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1.
Urol J ; 18(6): 699-702, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34549803

RESUMO

PURPOSE: To evaluate the short-term results of water vapor therapy (Rezum) for BPH/LUTS in the first cohort of Czech patients. MATERIALS AND METHODS: Patients with BPH and moderate to severe LUTS (N = 76) who underwent Rezum treatment from December 2019 to July 2020 were included in the prospective study. Prior to the procedure, they completed the IPSS and OABv8 questionnaires and underwent uroflowmetry, transrectal ultrasound of the prostate, and PSA sampling. The parameters before and 3 months after the procedure were compared and statistically evaluated. RESULTS: The study protocol was completed by 92% of patients (N = 70). We observed a significant increase in Qmax (median 17.7 vs. 8.8 mL/s, P < .001), Qave (9 vs. 4.5 mL/s, P = .001) and voided volume (241 vs. 171 mL, P < .001) and a significant reduction in post-void residual (average 17.5 vs. 67.7 mL), prostate volume (39.3 vs. 62.3 mL) and total PSA (median 1.9 vs. 2.5 ng/mL, resp. P values < .001). There was also a significant decrease in OABv8 score (average 7.6 vs. 16.6, P < .001) and IPSS QoL (1.6 vs. 4.0, P = .037). The improvement in the IPSS score was apparent, yet statistically insignificant (6.8 vs. 16, P = .079). CONCLUSION: Water vapor therapy is an effective and safe method of BPH/LUTS treatment in the short-term.


Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , República Tcheca , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Estudos Prospectivos , Hiperplasia Prostática/complicações , Qualidade de Vida , Vapor , Resultado do Tratamento
2.
Klin Onkol ; 33(5): 340-349, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33108878

RESUMO

BACKGROUND: To provide an overview of the importance of long non-coding RNAs (lncRNAs) in the pathogenesis of renal cell carcinoma and their utility as bio-markers for dia-gnosis, prognosis and prediction of treatment response. MATERIALS AND METHODS: A literature search in the Pubmed and Web of Science databases using the keywords variations of “long non-coding RNA” (“lncRNA”, “long noncoding RNA”, “long non-coding RNA”) and “renal cell carcinoma” (“renal cancer”, “renal cell carcinoma”, “kidney cancer”) was performed. The results related to the pathogenesis, dia-gnosis, prognosis and use as therapeutic targets were separated. RESULTS: Long non-coding RNAs regulate gene expression at different levels. They act both as oncogenes and tumor suppressors. The mechanism of their action has not been fully elucidated, but they are actively involved in the regulation of hypoxia inducible factors pathway, epithelial-mesenchymal transition, cell proliferation, cell cycle regulation, apoptosis, local invasion and development of metastases. Aberrant expression in tumor tissue compared to healthy parenchyma and the correlation of expression levels with clinical-pathological features allow the potential use of many lncRNAs as bio-markers for early detection and prognosis of the disease, including the response to targeted therapy. In vitro assays indicate the potential use of lncRNAs as therapeutic targets. CONCLUSION: Our knowledge of long non-coding RNAs in relation to renal cell carcinoma is increasing rapidly. At present, some of them can be considered as promising bio-markers. Further research is needed before they can be introduced into routine clinical practice.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , RNA Longo não Codificante/genética , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/terapia , Ciclo Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/mortalidade , Neoplasias Renais/terapia , Prognóstico
3.
Cesk Patol ; 55(4): 231-234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31842554

RESUMO

We present a case of 64 - year - old man with mantle cell lymphoma (MCL) diagnosed in radical prostatectomy for adenocarcinoma. Lymphoma of the prostate, either primary or secondary, is a rare entity. The prognosis of lymphoma involving the prostate is usually poor. The most common form of leukemia/lymphoma involving the prostate is that of chronic lymphocytic leukemia/lymphoma (CLL/SLL). Mantle cell lymphoma of the prostate is an exceedingly rare entity. The association between MCL and urologic cancer was previously described, however the etiologic connection between these two conditions remains unknown. The pathologists should pay attention to all lymphoid infiltrates in the prostate, especially in cases when these are dense.


