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Sample records for evolve anticancer phenotypes

  1. Phenotypic effect of mutations in evolving populations of RNA molecules

    Directory of Open Access Journals (Sweden)

    Manrubia Susanna C

    2010-02-01

    Full Text Available Abstract Background The secondary structure of folded RNA sequences is a good model to map phenotype onto genotype, as represented by the RNA sequence. Computational studies of the evolution of ensembles of RNA molecules towards target secondary structures yield valuable clues to the mechanisms behind adaptation of complex populations. The relationship between the space of sequences and structures, the organization of RNA ensembles at mutation-selection equilibrium, the time of adaptation as a function of the population parameters, the presence of collective effects in quasispecies, or the optimal mutation rates to promote adaptation all are issues that can be explored within this framework. Results We investigate the effect of microscopic mutations on the phenotype of RNA molecules during their in silico evolution and adaptation. We calculate the distribution of the effects of mutations on fitness, the relative fractions of beneficial and deleterious mutations and the corresponding selection coefficients for populations evolving under different mutation rates. Three different situations are explored: the mutation-selection equilibrium (optimized population in three different fitness landscapes, the dynamics during adaptation towards a goal structure (adapting population, and the behavior under periodic population bottlenecks (perturbed population. Conclusions The ratio between the number of beneficial and deleterious mutations experienced by a population of RNA sequences increases with the value of the mutation rate μ at which evolution proceeds. In contrast, the selective value of mutations remains almost constant, independent of μ, indicating that adaptation occurs through an increase in the amount of beneficial mutations, with little variations in the average effect they have on fitness. Statistical analyses of the distribution of fitness effects reveal that small effects, either beneficial or deleterious, are well described by a Pareto

  2. Relationship among phenotypic plasticity, phenotypic fluctuations, robustness, and evolvability; Waddington's legacy revisited under the spirit of Einstein.

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    Kaneko, Kunihiko

    2009-10-01

    Questions on possible relationship between phenotypic plasticity and evolvability, and that between robustness and evolution have been addressed over decades in the field of evolution-development. Based on laboratory evolution experiments and numerical simulations of gene expression dynamics model with an evolving transcription network, we propose quantitative relationships on plasticity, phenotypic fluctuations, and evolvability. By introducing an evolutionary stability assumption on the distribution of phenotype and genotype, the proportionality among phenotypic plasticity against environmental change, variances of phenotype fluctuations of genetic and developmental origins, and evolution speed is obtained. The correlation between developmental robustness to noise and evolutionary robustness to mutation is analysed by simulations of the gene network model. These results provide quantitative formulation on canalization and genetic assimilation, in terms of fluctuations of gene expression levels.

  3. Multivariate sexual selection in a rapidly evolving speciation phenotype.

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    Oh, Kevin P; Shaw, Kerry L

    2013-06-22

    Estimating the fitness surface of rapidly evolving secondary sexual traits can elucidate the origins of sexual isolation and thus speciation. Evidence suggests that sexual selection is highly complex in nature, often acting on multivariate sexual characters that sometimes include non-heritable components of variation, thus presenting a challenge for predicting patterns of sexual trait evolution. Laupala crickets have undergone an explosive species radiation marked by divergence in male courtship song and associated female preferences, yet patterns of sexual selection that might explain this diversification remain unknown. We used female phonotaxis trials to estimate the fitness surface for acoustic characters within one population of Laupala cerasina, a species with marked geographical variation in male song and female preferences. Results suggested significant directional sexual selection on three major song traits, while canonical rotation of the matrix of nonlinear selection coefficients (γ) revealed the presence of significant convex (stabilizing) sexual selection along combinations of characters. Analysis of song variation within and among males indicated significantly higher repeatability along the canonical axis of greatest stabilizing selection than along the axis of greatest linear selection. These results are largely consistent with patterns of song divergence that characterize speciation and suggest that different song characters have the potential to indicate distinct information to females during courtship.

  4. Experimentally evolved and phenotypically plastic responses to enforced monogamy in a hermaphroditic flatworm.

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    Janicke, T; Sandner, P; Ramm, S A; Vizoso, D B; Schärer, L

    2016-09-01

    Sexual selection is considered a potent evolutionary force in all sexually reproducing organisms, but direct tests in terms of experimental evolution of sexual traits are still lacking for simultaneously hermaphroditic animals. Here, we tested how evolution under enforced monogamy affected a suite of reproductive traits (including testis area, sex allocation, genital morphology, sperm morphology and mating behaviour) in the outcrossing hermaphroditic flatworm Macrostomum lignano, using an assay that also allowed the assessment of phenotypically plastic responses to group size. The experiment comprised 32 independent selection lines that evolved under either monogamy or polygamy for 20 generations. While we did not observe an evolutionary shift in sex allocation, we detected effects of the selection regime for two male morphological traits. Specifically, worms evolving under enforced monogamy had a distinct shape of the male copulatory organ and produced sperm with shorter appendages. Many traits that did not evolve under enforced monogamy showed phenotypic plasticity in response to group size. Notably, individuals that grew up in larger groups had a more male-biased sex allocation and produced slightly longer sperm than individuals raised in pairs. We conclude that, in this flatworm, enforced monogamy induced moderate evolutionary but substantial phenotypically plastic responses. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  5. EVOLVE

    CERN Document Server

    Deutz, André; Schütze, Oliver; Legrand, Pierrick; Tantar, Emilia; Tantar, Alexandru-Adrian

    2017-01-01

    This book comprises nine selected works on numerical and computational methods for solving multiobjective optimization, game theory, and machine learning problems. It provides extended versions of selected papers from various fields of science such as computer science, mathematics and engineering that were presented at EVOLVE 2013 held in July 2013 at Leiden University in the Netherlands. The internationally peer-reviewed papers include original work on important topics in both theory and applications, such as the role of diversity in optimization, statistical approaches to combinatorial optimization, computational game theory, and cell mapping techniques for numerical landscape exploration. Applications focus on aspects including robustness, handling multiple objectives, and complex search spaces in engineering design and computational biology.

  6. Evolution of adaptive phenotypic variation patterns by direct selection for evolvability

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    Pavlicev, Mihaela; Cheverud, James M.; Wagner, Günter P.

    2011-01-01

    A basic assumption of the Darwinian theory of evolution is that heritable variation arises randomly. In this context, randomness means that mutations arise irrespective of the current adaptive needs imposed by the environment. It is broadly accepted, however, that phenotypic variation is not uniformly distributed among phenotypic traits, some traits tend to covary, while others vary independently, and again others barely vary at all. Furthermore, it is well established that patterns of trait variation differ among species. Specifically, traits that serve different functions tend to be less correlated, as for instance forelimbs and hind limbs in bats and humans, compared with the limbs of quadrupedal mammals. Recently, a novel class of genetic elements has been identified in mouse gene-mapping studies that modify correlations among quantitative traits. These loci are called relationship loci, or relationship Quantitative Trait Loci (rQTL), and affect trait correlations by changing the expression of the existing genetic variation through gene interaction. Here, we present a population genetic model of how natural selection acts on rQTL. Contrary to the usual neo-Darwinian theory, in this model, new heritable phenotypic variation is produced along the selected dimension in response to directional selection. The results predict that selection on rQTL leads to higher correlations among traits that are simultaneously under directional selection. On the other hand, traits that are not simultaneously under directional selection are predicted to evolve lower correlations. These results and the previously demonstrated existence of rQTL variation, show a mechanism by which natural selection can directly enhance the evolvability of complex organisms along lines of adaptive change. PMID:21106581

  7. Genome duplication and mutations in ACE2 cause multicellular, fast-sedimenting phenotypes in evolved Saccharomyces cerevisiae.

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    Oud, Bart; Guadalupe-Medina, Victor; Nijkamp, Jurgen F; de Ridder, Dick; Pronk, Jack T; van Maris, Antonius J A; Daran, Jean-Marc

    2013-11-05

    Laboratory evolution of the yeast Saccharomyces cerevisiae in bioreactor batch cultures yielded variants that grow as multicellular, fast-sedimenting clusters. Knowledge of the molecular basis of this phenomenon may contribute to the understanding of natural evolution of multicellularity and to manipulating cell sedimentation in laboratory and industrial applications of S. cerevisiae. Multicellular, fast-sedimenting lineages obtained from a haploid S. cerevisiae strain in two independent evolution experiments were analyzed by whole genome resequencing. The two evolved cell lines showed different frameshift mutations in a stretch of eight adenosines in ACE2, which encodes a transcriptional regulator involved in cell cycle control and mother-daughter cell separation. Introduction of the two ace2 mutant alleles into the haploid parental strain led to slow-sedimenting cell clusters that consisted of just a few cells, thus representing only a partial reconstruction of the evolved phenotype. In addition to single-nucleotide mutations, a whole-genome duplication event had occurred in both evolved multicellular strains. Construction of a diploid reference strain with two mutant ace2 alleles led to complete reconstruction of the multicellular-fast sedimenting phenotype. This study shows that whole-genome duplication and a frameshift mutation in ACE2 are sufficient to generate a fast-sedimenting, multicellular phenotype in S. cerevisiae. The nature of the ace2 mutations and their occurrence in two independent evolution experiments encompassing fewer than 500 generations of selective growth suggest that switching between unicellular and multicellular phenotypes may be relevant for competitiveness of S. cerevisiae in natural environments.

  8. Genotype- or Phenotype-Targeting Anticancer Therapies? Lessons from Tumor Evolutionary Biology.

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    Escargueil, Alexandre E; Prado, Soizic; Dezaire, Ambre; Clairambault, Jean; Larsen, Annette K; Soares, Daniele G

    2016-01-01

    Despite the efficacy of most cancer therapies, drug resistance remains a major problem in the clinic. The eradication of the entire tumor and the cure of the patient by chemotherapy alone are rare, in particular for advanced disease. From an evolutionary perspective, the selective pressure exerted by chemotherapy leads to the emergence of resistant clones where resistance can be associated with many different functional mechanisms at the single cell level or can involve changes in the tumor micro-environment. In the last decade, tumor genomics has contributed to the improvement of our understanding of tumorigenesis and has led to the identification of numerous cellular targets for the development of novel therapies. However, since tumors are by nature extremely heterogeneous, the drug efficacy and economical sustainability of this approach is now debatable. Importantly, tumor cell heterogeneity depends not only on genetic modifications but also on non-genetic processes involving either stochastic events or epigenetic modifications making genetic biomarkers of uncertain utility. In this review, we wish to highlight how evolutionary biology can impact our understanding of carcinogenesis and resistance to therapies. We will discuss new approaches based on applied ecology and evolution dynamics that can be used to convert the cancer into a chronic disease where the drugs would control tumor growth. Finally, we will discuss the way metabolic dysfunction or phenotypic changes can help developing new delivery systems or phenotypetargeted drugs and how exploring new sources of active compounds can conduct to the development of drugs with original mechanisms of action. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Molecular and phenotypic distinction of the very recently evolved insular subspecies Mus musculus helgolandicus ZIMMERMANN, 1953.

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    Babiker, Hiba; Tautz, Diethard

    2015-08-14

    Populations and subspecies of the house mouse Mus musculus were able to invade new regions worldwide in the wake of human expansion. Here we investigate the origin and colonization history of the house mouse inhabiting the small island of Heligoland on the German Bight - Mus musculus helgolandicus. It was first described by Zimmermann in 1953, based on morphological descriptions which were considered to be a mosaic between the subspecies M. m. domesticus and M. m. musculus. Since mice on islands are excellent evolutionary model systems, we have focused here on a molecular characterization and an extended phenotype analysis. The molecular data show that the mice from Heligoland are derived from M. m. domesticus based on mitochondrial D-loop sequences as well as on four nuclear diagnostic markers, including one each from the sex-chromosomes. STRUCTURE analysis based on 21 microsatellite markers assigns Heligoland mice to a distinct population and D-loop network analysis suggests that they are derived from a single colonization event. In spite of mice from the mainland arriving by ships, they are apparently genetically refractory against further immigration. Mutation frequencies in complete mitochondrial genome sequences date the colonization age to approximately 400 years ago. Complete genome sequences from three animals revealed a genomic admixture with M. m. musculus genomic regions with at least 6.5% of the genome affected. Geometric morphometric analysis of mandible shapes including skull samples from two time points during the last century suggest specific adaptations to a more carnivorous diet. The molecular and morphological analyses confirm that M. m. helgolandicus consists of a distinct evolutionary lineage with specific adaptations. It shows a remarkable resilience against genetic mixture with mainland populations of M. m. domesticus despite major disturbances in the past century and a high ship traffic. The genomic admixture with M. m. musculus genetic

  10. Multivariate phenotypic divergence due to the fixation of beneficial mutations in experimentally evolved lineages of a filamentous fungus

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    Schoustra, S.E.; Punzalan, D.; Dali, R.; Rundle, H.D.; Kassen, R.

    2012-01-01

    The potential for evolutionary change is limited by the availability of genetic variation. Mutations are the ultimate source of new alleles, yet there have been few experimental investigations of the role of novel mutations in multivariate phenotypic evolution. Here, we evaluated the degree of

  11. Phenotypic characterization and anticancer capacity of CD8+ cytokine-induced killer cells after antigen-induced expansion.

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    Jianhua Liu

    Full Text Available Cytokine-induced killer cells (CIK have been used in clinic for adoptive immunotherapy in a variety of malignant tumors and have improved the prognosis of cancer patients. However, there are individual differences in the CIK cell preparations including the obvious differences in the ratio of effector CIK cells among different cancer patients. Infusion of such heterogeneous immune cell preparation is an important factor that would affect the therapeutic efficacy. We report here the enrichment and expansion of CD8+ cells from CIK cells cultured for one week using magnetic activated cell sorting (MACS. These enriched CD8+ CIK cells expressed T cell marker CD3 and antigen recognition receptor NKG2D. Phenotypic analysis showed that CD8+ CIK cells contained 32.4% of CD3+ CD56+ natural killer (NK-like T cells, 23.6% of CD45RO+ CD28+, and 50.5% of CD45RA+ CD27+ memory T cells. In vitro cytotoxic activity assay demonstrated that the enriched CD8+ CIK cells had significant cytotoxic activity against K562 cells and five ovarian cancer cell lines. Intriguingly, CD8+ CIK cells had strong cytotoxic activity against OVCAR3 cells that has weak binding capability to NKG2D. Flow cytometry and quantitative RT-PCR analysis revealed that OVCAR3 cells expressed HLA-I and OCT4 and Sox2, suggesting that CD8+ CIK cells recognize surface antigen via specific T cell receptor and effectively kill the target cells. The results suggest that transplantation of such in vitro enriched and expanded OCT4-specific CD8+ CIK cells may improve the specific immune defense mechanism against cancer stem cells, providing a novel avenue of cancer stem cell targeted immunotherapy for clinical treatment of ovarian cancer.

  12. Inactivation of the Saccharomyces cerevisiae SKY1 gene induces a specific modification of the yeast anticancer drug sensitivity profile accompanied by a mutator phenotype

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    P.W. Schenk (Paul); A.W.M. Boersma (Anton); M. Brok (Mariël); H. Burger (Herman); G. Stoter (Gerrit); K. Nooter (Kees)

    2002-01-01

    textabstractThe therapeutic potential of the highly active anticancer agent cisplatin is severely limited by the occurrence of cellular resistance. A better understanding of the molecular pathways involved in cisplatin-induced cell death could potentially indicate ways to overcome

  13. Evolving digital ecological networks.

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    Miguel A Fortuna

    Full Text Available "It is hard to realize that the living world as we know it is just one among many possibilities" [1]. Evolving digital ecological networks are webs of interacting, self-replicating, and evolving computer programs (i.e., digital organisms that experience the same major ecological interactions as biological organisms (e.g., competition, predation, parasitism, and mutualism. Despite being computational, these programs evolve quickly in an open-ended way, and starting from only one or two ancestral organisms, the formation of ecological networks can be observed in real-time by tracking interactions between the constantly evolving organism phenotypes. These phenotypes may be defined by combinations of logical computations (hereafter tasks that digital organisms perform and by expressed behaviors that have evolved. The types and outcomes of interactions between phenotypes are determined by task overlap for logic-defined phenotypes and by responses to encounters in the case of behavioral phenotypes. Biologists use these evolving networks to study active and fundamental topics within evolutionary ecology (e.g., the extent to which the architecture of multispecies networks shape coevolutionary outcomes, and the processes involved.

  14. Relationship among phenotypic plasticity, phenotypic fluctuations ...

    Indian Academy of Sciences (India)

    Prakash

    These results provide quantitative formulation on canalization and genetic assimilation, in terms of fluctuations of gene expression levels. [Kaneko K 2009 Relationship among phenotypic plasticity, phenotypic fluctuations, robustness, and evolvability; Waddington's legacy revisited under the spirit of Einstein; J. Biosci.

  15. Classification of current anticancer immunotherapies

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    Vacchelli, Erika; Pedro, José-Manuel Bravo-San; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N.; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P.; Coussens, Lisa; Dhodapkar, Madhav V.; Eggermont, Alexander M.; Fearon, Douglas T.; Fridman, Wolf H.; Fučíková, Jitka; Gabrilovich, Dmitry I.; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M.; Klein, Eva; Knuth, Alexander; Lewis, Claire E.; Liblau, Roland; Lotze, Michael T.; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J.; Mittendorf, Elizabeth A.; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E.; Pienta, Kenneth J.; Porgador, Angel; Prendergast, George C.; Rabinovich, Gabriel A.; Restifo, Nicholas P.; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J.; Speiser, Daniel E.; Spisek, Radek; Srivastava, Pramod K.; Talmadge, James E.; Tartour, Eric; Van Der Burg, Sjoerd H.; Van Den Eynde, Benoît J.; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S.; Whiteside, Theresa L.; Wolchok, Jedd D.; Zitvogel, Laurence; Zou, Weiping

    2014-01-01

    During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. PMID:25537519

  16. Melatonin Anticancer Effects: Review

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    Luigi Di Bella

    2013-01-01

    Full Text Available Melatonin (N-acetyl-5-methoxytryptamine, MLT, the main hormone produced by the pineal gland, not only regulates circadian rhythm, but also has antioxidant, anti-ageing and immunomodulatory properties. MLT plays an important role in blood composition, medullary dynamics, platelet genesis, vessel endothelia, and in platelet aggregation, leukocyte formula regulation and hemoglobin synthesis. Its significant atoxic, apoptotic, oncostatic, angiogenetic, differentiating and antiproliferative properties against all solid and liquid tumors have also been documented. Thanks, in fact, to its considerable functional versatility, MLT can exert both direct and indirect anticancer effects in factorial synergy with other differentiating, antiproliferative, immunomodulating and trophic molecules that form part of the anticancer treatment formulated by Luigi Di Bella (Di Bella Method, DBM: somatostatin, retinoids, ascorbic acid, vitamin D3, prolactin inhibitors, chondroitin-sulfate. The interaction between MLT and the DBM molecules counters the multiple processes that characterize the neoplastic phenotype (induction, promotion, progression and/or dissemination, tumoral mutation. All these particular characteristics suggest the use of MLT in oncological diseases.

  17. Evolving Concepts of Asthma

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    Ray, Anuradha; Wenzel, Sally E.

    2015-01-01

    Our understanding of asthma has evolved over time from a singular disease to a complex of various phenotypes, with varied natural histories, physiologies, and responses to treatment. Early therapies treated most patients with asthma similarly, with bronchodilators and corticosteroids, but these therapies had varying degrees of success. Similarly, despite initial studies that identified an underlying type 2 inflammation in the airways of patients with asthma, biologic therapies targeted toward these type 2 pathways were unsuccessful in all patients. These observations led to increased interest in phenotyping asthma. Clinical approaches, both biased and later unbiased/statistical approaches to large asthma patient cohorts, identified a variety of patient characteristics, but they also consistently identified the importance of age of onset of disease and the presence of eosinophils in determining clinically relevant phenotypes. These paralleled molecular approaches to phenotyping that developed an understanding that not all patients share a type 2 inflammatory pattern. Using biomarkers to select patients with type 2 inflammation, repeated trials of biologics directed toward type 2 cytokine pathways saw newfound success, confirming the importance of phenotyping in asthma. Further research is needed to clarify additional clinical and molecular phenotypes, validate predictive biomarkers, and identify new areas for possible interventions. PMID:26161792

  18. Maintaining evolvability.

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    Crow, James F

    2008-12-01

    Although molecular methods, such as QTL mapping, have revealed a number of loci with large effects, it is still likely that the bulk of quantitative variability is due to multiple factors, each with small effect. Typically, these have a large additive component. Conventional wisdom argues that selection, natural or artificial, uses up additive variance and thus depletes its supply. Over time, the variance should be reduced, and at equilibrium be near zero. This is especially expected for fitness and traits highly correlated with it. Yet, populations typically have a great deal of additive variance, and do not seem to run out of genetic variability even after many generations of directional selection. Long-term selection experiments show that populations continue to retain seemingly undiminished additive variance despite large changes in the mean value. I propose that there are several reasons for this. (i) The environment is continually changing so that what was formerly most fit no longer is. (ii) There is an input of genetic variance from mutation, and sometimes from migration. (iii) As intermediate-frequency alleles increase in frequency towards one, producing less variance (as p --> 1, p(1 - p) --> 0), others that were originally near zero become more common and increase the variance. Thus, a roughly constant variance is maintained. (iv) There is always selection for fitness and for characters closely related to it. To the extent that the trait is heritable, later generations inherit a disproportionate number of genes acting additively on the trait, thus increasing genetic variance. For these reasons a selected population retains its ability to evolve. Of course, genes with large effect are also important. Conspicuous examples are the small number of loci that changed teosinte to maize, and major phylogenetic changes in the animal kingdom. The relative importance of these along with duplications, chromosome rearrangements, horizontal transmission and polyploidy

  19. Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

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    Lefranc, Florence; Carbone, Marianna; Mollo, Ernesto; Gavagnin, Margherita; Betancourt, Tania; Dasari, Ramesh

    2016-01-01

    Abstract The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity. PMID:27925266

  20. Anticancer peptides from bacteria

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    Karpiński, Tomasz M.; Anna K. Szkaradkiewicz

    2013-01-01

    Cancer is a leading cause of death in the world. The rapid development of medicine and pharmacology allows to create new and effective anticancer drugs. Among modern anticancer drugs are bacterial proteins. Until now has been shown anticancer activity among others azurin and exotoxin A from Pseudomonas aeruginosa, Pep27anal2 from Streptococcus pneumoniae, diphtheria toxin from Corynebacterium diphtheriae, and recently discovered Entap from Enterococcus sp. The study presents the current data ...

  1. Anticancer peptides from bacteria

    Directory of Open Access Journals (Sweden)

    Tomasz M. Karpiński

    2013-08-01

    Full Text Available Cancer is a leading cause of death in the world. The rapid development of medicine and pharmacology allows to create new and effective anticancer drugs. Among modern anticancer drugs are bacterial proteins. Until now has been shown anticancer activity among others azurin and exotoxin A from Pseudomonas aeruginosa, Pep27anal2 from Streptococcus pneumoniae, diphtheria toxin from Corynebacterium diphtheriae, and recently discovered Entap from Enterococcus sp. The study presents the current data regarding the properties, action and anticancer activity of listed peptides.

  2. Indoles as anticancer agents

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    Mardia T El-sayed

    2015-10-01

    Full Text Available Indoles are natural products well known for their anticancer activity, which is related to their ability to induce cell death for many cancer cell lines. This review addresses indoles as natural products, mechanism of indoles, facilitated induction and recent studies with indoles and related compounds that were investigated via anticancer screening and that led to drug approval.

  3. Evolvable synthetic neural system

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    Curtis, Steven A. (Inventor)

    2009-01-01

    An evolvable synthetic neural system includes an evolvable neural interface operably coupled to at least one neural basis function. Each neural basis function includes an evolvable neural interface operably coupled to a heuristic neural system to perform high-level functions and an autonomic neural system to perform low-level functions. In some embodiments, the evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy.

  4. Anticancer drugs during pregnancy.

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    Miyamoto, Shingo; Yamada, Manabu; Kasai, Yasuyo; Miyauchi, Akito; Andoh, Kazumichi

    2016-09-01

    Although cancer diagnoses during pregnancy are rare, they have been increasing with the rise in maternal age and are now a topic of international concern. In some cases, the administration of chemotherapy is unavoidable, though there is a relative paucity of evidence regarding the administration of anticancer drugs during pregnancy. As more cases have gradually accumulated and further research has been conducted, we are beginning to elucidate the appropriate timing for the administration of chemotherapy, the regimens that can be administered with relative safety, various drug options and the effects of these drugs on both the mother and fetus. However, new challenges have arisen, such as the effects of novel anticancer drugs and the desire to bear children during chemotherapy. In this review, we outline the effects of administering cytotoxic anticancer drugs and molecular targeted drugs to pregnant women on both the mother and fetus, as well as the issues regarding patients who desire to bear children while being treated with anticancer drugs. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. The evolvability of programmable hardware

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    Raman, Karthik; Wagner, Andreas

    2011-01-01

    In biological systems, individual phenotypes are typically adopted by multiple genotypes. Examples include protein structure phenotypes, where each structure can be adopted by a myriad individual amino acid sequence genotypes. These genotypes form vast connected ‘neutral networks’ in genotype space. The size of such neutral networks endows biological systems not only with robustness to genetic change, but also with the ability to evolve a vast number of novel phenotypes that occur near any one neutral network. Whether technological systems can be designed to have similar properties is poorly understood. Here we ask this question for a class of programmable electronic circuits that compute digital logic functions. The functional flexibility of such circuits is important in many applications, including applications of evolutionary principles to circuit design. The functions they compute are at the heart of all digital computation. We explore a vast space of 1045 logic circuits (‘genotypes’) and 1019 logic functions (‘phenotypes’). We demonstrate that circuits that compute the same logic function are connected in large neutral networks that span circuit space. Their robustness or fault-tolerance varies very widely. The vicinity of each neutral network contains circuits with a broad range of novel functions. Two circuits computing different functions can usually be converted into one another via few changes in their architecture. These observations show that properties important for the evolvability of biological systems exist in a commercially important class of electronic circuitry. They also point to generic ways to generate fault-tolerant, adaptable and evolvable electronic circuitry. PMID:20534598

  6. Pharmacogenomics in drug-metabolizing enzymes catalyzing anticancer drugs for personalized cancer chemotherapy.

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    Fujita, Ken-Ichi; Sasaki, Yasutsuna

    2007-08-01

    Cancer chemotherapy is characterized by a broad range of efficacy and toxicity among patients. Most anticancer drugs show wide interindividual variability in pharmacokinetics and have narrow therapeutic windows. Since drug metabolism is often an essential determinant of interindividual variability in pharmacokinetics, pharmacogenomic studies of drug-metabolizing enzymes are expected to rationalize cancer chemotherapy in terms of patient, treatment, and dosage selection. Candidate gene approaches to pharmacogenomics are based on existing knowledge in clinical pharmacology, used to select the target(s) to be analyzed. So far, the candidate gene approach has provided important clues for pharmacogenomic-based personalized chemotherapy with 6-mercaptopurine (6-MP), solely metabolized by thiopurine S-methyltransferase (TPMT), and irinotecan, mainly detoxified by UDP-glucuronosyltransferase 1A1 (UGT1A1). Reduced activity of TPMT caused by polymorphisms in the TPMT gene and decreased activity of UGT1A1 caused by UGT1A1*28 are related to severe toxic effects of 6-MP and irinotecan, respectively. In response to these findings, the Food and Drug Administration in the United States has supported clinical pharmacogenetic testing by revising the package inserts for these anticancer drugs. The genome wide approach to pharmacogenomics has gradually evolved with continued progress in genome sciences and technologies. This approach can disclose previously unknown relations of factors, as well as identify potential multigenetic associations. The genome wide approach can also identify genes underlying the phenotypic effects of anticancer drugs. This approach may play a complemental role to the candidate gene approach in the future of cancer pharmacogenomics. This review describes recent progress in pharmacogenomics in the field of cancer chemotherapy.

  7. Information theory, evolutionary innovations and evolvability.

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    Wagner, Andreas

    2017-12-05

    How difficult is it to 'discover' an evolutionary adaptation or innovation? I here suggest that information theory, in combination with high-throughput DNA sequencing, can help answer this question by quantifying a new phenotype's information content. I apply this framework to compute the phenotypic information associated with novel gene regulation and with the ability to use novel carbon sources. The framework can also help quantify how DNA duplications affect evolvability, estimate the complexity of phenotypes and clarify the meaning of 'progress' in Darwinian evolution.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'. © 2017 The Author(s).

  8. Immune regulation of therapy-resistant niches: emerging targets for improving anticancer drug responses.

    Science.gov (United States)

    Jinushi, Masahisa

    2014-09-01

    Emerging evidence has unveiled a critical role for immunological parameters in predicting tumor prognosis and clinical responses to anticancer therapeutics. On the other hand, responsiveness to anticancer drugs greatly modifies the repertoires, phenotypes, and immunogenicity of tumor-infiltrating immune cells, serving as a critical factor to regulate tumorigenic activities and the emergence of therapy-resistant phenotypes. Tumor-associated immune functions are influenced by distinct or overlapping sets of therapeutic modalities, such as cytotoxic chemotherapy, radiotherapy, or molecular-targeted therapy, and various anticancer modalities have unique properties to influence the mode of cross-talk between tumor cells and immune cells in tumor microenvironments. Thus, it is critical to understand precise molecular machineries whereby each anticancer strategy has a distinct or overlapping role in regulating the dynamism of reciprocal communication between tumor and immune cells in tumor microenvironments. Such an understanding will open new therapeutic opportunities by harnessing the immune system to overcome resistance to conventional anticancer drugs.

  9. Efficacy of Acylfulvene Illudin analogues against a metastatic lung carcinoma MV522 xenograft nonresponsive to traditional anticancer agents: retention of activity against various mdr phenotypes and unusual cytotoxicity against ERCC2 and ERCC3 DNA helicase-deficient cells.

    Science.gov (United States)

    Kelner, M J; McMorris, T C; Estes, L; Starr, R J; Rutherford, M; Montoya, M; Samson, K M; Taetle, R

    1995-11-01

    Four second-generation Illudin analogues were synthesized and tested for antitumor activity using a metastatic lung carcinoma xenograft model resistant to conventional antitumor agents. One analogue, the parent illudofulvene-derivative called Acylfulvene, inhibited xenograft primary tumor growth and prolonged life span of tumor-bearing animals when administered i.p. or i.v. The efficacy of Acylfulvene exceeded that of mitomycin C, cisplatin, paclitaxol, the parent compound Illudin S, and an earlier analogue, dehydroilludin M. Promising features of this new analogue are: (a) the retention of in vitro activity against a variety of mdr tumor phenotypes including gp170+, gp150+, GSHTR-Pi, topoisomerase I, and topoisomerase II mutants; and (b) an apparent selective cytotoxicity toward cells deficient in either ERCC2 or ERCC3 DNA helicase activity.

  10. Evolvability Search: Directly Selecting for Evolvability in order to Study and Produce It

    DEFF Research Database (Denmark)

    Mengistu, Henok; Lehman, Joel Anthony; Clune, Jeff

    2016-01-01

    One hallmark of natural organisms is their significant evolvability, i.e.,their increased potential for further evolution. However, reproducing such evolvability in artificial evolution remains a challenge, which both reduces the performance of evolutionary algorithms and inhibits the study...... of evolvable digital phenotypes. Although some types of selection in evolutionary computation indirectly encourage evolvability, one unexplored possibility is to directly select for evolvability. To do so, we estimate an individual's future potential for diversity by calculating the behavioral diversity of its...... immediate offspring, and select organisms with increased offspring variation. While the technique is computationally expensive, we hypothesized that direct selection would better encourage evolvability than indirect methods. Experiments in two evolutionary robotics domains confirm this hypothesis: in both...

  11. Bacteriophages displaying anticancer peptides in combined antibacterial and anticancer treatment.

    Science.gov (United States)

    Dąbrowska, Krystyna; Kaźmierczak, Zuzanna; Majewska, Joanna; Miernikiewicz, Paulina; Piotrowicz, Agnieszka; Wietrzyk, Joanna; Lecion, Dorota; Hodyra, Katarzyna; Nasulewicz-Goldeman, Anna; Owczarek, Barbara; Górski, Andrzej

    2014-01-01

    Novel anticancer strategies have employed bacteriophages as drug carriers and display platforms for anticancer agents; however, bacteriophage-based platforms maintain their natural antibacterial activity. This study provides the assessment of combined anticancer (engineered) and antibacterial (natural) phage activity in therapies. An in vivo BALB/c mouse model of 4T1 tumor growth accompanied by surgical wound infection was applied. The wounds were located in the areas of tumors. Bacteriophages (T4) were modified with anticancer Tyr-Ile-Gly-Ser-Arg (YIGSR) peptides by phage display and injected intraperitoneally. Tumor growth was decreased in mice treated with YIGSR-displaying phages. The acuteness of wounds, bacterial load and inflammatory markers in phages-treated mice were markedly decreased. Thus, engineered bacteriophages combine antibacterial and anticancer activity.

  12. Glutamic acid as anticancer agent: An overview

    National Research Council Canada - National Science Library

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K

    2013-01-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents...

  13. Dose calculation of anticancer drugs

    NARCIS (Netherlands)

    Gao, Bo; Klumpen, Heinz-Josef; Gurney, Howard

    2008-01-01

    BACKGROUND: Anticancer drugs are characterized by a narrow therapeutic window and significant inter-patient variability in therapeutic and toxic effects. Current body surface area (BSA)-based dosing fails to standardize systemic anticancer drug exposure and other alternative dosing strategies also

  14. Anticancer substances of mushroom origin.

    Science.gov (United States)

    Ivanova, T S; Krupodorova, T A; Barshteyn, V Y; Artamonova, A B; Shlyakhovenko, V A

    2014-06-01

    The present status of investigations about the anticancer activity which is inherent to medicinal mushrooms, as well as their biomedical potential and future prospects are discussed. Mushroom products and extracts possess promising immunomodulating and anticancer effects, so the main biologically active substances of mushrooms responsible for immunomodulation and direct cytoto-xicity toward cancer cell lines (including rarely mentioned groups of anticancer mushroom proteins), and the mechanisms of their antitumor action were analyzed. The existing to date clinical trials of mushroom substances are mentioned. Mushroom anticancer extracts, obtained by the different solvents, are outlined. Modern approaches of cancer treatment with implication of mushroom products, including DNA vaccinotherapy with mushroom immunomodulatory adjuvants, creation of prodrugs with mushroom lectins that can recognize glycoconjugates on the cancer cell surface, development of nanovectors etc. are discussed. The future prospects of mushroom anticancer substances application, including chemical modification of polysaccharides and terpenoids, gene engineering of proteins, and implementation of vaccines are reviewed.

  15. Recent advances in anticancer drugs.

    Science.gov (United States)

    Niculescu Duvaz, I

    1998-08-01

    During the last few years, research in anticancer drug development has revealed a number of new approaches. These include new types of prodrugs, small peptides and synthetic molecules affecting signal transduction pathways and cell cycle, topoisomerase inhibitors, antisense compounds, anti-angiogenic and antimetastatic agents, gene therapy and vaccines. The aim of the meeting was to present and discuss the recent results in these areas, with respect to the R and D of new anticancer compounds. This review focuses on the most recent advances in anticancer drugs presented and discussed in the plenary sessions.

  16. Genotypes Affecting the Pharmacokinetics of Anticancer Drugs.

    Science.gov (United States)

    Bertholee, Daphne; Maring, Jan Gerard; van Kuilenburg, André B P

    2017-04-01

    Cancer treatment is becoming more and more individually based as a result of the large inter-individual differences that exist in treatment outcome and toxicity when patients are treated using population-based drug doses. Polymorphisms in genes encoding drug-metabolizing enzymes and transporters can significantly influence uptake, metabolism, and elimination of anticancer drugs. As a result, the altered pharmacokinetics can greatly influence drug efficacy and toxicity. Pharmacogenetic screening and/or drug-specific phenotyping of cancer patients eligible for treatment with chemotherapeutic drugs, prior to the start of anticancer treatment, can identify patients with tumors that are likely to be responsive or resistant to the proposed drugs. Similarly, the identification of patients with an increased risk of developing toxicity would allow either dose adaptation or the application of other targeted therapies. This review focuses on the role of genetic polymorphisms significantly altering the pharmacokinetics of anticancer drugs. Polymorphisms in DPYD, TPMT, and UGT1A1 have been described that have a major impact on the pharmacokinetics of 5-fluorouracil, mercaptopurine, and irinotecan, respectively. For other drugs, however, the association of polymorphisms with pharmacokinetics is less clear. To date, the influence of genetic variations on the pharmacokinetics of the increasingly used monoclonal antibodies has hardly been investigated. Some studies indicate that genes encoding the Fcγ-receptor family are of interest, but more research is needed to establish if screening before the start of therapy is beneficial. Considering the profound impact of polymorphisms in drug transporters and drug-metabolizing enzymes on the pharmacokinetics of chemotherapeutic drugs and hence, their toxicity and efficacy, pharmacogenetic and pharmacokinetic profiling should become the standard of care.

  17. Exploiting tumor cell senescence in anticancer therapy

    Science.gov (United States)

    Lee, Minyoung; Lee, Jae-Seon

    2014-01-01

    Cellular senescence is a physiological process of irreversible cell-cycle arrest that contributes to various physiological and pathological processes of aging. Whereas replicative senescence is associated with telomere attrition after repeated cell division, stress-induced premature senescence occurs in response to aberrant oncogenic signaling, oxidative stress, and DNA damage which is independent of telomere dysfunction. Recent evidence indicates that cellular senescence provides a barrier to tumorigenesis and is a determinant of the outcome of cancer treatment. However, the senescence-associated secretory phenotype, which contributes to multiple facets of senescent cancer cells, may influence both cancer-inhibitory and cancer-promoting mechanisms of neighboring cells. Conventional treatments, such as chemo- and radiotherapies, preferentially induce premature senescence instead of apoptosis in the appropriate cellular context. In addition, treatment-induced premature senescence could compensate for resistance to apoptosis via alternative signaling pathways. Therefore, we believe that an intensive effort to understand cancer cell senescence could facilitate the development of novel therapeutic strategies for improving the efficacy of anticancer therapies. This review summarizes the current understanding of molecular mechanisms, functions, and clinical applications of cellular senescence for anticancer therapy. [BMB Reports 2014; 47(2): 51-59] PMID:24411464

  18. Oral delivery of anticancer drugs

    DEFF Research Database (Denmark)

    Thanki, Kaushik; Gangwal, Rahul P; Sangamwar, Abhay T

    2013-01-01

    The present report focuses on the various aspects of oral delivery of anticancer drugs. The significance of oral delivery in cancer therapeutics has been highlighted which principally includes improvement in quality of life of patients and reduced health care costs. Subsequently, the challenges...... incurred in the oral delivery of anticancer agents have been especially emphasized. Sincere efforts have been made to compile the various physicochemical properties of anticancer drugs from either literature or predicted in silico via GastroPlus™. The later section of the paper reviews various emerging...... trends to tackle the challenges associated with oral delivery of anticancer drugs. These invariably include efflux transporter based-, functional excipient- and nanocarrier based-approaches. The role of drug nanocrystals and various others such as polymer based- and lipid based...

  19. Next-generation anticancer metallodrugs

    NARCIS (Netherlands)

    Komeda, Seiji; Casini, A.

    More than 99% of currently approved clinical drugs are organic compounds. In contrast, the percentage of metal-containing drugs (metallodrugs) is very low. In cancer chemotherapy, however, platinum coordination compounds represented by cisplatin and derivatives thereof are essential anticancer

  20. Cannabinoids as Anticancer Drugs.

    Science.gov (United States)

    Ramer, Robert; Hinz, Burkhard

    2017-01-01

    The endocannabinoid system encompassing cannabinoid receptors, endogenous receptor ligands (endocannabinoids), as well as enzymes conferring the synthesis and degradation of endocannabinoids has emerged as a considerable target for pharmacotherapeutical approaches of numerous diseases. Besides palliative effects of cannabinoids used in cancer treatment, phytocannabinoids, synthetic agonists, as well as substances that increase endogenous endocannabinoid levels have gained interest as potential agents for systemic cancer treatment. Accordingly, cannabinoid compounds have been reported to inhibit tumor growth and spreading in numerous rodent models. The underlying mechanisms include induction of apoptosis, autophagy, and cell cycle arrest in tumor cells as well as inhibition of tumor cell invasion and angiogenic features of endothelial cells. In addition, cannabinoids have been shown to suppress epithelial-to-mesenchymal transition, to enhance tumor immune surveillance, and to support chemotherapeutics' effects on drug-resistant cancer cells. However, unwanted side effects include psychoactivity and possibly pathogenic effects on liver health. Other cannabinoids such as the nonpsychoactive cannabidiol exert a comparatively good safety profile while exhibiting considerable anticancer properties. So far experience with anticarcinogenic effects of cannabinoids is confined to in vitro studies and animal models. Although a bench-to-bedside conversion remains to be established, the current knowledge suggests cannabinoid compounds to serve as a group of drugs that may offer significant advantages for patients suffering from cancer diseases. The present review summarizes the role of the endocannabinoid system and cannabinoid compounds in tumor progression. © 2017 Elsevier Inc. All rights reserved.

  1. Acupuncture as anticancer treatment?

    Directory of Open Access Journals (Sweden)

    Paulina Frączek

    2017-01-01

    Full Text Available The mystery of Traditional Chinese Medicine has been attracting people for years. Acupuncture, ranked among the most common services of Complementary and Alternative Medicine, has recently gained a lot of interest in the scientific world. Contemporary researchers have been continuously trying to shed light on its possible mechanism of action in human organism. Numerous studies pertaining to acupuncture’s application in cancer symptoms or treatment-related side effects management have already been published. Moreover, since the modern idea of acupuncture’s immunomodulating effect seems to be promising, scientists have propounded a concept of its potential application as part of direct anti-tumor therapy. In our previous study we summarized possible use of acupuncture in management of cancer symptoms and treatment-related ailments, such as chemotherapy-induced nausea and vomiting, pain, xerostomia, vasomotor symptoms, neutropenia, fatigue, anxiety, insomnia, lymphoedema after mastectomy and peripheral neuropathy. This article reviews the studies concerning acupuncture as a possible tool in modern anticancer treatment.

  2. Mentoring: An Evolving Relationship.

    Science.gov (United States)

    Block, Michelle; Florczak, Kristine L

    2017-04-01

    The column concerns itself with mentoring as an evolving relationship between mentor and mentee. The collegiate mentoring model, the transformational transcendence model, and the humanbecoming mentoring model are considered in light of a dialogue with mentors at a Midwest university and conclusions are drawn.

  3. Measurably evolving populations

    DEFF Research Database (Denmark)

    Drummond, Alexei James; Pybus, Oliver George; Rambaut, Andrew

    2003-01-01

    processes through time. Populations for which such studies are possible � measurably evolving populations (MEPs) � are characterized by sufficiently long or numerous sampled sequences and a fast mutation rate relative to the available range of sequence sampling times. The impact of sequences sampled through...... understanding of evolutionary processes in diverse organisms, from viruses to vertebrates....

  4. EVOLVE 2014 International Conference

    CERN Document Server

    Tantar, Emilia; Sun, Jian-Qiao; Zhang, Wei; Ding, Qian; Schütze, Oliver; Emmerich, Michael; Legrand, Pierrick; Moral, Pierre; Coello, Carlos

    2014-01-01

    This volume encloses research articles that were presented at the EVOLVE 2014 International Conference in Beijing, China, July 1–4, 2014.The book gathers contributions that emerged from the conference tracks, ranging from probability to set oriented numerics and evolutionary computation; all complemented by the bridging purpose of the conference, e.g. Complex Networks and Landscape Analysis, or by the more application oriented perspective. The novelty of the volume, when considering the EVOLVE series, comes from targeting also the practitioner’s view. This is supported by the Machine Learning Applied to Networks and Practical Aspects of Evolutionary Algorithms tracks, providing surveys on new application areas, as in the networking area and useful insights in the development of evolutionary techniques, from a practitioner’s perspective. Complementary to these directions, the conference tracks supporting the volume, follow on the individual advancements of the subareas constituting the scope of the confe...

  5. Evolvable Neural Software System

    Science.gov (United States)

    Curtis, Steven A.

    2009-01-01

    The Evolvable Neural Software System (ENSS) is composed of sets of Neural Basis Functions (NBFs), which can be totally autonomously created and removed according to the changing needs and requirements of the software system. The resulting structure is both hierarchical and self-similar in that a given set of NBFs may have a ruler NBF, which in turn communicates with other sets of NBFs. These sets of NBFs may function as nodes to a ruler node, which are also NBF constructs. In this manner, the synthetic neural system can exhibit the complexity, three-dimensional connectivity, and adaptability of biological neural systems. An added advantage of ENSS over a natural neural system is its ability to modify its core genetic code in response to environmental changes as reflected in needs and requirements. The neural system is fully adaptive and evolvable and is trainable before release. It continues to rewire itself while on the job. The NBF is a unique, bilevel intelligence neural system composed of a higher-level heuristic neural system (HNS) and a lower-level, autonomic neural system (ANS). Taken together, the HNS and the ANS give each NBF the complete capabilities of a biological neural system to match sensory inputs to actions. Another feature of the NBF is the Evolvable Neural Interface (ENI), which links the HNS and ANS. The ENI solves the interface problem between these two systems by actively adapting and evolving from a primitive initial state (a Neural Thread) to a complicated, operational ENI and successfully adapting to a training sequence of sensory input. This simulates the adaptation of a biological neural system in a developmental phase. Within the greater multi-NBF and multi-node ENSS, self-similar ENI s provide the basis for inter-NBF and inter-node connectivity.

  6. von Willebrand disease and aging : an evolving phenotype

    NARCIS (Netherlands)

    Sanders, Y. V.; Giezenaar, M. A.; Laros-van Gorkom, B. A. P.; Meijer, K.; van der Bom, J. G.; Cnossen, M. H.; Nijziel, M. R.; Ypma, P. F.; Fijnvandraat, K.; Eikenboom, J.; Mauser-Bunschoten, E. P.; Leebeek, F. W. G.

    Background: Because the number of elderly von Willebrand disease (VWD) patients is increasing, the pathophysiology of aging in VWD has become increasingly relevant. Objectives: To assess age-related changes in von Willebrand factor (VWF) and factor VIII (FVIII) levels and to compare age-related

  7. Targeting apoptotic machinery as approach for anticancer therapy: Smac mimetics as anticancer agents

    Directory of Open Access Journals (Sweden)

    Nevine M.Y. Elsayed

    2015-06-01

    Full Text Available Apoptosis is a chief regulator of cellular homeostasis. Impairment of apoptotic machinery is a main characteristic of several diseases such as cancer, where the evasion of apoptosis is a cardinal hallmark of cancer. Apoptosis is regulated by contribution of pro- and anti- apoptotic proteins, where caspases are the main executioners of the apoptotic machinery. IAP (inhibitors of apoptosis proteins is a family of endogenous inhibitors of apoptosis, which perform their function through interference with the function of caspases. Smac (second mitochondria-derived activator of caspases is endogenous inhibitor of IAPs, thus it is one of the major proapoptotic endogenous proteins. Thus, the development of Smac mimetics has evolved as an approach for anticancer therapy. Several Smac mimetic agents have been introduced to clinical trial such as birinapanet 12. Herein, the history of development of Smac mimetics along with the recent development in this field is briefly discussed.

  8. Regolith Evolved Gas Analyzer

    Science.gov (United States)

    Hoffman, John H.; Hedgecock, Jud; Nienaber, Terry; Cooper, Bonnie; Allen, Carlton; Ming, Doug

    2000-01-01

    The Regolith Evolved Gas Analyzer (REGA) is a high-temperature furnace and mass spectrometer instrument for determining the mineralogical composition and reactivity of soil samples. REGA provides key mineralogical and reactivity data that is needed to understand the soil chemistry of an asteroid, which then aids in determining in-situ which materials should be selected for return to earth. REGA is capable of conducting a number of direct soil measurements that are unique to this instrument. These experimental measurements include: (1) Mass spectrum analysis of evolved gases from soil samples as they are heated from ambient temperature to 900 C; and (2) Identification of liberated chemicals, e.g., water, oxygen, sulfur, chlorine, and fluorine. REGA would be placed on the surface of a near earth asteroid. It is an autonomous instrument that is controlled from earth but does the analysis of regolith materials automatically. The REGA instrument consists of four primary components: (1) a flight-proven mass spectrometer, (2) a high-temperature furnace, (3) a soil handling system, and (4) a microcontroller. An external arm containing a scoop or drill gathers regolith samples. A sample is placed in the inlet orifice where the finest-grained particles are sifted into a metering volume and subsequently moved into a crucible. A movable arm then places the crucible in the furnace. The furnace is closed, thereby sealing the inner volume to collect the evolved gases for analysis. Owing to the very low g forces on an asteroid compared to Mars or the moon, the sample must be moved from inlet to crucible by mechanical means rather than by gravity. As the soil sample is heated through a programmed pattern, the gases evolved at each temperature are passed through a transfer tube to the mass spectrometer for analysis and identification. Return data from the instrument will lead to new insights and discoveries including: (1) Identification of the molecular masses of all of the gases

  9. Preclinical evaluation of illudins as anticancer agents.

    Science.gov (United States)

    Kelner, M J; McMorris, T C; Beck, W T; Zamora, J M; Taetle, R

    1987-06-15

    Illudins are low molecular weight natural products which were previously evaluated as anticancer drugs using rodent tumor models. In the present studies, we used in vitro cultures of human cancer cells to reevaluate their potential as anticancer agents. Using continuous exposure, Illudins S and M were cytotoxic to human leukemia cells at concentrations of 6-100 nM, but dihydroilludin M was 3 orders of magnitude less toxic, thus identifying a ketone site as a structural feature critical for cytotoxicity. Cytokinetic studies showed that illudin S caused a complete block at the G1-S phase interface of the cell cycle. Kinetics of inhibition of radiolabeled thymidine, uridine, and leucine incorporation suggested a primary effect on DNA synthesis. In colony and liquid culture assays, cell killing was time dependent but near maximal with a 2-h exposure. Myeloid and T-lymphocyte leukemia cells were most sensitive (50% inhibitory concentration, 6-11 nM), but B-cell leukemia/lymphoma, melanoma, and ovarian carcinoma cells were at least 10 times more resistant. Bone marrow granulocyte/macrophage progenitors showed intermediate sensitivity. Illudin S was equally effective against CEM T-lymphocyte leukemia cells expressing the multidrug resistance phenotype associated with Mr 180,000 glycoprotein and the parental cell line. CEM cells resistant to doxorubicin, epipodophyllotoxins, and 1-beta-D-arabinofuranosylcytosine showed only a 2-fold increased resistance to illudin S. Illudins are novel and potent cytotoxins which may be preferentially active against human myeloid and T-cell leukemias, including cells resistant to more conventional chemotherapeutic agents. The present studies illustrate the breadth of information which can be obtained on a new agent using present in vitro screening procedures and human cells.

  10. Evolution of evolvability in gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Anton Crombach

    Full Text Available Gene regulatory networks are perhaps the most important organizational level in the cell where signals from the cell state and the outside environment are integrated in terms of activation and inhibition of genes. For the last decade, the study of such networks has been fueled by large-scale experiments and renewed attention from the theoretical field. Different models have been proposed to, for instance, investigate expression dynamics, explain the network topology we observe in bacteria and yeast, and for the analysis of evolvability and robustness of such networks. Yet how these gene regulatory networks evolve and become evolvable remains an open question. An individual-oriented evolutionary model is used to shed light on this matter. Each individual has a genome from which its gene regulatory network is derived. Mutations, such as gene duplications and deletions, alter the genome, while the resulting network determines the gene expression pattern and hence fitness. With this protocol we let a population of individuals evolve under Darwinian selection in an environment that changes through time. Our work demonstrates that long-term evolution of complex gene regulatory networks in a changing environment can lead to a striking increase in the efficiency of generating beneficial mutations. We show that the population evolves towards genotype-phenotype mappings that allow for an orchestrated network-wide change in the gene expression pattern, requiring only a few specific gene indels. The genes involved are hubs of the networks, or directly influencing the hubs. Moreover, throughout the evolutionary trajectory the networks maintain their mutational robustness. In other words, evolution in an alternating environment leads to a network that is sensitive to a small class of beneficial mutations, while the majority of mutations remain neutral: an example of evolution of evolvability.

  11. 36 - 39 Falodun - Anticancer paid

    African Journals Online (AJOL)

    DR. AMIN

    conventional medicine can be inefficient and expensive, coupled with the adverse side effects of synthetic drugs. However, there is little or no literature on the anticancer properties of the selected medicinal plants used in ethnomedicine in Nigeria. Hence, the need to scientifically validate the claimed biological activity of the ...

  12. Plant-derived anticancer agents: A green anticancer approach

    Directory of Open Access Journals (Sweden)

    Javed Iqbal

    2017-12-01

    Full Text Available Cancer is a frightful disease and represents one of the biggest health-care issues for the human race and demands a proactive strategy for cure. Plants are reservoirs for novel chemical entities and provide a promising line for research on cancer. Hitherto, being effective, chemotherapy is accompanied by certain unbearable side effects. Nevertheless, plants and plant derived products is a revolutionizing field as these are Simple, safer, eco-friendly, low-cost, fast, and less toxic as compared with conventional treatment methods. Phytochemicals are selective in their functions and acts specifically on tumor cells without affecting normal cells. Carcinogenesis is complex phenomena that involves many signaling cascades. Phytochemicals are considered suitable candidates for anticancer drug development due to their pleiotropic actions on target events with multiple manners. The research is in progress for developing potential candidates (those can block or slow down the growth of cancer cells without any side effects from these phytochemicals. Many phytochemicals and their derived analogs have been identified as potential candidates for anticancer therapy. Effort has been made through this comprehensive review to highlight the recent developments and milestones achieved in cancer therapies using phytomolecules with their mechanism of action on nuclear and cellular factors. Furthermore, drugs for cancer treatment and their limitations have also been discussed. Keywords: Cancer, Limitations of anticancer drugs, Phytochemicals, Analogs

  13. Fat: an evolving issue

    Directory of Open Access Journals (Sweden)

    John R. Speakman

    2012-09-01

    Work on obesity is evolving, and obesity is a consequence of our evolutionary history. In the space of 50 years, we have become an obese species. The reasons why can be addressed at a number of different levels. These include separating between whether the primary cause lies on the food intake or energy expenditure side of the energy balance equation, and determining how genetic and environmental effects contribute to weight variation between individuals. Opinion on whether increased food intake or decreased energy expenditure drives the obesity epidemic is still divided, but recent evidence favours the idea that food intake, rather than altered expenditure, is most important. There is more of a consensus that genetics explains most (probably around 65% of weight variation between individuals. Recent advances in genome-wide association studies have identified many polymorphisms that are linked to obesity, yet much of the genetic variance remains unexplained. Finding the causes of this unexplained variation will be an impetus of genetic and epigenetic research on obesity over the next decade. Many environmental factors – including gut microbiota, stress and endocrine disruptors – have been linked to the risk of developing obesity. A better understanding of gene-by-environment interactions will also be key to understanding obesity in the years to come.

  14. Evolving endoscopic surgery.

    Science.gov (United States)

    Sakai, Paulo; Faintuch, Joel

    2014-06-01

    Since the days of Albukasim in medieval Spain, natural orifices have been regarded not only as a rather repugnant source of bodily odors, fluids and excreta, but also as a convenient invitation to explore and treat the inner passages of the organism. However, surgical ingenuity needed to be matched by appropriate tools and devices. Lack of technologically advanced instrumentation was a strong deterrent during almost a millennium until recent decades when a quantum jump materialized. Endoscopic surgery is currently a vibrant and growing subspecialty, which successfully handles millions of patients every year. Additional opportunities lie ahead which might benefit millions more, however, requiring even more sophisticated apparatuses, particularly in the field of robotics, artificial intelligence, and tissue repair (surgical suturing). This is a particularly exciting and worthwhile challenge, namely of larger and safer endoscopic interventions, followed by seamless and scarless recovery. In synthesis, the future is widely open for those who use together intelligence and creativity to develop new prototypes, new accessories and new techniques. Yet there are many challenges in the path of endoscopic surgery. In this new era of robotic endoscopy, one will likely need a virtual simulator to train and assess the performance of younger doctors. More evidence will be essential in multiple evolving fields, particularly to elucidate whether more ambitious and complex pathways, such as intrathoracic and intraperitoneal surgery via natural orifice transluminal endoscopic surgery (NOTES), are superior or not to conventional techniques. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  15. Asymmetric evolving random networks

    Science.gov (United States)

    Coulomb, S.; Bauer, M.

    2003-10-01

    We generalize the Poissonian evolving random graph model of M. Bauer and D. Bernard (2003), to deal with arbitrary degree distributions. The motivation comes from biological networks, which are well-known to exhibit non Poissonian degree distributions. A node is added at each time step and is connected to the rest of the graph by oriented edges emerging from older nodes. This leads to a statistical asymmetry between incoming and outgoing edges. The law for the number of new edges at each time step is fixed but arbitrary. Thermodynamical behavior is expected when this law has a large time limit. Although (by construction) the incoming degree distributions depend on this law, this is not the case for most qualitative features concerning the size distribution of connected components, as long as the law has a finite variance. As the variance grows above 1/4, the average being < 1/2, a giant component emerges, which connects a finite fraction of the vertices. Below this threshold, the distribution of component sizes decreases algebraically with a continuously varying exponent. The transition is of infinite order, in sharp contrast with the case of static graphs. The local-in-time profiles for the components of finite size allow to give a refined description of the system.

  16. Evolving a photosynthetic organelle

    Directory of Open Access Journals (Sweden)

    Nakayama Takuro

    2012-04-01

    Full Text Available Abstract The evolution of plastids from cyanobacteria is believed to represent a singularity in the history of life. The enigmatic amoeba Paulinella and its 'recently' acquired photosynthetic inclusions provide a fascinating system through which to gain fresh insight into how endosymbionts become organelles. The plastids, or chloroplasts, of algae and plants evolved from cyanobacteria by endosymbiosis. This landmark event conferred on eukaryotes the benefits of photosynthesis - the conversion of solar energy into chemical energy - and in so doing had a huge impact on the course of evolution and the climate of Earth 1. From the present state of plastids, however, it is difficult to trace the evolutionary steps involved in this momentous development, because all modern-day plastids have fully integrated into their hosts. Paulinella chromatophora is a unicellular eukaryote that bears photosynthetic entities called chromatophores that are derived from cyanobacteria and has thus received much attention as a possible example of an organism in the early stages of organellogenesis. Recent studies have unlocked the genomic secrets of its chromatophore 23 and provided concrete evidence that the Paulinella chromatophore is a bona fide photosynthetic organelle 4. The question is how Paulinella can help us to understand the process by which an endosymbiont is converted into an organelle.

  17. Anticancer molecular mechanisms of resveratrol

    Directory of Open Access Journals (Sweden)

    Elena Maria Varoni

    2016-04-01

    Full Text Available Resveratrol is a pleiotropic phytochemical belonging to the stilbene family. Despite it is only significantly present in grape products, a huge amount of preclinical studies investigated its anticancer properties in a plethora of cellular and animal models. Molecular mechanisms of resveratrol involved signaling pathways related to: extracellular growth factors and receptor tyrosine kinases; formation of multiprotein complexes and cell metabolism; cell proliferation and genome instability; cytoplasmic tyrosine kinase signaling (cytokine, integrin and developmental pathways; signal transduction by the transforming growth factor-β super-family; apoptosis and inflammation; immune-surveillance and hormone signaling. Resveratrol also showed a promising role to counteract multi-drug resistance: in adjuvant therapy, associated with 5-fluoruracyl and cisplatin, resveratrol had additive and/or synergistic effects increasing the chemosensitization of cancer cells. Resveratrol, by acting on diverse mechanisms simultaneously, has been emphasized as a promising, multi-target, anticancer agent, relevant in both cancer prevention and treatment.

  18. Recent discoveries of anticancer flavonoids.

    Science.gov (United States)

    Raffa, Demetrio; Maggio, Benedetta; Raimondi, Maria Valeria; Plescia, Fabiana; Daidone, Giuseppe

    2017-12-15

    In this review we report the recent advances in anticancer activity of the family of natural occurring flavonoids, covering the time span of the last five years. The bibliographic data will be grouped, on the basis of biological information, in two great categories: reports in which the extract plants bioactivity is reported and the identification of each flavonoid is present or not, and reports in which the anticancer activity is attributable to purified and identified flavonoids from plants. Wherever possible, the targets and mechanisms of action as well as the structure-activity relationships of the molecules will be reported. Also, in the review it was thoroughly investigated the recent discovery on flavonoids containing the 2-phenyl-4H-chromen-4-one system even if some examples of unusual flavonoids, bearing a non-aromatic B-ring or other ring condensed to the base structure are reported. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Anticancer agents from medicinal plants

    Directory of Open Access Journals (Sweden)

    Mohammad Shoeb

    2006-06-01

    Full Text Available Cancer is a major public health burden in both developed and developing countries. Plant derived agents are being used for the treatment of cancer. Several anticancer agents including taxol, vinblastine, vincristine, the camptothecin derivatives, topotecan and irinotecan, and etoposide derived from epipodophyllotoxin are in clinical use all over the world. A number of promising agents such as flavopiridol, roscovitine, combretastatin A-4, betulinic acid and silvestrol are in clinical or preclinical development.

  20. Anticancer agents from medicinal plants

    Directory of Open Access Journals (Sweden)

    Mohammad Shoeb

    2006-12-01

    Full Text Available Cancer is a major public health burden in both developed and developing countries. Plant derived agents are being used for the treatment of cancer. Several anticancer agents including taxol, vinblas-tine, vincristine, the camptothecin derivatives, topotecan and irinotecan, and etoposide derived from epipodophyllotoxin are in clinical use all over the world. A number of promising agents such as flavopiridol, roscovitine, combretastatin A-4, betulinic acid and silvestrol are in clinical or preclinical development.

  1. Multidimensional Design of Anticancer Peptides

    OpenAIRE

    Lin YC; Lim YF; Russo E.; Schneider P; Bolliger L; Edenharter A; Altmann KH; Halin C; Hiss JA; Schneider G

    2015-01-01

    The computer assisted design and optimization of peptides with selective cancer cell killing activity was achieved through merging the features of anticancer peptides cell penetrating peptides and tumor homing peptides. Machine learning classifiers identified candidate peptides that possess the predicted properties. Starting from a template amino acid sequence peptide cytotoxicity against a range of cancer cell lines was systematically optimized while minimizing the effects on primary human e...

