8 research outputs found

    Comprehensive and user-analytics-friendly cancer patient database for physicians and researchers

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    Nuanced cancer patient care is needed, as the development and clinical course of cancer is multifactorial with influences from the general health status of the patient, germline and neoplastic mutations, co-morbidities, and environment. To effectively tailor an individualized treatment to each patient, such multifactorial data must be presented to providers in an easy-to-access and easy-to-analyze fashion. To address the need, a relational database has been developed integrating status of cancer-critical gene mutations, serum galectin profiles, serum and tumor glycomic profiles, with clinical, demographic, and lifestyle data points of individual cancer patients. The database, as a backend, provides physicians and researchers with a single, easily accessible repository of cancer profiling data to aid-in and enhance individualized treatment. Our interactive database allows care providers to amalgamate cohorts from these groups to find correlations between different data types with the possibility of finding "molecular signatures" based upon a combination of genetic mutations, galectin serum levels, glycan compositions, and patient clinical data and lifestyle choices. Our project provides a framework for an integrated, interactive, and growing database to analyze molecular and clinical patterns across cancer stages and subtypes and provides opportunities for increased diagnostic and prognostic power.Comment: 7 pages, 12 figures, peer reviewed and accepted in "International Conference on Computational Science and Computational Intelligence (CSCI 22)

    Galectins in the Pathogenesis of Cerebrovascular Accidents: An Overview

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    Due to limitations of neuroimaging, such as the isodense appearance of blood to neuronal tissue in subacute hemorrhagic stroke, a body of studies have been performed to evaluate candidate biomarkers which may aid in accurate determination of cerebrovascular accident type. Beyond aiding in the delineation of stroke cause, biomarkers could also confer useful prognostic information to help clinicians plan use of resources. One of the candidate biomarkers studied for detection of cerebrovascular accident (CVA) includes a class of proteins called galectins. Galectins bind β-galactoside through a highly conserved carbohydrate recognition domain, endowing an ability to interact with carbohydrate moieties on glycoproteins, some of which are relevant to CVA response. Furthermore, galectins-1, -2, -3, -9, and -12 are expressed in tissues relevant to CVA, and some exhibit characteristics (eg, extracellular secretion) that could render feasible their detection in serum. Galectins-1 and -3 appear to have the largest amounts of preclinical evidence, consistently demonstrating increased activity and expression levels during CVA. However, a lack of standardization of biochemical assays across cohort studies limits further translation of these basic science studies. This review aims to increase awareness of the biochemical roles of galectins in CVA, while also highlighting challenges and remaining questions preventing the translation of basic science observations into a clinically useful test

    Role of Human Galectins in Inflammation and Cancers Associated with Endometriosis

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    Galectins are a family of β-galactoside-binding proteins that contribute to multiple cellular functions, including immune surveillance and apoptosis. Human galectins are also important regulators of inflammation, making them a research target for various inflammatory diseases and tumorigenesis associated with pro-inflammatory conditions. This review focuses on the involvement of human galectins in modulation of inflammation and in the pathophysiology of endometriosis and endometriosis-associated neoplasms. Endometriosis is a chronic inflammatory disease with unknown etiology. Galectins-1, -3 and -9 were found to be overexpressed in ectopic and eutopic endometrium of females with endometriosis compared to those without endometriosis. These findings suggest galectins’ role in the progression on endometriotic lesions and their potential use as diagnostic biomarkers and/or targets for therapeutic approaches. Galectins-1, -3, and -9 have also been implicated in the development of endometriosis-associated neoplasms. Furthermore, galectin-3 has been shown to interact with KRAS protein and contribute to cellular growth, proliferation, inflammation, and the uptake of nutrients in endometriotic lesions and may be involved in the maintenance and propagation of endometriosis. These galectins have been shown to be upregulated in certain forms of cervical, ovarian, endometrial, and colon cancer associated with endometriosis and have become a potential target for anti-cancer therapies

    Rare missense variant p.Ala505Ser in the ZAK protein observed in a patient with split-hand/foot malformation from a non-consanguineous pedigree

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    ObjectiveSplit-hand/foot malformation (SHFM) is a rare, often debilitating, congenital limb malformation. A single nucleotide polymorphism within the leucine zipper containing kinase AZK (ZAK) gene was recently associated with SHFM in two consanguineous Pakistani pedigrees. We hypothesized that additional unrelated patients with the phenotype may carry a pathogenic mutation in ZAK.MethodsDNA samples were collected from 38 patients with SHFM and associated hearing loss for Sanger DNA sequencing and in silico analysis.ResultsTwo missense mutations within ZAK were detected in 11 patients, but only one missense variant, p.Ala505Ser, occurred with a presumed rare allele frequency. In silico modeling of the ZAK protein with the p.Ala505Ser substitution indicated a negative binding free energy change (mean ΔΔG = −0.9), representing destabilization of the ZAK tertiary structure. Additional laboratory analysis demonstrated a chromosome region 7q21.3-q22.1 deletion. This locus contains the SHFM-1 causative genes SHFM1, DLX5, and DLX6 (distal-less homeobox-5 and -6).ConclusionsWe report a novel and rare missense variant, ZAK p.Ala505Ser, in one patient with SHFM from a non-consanguineous pedigree. This variant mildly destabilizes the ZAK tertiary structure. Although this mutation involved a deletion at the SHFM1 locus (7q21.3-q22.1), ZAK signaling destabilization may have contributed to the phenotype, which included hearing loss

