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1.
Methods Mol Biol ; 2292: 17-22, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651348

RESUMO

Urine cell-free DNA is an important source of diagnostic markers for different diseases, especially for cancer. It could be important to achieve the urine cell-free DNA integrity to establish its provenience from cancer cells or dead inflammatory cells for necrosis in urine or from normal cells with the purpose to use it as an early diagnostic tool for urological cancers or other diseases. Here we describe a simple, noninvasive approach from urine collection to DNA integrity analysis using real-time PCR.


Assuntos
Ácidos Nucleicos Livres/urina , Neoplasias/urina , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/isolamento & purificação , Biomarcadores Tumorais/urina , Ácidos Nucleicos Livres/genética , Ácidos Nucleicos Livres/isolamento & purificação , Humanos , Neoplasias/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Coleta de Urina/métodos
2.
Methods Mol Biol ; 2292: 23-33, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651349

RESUMO

Urinary cell-free DNA offers an important noninvasive source of material for genomic testing also for nonurological tumors. Its clinical utility in monitoring tumor evolution and treatment failure is promising. Here we describe a method to detect cancer mutations into urine from patients affected by colorectal cancer.


Assuntos
Ácidos Nucleicos Livres/genética , Neoplasias Colorretais/genética , Análise Mutacional de DNA/métodos , Proteínas Proto-Oncogênicas p21(ras)/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/isolamento & purificação , Biomarcadores Tumorais/urina , Ácidos Nucleicos Livres/isolamento & purificação , Ácidos Nucleicos Livres/urina , Neoplasias Colorretais/urina , Humanos , Reação em Cadeia da Polimerase em Tempo Real/métodos
3.
Methods Mol Biol ; 2292: 3-15, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651347

RESUMO

Recent reports suggest that urine is a useful noninvasive tool for the identification of urogenital tumors, including bladder, prostate, kidney, and other nonurological cancers. As a liquid biopsy, urine represents an important source for the improvement of new promising biomarkers, a suitable tool to identify indolent cancer and avoid overtreatment. Urine is enriched with DNAs, RNAs, proteins, circulating tumor cells, exosomes, and other small molecules which can be detected with several diagnostic methodologies.We provide an overview of the ongoing state of urinary biomarkers underlying both their potential utilities to improve cancer prognosis, diagnosis, and therapeutic strategy and their limitations.


Assuntos
Biomarcadores Tumorais/urina , Neoplasias/urina , Animais , Ácidos Nucleicos Livres/urina , Exossomos/patologia , Humanos , Biópsia Líquida/métodos , Neoplasias/diagnóstico , Neoplasias/patologia , Ácidos Nucleicos/urina , Proteínas , Proteinúria/diagnóstico , Proteinúria/patologia , Proteinúria/urina , Urinálise/métodos
4.
Methods Mol Biol ; 2292: 49-56, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651351

RESUMO

Urine cell-free DNA has been shown as an informative noninvasive source of biomarkers for a number of diseases, especially for urological cancers. Starting from the hypothesis that the gain of c-Myc gene is a frequent aberration in several cancer types, including prostate cancer, we analyzed c-Myc copy number variation in urine, studying a little case series of prostate cancer patients, to test its feasibility. Here we report a general protocol that may be considered to analyze gene copy number variation in the urine cell-free fraction.


Assuntos
Ácidos Nucleicos Livres/genética , Variações do Número de Cópias de DNA , Genes myc , Neoplasias da Próstata/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Ácidos Nucleicos Livres/urina , Humanos , Masculino , Neoplasias da Próstata/urina
5.
Methods Mol Biol ; 2292: 57-72, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651352

RESUMO

Liquid biopsy is gaining importance in the context of analysis of circulating subcellular components, such as exosomes and nucleic acids, and the investigation of biological fluids is increasing because they express features common to the tissue of origin. Particularly, urine has become one of the most attractive biofluids in clinical practice due to its easy collection approach, its availability of large quantities, and its noninvasiveness. Furthermore, a peculiarity is that, compared to serum or plasma, urine is characterized by a simpler composition that improves isolation and identification of biomarkers. Recent studies have been associated with the investigation of mRNAs and microRNAs as potential noninvasive cancer biomarkers in urine, and to date, several approaches for isolating and measuring urinary nucleic acids have been established, despite still developing. This chapter aims at giving some main published evidences on urinary microRNAs and mRNAs, with the intent to consider their potential translational use in clinical practice.