Assuntos
Adenocarcinoma , Linfoma de Célula do Manto , Neoplasias da Próstata , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia
4.
MAGMA ; 32(4): 423-436, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30730022

RESUMO

OBJECTIVE: T2 maps are more vendor independent than other MRI protocols. Multi-echo spin-echo signal decays to a non-zero offset due to imperfect refocusing pulses and Rician noise, causing T2 overestimation by the vendor's 2-parameter algorithm. The accuracy of the T2 estimate is improved, if the non-zero offset is estimated as a third parameter. Three-parameter Levenberg-Marquardt (LM) T2 estimation takes several minutes to calculate, and it is sensitive to initial values. We aimed for a 3-parameter fitting algorithm that was comparably accurate, yet substantially faster. METHODS: Our approach gains speed by converting the 3-parameter minimisation problem into an empirically unimodal univariate problem, which is quickly minimised using the golden section line search (GS). RESULTS: To enable comparison, we propose a novel noise-masking algorithm. For clinical data, the agreement between the GS and the LM fit is excellent, yet the GS algorithm is two orders of magnitude faster. For synthetic data, the accuracy of the GS algorithm is on par with that of the LM fit, and the GS algorithm is significantly faster. The GS algorithm requires no parametrisation or initialisation by the user. DISCUSSION: The new GS T2 mapping algorithm offers a fast and much more accurate off-the-shelf replacement for the inaccurate 2-parameter fit in the vendor's software.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética , Algoritmos , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Análise dos Mínimos Quadrados , Masculino , Imagens de Fantasmas , Probabilidade , Neoplasias da Próstata/diagnóstico por imagem , Análise de Regressão , Reprodutibilidade dos Testes , Razão Sinal-Ruído , Software , Fatores de Tempo
5.
Mol Oncol ; 13(5): 1002-1017, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30628163

RESUMO

DNA hypermethylation is one of the most common epigenetic modifications in prostate cancer (PCa). Several studies have delineated sarcosine as a PCa oncometabolite that increases the migration of malignant prostate cells while decreasing their doubling time. Here, we show that incubation of prostate cells with sarcosine elicited the upregulation of sarcosine N-demethylation enzymes, sarcosine dehydrogenase and pipecolic acid oxidase. This process was accompanied by a considerable increase in the production of the major methyl-donor S-adenosylmethionine (SAMe), together with an elevation of cellular methylation potential. Global DNA methylation analyses revealed increases in methylated CpG islands in distinct prostate cell lines incubated with sarcosine, but not in cells of nonprostate origin. This phenomenon was further associated with marked upregulation of DNA methyltransferases (Dnmts). Epigenetic changes were recapitulated through blunting of Dnmts using the hypomethylating agent 5-azacytidine, which was able to inhibit sarcosine-induced migration of prostate cells. Moreover, spatial mapping revealed concomitant increases in sarcosine, SAMe and Dnmt1 in histologically confirmed malignant prostate tissue, but not in adjacent or nonmalignant tissue, which is in line with the obtained in vitro data. In summary, we show here for the first time that sarcosine acts as an epigenetic modifier of prostate cells and that this may contribute to its oncometabolic role.


Assuntos
Ilhas de CpG , Epigênese Genética/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Sarcosina/farmacologia , Regulação para Cima/efeitos dos fármacos , Linhagem Celular , Humanos , Masculino , Próstata/patologia , Neoplasias da Próstata/patologia
6.
Cancer Med ; 7(11): 5411-5419, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30209891

