Papel do município e relações federativas: atuação de municípios cearenses nas políticas de formação continuada de alfabetizadores

The investigation analyze s the role of the municipalities in the ongoing development of literacy teachers, having as a field of study the municipalities of Jaguaruana and Palhano, both in the State of Ceará. The political - educational space adopted as a sample of the study is the p eriod between the years 2003 and 2006, when the emphasis on cooperative action among the federated entities is observed in the Government’s guidelines and Brazilian educational policies, showing the municipal presence in the implementation and execution of these policies. T he historical - dialectical materialistic perspective, understood as an analysis of the social reality as historical elaboration and product of the human praxis, is expressed as the required theoretical - methodological path. The investigatio n is operationalized through interconnected stages: one that involves bibliographical and documental analysis, in which the theoretical input of the research is added, as well as the Federal, State and M unicipal documents accessed ; and another, regarding t he field work, studying the specific character of the object and its mutual rela tionships in the municipalities . The research brings the notion of intergovernmental relationships and cooperative mechanisms as central theoretical tools and, dialoguing with them, ideas such as decentralization, municipalization and municipal autonomy are inserted into a theoretical/practical body, through which the historical and logical aspects of the object are detailed. The study describes and interprets the policies of on going development of literacy teachers with focus on the national guidelines formulated since the 1990’s and on the govern mental incorporation in the national and subnational spaces. In this sense, the analysis is based on the comprehension of the interrel ationship between the municipal policies and the p olicies created by the S tate or Federal G overnments in order to offer ongoing development of literacy teachers. Considering the investigated sample, it shows how the municipal role and the relationships bet ween the State and municipalities of Ceará have emerged, as well as their characteristics regarding the education management policies, taking into account the practices of municipalization and cooperation between the State and municipalities in their histo rical composition. It shows the practices which aim at the ongoing development of literacy teachers observed in the researched municipalities, pointing out the realities and specific marks left by municipal presence in the area, demonstrating the assigned role and the role played. Based on the points of view of the managers interviewed in the municipalities of Jaguaruana e Palhano, it is possible to note the meaning and effectiveness of the policies carried out. With such elements, it discusses the municipa l asymmetries in their homogeneities and heterogeneities rega rding the execution of their federative role. The analysis shows that th e role of the municipalities vary according to the historical, political and social interventions in each municipality. In the fields of formulation and execution of educational policies, the actions of the municipal governments, situated and with expressive interferences, reveal asymmetries in the sense that some municipalities have bigger autonomy and participate more effect ively in the production and distribution of policies than others. In terms of the researched realities, the study shows that taking care of the policies of ongoing development of literacy teachers is not a task that should be assigned exclusively to the mu nicipalities, nonetheless it is a role that they play with varying degrees of success. This role is in fact a joint competence of the federated entities, in the scope the Brazilian cooperative federalism.

Buraco negros, correspondência AdS/BCFT e fluido/gravidade

Einstein’s equations with negative cosmological constant possess the so-called anti de Sitter space, AdSd+1, as one of its solutions. We will later refer to this space as to the "bulk". The holographic principle states that quantum gravity in the AdSd+1 space can be encoded by a d−dimensional quantum field theory on the boundary of AdSd+1 space, invariant under conformal transformations, a CFTd. In the most famous example, the precise statement is the duality of the type IIB string theory in the space AdS5 × S 5 and the 4−dimensional N = 4 supersymmetric Yang-Mills theory. Another example is provided by a relation between Einstein’s equations in the bulk and hydrodynamic equations describing the effective theory on the boundary, the so-called fluid/gravity correspondence. An extension of the "AdS/CFT duality"for the CFT’s with boundary was proposed by Takayanagi, which was dubbed the AdS/BCFT correspondence. The boundary of a CFT extends to the bulk and restricts a region of the AdSd+1. Neumann conditions imposed on the extension of the boundary yield a dynamic equation that determines the shape of the extension. From the perspective of fluid/gravity correspondence, the shape of the Neumann boundary, and the geometry of the bulk is sourced by the energy-momentum tensor Tµν of a fluid residing on this boundary. Clarifying the relation of the Takayanagi’s proposal to the fluid/gravity correspondence, we will study the consistence of the AdS/BCFT with finite temperature CFT’s, or equivalently black hole geometries in the bulk.