Assuntos
MicroRNAs/urina , Neoplasias/urina , RNA Mensageiro/urina , Biomarcadores Tumorais/urina , Humanos , Biópsia Líquida , Neoplasias/diagnóstico , Urinálise
6.
Methods Mol Biol ; 2292: 95-104, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651354

RESUMO

Application of next generation sequencing techniques in the field of liquid biopsy, in particular urine, requires specific bioinformatics methods in order to deal with its peculiarity. Many aspects of cancer can be explored starting from nucleic acids, especially from cell-free DNA and circulating tumor DNA in order to characterize cancer. It is possible to detect small mutations, as single nucleotide variants, small insertions and deletions, copy-number alterations, and epigenetic profiles. Due to the low fraction of circulating tumor DNA over the whole cell-free DNA, some methods have been exploited. One of them is the application of unique barcodes to each DNA fragment in order to lower the limit of detection of cancer-related variants. Some bioinformatics workflows and tools are the same of a classic analysis of tumor tissue, but there are some steps in which specific algorithms have to be introduced.


Assuntos
Ácidos Nucleicos Livres/urina , Neoplasias/urina , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Ácidos Nucleicos Livres/genética , Variações do Número de Cópias de DNA , Metilação de DNA , Epigênese Genética , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Biópsia Líquida/métodos , Neoplasias/genética
7.
Methods Mol Biol ; 2292: 73-94, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651353

RESUMO

The characterization of circulating tumor cells (CTCs) is now widely studied as a promising source of cancer-derived biomarkers because of their role in tumor formation and progression. However, CTCs analysis presents some limitations and no standardized method for CTCs isolation from urine has been defined so far. In fact, besides blood, urine represents an ideal source of noninvasive biomarkers, especially for the early detection of genitourinary tumors. Besides CTCs, long noncoding RNAs (lncRNAs) have also been proposed as potential noninvasive biomarkers, and the evaluation of the diagnostic accuracy of urinary lncRNAs has dramatically increased over the last years, with many studies being published. Therefore, this review provides an update on the clinical utility of urinary lncRNAs as novel biomarkers for the diagnosis of bladder and prostate cancers.


Assuntos
Neoplasias da Próstata/urina , RNA Longo não Codificante/urina , Neoplasias da Bexiga Urinária/urina , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética
8.
Methods Mol Biol ; 2292: 115-120, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651356

RESUMO

The analysis of liquid biopsy as a source of diagnostic, prognostic, and predictive biomarkers is still object of the main research in the prostate cancer field. Many advantages, such as less invasiveness compared to plasma or serum analysis and the rich content, confer to urine a role as an interesting fluid to be analysed especially in urological diseases. Here we report a workflow focused on profile, concentration, and protein surface characterization of EVs from urinary supernatant.


Assuntos
Exossomos/patologia , Neoplasias da Próstata/diagnóstico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/urina , Humanos , Biópsia Líquida/métodos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/urina , Proteínas/análise , Proteinúria/diagnóstico , Proteinúria/patologia , Proteinúria/urina , Coleta de Urina/métodos , Fluxo de Trabalho
9.
Methods Mol Biol ; 2292: 121-131, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651357

RESUMO

Bladder cancer has a very high frequency of recurrence and therefore requires close clinical surveillance throughout its life, with cystoscopies and serial cytological examinations. These tests are both invasive and expensive, with considerable interpersonal and inter-institutional variability. Moreover, cytological examination used for the diagnosis of low-grade tumors has a low sensitivity; thus, there is an increasing focus on the research for new, accurate, urinary markers. Herein, the biological basis, methodologies, and diagnostic performance of biomarkers are discussed.


