Revisiting CDK Inhibitors for Treatment of Glioblastoma Multiforme

Despite extensive efforts and continual progress in research and medicine, outcomes for patients with high-grade glioma remain exceptionally poor. Over the past decade, research has revealed a great deal about the complex biology behind glioma development, and has brought to light some of the major barriers preventing successful treatment. Glioblastoma multiforme (GBM) (stage 4 astrocytoma) is a highly dynamic tumour and one of the most extreme examples of intratumoural heterogeneity, making targeting with specific therapeutics an inefficient and highly unpredictable goal. The cancer stem cell hypothesis offers a new view on the possible mechanisms dictating the heterogeneous nature of this disease and contributes to our understanding of glioma resistance and recurrence. Revealing cell division characteristics of initiating cell populations within GBM may represent novel treatment targets and/or the effective repurposing of existing therapies. In this review, we discuss the potential role of targeting the cyclin-dependent kinases (CDKs) driving this specific population. We also describe developments using multi-omic approaches that may aid in stratifying patient populations for CDK inhibitor therapy

The Atypical Cell Cycle Regulator Spy1 Suppresses Differentiation of the Neuroblastoma Stem Cell Population

Neuroblastoma is an aggressive pediatric cancer originating embryonically from the neural crest. The heterogeneity of the disease, as most solid tumors, complicates diagnosis and treatment. In neuroblastoma this heterogeneity is well represented in both primary tumours and derived cell lines and has been shown to be driven by a population of stem-like tumour initiating cells. Resolving the molecular mediators driving the division of this population of cells may indicate effective therapeutic options for neuroblastoma patients. This study has determined that the atypical cyclin-like protein Spy1, recently indicated in driving symmetric division of glioma stem cells, is a critical factor in the stem-like properties of neuroblastoma tumor initiating cell populations. Spy1 activates Cyclin Dependent Kinases (CDK) in a manner that is unique from classical cyclins. Hence this discovery may represent an important opportunity to design CDK inhibitor drugs to uniquely target subpopulations of cells within these aggressive neural tumours

Benoit Revisited: Defense Spending and Economic Growth in LDCs

In the early 1970s, Emile Benoit shocked development economists by presenting positive cross-country correlations between military expenditures and economic growth rates in less developed countries. Skeptics have abounded, and Benoit's research has been much worked over, both conceptually and statistically. This paper reviews this debate. We conclude that Benoit's findings were aberrant: Most studies suggest that military spending does have an adverse impact on economic growth in developing countries, largely through its adverse effect on saving and investment.Center for Research on Economic Development, University of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/100729/1/ECON197.pd

Novel Approach in Resolving the Mechanism Behind Brain Tumour Heterogeneity and Therapy Response

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumour with 5-year survival rates of less than 10%. Data supports that select cell populations within the tumour mass, referred to as Brain Tumour Initiating Cells (BTICs), are the drivers of GBM growth. While the true origin of these cells is debatable, physiologically these cells possess immature properties of normal neural stem cells. They are highly resistant to drug treatment, radiation and form tumours at a high rate when transplanted into mice. Adding to GBM complexity is the fact that not all the tumours are the same; most patients can be grouped into at least 3 different ‘subtypes’ of GBM using modern genetic tools. This project builds on exciting data demonstrating that a unique cell cycle regulator, Spy1 (or RINGO by other groups) is found in normal neural stem cells during brain development, yet, it controls expansion of BTICs. Understanding which specific BTIC populations within the GBM heterogeneous mass are driven by Spy1 and whether this is subtype dependent, may represent novel and effective treatment strategies. Utilizing brain tumour patient-derived cells of genetically determined GBM subtype and based on expression of well defined BTIC markers, I established a BTIC bank through application of different cell sorting techniques. This approach allows me to further dissect the role of Spy1 in those dangerous cell populations, both in vitro and in vivo, to understand how specific BTICs grow, divide, and what role they play in each of the GBM subtypes, which is the aim of this project. Primary results revealed a strong association of specific combinations of markers within distinct GBM subtypes and significant correlation of Spy1 levels with specific BTIC populations, which sets a potential direction for assessment of new therapy targets and effective treatment strategies against GBM

Benoit Revisted: Defense Spending and Economic Growth in LDCS

In the early 1970s, Emile Benoit shocked development economists by presenting positive cross-country correlations between military expenditures and economic growth rates in less developed countries. Skeptics have abounded, and Benoit's research has been much worked over, both conceptually and statistically. this paper reviews this debate. We conclude that Benoit's findings were aberrant: Most studies suggest that military spending does have an adverse impact on economic growth in developing countries, largely through its adverse effect on saving and investment.Research Seminar in International Economics, Department of Economics, University of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/100728/1/ECON196.pd

The Implementation of Low Impact Development (LID) Stormwater Practices along the South Carolina Coast

2008 S.C. Water Resources Conference - Addressing Water Challenges Facing the State and Regio