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1.
Urol Oncol ; 37(4): 290.e17-290.e24, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30630733

RESUMO

OBJECTIVE: To create multivariable models with readily available clinicopathologic variables for predicting the prognosis of upper tract urothelial carcinomas (UTUC). PATIENTS AND METHODS: We retrospectively analyzed patients diagnosed as UTUC and underwent radical nephroureterectomy in 2 high volumes, tertiary care centers. A total of 445 patients and 227 patients met the inclusion criteria were included for constructing the prediction model and external validation, respectively. Univariable and multivariable Cox regression models were used to analyze independent risk factors, and nomogram and calibration curve were constructed by R project. RESULTS: The median follow-up for the development and external validation cohorts were 33.5 and 32.5 months, respectively. Multivariable analysis detected older age (≥65 years), with concurrent bladder cancer at diagnosis, with both ureter and renal pelvic tumor, lymphovascular invasion, urothelial carcinoma with divergent differentiation, higher pathological grade and stage, and positive lymph node were significantly associated with poorer outcome of UTUC. The c-index of the nomogram with these above-mentioned independent risk factors to predict the cancer specific survival was 0.74 (95% CI, 0.64-0.84) and 0.73 (95%CI, 0.59-0.87) for the development cohort and external validation cohort, respectively. CONCLUSIONS: We developed and externally validated a novel and accurate nomogram with readily available clinicopathological information for predicting the cancer specific survival of UTUC. This nomogram could help clinicians stratify patients with UTUC into different risk groups with distinct prognosis by the total scores obtained from the prediction tool, thus facilitate decision-making and clinical trial designing.

2.
Chin J Cancer ; 37(1): 2, 2018 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-29357946

RESUMO

BACKGROUND: We previously showed that the expression of follistatin-like protein 1 (FSTL1) was significantly down-regulated in metastatic clear-cell renal cell carcinoma (ccRCC). In this study, we aimed to characterize the role of FSTL1 in the development of ccRCC. METHODS: The effects of FSTL1 on cell activity and cell cycle were investigated in ccRCC cell lines with altered FSTL1 expression. Gene expression microarray assays were performed to identify the major signaling pathways affected by FSTL1 knockdown. The expression of FSTL1 in ccRCC and its effect on postoperative prognosis were estimated in a cohort with 89 patients. RESULTS: FSTL1 knockdown promoted anchorage-independent growth, migration, invasion, and cell cycle of ccRCC cell lines, whereas FSTL1 overexpression attenuated cell migration. FSTL1 knockdown up-regulated nuclear factor-κB (NF-κB) and hypoxia-inducible factor (HIF) signaling pathways, increased epithelial-to-mesenchymal transition, up-regulated interleukin-6 expression, and promoted tumor necrosis factor-α-induced degradation of NF-κB inhibitor (IκBα) in ccRCC cell lines. FSTL1 immunostaining was selectively positive in epithelial cytoplasm in the loop of Henle, and positive rate of FSTL1 was significantly lower in ccRCC tissues than in adjacent renal tissues (P < 0.001). The multivariate Cox regression analysis showed that the intratumoral FSTL1 expression conferred a favorable independent prognosis with a hazard ratio of 0.325 (95% confidence interval 0.118-0.894). HIF-2α expression was negatively correlated with FSTL1 expression in ccRCC specimens (r = - 0.229, P = 0.044). Intratumoral expression of HIF-2α, rather than HIF-1α, significantly predicted an unfavorable prognosis in ccRCC (log-rank, P = 0.038). CONCLUSIONS: FSTL1 plays a tumor suppression role possibly via repressing the NF-κB and HIF-2α signaling pathways. To increase FSTL1 expression might be a candidate therapeutic strategy for metastatic ccRCC.

3.
Nano Lett ; 18(2): 1373-1378, 2018 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-29337565

RESUMO

Quantum mechanical effects of single particles can affect the collective plasmon behaviors substantially. In this work, the quantum control of plasmon excitation and propagation in graphene is demonstrated by adopting the variable quantum transmission of carriers at Heaviside potential steps as a tuning knob. First, the plasmon reflection is revealed to be tunable within a broad range by varying the ratio γ between the carrier energy and potential height, which originates from the quantum mechanical effect of carrier propagation at potential steps. Moreover, the plasmon excitation by free-space photos can be regulated from fully suppressed to fully launched in graphene potential wells also through adjusting γ, which defines the degrees of the carrier confinement in the potential wells. These discovered quantum plasmon effects offer a unified quantum-mechanical solution toward ultimate control of both plasmon launching and propagating, which are indispensable processes in building plasmon circuitry.

