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1.
BMC Urol ; 21(1): 137, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34579682

RESUMO

BACKGROUND: Because of their specific and biologically relevant cargo, urine extracellular vesicles (EVs) constitute a valuable source of potential non-invasive biomarkers that could support the clinical decision-making to improve the management of prostate cancer (PCa) patients. Different EV isolation methods differ in terms of complexity and yield, conditioning, as consequence, the analytical result. METHODS: The aim of this study was to compare three different isolation methods for urine EVs: ultracentrifugation (UC), size exclusion chromatography (SEC), and a commercial kit (Exolute® Urine Kit). Urine samples were collected from 6 PCa patients and 4 healthy donors. After filtered through 0.22 µm filters, urine was divided in 3 equal volumes to perform EVs isolation with each of the three approaches. Isolated EVs were characterized by spectrophotometric protein quantification, nanoparticle tracking analysis, transmission electron microscopy, AlphaScreen Technology, and whole miRNA Transcriptome. RESULTS: Our results showed that UC and SEC provided better results in terms of EVs yield and purity than Exolute®, non-significant differences were observed in terms of EV-size. Interestingly, luminescent AlphaScreen assay demonstrated a significant enrichment of CD9 and CD63 positive microvesicles in SEC and UC methods compared with Exolute®. This heterogeneity was also demonstrated in terms of miRNA content indicating that the best correlation was observed between UC and SEC. CONCLUSIONS: Our study highlights the importance of standardizing the urine EV isolation methods to guaranty the analytical reproducibility necessary for their implementation in a clinical setting.


Assuntos
Vesículas Extracelulares , Neoplasias da Próstata/urina , Cromatografia em Gel , Humanos , Masculino , Ultracentrifugação , Urinálise
2.
J Proteome Res ; 19(10): 4082-4092, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-32924497

RESUMO

Prostate cancer (PCa) is a hormone-dependent tumor characterized by an extremely heterogeneous prognosis. Despite recent advances in partially uncovering some of the biological processes involved in its progression, there is still an urgent need for identifying more accurate and specific prognostic procedures to differentiate between disease stages. In this context, targeted approaches, focused on mapping dysregulated metabolic pathways, could play a critical role in identifying the mechanisms driving tumorigenesis and metastasis. In this study, a targeted analysis of the nuclear magnetic resonance-based metabolomic profile of PCa patients with different tumor grades, guided by transcriptomics profiles associated with their stages, was performed. Serum and urine samples were collected from 73 PCa patients. Samples were classified according to their Gleason score (GS) into low-GS (GS < 7) and high-GS PCa (GS ≥ 7) groups. A total of 36 metabolic pathways were found to be dysregulated in the comparison between different PCa grades. Particularly, the levels of glucose, glycine and 1-methlynicotinamide, metabolites involved in energy metabolism and nucleotide synthesis were significantly altered between both groups of patients. These results underscore the potential of targeted metabolomic profiling to characterize relevant metabolic changes involved in the progression of this neoplastic process.


Assuntos
Neoplasias da Próstata , Humanos , Masculino , Metabolômica , Gradação de Tumores , Prognóstico , Neoplasias da Próstata/diagnóstico
3.
Int J Mol Sci ; 21(8)2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32316350

RESUMO

The purpose of this study is to clinically validate a series of circulating miRNAs that distinguish between the 4 most prevalent tumor types (lung cancer (LC); breast cancer (BC); colorectal cancer (CRC); and prostate cancer (PCa)) and healthy donors (HDs). A total of 18 miRNAs and 3 housekeeping miRNA genes were evaluated by qRT-PCR on RNA extracted from serum of cancer patients, 44 LC, 45 BC, 27 CRC, and 40 PCa, and on 45 HDs. The cancer detection performance of the miRNA expression levels was evaluated by studying the area under the curve (AUC) of receiver operating characteristic (ROC) curves at univariate and multivariate levels. miR-21 was significantly overexpressed in all cancer types compared with HDs, with accuracy of 67.5% (p = 0.001) for all 4 tumor types and of 80.8% (p < 0.0001) when PCa cases were removed from the analysis. For each tumor type, a panel of miRNAs was defined that provided cancer-detection accuracies of 91%, 94%, 89%, and 77%, respectively. In conclusion, we have described a series of circulating miRNAs that define different tumor types with a very high diagnostic performance. These panels of miRNAs would constitute the basis of different approaches of cancer-detection systems for which clinical utility should be validated in prospective cohorts.