  2. Mouse phenotyping.

    Science.gov (United States)

    Fuchs, Helmut; Gailus-Durner, Valérie; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Calzada-Wack, Julia; Da Silva-Buttkus, Patricia; Neff, Frauke; Götz, Alexander; Hans, Wolfgang; Hölter, Sabine M; Horsch, Marion; Kastenmüller, Gabi; Kemter, Elisabeth; Lengger, Christoph; Maier, Holger; Matloka, Mikolaj; Möller, Gabriele; Naton, Beatrix; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Römisch-Margl, Werner; Rozman, Jan; Wang-Sattler, Rui; Schrewe, Anja; Stöger, Claudia; Tost, Monica; Adamski, Jerzy; Aigner, Bernhard; Beckers, Johannes; Behrendt, Heidrun; Busch, Dirk H; Esposito, Irene; Graw, Jochen; Illig, Thomas; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Kremmer, Elisabeth; Mempel, Martin; Neschen, Susanne; Ollert, Markus; Schulz, Holger; Suhre, Karsten; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Hrabě de Angelis, Martin

    2011-02-01

    Model organisms like the mouse are important tools to learn more about gene function in man. Within the last 20 years many mutant mouse lines have been generated by different methods such as ENU mutagenesis, constitutive and conditional knock-out approaches, knock-down, introduction of human genes, and knock-in techniques, thus creating models which mimic human conditions. Due to pleiotropic effects, one gene may have different functions in different organ systems or time points during development. Therefore mutant mouse lines have to be phenotyped comprehensively in a highly standardized manner to enable the detection of phenotypes which might otherwise remain hidden. The German Mouse Clinic (GMC) has been established at the Helmholtz Zentrum München as a phenotyping platform with open access to the scientific community (www.mousclinic.de; [1]). The GMC is a member of the EUMODIC consortium which created the European standard workflow EMPReSSslim for the systemic phenotyping of mouse models (http://www.eumodic.org/[2]). Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Saponins from Chinese Medicines as Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Xiao-Huang Xu

    2016-10-01

    Full Text Available Saponins are glycosides with triterpenoid or spirostane aglycones that demonstrate various pharmacological effects against mammalian diseases. To promote the research and development of anticancer agents from saponins, this review focuses on the anticancer properties of several typical naturally derived triterpenoid saponins (ginsenosides and saikosaponins and steroid saponins (dioscin, polyphyllin, and timosaponin isolated from Chinese medicines. These saponins exhibit in vitro and in vivo anticancer effects, such as anti-proliferation, anti-metastasis, anti-angiogenesis, anti-multidrug resistance, and autophagy regulation actions. In addition, related signaling pathways and target proteins involved in the anticancer effects of saponins are also summarized in this work.

  4. Development of liposomal anticancer drugs.

    Science.gov (United States)

    Hyodo, Kenji; Yamamoto, Eiichi; Suzuki, Takuya; Kikuchi, Hiroshi; Asano, Makoto; Ishihara, Hiroshi

    2013-01-01

    Liposomes are drug delivery systems that can alter the pharmacokinetic properties of compounds. The adverse effects of anticancer agents are a limiting factor for cancer chemotherapy, therefore, liposomal formulations have the potential to improve the therapeutic efficacy of anticancer agents by enhancing their accumulation in tumors and reducing non-selective distribution to normal tissues, which is known as the enhanced permeability and retention effect. To develop a liposomal anticancer agent as a drug product, its formulation must be designed to ensure its quality until it is administered to patients and to exert maximum potency in clinical use rather than in animal experiments. The chemical stability and physicochemical stability of the ingredients are key factors in the design of liposomal formulations. Drug release rates are critical factors in the therapeutic efficacy of liposomal drug products because the encapsulated drug has no pharmacological activity, and only released drug can exert antitumor/toxic activities. Liposomes should maintain the drug in a stable state in the circulation and then promptly release it after accumulation in the target tissue in order to achieve a sufficient drug concentration. To understand the profile of the formulation and to guarantee the quality of drug product, a reliable analytical method that can determine the released and encapsulated drugs in biological fluids is required. Simple online solid phase extractions of the released and encapsulated drugs using a column-switching HPLC system meet the requirements and this system enables accurate in vitro release testing and in vivo pharmacokinetic evaluation. This review introduces the process of liposomal drug product development from various viewpoints.

  5. Natural selection promotes antigenic evolvability

    NARCIS (Netherlands)

    Graves, C.J.; Ros, V.I.D.; Stevenson, B.; Sniegowski, P.D.; Brisson, D.

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide

  6. Disgust: Evolved function and structure

    NARCIS (Netherlands)

    Tybur, J.M.; Lieberman, D.; Kurzban, R.; DeScioli, P.

    2013-01-01

    Interest in and research on disgust has surged over the past few decades. The field, however, still lacks a coherent theoretical framework for understanding the evolved function or functions of disgust. Here we present such a framework, emphasizing 2 levels of analysis: that of evolved function and

  7. Evolving virtual creatures and catapults.

    Science.gov (United States)

    Chaumont, Nicolas; Egli, Richard; Adami, Christoph

    2007-01-01

    We present a system that can evolve the morphology and the controller of virtual walking and block-throwing creatures (catapults) using a genetic algorithm. The system is based on Sims' work, implemented as a flexible platform with an off-the-shelf dynamics engine. Experiments aimed at evolving Sims-type walkers resulted in the emergence of various realistic gaits while using fairly simple objective functions. Due to the flexibility of the system, drastically different morphologies and functions evolved with only minor modifications to the system and objective function. For example, various throwing techniques evolved when selecting for catapults that propel a block as far as possible. Among the strategies and morphologies evolved, we find the drop-kick strategy, as well as the systematic invention of the principle behind the wheel, when allowing mutations to the projectile.

  8. Rising cost of anticancer drugs in Australia.

    Science.gov (United States)

    Karikios, D J; Schofield, D; Salkeld, G; Mann, K P; Trotman, J; Stockler, M R

    2014-05-01

    Anticancer drugs are often expensive and are contributing to the growing cost of cancer care. Concerns have been raised about the effect rising costs may have on availability of new anticancer drugs. This study aims to determine the recent changes in the costs of anticancer drugs in Australia. Publicly available expenditure and prices paid by the Australian Pharmaceutical Benefits Scheme (PBS) for anticancer drugs from 2000 to 2012 were reviewed. The measures used to determine changes in cost were total PBS expenditure and average price paid by the PBS per prescription for anticancer drugs and for all PBS listed drugs. An estimated monthly price paid for newly listed anticancer drugs was also calculated. Annual PBS expenditure on anticancer drugs rose from A$65 million in 1999-2000 to A$466 million in 2011-2012; an average increase of 19% per annum. The average price paid by the PBS per anticancer drug prescription, adjusted for inflation, increased 133% from A$337 to A$786. The real average annual increase in the price per anticancer drug prescription was more than double that for all other PBS drugs combined (7.6% vs 2.8%, difference 4.8%, 95% confidence interval -0.4% to 10.1%, P = 0.07). The median price for a month's treatment of the new anticancer drugs listed was A$4919 (range A$1003 to A$12 578, 2012 prices). PBS expenditure and the price of anticancer drugs in Australia rose substantially from 2000 to 2012. Dealing with these burgeoning costs will be a major challenge for our health system and for those affected by cancer. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

  9. Ganoderma: insights into anticancer effects.

    Science.gov (United States)

    Kladar, Nebojša V; Gavarić, Neda S; Božin, Biljana N

    2016-09-01

    The genus Ganoderma includes about 80 species growing on cut or rotten trees. The most commonly used species is Ganoderma ludicum. Biomolecules responsible for the health benefits of Ganoderma are polysaccharides with an immunostimulative effect and triterpenes with a cytotoxic action. For more than 2000 years, it has been used traditionally in the treatment of various pathological conditions and recently, its immunoregulatory, antiviral, antibacterial, antioxidant, hepatoprotective, and anticancer potential has been confirmed. A wide range of Ganoderma extracts and preparations arrest the cell cycle in different phases and consequently inhibit the growth of various types of cancer cells. Extracts containing polysaccharides stimulate immunological reactions through the production of various cytokines and mobilization of immune system cells. In-vivo studies have confirmed the anticancer potential and the antimetastatic effects of compounds originating from Ganoderma. There is also evidence for the chemopreventive action of Ganoderma extracts in bladder, prostate, liver, and breast cancer. The results of clinical studies suggest the combined use of G. lucidum with conventional chemotherapy/radiotherapy, but the methodology and the results of these studies are being questioned. Therefore, a constant need for new clinical trials exists.

  10. Saponins from Chinese Medicines as Anticancer Agents

    OpenAIRE

    Xiao-Huang Xu; Ting Li; Chi Man Vivienne Fong; Xiuping Chen; Xiao-Jia Chen; Yi-Tao Wang; Ming-Qing Huang; Jin-Jian Lu

    2016-01-01

    Saponins are glycosides with triterpenoid or spirostane aglycones that demonstrate various pharmacological effects against mammalian diseases. To promote the research and development of anticancer agents from saponins, this review focuses on the anticancer properties of several typical naturally derived triterpenoid saponins (ginsenosides and saikosaponins) and steroid saponins (dioscin, polyphyllin, and timosaponin) isolated from Chinese medicines. These saponins exhibit in vitro and in vivo...

  11. When did oxygenic photosynthesis evolve?

    National Research Council Canada - National Science Library

    Roger Buick

    2008-01-01

    ...2.4 Ga ago, but when the photosynthetic oxygen production began is debatable. However, geological and geochemical evidence from older sedimentary rocks indicates that oxygenic photosynthesis evolved well before this oxygenation event...

  12. Marshal: Maintaining Evolving Models Project

    Data.gov (United States)

    National Aeronautics and Space Administration — SIFT proposes to design and develop the Marshal system, a mixed-initiative tool for maintaining task models over the course of evolving missions. Marshal-enabled...

  13. Natural selection promotes antigenic evolvability.

    Science.gov (United States)

    Graves, Christopher J; Ros, Vera I D; Stevenson, Brian; Sniegowski, Paul D; Brisson, Dustin

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections.

  14. Natural selection promotes antigenic evolvability.

    Directory of Open Access Journals (Sweden)

    Christopher J Graves

    Full Text Available The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish

  15. Anti-cancer Lead Molecule

    KAUST Repository

    Sagar, Sunil

    2014-04-17

    Derivatives of plumbagin can be selectively cytotoxic to breast cancer cells. Derivative `A` (Acetyl Plumbagin) has emerged as a lead molecule for testing against estrogen positive breast cancer and has shown low hepatotoxicity as well as overall lower toxicity in nude mice model. The toxicity of derivative `A` was determined to be even lower than vehicle control (ALT and AST markers). The possible mechanism of action identified based on the microarray experiments and pathway mapping shows that derivative `A` could be acting by altering the cholesterol-related mechanisms. The low toxicity profile of derivative `A` highlights its possible role as future anti-cancer drug and/or as an adjuvant drug to reduce the toxicity of highly toxic chemotherapeutic drugs

  16. Multidimensional Design of Anticancer Peptides.

    Science.gov (United States)

    Lin, Yen-Chu; Lim, Yi Fan; Russo, Erica; Schneider, Petra; Bolliger, Lea; Edenharter, Adriana; Altmann, Karl-Heinz; Halin, Cornelia; Hiss, Jan A; Schneider, Gisbert

    2015-08-24

    The computer-assisted design and optimization of peptides with selective cancer cell killing activity was achieved through merging the features of anticancer peptides, cell-penetrating peptides, and tumor-homing peptides. Machine-learning classifiers identified candidate peptides that possess the predicted properties. Starting from a template amino acid sequence, peptide cytotoxicity against a range of cancer cell lines was systematically optimized while minimizing the effects on primary human endothelial cells. The computer-generated sequences featured improved cancer-cell penetration, induced cancer-cell apoptosis, and were enabled a decrease in the cytotoxic concentration of co-administered chemotherapeutic agents in vitro. This study demonstrates the potential of multidimensional machine-learning methods for rapidly obtaining peptides with the desired cellular activities. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Survivability is more fundamental than evolvability.

    Directory of Open Access Journals (Sweden)

    Michael E Palmer

    Full Text Available For a lineage to survive over long time periods, it must sometimes change. This has given rise to the term evolvability, meaning the tendency to produce adaptive variation. One lineage may be superior to another in terms of its current standing variation, or it may tend to produce more adaptive variation. However, evolutionary outcomes depend on more than standing variation and produced adaptive variation: deleterious variation also matters. Evolvability, as most commonly interpreted, is not predictive of evolutionary outcomes. Here, we define a predictive measure of the evolutionary success of a lineage that we call the k-survivability, defined as the probability that the lineage avoids extinction for k generations. We estimate the k-survivability using multiple experimental replicates. Because we measure evolutionary outcomes, the initial standing variation, the full spectrum of generated variation, and the heritability of that variation are all incorporated. Survivability also accounts for the decreased joint likelihood of extinction of sub-lineages when they 1 disperse in space, or 2 diversify in lifestyle. We illustrate measurement of survivability with in silico models, and suggest that it may also be measured in vivo using multiple longitudinal replicates. The k-survivability is a metric that enables the quantitative study of, for example, the evolution of 1 mutation rates, 2 dispersal mechanisms, 3 the genotype-phenotype map, and 4 sexual reproduction, in temporally and spatially fluctuating environments. Although these disparate phenomena evolve by well-understood microevolutionary rules, they are also subject to the macroevolutionary constraint of long-term survivability.

  18. Immuno-thermal ablations - boosting the anticancer immune response.

    Science.gov (United States)

    Slovak, Ryan; Ludwig, Johannes M; Gettinger, Scott N; Herbst, Roy S; Kim, Hyun S

    2017-10-17

    The use of immunomodulation to treat malignancies has seen a recent explosion in interest. The therapeutic appeal of these treatments is far reaching, and many new applications continue to evolve. In particular, immune modulating drugs have the potential to enhance the systemic anticancer immune effects induced by locoregional thermal ablation. The immune responses induced by ablation monotherapy are well documented, but independently they tend to be incapable of evoking a robust antitumor response. By adding immunomodulators to traditional ablative techniques, several researchers have sought to amplify the induced immune response and trigger systemic antitumor activity. This paper summarizes the work done in animal models to investigate the immune effects induced by the combination of ablative therapy and immunomodulation. Combination therapy with radiofrequency ablation, cryoablation, and microwave ablation are all reviewed, and special attention has been paid to the addition of checkpoint blockades.

  19. Liposomal Drug Delivery of Anticancer Agents

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob

    In the first part of the thesis the work towards a new generation of liposomal drug delivery systems for anticancer agents is described. The drug delivery system takes advantage of the elevated level of secretory phospholipase A2 (sPLA2) IIA in many tumors and the enhanced permeability...... and retention (EPR) effect. The liposomes consists of sPLA2 IIA sensitive phospholipids having anticancer drugs covalently attached to the sn-2 position of the glycerol backbone in the phospholipids, hence drug leakage is avoided from the carrier system. Various known anticancer agents, like chlorambucil, all...

  20. Plant Antimicrobial Peptides as Potential Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Jaquelina Julia Guzmán-Rodríguez

    2015-01-01

    Full Text Available Antimicrobial peptides (AMPs are part of the innate immune defense mechanism of many organisms and are promising candidates to treat infections caused by pathogenic bacteria to animals and humans. AMPs also display anticancer activities because of their ability to inactivate a wide range of cancer cells. Cancer remains a cause of high morbidity and mortality worldwide. Therefore, the development of methods for its control is desirable. Attractive alternatives include plant AMP thionins, defensins, and cyclotides, which have anticancer activities. Here, we provide an overview of plant AMPs anticancer activities, with an emphasis on their mode of action, their selectivity, and their efficacy.

  1. Plant antimicrobial peptides as potential anticancer agents.

    Science.gov (United States)

    Guzmán-Rodríguez, Jaquelina Julia; Ochoa-Zarzosa, Alejandra; López-Gómez, Rodolfo; López-Meza, Joel E

    2015-01-01

    Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms and are promising candidates to treat infections caused by pathogenic bacteria to animals and humans. AMPs also display anticancer activities because of their ability to inactivate a wide range of cancer cells. Cancer remains a cause of high morbidity and mortality worldwide. Therefore, the development of methods for its control is desirable. Attractive alternatives include plant AMP thionins, defensins, and cyclotides, which have anticancer activities. Here, we provide an overview of plant AMPs anticancer activities, with an emphasis on their mode of action, their selectivity, and their efficacy.

  2. Anticancer Activity of the Cholesterol Exporter ABCA1 Gene

    Directory of Open Access Journals (Sweden)

    Bradley Smith

    2012-09-01

    Full Text Available The ABCA1 protein mediates the transfer of cellular cholesterol across the plasma membrane to apolipoprotein A-I. Loss-of-function mutations in the ABCA1 gene induce Tangier disease and familial hypoalphalipoproteinemia, both cardiovascular conditions characterized by abnormally low levels of serum cholesterol, increased cholesterol in macrophages, and subsequent formation of vascular plaque. Increased intracellular cholesterol levels are also frequently found in cancer cells. Here, we demonstrate anticancer activity of ABCA1 efflux function, which is compromised following inhibition of ABCA1 gene expression by oncogenic mutations or cancer-specific ABCA1 loss-of-function mutations. In concert with elevated cholesterol synthesis found in cancer cells, ABCA1 deficiency allows for increased mitochondrial cholesterol, inhibits release of mitochondrial cell death-promoting molecules, and thus facilitates cancer cell survival, suggesting that elevated mitochondrial cholesterol is essential to the cancer phenotype.

  3. Ligand based pharmacophore modelling of anticancer histone ...

    African Journals Online (AJOL)

    USER

    2010-06-21

    Jun 21, 2010 ... for designing the pharmacophore onto the set of 70 compounds of three different classes and two subclasses. ... More effective anticancer drug production with novel modes of action .... with Ligand Scout using default settings.

  4. Phytochemical, Anticancer and Antioxidant Evaluation of Potential ...

    African Journals Online (AJOL)

    BSN

    stem bark of Calliandria surinamensis were subjected to in vitro free radical scavenging and anticancer activities using DPPH free radical scavenging method and lung cancer cell lines ..... Linnaeus Memorial Symposium. Life Sci. 82: 445-449.

  5. Glutamic acid as anticancer agent: An overview.

    Science.gov (United States)

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K

    2013-10-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed.

  6. In Silico Design of Anticancer Peptides.

    Science.gov (United States)

    Kumar, Shailesh; Li, Hui

    2017-01-01

    In the past few years, small peptides having anticancer properties have emerged as a potential avenue for cancer therapy. Compared to current anti-cancer chemotherapeutic drugs (or small molecules), anticancer peptides (ACPs) have numerous advantageous properties, such as high specificity, low production cost, high tumor penetration, ease of synthesis and modification. However, in wet lab setups, identification and characterization of novel ACPs is a time-consuming and labor-intensive process. Therefore, in silico designing of anticancer peptides is beneficial, prior to their synthesis and characterization. This approach is less time consuming and more cost-effective. In this chapter, we discuss a web-based tool, AntiCP (http://crdd.osdd.net/raghava/anticp/), for designing ACPs.

  7. Anticancer Activity of Tetrahydrocorysamine against Pancreatic ...

    African Journals Online (AJOL)

    MTT) and flow cytometry assays. The effect of TCSM on the expressions of mitochondria-mediated apoptotic proteins were investigated by Western blot assay. Xenograft assay was used to evaluate the anticancer activity of TCSM in vivo.

  8. Oncolytic viruses as anticancer vaccines

    Directory of Open Access Journals (Sweden)

    Norman eWoller

    2014-07-01

    Full Text Available Oncolytic virotherapy has shown impressive results in preclinical studies and first promising therapeutic outcomes in clinical trials as well. Since viruses are known for a long time as excellent vaccination agents, oncolytic viruses are now designed as novel anticancer agents combining the aspect of lysis-dependent cytoreductive activity with concomitant induction of antitumoral immune responses. Antitumoral immune activation by oncolytic virus infection of tumor tissue comprises both, immediate effects of innate immunity and also adaptive responses for long lasting antitumoral activity which is regarded as the most prominent challenge in clinical oncology. To date, the complex effects of a viral tumor infection on the tumor microenvironment and the consequences for the tumor-infiltrating immune cell compartment are poorly understood. However, there is more and more evidence that a tumor infection by an oncolytic virus opens up a number of options for further immunomodulating interventions such as systemic chemotherapy, generic immunostimulating strategies, dendritic cell-based vaccines, and antigenic libraries to further support clinical efficacy of oncolytic virotherapy.

  9. Targeted anticancer therapy: overexpressed receptors and nanotechnology.

    Science.gov (United States)

    Akhtar, Mohd Javed; Ahamed, Maqusood; Alhadlaq, Hisham A; Alrokayan, Salman A; Kumar, Sudhir

    2014-09-25

    Targeted delivery of anticancer drugs to cancer cells and tissues is a promising field due to its potential to spare unaffected cells and tissues, but it has been a major challenge to achieve success in these therapeutic approaches. Several innovative approaches to targeted drug delivery have been devised based on available knowledge in cancer biology and on technological advancements. To achieve the desired selectivity of drug delivery, nanotechnology has enabled researchers to design nanoparticles (NPs) to incorporate anticancer drugs and act as nanocarriers. Recently, many receptor molecules known to be overexpressed in cancer have been explored as docking sites for the targeting of anticancer drugs. In principle, anticancer drugs can be concentrated specifically in cancer cells and tissues by conjugating drug-containing nanocarriers with ligands against these receptors. Several mechanisms can be employed to induce triggered drug release in response to either endogenous trigger or exogenous trigger so that the anticancer drug is only released upon reaching and preferentially accumulating in the tumor tissue. This review focuses on overexpressed receptors exploited in targeting drugs to cancerous tissues and the tumor microenvironment. We briefly evaluate the structure and function of these receptor molecules, emphasizing the elegant mechanisms by which certain characteristics of cancer can be exploited in cancer treatment. After this discussion of receptors, we review their respective ligands and then the anticancer drugs delivered by nanotechnology in preclinical models of cancer. Ligand-functionalized nanocarriers have delivered significantly higher amounts of anticancer drugs in many in vitro and in vivo models of cancer compared to cancer models lacking such receptors or drug carrying nanocarriers devoid of ligand. This increased concentration of anticancer drug in the tumor site enabled by nanotechnology could have a major impact on the efficiency of cancer

  10. Structural properties of genotype-phenotype maps.

    Science.gov (United States)

    Ahnert, S E

    2017-07-01

    The map between genotype and phenotype is fundamental to biology. Biological information is stored and passed on in the form of genotypes, and expressed in the form of phenotypes. A growing body of literature has examined a wide range of genotype-phenotype (GP) maps and has established a number of properties that appear to be shared by many GP maps. These properties are 'structural' in the sense that they are properties of the distribution of phenotypes across the point-mutation network of genotypes. They include: a redundancy of genotypes, meaning that many genotypes map to the same phenotypes, a highly non-uniform distribution of the number of genotypes per phenotype, a high robustness of phenotypes and the ability to reach a large number of new phenotypes within a small number of mutational steps. A further important property is that the robustness and evolvability of phenotypes are positively correlated. In this review, I give an overview of the study of GP maps with particular emphasis on these structural properties, and discuss a model that attempts to explain why these properties arise, as well as some of the fundamental ways in which the structure of GP maps can affect evolutionary outcomes. © 2017 The Author(s).

  11. Effectiveness of activated carbon masks in preventing anticancer drug inhalation

    OpenAIRE

    Sato, Junya; Kogure, Atushi; Kudo, Kenzo

    2016-01-01

    Background The exposure of healthcare workers to anticancer drugs such as cyclophosphamide (CPA) is a serious health concern. Anticancer drug pollution may spread outside biological safety cabinets even when a closed system is used. The inhalation of vaporized anticancer drugs is thought to be the primary route of exposure. Therefore, it is important that healthcare workers wear masks to prevent inhalation of anticancer drugs. However, the permeability of medical masks to vaporized anticancer...

  12. How could language have evolved?

    NARCIS (Netherlands)

    Bolhuis, Johan J.|info:eu-repo/dai/nl/074069454; Tattersall, Ian; Chomsky, Noam; Berwick, Robert C.

    The evolution of the faculty of language largely remains an enigma. In this essay, we ask why. Language’s evolutionary analysis is complicated because it has no equivalent in any nonhuman species. There is also no consensus regarding the essential nature of the language ‘‘phenotype.’’ According to

  13. Nonlinear Dynamics in Gene Regulation Promote Robustness and Evolvability of Gene Expression Levels.

    Directory of Open Access Journals (Sweden)

    Arno Steinacher

    Full Text Available Cellular phenotypes underpinned by regulatory networks need to respond to evolutionary pressures to allow adaptation, but at the same time be robust to perturbations. This creates a conflict in which mutations affecting regulatory networks must both generate variance but also be tolerated at the phenotype level. Here, we perform mathematical analyses and simulations of regulatory networks to better understand the potential trade-off between robustness and evolvability. Examining the phenotypic effects of mutations, we find an inverse correlation between robustness and evolvability that breaks only with nonlinearity in the network dynamics, through the creation of regions presenting sudden changes in phenotype with small changes in genotype. For genotypes embedding low levels of nonlinearity, robustness and evolvability correlate negatively and almost perfectly. By contrast, genotypes embedding nonlinear dynamics allow expression levels to be robust to small perturbations, while generating high diversity (evolvability under larger perturbations. Thus, nonlinearity breaks the robustness-evolvability trade-off in gene expression levels by allowing disparate responses to different mutations. Using analytical derivations of robustness and system sensitivity, we show that these findings extend to a large class of gene regulatory network architectures and also hold for experimentally observed parameter regimes. Further, the effect of nonlinearity on the robustness-evolvability trade-off is ensured as long as key parameters of the system display specific relations irrespective of their absolute values. We find that within this parameter regime genotypes display low and noisy expression levels. Examining the phenotypic effects of mutations, we find an inverse correlation between robustness and evolvability that breaks only with nonlinearity in the network dynamics. Our results provide a possible solution to the robustness-evolvability trade-off, suggest

  14. The Evolving Resource Metadata Infrastructure

    Science.gov (United States)

    Biemesderfer, Chris

    The search and discovery mechanisms that will facilitate and simplify systematic research on the Internet depend on systematic classifications of resources, as well as on standardized access to such metadata. The principles and technologies that will make this possible are evolving in the work of the Internet Engineering Task Force and the digital library initiatives, among others. The desired outcome is a set of standards, tools, and practices that permits both cataloging and retrieval to be comprehensive and efficient.

  15. Ranking in evolving complex networks

    Science.gov (United States)

    Liao, Hao; Mariani, Manuel Sebastian; Medo, Matúš; Zhang, Yi-Cheng; Zhou, Ming-Yang

    2017-05-01

    Complex networks have emerged as a simple yet powerful framework to represent and analyze a wide range of complex systems. The problem of ranking the nodes and the edges in complex networks is critical for a broad range of real-world problems because it affects how we access online information and products, how success and talent are evaluated in human activities, and how scarce resources are allocated by companies and policymakers, among others. This calls for a deep understanding of how existing ranking algorithms perform, and which are their possible biases that may impair their effectiveness. Many popular ranking algorithms (such as Google's PageRank) are static in nature and, as a consequence, they exhibit important shortcomings when applied to real networks that rapidly evolve in time. At the same time, recent advances in the understanding and modeling of evolving networks have enabled the development of a wide and diverse range of ranking algorithms that take the temporal dimension into account. The aim of this review is to survey the existing ranking algorithms, both static and time-aware, and their applications to evolving networks. We emphasize both the impact of network evolution on well-established static algorithms and the benefits from including the temporal dimension for tasks such as prediction of network traffic, prediction of future links, and identification of significant nodes.

  16. Anticancer metal drugs and immunogenic cell death.

    Science.gov (United States)

    Terenzi, Alessio; Pirker, Christine; Keppler, Bernhard K; Berger, Walter

    2016-12-01

    Conventional chemotherapeutics, but also innovative precision anticancer compounds, are commonly perceived to target primarily the cancer cell compartment. However, recently it was discovered that some of these compounds can also exert immunomodulatory activities which might be exploited to synergistically enhance their anticancer effects. One specific phenomenon of the interplay between chemotherapy and the anticancer immune response is the so-called "immunogenic cell death" (ICD). ICD was discovered based on a vaccination effect exerted by cancer cells dying from pretreatment with certain chemotherapeutics, termed ICD inducers, in syngeneic transplantation mouse models. Interestingly, only a minority of drugs is able to trigger ICD without a clear-cut relation to chemical structures or their primary modes-of-action. Nevertheless, generation of reactive oxygen species (ROS) and induction of endoplasmic reticulum (ER) stress are clearly linked to ICD. With regard to metal drugs, oxaliplatin but not cisplatin is considered a bona fide ICD inducer. Taken into account that several experimental metal compounds are efficient ROS and ER stress mediators, presence of potent ICD inducers within the plethora of novel metal complexes seems feasible and has occasionally been reported. In the light of recent successes in cancer immunotherapy, here we review existing literature regarding anticancer metal drugs and ICD induction. We recommend a more profound investigation of the immunogenic features of experimental anticancer metal drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. TAILORING IMMUNOTOXIN AS ANTICANCER DRUG

    Directory of Open Access Journals (Sweden)

    Santoso Cornain

    2012-09-01

    Full Text Available The conventional treatments for cancer have been considered unsatisfatory, with limited efficiency in terms of discriminative cancer cell adverse reaction against the normal compartments, a number of immunological approaches had been implemented. Since cancer cells could exhibit tumor specific antigen (s, a highly specific antibody could be used to direct any anticancer drug, biological agent or radioisotope selectively against the cancer cells and does not harm the normal cells. The specific antibody could be raised by immunization with purified tumor specific antigen (s. The biological agent could be obtained as toxin, either derived from bacteria e.g. diphtheria toxin or derived from plants e.g. castor ricin, which could destroy and kill cancer cells after contacts. A hybrid molecule constructed between antibody and toxin has been known as "immunotoxin". The selectivity of the antibody against a given tumor specific antigen could be increased by using a monoclonal antibody, made by hybridoma technique and immunological engineering. Accordingly, the efficiency of the destructive or killing effect of the toxin could be eventually increased by purification technique, biochemical and genetic engineering. In a preliminary study ricin from castor (Ricinus communis have been purified and separated into two protein fractions (RCAI = 12.000 dalton and RCA II = 60.000 - 65.000 dalton. The latter showed toxin property, and was tested in vitro both against normal cells and against cancer cells. In the microcy totoxicity assay the ricin showed both the short term and the long term killing effect as measured after 1, 4, 16 and 24 hours. The killing effect against cancer cells was stronger as compared to that against normal cells. The acute or short term effect was observed at lower concentration of ricin (10-6 and 10-12 g/ml after 1 and 4 hours contacts. The long term effect resulted in 90% and nearly 100% cytotoxicity in higher concentration of ricin

  18. How does cognition evolve? Phylogenetic comparative psychology

    Science.gov (United States)

    Matthews, Luke J.; Hare, Brian A.; Nunn, Charles L.; Anderson, Rindy C.; Aureli, Filippo; Brannon, Elizabeth M.; Call, Josep; Drea, Christine M.; Emery, Nathan J.; Haun, Daniel B. M.; Herrmann, Esther; Jacobs, Lucia F.; Platt, Michael L.; Rosati, Alexandra G.; Sandel, Aaron A.; Schroepfer, Kara K.; Seed, Amanda M.; Tan, Jingzhi; van Schaik, Carel P.; Wobber, Victoria

    2014-01-01

    Now more than ever animal studies have the potential to test hypotheses regarding how cognition evolves. Comparative psychologists have developed new techniques to probe the cognitive mechanisms underlying animal behavior, and they have become increasingly skillful at adapting methodologies to test multiple species. Meanwhile, evolutionary biologists have generated quantitative approaches to investigate the phylogenetic distribution and function of phenotypic traits, including cognition. In particular, phylogenetic methods can quantitatively (1) test whether specific cognitive abilities are correlated with life history (e.g., lifespan), morphology (e.g., brain size), or socio-ecological variables (e.g., social system), (2) measure how strongly phylogenetic relatedness predicts the distribution of cognitive skills across species, and (3) estimate the ancestral state of a given cognitive trait using measures of cognitive performance from extant species. Phylogenetic methods can also be used to guide the selection of species comparisons that offer the strongest tests of a priori predictions of cognitive evolutionary hypotheses (i.e., phylogenetic targeting). Here, we explain how an integration of comparative psychology and evolutionary biology will answer a host of questions regarding the phylogenetic distribution and history of cognitive traits, as well as the evolutionary processes that drove their evolution. PMID:21927850

  19. How does cognition evolve? Phylogenetic comparative psychology.

    Science.gov (United States)

    MacLean, Evan L; Matthews, Luke J; Hare, Brian A; Nunn, Charles L; Anderson, Rindy C; Aureli, Filippo; Brannon, Elizabeth M; Call, Josep; Drea, Christine M; Emery, Nathan J; Haun, Daniel B M; Herrmann, Esther; Jacobs, Lucia F; Platt, Michael L; Rosati, Alexandra G; Sandel, Aaron A; Schroepfer, Kara K; Seed, Amanda M; Tan, Jingzhi; van Schaik, Carel P; Wobber, Victoria

    2012-03-01

    Now more than ever animal studies have the potential to test hypotheses regarding how cognition evolves. Comparative psychologists have developed new techniques to probe the cognitive mechanisms underlying animal behavior, and they have become increasingly skillful at adapting methodologies to test multiple species. Meanwhile, evolutionary biologists have generated quantitative approaches to investigate the phylogenetic distribution and function of phenotypic traits, including cognition. In particular, phylogenetic methods can quantitatively (1) test whether specific cognitive abilities are correlated with life history (e.g., lifespan), morphology (e.g., brain size), or socio-ecological variables (e.g., social system), (2) measure how strongly phylogenetic relatedness predicts the distribution of cognitive skills across species, and (3) estimate the ancestral state of a given cognitive trait using measures of cognitive performance from extant species. Phylogenetic methods can also be used to guide the selection of species comparisons that offer the strongest tests of a priori predictions of cognitive evolutionary hypotheses (i.e., phylogenetic targeting). Here, we explain how an integration of comparative psychology and evolutionary biology will answer a host of questions regarding the phylogenetic distribution and history of cognitive traits, as well as the evolutionary processes that drove their evolution.

  20. The Evolving Classification of Pulmonary Hypertension.

    Science.gov (United States)

    Foshat, Michelle; Boroumand, Nahal

    2017-05-01

    - An explosion of information on pulmonary hypertension has occurred during the past few decades. The perception of this disease has shifted from purely clinical to incorporate new knowledge of the underlying pathology. This transfer has occurred in light of advancements in pathophysiology, histology, and molecular medical diagnostics. - To update readers about the evolving understanding of the etiology and pathogenesis of pulmonary hypertension and to demonstrate how pathology has shaped the current classification. - Information presented at the 5 World Symposia on pulmonary hypertension held since 1973, with the last meeting occurring in 2013, was used in this review. - Pulmonary hypertension represents a heterogeneous group of disorders that are differentiated based on differences in clinical, hemodynamic, and histopathologic features. Early concepts of pulmonary hypertension were largely influenced by pharmacotherapy, hemodynamic function, and clinical presentation of the disease. The initial nomenclature for pulmonary hypertension segregated the clinical classifications from pathologic subtypes. Major restructuring of this disease classification occurred between the first and second symposia, which was the first to unite clinical and pathologic information in the categorization scheme. Additional changes were introduced in subsequent meetings, particularly between the third and fourth World Symposia meetings, when additional pathophysiologic information was gained. Discoveries in molecular diagnostics significantly progressed the understanding of idiopathic pulmonary arterial hypertension. Continued advancements in imaging modalities, mechanistic pathogenicity, and molecular biomarkers will enable physicians to define pulmonary hypertension phenotypes based on the pathobiology and allow for treatment customization.

  1. Evolving the future: toward a science of intentional change.

    Science.gov (United States)

    Wilson, David Sloan; Hayes, Steven C; Biglan, Anthony; Embry, Dennis D

    2014-08-01

    Humans possess great capacity for behavioral and cultural change, but our ability to manage change is still limited. This article has two major objectives: first, to sketch a basic science of intentional change centered on evolution; second, to provide examples of intentional behavioral and cultural change from the applied behavioral sciences, which are largely unknown to the basic sciences community. All species have evolved mechanisms of phenotypic plasticity that enable them to respond adaptively to their environments. Some mechanisms of phenotypic plasticity count as evolutionary processes in their own right. The human capacity for symbolic thought provides an inheritance system having the same kind of combinatorial diversity as does genetic recombination and antibody formation. Taking these propositions seriously allows an integration of major traditions within the basic behavioral sciences, such as behaviorism, social constructivism, social psychology, cognitive psychology, and evolutionary psychology, which are often isolated and even conceptualized as opposed to one another. The applied behavioral sciences include well-validated examples of successfully managing behavioral and cultural change at scales ranging from individuals to small groups to large populations. However, these examples are largely unknown beyond their disciplinary boundaries, for lack of a unifying theoretical framework. Viewed from an evolutionary perspective, they are examples of managing evolved mechanisms of phenotypic plasticity, including open-ended processes of variation and selection. Once the many branches of the basic and applied behavioral sciences become conceptually unified, we are closer to a science of intentional change than one might think.

  2. Evolving the future: Toward a science of intentional change

    Science.gov (United States)

    Wilson, David Sloan; Hayes, Steven C.; Biglan, Anthony; Embry, Dennis D.

    2015-01-01

    Humans possess great capacity for behavioral and cultural change, but our ability to manage change is still limited. This article has two major objectives: first, to sketch a basic science of intentional change centered on evolution; second, to provide examples of intentional behavioral and cultural change from the applied behavioral sciences, which are largely unknown to the basic sciences community. All species have evolved mechanisms of phenotypic plasticity that enable them to respond adaptively to their environments. Some mechanisms of phenotypic plasticity count as evolutionary processes in their own right. The human capacity for symbolic thought provides an inheritance system having the same kind of combinatorial diversity as does genetic recombination and antibody formation. Taking these propositions seriously allows an integration of major traditions within the basic behavioral sciences, such as behaviorism, social constructivism, social psychology, cognitive psychology, and evolutionary psychology, which are often isolated and even conceptualized as opposed to one another. The applied behavioral sciences include well-validated examples of successfully managing behavioral and cultural change at scales ranging from individuals to small groups to large populations. However, these examples are largely unknown beyond their disciplinary boundaries, for lack of a unifying theoretical framework. Viewed from an evolutionary perspective, they are examples of managing evolved mechanisms of phenotypic plasticity, including open-ended processes of variation and selection. Once the many branches of the basic and applied behavioral sciences become conceptually unified, we are closer to a science of intentional change than one might think. PMID:24826907

  3. The 'E' factor -- evolving endodontics.

    Science.gov (United States)

    Hunter, M J

    2013-03-01

    Endodontics is a constantly developing field, with new instruments, preparation techniques and sealants competing with trusted and traditional approaches to tooth restoration. Thus general dental practitioners must question and understand the significance of these developments before adopting new practices. In view of this, the aim of this article, and the associated presentation at the 2013 British Dental Conference & Exhibition, is to provide an overview of endodontic methods and constantly evolving best practice. The presentation will review current preparation techniques, comparing rotary versus reciprocation, and question current trends in restoration of the endodontically treated tooth.

  4. Environmental noise, genetic diversity and the evolution of evolvability and robustness in model gene networks.

    Directory of Open Access Journals (Sweden)

    Christopher F Steiner

    Full Text Available The ability of organisms to adapt and persist in the face of environmental change is accepted as a fundamental feature of natural systems. More contentious is whether the capacity of organisms to adapt (or "evolvability" can itself evolve and the mechanisms underlying such responses. Using model gene networks, I provide evidence that evolvability emerges more readily when populations experience positively autocorrelated environmental noise (red noise compared to populations in stable or randomly varying (white noise environments. Evolvability was correlated with increasing genetic robustness to effects on network viability and decreasing robustness to effects on phenotypic expression; populations whose networks displayed greater viability robustness and lower phenotypic robustness produced more additive genetic variation and adapted more rapidly in novel environments. Patterns of selection for robustness varied antagonistically with epistatic effects of mutations on viability and phenotypic expression, suggesting that trade-offs between these properties may constrain their evolutionary responses. Evolution of evolvability and robustness was stronger in sexual populations compared to asexual populations indicating that enhanced genetic variation under fluctuating selection combined with recombination load is a primary driver of the emergence of evolvability. These results provide insight into the mechanisms potentially underlying rapid adaptation as well as the environmental conditions that drive the evolution of genetic interactions.

  5. CancerPPD: a database of anticancer peptides and proteins

    OpenAIRE

    Tyagi, Atul; Tuknait, Abhishek; Anand, Priya; Gupta, Sudheer; Sharma, Minakshi; Mathur, Deepika; Joshi, Anshika; Singh, Sandeep; Gautam, Ankur; Raghava, Gajendra P. S.

    2014-01-01

    CancerPPD (http://crdd.osdd.net/raghava/cancerppd/) is a repository of experimentally verified anticancer peptides (ACPs) and anticancer proteins. Data were manually collected from published research articles, patents and from other databases. The current release of CancerPPD consists of 3491 ACP and 121 anticancer protein entries. Each entry provides comprehensive information related to a peptide like its source of origin, nature of the peptide, anticancer activity, N- and C-terminal modific...

  6. Phenoscape: Identifying Candidate Genes for Evolutionary Phenotypes

    Science.gov (United States)

    Edmunds, Richard C.; Su, Baofeng; Balhoff, James P.; Eames, B. Frank; Dahdul, Wasila M.; Lapp, Hilmar; Lundberg, John G.; Vision, Todd J.; Dunham, Rex A.; Mabee, Paula M.; Westerfield, Monte

    2016-01-01

    Phenotypes resulting from mutations in genetic model organisms can help reveal candidate genes for evolutionarily important phenotypic changes in related taxa. Although testing candidate gene hypotheses experimentally in nonmodel organisms is typically difficult, ontology-driven information systems can help generate testable hypotheses about developmental processes in experimentally tractable organisms. Here, we tested candidate gene hypotheses suggested by expert use of the Phenoscape Knowledgebase, specifically looking for genes that are candidates responsible for evolutionarily interesting phenotypes in the ostariophysan fishes that bear resemblance to mutant phenotypes in zebrafish. For this, we searched ZFIN for genetic perturbations that result in either loss of basihyal element or loss of scales phenotypes, because these are the ancestral phenotypes observed in catfishes (Siluriformes). We tested the identified candidate genes by examining their endogenous expression patterns in the channel catfish, Ictalurus punctatus. The experimental results were consistent with the hypotheses that these features evolved through disruption in developmental pathways at, or upstream of, brpf1 and eda/edar for the ancestral losses of basihyal element and scales, respectively. These results demonstrate that ontological annotations of the phenotypic effects of genetic alterations in model organisms, when aggregated within a knowledgebase, can be used effectively to generate testable, and useful, hypotheses about evolutionary changes in morphology. PMID:26500251

  7. Primordial evolvability: Impasses and challenges.

    Science.gov (United States)

    Vasas, Vera; Fernando, Chrisantha; Szilágyi, András; Zachár, István; Santos, Mauro; Szathmáry, Eörs

    2015-09-21

    While it is generally agreed that some kind of replicating non-living compounds were the precursors of life, there is much debate over their possible chemical nature. Metabolism-first approaches propose that mutually catalytic sets of simple organic molecules could be capable of self-replication and rudimentary chemical evolution. In particular, the graded autocatalysis replication domain (GARD) model, depicting assemblies of amphiphilic molecules, has received considerable interest. The system propagates compositional information across generations and is suggested to be a target of natural selection. However, evolutionary simulations indicate that the system lacks selectability (i.e. selection has negligible effect on the equilibrium concentrations). We elaborate on the lessons learnt from the example of the GARD model and, more widely, on the issue of evolvability, and discuss the implications for similar metabolism-first scenarios. We found that simple incorporation-type chemistry based on non-covalent bonds, as assumed in GARD, is unlikely to result in alternative autocatalytic cycles when catalytic interactions are randomly distributed. An even more serious problem stems from the lognormal distribution of catalytic factors, causing inherent kinetic instability of such loops, due to the dominance of efficiently catalyzed components that fail to return catalytic aid. Accordingly, the dynamics of the GARD model is dominated by strongly catalytic, but not auto-catalytic, molecules. Without effective autocatalysis, stable hereditary propagation is not possible. Many repetitions and different scaling of the model come to no rescue. Despite all attempts to show the contrary, the GARD model is not evolvable, in contrast to reflexively autocatalytic networks, complemented by rare uncatalyzed reactions and compartmentation. The latter networks, resting on the creation and breakage of chemical bonds, can generate novel ('mutant') autocatalytic loops from a given set of

  8. Adaptive synonymous mutations in an experimentally evolved Pseudomonas fluorescens population

    DEFF Research Database (Denmark)

    Bailey, Susan; Hinz, Aaron; Kassen, Rees

    2014-01-01

    Conventional wisdom holds that synonymous mutations, nucleotide changes that do not alter the encoded amino acid, have no detectable effect on phenotype or fitness. However, a growing body of evidence from both comparative and experimental studies suggests otherwise. Synonymous mutations have been...... in an experimentally evolved population of Pseudomonas fluorescens. We show experimentally that these mutations increase fitness by an amount comparable to non-synonymous mutations and that the fitness increases stem from increased gene expression. These results provide unequivocal evidence that synonymous mutations...... can drive adaptive evolution and suggest that this class of mutation may be underappreciated as a cause of adaptation and evolutionary dynamics....

  9. Randomized anticancer and cytotoxicity activities of Guibourtia ...

    African Journals Online (AJOL)

    African Journal of Traditional, Complementary and Alternative Medicines ... In light of this, there is a constant demand for new treatment regimens for cancer. ... Anticancer screening was performed on a panel of three cancer cell lines, while cytotoxicity was determined using a human fibroblast cell line, both using the SRB ...

  10. Anticancer and antioxidant activities of Guiera senegalensis ...

    African Journals Online (AJOL)

    Background: Medicinal plants contain physiologically active principles that over the years have been exploited in traditional medicine for the treatment of various ailments. Objectives: The ethanolic extract of Guiera senegalensis was tested in vitro as anticancer and antioxidant agent as well as for its phenolic and ...

  11. Ligand based pharmacophore modelling of anticancer histone ...

    African Journals Online (AJOL)

    USER

    2010-06-21

    Jun 21, 2010 ... deacetylases (HDAC) have emerged as an important class of anticancer agents. Various side effects like myocardium damage and ... calculated through the software Jmol. The proposed model has been .... The study was carried out using the software Ligand Scout (version. 2.03[i2_001]). Ligand Scout is a ...

  12. Anticancer and antibacterial secondary metabolites from the ...

    African Journals Online (AJOL)

    Background: The emergence of multiple-drug resistance bacteria has become a major threat and thus calls for an urgent need to search for new effective and safe anti-bacterial agents. Objectives: This study aims to evaluate the anticancer and antibacterial activities of secondary metabolites from Penicillium sp., ...

  13. Phytochemical, Anticancer and Antioxidant Evaluation of Potential ...

    African Journals Online (AJOL)

    Some chemical constituents (β-Sitosterol, β-Sitosterol glucoside, β-amyrin, xanthone glycoside , and a flavanol glycoside) previously isolated and characterized from the stem bark of Calliandria surinamensis were subjected to in vitro free radical scavenging and anticancer activities using DPPH free radical scavenging ...

  14. Alpha-helical cationic anticancer peptides: a promising candidate for novel anticancer drugs.

    Science.gov (United States)

    Huang, Yibing; Feng, Qi; Yan, Qiuyan; Hao, Xueyu; Chen, Yuxin

    2015-01-01

    Cancer has become a serious concern in public health. Harmful side effects and multidrug resistance of traditional chemotherapy have prompted urgent needs for novel anticancer drugs or therapeutic approaches. Anticancer peptides (ACPs) have become promising molecules for novel anticancer agents because of their unique mechanism and several extraordinary properties. Most α-helical ACPs target the cell membrane, and interactions between ACPs and cell membrane components are believed to be the key factor in the selective killing of cancer cells. In this review, we focus on the exploitation of the structure and function of α-helical ACPs, including the distinction between cancer and normal cells, the proposed anticancer mechanisms, and the influence of physicochemical parameters of α-helical ACPs on the biological activities and selectivity against cancer cells. In addition, the design and modification methods to optimize the cell selectivity of α-helical ACPs are considered. Furthermore, the suitability of ACPs as cancer therapeutics is discussed.

  15. Anticancer activity of 5, 7-dimethoxyflavone against liver cancer cell ...

    African Journals Online (AJOL)

    Background: Flavonoids are considered potential anticancer agents owing to their properties to interact with a diversity of cellular entities. Among flavonoids, methylated flavones are more efficient anticancer agents due to their higher stability in vivo. The purpose of the present study was, therefore, to evaluate the anticancer ...

  16. Availability and affordability of anticancer medicines at the Ocean ...

    African Journals Online (AJOL)

    Background: To ensure effective control of cancer, patients undergoing chemotherapy should get continuous supply of anticancer medicines. In Tanzania and other East African countries little is documented regarding the availability and affordability of anticancer medicines at the patient level. The number of anticancer ...

  17. Scheduling of anticancer drugs: Timing may be everything

    OpenAIRE

    Astrid A M van der Veldt; Lammertsma, Adriaan A; Smit, Egbert F.

    2012-01-01

    Many cancer patients are treated with a combination of anticancer drugs. Here, we discuss the importance of drug scheduling and the need for studies that investigate the optimal timing of the various anticancer drugs. Positron emission tomography (PET) using radiolabeled anticancer drugs could be an important tool for those studies.

  18. Peripartum hysterectomy: an evolving picture.

    LENUS (Irish Health Repository)

    Turner, Michael J

    2012-02-01

    Peripartum hysterectomy (PH) is one of the obstetric catastrophes. Evidence is emerging that the role of PH in modern obstetrics is evolving. Improving management of postpartum hemorrhage and newer surgical techniques should decrease PH for uterine atony. Rising levels of repeat elective cesarean deliveries should decrease PH following uterine scar rupture in labor. Increasing cesarean rates, however, have led to an increase in the number of PHs for morbidly adherent placenta. In the case of uterine atony or rupture where PH is required, a subtotal PH is often sufficient. In the case of pathological placental localization involving the cervix, however, a total hysterectomy is required. Furthermore, the involvement of other pelvic structures may prospectively make the diagnosis difficult and the surgery challenging. If resources permit, PH for pathological placental localization merits a multidisciplinary approach. Despite advances in clinical practice, it is likely that peripartum hysterectomy will be more challenging for obstetricians in the future.

  19. Extreme evolved solar systems (EESS)

    Science.gov (United States)

    Gaensicke, Boris

    2017-08-01

    In just 20 years, we went from not knowing if the solar system is a fluke of Nature to realising that it is totally normal for stars to have planets. More remarkably, it is now clear that planet formation is a robust process, as rich multi-planet systems are found around stars more massive and less massive than the Sun. More recently, planetary systems have been identified in increasingly complex architectures, including circumbinary planets, wide binaries with planets orbiting one or both stellar components, and planets in triple stellar systems.We have also learned that many planetary systems will survive the evolution of their host stars into the white dwarf phase. Small bodies are scattered by unseen planets into the gravitational field of the white dwarfs, tidally disrupt, form dust discs, and eventually accrete onto the white dwarf, where they can be spectroscopically detected. HST/COS has played a critical role in the study these evolved planetary systems, demonstrating that overall the bulk composition of the debris is rocky and resembles in composition the inner the solar system, including evidence for water-rich planetesimals. Past observations of planetary systems at white dwarfs have focused on single stars with main-sequence progenitors of 1.5 to 2.5Msun. Here we propose to take the study of evolved planetary systems into the extremes of parameter ranges to answer questions such as: * How efficient is planet formation around 4-10Msun stars? * What are the metallicities of the progenitors of debris-accreting white dwarfs?* What is the fate of circumbinary planets?* Can star-planet interactions generate magnetic fields in the white dwarf host?

  20. Radiofrequency treatment alters cancer cell phenotype

    Science.gov (United States)

    Ware, Matthew J.; Tinger, Sophia; Colbert, Kevin L.; Corr, Stuart J.; Rees, Paul; Koshkina, Nadezhda; Curley, Steven; Summers, H. D.; Godin, Biana

    2015-07-01

    The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease. Here, we report that pancreatic cancer cell phenotype was altered in response to a physical method for cancer therapy, a non-invasive radiofrequency (RF) treatment, which is currently being developed for human trials. We provide a battery of tests to explore these phenotype characteristics. Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment. These may have consequences for tissue architecture, for diffusion of anti-cancer therapeutics and cancer cell susceptibility within the tumor. Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. We also report, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. Additionally, we provide evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment.

  1. Genetic Correlations Greatly Increase Mutational Robustness and Can Both Reduce and Enhance Evolvability.

    Directory of Open Access Journals (Sweden)

    Sam F Greenbury

    2016-03-01

    Full Text Available Mutational neighbourhoods in genotype-phenotype (GP maps are widely believed to be more likely to share characteristics than expected from random chance. Such genetic correlations should strongly influence evolutionary dynamics. We explore and quantify these intuitions by comparing three GP maps-a model for RNA secondary structure, the HP model for protein tertiary structure, and the Polyomino model for protein quaternary structure-to a simple random null model that maintains the number of genotypes mapping to each phenotype, but assigns genotypes randomly. The mutational neighbourhood of a genotype in these GP maps is much more likely to contain genotypes mapping to the same phenotype than in the random null model. Such neutral correlations can be quantified by the robustness to mutations, which can be many orders of magnitude larger than that of the null model, and crucially, above the critical threshold for the formation of large neutral networks of mutationally connected genotypes which enhance the capacity for the exploration of phenotypic novelty. Thus neutral correlations increase evolvability. We also study non-neutral correlations: Compared to the null model, i If a particular (non-neutral phenotype is found once in the 1-mutation neighbourhood of a genotype, then the chance of finding that phenotype multiple times in this neighbourhood is larger than expected; ii If two genotypes are connected by a single neutral mutation, then their respective non-neutral 1-mutation neighbourhoods are more likely to be similar; iii If a genotype maps to a folding or self-assembling phenotype, then its non-neutral neighbours are less likely to be a potentially deleterious non-folding or non-assembling phenotype. Non-neutral correlations of type i and ii reduce the rate at which new phenotypes can be found by neutral exploration, and so may diminish evolvability, while non-neutral correlations of type iii may instead facilitate evolutionary exploration

  2. Genetic Correlations Greatly Increase Mutational Robustness and Can Both Reduce and Enhance Evolvability.

    Science.gov (United States)

    Greenbury, Sam F; Schaper, Steffen; Ahnert, Sebastian E; Louis, Ard A

    2016-03-01

    Mutational neighbourhoods in genotype-phenotype (GP) maps are widely believed to be more likely to share characteristics than expected from random chance. Such genetic correlations should strongly influence evolutionary dynamics. We explore and quantify these intuitions by comparing three GP maps-a model for RNA secondary structure, the HP model for protein tertiary structure, and the Polyomino model for protein quaternary structure-to a simple random null model that maintains the number of genotypes mapping to each phenotype, but assigns genotypes randomly. The mutational neighbourhood of a genotype in these GP maps is much more likely to contain genotypes mapping to the same phenotype than in the random null model. Such neutral correlations can be quantified by the robustness to mutations, which can be many orders of magnitude larger than that of the null model, and crucially, above the critical threshold for the formation of large neutral networks of mutationally connected genotypes which enhance the capacity for the exploration of phenotypic novelty. Thus neutral correlations increase evolvability. We also study non-neutral correlations: Compared to the null model, i) If a particular (non-neutral) phenotype is found once in the 1-mutation neighbourhood of a genotype, then the chance of finding that phenotype multiple times in this neighbourhood is larger than expected; ii) If two genotypes are connected by a single neutral mutation, then their respective non-neutral 1-mutation neighbourhoods are more likely to be similar; iii) If a genotype maps to a folding or self-assembling phenotype, then its non-neutral neighbours are less likely to be a potentially deleterious non-folding or non-assembling phenotype. Non-neutral correlations of type i) and ii) reduce the rate at which new phenotypes can be found by neutral exploration, and so may diminish evolvability, while non-neutral correlations of type iii) may instead facilitate evolutionary exploration and so

  3. How could language have evolved?

    Directory of Open Access Journals (Sweden)

    Johan J Bolhuis

    2014-08-01

    Full Text Available The evolution of the faculty of language largely remains an enigma. In this essay, we ask why. Language's evolutionary analysis is complicated because it has no equivalent in any nonhuman species. There is also no consensus regarding the essential nature of the language "phenotype." According to the "Strong Minimalist Thesis," the key distinguishing feature of language (and what evolutionary theory must explain is hierarchical syntactic structure. The faculty of language is likely to have emerged quite recently in evolutionary terms, some 70,000-100,000 years ago, and does not seem to have undergone modification since then, though individual languages do of course change over time, operating within this basic framework. The recent emergence of language and its stability are both consistent with the Strong Minimalist Thesis, which has at its core a single repeatable operation that takes exactly two syntactic elements a and b and assembles them to form the set {a, b}.

  4. The evolving role of tiotropium in asthma

    Directory of Open Access Journals (Sweden)

    McIvor ER

    2017-08-01

    Full Text Available Emma R McIvor,1 R Andrew McIvor2 1Queen’s University, Belfast, UK; 2Department of Medicine, McMaster University, Firestone Institute for Respiratory Health, Hamilton, Ontario, Canada Abstract: Tiotropium is a long-acting muscarinic antagonist (LAMA that exerts its bronchodilatory effect by blocking endogenous acetylcholine receptors in the airways. Its safety and efficacy are well established for the treatment of COPD, and it is now being recognized for its role in improving lung function and control in asthma. This review discusses the evolving role of tiotropium delivered by the Respimat® in patients across the range of asthma severities and ages, and provides an overview of safety and efficacy data. Tiotropium is the only LAMA currently approved for the treatment of asthma, and evidence from a large-scale clinical trial program, including several Phase III studies in adults, has demonstrated that tiotropium improves lung function and asthma control, with a safety profile comparable with that of placebo. Clinical trials in adolescent patients (aged 12–17 years have also shown improvements in lung function and trends toward improved asthma control. Of note, the efficacy and safety profiles are consistent regardless of baseline characteristics and phenotype. Given the large and growing body of evidence, it is likely that as clinical experience with tiotropium increases, this treatment may possibly emerge as the key choice for add-on therapy to inhaled corticosteroids/long-acting β2-agonists, and in patients who do not tolerate long-acting bronchodilators or other medications, in the future. Keywords: tiotropium, anticholinergics, asthma, efficacy

  5. Challenges in pre-clinical testing of anti-cancer drugs in cell culture and in animal models

    OpenAIRE

    HogenEsch, Harm; Yu Nikitin, Alexander

    2012-01-01

    Experiments with cultures of human tumor cell lines, xenografts of human tumors into immunodeficient mice, and mouse models of human cancer are important tools in the development and testing of anti-cancer drugs. Tumors are complex structures composed of genetically and phenotypically heterogeneous cancer cells that interact in a reciprocal manner with the stromal microenvironment and the immune system. Modeling the complexity of human cancers in cell culture and in mouse models for preclinic...

  6. Identifying anticancer peptides by using improved hybrid compositions.

    Science.gov (United States)

    Li, Feng-Min; Wang, Xiao-Qian

    2016-09-27

    Cancer is one of the main causes of threats to human life. Identification of anticancer peptides is important for developing effective anticancer drugs. In this paper, we developed an improved predictor to identify the anticancer peptides. The amino acid composition (AAC), the average chemical shifts (acACS) and the reduced amino acid composition (RAAC) were selected to predict the anticancer peptides by using the support vector machine (SVM). The overall prediction accuracy reaches to 93.61% in jackknife test. The results indicated that the combined parameter was helpful to the prediction for anticancer peptides.

  7. CERN internal communication is evolving

    CERN Multimedia

    2016-01-01

    CERN news will now be regularly updated on the CERN People page (see here).      Dear readers, All over the world, communication is becoming increasingly instantaneous, with news published in real time on websites and social networks. In order to keep pace with these changes, CERN's internal communication is evolving too. From now on, you will be informed of what’s happening at CERN more often via the “CERN people” page, which will frequently be updated with news. The Bulletin is following this trend too: twice a month, we will compile the most important articles published on the CERN site, with a brand-new layout. You will receive an e-mail every two weeks as soon as this new form of the Bulletin is available. If you have interesting news or stories to share, tell us about them through the form at: https://communications.web.cern.ch/got-story-cern-website​. You can also find out about news from CERN in real time...

  8. How Could Language Have Evolved?

    Science.gov (United States)

    Bolhuis, Johan J.; Tattersall, Ian; Chomsky, Noam; Berwick, Robert C.

    2014-01-01

    The evolution of the faculty of language largely remains an enigma. In this essay, we ask why. Language's evolutionary analysis is complicated because it has no equivalent in any nonhuman species. There is also no consensus regarding the essential nature of the language “phenotype.” According to the “Strong Minimalist Thesis,” the key distinguishing feature of language (and what evolutionary theory must explain) is hierarchical syntactic structure. The faculty of language is likely to have emerged quite recently in evolutionary terms, some 70,000–100,000 years ago, and does not seem to have undergone modification since then, though individual languages do of course change over time, operating within this basic framework. The recent emergence of language and its stability are both consistent with the Strong Minimalist Thesis, which has at its core a single repeatable operation that takes exactly two syntactic elements a and b and assembles them to form the set {a, b}. PMID:25157536

  9. Anticancer Effect of Lycopene in Gastric Carcinogenesis.

    Science.gov (United States)

    Kim, Mi Jung; Kim, Hyeyoung

    2015-06-01

    Gastric cancer ranks as the most common cancer and the second leading cause of cancer-related death in the world. Risk factors of gastric carcinogenesis include oxidative stress, DNA damage, Helicobacter pylori infection, bad eating habits, and smoking. Since oxidative stress is related to DNA damage, smoking, and H. pylori infection, scavenging of reactive oxygen species may be beneficial for prevention of gastric carcinogenesis. Lycopene, one of the naturally occurring carotenoids, has unique structural and chemical features that contributes to a potent antioxidant activity. It shows a potential anticancer activity and reduces gastric cancer incidence. This review will summarize anticancer effect and mechanism of lycopene on gastric carcinogenesis based on the recent experimental and clinical studies.