Avaliação de sustentabilidade ambiental do sistema de abastecimento de água e esgotamento sanitário de Uberaba - MG

This paper analyses the sustainability under the environmental (ecological) perspective of Water Supply and Sanitary Sewers Systems from Uberaba city, MG. It was accomplished in this analysis, An Environmental Sustainability Assessment of those systems, by the means of specific sustainability indicators proposed for Uberaba, but which may be used for other simi-lar cities. To the characterization of the systems, visitations were made to the main units as well as a documental was elaborated. The definition of the level or stage of the sustainability by the indicators was made based on a literature review, on interviews with the technicians and managers of the systems and based on the characterization and observation of the system reality, being attributed to them the following classification: Non Sustainable, Low Sustaina-bility, Medium Sustainability and High Sustainability. It was verified that the indicators that have lower compatibility to the process of sustainability to the studied systems are those rela-ted to the water physical losses, to the water per capita consumption, to the electricity con-sumption and to the sludge from the water treatment plants disposal untreated into a water body, for the Water Supply System. And those ones related to the attendance with sewage treatment, to the electricity consumption and to the usage of the treated sewage, for the Sani-tary Sewers, all of them classified as Non Sustainable.

Cardiopulmonary bypass down-regulates NOD signaling and inflammatory response in children with congenital heart disease

In the present study, we aimed to examine the impact of cardiopulmonary bypass (CPB) on expression and function of NOD1 and NOD2 in children with congenital heart disease (CHD), in an attempt to clarify whether NOD1 and NOD2 signaling is involved in the modulation of host innate immunity against postoperative infection in pediatric CHD patients. Peripheral blood samples were collected from pediatric CHD patients at five different time points: before CPB, immediately after CPB, and 1, 3, and 7 days after CPB. Real-time PCR, Western blot, and ELISA were performed to measure the expression of NOD1 and NOD2, their downstream signaling pathways, and inflammatory cytokines at various time points. Proinflammatorycytokine IL-6 and TNF-α levels in response to stimulation with either the NOD1 agonist Tri-DAP or the NOD2 agonist MDP were significantly reduced after CPB compared with those before CPB, which is consistent with a suppressed inflammatory response postoperatively. The expression of phosphorylated RIP2 and activation of the downstream signaling pathways NF-κB p65 and MAPK p38 upon Tri-DAP or MDP stimulation in PBMCs were substantially inhibited after CPB. The mRNA level of NOD1 and protein levels of NOD1 and NOD2 were also markedly decreased after CPB. Our results demonstrated that NOD-mediated signaling pathways were substantially inhibited after CPB, which correlates with the suppressed inflammatory response and may account, at least in part, for the increased risk of postoperative infection in pediatric CHD patients.

EXAMINATION OF VALPROIC ACID-INDUCED PERTURBATIONS TO DNA REPAIR, NF-ΚB SIGNALING AND CBP/P300 TRANSCRIPTIONAL CO-ACTIVATORS

Exposure to the antiepileptic drug valproic acid (VPA) is associated with an increased risk of congenital malformations including heart, skeletal and most frequently neural tube defects. Although the mechanisms contributing to its teratogenesis are not well understood, VPA was previously shown to increase homologous recombination (HR)-mediated DNA repair and decrease protein expression of the transcription factor NF-κB/p65. The studies in this thesis utilized in vivo and in vitro models to evaluate the expression of HR mediators, investigate the implications of decreased p65 including DNA binding and transcriptional activation, and the expression and histone acetyltransferase activity of Cbp/p300 with an aim to provide mechanistic insight into VPA-mediated alterations. The first study demonstrated that following maternal administration of VPA, mouse embryonic mRNA expression of HR mediators Rad51, Brca1 and Brca2 exhibited temporal and tissue-specific alterations. Protein expression of Rad51 was similarly altered and preceded increased cleavage of caspase-3 and PARP; indicative of apoptosis. The second study confirms previous findings of decreased total cellular p65 protein using P19 cells, but is the first to demonstrate that nuclear p65 protein is unchanged. NF-κB DNA binding was decreased following VPA exposure and maybe mediated by decreased p50 protein, which dimerizes with p65 prior to DNA binding. Transcriptional activity of NF-κB was also increased with VPA exposure which was not due to increased p65 phosphorylation at Ser276. Furthermore, the transcriptional activation capacity was unaffected by VPA exposure as combined exposure to VPA and TNFα additively increased NF-κB activity. The third study demonstrated that VPA exposure in P19 cells decreased Cbp/p300 total cellular and nuclear protein attributed primarily to ubiquitin proteasome-mediated degradation. Histone acetyltransferase (HAT) activity of p300 was decreased proportionately to nuclear protein following VPA exposure. Inhibition of Cbp/p300 HAT activity decreased p65 total cellular protein, increased caspase-3 cleavage and ROS similar to VPA exposures. Furthermore, pre-treatment with the antioxidant enzyme catalase attenuated the increase in caspase-3 cleavage, but not p65 protein. Overall, this thesis demonstrates that VPA exposure impacts the expression and activity of the transcription factor NF-κB and transcriptional co-activators/HATs Cbp/p300, which has implications for downstream VPA targets including Rad51, Brca1 and Brca2.

