Translational Medical Research Commons^™

Genotype-Specific Insertion Of Cytotoxic Genetic Elements Into Cancer Cells, Ryan Englander

University Scholar Projects

The new gene editing system CRISPR/Cas9, composed of a complex composed of a guide RNA and the Cas9 endonuclease, promises to revolutionize biological research and potentially allow clinicians to directly modify patient DNA in vivo. While its applications in the treatment of genetic diseases and in modifying immune cells for immunotherapy are currently being explored, CRISPR/Cas9’s potential utility as a modular system for targeting tumor-specific mutated sequences has not as of yet been explored. While CRISPR/Cas9 is specific enough to target small insertions and deletions or gross chromosomal rearrangements, it is not specific enough to reliably restrict editing to …

Nitric Oxide And Cyclic Gmp Signaling In Cancer Therapy, Armond Dorsey, Ferid Murad, Md, Phd, Ka Bian, Md, Phd

Journal of Health Disparities Research and Practice

The nitric oxide-3’,5’-cyclic guanosine monophosphate signaling pathway (NO-cGMP signaling pathway) is a well-known signal transduction pathway which elicits several physiological processes including: cell proliferation, vasodilation, cardiac protection, etc. In this pathway, NO binds to the ferrous heme of histidine-105 on the prosthetic heme of the β₁ subunit of soluble guanylyl cyclase, resulting in the production of cGMP. This pathway, however, is inhibited in certain cancer cells—as observed in glioma cell lines. As a result, the production of cGMP is reduced. This mechanism may facilitate uncontrolled tumor cell growth.

The cancers under research—lung carcinoma, glioma, and pancreatic carcinoma—are all highly …

Understanding And Targeting The C-Terminal Binding Protein (Ctbp) Substrate-Binding Domain For Cancer Therapeutic Development, Benjamin L. Morris

Theses and Dissertations

Cancer involves the dysregulated proliferation and growth of cells throughout the body. C-terminal binding proteins (CtBP) 1 and 2 are transcriptional co-regulators upregulated in several cancers, including breast, colorectal, and ovarian tumors. CtBPs drive oncogenic properties, including migration, invasion, proliferation, and survival, in part through repression of tumor suppressor genes. CtBPs encode an intrinsic dehydrogenase activity, utilizing intracellular NADH concentrations and the substrate 4-methylthio-2-oxobutyric acid (MTOB), to regulate the recruitment of transcriptional regulatory complexes. High levels of MTOB inhibit CtBP dehydrogenase function and induce cytotoxicity among cancer cells in a CtBP-dependent manner. While encouraging, a good therapeutic would utilize >100-fold …