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Full-Text Articles in Medicine and Health Sciences

Marcks Is A Regulator Of Growth, Radiation Sensitivity And Is A Novel Prognostic Factor For Glioblastoma Multiforme, John Jarboe Jan 2013

Marcks Is A Regulator Of Growth, Radiation Sensitivity And Is A Novel Prognostic Factor For Glioblastoma Multiforme, John Jarboe

All ETDs from UAB

Glioblastoma multiforme (GBM) is the most common and deadly primary brain malignancy necessitating improved understanding of GBM biology. In this study, we explore the role of Myristoylated Alanine Rich C-Kinase Substrate (MARCKS) in the context of GBM. We have discovered that the MARCKS protein regulates GBM growth as well as response to radiation therapy through its effects on proliferation, senescence, and DNA repair based on our studies in cell culture and in patient-derived xenograft tumors implanted in mice. Importantly, our analysis of clinical patient data demonstrates that MARCKS is an independent predictor for outcome in GBM patients. Indeed, high MARCKS …


The Role Of Histone Deacetylase Inhibitors In Ameliorating Memory Dysfunction Of An Alzheimer's Disease Mouse Model, Mark Kilgore Jan 2013

The Role Of Histone Deacetylase Inhibitors In Ameliorating Memory Dysfunction Of An Alzheimer's Disease Mouse Model, Mark Kilgore

All ETDs from UAB

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid beta plaques and neurofibrillary tangles, along with cognitive impairments that progress to dementia and eventually death. The development of drug treatments that rescue memory deficits could be a promising therapy given in the early stages of AD. In the following studies, we tested the potential for systemic treatment with histone deacetylase (HDAC) inhibitors to ameliorate cognitive deficits in a mouse model of AD. Using the APPSwe/PS1dE9 mouse model of AD, we showed that giving HDAC inhibitors systemically for 3 weeks reversed contextual memory deficits, stably maintained memories over a 2-week …


Cyclic Gmp Phosphodiesterase As A Novel Target For Colorectal Cancer Chemoprevention, Nan Li Jan 2013

Cyclic Gmp Phosphodiesterase As A Novel Target For Colorectal Cancer Chemoprevention, Nan Li

All ETDs from UAB

Nonsteroidal anti-inflammatory drugs (NSAIDs) display promising antineoplastic activity for colorectal and other cancers, but toxicity from cyclooxygenase (COX) inhibition limits their long-term use for chemoprevention. However, many investigators have concluded that COX-independent mechanisms are responsible for their antineoplastic activity. We previously reported that cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) is a non-COX target of sulindac sulfide (SS). However, the specific isozyme families involved have not been well studied. Here we demonstrate that SS inhibits the growth of colon tumor cells through a novel mechanism involving inhibition of two cGMP degrading isozymes, PDE5 and PDE10, to activate cGMP-dependent protein kinase (PKG). …