Assuntos
Neoplasias da Mama/genética , MicroRNA Circulante/sangue , Neoplasias Colorretais/genética , Neoplasias Pulmonares/genética , Neoplasias da Próstata/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Detecção Precoce de Câncer , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Curva ROC
4.
BMC Cancer ; 17(1): 367, 2017 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-28545426

RESUMO

BACKGROUND: Prostate cancer (PCa) is characterized by clinical and biological heterogeneity and has differential outcomes and mortality rates. Therefore, it is necessary to identify molecular alterations to define new therapeutic strategies based on the risk of progression. In this study, the prognostic relevance of the insulin-like growth factor (IGF) system was examined in molecular subtypes defined by TMPRSS2-ERG (T2E) gene fusion within a series of patients with primary localized PCa. METHODS: A cohort of 270 formalin-fixed and paraffin-embedded (FFPE) primary PCa samples from patients with more than 5 years' follow-up was collected. IGF-1R, IGF-1, IGFBP-3 and INSR expression was analyzed using quantitative RT-PCR. The T2E status and immunohistochemical ERG findings were considered in the analyses. The association with both biochemical and clinical progression-free survival (BPFS and PFS, respectively) was evaluated for the different molecular subtypes using the Kaplan-Meier proportional risk log-rank test and the Cox proportional hazards model. RESULTS: An association between IGF-1R overexpression and better BPFS was found in T2E-negative patients (35.3% BPFS, p-value = 0.016). Multivariate analysis demonstrated that IGF-1R expression constitutes an independent variable in T2E-negative patients [HR: 0.41. CI 95% (0.2-0.82), p = 0.013]. These data were confirmed using immunohistochemistry of ERG as subrogate of T2E. High IGF-1 expression correlated with prolonged BPFS and PFS independent of the T2E status. CONCLUSIONS: IGF-1R, a reported target of T2E, constitutes an independent factor for good prognosis in T2E-negative PCa. Quantitative evaluation of IGF-1/IGF-1R expression combined with molecular assessment of T2E status or ERG protein expression represents a useful marker for tumor progression in localized PCa.


Assuntos
Proteínas de Fusão Oncogênica , Neoplasias da Próstata/metabolismo , Receptores de Somatomedina/metabolismo , Serina Endopeptidases/genética , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Progressão da Doença , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade , Receptor IGF Tipo 1 , Receptores de Somatomedina/análise , Receptores de Somatomedina/genética , Regulador Transcricional ERG/genética
5.
Arch Esp Urol ; 67(5): 462-72, 2014 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-24914846

RESUMO

Identification of biomarkers that, at the time of diagnosis of prostate cancer (PCa), are associated with presence of disease or a more aggressive behavior will transform the clinical management of this disease. If both patients and clinicians would have reproducible and valid tools to estimate the specific risk of morbidity associated with PCa, then many patients would opt to and join active surveillance (AS) protocols, and consequently costs and comorbidities associated with the current overtreatment of prostate cancer would be reduced. Thus, a biomarker, or a panel of biomarkers, with high specificity to identify patients at risk for progression in AS protocols, would identify those men who could benefit from less intensive AS protocols with less repeated biopsies, so reducing the risk and cost of these invasive procedures. In this review we try to offer an overview of the new markers identified by genomic techniques and to discuss their potential role in an AS context. Moreover, the AS protocol offers an adequate setting for validation of biomarkers associated to disease progression.


