Open Access. Powered by Scholars. Published by Universities.®
Translational Medical Research Commons™
Open Access. Powered by Scholars. Published by Universities.®
- Keyword
Articles 1 - 3 of 3
Full-Text Articles in Translational Medical Research
Blood-Tissue Barriers And Autoantibodies In Neurodegenerative Disease Pathogenesis: An Approach To Diagnostics And Disease Mechanism, Eric Luria Goldwaser
Blood-Tissue Barriers And Autoantibodies In Neurodegenerative Disease Pathogenesis: An Approach To Diagnostics And Disease Mechanism, Eric Luria Goldwaser
Graduate School of Biomedical Sciences Theses and Dissertations
Brain homeostasis can be affected in a number of ways that lead to gross anatomical, cellular, and molecular disturbances giving rise to diseases like Alzheimer’s disease (AD) and related dementias. Unfortunately, the mechanistic pathoetiology of AD’s hallmark features of cerebral amyloid plaque buildup and neuronal death are still disputed. Using human brain AD sections, immunohistochemistry experiments revealed internalized surface proteins, co-localized to an expanded lysosomal compartment. Other stains for amyloid-β1-42 (Aβ42) and various immunoglobulin (Ig) species displayed them leaking out of the cerebrovasculature through a dysfunctional blood-brain barrier (BBB), binding to neurons in the vicinity, and localizing to intracellular vesicles …
Introducing Novel Combinatorial Targeted Therapies In Multiple Types Of Cancer, Mehrad Tavallai
Introducing Novel Combinatorial Targeted Therapies In Multiple Types Of Cancer, Mehrad Tavallai
Theses and Dissertations
The cancers of liver, colon and breast are amongst the top five most prevalent and most fatal worldwide. As the Raf/MEK/ERK pathway is frequently deregulated in hepatocellular carcinoma (HCC), sorafenib, a Raf kinase inhibitor, became the first systemic therapy approved for the treatment of patients with HCC. However, sorafenib only produced modest effects with low response rates in the clinic. Similarly, regorafenib, which was approved for the treatment of metastatic colorectal cancer (CRC), has had a poor response rate in the clinic. Since phosphodiesterase type 5 has been reported to be overexpressed in HCC and CRC, we hypothesized that sildenafil, …
Overcoming Treatment Resistance In Heterogeneous Tumors, Nikhil Hebbar
Overcoming Treatment Resistance In Heterogeneous Tumors, Nikhil Hebbar
Theses and Dissertations--Toxicology and Cancer Biology
Most primary tumors are heterogeneous and are often composed of therapy-sensitive and emerging therapy-resistant cancer cells. Rather unexpectedly, treatment of therapy-sensitive tumor cells in heterogeneous tumor microenvironments resulted in apoptosis of the therapy-resistant cancer cells. We identified a novel Par-4 amino-terminal fragment (PAF, which includes amino acids 1-131 of Par-4) that is produced and released by therapy-sensitive cancer cells following therapy-induced caspase-dependent cleavage of the tumor suppressor Par-4. PAF caused paracrine apoptosis in therapy-resistant cancer cells. Unlike Par-4-inducible apoptosis, which is dependent on the cell surface GRP78 receptor, PAF produced cancer-selective apoptosis independent of cell surface GRP78 function. Par-4 contains …