Suppression of nuclear factor-κB activity in macrophages by chylomicron remnants: modulation by the fatty acid composition of the particles

Current evidence indicates that chylomicron remnants (CMR) induce macrophage foam cell formation, an early event in atherosclerosis. Inflammation also plays a part in atherogenesis and the transcription factor nuclear factor-kappaB (NF-kappaB) has been implicated. In this study, the influence of CMR on the activity of NF-kappaB in macrophages and its modulation by the fatty acid composition of the particles were investigated using macrophages derived from the human monocyte cell line THP-1 and CMR-like particles (CRLPs). Incubation of THP-1 macrophages with CRLPs caused decreased NF-kappaB activation and downregulated the expression of phospho-p65-NF-kappaB and phospho-IkappaBalpha (pIkappaBalpha). Secretion of the inflammatory cytokines tumour necrosis factor alpha, interleukin-6 and monocyte chemoattractant protein-1, which are under NF-kappaB transcriptional control, was inhibited and mRNA expression for cyclooxygenase-2, an NF-kappaB target gene, was reduced. CRLPs enriched in polyunsaturated fatty acids compared with saturated or monounsaturated fatty acids had a markedly greater inhibitory effect on NF-kappaB binding to DNA and the expression of phospho-p65-NF-kappaB and pIkappaB. Lipid loading of macrophages with CRLPs enriched in polyunsaturated fatty acids compared with monounsaturated fatty acids or saturated fatty acids also increased the subsequent rate of cholesterol efflux, an effect which may be linked to the inhibition of NF-kappaB activity. These findings demonstrate that CMR suppress NF-kappaB activity in macrophages, and that this effect is modulated by their fatty acid composition. This downregulation of inflammatory processes in macrophages may represent a protective effect of CMR which is enhanced by dietary polyunsaturated fatty acids.

Crisis y creación. Las ambivalentes relaciones germano-españolas en la producción cinematográfica de la primera mitad del siglo veinte

Las épocas de crisis político-social propician en especial medida la creación y el afianzamiento de determinados auto y heteroestereotipos. Esta afirmación resulta concluyente cuando se analiza cómo las distintas fases políticas de España a lo largo de la historia han condicionado de manera definitiva su imagen en el extranjero, en especial en Alemania. Las imágenes y estereotipos románticos creados a partir de la Guerra de la Independencia (1808-1814) sirvieron durante la primera mitad del siglo veinte de instrumento de manipulación propagandística que debía contribuir a ensalzar la ejemplaridad del aliado español. Este artificio político, que buscaba la simpatía ideológica con el sistema de valores nacionalsocialista, se valió de manera particular de las producciones cinematográficas hispano-alemanas para lograr su objetivo.

Administración pública local y construcción de la central hidroeléctrica en la Amazonia

Exponemos los resultados de una observación exploratoria en la que se analizan los impactos funcionales en el sistema administrativo como consecuencia de la construcción de la Central Hidroeléctrica de Belo Monte (CHB) en el municipio de Altamira (Amazonia oriental brasileña). En la perspectiva teórico-conceptual de la teoría de sistemas sociales de Niklas Luhmann, realizamos una observación del sistema administrativo local sobre sus operaciones y funciones, en base a cuatro códigos preestablecidos: toma de decisiones, contingencia, significación simbólica del proyecto y planificación. Las conclusiones permiten entrever en un aplano conceptual la utilidad de los conceptos sistémicos de Luhmann, y en el empírico, una planificación y administración pública municipal reactivas.

