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1.
J Cancer ; 6(3): 292-301, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25663948

RESUMO

The search for biomarkers to characterize prostate cancer aggressiveness has been the objective for the majority of researchers involved with the most prevalent tumor in men. MiRNAs are important for the control of many cellular functions and their deregulation is involved with tumor development and progression. To find miRNAs differentially expressed in prostate cancer and their relation to prognostic factors and biochemical recurrence we studied 53 surgical specimens from men who underwent radical prostatectomy, through a microarray analysis using the microarray platform (GeneChip® miRNA Array - Affymetrix) with more than 46,000 probes and 847 mature human miRNAs and transcripts. We defined different as an expression level greater or less than 1.1 with p<0.05. The validation study using qRT-PCR had confirmed miR21 as overexpressed in tumor that have recurred with a risk of 2.5. Transfection of miR-21 using lipid based assay in DU145 cell line, showed decrease in expression of RECK resulting in increase in expression of MMP9. Invasion assay with Matrigel showed increase in tumor cell invasion after miR-21 transfection. We conclude that miR-21 overexpression is related to increased biochemical recurrence after surgical treatment of prostate cancer. And the negative control of RECK results in overexpression of MMP9 promotes increasing tumor cell invasion supporting miR-21 as an oncomiR related to aggressiveness in prostate cancer.

2.
Int Braz J Urol ; 40(5): 644-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25498275

RESUMO

PURPOSE: To analyze a possible correlation between a miRNA expression profile and important prognostic factors for pTa urothelial carcinomas (UC), including tumor size, multiplicity and episodes of recurrence. MATERIALS AND METHODS: Thirty low-grade non-invasive pTa bladder UC from patients submitted to transurethral resection were studied, in a mean follow-up of 17.7 months. As controls, we used normal bladder tissue from five patients submitted to retropubic prostatectomy to treat benign prostatic hyperplasia. Extraction, cDNA and amplification were performed for 14 miRNAs (miR-100, -10a, -21, -205, -let7c, -143, -145, -221, -223, -15a, -16, -199a and -452) using specific kits, and RNU-43 and -48 were used as endogenous controls. Statistical tests were used to compare tumor size, multiplicity and episodes of recurrence with miRNAs expression profiles. RESULTS: There was a marginal correlation between multiplicity and miR-let7c over-expression. For all others miRNA no correlation between their expression and prognostic factors was found. CONCLUSION: We did not find differences for miRNAs expression profiles associated with prognostic factors in tumor group studied. The majority of miRNAs are down-regulated, except mir-10a, over-expressed in most of cases, seeming to have increased levels as tumor with more unfavorable prognostic factors. More studies are needed in order to find a miRNA profile able to provide prognosis in pTa UC to be used in clinical practice.


Assuntos
Carcinoma/genética , MicroRNAs/análise , Neoplasias Ureterais/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Biomarcadores Tumorais/análise , Carcinoma/patologia , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Valores de Referência , Estatísticas não Paramétricas , Carga Tumoral/genética , Neoplasias Ureterais/patologia , Neoplasias da Bexiga Urinária/patologia
3.
PLoS One ; 9(11): e113700, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25409297

RESUMO

Prostate cancer is the most common cancer in men, and most patients have localized disease at the time of diagnosis. However, 4% already present with metastatic disease. Epithelial-mesenchymal transition is a fundamental process in carcinogenesis that has been shown to be involved in prostate cancer progression. The main event in epithelial-mesenchymal transition is the repression of E-cadherin by transcription factors, but the process is also regulated by microRNAs. The aim of this study was to analyze gene and microRNA expression involved in epithelial-mesenchymal transition in localized prostate cancer and metastatic prostate cancer cell lines and correlate with clinicopathological findings. We studied 51 fresh frozen tissue samples from patients with localized prostate cancer (PCa) treated by radical prostatectomy and three metastatic prostate cancer cell lines (LNCaP, DU145, PC3). The expression of 10 genes and 18 miRNAs were assessed by real-time PCR. The patients were divided into groups according to Gleason score, pathological stage, preoperative PSA, biochemical recurrence, and risk group for correlation with clinicopathological findings. The majority of localized PCa cases showed an epithelial phenotype, with overexpression of E-cadherin and underexpression of the mesenchymal markers. MiRNA-200 family members and miRNAs 203, 205, 183, 373, and 21 were overexpressed, while miRNAs 9, 495, 29b, and 1 were underexpressed. Low-expression levels of miRNAs 200b, 30a, and 1 were significantly associated with pathological stage. Lower expression of miR-200b was also associated with a Gleason score ≥ 8 and shorter biochemical recurrence-free survival. Furthermore, low-expression levels of miR-30a and high-expression levels of Vimentin and Twist1 were observed in the high-risk group. Compared with the primary tumor, the metastatic cell lines showed significantly higher expression levels of miR-183 and Twist1. In summary, miRNAs 200b, 30a, 1, and 183 and the genes Twist1 and Vimentin might play important roles in the progression of prostate cancer and may eventually become important prognostic markers.


