The expression of monocarboxylate transporters in thyroid carcinoma can be associated with the morphological features of BRAF (V600E) mutation

BRAF (V600E) mutation, usually performed by DNA techniques, is one of the most common diagnostic markers in papillary thyroid carcinoma. Few papers have demonstrated that plump cells (eosinophilic cytoplasms and papillary thyroid carcinoma nuclei) and peculiar sickle-shaped nuclei represent morphological features of BRAF (V600E) on papillary thyroid carcinomas. These features seem to be linked to glycolytic phenotype whereby monocarboxylate transporters 1-4 are hypothesized to have a dominant role as lactate transporters. We investigated the association between these morphological features and monocarboxylate transporters 1 and 4 in 48 cyto-histological samples diagnosed as "positive for malignancy-favoring papillary thyroid carcinoma". These cases were processed with liquid-based cytology and underwent BRAF (V600E) mutational analysis (pyrosequencing) on liquid-based cytology and monocarboxylate transporters immunostaining on histology. The expression of monocarboxylate transporter 1, monocarboxylate transporter 4, glucose trasporter-1 and carbonic anhidrase were scored semi-quantitatively with expression from 0 to 3+ (strong positivity). The 33 mutated and 15 wild type cases showed 100 % cyto-histological concordance. The cytological evaluation revealed plump cells and sickle nuclear shape in 100 % mutated cases. Monocarboxylate transporter 1 yielded 76 % positivity in the mutated cases especially in both the plump cells and sickle-shaped nuclei, whereas the wild types showed 13.3 % positive monocarboxylate transporter 1 (p = 0.00013). Monocarboxylate transporter 4 resulted in 100 % positivity in mutated and 40 % in wild types (p 0.05). This is the first report analyzing the association between monocarboxylate transporter expression and the morphological features of BRAF (V600E) mutated papillary thyroid carcinomas suggesting the possible involvement of lactate in the morphological features.info:eu-repo/semantics/publishedVersio

Recommended age groups and frequency of mammography screening : a systematic review

Esta revisão teve por objetivo avaliar a força de evidência do atual indicador de desempenho português relativo ao rastreio do Câncer da Mama através da mamografia, de modo a determinar o grupo etário e a periodicidade recomendadas. Foram pesquisados artigos nas principais bases de dados internacionais de literatura médica. Incluímos artigos publicados entre Janeiro de 2006 e Janeiro de 2012 que correspondiam aos objetivos da revisão. Foi utilizada a taxonomia SORT para a classificação dos resultados. Dos 253 artigos encontrados foram selecionados cinco que cumpriam os critérios de inclusão. Estes incluem três revisões sistemáticas (RS), uma meta-análise (MA) e uma norma de orientação clínica (NOC) baseada numa RS. Os artigos selecionados avaliaram a redução da mortalidade por câncer da mama através do rastreio com mamografia. A realização do rastreio mamográfico entre os 50 e os 69 anos é recomendado em todos os artigos que avaliam esta faixa etária. A NOC recomenda o rastreio bienal. Em suma, a mamografia deverá ser realizada entre os 50 e os 69 anos com uma periodicidade bienal. Estes resultados vão ao encontro do atual indicador de desempenho do rastreio do câncer da mama em Portugal.The scope of this review was to assess the strength of evidence for the current Portuguese performance indicator on breast cancer screening with mammography in order to determine the recommended age group and periodicity for screening. A search for articles was conducted in the main international databases of medical literature. Articles published between January 2006 and January 2012 addressing the objectives of this review were included. The SORT taxonomy was used to classify the results. Of the 253 articles, five articles met the inclusion criteria and were selected for review. These included three systematic reviews, one meta-analysis and one clinical guideline based on a systematic review. A reduction in breast cancer mortality with mamography screening was the outcome in all articles selected. Mammography screening between 50 and 69 years was recommended in all articles that assess this age group. The clinical guidelines recommended screening every two years. In conclusion, the current literature recommends mammography for women every two years between the ages of 50 and 69 years. This is consistent with the current performance indicator for breast cancer screening in Portugal

Cervical cancer screening: target age bracket, screening frequency and screening method: review of recent evidence and comparison with the Portuguese performance indicator