4.
Eur Urol ; 2017 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-28927585

RESUMO

BACKGROUND: Global disparities in prostate cancer (PCa) incidence highlight the urgent need to identify genomic abnormalities in prostate tumors in different ethnic populations including Asian men. OBJECTIVE: To systematically explore the genomic complexity and define disease-driven genetic alterations in PCa. DESIGN, SETTING, AND PARTICIPANTS: The study sequenced whole-genome and transcriptome of tumor-benign paired tissues from 65 treatment-naive Chinese PCa patients. Subsequent targeted deep sequencing of 293 PCa-relevant genes was performed in another cohort of 145 prostate tumors. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The genomic alteration landscape in PCa was analyzed using an integrated computational pipeline. Relationships with PCa progression and survival were analyzed using nonparametric test, log-rank, and multivariable Cox regression analyses. RESULTS AND LIMITATIONS: We demonstrated an association of high frequency of CHD1 deletion with a low rate of TMPRSS2-ERG fusion and relatively high percentage of mutations in androgen receptor upstream activator genes in Chinese patients. We identified five putative clustered deleted tumor suppressor genes and provided experimental and clinical evidence that PCDH9, deleted/loss in approximately 23% of tumors, functions as a novel tumor suppressor gene with prognostic potential in PCa. Furthermore, axon guidance pathway genes were frequently deregulated, including gain/amplification of PLXNA1 gene in approximately 17% of tumors. Functional and clinical data analyses showed that increased expression of PLXNA1 promoted prostate tumor growth and independently predicted prostate tumor biochemical recurrence, metastasis, and poor survival in multi-institutional cohorts of patients with PCa. A limitation of this study is that other genetic alterations were not experimentally investigated. CONCLUSIONS: There are shared and salient genetic characteristics of PCa in Chinese and Caucasian men. Novel genetic alterations in PCDH9 and PLXNA1 were associated with disease progression. PATIENT SUMMARY: We reported the first large-scale and comprehensive genomic data of prostate cancer from Asian population. Identification of these genetic alterations may help advance prostate cancer diagnosis, prognosis, and treatment.

5.
Asian J Androl ; 19(2): 238-243, 2017 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26780868

RESUMO

Prostate cancer antigen 3 (PCA3) is a biomarker for diagnosing prostate cancer (PCa) identified in the Caucasian population. We evaluated the effectiveness of urinary PCA3 in predicting the biopsy result in 500 men undergoing initial prostate biopsy. The predictive power of the PCA3 score was evaluated by the area under receiver operating characteristic (ROC) curve (AUC) and by decision curve analysis. PCA3 score sufficed to discriminate positive from negative prostate biopsy results but was not correlated with the aggressiveness of PCa. The ROC analysis showed a higher AUC for the PCA3 score than %fPSA (0.750 vs 0.622, P = 0.046) in patients with a PSA of 4.0-10.0 ng ml-1 , but the PCA3-based model is not significantly better than the base model. Decision curve analysis indicates the PCA3-based model was superior to the base model with a higher net benefit for almost all threshold probabilities, especially the threshold probabilities of 25%-40% in patients with a PSA of 4.0-10.0 ng ml-1 . However, the AUC of the PCA3 score (0.712) is not superior to %fPSA (0.698) or PSAD (0.773) in patients with a PSA >10.0 ng ml-1 . Our results confirmed that the RT-PCR-based PCA3 test moderately improved diagnostic accuracy in Chinese patients undergoing first prostate biopsy with a PSA of 4.0-10.0 ng ml-1 .