Assuntos
Biomarcadores Tumorais/sangue , Seleção de Pacientes , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Progressão da Doença , Humanos , Masculino , Neoplasias da Próstata/genética , Conduta Expectante
6.
ScientificWorldJournal ; 2013: 904067, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24302878

RESUMO

An increased number of dengue cases with neurological complications have been reported in recent years. The lack of reliable animal models for dengue has hindered studies on dengue virus (DENV) pathogenesis and cellular tropism in vivo. We further investigate the tropism of DENV for the human central nervous system (CNS), characterizing DENV interactions with cell surface proteins in human CNS cells by virus overlay protein binding assays (VOPBA) and coimmunoprecipitations. In VOPBA, three membrane proteins (60, 70, and 130 kDa) from the gray matter bound the entire virus particle, whereas only a 70 kDa protein bound in white matter. The coimmunoprecipitation assays revealed three proteins from gray matter consistently binding virus particles, one clearly distinguishable protein (~32 kDa) and two less apparent proteins (100 and 130 kDa). Monoclonal anti-NS3 targeted the virus protein in primary cell cultures of human CNS treated with DENV-2, which also stained positive for NeuH, a neuron-specific marker. Thus, our results indicate (1) that DENV-2 exhibited a direct tropism for human neurons and (2) that human neurons sustain an active DENV replication as was demonstrated by the presence of the NS3 viral antigen in primary cultures of these cells treated with DENV-2.


Assuntos
Vírus da Dengue/fisiologia , Proteínas Virais/metabolismo , Replicação Viral , Adolescente , Encéfalo/virologia , Criança , Vírus da Dengue/metabolismo , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Imunoprecipitação , Técnicas In Vitro , Masculino , Ligação Proteica
7.
Arch Esp Urol ; 75(2): 203-214, 2022 Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35332890

RESUMO

In the recent years, research in oncologyhas focused on liquid biopsies, which rely on thedetection of cancer-derived components, includingcirculating tumor cells (CTCs), circulating tumor DNA(ctDNA), circulating free RNA (cfRNA), and extracellularvesicles (EVs), in the biofluids of patients, providinggenomic, epigenetic and transcriptomic, informationabout tumors and metastatic sites. In this reviewwe collect current evidence regarding the potentialof liquid biopsies for the diagnosis and follow-up ofuro-oncology patients, as well as the advantages andlimitations of these approaches. Although promising,the way in which this methodology must be incorporatedinto the clinical routine needs to be still definedboth at the pre-analytical and analytical level beforetheir clinical utility is demonstrated.


En los últimos años, la investigación enoncología se ha centrado en las biopsias líquidas, quese basan en la detección de elementos derivados delcáncer, incluyendo las células tumorales circulantes(CTCs), el ADN tumoral circulante (ctDNA), el ARN librecirculante (cfRNA), y las vesículas extracelulares(EVs) en los biofluidos de los pacientes, proporcionandoinformación genómica, epigenética y transcriptómicade los tumores y sus metástasis. En estarevisión recogemos la evidencia actual a cerca delpotencial de las biopsias líquidas para el diagnósticoy el seguimiento de los pacientes uro-oncológicos,sus ventajas y sus limitaciones. Aunque su potenciales prometedor, la forma en que esta metodología hade incorporarse a la clínica asistencial necesita definirsetanto a nivel pre-analítico como analítico antesde que se pueda demostrar su utilidad clínica.


Assuntos
DNA Tumoral Circulante , Células Neoplásicas Circulantes , Biomarcadores Tumorais , DNA Tumoral Circulante/genética , Humanos , Biópsia Líquida/métodos , Células Neoplásicas Circulantes/patologia , Prognóstico
8.
Transbound Emerg Dis ; 67(5): 1768-1775, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32129921

RESUMO

This study set out to identify the presence of bovine immunodeficiency virus (BIV) in animals geographically located in Mexico. BIV was first discovered in the United States in a dairy cow with persistent lymphocytosis, lymphoid hyperplasia and lymphocytic encephalitis. Many studies indicate that BIV infection is globally distributed, but its presence in Mexico remains unknown. We collected 1,168 heparinized blood samples from cattle in ten states across the Mexican Republic, then separated plasma using centrifugation and tested for antibodies against BIV. We used an indirect ELISA based on the use of a synthetic peptide derived from transmembrane glycoprotein (gp45/TM). In order to identify the viral genome, we designed a synthetic gene as a PCR control, as well as a pair of oligonucleotides for amplifying a 519 bp product of the env gene which encodes the surface protein. Positive amplicons were purified and subjected to nucleotide sequencing. A total of 189 (28.94%) tested plasma samples suggest the presence of specific anti-BIV antibodies in all states studied except for Chiapas. Additionally, PCR results identified six positive cows in the states of Puebla and Coahuila. BIV in these cows was confirmed via nucleotide sequencing and in silico analysis of these samples. This is the first report of the presence of BIV in Mexican cattle.