Assuntos
Transição Epitelial-Mesenquimal/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/patologia , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade , Reação em Cadeia da Polimerase em Tempo Real , Índice de Gravidade de Doença , Proteína 1 Relacionada a Twist/genética , Proteína 1 Relacionada a Twist/metabolismo , Vimentina/genética , Vimentina/metabolismo
4.
Int. braz. j. urol ; 40(5): 644-649, 12/2014. tab
Artigo em Inglês | LILACS | ID: lil-731132

RESUMO

Purpose To analyze a possible correlation between a miRNA expression profile and important prognostic factors for pTa urothelial carcinomas (UC), including tumor size, multiplicity and episodes of recurrence. Materials and Methods Thirty low-grade non-invasive pTa bladder UC from patients submitted to transurethral resection were studied, in a mean follow-up of 17.7 months. As controls, we used normal bladder tissue from five patients submitted to retropubic prostatectomy to treat benign prostatic hyperplasia. Extraction, cDNA and amplification were performed for 14 miRNAs (miR-100, -10a, -21, -205, -let7c, -143, -145, -221, -223, -15a, -16, -199a and -452) using specific kits, and RNU-43 and -48 were used as endogenous controls. Statistical tests were used to compare tumor size, multiplicity and episodes of recurrence with miRNAs expression profiles. Results There was a marginal correlation between multiplicity and miR-let7c over-expression. For all others miRNA no correlation between their expression and prognostic factors was found. Conclusion We did not find differences for miRNAs expression profiles associated with prognostic factors in tumor group studied. The majority of miRNAs are down-regulated, except miR-10a, over-expressed in most of cases, seeming to have increased levels in tumor with more unfavorable prognostic factors. More studies are needed in order to find a miRNA profile able to provide prognosis in pTa UC to be used in clinical practice. .


Assuntos
Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma/genética , MicroRNAs/análise , Neoplasias Ureterais/genética , Neoplasias da Bexiga Urinária/genética , Análise de Variância , Estudos de Casos e Controles , Carcinoma/patologia , Regulação para Baixo , Expressão Gênica , Perfilação da Expressão Gênica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Valores de Referência , Estatísticas não Paramétricas , Carga Tumoral/genética , Biomarcadores Tumorais/análise , Neoplasias Ureterais/patologia , Neoplasias da Bexiga Urinária/patologia
5.
São Paulo; s.n; 2014. [151] p. ilus, graf, tab.
Tese em Português | LILACS | ID: lil-719944

RESUMO

Introdução: O câncer de próstata (CaP) é o tumor mais comum em homens e a segunda causa de óbito por câncer no Brasil. Com a adoção do rastreamento, a maioria dos pacientes apresenta doença localizada ao diagnóstico, enquanto apenas 4% têm doença metastática. Um dos principais mecanismos responsáveis pela progressão tumoral é a transição epitélio-mesenquimal (TEM). Esse é um programa celular reversível no qual a célula epitelial perde a capacidade de aderência intercelular e assume um fenótipo mesenquimal com potencial invasivo e metastático. A principal característica da TEM é a repressão da E-caderina através de fatores de transcrição que incluem ZEB1, ZEB2, Snail, Slug e Twist1. Os microRNAs também estão envolvidos na regulação do processo, sendo a família do miR-200 uma das mais importantes e uma potente indutora da diferenciação epitelial. Assim sendo, o conhecimento dos fatores envolvidos na TEM no CaP é fundamental para a compreensão do comportamento biológico dessa neoplasia. Objetivos: Analisar a expressão dos genes e microRNAs envolvidos na transição epitélio-mesenquimal em espécimes de câncer de próstata localizado e em linhagens celulares de câncer de próstata metastático. Além disso, correlacionar o perfil de expressão dos genes e microRNAs com parâmetros clínico-patológicos. Material e métodos: O estudo consistiu na análise de espécimes de 51 pacientes com CaP localizado tratados por prostatectomia radical e de linhagens celulares de CaP metastático (LNCaP, DU145 e PC3). O grupo controle foi composto por 10 casos de hiperplasia prostática benigna. A expressão dos genes E-caderina, N-caderina, Vimentina, TGF-beta1, ZEB1, ZEB2, Snail, Slug, Twist1 e PDGF-D e dos microRNAs 200a, 200b, 200c, 429, 141, 203, 205, 183, 373, 21, 9, 1, 495, 29b, 30a, 34a, 155 e 10b foi avaliada através da técnica de PCR em tempo real (qRT-PCR) nos espécimes e nas linhagens. Para correlação com parâmetros clínico-patológicos, os pacientes foram divididos em grupos em...