RESUMO

To date, there has been no evidence regarding the association between urinary sarcosine content and prostate cancer survival. Our main objective was to investigate whether levels of post-treatment urinary sarcosine are associated with relapse. The inclusion criteria were (in accordance with EAU 2017) as follows: histopathologically verified adenocarcinoma in prostate biopsy cores or specimens from transurethral resection of the prostate (TURP) or prostatectomy for benign prostatic enlargement (BPE) with retained ability to urinate. The median follow-up was 53 months. In the study, we retrospectively evaluated a cohort of 511 patients with prostate cancer with various risk factors and treatment strategies. Post-treatment sarcosine levels were elevated in 266 (52%) patients and highly elevated (≥200 nmol/L) in 71 (13%) patients. Urinary sarcosine content was significantly associated with number of relapses that patients experienced, P = 0.002 for sarcosine ≥200 vs ≤30 nmol/L. Multivariate analysis revealed that sarcosine was an independent predictor of recurrent relapses (≥2 relapses with an intermediate period of remission), HR = 3.89 (95% CI 1.29-11.7) for sarcosine >200 vs <30 nmol/L. This trend was even more pronounced in a subgroup of patients who underwent radical prostatectomy, HR = 3.29 (95% CI 1.06-10.18), where (single) relapse-free survival could also be predicted by sarcosine levels, HR = 1.96 (1.05-3.66). Urinary sarcosine may become a possible predictor for patients' outcomes, because patients with elevated post-treatment sarcosine could be predicted to have recurrent relapses of the disease.


Assuntos
Adenocarcinoma/urina , Recidiva Local de Neoplasia/urina , Neoplasias da Próstata/urina , Sarcosina/urina , Adenocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Humanos , Masculino , Período Pós-Operatório , Prostatectomia , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/urina , Neoplasias da Próstata/cirurgia , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
7.
Sci Rep ; 8(1): 4958, 2018 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-29563505

RESUMO

The hypothesis that dogs can detect malignant tumours through the identification of specific molecules is nearly 30 years old. To date, several reports have described the successful detection of distinct types of cancer. However, is still a lack of data regarding the specific molecules that can be recognized by a dog's olfactory apparatus. Hence, we performed a study with artificially prepared, well-characterized urinary specimens that were enriched with sarcosine, a widely reported urinary biomarker for prostate cancer (PCa). For the purposes of the study, a German shepherd dog was utilized for analyses of 60 positive and 120 negative samples. Our study provides the first evidence that a sniffer dog specially trained for the olfactory detection of PCa can recognize sarcosine in artificial urine with a performance [sensitivity of 90%, specificity of 95%, and precision of 90% for the highest amount of sarcosine (10 µmol/L)] that is comparable to the identification of PCa-diagnosed subjects (sensitivity of 93.5% and specificity of 91.6%). This study casts light on the unrevealed phenomenon of PCa olfactory detection and opens the door for further studies with canine olfactory detection and cancer diagnostics.


Assuntos
Cães/fisiologia , Neoplasias da Próstata/diagnóstico , Sarcosina/química , Olfato/fisiologia , Urinálise/métodos , Animais , Estudos de Viabilidade , Humanos , Masculino , Neoplasias da Próstata/urina , Sarcosina/urina , Sensibilidade e Especificidade
8.
J Cell Mol Med ; 22(3): 2033-2038, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29363887

RESUMO

Urinary microRNAs (miRNAs) are emerging as clinically useful tool for early and non-invasive detection of various types of cancer including bladder cancer (BCA). In this study, 205 patients with BCA and 99 healthy controls were prospectively enrolled. Expression profiles of urinary miRNAs were obtained using Affymetrix miRNA microarrays (2578 miRNAs) and candidate miRNAs further validated in independent cohorts using qRT-PCR. Whole-genome profiling identified 76 miRNAs with significantly different concentrations in urine of BCA compared to controls (P < 0.01). In the training and independent validation phase of the study, miR-31-5p, miR-93-5p and miR-191-5p were confirmed to have significantly higher levels in urine of patients with BCA in comparison with controls (P < 0.01). We further established 2-miRNA-based urinary DxScore (miR-93-5p, miR-31-5p) enabling sensitive BCA detection with AUC being 0.84 and 0.81 in the training and validation phase, respectively. Moreover, DxScore significantly differed in the various histopathological subgroups of BCA and decreased post-operatively. In conclusion, we identified and independently validated cell-free urinary miRNAs as promising biomarkers enabling non-invasive detection of BCA.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/urina , Carcinoma/diagnóstico , Carcinoma/patologia , Carcinoma/urina , Estudos de Casos e Controles , Feminino , Genoma Humano , Estudo de Associação Genômica Ampla , Humanos , Masculino , MicroRNAs/urina , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/urina
9.
J Endourol ; 32(4): 297-303, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29256629