9.
Virus Res ; 280: 197900, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32070688

RESUMO

The env gene in Small Ruminant Lentiviruses (SRLV) encodes the surface glycoprotein (SU) that divides into conserved (C1-C4) and variable regions (V1-V5). SRLV region V4 has been found to be homologous to the V3 region of human lentivirus (HIV). HIV V3 is responsible for tropism and the development of nervous clinical patterns when there is a tendency to conserve amino acids in specific "signature pattern" positions. The goal of this study was to identify signature patterns in the V4 region of the SU, which is encoded by the SRLV env gene. Secondarily, to understand how these signature patterns are associated with different clinical status in naturally infected sheep and goats. Starting with 244 samples from seropositive animals from nine Mexican states, we amplified the V4 region using nested PCR and obtained 49 SRLV sequences from peripheral blood leukocytes. Based on phylogenetic analysis results, we identified three groups: asymptomatic genotypes A (Ssx GA) and B (Ssx GB), as well as animals with arthritic presentation, genotype B (A GB). Similarity levels between group sequences ranged from 67.9%-86.7%, with a genetic diversity ranging from 12.7%-29.5% and a dN / dS ratio that indicated negative selection. Analyses using Vespa and Entropy programs identified four residues at positions 54, 78, 79 and 82 in SU region V4 as possible signature patterns, although with variable statistical significance. However, position 54 residues "N" (p = 0.017), "T" (p = 0.001) and "G" (p = 0.024) in groups A GB, Ssx GA and Ssx GB respectively, best characterized the signature patterns. The results obtained identified a signature pattern related to different genotypes and clinical status by SRLV in sheep and goats.


Assuntos
Variação Genética , Infecções por Lentivirus/veterinária , Lentivirus/genética , Proteínas do Envelope Viral/genética , Animais , Infecções Assintomáticas , Feminino , Genótipo , Doenças das Cabras/virologia , Cabras , Lentivirus/classificação , Infecções por Lentivirus/virologia , Masculino , Filogenia , Análise de Sequência de DNA , Ovinos , Doenças dos Ovinos/virologia , Transcriptoma
10.
Trop Med Infect Dis ; 4(2)2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31083297

RESUMO

Bats can host pathogenic organisms such as viruses and fungi, but little is known about the pathogenicity of their parasites. Hemoparasites are frequently recorded in Neotropical bats, particularly Litomosoides (Filarioidea: Onchocercidae), but their pathogenic effect on bats is scarcely known. In this work, Litomosoides microfilariae were identified in four (8%) out of 51 sampled frugivorous bats belonging to three different species: Artibeus aztecus, Artibeus jamaicensis, and Artibeus lituratus, which are located in Yautepec, Morelos, Mexico. Two infected animals showed weakness, tachypnoea, and ecchymosis on their wings. In these animals, histopathology revealed microfilariae in the blood vessels of the lung, liver, and spleen. Both animals presented exudative pneumonia with congestion and concomitant edema, in addition to moderate arterial hypertrophy. Parasitemia was quantified in blood samples of the infected animals (>3000 parasites/mL). Phylogenetic analysis placed the obtained sequence inside the Litomosoides genus, reaching over 98% identity to the related species. Due to the relevance of bats in ecosystems, any new record of their parasite repertoire offers noteworthy insights into our understanding of the ecology and impact of new parasite species in bats.

