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1.
Biochem Biophys Res Commun ; 446(4): 863-9, 2014 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-24657443

RESUMO

Gallbladder cancer is an uncommon but lethal malignancy with particularly high incidence in Chile, India, Japan and China. There is a paucity of unbiased large-scale studies investigating molecular basis of gallbladder cancer. To systematically identify differentially regulated proteins in gallbladder cancer, iTRAQ-based quantitative proteomics of gallbladder cancer was carried out using Fourier transform high resolution mass spectrometry. Of the 2575 proteins identified, proteins upregulated in gallbladder cancer included several lysosomal proteins such as prosaposin, cathepsin Z and cathepsin H. Downregulated proteins included serine protease HTRA1 and transgelin, which have been reported to be downregulated in several other cancers. Novel biomarker candidates including prosaposin and transgelin were validated to be upregulated and downregulated, respectively, in gallbladder cancer using tissue microarrays. Our study provides the first large scale proteomic characterization of gallbladder cancer which will serve as a resource for future discovery of biomarkers for gallbladder cancer.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Vesícula Biliar/patologia , Vesícula Biliar/patologia , Proteínas dos Microfilamentos/análise , Proteínas Musculares/análise , Saposinas/análise , Biomarcadores Tumorais/genética , Cromatografia Líquida , Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Proteínas dos Microfilamentos/genética , Proteínas Musculares/genética , Proteoma/análise , Proteoma/genética , Proteômica , Saposinas/genética , Espectrometria de Massas em Tandem , Análise Serial de Tecidos
2.
Pathologe ; 35(3): 277-82, 2014 May.
Artigo em Alemão | MEDLINE | ID: mdl-24043213

RESUMO

Primary presacral neuroendocrine tumors are a rare entity with less than 30 cases described in the literature so far. Here we report of a primary presacral neuroendocrine tumor diagnosed at autopsy which was wrongly diagnosed as metastasized prostate cancer before. Misdiagnosis was due to the localization of the tumor, its morphology and its positivity for prostate-specific acid phosphatase (PSAP) when the patient was alive. This is the first report of PSAP and somatostatin receptor expression in this type of tumor.


Assuntos
Tumores Neuroendócrinos/patologia , Neoplasias da Próstata/patologia , Sacro/patologia , Saposinas/análise , Neoplasias da Coluna Vertebral/patologia , Idoso , Biomarcadores Tumorais/análise , Biópsia por Agulha , Transformação Celular Neoplásica/patologia , Erros de Diagnóstico , Progressão da Doença , Evolução Fatal , Humanos , Aumento da Imagem , Imageamento por Ressonância Magnética , Masculino , Tumores Neuroendócrinos/secundário , Polirradiculopatia/patologia , Próstata/patologia , Compressão da Medula Espinal/patologia , Neoplasias da Coluna Vertebral/secundário , Tomografia Computadorizada por Raios X
3.
Acta Trop ; 128(3): 591-7, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23988299

RESUMO

FhSAP2 is a novel antigen isolated from the adult fluke of Fasciola hepatica. Based on sequence similarity with amoebapores and other related proteins, it belongs to the saposin-like protein (SAPLIP) family. FhSAP2 has been shown to be highly immunogenic and capable of inducing protective immune responses in mice and rabbits challenged with F. hepatica. Moreover, FhSAP2 is also reactive with sera from humans with chronic fascioliasis. In the present study, we investigated the expression of FhSAP2 in various developmental stages of F. hepatica by qPCR and demonstrated that FhSAP2-mRNA species are up-regulated in undeveloped eggs, newly excysted juveniles, and adults, but down-regulated in the miracidium stage. Monoclonal antibodies against FhSAP2 were produced, and two clones that are positive to F. hepatica whole-body extract, but not reactive with extracts from other trematodes, were selected, expanded and used for histolocalization studies. Confocal immunofluorescence revealed the presence of native FhSAP2 in epithelial cells surrounding the gut, toward the outermost part of the tegument, and toward the tegumental cells of both adults and newly excysted juveniles.