Esta revisão teve por objetivo avaliar a força de evidência do indicador de desempenho português relativo ao rastreio do Câncer do Colo do Útero (CCU): (1) limites etários das mulheres da população geral que o devem realizar, a (2) periodicidade com que deve ser realizado e (3) qual o melhor exame de rastreio. Foram pesquisados os seguintes termos MeSH: vaginal smears, age groups, periodicity, methods, uterine cervical cancer. Foram excluídos os artigos que não abordavam o objetivo da investigação ou que não fossem redigidos em Inglês, Português ou Espanhol. Para interpretar os artigos selecionados foi utilizada a classificação SORT. Foram encontrados 197 artigos, dos quais seleccionados 9: 1 revisão sistemática (RS), 1 estudo clínico controlado aleatorizado, 2 estudos observacionais retrospectivos e 5 normas de orientação clínica (NOC). Os autores optaram por incluir nesta revisão mais 4 NOCs e 2 RSs por considerarem ser relevantes para a população Portuguesa, apesar de não resultarem da pesquisa efectuada. Os estudos sugerem realização do rastreio entre os 21 e 25 até aos 65 anos, com uma periodicidade trienal usando a citologia convencional. Existe ainda controvérsia no que toca aos 3 objetivos deste artigo (limites etários, frequência e método).The scope of this review was to assess the strength of evidence of Portuguese performance indicators on Cervical Cancer screening: (1) age group of the women that should be screened for cervical cancer; (2) frequency of screening; and (3) the best method for screening. The following MeSH terms were searched: vaginal smears, age groups, periodicity, methods, uterine cervical cancer. Articles not reflecting the study objectives or not available in English, Portuguese or Spanish were excluded. The SORT classification was used to rate the articles selected.Of the 197 articles found, 9 that met all study criteria were selected for inclusion in this review. These included 1 systematic review, 1 randomized controlled clinical trial, 2 retrospective studies and 5 clinical guidelines. The authors also chose to include 4 clinical guidelines and two systematic reviews relevant to the Portuguese population even though they did not appear in the initial search of the literature. The studies suggest screening women between the ages of 21 to 25 years and 65 years of age, once every three years using conventional cytology. There is still controversy regarding the three objectives of this study (target age bracket, screening frequency and screening method)

Role of monocarboxylate transporters in human cancers : state of the art

Monocarboxylate transporters (MCTs) belong to the SLC16 gene family, presently composed by 14 members. MCT1-MCT4 are proton symporters, which mediate the transmembrane transport of pyruvate, lactate and ketone bodies. The role of MCTs in cell homeostasis has been characterized in detail in normal tissues, however, their role in cancer is still far from understood. Most solid tumors are known to rely on glycolysis for energy production and this activity leads to production of important amounts of lactate, which are exported into the extracellular milieu, contributing to the acidic microenvironment. In this context, MCTs will play a dual role in the maintenance of the hyper-glycolytic acidresistant phenotype of cancer, allowing the maintenance of the high glycolytic rates by performing lactate efflux, and pH regulation by the co-transport of protons. Thus, they constitute attractive targets for cancer therapy, which have been little explored. Here we review the literature on the role of MCTs in solid tumors in different locations, such as colon, central nervous system, breast, lung, gynecologic tract, prostate, stomach, however, there are many conflicting results and in most cases there are no functional studies showing the dependence of the tumors on MCT expression and activity. Additional studies on MCT expression in other tumor types, confirmation of the results already published as well as additional functional studies are needed to deeply understand the role of MCTs in cancer maintenance and aggressiveness

E. coli promotes human Vγ9Vδ2 T cell transition from cytokine-producing bactericidal effectors to professional phagocytic killers in a TCR-dependent manner

γδT cells provide immune-surveillance and host defense against infection and cancer. Surprisingly, functional details of γδT cell antimicrobial immunity to infection remain largely unexplored. Limited data suggests that γδT cells can phagocytose particles and act as professional antigen-presenting cells (pAPC). These potential functions, however, remain controversial. To better understand γδT cell-bacterial interactions, an ex vivo co-culture model of human peripheral blood mononuclear cell (PBMC) responses to Escherichia coli was employed. Vγ9Vδ2 cells underwent rapid T cell receptor (TCR)-dependent proliferation and functional transition from cytotoxic, inflammatory cytokine immunity, to cell expansion with diminished cytokine but increased costimulatory molecule expression, and capacity for professional phagocytosis. Phagocytosis was augmented by IgG opsonization, and inhibited by TCR-blockade, suggesting a licensing interaction involving the TCR and FcγR. Vγ9Vδ2 cells displayed potent cytotoxicity through TCR-dependent and independent mechanisms. We conclude that γδT cells transition from early inflammatory cytotoxic killers to myeloid-like APC in response to infectious stimuli