    <i>KIT</i> Mutations Correlate with Higher Galectin Levels and Brain Metastasis in Breast and Non-Small Cell Lung Cancer

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    To investigate a potential role for galectins as biomarkers that enable diagnosis or prognostication of breast or non-small cell lung cancer, the serum levels of galectins -1, -3, -7, -8, and -9 of cancer patients determined by ELISA assays were compared to the mutation status of 50 known cancer-critical genes, which were determined using multiplex PCR in tumors of the same patients. Mutations in the KIT proto-oncogene, which codes for the c-Kit protein, a receptor tyrosine kinase, correlated with higher levels of galectins -1, -3, -8, and -9 in breast cancer patients and galectin-1 in non-small cell lung cancer patients. Mutations in the KIT gene were more likely found in brain metastases from both of these primary cancers. The most common KIT mutation in our panel was p.M541L, a missense mutation in the transmembrane domain of the c-Kit protein. These results demonstrate an association between KIT oncogenic signaling and elevated serum galectins in patients with metastatic disease. Changes in protein trafficking and the glycocalyx composition of cancer cells may explain the observed alterations in galectin expression. This study can be useful for the targeted selection of receptor tyrosine kinase and galectin inhibitor anti-cancer treatments

    The changing epidemiology of Acinetobacter spp. producing MA. carbapenemases causing bloodstream infections in Brazil: a BrasNet report

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    Made available in DSpace on 2019-09-12T16:53:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2015Merieux Research Grants - Institut MerieuxWe evaluated the epidemiology of Acinetobacter spp. recovered from patients diagnosed with bloodstream infections in 9 tertiary hospitals located in all Brazilian geographic regions between April and August 2014. Although OXA-23-producing Acinetobacter baumannii clones were disseminated in most hospitals, it was observed for the first time the spread of OXA-72 among clonally related A. baumannii isolated from distinct hospitals. Interestingly, Acinetobacter pittii was the most frequent species found in a Northern region hospital. Contrasting with the multisusceptible profile displayed by A. pittii isolates, the tetracyclines and polymyxins were the only antimicrobials active against all A. baumannii isolates. (C) 2015 Elsevier Inc. All rights reserved.[Vasconcelos, Ana Tereza R.] Lab Nacl Comp Cient LNCC MCTI, Petropolis, RJ, Brazil[Barth, Afonso L.; Zavascki, Alexandre P.] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Lab Pesquisa Resistencia Bacteriana LABRESIS, Porto Alegre, RS, Brazil[Gales, Ana C.; Furtado, Guilherme H. C.; da Silva, Juliana O.; Correa, Luci; Cayo, Rodrigo; Martins, Willames M. B. S.] Univ Fed Sao Paulo UNIFESP, Disciplina Infectol, Dept Med, Sao Paulo, SP, Brazil[Levin, Anna S.; Rossi, Flavia; Silva, Mariama T.; Oliveira, Maura S.; Dalben, Mirian F.; Santos, Sania A.] Univ Sao Paulo, Inst Med Trop USP LIM 54, Dept Patol LIM 03, Hosp Clin,Fac Med, Sao Paulo, SP, Brazil[Lucarevschi, Bianca R.; Moreira, Marina] Universidade de Taubaté (Unitau) , Dept Med[Cabral, Blenda G.; Brasiliense, Danielle M.; Carneiro, Irna Carla R. S.; Lima, Karla V. B.; da Conceicao, Marilia L.] Fundacao Santa Casa Misericordia Para UFPA, Belem, Para, Brazil[Cabral, Blenda G.; Brasiliense, Danielle M.; Carneiro, Irna Carla R. S.; Lima, Karla V. B.; da Conceicao, Marilia L.] Inst Evandro Chagas SVS MS, Belem, Para, Brazil[Ribeiro, Julival; Guzman, Ricardo D.] Hosp Base, Brasilia, DF, Brazil[Correa, Luci; Martino, Marines D. V.] Hosp Israelita Albert Einstein HIAE, Sao Paulo, SP, Brazil[Correa, Luci; Martino, Marines D. V.] Fac Ciencias Med Santa Casa Sao Paulo, Sao Paulo, SP, Brazil[Britto, Maria H.; de Freitas, Manse R.; Morais, Rosangela] Univ Fed Rio Grande Norte UFRN, Ctr Patol Clin, Natal, RN, Brazi
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