11.
Vector Borne Zoonotic Dis ; 18(5): 258-265, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29652641

RESUMO

Bartonellae are emerging blood-borne bacteria that have been recovered from a wide range of mammalian species and arthropod vectors around the world. Bats are now recognized as a potential wildlife reservoir for a diverse number of Bartonella species, including the zoonotic Candidatus B. mayotimonensis. These bat-borne Bartonella species have also been detected in the obligate ectoparasites of bats, such as blood-feeding flies, which could transmit these bacteria within bat populations. To better understand this potential for transmission, we investigated the relatedness between Bartonella detected or isolated from bat hosts sampled in Mexico and their ectoparasites. Bartonella spp. were identified in bat flies collected on two bat species, with the highest prevalence in Trichobius parasiticus and Strebla wiedemanni collected from common vampire bats (Desmodus rotundus). When comparing Bartonella sequences from a fragment of the citrate synthase gene (gltA), vector-associated strains were diverse and generally close to, but distinct from, those recovered from their bacteremic bat hosts in Mexico. Complete Bartonella sequence concordance was observed in only one bat-vector pair. The diversity of Bartonella strains in bat flies reflects the frequent host switch by bat flies, as they usually do not live permanently on their bat host. It may also suggest a possible endosymbiotic relationship with these vectors for some of the Bartonella species carried by bat flies, whereas others could have a mammalian host.


Assuntos
Infecções por Bartonella/veterinária , Bartonella/isolamento & purificação , Quirópteros/parasitologia , Dípteros/microbiologia , Reservatórios de Doenças/parasitologia , Animais , Bartonella/genética , Infecções por Bartonella/epidemiologia , Infecções por Bartonella/microbiologia , Quirópteros/microbiologia , Dípteros/classificação , Reservatórios de Doenças/microbiologia , Variação Genética , Humanos , México/epidemiologia , Filogenia , Prevalência , Zoonoses
12.
Arch. esp. urol. (Ed. impr.) ; 75(2): 203-214, mar. 28, 2022.
Artigo em Espanhol | IBECS (Espanha) | ID: ibc-203682

RESUMO

En los últimos años, la investigación enoncología se ha centrado en las biopsias líquidas, quese basan en la detección de elementos derivados delcáncer, incluyendo las células tumorales circulantes(CTCs), el ADN tumoral circulante (ctDNA), el ARN librecirculante (cfRNA), y las vesículas extracelulares(EVs) en los biofluidos de los pacientes, proporcionandoinformación genómica, epigenética y transcriptómicade los tumores y sus metástasis. En estarevisión recogemos la evidencia actual a cerca delpotencial de las biopsias líquidas para el diagnósticoy el seguimiento de los pacientes uro-oncológicos,sus ventajas y sus limitaciones. Aunque su potenciales prometedor, la forma en que esta metodología hade incorporarse a la clínica asistencial necesita definirsetanto a nivel pre-analítico como analítico antesde que se pueda demostrar su utilidad clínica. (AU)


In the recent years, research in oncologyhas focused on liquid biopsies, which rely on thedetection of cancer-derived components, includingcirculating tumor cells (CTCs), circulating tumor DNA(ctDNA), circulating free RNA (cfRNA), and extracellularvesicles (EVs), in the biofluids of patients, providinggenomic, epigenetic and transcriptomic, informationabout tumors and metastatic sites. In this reviewwe collect current evidence regarding the potentialof liquid biopsies for the diagnosis and follow-up ofuro-oncology patients, as well as the advantages andlimitations of these approaches. Although promising,the way in which this methodology must be incorporatedinto the clinical routine needs to be still definedboth at the pre-analytical and analytical level beforetheir clinical utility is demonstrated. (AU)


Assuntos
Humanos , DNA Tumoral Circulante/genética , Células Neoplásicas Circulantes , Biomarcadores Tumorais , Biópsia Líquida/métodos , Prognóstico
13.
Rev Med Inst Mex Seguro Soc ; 55(Suppl 3): S222-S330, 2017.
Artigo em Espanhol | MEDLINE | ID: mdl-29192747