Connectivity Mapping (ssCMap) To Predict A20 Inducing Drugs: Anti-inflammatory Action In Cystic Fibrosis

Cystic Fibrosis (CF) lung disease is characterised by a chronic and exaggerated inflammation in the airways. Despite recent developments to therapeutically overcome the underlying functional defect in CFTR (cystic fibrosis transmembrane conductance regulator), there is still an unmet need to also normalise the inflammatory response. The prolonged and heightened inflammatory response in CF is in part mediated by a lack of intrinsic downregulation of the pro-inflammatory NF-kB pathway. We have previously identified reduced expression of the NF-kB down-regulator A20 in CF as a key target to normalise the inflammatory response. Here we have used publically available gene array expression data together with sscMap (statistically significant connections’map)to successfully predict drugs already licensed for the use in humans to induce A20 mRNA and protein expression and thereby reduce inflammation. The effect of the predicted drugs on A20 and NFkB (p65) expression (mRNA) as well as pro-inflammatory cytokine release (IL-8) in the presence and absence of bacterial LPS was shown in bronchial epithelial cells lines (16HBE14o-, CFBE41o-) and in primary nasal epithelial cells (PNECs) from patients with CF (Phe508del homozygous) and non-CF controls. Additionally, the specificity of the drug action on A20 was confirmed using cell lines with TNFAIP3 (A20) knockdown (siRNA). We also show that the A20 inducing effect of ikarugamycin and quercetin is lower in CF derived airway epithelial cells than in non-CF cells.

Btk regulates macrophage polarization in response to lipopolysaccharide

Bacterial Lipopolysaccharide (LPS) is a strong inducer of inflammation and does so by inducing polarization of macrophages to the classic inflammatory M1 population. Given the role of Btk as a critical signal transducer downstream of TLR4, we investigated its role in M1/M2 induction. In Btk deficient (Btk (-\-)) mice we observed markedly reduced recruitment of M1 macrophages following intraperitoneal administration of LPS. Ex vivo analysis demonstrated an impaired ability of Btk(-/-) macrophages to polarize into M1 macrophages, instead showing enhanced induction of immunosuppressive M2-associated markers in response to M1 polarizing stimuli, a finding accompanied by reduced phosphorylation of STAT1 and enhanced STAT6 phosphorylation. In addition to STAT activation, M1 and M2 polarizing signals modulate the expression of inflammatory genes via differential activation of transcription factors and regulatory proteins, including NF-κB and SHIP1. In keeping with a critical role for Btk in macrophage polarization, we observed reduced levels of NF-κB p65 and Akt phosphorylation, as well as reduced induction of the M1 associated marker iNOS in Btk(-/-) macrophages in response to M1 polarizing stimuli. Additionally enhanced expression of SHIP1, a key negative regulator of macrophage polarisation, was observed in Btk(-/-) macrophages in response to M2 polarizing stimuli. Employing classic models of allergic M2 inflammation, treatment of Btk (-/-) mice with either Schistosoma mansoni eggs or chitin resulted in increased recruitment of M2 macrophages and induction of M2-associated genes. This demonstrates an enhanced M2 skew in the absence of Btk, thus promoting the development of allergic inflammation.

La importancia de Azores y Madeira en el Atlántico: de territorio fronterizo a base estratégica

Seminario Formativo del Programa de Doctorado Islas Atlánticas. Línea de investigación 1: Retos de la investigación en las dinámicas históricas y sociales del mundo atlántico, 2 y 3 de junio de 2016. Coordinado por Santiago de Luxán Meléndez. Aula Máster de la Escuela de Arquitectura de la Universidad de Las Palmas de Gran Canaria.

Regulation of osteoclast activation and autophagy through altered protein kinase pathways in Paget's disease of bone

Résumé : La maladie osseuse de Paget (MP) est un désordre squelettique caractérisé par une augmentation focale et désorganisée du remodelage osseux. Les ostéoclastes (OCs) de MP sont plus larges, actifs et nombreux, en plus d’être résistants à l’apoptose. Même si la cause précise de la MP demeure inconnue, des mutations du gène SQSTM1, codant pour la protéine p62, ont été décrites dans une proportion importante de patients avec MP. Parmi ces mutations, la substitution P392L est la plus fréquente, et la surexpression de p62P392L dans les OCs génère un phénotype pagétique partiel. La protéine p62 est impliquée dans de multiples processus, allant du contrôle de la signalisation NF-κB à l’autophagie. Dans les OCs humains, un complexe multiprotéique composé de p62 et des kinases PKCζ et PDK1 est formé en réponse à une stimulation par Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL), principale cytokine impliquée dans la formation et l'activation des OCs. Nous avons démontré que PKCζ est impliquée dans l’activation de NF-κB induite par RANKL dans les OCs, et dans son activation constitutive en présence de p62P392L. Nous avons également observé une augmentation de phosphorylation de Ser536 de p65 par PKCζ, qui est indépendante d’IκB et qui pourrait représenter une voie alternative d'activation de NF-κB en présence de la mutation de p62. Nous avons démontré que les niveaux de phosphorylation des régulateurs de survie ERK et Akt sont augmentés dans les OCs MP, et réduits suite à l'inhibition de PDK1. La phosphorylation des substrats de mTOR, 4EBP1 et la protéine régulatrice Raptor, a été évaluée, et une augmentation des deux a été observée dans les OCs pagétiques, et est régulée par l'inhibition de PDK1. Également, l'augmentation des niveaux de base de LC3II (associée aux structures autophagiques) observée dans les OCs pagétiques a été associée à un défaut de dégradation des autophagosomes, indépendante de la mutation p62P392L. Il existe aussi une réduction de sensibilité à l’induction de l'autophagie dépendante de PDK1. De plus, l’inhibition de PDK1 induit l’apoptose autant dans les OCs contrôles que pagétiques, et mène à une réduction significative de la résorption osseuse. La signalisation PDK1/Akt pourrait donc représenter un point de contrôle important dans l’activation des OCs pagétiques. Ces résultats démontrent l’importance de plusieurs kinases associées à p62 dans la sur-activation des OCs pagétiques, dont la signalisation converge vers une augmentation de leur survie et de leur fonction de résorption, et affecte également le processus autophagique.

