scholarly journals Evolutionary Dynamics of Treatment-Induced Resistance in Cancer Informs Understanding of Rapid Evolution in Natural Systems

2021 ◽  
Vol 9 ◽  
Author(s):  
Mariyah Pressley ◽  
Monica Salvioli ◽  
David B. Lewis ◽  
Christina L. Richards ◽  
Joel S. Brown ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Induced Resistance ◽  
Evolutionary Dynamics ◽  
Management Strategies ◽  
Rapid Evolution ◽  
Maximum Tolerable Dose ◽  
Time To Progression ◽  
Speed Of Evolution ◽  
Adaptive Therapy ◽  
Tolerable Dose

Rapid evolution is ubiquitous in nature. We briefly review some of this quite broadly, particularly in the context of response to anthropogenic disturbances. Nowhere is this more evident, replicated and accessible to study than in cancer. Curiously cancer has been late - relative to fisheries, antibiotic resistance, pest management and evolution in human dominated landscapes - in recognizing the need for evolutionarily informed management strategies. The speed of evolution matters. Here, we employ game-theoretic modeling to compare time to progression with continuous maximum tolerable dose to that of adaptive therapy where treatment is discontinued when the population of cancer cells gets below half of its initial size and re-administered when the cancer cells recover, forming cycles with and without treatment. We show that the success of adaptive therapy relative to continuous maximum tolerable dose therapy is much higher if the population of cancer cells is defined by two cell types (sensitive vs. resistant in a polymorphic population). Additionally, the relative increase in time to progression increases with the speed of evolution. These results hold with and without a cost of resistance in cancer cells. On the other hand, treatment-induced resistance can be modeled as a quantitative trait in a monomorphic population of cancer cells. In that case, when evolution is rapid, there is no advantage to adaptive therapy. Initial responses to therapy are blunted by the cancer cells evolving too quickly. Our study emphasizes how cancer provides a unique system for studying rapid evolutionary changes within tumor ecosystems in response to human interventions; and allows us to contrast and compare this system to other human managed or dominated systems in nature.

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

2021 ◽  
Vol 17 ◽  
Author(s):  
Shruthi Suresh ◽  
Srikanth Raghavendran ◽  
Stalin Selvaraj
Keyword(s):  
Cancer Therapy ◽  
Evolutionary Dynamics ◽  
Treatment Strategies ◽  
The Body ◽  
Maximum Tolerable Dose ◽  
Mathematical Approach ◽  
Therapy Failure ◽  
Resistance Development ◽  
Tolerable Dose ◽  
Delay Progression

: 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.

scholarly journals Efficacy of a novel lantibiotic, CMB001, against MRSA

2021 ◽  
Author(s):  
Jerzy Karczewski ◽  
Christine M Brown ◽  
Yukari Maezato ◽  
Stephen P Krasucki ◽  
Stephen J Streatfield
Keyword(s):  
Antibacterial Activity ◽  
Pharmacokinetic Analysis ◽  
Maximum Tolerable Dose ◽  
In Vivo Efficacy ◽  
Clostridioides Difficile ◽  
Alternative Treatment Option ◽  
Significant Damage ◽  
Tolerable Dose

Abstract Objectives To evaluate the efficacy of a novel lantibiotic, CMB001, against MRSA biofilms in vitro and in an in vivo experimental model of bacterial infection. Methods Antibacterial activity of CMB001 was measured in vitro after its exposure to whole blood or to platelet-poor plasma. In vitro efficacy of CMB001 against a Staphylococcus aureus biofilm was studied using scanning electron microscopy. The maximum tolerable dose in mice was determined and a preliminary pharmacokinetic analysis for CMB001 was performed in mice. In vivo efficacy was evaluated in a neutropenic mouse thigh model of infection. Results CMB001 maintained its antibacterial activity in the presence of blood or plasma for up to 24 h at 37°C. CMB001 efficiently killed S. aureus within the biofilm by causing significant damage to the bacterial cell wall. The maximum tolerable dose in mice was established to be 10 mg/kg and could be increased to 30 mg/kg in mice pretreated with antihistamines. In neutropenic mice infected with MRSA, treatment with CMB001 reduced the bacterial burden with an efficacy equivalent to that of vancomycin. Conclusions CMB001 offers potential as an alternative treatment option to combat MRSA. It will be of interest to evaluate the in vivo efficacy of CMB001 against infections caused by other pathogens, including Clostridioides difficile and Acinetobacter baumannii, and to expand its pharmacokinetic/pharmacodynamic parameters and safety profile.

scholarly journals Genetic Dissimilarity in Conyza sumatrensis Revealed by Simple Sequence Repeat (SSR) Markers