RESUMO

INTRODUCTION: Retropulsion, defined as unintended migration of a stone under the influence of the fragmentation device in ureteroscopy (URS) procedures, occurs in 2% to 60% of the cases. Antiretropulsive devices (ARDs) have been studied in experimental and small clinical studies. The current study aims at describing the worldwide usage of ARD and the outcomes related to their usage. METHODS: The Clinical Research Office of the Endourological Society URS Global Study enrolled 11,885 patients who underwent URS and stone fragmentation for ureteral and/or renal stones. Of the 11,885 treated patients, 9877 were treated for ureteral stones, and data were available on stone migration and ARD use. RESULTS: Of all procedures, 14.5% were performed with the use of an ARD. Less stone migration (-2.0%; p = 0.050), higher stone-free rates (SFRs) (2.8%; p < 0.001), and shorter length of stay (-4.7%; p = 0.001) were observed in the antiretropulsive group. CONCLUSIONS: When an ARD is used during URS, less migration, higher SFRs, and shorter length of hospital stay are observed. This effect is independent from baseline differences and corrected for other treatment characteristics.


Assuntos
Saúde Global/estatística & dados numéricos , Complicações Intraoperatórias/prevenção & controle , Cálculos Renais/cirurgia , Litotripsia/métodos , Cálculos Ureterais/cirurgia , Ureteroscopia/métodos , Idoso , Feminino , Humanos , Complicações Intraoperatórias/etiologia , Tempo de Internação , Litotripsia/efeitos adversos , Litotripsia/instrumentação , Litotripsia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sociedades Médicas , Resultado do Tratamento , Ureteroscopia/instrumentação
10.
Biochem Med (Zagreb) ; 27(2): 411-417, 2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28694731

RESUMO

INTRODUCTION: Urinary microRNAs (miRNAs) are emerging as a clinically useful tool for early and non-invasive detection of various types of cancer. The aim of this study was to evaluate whether let-7 family miRNAs differ in their urinary concentrations between renal cell carcinoma (RCC) cases and healthy controls. MATERIALS AND METHODS: In the case-control study, 69 non-metastatic clear-cell RCC patients and 36 gender/age-matched healthy controls were prospectively enrolled. Total RNA was purified from cell-free supernatant of the 105 first morning urine specimens. Let-7 family miRNAs were determined in cell-free supernatant using quantitative miRNA real-time reverse-transcription PCR and absolute quantification approach. RESULTS: Concentrations of all let-7 miRNAs (let-7a, let-7b, let-7c, let-7d, let-7e and let-7g) were significantly higher in urine samples obtained from RCC patients compared to healthy controls (P < 0.001; P < 0.001; P = 0.005; P = 0.006; P = 0.015 and P = 0.002, respectively). Subsequent ROC analysis has shown that let-7a concentration possesses good ability to differentiate between cases and controls with area under curve being 0.8307 (sensitivity 71%, specificity 81%). CONCLUSIONS: We have shown that let-7 miRNAs are abundant in the urine samples of patients with clear-cell RCC, and out of six let-7 family members, let-7a outperforms the others and presents promising non-invasive biomarker for the detection of RCC.


Assuntos
Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/urina , Feminino , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/urina , Masculino , MicroRNAs/urina , Pessoa de Meia-Idade , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa
11.
Saudi Med J ; 38(1): 9-17, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28042624

RESUMO

Radical prostatectomy (RP) is the most common cause of stress urinary incontinence (UI) in men. Several anatomic structures affect or may affect urinary continence - urethral sphincter, levator ani muscle, puboprostatic ligaments, bladder neck, endopelvic fascia, neurovascular bundle - and understanding of the anatomy of pelvic floor and urethra is crucial for satisfactory functional outcome of the procedure. Surgical techniques implemented to improve continence rates include nerve-sparing procedure, bladder neck preservation/plication, urethral length preservation, musculofascial reconstruction, puboprostatic ligaments preservation or seminal vesicle preservation. Perioperative (preoperative and postoperative) pelvic floor muscle training (PFMT) aims to shorten the duration of postoperative UI and thus, improve early continence rates postoperatively. In the review, complex information regarding anatomical, intra- and perioperative factors affecting urinary continence after RP is provided, including description of important anatomical structures, possible implications for surgical technique and evaluation of different PFMT strategies in perioperative period.