Novel IgG-degrading enzymes of the IgdE protease family link substrate specificity to host tropism of <i>Streptococcus</i> species

Recently we have discovered an IgG degrading enzyme of the endemic pig pathogen S. suis designated IgdE that is highly specific for porcine IgG. This protease is the founding member of a novel cysteine protease family assigned C113 in the MEROPS peptidase database. Bioinformatical analyses revealed putative members of the IgdE protease family in eight other Streptococcus species. The genes of the putative IgdE family proteases of S. agalactiae, S. porcinus, S. pseudoporcinus and S. equi subsp. zooepidemicus were cloned for production of recombinant protein into expression vectors. Recombinant proteins of all four IgdE family proteases were proteolytically active against IgG of the respective Streptococcus species hosts, but not against IgG from other tested species or other classes of immunoglobulins, thereby linking the substrate specificity to the known host tropism. The novel IgdE family proteases of S. agalactiae, S. pseudoporcinus and S. equi showed IgG subtype specificity, i.e. IgdE from S. agalactiae and S. pseudoporcinus cleaved human IgG1, while IgdE from S. equi was subtype specific for equine IgG7. Porcine IgG subtype specificities of the IgdE family proteases of S. porcinus and S. pseudoporcinus remain to be determined. Cleavage of porcine IgG by IgdE of S. pseudoporcinus is suggested to be an evolutionary remaining activity reflecting ancestry of the human pathogen to the porcine pathogen S. porcinus. The IgG subtype specificity of bacterial proteases indicates the special importance of these IgG subtypes in counteracting infection or colonization and opportunistic streptococci neutralize such antibodies through expression of IgdE family proteases as putative immune evasion factors. We suggest that IgdE family proteases might be valid vaccine targets against streptococci of both human and veterinary medical concerns and could also be of therapeutic as well as biotechnological use

Approaches in biotechnological applications of natural polymers

Natural polymers, such as gums and mucilage, are biocompatible, cheap, easily available and non-toxic materials of native origin. These polymers are increasingly preferred over synthetic materials for industrial applications due to their intrinsic properties, as well as they are considered alternative sources of raw materials since they present characteristics of sustainability, biodegradability and biosafety. As definition, gums and mucilages are polysaccharides or complex carbohydrates consisting of one or more monosaccharides or their derivatives linked in bewildering variety of linkages and structures. Natural gums are considered polysaccharides naturally occurring in varieties of plant seeds and exudates, tree or shrub exudates, seaweed extracts, fungi, bacteria, and animal sources. Water-soluble gums, also known as hydrocolloids, are considered exudates and are pathological products; therefore, they do not form a part of cell wall. On the other hand, mucilages are part of cell and physiological products. It is important to highlight that gums represent the largest amounts of polymer materials derived from plants. Gums have enormously large and broad applications in both food and non-food industries, being commonly used as thickening, binding, emulsifying, suspending, stabilizing agents and matrices for drug release in pharmaceutical and cosmetic industries. In the food industry, their gelling properties and the ability to mold edible films and coatings are extensively studied. The use of gums depends on the intrinsic properties that they provide, often at costs below those of synthetic polymers. For upgrading the value of gums, they are being processed into various forms, including the most recent nanomaterials, for various biotechnological applications. Thus, the main natural polymers including galactomannans, cellulose, chitin, agar, carrageenan, alginate, cashew gum, pectin and starch, in addition to the current researches about them are reviewed in this article.. }To the Conselho Nacional de Desenvolvimento Cientfíico e Tecnológico (CNPq) for fellowships (LCBBC and MGCC) and the Coordenação de Aperfeiçoamento de Pessoal de Nvíel Superior (CAPES) (PBSA). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and COMPETE 2020 (POCI-01-0145-FEDER-006684) (JAT)

The Percentage of [−2]Pro–Prostate-Specific Antigen and the Prostate Health Index Outperform Prostate-Specific Antigen and the Percentage of Free Prostate-Specific Antigen in the Detection of Clinically Significant Prostate Cancer and Can Be Used as Reflex Tests