Introduction: Prostate cancer (PCa) is the most common cancer in men and the second leading cause of cancer-related mortality in Brazil. After the adoption of screening, most patients present with localized disease at the time of diagnosis, while only 4% have metastatic disease. One of the main mechanisms of tumor progression is the epithelial-mesenchymal transition (EMT). This is a reversible cell-biological program in which an epithelial cell loses intercellular adhesion and acquires a mesenchymal phenotype with invasiveness and metastatic potential. The main event in EMT is the repression of E-cadherin by transcriptional factors, including ZEB1, ZEB2, Snail, Slug, and Twist1. microRNAs are also involved in the regulation of this process, and one of the most important ones is the miR-200 family, which is a powerful inducer of epithelial differentiation. Therefore, the knowledge of the factors involved in EMT in PCa is essential to understand the biological behavior of this neoplasia. Objectives: Analysis of gene and miRNA expression involved in epithelial-mesenchymal transition in specimens of localized prostate cancer and metastatic prostate cancer cell lines. Correlation between the gene and miRNA expression profiles and clinicopathological features. Material and Methods: This study consisted in the analysis of specimens from 51 patients with localized PCa treated by radical prostatectomy and of metastatic PCa cell lines (LNCaP, DU145, PC3). The control group was composed by 10 cases of benign prostatic hyperplasia. Gene expression of E-cadherin, N-cadherin, Vimentin, TGF-beta1, ZEB1, ZEB2, Snail, Slug, Twist1, and PDGF-D as well as miRNA expression of 200a, 200b, 200c, 429, 141, 203, 205, 183, 373, 21, 9, 1, 495, 29b, 30a, 34a, 155, and 10b were assessed by Real-Time PCR (qRT-PCR). The patients were divided into groups according to Gleason score, pathological stage, preoperative PSA, biochemical recurrence, and low and high-risk disease. For evaluation...


Assuntos
Humanos , Masculino , Transição Epitelial-Mesenquimal , MicroRNAs , Biologia Molecular , Biomarcadores Tumorais , Prognóstico , Neoplasias da Próstata
6.
Acta cir. bras ; Acta cir. bras;28(8): 568-573, Aug. 2013. ilus, graf
Artigo em Inglês | LILACS | ID: lil-680610

RESUMO

PURPOSE:To design an animal model of ischemia-reperfusion (I/R) in kidneys and evaluate the role that predetermined ranges of local hypothermia plays on markers of stress-oxydative as well as on histologic sections. METHODS: Twenty eight male rats Wistar, under general anesthesia, undergone right nephrectomy (G0, control group) followed by left kidney ischemia during 40 min. Four temperatures groups were designed, with seven animals randomized for each group: normothermic (G1, ±37ºC), mild hypothermia (G2, 26ºC), moderate hypothermia (G3, 15ºC) and deep hypothermia (G4, 4ºC). Left kidney temperature was assessed with an intraparenchymal probe. Left nephrectomy was performed after 240 min of reperfusion. After I/R a blood sample was obtained for f2-IP. Half of each kidney was sent to pathological evaluation and half to analyze CAT, SOD, TBARS, NO3, NO2. RESULTS:Histopathology showed that all kidneys under I/R were significantly more injured than the G0 (p<0.001). TBARS had increased levels in all I/R groups compared with the G0 (p<0.001). CAT had a significant difference (p<0.03) between G1 and G4. Finally, no difference was found on SOD, NO3, NO2 nor on f2-IP. CONCLUSION: This model of I/R was efficient to produce oxidative-stress in the kidney, showing that 4ºC offered significant decrease in free radicals production, although tissue protection was not observed.