RESUMO

Cancer is a public health problem with an impact on Health Services in Mexico; it is also, one of the leading causes of mortality (mortality rate: 610.6 / 100 000) and is expected to double the total number of new cases by 2035 (GLOBOCAN). The most frequent neoplasms are the malignant tumor of breast, prostate, cervix and uterin, colorectal and pulmonary. The most affected groups are the female, and by age the 65 years and older (INEGI). At the IMSS, the mortality rate for malignant tumors has varied, with a sustained decline since 2010. In the last 15 years there has been a growth of 15% of the Disability Adjusted Life Years; during which the IMSS spent 2% of its current expenditure resources of the Health Insurance and Maternity. The IMSS has a network of medical units capable of attending to the process of prevention, early detection, diagnosis, treatment and rehabilitation of cancer patients. With the commitment of its improvement and to fulfill the National Health Programs, the OncoIMSS Program was created, with a reorganization of the care process with opportunity, quality, optimization of resources, regionalization, strengthening of infrastructure and trained human capital.


El cáncer es un problema de salud pública con impacto en los Servicios de Salud en México; es una de las principales causas de mortalidad (tasa de mortalidad: 610.6 / 100 000 habitantes) y se espera que duplique el total de casos nuevos para el año 2035 (GLOBOCAN). Las neoplasias más frecuentes son el tumor maligno de mama, próstata, cervicouterino, colorrectal y pulmonar. Los grupos más afectados son: el femenino y por grupo etario el mayor a 65 años (INEGI). En el IMSS, la tasa de mortalidad por tumores malignos ha variado, con disminución sostenida desde el 2010. En los últimos 15 años ha habido un crecimiento del 15% de Años de Vida Ajustados por Discapacidad; durante el cual el Instituto erogó el 2% de los recursos del gasto corriente del Seguro de Enfermedades y Maternidad. El Instituto cuenta con una red de unidades médicas con capacidad para atender el proceso de prevención, detección precoz, diagnóstico, tratamiento y rehabilitación del paciente oncológico. Con el compromiso de su mejora y para dar cumplimiento a los Programas Nacionales de Salud se crea el Programa OncoIMSS, con reordenamiento del proceso de atención con oportunidad, calidad, optimización de recursos, regionalización, fortalecimiento de infraestructura y capital humano capacitado.


Assuntos
Academias e Institutos/organização & administração , Programas Nacionais de Saúde/organização & administração , Neoplasias/terapia , Previdência Social/organização & administração , Adulto , Idoso , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Qualidade da Assistência à Saúde , Anos de Vida Ajustados por Qualidade de Vida
14.
Metabolomics ; 13(5): 52, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28804274

RESUMO

INTRODUCTION: Prostate cancer (PCa) is one of the most common malignancies in men worldwide. Serum prostate specific antigen (PSA) level has been extensively used as a biomarker to detect PCa. However, PSA is not cancer-specific and various non-malignant conditions, including benign prostatic hyperplasia (BPH), can cause a rise in PSA blood levels, thus leading to many false positive results. OBJECTIVES: In this study, we evaluated the potential of urinary metabolomic profiling for discriminating PCa from BPH. METHODS: Urine samples from 64 PCa patients and 51 individuals diagnosed with BPH were analysed using 1H nuclear magnetic resonance (1H-NMR). Comparative analysis of urinary metabolomic profiles was carried out using multivariate and univariate statistical approaches. RESULTS: The urine metabolomic profile of PCa patients is characterised by increased concentrations of branched-chain amino acids (BCAA), glutamate and pseudouridine, and decreased concentrations of glycine, dimethylglycine, fumarate and 4-imidazole-acetate compared with individuals diagnosed with BPH. CONCLUSION: PCa patients have a specific urinary metabolomic profile. The results of our study underscore the clinical potential of metabolomic profiling to uncover metabolic changes that could be useful to discriminate PCa from BPH in a clinical context.

