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Small Molecule Targeted Imaging and Therapeutic Agent for Luteinizing Hormone Releasing Hormone Receptor and Fibroblast Activation Protein Alpha
Başlık:
Small Molecule Targeted Imaging and Therapeutic Agent for Luteinizing Hormone Releasing Hormone Receptor and Fibroblast Activation Protein Alpha
Yazar:
Roy, Jyoti, author.
ISBN:
9780438120754
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (148 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: Philip S. Low Committee members: Mingji Dai; Timothy Ratliff; Nikolai R. Skrynnikov.
Özet:
The conventional way of treating cancer popularly includes surgery or chemotherapy but unfortunately, none of these methods are free of side-effects. Targeted therapy has gained attention due to its ability to reduce or limit the adverse effects of conventional chemotherapy. Luteinizing Hormone-Releasing Hormone receptor (LHRH-R) among the receptors that are overexpressed on a range of cancers and have limited expression on healthy tissues. Herein, we have developed and synthesized LHRH-R targeted imaging and therapeutic agents. The in vitro studies showed low nanomolar binding affinity or IC50 for the imaging conjugates or therapeutic conjugate respectively. In vivo, the imaging conjugates showed receptor-mediated accumulation in the tumor. LHRH-R targeted therapeutic conjugate was able to completely eliminate the tumor in vivo.
In addition to cancer cells, tumor mass also consists of cancer-associated fibroblast (CAFs), infiltrating T cells, MDSCS, pericytes, tumor-associated macrophages etc. Among this variety of cell type CAFs contribute the majority of the tumor microenvironment. Fibroblast activation protein alpha (FAP) expressed on CAFs has interested researchers due to its overexpression in solid tumors and its limited expression in healthy tissues. We synthesized FAP-targeted near infra-red imaging conjugate which showed low nanomolar binding affinity in vitro. When tested in vivo in various cancer xenograft models the conjugate showed FAP mediated accumulation in the tumor microenvironment. In conclusion, the NIR dye conjugate has a potential to be used for fluorescence guided surgery.
Notlar:
School code: 0183
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
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XX(687755.1) | 687755-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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