Assuntos
Antígenos de Neoplasias/genética , Neoplasias da Próstata/urina , RNA Mensageiro/urina , Idoso , Antígenos de Neoplasias/urina , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , Biópsia com Agulha de Grande Calibre , China , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade
6.
Anal Bioanal Chem ; 408(24): 6741-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27473428

RESUMO

Bladder cancer (BC) is a fatal malignancy with considerable mortality. BC urinary metabolomics has been extensively investigated for biomarker discovery, but few BC blood metabolomic studies have been performed. Hence, a plasma pseudotargeted metabolomic method based on gas chromatography-mass spectrometry with selected ion monitoring (GC-MS-SIM) was developed to study metabolic alterations in BC. The analytical performance of the developed method was compared with that of a nontargeted method. The relative standard deviation (RSD) values of 89 and 70.7 % of the peaks obtained using the pseudotargeted and nontargeted methods, respectively, were less than 20 %. The Pearson correlations of 90.7 and 78.3 % of the peaks obtained using the pseudotargeted and nontargeted methods, respectively, exceeded 0.90 in the linearity evaluation. Compared with the nontargeted method, the signal-to-noise ratios (S/N) of 97.9 and 69.3 % of the peaks increased two- and fivefold, respectively. The developed method was fully validated, with good precision, recovery, and stability of the trimethylsilyl (TMS) derivatives. The method was applied to investigate BC. Significant increases in the contents of metabolites involved in, for example, the pentose phosphate pathway (PPP) and nucleotide and fatty acid synthesis were found in the high-grade (HG) BC group compared to the healthy control (HC) group. These differences imply that the activated PPP may regulate BC cell proliferation by promoting lipid and nucleotide biosynthesis and the detoxification of reactive oxygen species (ROS). These results illustrate that the plasma pseudotargeted method is a powerful tool for metabolic profiling. Graphical abstract The plasma pseudotargeted metabolic profiling suggested the metabolic alterations in bladder cancer (BC) and the significantly differential metabolites for BC discrimination.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Metaboloma , Metabolômica/métodos , Neoplasias da Bexiga Urinária/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/metabolismo
7.
Sci Rep ; 6: 26689, 2016 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-27225192

RESUMO

Few single nucleotide polymorphisms (SNPs) associated with the risk of renal cell carcinoma (RCC) have been identified, yet genetic predisposition contributes significantly to this malignancy. We previously showed that follistatin-like 1 (FSTL1) was significantly down-regulated in clear cell RCC (ccRCC), in particular metastatic ccRCC. In the present study, we systemically investigated the associations of the 6 SNPs within FSTL1-coding genomic region with RCC risk and postoperative prognosis. Age- and gender-matched case-control study (417 vs 855) indicated that rs1259293 variant genotype CC was significantly associated with an increased risk of RCC, with an odds ratio of 2.004 (95% confidence internal [CI] = 1.190-3.375). Multivariate Cox regression analysis in 309 of 417 cases showed that rs1259293 genotype (CC vs TT + CT) independently predicted an unfavorable prognosis, with a hazard ratio of 2.531 (95% CI = 1.052-6.086). Expression of FSTL1 was significantly higher in adjacent renal tissues than in tumors, and significantly higher in the tissues with rs1259293 TT genotype than in those with rs1259293 TC+CC genotypes. rs1259293 C allele might generate a CTCF binding site that blocks trans-activation of FSTL1 expression. Our results indicate that rs1259293 is associated with an increased risk and unfavorable postoperative prognosis of RCC, possibly by down-regulating FSTL1 expression in renal tissues.


Assuntos
Carcinoma de Células Renais , Proteínas Relacionadas à Folistatina , Neoplasias Renais , Proteínas de Neoplasias , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Intervalo Livre de Doença , Feminino , Proteínas Relacionadas à Folistatina/biossíntese , Proteínas Relacionadas à Folistatina/genética , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Fatores de Risco , Taxa de Sobrevida
8.
Oncotarget ; 7(13): 17275-85, 2016 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-26943768

RESUMO

The current strategy for the histological assessment of prostate cancer (PCa) is mainly based on the Gleason score (GS). However, 30-40% of patients who undergo radical prostatectomy (RP) are misclassified at biopsy pathologically. Thus, we developed and validated nomograms for the prediction of Gleason score upgrading (GSU) in patients who underwent radical prostatectomy after extended prostate biopsy in a Chinese population. This retrospective study included a total of 411 patients who underwent radical prostatectomy at our institute after having prostate biopsies between 2011 and 2015. The final pathologic GS was upgraded in 151 (36.74%) of the cases in all patients and 92 (60.13%) cases in men with GS=6. In multivariate analyses, the primary biopsy GS, secondary biopsy GS and obesity were predictive of GSU in the patient cohort assessed. In patients with GS=6, the significant predictors of GSU included the body mass index (BMI), prostate-specific antigen density(PSAD) and percentage of positive cores. The area under the curve (AUC) of the prediction models was 0.753 for the entire patient population and 0.727 for the patients with GS=6. Both nomograms were well calibrated, and decision curve analysis demonstrated a high net benefit across a wide range of threshold probabilities. This study may be relevant for improved risk assessment and clinical decision-making in PCa patients.


