Dataset Information

Delayed Onset of Symptoms Through Feedback Interference in Chronic Cancers.

ABSTRACT: In many cancers, such as Chronic Myelogenous Leukemia (CML), pancreatic, and colorectal cancer, long delays exist between the initiation of the disease and the onset of debilitating symptoms. The early stages of these diseases present manageable symptoms and, in the case of CML, highly effective treatment options. Progression to the more aggressive stages of the diseases limits effective treatment and significantly exacerbates patient prognosis. The mechanisms causing delay and disease progression are largely unknown. The later stages of these diseases are characterized by excessive build up of primitive cell types, indicating a disruption in the normal cell differentiation process that is commonly regulated through feedback from differentiated types. In this study, we propose a mechanism where mutated primitive cells produce a feedback interference signal that desensitizes them to a normal homeostatic feedback. Using a mathematical model, we show that this mechanism can account for the long delay period between occurrence of genetic changes and symptomatic onset characterized by fast growth of cancerous cell population. Finally, we explore novel concepts for potential treatment of chronic cancers.

SUBMITTER: Haney S

PROVIDER: S-EPMC5937283 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Delayed Onset of Symptoms Through Feedback Interference in Chronic Cancers.

Haney Seth S Reya Tannishtha T Bazhenov Maxim M

Convergent science physical oncology 20161021 4

In many cancers, such as Chronic Myelogenous Leukemia (CML), pancreatic, and colorectal cancer, long delays exist between the initiation of the disease and the onset of debilitating symptoms. The early stages of these diseases present manageable symptoms and, in the case of CML, highly effective treatment options. Progression to the more aggressive stages of the diseases limits effective treatment and significantly exacerbates patient prognosis. The mechanisms causing delay and disease progressi ...[more]

PMID: 29744132

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Project description:Demand-controlled deep brain stimulation (DBS) appears to be a promising approach for the treatment of Parkinson's disease (PD) as revealed by computational, pre-clinical and clinical studies. Stimulation delivery is adapted to brain activity, for example, to the amount of neuronal activity considered to be abnormal. Such a closed-loop stimulation setup might help to reduce the amount of stimulation current, thereby maintaining therapeutic efficacy. In the context of the development of stimulation techniques that aim to restore desynchronized neuronal activity on a long-term basis, specific closed-loop stimulation protocols were designed computationally. These feedback techniques, e.g., pulsatile linear delayed feedback (LDF) or pulsatile nonlinear delayed feedback (NDF), were computationally developed to counteract abnormal neuronal synchronization characteristic for PD and other neurological disorders. By design, these techniques are intrinsically demand-controlled methods, where the amplitude of the stimulation signal is reduced when the desired desynchronized regime is reached. We here introduce a novel demand-controlled stimulation method, pulsatile multisite linear delayed feedback (MLDF), by employing MLDF to modulate the pulse amplitude of high-frequency (HF) DBS, in this way aiming at a specific, MLDF-related desynchronizing impact, while maintaining safety requirements with the charge-balanced HF DBS. Previously, MLDF was computationally developed for the control of spatio-temporal synchronized patterns and cluster states in neuronal populations. Here, in a physiologically motivated model network comprising neurons from subthalamic nucleus (STN) and external globus pallidus (GPe), we compare pulsatile MLDF to pulsatile LDF for the case where the smooth feedback signals are used to modulate the amplitude of charge-balanced HF DBS and suggest a modification of pulsatile MLDF which enables a pronounced desynchronizing impact. Our results may contribute to further clinical development of closed-loop DBS techniques.

Dataset Information

Delayed Onset of Symptoms Through Feedback Interference in Chronic Cancers.

Publications

Delayed Onset of Symptoms Through Feedback Interference in Chronic Cancers.

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