Assuntos
Prostatectomia/efeitos adversos , Incontinência Urinária/etiologia , Humanos , Masculino , Fatores de Risco
12.
Anticancer Res ; 36(12): 6419-6423, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27919963

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) is the most common neoplasm of adult kidney accounting for about 3% of adult malignancies. P-Element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a new class of naturally occurring, short non-coding RNAs involved in silencing of transposable elements and in sequence-specific chromatin modifications. There were preliminary data published indicating that piR-823 expression is deregulated in circulating tumor cells and tumor tissue in gastric and kidney cancer, respectively. PATIENTS AND METHODS: In our study, we analyzed piR-823 levels in 588 biological specimens: tumor tissue (N=153), adjacent renal parenchyma (N=121), blood serum (N=178) and urine (N=20) of patients undergoing nephrectomy for RCC; and in blood serum (N=101) and urine (N=15) of matched healthy controls. Expression levels of piR-823 were determined in all biological specimens by quantitative real-time polymerase chain reaction, compared in patients and controls, and correlated with clinicopathological features of RCC. RESULTS: We identified a significant down-regulation of piR-823 in tumor tissue [p<0.0001, area under the curve (AUC)=0.7945]. On the contrary in blood serum and urine, the expression of piR-823 was significantly higher in patients with RCC compared to healthy individuals (p=0.0005, AUC=0.6264 and p=0.0157, AUC=0.7433, respectively). We further observed higher levels of piR-823 in tumor tissue to be associated with shorter disease-free survival of patients (p=0.0186) and a trend for higher piR-823 levels in serum to be associated with advanced clinical stages of RCC (p=0.0691). There were no other significant associations of piR-823 levels in any type of biological specimen with clinicopathological features of RCC. CONCLUSION: piR-823 is down-regulated in tumor tissue, but positively correlated with worse outcome, indicating its complex role in RCC pathogenesis. In blood serum, piR-823 is up-regulated, but with unsatisfactory analytical performance. Preliminary data indicate the promising diagnostic utility of urinary piR-823 in patients with RCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , RNA Interferente Pequeno/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/urina , Humanos , Neoplasias Renais/sangue , Neoplasias Renais/urina , Pessoa de Meia-Idade , RNA Interferente Pequeno/sangue , RNA Interferente Pequeno/urina , Adulto Jovem
13.
Res Rep Urol ; 8: 207-216, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27921028

RESUMO

OBJECTIVE: The objective of this study was to assess the effectiveness and safety of convective radiofrequency (RF) water vapor thermal therapy in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH); a pilot study design with 2-year follow-up evaluations. PATIENTS AND METHODS: Men aged ≥45 years with an International Prostate Symptom Score ≥13, a maximum urinary flow rate (Qmax) ≤15 mL/s, and prostate volume 20-120 cc were enrolled in a prospective, open-label pilot study using convective RF water vapor energy with the Rezum System. Patients were followed up for 2 years after transurethral thermal treatment at 3 international centers in the Dominican Republic, Czech Republic, and Sweden. The transurethral thermal therapy utilizes radiofrequency to generate wet thermal energy in the form of water vapor injected through a rigid endoscope into the lateral lobes and median lobe as needed. Urinary symptom relief, urinary flow, quality of life (QOL) impact, sexual function, and adverse events (AEs) were assessed at 1 week, 1, 3, 6, 12, and 24 months. RESULTS: LUTS, flow rate, and QOL showed significant improvements from baseline; prostate volumes were appreciably reduced. Sexual function was maintained and no de novo erectile dysfunction occurred. The responses evident as early as 1 month after treatment remained consistent and durable over the 24 months of study. Early AEs were typically transient and mild to moderate; most were related to endoscopic instrumentation. No procedure related to late AEs were seen. CONCLUSION: The Rezum System convective RF thermal therapy is a minimally invasive treatment for BPH/LUTS which can be performed in the office or as an outpatient procedure with minimal associated perioperative AEs. It has no discernable effect on sexual function and provides significant improvement of LUTS that remain durable at 2 years.