Assuntos
Animais , Masculino , Ratos , Hipotermia Induzida , Isquemia/metabolismo , Rim/irrigação sanguínea , Estresse Oxidativo/fisiologia , Traumatismo por Reperfusão/metabolismo , Biomarcadores , Radicais Livres/metabolismo , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos , Modelos Animais , Nefrectomia , Óxido Nítrico/metabolismo , Distribuição Aleatória , Ratos Wistar , Traumatismo por Reperfusão/patologia , Fatores de Tempo
7.
Acta cir. bras. ; 28(8): 568-573, Aug. 2013. ilus, graf
Artigo em Inglês | VETINDEX | ID: vti-9030

RESUMO

PURPOSE:To design an animal model of ischemia-reperfusion (I/R) in kidneys and evaluate the role that predetermined ranges of local hypothermia plays on markers of stress-oxydative as well as on histologic sections. METHODS: Twenty eight male rats Wistar, under general anesthesia, undergone right nephrectomy (G0, control group) followed by left kidney ischemia during 40 min. Four temperatures groups were designed, with seven animals randomized for each group: normothermic (G1, ±37ºC), mild hypothermia (G2, 26ºC), moderate hypothermia (G3, 15ºC) and deep hypothermia (G4, 4ºC). Left kidney temperature was assessed with an intraparenchymal probe. Left nephrectomy was performed after 240 min of reperfusion. After I/R a blood sample was obtained for f2-IP. Half of each kidney was sent to pathological evaluation and half to analyze CAT, SOD, TBARS, NO3, NO2. RESULTS:Histopathology showed that all kidneys under I/R were significantly more injured than the G0 (p<0.001). TBARS had increased levels in all I/R groups compared with the G0 (p<0.001). CAT had a significant difference (p<0.03) between G1 and G4. Finally, no difference was found on SOD, NO3, NO2 nor on f2-IP. CONCLUSION: This model of I/R was efficient to produce oxidative-stress in the kidney, showing that 4ºC offered significant decrease in free radicals production, although tissue protection was not observed.(AU)


Assuntos
Animais , Ratos , Estresse Oxidativo/fisiologia , Hipotermia , Rim/anatomia & histologia , Ratos/classificação , Anestesia
8.
Acta Cir Bras ; 28(8): 568-73, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23896835

RESUMO

PURPOSE: To design an animal model of ischemia-reperfusion (I/R) in kidneys and evaluate the role that predetermined ranges of local hypothermia plays on markers of stress-oxydative as well as on histologic sections. METHODS: Twenty eight male rats Wistar, under general anesthesia, undergone right nephrectomy (G0, control group) followed by left kidney ischemia during 40 min. Four temperatures groups were designed, with seven animals randomized for each group: normothermic (G1, ±37ºC), mild hypothermia (G2, 26ºC), moderate hypothermia (G3, 15ºC) and deep hypothermia (G4, 4ºC). Left kidney temperature was assessed with an intraparenchymal probe. Left nephrectomy was performed after 240 min of reperfusion. After I/R a blood sample was obtained for f2-IP. Half of each kidney was sent to pathological evaluation and half to analyze CAT, SOD, TBARS, NO3, NO2. RESULTS: Histopathology showed that all kidneys under I/R were significantly more injured than the G0 (p<0.001). TBARS had increased levels in all I/R groups compared with the G0 (p<0.001). CAT had a significant difference (p<0.03) between G1 and G4. Finally, no difference was found on SOD, NO3, NO2 nor on f2-IP. CONCLUSION: This model of I/R was efficient to produce oxidative-stress in the kidney, showing that 4ºC offered significant decrease in free radicals production, although tissue protection was not observed.


