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020 ▼a 9780438194984
035 ▼a (MiAaPQ)AAI10927928
040 ▼a MiAaPQ ▼c MiAaPQ ▼d 248032
0820 ▼a 575
1001 ▼a Turchick, Audrey Lauren.
24510 ▼a Biochemical and Therapeutic Characterization of the Cell-Penetrating Autoantibody 3E10.
260 ▼a [S.l.] : ▼b Yale University., ▼c 2018
260 1 ▼a Ann Arbor : ▼b ProQuest Dissertations & Theses, ▼c 2018
300 ▼a 130 p.
500 ▼a Source: Dissertation Abstracts International, Volume: 79-12(E), Section: B.
500 ▼a Adviser: Peter M. Glazer.
5021 ▼a Thesis (Ph.D.)--Yale University, 2018.
520 ▼a Despite advances in diagnostic and therapeutic approaches, cancer continues to be a leading cause of death worldwide, and the need for a better understanding of the molecular mechanisms underlying the initiation and progression of cancer still r
520 ▼a One new anti-cancer agent of interest is 3E10, a unique cell-penetrating, anti-DNA autoantibody. 3E10 by itself is considered non-toxic to normal cells, but has been shown to inhibit homology directed repair (HDR). This had been attributed to 3E
520 ▼a Prior work has shown that treatment with 3E10 alone can selectively kill cells with genetic mutations that lead to abnormal DNA repair. For example, 3E10 has been shown to be synthetically lethal in BRCA2 deficient human cancer cells. Recent fin
520 ▼a Further, the cell penetrating ability of 3E10's scFv has led to the use of 3E10 as a delivery agent for peptides or additional scFvs for therapeutic approaches. One such example is the conjugation of the 3E10 scFv to the scFv of 3G5. 3G5 is a mo
520 ▼a The 3E10-3G5 bispecific antibody retains the ability to penetrate cells to a similar extent of the 3E10 scFv alone. Moreover, 3E10-3G5 was shown to impair the growth of a variety of melanoma cells with aberrant MDM2 expression both in vitro and
520 ▼a Because NHEJ is a critical repair pathway for maintaining genomic integrity, we hypothesize that the cytotoxicity observed in the melanoma cells is likely due to 3E10-3G5's inhibition of NHEJ. 3E10-3G5's ability to inhibit MDM2 may lead to p53 r
590 ▼a School code: 0265.
650 4 ▼a Genetics.
650 4 ▼a Oncology.
650 4 ▼a Biochemistry.
690 ▼a 0369
690 ▼a 0992
690 ▼a 0487
71020 ▼a Yale University.
7730 ▼t Dissertation Abstracts International ▼g 79-12B(E).
773 ▼t Dissertation Abstract International
790 ▼a 0265
791 ▼a Ph.D.
792 ▼a 2018
793 ▼a English
85640 ▼u http://www.riss.kr/pdu/ddodLink.do?id=T15000868 ▼n KERIS
980 ▼a 201812 ▼f 2019
990 ▼a 관리자