Combining Evolution and Cancer therapy: A review of the Mathematical Approach

: Conventional cancer therapy kills tumors by applying the maximum tolerable dose of therapy. However, it leads to the development of tumoral heterogeneity and resistance, hence leading to therapy failure and progression. It is necessary to design therapies keeping in mind the evolutionary dynamics of tumors to minimize resistance and delay progression. Mathematical models are of great importance in oncology as they assist in the recreation of the tumor microenvironment, predict the outcomes of treatment strategies and elucidate fundamentals of tumor growth and resistance development. The body of literature covering models which incorporate evolutionary dynamics is vast. This paper provides an overview of existing models of “evolutionary therapy”, including ordinary differential equations, fitness, and probability functions.

Medical Health Records-Based Mild Cognitive Impairment (MCI) Prediction for Effective Dementia Care

Dementia is a cognitive impairment that poses a global threat. Current dementia treatments slow the progression of the disease. The timing of starting such treatment markedly affects the effectiveness of the treatment. Some experts mentioned that the optimal timing for starting the currently available treatment in order to delay progression to dementia is the mild cognitive impairment stage, which is the prior stage of dementia. However, medical records are typically only available at a later stage, i.e., from the early or middle stage of dementia. In order to address this limitation, this study developed a model using national health information data from 5 years prior, to predict dementia development 5 years in the future. The Senior Cohort Database, comprising 550,000 samples, were used for model development. The F-measure of the model predicting dementia development after a 5-year incubation period was 77.38%. Models for a 1- and 3-year incubation period were also developed for comparative analysis of dementia risk factors. The three models had some risk factors in common, but also had unique risk factors, depending on the stage. For the common risk factors, a difference in disease severity was confirmed. These findings indicate that the diagnostic criteria and treatment strategy for dementia should differ depending on the timing. Furthermore, since the results of this study present new dementia risk factors that have not been reported previously, this study may also contribute to identification of new dementia risk factors.

Guanabenz modulates microglia and macrophages during demyelination

Multiple sclerosis (MS) is an autoimmune disease characterized by infiltration of peripheral immune cells into the central nervous system, demyelination, and neuronal damage. There is no cure for MS, but available disease-modifying therapies can lessen severity and delay progression. However, current therapies are suboptimal due to adverse effects. Here, we investigate how the FDA-approved antihypertensive drug, guanabenz, which has a favorable safety profile and was recently reported to enhance oligodendrocyte survival, exerts effects on immune cells, specifically microglia and macrophages. We first employed the experimental autoimmune encephalomyelitis (EAE) model and observed pronounced immunomodulation evident by a reduction in pro-inflammatory microglia and macrophages. When guanabenz was administered in the cuprizone model, in which demyelination is less dependent upon immune cells, we did not observe improvements in remyelination, oligodendrocyte numbers, and effects on microglial activation were less dramatic. Thus, guanabenz may be a promising therapeutic to minimize inflammation without exerting severe off-target effects.

Reactive Species in Huntington Disease: Are They Really the Radicals You Want to Catch?

Huntington disease (HD) is a neurodegenerative condition and one of the so-called rare or minority diseases, due to its low prevalence (affecting 1–10 of every 100,000 people in western countries). The causative gene, HTT, encodes huntingtin, a protein with a yet unknown function. Mutant huntingtin causes a range of phenotypes, including oxidative stress and the activation of microglia and astrocytes, which leads to chronic inflammation of the brain. Although substantial efforts have been made to find a cure for HD, there is currently no medical intervention able to stop or even delay progression of the disease. Among the many targets of therapeutic intervention, oxidative stress and inflammation have been extensively studied and some clinical trials have been promoted to target them. In the present work, we review the basic research on oxidative stress in HD and the strategies used to fight it. Many of the strategies to reduce the phenotypes associated with oxidative stress have produced positive results, yet no substantial functional recovery has been observed in animal models or patients with the disease. We discuss possible explanations for this and suggest potential ways to overcome it.