Assuntos
Gradação de Tumores/métodos , Nomogramas , Neoplasias da Próstata/patologia , Idoso , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , Biópsia , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia , Neoplasias da Próstata/cirurgia , Curva ROC , Estudos Retrospectivos
9.
J Endourol ; 30(6): 704-8, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26998959

RESUMO

PURPOSE: To introduce scrotoscopy in the diagnosis of testicular torsion and evaluate its value in clinical application. PATIENTS AND METHODS: From February 2010 to June 2013, 14 patients, aged 12 to 24 years, were included into this study due to acute onset of scrotal pain. On Doppler ultrasound imaging, the blood flow decreased in seven cases (including two "no flow" cases) and remained normal in the other seven. Following anesthesia, a 10F pediatric cystoscope employed as scrotoscope was inserted into the cavity of tunica vaginalis of the testis with continued saline washing to exam the testis and epididymis. RESULTS: The scrotoscope had a diagnostic accuracy of 100% (100% specificity and 100% sensitivity), and the color Doppler ultrasound had 77.8% specificity. Five cases were diagnosed with testicular torsion, among which four were corrected and one underwent orchiectomy. No complications were observed in these patients. Nine patients with epididymitis were given oral antibiotics, and the blood flow of the testis was normal in the testis-preserving patient. CONCLUSIONS: Our study showed that scrotoscopy could serve as a minimally invasive, safe, and effective approach in the early diagnosis of testicular torsion.


Assuntos
Torção do Cordão Espermático/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Administração Oral , Adolescente , Antibacterianos/administração & dosagem , Criança , Epididimite/diagnóstico por imagem , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Testículo/diagnóstico por imagem , Testículo/cirurgia , Adulto Jovem
10.
Oncotarget ; 7(16): 21393-403, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-26881390

RESUMO

Prostate cancer predisposition has been extensively investigated in European populations, but there have been few studies of other ethnic groups. To investigate prostate cancer susceptibility in the under-investigated Chinese population, we performed single-nucleotide polymorphism (SNP) array analysis on a cohort of Chinese cases and controls and then meta-analysis with data from the existing Chinese prostate cancer genome-wide association study (GWAS). Genotyping 211,155 SNPs in 495 cases and 640 controls of Chinese ancestry identified several new suggestive Chinese prostate cancer predisposition loci. However, none of them reached genome-wide significance level either by meta-analysis or replication study. The meta-analysis with the Chinese GWAS data revealed that four 8q24 loci are the main contributors to Chinese prostate cancer risk and the risk alleles from three of them exist at much higher frequencies in Chinese than European populations. We also found that several predisposition loci reported in Western populations have different effect on Chinese men. Therefore, this first extensive single-nucleotide polymorphism study of Chinese prostate cancer in comparison with European population indicates that four loci on 8q24 contribute to a great risk of prostate cancer in a considerable large proportion of Chinese men. Based on those four loci, the top 10% of the population have six- or two-fold prostate cancer risk compared with men of the bottom 10% or median risk respectively, which may facilitate the design of prostate cancer genetic risk screening and prevention in Chinese men. These findings also provide additional insights into the etiology and pathogenesis of prostate cancer.


Assuntos
Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Grupo com Ancestrais do Continente Asiático/genética , China , Cromossomos Humanos Par 8/genética , Grupo com Ancestrais do Continente Europeu/genética , Frequência do Gene , Loci Gênicos/genética , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Masculino , Neoplasias da Próstata/etnologia , Fatores de Risco
11.
Cancer Lett ; 374(1): 62-74, 2016 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-26808578