Assuntos
Antígenos de Helmintos/análise , Antígenos de Helmintos/genética , Fasciola hepatica/química , Fasciola hepatica/genética , Perfilação da Expressão Gênica , Saposinas/análise , Saposinas/genética , Animais , Células Epiteliais/química , Trato Gastrointestinal/química , Humanos , Tegumento Comum , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Microscopia de Fluorescência , Coelhos
4.
Electrophoresis ; 34(11): 1663-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23417432

RESUMO

The present study was aimed at the identification of proteins that are differentially expressed in the urine of patients with prostate cancer (PCa), those with benign prostatic hyperplasia (BPH) and age-matched healthy male control subjects. Using a combination of 2DE and MS/MS, significantly lower expression of urinary saposin B and two different fragments of inter-alpha-trypsin inhibitor light chain (ITIL) was demonstrated in the PCa patients compared to the controls. However, only one of the ITIL fragments was significantly different between the PCa and BPH patients. When image analysis was performed on urinary proteins that were transferred onto NC membranes and detected using a lectin that binds to O-glycans, a truncated fragment of inter-alpha-trypsin inhibitor heavy chain 4 was the sole protein found to be significantly enhanced in the PCa patients compared to the controls. Together, these urinary peptide fragments might be useful complementary biomarkers to indicate PCa as well as to distinguish it from BPH, although further epidemiological evidence on the specificity and sensitivity of the protein candidates is required.


Assuntos
alfa-Globulinas/urina , Biomarcadores Tumorais/urina , Hiperplasia Prostática/urina , Neoplasias da Próstata/urina , Saposinas/urina , Idoso , alfa-Globulinas/análise , Sequência de Aminoácidos , Biomarcadores Tumorais/análise , Eletroforese em Gel Bidimensional , Glicosilação , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Próstata/patologia , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , Saposinas/análise , Espectrometria de Massas em Tandem
5.
Diagn Pathol ; 7: 106, 2012 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-22901743

RESUMO

AIM: The current paper describes a case of prostatic adenocarcinoma metastatic to the skin presenting as an extrammamary Paget's disease, a very rare and poorly characterised morphological entity. We report a case of prostatic carcinoma metastatic to skin showing a pattern of extramammary Paget's disease which has not been clearly illustrated in the literature Case presentation: A 63 year-old man with prostatic adenocarcinoma developed cutaneous metastases after 16 years. The inguinal metastases were sessile and 'keratotic.' The tumour displayed solid, glandular areas as well as a polypoid region suggestive of extramammary Paget's disease were identified. DISCUSSION AND CONCLUSIONS: We review the diagnostic criteria that have led to the correct histopathological diagnosis in this case. A differential diagnosis of the pagetoid spread in the skin and various forms of cutaneous metastases determined by a prostatic adenocarcinoma as well as the role of immunohistochemistry in establishing the prostatic origin are presented in the context of this case. Although, morphologically the cells presented in the skin deposits were not characteristic for adenocarcinoma of prostate, immunohistochemistry for PSA and PSAP suggested a prostatic origin. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1395450057455276.


Assuntos
Adenocarcinoma/secundário , Doença de Paget Extramamária/patologia , Neoplasias da Próstata/patologia , Neoplasias Cutâneas/secundário , Adenocarcinoma/química , Biópsia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Calicreínas/análise , Masculino , Pessoa de Meia-Idade , Doença de Paget Extramamária/química , Valor Preditivo dos Testes , Antígeno Prostático Específico/análise , Neoplasias da Próstata/química , Saposinas/análise , Neoplasias Cutâneas/química
6.
Dev Comp Immunol ; 36(3): 502-20, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21978453

RESUMO

Several groups of antimicrobial effector molecules have been identified in nematodes, but most studies have been limited to Caenorhabditis elegans and, to a lesser extent, Ascaris suum. Although these two species are not closely related, they are not representative of overall nematode diversity. This study utilized available sequence information to investigate whether four groups of antimicrobial effectors (defensin-like antibacterial factors [ABFs], cecropins, saposin domain-containing proteins, and lysozymes) are components of an archetypal nematode immune system or more narrowly restricted. Saposin domain-containing proteins (caenopores in C. elegans) and lysozymes were widely distributed and found in most taxa, but likely have digestive as well as defensive functions. ABFs were widely distributed in fewer taxa, suggesting selective loss in some lineages. In contrast, cecropins were identified in only three related species, suggesting acquisition of this effector molecule in their common ancestor.