  10. The use of cannabinoids as anticancer agents.

    Science.gov (United States)

    Velasco, Guillermo; Hernández-Tiedra, Sonia; Dávila, David; Lorente, Mar

    2016-01-04

    It is well-established that cannabinoids exert palliative effects on some cancer-associated symptoms. In addition evidences obtained during the last fifteen years support that these compounds can reduce tumor growth in animal models of cancer. Cannabinoids have been shown to activate an ER-stress related pathway that leads to the stimulation of autophagy-mediated cancer cell death. In addition, cannabinoids inhibit tumor angiogenesis and decrease cancer cell migration. The mechanisms of resistance to cannabinoid anticancer action as well as the possible strategies to develop cannabinoid-based combinational therapies to fight cancer have also started to be explored. In this review we will summarize these observations (that have already helped to set the bases for the development of the first clinical studies to investigate the potential clinical benefit of using cannabinoids in anticancer therapies) and will discuss the possible future avenues of research in this area. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. PEGylated Silk Nanoparticles for Anticancer Drug Delivery

    DEFF Research Database (Denmark)

    Wongpinyochit, Thidarat; Uhlmann, Petra; Urquhart, Andrew

    2015-01-01

    is especially necessary to support their evolution. The aim of this study was to develop and examine the potential of PEGylated silk nanoparticles as an anticancer drug delivery system. We first generated B. mori derived silk nanoparticles by driving β-sheet assembly (size 104 ± 1.7 nm, zeta potential −56 ± 5.......6 mV) using nanoprecipitation. We then surface grafted polyethylene glycol (PEG) to the fabricated silk nanoparticles and verified the aqueous stability and morphology of the resulting PEGylated silk nanoparticles. We assessed the drug loading and release behavior of these nanoparticles using...... clinically established and emerging anticancer drugs. Overall, PEGylated silk nanoparticles showed high encapsulation efficiency (>93%) and a pH-dependent release over 14 days. Finally, we demonstrated significant cytotoxicity of drug loaded silk nanoparticles applied as single and combination nanomedicines...

  12. Anticancer Activity of Key Lime, Citrus aurantifolia

    OpenAIRE

    Nithithep Narang; Wannee Jiraungkoorskul

    2016-01-01

    Citrus aurantifolia (family: Rutaceae) is mainly used in daily consumption, in many cultural cuisines, and in juice production. It is widely used because of its antibacterial, anticancer, antidiabetic, antifungal, anti-hypertensive, anti-inflammation, anti-lipidemia, and antioxidant properties; moreover, it can protect heart, liver, bone, and prevent urinary diseases. Its secondary metabolites are alkaloids, carotenoids, coumarins, essential oils, flavonoids, phenolic acids, and triterpenoids...

  13. Plant Antimicrobial Peptides as Potential Anticancer Agents

    OpenAIRE

    Jaquelina Julia Guzmán-Rodríguez; Alejandra Ochoa-Zarzosa; Rodolfo López-Gómez; López-Meza, Joel E.

    2015-01-01

    Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms and are promising candidates to treat infections caused by pathogenic bacteria to animals and humans. AMPs also display anticancer activities because of their ability to inactivate a wide range of cancer cells. Cancer remains a cause of high morbidity and mortality worldwide. Therefore, the development of methods for its control is desirable. Attractive alternatives include plant AMP thionins, defe...

  14. Peptides: A new class of anticancer drugs

    OpenAIRE

    Ryszard Smolarczyk; Tomasz Cichoń; Stanisław Szala

    2009-01-01

    Peptides are a novel class of anticancer agents embracing two distinct categories: natural antibacterial peptides, which are preferentially bound by cancer cells, and chemically synthesized peptides, which bind specifically to precise molecular targets located on the surface of tumor cells. Antibacterial peptides bind to both cell and mitochondrial membranes. Some of these peptides attach to the cell membrane, resulting in its disorganization. Other antibacterial peptides penetrate cancer cel...

  15. Green tea phytocompounds as anticancer: A review

    Directory of Open Access Journals (Sweden)

    Najeeb Ullah

    2016-04-01

    Full Text Available Green tea is universally considered significant and its benefits have been experimentally explored by researchers and scientists. Anticancer potential of green tea has been completely recognized now. Green tea contains anti-cancerous constituents and nutrients that have powerful remedial effects. By using electronic data base (1998–2015, different compounds in green tea possessing anticancer activity including epigallocatechin-3-gallate, paclitaxel and docetaxel combinations, ascorbic acid, catechins, lysine, synergistic arginine, green tea extract, proline, and green tea polyphenols has been reported. Green tea extracts exhibited remedial potential against cancer of lung, colon, liver, stomach, leukemic cells, prostate, breast, human cervical cells, head, and neck. For centuries, green tea has been utilized as medicine for therapeutic purposes. It originated in China and extensively used in Asian countries for blood pressure depression and as anticancer medicine. Green tea has therapeutic potential against many diseases such as lowering of blood pressure, Parkinson’s disease, weight loss, esophageal disease, skin-care, cholesterol, Alzheimer’s disease and diabetes.

  16. Anticancer activity of Carica papaya: a review.

    Science.gov (United States)

    Nguyen, Thao T T; Shaw, Paul N; Parat, Marie-Odile; Hewavitharana, Amitha K

    2013-01-01

    Carica papaya is widely cultivated in tropical and subtropical countries and is used as food as well as traditional medicine to treat a range of diseases. Increasing anecdotal reports of its effects in cancer treatment and prevention, with many successful cases, have warranted that these pharmacological properties be scientifically validated. A bibliographic search was conducted using the key words "papaya", "anticancer", and "antitumor" along with cross-referencing. No clinical or animal cancer studies were identified and only seven in vitro cell-culture-based studies were reported; these indicate that C. papaya extracts may alter the growth of several types of cancer cell lines. However, many studies focused on specific compounds in papaya and reported bioactivity including anticancer effects. This review summarizes the results of extract-based or specific compound-based investigations and emphasizes the aspects that warrant future research to explore the bioactives in C. papaya for their anticancer activities. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Nitroxides as Antioxidants and Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Marcin Lewandowski

    2017-11-01

    Full Text Available Nitroxides are stable free radicals that contain a nitroxyl group with an unpaired electron. In this paper, we present the properties and application of nitroxides as antioxidants and anticancer drugs. The mostly used nitroxides in biology and medicine are a group of heterocyclic nitroxide derivatives of piperidine, pyrroline and pyrrolidine. The antioxidant action of nitroxides is associated with their redox cycle. Nitroxides, unlike other antioxidants, are characterized by a catalytic mechanism of action associated with a single electron oxidation and reduction reaction. In biological conditions, they mimic superoxide dismutase (SOD, modulate hemoprotein’s catalase-like activity, scavenge reactive free radicals, inhibit the Fenton and Haber-Weiss reactions and suppress the oxidation of biological materials (peptides, proteins, lipids, etc.. The use of nitroxides as antioxidants against oxidative stress induced by anticancer drugs has also been investigated. The application of nitroxides and their derivatives as anticancer drugs is discussed in the contexts of breast, hepatic, lung, ovarian, lymphatic and thyroid cancers under in vivo and in vitro experiments. In this article, we focus on new natural spin-labelled derivatives such as camptothecin, rotenone, combretastatin, podophyllotoxin and others. The applications of nitroxides in the aging process, cardiovascular disease and pathological conditions were also discussed.

  18. Studies on Anticancer Activities of Antimicrobial Peptides

    Science.gov (United States)

    Hoskin, David W.; Ramamoorthy, Ayyalusamy

    2008-01-01

    In spite of great advances in cancer therapy, there is considerable current interest in developing anticancer agents with a new mode of action because of the development of resistance by cancer cells towards current anticancer drugs. A growing number of studies have shown that some of the cationic antimicrobial peptides (AMPs), which are toxic to bacteria but not to normal mammalian cells, exhibit a broad spectrum of cytotoxic activity against cancer cells. Such studies have considerably enhanced the significance of AMPs, both synthetic and from natural sources, which have been of importance both for an increased understanding of the immune system and for their potential as clinical antibiotics. The electrostatic attraction between the negatively charged components of bacterial and cancer cells and the positively charged AMPs is believed to play a major role in the strong binding and selective disruption of bacterial and cancer cell membranes, respectively. However, it is unclear why some host defense peptides are able to kill cancer cells when others do not. In addition, it is not clear whether the molecular mechanism(s) underlying the antibacterial and anticancer activities of AMPs are the same or different. In this article, we review various studies on different AMPs that exhibit cytotoxic activity against cancer cells. The suitability of cancer cell-targeting AMPs as cancer therapeutics is also discussed. PMID:18078805

  19. Histone Deacetylase Inhibitors as Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Tomas Eckschlager

    2017-07-01

    Full Text Available Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC and histone acetyltransferases (HAT. HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

  20. Histone Deacetylase Inhibitors as Anticancer Drugs.

    Science.gov (United States)

    Eckschlager, Tomas; Plch, Johana; Stiborova, Marie; Hrabeta, Jan

    2017-07-01

    Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

  1. Taxane anticancer agents: a patent perspective

    Science.gov (United States)

    Ojima, Iwao; Lichtenthal, Brendan; Lee, Siyeon; Wang, Changwei; Wang, Xin

    2016-01-01

    Introduction Paclitaxel and docetaxel were two epoch-making anticancer drugs and have been successfully used in chemotherapy for a variety of cancer types. In 2010, a new taxane, cabazitaxel, was approved by FDA for use in combination with prednisone for the treatment of metastatic hormone-refractory prostate cancer. Albumin-bound paclitaxel (nab™-paclitaxel; abraxane) nanodroplet formulation was another notable invention (FDA approval 2005 for refractory, metastatic, or relapsed breast cancer). Abraxane in combination with gemcitabine for the treatment of pancreatic cancer was approved by FDA in 2013. Accordingly, there have been a huge number of patent applications dealing with taxane anticancer agents in the last five years. Thus, it is a good time to review the progress in this area and find the next wave for new developments. Area covered This review article covers the patent literature from 2010 to early 2015 on various aspects of taxane-based chemotherapies and drug developments. Expert opinion Three FDA-approved taxane anticancer drugs will continue to expand their therapeutic applications, especially through drug combinations and new formulations. Inspired by the success of abraxane, new nano-formulations are emerging. Highly potent new-generation taxanes will play a key role in the development of efficacious tumor-targeted drug delivery systems. PMID:26651178

  2. Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity.

    Science.gov (United States)

    Rayan, Anwar; Raiyn, Jamal; Falah, Mizied

    2017-01-01

    Cancer is considered one of the primary diseases that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. However, the traditional process of drug discovery and development is lengthy and expensive, so the application of in silico techniques and optimization algorithms in drug discovery projects can provide a solution, saving time and costs. A set of 617 approved anticancer drugs, constituting the active domain, and a set of 2,892 natural products, constituting the inactive domain, were employed to build predictive models and to index natural products for their anticancer bioactivity. Using the iterative stochastic elimination optimization technique, we obtained a highly discriminative and robust model, with an area under the curve of 0.95. Twelve natural products that scored highly as potential anticancer drug candidates are disclosed. Searching the scientific literature revealed that few of those molecules (Neoechinulin, Colchicine, and Piperolactam) have already been experimentally screened for their anticancer activity and found active. The other phytochemicals await evaluation for their anticancerous activity in wet lab.

  3. Organoiridium Complexes: Anticancer Agents and Catalysts

    Science.gov (United States)

    2014-01-01

    Conspectus Iridium is a relatively rare precious heavy metal, only slightly less dense than osmium. Researchers have long recognized the catalytic properties of square-planar IrI complexes, such as Crabtree’s hydrogenation catalyst, an organometallic complex with cyclooctadiene, phosphane, and pyridine ligands. More recently, chemists have developed half-sandwich pseudo-octahedral pentamethylcyclopentadienyl IrIII complexes containing diamine ligands that efficiently catalyze transfer hydrogenation reactions of ketones and aldehydes in water using H2 or formate as the hydrogen source. Although sometimes assumed to be chemically inert, the reactivity of low-spin 5d6 IrIII centers is highly dependent on the set of ligands. Cp* complexes with strong σ-donor C∧C-chelating ligands can even stabilize IrIV and catalyze the oxidation of water. In comparison with well developed Ir catalysts, Ir-based pharmaceuticals are still in their infancy. In this Account, we review recent developments in organoiridium complexes as both catalysts and anticancer agents. Initial studies of anticancer activity with organoiridium complexes focused on square-planar IrI complexes because of their structural and electronic similarity to PtII anticancer complexes such as cisplatin. Recently, researchers have studied half-sandwich IrIII anticancer complexes. These complexes with the formula [(Cpx)Ir(L∧L′)Z]0/n+ (with Cp* or extended Cp* and L∧L′ = chelated C∧N or N∧N ligands) have a much greater potency (nanomolar) toward a range of cancer cells (especially leukemia, colon cancer, breast cancer, prostate cancer, and melanoma) than cisplatin. Their mechanism of action may involve both an attack on DNA and a perturbation of the redox status of cells. Some of these complexes can form IrIII-hydride complexes using coenzyme NAD(P)H as a source of hydride to catalyze the generation of H2 or the reduction of quinones to semiquinones. Intriguingly, relatively unreactive organoiridium

  4. Anticancer Efficacy of Polyphenols and Their Combinations

    Directory of Open Access Journals (Sweden)

    Aleksandra Niedzwiecki

    2016-09-01

    Full Text Available Polyphenols, found abundantly in plants, display many anticarcinogenic properties including their inhibitory effects on cancer cell proliferation, tumor growth, angiogenesis, metastasis, and inflammation as well as inducing apoptosis. In addition, they can modulate immune system response and protect normal cells against free radicals damage. Most investigations on anticancer mechanisms of polyphenols were conducted with individual compounds. However, several studies, including ours, have indicated that anti-cancer efficacy and scope of action can be further enhanced by combining them synergistically with chemically similar or different compounds. While most studies investigated the anti-cancer effects of combinations of two or three compounds, we used more comprehensive mixtures of specific polyphenols and mixtures of polyphenols with vitamins, amino acids and other micronutrients. The mixture containing quercetin, curcumin, green tea, cruciferex, and resveratrol (PB demonstrated significant inhibition of the growth of Fanconi anemia head and neck squamous cell carcinoma and dose-dependent inhibition of cell proliferation, matrix metalloproteinase (MMP-2 and -9 secretion, cell migration and invasion through Matrigel. PB was found effective in inhibition of fibrosarcoma HT-1080 and melanoma A2058 cell proliferation, MMP-2 and -9 expression, invasion through Matrigel and inducing apoptosis, important parameters for cancer prevention. A combination of polyphenols (quercetin and green tea extract with vitamin C, amino acids and other micronutrients (EPQ demonstrated significant suppression of ovarian cancer ES-2 xenograft tumor growth and suppression of ovarian tumor growth and lung metastasis from IP injection of ovarian cancer A-2780 cells. The EPQ mixture without quercetin (NM also has shown potent anticancer activity in vivo and in vitro in a few dozen cancer cell lines by inhibiting tumor growth and metastasis, MMP-2 and -9 secretion, invasion

  5. Green tea catechins: a fresh flavor to anticancer therapy.

    Science.gov (United States)

    Yu, Yang; Deng, Yuan; Lu, Bang-Min; Liu, Yong-Xi; Li, Jian; Bao, Jin-Ku

    2014-01-01

    Green tea catechins have been extensively studied for their cancer preventive effects. Accumulating evidence has shown that green tea catechins, like (-)-epigallocatechin-3-gallate, have strong anti-oxidant activity and affect several signal transduction pathways relevant to cancer development. Here, we review the biological properties of green tea catechins and the molecular mechanisms of their anticancer effects, including the suppression of cancer cell proliferation, induction of apoptosis, and inhibition of tumor metastasis and angiogenesis. We summarize the efficacy of a single catechin and the synergetic effects of multiple catechins. We also discuss the enhanced anticancer effects of green tea catechins when they are combined with anticancer drugs. The information present in this review might promote the development of strategy for the co-administration of green tea catechins with other anticancer drugs to increase the potency of currently available anticancer medicine. This new strategy should in turn lower the cytotoxicity and cost of anticancer treatment.

  6. In Silico Models for Designing and Discovering Novel Anticancer Peptides

    Science.gov (United States)

    Tyagi, Atul; Kapoor, Pallavi; Kumar, Rahul; Chaudhary, Kumardeep; Gautam, Ankur; Raghava, G. P. S.

    2013-10-01

    Use of therapeutic peptides in cancer therapy has been receiving considerable attention in the recent years. Present study describes the development of computational models for predicting and discovering novel anticancer peptides. Preliminary analysis revealed that Cys, Gly, Ile, Lys, and Trp are dominated at various positions in anticancer peptides. Support vector machine models were developed using amino acid composition and binary profiles as input features on main dataset that contains experimentally validated anticancer peptides and random peptides derived from SwissProt database. In addition, models were developed on alternate dataset that contains antimicrobial peptides instead of random peptides. Binary profiles-based model achieved maximum accuracy 91.44% with MCC 0.83. We have developed a webserver, which would be helpful in: (i) predicting minimum mutations required for improving anticancer potency; (ii) virtual screening of peptides for discovering novel anticancer peptides, and (iii) scanning natural proteins for identification of anticancer peptides (http://crdd.osdd.net/raghava/anticp/).

  7. Lessons Learned from Two Decades of Anticancer Drugs.

    Science.gov (United States)

    Liu, Zhichao; Delavan, Brian; Roberts, Ruth; Tong, Weida

    2017-10-01

    Tremendous efforts have been made to elucidate the basis of cancer biology with the aim of promoting anticancer drug development. Especially over the past 20 years, anticancer drug development has developed from conventional cytotoxic agents to target-based and immune-related therapies. Consequently, more than 200 anticancer drugs are available on the market. However, anticancer drug development still suffers high attrition during the later phases of clinical development and is considered to be a difficult and risky therapeutic category within the drug development arena. The disappointing performance of investigational anticancer candidates implies that there are some shortcomings in the translation of preclinical in vitro and in vivo models to humans, and that heterogeneity in the patient population presents a significant challenge. Here, we summarize both successful and failed experiences in anticancer development during the past 20 years and help identify why the current paradigm may be suboptimal. We also offer potential strategies for improvement. Published by Elsevier Ltd.

  8. DNA evolved to minimize frameshift mutations

    OpenAIRE

    Agoni, Valentina

    2013-01-01

    Point mutations can surely be dangerous but what is worst than to lose the reading frame?! Does DNA evolved a strategy to try to limit frameshift mutations?! Here we investigate if DNA sequences effectively evolved a system to minimize frameshift mutations analyzing the transcripts of proteins with high molecular weights.

  9. Genotype to phenotype

    National Research Council Canada - National Science Library

    Malcolm, Sue; Goodship, Timothy H. J

    2001-01-01

    ... Disorders Molecular Genetics of Hypertension Human Gene EvolutionAnalysis of Multifactorial Disease Transcription Factors Molecular Genetics of Cancer, Second edition Genotype to Phenotype, second e...

  10. Evolutionary history of human disease genes reveals phenotypic connections and comorbidity among genetic diseases

    Science.gov (United States)

    Park, Solip; Yang, Jae-Seong; Kim, Jinho; Shin, Young-Eun; Hwang, Jihye; Park, Juyong; Jang, Sung Key; Kim, Sanguk

    2012-10-01

    The extent to which evolutionary changes have impacted the phenotypic relationships among human diseases remains unclear. In this work, we report that phenotypically similar diseases are connected by the evolutionary constraints on human disease genes. Human disease groups can be classified into slowly or rapidly evolving classes, where the diseases in the slowly evolving class are enriched with morphological phenotypes and those in the rapidly evolving class are enriched with physiological phenotypes. Our findings establish a clear evolutionary connection between disease classes and disease phenotypes for the first time. Furthermore, the high comorbidity found between diseases connected by similar evolutionary constraints enables us to improve the predictability of the relative risk of human diseases. We find the evolutionary constraints on disease genes are a new layer of molecular connection in the network-based exploration of human diseases.

  11. CancerHSP: anticancer herbs database of systems pharmacology

    Science.gov (United States)

    Tao, Weiyang; Li, Bohui; Gao, Shuo; Bai, Yaofei; Shar, Piar Ali; Zhang, Wenjuan; Guo, Zihu; Sun, Ke; Fu, Yingxue; Huang, Chao; Zheng, Chunli; Mu, Jiexin; Pei, Tianli; Wang, Yuan; Li, Yan; Wang, Yonghua

    2015-06-01

    The numerous natural products and their bioactivity potentially afford an extraordinary resource for new drug discovery and have been employed in cancer treatment. However, the underlying pharmacological mechanisms of most natural anticancer compounds remain elusive, which has become one of the major obstacles in developing novel effective anticancer agents. Here, to address these unmet needs, we developed an anticancer herbs database of systems pharmacology (CancerHSP), which records anticancer herbs related information through manual curation. Currently, CancerHSP contains 2439 anticancer herbal medicines with 3575 anticancer ingredients. For each ingredient, the molecular structure and nine key ADME parameters are provided. Moreover, we also provide the anticancer activities of these compounds based on 492 different cancer cell lines. Further, the protein targets of the compounds are predicted by state-of-art methods or collected from literatures. CancerHSP will help reveal the molecular mechanisms of natural anticancer products and accelerate anticancer drug development, especially facilitate future investigations on drug repositioning and drug discovery. CancerHSP is freely available on the web at http://lsp.nwsuaf.edu.cn/CancerHSP.php.

  12. Advances in the development of hybrid anticancer drugs.

    Science.gov (United States)

    Fortin, Sébastien; Bérubé, Gervais

    2013-08-01

    Hybrid anticancer drugs are of great therapeutic interests as they can potentially overcome most of the pharmacokinetic drawbacks encountered when using conventional anticancer drugs. In fact, the future of hybrid anticancer drugs is very bright for the discovery of highly potent and selective molecules that triggers two or more cytocidal pharmacological mechanisms of action acting in synergy to inhibit cancer tumor growth. This review represents the most advanced and recent data in the field of hybrid anticancer agents covering mainly the past 5 years of research. It also accounts for other significant reviews already published on the topic of anticancer hybrids. The review showcases the research that is at the leading edge of hybrid anticancer drug discovery. The main areas covered by the present review are: DNA alkylating agent hybrids (e.g., platinum(II), nitrogen mustard, etc.), vitamin-D receptor, agonist-histone deacetylase inhibitors, combi-molecule therapies and other types of hybrid anticancer agents. The current development in the field describes strategies that have never been used before for the design of hybrid anticancer drugs. The information currently available and described in this section allows us to identify the main parameters required to design such molecules. It also provides a clear view of the future directions that must be explored for the successful development and discovery of useful hybrid anticancer drugs.

  13. Phytochemicals as Adjunctive with Conventional Anticancer Therapies.

    Science.gov (United States)

    Farzaei, Mohammad Hosein; Bahramsoltani, Roodabeh; Rahimi, Roja

    2016-01-01

    Cancer is defined as the abnormal proliferations of cells which could occur in any tissue and can cause life-threatening malignancies with high financial costs for both patients and health care system. Plant-derived secondary metabolites are shown to have positive role in various diseases and conditions. The aim of the present study is to summarize clinical evidences on the benefits of phytochemicals as adjuvant therapy along with conventional anticancer therapies. Electronic databases including Pubmed, Scopus and Cochrane library were searched with the keywords "chemotherapeutic", "anticancer", "antineoplastic" or "radiotherapy" with "plant", "extract", "herb", or "phytochemical", until July 2015. Only clinical studies were included in this review. The findings showed that positive effects of phytochemicals are due to their direct anticarcinogenic activity, induction of relief in cancer complications, as well as their protective role against side effects of conventional chemotherapeutic agents. Results obtained from current review demonstrated that numerous phytochemical agents from different chemical categories including alkaloid, benzopyran, coumarin, carotenoid, diarylheptanoid, flavonoid, indole, polysaccharide, protein, stilbene, terpene, and xanthonoid possess therapeutic effect in patients with different types of cancer. Polyphenols are the most studied components. Curcumin, ginsenosides, lycopene, homoharringtonine, aviscumine, and resveratrol are amongst the major components with remarkable volumes of clinical evidence indicating their direct anticancer activities in different types of cancer including hepatocarcinoma, prostate cancer, leukemia and lymphoma, breast and ovarian cancer, and gastrointestinal cancers. Cannabinoids, cumarin, curcumin, ginsenosides, epigallocatechin gallate, vitexin, and salidroside are phytochemicals with significant alleviative effect on synthetic chemotherapy- induced toxicities. There is lack of evidence from clinical

  14. Anticancer and Immunogenic Properties of Cardiac Glycosides

    Directory of Open Access Journals (Sweden)

    Naira Fernanda Zanchett Schneider

    2017-11-01

    Full Text Available Cardiac glycosides (CGs are natural compounds widely used in the treatment of several cardiac conditions and more recently have been recognized as potential antitumor compounds. They are known to be ligands for Na/K-ATPase, which is a promising drug target in cancer. More recently, in addition to their antitumor effects, it has been suggested that CGs activate tumor-specific immune responses. This review summarizes the anticancer aspects of CGs as new strategies for immunotherapy and drug repositioning (new horizons for old players, and the possible new targets for CGs in cancer cells.

  15. Maximin H5 is an anticancer peptide

    OpenAIRE

    Dennison, SR; Harris, F; Phoenix, DA

    2017-01-01

    Here we report the first major example of anionic amphibian host defence peptides (HDPs) with anticancer activity. Maximin H5 is a C-terminally amidated, anionic host defence peptide (MH5N) from toads of the Bombina genus, which was shown to possess activity against the glioma cell line, T98G (EC50 = 125 μM). The peptide adopted high levels of α-helical structure (57.3%) in the presence of model cancer membranes (DMPC:DMPS in a molar ratio of 10:1). MH5N also showed a strong ability to penetr...

  16. Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity

    National Research Council Canada - National Science Library

    Anwar Rayan; Jamal Raiyn; Mizied Falah

    2017-01-01

    ... can provide a solution, saving time and costs. A set of 617 approved anticancer drugs, constituting the active domain, and a set of 2,892 natural products, constituting the inactive domain, were employed to build predictive models and to index...

  17. Thermal phenotypic plasticity of body size in Drosophila ...

    Indian Academy of Sciences (India)

    2011-08-19

    Aug 19, 2011 ... For the female/male ratio, heritability (intraclass correlation) was about 0.20 and evolvability. (genetic coefficient of variation) close to 1. Although significant, these values are much less than for the traits themselves. Phenotypic plasticity ... In most insect species, temperature is known to play a major role in ...

  18. Clinical phenotypes of asthma

    NARCIS (Netherlands)

    Bel, Elisabeth H.

    2004-01-01

    PURPOSE OF REVIEW: Asthma is a phenotypically heterogeneous disorder and, over the years, many different clinical subtypes of asthma have been described. A precise definition of asthma phenotypes is now becoming more and more important, not only for a better understanding of pathophysiologic

  19. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Directory of Open Access Journals (Sweden)

    Danbo Yang

    2010-12-01

    Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  20. Peptides with Dual Antimicrobial and Anticancer Activities

    Science.gov (United States)

    Felício, Mário R.; Silva, Osmar N.; Gonçalves, Sônia; Santos, Nuno C.; Franco, Octávio L.

    2017-02-01

    In recent years, the number of people suffering from cancer and multi-resistant infections has increased, such that both diseases are already seen as current and future major causes of death. Moreover, chronic infections are one of the main causes of cancer, due to the instability in the immune system that allows cancer cells to proliferate. Likewise, the physical debility associated with cancer or with anticancer therapy itself often paves the way for opportunistic infections. It is urgent to develop new therapeutic methods, with higher efficiency and lower side effects. Antimicrobial peptides (AMPs) are found in the innate immune system of a wide range of organisms. Identified as the most promising alternative to conventional molecules used nowadays against infections, some of them have been shown to have dual activity, both as antimicrobial and anticancer peptides (ACPs). Highly cationic and amphipathic, they have demonstrated efficacy against both conditions, with the number of nature-driven or synthetically designed peptides increasing year by year. With similar properties, AMPs that can also act as ACPs are viewed as future chemotherapeutic drugs, with the advantage of low propensity to resistance, which started this paradigm in the pharmaceutical market. These peptides have already been described as molecules presenting killing mechanisms at the membrane level, but also acting towards intracellular targets, which increases their success comparatively to specific one-target drugs. This review will approach the desirable characteristics of small peptides that demonstrated dual activity against microbial infections and cancer, as well as the peptides engaged in clinical trials.

  1. Trial Watch: Peptide-based anticancer vaccines.

    Science.gov (United States)

    Pol, Jonathan; Bloy, Norma; Buqué, Aitziber; Eggermont, Alexander; Cremer, Isabelle; Sautès-Fridman, Catherine; Galon, Jérôme; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2015-04-01

    Malignant cells express antigens that can be harnessed to elicit anticancer immune responses. One approach to achieve such goal consists in the administration of tumor-associated antigens (TAAs) or peptides thereof as recombinant proteins in the presence of adequate adjuvants. Throughout the past decade, peptide vaccines have been shown to mediate antineoplastic effects in various murine tumor models, especially when administered in the context of potent immunostimulatory regimens. In spite of multiple limitations, first of all the fact that anticancer vaccines are often employed as therapeutic (rather than prophylactic) agents, this immunotherapeutic paradigm has been intensively investigated in clinical scenarios, with promising results. Currently, both experimentalists and clinicians are focusing their efforts on the identification of so-called tumor rejection antigens, i.e., TAAs that can elicit an immune response leading to disease eradication, as well as to combinatorial immunostimulatory interventions with superior adjuvant activity in patients. Here, we summarize the latest advances in the development of peptide vaccines for cancer therapy.

  2. Cancer stem cells: constantly evolving and functionally heterogeneous therapeutic targets.

    Science.gov (United States)

    Yang, Tao; Rycaj, Kiera; Liu, Zhong-Min; Tang, Dean G

    2014-06-01

    Elucidating the origin of and dynamic interrelationship between intratumoral cell subpopulations has clear clinical significance in helping to understand the cellular basis of treatment response, therapeutic resistance, and tumor relapse. Cancer stem cells (CSC), together with clonal evolution driven by genetic alterations, generate cancer cell heterogeneity commonly observed in clinical samples. The 2013 Shanghai International Symposium on Cancer Stem Cells brought together leaders in the field to highlight the most recent progress in phenotyping, characterizing, and targeting CSCs and in elucidating the relationship between the cell-of-origin of cancer and CSCs. Discussions from the symposium emphasize the urgent need in developing novel therapeutics to target the constantly evolving CSCs. ©2014 American Association for Cancer Research.

  3. Phenotypes in phylogeography: Species’ traits, environmental variation, and vertebrate diversification

    Science.gov (United States)

    Bell, Rayna C.; Mason, Nicholas A.

    2016-01-01

    Almost 30 y ago, the field of intraspecific phylogeography laid the foundation for spatially explicit and genealogically informed studies of population divergence. With new methods and markers, the focus in phylogeography shifted to previously unrecognized geographic genetic variation, thus reducing the attention paid to phenotypic variation in those same diverging lineages. Although phenotypic differences among lineages once provided the main data for studies of evolutionary change, the mechanisms shaping phenotypic differentiation and their integration with intraspecific genetic structure have been underexplored in phylogeographic studies. However, phenotypes are targets of selection and play important roles in species performance, recognition, and diversification. Here, we focus on three questions. First, how can phenotypes elucidate mechanisms underlying concordant or idiosyncratic responses of vertebrate species evolving in shared landscapes? Second, what mechanisms underlie the concordance or discordance of phenotypic and phylogeographic differentiation? Third, how can phylogeography contribute to our understanding of functional phenotypic evolution? We demonstrate that the integration of phenotypic data extends the reach of phylogeography to explain the origin and maintenance of biodiversity. Finally, we stress the importance of natural history collections as sources of high-quality phenotypic data that span temporal and spatial axes. PMID:27432983

  4. No phenotypic plasticity in nest-site selection in response to extreme flooding events

    NARCIS (Netherlands)

    Bailey, Liam; Ens, B.J.; Both, C.; Heg, D.; Oosterbeek, K.; Van de Pol, M.

    2017-01-01

    Phenotypic plasticity is a crucial mechanism for responding to changes in climatic means, yet we know little about its role in responding to extreme climatic events (ECEs). ECEs may lack the reliable cues necessary for phenotypic plasticity to evolve; however, this has not been empirically tested.

  5. Comparative anticancer activity of dolaborane diterpenes from the ...

    African Journals Online (AJOL)

    This study aimed at investigating the anticancer activity of tagalsins A, B, C, D, E, F and G isolated from the roots of Ceriops tagal. Their structures were established based on the IR, MS and NMR spectral data. Anticancer activity was evaluated using caspase-3 colourimetric assays and the minimum activation concentrations ...

  6. Prediction of anticancer activity of aliphatic nitrosoureas using ...

    African Journals Online (AJOL)

    Design and development of new anticancer drugs with low toxicity is a very challenging task and computer aided methods are being increasingly used to solve this problem. In this study, we investigated the anticancer activity of aliphatic nitrosoureas using quantum chemical quantitative structure activity relation (QSAR) ...

  7. Antimicrobial and anticancer activities of extracts from Urginea ...

    African Journals Online (AJOL)

    Background: Increasing antibiotic resistance among human pathogenic microorganisms and the failure of conventional cancer therapies attracting great attention among scientists in the field of herbal medicine to develop natural antimicrobial and anticancer drugs. Thus, the antimicrobial and anticancer activities from fruits ...

  8. Bioactivity-Guided Isolation of Anticancer Agents from Bauhinia ...

    African Journals Online (AJOL)

    Conclusion: It was observed that pyrogallol moiety was one of the essential functional structures of the phenolic compounds in exhibiting anticancer activity. Also, the carboxyl group of compound 1 was also important in anticancer activity. Examination of the PC-3 cells treated with compound 1 using fluorescence ...

  9. Methods for improving the safety of fluoropyrimidine anticancer drugs

    NARCIS (Netherlands)

    Jacobs, Bart A W

    2016-01-01

    Jacobs’ thesis is about a commonly used class of anti-cancer drugs called fluoropyrimidines. Approximately one in four patients who receive chemotherapy with these drugs experience serious and sometimes even lethal side effects. The goal of Jacobs work was to improve the safety of these anti-cancer

  10. Chalcone Scaffold in Anticancer Armamentarium: A Molecular Insight

    Science.gov (United States)

    Manna, Kuntal

    2016-01-01

    Cancer is an inevitable matter of concern in the medicinal chemistry era. Chalcone is the well exploited scaffold in the anticancer domain. The molecular mechanism of chalcone at cellular level was explored in past decades. This mini review provides the most recent updates on anticancer potential of chalcones. PMID:26880913

  11. Development of Combination Therapy with Anti-Cancer Drugs

    NARCIS (Netherlands)

    Leijen, S.

    2013-01-01

    This thesis describes early clinical trials with anti-cancer drugs in combination with commonly applied and registered chemotherapy and single agent studies with compounds that are intended for use in combination with registered or other targeted anti-cancer drugs. Gemcitabine is a prodrug that

  12. WSC-07: Evolving the Web Services Challenge

    NARCIS (Netherlands)

    Blake, M. Brian; Cheung, William K.W.; Jaeger, Michael C.; Wombacher, Andreas

    Service-oriented architecture (SOA) is an evolving architectural paradigm where businesses can expose their capabilities as modular, network-accessible software services. By decomposing capabilities into modular services, organizations can share their offerings at multiple levels of granularity

  13. Satcom access in the evolved packet core

    NARCIS (Netherlands)

    Cano, M.D.; Norp, A.H.J.; Popova, M.P.

    2012-01-01

    Satellite communications (Satcom) networks are increasingly integrating with terrestrial communications networks, namely Next Generation Networks (NGN). In the area of NGN the Evolved Packet Core (EPC) is a new network architecture that can support multiple access technologies. When Satcom is

  14. Acquisition: Acquisition of the Evolved SEASPARROW Missile

    National Research Council Canada - National Science Library

    2002-01-01

    .... The Evolved SEASPARROW Missile, a Navy Acquisition Category II program, is an improved version of the RIM-7P SEASPARROW missile that will intercept high-speed maneuvering, anti-ship cruise missiles...

  15. Challenges in pre-clinical testing of anti-cancer drugs in cell culture and in animal models.

    Science.gov (United States)

    HogenEsch, Harm; Nikitin, Alexander Yu

    2012-12-10

    Experiments with cultures of human tumor cell lines, xenografts of human tumors into immunodeficient mice, and mouse models of human cancer are important tools in the development and testing of anti-cancer drugs. Tumors are complex structures composed of genetically and phenotypically heterogeneous cancer cells that interact in a reciprocal manner with the stromal microenvironment and the immune system. Modeling the complexity of human cancers in cell culture and in mouse models for preclinical testing is a challenge that has not yet been met although tremendous advances have been made. A combined approach of cell culture and mouse models of human cancer is most likely to predict the efficacy of novel anti-cancer treatments in human clinical trials. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Cyberspace Operations: Influence Upon Evolving War Theory

    Science.gov (United States)

    2011-03-18

    St ra te gy R es ea rc h Pr oj ec t CYBERSPACE OPERATIONS: INFLUENCE UPON EVOLVING WAR THEORY BY COLONEL KRISTIN BAKER United States...DATES COVERED (From - To) 4. TITLE AND SUBTITLE Cyberspace Operations: Influence Upon Evolving War Theory 5a. CONTRACT NUMBER... Leadership 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S

  17. Evolving effective incremental SAT solvers with GP

    OpenAIRE

    Bader, Mohamed; Poli, R.

    2008-01-01

    Hyper-Heuristics could simply be defined as heuristics to choose other heuristics, and it is a way of combining existing heuristics to generate new ones. In a Hyper-Heuristic framework, the framework is used for evolving effective incremental (Inc*) solvers for SAT. We test the evolved heuristics (IncHH) against other known local search heuristics on a variety of benchmark SAT problems.

  18. [Study on the regulation of autophagy against anticancer drugs' toxicity].

    Science.gov (United States)

    Lou, Xiao-e; Zhu, Yi; He, Qiao-jun

    2016-01-01

    Autophagy is a crucial biological process in eukaryotes, which is involved in cell growth, survival and energy metabolism. It has been confirmed that autophagy mediates toxicity of anticancer drugs, especially in heart, liver and neuron. It is important to understand the function and mechanism of autophagy in anticancer drugs-induced toxicity. Given that autophagy is a double-edged sword in the maintenance of the function of heart, liver and neuron, the autophagy-mediated toxicity are very complicated in the body. We provide a review on the concept of autophagy and current status about autophagy-mediated toxicity of anticancer drugs. The knowledge is crucial in the basic study of anticancer drugs-induced toxicity, and provides some strategies for the development of alleviating the toxicity of anticancer drugs.

  19. Discussing and prescribing expensive unfunded anticancer drugs in Australia.

    Science.gov (United States)

    Karikios, Deme John; Mileshkin, Linda; Martin, Andrew; Ferraro, Danielle; Stockler, Martin R

    2017-01-01

    Australia has a publicly funded universal healthcare system which heavily subsidises the cost of most registered anticancer drugs. The use of anticancer drugs that are unfunded, that is, not subsidised by the government, entails substantial out-of-pocket costs for patients. We sought to determine how frequently Australian medical oncologists discuss and prescribe unfunded anticancer drugs, and their attitudes and beliefs about their use. Members of the Medical Oncology Group of Australia (MOGA) completed an online survey about their clinical practices over a recent 3-month period. A negative binomial regression model was used to examine the influence of respondent characteristics on the rate of discussions about, and prescription of, unfunded anticancer drugs. Of the 154 respondents (27% of 575 MOGA members), 92% had discussed and 68% had prescribed at least one unfunded anticancer drug in the last 3 months. Respondents reported discussing unfunded anticancer drugs with an average of 2.5 patients per month (95% CI 2.1 to 2.9), and prescribed them to an average of 0.9 patients per month (95% CI 0.7 to 1.2). The rate of discussing unfunded anticancer drugs was associated with being fully qualified (p=0.01), and being in a metropolitan practice (p=0.009), the rate of prescription was associated only with being in metropolitan practice (p=0.006). The concerns about discussing and prescribing unfunded anticancer drugs rated most important were as follows: 'potential to cause financial hardship' and 'difficulty for patients to evaluate the benefits versus the costs'. Australian medical oncologists frequently discuss and prescribe unfunded anticancer drugs, and are concerned about their patients having to face difficult decisions and financial hardship. Further research is needed to better understand the factors that affect how oncologists and patients value expensive, unfunded anticancer drugs.

  20. New genes as drivers of phenotypic evolution

    Science.gov (United States)

    Chen, Sidi; Krinsky, Benjamin H.; Long, Manyuan

    2014-01-01

    During the course of evolution, genomes acquire novel genetic elements as sources of functional and phenotypic diversity, including new genes that originated in recent evolution. In the past few years, substantial progress has been made in understanding the evolution and phenotypic effects of new genes. In particular, an emerging picture is that new genes, despite being present in the genomes of only a subset of species, can rapidly evolve indispensable roles in fundamental biological processes, including development, reproduction, brain function and behaviour. The molecular underpinnings of how new genes can develop these roles are starting to be characterized. These recent discoveries yield fresh insights into our broad understanding of biological diversity at refined resolution. PMID:23949544

  1. Evolution of environmental cues for phenotypic plasticity.

    Science.gov (United States)

    Chevin, Luis-Miguel; Lande, Russell

    2015-10-01

    Phenotypically plastic characters may respond to multiple variables in their environment, but the evolutionary consequences of this phenomenon have rarely been addressed theoretically. We model the evolution of linear reaction norms in response to several correlated environmental variables, in a population undergoing stationary environmental fluctuations. At evolutionary equilibrium, the linear combination of environmental variables that acts as a developmental cue for the plastic trait is the multivariate best linear predictor of changes in the optimum. However, the reaction norm with respect to any single environmental variable may exhibit nonintuitive patterns. Apparently maladaptive, or hyperadaptive plasticity can evolve with respect to single environmental variables, and costs of plasticity may increase, rather than reduce, plasticity in response to some variables. We also find conditions for the evolution of an indirect environmental indicator that affects expression of a plastic phenotype, despite not influencing natural selection on it. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  2. Kefir: a powerful probiotics with anticancer properties.

    Science.gov (United States)

    Sharifi, Mohammadreza; Moridnia, Abbas; Mortazavi, Deniz; Salehi, Mahsa; Bagheri, Marzieh; Sheikhi, Abdolkarim

    2017-09-27

    Probiotics and fermented milk products have attracted the attention of scientists from various fields, such as health care, industry and pharmacy. In recent years, reports have shown that dietary probiotics such as kefir have a great potential for cancer prevention and treatment. Kefir is fermented milk with Caucasian and Tibet origin, made from the incubation of kefir grains with raw milk or water. Kefir grains are a mixture of yeast and bacteria, living in a symbiotic association. Antibacterial, antifungal, anti-allergic and anti-inflammatory effects are some of the health beneficial properties of kefir grains. Furthermore, it is suggested that some of the bioactive compounds of kefir such as polysaccharides and peptides have great potential for inhibition of proliferation and induction of apoptosis in tumor cells. Many studies revealed that kefir acts on different cancers such as colorectal cancer, malignant T lymphocytes, breast cancer and lung carcinoma. In this review, we have focused on anticancer properties of kefir.

  3. Anticancer Activity of Key Lime, Citrus aurantifolia.

    Science.gov (United States)

    Narang, Nithithep; Jiraungkoorskul, Wannee

    2016-01-01

    Citrus aurantifolia (family: Rutaceae) is mainly used in daily consumption, in many cultural cuisines, and in juice production. It is widely used because of its antibacterial, anticancer, antidiabetic, antifungal, anti-hypertensive, anti-inflammation, anti-lipidemia, and antioxidant properties; moreover, it can protect heart, liver, bone, and prevent urinary diseases. Its secondary metabolites are alkaloids, carotenoids, coumarins, essential oils, flavonoids, phenolic acids, and triterpenoids. The other important constituents are apigenin, hesperetin, kaempferol, limonoids, quercetin, naringenin, nobiletin, and rutin, all of these contribute to its remedial properties. The scientific searching platforms were used for publications from 1990 to present. The abstracts and titles were screened, and the full-text articles were selected. The present review is up-to-date of the phytochemical property of C. aurantifolia to provide a reference for further study.

  4. Synthesis and anticancer evaluation of spermatinamine analogues.

    Science.gov (United States)

    Moosa, Basem A; Sagar, Sunil; Li, Song; Esau, Luke; Kaur, Mandeep; Khashab, Niveen M

    2016-03-15

    Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcysteine carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines, that is, cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5-10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Integrative oncoproteomics strategies for anticancer drug discovery.

    Science.gov (United States)

    Liu, Rui; Wang, Kui; Yuan, Kefei; Wei, Yuquan; Huang, Canhua

    2010-06-01

    The most significant advantage of proteomic technology is its ability to profile a whole proteome or subproteome in a single experiment, so that the protein alterations corresponding to a pathological or biochemical condition at a given time can be annotated in an integrated way. In oncology and pharmacology these technologies led to the identification of biological markers, which may provide the starting point for the identification of diagnostic markers and therapeutic targets; thus greatly broadening our knowledge and accelerating our path in medical research. In combination with other new technologies in immunology and chemistry, proteomics shows significant potential to make considerable contribution to the drug development process. This article provides a brief overview of the integrative oncoproteomics strategies for anticancer drug discovery, including comparative proteomics, signaling proteomics, membrane proteomics, immunoproteomics and chemistry-based functional proteomics.

  6. Synthesis and anticancer evaluation of spermatinamine analogues

    KAUST Repository

    Moosa, Basem

    2016-02-04

    Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcystiene carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines i.e. cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5 - 10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines.

  7. System engineering approach to planning anticancer therapies

    CERN Document Server

    Świerniak, Andrzej; Smieja, Jaroslaw; Puszynski, Krzysztof; Psiuk-Maksymowicz, Krzysztof

    2016-01-01

    This book focuses on the analysis of cancer dynamics and the mathematically based synthesis of anticancer therapy. It summarizes the current state-of-the-art in this field and clarifies common misconceptions about mathematical modeling in cancer. Additionally, it encourages closer cooperation between engineers, physicians and mathematicians by showing the clear benefits of this without stating unrealistic goals. Development of therapy protocols is realized from an engineering point of view, such as the search for a solution to a specific control-optimization problem. Since in the case of cancer patients, consecutive measurements providing information about the current state of the disease are not available, the control laws are derived for an open loop structure. Different forms of therapy are incorporated into the models, from chemotherapy and antiangiogenic therapy to immunotherapy and gene therapy, but the class of models introduced is broad enough to incorporate other forms of therapy as well. The book be...

  8. [Peptides: a new class of anticancer drugs].

    Science.gov (United States)

    Smolarczyk, Ryszard; Cichoń, Tomasz; Szala, Stanisław

    2009-07-22

    Peptides are a novel class of anticancer agents embracing two distinct categories: natural antibacterial peptides, which are preferentially bound by cancer cells, and chemically synthesized peptides, which bind specifically to precise molecular targets located on the surface of tumor cells. Antibacterial peptides bind to both cell and mitochondrial membranes. Some of these peptides attach to the cell membrane, resulting in its disorganization. Other antibacterial peptides penetrate cancer cells without causing cell membrane damage, but they disrupt mitochondrial membranes. Thanks to phage and aptamer libraries, it has become possible to obtain synthetic peptides blocking or activating some target proteins found in cancer cells as well as in cells forming the tumor environment. These synthetic peptides can feature anti-angiogenic properties, block enzymes indispensable for sustained tumor growth, and reduce tumor ability to metastasize. In this review the properties of peptides belonging to both categories are discussed and attempts of their application for therapeutic purposes are outlined.

  9. Peptides: A new class of anticancer drugs

    Directory of Open Access Journals (Sweden)

    Ryszard Smolarczyk

    2009-07-01

    Full Text Available Peptides are a novel class of anticancer agents embracing two distinct categories: natural antibacterial peptides, which are preferentially bound by cancer cells, and chemically synthesized peptides, which bind specifically to precise molecular targets located on the surface of tumor cells. Antibacterial peptides bind to both cell and mitochondrial membranes. Some of these peptides attach to the cell membrane, resulting in its disorganization. Other antibacterial peptides penetrate cancer cells without causing cell membrane damage, but they disrupt mitochondrial membranes. Thanks to phage and aptamer libraries, it has become possible to obtain synthetic peptides blocking or activating some target proteins found in cancer cells as well as in cells forming the tumor environment. These synthetic peptides can feature anti-angiogenic properties, block enzymes indispensable for sustained tumor growth, and reduce tumor ability to metastasize. In this review the properties of peptides belonging to both categories are discussed and attempts of their application for therapeutic purposes are outlined.

  10. Phenotypic and Functional Properties of Tumor-Infiltrating Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Gap Ryol Lee

    2017-01-01

    Full Text Available Regulatory T (Treg cells maintain immune homeostasis by suppressing excessive immune responses. Treg cells induce tolerance against self- and foreign antigens, thus preventing autoimmunity, allergy, graft rejection, and fetus rejection during pregnancy. However, Treg cells also infiltrate into tumors and inhibit antitumor immune responses, thus inhibiting anticancer therapy. Depleting whole Treg cell populations in the body to enhance anticancer treatments will produce deleterious autoimmune diseases. Therefore, understanding the precise nature of tumor-infiltrating Treg cells is essential for effectively targeting Treg cells in tumors. This review summarizes recent results relating to Treg cells in the tumor microenvironment, with particular emphasis on their accumulation, phenotypic, and functional properties, and targeting to enhance the efficacy of anticancer treatment.

  11. Novel anticancer alkene lactone from Persea americana.

    Science.gov (United States)

    Falodun, Abiodun; Engel, Nadja; Kragl, Udo; Nebe, Barbara; Langer, Peter

    2013-06-01

    Persea americana Mill (Lauraceae) root bark is used in ethnomedicine for a variety of diseases including cancer. To isolate and characterize the chemical constituent in P. americana, and also to determine the anticancer property of a new alkene lactone from the root bark of P. americana. The MCF-7 cells were treated with different concentrations of the pure compound for 48 h. The percentage of cells in the various phases, online monitoring of metabolic changes and integrin receptor expression determined by flow cytometry. One novel alkene lactone (4-hydroxy-5-methylene-3-undecyclidenedihydrofuran-2 (3H)-one) (1) was isolated and characterized using 1D-NMR, 2D-NMR, infrared, UV and MS. At a concentration of 10 µg/mL, significant reduction of proliferation of MCF-7 was induced while MCF-12 A cell was significantly stimulated by 10 µg/mL. The IC50 value for MCF-7 cells is 20.48 µg/mL. Lower concentration of 1 harbor no significant effect on either MCF-7 or MCF-12A. The apoptotic rates of MCF-7 cells were increased significantly. At the final concentration 10 µg/mL, up to 80% of all breast cancer cells were dead. On the non-tumorigenic cell line MCF-12A, the same concentrations (1 and 10 µg/mL) of compound 1 caused significant enhanced apoptotic rates. A total of 1 µg/mL of 1 caused a decrease of α4-, α6-, β1- and β3-integrin expression. The compound caused a stimulatory effect on non-tumorigenic MCF-12A cells with respect to cell adhesion while tumorigenic MCF-7 cells detached continuously. This is the first report on the anticancer effects of this class of compound.

  12. Anticancer properties of distinct antimalarial drug classes.

    Directory of Open Access Journals (Sweden)

    Rob Hooft van Huijsduijnen

    Full Text Available We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor, emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings.

  13. In search of intelligence: evolving a developmental neuron capable of learning

    Science.gov (United States)

    Khan, Gul Muhammad; Miller, Julian Francis

    2014-10-01

    A neuro-inspired multi-chromosomal genotype for a single developmental neuron capable of learning and developing memory is proposed. This genotype is evolved so that the phenotype which changes and develops during an agent's lifetime (while problem-solving) gives the agent the capacity for learning by experience. Seven important processes of signal processing and neural structure development are identified from biology and encoded using Cartesian Genetic Programming. These chromosomes represent the electrical and developmental aspects of dendrites, axonal branches, synapses and the neuron soma. The neural morphology that occurs by running these chromosomes is highly dynamic. The dendritic/axonal branches and synaptic connections form and change in response to situations encountered in the learning task. The approach has been evaluated in the context of maze-solving and the board game of checkers (draughts) demonstrating interesting learning capabilities. The motivation underlying this research is to, ab initio, evolve genotypes that build phenotypes with an ability to learn.

  14. Voreloxin is an anticancer quinolone derivative that intercalates DNA and poisons topoisomerase II.

    Directory of Open Access Journals (Sweden)

    Rachael E Hawtin

    2010-04-01

    Full Text Available Topoisomerase II is critical for DNA replication, transcription and chromosome segregation and is a well validated target of anti-neoplastic drugs including the anthracyclines and epipodophyllotoxins. However, these drugs are limited by common tumor resistance mechanisms and side-effect profiles. Novel topoisomerase II-targeting agents may benefit patients who prove resistant to currently available topoisomerase II-targeting drugs or encounter unacceptable toxicities. Voreloxin is an anticancer quinolone derivative, a chemical scaffold not used previously for cancer treatment. Voreloxin is completing Phase 2 clinical trials in acute myeloid leukemia and platinum-resistant ovarian cancer. This study defined voreloxin's anticancer mechanism of action as a critical component of rational clinical development informed by translational research.Biochemical and cell-based studies established that voreloxin intercalates DNA and poisons topoisomerase II, causing DNA double-strand breaks, G2 arrest, and apoptosis. Voreloxin is differentiated both structurally and mechanistically from other topoisomerase II poisons currently in use as chemotherapeutics. In cell-based studies, voreloxin poisoned topoisomerase II and caused dose-dependent, site-selective DNA fragmentation analogous to that of quinolone antibacterials in prokaryotes; in contrast etoposide, the nonintercalating epipodophyllotoxin topoisomerase II poison, caused extensive DNA fragmentation. Etoposide's activity was highly dependent on topoisomerase II while voreloxin and the intercalating anthracycline topoisomerase II poison, doxorubicin, had comparable dependence on this enzyme for inducing G2 arrest. Mechanistic interrogation with voreloxin analogs revealed that intercalation is required for voreloxin's activity; a nonintercalating analog did not inhibit proliferation or induce G2 arrest, while an analog with enhanced intercalation was 9.5-fold more potent.As a first-in-class anticancer

  15. Evolved genetic and phenotypic differences due to mitochondrial-nuclear interactions.

    Directory of Open Access Journals (Sweden)

    Tara Z Baris

    2017-03-01

    Full Text Available The oxidative phosphorylation (OxPhos pathway is responsible for most aerobic ATP production and is the only pathway with both nuclear and mitochondrial encoded proteins. The importance of the interactions between these two genomes has recently received more attention because of their potential evolutionary effects and how they may affect human health and disease. In many different organisms, healthy nuclear and mitochondrial genome hybrids between species or among distant populations within a species affect fitness and OxPhos functions. However, what is less understood is whether these interactions impact individuals within a single natural population. The significance of this impact depends on the strength of selection for mito-nuclear interactions. We examined whether mito-nuclear interactions alter allele frequencies for ~11,000 nuclear SNPs within a single, natural Fundulus heteroclitus population containing two divergent mitochondrial haplotypes (mt-haplotypes. Between the two mt-haplotypes, there are significant nuclear allele frequency differences for 349 SNPs with a p-value of 1% (236 with 10% FDR. Unlike the rest of the genome, these 349 outlier SNPs form two groups associated with each mt-haplotype, with a minority of individuals having mixed ancestry. We use this mixed ancestry in combination with mt-haplotype as a polygenic factor to explain a significant fraction of the individual OxPhos variation. These data suggest that mito-nuclear interactions affect cardiac OxPhos function. The 349 outlier SNPs occur in genes involved in regulating metabolic processes but are not directly associated with the 79 nuclear OxPhos proteins. Therefore, we postulate that the evolution of mito-nuclear interactions affects OxPhos function by acting upstream of OxPhos.

  16. Clinical and Cognitive Phenotype of Mild Cognitive Impairment Evolving to Dementia with Lewy Bodies

    Directory of Open Access Journals (Sweden)

    Annachiara Cagnin

    2015-11-01

    Full Text Available Objective: The aim of this study was to determine which characteristics could better distinguish dementia with Lewy bodies (DLB from Alzheimer's disease (AD at the mild cognitive impairment (MCI stage, with particular emphasis on visual space and object perception abilities. Methods: Fifty-three patients with mild cognitive deficits that were eventually diagnosed with probable DLB (MCI-DLB: n = 25 and AD (MCI-AD: n = 28 at a 3-year follow-up were retrospectively studied. At the first visit, the patients underwent cognitive assessment including the Qualitative Scoring Mini Mental State Examination Pentagon Test and the Visual Object and Space Perception Battery. The Neuropsychiatric Inventory Questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS and questionnaires for cognitive fluctuations and sleep disorders were also administered. Results: The best clinical predictor of DLB was the presence of soft extrapyramidal signs (mean UPDRS score: 4.04 ± 5.9 detected in 72% of patients, followed by REM sleep behavior disorder (60% and fluctuations (60%. Wrong performances in the pentagon's number of angles were obtained in 44% of DLB and 3.7% of AD patients and correlated with speed of visual attention. Executive functions, visual attention and visuospatial abilities were worse in DLB, while verbal episodic memory impairment was greater in AD. Deficits in the visual-perceptual domain were present in both MCI-DLB and AD. Conclusions: Poor performance in the pentagon's number of angles is specific of DLB and correlates with speed of visual attention. The dorsal visual stream seems specifically more impaired in MCI-DLB with respect to the ventral visual stream, the latter being involved in both DLB and AD. These cognitive features, associated with subtle extrapyramidal signs, should alert clinicians to a diagnostic hypothesis of DLB.

  17. Evolved atmospheric entry corridor with safety factor

    Science.gov (United States)

    Liang, Zixuan; Ren, Zhang; Li, Qingdong

    2018-02-01

    Atmospheric entry corridors are established in previous research based on the equilibrium glide condition which assumes the flight-path angle to be zero. To get a better understanding of the highly constrained entry flight, an evolved entry corridor that considers the exact flight-path angle is developed in this study. Firstly, the conventional corridor in the altitude vs. velocity plane is extended into a three-dimensional one in the space of altitude, velocity, and flight-path angle. The three-dimensional corridor is generated by a series of constraint boxes. Then, based on a simple mapping method, an evolved two-dimensional entry corridor with safety factor is obtained. The safety factor is defined to describe the flexibility of the flight-path angle for a state within the corridor. Finally, the evolved entry corridor is simulated for the Space Shuttle and the Common Aero Vehicle (CAV) to demonstrate the effectiveness of the corridor generation approach. Compared with the conventional corridor, the evolved corridor is much wider and provides additional information. Therefore, the evolved corridor would benefit more to the entry trajectory design and analysis.

  18. Application of ozone gas for decontamination of nucleoside anticancer drugs.

    Science.gov (United States)

    Tsukamoto, Ayumi; Ishiwata, Shunji; Kajimoto, Asami; Murata, Ryusuke; Kitano, Rika; Inoue, Tomomi; Kotake, Takeshi

    2016-01-01

    Exposure to anticancer drugs is hazardous and may lead to chromosomal abnormalities and spontaneous abortion in healthcare workers. Guidelines recommend surface decontamination and cleaning in order to minimize the occupational exposure to anticancer drugs, although no single process has been found to deactivate all currently available hazardous drugs. Ozone gas is oxidative and a decontaminant for bacteria; its characteristic as a gas has advantages in that it does not need to be wiped off or neutralized after use. The nucleoside anticancer drugs, cytarabine and fluorouracil, were exposed to ozone gas on plates under controlled humidity. The levels of exposed ozone were evaluated using the concentration-time (CT) value, which is the mathematical product of ozone concentration and exposure time. The effects of exposure to ozone on levels of the anticancer drugs were determined by high-performance liquid chromatography (HPLC). The levels of cytarabine decreased with increasing CT value and were not detected beyond 40,000 CT. The decomposition levels of the anticancer drug by ozone were CT-dependent irrespective of the maximum concentration of ozone. Higher humidity in the range from 70 to 90 % accelerated the decomposition of cytarabine and fluorouracil, and neither of the drugs were detected at 90 % humidity after exposure to ozone gas. Ozone gas decomposed these nucleoside anticancer drugs. This is the first report of the applicability of ozone gas as a decontaminator for anticancer drugs.

  19. Interactively Evolving Compositional Sound Synthesis Networks

    DEFF Research Database (Denmark)

    Jónsson, Björn Þór; Hoover, Amy K.; Risi, Sebastian

    2015-01-01

    While the success of electronic music often relies on the uniqueness and quality of selected timbres, many musicians struggle with complicated and expensive equipment and techniques to create their desired sounds. Instead, this paper presents a technique for producing novel timbres that are evolved......, CPPNs can theoretically compute any function and can build on those present in traditional synthesizers (e.g. square, sawtooth, triangle, and sine waves functions) to produce completely novel timbres. Evolved with NeuroEvolution of Augmenting Topologies (NEAT), the aim of this paper is to explore...... the space of potential sounds that can be generated through such compositional sound synthesis networks (CSSNs). To study the effect of evolution on subjective appreciation, participants in a listener study ranked evolved timbres by personal preference, resulting in preferences skewed toward the first...

  20. Quantifying evolvability in small biological networks

    Energy Technology Data Exchange (ETDEWEB)

    Nemenman, Ilya [Los Alamos National Laboratory; Mugler, Andrew [COLUMBIA UNIV; Ziv, Etay [COLUMBIA UNIV; Wiggins, Chris H [COLUMBIA UNIV

    2008-01-01

    The authors introduce a quantitative measure of the capacity of a small biological network to evolve. The measure is applied to a stochastic description of the experimental setup of Guet et al. (Science 2002, 296, pp. 1466), treating chemical inducers as functional inputs to biochemical networks and the expression of a reporter gene as the functional output. The authors take an information-theoretic approach, allowing the system to set parameters that optimise signal processing ability, thus enumerating each network's highest-fidelity functions. All networks studied are highly evolvable by the measure, meaning that change in function has little dependence on change in parameters. Moreover, each network's functions are connected by paths in the parameter space along which information is not significantly lowered, meaning a network may continuously change its functionality without completely losing it along the way. This property further underscores the evolvability of the networks.

  1. Anticancer drugs discovery and development from marine organism.

    Science.gov (United States)

    Chakraborty, Chiranjib; Hsu, Chi-Hsin; Wen, Zhi-Hong; Lin, Chan-Shing

    2009-01-01

    The chemical and biological diversity of the different marine evolutionary group is endless and therefore, this is an amazing resource for the discovery of new anticancer drugs. Comprising 34 of the 36 Phyla of life, marine ecosystems are indeed our last genetic diversity and biotechnological boundary; terrestrial systems possess only 17 Phyla. Sponges, coelenterates and microorganisms are the foremost resources of therapeutic compounds. Algae, echinoderms, tunicates, mollusks, bryozoans are also the sources of anticancer drugs from marine resources. We highlight the past and current status of marine anticancer pharmacology using different marine groups.