RESUMO

We previously reported that PlncRNA-1, a long non-coding RNA that is up-regulated in prostate cancer (PCa), affects the proliferation and apoptosis of PCa cells. However, the molecular mechanisms underlying these effects remain largely unknown. In this study, we demonstrated that long non-coding RNA PlncRNA-1, whose expression is promoted by Androgen Receptor (AR), protects AR from microRNA-mediated suppression in PCa cells. PlncRNA-1 knockdown resulted in the up-regulation of a series of AR-targeting microRNAs, among which miR-34c and miR-297 were found to regulate both AR and PlncRNA-1 expression at the post-transcriptional level. Functional analysis revealed that miR-34c and miR-297 overexpression down-regulated AR expression and inhibited the expression of downstream AR targets and that PlncRNA-1 overexpression rescued these effects. The association of PlncRNA-1 with tumor progression was also evaluated in mouse xenograft models, PCa tissues (16 paired samples), and blood samples (35 biopsy-negative and 37 biopsy-positive). Together, the data generated in this study indicate that PlncRNA-1 sponges AR-targeting microRNAs to protect AR from microRNA-mediated down-regulation and that these events form a regulatory feed-forward loop in the development of PCa. These findings suggest that PlncRNA-1 might potentially serve as a novel biomarker in PCa and that PlncRNA-1 might warrant further investigation to determine its potential role as a promising therapeutic target in PCa.


Assuntos
Neoplasias da Próstata/metabolismo , RNA Longo não Codificante/metabolismo , Receptores Androgênicos/metabolismo , Animais , Apoptose/fisiologia , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Citoplasma/genética , Citoplasma/metabolismo , Progressão da Doença , Células HEK293 , Xenoenxertos , Humanos , Hibridização in Situ Fluorescente , Masculino , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética , Receptores Androgênicos/genética , Transfecção , Regulação para Cima
12.
Zhonghua Nan Ke Xue ; 22(7): 626-629, 2016 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-28965381

RESUMO

Objective: To investigate the treatment of azoospermia induced by iatrogenic injury to the bilateral vas deferens. METHODS: We retrospectively analyzed 11 cases of azoospermia caused by iatrogenic injury to bilateral vas deferens. The patients were aged 20-33 years, all diagnosed with azoospermia preoperatively and none with a history of pelvic operation. Seven of them had received bilateral inguinal hernia repair and the other 4 undergone bilateral orchidopexy in the childhood. RESULTS: Intraoperative exploration of the bilateral inguinal region was performed in all the patients. Bilateral vas deference atresia was found in the inguinal canal in 6 cases, which was treated by microscopic vasovasostomy following removal of the atresic segment. Vas deferens residual was observed in or near the deep inguinal ring in the other 5 cases, with the distal vas deferens inaccessible, which was treated by bilateral vasovasostomy in 3 cases and unilateral vasovasostomy in 2 (for longer defect segment than could be anastomosed) following combined laparoscopic exploration of the abdominal cavity. The patients were followed up for 3-12 months postoperatively, during which sperm were detected in 7 cases, with sperm concentration ranging from 0.4×106/ml to 35×106/ml and grade a+b sperm from 15% to 46%. CONCLUSIONS: For the diagnosis of azoospermia, especially in patients with no history of pelvic operation, special attention should be paid to iatrogenic injury to the vas deferens. For the treatment of the disease, non-tension vasovasostomy is essential and, when necessary, the vas deferens can be reconstructed by changing its anatomical path and shortening its length.


Assuntos
Azoospermia/cirurgia , Doença Iatrogênica , Ducto Deferente/lesões , Adulto , Hérnia Inguinal/cirurgia , Humanos , Laparoscopia , Masculino , Microcirurgia , Pelve/cirurgia , Estudos Retrospectivos , Contagem de Espermatozoides , Vasovasostomia , Adulto Jovem
13.
World J Gastroenterol ; 21(21): 6764-8, 2015 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-26074716

RESUMO

Gastric cancer (GC) is the most prevalent malignancy in the world, especially in China. GC has been postulated to spread via several different routes, including through hematogenous channels, lymphatic vessels, the seeding of peritoneal surfaces, direct extension through the gastric wall, and retrograde extension through the vas deferens or lymphatics. Testicular metastasis is rare. We show here a 53-year-old patient with GC who underwent a radical total gastrectomy approximately 22 mo ago after he presented with a sensation of heaviness and swelling of the right hemiscrotum. The diagnosis of metastatic adenocarcinoma was made after a right-side orchiectomy. We report the first case of testicular metastasis from gastric adenocarcinoma in mainland China and summarize the clinicopathologic features of the disease based on previously published papers.