Assuntos
Neoplasias da Bexiga Urinária/urina , Antígenos de Neoplasias/urina , Biomarcadores Tumorais/urina , Humanos , Imuno-Histoquímica/métodos , Hibridização in Situ Fluorescente/métodos , Proteínas Nucleares/urina , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Neoplasias da Bexiga Urinária/diagnóstico
10.
Methods Mol Biol ; 2292: 133-141, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651358

RESUMO

Bladder cancer with an incidence of 15 cases per 100,000 persons in the global population is the most common tumor of the urinary tract. Imaging techniques, cytoscopy, and cytology are not sufficiently accurate to detect early stage tumors, and the need for new diagnostic markers is still an urgency. Among the biomarkers most recently proposed to improve diagnostic accuracy and especially sensitivity, increasing attention has been focused on the role of the ribonucleoprotein, telomerase. Previous studies have shown that the quantitative telomerase repeat amplification protocol (TRAP) assay performed in voided urine is an important noninvasive tool for the diagnosis of bladder tumors since it has very high sensitivity and specificity, even for early stage and low-grade tumors. Telomerase activity in urine determined by TRAP seems to be marker of great potential, even more advantageous in cost-benefit terms when used in selected symptomatic patients or professionally high-risk subgroups. Here we report the real-time PCR protocol to detect telomerase activity in urine sediment for bladder cancer.


Assuntos
Telomerase/urina , Neoplasias da Bexiga Urinária/urina , Biomarcadores Tumorais/urina , Ensaios Enzimáticos/métodos , Humanos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Coleta de Urina/métodos
11.
Methods Mol Biol ; 2292: 143-150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651359

RESUMO

Advances in mass spectrometry instrumentation have revolutionized analytical capability in clinical proteomics. In parallel, various sample preparation methods have been developed to try to address the inherent complexity and dynamic range of clinical samples, typically involving a combination of depletion of abundant proteins followed by extensive prefractionation. However, the depth of coverage routinely achieved in discovery proteomics experiments on peripheral fluids such as serum, still leaves something to be desired, especially if no depletion or prefractionation is done in order to increase the throughput of clinical samples. Remarkably, despite being an easily accessible, typically sterile and diagnostically rich clinical sample, urine is often overlooked and as such has received less development effort. As an ultrafiltrate of blood, urine contains proteins and protein fragments originating from all parts of the body which may have diagnostic or prognostic potential if accurately and reproducibly quantified. Here, we describe an efficient and simple method for the concentration of urine samples by methanol-chloroform precipitation and subsequent in-solution tryptic digestion prior to discovery or targeted mass spectrometry analysis. We exemplify this method by reference to the discovery of novel candidate urinary biomarkers of schistosomiasis. Importantly, the methods described here have been used to identify >1900 protein groups in human urine by label-free discovery proteomics, without requiring any prior depletion or prefractionation, making this approach amenable to high throughput clinical biomarker studies in many diseases.


Assuntos
Proteinúria/urina , Proteômica/métodos , Esquistossomose/urina , Espectrometria de Massas em Tandem/métodos , Neoplasias da Bexiga Urinária/urina , Animais , Biomarcadores Tumorais/urina , Humanos , Proteinúria/parasitologia , Schistosoma/isolamento & purificação , Esquistossomose/parasitologia , Neoplasias da Bexiga Urinária/parasitologia
12.
Methods Mol Biol ; 2292: 203-212, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651364

RESUMO

The pathogenesis of cancer involves multiple molecular alterations at the level of genome, epigenome, and stromal environment, resulting in several deregulated signal transduction pathways. Metabolites are not only end products of gene and protein expression but also a consequence of the mutual relationship between the genome and the internal environment. Considering that metabolites serve as a comprehensive chemical fingerprint of cell metabolism, metabolomics is emerging as the method able to discover metabolite biomarkers that can be developed for early cancer detection, prognosis, and response to treatment. Urine represents a noninvasive source, available and rich in metabolites, useful for cancer diagnosis, prognosis, and treatment monitoring. In this chapter, we reported the main published evidences on urinary metabolic biomarkers in the studied cancers related to hepatopancreatic and urinary tract with the aim at discussing their promising role in clinical practice.


Assuntos
Redes e Vias Metabólicas , Neoplasias/metabolismo , Neoplasias/urina , Animais , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/urina , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/urina , Metaboloma , Metabolômica/métodos , Neoplasias/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/urina , Prognóstico , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/metabolismo , Neoplasias Urológicas/urina
13.
Cancer Sci ; 112(5): 2033-2045, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33721374