Lifestyles of higher education students: the influence of self- esteem and psychological well-being

Background The transition to higher education can affect lifestyle-related factors. Objectives: To identify lifestyles of higher education students and analyse the influence of self-esteem and psychological well-being. Methods Correlational cross-sectional study. A total of 4,314 students partici- pated in the study. Online questionnaires were used: Estilo de Vida Fantástico (Fantastic Lifestyle Assessment) [1]; Questionário de Bem- estar Psicológico (Psychological General Well-Being Questionnaire) [2], and Escala de auto-estima de Rosenberg (Rosenberg Self-Esteem Scale [3]. Results Most students (85.3 %) have a healthy lifestyle. Lifestyle is strongly correlated with self-esteem and psychological well-being (p < 0.001). While analysing the association between self-esteem and psycho- logical well-being and the various lifestyle domains according to gen- der, a positive and significant correlation (p < 0.001) was found among female students, except for the Smoking domain (p = 0.393); in relation to psychological well-being, positive correlations were found in all domains. Among male students, positive and significant correlations (p < 0.001) were found in most lifestyle domains and self-esteem, except for the Smoking (p = 0.992), Alcohol and other drugs (p = 0.181) and Other behaviours (p = 0.442) domains; in rela- tion to psychological well-being, positive and significant correlations (p < 0.001) were found in most lifestyle domains, except for the Smoking (p = 0.458) and Other behaviours (p = 0.128) domains. Conclusions Based on the results, higher education institutions should support intervention projects to maintain high levels of psychological well- being and self-esteem, promoting healthy lifestyles.

Avaliação do efeito citotóxico da lectina da esponja marinha Cliona varians contra células de leucemia mielóide crônica

In this study, a BCR-ABL expressing human chronic myelogenous leukaemia cell line (K562) was used to investigate the antitumoral potential of a novel lectin (CvL) purified from the marine sponge Cliona varians. CvL inhibited the growth of K562 cells with an IC50 value of 70 g/ml, but was ineffective to normal human peripheral blood lymphocytes in the same range of concentrations tested (180 g/ml). Cell death occurred after 72 h of exposure to the lectin and with sign of apoptosis as analysed by DAPI staining. Investigation of the possible effectors of this process showed that cell death occurred in the presence of Bcl-2 and Bax expression, and involved a caspase-independent pathway. Confocal fluorescence microscopy indicated a major role for the lysosomal protease cathepsin B in mediating cell death. Accordingly, pre-incubation of K562 cells with the cathepsin inhibitor L-trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane (E-64) abolished the cytotoxic effect of CvL. Furthermore, we found upregulation of tumor necrosis factor receptor 1 (TNFR1) and down-modulation of p65 subunit of nuclear factor kappa B (NFB) expression in CvL-treated cells. These effects were accompanied by increased levels of p21 and downmodulation of pRb, suggesting that CvL is capable of cell cycle arrest. Collectively, these findings suggest that cathepsin B acts as death mediator in CvL-induced cytotoxicity possibly in a still uncharacterized connection with the membrane death receptor pathway

Soybean lunasin mediates colon carcinogenesis by inducing apoptosis and preventing outgrowth of metastasis