  2. Anticancer Drug Combinations, How Far We can Go Through?

    Science.gov (United States)

    Lu, Da-Yong; Chen, En-Hong; Wu, Hong-Ying; Lu, Ting-Ren; Xu, Bin; Ding, Jian

    2017-01-01

    Many clinical cancer therapies are less effective by using one anticancer drug only due to refractory properties of cancer pathogenesis and drug resistance property in advanced cancer patients. A general consensus among clinicians is that anticancer drug cocktail might better control cancer progresses and metastasis than single drug therapeutics in clinical trials. Despite great popularity, the anticancer drug combination dogma has not been established. The complexity of drug combination dogma discovery is more than we can expect now. This article speculates possible routes we can undertake in this matter. The background knowledge of drug combination therapy presently practiced and possible future landscapes and drawbacks of cancer drug combinative therapies are highlighted.

  3. How the first biopolymers could have evolved.

    Science.gov (United States)

    Abkevich, V I; Gutin, A M; Shakhnovich, E I

    1996-01-01

    In this work, we discuss a possible origin of the first biopolymers with stable unique structures. We suggest that at the prebiotic stage of evolution, long organic polymers had to be compact to avoid hydrolysis and had to be soluble and thus must not be exceedingly hydrophobic. We present an algorithm that generates such sequences for model proteins. The evolved sequences turn out to have a stable unique structure, into which they quickly fold. This result illustrates the idea that the unique three-dimensional native structures of first biopolymers could have evolved as a side effect of nonspecific physicochemical factors acting at the prebiotic stage of evolution. PMID:8570645

  4. Evolving Intelligent Systems Methodology and Applications

    CERN Document Server

    Angelov, Plamen; Kasabov, Nik

    2010-01-01

    From theory to techniques, the first all-in-one resource for EIS. There is a clear demand in advanced process industries, defense, and Internet and communication (VoIP) applications for intelligent yet adaptive/evolving systems. Evolving Intelligent Systems is the first self- contained volume that covers this newly established concept in its entirety, from a systematic methodology to case studies to industrial applications. Featuring chapters written by leading world experts, it addresses the progress, trends, and major achievements in this emerging research field, with a strong emphasis on th

  5. Anticancer activity of Aristolochia ringens Vahl. (Aristolochiaceae

    Directory of Open Access Journals (Sweden)

    Abidemi James Akindele

    2015-01-01

    Full Text Available Cancer is a leading cause of death worldwide and sustained focus is on the discovery and development of newer and better tolerated anticancer drugs especially from plants. The sulforhodamine B (SRB in vitro cytotoxicity assay, sarcoma-180 (S-180 ascites and solid tumor, and L1210 lymphoid leukemia in vivo models were used to investigate the anticancer activity of root extracts of Aristolochia ringens Vahl. (Aristolochiaceae; 馬兜鈴 mǎ dōu líng. AR-A001 (IC50 values of 20 μg/mL, 22 μg/mL, 3 μg/mL, and 24 μg/mL for A549, HCT-116, PC3, and THP-1 cell lines, respectively, and AR-A004 (IC50 values of 26 μg/mL, 19.5 μg/mL, 12 μg/mL, 28 μg/mL, 30 μg/mL, and 22 μg/mL for A549, HCT-116, PC3, A431, HeLa, and THP-1, respectively, were observed to be significantly active in vitro. Potency was highest with AR-A001 and AR-A004 for PC3 with IC50 values of 3 μg/mL and 12 μg/mL, respectively. AR-A001 and AR-A004 produced significant (p < 0.05–0.001 dose-dependent inhibition of tumor growth in the S-180 ascites model with peak effects produced at the highest dose of 120 mg/kg. Inhibition values were 79.51% and 89.98% for AR-A001 and AR-A004, respectively. In the S-180 solid tumor model, the inhibition of tumor growth was 29.45% and 50.50% for AR-A001 (120 mg/kg and AR-A004 (110 mg/kg, respectively, compared to 50.18% for 5-fluorouracil (5-FU; 20 mg/kg. AR-A001 and AR-A004 were also significantly active in the leukemia model with 211.11% and 155.56% increase in mean survival time (MST compared to a value of 211.11% for 5-FU. In conclusion, the ethanolic (AR-A001 and dichloromethane:methanol (AR-A004 root extracts of AR possess significant anticancer activities in vitro and in vivo.

  6. Early constraints in sexual dimorphism: survival benefits of feminized phenotypes.

    Science.gov (United States)

    López-Rull, I; Vergara, P; Martínez-Padilla, J; Fargallo, J A

    2016-02-01

    Sexual dimorphism (SD) has evolved in response to selection pressures that differ between sexes. Since such pressures change across an individual's life, SD may vary within age classes. Yet, little is known about how selection on early phenotypes may drive the final SD observed in adults. In many dimorphic species, juveniles resemble adult females rather than adult males, meaning that out of the selective pressures established by sexual selection feminized phenotypes may be adaptive. If true, fitness benefits of early female-like phenotypes may constrain the expression of male phenotypes in adulthood. Using the common kestrel Falco tinnunculus as a study model, we evaluated the fitness advantages of expressing more feminized phenotypes at youth. Although more similar to adult females than to adult males, common kestrel fledglings are still sexually dimorphic in size and coloration. Integrating morphological and chromatic variables, we analysed the phenotypic divergence between sexes as a measure of how much each individual looks like the sex to which it belongs (phenotypic sexual resemblance, PSR). We then tested the fitness benefits associated with PSR by means of the probability of recruitment in the population. We found a significant interaction between PSR and sex, showing that in both sexes more feminized phenotypes recruited more into the population than less feminized phenotypes. Moreover, males showed lower PSR than females and a higher proportion of incorrect sex classifications. These findings suggest that the mechanisms in males devoted to resembling female phenotypes in youth, due to a trend to increase fitness through more feminized phenotypes, may provide a mechanism to constrain the SD in adulthood. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  7. Adaptive developmental plasticity: what is it, how can we recognize it and when can it evolve?

    Science.gov (United States)

    Nettle, Daniel; Bateson, Melissa

    2015-08-07

    Developmental plasticity describes situations where a specific input during an individual's development produces a lasting alteration in phenotype. Some instances of developmental plasticity may be adaptive, meaning that the tendency to produce the phenotype conditional on having experienced the developmental input has been under positive selection. We discuss the necessary assumptions and predictions of hypotheses concerning adaptive developmental plasticity (ADP) and develop guidelines for how to test empirically whether a particular example is adaptive. Central to our analysis is the distinction between two kinds of ADP: informational, where the developmental input provides information about the future environment, and somatic state-based, where the developmental input enduringly alters some aspect of the individual's somatic state. Both types are likely to exist in nature, but evolve under different conditions. In all cases of ADP, the expected fitness of individuals who experience the input and develop the phenotype should be higher than that of those who experience the input and do not develop the phenotype, while the expected fitness of those who do not experience the input and do not develop the phenotype should be higher than those who do not experience the input and do develop the phenotype. We describe ancillary predictions that are specific to just one of the two types of ADP and thus distinguish between them. © 2015 The Author(s).

  8. Synthesis and Evaluation of New Pyrazoline Derivatives as Potential Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Muhammed Karabacak

    2015-10-01

    Full Text Available New pyrazoline derivatives were synthesized and evaluated for their cytotoxic effects on AsPC-1 human pancreatic adenocarcinoma, U87 and U251 human glioblastoma cell lines. 1-[((5-(4-Methylphenyl-1,3,4-oxadiazol-2-ylthioacetyl]-3-(2-thienyl-5-(4-chlorophenyl-2-pyrazoline (11 was found to be the most effective anticancer agent against AsPC-1 and U251 cell lines, with IC50 values of 16.8 µM and 11.9 µM, respectively. Tumor selectivity of compound 11 was clearly seen between Jurkat human leukemic T-cell line and human peripheral blood mononuclear cells (PBMC. Due to its promising anticancer activity, compound 11 was chosen for apoptosis/necrosis evaluation and DNA-cleavage analysis in U251 cells. Compound 11-treated U251 cells exhibited apoptotic phenotype at low concentration (1.5 µM. DNA-cleaving efficiency of this ligand was more significant than cisplatin and was clearly enhanced by Fe(II-H2O2-ascorbic acid systems. This result pointed out the relationship between the DNA cleavage and the cell death.

  9. The molecular aspects of personalized anticancer treatment

    OpenAIRE

    Cherdyntseva, N.; Litviakov, N.; Ivanova, F.; Denisov, E.; P. Gervas; Cherdyntsev, Evgeny Sergeevich

    2016-01-01

    Only 25% of cancer patients, on average, benefit from therapy. Even in the cases of complete clinical response the tumor progression is an event of high level expectation. The main reasons for tumor progression are: intratumor heterogeneity resulted from clonal evolution, drug resistance, and tumor-promoting microenvironment. The reprogramming of microenvironmental stromal-inflammatory components is expected to allow tumor phenotype reversion. So, to find the new effective markers of tumor pr...

  10. Preface: evolving rotifers, evolving science: Proceedings of the XIV International Rotifer Symposium

    Czech Academy of Sciences Publication Activity Database

    Devetter, Miloslav; Fontaneto, D.; Jersabek, Ch.D.; Welch, D.B.M.; May, L.; Walsh, E.J.

    2017-01-01

    Roč. 796, č. 1 (2017), s. 1-6 ISSN 0018-8158 Institutional support: RVO:60077344 Keywords : evolving rotifers * 14th International Rotifer Symposium * evolving science Subject RIV: EG - Zoology OBOR OECD: Zoology Impact factor: 2.056, year: 2016

  11. "(Not) all (dead) things share the same breath": identification of cell death mechanisms in anticancer therapy.

    Science.gov (United States)

    Rello-Varona, Santiago; Herrero-Martín, David; López-Alemany, Roser; Muñoz-Pinedo, Cristina; Tirado, Oscar M

    2015-03-15

    During the last decades, the knowledge of cell death mechanisms involved in anticancer therapy has grown exponentially. However, in many studies, cell death is still described in an incomplete manner. The frequent use of indirect proliferation assays, unspecific probes, or bulk analyses leads too often to misunderstandings regarding cell death events. There is a trend to focus on molecular or genetic regulations of cell demise without a proper characterization of the phenotype that is the object of this study. Sometimes, cancer researchers can feel overwhelmed or confused when faced with such a corpus of detailed insights, nomenclature rules, and debates about the accuracy of a particular probe or assay. On the basis of the information available, we propose a simple guide to distinguish forms of cell death in experimental settings using cancer cell lines. ©2015 American Association for Cancer Research.

  12. Bisphosphonate anticancer activity in prostate cancer and other genitourinary cancers.

    NARCIS (Netherlands)

    Saad, F.; Mulders, P.F.A.

    2012-01-01

    Anticancer therapies have traditionally been targeted directly against cancer cell growth. However, newer treatment strategies also target the microenvironment that supports metastatic cancer cell growth. Bisphosphonates are the standard of care for maintaining bone health in patients with bone

  13. Supramolecular "Trojan Horse" for Nuclear Delivery of Dual Anticancer Drugs.

    Science.gov (United States)

    Cai, Yanbin; Shen, Haosheng; Zhan, Jie; Lin, Mingliang; Dai, Liuhan; Ren, Chunhua; Shi, Yang; Liu, Jianfeng; Gao, Jie; Yang, Zhimou

    2017-03-01

    Nuclear delivery and accumulation are very important for many anticancer drugs that interact with DNA or its associated enzymes in the nucleus. However, it is very difficult for neutrally and negatively charged anticancer drugs such as 10-hydroxycamptothecine (HCPT). Here we report a simple strategy to construct supramolecular nanomedicines for nuclear delivery of dual synergistic anticancer drugs. Our strategy utilizes the coassembly of a negatively charged HCPT-peptide amphiphile and the positively charged cisplatin. The resulting nanomaterials behave as the "Trojan Horse" that transported soldiers (anticancer drugs) across the walls of the castle (cell and nucleus membranes). Therefore, they show improved inhibition capacity to cancer cells including the drug resistant cancer cell and promote the synergistic tumor suppression property in vivo. We envision that our strategy of constructing nanomaterials by metal chelation would offer new opportunities to develop nanomedicines for combination chemotherapy.

  14. Anticancer potential of bioactive peptides from animal sources (Review).

    Science.gov (United States)

    Wang, Linghong; Dong, Chao; Li, Xian; Han, Wenyan; Su, Xiulan

    2017-08-01

    Cancer is the most common cause of human death worldwide. Conventional anticancer therapies, including chemotherapy and radiation, are associated with severe side effects and toxicities as well as low specificity. Peptides are rapidly being developed as potential anticancer agents that specifically target cancer cells and are less toxic to normal tissues, thus making them a better alternative for the prevention and management of cancer. Recent research has focused on anticancer peptides from natural animal sources, such as terrestrial mammals, marine animals, amphibians, and animal venoms. However, the mode of action by which bioactive peptides inhibit the proliferation of cancer cells remains unclear. In this review, we present the animal sources from which bioactive peptides with anticancer activity are derived and discuss multiple proposed mechanisms by which these peptides exert cytotoxic effects against cancer cells.

  15. Study of the anticancer efficacy of virus Langat

    OpenAIRE

    FORNBAUMOVÁ, Iva

    2011-01-01

    The aim of this thesis was to study the efficacy of Langat virus as an oncolytic virus. We subsequently tried to increase its anticancer influence on the basis of combination with some imunomodulators.

  16. Thermal and Evolved-Gas Analyzer Illustration

    Science.gov (United States)

    2008-01-01

    This is a computer-aided drawing of the Thermal and Evolved-Gas Analyzer, or TEGA, on NASA's Phoenix Mars Lander. The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  17. Apollo 16 Evolved Lithology Sodic Ferrogabbro

    Science.gov (United States)

    Zeigler, Ryan; Jolliff, B. L.; Korotev, R. L.

    2014-01-01

    Evolved lunar igneous lithologies, often referred to as the alkali suite, are a minor but important component of the lunar crust. These evolved samples are incompatible-element rich samples, and are, not surprisingly, most common in the Apollo sites in (or near) the incompatible-element rich region of the Moon known as the Procellarum KREEP Terrane (PKT). The most commonly occurring lithologies are granites (A12, A14, A15, A17), monzogabbro (A14, A15), alkali anorthosites (A12, A14), and KREEP basalts (A15, A17). The Feldspathic Highlands Terrane is not entirely devoid of evolved lithologies, and rare clasts of alkali gabbronorite and sodic ferrogabbro (SFG) have been identified in Apollo 16 station 11 breccias 67915 and 67016. Curiously, nearly all pristine evolved lithologies have been found as small clasts or soil particles, exceptions being KREEP basalts 15382/6 and granitic sample 12013 (which is itself a breccia). Here we reexamine the petrography and geochemistry of two SFG-like particles found in a survey of Apollo 16 2-4 mm particles from the Cayley Plains 62283,7-15 and 62243,10-3 (hereafter 7-15 and 10-3 respectively). We will compare these to previously reported SFG samples, including recent analyses on the type specimen of SFG from lunar breccia 67915.

  18. Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes

    OpenAIRE

    Yo-Han Han; Ji-Ye Kee; Dae-Seung Kim; Jeong-geon Mun; Mi-Young Jeong; Sang-Hyun Park; Byung-Min Choi; Sung-Joo Park; Hyun-Jung Kim; Jae-Young Um; Seung-Heon Hong

    2016-01-01

    Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mese...

  19. Ethnopharmacological and bioactivity guided investigation of five TCM anticancer herbs.

    Science.gov (United States)

    Meng, Qiu-Xia; Roubin, Rebecca H; Hanrahan, Jane R

    2013-06-21

    Five herbs, Curcuma longa L. (CL), Scutellaria baicalensis Georgi (SBC), Scutellaria barbata D. Don (SBB), Hedyotis diffusa Willd. (HD) and Solanum nigrum L. (SN), are often prescribed in the polyherbal formulas for cancer treatment by traditional Chinese medicine (TCM) practitioners. The purpose of the present study was to identify important anticancer herbs used in TCM and carry out bioactivity-directed fractionation and isolation (BDFI) using six cancer cell lines as well as peripheral blood mononuclear cells (PBMCs), to identify constituents with anticancer activity but devoid of toxic effects against healthy immune cells. Of 243 document anticancer TCM treatments, 199 anticancer TCM herbs were ranked by the number of literature reports for each herb. Five herbs were identified from the top 50 ranked herbs by at least two out of three TCM practitioners as frequently used in the TCM treatment of cancer. BDFI using MTS assay was applied to determine the active anticancer extracts, fractions, and finally discrete compounds. Five herbs were selected for study of their anticancer activities. The extracts of Curcuma longa L., Scutellaria barbata D. Don, and Hedyotis diffusa showed antiproliferative activity to various extents, extracts of Scutellaria baicalensis Georgi and Solanum nigrum L. showed little anticancer activity. Seven out of the 21 fractions obtained from Hedyotis diffusa Willd. showed anticancer activity. One new compound, ethyl 13(2) (S)-hydroxy-chlorophyllide a(1), along with 10 known compounds, i.e. 2-methyl-3-methoxyanthraquinone (2), 2-hydroxymethylanthraquinone(3), 2-hydroxy-3-methylanthraquinone(4), 2-hydroxymethy-1-hydroxyanthraquinone(5), 1-methoxy-2-hydroxyanthraquinone(6), 2-hydroxy-3-methyl-1-methoxyanthraquinone (7), oleanolic acid (8), ursolic acid (9), stigmasterol (10) and docosanoic acid (11), were isolated and identified. Compounds 2-6, 8 and 9 dose-dependently inhibited the cell viability of cancer cells within a concentration range

  20. Natural products as leads to anticancer drugs.

    Science.gov (United States)

    Gordaliza, M

    2007-12-01

    Throughout history, natural products have afforded a rich source of compounds that have found many applications in the fields of medicine, pharmacy and biology. Within the sphere of cancer, a number of important new commercialised drugs have been obtained from natural sources, by structural modification of natural compounds, or by the synthesis of new compounds, designed following a natural compound as model. The search for improved cytotoxic agents continues to be an important line in the discovery of modern anticancer drugs. The huge structural diversity of natural compounds and their bioactivity potential have meant that several products isolated from plants, marine flora and microorganisms can serve as "lead" compounds for improvement of their therapeutic potential by molecular modification. Additionally, semisynthesis processes of new compounds, obtained by molecular modification of the functional groups of lead compounds, are able to generate structural analogues with greater pharmacological activity and with fewer side effects. These processes, complemented with high-throughput screening protocols, combinatorial chemistry, computational chemistry and bioinformatics are able to afford compounds that are far more efficient than those currently used in clinical practice. Combinatorial biosynthesis is also applied for the modification of natural microbial products. Likewise, advances in genomics and the advent of biotechnology have improved both the discovery and production of new natural compounds.

  1. Anticancer Activity of Sea Cucumber Triterpene Glycosides

    Science.gov (United States)

    Aminin, Dmitry L.; Menchinskaya, Ekaterina S.; Pisliagin, Evgeny A.; Silchenko, Alexandra S.; Avilov, Sergey A.; Kalinin, Vladimir I.

    2015-01-01

    Triterpene glycosides are characteristic secondary metabolites of sea cucumbers (Holothurioidea, Echinodermata). They have hemolytic, cytotoxic, antifungal, and other biological activities caused by membranotropic action. These natural products suppress the proliferation of various human tumor cell lines in vitro and, more importantly, intraperitoneal administration in rodents of solutions of some sea cucumber triterpene glycosides significantly reduces both tumor burden and metastasis. The anticancer molecular mechanisms include the induction of tumor cell apoptosis through the activation of intracellular caspase cell death pathways, arrest of the cell cycle at S or G2/M phases, influence on nuclear factors, NF-κB, and up-down regulation of certain cellular receptors and enzymes participating in cancerogenesis, such as EGFR (epidermal growth factor receptor), Akt (protein kinase B), ERK (extracellular signal-regulated kinases), FAK (focal adhesion kinase), MMP-9 (matrix metalloproteinase-9) and others. Administration of some glycosides leads to a reduction of cancer cell adhesion, suppression of cell migration and tube formation in those cells, suppression of angiogenesis, inhibition of cell proliferation, colony formation and tumor invasion. As a result, marked growth inhibition of tumors occurs in vitro and in vivo. Some holothurian triterpene glycosides have the potential to be used as P-gp mediated MDR reversal agents in combined therapy with standard cytostatics. PMID:25756523

  2. PP2A-Mediated Anticancer Therapy

    Directory of Open Access Journals (Sweden)

    Weibo Chen

    2013-01-01

    Full Text Available PP2A is a family of mammalian serine/threonine phosphatases that is involved in the control of many cellular functions including protein synthesis, cellular signaling, cell cycle determination, apoptosis, metabolism, and stress responses through the negative regulation of signaling pathways initiated by protein kinases. Rapid progress is being made in the understanding of PP2A complex and its functions. Emerging studies have correlated changes in PP2A with human diseases, especially cancer. PP2A is comprised of 3 subunits: a catalytic subunit, a scaffolding subunit, and a regulatory subunit. The alternations of the subunits have been shown to be in association with many human malignancies. Therapeutic agents targeting PP2A inhibitors or activating PP2A directly have shed light on the therapy of cancers. This review focuses on PP2A structure, cancer-associated mutations, and the targeting of PP2A-related molecules to restore or reactivate PP2A in anticancer therapy, especially in digestive system cancer therapy.

  3. Potential Anticancer Properties of Grape Antioxidants

    Directory of Open Access Journals (Sweden)

    Kequan Zhou

    2012-01-01

    Full Text Available Dietary intake of foods rich in antioxidant properties is suggested to be cancer protective. Foods rich in antioxidant properties include grape (Vitis vinifera, one of the world’s largest fruit crops and most commonly consumed fruits in the world. The composition and cancer-protective effects of major phenolic antioxidants in grape skin and seed extracts are discussed in this review. Grape skin and seed extracts exert strong free radical scavenging and chelating activities and inhibit lipid oxidation in various food and cell models in vitro. The use of grape antioxidants are promising against a broad range of cancer cells by targeting epidermal growth factor receptor (EGFR and its downstream pathways, inhibiting over-expression of COX-2 and prostaglandin E2 receptors, or modifying estrogen receptor pathways, resulting in cell cycle arrest and apoptosis. Interestingly, some of these activities were also demonstrated in animal models. However, in vivo studies have demonstrated inconsistent antioxidant efficacy. Nonetheless, a growing body of evidence from human clinical trials has demonstrated that consumption of grape, wine and grape juice exerts many health-promoting and possible anti-cancer effects. Thus, grape skin and seed extracts have great potential in cancer prevention and further investigation into this exciting field is warranted.

  4. Indigofera suffruticosa: An Alternative Anticancer Therapy

    Directory of Open Access Journals (Sweden)

    Jeymesson Raphael Cardoso Vieira

    2007-01-01

    Full Text Available Indigofera suffruticosa Mill (Fabeceae occurs in the Northeast countryside and has intensive popular use in the treatment of infectious, inflammatory and other processes. The main aim of the present work was to investigate the cytotoxic and antitumor effects of aqueous extracts of leaves of I. suffruticosa obtained by infusion and maceration as well as to evaluate the toxicological properties. Aqueous extracts did not exhibit cytotoxicity against HEp-2 (human epidermoid cancer cell cell lines by MTT method. From the aqueous extract by infusion, the toxicological assay showed low order of toxicity. The antitumor effect of aqueous extracts by infusion (64.53% and maceration (62.62% against sarcoma 180 in mice at a dose of 50 mg kg−1 (intraperitoneally, based on low order of toxicity was comparable to the control group, which showed 100% development. Considering the low order of toxicity and that it is highly effective in inhibiting growth of solid tumors, the aqueous extracts of leaves of I. suffruticosa may be used as an alternative anticancer agent.

  5. NSAIDs: Old Drugs Reveal New Anticancer Targets

    Directory of Open Access Journals (Sweden)

    Gary A. Piazza

    2010-05-01

    Full Text Available There is compelling evidence that nonsteroidal anti-inflammatory drugs (NSAIDs and cyclooxygenase-2 selective inhibitors have antineoplastic activity, but toxicity from cyclooxygenase (COX inhibition and the suppression of physiologically important prostaglandins limits their use for cancer chemoprevention. Previous studies as reviewed here suggest that the mechanism for their anticancer properties does not require COX inhibition, but instead involves an off-target effect. In support of this possibility, recent molecular modeling studies have shown that the NSAID sulindac can be chemically modified to selectively design out its COX-1 and COX-2 inhibitory activity. Unexpectedly, certain derivatives that were synthesized based on in silico modeling displayed increased potency to inhibit tumor cell growth. Other experiments have shown that sulindac can inhibit phosphodiesterase to increase intracellular cyclic GMP levels and that this activity is closely associated with its ability to selectively induce apoptosis of tumor cells. Together, these studies suggest that COX-independent mechanisms can be targeted to develop safer and more efficacious drugs for cancer chemoprevention.

  6. Potential Anticancer Properties of Grape Antioxidants

    Science.gov (United States)

    Zhou, Kequan; Raffoul, Julian J.

    2012-01-01

    Dietary intake of foods rich in antioxidant properties is suggested to be cancer protective. Foods rich in antioxidant properties include grape (Vitis vinifera), one of the world's largest fruit crops and most commonly consumed fruits in the world. The composition and cancer-protective effects of major phenolic antioxidants in grape skin and seed extracts are discussed in this review. Grape skin and seed extracts exert strong free radical scavenging and chelating activities and inhibit lipid oxidation in various food and cell models in vitro. The use of grape antioxidants are promising against a broad range of cancer cells by targeting epidermal growth factor receptor (EGFR) and its downstream pathways, inhibiting over-expression of COX-2 and prostaglandin E2 receptors, or modifying estrogen receptor pathways, resulting in cell cycle arrest and apoptosis. Interestingly, some of these activities were also demonstrated in animal models. However, in vivo studies have demonstrated inconsistent antioxidant efficacy. Nonetheless, a growing body of evidence from human clinical trials has demonstrated that consumption of grape, wine and grape juice exerts many health-promoting and possible anti-cancer effects. Thus, grape skin and seed extracts have great potential in cancer prevention and further investigation into this exciting field is warranted. PMID:22919383

  7. Anticancer Activity of Sea Cucumber Triterpene Glycosides

    Directory of Open Access Journals (Sweden)

    Dmitry L. Aminin

    2015-03-01

    Full Text Available Triterpene glycosides are characteristic secondary metabolites of sea cucumbers (Holothurioidea, Echinodermata. They have hemolytic, cytotoxic, antifungal, and other biological activities caused by membranotropic action. These natural products suppress the proliferation of various human tumor cell lines in vitro and, more importantly, intraperitoneal administration in rodents of solutions of some sea cucumber triterpene glycosides significantly reduces both tumor burden and metastasis. The anticancer molecular mechanisms include the induction of tumor cell apoptosis through the activation of intracellular caspase cell death pathways, arrest of the cell cycle at S or G2/M phases, influence on nuclear factors, NF-κB, and up-down regulation of certain cellular receptors and enzymes participating in cancerogenesis, such as EGFR (epidermal growth factor receptor, Akt (protein kinase B, ERK (extracellular signal-regulated kinases, FAK (focal adhesion kinase, MMP-9 (matrix metalloproteinase-9 and others. Administration of some glycosides leads to a reduction of cancer cell adhesion, suppression of cell migration and tube formation in those cells, suppression of angiogenesis, inhibition of cell proliferation, colony formation and tumor invasion. As a result, marked growth inhibition of tumors occurs in vitro and in vivo. Some holothurian triterpene glycosides have the potential to be used as P-gp mediated MDR reversal agents in combined therapy with standard cytostatics.

  8. The retinoid anticancer signal: mechanisms of target gene regulation

    OpenAIRE

    Liu, T.; Bohlken, A; Kuljaca, S; Lee, M.; Nguyen, T; S.; Smith; Cheung, B; Norris, M D; Haber, M; Holloway, A.J.; Bowtell, D D L; Marshall, G M

    2005-01-01

    Retinoids induce growth arrest, differentiation, and cell death in many cancer cell types. One factor determining the sensitivity or resistance to the retinoid anticancer signal is the transcriptional response of retinoid-regulated target genes in cancer cells. We used cDNA microarray to identify 31 retinoid-regulated target genes shared by two retinoid-sensitive neuroblastoma cell lines, and then sought to determine the relevance of the target gene responses to the retinoid anticancer signal...

  9. CNS Anticancer Drug Discovery and Development Conference White Paper

    OpenAIRE

    Victor A Levin; Tonge, Peter J.; Gallo, James M.; Birtwistle, Marc R.; Dar, Arvin C.; Iavarone, Antonio; Paddison, Patrick J.; Heffron, Timothy P.; Elmquist, William F.; Lachowicz, Jean E.; Johnson, Ted W.; White, Forest M.; Sul, Joohee; Smith, Quentin R.; Shen, Wang

    2015-01-01

    Following the first CNS Anticancer Drug Discovery and Development Conference, the speakers from the first 4 sessions and organizers of the conference created this White Paper hoping to stimulate more and better CNS anticancer drug discovery and development. The first part of the White Paper reviews, comments, and, in some cases, expands on the 4 session areas critical to new drug development: pharmacological challenges, recent drug approaches, drug targets and discovery, and clinical paths. F...

  10. Alkaloids Isolated from Natural Herbs as the Anticancer Agents

    OpenAIRE

    Lu, Jin-Jian; Bao, Jiao-Lin; Chen, Xiu-Ping; Huang, Min; Wang, Yi-Tao

    2012-01-01

    Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation and antimetastasis effects on various types of cancers both in vitro and in vivo. Alkaloids, such as camptothecin and vinblastine, have already been successfully developed into anticancer drugs. This paper focuses on the naturally derived alkaloids with prospective anticancer properties, such as berberine, evodiamine, matrine, pi...

  11. Anti-cancer natural products isolated from chinese medicinal herbs

    OpenAIRE

    Wu Guosheng; Chen Meiwan; Li Yingbo; Huang Mingqing; Lu Jinjian; Tan Wen; Gong Jian; Zhong Zhangfeng; Xu Zengtao; Dang Yuanye; Guo Jiajie; Chen Xiuping; Wang Yitao

    2011-01-01

    Abstract In recent years, a number of natural products isolated from Chinese herbs have been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, retard metastasis and enhance chemotherapy, exhibiting anti-cancer potential both in vitro and in vivo. This article summarizes recent advances in in vitro and in vivo research on the anti-cancer effects and related mechanisms of some promising natural products. These natural products are also reviewed for their therapeutic poten...

  12. A Systematic Review of Iran's Medicinal Plants With Anticancer Effects.

    Science.gov (United States)

    Asadi-Samani, Majid; Kooti, Wesam; Aslani, Elahe; Shirzad, Hedayatollah

    2016-04-01

    Increase in cases of various cancers has encouraged the researchers to discover novel, more effective drugs from plant sources. This study is a review of medicinal plants in Iran with already investigated anticancer effects on various cell lines. Thirty-six medicinal plants alongside their products with anticancer effects as well as the most important plant compounds responsible for the plants' anticancer effect were introduced. Phenolic and alkaloid compounds were demonstrated to have anticancer effects on various cancers in most studies. The plants and their active compounds exerted anticancer effects by removing free radicals and antioxidant effects, cell cycle arrest, induction of apoptosis, and inhibition of angiogenesis. The investigated plants in Iran contain the compounds that are able to contribute effectively to fighting cancer cells. Therefore, the extract and active compounds of the medicinal plants introduced in this review article could open a way to conduct clinical trials on cancer and greatly help researchers and pharmacists develop new anticancer drugs. © The Author(s) 2015.

  13. Canonical and new generation anticancer drugs also target energy metabolism.

    Science.gov (United States)

    Rodríguez-Enríquez, Sara; Gallardo-Pérez, Juan Carlos; Hernández-Reséndiz, Ileana; Marín-Hernández, Alvaro; Pacheco-Velázquez, Silvia C; López-Ramírez, Sayra Y; Rumjanek, Franklin D; Moreno-Sánchez, Rafael

    2014-07-01

    Significant efforts have been made for the development of new anticancer drugs (protein kinase or proteasome inhibitors, monoclonal humanized antibodies) with presumably low or negligible side effects and high specificity. However, an in-depth analysis of the side effects of several currently used canonical (platin-based drugs, taxanes, anthracyclines, etoposides, antimetabolites) and new generation anticancer drugs as the first line of clinical treatment reveals significant perturbation of glycolysis and oxidative phosphorylation. Canonical and new generation drug side effects include decreased (1) intracellular ATP levels, (2) glycolytic/mitochondrial enzyme/transporter activities and/or (3) mitochondrial electrical membrane potentials. Furthermore, the anti-proliferative effects of these drugs are markedly attenuated in tumor rho (0) cells, in which functional mitochondria are absent; in addition, several anticancer drugs directly interact with isolated mitochondria affecting their functions. Therefore, several anticancer drugs also target the energy metabolism, and hence, the documented inhibitory effect of anticancer drugs on cancer growth should also be linked to the blocking of ATP supply pathways. These often overlooked effects of canonical and new generation anticancer drugs emphasize the role of energy metabolism in maintaining cancer cells viable and its targeting as a complementary and successful strategy for cancer treatment.

  14. Glutathione-s-transferase modified electrodes for detecting anticancer drugs.

    Science.gov (United States)

    Materon, Elsa M; Jimmy Huang, Po-Jung; Wong, Ademar; Pupim Ferreira, Antonio A; Sotomayor, Maria Del Pilar Taboada; Liu, Juewen

    2014-08-15

    With the fast growth of cancer research, new analytical methods are needed to measure anticancer drugs. This is usually accomplished by using sophisticated analytical instruments. Biosensors are attractive candidates for measuring anticancer drugs, but currently few biosensors can achieve this goal. In particular, it is challenging to have a general method to monitor various types of anticancer drugs with different structures. In this work, a biosensor was developed to detect anticancer drugs by modifying carbon paste electrodes with glutathione-s-transferase (GST) enzymes. GST is widely studied in the metabolism of xenobiotics and is a major contributing factor in resistance to anticancer drugs. The measurement of anticancer drugs is based on competition between 1-chloro-2,4-dinitrobenzene (CDNB) and the drugs for the GST enzyme in the electrochemical potential at 0.1V vs. Ag/AgCl by square wave voltammetry (SWV) or using a colorimetric method. The sensor shows a detection limit of 8.8μM cisplatin and exhibits relatively long life time in daily measurements. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. A possible molecular metric for biological evolvability

    Indian Academy of Sciences (India)

    Proteins manifest themselves as phenotypic traits, retained or lost in living systems via evolutionary pressures. Simply put, survival is essentially the ability of a living system to synthesize a functional protein that allows for a response to environmental perturbations (adaptation). Loss of functional proteins leads to extinction.

  16. Down Syndrome: Cognitive Phenotype

    Science.gov (United States)

    Silverman, Wayne

    2007-01-01

    Down syndrome is the most prevalent cause of intellectual impairment associated with a genetic anomaly, in this case, trisomy of chromosome 21. It affects both physical and cognitive development and produces a characteristic phenotype, although affected individuals vary considerably with respect to severity of specific impairments. Studies…

  17. The DFNA10 phenotype.

    NARCIS (Netherlands)

    Leenheer, E. de; Huygen, P.L.M.; Wayne, S.; Smith, R.J.H.; Cremers, C.W.R.J.

    2001-01-01

    We present a detailed analysis of the DFNA10 phenotype based on data from 25 hearing-impaired persons coming from a large American pedigree segregating for deafness at the DFNA10 locus (chromosome 6q22.3-23.2). Cross-sectional analysis of air conduction threshold-on-age data from all available

  18. COPD: Definition and Phenotypes

    DEFF Research Database (Denmark)

    Vestbo, J.

    2014-01-01

    particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. The evolution of this definition and the diagnostic criteria currently in use are discussed. COPD is increasingly divided in subgroups or phenotypes based on specific features and association...

  19. Anticancer activity of newly synthesized azaphenothiazines from NCI's anticancer screening bank.

    Science.gov (United States)

    Pluta, Krystian; Jeleń, Małgorzata; Morak-Młodawska, Beata; Zimecki, Michał; Artym, Jolanta; Kocieba, Maja

    2010-01-01

    The activity of the newly synthesized azaphenothiazines: tricyclic 10-substituted dipyridothiazines 1-9, pentacyclic 6-substituted diquinothiazines 10-22 and hexacyclic diquinothiazinium salt 23 was tested on 55-60 in vitro cell lines. The cell lines included nine types of cancer: leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer (National Cancer Institute, Bethesda, MD, USA). The features of the chemical substituent at the thiazine nitrogen atom confer the anticancer activity of diquinothiazines 10-23. Unexpectedly, the most active of the dipyridothiazines 1-9 was the unsubstituted compound 1 (the substituent is a hydrogen atom). The most cytotoxic compound was the half-mustard derivative 18. The GI(50) value of this compound was -7.06 (corresponding to 40 ng/ml) when tested on the melanoma cell line SK-MEL-5 and -6.0 - -6.62 using cell lines from various cancers including: leukemia (CCRF-CEM), the MOLT-4 cell line, colon cancer (HCT-116), central nervous system cancer (SNB-75 and SF-295), prostate cancer (PC-3), non-small cell lung cancer (NCI-H460 and HOP-92), ovarian cancer (IGROV1 and OVCAR-4) and breast cancer (MDA-MB-460). The ethylene group in the aminoalkylazaphenothiazines is as a good linker and is similar to the propylene and butylene linkers in aminoalkylphenothiazines. To our knowledge, this is the first demonstration of significant azaphenothiazine anticancer activity.

  20. From antimicrobial to anticancer peptides. A review.

    Directory of Open Access Journals (Sweden)

    Diana eGaspar

    2013-10-01

    Full Text Available Antimicrobial peptides (AMPs are part of the innate immune defense mechanism of many organisms. Although AMPs have been essentially studied and developed as potential alternatives for fighting infectious diseases, their use as anticancer peptides (ACPs in cancer therapy either alone or in combination with other conventional drugs has been regarded as a therapeutic strategy to explore. As human cancer remains a cause of high morbidity and mortality worldwide, an urgent need of new, selective and more efficient drugs is evident. Even though ACPs are expected to be selective towards tumor cells without impairing the normal body physiological functions, the development of a selective ACP has been a challenge. It is not yet possible to predict antitumor activity based on ACPs structures. ACPs are unique molecules when compared to the actual chemotherapeutic arsenal available for cancer treatment and display a variety of modes of action which in some types of cancer seem to co-exist. Regardless the debate surrounding the definition of structure-activity relationships for ACPs, great effort has been invested in ACP design and the challenge of improving effective killing of tumor cells remains. As detailed studies on ACPs mechanisms of action are crucial for optimizing drug development, in this review we provide an overview of the literature concerning peptides’ structure, modes of action, selectivity and efficacy and also summarize some of the many ACPs studied and/or developed for targeting different solid and hematologic malignancies with special emphasis on the first group. Strategies described for drug development and for increasing peptide selectivity towards specific cells while reducing toxicity are also discussed.

  1. Use of proteasome inhibitors in anticancer therapy

    Directory of Open Access Journals (Sweden)

    Sara M. Schmitt

    2011-10-01

    Full Text Available The importance of the ubiquitin-proteasome pathway to cellular function has brought it to the forefront in the search for new anticancer therapies. The ubiquitin-proteasome pathway has proven promising in targeting various human cancers. The approval of the proteasome inhibitor bortezomib for clinical treatment of relapsed/refractory multiple myeloma and mantle cell lymphoma has validated the ubiquitin-proteasome as a rational target. Bortezomib has shown positive results in clinical use but some toxicity and side effects, as well as resistance, have been observed, indicating that further development of novel, less toxic drugs is necessary. Because less toxic drugs are necessary and drug development can be expensive and time-consuming, using existing drugs that can target the ubiquitin-proteasome pathway in new applications, such as cancer therapy, may be effective in expediting the regulatory process and bringing new drugs to the clinic. Toward this goal, previously approved drugs, such as disulfiram, as well as natural compounds found in common foods, such as green tea polyphenol (--EGCG and the flavonoid apigenin, have been investigated for their possible proteasome inhibitory and cell death inducing abilities. These compounds proved quite promising in preclinical studies and have now moved into clinical trials, with preliminary results that are encouraging. In addition to targeting the catalytic activity of the proteasome pathway, upstream regulators, such as the 19S regulatory cap, as well as E1, E2, and E3, are now being investigated as potential drug targets. This review outlines the development of novel proteasome inhibitors from preclinical to clinical studies, highlighting their abilities to inhibit the tumor proteasome and induce apoptosis in several human cancers.

  2. From antimicrobial to anticancer peptides. A review.

    Science.gov (United States)

    Gaspar, Diana; Veiga, A Salomé; Castanho, Miguel A R B

    2013-10-01

    Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms. Although AMPs have been essentially studied and developed as potential alternatives for fighting infectious diseases, their use as anticancer peptides (ACPs) in cancer therapy either alone or in combination with other conventional drugs has been regarded as a therapeutic strategy to explore. As human cancer remains a cause of high morbidity and mortality worldwide, an urgent need of new, selective, and more efficient drugs is evident. Even though ACPs are expected to be selective toward tumor cells without impairing the normal body physiological functions, the development of a selective ACP has been a challenge. It is not yet possible to predict antitumor activity based on ACPs structures. ACPs are unique molecules when compared to the actual chemotherapeutic arsenal available for cancer treatment and display a variety of modes of action which in some types of cancer seem to co-exist. Regardless the debate surrounding the definition of structure-activity relationships for ACPs, great effort has been invested in ACP design and the challenge of improving effective killing of tumor cells remains. As detailed studies on ACPs mechanisms of action are crucial for optimizing drug development, in this review we provide an overview of the literature concerning peptides' structure, modes of action, selectivity, and efficacy and also summarize some of the many ACPs studied and/or developed for targeting different solid and hematologic malignancies with special emphasis on the first group. Strategies described for drug development and for increasing peptide selectivity toward specific cells while reducing toxicity are also discussed.

  3. Evolving wormhole geometries within nonlinear electrodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Arellano, Aaron V B [Facultad de Ciencias, Universidad Autonoma del Estado de Mexico, El Cerrillo, Piedras Blancas, CP 50200, Toluca (Mexico); Lobo, Francisco S N [Centro de Astronomia e Astrofisica da Universidade de Lisboa, Campo Grande, Ed C8 1749-016 Lisbon (Portugal)

    2006-10-21

    In this work, we explore the possibility of evolving (2 + 1) and (3 + 1)-dimensional wormhole spacetimes, conformally related to the respective static geometries, within the context of nonlinear electrodynamics. For (3 + 1)-dimensional spacetime, it is found that the Einstein field equation imposes a contracting wormhole solution and the obedience of the weak energy condition. Nevertheless, in the presence of an electric field, the latter presents a singularity at the throat; however, for a pure magnetic field the solution is regular. For (2 + 1)-dimensional case, it is also found that the physical fields are singular at the throat. Thus, taking into account the principle of finiteness, which states that a satisfactory theory should avoid physical quantities becoming infinite, one may rule out evolving (3 + 1)-dimensional wormhole solutions, in the presence of an electric field, and (2 + 1)-dimensional case coupled to nonlinear electrodynamics.

  4. Continual Learning through Evolvable Neural Turing Machines

    DEFF Research Database (Denmark)

    Lüders, Benno; Schläger, Mikkel; Risi, Sebastian

    2016-01-01

    Continual learning, i.e. the ability to sequentially learn tasks without catastrophic forgetting of previously learned ones, is an important open challenge in machine learning. In this paper we take a step in this direction by showing that the recently proposed Evolving Neural Turing Machine (ENT......) approach is able to perform one-shot learning in a reinforcement learning task without catastrophic forgetting of previously stored associations.......Continual learning, i.e. the ability to sequentially learn tasks without catastrophic forgetting of previously learned ones, is an important open challenge in machine learning. In this paper we take a step in this direction by showing that the recently proposed Evolving Neural Turing Machine (ENTM...

  5. Designing Garments to Evolve Over Time

    DEFF Research Database (Denmark)

    Riisberg, Vibeke; Grose, Lynda

    2017-01-01

    This paper proposes a REDO of the current fashion paradigm by investigating how garments might be designed to evolve over time. The purpose is to discuss ways of expanding the traditional role of the designer to include temporal dimensions of creating, producing and using clothes and to suggest a...... to a REDO of design education, to further research and the future fashion and textile industry.......This paper proposes a REDO of the current fashion paradigm by investigating how garments might be designed to evolve over time. The purpose is to discuss ways of expanding the traditional role of the designer to include temporal dimensions of creating, producing and using clothes and to suggest...... a range of potential fashion futures that decouple from declining resources. In the first part literature on 'Past and Present' historical and current aspects of sustainability in fashion and textiles are presented. In the second part, three exploratory case studies are described: Two projects by students...

  6. Antibody therapeutics - the evolving patent landscape.

    Science.gov (United States)

    Petering, Jenny; McManamny, Patrick; Honeyman, Jane

    2011-09-01

    The antibody patent landscape has evolved dramatically over the past 30 years, particularly in areas of technology relating to antibody modification to reduce immunogenicity in humans or improve antibody function. In some cases antibody techniques that were developed in the 1980s are still the subject of patent protection in the United States or Canada. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. The evolving epidemiology of inflammatory bowel disease.

    LENUS (Irish Health Repository)

    Shanahan, Fergus

    2009-07-01

    Epidemiologic studies in inflammatory bowel disease (IBD) include assessments of disease burden and evolving patterns of disease presentation. Although it is hoped that sound epidemiologic studies provide aetiological clues, traditional risk factor-based epidemiology has provided limited insights into either Crohn\\'s disease or ulcerative colitis etiopathogenesis. In this update, we will summarize how the changing epidemiology of IBD associated with modernization can be reconciled with current concepts of disease mechanisms and will discuss studies of clinically significant comorbidity in IBD.

  8. Directional Communication in Evolved Multiagent Teams

    Science.gov (United States)

    2013-06-10

    networks. Artificial Life, 15(2):185– 212, 2009. [23] K. O. Stanley and R. Miikkulainen. Evolving neural networks through augmenting topologies ...paper. 2.2 Neuroevolution of Augmenting Topologies The HyperNEAT approach is itself an extension of the original NEAT (Neu- roevolution of Augmenting ...Gauci and K. O. Stanley. Autonomous evolution of topographic regu- larities in artificial neural networks. Neural Computation, 22(7):1860–1898, 2010

  9. The Evolving Leadership Path of Visual Analytics

    Energy Technology Data Exchange (ETDEWEB)

    Kluse, Michael; Peurrung, Anthony J.; Gracio, Deborah K.

    2012-01-02

    This is a requested book chapter for an internationally authored book on visual analytics and related fields, coordianted by a UK university and to be published by Springer in 2012. This chapter is an overview of the leadship strategies that PNNL's Jim Thomas and other stakeholders used to establish visual analytics as a field, and how those strategies may evolve in the future.

  10. Raeder paratrigeminal neuralgia evolving to hemicrania continua.

    Science.gov (United States)

    Porzukowiak, Tina Renae

    2015-04-01

    Raeder paratrigeminal neuralgia is most commonly characterized as deep, boring, nonpulsatile, severe, unilateral facial and head pain in the distribution of the V1 area combined with ipsilateral oculosympathetic palsy and autonomic symptoms. Raeder paratrigeminal neuralgia evolving into hemicrania continua, a rare primary, chronic headache syndrome characterized by unilateral pain and response to indomethacin, has rarely been documented. The purpose of this case report is to contribute to the medical literature a single case of Raeder paratrigeminal neuralgia presenting as multiple cranial nerve palsies that evolved into hemicrania continua that was successfully treated with onabotulinumtoxinA. A 52-year-old white woman presented to the emergency department with the complaint of severe, aching, constant eye pain radiating to the V1 area for 1 week with associated ptosis and photophobia of the left eye. Ocular examination revealed involvement of cranial nerves II, III, V, and VI. Additional symptoms included ipsilateral lacrimation, eyelid edema, and rhinorrhea. Extensive medical work-up showed normal results. Raeder paratrigeminal neuralgia was diagnosed with multiple cranial nerve involvement; the headache component became chronic with periodic exacerbations of autonomic symptoms evolving to a diagnosis of hemicrania continua. The patient was intolerant to traditional indomethacin treatment, and the headache was successfully treated with onabotulinumtoxinA injections. Recognition of ipsilateral signs such as miosis, ptosis, hydrosis, eyelid edema, hyperemia, rhinorrhea, or nasal congestion is useful in the differential diagnosis of painful ophthalmoplegia, particularly in the diagnosis of Raeder paratrigeminal neuralgia and hemicrania continua. This case study illustrates a rare presentation of Raeder paratrigeminal neuralgia evolving into hemicrania continua presenting as a painful ophthalmoplegia with multiple cranial nerve involvement. The example supports the

  11. Evolvability of Amyloidogenic Proteins in Human Brain

    Science.gov (United States)

    Hashimoto, Makoto; Ho, Gilbert; Sugama, Shuei; Takamatsu, Yoshiki; Shimizu, Yuka; Takenouchi, Takato; Waragai, Masaaki; Masliah, Eliezer

    2018-01-01

     Currently, the physiological roles of amyloidogenic proteins (APs) in human brain, such as amyloid-β and α-synuclein, are elusive. Given that many APs arose by gene duplication and have been resistant against the pressures of natural selection, APs may be associated with some functions that are advantageous for survival of offspring. Nonetheless, evolvability is the sole physiological quality of APs that has been characterized in microorganisms such as yeast. Since yeast and human brain may share similar strategies in coping with diverse range of critical environmental stresses, the objective of this paper was to discuss the potential role of evolvability of APs in aging-associated neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. Given the heterogeneity of APs in terms of structure and cytotoxicity, it is argued that APs might be involved in preconditioning against diverse stresses in human brain. It is further speculated that these stress-related APs, most likely protofibrillar forms, might be transmitted to offspring via the germline, conferring preconditioning against forthcoming stresses. Thus, APs might represent a vehicle for the inheritance of the acquired characteristics against environmental stresses. Curiously, such a characteristic of APs is reminiscent of Charles Darwin’s ‘gemmules’, imagined molecules of heritability described in his pangenesis theory. We propose that evolvability might be a physiological function of APs during the reproductive stage and neurodegenerative diseases could be a by-product effect manifested later in aging. Collectively, our evolvability hypothesis may play a complementary role in the pathophysiology of APs with the conventional amyloid cascade hypothesis. PMID:29439348

  12. Phenotypic integration: studying the ecology and evolution of complex phenotypes

    National Research Council Canada - National Science Library

    Pigliucci, Massimo; Preston, Katherine

    2004-01-01

    .... Studying the Plasticity of Phenotypic Integration in a Model Organism, 155 Massimo Pigliucci 8. Integrating Phenotypic Plasticity When Death Is on the Line: Insights from Predator-Prey Systems...

  13. High-order evolving surface finite element method for parabolic problems on evolving surfaces

    OpenAIRE

    Kovács, Balázs

    2016-01-01

    High-order spatial discretisations and full discretisations of parabolic partial differential equations on evolving surfaces are studied. We prove convergence of the high-order evolving surface finite element method, by showing high-order versions of geometric approximation errors and perturbation error estimates and by the careful error analysis of a modified Ritz map. Furthermore, convergence of full discretisations using backward difference formulae and implicit Runge-Kutta methods are als...

  14. PhenoLines: Phenotype Comparison Visualizations for Disease Subtyping via Topic Models.

    Science.gov (United States)

    Glueck, Michael; Naeini, Mahdi Pakdaman; Doshi-Velez, Finale; Chevalier, Fanny; Khan, Azam; Wigdor, Daniel; Brudno, Michael

    2018-01-01

    PhenoLines is a visual analysis tool for the interpretation of disease subtypes, derived from the application of topic models to clinical data. Topic models enable one to mine cross-sectional patient comorbidity data (e.g., electronic health records) and construct disease subtypes-each with its own temporally evolving prevalence and co-occurrence of phenotypes-without requiring aligned longitudinal phenotype data for all patients. However, the dimensionality of topic models makes interpretation challenging, and de facto analyses provide little intuition regarding phenotype relevance or phenotype interrelationships. PhenoLines enables one to compare phenotype prevalence within and across disease subtype topics, thus supporting subtype characterization, a task that involves identifying a proposed subtype's dominant phenotypes, ages of effect, and clinical validity. We contribute a data transformation workflow that employs the Human Phenotype Ontology to hierarchically organize phenotypes and aggregate the evolving probabilities produced by topic models. We introduce a novel measure of phenotype relevance that can be used to simplify the resulting topology. The design of PhenoLines was motivated by formative interviews with machine learning and clinical experts. We describe the collaborative design process, distill high-level tasks, and report on initial evaluations with machine learning experts and a medical domain expert. These results suggest that PhenoLines demonstrates promising approaches to support the characterization and optimization of topic models.

  15. Collective properties of evolving molecular quasispecies

    Directory of Open Access Journals (Sweden)

    Manrubia Susanna C

    2007-07-01

    Full Text Available Abstract Background RNA molecules, through their dual appearance as sequence and structure, represent a suitable model to study evolutionary properties of quasispecies. The essential ingredient in this model is the differentiation between genotype (molecular sequences which are affected by mutation and phenotype (molecular structure, affected by selection. This framework allows a quantitative analysis of organizational properties of quasispecies as they adapt to different environments, such as their robustness, the effect of the degeneration of the sequence space, or the adaptation under different mutation rates and the error threshold associated. Results We describe and analyze the structural properties of molecular quasispecies adapting to different environments both during the transient time before adaptation takes place and in the asymptotic state, once optimization has occurred. We observe a minimum in the adaptation time at values of the mutation rate relatively far from the phenotypic error threshold. Through the definition of a consensus structure, it is shown that the quasispecies retains relevant structural information in a distributed fashion even above the error threshold. This structural robustness depends on the precise shape of the secondary structure used as target of selection. Experimental results available for natural RNA populations are in qualitative agreement with our observations. Conclusion Adaptation time of molecular quasispecies to a given environment is optimized at values of the mutation rate well below the phenotypic error threshold. The optimal value results from a trade-off between diversity generation and fixation of advantageous mutants. The critical value of the mutation rate is a function not only of the sequence length, but also of the specific properties of the environment, in this case the selection pressure and the shape of the secondary structure used as target phenotype. Certain functional motifs of RNA

  16. From metabolome to phenotype

    DEFF Research Database (Denmark)

    Khakimov, Bekzod; Rasmussen, Morten Arendt; Kannangara, Rubini Maya

    2017-01-01

    The development of crop varieties tolerant to growth temperature fluctuations and improved nutritional value is crucial due to climate change and global population growth. This study investigated the metabolite patterns of developing barley seed as a function of genotype and growth temperature fo...... their successful application to link genetic and environmental factors with the seed phenotype of unique and agro-economically important barley models for optimal vegetable protein and dietary fibre production....

  17. Extracellular Vesicles: Evolving Factors in Stem Cell Biology

    Directory of Open Access Journals (Sweden)

    Muhammad Nawaz

    2016-01-01

    Full Text Available Stem cells are proposed to continuously secrete trophic factors that potentially serve as mediators of autocrine and paracrine activities, associated with reprogramming of the tumor microenvironment, tissue regeneration, and repair. Hitherto, significant efforts have been made to understand the level of underlying paracrine activities influenced by stem cell secreted trophic factors, as little is known about these interactions. Recent findings, however, elucidate this role by reporting the effects of stem cell derived extracellular vesicles (EVs that mimic the phenotypes of the cells from which they originate. Exchange of genetic information utilizing persistent bidirectional communication mediated by stem cell-EVs could regulate stemness, self-renewal, and differentiation in stem cells and their subpopulations. This review therefore discusses stem cell-EVs as evolving communication factors in stem cell biology, focusing on how they regulate cell fates by inducing persistent and prolonged genetic reprogramming of resident cells in a paracrine fashion. In addition, we address the role of stem cell-secreted vesicles in shaping the tumor microenvironment and immunomodulation and in their ability to stimulate endogenous repair processes during tissue damage. Collectively, these functions ensure an enormous potential for future therapies.

  18. Extracellular Vesicles: Evolving Factors in Stem Cell Biology

    Science.gov (United States)

    Nawaz, Muhammad; Fatima, Farah; Vallabhaneni, Krishna C.; Penfornis, Patrice; Valadi, Hadi; Ekström, Karin; Kholia, Sharad; Whitt, Jason D.; Fernandes, Joseph D.; Pochampally, Radhika; Squire, Jeremy A.; Camussi, Giovanni

    2016-01-01

    Stem cells are proposed to continuously secrete trophic factors that potentially serve as mediators of autocrine and paracrine activities, associated with reprogramming of the tumor microenvironment, tissue regeneration, and repair. Hitherto, significant efforts have been made to understand the level of underlying paracrine activities influenced by stem cell secreted trophic factors, as little is known about these interactions. Recent findings, however, elucidate this role by reporting the effects of stem cell derived extracellular vesicles (EVs) that mimic the phenotypes of the cells from which they originate. Exchange of genetic information utilizing persistent bidirectional communication mediated by stem cell-EVs could regulate stemness, self-renewal, and differentiation in stem cells and their subpopulations. This review therefore discusses stem cell-EVs as evolving communication factors in stem cell biology, focusing on how they regulate cell fates by inducing persistent and prolonged genetic reprogramming of resident cells in a paracrine fashion. In addition, we address the role of stem cell-secreted vesicles in shaping the tumor microenvironment and immunomodulation and in their ability to stimulate endogenous repair processes during tissue damage. Collectively, these functions ensure an enormous potential for future therapies. PMID:26649044

  19. Reproductive behaviour evolves rapidly when intralocus sexual conflict is removed.

    Directory of Open Access Journals (Sweden)

    Stéphanie Bedhomme

    Full Text Available BACKGROUND: Intralocus sexual conflict can inhibit the evolution of each sex towards its own fitness optimum. In a previous study, we confirmed this prediction through the experimental removal of female selection pressures in Drosophila melanogaster, achieved by limiting the expression of all major chromosomes to males. Compared to the control populations (C(1-4 where the genomes are exposed to selection in both sexes, the populations with male-limited genomes (ML(1-4 showed rapid increases in male fitness, whereas the fitness of females expressing ML-evolved chromosomes decreased. METHODOLOGY/PRINCIPAL FINDINGS: Here we examine the behavioural phenotype underlying this sexual antagonism. We show that males expressing the ML genomes have a reduced courtship level but acquire the same number of matings. On the other hand, our data suggest that females expressing the ML genomes had reduced attractiveness, stimulating a lower rate of courtship from males. Moreover, females expressing ML genomes tend to display reduced yeast-feeding behaviour, which is probably linked to the reduction of their fecundity. CONCLUSION/SIGNIFICANCE: These results suggest that reproductive behaviour is shaped by opposing selection on males and females, and that loci influencing attractiveness and foraging were polymorphic for alleles with sexually antagonistic expression patterns prior to ML selection. Hence, intralocus sexual conflict appears to play a role in the evolution of a wide range of fitness-related traits and may be a powerful mechanism for the maintenance of genetic variation in fitness.

  20. The Evolving Diagnostic and Genetic Landscapes of Autism Spectrum Disorder.

    Science.gov (United States)

    Ziats, Mark N; Rennert, Owen M

    2016-01-01

    The autism spectrum disorders (ASD) are a heterogeneous set of neurodevelopmental syndromes defined by impairments in verbal and non-verbal communication, restricted social interaction, and the presence of stereotyped patterns of behavior. The prevalence of ASD is rising, and the diagnostic criteria and clinical perspectives on the disorder continue to evolve in parallel. Although the majority of individuals with ASD will not have an identifiable genetic cause, almost 25% of cases have identifiable causative DNA variants. The rapidly improving ability to identify genetic mutations because of advances in next generation sequencing, coupled with previous epidemiological studies demonstrating high heritability of ASD, have led to many recent attempts to identify causative genetic mutations underlying the ASD phenotype. However, although hundreds of mutations have been identified to date, they are either rare variants affecting only a handful of ASD patients, or are common variants in the general population conferring only a small risk for ASD. Furthermore, the genes implicated thus far are heterogeneous in their structure and function, hampering attempts to understand shared molecular mechanisms among all ASD patients; an understanding that is crucial for the development of targeted diagnostics and therapies. However, new work is beginning to suggest that the heterogeneous set of genes implicated in ASD may ultimately converge on a few common pathways. In this review, we discuss the parallel evolution of our diagnostic and genetic understanding of autism spectrum disorders, and highlight recent attempts to infer common biology underlying this complicated syndrome.

  1. The evolving diagnostic and genetic landscapes of autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Mark Nicholas Ziats

    2016-04-01

    Full Text Available The autism spectrum disorders (ASD are a heterogeneous set of neurodevelopmental syndromes defined by impairments in verbal and non-verbal communication, restricted social interaction, and the presence of stereotyped patterns of behavior. The prevalence of ASD is rising, and the diagnostic criteria and clinical perspectives on the disorder continue to evolve in parallel. Although the majority of individuals with ASD will not have an identifiable genetic cause, almost 25% of cases have identifiable causative DNA variants. The rapidly improving ability to identify genetic mutations because of advances in next generation sequencing, coupled with previous epidemiological studies demonstrating high heritability of ASD, have led to many recent attempts to identify causative genetic mutations underlying the ASD phenotype. However, although hundreds of mutations have been identified to date, they are either rare variants affecting only a handful of ASD patients, or are common variants in the general population conferring only a small risk for ASD. Furthermore, the genes implicated thus far are heterogeneous in their structure and function, hampering attempts to understand shared molecular mechanisms among all ASD patients; an understanding that is crucial for the development of targeted diagnostics and therapies. However, new work is beginning to suggest that the heterogeneous set of genes implicated in ASD may ultimately converge on a few common pathways. In this review, we discuss the parallel evolution of our diagnostic and genetic understanding of autism spectrum disorders, and highlight recent attempts to infer common biology underlying this complicated syndrome.

  2. Recent developments in the field of anticancer platinum complexes.

    Science.gov (United States)

    Galanski, Markus

    2006-06-01

    Cisplatin, carboplatin and oxaliplatin continue to be among the most efficient anticancer drugs in world-wide clinical use so far. In particular, cisplatin has shown a remarkable therapeutic efficacy in a broad spectrum of solid tumors and outstanding activity against metastatic testicular germ-cell cancer with cure rates of about 90% of cases. Nevertheless, the dose-limiting severe toxic side-effects of platinum-based chemotherapy, the problem of inherent or therapy-induced resistance, the limited activity in a range of tumors, and the meager tumor selectivity are the motivation for tremendous efforts and inventions in the development of novel anticancer platinum drugs. This article reviews the most recent patents in this field of research, covering the following strategies in the design of promising anticancer platinum complexes: (i) synthesis of new anticancer platinum complexes, using combinatorial chemistry and high throughput synthesis and screening, (ii) activation of platinum complexes in the tumor tissue, (iii) accumulation of platinum complexes at the tumor site, (iv) novel platinum complexes, displaying activity against cisplatin resistant cells and as inhibitors of specific biological functions, and (v) direct derivatives of classical anticancer platinum drugs in clinical use.