RESUMO

Proteomic analysis of urinary extracellular vesicles (EVs) is a powerful approach to discover potential bladder cancer (BCa) biomarkers, however urine contains numerous EVs derived from the kidney and normal urothelial epithelium, which can obfuscate information related to BCa cell-derived EVs. In this study, we combined proteomic analysis of urinary EVs and tissue-exudative EVs (Te-EVs), which were isolated from culture medium of freshly resected viable BCa tissues. Urinary EVs were isolated from urine samples of 11 individuals (7 BCa patients and 4 healthy individuals), and Te-EVs were isolated from 7 BCa tissues. We performed tandem mass tag (TMT)-labeling liquid chromatography (LC-MS/MS) analysis for both urinary EVs and Te-EVs and identified 1960 proteins in urinary EVs and 1538 proteins in Te-EVs. Most of the proteins identified in Te-EVs were also present in urinary EVs (82.4%), with 55 of these proteins showing upregulated levels in the urine of BCa patients (fold change > 2.0; P < .1). Among them, we selected 22 membrane proteins as BCa biomarker candidates for validation using selected reaction monitoring/multiple reaction monitoring (SRM/MRM) analysis on urine samples from 70 individuals (40 BCa patients and 30 healthy individuals). Six urinary EV proteins (heat-shock protein 90, syndecan-1, myristoylated alanine-rich C-kinase substrate (MARCKS), MARCKS-related protein, tight junction protein ZO-2, and complement decay-accelerating factor) were quantified using SRM/MRM analysis and validated as significantly upregulated in BCa patients (P < .05). In conclusion, the novel strategy that combined proteomic analysis of urinary EVs and Te-EVs enabled selective detection of urinary BCa biomarkers.


Assuntos
Biomarcadores Tumorais/urina , Vesículas Extracelulares/química , Exsudatos e Transudatos , Proteínas de Neoplasias/urina , Proteômica/métodos , Neoplasias da Bexiga Urinária/urina , Adulto , Idoso , Estudos de Casos e Controles , Cromatografia Líquida/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Regulação para Cima
15.
Prostate ; 81(1): 41-49, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33095939

RESUMO

INTRODUCTION OR OBJECTIVE: Men with favorable-risk prostate cancer (PCa) on active surveillance may benefit from intervention strategies to slow or prevent disease progression and the need for definitive treatment. Pomegranate and its extracts have shown antiproliferative and proapoptotic effects in cell lines and animal models, but its effect on human prostate cancer as a target tissue remain unclear. Objectives of this trial include pomegranate's ability to alter serum and prostate tissue biomarkers and the ability of an active surveillance cohort to adhere to a chemoprevention trial for 1 year. METHODS: Men with organ-confined, favorable-risk PCa on AS were randomly assigned to receive pomegranate fruit extract (PFE) 1000 mg (n = 15) or placebo (n = 15) once daily for twelve months. Prostate biopsies were performed at study entry and upon completion of the 1-year intervention. Plasma and urinary biomarkers were analyzed utilizing immunoassays and HPLC. Tissue proteins were assessed by immunohistochemistry (IHC) and measured by automated quantitation. RESULTS: PFE was well-tolerated with no significant toxicities. One patient withdrew before study initiation and 29 completed the 1-year intervention. No differences in plasma insulin-like growth factor-1 (IGF-1) levels, prostate-specific antigen doubling time, or biopsy kinetics were observed. Metabolites including urolithin A and urolithin A-gluc were detected more frequently in the PFE arm in both urine and plasma (p < .001 and p = .006, respectively). IHC analyses revealed reductions from baseline in 8-OHdG (a DNA damage marker) (p = .01) and androgen receptor expression (p = .04) in prostate tumor associated with PFE treatment. CONCLUSION: PFE administration for 12-month was well-tolerated and the protocol followed in an active surveillance population. Analyses suggest that PFE contains bioactive compounds capable of altering biomarkers involving oxidative stress and androgen signaling in prostate tumor and normal-appearing adjacent tissue. No alterations in the IGF axis were noted. This finding of study adherence and target activity provides a rationale for the further investigation of PFE in the active surveillance population.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Extratos Vegetais/administração & dosagem , Romã (Fruta)/química , Neoplasias da Próstata/tratamento farmacológico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Biópsia , Frutas/química , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Fitoterapia , Placebos , Extratos Vegetais/isolamento & purificação , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/urina , Conduta Expectante
16.
PLoS One ; 15(8): e0237070, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822394