15.
Eur J Cancer ; 50(17): 2994-3002, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25204806

RESUMO

AIMS: Speckle-type POZ protein (SPOP) is an E3 ubiquitin ligase adaptor recently described to be mutated in prostate cancer (PCa). Hence, studying the gene expression profile and the presence of SPOP mutations in PCa and understanding its clinico-pathological significance as prognostic and therapeutic biomarker are important to further understand its role in PCa development. PATIENTS AND METHODS: A cohort of 265 paraffin-embedded PCa samples from patients with more than 5 years of follow-up and treated with radical prostatectomy were collected at our institution for SPOP evaluation. RT-qPCR analysis was performed for expression studies while mutations were assessed by next generation sequencing. Relationship with prognosis was analysed using log-rank analysis and multivariable Cox regression. RESULTS: SPOP was found to be strongly down-regulated in PCa (median=0.24; range=0.04-9.98) and its expression was associated with both, biochemical (p=0.003) and clinical progression free survival (p=0.023), the very low SPOP expression levels being associated to the worst prognosis. Multivariate analysis demonstrated that low levels of SPOP independently predicted a worse prognosis for both, biochemical (Hazard ratio (HR)=0.5; confidence interval (CI) 95% [0.4-0.9], p=0.011) and clinical progression (HR=0.6; IC 95% [0.4-1], p=0.046). SPOP mutations were found in 10% of TMPRSS2-ERG (T2E)-negative cases. Log-rank tests showed that mutations were significantly associated with biochemical progression free survival (BPFS) (p=0.009) and also were significant in the multivariable analysis (HR=3.4; IC 95% [1.5-7.6], p=0.004). CONCLUSIONS: The present study demonstrates that prognosis varies depending on SPOP expression and mutational status, hence, defining a new biotype of PCa associated with a worse prognosis.


Assuntos
Mutação/genética , Proteínas Nucleares/genética , Neoplasias da Próstata/genética , Proteínas Repressoras/genética , Adulto , Idoso , Progressão da Doença , Regulação para Baixo , Marcadores Genéticos/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas Nucleares/metabolismo , Prognóstico , Neoplasias da Próstata/patologia , RNA Neoplásico/análise , Proteínas Repressoras/metabolismo
16.
Arch. esp. urol. (Ed. impr.) ; 67(5): 462-472, jun. 2014. ilus, tab, graf
Artigo em Espanhol | IBECS (Espanha) | ID: ibc-124042

RESUMO

La identificación de biomarcadores que, en el momento del diagnóstico del CaP, se asocian con la presencia de enfermedad o de un comportamiento más agresivo del CaP transformará el manejo clínico de esta enfermedad. Si tanto los pacientes como los clínicos contaran con herramientas reproducibles y válidas para estimar el riesgo específico de la morbilidad asociada al CaP, entonces muchos pacientes optarían y se adherirían a los protocolos de vigilancia activa (VA), y consecuentemente se reducirían los costes y comorbilidades asociados al sobretratamiento actual del CaP. Así un biomarcador, o un panel de biomarcadores, con elevada especificidad para identificar pacientes con riesgo de progresión en protocolos de VA, identificaría a aquellos hombres que pudieran beneficiarse de protocolos de VA menos intensos con menos biopsias de repetición, reduciendo así el riesgo y los costes de estos procedimientos invasivos. En esta revisión se pretende ofrecer una visión de los nuevos biomarcadores identificados por técnicas genómicas y discutir su posible papel en un contexto de VA. Por otra parte, el protocolo de VA, ofrece un marco adecuado para la validación de biomarcadores asociados a la progresión de la enfermedad


Identification of biomarkers that, at the time of diagnosis of prostate cancer (PCa) , are associated with presence of disease or a more aggressive behavior will transform the clinical management of this disease. If both patients and clinicians would have reproducible and valid tools to estimate the specific risk of morbidity associated with PCa, then many patients would opt to and join active surveillance (AS) protocols, and consequently costs and comorbidities associated with the current overtreatment of prostate cancer would be reduced. Thus, a biomarker, or a panel of biomarkers, with high specificity to identify patients at risk for progression in AS protocols, would identify those men who could benefit from less intensive AS protocols with less repeated biopsies, so reducing the risk and cost of these invasive procedures. In this review we try to offer an overview of the new markers identified by genomic techniques and to discuss their potential role in an AS context. Moreover, the AS protocol offers an adequate setting for validation of biomarkers associated to disease progression