  3. CancerPPD: a database of anticancer peptides and proteins.

    Science.gov (United States)

    Tyagi, Atul; Tuknait, Abhishek; Anand, Priya; Gupta, Sudheer; Sharma, Minakshi; Mathur, Deepika; Joshi, Anshika; Singh, Sandeep; Gautam, Ankur; Raghava, Gajendra P S

    2015-01-01

    CancerPPD (http://crdd.osdd.net/raghava/cancerppd/) is a repository of experimentally verified anticancer peptides (ACPs) and anticancer proteins. Data were manually collected from published research articles, patents and from other databases. The current release of CancerPPD consists of 3491 ACP and 121 anticancer protein entries. Each entry provides comprehensive information related to a peptide like its source of origin, nature of the peptide, anticancer activity, N- and C-terminal modifications, conformation, etc. Additionally, CancerPPD provides the information of around 249 types of cancer cell lines and 16 different assays used for testing the ACPs. In addition to natural peptides, CancerPPD contains peptides having non-natural, chemically modified residues and D-amino acids. Besides this primary information, CancerPPD stores predicted tertiary structures as well as peptide sequences in SMILES format. Tertiary structures of peptides were predicted using the state-of-art method, PEPstr and secondary structural states were assigned using DSSP. In order to assist users, a number of web-based tools have been integrated, these include keyword search, data browsing, sequence and structural similarity search. We believe that CancerPPD will be very useful in designing peptide-based anticancer therapeutics. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Endophytic fungi with antitumor activities: Their occurrence and anticancer compounds.

    Science.gov (United States)

    Chen, Ling; Zhang, Qiao-Yan; Jia, Min; Ming, Qian-Liang; Yue, Wei; Rahman, Khalid; Qin, Lu-Ping; Han, Ting

    2016-05-01

    Plant endophytic fungi have been recognized as an important and novel resource of natural bioactive products, especially in anticancer application. This review mainly deals with the research progress on the production of anticancer compounds by endophytic fungi between 1990 and 2013. Anticancer activity is generally associated with the cytotoxicity of the compounds present in the endophytic fungi. All strains of endophytes producing antitumor chemicals were classified taxonomically and the genera of Pestalotiopsis and Aspergillus as well as the taxol producing endophytes were focused on. Classification of endophytic fungi producing antitumor compounds has received more attention from mycologists, and it can also lead to the discovery of novel compounds with antitumor activity due to phylogenetic relationships. In this review, the structures of the anticancer compounds isolated from the newly reported endophytes between 2010 and 2013 are discussed including strategies for the efficient production of the desired compounds. The purpose of this review is to provide new directions in endophytic fungi research including integrated information relating to its anticancer compounds.

  5. Relationship between Antioxidant and Anticancer Activity of Trihydroxyflavones

    Directory of Open Access Journals (Sweden)

    Ignas Grigalius

    2017-12-01

    Full Text Available Plant polyphenols have been highlighted not only as chemopreventive, but also as potential anticancer substances. Flavones are a subclass of natural flavonoids reported to have an antioxidant and anticancer activity. The aim of our study was to evaluate antioxidant and anticancer activity of seventeen trihydroxyflavone derivatives, including apigenin (API and baicalein (BCL. Also, we wanted to find out if there is a correlation between those two effects. Cell growth inhibition testing was carried out using MTT assay in three different human cancer cell lines: lung (A549, breast (MCF-7 and brain epithelial (U87. Antioxidant activity was determined by the DPPH radical scavenging method. Thirteen trihydroxyflavones possessed anticancer activity against at least one tested cancer cell line. They were more active against the MCF-7 cell line, and the lowest activity was determined against the U87 cell line. The majority of compounds inhibited cancer cell growth at EC50 values between 10–50 µM. The most active compound was 3’,4’,5-trihydroxyflavone 7, especially against A549 and MCF-7 cell lines. The correlation between anti-proliferative and antioxidant activity was only moderate, and it was determined for A549 and U87 cancer cell lines. The most important fragment for those two effects is the ortho-dihydroxy group in ring B. Conclusions. Trihydroxyflavones demonstrated anticancer activity. Further and more detailed studies should to be carried out to estimate the structure–activity relationship of these compounds.

  6. Teratogenic effects of five anticancer drugs on Xenopus laevis embryos.

    Science.gov (United States)

    Isidori, Marina; Piscitelli, Concetta; Russo, Chiara; Smutná, Marie; Bláha, Luděk

    2016-11-01

    In recent years, the environmental presence of pharmaceuticals - including anticancer drugs - is an emerging issue. Because of the lack of appropriate critical studies about anticancer drug effects in frogs, the aim of the present study was to investigate lethal and teratogenic effects of five anticancer drugs widely used in large quantities, i.e. 5-flourouracil, capecitabine, cisplatin, etoposide, and imatinib, in the embryos of the South African clawed frog, Xenopus laevis, using FETAX - Frog Embryo Teratogenesis Assay in Xenopus. None of the studied anticancer drugs induced statistically significant mortality within the concentrations tested (0.01-50mg/L, depending on the studied compound), and no growth inhibition of embryos after a 96-h exposure was observed. Except for cisplatin, the other pharmaceuticals induced an increase of developmental malformations such as abdominal edema, axial flexure, head, eyes, gut and heart malformations with statistically significant effects observed at the highest concentrations tested (50mg/L for 5-flourouracil; 30mg/L for etoposide and 20mg/L for capecitabine and imatinib). The results indicate that anticancer drugs can affect embryogenesis mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Evolving definitions of hope in oncology.

    Science.gov (United States)

    Olver, Ian N

    2012-06-01

    This review updates the literature on hope and oncology following a prior review of studies up until 2009. It particularly focusses on the evolution of the definition of hope in the light of the clinical experience of patients with cancer, their carers and health professionals. Hope creates meaning for patients and is an important coping mechanism. Clinicians are wary of communicating bad news because it may deprive patients of hope, but work with decision aids suggests that this communication can be managed successfully. Hope and optimism negatively correlate with anxiety and depression. Maintaining hope may result in patients with incurable cancer accepting treatments or trials with little chance of benefit. Hope also needs to be maintained by palliative care nurses who harmonize their hopes with the different degrees and constructs of hope around them. Hope interventions can be successful in increasing hope and decreasing psychological distress. More research is required into how to communicate about active anticancer treatment withdrawal and prognosis without depriving patients with cancer of hope, given how important hope is in alleviating psychological distress. The optimal intervention to increase levels of hope needs further investigation.

  8. Anti-cancer agents in Saudi Arabian herbals revealed by automated high-content imaging

    KAUST Repository

    Hajjar, Dina

    2017-06-13

    Natural products have been used for medical applications since ancient times. Commonly, natural products are structurally complex chemical compounds that efficiently interact with their biological targets, making them useful drug candidates in cancer therapy. Here, we used cell-based phenotypic profiling and image-based high-content screening to study the mode of action and potential cellular targets of plants historically used in Saudi Arabia\\'s traditional medicine. We compared the cytological profiles of fractions taken from Juniperus phoenicea (Arar), Anastatica hierochuntica (Kaff Maryam), and Citrullus colocynthis (Hanzal) with a set of reference compounds with established modes of action. Cluster analyses of the cytological profiles of the tested compounds suggested that these plants contain possible topoisomerase inhibitors that could be effective in cancer treatment. Using histone H2AX phosphorylation as a marker for DNA damage, we discovered that some of the compounds induced double-strand DNA breaks. Furthermore, chemical analysis of the active fraction isolated from Juniperus phoenicea revealed possible anti-cancer compounds. Our results demonstrate the usefulness of cell-based phenotypic screening of natural products to reveal their biological activities.

  9. Evolvability Is an Evolved Ability: The Coding Concept as the Arch-Unit of Natural Selection.

    Science.gov (United States)

    Janković, Srdja; Ćirković, Milan M

    2016-03-01

    Physical processes that characterize living matter are qualitatively distinct in that they involve encoding and transfer of specific types of information. Such information plays an active part in the control of events that are ultimately linked to the capacity of the system to persist and multiply. This algorithmicity of life is a key prerequisite for its Darwinian evolution, driven by natural selection acting upon stochastically arising variations of the encoded information. The concept of evolvability attempts to define the total capacity of a system to evolve new encoded traits under appropriate conditions, i.e., the accessible section of total morphological space. Since this is dependent on previously evolved regulatory networks that govern information flow in the system, evolvability itself may be regarded as an evolved ability. The way information is physically written, read and modified in living cells (the "coding concept") has not changed substantially during the whole history of the Earth's biosphere. This biosphere, be it alone or one of many, is, accordingly, itself a product of natural selection, since the overall evolvability conferred by its coding concept (nucleic acids as information carriers with the "rulebook of meanings" provided by codons, as well as all the subsystems that regulate various conditional information-reading modes) certainly played a key role in enabling this biosphere to survive up to the present, through alterations of planetary conditions, including at least five catastrophic events linked to major mass extinctions. We submit that, whatever the actual prebiotic physical and chemical processes may have been on our home planet, or may, in principle, occur at some time and place in the Universe, a particular coding concept, with its respective potential to give rise to a biosphere, or class of biospheres, of a certain evolvability, may itself be regarded as a unit (indeed the arch-unit) of natural selection.

  10. Rethinking the evolution of specialization: A model for the evolution of phenotypic heterogeneity.

    Science.gov (United States)

    Rubin, Ilan N; Doebeli, Michael

    2017-12-21

    Phenotypic heterogeneity refers to genetically identical individuals that express different phenotypes, even when in the same environment. Traditionally, "bet-hedging" in fluctuating environments is offered as the explanation for the evolution of phenotypic heterogeneity. However, there are an increasing number of examples of microbial populations that display phenotypic heterogeneity in stable environments. Here we present an evolutionary model of phenotypic heterogeneity of microbial metabolism and a resultant theory for the evolution of phenotypic versus genetic specialization. We use two-dimensional adaptive dynamics to track the evolution of the population phenotype distribution of the expression of two metabolic processes with a concave trade-off. Rather than assume a Gaussian phenotype distribution, we use a Beta distribution that is capable of describing genotypes that manifest as individuals with two distinct phenotypes. Doing so, we find that environmental variation is not a necessary condition for the evolution of phenotypic heterogeneity, which can evolve as a form of specialization in a stable environment. There are two competing pressures driving the evolution of specialization: directional selection toward the evolution of phenotypic heterogeneity and disruptive selection toward genetically determined specialists. Because of the lack of a singular point in the two-dimensional adaptive dynamics and the fact that directional selection is a first order process, while disruptive selection is of second order, the evolution of phenotypic heterogeneity dominates and often precludes speciation. We find that branching, and therefore genetic specialization, occurs mainly under two conditions: the presence of a cost to maintaining a high phenotypic variance or when the effect of mutations is large. A cost to high phenotypic variance dampens the strength of selection toward phenotypic heterogeneity and, when sufficiently large, introduces a singular point into

  11. In vivo evaluation on the effects of HemoHIM in promoting anticancer activities and reducing the side-effects of anticancer drugs

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Sung Kee; Jung, U Hee; Park, Hae Ran; Ju, Eun Jin; Cho, Eun Hee

    2009-07-15

    In this project, we aimed to obtain the preclinical in vivo evaluation data for the development of the herbal composition (HemoHIM) as the auxiliary agent for the anticancer treatment that can reduce the side-effects of anticancer drugs and enhance their anticancer activities. Firstly, in vitro studies showed that HemoHIM did not show any effects on the tumor cell growth inhibition by 2 anticancer drugs (cisplatin, 5-FU), which indicated that at least HemoHIM does not exert any adverse effects on the activities of anticancer drugs. Next, the in vivo studies with mice implanted with tumor cells(B16F0, LLC1) showed that HemoHIM partially enhanced the anticancer activities of drugs (cisplatin, 5-FU), and improved endogenous anticancer immune activities. Furthermore, in the same animal models, HemoHIM effectively reduced the side-effects of anticancer drugs (liver and renal toxicities by cisplatin, immune and hematopoietic disorders by 5-FU). These results collectively showed that HemoHIM can enhance the activities of anticancer drugs and reduce their side-effects in vitro and in vivo and HemoHIM does not exert any adverse effects on the efficacy of anticancer drugs. The results of this project can be utilized as the basic preclinical data for the development and approval of HemoHIM as the auxiliary agent for the anticancer treatment

  12. Present weather and climate: evolving conditions

    Science.gov (United States)

    Hoerling, Martin P; Dettinger, Michael; Wolter, Klaus; Lukas, Jeff; Eischeid, Jon K.; Nemani, Rama; Liebmann, Brant; Kunkel, Kenneth E.

    2013-01-01

    This chapter assesses weather and climate variability and trends in the Southwest, using observed climate and paleoclimate records. It analyzes the last 100 years of climate variability in comparison to the last 1,000 years, and links the important features of evolving climate conditions to river flow variability in four of the region’s major drainage basins. The chapter closes with an assessment of the monitoring and scientific research needed to increase confidence in understanding when climate episodes, events, and phenomena are attributable to human-caused climate change.

  13. f( R) gravity solutions for evolving wormholes

    Science.gov (United States)

    Bhattacharya, Subhra; Chakraborty, Subenoy

    2017-08-01

    The scalar-tensor f( R) theory of gravity is considered in the framework of a simple inhomogeneous space-time model. In this research we use the reconstruction technique to look for possible evolving wormhole solutions within viable f( R) gravity formalism. These f( R) models are then constrained so that they are consistent with existing experimental data. Energy conditions related to the matter threading the wormhole are analyzed graphically and are in general found to obey the null energy conditions (NEC) in regions around the throat, while in the limit f(R)=R, NEC can be violated at large in regions around the throat.

  14. Evolving Random Forest for Preference Learning

    DEFF Research Database (Denmark)

    Abou-Zleikha, Mohamed; Shaker, Noor

    2015-01-01

    This paper introduces a novel approach for pairwise preference learning through a combination of an evolutionary method and random forest. Grammatical evolution is used to describe the structure of the trees in the Random Forest (RF) and to handle the process of evolution. Evolved random forests ...... obtained for predicting pairwise self-reports of users for the three emotional states engagement, frustration and challenge show very promising results that are comparable and in some cases superior to those obtained from state-of-the-art methods....

  15. Microtubule-targeting Anticancer Agents from Marine Natural Source.

    Science.gov (United States)

    Liu, Zhiguo; Xu, Pengfei; Yu, Lun; Zeng, Wenbin

    2013-02-07

    The effective novel therapeutics is urgently needed due to the increasing incidence of malignant cancers and drug multi-resistance. It is particularly imperative to find efficacious and specific anticancer agents. Microtubule-targeting drugs are among the most commonly prescribed agents in the combat against cancer. Natural products and their derivatives have historically been invaluable as a source of pharmaceutical leads and therapeutic agents. In particular, marine natural products (MNPs) have demonstrated exceptional potency and potential as anticancer agents. Drug discovery from MNPs provides new pathway and ideas to find original anticancer agents, and enjoys a renaissance in the past few years. In this review, nine classes of typical MNPs are summarized, including novel compounds with diverse structures. Most bioactive marine compounds from different organism include invertebrate animals, algae, fungi and bacteria are concluded.

  16. Preclinical Evidence on the Anticancer Properties of Food Peptides.

    Science.gov (United States)

    Rajendran, Subin R C K; Ejike, Chukwunonso E C C; Gong, Min; Hannah, William; Udenigwe, Chibuike C

    2017-01-01

    Natural, synthetic and analogues of peptides have shown prospects for application in cancer chemotherapy. Notably, some food protein-derived peptides are known to possess anticancer activities in cultured cancer cells, and also in animal cancer models via different mechanisms including induction of apoptosis, cell cycle arrest, cellular membrane disruption, inhibition of intracellular signalling, topoisomerases and proteases, and antiangiogenic activity. Although the mechanism of several anticancer food peptides is yet to be clearly elucidated, there is potential for practical applications of the peptides as functional food and nutraceutical ingredients, especially in adjuvant cancer therapy. This review describes the aetiological mechanisms of cancers and the production, structures, mechanisms of action, availability, and cellular and physiological anticancer activities of the food peptides. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Anti-cancer natural products isolated from chinese medicinal herbs

    Directory of Open Access Journals (Sweden)

    Wu Guosheng

    2011-07-01

    Full Text Available Abstract In recent years, a number of natural products isolated from Chinese herbs have been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, retard metastasis and enhance chemotherapy, exhibiting anti-cancer potential both in vitro and in vivo. This article summarizes recent advances in in vitro and in vivo research on the anti-cancer effects and related mechanisms of some promising natural products. These natural products are also reviewed for their therapeutic potentials, including flavonoids (gambogic acid, curcumin, wogonin and silibinin, alkaloids (berberine, terpenes (artemisinin, β-elemene, oridonin, triptolide, and ursolic acid, quinones (shikonin and emodin and saponins (ginsenoside Rg3, which are isolated from Chinese medicinal herbs. In particular, the discovery of the new use of artemisinin derivatives as excellent anti-cancer drugs is also reviewed.

  18. Alkaloids Isolated from Natural Herbs as the Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Jin-Jian Lu

    2012-01-01

    Full Text Available Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation and antimetastasis effects on various types of cancers both in vitro and in vivo. Alkaloids, such as camptothecin and vinblastine, have already been successfully developed into anticancer drugs. This paper focuses on the naturally derived alkaloids with prospective anticancer properties, such as berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine, and summarizes the mechanisms of action of these compounds. Based on the information in the literature that is summarized in this paper, the use of alkaloids as anticancer agents is very promising, but more research and clinical trials are necessary before final recommendations on specific alkaloids can be made.

  19. Neurological complications of medical anti-cancer therapies

    Directory of Open Access Journals (Sweden)

    Jerzy Hildebrand

    2011-12-01

    Full Text Available This review describes the features of central and peripheral neurological disorders caused by anti-cancer chemotherapy and supportive medications, such as antiepileptic drugs, glucocorticosteroids and opioids, frequently used in cancer patients. Diffuse encephalopathy with or without epileptic seizures, cerebellar disorders and aseptic meningitis may occur after systemic administration of conventional drug doses, but their incidence is much higher when either high-dose chemotherapy, or intrathecal or intracarotid administration is used. Spinal cord and/or spinal root lesions have been reported after intrathecal administration of methotrexate or cytosinearabinoside. Anti-cancer chemotherapy is the leading cause of peripheral neuropathy in cancer patients. The main culprits are vinca alkaloids, platinum derivatives and taxanes. Anti-cancer chemotherapy has no significant toxic effect on muscle tissue, but heavy administration of glucocorticosteroids is a common cause of disabling, predominantly pelvic, muscle atrophy.

  20. Targeted Drug Delivery System for Platinum-based Anticancer Drugs.

    Science.gov (United States)

    Gao, Chuanzhu; Zhang, Yan; Chen, Ji; Wang, Tianshuai; Qian, Yunxu; Yang, Bo; Dong, Peng; Zhang, Yingjie

    2016-01-01

    Platinum-based (Pt-based) anticancer drugs have been recognised as one of the most effective drugs for clinical treatment of malignant tumors due to its unique mechanism of action and broad range of anticancer spectrum. But, there are still some limitations such as side effects, drug resistance/cross resistance, no-specific targeting, becoming obstacles to restrict its expanding of clinical application. Targeted drug delivery system (TDDS) is a promising strategy for the research of novel Pt-based anticancer drugs. A variety of TDDS have been explored to improve the antitumor activity of Pt-based drugs such as nanoparticle drug systems, polymer-drug systems, drugs-macrocyclic compounds systems, etc. The review concentrates on recent development of various targeted drug delivery techniques, which could provide more opportunities for the development of Pt-based drugs with better efficiency, lower toxicity and less resistance.

  1. Analyses of anticancer drugs by capillary electrophoresis: a review.

    Science.gov (United States)

    Ali, Imran; Haque, Ashanul; Wani, Waseem A; Saleem, Kishwar; Al Za'abi, Mohammed

    2013-10-01

    Capillary electrophoresis is a fast, inexpensive and low detection limit technique for the analysis of anticancer drugs. It has been used to analyze various anticancer drugs in biological samples, pharmaceutical preparations and environmental matrices. It has also been used to detect various cancer biomarkers in cancer patients. The present article describes the state-of-the art of capillary electrophoresis for the analyses of anticancer drugs. Various drugs discussed belong to several groups such as antimitotic agents, nucleoside analogs, antibiotics, topoisomerase inhibitors and DNA intercalating agents. In addition, efforts have also been made to discuss sample preparation, applications of capillary electrophoresis in genomic research, optimization and future perspectives. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Sheep models of polycystic ovary syndrome phenotype

    Science.gov (United States)

    Veiga-Lopez, Almudena

    2012-01-01

    Polycystic ovary syndrome (PCOS) is a fertility disorder affecting 5–7% of reproductive-aged women. Women with PCOS manifest both reproductive and metabolic defects. Several animal models have evolved, which implicate excess steroid exposure during fetal life in the development of the PCOS phenotype. This review addresses the fetal and adult reproductive and metabolic consequences of prenatal steroid excess in sheep and the translational relevance of these findings to PCOS. By comparing findings in various breeds of sheep, the review targets the role of genetic susceptibility to fetal insults. Disruptions induced by prenatal testosterone excess are evident at both the reproductive and metabolic level with each influencing the other thus creating a self-perpetuating vicious cycle. The review highlights the need for identifying a common mediator of the dysfunctions at the reproductive and metabolic levels and developing prevention and treatment interventions targeting all sites of disruption in unison for achieving optimal success. PMID:23084976

  3. Flavonoids as anticancer agents: structure-activity relationship study.

    Science.gov (United States)

    López-Lázaro, M

    2002-11-01

    The protection against some forms of cancer provided by many common foods has been observed in multiple epidemiological studies. Non-nutritive dietary compounds, such as flavonoids, have been considered as the responsible agents for such observations and since then, much research activity has been done about their potential anticancer effect. As a result, these compounds have been shown to regulate proliferation and cell death pathways leading to cancer. Thus, flavonoids such as the synthetic flavone, flavopiridol; the soy isoflavonoid, genistein; the tea catechin epigallocatechin gallate; or the common dietary flavonol, quercetin, are emerging as prospective anticancer drug candidates and some of them have already entered in clinical trials. In view of the therapeutic potential of flavonoids, many researchers have tried to elucidate possible structure-activity relationships that might lead to new drug discovery. However, and possibly due to the information being very scattered, there is very little understanding about a possible relationship between the flavonoid structure and their anticancer activity. Besides their therapeutic potential, since lots of flavonoids are present in our diet, a greater understanding of their anticancer properties might also modify our dietary habits in order to attack cancer with an effective weapon, prevention. This paper seeks to show, in a brief but comprehensive way, the anticancer properties of flavonoids. Through an understanding of the cancer process and its treatment, flavonoids are studied as possible useful compounds in cancer prevention and cancer therapy. Furthermore, this review attempts to compile and discuss the literature studying structure-activity relationships, in order to show structural requirements implicated in the anticancer activity of flavonoids, which might help to rationalize their development as antitumor agents.

  4. Testing the grain-size model for the evolution of phenotypic plasticity.

    Science.gov (United States)

    Hollander, Johan

    2008-06-01

    Phenotypic plasticity is the ability of a genotype to modify its phenotypic characteristics in response to different environments. Theory predicts that adaptive plasticity should primarily evolve in organisms that experience heterogeneous environments. An organism's dispersal rate is a key component in these models, because the degree of dispersal partly determines the extent of environmental heterogeneity. Here, I provide the first large-scale test of the theoretical prediction that phenotypic plasticity evolves in association with dispersal rate using meta-analysis of data from 258 experiments from the literature on plasticity in marine invertebrates. In line with predictions, phenotypic plasticity is generally greater in species with higher dispersal rates, suggesting that dispersal and environmental heterogeneity are important selective agents for evolution of plasticity in marine habitats.

  5. Netgram: Visualizing Communities in Evolving Networks.

    Directory of Open Access Journals (Sweden)

    Raghvendra Mall

    Full Text Available Real-world complex networks are dynamic in nature and change over time. The change is usually observed in the interactions within the network over time. Complex networks exhibit community like structures. A key feature of the dynamics of complex networks is the evolution of communities over time. Several methods have been proposed to detect and track the evolution of these groups over time. However, there is no generic tool which visualizes all the aspects of group evolution in dynamic networks including birth, death, splitting, merging, expansion, shrinkage and continuation of groups. In this paper, we propose Netgram: a tool for visualizing evolution of communities in time-evolving graphs. Netgram maintains evolution of communities over 2 consecutive time-stamps in tables which are used to create a query database using the sql outer-join operation. It uses a line-based visualization technique which adheres to certain design principles and aesthetic guidelines. Netgram uses a greedy solution to order the initial community information provided by the evolutionary clustering technique such that we have fewer line cross-overs in the visualization. This makes it easier to track the progress of individual communities in time evolving graphs. Netgram is a generic toolkit which can be used with any evolutionary community detection algorithm as illustrated in our experiments. We use Netgram for visualization of topic evolution in the NIPS conference over a period of 11 years and observe the emergence and merging of several disciplines in the field of information processing systems.

  6. Evolving MEMS Resonator Designs for Fabrication

    Science.gov (United States)

    Hornby, Gregory S.; Kraus, William F.; Lohn, Jason D.

    2008-01-01

    Because of their small size and high reliability, microelectromechanical (MEMS) devices have the potential to revolution many areas of engineering. As with conventionally-sized engineering design, there is likely to be a demand for the automated design of MEMS devices. This paper describes our current status as we progress toward our ultimate goal of using an evolutionary algorithm and a generative representation to produce designs of a MEMS device and successfully demonstrate its transfer to an actual chip. To produce designs that are likely to transfer to reality, we present two ways to modify evaluation of designs. The first is to add location noise, differences between the actual dimensions of the design and the design blueprint, which is a technique we have used for our work in evolving antennas and robots. The second method is to add prestress to model the warping that occurs during the extreme heat of fabrication. In future we expect to fabricate and test some MEMS resonators that are evolved in this way.

  7. Netgram: Visualizing Communities in Evolving Networks

    Science.gov (United States)

    Mall, Raghvendra; Langone, Rocco; Suykens, Johan A. K.

    2015-01-01

    Real-world complex networks are dynamic in nature and change over time. The change is usually observed in the interactions within the network over time. Complex networks exhibit community like structures. A key feature of the dynamics of complex networks is the evolution of communities over time. Several methods have been proposed to detect and track the evolution of these groups over time. However, there is no generic tool which visualizes all the aspects of group evolution in dynamic networks including birth, death, splitting, merging, expansion, shrinkage and continuation of groups. In this paper, we propose Netgram: a tool for visualizing evolution of communities in time-evolving graphs. Netgram maintains evolution of communities over 2 consecutive time-stamps in tables which are used to create a query database using the sql outer-join operation. It uses a line-based visualization technique which adheres to certain design principles and aesthetic guidelines. Netgram uses a greedy solution to order the initial community information provided by the evolutionary clustering technique such that we have fewer line cross-overs in the visualization. This makes it easier to track the progress of individual communities in time evolving graphs. Netgram is a generic toolkit which can be used with any evolutionary community detection algorithm as illustrated in our experiments. We use Netgram for visualization of topic evolution in the NIPS conference over a period of 11 years and observe the emergence and merging of several disciplines in the field of information processing systems. PMID:26356538

  8. BOOK REVIEW: OPENING SCIENCE, THE EVOLVING GUIDE ...

    Science.gov (United States)

    The way we get our funding, collaborate, do our research, and get the word out has evolved over hundreds of years but we can imagine a more open science world, largely facilitated by the internet. The movement towards this more open way of doing and presenting science is coming, and it is not taking hundreds of years. If you are interested in these trends, and would like to find out more about where this is all headed and what it means to you, consider downloding Opening Science, edited by Sönke Bartling and Sascha Friesike, subtitled The Evolving Guide on How the Internet is Changing Research, Collaboration, and Scholarly Publishing. In 26 chapters by various authors from a range of disciplines the book explores the developing world of open science, starting from the first scientific revolution and bringing us to the next scientific revolution, sometimes referred to as “Science 2.0”. Some of the articles deal with the impact of the changing landscape of how science is done, looking at the impact of open science on Academia, or journal publishing, or medical research. Many of the articles look at the uses, pitfalls, and impact of specific tools, like microblogging (think Twitter), social networking, and reference management. There is lots of discussion and definition of terms you might use or misuse like “altmetrics” and “impact factor”. Science will probably never be completely open, and Twitter will probably never replace the journal article,

  9. Microtubule-targeting anticancer agents from marine natural substance.

    Science.gov (United States)

    Liu, Zhiguo; Xu, Pengfei; Wu, Tao; Zeng, Wenbin

    2014-03-01

    Effective novel therapeutics is urgently needed due to increasing incidence of malignant cancer and drug multi-resistance. Natural products and their derivatives have historically been a source of pharmaceutical leads and therapeutic drugs. Microtubule-targeting compounds are among the most promising candidates in the combat against cancer. In particular, marine natural products (MNPs) have demonstrated exceptional potency and potential as anticancer agents. Drug discovery from MNPs provides a new pathway to develop original anticancer agents. In this review, seven classes of typical MNPs with diverse structures are summarized. Bioactive marine compounds isolated from different organisms including invertebrate animals, algae, fungi and bacteria are also discussed.

  10. Hydrofocusing Bioreactor Produces Anti-Cancer Alkaloids

    Science.gov (United States)

    Gonda, Steve R.; Valluri, Jagan V.

    2011-01-01

    microgravitation of an HFB do not need to maintain the same surface forces as in normal Earth gravitation, they can divert more energy sources to growth and differentiation and, perhaps, to biosynthesis of greater quantities of desired medicinal compounds. Because one can adjust the HFB to vary effective gravitation, one can also test the effects of intermediate levels of gravitation on biosynthesis of various products. The potential utility of this methodology for producing drugs was demonstrated in experiments in which sandalwood and Madagascar periwinkle cells were grown in an HFB. The conditions in the HFB were chosen to induce the cells to form into aggregate cultures that produced anti-cancer indole alkaloids in amounts greater than do comparable numbers of cells of the same species cultured according to previously known methodologies. The observations made in these experiments were interpreted as suggesting that the aggregation of the cells might be responsible for the enhancement of production of alkaloids.

  11. Quantification of Microbial Phenotypes

    Science.gov (United States)

    Martínez, Verónica S.; Krömer, Jens O.

    2016-01-01

    Metabolite profiling technologies have improved to generate close to quantitative metabolomics data, which can be employed to quantitatively describe the metabolic phenotype of an organism. Here, we review the current technologies available for quantitative metabolomics, present their advantages and drawbacks, and the current challenges to generate fully quantitative metabolomics data. Metabolomics data can be integrated into metabolic networks using thermodynamic principles to constrain the directionality of reactions. Here we explain how to estimate Gibbs energy under physiological conditions, including examples of the estimations, and the different methods for thermodynamics-based network analysis. The fundamentals of the methods and how to perform the analyses are described. Finally, an example applying quantitative metabolomics to a yeast model by 13C fluxomics and thermodynamics-based network analysis is presented. The example shows that (1) these two methods are complementary to each other; and (2) there is a need to take into account Gibbs energy errors. Better estimations of metabolic phenotypes will be obtained when further constraints are included in the analysis. PMID:27941694

  12. Social parasitism and the molecular basis of phenotypic evolution

    Directory of Open Access Journals (Sweden)

    Alessandro eCini

    2015-02-01

    Full Text Available Contrasting phenotypes arise from similar genomes through a combination of losses, gains, co-option and modifications of inherited genomic material. Understanding the molecular basis of this phenotypic diversity is a fundamental challenge in modern evolutionary biology. Comparisons of the genes and their expression patterns underlying traits in pairs of closely related species offer an unrivalled opportunity to evaluate the extent to which genomic material is reorganised to produce novel traits. Advances in molecular methods now allow us to dissect the molecular machinery underlying phenotypic diversity in almost any organism, from single-celled organisms to the most complex vertebrates. Here we discuss how comparisons of social parasites and their free-living hosts may provide unique insights into the molecular basis of phenotypic evolution. Social parasites evolve from a social ancestor and are specialised to exploit the socially acquired resources of their closely-related, free-living social host. Molecular comparisons of such species pairs can reveal how genomic material is re-organised in the loss of ancestral traits (i.e. of free-living traits in the parasites and the gain of new ones (i.e. specialist traits required for a parasitic lifestyle. We define hypotheses on the molecular basis of phenotypes in the evolution of social parasitism and discuss their wider application in understanding the molecular basis of phenotypic diversity within the theoretical framework of phenotypic plasticity and shifting reaction norms. Currently there are no data available to test these hypotheses, and so we also provide some proof of concept data for our conceptual model using the paper wasp social parasite-host system (Polistes sulcifer - Polistes dominula. This conceptual framework and first empirical data provide a spring-board for directing future genomic analyses on exploiting social parasites as a route to understanding the evolution of phenotypic

  13. Evolvability as a Quality Attribute of Software Architectures

    NARCIS (Netherlands)

    Ciraci, S.; van den Broek, P.M.; Duchien, Laurence; D'Hondt, Maja; Mens, Tom

    We review the definition of evolvability as it appears on the literature. In particular, the concept of software evolvability is compared with other system quality attributes, such as adaptability, maintainability and modifiability.

  14. Environmental change, phenotypic plasticity, and genetic compensation.

    Science.gov (United States)

    Grether, Gregory F

    2005-10-01

    When a species encounters novel environmental conditions, some phenotypic characters may develop differently than in the ancestral environment. Most environmental perturbations of development are likely to reduce fitness, and thus selection would usually be expected to favor genetic changes that restore the ancestral phenotype. I propose the term "genetic compensation" to refer to this form of adaptive evolution. Genetic compensation is a subset of genetic accommodation and the reverse of genetic assimilation. When genetic compensation has occurred along a spatial environmental gradient, the mean trait values of populations in different environments may be more similar in the field than when representatives of the same populations are raised in a common environment (i.e., countergradient variation). If compensation is complete, genetic divergence between populations may be cryptic, that is, not detectable in the field. Here I apply the concept of genetic compensation to three examples involving carotenoid-based sexual coloration and then use these and other examples to discuss the concept in a broader context. I show that genetic compensation may lead to a cryptic form of reproductive isolation between populations evolving in different environments, may explain some puzzling cases in which heritable traits exposed to strong directional selection fail to show the expected evolutionary response, and may complicate efforts to monitor populations for signs of environmental deterioration.

  15. Evolution of phenotypic plasticity in extreme environments.

    Science.gov (United States)

    Chevin, Luis-Miguel; Hoffmann, Ary A

    2017-06-19

    Phenotypic plasticity, if adaptive, may allow species to counter the detrimental effects of extreme conditions, but the infrequent occurrence of extreme environments and/or their restriction to low-quality habitats within a species range means that they exert little direct selection on reaction norms. Plasticity could, therefore, be maladaptive under extreme environments, unless genetic correlations are strong between extreme and non-extreme environmental states, and the optimum phenotype changes smoothly with the environment. Empirical evidence suggests that populations and species from more variable environments show higher levels of plasticity that might preadapt them to extremes, but genetic variance for plastic responses can also be low, and genetic variation may not be expressed for some classes of traits under extreme conditions. Much of the empirical literature on plastic responses to extremes has not yet been linked to ecologically relevant conditions, such as asymmetrical fluctuations in the case of temperature extremes. Nevertheless, evolved plastic responses are likely to be important for natural and agricultural species increasingly exposed to climate extremes, and there is an urgent need to collect empirical information and link this to model predictions.This article is part of the themed issue 'Behavioural, ecological and evolutionary responses to extreme climatic events'. © 2017 The Author(s).

  16. Tracking correlated, simultaneously evolving target populations, II

    Science.gov (United States)

    Mahler, Ronald

    2017-05-01

    This paper is the sixth in a series aimed at weakening the independence assumptions that are typically presumed in multitarget tracking. Earlier papers investigated Bayes …lters that propagate the correlations between two evolving multitarget systems. Last year at this conference we attempted to derive PHD …lter-type approximations that account for both spatial correlation and cardinality correlation (i.e., correlation between the target numbers of the two systems). Unfortunately, this approach required heuristic models of both clutter and target appearance in order to incorporate both spatial and cardinality correlation. This paper describes a fully rigorous approach- provided, however, that spatial correlation between the two populations is ignored and only their cardinality correlations are taken into account. We derive the time-update and measurement-update equations for a CPHD …lter describing the evolution of such correlated multitarget populations.

  17. Resiliently evolving supply-demand networks.

    Science.gov (United States)

    Rubido, Nicolás; Grebogi, Celso; Baptista, Murilo S

    2014-01-01

    The ability to design a transport network such that commodities are brought from suppliers to consumers in a steady, optimal, and stable way is of great importance for distribution systems nowadays. In this work, by using the circuit laws of Kirchhoff and Ohm, we provide the exact capacities of the edges that an optimal supply-demand network should have to operate stably under perturbations, i.e., without overloading. The perturbations we consider are the evolution of the connecting topology, the decentralization of hub sources or sinks, and the intermittence of supplier and consumer characteristics. We analyze these conditions and the impact of our results, both on the current United Kingdom power-grid structure and on numerically generated evolving archetypal network topologies.

  18. A local-world evolving hypernetwork model

    Science.gov (United States)

    Yang, Guang-Yong; Liu, Jian-Guo

    2014-01-01

    Complex hypernetworks are ubiquitous in the real system. It is very important to investigate the evolution mechanisms. In this paper, we present a local-world evolving hypernetwork model by taking into account the hyperedge growth and local-world hyperedge preferential attachment mechanisms. At each time step, a newly added hyperedge encircles a new coming node and a number of nodes from a randomly selected local world. The number of the selected nodes from the local world obeys the uniform distribution and its mean value is m. The analytical and simulation results show that the hyperdegree approximately obeys the power-law form and the exponent of hyperdegree distribution is γ = 2 + 1/m. Furthermore, we numerically investigate the node degree, hyperedge degree, clustering coefficient, as well as the average distance, and find that the hypernetwork model shares the scale-free and small-world properties, which shed some light for deeply understanding the evolution mechanism of the real systems.

  19. The Evolving Theory of Evolutionary Radiations.

    Science.gov (United States)

    Simões, M; Breitkreuz, L; Alvarado, M; Baca, S; Cooper, J C; Heins, L; Herzog, K; Lieberman, B S

    2016-01-01

    Evolutionary radiations have intrigued biologists for more than 100 years, and our understanding of the patterns and processes associated with these radiations continues to grow and evolve. Recently it has been recognized that there are many different types of evolutionary radiation beyond the well-studied adaptive radiations. We focus here on multifarious types of evolutionary radiations, paying special attention to the abiotic factors that might trigger diversification in clades. We integrate concepts such as exaptation, species selection, coevolution, and the turnover-pulse hypothesis (TPH) into the theoretical framework of evolutionary radiations. We also discuss other phenomena that are related to, but distinct from, evolutionary radiations that have relevance for evolutionary biology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Epidemic spreading on evolving signed networks

    CERN Document Server

    Saeedian, M; Jafari, G R; Kertesz, J

    2016-01-01

    Most studies of disease spreading consider the underlying social network as obtained without the contagion, though epidemic influences peoples willingness to contact others: A friendly contact may be turned to unfriendly to avoid infection. We study the susceptible-infected (SI) disease spreading model on signed networks, in which each edge is associated with a positive or negative sign representing the friendly or unfriendly relation between its end nodes. In a signed network, according to Heiders theory, edge signs evolve such that finally a state of structural balance is achieved, corresponding to no frustration in physics terms. However, the danger of infection affects the evolution of its edge signs. To describe the coupled problem of the sign evolution and disease spreading, we generalize the notion of structural balance by taking into account the state of the nodes. We introduce an energy function and carry out Monte-Carlo simulations on complete networks to test the energy landscape, where we find loc...

  1. Finch: A System for Evolving Java (Bytecode)

    Science.gov (United States)

    Orlov, Michael; Sipper, Moshe

    The established approach in genetic programming (GP) involves the definition of functions and terminals appropriate to the problem at hand, after which evolution of expressions using these definitions takes place. We have recently developed a system, dubbed FINCH (Fertile Darwinian Bytecode Harvester), to evolutionarily improve actual, extant software, which was not intentionally written for the purpose of serving as a GP representation in particular, nor for evolution in general. This is in contrast to existing work that uses restricted subsets of the Java bytecode instruction set as a representation language for individuals in genetic programming. The ability to evolve Java programs will hopefully lead to a valuable new tool in the software engineer's toolkit.

  2. Marine bioactive peptides with anti-cancer potential

    Directory of Open Access Journals (Sweden)

    Mohammad Nazarian

    2015-07-01

    Full Text Available In the developing world, the cancer as a prevalent cause of mortality is a new emerging challenges in medical and pharmaceutical sciences. Marine environs are regarded as a rich source of natural products with broad of therapeutic uses. Numerous bioactive peptides and depsi-peptides have been extracted from various marine organisms such as tunicates, sponges, molluscs and other marine organisms, with anti-cancer potential. They can produce the complex compounds which are more effective than presented anti-cancer drugs. Some of these marine peptides are under different clinical trials phases they are secondary metabolites that produced by these organisms. According to different studies, their anti-cancer potential is related to some properties like antioxidant, anti- proliferative and anti-mutations effects. These peptides can stimulate cell death by various mechanisms, such as apoptosis, affecting the balance tubulin- microtubules (antimicrotubules, inhibition of angiogenesis, antiproliferative and cytotoxicity effects. Further studies on the reaction states of these compounds on cell cycle or apoptosis in cancer cells, are essential. The future of remedies, belong to the sea and the sea, will have the major percentage in drug discovery, particularly in anti-cancer drugs.

  3. Natural flora and anticancer regime: milestones and roadmap.

    Science.gov (United States)

    Bhatnagar, Ira; Thomas, Noel Vinay; Kim, Se-Kwon

    2013-07-01

    Cancer has long been an area of extensive research both at the molecular as well as pharmaceutical level. However, lack of understanding of the underlying molecular signalling and the probable targets of therapeutics is a major concern in successful treatment of cancer. The situation becomes even worse, with the increasing side effects of the existing synthetic commercial drugs. Natural compounds especially those derived from plants have been best explored for their anticancer properties and most of them have been efficient against the known molecular targets of cancer. However, advent of biotechnology and resulting advances in medical arena have let to the increasing knowledge of newer carcinogenic signaling agents which has made the anticancer drug discovery even more demanding. The present review aims to bring forward the molecular mediators of cancer and compiles the plant derived anticancer agents with special emphasis on their clinical status. Since marine arena has proved to be a tremendous source of pharmaceutical agents, this review also focuses on the anticancer potential of marine plants especially algae. This is a comprehensive review covering major aspects of cancer mediation and utilization of marine flora for remediation of this deadly disease.

  4. Anticancer Activities of Nigella sativa (Black Cumin) | Khan | African ...

    African Journals Online (AJOL)

    African Journal of Traditional, Complementary and Alternative Medicines ... Nigella sativa has been used as traditional medicine for centuries. ... Although the anti-cancer activity of N. sativa components was recognized thousands of years ago but proper scientific research with this important traditional medicine is a history ...

  5. Anti-cancer and antioxidant properties of phenolics isolated from ...

    African Journals Online (AJOL)

    Purpose: To investigate the antioxidant and anticancer activities of phenolics from the leaf extract of. Toona sinensis (TS). Methods: Acetone leaf extract of TS was screened for total phenolic and flavanoid contents, and the flanonoids were subjected to high performance liquid chromatographic (HPLC) analysis. Antioxidant.

  6. Anticancer Constituents and Cytotoxic Activity of Methanol-Water ...

    African Journals Online (AJOL)

    This study was specifically designed to identify anticancer constituents in methanol-water extract of Polygonum bistorta L. and evaluate its cytotoxicity. For this purpose methanol-water (40:60 v/v) extract was subjected to conventional preparative high pressure liquid chromatography and 13 fractions were obtained.

  7. Synthesis, docking and anticancer activity studies of D-proline ...

    Indian Academy of Sciences (India)

    Synthesis, docking and anticancer activity studies of D-proline-incorporated wainunuamide. M HIMAJAa,∗, A RANJITHAa and SUNIL V MALIb. aSchool of Advanced Sciences, Pharmaceutical Chemistry Division, VIT University, Vellore 632 014, India. bMedicinal Chemistry Division, Piramal Life Science Ltd., Mumbai 400 ...

  8. Ethnomedicine claim directed in Silico prediction of anticancer activity

    African Journals Online (AJOL)

    Background: The merits of ethnomedicine-led approach to identify and prioritize anticancer medicinal plants have been challenged as cancer is more likely to be poorly understood in traditional medicine practices. Nonetheless, it is also believed that useful data can be generated by combining ethnobotanical findings with ...

  9. Anticancer Activity of Extracts from some Endemic Tanzanian Plants ...

    African Journals Online (AJOL)

    Plants have shown to be good sources of a variety of drugs for human ailments including cancer. Tanzania is rich in plant species most of which have not been investigated for any biological activity. In the continuing effort to screen Tanzanian plants for anticancer activity, plants were collected from Lindi region and extracts ...

  10. Isolation and identification of flavonoids from anticancer and ...

    African Journals Online (AJOL)

    Moreover, the extracts exhibited anticancer activity against Hep2 and MCF-7cells and low cytotoxicity against HCEC, sparing healthy cells in-vitro. In addition, two flavonoids amurensin and cosmosiin were isolated from T. foenum graecum extracts. Conclusion: Amurensin and cosmosiin from T. foenum extracts are reported ...

  11. Evaluation of anticancer potential of eight vegetal species from the ...

    African Journals Online (AJOL)

    Background: Eight plant species from Oaxaca, some of them used in traditional medicine, were subjected to screening of several biological activities to provide data regarding their anticancer potential, although no scientific information is available about their pharmacological effects. Materials and methods: Methanol ...

  12. Anticancer Effect of AntiMalarial Artemisinin Compounds | Das ...

    African Journals Online (AJOL)

    A PubMed search of about 127 papers on anti‑cancer effects of antimalarials has revealed that this class of drug, including other antimalarials, have several biological characteristics that include anticancer properties. Experimental evidences suggest that artemisinin compounds may be a therapeutic alternative in highly ...

  13. Screening of Chinese brassica species for anti-cancer sulforaphane ...

    African Journals Online (AJOL)

    SERVER

    2008-01-18

    Jan 18, 2008 ... China. 2Institute of Farming Products Processing, Hangzhou Academy of Agricultural Sciences, Hanzhou 310024, China. Accepted 5 December, 2007. Natural sulforaphane and erucin have been of increasing interest for nutraceutical and pharmaceutical industries due to their anti-cancer effect.

  14. Anticancer Activity of Chamaejasmine: Effect on Tubulin Protein

    Directory of Open Access Journals (Sweden)

    Yingkun Nie

    2011-07-01

    Full Text Available In this work, the anticancer activity of chamaejasmine was studied by evaluating its in vitro cytotoxicity against several human cancer cell lines (MCF-7, A549, SGC-7901, HCT-8, HO-4980, Hela, HepG2, PC-3, LNCap, Vero and MDCK using the MTT assay. Results indicated chamaejasmine showed more notable anticancer activity than taxol against PC-3 cells, with IC50 values of 2.28 and 3.98 µM, respectively. Furthermore, Western blot analysis showed that chamaejasmine was able to increase the expression of β-tubulin, but not α-tubulin. In silico simulations indicated that chamaejasmine specifically interacts with the active site which is located at the top of β-tubulin, thanks to the presence of strong hydrophobic effects between the core templates and the hydrophobic surface of the TB active site. The binding energy (Einter was calculated to be −164.77 kcal·mol−1. Results presented here suggest that chamaejasmine possesses anti-cancer properties relating to β-tubulin depolymerization inhibition, and therefore is a potential source of anticancer leads for the pharmaceutical industry.

  15. Anticancer biology of Azadirachta indica L (neem): a mini review.

    Science.gov (United States)

    Paul, Rajkumar; Prasad, Murari; Sah, Nand K

    2011-09-15

    Neem (Azadirachta indica), a member of the Meliaceae family, is a fast growing tropical evergreen tree with a highly branched and stout, solid stem. Because of its tremendous therapeutic, domestic, agricultural and ethnomedicinal significance, and its proximity with human culture and civilization, neem has been called "the wonder tree" and "nature's drug store." All parts of this tree, particularly the leaves, bark, seed-oil and their purified products are widely used for treatment of cancer. Over 60 different types of biochemicals including terpenoids and steroids have been purified from this plant. Pre-clinical research work done during the last decade has fine-tuned our understanding of the anticancer properties of the crude and purified products from this plant. The anticancer properties of the plant have been studied largely in terms of its preventive, protective, tumor-suppressive, immunomodulatory and apoptotic effects against various types of cancer and their molecular mechanisms. This review aims at scanning scattered literature on "the anticancer biology of A. indica," related toxicity problems and future perspectives. The cogent data on the anticancer biology of products from A. indica deserve multi-institutional clinical trials as early as possible. The prospects of relatively cheaper cancer drugs could then be brighter, particularly for the under-privileged cancer patients of the world.

  16. Sphingolipid metabolism enzymes as targets for anticancer therapy

    NARCIS (Netherlands)

    Kok, JW; Sietsma, H

    Treatment with anti-cancer agents in most cases ultimately results in apoptotic cell death of the target tumour cells. Unfortunately, tumour cells can develop multidrug resistance, e.g., by a reduced propensity to engage in apoptosis by which they become insensitive to multiple chemotherapeutics.

  17. Anticancer effects of Chinese herbal medicine, science or myth?

    Science.gov (United States)

    Ruan, Wen-jing; Lai, Mao-de; Zhou, Jian-guang

    2006-12-01

    Currently there is considerable interest among oncologists to find anticancer drugs in Chinese herbal medicine (CHM). In the past, clinical data showed that some herbs possessed anticancer properties, but western scientists have doubted the scientific validity of CHM due to the lack of scientific evidence from their perspective. Recently there have been encouraging results, from a western perspective, in the cancer research field regarding the anticancer effects of CHM. Experiments showed that CHM played its anticancer role by inducing apoptosis and differentiation, enhancing the immune system, inhibiting angiogenesis, reversing multidrug resistance (MDR), etc. Clinical trials demonstrated that CHM could improve survival, increase tumor response, improve quality of life, or reduce chemotherapy toxicity, although much remained to be determined regarding the objective effects of CHM in human in the context of clinical trials. Interestingly, both laboratory experiments and clinical trials have demonstrated that when combined with chemotherapy, CHM could raise the efficacy level and lower toxic reactions. These facts raised the feasibility of the combination of herbal medicines and chemotherapy, although much remained to be investigated in this area.

  18. Studies of anticancer and antipyretic activity of Bidens pilosa whole ...

    African Journals Online (AJOL)

    . (Asteraceae) has been conducted using the in – vitro comet assay for anticancer and the antipyretic action, which was done with in – vivo models. The extract from whole plant was extracted with n – hexane, chloroform and methanol extract ...

  19. Antibody Positron Emission Tomography Imaging in Anticancer Drug Development

    NARCIS (Netherlands)

    Lamberts, Laetitia E.; Williams, Simon P.; Terwisscha Van Scheltinga, Anton; Lub-de Hooge, Marjolijn N.; Schroeder, Carolien P.; Gietema, Jourik A.; Brouwers, Adrienne H.; de Vries, Elisabeth G. E.

    2015-01-01

    More than 50 monoclonal antibodies (mAbs), including several antibody-drug conjugates, are in advanced clinical development, forming an important part of the many molecularly targeted anticancer therapeutics currently in development. Drug development is a relatively slow and expensive process,

  20. Syntheses, characterization, and anti-cancer activities of pyridine ...

    Indian Academy of Sciences (India)

    Syntheses, characterization, and anti-cancer activities of pyridine-amide based compounds containing appended phenol or catechol groups. AFSAR ALIa, DEEPAK BANSALa, NAGENDRA K KAUSHIKb, NEHA KAUSHIKb,. EUN HA CHOIb and RAJEEV GUPTAa,∗. aDepartment of Chemistry, University of Delhi, Delhi 110 ...

  1. Anti-cancer and antioxidant properties of phenolics isolated from ...

    African Journals Online (AJOL)

    Purpose: To investigate the antioxidant and anticancer activities of phenolics from the leaf extract of Toona sinensis (TS). Methods: Acetone leaf extract of TS was screened for total phenolic and flavanoid contents, and the flanonoids were subjected to high performance liquid chromatographic (HPLC) analysis. Antioxidant ...

  2. Mitochondrial chaperones may be targets for anti-cancer drugs

    Science.gov (United States)

    Scientists at NCI have found that a mitochondrial chaperone protein, TRAP1, may act indirectly as a tumor suppressor as well as a novel target for developing anti-cancer drugs. Chaperone proteins, such as TRAP1, help other proteins adapt to stress, but sc

  3. Safety, pharmacokinetics and pharmacodynamics of targeted anti-cancer drugs

    NARCIS (Netherlands)

    Boss, D.S.

    2009-01-01

    With the emergence of novel, rationally designed anti-cancer drugs there is also a need for novel endpoints when evaluating these drugs in clinical trials. The combined PET/CT scanner can be a very useful tool in the process of drug development in several ways, which is described in the first

  4. New pyridocarbazole derivatives. Synthesis and their in vitro anticancer activity

    National Research Council Canada - National Science Library

    Jasztold-Howorko, Ryszard; Tylińska, Beata; Biaduń, Bogusława; Gebarowski, Tomasz; Gasiorowski, Kazimierz

    2013-01-01

    .... The anticancer activity of 9-methoxy-5,6-dimethyl-1-[(1,1-bis-hydroxymethyI-propylamino)-methyl]-6H-pyrido[4,3-b]carbazole (compound 9) was the strongest amongst compounds tested on the three cancer cell lines...

  5. Screening of Chinese brassica species for anti-cancer sulforaphane ...

    African Journals Online (AJOL)

    Natural sulforaphane and erucin have been of increasing interest for nutraceutical and pharmaceutical industries due to their anti-cancer effect. The sulforaphane and/or erucin contents in seeds of 43 different Chinese Brassica oleracea L. varieties were analyzed by HPLC and GC-MS. Among them, 21 cultivars seed meal ...

  6. Synthesis and Biophysical Characterization of Chlorambucil Anticancer Ether Lipid Prodrugs

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob; Christensen, Mikkel Stochkendahl; Ruysschaert, Tristan

    2009-01-01

    The synthesis and biophysical characterization of four prodrug ether phospholipid conjugates are described. The lipids are prepared from the anticancer drug chlorambucil and have C16 and C18 ether chains with phosphatidylcholine or phosphatidylglycerol headgroups. All four prodrugs have the ability...

  7. Therapeutic Effectiveness of Anticancer Phytochemicals on Cancer Stem Cells.

    Science.gov (United States)

    Oh, Jisun; Hlatky, Lynn; Jeong, Yong-Seob; Kim, Dohoon

    2016-06-30

    Understanding how to target cancer stem cells (CSCs) may provide helpful insights for the development of therapeutic or preventive strategies against cancers. Dietary phytochemicals with anticancer properties are promising candidates and have selective impact on CSCs. This review summarizes the influence of phytochemicals on heterogeneous cancer cell populations as well as on specific targeting of CSCs.

  8. Antidiabetic and anticancer activities of Mangifera indica cv. Okrong leaves.

    Science.gov (United States)

    Ganogpichayagrai, Aunyachulee; Palanuvej, Chanida; Ruangrungsi, Nijsiri

    2017-01-01

    Diabetes and cancer are a major global public health problem. Plant-derived agents with undesirable side-effects were required. This study aimed to evaluate antidiabetic and anticancer activities of the ethanolic leaf extract of Mangifera indica cv. Okrong and its active phytochemical compound, mangiferin. Antidiabetic activities against yeast α-glucosidase and rat intestinal α-glucosidase were determined using 1 mM of p-nitro phenyl-α-D-glucopyranoside as substrate. Inhibitory activity against porcine pancreatic α-amylase was performed using 1 mM of 2-chloro-4 nitrophenol-α-D-maltotroside-3 as substrate. Nitrophenol product was spectrophotometrically measured at 405 nm. Anticancer activity was evaluated against five human cancer cell lines compared to two human normal cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Mango leaf extract and mangiferin exhibited dose-dependent inhibition against yeast α-glucosidase with the IC50 of 0.0503 and 0.5813 mg/ml, respectively, against rat α-glucosidase with the IC50 of 1.4528 and 0.4333 mg/ml, respectively, compared to acarbose with the IC50 of 11.9285 and 0.4493 mg/ml, respectively. For anticancer activity, mango leaf extract, at ≥200 μg/ml showed cytotoxic potential against all tested cancer cell lines. In conclusion, mango leaf possessed antidiabetic and anticancer potential in vitro.

  9. Antidiabetic and anticancer activities of Mangifera indica cv. Okrong leaves

    Directory of Open Access Journals (Sweden)

    Aunyachulee Ganogpichayagrai

    2017-01-01

    Full Text Available Diabetes and cancer are a major global public health problem. Plant-derived agents with undesirable side-effects were required. This study aimed to evaluate antidiabetic and anticancer activities of the ethanolic leaf extract of Mangifera indica cv. Okrong and its active phytochemical compound, mangiferin. Antidiabetic activities against yeast α-glucosidase and rat intestinal α-glucosidase were determined using 1 mM of p-nitrophenyl-α-D-glucopyranoside as substrate. Inhibitory activity against porcine pancreatic α-amylase was performed using 1 mM of 2-chloro-4 nitrophenol-α-D-maltotroside-3 as substrate. Nitrophenol product was spectrophotometrically measured at 405 nm. Anticancer activity was evaluated against five human cancer cell lines compared to two human normal cell lines using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Mango leaf extract and mangiferin exhibited dose-dependent inhibition against yeast α-glucosidase with the IC 50 of 0.0503 and 0.5813 mg/ml, respectively, against rat α-glucosidase with the IC 50 of 1.4528 and 0.4333 mg/ml, respectively, compared to acarbose with the IC 50 of 11.9285 and 0.4493 mg/ml, respectively. For anticancer activity, mango leaf extract, at ≥200 μg/ml showed cytotoxic potential against all tested cancer cell lines. In conclusion, mango leaf possessed antidiabetic and anticancer potential in vitro.

  10. Isoflavones from Calpurnia aurea subsp. Aurea and their Anticancer ...

    African Journals Online (AJOL)

    Conclusion: The isoflavones showed moderate activity against the renal, melanoma and breast cancer cell lines tested against, with the isoflavones 2 and 5 showing the best activity of the compounds tested. These isoflavones may have a synergistic effect with other anticancer drugs. Key words: Calpurnia aurea, Fabaceae, ...

  11. Anticancer activities of bovine and human lactoferricin-derived peptides.

    Science.gov (United States)

    Arias, Mauricio; Hilchie, Ashley L; Haney, Evan F; Bolscher, Jan G M; Hyndman, M Eric; Hancock, Robert E W; Vogel, Hans J

    2017-02-01

    Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits broad-spectrum anticancer activity, while a similar peptide derived from human LF (hLF) is not as active. In this work, several peptides derived from the N-terminal regions of bLF and hLF were studied for their anticancer activities against leukemia and breast-cancer cells, as well as normal peripheral blood mononuclear cells. The cyclized LFcinB-CLICK peptide, which possesses a stable triazole linkage, showed improved anticancer activity, while short peptides hLF11 and bLF10 were not cytotoxic to cancer cells. Interestingly, hLF11 can act as a cell-penetrating peptide; when combined with the antimicrobial core sequence of LFcinB (RRWQWR) through either a Pro or Gly-Gly linker, toxicity to Jurkat cells increased. Together, our work extends the library of LF-derived peptides tested for anticancer activity, and identified new chimeric peptides with high cytotoxicity towards cancerous cells. Additionally, these results support the notion that short cell-penetrating peptides and antimicrobial peptides can be combined to create new adducts with increased potency.

  12. Recent advancements in oxadiazole-based anticancer agents

    African Journals Online (AJOL)

    oxadiazole thioglycosides. Eur J Med Chem 2011; 46: 229-235. 21. Kumar D, Sundaree S, Johnson EO, Shah K. An efficient synthesis and biological study of novel indolyl-1,3,4- oxadiazoles as potent anticancer agents. Bioorg Med. Chem Lett 2009; 19: 4492–4494. 22. Tong Y, Bouska JJ, Ellis PA, Johnson EF, Leverson J,.

  13. Development of Anticancer Agents from Plant-Derived Sesquiterpene Lactones.

    Science.gov (United States)

    Ren, Yulin; Yu, Jianhua; Kinghorn, A Douglas

    2016-01-01

    Sesquiterpene lactones are of considerable interest due to their potent bioactivities, including cancer cell cytotoxicity and antineoplastic efficacy in in vivo studies. Among these compounds, artesunate, dimethylaminoparthenolide, and L12ADT peptide prodrug, a derivative of thapsigargin, are being evaluated in the current cancer clinical or preclinical trials. Based on the structures of several antitumor sesquiterpene lactones, a number of analogues showing greater potency have been either isolated as natural products or partially synthesized, and some potential anticancer agents that have emerged from this group of lead compounds have been investigated extensively. The present review focuses on artemisinin, parthenolide, thapsigargin, and their naturally occurring or synthetic analogues showing potential anticancer activity. This provides an overview of the advances in the development of these types of sesquiterpene lactones as potential anticancer agents, including their structural characterization, synthesis and synthetic modification, and antitumor potential, with the mechanism of action and structure-activity relationships also discussed. It is hoped that this will be helpful in stimulating the further interest in developing sesquiterpene lactones and their derivatives as new anticancer agents.

  14. a review of the anticancer potential of the antimalarial herbal ...

    African Journals Online (AJOL)

    David Ofori-Adjei

    2013-09-01

    Sep 1, 2013 ... inflammatory activity. This review looks at the mechanisms of cryptolepis-induced cytotoxicity, its ... inhibition is a major mechanism of several anticancer agents including etoposide to induce apoptosis.11 ... genes, induce genomic instability, increase angiogenesis, alter the genomic epigenetic state and.

  15. Phytochemical and Anticancer Studies on Ten Medicinal Plants ...

    African Journals Online (AJOL)

    Ten medicinal plants used in Nigerian ethno medicine were subjected to phytochemical and anticancer studies using established standard procedures. The result of the study revealed the presence of phytochemical constituents such as alkaloids, saponins, tannins and flavonoids. Anona muricata, Andrographis paniculata ...

  16. Betulinic acid, a natural compound with potent anticancer effects

    NARCIS (Netherlands)

    Mullauer, Franziska B.; Kessler, Jan H.; Medema, Jan Paul

    2010-01-01

    New therapies using novel mechanisms to induce tumor cell death are needed with plants playing a crucial role as a source for potential anticancer compounds. One highly promising class of natural compounds are the triterpenoids with betulinic acid (BetA) as the most prominent representative.