RESUMO

Bladder cancer (BCA) is relatively common and potentially recurrent/progressive disease. It is also costly to detect, treat, and control. Definitive diagnosis is made by examination of urine sediment, imaging, direct visualization (cystoscopy), and invasive biopsy of suspect bladder lesions. There are currently no widely-used BCA-specific biomarker urine screening tests for early BCA or for following patients during/after therapy. Urine metabolomic screening for biomarkers is costly and generally unavailable for clinical use. In response, we developed Raman spectroscopy-based chemometric urinalysis (Rametrix™) as a direct liquid urine screening method for detecting complex molecular signatures in urine associated with BCA and other genitourinary tract pathologies. In particular, the RametrixTM screen used principal components (PCs) of urine Raman spectra to build discriminant analysis models that indicate the presence/absence of disease. The number of PCs included was varied, and all models were cross-validated by leave-one-out analysis. In Study 1 reported here, we tested the Rametrix™ screen using urine specimens from 56 consented patients from a urology clinic. This proof-of-concept study contained 17 urine specimens with active BCA (BCA-positive), 32 urine specimens from patients with other genitourinary tract pathologies, seven specimens from healthy patients, and the urinalysis control SurineTM. Using a model built with 22 PCs, BCA was detected with 80.4% accuracy, 82.4% sensitivity, 79.5% specificity, 63.6% positive predictive value (PPV), and 91.2% negative predictive value (NPV). Based on the number of PCs included, we found the RametrixTM screen could be fine-tuned for either high sensitivity or specificity. In other studies reported here, RametrixTM was also able to differentiate between urine specimens from patients with BCA and other genitourinary pathologies and those obtained from patients with end-stage kidney disease (ESKD). While larger studies are needed to improve RametrixTM models and demonstrate clinical relevance, this study demonstrates the ability of the RametrixTM screen to differentiate urine of BCA-positive patients. Molecular signature variances in the urine metabolome of BCA patients included changes in: phosphatidylinositol, nucleic acids, protein (particularly collagen), aromatic amino acids, and carotenoids.


Assuntos
Detecção Precoce de Câncer/métodos , Análise Espectral Raman/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/urina , Cistoscopia , Análise Discriminante , Feminino , Humanos , Masculino , Metaboloma , Metabolômica , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Urinálise/métodos , Neoplasias da Bexiga Urinária/patologia
17.
Rev. esp. enferm. dig ; 112(8): 642-648, ago. 2020. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-199970

RESUMO

El cáncer colorrectal (CCR) representa una de las neoplasias más comunes en los países desarrollados y la segunda causa de muerte por cáncer en España. Se desarrolla mediante la acumulación de alteraciones genéticas y epigenéticas en la mucosa colónica, dando lugar a adenomas colorrectales y carcinomas invasivos. Este proceso multietapa hace que el CCR sea susceptible a la implementación de medidas preventivas como los programas de cribado. Para ello, hoy en día existen diferentes estrategias, aunque ninguna cumple las condiciones ideales de una prueba de cribado. En este contexto, se ha visto que diversas alteraciones moleculares implicadas en la carcinogénesis del CCR podrían contribuir a la generación de nuevos métodos no invasivos, sensibles y específicos. En la siguiente revisión se comentarán brevemente algunos de los biomarcadores no invasivos más relevantes para el diagnóstico del CCR


No disponible


Assuntos
Humanos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Saliva/química , Fezes/química
18.
Actas urol. esp ; 44(6): 400-407, jul.-ago. 2020. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-199416

RESUMO

INTRODUCCIÓN: El uso de biomarcadores en la detección del cáncer de próstata (CP) puede disminuir el sobrediagnóstico y sobretratamiento de CP no significativos. Analizamos la utilidad y aplicabilidad del marcador SelectMDx® en un entorno de práctica clínica habitual. MATERIAL Y MÉTODOS: Estudio retrospectivo de 48 pacientes evaluados mediante el test SelectMDx® entre julio de 2017 y abril de 2019. Los pacientes se estratificaron en dos grupos según el riesgo estimado por el test de CP clínicamente significativo (CP-CS): < 2% o «muy bajo riesgo», y > 2%. Los resultados se expresaron en función de los antecedentes de biopsia prostática (BP) y resonancia magnética multiparamétrica (RMmp). RESULTADOS: En pacientes con BP negativa y RMmp normal/dudosa el riesgo fue < 2% en 7/9 casos. En pacientes sin BP y RMmp normal/dudosa el riesgo fue < 2% en 12/18 casos, y 2/6 casos con un riesgo % presentaron un CP-CS. De los 14 pacientes sin BP ni RMmp previas, 9 presentaron un riesgo < 2%, con 2 casos diagnosticados de CP en los 5 pacientes con riesgo > 2%. En el resto de subgrupos el número de pacientes es pequeño como para poder extraer conclusiones. En todos los casos con tacto rectal patológico el test demostraba un riesgo de padecer CP > 2%. CONCLUSIÓN: SelectMDx® es un test prometedor para detectar pacientes con un riesgo muy bajo de CP-CS, especialmente en pacientes con sospecha de CP con o sin BP negativas, en los que la RMmp muestre un resultado normal/dudoso. La presencia de un tacto rectal patológico puede condicionar el resultado del test