14.
PLoS One ; 11(11): e0165830, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27824899

RESUMO

The effects of sarcosine on the processes driving prostate cancer (PCa) development remain still unclear. Herein, we show that a supplementation of metastatic PCa cells (androgen independent PC-3 and androgen dependent LNCaP) with sarcosine stimulates cells proliferation in vitro. Similar stimulatory effects were observed also in PCa murine xenografts, in which sarcosine treatment induced a tumor growth and significantly reduced weight of treated mice (p < 0.05). Determination of sarcosine metabolism-related amino acids and enzymes within tumor mass revealed significantly increased glycine, serine and sarcosine concentrations after treatment accompanied with the increased amount of sarcosine dehydrogenase. In both tumor types, dimethylglycine and glycine-N-methyltransferase were affected slightly, only. To identify the effects of sarcosine treatment on the expression of genes involved in any aspect of cancer development, we further investigated expression profiles of excised tumors using cDNA electrochemical microarray followed by validation using the semi-quantitative PCR. We found 25 differentially expressed genes in PC-3, 32 in LNCaP tumors and 18 overlapping genes. Bioinformatical processing revealed strong sarcosine-related induction of genes involved particularly in a cell cycle progression. Our exploratory study demonstrates that sarcosine stimulates PCa metastatic cells irrespectively of androgen dependence. Overall, the obtained data provides valuable information towards understanding the role of sarcosine in PCa progression and adds another piece of puzzle into a picture of sarcosine oncometabolic potential.


Assuntos
Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes Neoplásicos/fisiologia , Neoplasias da Próstata/metabolismo , Sarcosina/farmacologia , Animais , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/fisiologia , Glicina N-Metiltransferase/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Reação em Cadeia da Polimerase , Neoplasias da Próstata/fisiopatologia , Sarcosina/metabolismo , Sarcosina Desidrogenase/metabolismo , Transcriptoma , Regulação para Cima
15.
Tumour Biol ; 37(11): 14653-14658, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27619681

RESUMO

MicroRNAs (miRNAs) have been proven to be important oncogenes and tumor suppressors in wide range of cancers, including renal cell carcinoma (RCC). In our study, we evaluated miRNA-429 as potential diagnostic/prognostic biomarker in 172 clear cell RCC patients and as a potential regulator of epithelial-mesenchymal transition (EMT) in vitro. We demonstrated that miR-429 is down-regulated in tumor tissue samples (P < 0.0001) and is significantly associated with cancer metastasis (P < 0.0001), shorter disease-free (P = 0.0105), and overall survival (P = 0.0020). In addition, ectopic expression of miR-429 in 786-0 RCC cells followed by TGF-ß treatment led to increase in the levels of E-cadherin expression (P < 0.0001) and suppression of cellular migration (P < 0.0001) in comparison to TGF-ß-treated controls. Taken together, our findings suggest that miR-429 may serve as promising diagnostic and prognostic biomarker in RCC patients. We further suggest that miR-429 has a capacity to inhibit loss of E-cadherin in RCC cells undergoing EMT and consequently attenuate their motility.


Assuntos
Carcinoma de Células Renais/secundário , Movimento Celular , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/patologia , MicroRNAs/genética , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD , Biomarcadores Tumorais , Caderinas/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , Estudos de Casos e Controles , Proliferação de Células , Terapia Combinada , Regulação para Baixo , Feminino , Seguimentos , Humanos , Neoplasias Renais/genética , Neoplasias Renais/terapia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Fator de Crescimento Transformador beta/genética , Células Tumorais Cultivadas
16.
Tumour Biol ; 37(10): 13385-13390, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27460088