Assuntos
Adenocarcinoma Mucinoso/secundário , Neoplasias Gástricas/patologia , Neoplasias Testiculares/secundário , Adenocarcinoma Mucinoso/química , Adenocarcinoma Mucinoso/cirurgia , Biomarcadores Tumorais/análise , Biópsia , Gastrectomia , Humanos , Imuno-Histoquímica , Masculino , Metastasectomia/métodos , Pessoa de Meia-Idade , Orquiectomia , Valor Preditivo dos Testes , Neoplasias Gástricas/química , Neoplasias Gástricas/cirurgia , Neoplasias Testiculares/química , Neoplasias Testiculares/cirurgia , Resultado do Tratamento
14.
Urol Oncol ; 33(9): 384.e9-20, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26008593

RESUMO

OBJECTIVE: In recent years, great effort has been made to explore new biomarkers for early detection of prostate cancer. Our previous study has demonstrated the high prevalence of TTTY15-USP9Y in prostate cancer samples from a Chinese population. Our aim was to evaluate the clinical utility of TTTY15-USP9Y in predicting the prostate biopsy outcome. MATERIALS AND METHODS: We retrospectively examined the expression of TTTY15-USP9Y in 226 qualified urine sediment samples. Total RNA was extracted from the urine sediment by using TRIzol reagent, and complementary DNA was synthesized using TransPlex Complete Whole Transcriptome Amplification Kit (WTA2). Real-time quantitative polymerase chain reaction was performed to evaluate the expression of TTTY15-USP9Y and the prostate cancer-specific antigen (PSA) level. The TTTY15-USP9Y score was calculated as 2(Ct(PSA)-Ct(TTTY15-USP9Y))× 1,000. RESULTS: The TTTY15-USP9Y score was statistically significantly higher in men with positive biopsy outcome than in men with negative biopsy outcome (P<0.001). The area under the curve was 0.828 for the TTTY15-USP9Y score in the entire patient cohort. The TTTY15-USP9Y score׳s cutoff of 90.28 provided the optimal balance between sensitivity (84.0%) and specificity (77.5%). The combination of PSA level and the TTTY15-USP9Y score significantly improved the diagnostic performance of PSA level (P = 0.001). The TTTY15-USP9Y score alone was superior to PSA level, percent free PSA, and PSA density (serum PSA/prostate volume) in the subgroup of clinical interest (PSA level: 4-10ng/ml, gray zone). Univariable and multivariable logistic analyses indicated that TTTY15-USP9Y score, PSA level, age, and prostate volume were independent predictors of PCa. Adding the TTTY15-USP9Y score in the clinical base model (PSA level, age, and prostate volume) could bring a higher net benefit and reduce more unnecessary biopsies in the defined range of interest (10%-40% threshold probability). CONCLUSION: In conclusion, our study explored the potential utility of measuring the TTTY15-USP9Y score in post-digital rectal examination urine samples to predict biopsy outcome and provided the basis for the utility of this novel gene fusion in multicenter and large cohort studies.


Assuntos
Biomarcadores Tumorais/genética , Proteínas de Fusão Oncogênica/genética , Neoplasias da Próstata/genética , Ubiquitina Tiolesterase/genética , Idoso , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , Biomarcadores Tumorais/urina , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade Menor , Proteínas de Fusão Oncogênica/urina , Prognóstico , Neoplasias da Próstata/urina , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Sensibilidade e Especificidade , Ubiquitina Tiolesterase/urina
15.
Onco Targets Ther ; 8: 313-21, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25674006

RESUMO

Renal cell carcinoma (RCC) is the most common type of cancer arising from the kidney, with a male to female ratio of 2:1. The incidence of RCC is rising. In males, it was the seventh most common cancer in the People's Republic of China in 2012. RCC is resistant to radiotherapy and chemotherapy, but approximately 20% of patients with advanced RCC respond to immunotherapy. Novel therapies targeting angiogenesis and signaling pathways have been proven to be effective for advanced or metastatic RCC in Western countries. Due to the heterogeneity of RCC between races, it is necessary to have an overview of targeted therapies, especially everolimus, for patients with advanced RCC in the People's Republic of China. Three targeted therapeutic agents have been approved in Mainland China for the treatment of patients with advanced RCC, ie, two tyrosine kinase inhibitors (sorafenib and sunitinib) and one mammalian target of rapamycin (mTOR) inhibitor (everolimus). Compared with Western patients with advanced or metastatic RCC, Chinese patients with the same disease respond better to sorafenib and sunitinib as first-line targeted therapy, but sunitinib has a relatively higher risk of toxicity. Everolimus, an mTOR inhibitor that can be administered orally, is well tolerated and acceptable to Chinese patients. Everolimus has competitive advantages as second-line targeted treatment for Chinese patients with advanced RCC who are resistant to first-line tyrosine kinase inhibitors. Despite a lack of noninferiority when compared with sunitinib as first-line therapy, the sunitinib-everolimus paradigm is still recommended as standard therapy for patients with advanced RCC. Although most studies of targeted therapies for advanced RCC have obvious limitations, such as small sample size and retrospective design, up-to-date evidence indicates that everolimus would be an ideal agent as second-line targeted treatment for advanced or metastatic RCC in the People's Republic of China.