2020 ◽  
Vol 38 ◽  
Author(s):  
T. SCHNEIDER ◽  
M.A. RIZZARDI ◽  
S.P. BRAMMER ◽  
S.M. SCHEFFER-BASSO ◽  
A.L. NUNES
Keyword(s):  
Genetic Diversity ◽  
Management Strategies ◽  
Rapid Evolution ◽  
Jaccard Coefficient ◽  
Mechanisms Of Resistance ◽  
High Genetic Diversity ◽  
Resistance To Herbicides ◽  
Geographic Regions ◽  
Genetic Dissimilarity ◽  
Simple Sequence

ABSTRACT: In view of the rapid evolution of Conyza sumatrensis populations resistant to glyphosate, it is necessary to understand the genetic diversity aimed to improve strategies for managing this weed. We investigated the genetic dissimilarity among 15 biotypes of C. sumatrensis from different geographic regions using microsatellite loci. The biotypes, were cultivated in a greenhouse to obtain vegetal material for DNA extraction. Nineteen microsatellite markers (SSR), were developed for C. sumatrensis biotypes. The genetic dissimilarity was estimated by the Jaccard coefficient (JC) and the biotypes grouped by the UPGMA method. The results demonstrated a high dissimilarity (JC = 7.14 to 82.62) of the analyzed material, with the biotypes forming five groups, being one group formed just by the susceptible biotype and in the others grouped by biotypes from distinct locations in the same group The high genetic diversity of C. sumatrensis indicates that the biotypes may show different responses to different management strategies, and that the mechanisms of resistance to herbicides and characteristics of evolution of populations due to adaptability may be some of the factors involved in the genetic variability of the species.

scholarly journals Genomic evidence of adaptive evolution in the reptilian SOCS gene family

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11677
Author(s):  
Tian Xia ◽  
Lei Zhang ◽  
Guolei Sun ◽  
Xiufeng Yang ◽  
Honghai Zhang
Keyword(s):  
Negative Selection ◽  
Molecular Mechanisms ◽  
Evolutionary Dynamics ◽  
Theoretical Foundation ◽  
Selective Pressure ◽  
Rapid Evolution ◽  
Cytokine Signaling ◽  
Signal Pathways ◽  
Branch Model ◽  
Comprehensive Study

The suppressor of the cytokine signaling (SOCS) family of proteins play an essential role in inhibiting cytokine receptor signaling by regulating immune signal pathways. Although SOCS gene functions have been examined extensively, no comprehensive study has been performed on this gene family’s molecular evolution in reptiles. In this study, we identified eight canonical SOCS genes using recently-published reptilian genomes. We used phylogenetic analysis to determine that the SOCS genes had highly conserved evolutionary dynamics that we classified into two types. We identified positive SOCS4 selection signals in whole reptile lineages and SOCS2 selection signals in the crocodilian lineage. Selective pressure analyses using the branch model and Z-test revealed that these genes were under different negative selection pressures compared to reptile lineages. We also concluded that the nature of selection pressure varies across different reptile lineages on SOCS3, and the crocodilian lineage has experienced rapid evolution. Our results may provide a theoretical foundation for further analyses of reptilian SOCS genes’ functional and molecular mechanisms, as well as their roles in reptile growth and development.

Evolutionary Stable Strategies for Supply Chains: Selfishness, Fairness, and Altruism

2018 ◽  
Vol 6 (6) ◽  
pp. 532-551 ◽  
Author(s):  
Caichun Chai ◽  
Hailong Zhu ◽  
Zhangwei Feng
Keyword(s):  
Supply Chains ◽  
Evolutionary Dynamics ◽  
Replicator Dynamics ◽  
Management Strategies ◽  
Individual Preference ◽  
Short Term ◽  
Evolutionary Stable Strategies ◽  
Pure Strategies ◽  
The Stability

Abstract The management strategies of a firm are inevitable affected by individual behavior preferences. The effect of individual preference on the evolutionary dynamics for supply chains is studied by employing replicator dynamics. Each firm has three behavior preferences: selfishness, fairness, and altruism. Firstly, the case that the strategy set of manufacturers and retailers including two pure strategies is considered and the effect of preference parameter on the equilibrium outcome in the short-term interaction is discussed. Secondly, the equilibrium state in the short-term is always disturbed because the change of the environment, firm’s structure, and so forth. Using the replicator dynamics, the evolutionary stable strategies of manufacturers and retailers in the long-term interaction are analyzed. Finally, the extend case that the strategy set of manufacturers and retailers include three pure strategies is investigated. These results are found that the strategy profile in which both manufacturer and retailer choose fairness or altruism, or one player chooses fair or altruistic strategy and the other player chooses selfish strategy may be evolutionary stable, the stability of these equilibria depends on the the preference parameters.

scholarly journals PRDM9 Diversity at Fine Geographical Scale Reveals Contrasting Evolutionary Patterns and Functional Constraints in Natural Populations of House Mice