  17. Synergistic effect of PEGylated resveratrol on delivery of anticancer drugs.

    Science.gov (United States)

    Wang, Wenlong; Zhang, Liang; Le, Yuan; Chen, Jian-Feng; Wang, Jiexin; Yun, Jimmy

    2016-02-10

    Resveratrol (RES) is a natural polyphenol which can be considered as a nutraceutical because of its benefits such as anticancer and antioxidant activity. In this paper, we designed polymer-RES conjugates as anticancer drug carrier for synergistic therapeutic effect in cancer treatment. Bicalutamide (BIC) was used as a model drug to investigate the drug release behaviors and in vitro anticancer performance. PEG-RES and PEG-Glycine-RES nanoparticles were prepared and characterized. The size of the prepared particles was around 50 nm with RES content of 17.2 and 16.3 wt% for PEG-RES and PEG-Glycine-RES, respectively, and BIC loading efficiency were of 81.6% and 84.5%, separately. Release rate of RES from conjugates depended on the stability of ester group against hydrolysis. BIC release was much faster than RES release. The anticancer activity of BIC loaded PEGylated RES nanoparticles was much better than that of free BIC, indicating the conjugates provided a synergetic cytotoxicity to cancer cells. Confocal laser scanning microscopy observation and flow cytometry analyses indicated that PEGylated RES conjugates were more efficiently internalized into cells, released drug into cytoplasm. These results suggest that PEGylated RES conjugates show great potential for cancer therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Preclinical and clinical pharmacology of oral anticancer drugs

    NARCIS (Netherlands)

    Oostendorp, R.L.

    2009-01-01

    Nowadays, more than 25% of all anticancer drugs are developed as oral formulations. Oral administration of drugs has several advantages over intravenous (i.v.) administration. It will on average be more convenient for patients, because they can take oral medication themselves, there is no need for

  19. Electrolyte disorders associated with the use of anticancer drugs.

    Science.gov (United States)

    Liamis, George; Filippatos, Theodosios D; Elisaf, Moses S

    2016-04-15

    The use of anticancer drugs is beneficial for patients with malignancies but is frequently associated with the occurrence of electrolyte disorders, which can be hazardous and in many cases fatal. The review presents the electrolyte abnormalities that can occur with the use of anticancer drugs and provides the related mechanisms. Platinum-containing anticancer drugs induce hypomagnesemia, hypokalemia and hypocalcemia. Moreover, platinum-containing drugs are associated with hyponatremia, especially when combined with large volumes of hypotonic fluids aiming to prevent nephrotoxicity. Alkylating agents have been linked with the occurrence of hyponatremia [due to syndrome of inappropriate antidiuretic hormone secretion (SIADH)] and Fanconi's syndrome (hypophosphatemia, aminoaciduria, hypouricemia and/or glucosuria). Vinca alkaloids are associated with hyponatremia due to SIADH. Epidermal growth factor receptor monoclonal antibody inhibitors induce hypomagnesemia, hypokalemia and hypocalcemia. Other, monoclonal antibodies, such as cixutumumab, cause hyponatremia due to SIADH. Tyrosine kinase inhibitors are linked to hyponatremia and hypophosphatemia. Mammalian target of rapamycin inhibitors induce hyponatremia (due to aldosterone resistance), hypokalemia and hypophosphatemia. Other drugs such as immunomodulators or methotrexate have been also associated with hyponatremia. The administration of estrogens at high doses, streptozocin, azacitidine and suramin may induce hypophosphatemia. Finally, the drug-related tumor lysis syndrome is associated with hyperphosphatemia, hyperkalemia and hypocalcemia. The prevention of electrolyte derangements may lead to reduction of adverse events during the administration of anticancer drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. A systematic analysis of FDA-approved anticancer drugs.

    Science.gov (United States)

    Sun, Jingchun; Wei, Qiang; Zhou, Yubo; Wang, Jingqi; Liu, Qi; Xu, Hua

    2017-10-03

    The discovery of novel anticancer drugs is critical for the pharmaceutical research and development, and patient treatment. Repurposing existing drugs that may have unanticipated effects as potential candidates is one way to meet this important goal. Systematic investigation of efficient anticancer drugs could provide valuable insights into trends in the discovery of anticancer drugs, which may contribute to the systematic discovery of new anticancer drugs. In this study, we collected and analyzed 150 anticancer drugs approved by the US Food and Drug Administration (FDA). Based on drug mechanism of action, these agents are divided into two groups: 61 cytotoxic-based drugs and 89 target-based drugs. We found that in the recent years, the proportion of targeted agents tended to be increasing, and the targeted drugs tended to be delivered as signal drugs. For 89 target-based drugs, we collected 102 effect-mediating drug targets in the human genome and found that most targets located on the plasma membrane and most of them belonged to the enzyme, especially tyrosine kinase. From above 150 drugs, we built a drug-cancer network, which contained 183 nodes (150 drugs and 33 cancer types) and 248 drug-cancer associations. The network indicated that the cytotoxic drugs tended to be used to treat more cancer types than targeted drugs. From 89 targeted drugs, we built a cancer-drug-target network, which contained 214 nodes (23 cancer types, 89 drugs, and 102 targets) and 313 edges (118 drug-cancer associations and 195 drug-target associations). Starting from the network, we discovered 133 novel drug-cancer associations among 52 drugs and 16 cancer types by applying the common target-based approach. Most novel drug-cancer associations (116, 87%) are supported by at least one clinical trial study. In this study, we provided a comprehensive data source, including anticancer drugs and their targets and performed a detailed analysis in term of historical tendency and networks. Its

  1. Observation and Analysis of Anti-cancer Drug Use and Dose ...

    African Journals Online (AJOL)

    As all anti-cancer drugs are of narrow therapeutic window so dose individualization is required to be done. A study was conducted to check the use of anti-cancer drugs in the local anti-cancer facility of Bahawalpur i.e. Bahawalpur Institute of Nuclear Medicine and Oncology (BINO). In this study, the dose individualization ...

  2. [Review in the studies on tannins activity of cancer prevention and anticancer].

    Science.gov (United States)

    Li, Haixia; Wang, Zhao; Liu, Yanze

    2003-06-01

    This paper reviewed the biological activities of tannins in cancer prevention and anticancer, and mainly discussed related mechanisms. The results suggest that tannins, whether total tannins or pure tannin compound, have remarkable activity in cancer prevention and anticancer. It has wealthy foreground for developing new cancer prevention agents and/or new anticancer drugs screening among tannin compounds.

  3. In silico identification of anti-cancer compounds and plants from traditional Chinese medicine database

    Science.gov (United States)

    Dai, Shao-Xing; Li, Wen-Xing; Han, Fei-Fei; Guo, Yi-Cheng; Zheng, Jun-Juan; Liu, Jia-Qian; Wang, Qian; Gao, Yue-Dong; Li, Gong-Hua; Huang, Jing-Fei

    2016-05-01

    There is a constant demand to develop new, effective, and affordable anti-cancer drugs. The traditional Chinese medicine (TCM) is a valuable and alternative resource for identifying novel anti-cancer agents. In this study, we aim to identify the anti-cancer compounds and plants from the TCM database by using cheminformatics. We first predicted 5278 anti-cancer compounds from TCM database. The top 346 compounds were highly potent active in the 60 cell lines test. Similarity analysis revealed that 75% of the 5278 compounds are highly similar to the approved anti-cancer drugs. Based on the predicted anti-cancer compounds, we identified 57 anti-cancer plants by activity enrichment. The identified plants are widely distributed in 46 genera and 28 families, which broadens the scope of the anti-cancer drug screening. Finally, we constructed a network of predicted anti-cancer plants and approved drugs based on the above results. The network highlighted the supportive role of the predicted plant in the development of anti-cancer drug and suggested different molecular anti-cancer mechanisms of the plants. Our study suggests that the predicted compounds and plants from TCM database offer an attractive starting point and a broader scope to mine for potential anti-cancer agents.

  4. Diversity Generation in Evolving Microbial Populations

    DEFF Research Database (Denmark)

    Markussen, Trine

    to get a better understanding of how bacterial populations adapt to new, complex and heterogeneous environments with multiple selective pressures over long periods, and to analyse diversification during this adaptation. Using the P. aeruginosa chronic infection as a model system, and by combining...... bacterial genome sequencing, phenotypic profiling and unique sampling materials which included clonal bacterial isolates sampled for more than 4 decades from chronically infected CF patients, we were able to investigate the diversity generation of the clinical important and highly successful P. aeruginosa...... and maintenance of population diversity of infecting pathogens. Furthermore, fine-tuning of global regulatory networks by modification of transcriptional regulators has fundamental roles in successful adaptation of P. aeruginosa to the CF environment....

  5. Circadian rhythms and new options for novel anticancer therapies

    Directory of Open Access Journals (Sweden)

    Prosenc Zmrzljak U

    2015-01-01

    Full Text Available Ursula Prosenc ZmrzljakFaculty of Medicine, Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, University of Ljubljana, Ljubljana, SloveniaAbstract: The patterns of activity/sleep, eating/fasting, etc show that our lives are under the control of an internal clock. Cancer is a systemic disease that affects sleep, feeding, and metabolism. All these processes are regulated by the circadian clock on the one hand, but on the other hand, they can serve as signals to tighten up the patient's circadian clock by robust daily routine. Usually, anticancer treatments take place in hospitals, where the patient's daily rest/activity pattern is changed. However, it has been shown that oncology patients with a disturbed circadian clock have poorer survival outcomes. The administration of different anticancer therapies can disturb the circadian cycle, but many cases show that circadian rhythms in tumors are deregulated per se. This fact can be used to plan anticancer therapies in such a manner that they will be most effective in antitumor action, but least toxic for the surrounding healthy tissue. Metabolic processes are highly regulated to prevent waste of energy and to ensure sufficient detoxification; as a consequence, xenobiotic metabolism is under tight circadian control. This gives the rationale for planning the administration of anticancer therapies in a chronomodulated manner. We review some of the potentially useful clinical praxes of anticancer therapies and discuss different possible approaches to be used in drug development and design in the future.Keywords: circadian rhythms, cancer, chronotherapy, detoxification metabolism

  6. A functional perspective of nitazoxanide as a potential anticancer drug

    Energy Technology Data Exchange (ETDEWEB)

    Di Santo, Nicola, E-mail: nico.disanto@duke.edu; Ehrisman, Jessie, E-mail: jessie.ehrisman@duke.edu

    2014-10-15

    Highlights: • Combination anti-cancer therapies are associated with increased toxicity and cross-resistance. • Some antiparasitic compounds may have anti-cancer potential. • Nitazoxanide interferes with metabolic and pro-death signaling. • Preclinical studies are needed to confirm anticancer ability of nitazoxanide. - Abstract: Cancer is a group of diseases characterized by uncontrolled cell proliferation, evasion of cell death and the ability to invade and disrupt vital tissue function. The classic model of carcinogenesis describes successive clonal expansion driven by the accumulation of mutations that eliminate restraints on proliferation and cell survival. It has been proposed that during cancer's development, the loose-knit colonies of only partially differentiated cells display some unicellular/prokaryotic behavior reminiscent of robust ancient life forms. The seeming “regression” of cancer cells involves changes within metabolic machinery and survival strategies. This atavist change in physiology enables cancer cells to behave as selfish “neo-endo-parasites” that exploit the tumor stromal cells in order to extract nutrients from the surrounding microenvironment. In this framework, it is conceivable that anti-parasitic compounds might serve as promising anticancer drugs. Nitazoxanide (NTZ), a thiazolide compound, has shown antimicrobial properties against anaerobic bacteria, as well as against helminths and protozoa. NTZ has also been successfully used to promote Hepatitis C virus (HCV) elimination by improving interferon signaling and promoting autophagy. More compelling however are the potential anti-cancer properties that have been observed. NTZ seems to be able to interfere with crucial metabolic and pro-death signaling such as drug detoxification, unfolded protein response (UPR), autophagy, anti-cytokine activities and c-Myc inhibition. In this article, we review the ability of NTZ to interfere with integrated survival mechanisms of

  7. A tractable genotype-phenotype map modelling the self-assembly of protein quaternary structure.

    Science.gov (United States)

    Greenbury, Sam F; Johnston, Iain G; Louis, Ard A; Ahnert, Sebastian E

    2014-06-06

    The mapping between biological genotypes and phenotypes is central to the study of biological evolution. Here, we introduce a rich, intuitive and biologically realistic genotype-phenotype (GP) map that serves as a model of self-assembling biological structures, such as protein complexes, and remains computationally and analytically tractable. Our GP map arises naturally from the self-assembly of polyomino structures on a two-dimensional lattice and exhibits a number of properties: redundancy (genotypes vastly outnumber phenotypes), phenotype bias (genotypic redundancy varies greatly between phenotypes), genotype component disconnectivity (phenotypes consist of disconnected mutational networks) and shape space covering (most phenotypes can be reached in a small number of mutations). We also show that the mutational robustness of phenotypes scales very roughly logarithmically with phenotype redundancy and is positively correlated with phenotypic evolvability. Although our GP map describes the assembly of disconnected objects, it shares many properties with other popular GP maps for connected units, such as models for RNA secondary structure or the hydrophobic-polar (HP) lattice model for protein tertiary structure. The remarkable fact that these important properties similarly emerge from such different models suggests the possibility that universal features underlie a much wider class of biologically realistic GP maps.

  8. High-throughput mouse phenotyping.

    Science.gov (United States)

    Gates, Hilary; Mallon, Ann-Marie; Brown, Steve D M

    2011-04-01

    Comprehensive phenotyping will be required to reveal the pleiotropic functions of a gene and to uncover the wider role of genetic loci within diverse biological systems. The challenge will be to devise phenotyping approaches to characterise the thousands of mutants that are being generated as part of international efforts to acquire a mutant for every gene in the mouse genome. In order to acquire robust datasets of broad based phenotypes from mouse mutants it is necessary to design and implement pipelines that incorporate standardised phenotyping platforms that are validated across diverse mouse genetics centres or mouse clinics. We describe here the rationale and methodology behind one phenotyping pipeline, EMPReSSslim, that was designed as part of the work of the EUMORPHIA and EUMODIC consortia, and which exemplifies some of the challenges facing large-scale phenotyping. EMPReSSslim captures a broad range of data on diverse biological systems, from biochemical to physiological amongst others. Data capture and dissemination is pivotal to the operation of large-scale phenotyping pipelines, including the definition of parameters integral to each phenotyping test and the associated ontological descriptions. EMPReSSslim data is displayed within the EuroPhenome database, where a variety of tools are available to allow the user to search for interesting biological or clinical phenotypes. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Anticancer Drug-Incorporated Layered Double Hydroxide Nanohybrids and Their Enhanced Anticancer Therapeutic Efficacy in Combination Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tae-Hyun Kim

    2014-01-01

    Full Text Available Objective. Layered double hydroxide (LDH nanoparticles have been studied as cellular delivery carriers for anionic anticancer agents. As MTX and 5-FU are clinically utilized anticancer drugs in combination therapy, we aimed to enhance the therapeutic performance with the help of LDH nanoparticles. Method. Anticancer drugs, MTX and 5-FU, and their combination, were incorporated into LDH by reconstruction method. Simply, LDHs were thermally pretreated at 400°C, and then reacted with drug solution to simultaneously form drug-incorporated LDH. Thus prepared MTX/LDH (ML, 5-FU/LDH (FL, and (MTX + 5-FU/LDH (MFL nanohybrids were characterized by X-ray diffractometer, scanning electron microscopy, infrared spectroscopy, thermal analysis, zeta potential measurement, dynamic light scattering, and so forth. The nanohybrids were administrated to the human cervical adenocarcinoma, HeLa cells, in concentration-dependent manner, comparing with drug itself to verify the enhanced therapeutic efficacy. Conclusion. All the nanohybrids successfully accommodated intended drug molecules in their house-of-card-like structures during reconstruction reaction. It was found that the anticancer efficacy of MFL nanohybrid was higher than other nanohybrids, free drugs, or their mixtures, which means the multidrug-incorporated LDH nanohybrids could be potential drug delivery carriers for efficient cancer treatment via combination therapy.

  10. The evolving energy budget of accretionary wedges

    Science.gov (United States)

    McBeck, Jessica; Cooke, Michele; Maillot, Bertrand; Souloumiac, Pauline

    2017-04-01

    The energy budget of evolving accretionary systems reveals how deformational processes partition energy as faults slip, topography uplifts, and layer-parallel shortening produces distributed off-fault deformation. The energy budget provides a quantitative framework for evaluating the energetic contribution or consumption of diverse deformation mechanisms. We investigate energy partitioning in evolving accretionary prisms by synthesizing data from physical sand accretion experiments and numerical accretion simulations. We incorporate incremental strain fields and cumulative force measurements from two suites of experiments to design numerical simulations that represent accretionary wedges with stronger and weaker detachment faults. One suite of the physical experiments includes a basal glass bead layer and the other does not. Two physical experiments within each suite implement different boundary conditions (stable base versus moving base configuration). Synthesizing observations from the differing base configurations reduces the influence of sidewall friction because the force vector produced by sidewall friction points in opposite directions depending on whether the base is fixed or moving. With the numerical simulations, we calculate the energy budget at two stages of accretion: at the maximum force preceding the development of the first thrust pair, and at the minimum force following the development of the pair. To identify the appropriate combination of material and fault properties to apply in the simulations, we systematically vary the Young's modulus and the fault static and dynamic friction coefficients in numerical accretion simulations, and identify the set of parameters that minimizes the misfit between the normal force measured on the physical backwall and the numerically simulated force. Following this derivation of the appropriate material and fault properties, we calculate the components of the work budget in the numerical simulations and in the

  11. Population dynamics of metastable growth-rate phenotypes.

    Directory of Open Access Journals (Sweden)

    Lindsay S Moore

    Full Text Available Neo-Darwinian evolution has presented a paradigm for population dynamics built on random mutations and selection with a clear separation of time-scales between single-cell mutation rates and the rate of reproduction. Laboratory experiments on evolving populations until now have concentrated on the fixation of beneficial mutations. Following the Darwinian paradigm, these experiments probed populations at low temporal resolution dictated by the rate of rare mutations, ignoring the intermediate evolving phenotypes. Selection however, works on phenotypes rather than genotypes. Research in recent years has uncovered the complexity of genotype-to-phenotype transformation and a wealth of intracellular processes including epigenetic inheritance, which operate on a wide range of time-scales. Here, by studying the adaptation dynamics of genetically rewired yeast cells, we show a novel type of population dynamics in which the intracellular processes intervene in shaping the population structure. Under constant environmental conditions, we measure a wide distribution of growth rates that coexist in the population for very long durations (>100 generations. Remarkably, the fastest growing cells do not take over the population on the time-scale dictated by the width of the growth-rate distributions and simple selection. Additionally, we measure significant fluctuations in the population distribution of various phenotypes: the fraction of exponentially-growing cells, the distributions of single-cell growth-rates and protein content. The observed fluctuations relax on time-scales of many generations and thus do not reflect noisy processes. Rather, our data show that the phenotypic state of the cells, including the growth-rate, for large populations in a constant environment is metastable and varies on time-scales that reflect the importance of long-term intracellular processes in shaping the population structure. This lack of time-scale separation between the

  12. Proximate effects of temperature versus evolved intrinsic constraints for embryonic development times among temperate and tropical songbirds.

    Science.gov (United States)

    Ton, Riccardo; Martin, Thomas E

    2017-04-18

    The relative importance of intrinsic constraints imposed by evolved physiological trade-offs versus the proximate effects of temperature for interspecific variation in embryonic development time remains unclear. Understanding this distinction is important because slow development due to evolved trade-offs can yield phenotypic benefits, whereas slow development from low temperature can yield costs. We experimentally increased embryonic temperature in free-living tropical and north temperate songbird species to test these alternatives. Warmer temperatures consistently shortened development time without costs to embryo mass or metabolism. However, proximate effects of temperature played an increasingly stronger role than intrinsic constraints for development time among species with colder natural incubation temperatures. Long development times of tropical birds have been thought to primarily reflect evolved physiological trade-offs that facilitate their greater longevity. In contrast, our results indicate a much stronger role of temperature in embryonic development time than currently thought.

  13. Proximate effects of temperature versus evolved intrinsic constraints for embryonic development times among temperate and tropical songbirds

    Science.gov (United States)

    Ton, Riccardo; Martin, Thomas E.

    2017-01-01

    The relative importance of intrinsic constraints imposed by evolved physiological trade-offs versus the proximate effects of temperature for interspecific variation in embryonic development time remains unclear. Understanding this distinction is important because slow development due to evolved trade-offs can yield phenotypic benefits, whereas slow development from low temperature can yield costs. We experimentally increased embryonic temperature in free-living tropical and north temperate songbird species to test these alternatives. Warmer temperatures consistently shortened development time without costs to embryo mass or metabolism. However, proximate effects of temperature played an increasingly stronger role than intrinsic constraints for development time among species with colder natural incubation temperatures. Long development times of tropical birds have been thought to primarily reflect evolved physiological trade-offs that facilitate their greater longevity. In contrast, our results indicate a much stronger role of temperature in embryonic development time than currently thought.

  14. On the Critical Role of Divergent Selection in Evolvability

    Directory of Open Access Journals (Sweden)

    Joel Lehman

    2016-08-01

    Full Text Available An ambitious goal in evolutionary robotics is to evolve increasingly complex robotic behaviors with minimal human design effort. Reaching this goal requires evolutionary algorithms that can unlock from genetic encodings their latent potential for evolvability. One issue clouding this goal is conceptual confusion about evolvability, which often obscures the aspects of evolvability that are important or desirable. The danger from such confusion is that it may establish unrealistic goals for evolvability that prove unproductive in practice. An important issue separate from conceptual confusion is the common misalignment between selection and evolvability in evolutionary robotics. While more expressive encodings can represent higher-level adaptations (e.g. sexual reproduction or developmental systems that increase long-term evolutionary potential (i.e. evolvability, realizing such potential requires gradients of fitness and evolvability to align. In other words, selection is often a critical factor limiting increasing evolvability. Thus, drawing from a series of recent papers, this article seeks to both (1 clarify and focus the ways in which the term evolvability is used within artificial evolution, and (2 argue for the importance of one type of selection, i.e. divergent selection, for enabling evolvability. The main argument is that there is a fundamental connection between divergent selection and evolvability (on both the individual and population level that does not hold for typical goal-oriented selection. The conclusion is that selection pressure plays a critical role in realizing the potential for evolvability, and that divergent selection in particular provides a principled mechanism for encouraging evolvability in artificial evolution.

  15. Approximating centrality in evolving graphs: toward sublinearity

    Science.gov (United States)

    Priest, Benjamin W.; Cybenko, George

    2017-05-01

    The identification of important nodes is a ubiquitous problem in the analysis of social networks. Centrality indices (such as degree centrality, closeness centrality, betweenness centrality, PageRank, and others) are used across many domains to accomplish this task. However, the computation of such indices is expensive on large graphs. Moreover, evolving graphs are becoming increasingly important in many applications. It is therefore desirable to develop on-line algorithms that can approximate centrality measures using memory sublinear in the size of the graph. We discuss the challenges facing the semi-streaming computation of many centrality indices. In particular, we apply recent advances in the streaming and sketching literature to provide a preliminary streaming approximation algorithm for degree centrality utilizing CountSketch and a multi-pass semi-streaming approximation algorithm for closeness centrality leveraging a spanner obtained through iteratively sketching the vertex-edge adjacency matrix. We also discuss possible ways forward for approximating betweenness centrality, as well as spectral measures of centrality. We provide a preliminary result using sketched low-rank approximations to approximate the output of the HITS algorithm.

  16. On the Discovery of Evolving Truth.

    Science.gov (United States)

    Li, Yaliang; Li, Qi; Gao, Jing; Su, Lu; Zhao, Bo; Fan, Wei; Han, Jiawei

    2015-08-01

    In the era of big data, information regarding the same objects can be collected from increasingly more sources. Unfortunately, there usually exist conflicts among the information coming from different sources. To tackle this challenge, truth discovery, i.e., to integrate multi-source noisy information by estimating the reliability of each source, has emerged as a hot topic. In many real world applications, however, the information may come sequentially, and as a consequence, the truth of objects as well as the reliability of sources may be dynamically evolving. Existing truth discovery methods, unfortunately, cannot handle such scenarios. To address this problem, we investigate the temporal relations among both object truths and source reliability, and propose an incremental truth discovery framework that can dynamically update object truths and source weights upon the arrival of new data. Theoretical analysis is provided to show that the proposed method is guaranteed to converge at a fast rate. The experiments on three real world applications and a set of synthetic data demonstrate the advantages of the proposed method over state-of-the-art truth discovery methods.

  17. Sexual regret: evidence for evolved sex differences.

    Science.gov (United States)

    Galperin, Andrew; Haselton, Martie G; Frederick, David A; Poore, Joshua; von Hippel, William; Buss, David M; Gonzaga, Gian C

    2013-10-01

    Regret and anticipated regret enhance decision quality by helping people avoid making and repeating mistakes. Some of people's most intense regrets concern sexual decisions. We hypothesized evolved sex differences in women's and men's experiences of sexual regret. Because of women's higher obligatory costs of reproduction throughout evolutionary history, we hypothesized that sexual actions, particularly those involving casual sex, would be regretted more intensely by women than by men. In contrast, because missed sexual opportunities historically carried higher reproductive fitness costs for men than for women, we hypothesized that poorly chosen sexual inactions would be regretted more by men than by women. Across three studies (Ns = 200, 395, and 24,230), we tested these hypotheses using free responses, written scenarios, detailed checklists, and Internet sampling to achieve participant diversity, including diversity in sexual orientation. Across all data sources, results supported predicted psychological sex differences and these differences were localized in casual sex contexts. These findings are consistent with the notion that the psychology of sexual regret was shaped by recurrent sex differences in selection pressures operating over deep time.

  18. Extracting evolving pathologies via spectral clustering.

    Science.gov (United States)

    Bernardis, Elena; Pohl, Kilian M; Davatzikos, Christos

    2013-01-01

    A bottleneck in the analysis of longitudinal MR scans with white matter brain lesions is the temporally consistent segmentation of the pathology. We identify pathologies in 3D+t(ime) within a spectral graph clustering framework. Our clustering approach simultaneously segments and tracks the evolving lesions by identifying characteristic image patterns at each time-point and voxel correspondences across time-points. For each 3D image, our method constructs a graph where weights between nodes capture the likeliness of two voxels belonging to the same region. Based on these weights, we then establish rough correspondences between graph nodes at different time-points along estimated pathology evolution directions. We combine the graphs by aligning the weights to a reference time-point, thus integrating temporal information across the 3D images, and formulate the 3D+t segmentation problem as a binary partitioning of this graph. The resulting segmentation is very robust to local intensity fluctuations and yields better results than segmentations generated for each time-point.

  19. Functional Topology of Evolving Urban Drainage Networks

    Science.gov (United States)

    Yang, Soohyun; Paik, Kyungrock; McGrath, Gavan S.; Urich, Christian; Krueger, Elisabeth; Kumar, Praveen; Rao, P. Suresh C.

    2017-11-01

    We investigated the scaling and topology of engineered urban drainage networks (UDNs) in two cities, and further examined UDN evolution over decades. UDN scaling was analyzed using two power law scaling characteristics widely employed for river networks: (1) Hack's law of length (L)-area (A) [L∝Ah] and (2) exceedance probability distribution of upstream contributing area (δ) [P>(A≥δ>)˜aδ-ɛ]. For the smallest UDNs ((A≥δ>) plots for river networks are abruptly truncated, those for UDNs display exponential tempering [P>(A≥δ>)=aδ-ɛexp⁡>(-cδ>)]. The tempering parameter c decreases as the UDNs grow, implying that the distribution evolves in time to resemble those for river networks. However, the power law exponent ɛ for large UDNs tends to be greater than the range reported for river networks. Differences in generative processes and engineering design constraints contribute to observed differences in the evolution of UDNs and river networks, including subnet heterogeneity and nonrandom branching.

  20. Evolving application of biomimetic nanostructured hydroxyapatite

    Directory of Open Access Journals (Sweden)

    Norberto Roveri

    2010-11-01

    Full Text Available Norberto Roveri, Michele IafiscoLaboratory of Environmental and Biological Structural Chemistry (LEBSC, Dipartimento di Chimica ‘G. Ciamician’, Alma Mater Studiorum, Università di Bologna, Bologna, ItalyAbstract: By mimicking Nature, we can design and synthesize inorganic smart materials that are reactive to biological tissues. These smart materials can be utilized to design innovative third-generation biomaterials, which are able to not only optimize their interaction with biological tissues and environment, but also mimic biogenic materials in their functionalities. The biomedical applications involve increasing the biomimetic levels from chemical composition, structural organization, morphology, mechanical behavior, nanostructure, and bulk and surface chemical–physical properties until the surface becomes bioreactive and stimulates cellular materials. The chemical–physical characteristics of biogenic hydroxyapatites from bone and tooth have been described, in order to point out the elective sides, which are important to reproduce the design of a new biomimetic synthetic hydroxyapatite. This review outlines the evolving applications of biomimetic synthetic calcium phosphates, details the main characteristics of bone and tooth, where the calcium phosphates are present, and discusses the chemical–physical characteristics of biomimetic calcium phosphates, methods of synthesizing them, and some of their biomedical applications.Keywords: hydroxyapatite, nanocrystals, biomimetism, biomaterials, drug delivery, remineralization

  1. Evolving application of biomimetic nanostructured hydroxyapatite.

    Science.gov (United States)

    Roveri, Norberto; Iafisco, Michele

    2010-11-09

    By mimicking Nature, we can design and synthesize inorganic smart materials that are reactive to biological tissues. These smart materials can be utilized to design innovative third-generation biomaterials, which are able to not only optimize their interaction with biological tissues and environment, but also mimic biogenic materials in their functionalities. The biomedical applications involve increasing the biomimetic levels from chemical composition, structural organization, morphology, mechanical behavior, nanostructure, and bulk and surface chemical-physical properties until the surface becomes bioreactive and stimulates cellular materials. The chemical-physical characteristics of biogenic hydroxyapatites from bone and tooth have been described, in order to point out the elective sides, which are important to reproduce the design of a new biomimetic synthetic hydroxyapatite. This review outlines the evolving applications of biomimetic synthetic calcium phosphates, details the main characteristics of bone and tooth, where the calcium phosphates are present, and discusses the chemical-physical characteristics of biomimetic calcium phosphates, methods of synthesizing them, and some of their biomedical applications.

  2. Epidemic spreading on evolving signed networks

    Science.gov (United States)

    Saeedian, M.; Azimi-Tafreshi, N.; Jafari, G. R.; Kertesz, J.

    2017-02-01

    Most studies of disease spreading consider the underlying social network as obtained without the contagion, though epidemic influences people's willingness to contact others: A "friendly" contact may be turned to "unfriendly" to avoid infection. We study the susceptible-infected disease-spreading model on signed networks, in which each edge is associated with a positive or negative sign representing the friendly or unfriendly relation between its end nodes. In a signed network, according to Heider's theory, edge signs evolve such that finally a state of structural balance is achieved, corresponding to no frustration in physics terms. However, the danger of infection affects the evolution of its edge signs. To describe the coupled problem of the sign evolution and disease spreading, we generalize the notion of structural balance by taking into account the state of the nodes. We introduce an energy function and carry out Monte Carlo simulations on complete networks to test the energy landscape, where we find local minima corresponding to the so-called jammed states. We study the effect of the ratio of initial friendly to unfriendly connections on the propagation of disease. The steady state can be balanced or a jammed state such that a coexistence occurs between susceptible and infected nodes in the system.

  3. Orbital Decay in Binaries with Evolved Stars

    Science.gov (United States)

    Sun, Meng; Arras, Phil; Weinberg, Nevin N.; Troup, Nicholas; Majewski, Steven R.

    2018-01-01

    Two mechanisms are often invoked to explain tidal friction in binary systems. The ``dynamical tide” is the resonant excitation of internal gravity waves by the tide, and their subsequent damping by nonlinear fluid processes or thermal diffusion. The ``equilibrium tide” refers to non-resonant excitation of fluid motion in the star’s convection zone, with damping by interaction with the turbulent eddies. There have been numerous studies of these processes in main sequence stars, but less so on the subgiant and red giant branches. Motivated by the newly discovered close binary systems in the Apache Point Observatory Galactic Evolution Experiment (APOGEE-1), we have performed calculations of both the dynamical and equilibrium tide processes for stars over a range of mass as the star’s cease core hydrogen burning and evolve to shell burning. Even for stars which had a radiative core on the main sequence, the dynamical tide may have very large amplitude in the newly radiative core in post-main sequence, giving rise to wave breaking. The resulting large dynamical tide dissipation rate is compared to the equilibrium tide, and the range of secondary masses and orbital periods over which rapid orbital decay may occur will be discussed, as well as applications to close APOGEE binaries.

  4. UKAEA'S evolving contract philosophy

    Energy Technology Data Exchange (ETDEWEB)

    Nicol, R. D. [UK Atomic Energy Authority, UKAEA, Harwell, Oxfordshire (United Kingdom)

    2003-07-01

    The United Kingdom Atomic Energy Authority (UKAEA) has gone through fundamental change over the last ten years. At the heart of this change has been UKAEA's relationship with the contracting and supply market. This paper describes the way in which UKAEA actively developed the market to support the decommissioning programme, and how the approach to contracting has evolved as external pressures and demands have changed. UKAEA's pro-active approach to industry has greatly assisted the development of a healthy, competitive market for services supporting decommissioning in the UK. There have been difficult changes and many challenges along the way, and some retrenchment was necessary to meet regulatory requirements. Nevertheless, UKAEA has sustained a high level of competition - now measured in terms of competed spend as a proportion of competable spend - with annual out-turns consistently over 80%. The prime responsibility for market development will pass to the new Nuclear Decommissioning Authority (NDA) in 2005, as the owner, on behalf of the Government, of the UK's civil nuclear liabilities. The preparatory work for the NDA indicates that the principles established by UKAEA will be carried forward. (author)

  5. An evolving model of online bipartite networks

    Science.gov (United States)

    Zhang, Chu-Xu; Zhang, Zi-Ke; Liu, Chuang

    2013-12-01

    Understanding the structure and evolution of online bipartite networks is a significant task since they play a crucial role in various e-commerce services nowadays. Recently, various attempts have been tried to propose different models, resulting in either power-law or exponential degree distributions. However, many empirical results show that the user degree distribution actually follows a shifted power-law distribution, the so-called Mandelbrot’s law, which cannot be fully described by previous models. In this paper, we propose an evolving model, considering two different user behaviors: random and preferential attachment. Extensive empirical results on two real bipartite networks, Delicious and CiteULike, show that the theoretical model can well characterize the structure of real networks for both user and object degree distributions. In addition, we introduce a structural parameter p, to demonstrate that the hybrid user behavior leads to the shifted power-law degree distribution, and the region of power-law tail will increase with the increment of p. The proposed model might shed some lights in understanding the underlying laws governing the structure of real online bipartite networks.

  6. Phenotypic differences between the sexes in the sexually plastic mangrove rivulus fish (Kryptolebias marmoratus)

    DEFF Research Database (Denmark)

    Garcia, Mark J.; Ferro, Jack M.; Mattox, Tyler

    2016-01-01

    To maximize reproductive success, many animal species have evolved functional sex change. Theory predicts that transitions between sexes should occur when the fitness payoff of the current sex is exceeded by the fitness payoff of the opposite sex. We examined phenotypic differences between the se...

  7. Effectiveness of activated carbon masks in preventing anticancer drug inhalation.

    Science.gov (United States)

    Sato, Junya; Kogure, Atushi; Kudo, Kenzo

    2016-01-01

    The exposure of healthcare workers to anticancer drugs such as cyclophosphamide (CPA) is a serious health concern. Anticancer drug pollution may spread outside biological safety cabinets even when a closed system is used. The inhalation of vaporized anticancer drugs is thought to be the primary route of exposure. Therefore, it is important that healthcare workers wear masks to prevent inhalation of anticancer drugs. However, the permeability of medical masks to vaporized anticancer drugs has not been examined. Furthermore, the performance differences between masks including activated carbon with chemical adsorptivity and non-activated carbon masks are uncertain. We investigated activated carbon mask permeability to vaporized CPA, and assessed whether inhibition of vaporized CPA permeability was attributable to the masks' adsorption abilities. A CPA solution (4 mg) was vaporized in a chamber and passed through three types of masks: Pleated-type cotton mask (PCM), pleated-type activated carbon mask (PAM), and stereoscopic-type activated carbon mask (SAM); the flow rate was 1.0 L/min for 1 h. The air was then recovered in 50 % ethanol. CPA quantities in the solution were determined by liquid chromatography time-of-flight mass spectrometry. To determine CPA adsorption by the mask, 5 cm 2 of each mask was immersed in 10 mL of CPA solution (50-2500 μg/mL) for 1 h. CPA concentrations were measured by high-performance liquid chromatography with ultraviolet detection. For the control (no mask), 3.735 ± 0.543 μg of CPA was recovered from the aerated solution. Significantly lower quantities were recovered from PCM (0.538 ± 0.098 μg) and PAM (0.236 ± 0.193 μg) ( p  SAM samples were below the quantification limit. When a piece of the SAM was immersed in the CPA solution, a marked decrease to less than 3.1 % of the initial CPA concentration was observed. The SAM exhibited good adsorption ability, and this characteristic may contribute to avoiding

  8. Independently Evolving Species in Asexual Bdelloid Rotifers

    Science.gov (United States)

    Boschetti, Chiara; Caprioli, Manuela; Melone, Giulio; Ricci, Claudia; Barraclough, Timothy G

    2007-01-01

    Asexuals are an important test case for theories of why species exist. If asexual clades displayed the same pattern of discrete variation as sexual clades, this would challenge the traditional view that sex is necessary for diversification into species. However, critical evidence has been lacking: all putative examples have involved organisms with recent or ongoing histories of recombination and have relied on visual interpretation of patterns of genetic and phenotypic variation rather than on formal tests of alternative evolutionary scenarios. Here we show that a classic asexual clade, the bdelloid rotifers, has diversified into distinct evolutionary species. Intensive sampling of the genus Rotaria reveals the presence of well-separated genetic clusters indicative of independent evolution. Moreover, combined genetic and morphological analyses reveal divergent selection in feeding morphology, indicative of niche divergence. Some of the morphologically coherent groups experiencing divergent selection contain several genetic clusters, in common with findings of cryptic species in sexual organisms. Our results show that the main causes of speciation in sexual organisms, population isolation and divergent selection, have the same qualitative effects in an asexual clade. The study also demonstrates how combined molecular and morphological analyses can shed new light on the evolutionary nature of species. PMID:17373857

  9. Independently evolving species in asexual bdelloid rotifers.

    Directory of Open Access Journals (Sweden)

    Diego Fontaneto

    2007-04-01

    Full Text Available Asexuals are an important test case for theories of why species exist. If asexual clades displayed the same pattern of discrete variation as sexual clades, this would challenge the traditional view that sex is necessary for diversification into species. However, critical evidence has been lacking: all putative examples have involved organisms with recent or ongoing histories of recombination and have relied on visual interpretation of patterns of genetic and phenotypic variation rather than on formal tests of alternative evolutionary scenarios. Here we show that a classic asexual clade, the bdelloid rotifers, has diversified into distinct evolutionary species. Intensive sampling of the genus Rotaria reveals the presence of well-separated genetic clusters indicative of independent evolution. Moreover, combined genetic and morphological analyses reveal divergent selection in feeding morphology, indicative of niche divergence. Some of the morphologically coherent groups experiencing divergent selection contain several genetic clusters, in common with findings of cryptic species in sexual organisms. Our results show that the main causes of speciation in sexual organisms, population isolation and divergent selection, have the same qualitative effects in an asexual clade. The study also demonstrates how combined molecular and morphological analyses can shed new light on the evolutionary nature of species.

  10. Plant Phenotype Characterization System

    Energy Technology Data Exchange (ETDEWEB)

    Daniel W McDonald; Ronald B Michaels

    2005-09-09

    This report is the final scientific report for the DOE Inventions and Innovations Project: Plant Phenotype Characterization System, DE-FG36-04GO14334. The period of performance was September 30, 2004 through July 15, 2005. The project objective is to demonstrate the viability of a new scientific instrument concept for the study of plant root systems. The root systems of plants are thought to be important in plant yield and thus important to DOE goals in renewable energy sources. The scientific study and understanding of plant root systems is hampered by the difficulty in observing root activity and the inadequacy of existing root study instrumentation options. We have demonstrated a high throughput, non-invasive, high resolution technique for visualizing plant root systems in-situ. Our approach is based upon low-energy x-ray radiography and the use of containers and substrates (artificial soil) which are virtually transparent to x-rays. The system allows us to germinate and grow plant specimens in our containers and substrates and to generate x-ray images of the developing root system over time. The same plant can be imaged at different times in its development. The system can be used for root studies in plant physiology, plant morphology, plant breeding, plant functional genomics and plant genotype screening.

  11. Emerging molecular phenotypes of asthma

    Science.gov (United States)

    Ray, Anuradha; Oriss, Timothy B.

    2014-01-01

    Although asthma has long been considered a heterogeneous disease, attempts to define subgroups of asthma have been limited. In recent years, both clinical and statistical approaches have been utilized to better merge clinical characteristics, biology, and genetics. These combined characteristics have been used to define phenotypes of asthma, the observable characteristics of a patient determined by the interaction of genes and environment. Identification of consistent clinical phenotypes has now been reported across studies. Now the addition of various 'omics and identification of specific molecular pathways have moved the concept of clinical phenotypes toward the concept of molecular phenotypes. The importance of these molecular phenotypes is being confirmed through the integration of molecularly targeted biological therapies. Thus the global term asthma is poised to become obsolete, being replaced by terms that more specifically identify the pathology associated with the disease. PMID:25326577

  12. Quantum mechanics in an evolving Hilbert space

    Science.gov (United States)

    Artacho, Emilio; O'Regan, David D.

    2017-03-01

    Many basis sets for electronic structure calculations evolve with varying external parameters, such as moving atoms in dynamic simulations, giving rise to extra derivative terms in the dynamical equations. Here we revisit these derivatives in the context of differential geometry, thereby obtaining a more transparent formalization, and a geometrical perspective for better understanding the resulting equations. The effect of the evolution of the basis set within the spanned Hilbert space separates explicitly from the effect of the turning of the space itself when moving in parameter space, as the tangent space turns when moving in a curved space. New insights are obtained using familiar concepts in that context such as the Riemann curvature. The differential geometry is not strictly that for curved spaces as in general relativity, a more adequate mathematical framework being provided by fiber bundles. The language used here, however, will be restricted to tensors and basic quantum mechanics. The local gauge implied by a smoothly varying basis set readily connects with Berry's formalism for geometric phases. Generalized expressions for the Berry connection and curvature are obtained for a parameter-dependent occupied Hilbert space spanned by nonorthogonal Wannier functions. The formalism is applicable to basis sets made of atomic-like orbitals and also more adaptative moving basis functions (such as in methods using Wannier functions as intermediate or support bases), but should also apply to other situations in which nonorthogonal functions or related projectors should arise. The formalism is applied to the time-dependent quantum evolution of electrons for moving atoms. The geometric insights provided here allow us to propose new finite-difference time integrators, and also better understand those already proposed.

  13. Emergent spacetime in stochastically evolving dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Afshordi, Niayesh [Perimeter Institute for Theoretical Physics, 31 Caroline St. N., Waterloo, ON, N2L 2Y5 (Canada); Department of Physics and Astronomy, University of Waterloo, Waterloo, ON, N2L 3G1 (Canada); HEPCOS, Department of Physics, SUNY at Buffalo, Buffalo, NY 14260-1500 (United States); Stojkovic, Dejan, E-mail: ds77@buffalo.edu [Perimeter Institute for Theoretical Physics, 31 Caroline St. N., Waterloo, ON, N2L 2Y5 (Canada); HEPCOS, Department of Physics, SUNY at Buffalo, Buffalo, NY 14260-1500 (United States)

    2014-12-12

    Changing the dimensionality of the space–time at the smallest and largest distances has manifold theoretical advantages. If the space is lower dimensional in the high energy regime, then there are no ultraviolet divergencies in field theories, it is possible to quantize gravity, and the theory of matter plus gravity is free of divergencies or renormalizable. If the space is higher dimensional at cosmological scales, then some cosmological problems (including the cosmological constant problem) can be attacked from a completely new perspective. In this paper, we construct an explicit model of “evolving dimensions” in which the dimensions open up as the temperature of the universe drops. We adopt the string theory framework in which the dimensions are fields that live on the string worldsheet, and add temperature dependent mass terms for them. At the Big Bang, all the dimensions are very heavy and are not excited. As the universe cools down, dimensions open up one by one. Thus, the dimensionality of the space we live in depends on the energy or temperature that we are probing. In particular, we provide a kinematic Brandenberger–Vafa argument for how a discrete causal set, and eventually a continuum (3+1)-dim spacetime along with Einstein gravity emerges in the Infrared from the worldsheet action. The (3+1)-dim Planck mass and the string scale become directly related, without any compactification. Amongst other predictions, we argue that LHC might be blind to new physics even if it comes at the TeV scale. In contrast, cosmic ray experiments, especially those that can register the very beginning of the shower, and collisions with high multiplicity and density of particles, might be sensitive to the dimensional cross-over.

  14. Emergent spacetime in stochastically evolving dimensions

    Science.gov (United States)

    Afshordi, Niayesh; Stojkovic, Dejan

    2014-12-01

    Changing the dimensionality of the space-time at the smallest and largest distances has manifold theoretical advantages. If the space is lower dimensional in the high energy regime, then there are no ultraviolet divergencies in field theories, it is possible to quantize gravity, and the theory of matter plus gravity is free of divergencies or renormalizable. If the space is higher dimensional at cosmological scales, then some cosmological problems (including the cosmological constant problem) can be attacked from a completely new perspective. In this paper, we construct an explicit model of ;evolving dimensions; in which the dimensions open up as the temperature of the universe drops. We adopt the string theory framework in which the dimensions are fields that live on the string worldsheet, and add temperature dependent mass terms for them. At the Big Bang, all the dimensions are very heavy and are not excited. As the universe cools down, dimensions open up one by one. Thus, the dimensionality of the space we live in depends on the energy or temperature that we are probing. In particular, we provide a kinematic Brandenberger-Vafa argument for how a discrete causal set, and eventually a continuum (3 + 1)-dim spacetime along with Einstein gravity emerges in the Infrared from the worldsheet action. The (3 + 1)-dim Planck mass and the string scale become directly related, without any compactification. Amongst other predictions, we argue that LHC might be blind to new physics even if it comes at the TeV scale. In contrast, cosmic ray experiments, especially those that can register the very beginning of the shower, and collisions with high multiplicity and density of particles, might be sensitive to the dimensional cross-over.

  15. Emergent spacetime in stochastically evolving dimensions

    Directory of Open Access Journals (Sweden)

    Niayesh Afshordi

    2014-12-01

    Full Text Available Changing the dimensionality of the space–time at the smallest and largest distances has manifold theoretical advantages. If the space is lower dimensional in the high energy regime, then there are no ultraviolet divergencies in field theories, it is possible to quantize gravity, and the theory of matter plus gravity is free of divergencies or renormalizable. If the space is higher dimensional at cosmological scales, then some cosmological problems (including the cosmological constant problem can be attacked from a completely new perspective. In this paper, we construct an explicit model of “evolving dimensions” in which the dimensions open up as the temperature of the universe drops. We adopt the string theory framework in which the dimensions are fields that live on the string worldsheet, and add temperature dependent mass terms for them. At the Big Bang, all the dimensions are very heavy and are not excited. As the universe cools down, dimensions open up one by one. Thus, the dimensionality of the space we live in depends on the energy or temperature that we are probing. In particular, we provide a kinematic Brandenberger–Vafa argument for how a discrete causal set, and eventually a continuum (3+1-dim spacetime along with Einstein gravity emerges in the Infrared from the worldsheet action. The (3+1-dim Planck mass and the string scale become directly related, without any compactification. Amongst other predictions, we argue that LHC might be blind to new physics even if it comes at the TeV scale. In contrast, cosmic ray experiments, especially those that can register the very beginning of the shower, and collisions with high multiplicity and density of particles, might be sensitive to the dimensional cross-over.

  16. Evolvable Cryogenics (ECRYO) Pressure Transducer Calibration Test

    Science.gov (United States)

    Diaz, Carlos E., Jr.

    2015-01-01

    This paper provides a summary of the findings of recent activities conducted by Marshall Space Flight Center's (MSFC) In-Space Propulsion Branch and MSFC's Metrology and Calibration Lab to assess the performance of current "state of the art" pressure transducers for use in long duration storage and transfer of cryogenic propellants. A brief historical narrative in this paper describes the Evolvable Cryogenics program and the relevance of these activities to the program. This paper also provides a review of three separate test activities performed throughout this effort, including: (1) the calibration of several pressure transducer designs in a liquid nitrogen cryogenic environmental chamber, (2) the calibration of a pressure transducer in a liquid helium Dewar, and (3) the calibration of several pressure transducers at temperatures ranging from 20 to 70 degrees Kelvin (K) using a "cryostat" environmental chamber. These three separate test activities allowed for study of the sensors along a temperature range from 4 to 300 K. The combined data shows that both the slope and intercept of the sensor's calibration curve vary as a function of temperature. This homogeneous function is contrary to the linearly decreasing relationship assumed at the start of this investigation. Consequently, the data demonstrates the need for lookup tables to change the slope and intercept used by any data acquisition system. This ultimately would allow for more accurate pressure measurements at the desired temperature range. This paper concludes with a review of a request for information (RFI) survey conducted amongst different suppliers to determine the availability of current "state of the art" flight-qualified pressure transducers. The survey identifies requirements that are most difficult for the suppliers to meet, most notably the capability to validate the sensor's performance at temperatures below 70 K.

  17. A Mn(II) complex of boradiazaindacene (BODIPY) loaded graphene oxide as both LED light and H2O2 enhanced anticancer agent.

    Science.gov (United States)

    Xu, Xiao-Lei; Shao, Jian; Chen, Qiu-Yun; Li, Cheng-Hao; Kong, Meng-Yun; Fang, Fang; Ji, Ling; Boison, Daniel; Huang, Tao; Gao, Jing; Feng, Chang-Jian

    2016-06-01

    Cancer cells are more susceptible to H2O2 induced cell death than normal cells. H2O2-activatable and O2-evolving nanoparticles could be used as photodynamic therapy agents in hypoxic environments. In this report, a photo-active Mn(II) complex of boradiazaindacene derivatives (Mn1) was used as a dioxygen generator under irradiation with LED light in water. Moreover, the in vitro biological evaluation for Mn1 and its loaded graphene oxide (herein called Mn1@GO) on HepG-2 cells in normal and hypoxic conditions has been performed. In particular, Mn1@GO can react with H2O2 resulting active anticancer species, which show high inhibition on both HepG-2 cells and CoCl2-treated HepG-2 cells (hypoxic cancer cells). The mechanism of LED light enhanced anticancer activity for Mn1@GO on HepG-2 cells was discussed. Our results show that Mn(II) complexes of boradiazaindacene (BODIPY) derivatives loaded GO can be both LED light and H2O2-activated anticancer agents in hypoxic environments. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Anti-inflammatory and anticancer drugs from nature.

    Science.gov (United States)

    Orlikova, Barbora; Legrand, Noémie; Panning, Jana; Dicato, Mario; Diederich, Marc

    2014-01-01

    Over the centuries, plant extracts have been used to treat various diseases. Until now, natural products have played an important role in anticancer therapy as there are more than 500 compounds from terrestrial and marine plants or microorganisms, which have antioxidant, antiproliferative, or antiangiogenic properties and are therefore able to reduce tumor growth. The recent discovery of new natural products has been accelerated by novel technologies (high throughput screening of natural products in plants, animals, marine organisms, and microorganisms). Vincristine, irinotecan, etoposide, and paclitaxel are examples of compounds derived from plants that are used in cancer treatment. Similarly, actinomycin D, mitomycin C, bleomycin, doxorubicin, and L-asparaginase are drugs derived from microorganisms. In this review, we describe the molecular mechanisms of natural compounds with anti-inflammatory and anticancer activities.

  19. Anti-cancer activities of diospyrin, its derivatives and analogues

    KAUST Repository

    Sagar, Sunil

    2010-09-01

    Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

  20. The anticancer and antiobesity effects of Mediterranean diet.

    Science.gov (United States)

    Kwan, Hiu Yee; Chao, Xiaojuan; Su, Tao; Fu, Xiuqiong; Tse, Anfernee Kai Wing; Fong, Wang Fun; Yu, Zhi-Ling

    2017-01-02

    Cancers have been the leading cause of death worldwide and the prevalence of obesity is also increasing in these few decades. Interestingly, there is a direct association between cancer and obesity. Each year, more than 90,000 cancer deaths are caused by obesity or overweight. The dietary pattern in Crete, referred as the traditional Mediterranean diet, is believed to confer Crete people the low mortality rates from cancers. Nevertheless, the antiobesity effect of the Mediterranean diet is less studied. Given the causal relationship between obesity and cancer, the antiobesity effect of traditional Mediterranean diet might contribute to its anticancer effects. In this regard, we will critically review the anticancer and antiobesity effects of this diet and its dietary factors. The possible mechanisms underlying these effects will also be discussed.

  1. New pyridocarbazole derivatives. Synthesis and their in vitro anticancer activity.

    Science.gov (United States)

    Jasztold-Howorko, Ryszard; Tylińska, Beata; Biaduń, Bogusława; Gebarowski, Tomasz; Gasiorowski, Kazimierz

    2013-01-01

    In this paper, we describe our results of the synthesis and biological testing of analogues of the natural alkaloids olivacine and ellipticine. We have synthesized fourteen new 1-substituted pyrido[4,3-b]carbazole derivatives. All of them were tested in vitro for their anticancer activity on three human tumor cell lines: CCRF/CEM (T lymphoblast leukemia), A549 (lung adenocarcinoma), and MCF7 (breast cancer). Cytotoxicity to non-cancer cells was estimated in cultures of the mice fibroblast cell line 3T3 BALB. The anticancer activity of 9-methoxy-5,6-dimethyl-1-[(1,1-bis-hydroxymethyI-propylamino)-methyl]-6H-pyrido[4,3-b]carbazole (compound 9) was the strongest amongst compounds tested on the three cancer cell lines; it was about 5 times higher than ellipticine and about 10% higher than doxorubicin.

  2. Anticancer Effect of Thymol on AGS Human Gastric Carcinoma Cells.

    Science.gov (United States)

    Kang, Seo-Hee; Kim, Yon-Suk; Kim, Eun-Kyung; Hwang, Jin-Woo; Jeong, Jae-Hyun; Dong, Xin; Lee, Jae-Woong; Moon, Sang-Ho; Jeon, Byong-Tae; Park, Pyo-Jam

    2016-01-01

    Numerous plants have been documented to contain phenolic compounds. Thymol is one among these phenolic compounds that possess a repertoire of pharmacological activities, including anti-inflammatory, anticancer, antioxidant, antibacterial, and antimicrobial effects. Despite of the plethora of affects elicited by thymol, its activity profile on gastric cancer cells is not explored. In this study, we discovered that thymol exerts anticancer effects by suppressing cell growth, inducing apoptosis, producing intracellular reactive oxygen species, depolarizing mitochondrial membrane potential, and activating the proapoptotic mitochondrial proteins Bax, cysteine aspartases (caspases), and poly ADP ribose polymerase in human gastric AGS cells. The outcomes of this study displayed that thymol, via an intrinsic mitochondrial pathway, was responsible for inducing apoptosis in gastric AGS cells. Hence, thymol might serve as a tentative agent in the future to treat cancer.

  3. Beneficial effect of peptides from microalgae on anticancer.

    Science.gov (United States)

    Kang, Kyong-Hwa; Kim, Se-Kwon

    2013-05-01

    Biologically active compounds with different modes of action, such as, antiproliferative, antioxidant, antimicrotubule, have been isolated from marine sources, specifically microalgae, cyanobacteria and seaweed. The structural characteristics of these peptides include various unusual amino acid residues, which may be responsible for their properties. Moreover, protein hydrolysates formed by the enzymatic digestion of aquatic and marine by-products are an important source of bioactive peptides. Purified peptides from these sources have been shown to have antioxidant activity and cytotoxic effect on several human cancer cell lines such as HepG2, HeLa, AGS, and MCF-7. These characteristics imply that the use of peptides from marine sources has potential for the prevention and treatment of cancer, and that they might also be useful as molecular models in anticancer drug research.This review focuses about the anticancer activating of peptides were prepared from microalgae in detail.

  4. Novel antimicrobial peptides with high anticancer activity and selectivity.

    Science.gov (United States)

    Chu, Hung-Lun; Yip, Bak-Sau; Chen, Kuan-Hao; Yu, Hui-Yuan; Chih, Ya-Han; Cheng, Hsi-Tsung; Chou, Yu-Ting; Cheng, Jya-Wei

    2015-01-01

    We describe a strategy to boost anticancer activity and reduce normal cell toxicity of short antimicrobial peptides by adding positive charge amino acids and non-nature bulky amino acid β-naphthylalanine residues to their termini. Among the designed peptides, K4R2-Nal2-S1 displayed better salt resistance and less toxicity to hRBCs and human fibroblast than Nal2-S1 and K6-Nal2-S1. Fluorescence microscopic studies indicated that the FITC-labeled K4R2-Nal2-S1 preferentially binds cancer cells and causes apoptotic cell death. Moreover, a significant inhibition in human lung tumor growth was observed in the xenograft mice treated with K4R2-Nal2-S1. Our strategy provides new opportunities in the development of highly effective and selective antimicrobial and anticancer peptide-based therapeutics.

  5. Novel antimicrobial peptides with high anticancer activity and selectivity.

    Directory of Open Access Journals (Sweden)

    Hung-Lun Chu

    Full Text Available We describe a strategy to boost anticancer activity and reduce normal cell toxicity of short antimicrobial peptides by adding positive charge amino acids and non-nature bulky amino acid β-naphthylalanine residues to their termini. Among the designed peptides, K4R2-Nal2-S1 displayed better salt resistance and less toxicity to hRBCs and human fibroblast than Nal2-S1 and K6-Nal2-S1. Fluorescence microscopic studies indicated that the FITC-labeled K4R2-Nal2-S1 preferentially binds cancer cells and causes apoptotic cell death. Moreover, a significant inhibition in human lung tumor growth was observed in the xenograft mice treated with K4R2-Nal2-S1. Our strategy provides new opportunities in the development of highly effective and selective antimicrobial and anticancer peptide-based therapeutics.

  6. Costunolide: A novel anti-cancer sesquiterpene lactone

    Directory of Open Access Journals (Sweden)

    Azhar Rasul

    2012-03-01

    Full Text Available Currently an ample interest is found among oncologists to explore anticancer compounds from herbs. Sesquiterpene lactones have accredited significant attention in pharmacological research. Costunolide is a well-known sesquiterpene lactone present in plants used as popular herbal remedy. Several plant-derived compounds are currently successfully employed in cancer treatment. Growing evidences demonstrated that costunolide possesses anticancer activities by inhibiting cell proliferation, tumor invasion, angiogenesis, metastasis and inducing apoptosis of a variety of tumor cell lines. This review is aimed to summarize the recent researches about costunolide focusing on anti-tumor activity and to lay emphasis on its molecular targets and its mechanisms, which may help the further design and conduct of preclinical and clinical trials.

  7. Botanical, Phytochemical, and Anticancer Properties of the Eucalyptus Species.

    Science.gov (United States)

    Vuong, Quan V; Chalmers, Anita C; Jyoti Bhuyan, Deep; Bowyer, Michael C; Scarlett, Christopher J

    2015-06-01

    The genus Eucalyptus (Myrtaceae) is mainly native to Australia; however, some species are now distributed globally. Eucalyptus has been used in indigenous Australian medicines for the treatment of a range of aliments including colds, flu, fever, muscular aches, sores, internal pains, and inflammation. Eucalyptus oils containing volatile compounds have been widely used in the pharmaceutical and cosmetics industries for a multitude of purposes. In addition, Eucalyptus extracts containing nonvolatile compounds are also an important source of key bioactive compounds, and several studies have linked Eucalyptus extracts with anticancer properties. With the increasing research interest in Eucalyptus and its health properties, this review briefly outlines the botanical features of Eucalyptus, discusses its traditional use as medicine, and comprehensively reviews its phytochemical and anticancer properties and, finally, proposes trends for future studies. Copyright © 2015 Verlag Helvetica Chimica Acta AG, Zürich.

  8. Anticancer Natural Compounds as Epigenetic Modulators of Gene Expression.

    Science.gov (United States)

    Ratovitski, Edward A

    2017-04-01

    Accumulating evidence shows that hallmarks of cancer include: "genetic and epigenetic alterations leading to inactivation of cancer suppressors, overexpression of oncogenes, deregulation of intracellular signaling cascades, alterations of cancer cell metabolism, failure to undergo cancer cell death, induction of epithelial to mesenchymal transition, invasiveness, metastasis, deregulation of immune response and changes in cancer microenvironment, which underpin cancer development". Natural compounds as bioactive ingredients isolated from natural sources (plants, fungi, marine life forms) have revolutionized the field of anticancer therapeutics and rapid developments in preclinical studies are encouraging. Natural compounds could affect the epigenetic molecular mechanisms that modulate gene expression, as well as DNA damage and repair mechanisms. The current review will describe the latest achievements in using naturally produced compounds targeting epigenetic regulators and modulators of gene transcription in vitro and in vivo to generate novel anticancer therapeutics.

  9. Lung cancer and renal insufficiency: prevalence and anticancer drug issues.

    Science.gov (United States)

    Launay-Vacher, Vincent; Etessami, Reza; Janus, Nicolas; Spano, Jean-Philippe; Ray-Coquard, Isabelle; Oudard, Stéphane; Gligorov, Joseph; Pourrat, Xavier; Beuzeboc, Philippe; Deray, Gilbert; Morere, Jean-François

    2009-01-01

    The Renal Insufficiency and Anticancer Medications (IRMA) study reported the high prevalence of renal insufficiency in cancer patients. In this special report, we focused on patients with lung cancer, emphasizing some specific findings in this population of patients. Data on patients with lung cancer who were in the IRMA study were analyzed. Renal function was calculated using Cockcroft-Gault and abbreviated Modification of Diet in Renal Disease (aMDRD) formulas to estimate the prevalence of renal insufficiency (RI) according to the KDOQI-KDIGO definition. Anticancer drugs were studied with regard to their potential renal toxicity and need for dosage adjustment. Of the 445 IRMA lung cancer patients, 14.4% had a serum creatinine (SCR) level > or =110 micromol/L. However, when they were assessed using the formulas, 62.1 and 55.9% had abnormal renal function. Of the 644 anticancer drug prescriptions, 67.5% required dose adjustments for RI or were drugs with no available data, and 78.3% of the patients received at least one such drug. Furthermore, 71.6% received potentially nephrotoxic drugs. Seventy percent of the patients had anemia but prevalence was not significantly associated with the existence of associated renal insufficiency. In the 445 IRMA patients with lung cancer, the prevalence of RI was high in spite of a normal SCR in most cases. Some anticancer drugs such as platinum salts may be nephrotoxic and need dosage adjustment. However, other important drugs such as gemcitabine do not require dose reduction and do not present with a high potential for nephrotoxicity. Lung cancer patients often present with anemia, which was not associated with the presence of RI.

