | 10/31/2022 |
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| title fr |
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| title nl | Identificatie van therapieën voor laaggradig sereus ovarium carcinoom (LGSOC) gebruikmakend van klinisch relevante sferoïd en tumor-engineerde modellen voor peritoneale metastasen.
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| title en | Identification of Low-Grade Serous Ovarian Carcinoma (LGSOC) therapeutics using clinical relevant spheroid and tumor-engineered models for peritoneal metastasis.
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| Description fr |
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| Description nl | Laaggradig sereus ovarium carcinoom (LGSOC) maakt een klein deel uit van ovariumcarcinoom, de dodelijkste gynaecologische kanker, en de meerderheid van de patiënten vertoont peritoneale metastasen (PM). De huidige therapieën zijn niet succesvol. Er is nood aan preklinische modellen dat de biologische eigenschappen voor geneesmiddelenscreening accuraat nabootsen. Om de 3D context van deze PM na te bootsen, zal ik sferoïd en tumor engineering technologie implementeren dat rekening houdt met stromale elementen zoals kanker geassocieerde fibroblasten (CAF). Heterocellulaire LGSOC sferoïden zullen gescreend worden voor drug dat momenteel gebruikt worden in klinische trials/praktijk van andere tumortypes. Hits zullen gevalideerd worden met RNA interferentie en CRISPR/Cas9 technologie. Mechanistische informatie zal verkregen worden door proteomics. Ik zal een LGSOC model ontwikkelen dat biofysisch de PM nabootst, gebruikmakend van acrylate-terminated, urethane-based PEG (AUP) polymeer. Ik zal de optimale PEG lengte selecteren waarbij de stijfheid is gegenereerd door de kanker en stromale celmassa. Scaffolds zullen peritoneaal ingebracht worden in muizen om de microscopische en biofysische analogie met de PM te bevestigen. Concluderend, mijn doel is om tumor engineering te implementeren om PM van genetisch verschillende LGSOC getrouw na te bootsen. Drug geïdentificeerd via in vitro sferoïd modellering zal worden geëvalueerd in dit in vivo model.
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| Description en | Low-Grade Serous Ovarian Carcinoma (LGSOC) accounts for a smaller proportion of all ovarian cancer, the deadliest gynaecological cancer, and the majority of patients presents with peritoneal metastasis (PM). Standard of care therapies are not successful in improving patient outcome. There is a need of preclinical models accurately mimicking the biological properties for drug discovery. To mimic the 3D context of these PM I will implement spheroid and tumor-engineering technology that takes into account stromal elements such as cancer-associated fibroblasts (CAF). Heterocellular LGSOC spheroid models will be screened for compounds currently used in clinical trials/practise of other tumor types. Targets will be validated by RNA interference and CRISPR/Cas9 technology. Mechanistic information will be obtained by proteomics. I will tumor engineer a LGSOC model that biophysically mimics PM using acrylate-terminated, urethane-based PEG (AUP) polymer. I will select the optimal PEG length whereby the stiffness, comparable to the in vivo PM, is generated by the cancer and stromal cell mass and is not imposed by scaffold characteristics. Scaffolds will be peritoneally engrafted in mice to confirm the microscopic and biophysical resemblances of in vivo PM. In conclusion, my goal is to implement tumor engineering to faithfully recapitulate PM of genetically different LGSOC. Therapeutics identified through in vitro spheroid modelling will be evaluated using this in vivo model.
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| Qualifiers | - 3D spheroid models and tumor engineered scaffolds as clinical relevant in vitro and in vivo models. - Low-Grade Serous Ovarian Carcinoma and peritoneal metastasis. - Tumor-microenvironment - including cancer-associated fibroblasts. - |
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| Personal | De Wever Olivier, Blondeel Eva |
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