2019 ◽  
Vol 36 (8) ◽  
pp. 1686-1700 ◽  
Author(s):  
Covadonga Vara ◽  
Laia Capilla ◽  
Luca Ferretti ◽  
Alice Ledda ◽  
Rosa A Sánchez-Guillén ◽  
...  
Keyword(s):  
Reproductive Isolation ◽  
Evolutionary Biology ◽  
Evolutionary Dynamics ◽  
Rapid Evolution ◽  
Natural Populations ◽  
Global Scale ◽  
House Mice ◽  
Functional Constraints ◽  
Evolutionary Patterns ◽  
Data Set

Abstract One of the major challenges in evolutionary biology is the identification of the genetic basis of postzygotic reproductive isolation. Given its pivotal role in this process, here we explore the drivers that may account for the evolutionary dynamics of the PRDM9 gene between continental and island systems of chromosomal variation in house mice. Using a data set of nearly 400 wild-caught mice of Robertsonian systems, we identify the extent of PRDM9 diversity in natural house mouse populations, determine the phylogeography of PRDM9 at a local and global scale based on a new measure of pairwise genetic divergence, and analyze selective constraints. We find 57 newly described PRDM9 variants, this diversity being especially high on Madeira Island, a result that is contrary to the expectations of reduced variation for island populations. Our analysis suggest that the PRDM9 allelic variability observed in Madeira mice might be influenced by the presence of distinct chromosomal fusions resulting from a complex pattern of introgression or multiple colonization events onto the island. Importantly, we detect a significant reduction in the proportion of PRDM9 heterozygotes in Robertsonian mice, which showed a high degree of similarity in the amino acids responsible for protein–DNA binding. Our results suggest that despite the rapid evolution of PRDM9 and the variability detected in natural populations, functional constraints could facilitate the accumulation of allelic combinations that maintain recombination hotspot symmetry. We anticipate that our study will provide the basis for examining the role of different PRDM9 genetic backgrounds in reproductive isolation in natural populations.

scholarly journals EXTH-25. MAXIMUM TOLERABLE DOSE AND EFFICACY OF RHENIUM-186 NANOLIPOSOMES ON WISTAR RATS FOR TREATMENT OF LEPTOMENINGEAL CARCINOMATOSIS

2017 ◽  
Vol 19 (suppl_6) ◽  
pp. vi78-vi78
Author(s):  
Maria Guerra Garcia ◽  
Beth Goins ◽  
Aleksandra Gruslova ◽  
Michael Garcia ◽  
Andrew Brenner
Keyword(s):  
Wistar Rats ◽  
Leptomeningeal Carcinomatosis ◽  
Maximum Tolerable Dose ◽  
Tolerable Dose

scholarly journals Variable Rates of Simple Satellite Gains across the Drosophila Phylogeny

2018 ◽  
Vol 35 (4) ◽  
pp. 925-941 ◽  
Author(s):  
Kevin H -C Wei ◽  
Sarah E Lower ◽  
Ian V Caldas ◽  
Trevor J S Sless ◽  
Daniel A Barbash ◽  
...  
Keyword(s):  
Evolutionary Dynamics ◽  
Rapid Evolution ◽  
Single Mutation ◽  
Closely Related Species ◽  
Interspecific Differences ◽  
Limited Sampling ◽  
Drosophila Phylogeny ◽  
Males And Females ◽  
Species Specific ◽  
Turn Over

Abstract Simple satellites are tandemly repeating short DNA motifs that can span megabases in eukaryotic genomes. Because they can cause genomic instability through nonallelic homologous exchange, they are primarily found in the repressive heterochromatin near centromeres and telomeres where recombination is minimal, and on the Y chromosome, where they accumulate as the chromosome degenerates. Interestingly, the types and abundances of simple satellites often vary dramatically between closely related species, suggesting that they turn over rapidly. However, limited sampling has prevented detailed understanding of their evolutionary dynamics. Here, we characterize simple satellites from whole-genome sequences generated from males and females of nine Drosophila species, spanning 40 Ma of evolution. We show that PCR-free library preparation and postsequencing GC-correction better capture satellite quantities than conventional methods. We find that over half of the 207 simple satellites identified are species-specific, consistent with previous descriptions of their rapid evolution. Based on a maximum parsimony framework, we determined that most interspecific differences are due to lineage-specific gains. Simple satellites gained within a species are typically a single mutation away from abundant existing satellites, suggesting that they likely emerge from existing satellites, especially in the genomes of satellite-rich species. Interestingly, unlike most of the other lineages which experience various degrees of gains, the lineage leading up to the satellite-poor D. pseudoobscura and D. persimilis appears to be recalcitrant to gains, providing a counterpoint to the notion that simple satellites are universally rapidly evolving.

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