Assuntos
Hipotermia Induzida , Isquemia/metabolismo , Rim/irrigação sanguínea , Estresse Oxidativo/fisiologia , Traumatismo por Reperfusão/metabolismo , Animais , Biomarcadores , Radicais Livres/metabolismo , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos , Masculino , Modelos Animais , Nefrectomia , Óxido Nítrico/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia , Fatores de Tempo
9.
Urol Oncol ; 31(2): 175-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21795075

RESUMO

OBJECTIVE: Perineural invasion (PNI) is detected in almost 20% of prostate biopsies and has been related to worse prognostic factors in radical prostatectomy (RP) specimens and lower disease-free survival rates. The aim of this study was to evaluate the importance of PNI during periods of extended prostate biopsies and to determine the value of this preoperative parameter as a predictor of pathologic findings in surgical specimens and in biochemical recurrence. MATERIALS AND METHODS: Between 2001 and 2009, 599 prostate biopsies and their respective RP specimens were examined in our laboratory. The RP specimens were always examined completely. The mean age of the patients was 61 years, and the mean PSA was 6.4 ng/mL. The mean and median number of biopsy cores obtained was 14.4 and 14, respectively. PNI was identified in 105 biopsies (17.5%). We studied the ability of PNI in prostate biopsies to determine the tumor stage in surgical specimens and the relationship of PNI with biochemical recurrence during a mean follow-up time of 51.4 months. RESULTS: The presence of PNI in prostate biopsies was observed in older patients (63 vs. 61 years old, P = 0.008). All of the prognostic factors determined for the RP specimens were significantly worse in patients with PNI compared with those without PNI. PNI was strongly associated with a higher pathologic stage (87% specificity, 40% sensitivity, odds ratio 4.8). Stage pT3 prostatic cancer was determined in 46 (43.8%) of 105 patients with PNI on biopsy compared to 69 (14%) of 494 patients without PNI (P = 0.01). Fifty-six (19.6%) patients had a biochemical recurrence, and PNI correlated significantly with PSA recurrence. A Kaplan-Meier analysis revealed a significant difference in recurrence-free survival between patients with and without PNI (45% vs. 53%, respectively, P = 0.021, log-rank test = 0.19). CONCLUSION: PNI is an important morphologic preoperative predictor of the pathologic stage as well as biochemical recurrence and must always be mentioned when adenocarcinoma is diagnosed on prostate biopsies.


Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Adenocarcinoma/cirurgia , Adulto , Biópsia , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prostatectomia , Neoplasias da Próstata/cirurgia
10.
Int. braz. j. urol ; 38(6): 760-768, Nov-Dec/2012. tab, graf
Artigo em Inglês | LILACS | ID: lil-666022

RESUMO

Introduction

The widespread screening programs prompted a decrease in prostate cancer stage at diagnosis, and active surveillance is an option for patients who may harbor clinically insignificant prostate cancer (IPC). Pathologists include the possibility of an IPC in their reports based on the Gleason score and tumor volume. This study determined the accuracy of pathological data in the identification of IPC in radical prostatectomy (RP) specimens. Materials and Methods

Of 592 radical prostatectomy specimens examined in our laboratory from 2001 to 2010, 20 patients harbored IPC and exhibited biopsy findings suggestive of IPC. These biopsy features served as the criteria to define patients with potentially insignificant tumor in this population. The results of the prostate biopsies and surgical specimens of the 592 patients were compared. Results

The twenty patients who had IPC in both biopsy and RP were considered real positive cases. All patients were divided into groups based on their diagnoses following RP: true positives (n = 20), false positives (n = 149), true negatives (n = 421), false negatives (n = 2). The accuracy of the pathological data alone for the prediction of IPC was 91.4%, the sensitivity was 91% and the specificity was 74%. Conclusion

The identification of IPC using pathological data exclusively is accurate, and pathologists should suggest this in their reports to aid surgeons, urologists and radiotherapists to decide the best treatment for their patients. .


Assuntos
Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma/patologia , Próstata/patologia , Neoplasias da Próstata/patologia , Biópsia , Carcinoma/cirurgia , Gradação de Tumores , Valor Preditivo dos Testes , Prostatectomia , Neoplasias da Próstata/cirurgia , Reprodutibilidade dos Testes , Carga Tumoral
11.
Int Braz J Urol ; 38(6): 760-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23302398