  10. Encapsulation in Nanoparticles Improves Anti-cancer Efficacy of Carboplatin

    OpenAIRE

    Sadhukha, Tanmoy; Prabha, Swayam

    2014-01-01

    Poor cellular uptake contributes to high dose requirement and limited therapeutic efficacy of the platinum-based anticancer drug carboplatin. Delivery systems that can improve the cellular accumulation of carboplatin will, therefore, likely improve its therapeutic potential. The objective of this study was to evaluate nanoparticles composed of the biodegradable polymer, poly(d, l-lactide-co-glycolide), for carboplatin delivery to tumor cells. Carboplatin-loaded nanoparticles were formulated b...

  11. Functional and structural characteristics of anticancer peptide Pep27 analogues

    Directory of Open Access Journals (Sweden)

    Seo Youn-Kyung

    2005-07-01

    Full Text Available Abstract Background A secreted peptide Pep27 initiates the cell death program in S. pneumoniae through signal transduction. This study was undertaken to evaluate the relation between the structure and cytotoxic activity of Pep27 and its analogues on cancer cells. Results Pep27anal2 characterized substituting (2R→W, (4E→W, (11S→W and (13Q→W in native Pep27, exhibited greater hydrophobicity and anticancer activity than Pep27 and other analogues. The IC50 values of Pep27anal2 were approximately 10 – 30 μM in a number of cell lines (AML-2, HL-60, Jurkat, MCF-7 and SNU-601. Confocal microscopy showed that Pep27anal2-FITC was localized in the plasma membrane, and then moving from the membrane to subcellular compartments with the initiation of membrane blebbing. Flow cytometric analysis using propidium iodide and Annexin V also revealed that Pep27anal2 induced apoptosis with minor membrane damage. Electron microscopy revealed that Pep27 induced apoptosis in Jurkat cells. The anticancer activity of Pep27anal2 was neither abrogated by pan-caspase inhibitor (Z-VAD-fmk nor related to cytochrome c release from mitochondria. The 3D solution structures of these two Pep27 peptides revealed that both form a random coil conformation in water; however, they adopted stable α-helical conformations in solutions. Conclusion The results indicate that Pep27anal2 can penetrate the plasma membrane, and then induce apoptosis in both caspase-and cytochrome c-independent manner. The hydrophobicity of Pep27anal2 appears to play an important role in membrane permeabilization and/or anticancer properties. The structure-functional relationships of these peptides are also discussed. It is proposed that Pep27anal2 is a potential candidate for anticancer therapeutic agents.

  12. Antimicrobial, antioxidant, anticancer activities of Syzygium caryophyllatum (L.) Alston

    OpenAIRE

    Gayathri Annadurai; Benish Rose Pious Masilla; Saranya Jothiramshekar; Eganathan Palanisami; Sujanapal Puthiyapurayil; Ajay Kumar Parida

    2012-01-01

    Background: Syzygium caryophyllatum (L.) Alston is an endangered tree species belonging to the Myrtaceae family. Objective: To evaluate the antimicrobial, antioxidant and anticancer activities of the leaf extract. Materials and Methods: Disc diffusion method was used for antimicrobial screening of four bacterial and three fungal strains. Scavenging ability of the extract was determined using 2,2-diphenyl-1-picrylhydrazyl assay. Hep2 cell line was used to evaluate the cytotoxicity by 3-(4, 5-d...

  13. Synthesis and Anticancer Activity of Novel Thiazole-5-Carboxamide Derivatives

    Directory of Open Access Journals (Sweden)

    Wen-Xi Cai

    2016-01-01

    Full Text Available A series of novel 2-phenyl-4-trifluoromethyl thiazole-5-carboxamide derivatives have been synthesized and evaluated for their anticancer activity against A-549, Bel7402, and HCT-8 cell lines. Among the tested compounds, highest activity (48% was achieved with the 4-chloro-2-methylphenyl amido substituted thiazole containing the 2-chlorophenyl group on the two position of the heterocyclic ring. Other structurally similar compounds displayed moderate activity. The key intermediates have been fully characterized.

  14. Marine bioactive peptides with anti-cancer potential

    OpenAIRE

    Mohammad Nazarian; Seyed Javad Hosseini; Iraj Nabipour; Gholamhosean Mohebbi

    2015-01-01

    In the developing world, the cancer as a prevalent cause of mortality is a new emerging challenges in medical and pharmaceutical sciences. Marine environs are regarded as a rich source of natural products with broad of therapeutic uses. Numerous bioactive peptides and depsi-peptides have been extracted from various marine organisms such as tunicates, sponges, molluscs and other marine organisms, with anti-cancer potential. They can produce the complex compounds which are more effective than p...

  15. Synergistic Anticancer Action of Lysosomal Membrane Permeabilization and Glycolysis Inhibition.

    Science.gov (United States)

    Kosic, Milica; Arsikin-Csordas, Katarina; Paunovic, Verica; Firestone, Raymond A; Ristic, Biljana; Mircic, Aleksandar; Petricevic, Sasa; Bosnjak, Mihajlo; Zogovic, Nevena; Mandic, Milos; Bumbasirevic, Vladimir; Trajkovic, Vladimir; Harhaji-Trajkovic, Ljubica

    2016-10-28

    We investigated the in vitro and in vivo anticancer effect of combining lysosomal membrane permeabilization (LMP)-inducing agent N-dodecylimidazole (NDI) with glycolytic inhibitor 2-deoxy-d-glucose (2DG). NDI-triggered LMP and 2DG-mediated glycolysis block synergized in inducing rapid ATP depletion, mitochondrial damage, and reactive oxygen species production, eventually leading to necrotic death of U251 glioma cells but not primary astrocytes. NDI/2DG-induced death of glioma cells was partly prevented by lysosomal cathepsin inhibitor E64 and antioxidant α-tocopherol, suggesting the involvement of LMP and oxidative stress in the observed cytotoxicity. LMP-inducing agent chloroquine also displayed a synergistic anticancer effect with 2DG, whereas glucose deprivation or glycolytic inhibitors iodoacetate and sodium fluoride synergistically cooperated with NDI, thus further indicating that the anticancer effect of NDI/2DG combination was indeed due to LMP and glycolysis block. The two agents synergistically induced ATP depletion, mitochondrial depolarization, oxidative stress, and necrotic death also in B16 mouse melanoma cells. Moreover, the combined oral administration of NDI and 2DG reduced in vivo melanoma growth in C57BL/6 mice by inducing necrotic death of tumor cells, without causing liver, spleen, or kidney toxicity. Based on these results, we propose that NDI-triggered LMP causes initial mitochondrial damage that is further increased by 2DG due to the lack of glycolytic ATP required to maintain mitochondrial health. This leads to a positive feedback cycle of mitochondrial dysfunction, ATP loss, and reactive oxygen species production, culminating in necrotic cell death. Therefore, the combination of LMP-inducing agents and glycolysis inhibitors seems worthy of further exploration as an anticancer strategy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Evolvability of feed-forward loop architecture biases its abundance in transcription networks

    Directory of Open Access Journals (Sweden)

    Widder Stefanie

    2012-01-01

    Full Text Available Abstract Background Transcription networks define the core of the regulatory machinery of cellular life and are largely responsible for information processing and decision making. At the small scale, interaction motifs have been characterized based on their abundance and some seemingly general patterns have been described. In particular, the abundance of different feed-forward loop motifs in gene regulatory networks displays systematic biases towards some particular topologies, which are much more common than others. The causative process of this pattern is still matter of debate. Results We analyzed the entire motif-function landscape of the feed-forward loop using the formalism developed in a previous work. We evaluated the probabilities to implement possible functions for each motif and found that the kurtosis of these distributions correlate well with the natural abundance pattern. Kurtosis is a standard measure for the peakedness of probability distributions. Furthermore, we examined the functional robustness of the motifs facing mutational pressure in silico and observed that the abundance pattern is biased by the degree of their evolvability. Conclusions The natural abundance pattern of the feed-forward loop can be reconstructed concerning its intrinsic plasticity. Intrinsic plasticity is associated to each motif in terms of its capacity of implementing a repertoire of possible functions and it is directly linked to the motif's evolvability. Since evolvability is defined as the potential phenotypic variation of the motif upon mutation, the link plausibly explains the abundance pattern.

  17. Evolvability of feed-forward loop architecture biases its abundance in transcription networks.

    Science.gov (United States)

    Widder, Stefanie; Solé, Ricard; Macía, Javier

    2012-01-19

    Transcription networks define the core of the regulatory machinery of cellular life and are largely responsible for information processing and decision making. At the small scale, interaction motifs have been characterized based on their abundance and some seemingly general patterns have been described. In particular, the abundance of different feed-forward loop motifs in gene regulatory networks displays systematic biases towards some particular topologies, which are much more common than others. The causative process of this pattern is still matter of debate. We analyzed the entire motif-function landscape of the feed-forward loop using the formalism developed in a previous work. We evaluated the probabilities to implement possible functions for each motif and found that the kurtosis of these distributions correlate well with the natural abundance pattern. Kurtosis is a standard measure for the peakedness of probability distributions. Furthermore, we examined the functional robustness of the motifs facing mutational pressure in silico and observed that the abundance pattern is biased by the degree of their evolvability. The natural abundance pattern of the feed-forward loop can be reconstructed concerning its intrinsic plasticity. Intrinsic plasticity is associated to each motif in terms of its capacity of implementing a repertoire of possible functions and it is directly linked to the motif's evolvability. Since evolvability is defined as the potential phenotypic variation of the motif upon mutation, the link plausibly explains the abundance pattern.

  18. The ancestral levels of transcription and the evolution of sexual phenotypes in filamentous fungi.

    Science.gov (United States)

    Trail, Frances; Wang, Zheng; Stefanko, Kayla; Cubba, Caitlyn; Townsend, Jeffrey P

    2017-07-01

    Changes in gene expression have been hypothesized to play an important role in the evolution of divergent morphologies. To test this hypothesis in a model system, we examined differences in fruiting body morphology of five filamentous fungi in the Sordariomycetes, culturing them in a common garden environment and profiling genome-wide gene expression at five developmental stages. We reconstructed ancestral gene expression phenotypes, identifying genes with the largest evolved increases in gene expression across development. Conducting knockouts and performing phenotypic analysis in two divergent species typically demonstrated altered fruiting body development in the species that had evolved increased expression. Our evolutionary approach to finding relevant genes proved far more efficient than other gene deletion studies targeting whole genomes or gene families. Combining gene expression measurements with knockout phenotypes facilitated the refinement of Bayesian networks of the genes underlying fruiting body development, regulation of which is one of the least understood processes of multicellular development.

  19. The ancestral levels of transcription and the evolution of sexual phenotypes in filamentous fungi.

    Directory of Open Access Journals (Sweden)

    Frances Trail

    2017-07-01

    Full Text Available Changes in gene expression have been hypothesized to play an important role in the evolution of divergent morphologies. To test this hypothesis in a model system, we examined differences in fruiting body morphology of five filamentous fungi in the Sordariomycetes, culturing them in a common garden environment and profiling genome-wide gene expression at five developmental stages. We reconstructed ancestral gene expression phenotypes, identifying genes with the largest evolved increases in gene expression across development. Conducting knockouts and performing phenotypic analysis in two divergent species typically demonstrated altered fruiting body development in the species that had evolved increased expression. Our evolutionary approach to finding relevant genes proved far more efficient than other gene deletion studies targeting whole genomes or gene families. Combining gene expression measurements with knockout phenotypes facilitated the refinement of Bayesian networks of the genes underlying fruiting body development, regulation of which is one of the least understood processes of multicellular development.

  20. Green tea and anticancer perspectives: updates from last decade.

    Science.gov (United States)

    Butt, Masood Sadiq; Ahmad, Rabia Shabir; Sultan, M Tauseef; Qayyum, Mir M Nasir; Naz, Ambreen

    2015-01-01

    Green tea is the most widely consumed beverage besides water and has attained significant attention owing to health benefits against array of maladies, e.g., obesity, diabetes mellitus, cardiovascular disorders, and cancer insurgence. The major bioactive molecules are epigallocatechin-3-gallate, epicatechin, epicatechin-3-gallate, epigallocatechin, etc. The anticarcinogenic and antimutagenic activities of green tea were highlighted some years ago. Several cohort studies and controlled randomized trials suggested the inverse association of green tea consumption and cancer prevalence. Cell culture and animal studies depicted the mechanisms of green tea to control cancer insurgence, i.e., induction of apoptosis to control cell growth arrest, altered expression of cell-cycle regulatory proteins, activation of killer caspases, and suppression of nuclear factor kappa-B activation. It acts as carcinoma blocker by modulating the signal transduction pathways involved in cell proliferation, transformation, inflammation, and metastasis. However, results generated from some research interventions conducted in different groups like smokers and nonsmokers, etc. contradicted with aforementioned anticancer perspectives. In this review paper, anticancer perspectives of green tea and its components have been described. Recent findings and literature have been surfed and arguments are presented to clarify the ambiguities regarding anticancer perspectives of green tea and its component especially against colon, skin, lung, prostate, and breast cancer. The heading of discussion and future trends is limelight of the manuscript. The compiled manuscript provides new avenues for researchers to be explored in relation to green tea and its bioactive components.

  1. Anticancer effects and molecular mechanisms of epigallocatechin-3-gallate

    Directory of Open Access Journals (Sweden)

    Kyoung-jin Min

    2014-03-01

    Full Text Available Epigallocatechin-3-gallate (EGCG is a type of catechin found in green tea. EGCG exhibits a variety of activities, including anti-inflammatory, antidiabetes, antiobesity, and antitumor. In this review, we focus on the antitumor effects of EGCG. EGCG inhibits carcinogen activity, tumorigenesis, proliferation, and angiogenesis, and induces cell death. These effects are associated with modulation of reactive oxygen species (ROS production. Although EGCG has a dual function of antioxidant and pro-oxidant potential, EGCG-mediated modulation of ROS production is reported to be responsible for its anticancer effects. The EGCG-mediated inhibition of nuclear factor-κB signaling is also associated with inhibition of migration, angiogenesis, and cell viability. Activation of mitogen-activated protein kinases activity upregulates the anticancer effect of EGCG on migration, invasion, and apoptosis. In addition, EGCG could also induce epigenetic modification by inhibition of DNA methyltransferase activity and regulation of acetylation on histone, leading to an upregulation of apoptosis. Although EGCG promotes strong anticancer effects by multiple mechanisms, further studies are needed to define the use of EGCG in clinical treatment.

  2. CNS Anticancer Drug Discovery and Development: 2016 conference insights.

    Science.gov (United States)

    Levin, Victor A; Abrey, Lauren E; Heffron, Timothy P; Tonge, Peter J; Dar, Arvin C; Weiss, William A; Gallo, James M

    2017-07-18

    CNS Anticancer Drug Discovery and Development November 2016, AZ, USA The 2016 second CNS Anticancer Drug Discovery and Development Conference addressed diverse viewpoints about why new drug discovery/development focused on CNS cancers has been sorely lacking. Despite more than 70,000 individuals in the USA being diagnosed with a primary brain malignancy and 151,669-286,486 suffering from metastatic CNS cancer, in 1999, temozolomide was the last drug approved by the US FDA as an anticancer agent for high-grade gliomas. Among the topics discussed were economic factors and pharmaceutical risk assessments, regulatory constraints and perceptions and the need for improved imaging surrogates of drug activity. Included were modeling tumor growth and drug effects in a medical environment in which direct tumor sampling for biological effects can be problematic, potential new drugs under investigation and targets for drug discovery and development. The long trajectory and diverse impediments to novel drug discovery, and expectation that more than one drug will be needed to adequately inhibit critical intracellular tumor pathways were viewed as major disincentives for most pharmaceutical/biotechnology companies. While there were a few unanimities, one consensus is the need for continued and focused discussion among academic and industry scientists and clinicians to address tumor targets, new drug chemistry, and more time- and cost-efficient clinical trials based on surrogate end points.

  3. Anti-cancer activity of compounds from Cassia garrettiana heartwood

    Directory of Open Access Journals (Sweden)

    Supreeya Yuenyongsawad

    2014-04-01

    Full Text Available The ethanol extract of Cassia garrettiana heartwood showed marked inhibitory activity against several cancer cell lines including HT-29, HeLa, MCF-7 and KB cells. Therefore, its extract and compounds were investigated for their anticancer effect using the Sulforhodamine B (SRB assay. The ethanol extract of C. garrettiana heartwood was separated to give five compounds which are chrysophanol (1, piceatannol (2, aloe-emodin (3, emodin (4 and cassigarol E (5. Of the tested samples, chrysophanol (1 showed the highest anti-cancer activity against KB cells (IC50 = 0.045 g/mL, aloe emodin (3 was the most active against HT-29 (IC50 = 0.29 g/mL, emodin (4 was against HeLa cells (IC50 = 0.82 g/mL, and cassigarol E (5 was active against MCF-7 (IC50 = 0.021 g/mL, whereas piceatannol (2 was inactive in all tested cell lines. This is the first report of anti-cancer effect against HT-29, HeLa, MCF-7 and KB cells of C. garrettiana heartwood.

  4. Antifungal and Anticancer Potential of Argemone mexicana L.

    Science.gov (United States)

    More, Nilesh V; Kharat, Arun S

    2016-11-03

    Background: Medicinal plants are widely used to treat infectious diseases, metabolic disorders and cancer. Argemone mexicana L. (A. mexicana), commonly found on desolate land of Marathwada (Maharashtra, India) has been used to treat oral cavity infections. Methods: In this study, cold aqueous and methanolic extracts were prepared from A. mexicana stem and leaves. These extracts were tested for their antifungal and anticancer activities. The antifungal activity was tested using the agar well diffusion method, while the anticancer activity against immortalized cell lines was assessed by trypan blue assay. Results: It was observed that both cold aqueous and methanolic extracts of A. mexicana stem and leaves inhibited the growth of Mucor indicus, Aspergillus flavus, Aspergillus niger and Penicillum notatum. Antifungal activity of the extract was comparable to that of Amphoterecin-B. A. mexicana extracts had a cytotoxic effect on A549, SiHa and KB immortalized cell lines that were similar to that of berberine. Conclusion: The A. mexicana leaf and stems exhibit strong antifungal and anticancer potential.

  5. Antifungal and Anticancer Potential of Argemone mexicana L.

    Directory of Open Access Journals (Sweden)

    Nilesh V. More

    2016-11-01

    Full Text Available Background: Medicinal plants are widely used to treat infectious diseases, metabolic disorders and cancer. Argemone mexicana L. (A. mexicana, commonly found on desolate land of Marathwada (Maharashtra, India has been used to treat oral cavity infections. Methods: In this study, cold aqueous and methanolic extracts were prepared from A. mexicana stem and leaves. These extracts were tested for their antifungal and anticancer activities. The antifungal activity was tested using the agar well diffusion method, while the anticancer activity against immortalized cell lines was assessed by trypan blue assay. Results: It was observed that both cold aqueous and methanolic extracts of A. mexicana stem and leaves inhibited the growth of Mucor indicus, Aspergillus flavus, Aspergillus niger and Penicillum notatum. Antifungal activity of the extract was comparable to that of Amphoterecin-B. A. mexicana extracts had a cytotoxic effect on A549, SiHa and KB immortalized cell lines that were similar to that of berberine. Conclusion: The A. mexicana leaf and stems exhibit strong antifungal and anticancer potential.

  6. Terpenoid composition and the anticancer activity of Acanthopanax trifoliatus.

    Science.gov (United States)

    Li, Dong-Li; Zheng, Xi; Chen, Yu-Chan; Jiang, Sen; Zhang, Yuan; Zhang, Wei-Min; Wang, Hua-Qian; Du, Zhi-Yun; Zhang, Kun

    2016-01-01

    The petroleum ether and ethyl acetate fractions of extract from an edible and medicinal plant Acanthopanax trifoliatus were found to show significant inhibitory effects against SF-268, MCF-7, HepG2 and NCI-H460 cancer cells. Two new ursane-type triterpenoids, acantrifoic acid C (1) and acantrifoic acid D (2), along with five known triterpenoids (3-7) and eight known diterpenoids (8-15) were obtained from these two fractions. To the best of our knowledge, this is the first report concerning the isolation of compounds (5-12, 14, 15) from A. trifoliatus. Among all the isolated compounds, 3, 5 and 8 from the ethyl acetate fraction showed the strongest inhibitory effects against cancer cells, while 12 and 13 from the petroleum ether fraction showed moderate activities. These terpenoid compounds may be responsible for the anticancer activities of A. trifoliatus. Our study provides the first evidence that terpenoids from A. trifoliatus exert anticancer activities and indicates that A. trifoliatus may be a useful edible plant for further development of anticancer health supplement.

  7. Mode of action of anticancer peptides (ACPs) from amphibian origin.

    Science.gov (United States)

    Oelkrug, Christopher; Hartke, Martin; Schubert, Andreas

    2015-02-01

    Although cancer belongs to one of the leading causes of death around the world, fortunately studies have shown that tumor cells have various targets that are susceptible to attack. Interestingly, tumor cells are comprised of cellular membranes, which are altered in chemical composition relative to non-neoplastic cells, giving them an increased net negative charge. These altered membranes are ideal targets for antimicrobial peptides (AMPs) shown to have additional tumoricidal properties and, hence, named anticancer peptides (ACPs). Several hundred ACPs have been explored in vitro and in vivo on various types of cancer. Novel anticancer agents are supposed not to cause serious side effects and the formation of multidrug-resistant tumor cells. During the quest for potent ACPs, promising candidates were isolated from skin secretions of amphibians, such as the granular glands of the Chinese brown frog, Rana chensinensis. ACPs have to be selective to cancer cells and should not induce strong immune responses or be cleared from the body rapidly. Several modifications can improve ACPs either by optimizing the primary structure rationally or randomly or even by introducing other chemical modifications. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  8. Redesigned Spider Peptide with Improved Antimicrobial and Anticancer Properties.

    Science.gov (United States)

    Troeira Henriques, Sónia; Lawrence, Nicole; Chaousis, Stephanie; Ravipati, Anjaneya S; Cheneval, Olivier; Benfield, Aurélie H; Elliott, Alysha G; Kavanagh, Angela Maria; Cooper, Matthew A; Chan, Lai Yue; Huang, Yen-Hua; Craik, David J

    2017-09-15

    Gomesin, a disulfide-rich antimicrobial peptide produced by the Brazilian spider Acanthoscurria gomesiana, has been shown to be potent against Gram-negative bacteria and to possess selective anticancer properties against melanoma cells. In a recent study, a backbone cyclized analogue of gomesin was shown to be as active but more stable than its native form. In the current study, we were interested in improving the antimicrobial properties of the cyclic gomesin, understanding its selectivity toward melanoma cells and elucidating its antimicrobial and anticancer mode of action. Rationally designed analogues of cyclic gomesin were examined for their antimicrobial potency, selectivity toward cancer cells, membrane-binding affinity, and ability to disrupt cell and model membranes. We improved the activity of cyclic gomesin by ∼10-fold against tested Gram-negative and Gram-positive bacteria without increasing toxicity to human red blood cells. In addition, we showed that gomesin and its analogues are more toxic toward melanoma and leukemia cells than toward red blood cells and act by selectively targeting and disrupting cancer cell membranes. Preference toward some cancer types is likely dependent on their different cell membrane properties. Our findings highlight the potential of peptides as antimicrobial and anticancer leads and the importance of selectively targeting cancer cell membranes for drug development.

  9. The aldehyde dehydrogenase, AldA, is essential for L-1,2-propanediol utilization in laboratory-evolved Escherichia coli.

    Science.gov (United States)

    Aziz, Ramy K; Monk, Jonathan M; Andrews, Kathleen A; Nhan, Jenny; Khaw, Valerie L; Wong, Hesper; Palsson, Bernhard O; Charusanti, Pep

    2017-01-01

    Most Escherichia coli strains are naturally unable to grow on 1,2-propanediol (PDO) as a sole carbon source. Recently, however, a K-12 descendent E. coli strain was evolved to grow on 1,2-PDO, and it was hypothesized that this evolved ability was dependent on the aldehyde dehydrogenase, AldA, which is highly conserved among members of the family Enterobacteriacea. To test this hypothesis, we first performed computational model simulation, which confirmed the essentiality of the aldA gene for 1,2-PDO utilization by the evolved PDO-degrading E. coli. Next, we deleted the aldA gene from the evolved strain, and this deletion was sufficient to abolish the evolved phenotype. On re-introducing the gene on a plasmid, the evolved phenotype was restored. These findings provide experimental evidence for the computationally predicted role of AldA in 1,2-PDO utilization, and represent a good example of E. coli robustness, demonstrated by the bacterial deployment of a generalist enzyme (here AldA) in multiple pathways to survive carbon starvation and to grow on a non-native substrate when no native carbon source is available. Copyright © 2016 Elsevier GmbH. All rights reserved.

  10. Orthogonally Evolved AI to Improve Difficulty Adjustment in Video Games

    DEFF Research Database (Denmark)

    Hintze, Arend; Olson, Randal; Lehman, Joel Anthony

    2016-01-01

    (i.e. agents subject to fewer generations of evolution) make for easier opponents, while highly-evolved agents are more challenging to overcome. In this publication we test a new approach for difficulty adjustment in games: orthogonally evolved AI, where the player receives support from collaborating...... opponents. Furthermore, human interaction can modulate (and be informed by) the performance and behavior of collaborating agents. In this way, orthogonally evolved AI both facilitates smoother difficulty adjustment and enables new game experiences....

  11. Effects of Anticancer Drugs on Chromosome Instability and New Clinical Implications for Tumor-Suppressing Therapies.

    Science.gov (United States)

    Lee, Hee-Sheung; Lee, Nicholas C O; Kouprina, Natalay; Kim, Jung-Hyun; Kagansky, Alex; Bates, Susan; Trepel, Jane B; Pommier, Yves; Sackett, Dan; Larionov, Vladimir

    2016-02-15

    Whole chromosomal instability (CIN), manifested as unequal chromosome distribution during cell division, is a distinguishing feature of most cancer types. CIN is generally considered to drive tumorigenesis, but a threshold level exists whereby further increases in CIN frequency in fact hinder tumor growth. While this attribute is appealing for therapeutic exploitation, drugs that increase CIN beyond this therapeutic threshold are currently limited. In our previous work, we developed a quantitative assay for measuring CIN based on the use of a nonessential human artificial chromosome (HAC) carrying a constitutively expressed EGFP transgene. Here, we used this assay to rank 62 different anticancer drugs with respect to their effects on chromosome transmission fidelity. Drugs with various mechanisms of action, such as antimicrotubule activity, histone deacetylase inhibition, mitotic checkpoint inhibition, and targeting of DNA replication and damage responses, were included in the analysis. Ranking of the drugs based on their ability to induce HAC loss revealed that paclitaxel, gemcitabine, dactylolide, LMP400, talazoparib, olaparib, peloruside A, GW843682, VX-680, and cisplatin were the top 10 drugs demonstrating HAC loss at a high frequency. Therefore, identification of currently used compounds that greatly increase chromosome mis-segregation rates should expedite the development of new therapeutic strategies to target and leverage the CIN phenotype in cancer cells. ©2016 American Association for Cancer Research.

  12. Natural product modulators of transient receptor potential (TRP) channels as potential anti-cancer agents.

    Science.gov (United States)

    Rodrigues, Tiago; Sieglitz, Florian; Bernardes, Gonçalo J L

    2016-11-07

    Treatment of cancer is a significant challenge in clinical medicine, and its research is a top priority in chemical biology and drug discovery. Consequently, there is an urgent need for identifying innovative chemotypes capable of modulating unexploited drug targets. The transient receptor potential (TRPs) channels persist scarcely explored as targets, despite intervening in a plethora of pathophysiological events in numerous diseases, including cancer. Both agonists and antagonists have proven capable of evoking phenotype changes leading to either cell death or reduced cell migration. Among these, natural products entail biologically pre-validated and privileged architectures for TRP recognition. Furthermore, several natural products have significantly contributed to our current knowledge on TRP biology. In this Tutorial Review we focus on selected natural products, e.g. capsaicinoids, cannabinoids and terpenes, by highlighting challenges and opportunities in their use as starting points for designing natural product-inspired TRP channel modulators. Importantly, the de-orphanization of natural products as TRP channel ligands may leverage their exploration as viable strategy for developing anticancer therapies. Finally, we foresee that TRP channels may be explored for the selective pharmacodelivery of cytotoxic payloads to diseased tissues, providing an innovative platform in chemical biology and molecular medicine.

  13. Phenotypic plasticity, costs of phenotypes, and costs of plasticity

    DEFF Research Database (Denmark)

    Callahan, Hilary S; Maughan, Heather; Steiner, Uli

    2008-01-01

    Why are some traits constitutive and others inducible? The term costs often appears in work addressing this issue but may be ambiguously defined. This review distinguishes two conceptually distinct types of costs: phenotypic costs and plasticity costs. Phenotypic costs are assessed from patterns...... of covariation, typically between a focal trait and a separate trait relevant to fitness. Plasticity costs, separable from phenotypic costs, are gauged by comparing the fitness of genotypes with equivalent phenotypes within two environments but differing in plasticity and fitness. Subtleties associated with both...... types of costs are illustrated by a body of work addressing predator-induced plasticity. Such subtleties, and potential interplay between the two types of costs, have also been addressed, often in studies involving genetic model organisms. In some instances, investigators have pinpointed the mechanistic...

  14. Evolving R Coronae Borealis Stars with MESA

    Science.gov (United States)

    Clayton, Geoffrey C.; Lauer, Amber; Chatzopoulos, Emmanouil; Frank, Juhan

    2018-01-01

    being a WD. Solving the mystery of how the RCB stars evolve will lead to a better understanding of other important types of stellar merger events such as Type Ia SNe.

  15. Novel walnut peptide-selenium hybrids with enhanced anticancer synergism: facile synthesis and mechanistic investigation of anticancer activity.

    Science.gov (United States)

    Liao, Wenzhen; Zhang, Rong; Dong, Chenbo; Yu, Zhiqiang; Ren, Jiaoyan

    2016-01-01

    This contribution reports a facile synthesis of degreased walnut peptides (WP1)-functionalized selenium nanoparticles (SeNPs) hybrids with enhanced anticancer activity and a detailed mechanistic evaluation of its superior anticancer activity. Structural and chemical characterizations proved that SeNPs are effectively capped with WP1 via physical absorption, resulting in a stable hybrid structure with an average diameter of 89.22 nm. A panel of selected human cancer cell lines demonstrated high susceptibility toward WP1-SeNPs and displayed significantly reduced proliferative behavior. The as-synthesized WP1-SeNPs exhibited excellent selectivity between cancer cells and normal cells. The targeted induction of apoptosis in human breast adenocarcinoma cells (MCF-7) was confirmed by the accumulation of arrested S-phase cells, nuclear condensation, and DNA breakage. Careful investigations revealed that an extrinsic apoptotic pathway can be attributed to the cell apoptosis and the same was confirmed by activation of the Fas-associated with death domain protein and caspases 3, 8, and 9. In addition, it was also understood that intrinsic apoptotic pathways including reactive oxygen species generation, as well as the reduction in mitochondrial membrane potential, are also involved in the WP1-SeNP-induced apoptosis. This suggested the involvement of multiple apoptosis pathways in the anticancer activity. Our results indicated that WP1-SeNP hybrids with Se core encapsulated in a WP1 shell could be a highly effective method to achieve anticancer synergism. Moreover, the great potential exhibited by WP1-SeNPs could make them an ideal candidate as a chemotherapeutic agent for human cancers, especially for breast cancer.

  16. Strategies to potentiate antimicrobial photoinactivation by overcoming resistant phenotypes.

    Science.gov (United States)

    Vera, Domingo Mariano Adolfo; Haynes, Mark H; Ball, Anthony R; Dai, Tianhong; Astrakas, Christos; Kelso, Michael J; Hamblin, Michael R; Tegos, George P

    2012-01-01

    Conventional antimicrobial strategies have become increasingly ineffective due to the emergence of multidrug resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered the exploration of alternative treatments and unconventional approaches towards controlling microbial infections. Photodynamic therapy (PDT) was originally established as an anticancer modality and is currently used in the treatment of age-related macular degeneration. The concept of photodynamic inactivation requires cell exposure to light energy, typically wavelengths in the visible region that causes the excitation of photosensitizer molecules either exogenous or endogenous, which results in the production of reactive oxygen species (ROS). ROS produce cell inactivation and death through modification of intracellular components. The versatile characteristics of PDT prompted its investigation as an anti-infective discovery platform. Advances in understanding of microbial physiology have shed light on a series of pathways, and phenotypes that serve as putative targets for antimicrobial drug discovery. Investigations of these phenotypic elements in concert with PDT have been reported focused on multidrug efflux systems, biofilms, virulence and pathogenesis determinants. In many instances the results are promising but only preliminary and require further investigation. This review discusses the different antimicrobial PDT strategies and highlights the need for highly informative and comprehensive discovery approaches. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  17. Tryptophan as a Probe to Study the Anticancer Mechanism of Action and Specificity of α-Helical Anticancer Peptides

    Directory of Open Access Journals (Sweden)

    Guirong Li

    2014-08-01

    Full Text Available In the present study, a single tryptophan, as a fluorescence probe, was shifted from the N-terminus to the middle and to the C-terminus of a 26-residue α-helical anticancer peptide sequence to study the mechanism of action and specificity. The hydrophobicity of peptides, as well as peptide helicity and self-associating ability, were slightly influenced by the position change of tryptophan in the peptide sequence, while the hemolytic activity and anticancer activity of the peptide analogs remained the same. The tryptophan fluorescence experiment demonstrated that peptide analogs were more selective against LUVs mimicking cancer cell membranes than LUVs mimicking normal cell membranes. During the interaction with target membranes, the N-terminus of an anticancer peptide may be inserted vertically or tilted into the hydrophobic components of the phospholipid bilayer first. The thermodynamic parameters of the peptides PNW and PCW, when interacting with zwitterionic DMPC or negatively charged DMPS, were determined by ITC. DSC experiments showed that peptide analogs significantly altered the phase transition profiles of DMPC, but did not dramatically modify the phase transition of DMPS. It is demonstrated that hydrophobic interactions are the main driving force for peptides interacting with normal cell membranes, whilst, electrostatic interactions dominate the interactions between peptides and cancer cell membranes. Utilizing tryptophan as a fluorescence probe molecule appears to be a practicable approach to determine the interaction of peptides with phospholipid bilayers.

  18. Tryptophan as a probe to study the anticancer mechanism of action and specificity of α-helical anticancer peptides.

    Science.gov (United States)

    Li, Guirong; Huang, Yibing; Feng, Qi; Chen, Yuxin

    2014-08-13

    In the present study, a single tryptophan, as a fluorescence probe, was shifted from the N-terminus to the middle and to the C-terminus of a 26-residue α-helical anticancer peptide sequence to study the mechanism of action and specificity. The hydrophobicity of peptides, as well as peptide helicity and self-associating ability, were slightly influenced by the position change of tryptophan in the peptide sequence, while the hemolytic activity and anticancer activity of the peptide analogs remained the same. The tryptophan fluorescence experiment demonstrated that peptide analogs were more selective against LUVs mimicking cancer cell membranes than LUVs mimicking normal cell membranes. During the interaction with target membranes, the N-terminus of an anticancer peptide may be inserted vertically or tilted into the hydrophobic components of the phospholipid bilayer first. The thermodynamic parameters of the peptides PNW and PCW, when interacting with zwitterionic DMPC or negatively charged DMPS, were determined by ITC. DSC experiments showed that peptide analogs significantly altered the phase transition profiles of DMPC, but did not dramatically modify the phase transition of DMPS. It is demonstrated that hydrophobic interactions are the main driving force for peptides interacting with normal cell membranes, whilst, electrostatic interactions dominate the interactions between peptides and cancer cell membranes. Utilizing tryptophan as a fluorescence probe molecule appears to be a practicable approach to determine the interaction of peptides with phospholipid bilayers.

  19. Finding our way through phenotypes.

    Directory of Open Access Journals (Sweden)

    Andrew R Deans

    2015-01-01

    Full Text Available Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.

  20. Phenotypical Behavior and Evolutionary Slavery

    OpenAIRE

    Martins, Andre C. R.

    2000-01-01

    A new evolutionary solution to Prisoner Dilemma situations is proposed in this paper. A specific genetic code may have different phenotypes, meaning different strategies for different individuals carrying that gene. This means that, under the right parameters, it is a good evolutionary solution to create two types of phenotypes with different strategies, here called as leaders and servants. In this solution, servants always cooperate with the leaders and leaders never do with the servants. In...

  1. Microsymbiont and Morphological Phenotype Analysis

    OpenAIRE

    Marzuki, Ismail

    2016-01-01

    Determination biomass and phenotypic analysis of microsymbionts sponge is a comprehensive effort to discover the specificity of the sponge, not only on the identification and characterization studies that have been growing. Research directed at diversification of knowledge of the functions and benefits of a sponge for the life and welfare of mankind. The purpose of this research is the analysis of biomass morphology and phenotype test microsymbionts sponge. Histomorfologi analysis method to d...

  2. An end to endless forms: epistasis, phenotype distribution bias, and nonuniform evolution.

    Science.gov (United States)

    Borenstein, Elhanan; Krakauer, David C

    2008-10-01

    Studies of the evolution of development characterize the way in which gene regulatory dynamics during ontogeny constructs and channels phenotypic variation. These studies have identified a number of evolutionary regularities: (1) phenotypes occupy only a small subspace of possible phenotypes, (2) the influence of mutation is not uniform and is often canalized, and (3) a great deal of morphological variation evolved early in the history of multicellular life. An important implication of these studies is that diversity is largely the outcome of the evolution of gene regulation rather than the emergence of new, structural genes. Using a simple model that considers a generic property of developmental maps-the interaction between multiple genetic elements and the nonlinearity of gene interaction in shaping phenotypic traits-we are able to recover many of these empirical regularities. We show that visible phenotypes represent only a small fraction of possibilities. Epistasis ensures that phenotypes are highly clustered in morphospace and that the most frequent phenotypes are the most similar. We perform phylogenetic analyses on an evolving, developmental model and find that species become more alike through time, whereas higher-level grades have a tendency to diverge. Ancestral phenotypes, produced by early developmental programs with a low level of gene interaction, are found to span a significantly greater volume of the total phenotypic space than derived taxa. We suggest that early and late evolution have a different character that we classify into micro- and macroevolutionary configurations. These findings complement the view of development as a key component in the production of endless forms and highlight the crucial role of development in constraining biotic diversity and evolutionary trajectories.

  3. An end to endless forms: epistasis, phenotype distribution bias, and nonuniform evolution.

    Directory of Open Access Journals (Sweden)

    Elhanan Borenstein

    2008-10-01

    Full Text Available Studies of the evolution of development characterize the way in which gene regulatory dynamics during ontogeny constructs and channels phenotypic variation. These studies have identified a number of evolutionary regularities: (1 phenotypes occupy only a small subspace of possible phenotypes, (2 the influence of mutation is not uniform and is often canalized, and (3 a great deal of morphological variation evolved early in the history of multicellular life. An important implication of these studies is that diversity is largely the outcome of the evolution of gene regulation rather than the emergence of new, structural genes. Using a simple model that considers a generic property of developmental maps-the interaction between multiple genetic elements and the nonlinearity of gene interaction in shaping phenotypic traits-we are able to recover many of these empirical regularities. We show that visible phenotypes represent only a small fraction of possibilities. Epistasis ensures that phenotypes are highly clustered in morphospace and that the most frequent phenotypes are the most similar. We perform phylogenetic analyses on an evolving, developmental model and find that species become more alike through time, whereas higher-level grades have a tendency to diverge. Ancestral phenotypes, produced by early developmental programs with a low level of gene interaction, are found to span a significantly greater volume of the total phenotypic space than derived taxa. We suggest that early and late evolution have a different character that we classify into micro- and macroevolutionary configurations. These findings complement the view of development as a key component in the production of endless forms and highlight the crucial role of development in constraining biotic diversity and evolutionary trajectories.

  4. Loops and autonomy promote evolvability of ecosystem networks.

    Science.gov (United States)

    Luo, Jianxi

    2014-09-29

    The structure of ecological networks, in particular food webs, determines their ability to evolve further, i.e. evolvability. The knowledge about how food web evolvability is determined by the structures of diverse ecological networks can guide human interventions purposefully to either promote or limit evolvability of ecosystems. However, the focus of prior food web studies was on stability and robustness; little is known regarding the impact of ecological network structures on their evolvability. To correlate ecosystem structure and evolvability, we adopt the NK model originally from evolutionary biology to generate and assess the ruggedness of fitness landscapes of a wide spectrum of model food webs with gradual variation in the amount of feeding loops and link density. The variation in network structures is controlled by linkage rewiring. Our results show that more feeding loops and lower trophic link density, i.e. higher autonomy of species, of food webs increase the potential for the ecosystem to generate heritable variations with improved fitness. Our findings allow the prediction of the evolvability of actual food webs according to their network structures, and provide guidance to enhancing or controlling the evolvability of specific ecosystems.

  5. Protein structural modularity and robustness are associated with evolvability.

    Science.gov (United States)

    Rorick, Mary M; Wagner, Günter P

    2011-01-01

    Theory suggests that biological modularity and robustness allow for maintenance of fitness under mutational change, and when this change is adaptive, for evolvability. Empirical demonstrations that these traits promote evolvability in nature remain scant however. This is in part because modularity, robustness, and evolvability are difficult to define and measure in real biological systems. Here, we address whether structural modularity and/or robustness confer evolvability at the level of proteins by looking for associations between indices of protein structural modularity, structural robustness, and evolvability. We propose a novel index for protein structural modularity: the number of regular secondary structure elements (helices and strands) divided by the number of residues in the structure. We index protein evolvability as the proportion of sites with evidence of being under positive selection multiplied by the average rate of adaptive evolution at these sites, and we measure this as an average over a phylogeny of 25 mammalian species. We use contact density as an index of protein designability, and thus, structural robustness. We find that protein evolvability is positively associated with structural modularity as well as structural robustness and that the effect of structural modularity on evolvability is independent of the structural robustness index. We interpret these associations to be the result of reduced constraints on amino acid substitutions in highly modular and robust protein structures, which results in faster adaptation through natural selection.

  6. Adaptation of Escherichia coli to glucose promotes evolvability in lactose.

    Science.gov (United States)

    Phillips, Kelly N; Castillo, Gerardo; Wünsche, Andrea; Cooper, Tim F

    2016-02-01

    The selective history of a population can influence its subsequent evolution, an effect known as historical contingency. We previously observed that five of six replicate populations that were evolved in a glucose-limited environment for 2000 generations, then switched to lactose for 1000 generations, had higher fitness increases in lactose than populations started directly from the ancestor. To test if selection in glucose systematically increased lactose evolvability, we started 12 replay populations--six from a population subsample and six from a single randomly selected clone--from each of the six glucose-evolved founder populations. These replay populations and 18 ancestral populations were evolved for 1000 generations in a lactose-limited environment. We found that replay populations were initially slightly less fit in lactose than the ancestor, but were more evolvable, in that they increased in fitness at a faster rate and to higher levels. This result indicates that evolution in the glucose environment resulted in genetic changes that increased the potential of genotypes to adapt to lactose. Genome sequencing identified four genes--iclR, nadR, spoT, and rbs--that were mutated in most glucose-evolved clones and are candidates for mediating increased evolvability. Our results demonstrate that short-term selective costs during selection in one environment can lead to changes in evolvability that confer longer term benefits. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

  7. The interactions of anticancer agents with tea catechins: current evidence from preclinical studies.

    Science.gov (United States)

    Shang, Weihu; Lu, Weidong; Han, Mei; Qiao, Jinping

    2014-01-01

    Tea catechins exhibit a broad range of pharmacological activities that impart beneficial effects on human health. Epigallocatechin-3-gallate (EGCG), one of the major tea catechins, has been widely associated with cancer prevention and treatment. In addition, tea catechins in combination with anticancer drugs are being evaluated as a new cancer treatment strategy. However, the interactions of anticancer drugs with tea catechins are largely unknown. Accumulated data indicate significant interactions between anticancer drugs and tea catechins, such as synergistic tumor inhibition or antagonist activity. Therefore, it is critical to understand comprehensively the effects of tea catechins on anticancer drugs. Focusing on evidence from preclinical studies, this paper will review the interactions between anticancer drugs and tea catechins, including pharmacodynamics and pharmacokinetics effects. We hope that by detailing the interactions between anticancer drugs and tea catechins, more attention will be directed to this important therapeutic combination in the future.

  8. Nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs.

    Science.gov (United States)

    Huang, Wei; Chen, Liqing; Kang, Lin; Jin, Mingji; Sun, Ping; Xin, Xin; Gao, Zhonggao; Bae, You Han

    2017-06-01

    Anticancer therapy has always been a vital challenge for the development of nanomedicine. Repeated single therapeutic agent may lead to undesirable and severe side effects, unbearable toxicity and multidrug resistance due to complex nature of tumor. Nanomedicine-based combination anticancer therapy can synergistically improve antitumor outcomes through multiple-target therapy, decreasing the dose of each therapeutic agent and reducing side effects. There are versatile combinational anticancer strategies such as chemotherapeutic combination, nucleic acid-based co-delivery, intrinsic sensitive and extrinsic stimulus combinational patterns. Based on these combination strategies, various nanocarriers and drug delivery systems were engineered to carry out the efficient co-delivery of combined therapeutic agents for combination anticancer therapy. This review focused on illustrating nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs for synergistically improving anticancer efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Lineage Tracking for Probing Heritable Phenotypes at Single-Cell Resolution

    Science.gov (United States)

    Cottinet, Denis; Condamine, Florence; Bremond, Nicolas; Griffiths, Andrew D.; Rainey, Paul B.; de Visser, J. Arjan G. M.; Baudry, Jean; Bibette, Jérôme

    2016-01-01

    Determining the phenotype and genotype of single cells is central to understand microbial evolution. DNA sequencing technologies allow the detection of mutants at high resolution, but similar approaches for phenotypic analyses are still lacking. We show that a drop-based millifluidic system enables the detection of heritable phenotypic changes in evolving bacterial populations. At time intervals, cells were sampled and individually compartmentalized in 100 nL drops. Growth through 15 generations was monitored using a fluorescent protein reporter. Amplification of heritable changes–via growth–over multiple generations yields phenotypically distinct clusters reflecting variation relevant for evolution. To demonstrate the utility of this approach, we follow the evolution of Escherichia coli populations during 30 days of starvation. Phenotypic diversity was observed to rapidly increase upon starvation with the emergence of heritable phenotypes. Mutations corresponding to each phenotypic class were identified by DNA sequencing. This scalable lineage-tracking technology opens the door to large-scale phenotyping methods with special utility for microbiology and microbial population biology. PMID:27077662

  10. The Evolution of Phenotypic Plasticity in Spatially Structured Environments: Implications of Intraspecific Competition, Plasticity Costs, and Environmental Characteristics

    OpenAIRE

    Ernande, B.; Dieckmann, U.

    2004-01-01

    We model the evolution of reaction norms focusing on three aspects: frequency dependent selection arising from resource competition, maintenance and production costs of phenotypic plasticity, and three characteristics of environmental heterogeneity (frequency of environments, their intrinsic carrying capacity, and the sensitivity to phenotypic maladaptation in these environments). We show that (i) reaction norms evolve so as to trade adaptation for acquiring resources against cost avoidance; ...

  11. Anti-cancer activities of Ganoderma lucidum: active ingredients and pathways

    Directory of Open Access Journals (Sweden)

    Chi H.J. Kao

    2013-02-01

    Full Text Available ABSTRACTGanoderma lucidum, commonly referred to as Lingzhi, has been used in Asia for health promotion for centuries. The anti-cancer effects of G. lucidum have been demonstrated in both in vitro and in vivo studies. In addition, the observed anti-cancer activities of Ganoderma have prompted its usage by cancer patients alongside chemotherapy.The main two bioactive components of G. lucidum can be broadly grouped into triterpenes and polysaccharides. Despite triterpenes and polysaccharides being widely known as the major active ingredients, the different biological pathways by which they exert their anti-cancer effect remain poorly defined. Therefore, understanding the mechanisms of action may lead to more widespread use of Ganoderma as an anti-cancer agent.The aim of this paper is to summarise the various bioactive mechanisms that have been proposed for the anti-cancer properties of triterpenes and polysaccharides extracted from G. lucidum. A literature search of published papers on NCBI with keywords “Ganoderma” and “cancer” was performed. Among those, studies which specifically examined the anti-cancer activities of Ganoderma triterpenes and polysaccharides were selected to be included in this paper.We have found five potential mechanisms which are associated with the anti-cancer activities of Ganoderma triterpenes and three potential mechanisms for Ganoderma polysaccharides. In addition, G. lucidum has been used in combination with known anti-cancer agents to improve the anti-cancer efficacies. This suggests Ganoderma’s bioactive pathways may compliment that of anti-cancer agents. In this paper we present several potential anti-cancer mechanisms of Ganoderma triterpenes and polysaccharides which can be used for the development of Ganoderma as an anti-cancer agent.

  12. Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jian-Zheng, E-mail: wppzheng@126.com [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000 (China); Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000 (China); Zhu, Yu-Xia [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000 (China); Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000 (China); Ma, Hui-Chao; Chen, Si-Nan; Chao, Ji-Ye; Ruan, Wen-Ding; Wang, Duo; Du, Feng-guang [Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000 (China); Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000 (China); Meng, Yue-Zhong [State Key Laboratory of Optoelectronic Materials and Technologies, Sun Yat-sen University, Guangzhou 510275 (China)

    2016-05-01

    In this work, a 3D MCTS-CCA system was constructed by culturing multi-cellular tumor spheroid (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. The CCA scaffolds were fabricated by spray-spinning. The interactions between the components of the spray-spun fibers were evidenced by methods of Coomassie Blue stain, X-ray diffraction (XRD) and Fourier transform-infrared spectroscopy (FTIR). Co-culture indicated that MCF-7 cells showed a spatial growth pattern of multi-cellular tumor spheroid (MCTS) in the CCA fibrous scaffold with increased proliferation rate and drug-resistance to MMC, ADM and 5-Aza comparing with the 2D culture cells. Significant increases of total viable cells were found in 3D MCTS groups after drug administration by method of apoptotic analysis. Glucose–lactate analysis indicated that the metabolism of MCTS in CCA scaffold was closer to the tumor issue in vivo than the monolayer cells. In addition, MCTS showed the characteristic of epithelial mesenchymal transition (EMT) which is subverted by carcinoma cells to facilitate metastatic spread. These results demonstrated that MCTS in CCA scaffold possessed a more conservative phenotype of tumor than monolayer cells, and anticancer drug screening in 3D MCTS-CCA system might be superior to the 2D culture system. - Highlights: • Chitosan/collagen/alginate (CCA) scaffolds were fabricated by spray-spinning. • MCF-7 cells presented a multi-cellular tumor spheroid model (MCTS) in CCA scaffold. • MCTS in CCA possessed a more conservative phenotype of tumor than monolayer cells. • Anticancer drug screening in MCTS-CCA system is superior to 2D culture system.

  13. Network analysis of breast cancer progression and reversal using a tree-evolving network algorithm.

    Directory of Open Access Journals (Sweden)

    Ankur P Parikh

    2014-07-01

    Full Text Available The HMT3522 progression series of human breast cells have been used to discover how tissue architecture, microenvironment and signaling molecules affect breast cell growth and behaviors. However, much remains to be elucidated about malignant and phenotypic reversion behaviors of the HMT3522-T4-2 cells of this series. We employed a "pan-cell-state" strategy, and analyzed jointly microarray profiles obtained from different state-specific cell populations from this progression and reversion model of the breast cells using a tree-lineage multi-network inference algorithm, Treegl. We found that different breast cell states contain distinct gene networks. The network specific to non-malignant HMT3522-S1 cells is dominated by genes involved in normal processes, whereas the T4-2-specific network is enriched with cancer-related genes. The networks specific to various conditions of the reverted T4-2 cells are enriched with pathways suggestive of compensatory effects, consistent with clinical data showing patient resistance to anticancer drugs. We validated the findings using an external dataset, and showed that aberrant expression values of certain hubs in the identified networks are associated with poor clinical outcomes. Thus, analysis of various reversion conditions (including non-reverted of HMT3522 cells using Treegl can be a good model system to study drug effects on breast cancer.

  14. The spatial patterns of directional phenotypic selection

    KAUST Repository

    Siepielski, Adam M.

    2013-09-12

    Local adaptation, adaptive population divergence and speciation are often expected to result from populations evolving in response to spatial variation in selection. Yet, we lack a comprehensive understanding of the major features that characterise the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data set includes 60 studies, consisting of 3937 estimates of selection across an average of five populations. We performed meta-analyses to explore features characterising spatial variation in directional selection. We found that selection tends to vary mainly in strength and less in direction among populations. Although differences in the direction of selection occur among populations they do so where selection is often weakest, which may limit the potential for ongoing adaptive population divergence. Overall, we also found that spatial variation in selection appears comparable to temporal (annual) variation in selection within populations; however, several deficiencies in available data currently complicate this comparison. We discuss future research needs to further advance our understanding of spatial variation in selection. © 2013 John Wiley & Sons Ltd/CNRS.

  15. The spatial patterns of directional phenotypic selection.

    Science.gov (United States)

    Siepielski, Adam M; Gotanda, Kiyoko M; Morrissey, Michael B; Diamond, Sarah E; DiBattista, Joseph D; Carlson, Stephanie M

    2013-11-01

    Local adaptation, adaptive population divergence and speciation are often expected to result from populations evolving in response to spatial variation in selection. Yet, we lack a comprehensive understanding of the major features that characterise the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data set includes 60 studies, consisting of 3937 estimates of selection across an average of five populations. We performed meta-analyses to explore features characterising spatial variation in directional selection. We found that selection tends to vary mainly in strength and less in direction among populations. Although differences in the direction of selection occur among populations they do so where selection is often weakest, which may limit the potential for ongoing adaptive population divergence. Overall, we also found that spatial variation in selection appears comparable to temporal (annual) variation in selection within populations; however, several deficiencies in available data currently complicate this comparison. We discuss future research needs to further advance our understanding of spatial variation in selection. © 2013 John Wiley & Sons Ltd/CNRS.

  16. Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models

    National Research Council Canada - National Science Library

    Plengsuriyakarn, Tullayakorn; Viyanant, Vithoon; Eursitthichai, Veerachai; Picha, Porntipa; Kupradinun, Piengchai; Itharat, Arunporn; Na-Bangchang, Kesara

    2012-01-01

    .... The discovery and development of effective chemotherapeutics is urgently needed. The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR...

  17. Determinants and associated factors influencing medication adherence and persistence to oral anticancer drugs: a systematic review.

    Science.gov (United States)

    Verbrugghe, M; Verhaeghe, S; Lauwaert, K; Beeckman, D; Van Hecke, A

    2013-10-01

    The use of oral anticancer drugs has increased in modern oncology treatment. The move from intravenous treatments towards oral anticancer drugs has increased the patients' own responsibility to take oral anticancer drugs as being prescribed. High rates of non-adherence to oral anticancer drugs have been reported. A systematic literature review was conducted to gain insight into determinants and associated factors of non-adherence and non-persistence in patients taking oral anticancer therapy. PubMed, Cochrane, Web of Science and Cinahl were systematically searched for studies focusing on determinants and associated factors of medication non-adherence and non-persistence to oral anticancer drugs. The methodological quality of the included studies was assessed by two independent reviewers. No studies were excluded based on the quality assessment. Twenty-five studies were included and systematically reviewed. The quality of the studies was moderate. Associated factors influencing medication non-adherence and non-persistence to oral anticancer drugs are multifactorial and interrelated. Older and younger age, and the influence of therapy related side effects were found to be predominant factors. Non-adherence and non-persistence to oral anticancer drug therapy are complex phenomena. More qualitative research is needed to facilitate the development of patient tailored complex interventions by exploring patients' needs and underlying processes influencing medication non-adherence and non-persistence to oral anticancer drugs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Targeted anticancer prodrug with mesoporous silica nanoparticles as vehicles

    Science.gov (United States)

    Fan, Jianquan; Fang, Gang; Wang, Xiaodan; Zeng, Fang; Xiang, Yufei; Wu, Shuizhu

    2011-11-01

    A targeted anticancer prodrug system was fabricated with 180 nm mesoporous silica nanoparticles (MSNs) as carriers. The anticancer drug doxorubicin (DOX) was conjugated to the particles through an acid-sensitive carboxylic hydrazone linker which is cleavable under acidic conditions. Moreover, folic acid (FA) was covalently conjugated to the particle surface as the targeting ligand for folate receptors (FRs) overexpressed in some cancer cells. The in vitro release profiles of DOX from the MSN-based prodrug systems showed a strong dependence on the environmental pH values. The fluorescent dye FITC was incorporated in the MSNs so as to trace the cellular uptake on a fluorescence microscope. Cellular uptakes by HeLa, A549 and L929 cell lines were tested for FA-conjugated MSNs and plain MSNs respectively, and a much more efficient uptake by FR-positive cancer cells (HeLa) can be achieved by conjugation of folic acid onto the particles because of the folate-receptor-mediated endocytosis. The cytotoxicities for the FA-conjugated MSN prodrug, the plain MSN prodrug and free DOX against three cell lines were determined, and the result indicates that the FA-conjugated MSN prodrug exhibits higher cytotoxicity to FR-positive cells, and reduced cytotoxicity to FR-negative cells. Thus, with 180 nm MSNs as the carriers for the prodrug system, good drug loading, selective targeting and sustained release of drug molecules within targeted cancer cells can be realized. This study may provide useful insights for designing and improving the applicability of MSNs in targeted anticancer prodrug systems.

  19. Anticancer activity of Ficus religiosa engineered copper oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Sankar, Renu; Maheswari, Ramasamy; Karthik, Selvaraju [Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu (India); Shivashangari, Kanchi Subramanian, E-mail: shivashangari@gmail.com [Regional Forensic Science Laboratory, Tiruchirapalli, Tamilnadu (India); Ravikumar, Vilwanathan, E-mail: ravikumarbdu@gmail.com [Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu (India)

    2014-11-01

    The design, synthesis, characterization and application of biologically synthesized nanomaterials have become a vital branch of nanotechnology. There is a budding need to develop a method for environmentally benign metal nanoparticle synthesis, that do not use toxic chemicals in the synthesis protocols to avoid adverse effects in medical applications. Here, it is a report on an eco-friendly process for rapid synthesis of copper oxide nanoparticles using Ficus religiosa leaf extract as reducing and protecting agent. The synthesized copper oxide nanoparticles were confirmed by UV–vis spectrophotometer, absorbance peaks at 285 nm. The copper oxide nanoparticles were analyzed with field emission-scanning electron microscope (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) and X-ray diffraction (XRD) spectrum. The FE-SEM and DLS analyses exposed that copper oxide nanoparticles are spherical in shape with an average particle size of 577 nm. FT-IR spectral analysis elucidates the occurrence of biomolecules required for the reduction of copper oxide ions. Zeta potential studies showed that the surface charge of the formed nanoparticles was highly negative. The XRD pattern revealed that synthesized nanoparticles are crystalline in nature. Further, biological activities of the synthesized nanoparticles were confirmed based on its stable anti-cancer effects. The apoptotic effect of copper oxide nanoparticles is mediated by the generation of reactive oxygen species (ROS) involving the disruption of mitochondrial membrane potential (Δψm) in A549 cells. The observed characteristics and results obtained in our in vitro assays suggest that the copper nanoparticles might be a potential anticancer agent. - Highlights: • Biogenic synthesis of copper oxide nanoparticles by leaf extract of Ficus religiosa • Characterized via UV–vis, FT-IR, DLS, FE-SEM with EDAX and XRD • Protein may act as an encapsulating, reducing and stabilizing

  20. Anti-Cancer Effects of Xanthones from Pericarps of Mangosteen

    Science.gov (United States)

    Akao, Yukihiro; Nakagawa, Yoshihito; Iinuma, Munekazu; Nozawa, Yoshinori

    2008-01-01

    Mangosteen, Garcinia mangostana Linn, is a tree found in South East Asia, and its pericarps have been used as traditional medicine. Phytochemical studies have shown that they contain a variety of secondary metabolites, such as oxygenated and prenylated xanthones. Recent studies revealed that these xanthones exhibited a variety of biological activities containing anti-inflammatory, anti-bacterial, and anti-cancer effects. We previously investigated the anti-proliferative effects of four prenylated xanthones from the pericarps; α-mangostin, β-mangostin, γ-mangostin, and methoxy-β-mangostin in various human cancer cells. These xanthones are different in the number of hydroxyl and methoxy groups. Except for methoxy-β-mangostin, the other three xanthones strongly inhibited cell growth at low concentrations from 5 to 20 μM in human colon cancer DLD-1 cells. Our recent study focused on the mechanism of α-mangostin-induced growth inhibition in DLD-1 cells. It was shown that the anti-proliferative effects of the xanthones were associated with cell-cycle arrest by affecting the expression of cyclins, cdc2, and p27; G1 arrest by α-mangostin and β-Mangostin, and S arrest by γ-mangostin. α-Mangostin found to induce apoptosis through the activation of intrinsic pathway following the down-regulation of signaling cascades involving MAP kinases and the serine/threonine kinase Akt. Synergistic effects by the combined treatment of α-mangostin and anti-cancer drug 5-FU was to be noted. α-Mangostin was found to have a cancer preventive effect in rat carcinogenesis bioassay and the extract from pericarps, which contains mainly α-mangostin and γ-mangostin, exhibited an enhancement of NK cell activity in a mouse model. These findings could provide a relevant basis for the development of xanthones as an agent for cancer prevention and the combination therapy with anti-cancer drugs. PMID:19325754

  1. Antioxidative and anticancer properties of Licochalcone A from licorice.

    Science.gov (United States)

    Chen, Xiangrong; Liu, Zuojia; Meng, Rizeng; Shi, Ce; Guo, Na

    2017-02-23

    Licochalcone A (LCA) is a characteristic chalcone that is found in licorice, which is a traditional medicinal plant. In traditional medicine, LCA possesses many potential biological activities, including anti-parasitic, anti-inflammatory and antitumor activities. To determine the antioxidant activity of LCA and, on this basis, to investigate the role of its anticancer activity. To validate the antioxidant activity of LCA, the proteins SOD, CAT and GPx1 were analyzed using western blotting and cellular antioxidant activity (CAA) assays. Oxidative free radicals are associated with cancer cells. Therefore, the anticancer activity of LCA was also evaluated. To assess the anticancer activity, cell viability assays were performed and apoptosis was evaluated. In addition, MAPK-related proteins were analyzed using western blotting. The experimental data showed that the EC 50 of LCA is 58.79±0.05μg/mL and 46.29±0.05μg/mL under the two conditions tested, with or without PBS. In addition, LCA at a concentration of approximately 2-8μg/mL can induce the expression of SOD, CAT and GPx1 proteins. Further, LCA inhibits the growth of HepG2 cells through cell proliferation arrest and the subsequent induction of apoptosis, and LCA attenuated the p38/JNK/ERK signaling pathway in a dose-dependent manner. The results showed that LCA suppresses the oxidation of cells and markedly inhibits the proliferation of cancer cells. These findings confirm the traditional use of LCA in folk medicine. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  2. NASA's Space Launch System: An Evolving Capability for Exploration An Evolving Capability for Exploration

    Science.gov (United States)

    Creech, Stephen D.; Crumbly, Christopher M.; Robinson, Kimerly F.