16.
Prostate ; 75(6): 653-61, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25597901

RESUMO

BACKGROUND: Long non-coding RNA (LncRNA) PCA3 has been a well-established urine biomarker for the detection of prostate cancer (PCa). Our previous study showed a novel LncRNA FR0348383 is up-regulated in over 70% of PCa compared with matched benign tissues. The aim of this study was to evaluate the diagnostic value of urinary FR0348383 for men undergoing prostate biopsy due to elevated PSA (PSA > 4.0 ng/ml) and/or abnormal digital rectal examination (DRE). METHODS: Post-DRE first-catch urine specimens prior to prostate biopsies were prospectively collected. After the whole transcriptome amplification, quantitative real time polymerase chain reaction was applied to quantify urine FR0348383 and PSA levels. The FR0348383 score was calculated as the ratio of PSA and FR0348383 mRNA (PSA mRNA/FR0348383 mRNA × 1000). The diagnostic value of FR0348383 score was evaluated by logistic regression and decision curve analysis. RESULTS: 213 cases with urine samples containing sufficient mRNA were included, 94 cases had serum PSA level 4.0-10.0 ng/ml. PCa was identified in 72 cases. An increasing FR0348383 score was correlated with an increasing probability of a positive biopsy (P < 0.001). Multivariable logistic analysis indicated FR0348383 score (P < 0.001), PSA (P = 0.004), age (P = 0.007), prostate volume (P < 0.001) were independent predictors of PCa. ROC analysis demonstrated FR0348383 score outperformed PSA, %free PSA, and PSA Density in the prediction of PCa in the subgroup of patients with grey area PSA (AUC: 0.815 vs. 0.562 vs. 0.599 vs. 0.645). When using a probability threshold of 30% in the grey zone cohort, The FR0348383 score would save 52.0% of avoidable biopsies without missing any high grade cancers. CONCLUSIONS: FR0348383 transcript in post-DRE urine may be a novel biomarker for detection of PCa with great diagnostic value, especially in the grey zone cohort. The application of FR0348383 score in clinical practice might avoid unnecessary prostate biopsies and increase the specificity of PCa diagnosis.


Assuntos
Biópsia , Próstata/patologia , Neoplasias da Próstata/diagnóstico , RNA Longo não Codificante/urina , Idoso , Biomarcadores Tumorais/urina , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/urina
17.
J Endourol ; 29(1): 90-4, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24984054

RESUMO

PURPOSE: To evaluate the safety and efficacy of retrograde placement of single-J stent guided by a flexible cystoscope for management of ureteroenteral anastomotic stricture in patients after radical cystectomy and Bricker urinary diversion. PATIENTS AND METHODS: Between January 2008 and June 2012, 11 patients with ureteroenteral anastomotic stricture after open radical cystectomy and Bricker urinary diversion were enrolled in this study. All patients were treated with retrograde placement of single-J stent guided by a flexible cystoscope. A 7F single-J stent was placed for 6 weeks. RESULTS: Of the 11 patients, seven strictures occurred on the left side, two on the right side, and two on both sides. The retrograde procedure was successfully performed in 10 cases, and the remaining 1 was successful on the right side but failed on the left side. Upper urinary tract infection was well controlled in all three patients with fever. After a follow-up of 12 to 66 months, eight patients had long-term symptom relief, one patient had open surgery to remove the stricture and re-implant the ureter, and one patient died because of tumor recurrence. The only failed case was that of a left side percutaneous nephrostomy, but the patient was lost to follow-up. CONCLUSIONS: Retrograde placement of a single-J ureteral stent guided by a flexible cystoscope is safe and effective for ureteroenteral anastomotic stricture in patients with Bricker urinary diversion, and it brings fewer complications. The procedure is minimally invasive and could avoid immediate surgery for most patients.