RESUMO

INTRODUCTION: The widespread screening programs prompted a decrease in prostate cancer stage at diagnosis, and active surveillance is an option for patients who may harbor clinically insignificant prostate cancer (IPC). Pathologists include the possibility of an IPC in their reports based on the Gleason score and tumor volume. This study determined the accuracy of pathological data in the identification of IPC in radical prostatectomy (RP) specimens. MATERIALS AND METHODS: Of 592 radical prostatectomy specimens examined in our laboratory from 2001 to 2010, 20 patients harbored IPC and exhibited biopsy findings suggestive of IPC. These biopsy features served as the criteria to define patients with potentially insignificant tumor in this population. The results of the prostate biopsies and surgical specimens of the 592 patients were compared. RESULTS: The twenty patients who had IPC in both biopsy and RP were considered real positive cases. All patients were divided into groups based on their diagnoses following RP: true positives (n = 20), false positives (n = 149), true negatives (n = 421), false negatives (n = 2). The accuracy of the pathological data alone for the prediction of IPC was 91.4%, the sensitivity was 91% and the specificity was 74%. CONCLUSION: The identification of IPC using pathological data exclusively is accurate, and pathologists should suggest this in their reports to aid surgeons, urologists and radiotherapists to decide the best treatment for their patients.


Assuntos
Carcinoma/patologia , Próstata/patologia , Neoplasias da Próstata/patologia , Adulto , Idoso , Biópsia , Carcinoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Prostatectomia , Neoplasias da Próstata/cirurgia , Reprodutibilidade dos Testes , Carga Tumoral
12.
Urol Oncol ; 30(6): 794-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21458310

RESUMO

INTRODUCTION AND OBJECTIVE: Because of the improvements on detection of early stage prostate cancer over the last decade, focal therapy for localized prostate cancer (PC) has been proposed for patients with low-risk disease. Such treatment would allow the control of cancer, thereby diminishing side effects, such as urinary incontinence and sexual dysfunction, which have an enormous impact on quality of life. The critical issue is whether it is possible to preoperatively predict clinically significant unifocal or unilateral prostate cancer with sufficient accuracy. Our aim is to determine whether there is any preoperative feature that can help select the ideal patient for focal therapy. MATERIAL AND METHODS: A total of 599 patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy followed by radical prostatectomy to treat PC were examined in our laboratory between 2001 and 2009. We established very restricted criteria to select patients with very-low-risk disease for whom focal therapy would be suitable (only 1 biopsy core positive, tumor no larger than 80% of a single core, no perineural invasion, PSA serum level < 10 ng/ml, Gleason score < 7 and clinical stage T1c, T2a-b). We defined 2 groups of patients who would be either adequately treated or not treated by focal therapy. The primary endpoint was the evaluation of preoperative features in order to identify which parameters should be considered when choosing good candidates for focal therapy. RESULTS: Fifty-six out of 599 patients met our criteria. The mean age was 59 years, and the mean number of biopsy cores was 14.4. Forty-seven (83.9%) were staged T1c, and 9 (16.1%) were staged T2a-b. Forty-four (78.6%) patients could be considered to have been adequately treated by focal therapy, and 12 (21.4%) could not. There was no statistical difference between the 2 groups considering age, clinical stage, PSA levels, Gleason score, and tumor volume in the biopsy. All 12 patients who could be considered inadequately treated had a bilateral, significant secondary tumor, 58.3% had Gleason ≥ 7, and 25% were staged pT3. CONCLUSION: Although focal therapy might be a good option for patients with localized prostate cancer, we are so far unable to select which of them would benefit from it based on preoperative data, even using very restricted criteria, and a considerable proportion of men would still be left undertreated.


Assuntos
Adenocarcinoma , Neoplasias da Próstata , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Fatores de Risco
13.
J Child Adolesc Psychopharmacol ; 19(4): 461-5, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19702499

RESUMO

In this naturalistic study, we assessed the effect of sluggish cognitive tempo (SCT) symptoms in the response to methylphenidate (MPH) in 88 children and adolescents with attention-deficit/hyperactivity disorder-Inattentive Type (ADHD-I) according to Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) criteria. SCT symptoms were assessed in these subjects by means of the Child Behavior Checklist (CBCL) scale. The response to MPH after 1 month of treatment was assessed by parental scores in the Swanson, Nolan, and Pelham Questionnaire-Version IV (SNAP-IV) scale. No significant differences were found between subjects with and without SCT symptoms in the response to MPH either assessing presence of SCT symptoms categorically (at least 1 symptom) or dimensionally (p < 0.5 for both analyses; effect size [ES] = 0.24). Our findings corroborate previous phenotypic data suggesting that SCT symptoms do not define a clinically relevant type of ADHD-I.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Atenção , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/psicologia , Metilfenidato/uso terapêutico , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Criança , Pré-Escolar , Transtornos Cognitivos/complicações , Estudos de Coortes , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento
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