INTRODUCTION: The use of biomarkers in the detection of prostate cancer (PC) can decrease overdiagnosis and overtreatment of non-significant PC. We analyze the usefulness and applicability of the SelectMDx® marker in a routine clinical practice setting. MATERIAL AND METHODS: Retrospective study of 48 patients evaluated by the SelectMDx® test between July 2017 and April 2019. Patients were stratified into two groups according to the risk estimated by the clinically significant CP test (CS-PC): < 2% or 'very low risk', and > 2%. Results were expressed based on previous prostate biopsy (PB) and multi-parametric magnetic resonance imaging (mpMRI) outcomes. RESULTS: Patients with negative PB and normal/doubtful mpMRI had < 2% risk in 7/9 cases. Patients without PB and normal/doubtful mpMRI had < 2% risk in 12/18 cases, and 2/6 cases with a > 2% risk presented CS-PC. Of the 14 patients with no previous PB or mpMRI, 9 had < 2% risk, and 2 cases were diagnosed with PC from the group of patients (5) with risk >2%. The number of patients in the remaining subgroups is too small to draw any conclusions. In all cases with pathological digital rectal examination, the test showed a > 2% PC risk. CONCLUSION: SelectMDx® is a promising test for detecting patients with a very low risk of CS-PC, especially in patients with suspected PC, with or without negative PB, with normal/doubtful mpMRI. The presence of a pathological digital rectal examination may condition the result of the test


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/urina , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/urina , Biópsia Líquida , Próstata/patologia , Estudos Retrospectivos , Urinálise/métodos
19.
PLoS One ; 15(7): e0229193, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614890

RESUMO

BACKGROUND: Urine-based diagnostics indicated involvement of oncoprotein 18 (OP18) in bladder cancer. In cell culture models we investigated the role of OP18 for malignant cell growth. METHODS: We analyzed 113 urine samples and investigated two human BCa cell lines as a dual model: RT-4 and ECV-304, which represented differentiated (G1) and poorly differentiated (G3) BCa. We designed specific siRNA for down-regulation of OP18 in both cell lines. Phenotypes were characterized by cell viability, proliferation, and expression of apoptosis-related genes. Besides, sensitivity to cisplatin treatment was evaluated. RESULTS: Analysis of urine samples from patients with urothelial BCa revealed a significant correlation of the RNA-ratio OP18:uroplakin 1A with bladder cancer. High urinary ratios were mainly found in moderately to poorly differentiated tumors (grade G2-3) that were muscle invasive (stage T2-3), whereas samples from patients with more differentiated non-invasive BCa (G1) showed low OP18:UPK1A RNA ratios. Down-regulation of OP18 expression in ECV-304 shifted its phenotype towards G1 state. Further, OP18-directed siRNA induced apoptosis and increased chemo-sensitivity to cisplatin. CONCLUSIONS: This study provides conclusive experimental evidence for the link between OP18-derived RNA as a diagnostic marker for molecular staging of BCa in non-invasive urine-based diagnostics and the patho-mechanistic role of OP18 suggesting this gene as a therapeutic target.


Assuntos
Biomarcadores Tumorais/urina , RNA/urina , Estatmina/genética , Neoplasias da Bexiga Urinária/diagnóstico , Idoso , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/secundário , Gradação de Tumores , Fenótipo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Estatmina/antagonistas & inibidores , Estatmina/metabolismo , Estatmina/urina , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Uroplaquina Ia/genética
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