Assuntos
Humanos , Masculino , Neoplasias da Próstata/terapia , Cuidados Pré-Operatórios/métodos , Biomarcadores Tumorais/análise , Conduta Expectante , Complicações Pós-Operatórias/prevenção & controle , Efeitos Psicossociais da Doença
17.
Cochabamba; s.n; marzo 2010. 60 p. ilus, tab, graf.
Tese em Espanhol | LIBOCS, LIBOSP | ID: biblio-1305714

RESUMO

El presente proyecto tiene la finalidad de solucionar el problema de la dotación de agua potable a nivel domiciliario, con la construccion de un sistema de aducción y distribución, utilizando para ello dos vertientes como fuente de agua


Assuntos
Água Potável , Consumo Doméstico de Água , Consumo de Água (Saúde Ambiental) , Grupos Populacionais , Bolívia , População Rural
18.
Cochabamba; s.n; 201003. 50 p. ^eEmpastado.
Tese em Espanhol | LIBOCS, LILACS, LIBOSP | ID: biblio-1308000

RESUMO

El presente proyecto tiene la finalidad de solucionar el problema de la dotación de agua potable a nivel domiciliario, con la construcción de un sistema de aducción y disribución, utilizando para ello dos vertientes como fuente de agua, las cuales serán llevadas a un tanque para ser distribuidas después de cada uno de los domicilios de las familias que viven en el área del Sindicato Villa Bolivar A y la Comunidad Indígena Yucaré Secejsamma e indirectamente a los sindicatos que se encuentran alrededor de este sindicato como son 1ro de Diciembre, 4 de octubre, 9 de abril, Santa Ana, Sucre, Comuna y Uncia A. Objetivo General.- Contribuir a mejorar la calidad de vida de los pobladores de las comunidades de la Central Isoboro A, disminuyendo los casos de enfermedades diarreícas, enteroparasitosis e infecciones de la piel ocasionadas por el agua, proporcionando el servicio de agua potable segura para el consumo y el aseo.


Assuntos
Água , Grupos Populacionais , Medicina de Família e Comunidade
19.
Cochabamba; s.n; 201003. 50 p. ^eEmpastado.
Tese em Espanhol | LIBOCS, LILACS, LIBOSP | ID: biblio-1308001

RESUMO

El presente proyecto tiene la finalidad de solucionar el problema de la dotación de agua potable a nivel domiciliario, con la construcción de un sistema de aducción y disribución, utilizando para ello dos vertientes como fuente de agua, las cuales serán llevadas a un tanque para ser distribuidas después de cada uno de los domicilios de las familias que viven en el área del Sindicato Villa Bolivar A y la Comunidad Indígena Yucaré Secejsamma e indirectamente a los sindicatos que se encuentran alrededor de este sindicato como son 1ro de Diciembre, 4 de octubre, 9 de abril, Santa Ana, Sucre, Comuna y Uncia A. Objetivo General.- Contribuir a mejorar la calidad de vida de los pobladores de las comunidades de la Central Isoboro A, disminuyendo los casos de enfermedades diarreícas, enteroparasitosis e infecciones de la piel ocasionadas por el agua, proporcionando el servicio de agua potable segura para el consumo y el aseo.


Assuntos
Água , Grupos Populacionais , Medicina de Família e Comunidade
20.
Cochabamba; s.n; 200906. 90 p. ^eEmpastado.
Tese em Espanhol | LIBOCS, LILACS, LIBOSP | ID: biblio-1308032

RESUMO

La información sobre el diagnóstico Socioeconómico, político y cultural de la población de la Central Isiboro "A", constituye un instrumento importante para los pobladores y otras personas que quieran saber del lugar, al permitir la elaboración de programas, líneas de acción y proyectos basados en hechos y objetivos de la realidad de las comunidades de esta Central. Los avances metodológicos en relación a este trabajo descriptivo y observacional de corte transversal, que tiene universos delimitados, representan un marco de referencia para profundizar el conocimiento de la forma de vida de estas comunidades, de los problemas que afectan a su salud y las causas que los determinan. En esta oportunidad trato de realizar un análisis de las características sociales, económicas, políticas y culturales que inciden en el proceso salud y enfermedad de estas comunidades y por ende en su desarrollo y su buen vivir.


Assuntos
Cultura , População , Saúde , Medicina
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