Assuntos
Cecropinas/imunologia , Muramidase/imunologia , Nematoides/química , Nematoides/imunologia , Animais , Cecropinas/análise , Cecropinas/genética , Biologia Computacional , Defensinas/análise , Defensinas/genética , Defensinas/imunologia , Muramidase/análise , Muramidase/genética , Nematoides/classificação , Nematoides/metabolismo , Filogenia , Estrutura Terciária de Proteína , Saposinas/análise , Saposinas/genética , Saposinas/imunologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-19907127

RESUMO

Prosaposin is a precursor of saposins A, B, C, and D. Saposins are indispensable for lysosomal hydrolysis of sphingolipids. The notion that prosaposin itself is likely involved in brain development led us to generate an anti-mouse prosaposin-specific antibody that do not cross-react with any of the processed saposins. We have used it to study expression of prosaposin in the brain of wild-type (WT) and saposin D knockout mice (Sap-D(-/-)). Immunoblot studies indicated that prosaposin, already abundant in the brain of WT, was dramatically increased in Sap-D(-/-). By immunohistochemistry, the brain of WT was rich in prosaposin in hippocampal CA3 pyramidal neurons, tufted cells and mitral cells in olfactory bulb, and cerebellar Purkinje cells. In Sap-D(-/-), immunoreactivity of prosaposin was increased in these neurons, most notably in the CA3 pyramidal neurons which contained prosaposin immuno-positive inclusion bodies in the endoplasmic reticulum. Further characterization of these prosaposin-rich neurons may provide new insights into the physiological functions of prosaposin in the nervous system.


Assuntos
Anticorpos/imunologia , Encéfalo/metabolismo , Saposinas/deficiência , Saposinas/metabolismo , Animais , Reações Antígeno-Anticorpo/imunologia , Encéfalo/patologia , Regulação da Expressão Gênica , Immunoblotting , Imuno-Histoquímica , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Neurônios/patologia , Saposinas/análise , Saposinas/genética , Saposinas/imunologia
8.
Biochim Biophys Acta ; 1783(8): 1480-9, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18346466

RESUMO

The notion that prosaposin (Prosap) is likely involved in brain development and regeneration led us to explore its expression in stem/progenitor neural cells and its fate after cell differentiation. The expression of procathepsin-cathepsin D (proCath-Cath D), an endoprotease that plays an important role in the processing and sorting of Prosap, has been concomitantly examined. Our data evidenced that in embryonic human neural progenitor cells (eHNPCs) intact and high molecular weight intermediate forms of Prosap and intermediate forms of Cath D accumulated inside the cells, while the formation of saposins and mature Cath D was impaired. Furthermore, neither Prosap nor proCath D were secreted from eHNPCs. The block of the processing and secretion shared by Prosap and proCath D was overcome during the course of differentiation of eHNPCs into a mixed population of astrocytes and neuronal cells. Upon differentiation, large amounts of Prosap and proCath D were secreted from the cells, while saposins and mature Cath D were produced inside the cells. The dramatic accumulation of Prosap (an antiapoptotic factor) and reduction of mature Cath D (a proapoptotic factor) in the undifferentiated eHNPCs most likely play a role in the molecular mechanisms regulating the resistance to apoptotic signals of these cells and might represent a critically important issue in HNPCs biology.