Assuntos
Carcinoma de Células de Transição/cirurgia , Cistoscopia/métodos , Dilatação/métodos , Complicações Pós-Operatórias/cirurgia , Stents , Ureter/cirurgia , Obstrução Ureteral/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária , Adulto , Idoso , Anastomose Cirúrgica , Constrição Patológica/cirurgia , Cistectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
19.
BJU Int ; 115(3): 437-45, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24731125

RESUMO

OBJECTIVES: To compare the peri-operative and early renal functional outcomes of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) for kidney tumours. MATERIALS AND METHODS: A total of 237 patients fulfilling the selection criteria were included, of whom 146 and 91 patients were treated with LPN and RAPN, respectively. To adjust for potential baseline confounders, propensity-score matching was performed. A favourable outcome was defined as a warm ischaemia time (WIT) of ≤20 min, negative surgical margins, no surgical conversion, no Clavien ≥3 complications and no postoperative chronic kidney disease (CKD) upstaging. Descriptive statistics and multivariable logistic regression analyses were performed before and after propensity-score matching. RESULTS: Within the propensity-score-matched cohort, the RAPN group was associated with significantly lower estimated blood loss (EBL; 156 vs 198 mL, mean difference [MD] = -42; P = 0.025), a shorter WIT (22.8 vs 31 min, MD = -8.2; P < 0.001) and a higher proportion of malignant lesions (88.4 vs 67.5%; odds ratio [OR]: 2.6; 95% confidence interval [CI]: 1.2-5.67; P = 0.023). With regard to early renal functional outcomes, the mean last estimated glomerular filtration rate was 95.8 and 89.4 mL/min per 1.73 m(2) (MD = 6.4; P = 0.01), with a mean ± sd percentage change of -4.8 ± 17.9 and -12.2 ± 16.6 (MD = 7.4; P = 0.018) in the RAPN and LPN groups, respectively. The intra-operative complication rate was significantly lower in the RAPN group (1.3 vs 11.7%; OR 0.1, 95% CI 0.01-0.81; P = 0.018). On multivariable analysis, surgical approach (RAPN vs LPN, OR 5.457, 95% CI 2.075-14.346; P = 0.001), Charlson Comorbidity Index (OR 0.223; 95% CI 0.062-0.811; P = 0.023), diameter-axial-polar score (OR 0.488, 95% CI 0.329-0.723; P < 0.001) and preoperative CKD stage (OR 3.189, 95% CI 1.204-8.446; P = 0.020) were found to be independent predictors of obtaining a favourable outcome. CONCLUSIONS: After adjusting for potential treatment selection biases, RAPN was found to be superior to LPN for peri-operative outcomes (EBL, WIT and intra-operative complications) and early renal functional preservation.


Assuntos
Neoplasias Renais/cirurgia , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/efeitos adversos , Tratamentos com Preservação do Órgão/métodos , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
20.
Oncotarget ; 5(22): 11091-102, 2014 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-25526029

RESUMO

The current strategy for diagnosing prostate cancer (PCa) is mainly based on the serum prostate-specific antigen (PSA) test. However, PSA has low specificity and has led to numerous unnecessary biopsies. We evaluated the effectiveness of urinary metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), a long noncoding RNA, for predicting the risk of PCa before biopsy. The MALAT-1 score was tested in a discovery phase and a multi-center validation phase. The predictive power of the MALAT-1 score was evaluated by the area under receiver operating characteristic (ROC) curve (AUC) and by decision curve analysis. As an independent predictor of PCa, the MALAT-1 score was significantly higher in men with a positive biopsy than in those with a negative biopsy. The ROC analysis showed a higher AUC for the MALAT-1 score (0.670 and 0.742) vs. the total PSA (0.545 and 0.601) and percent free PSA (0.622 and 0.627) in patients with PSA values of 4.0-10 ng/ml. According to the decision curve analysis, using a probability threshold of 25%, the MALAT-1 model would prevent 30.2%-46.5% of unnecessary biopsies in PSA 4-10 ng/ml cohorts, without missing any high-grade cancers. Our results demonstrate that urine MALAT-1 is a promising biomarker for predicting prostate cancer risk.


Assuntos
Biomarcadores Tumorais/urina , Neoplasias da Próstata/urina , RNA Longo não Codificante/urina , Biomarcadores Tumorais/genética , Biópsia , Estudos de Coortes , Humanos , Calicreínas/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Valor Preditivo dos Testes , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Estudos Retrospectivos
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