    2016-01-01

    A foundational capability for international human deep-space exploration, NASA's Space Launch System (SLS) vehicle represents a new spaceflight infrastructure asset, creating opportunities for mission profiles and space systems that cannot currently be executed. While the primary purpose of SLS, which is making rapid progress towards initial launch readiness in two years, will be to support NASA's Journey to Mars, discussions are already well underway regarding other potential utilization of the vehicle's unique capabilities. In its initial Block 1 configuration, capable of launching 70 metric tons (t) to low Earth orbit (LEO), SLS is capable of propelling the Orion crew vehicle to cislunar space, while also delivering small CubeSat-class spacecraft to deep-space destinations. With the addition of a more powerful upper stage, the Block 1B configuration of SLS will be able to deliver 105 t to LEO and enable more ambitious human missions into the proving ground of space. This configuration offers opportunities for launching co-manifested payloads with the Orion crew vehicle, and a class of secondary payloads, larger than today's CubeSats. Further upgrades to the vehicle, including advanced boosters, will evolve its performance to 130 t in its Block 2 configuration. Both Block 1B and Block 2 also offer the capability to carry 8.4- or 10-m payload fairings, larger than any contemporary launch vehicle. With unmatched mass-lift capability, payload volume, and C3, SLS not only enables spacecraft or mission designs currently impossible with contemporary EELVs, it also offers enhancing benefits, such as reduced risk, operational costs and/or complexity, shorter transit time to destination or launching large systems either monolithically or in fewer components. This paper will discuss both the performance and capabilities of Space Launch System as it evolves, and the current state of SLS utilization planning.

  3. (-)-Arctigenin as a lead compound for anticancer agent.

    Science.gov (United States)

    Chen, Gui-Rong; Li, Hong-Fu; Dou, De-Qiang; Xu, Yu-Bin; Jiang, Hong-Shuai; Li, Fu-Rui; Kang, Ting-Guo

    2013-01-01

    (-)-Arctigenin, an important active constituent of the traditional Chinese herb Fructus Arctii, was found to exhibit various bioactivities, so it can be used as a good lead compound for further structure modification in order to find a safer and more potent medicine. (-)-Arctigenin derivatives 1-5 of (-)-arctingen were obtained by modifying with ammonolysis at the lactone ring and sulphonylation at C (6') and C (6″) and O-demethylation at CH3O-C (3'), CH3O-C (3″) and CH3O-C (4″), and their anticancer bioactivities were examined.

  4. uPAR as anti-cancer target

    DEFF Research Database (Denmark)

    Lund, Ida K; Illemann, Martin; Thurison, Tine

    2011-01-01

    , and a potential diagnostic and predictive impact of the different uPAR forms has been reported. Hence, pericellular proteolysis seems to be a suitable target for anti-cancer therapy and numerous approaches have been pursued. Targeting of this process may be achieved by preventing the binding of uPA to u...... using mouse monoclonal antibodies (mAbs) against mouse uPA or uPAR. These reagents will target uPA and uPAR in both stromal cells and cancer cells, and their therapeutic potential can now be assessed in syngenic mouse cancer models....

  5. Black cumin seeds show promising anti-cancer effects

    Directory of Open Access Journals (Sweden)

    Editorial Office

    2017-02-01

    Full Text Available Lung cancer is responsible for millions of death worldwide each year and it is the second most common cancer in both men and women. According to the American Cancer Society, lung cancer is responsible for about 1 in 4 cancer deaths and 14% of all new cases. More and more people require treatment, but due to the side effects and complications of modern drugs, there has been a growing interest in naturally occurring compounds with anti-cancer potential. Black cumin seed is one of the most promising and extensively studied plants which could provide support in considering this compound as an emerging drug.

  6. Nanocarriers for anticancer drugs--new trends in nanomedicine.

    Science.gov (United States)

    Drbohlavova, Jana; Chomoucka, Jana; Adam, Vojtech; Ryvolova, Marketa; Eckschlager, Tomas; Hubalek, Jaromir; Kizek, Rene

    2013-06-01

    This review provides a brief overview of the variety of carriers employed for targeted drug delivery used in cancer therapy and summarizes advantages and disadvantages of each approach. Particularly, the attention was paid to polymeric nanocarriers, liposomes, micelles, polyethylene glycol, poly(lactic-co-glycolic acid), dendrimers, gold and magnetic nanoparticles, quantum dots, silica nanoparticles, and carbon nanotubes. Further, this paper briefly focuses on several anticancer agents (paclitaxel, docetaxel, camptothecin, doxorubicin, daunorubicin, cisplatin, curcumin, and geldanamycin) and on the influence of their combination with nanoparticulate transporters to their properties such as cytotoxicity, short life time and/or solubility.

  7. Isoflavones from Calpurnia Aurea subsp. Aurea and their anticancer activity

    CSIR Research Space (South Africa)

    Korir, E

    2014-01-01

    Full Text Available the renal, melanoma and breast cancer cell lines tested against, with the isoflavones 2 and 5 showing the best activity of the compounds tested. These isoflavones may have a synergistic effect with other anticancer drugs. ... activity against breast (MCF7), renal (TK10) and melanoma (UACC62) human cell lines using an in house method developed at the CSIR, South Africa. Results: The isoflavones, 4′,5,7-trihydroxyisoflavone (1), 7,3′- dihydroxy-5′-methoxyisoflavone (2), 7...

  8. Medicinal organometallic chemistry: designing metal arene complexes as anticancer agents.

    Science.gov (United States)

    Peacock, Anna F A; Sadler, Peter J

    2008-11-13

    The field of medicinal inorganic chemistry is rapidly advancing. In particular organometallic complexes have much potential as therapeutic and diagnostic agents. The carbon-bound and other ligands allow the thermodynamic and kinetic reactivity of the metal ion to be controlled and also provide a scaffold for functionalization. The establishment of structure-activity relationships and elucidation of the speciation of complexes under conditions relevant to drug testing and formulation are crucial for the further development of promising medicinal applications of organometallic complexes. Specific examples involving the design of ruthenium and osmium arene complexes as anticancer agents are discussed.

  9. Thalidomide–A Notorious Sedative to a Wonder Anticancer Drug

    Science.gov (United States)

    Zhou, Shuang; Wang, Fengfei; Hsieh, Tze-Chen; Wu, Joseph M.; Wu, Erxi

    2014-01-01

    In the past 50 years, thalidomide has undergone a remarkable metamorphosis from a notorious drug inducing birth defects into a highly effective therapy for treating leprosy and multiple myeloma. Today, most notably, thalidomide and its analogs have shown efficacy against a wide variety of diseases, including inflammation and cancer. The mechanism underlying its teratogenicity as well as its anticancer activities has been intensively studied. This review summarizes the biological effects and therapeutic uses of thalidomide and its analogs, and the underlying mechanisms of thalidomide’s action with a focus on its suppression of tumor growth. PMID:23931282

  10. ANTICANCER DNA VACCINATION: PRINCIPLE AND PERSPECTIVES OF THE METHOD

    Directory of Open Access Journals (Sweden)

    M. V. Stegantseva

    2017-01-01

    Full Text Available Conventional strategies for cancer treatment are close to their efficiency limits. Meanwhile, rapid development of experimental immunology and immunotherapy led to first successful experiences in antitumor vaccination. Over last decade, remarkable results were obtained by means of anticancer vaccination being implemented into clinical settings thus causing popularity and growth of interest to tumor-specific DNA vaccines. In this review, we discuss basic principles of a DNA vaccine construction, their structural characteristics and diversity, mechanisms of their biological action, pharmaceutical forms and delivery routes into the body. 

  11. Discovery of Anticancer Agents of Diverse Natural Origin

    Science.gov (United States)

    KINGHORN, A. DOUGLAS; CARCACHE DE BLANCO, ESPERANZA J.; LUCAS, DAVID M.; RAKOTONDRAIBE, H. LIVA; ORJALA, JIMMY; SOEJARTO, D. DOEL; OBERLIES, NICHOLAS H.; PEARCE, CEDRIC J.; WANI, MANSUKH C.; STOCKWELL, BRENT R.; BURDETTE, JOANNA E.; SWANSON, STEVEN M.; FUCHS, JAMES R.; PHELPS, MITCHELL A.; XU, LIHUI; ZHANG, XIAOLI; SHEN, YOUNG YONGCHUN

    2016-01-01

    Recent progress is described in an ongoing collaborative multidisciplinary research project directed towards the purification, structural characterization, chemical modification, and biological evaluation of new potential natural product anticancer agents obtained from a diverse group of organisms, comprising tropical plants, aquatic and terrestrial cyanobacteria, and filamentous fungi. Information is provided on how these organisms are collected and processed. The types of bioassays are indicated in which initial extracts, chromatographic fractions, and purified isolated compounds of these acquisitions are tested. Several promising biologically active lead compounds from each major organism major class investigated are described, and these may be seen to be representative of very wide chemical diversity. PMID:27793884

  12. Self-Evolvable Systems Machine Learning in Social Media

    CERN Document Server

    Iordache, Octavian

    2012-01-01

    This monograph presents key method to successfully manage the growing  complexity of systems  where conventional engineering and scientific methodologies and technologies based on learning and adaptability come to their limits and new ways are nowadays required. The transition from adaptable to evolvable and finally to self-evolvable systems is highlighted, self-properties such as self-organization, self-configuration, and self-repairing are introduced and challenges and limitations of the self-evolvable engineering systems are evaluated.

  13. [STRENGTHS AND WEAKNESSES OF RANDOMISED CLINICAL TRIALS: EVOLVING CHANGES ACCORDING TO PERSONALIZED MEDICINE].

    Science.gov (United States)

    Ernest, Ph; Jandrain, B; Scheen, A J

    2015-01-01

    Randomised Controlled Trials (RCTs) represent the cornerstone of Evidence-Based Medicine (EBM). Based upon the rules of Good Clinical Practice (GCP), they offer many strengths but also present some weaknesses. The rigorous methodology used allows avoid bias related to confounding factors (through a control group), selection bias (through randomisation) and interpretation bias (through double blinding). However, patients recruited in clinical trials and study experimental conditions markedly differ from the situation in real life. Furthermore, clinical trials recruit a mix of good and poor responders, so that the average therapeutic response is most often mitigated. Clinical trials must evolve according to the new concepts of personalized medicine to become even more performing. In a near future, they must progress from a statistical analysis on large cohorts of patients to a more individualized analysis guided by patient phenotype and genotype characteristics.

  14. Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications

    Science.gov (United States)

    Deslouches, Berthony; Di, Y. Peter

    2017-01-01

    In the last several decades, there have been significant advances in anticancer therapy. However, the development of resistance to cancer drugs and the lack of specificity related to actively dividing cells leading to toxic side effects have undermined these achievements. As a result, there is considerable interest in alternative drugs with novel antitumor mechanisms. In addition to the recent approach using immunotherapy, an effective but much cheaper therapeutic option of pharmaceutical drugs would still provide the best choice for cancer patients as the first line treatment. Ribosomally synthesized cationic antimicrobial peptides (AMPs) or host defense peptides (HDP) display broad-spectrum activity against bacteria based on electrostatic interactions with negatively charged lipids on the bacterial surface. Because of increased proportions of phosphatidylserine (negatively charged) on the surface of cancer cells compared to normal cells, cationic amphipathic peptides could be an effective source of anticancer agents that are both selective and refractory to current resistance mechanisms. We reviewed herein the prospect for AMP application to cancer treatment, with a focus on modes of action of cationic AMPs. PMID:28422728

  15. Anticancer and Antioxidant Activity of Bread Enriched with Broccoli Sprouts

    Science.gov (United States)

    Gawlik-Dziki, Urszula; Świeca, Michał; Dziki, Dariusz; Sęczyk, Łukasz; Złotek, Urszula; Różyło, Renata; Kaszuba, Kinga; Ryszawy, Damian; Czyż, Jarosław

    2014-01-01

    This study is focused on antioxidant and anticancer capacity of bread enriched with broccoli sprouts (BS) in the light of their potential bioaccessibility and bioavailability. Generally, bread supplementation elevated antioxidant potential of product (both nonenzymatic and enzymatic antioxidant capacities); however, the increase was not correlated with the percent of BS. A replacement up to 2% of BS gives satisfactory overall consumers acceptability and desirable elevation of antioxidant potential. High activity was especially found for extracts obtained after simulated digestion, which allows assuming their protective effect for upper gastrointestinal tract; thus, the anticancer activity against human stomach cancer cells (AGS) was evaluated. A prominent cytostatic response paralleled by the inhibition of AGS motility in the presence of potentially mastication-extractable phytochemicals indicates that phenolic compounds of BS retain their biological activity in bread. Importantly, the efficient phenolics concentration was about 12 μM for buffer extract, 13 μM for extracts after digestion in vitro, and 7 μM for extract after absorption in vitro. Our data confirm chemopreventive potential of bread enriched with BS and indicate that BS comprise valuable food supplement for stomach cancer chemoprevention. PMID:25050366

  16. Synthesis, Characterization, and Anticancer Activity of New Benzofuran Substituted Chalcones

    Directory of Open Access Journals (Sweden)

    Demet Coşkun

    2016-01-01

    Full Text Available Benzofuran derivatives are of great interest in medicinal chemistry and have drawn considerable attention due to their diverse pharmacological profiles including anticancer activity. Similarly, chalcones, which are common substructures of numerous natural products belonging to the flavonoid class, feature strong anticancer properties. A novel series of chalcones, 3-aryl-1-(5-bromo-1-benzofuran-2-yl-2-propanones propenones (3a–f, were designed, synthesized, and characterized. In vitro antitumor activities of the newly synthesized (3a–f and previously synthesized (3g–j chalcone compounds were determined by using human breast (MCF-7 and prostate (PC-3 cancer cell lines. Antitumor properties of all compounds were determined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Cell viability assay for the tested chalcone compounds was performed and the log⁡IC50 values of the compounds were calculated after 24-hour treatment. Our results indicate that the tested chalcone compounds show antitumor activity against MCF-7 and PC-3 cell lines (p<0.05.

  17. Genetic Interactions of STAT3 and Anticancer Drug Development

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Bingliang [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States)

    2014-03-06

    Signal transducer and activator of transcription 3 (STAT3) plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated for their antitumor activity in vitro and in vivo in experimental tumor models and several approved therapeutic agents have been reported to function as STAT3 inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to clinical evaluation for cancer treatment, presumably because of pharmacokinetic, efficacy, and safety issues. In fact, a major cause of failure of anticancer drug development is lack of efficacy. Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. Exploiting genetic interactions of STAT3 with other cancer-related pathways may provide molecular insight into mechanisms of cancer resistance to pathway-targeted therapies and strategies for development of more effective anticancer agents and treatment regimens. This review focuses on functional regulation of STAT3 activity; possible interactions of the STAT3, RAS, epidermal growth factor receptor, and reduction-oxidation pathways; and molecular mechanisms that modulate therapeutic efficacies of STAT3 inhibitors.

  18. Curcumin AntiCancer Studies in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Sabrina Bimonte

    2016-07-01

    Full Text Available Pancreatic cancer (PC is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC.

  19. Pharmaceutical nanotechnology for oral delivery of anticancer drugs.

    Science.gov (United States)

    Mei, Lin; Zhang, Zhiping; Zhao, Lingyun; Huang, Laiqiang; Yang, Xiang-Liang; Tang, Jintian; Feng, Si-Shen

    2013-06-15

    Oral chemotherapy is an important topic in the 21st century medicine, which may radically change the current regimen of chemotherapy and greatly improve the quality of life of the patients. Unfortunately, most anticancer drugs, especially those of high therapeutic efficacy such as paclitaxel and docetaxel, are not orally bioavailable due to the gastrointestinal (GI) drug barrier. The molecular basis of the GI barrier has been found mainly due to the multidrug efflux proteins, i.e. P-type glycoproteins (P-gp), which are rich in the epithelial cell membranes in the GI tract. Medical solution for oral chemotherapy is to apply P-gp inhibitors such as cyclosporine A, which, however, suppress the body's immune system either, thus causing medical complication. Pharmaceutical nanotechnology, which is to apply and further develop nanotechnology to solve the problems in drug delivery, may provide a better solution and thus change the way we make drug and the way we take drug. This review is focused on the problems encountered in oral chemotherapy and the pharmaceutical nanotechnology solutions such as prodrugs, nanoemulsions, dendrimers, micelles, liposomes, solid lipid nanoparticles and nanoparticles of biodegradable polymers. Proof-of-concept in vitro and in vivo results for oral delivery of anticancer drugs by the various nanocarriers, which can be found so far from the literature, are provided. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. [Vitamin D anti-cancer activities: observations, doubts and certainties].

    Science.gov (United States)

    Castronovo, C; Castronovo, V; Nikkels, A; Peulen, O

    2015-10-01

    The importance of vitamin D in bone and phosphocalcic status is well recognized by the scientific and medical communities; however, recently identified properties of this cholesterol derived molecule, such as immunomodulator and anticancer activities, are yet discussed. Actually, the debate is not so much about the new vitamin D properties, but rather about the optimal concentration required to reach these properties. The difficulty in determining the norms is rendered even more complex by the existence of a vitamin D receptor gene polymorphism. The body pool of this vitamin depends essentially on its endogenous synthesis, but also on its dietary intakes. Many epidemiological studies interested in Vitamin D serum level and cancer suggest a relation between low Vitamin D level and cancer risk, especially in breast and colon adenocarcinomas. In vitro, many studies showed, in different human and animal malignant cell lines, that this molecule exerts anticancer activities: it induces apoptosis and cell differentiation as well as it inhibits proliferation and angiogenesis. This review tries to update the current knowledge on vitamin D and, more particularly, the potential interest of this molecule in cancer prevention and management.

  1. Genomic DNA Interactions Mechanize Peptidotoxin-Mediated Anticancer Nanotherapy.

    Science.gov (United States)

    Misra, Santosh K; Schwartz-Duval, Aaron S; Pan, Dipanjan

    2017-07-03

    Host defense peptides (HDPs) are a class of evolutionarily conserved substances of the innate immune response that have been identified as major players in the defense system in many living organisms. Some of the HDPs are also referred to as peptidotoxins, which offer immense potential for anticancer therapy. However, their therapeutic potential is yet to be fully translated mainly due to their off-target toxicity. Here we show that their nanoenabled delivery may become beneficial in controlling their delivery in intracellular space. We introduced an amphiphilic polymer to synthesize a well-defined, self-assembled, rigid-cored polymeric nanoarchitecture for controlled delivery of three model peptidotoxins, i.e., melittin, TSAP-1, and a negative control peptide of synthetic origin. Interestingly, our results revealed strong interaction of peptidotoxins with duplex plasmid DNA. Extensive biophysical characterization (UV-vis spectroscopy, gel electrophoresis, MTT assay, and flow assisted cell sorting) experimentally verified that peptidotoxins were able to interact with genomic DNA in vitro and in turn influence the cancer cell growth. Thus, we unraveled that, through genomic DNA regulation, peptidotoxins can play a role in cell cycle regulation and exert their anticancer activities.

  2. Naturally occurring anti-cancer agents targeting EZH2.

    Science.gov (United States)

    Shahabipour, Fahimeh; Caraglia, Michele; Majeed, Muhammed; Derosa, Giuseppe; Maffioli, Pamela; Sahebkar, Amirhossein

    2017-08-01

    Natural products are considered as promising tools for the prevention and treatment of cancer. The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase unit of polycomb repressor complexes such as PRC2 complex that has oncogenic roles through interference with growth and metastatic potential. Several agents targeting EZH2 has been discovered but they often induce side effects in clinical trials. Recently, EZH2 has emerged as a potential target of natural products with documented anti-cancer effects and this discloses a new scenario for the development of EZH2 inhibitory strategies with agents with low cytotoxic detrimental effects. In fact, several natural products such as curcumin, triptolide, ursolic acid, sulforaphane, davidiin, tanshindiols, gambogic acid, berberine and Alcea rosea have been shown to serve as EZH2 modulators. Mechanisms like inhibition of histone H3K4, H3K27 and H3K36 trimethylation, down-regulation of matrix metalloproteinase expression, competitive binding to the S-adenosylmethionine binding site of EZH2 and modulation of tumor-suppressive microRNAs have been demonstrated to mediate the EZH2-inhibitory activity of the mentioned natural products. This review summarizes the pathways that are regulated by various natural products resulting in the suppression of EZH2, and provides a plausible molecular mechanism for the putative anti-cancer effects of these compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. ZnO Nanoparticles: A Promising Anticancer Agent

    Directory of Open Access Journals (Sweden)

    Gunjan Bisht

    2016-04-01

    Full Text Available Nanoparticles, with their selective targeting capabilities and superior efficacy, are becoming increasingly important in modern cancer therapy and starting to overshadow traditional cancer therapies such as chemotherapy radiation and surgery. ZnO nanoparticles, with their unique properties such as biocompatibility, high selectivity, enhanced cytotoxicity and easy synthesis, may be a promising anticancer agent. Zinc, as one of the major trace elements of the human body and co-factor of more than 300 mammalian enzymes, plays an important role in maintaining crucial cellular processes including oxidative stress, DNA replication, DNA repair, cell cycle progression and apoptosis. Thus, it is evident that an alteration in zinc levels in cancer cells can cause a deleterious effect. Research has shown that low zinc concentration in cells leads to the initiation and progression of cancer and high zinc concentration shows toxic effects. Zinc-mediated protein activity disequilibrium and oxidative stress through reactive oxygen species (ROS may be the probable mechanism of this cytotoxic effect. The selective localization of ZnO nanoparticles towards cancer cells due to enhanced permeability and retention (EPR effect and electrostatic interaction and selective cytotoxicity due to increased ROS present in cancer cells show that ZnO nanoparticles can selectively target and kill cancer cells, making them a promising anticancer agent.

  4. Characterisation of anticancer peptides at the single-cell level.

    Science.gov (United States)

    Armbrecht, L; Gabernet, G; Kurth, F; Hiss, J A; Schneider, G; Dittrich, P S

    2017-08-22

    The development of efficacious anticancer therapeutics is difficult due to the heterogeneity of the cellular response to chemotherapy. Anticancer peptides (ACPs) are promising drug candidates that have been shown to be active against a range of cancer cells. However, few ACP studies focus on tumour single-cell heterogeneities. In order to address this need, we developed a microfluidic device and an imaging procedure that enable the capture, monitoring, and analysis of several hundred single cells for the study of drug response. MCF-7 human breast adenocarcinoma cells were captured in hydrodynamic traps and isolated in individual microchambers of less than 100 pL volume. With pneumatic valves, different sets of microchambers were actuated to expose the cells to various drugs. Here, the effect of three membranolytic ACPs - melittin, aurein 1.2 and aurein 2.2 - was investigated by monitoring the efflux of calcein from single MCF-7 cells. The loss of membrane integrity was observed with two different strategies that allow either focusing on one cell for mechanistic studies or parallel analysis of hundreds of individual cells. In general, the device is applicable to the analysis of the effect of various drugs on a large number of different cell types. The platform will enable us in the future to determine the origin of heterogeneous responses on pharmacological substances like ACPs within cell populations by combining it with other on-chip analytical methods.

  5. Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications.

    Science.gov (United States)

    Deslouches, Berthony; Di, Y Peter

    2017-07-11

    In the last several decades, there have been significant advances in anticancer therapy. However, the development of resistance to cancer drugs and the lack of specificity related to actively dividing cells leading to toxic side effects have undermined these achievements. As a result, there is considerable interest in alternative drugs with novel antitumor mechanisms. In addition to the recent approach using immunotherapy, an effective but much cheaper therapeutic option of pharmaceutical drugs would still provide the best choice for cancer patients as the first line treatment. Ribosomally synthesized cationic antimicrobial peptides (AMPs) or host defense peptides (HDP) display broad-spectrum activity against bacteria based on electrostatic interactions with negatively charged lipids on the bacterial surface. Because of increased proportions of phosphatidylserine (negatively charged) on the surface of cancer cells compared to normal cells, cationic amphipathic peptides could be an effective source of anticancer agents that are both selective and refractory to current resistance mechanisms. We reviewed herein the prospect for AMP application to cancer treatment, with a focus on modes of action of cationic AMPs.

  6. Antioxidant and anticancer effects of functional peptides from ovotransferrin hydrolysates.

    Science.gov (United States)

    Lee, Jae Hoon; Moon, Sun Hee; Kim, Hyun Suk; Park, Eunju; Ahn, Dong Uk; Paik, Hyun-Dong

    2017-11-01

    Egg white is a good source for making functional peptides that can be used in the food industry. Ovotransferrin (OTF) is one of the major egg white proteins, with many functional properties, including antioxidant, antimicrobial and antiviral activities. However, enzymatic hydrolysis of ovotransferrin is known to further improve the functional activities of OTF. The aim of this study was to investigate the antioxidant and anticancer activities of functional peptides produced by two-step enzyme hydrolysis of OTF. OTF hydrolysates were prepared using promod 278P, thermolysin and a combination of the two enzymes. OTF and OTF hydrolysates showed strong antioxidant activities when analyzed using the DPPH assay. However, only OTF hydrolysates showed a strong free radical scavenging activity when NO- or ABTS-scavenging activity was measured. OTF hydrolysates showed stronger cytotoxic activities than the natural OTF against human cancer cell lines. Furthermore, OTF hydrolysates prepared with promod 278P + thermolysin combination showed the strongest cytotoxic activity, and their IC50 values were 0.79, 0.78, 0.92 and 0.78 mg mL-1 against AGS, LoVo, HT-29 and HeLa, respectively. These results indicated that the two-step enzyme hydrolysates of OTF have great potential for use as a food ingredient with antioxidant and anticancer activities. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  7. A theoretical analysis of secondary structural characteristics of anticancer peptides.

    Science.gov (United States)

    Dennison, Sarah R; Harris, Frederick; Bhatt, Tailap; Singh, Jaipaul; Phoenix, David A

    2010-01-01

    Here, cluster analysis showed that a database of 158 anticancer peptides formed 21 clusters based on net positive charge, hydrophobicity and amphiphilicity. In general, these clusters showed similar median toxicities (P = 0.176) against eukaryotic cell lines and no single combination of these properties was found optimal for efficacy. The database contained 14 peptides, which showed selectivity for tumour cell lines only (ACP(CT)), 123 peptides with general toxicity to eukaryotic cells (ACP(GT)) and 21 inactive peptides (ACP(I)). Hydrophobic arc size analysis showed that there was no significant difference across the datasets although peptides with wide hydrophobic arcs (>270 degrees) appeared to be associated with decreased toxicity. Extended hydrophobic moment plot analysis predicted that over 50% of ACP(CT) and ACP(GT) peptides would be surface active, which led to the suggestion that amphiphilicity is a key driver of the membrane interactions for these peptides but probably plays a role in their efficacy rather than their selectivity. This analysis also predicted that only 14% of ACP(CT) peptides compared to 45% of ACP(GT) peptides were candidates for tilted peptide formation, which led to the suggestion that the absence of this structure may support cancer cell selectivity. However, these analyses predicted that ACP(I) peptides, which possess no anticancer activity, would also form surface active and tilted alpha-helices, clearly showing that other factors are involved in determining the efficacy and selectivity of ACPs.

  8. Protocols for Studying Antimicrobial Peptides (AMPs) as Anticancer Agents.

    Science.gov (United States)

    Madera, Laurence; Hoskin, David W

    2017-01-01

    Antimicrobial peptides (AMPs) are a class of small cationic peptides that are important for host defense. In a manner that is similar to AMP-mediated destruction of microbial pathogens, certain AMPs can physically associate with the anionic lipid membrane components of cancer cells, resulting in destabilization of the lipid membrane and subsequent peptide binding to intracellular targets, which ultimately leads to the death of the cancer cell. In comparison, normal healthy cells possess a neutral membrane charge and are therefore less affected by AMPs. Based on the selective cytotoxicity of certain AMPs for cancer cells, these peptides represent a potential reservoir of novel anticancer therapeutic agents. The development and improvement of AMPs as anticancer agents requires appropriate methods for determining the effects of these peptides on the viability and function of cancer cells. In this chapter, we describe methods to assess the ability of AMPs to cause cell membrane damage (measured by propidium iodide uptake), apoptosis and/or necrosis (measured by annexin V-FLUOS/propidium iodide staining), and mitochondrial membrane destabilization (measured by 3,3'-dihexyloxacarbocyanine iodide staining), as well as reduced motility (measured by a migration and invasion assay) of cancer cells growing in suspension or as monolayers. We also describe a tubule-forming assay that can be used to assess the effect of AMPs on angiogenesis.

  9. The Potent Oxidant Anticancer Activity of Organoiridium Catalysts**

    Science.gov (United States)

    Liu, Zhe; Romero-Canelón, Isolda; Qamar, Bushra; Hearn, Jessica M; Habtemariam, Abraha; Barry, Nicolas P E; Pizarro, Ana M; Clarkson, Guy J; Sadler, Peter J

    2014-01-01

    Platinum complexes are the most widely used anticancer drugs; however, new generations of agents are needed. The organoiridium(III) complex [(η5-Cpxbiph)Ir(phpy)(Cl)] (1-Cl), which contains π-bonded biphenyltetramethylcyclopentadienyl (Cpxbiph) and C∧N-chelated phenylpyridine (phpy) ligands, undergoes rapid hydrolysis of the chlorido ligand. In contrast, the pyridine complex [(η5-Cpxbiph)Ir(phpy)(py)]+ (1-py) aquates slowly, and is more potent (in nanomolar amounts) than both 1-Cl and cisplatin towards a wide range of cancer cells. The pyridine ligand protects 1-py from rapid reaction with intracellular glutathione. The high potency of 1-py correlates with its ability to increase substantially the level of reactive oxygen species (ROS) in cancer cells. The unprecedented ability of these iridium complexes to generate H2O2 by catalytic hydride transfer from the coenzyme NADH to oxygen is demonstrated. Such organoiridium complexes are promising as a new generation of anticancer drugs for effective oxidant therapy. PMID:24616129

  10. Anticancer Activity of Punica granatum (Pomegranate): A Review.

    Science.gov (United States)

    Panth, Nisha; Manandhar, Bikash; Paudel, Keshav Raj

    2017-04-01

    Cancer is a pathological condition where excessive and abnormal cell growth leads to widespread invasion within the body to affect various organ functions. It is known that chemotherapeutic agents are themselves possible candidate of cancer generation as they can kill normal cells. So, therapeutic approach for cancer treatment and prevention is weighed in terms of benefit to risk ratio. Nowadays, there is an immense interest for the search herbal formulation with cancer preventive effect because of the problems, generated with existing chemotherapeutic regimens. Research interest in fruits rich in polyphenols is increasing because of their anticancer potential. In this review, we highlight the potential health benefits of pomegranate (Punica granatum) fruit and the underlying mechanism of its inhibition of cancer progression. Pomegranate has demonstrated anti-proliferative, anti-metastatic and anti-invasive effects on various cancer cell line in vitro as well as in vivo animal model or human clinical trial. Although several clinical trials are in progress for identifying the pomegranate as a candidate for various cancer treatment. It is necessary to replicate and validate its therapeutic efficacy by multiple clinical studies in order to formulate pomegranate products as an integral part of the dietary and pharmacological intervention in anticancer therapy. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Anticancer Activity from Active Fraction of Sea Cucumber

    Directory of Open Access Journals (Sweden)

    Nurul Mutia Putram

    2017-05-01

    Full Text Available Sea Cucumber Holothuria atra is one of marine organisms has been used as a new source of novel bioactive compounds. Many of them have been used as the lead compounds in discovery of new anticancer drugs. The objective of this study was to determine the active fractions of sea cucumber (H. atra which have anticancer activity. H. atra was macerated using ethanol and the extract was freezedried using a freeze dryer. The crude extract was partitioned using n-hexane, ethyl acetate, and methanol-water (3:1:1:1. Cytotoxicity test was performed using HeLa (cervic cancer cell line and MCF-7 (breast cancer cell line based on the MTT assay. The crude extract of H. atra showed the best cytotoxic activity against HeLa cells (IC50 = 12.48 µg/mL and MCF-7 cells (IC50 = 17.90 µg/mL. The toxicity tests showed the IC50 value of the n-hexane fraction, ethyl acetate fraction, and methanol-water fraction against HeLa cells HeLa (IC50 = 76.45 µg/mL; 77.95 µg/mL;  14.27 µg/mL and MCF-7 cells (IC50 = 58.50 µg/mL; 59.59 µg/mL; 14.33 µg/mL.

  12. Anticancer and Antioxidant Activity of Bread Enriched with Broccoli Sprouts

    Directory of Open Access Journals (Sweden)

    Urszula Gawlik-Dziki

    2014-01-01

    Full Text Available This study is focused on antioxidant and anticancer capacity of bread enriched with broccoli sprouts (BS in the light of their potential bioaccessibility and bioavailability. Generally, bread supplementation elevated antioxidant potential of product (both nonenzymatic and enzymatic antioxidant capacities; however, the increase was not correlated with the percent of BS. A replacement up to 2% of BS gives satisfactory overall consumers acceptability and desirable elevation of antioxidant potential. High activity was especially found for extracts obtained after simulated digestion, which allows assuming their protective effect for upper gastrointestinal tract; thus, the anticancer activity against human stomach cancer cells (AGS was evaluated. A prominent cytostatic response paralleled by the inhibition of AGS motility in the presence of potentially mastication-extractable phytochemicals indicates that phenolic compounds of BS retain their biological activity in bread. Importantly, the efficient phenolics concentration was about 12 μM for buffer extract, 13 μM for extracts after digestion in vitro, and 7 μM for extract after absorption in vitro. Our data confirm chemopreventive potential of bread enriched with BS and indicate that BS comprise valuable food supplement for stomach cancer chemoprevention.

  13. Granulocytes as effective anticancer agent in experimental solid tumor models.

    Science.gov (United States)

    Jaganjac, Morana; Poljak-Blazi, Marija; Kirac, Iva; Borovic, Suzana; Joerg Schaur, Rudolf; Zarkovic, Neven

    2010-12-01

    The aim of the study was to elucidate the effects of murine granulocytes on the growth of solid murine tumors when administrated in the vicinity of W256 carcinoma growing in Sprague Dawley rats, and in the vicinity of Ehrlich ascites tumor (EAT) growing in BALBc mice. The administration of granulocytes significantly improved the survival of W256-bearing rats, and increased the tumor regression incidence from 17% up to 75%. Rats with regressing tumors had 2.5 times increased levels of granulocytes in peripheral blood, which were also cytotoxic in vitro for W256 carcinoma cells. However, blood levels of cytokine-induced neutrophil chemoattractant-2, tumor necrosis factor α and interleukin 6 were similar between rats with regressing tumors and control healthy rats, suggesting that the observed regression of W256 carcinoma was caused by specific anticancer effects of the applied granulocytes. Anticancer effects of granulocytes were also found in BALBc mice bearing solid form of EAT, resulting in a 20% increase of survival in EAT-bearing mice. Therefore, the administration of granulocytes, isolated from healthy animals and applied at the site of solid tumors in rats and in mice, reduced experimental tumor growth, and extended the survival of tumor-bearing animals, while in some rats it even caused a W256 regression. Copyright © 2010 Elsevier GmbH. All rights reserved.

  14. The thrifty phenotype hypothesis revisited

    DEFF Research Database (Denmark)

    Vaag, A A; Grunnet, L G; Arora, G P

    2012-01-01

    Twenty years ago, Hales and Barker along with their co-workers published some of their pioneering papers proposing the 'thrifty phenotype hypothesis' in Diabetologia (4;35:595-601 and 3;36:62-67). Their postulate that fetal programming could represent an important player in the origin of type 2...... control is inadequate to reduce the excess CVD mortality in type 2 diabetic patients. Today, the thrifty phenotype hypothesis has been established as a promising conceptual framework for a more sustainable intergenerational prevention of type 2 diabetes....

  15. Genome duplication and mutations in ACE2 cause multicellular, fast-sedimenting phenotypes in evolved Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Oud, B.; Guadalupe-Medina, V.; Nijkamp, J.F.; De Ridder, D.; Pronk, J.T.; Van Maris, A.J.A.; Daran, J.G.

    2013-01-01

    Laboratory evolution of the yeast Saccharomyces cerevisiae in bioreactor batch cultures yielded variants that grow as multicellular, fast-sedimenting clusters. Knowledge of the molecular basis of this phenomenon may contribute to the understanding of natural evolution of multicellularity and to

  16. Directional selection effects on patterns of phenotypic (co)variation in wild populations.

    Science.gov (United States)

    Assis, A P A; Patton, J L; Hubbe, A; Marroig, G

    2016-11-30

    Phenotypic (co)variation is a prerequisite for evolutionary change, and understanding how (co)variation evolves is of crucial importance to the biological sciences. Theoretical models predict that under directional selection, phenotypic (co)variation should evolve in step with the underlying adaptive landscape, increasing the degree of correlation among co-selected traits as well as the amount of genetic variance in the direction of selection. Whether either of these outcomes occurs in natural populations is an open question and thus an important gap in evolutionary theory. Here, we documented changes in the phenotypic (co)variation structure in two separate natural populations in each of two chipmunk species (Tamias alpinus and T. speciosus) undergoing directional selection. In populations where selection was strongest (those of T. alpinus), we observed changes, at least for one population, in phenotypic (co)variation that matched theoretical expectations, namely an increase of both phenotypic integration and (co)variance in the direction of selection and a re-alignment of the major axis of variation with the selection gradient. © 2016 The Author(s).

  17. Adapting Morphology to Multiple Tasks in Evolved Virtual Creatures

    DEFF Research Database (Denmark)

    Lessin, Dan; Fussell, Don; Miikkulainen, Risto

    2014-01-01

    The ESP method for evolving virtual creatures (Lessin et al., 2013) consisted of an encapsulation mechanism to preserve learned skills, a human-designed syllabus to build higherlevel skills by combining lower-level skills systematically, and a pandemonium mechanism to resolve conflicts between...... encapsulated skills in a single creature’s brain. Previous work with ESP showed that it is possible to evolve much more complex behavior than before, even when fundamental morphology (i.e., skeletal segments and joints) was evolved only for the first skill. This paper introduces a more general form of ESP...... in which full morphological development can continue beyond the first skill, allowing creatures to adapt their morphology to multiple tasks. This extension increases the variety and quality of evolved creature results significantly, while maintaining the original ESP system’s ability to incrementally...

  18. Orthogonally Evolved AI to Improve Difficulty Adjustment in Video Games

    DEFF Research Database (Denmark)

    Hintze, Arend; Olson, Randal; Lehman, Joel Anthony

    2016-01-01

    (i.e. agents subject to fewer generations of evolution) make for easier opponents, while highly-evolved agents are more challenging to overcome. In this publication we test a new approach for difficulty adjustment in games: orthogonally evolved AI, where the player receives support from collaborating...... agents that are co-evolved with opponent agents (where collaborators and opponents have orthogonal incentives). The advantage is that game difficulty can be adjusted more granularly by manipulating two independent axes: by having more or less adept collaborators, and by having more or less adept...... opponents. Furthermore, human interaction can modulate (and be informed by) the performance and behavior of collaborating agents. In this way, orthogonally evolved AI both facilitates smoother difficulty adjustment and enables new game experiences....

  19. Enteroaggregative Escherichia coli have evolved independently as distinct complexes within the E. coli population with varying ability to cause disease.

    Directory of Open Access Journals (Sweden)

    Marie Anne Chattaway

    Full Text Available Enteroaggregative E. coli (EAEC is an established diarrhoeagenic pathotype. The association with virulence gene content and ability to cause disease has been studied but little is known about the population structure of EAEC and how this pathotype evolved. Analysis by Multi Locus Sequence Typing of 564 EAEC isolates from cases and controls in Bangladesh, Nigeria and the UK spanning the past 29 years, revealed multiple successful lineages of EAEC. The population structure of EAEC indicates some clusters are statistically associated with disease or carriage, further highlighting the heterogeneous nature of this group of organisms. Different clusters have evolved independently as a result of both mutational and recombination events; the EAEC phenotype is distributed throughout the population of E. coli.

  20. Phenotypic Heterogeneity of Genomically-Diverse Isolates of Streptococcus mutans

    Science.gov (United States)

    Palmer, Sara R.; Miller, James H.; Abranches, Jacqueline; Zeng, Lin; Lefebure, Tristan; Richards, Vincent P.; Lemos, José A.; Stanhope, Michael J.; Burne, Robert A.

    2013-01-01

    High coverage, whole genome shotgun (WGS) sequencing of 57 geographically- and genetically-diverse isolates of Streptococcus mutans from individuals of known dental caries status was recently completed. Of the 57 sequenced strains, fifteen isolates, were selected based primarily on differences in gene content and phenotypic characteristics known to affect virulence and compared with the reference strain UA159. A high degree of variability in these properties was observed between strains, with a broad spectrum of sensitivities to low pH, oxidative stress (air and paraquat) and exposure to competence stimulating peptide (CSP). Significant differences in autolytic behavior and in biofilm development in glucose or sucrose were also observed. Natural genetic competence varied among isolates, and this was correlated to the presence or absence of competence genes, comCDE and comX, and to bacteriocins. In general strains that lacked the ability to become competent possessed fewer genes for bacteriocins and immunity proteins or contained polymorphic variants of these genes. WGS sequence analysis of the pan-genome revealed, for the first time, components of a Type VII secretion system in several S. mutans strains, as well as two putative ORFs that encode possible collagen binding proteins located upstream of the cnm gene, which is associated with host cell invasiveness. The virulence of these particular strains was assessed in a wax-worm model. This is the first study to combine a comprehensive analysis of key virulence-related phenotypes with extensive genomic analysis of a pathogen that evolved closely with humans. Our analysis highlights the phenotypic diversity of S. mutans isolates and indicates that the species has evolved a variety of adaptive strategies to persist in the human oral cavity and, when conditions are favorable, to initiate disease. PMID:23613838

  1. Phenotypic heterogeneity of genomically-diverse isolates of Streptococcus mutans.

    Directory of Open Access Journals (Sweden)

    Sara R Palmer

    Full Text Available High coverage, whole genome shotgun (WGS sequencing of 57 geographically- and genetically-diverse isolates of Streptococcus mutans from individuals of known dental caries status was recently completed. Of the 57 sequenced strains, fifteen isolates, were selected based primarily on differences in gene content and phenotypic characteristics known to affect virulence and compared with the reference strain UA159. A high degree of variability in these properties was observed between strains, with a broad spectrum of sensitivities to low pH, oxidative stress (air and paraquat and exposure to competence stimulating peptide (CSP. Significant differences in autolytic behavior and in biofilm development in glucose or sucrose were also observed. Natural genetic competence varied among isolates, and this was correlated to the presence or absence of competence genes, comCDE and comX, and to bacteriocins. In general strains that lacked the ability to become competent possessed fewer genes for bacteriocins and immunity proteins or contained polymorphic variants of these genes. WGS sequence analysis of the pan-genome revealed, for the first time, components of a Type VII secretion system in several S. mutans strains, as well as two putative ORFs that encode possible collagen binding proteins located upstream of the cnm gene, which is associated with host cell invasiveness. The virulence of these particular strains was assessed in a wax-worm model. This is the first study to combine a comprehensive analysis of key virulence-related phenotypes with extensive genomic analysis of a pathogen that evolved closely with humans. Our analysis highlights the phenotypic diversity of S. mutans isolates and indicates that the species has evolved a variety of adaptive strategies to persist in the human oral cavity and, when conditions are favorable, to initiate disease.

  2. Evolving the Evolving: Territory, Place and Rewilding in the California Delta

    Directory of Open Access Journals (Sweden)

    Brett Milligan

    2017-10-01

    Full Text Available Current planning and legislation in California’s Sacramento-San Joaquin Delta call for the large-scale ecological restoration of aquatic and terrestrial habitats. These ecological mandates have emerged in response to the region’s infrastructural transformation and the Delta’s predominant use as the central logistical hub in the state’s vast water conveyance network. Restoration is an attempt to recover what was externalized by the logic and abstractions of this logistical infrastructure. However, based on findings from our research, which examined how people are using restored and naturalized landscapes in the Delta and how these landscapes are currently planned for, we argue that as mitigatory response, restoration planning continues some of the same spatial abstractions and inequities by failing to account for the Delta as an urbanized, cultural and unique place. In interpreting how these conditions have come to be, we give attention to a pluralistic landscape approach and a coevolutionary reading of planning, policy, science and landscapes to discuss the conservation challenges presented by “Delta as an Evolving Place”. We suggest that for rewilding efforts to be successful in the Delta, a range of proactive, opportunistic, grounded and participatory tactics will be required to shift towards a more socio-ecological approach.

  3. (N+1)-dimensional Lorentzian evolving wormholes supported by polytropic matter

    Energy Technology Data Exchange (ETDEWEB)

    Cataldo, Mauricio [Universidad del Bio-Bio, Departamento de Fisica, Facultad de Ciencias, Concepcion (Chile); Arostica, Fernanda; Bahamonde, Sebastian [Universidad de Concepcion, Departamento de Fisica, Concepcion (Chile)

    2013-08-15

    In this paper we study (N+1)-dimensional evolving wormholes supported by energy satisfying a polytropic equation of state. The considered evolving wormhole models are described by a constant redshift function and generalizes the standard flat Friedmann-Robertson-Walker spacetime. The polytropic equation of state allows us to consider in (3+1)-dimensions generalizations of the phantom energy and the generalized Chaplygin gas sources. (orig.)

  4. In vitro and in vivo anticancer activities of a novel antibiotic

    African Journals Online (AJOL)

    Jane

    2011-08-03

    Aug 3, 2011 ... In vitro and in vivo anticancer activities of a novel antibiotic. Chen Xiaoxi. Basic Medicine College, Zhejiang ... paper is to assay the BS's in vitro anticancer activity via. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium .... practice of oncology. Philadelphia, Lippincott Raven, pp. 328-339. Karikas GA (2010) ...

  5. Towards safety of oral anti-cancer agents, the need to educate our pharmacists

    Directory of Open Access Journals (Sweden)

    Sanaa Saeed Mekdad

    2017-01-01

    Full Text Available Introduction: The global prevalence of cancer is rising. Use of oral anticancer medications has expanded exponentially. Knowledge about these medications as well as safe handling guidelines has not kept abreast with the rapidity these medications are applied in clinical practice. They pose serious hazards on all personal involved in handling these medications as well as on patients and their caregivers. We addressed the gaps in knowledge and safe handling of oral anticancer agents among pharmacists in institutional based cancer care. Materials and Methods: We used a 41 item questionnaire to explore three domains, pharmacists’ knowledge, safe handling practice and confidence and self-improving strategies towards these agents among pharmacists in multicentre specialized cancer care. Results: Participants included 120 pharmacists dedicated to handle and dispense oral anticancer agents. About 20% of Pharmacists have adequate knowledge about oral anticancer agents. Less than 50% apply safe handling principles adequately. Only a quarter are confident in educating cancer patients and their caregivers about Oral Anti-Cancer Agents. Conclusions: Pharmacists’ knowledge about Oral Anticancer agents needs to be improved. Safe handling and dispensing practice of these medications should be optimized. Pharmacists’ confidence towards educating patients and their caregiver needs to be addressed. Enhancing safety of oral anticancer agents should be a priority. Involving all key players, research and quality improving projects are needed to improve all aspects of the safety of oral anticancer agents.

  6. Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs

    NARCIS (Netherlands)

    R.W.F. van Leeuwen (Roelof); D.H.S. Brundel (D. H S); C. Neef (Cees); T. van Gelder (Teun); A.H.J. Mathijssen (Ron); D.M. Burger (David); F.G.A. Jansman (Frank)

    2013-01-01

    textabstractBackground: Potential drug-drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment.

  7. Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs

    NARCIS (Netherlands)

    van Leeuwen, R. W. F.; Brundel, D. H. S.; Neef, C.; van Gelder, T.; Mathijssen, R. H. J.; Burger, D. M.; Jansman, F. G. A.

    2013-01-01

    Background: Potential drug-drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment. Methods: A

  8. Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs

    NARCIS (Netherlands)

    Leeuwen, R. van; Brundel, D.H.; Neef, C.; Gelder, T. van; Mathijssen, R.H.; Burger, D.M.; Jansman, F.G.A.

    2013-01-01

    Background:Potential drug-drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment.Methods:A search

  9. Pharmacokinetic-Pharmacodynamic Modelling & Simulation for Anticancer Drugs with Complex Absorption Characteristics

    NARCIS (Netherlands)

    Yu, Huixin

    2016-01-01

    Cancer is still one of the leading causes of death in the world. In recent years, targeted anticancer agents have shown to be a major breakthrough in the battle against cancer. These targeted anticancer agents, mostly administered orally, specifically target molecular defects of tumour cells

  10. Preparation and characterization of polymeric micelles loaded with a potential anticancer prodrug

    NARCIS (Netherlands)

    Marinelli, Lisa; Cacciatore, Ivana; Fornasari, Erika; Gasbarri, Carla; Angelini, Guido; Marrazzo, Agostino; Pandolfi, Assunta; Mandatori, Domitilla; Shi, Yang; Van Nostrum, Cornelus F.; Hennink, Wim E.; Di Stefano, Antonio

    2016-01-01

    Polymeric micelles based on HPMA [N-(2-hydroxypropyl) methacrylamide] polymers were recently evaluated as drug delivery systems of several anticancer drugs. The development of polymeric micelles to solubilize R-(+)-MRJF4, a potential anticancer prodrug, is reported in this paper. Two different

  11. Advances in P-glycoprotein-based approaches for delivering anticancer drugs: pharmacokinetic perspective and clinical relevance.

    Science.gov (United States)

    Saneja, Ankit; Khare, Vaibhav; Alam, Noor; Dubey, Ravindra Dhar; Gupta, Prem N

    2014-01-01

    P-glycoprotein (P-gp) is a multi-specific efflux transporter belonging to ATP-binding cassette (ABC) transporter family, encoded by the ABCB1 gene, which significantly impacts the pharmacokinetics as well as multidrug resistance of anticancer drugs. This review explores how human P-gp transporters modulate the pharmacokinetics of anticancer drugs and emerging strategies to modulate their function. The key findings in direct modulation by various P-gp inhibitors on pharmacokinetics of various anticancer P-gp substrates are described. The role of pharmaceutical excipients as P-gp inhibitor with the focus on the recent development in novel drug delivery systems to modulate pharmacokinetics of anticancer drugs is also outlined. The concomitant use of anticancer P-gp substrate and P-gp inhibitor is an effective and safe way to enhance the bioavailability of anticancer drugs. The poor bioavailability and toxicity of anticancer drugs limit their therapeutic efficacy. These characteristics can be improved by using various nanocarriers which exhibited a high potential to bypass this efflux protein. The best combination of P-gp inhibitor and substrate anticancer drug in a single nanocarrier formulation is a future challenge and is still probably some years away from the marketplace.

  12. Leaf segmentation in plant phenotyping

    NARCIS (Netherlands)

    Scharr, Hanno; Minervini, Massimo; French, Andrew P.; Klukas, Christian; Kramer, David M.; Liu, Xiaoming; Luengo, Imanol; Pape, Jean Michel; Polder, Gerrit; Vukadinovic, Danijela; Yin, Xi; Tsaftaris, Sotirios A.

    2016-01-01

    Image-based plant phenotyping is a growing application area of computer vision in agriculture. A key task is the segmentation of all individual leaves in images. Here we focus on the most common rosette model plants, Arabidopsis and young tobacco. Although leaves do share appearance and shape

  13. linking genetic to phenotypic variation

    Indian Academy of Sciences (India)

    Unknown

    phenotypic variation. SHAMPA GHOSH and N. SHARMILA BHARATHI. Evolutionary Biology Laboratory, Evolutionary and Organismal Biology Unit, Jawaharlal Nehru Centre for. Advanced Scientific Research, P.O. Box 6436, Jakkur, Bangalore 560 064, India. Immunity can be classified into two types, namely innate.

  14. Forensic DNA phenotyping : Regulatory issues

    NARCIS (Netherlands)

    Koops, E.J.; Schellekens, M.H.M.

    2008-01-01

    Forensic DNA phenotyping is an interesting new investigation method: crime-scene DNA is analyzed to compose a description of the unknown suspect, including external and behavioral features, geographic origin and perhaps surname. This method is allowed in some countries but prohibited in a few

  15. Phenotypic spectrum of GABRA1

    DEFF Research Database (Denmark)

    Johannesen, Katrine; Marini, Carla; Pfeffer, Siona

    2016-01-01

    analysis of 4 selected mutations was performed using the Xenopus laevis oocyte expression system. RESULTS: The study included 16 novel probands and 3 additional family members with a disease-causing mutation in the GABRA1 gene. The phenotypic spectrum varied from unspecified epilepsy (1), juvenile...

  16. Improved anticancer potency by head-to-tail cyclization of short cationic anticancer peptides containing a lipophilic β(2,2) -amino acid.

    Science.gov (United States)

    Tørfoss, Veronika; Isaksson, Johan; Ausbacher, Dominik; Brandsdal, Bjørn-Olav; Flaten, Gøril E; Anderssen, Trude; Cavalcanti-Jacobsen, Cristiane de A; Havelkova, Martina; Nguyen, Leonard T; Vogel, Hans J; Strøm, Morten B

    2012-10-01

    We have recently reported a series of synthetic anticancer heptapeptides (H-KKWβ(2,2) WKK-NH(2) ) containing a central achiral and lipophilic β(2,2) -amino acid that display low toxicity against non-malignant cells and high proteolytic stability. In the present study, we have further investigated the effects of increasing the rigidity and amphipathicity of two of our lead heptapeptides by preparing a series of seven to five residue cyclic peptides containing the two most promising β(2,2) -amino acid derivatives as part of the central lipophilic core. The peptides were tested for anticancer activity against human Burkitt's lymphoma (Ramos cells), haemolytic activity against human red blood cells (RBC) and cytotoxicity against healthy human lung fibroblast cells (MRC-5). The results demonstrated a considerable increase in anticancer potency following head-to-tail peptide cyclization, especially for the shortest derivatives lacking a tryptophan residue. High-resolution NMR studies and molecular dynamics simulations together with an annexin-V-FITC and propidium iodide fluorescent assay showed that the peptides had a membrane disruptive mode of action and that the more potent peptides penetrated deeper into the lipid bilayer. The need for new anticancer drugs with novel modes of action is demanding, and development of short cyclic anticancer peptides with an overall rigidified and amphipathic structure is a promising approach to new anticancer agents. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

  17. Study of selected phenotype switching strategies in time varying environment

    Energy Technology Data Exchange (ETDEWEB)

    Horvath, Denis, E-mail: horvath.denis@gmail.com [Centre of Interdisciplinary Biosciences, Institute of Physics, Faculty of Science, P.J. Šafárik University in Košice, Jesenná 5, 040 01 Košice (Slovakia); Brutovsky, Branislav, E-mail: branislav.brutovsky@upjs.sk [Department of Biophysics, Institute of Physics, P.J. Šafárik University in Košice, Jesenná 5, 040 01 Košice (Slovakia)

    2016-03-22

    Population heterogeneity plays an important role across many research, as well as the real-world, problems. The population heterogeneity relates to the ability of a population to cope with an environment change (or uncertainty) preventing its extinction. However, this ability is not always desirable as can be exemplified by an intratumor heterogeneity which positively correlates with the development of resistance to therapy. Causation of population heterogeneity is therefore in biology and medicine an intensively studied topic. In this paper the evolution of a specific strategy of population diversification, the phenotype switching, is studied at a conceptual level. The presented simulation model studies evolution of a large population of asexual organisms in a time-varying environment represented by a stochastic Markov process. Each organism disposes with a stochastic or nonlinear deterministic switching strategy realized by discrete-time models with evolvable parameters. We demonstrate that under rapidly varying exogenous conditions organisms operate in the vicinity of the bet-hedging strategy, while the deterministic patterns become relevant as the environmental variations are less frequent. Statistical characterization of the steady state regimes of the populations is done using the Hellinger and Kullback–Leibler functional distances and the Hamming distance. - Highlights: • Relation between phenotype switching and environment is studied. • The Markov chain Monte Carlo based model is developed. • Stochastic and deterministic strategies of phenotype switching are utilized. • Statistical measures of the dynamic heterogeneity reveal universal properties. • The results extend to higher lattice dimensions.

  18. A mouse informatics platform for phenotypic and translational discovery.

    Science.gov (United States)

    Ring, Natalie; Meehan, Terrence F; Blake, Andrew; Brown, James; Chen, Chao-Kung; Conte, Nathalie; Di Fenza, Armida; Fiegel, Tanja; Horner, Neil; Jacobsen, Julius O B; Karp, Natasha; Lawson, Thomas; Mason, Jeremy C; Matthews, Peter; Morgan, Hugh; Relac, Mike; Santos, Luis; Smedley, Damian; Sneddon, Duncan; Pengelly, Alice; Tudose, Ilinca; Warren, Jonathan W G; Westerberg, Henrik; Yaikhom, Gagarine; Parkinson, Helen; Mallon, Ann-Marie

    2015-10-01

    The International Mouse Phenotyping Consortium (IMPC) is providing the world's first functional catalogue of a mammalian genome by characterising a knockout mouse strain for every gene. A robust and highly structured informatics platform has been developed to systematically collate, analyse and disseminate the data produced by the IMPC. As the first phase of the project, in which 5000 new knockout strains are being broadly phenotyped, nears completion, the informatics platform is extending and adapting to support the increasing volume and complexity of the data produced as well as addressing a large volume of users and emerging user groups. An intuitive interface helps researchers explore IMPC data by giving overviews and the ability to find and visualise data that support a phenotype assertion. Dedicated disease pages allow researchers to find new mouse models of human diseases, and novel viewers provide high-resolution images of embryonic and adult dysmorphologies. With each monthly release, the informatics platform will continue to evolve to support the increased data volume and to maintain its position as the primary route of access to IMPC data and as an invaluable resource for clinical and non-clinical researchers.

  19. Anticancer effects of pyocyanin on HepG2 human hepatoma cells.

    Science.gov (United States)

    Zhao, J; Wu, Y; Alfred, A T; Wei, P; Yang, S

    2014-06-01

    Pyocyanin, a major virulence factor produced by Pseudomonas aeruginosa, displays redox activity and damaging effects on mammalian cells. In this study, we investigated the effects of pyocyanin on the proliferation of HepG2 tumour cells. Interestingly, pyocyanin significantly inhibited cell proliferation and triggered the production of large amounts of reactive oxygen species (ROS), thereby upregulating superoxide dismutase (SOD) and catalase (CAT). Additionally, pyocyanin treatment significantly depleted reduced glutathione (GSH) and decreased the GSH/oxidized GSH (GSSG) ratio. These results supported that pyocyanin-induced cytotoxicity in HepG2 cells was mediated by acute ROS production and subsequent oxidative stress. SA-β-Gal, acridine orange (AO)/ethidium bromide (EB) double staining, caspase-3 measurements and comet assay results revealed that cell death induced by pyocyanin involved DNA damage and activation of caspase-3, accelerating cell senescence and apoptosis. Thus, our data provided insights into the mechanisms underlying pyocyanin-induced cytotoxicity and may lead to better treatment strategies for cancer. Pyocyanin is a redox-active phenazine toxin. Here, we investigated the ability of pyocyanin to inhibit cancer-related phenotypes in HepG2 human hepatoma cells. Our results indicated that pyocyanin accelerated cellular senescence and apoptosis and induced oxidative stress-associated DNA damage in HepG2 cells. The potential anticancer applications of pyocyanin should be investigated further in clinical studies. © 2014 The Society for Applied Microbiology Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  20. A Pleiotrophin C-terminus peptide induces anti-cancer effects through RPTPβ/ζ

    Directory of Open Access Journals (Sweden)

    Diamantopoulou Zoi

    2010-08-01

    Full Text Available Abstract Background Pleiotrophin, also known as HARP (Heparin Affin Regulatory Peptide is a growth factor expressed in various tissues and cell lines. Pleiotrophin participates in multiple biological actions including the induction of cellular proliferation, migration and angiogenesis, and is involved in carcinogenesis. Recently, we identified and characterized several pleiotrophin proteolytic fragments with biological activities similar or opposite to that of pleiotrophin. Here, we investigated the biological actions of P(122-131, a synthetic peptide corresponding to the carboxy terminal region of this growth factor. Results Our results show that P(122-131 inhibits in vitro adhesion, anchorage-independent proliferation, and migration of DU145 and LNCaP cells, which express pleiotrophin and its receptor RPTPβ/ζ. In addition, P(122-131 inhibits angiogenesis in vivo, as determined by the chicken embryo CAM assay. Investigation of the transduction mechanisms revealed that P(122-131 reduces the phosphorylation levels of Src, Pten, Fak, and Erk1/2. Finally, P(122-131 not only interacts with RPTPβ/ζ, but also interferes with other pleiotrophin receptors, as demonstrated by selective knockdown of pleiotrophin or RPTPβ/ζ expression with the RNAi technology. Conclusions In conclusion, our results demonstrate that P(122-131 inhibits biological activities that are related to the induction of a transformed phenotype in PCa cells, by interacing with RPTPβ/ζ and interfering with other pleiotrophin receptors. Cumulatively, these results indicate that P(122-131 may be a potential anticancer agent, and they warrant further study of this peptide.