Assuntos
Catepsina D/metabolismo , Precursores Enzimáticos/metabolismo , Neurônios/metabolismo , Precursores de Proteínas/metabolismo , Saposinas/metabolismo , Células-Tronco/metabolismo , Processamento Alternativo , Catepsina D/análise , Diferenciação Celular , Células Cultivadas , Precursores Enzimáticos/análise , Glicosídeo Hidrolases/metabolismo , Humanos , Neurônios/citologia , Neurônios/enzimologia , Bulbo Olfatório/citologia , Bulbo Olfatório/embriologia , Precursores de Proteínas/análise , Precursores de Proteínas/genética , Saposinas/análise , Saposinas/genética , Células-Tronco/citologia , Células-Tronco/enzimologia
9.
J Lipid Res ; 46(10): 2254-64, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16061947

RESUMO

A mass spectrometric method is described for monitoring cerebrosides in the presence of excess concentrations of alkali metal salts. This method has been adapted for use in the assay of arylsulfatase A (ASA) and the cerebroside sulfate activator protein (CSAct or saposin B). Detection of the neutral glycosphingolipid cerebroside product was achieved via enhancement of ionization efficiency in the presence of lithium ions. Assay samples were extracted into the chloroform phase as for the existing assays, dried, and diluted in methanol-chloroform-containing lithium chloride. Samples were analyzed by electrospray ionization mass spectrometry with a triple quadrupole mass spectrometer in the multiple reaction monitoring tandem mass spectrometric mode. The assay has been used to demonstrate several previously unknown or ambiguous aspects of the coupled ASA/CSAct reaction, including an absolute in vitro preference for CSAct over the other saposins (A, C, and D) and a preference for the non-hydroxylated species of the sulfatide substrate over the corresponding hydroxylated species. The modified assay for the coupled ASA/CSAct reaction could find applicability in settings in which the assay could not be performed previously because of the need for radiolabeled substrate, which is now not required.


Assuntos
Cerebrosídeo Sulfatase/análise , Saposinas/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Animais , Bovinos , Lítio/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
10.
Mol Genet Metab ; 83(3): 231-8, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15542394

RESUMO

Prenatal diagnosis is available for many lysosomal storage disorders (LSD) using chorionic villus samples or amniocytes. Such diagnoses can be problematical if sample transport and culture are required prior to analysis. The purpose of this study was to identify useful biochemical markers for the diagnosis of lysosomal storage disorders from amniotic fluid. Amniotic fluid samples from control (n=49) and LSD affected (n=36) pregnancies were analysed for the protein markers LAMP-1 and saposin C by ELISA, and for oligosaccharide and lipid metabolite markers by electrospray ionisation-tandem mass spectrometry. Lysosomal storage disorder samples include; aspartylglucosaminuria, galactosialidosis, Gaucher disease, GM1 gangliosidosis, mucopolysaccharidosis types I, II, IIIC, IVA, VI, and VII, mucolipidosis type II, multiple sulfatase deficiency, and sialidosis type II. Each disorder produced a unique signature metabolic profile of protein, oligosaccharide, and glycolipid markers. Some metabolite elevations directly related to the disorder whilst others appeared unrelated to the primary defect. Many lysosomal storage disorders were clearly distinguishable from control populations by the second trimester and in one case in the first trimester. Samples from GM1 gangliosidosis and mucopolysaccharidosis type VII displayed a correlation between gestational age and amount of stored metabolite. These preliminary results provide proof of principal for the use of biomarkers contained in amniotic fluid as clinical tests for some of the more frequent lysosomal storage disorders causal for hydrops fetalis.


Assuntos
Líquido Amniótico/química , Doenças Fetais/diagnóstico , Glicolipídeos/análise , Doenças por Armazenamento dos Lisossomos/diagnóstico , Oligossacarídeos/análise , Diagnóstico Pré-Natal/métodos , Antígenos CD/análise , Ensaio de Imunoadsorção Enzimática , Feminino , França , Idade Gestacional , Humanos , Proteínas de Membrana Lisossomal , Espectrometria de Massas/métodos , Gravidez , Saposinas/análise
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