Colorectal cancer (CRC) is the third most common cancer worldwide. Various factors such as age, lifestyle and dietary patterns affect the risk of having CRC. Epidemiological studies showed a chemopreventive effect of soy consumption against CRC. However, which component(s) of soybean is associated with this reduced risk is not yet fully delineated. The objective of this research was to evaluate the anti-colon cancer potential of lunasin isolated from defatted soybean flour using in vitro and in vivo models of CRC. Lunasin was isolated from defatted soybean flour by a combination of different chromatographic and ultrafiltration techniques. The anti-colon cancer potential of lunasin was determined using different human colon cancer cell lines in vitro and a CRC liver metastasis model in vivo. Lunasin caused cytotoxicity to different human colon cancer cells with an IC50 value of 13.0, 21.6, 26.3 and 61.7 µM for KM12L4, RKO, HCT-116 and HT-29 human colon cancer cells, respectively. This cytotoxicity correlated with the expression of the α5 integrin on human colon cancer cells with a correlation coefficient of 0.78. The mechanism involved in the cytotoxic effect of lunasin was through cell cycle arrest and induction of the mitochondrial pathway of apoptosis. In KM12L4 human colon cancer cells, lunasin caused a G2/M phase arrest increasing the percentage of cells at G2/M phase from 12% (PBS-treated) to 24% (treated with 10 µM lunasin). This arrest was attributed to the capability of lunasin to increase the expression of cyclin dependent kinase inhibitors p21 and p27. At 10 µM, lunasin increased the expression of p21 and p27 in KM12L4 colon cancer cells by 2.2- and 2.3-fold, respectively. Flow cytometric analysis showed that lunasin at 10 µM increased the percentage of cells undergoing apoptosis from 13.6% to 24.7%. This is further supported by fluorescence microscopic analysis of KM12L4 cells treated with 10 µM lunasin showing chromatin condensation and DNA fragmentation. The mechanism involved is through modification of proteins involved in the mitochondrial pathway of apoptosis in KM12L4 cells as 10 µM lunasin reduced the expression of the anti-apoptotic Bcl-2 protein by 2-fold and increased the expression of the pro-apoptotic proteins Bax, cytochrome c and nuclear clusterin by 2.2-, 2.1- and 2.3- fold, respectively. This led to increased expression and activity of the executioner of apoptosis, caspase-3 by 1.8- and 2.3-fold, respectively. This pro-apoptotic property of lunasin can be attributed to its capability to internalize into the cytoplasm and nucleus of colon cancer cells 24 h and 72 h after treatment, respectively. In addition, lunasin mediated metastasis of colon cancer cells in vitro by inhibiting the focal adhesion kinase activation thereby reducing expression of extracellular regulated kinase and nuclear factor kappa B and finally inhibiting migration of colon cancer cells. In KM12L4 colon cancer cells, 10 µM lunasin resulted in the reduction of phosphorylation of focal adhesion kinase and extracellular regulated kinase by 2.5-fold, resulting in the reduced nuclear translocation of p50 and p65 NF-κB subunits by 3.8- and 1.4-fold, respectively. In an in vivo model of CRC liver metastasis, daily intraperitoneal administration of lunasin at 4 mg/kg body weight resulted in the inhibition of KM12L4 liver metastasis as shown by the reduction of the number of liver metastases from 28 (PBS-treated) to 14 (lunasin-treated, P = 0.047) and reduction in tumor burden as measured by liver weight/body weight from 0.13 (PBS-treated) to 0.10 (lunasin-treated, P = 0.039). Moreover, lunasin potentiated the anti-metastatic effect of the chemotherapeutic drug oxaliplatin given at 5 mg/kg body weight twice per week. Lunasin and oxaliplatin combination resulted in a more potent inhibition of outgrowth of KM12L4 cell metastases to the liver reducing the number of liver metastases by 6-fold and reducing the tumor burden in the liver by 3-fold when compared to PBS-treated group. This can be attributed by the capability of lunasin and oxaliplatin to reduce expression of proliferating cell nuclear antigen in liver-tumor tissue as measured by immunohistochemical staining. The results of this research for the first time demonstrated the anti-colon cancer potential of lunasin isolated from defatted soybean flour which might contribute to the chemopreventive effect of soybean in CRC as seen in different epidemiological studies. In conclusion, lunasin isolated from defatted soybean flour mediated colon carcinogenesis by inducing apoptosis and preventing outgrowth of metastasis. We suggest that the results of this research serve as a basis for further study on the chemopreventive effect of lunasin against CRC and a possible adjuvant role for lunasin in therapy of patients with metastatic CRC.