RESUMO

Long non-coding RNA TUG1 is involved in the development and progression of a variety of tumors. Little is known about TUG1 function in high-grade muscle-invasive bladder cancer (MIBC). The aims of our study were to determine expression levels of long non-coding RNA TUG1 in tumor tissue, to evaluate its relationship with clinico-pathological features of high-grade MIBC, and to describe its function in MIBC cells in vitro. TUG1 expression levels were determined in paired tumor and adjacent non-tumor bladder tissues of 47 patients with high-grade MIBC using real-time PCR. Cell line T-24 and siRNA silencing were used to study the TUG1 function in vitro. We observed significantly increased levels of TUG1 in tumor tissue in comparison to adjacent non-tumor bladder tissue (P < 0.0001). TUG1 levels were significantly increased in metastatic tumors (P = 0.0147) and were associated with shorter overall survival of MIBC patients (P = 0.0241). TUG1 silencing in vitro led to 34 % decrease in cancer cell proliferation (P = 0.0004) and 23 % reduction in migration capacity of cancer cells (P < 0.0001). We did not observe any significant effects of TUG1 silencing on cell cycle distribution and number of apoptotic cells. Our study confirmed overexpression of TUG1 in MIBC tumor tissue and described its association with worse overall survival in high-grade MIBC patients. Together with in vitro observations, these data suggest an oncogenic role of TUG1 and its potential usage as biomarker or therapeutic target in MIBC.


Assuntos
Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Musculares/patologia , RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/patologia , Apoptose , Ciclo Celular , Progressão da Doença , Feminino , Humanos , Neoplasias Musculares/genética , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , RNA Longo não Codificante/antagonistas & inibidores , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/genética
17.
Onco Targets Ther ; 9: 217-22, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26811690

RESUMO

Piwi-interacting RNAs (piRNAs) are a newly discovered class of small non-coding RNAs involved in silencing of transposable elements and in sequence-specific chromatin modifications. PIWI proteins (PIWIL), which belong to the family of Argonaute genes/proteins, bind to piRNAs and function mainly in germ line cells, but more recently were described to be functional also in stem cells and cancer cells. To date, there have been four PIWI proteins discovered in humans: PIWIL1, PIWIL2, PIWIL3, and PIWIL4. Recent studies suggested that deregulated expression of PIWI proteins and selected piRNAs is common to many types of cancers. We found significantly lower expression of PIWIL1 (P<0.0001) and piR-823 (P=0.0001) in tumor tissue in comparison to paired renal parenchyma. Further, we observed a progressive decrease in PIWIL1 (P=0.0228), PIWIL2 (P=0.0015), and PIWIL4 (P=0.0028) expression levels together with increasing clinical stage. PIWIL2 (P=0.0073) and PIWIL4 (P=0.0001) expression also progressively decreased with increasing Fuhrman grade. Most importantly, low-expression levels of PIWIL1 (P=0.009), PIWIL2 (P<0.0001), and PIWIL4 (P=0.0065) were significantly associated with worse overall survival in renal cell carcinoma (RCC) patients. Our results suggest the involvement of PIWIL genes and piR-823 in RCC pathogenesis, and indicate PIWIL1, PIWIL2, and PIWIL4 as potential prognostic biomarkers in patients with RCC.