Context.—: There is a need to avoid the overdiagnosis of prostate cancer (PCa) and to find more specific biomarkers. Objective.—: To evaluate the clinical utility of [-2]pro-prostate-specific antigen ([-2]proPSA) derivatives in detecting clinically significant PCa (csPCa) and to compare it with prostate-specific antigen (PSA) and with the percentage of free PSA (%fPSA). Design.—: Two hundred thirty-seven men (PSA: 2-10 ng/mL) scheduled for a prostate biopsy were enrolled. Parametric and nonparametric tests, receiver operating characteristic curves, and logistic regression analysis were applied. Outcomes were csPCa and overall PCa. Results.—: Both [-2]proPSA derivatives were significantly higher in csPCa and overall PCa (P < .001). The areas under the curves for the prediction of csPCa were higher for the percentage of [-2]proPSA (%[-2]proPSA) (0.781) and the prostate health index (PHI) (0.814) than for PSA (0.651) and %fPSA (0.724). There was a gain of 11% in diagnostic accuracy when %[-2]proPSA or PHI were added to a base model with PSA and %fPSA. Twenty-five percent to 29% of biopsies could have been spared with %[-2]proPSA (cutoff: ≥1.25%) and PHI (cutoff: ≥27), missing 10% of csPCas. The same results could have been achieved by using [-2]proPSA as a reflex test, when %fPSA was 25% or less (cutoffs: ≥1.12% and ≥24 for %[-2]proPSA and PHI, respectively). Conclusions.—: The [-2]proPSA derivatives improve the diagnostic accuracy of csPCa when the PSA value is between 2 and 10 ng/mL, sparing unnecessary biopsies and selecting patients for active surveillance. [-2]proPSA can be used as a reflex test when %fPSA is 25% or less, without reducing the diagnostic accuracy for csPCa and the number of spared biopsies.info:eu-repo/semantics/publishedVersio

Nematode and Arthropod Genomes Provide New Insights into the Evolution of Class 2 B1 GPCRs

Nematodes and arthropods are the most speciose animal groups and possess Class 2 B1 G-protein coupled receptors (GPCRs). Existing models of invertebrate Class 2 B1 GPCR evolution are mainly centered on Caenorhabditis elegans and Drosophila melanogaster and a few other nematode and arthropod representatives. The present study reevaluates the evolution of metazoan Class 2 B1 GPCRs and orthologues by exploring the receptors in several nematode and arthropod genomes and comparing them to the human receptors. Three novel receptor phylogenetic clusters were identified and designated cluster A, cluster B and PDF-R-related cluster. Clusters A and B were identified in several nematode and arthropod genomes but were absent from D. melanogaster and Culicidae genomes, whereas the majority of the members of the PDF-R-related cluster were from nematodes. Cluster A receptors were nematode and arthropod-specific but shared a conserved gene environment with human receptor loci. Cluster B members were orthologous to human GCGR, PTHR and Secretin members with which they probably shared a common origin. PDF-R and PDF-R related clusters were present in representatives of both nematodes and arthropods. The results of comparative analysis of GPCR evolution and diversity in protostomes confirm previous notions that C. elegans and D. melanogaster genomes are not good representatives of nematode and arthropod phyla. We hypothesize that at least four ancestral Class 2 B1 genes emerged early in the metazoan radiation, which after the protostome-deuterostome split underwent distinct selective pressures that resulted in duplication and deletion events that originated the current Class 2 B1 GPCRs in nematode and arthropod genomes.This work was supported by the Portuguese Foundation for Science and Technology (FCT) project PTDC/BIA-BCM/114395/2009, by the European Regional Development Fund through COMPETE and FCT under the project ‘‘PEst-C/MAR/LA0015/2011.’’ RCF is in receipt of an FCT grant (SFRH/BPD/89811/2012) and JCRC is supported by auxiliary research contract FCT Pluriannual funds attributed to CCMAR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

AB0747 MATERNAL AND FETAL OUTCOMES IN PREGNANT WOMEN WITH JUVENILE IDIOPATHIC ARTHRITIS: A SYSTEMATIC LITERATURE REVIEW

info:eu-repo/semantics/publishedVersio