18.
Int J Biol Markers ; 31(1): e26-37, 2016 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-26481440

RESUMO

PURPOSE: To provide information about the role of microRNAs in the pathogenesis of renal cell carcinoma (RCC) and their diagnostic and prognostic utility as cancer biomarkers. METHODS: A literature search was performed in the PubMed and Web of Science databases using the keywords "renal cancer/renal cell carcinoma/kidney cancer" and "miR*/miRNA*/microRNA*". Articles dealing with the role of miRNAs in the pathogenesis of RCC, diagnostic miRNAs and prognostic miRNAs were separated. RESULTS: MiRNAs act both as oncogenes and tumor suppressors. They regulate apoptosis, cell growth, migration, invasion, proliferation, colony formation and angiogenesis through target proteins involved in several signaling pathways, and they are involved in key pathogenetic mechanisms such as hypoxia (HIF/VHL dependent) and epithelial-to-mesenchymal transition. Differentially expressed miRNAs can discriminate either tumor tissue from healthy renal tissue or different RCC subtypes. Circulating miRNAs are promissing as diagnostic biomarkers of RCC. Information about urinary miRNAs associated with RCC is sparse. Detection of a relapse is another implication of diagnostic miRNAs. The expression profiles of several miRNAs correlate with the prognosis of RCC patients. Comparison between primary tumor tissue and metastasis may help identify high-risk primary tumors. Finally, response to target therapy can be estimated thanks to differences in miRNA expression in tissue and serum of therapy-resistant versus therapy-sensitive patients. CONCLUSIONS: Our understanding of the role of microRNAs in RCC pathogenesis has been increasing dramatically. Identification and validation of their gene targets may have direct impact on developing microRNA-based anticancer therapy. Several microRNAs can serve as diagnostic and prognostic biomarkers.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , MicroRNAs/genética , Biomarcadores Tumorais/biossíntese , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/biossíntese , Prognóstico , PubMed
19.
Int J Mol Sci ; 16(10): 23382-9, 2015 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-26426010

RESUMO

Serum microRNAs are emerging as a clinically useful tool for early and non-invasive detection of various cancer types including renal cell carcinoma (RCC). Based on our previous results, we performed the study to analyze circulating serum miR-378 and miR-210 in patients with various histological subtypes of RCC. RNA was purified from blood serum samples of 195 RCC patients and 100 healthy controls. The levels of miR-378 and miR-210 in serum were determined absolutely using quantitative real-time PCR. Pre- and postoperative levels of both microRNAs were compared in 20 RCC patients. Significantly increased serum levels of both miR-378 and miR-210 enabled to clearly distinguish RCC patients and healthy controls with 80% sensitivity and 78% specificity if analyzed in combination (p<0.0001), and their levels significantly decreased in the time period of three months after radical nephrectomy (p<0.0001). Increased level of miR-378 positively correlates with disease-free survival (p=0.036) and clinical stage (p=0.0476). The analysis of serum miR-378 and miR-210 proved their potential to serve as powerful non-invasive diagnostic and prognostic biomarkers in RCC.


Assuntos
Carcinoma de Células Renais/sangue , Neoplasias Renais/sangue , MicroRNAs/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Renais/genética , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Masculino , Pessoa de Meia-Idade
20.
Urology ; 86(5): 1042-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26216644

RESUMO

OBJECTIVE: To assess 1-year efficacy and safety data from pilot trials of the Rezum System water vapor to treat lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 65 men with symptoms of moderate to severe BPH were enrolled in pilot studies at centers in the Dominican Republic, the Czech Republic, and Sweden. Each patient was treated with transurethral delivery of sterile water vapor (steam). International Prostate Symptom Score (IPSS), peak urinary flow (Qmax), quality of life (QoL), postvoid residual, International Index of Erectile Function, and prostate-specific antigen were evaluated at 1 week and 1, 3, 6, and 12 months post-treatment. Safety was also assessed. RESULTS: Statistically significant clinical improvements at 1, 3, 6, and 12 months were reported for IPSS (decreased by 6.8, 13.4, 13.1, and 12.5 points, respectively) and Qmax (increased by 2.0, 4.7, 4.3, and 4.6 mL/sec, respectively). At 12 months, these results equated to a 56% improvement in IPSS (P <.001) and an 87% improvement in Qmax (P <.001). QoL also improved at 12 months with a 61% improvement. Sexual function was maintained. Most of the adverse events (AEs) were related to endoscopic instrumentation and were of short duration. One case of urinary retention was classified as a procedure/device-related serious AE. CONCLUSION: The Rezum System provides effective relief of LUTS associated with BPH at 1 year. The procedure is safe with an acceptable side effect profile.


Assuntos
Terapia a Laser/instrumentação , Sintomas do Trato Urinário Inferior/cirurgia , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/métodos , Idoso , Intervalos de Confiança , Seguimentos , Humanos , Internacionalidade , Terapia a Laser/métodos , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Segurança do Paciente , Projetos Piloto , Estudos Prospectivos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/diagnóstico , Recuperação de Função Fisiológica , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Urodinâmica
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