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1.
Urol Oncol ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31952997

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) is the second common malignant tumor in the urinary system, and 85% of RCC cases are clear cell RCC (ccRCC). This study is designed to build a risk score system for ccRCC. METHODS: The gene methylation and expression data of ccRCC samples were downloaded from The Cancer Genome Atlas database (training set) and ArrayExpress database (validation set). The differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were identified by limma package, and their intersecting genes with negative Pearson correlation coefficients were remained using cor.test function. Prognosis-associated genes were identified by survival package, and the optimal DMGs were obtained using penalized package. After risk score system was built, nomogram survival model was constructed using rms package. Additionally, pathways were enriched for the DEGs between high- and low-risk groups using Gene Set Enrichment Analysis. RESULTS: There were 3,638 DMGs and 2,702 DEGs between tumor and normal samples. Among the 312 intersecting genes, 43 prognosis-associated genes were identified. A total of 13 optimal DMGs (BTBD19, ADAM8, BGLAP, TNFRSF13C, JPH4, BEST1, GNRH2, UBE2QL1, CHODL, GDF9, UPB1, KCNH3; and ADAMTSL4) were obtained for building the risk score system. After pathological M, pathological T, platelet qualitative, and RS status were revealed to be independent prognostic factors, a nomogram survival model was constructed. For the 920 DEGs between the high- and low-risk samples, 6 significant pathways were enriched. CONCLUSION: The 13-gene risk score system and the nomogram survival model might be used for prognostic prediction of ccRCC patients.

2.
Surg Endosc ; 34(1): 384-395, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30972621

RESUMO

BACKGROUND: The number of publications of systematic reviews and meta-analyses (MAs) on robotic surgery have been increasing, including many investigating the same topic. Their quality and extent of overlap remains unclear. We assessed the quality of the MAs in this area and investigated the extent of their overlap. METHODS: Relevant studies were identified by searching the MEDLINE, EMBASE, and Cochrane Library databases up to August 1, 2017. Reporting and methodological quality levels were assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Assessment of Multiple Systematic Reviews (AMSTAR) checklists. A thorough investigation of the extent of overlap was performed. RESULTS: In total, 90 MAs in 5 surgical subspecialties were included after full-text review. The mean reporting and methodological quality scores were 22.5 (83.2%) and 7.6 (69.2%), respectively. Authors from university-affiliated institutions and the presence of statistician or epidemiologist coauthors were associated with better-reporting quality scores. The topics with the most overlapping MAs (all ≥ 6) were robot-assisted thyroidectomy, prostatectomy, gastrectomy, colectomy, and fundoplication. 36 (40%) of the included MAs cited previous MAs on the same topic. Among the 7 MAs comparing robot-assisted radical prostatectomy to the open procedure, most (6/7) drew the same conclusion. 50 to 86% of MAs on this topic included the same trials as primary studies. CONCLUSION: Conducting multiple overlapping MAs with identical conclusions on the same topic that are of suboptimal quality may be a waste of resource and effort. Authors from university-affiliated institutes and experts in epidemiology and statistics are more likely to conduct MAs that have better quality. More guidelines and registries are needed to avoid overlapping MAs.

3.
Asian J Surg ; 43(2): 417-422, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31253384

RESUMO

OBJECTIVE: To evaluate the possibility and efficiency of a modified margin strategy in laparoscopic partial nephrectomy with selective renal artery clamping. METHODS: Seventy-six cases of laparoscopic partial nephrectomy with segmental renal artery clamping in Shanghai Changhai Hospital between July 2014 and September 2017 were retrospectively reviewed. Relevant clinical data were recorded including baseline patient and tumor characteristics, and surgical outcomes (segmental artery mobilization time, operating time, warm ischemic time, estimated blood loss, complications, and so on). A comparative analysis between standard technique and margin strategy was performed. RESULTS: In 38 cases, margin strategy to mobilize segmental artery was successfully performed. In the other 38 cases, the surgery was performed in traditional method. The use of new strategy led to a shortened segmental artery mobilization time (5 min vs 12 min, p < 0.001). There was no difference in terms of perioperative complications between the two techniques. CONCLUSIONS: The margin strategy is a practical method in laparoscopic partial nephrectomy with selective renal artery clamping. It provides a simplified way of finding segmental arteries. Further studies are needed to confirm these preliminary findings.

4.
Int J Cancer ; 146(2): 475-486, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31107971

RESUMO

Long noncoding RNAs (lncRNAs) promote cell proliferation, migration, invasion and castration resistance in prostate cancer (PCa). Understanding the inherited molecular mechanisms by which lncRNAs contribute to the progression of PCa to a lethal disease could have an important impact on cancer detection, diagnosis and prognosis. In our study, PCa-associated lncRNA transcripts from RNA-seq data were identified and screened via bioinformatics analysis, NCBI annotations and literature review. We identified a novel lncRNA, lncAPP (lncRNA activated in PCa progression), which activates in PCa progression and is expressed in primary tumor tissues and urine samples of patients with localized or advanced PCa. Urinary-based lncAPP is a promising biomarker for predicting PCa progression. In vitro and in vivo studies demonstrated that lncAPP enhanced cell proliferation and promoted migration and invasion. The underlying mechanism of lncRNA was investigated by RNA immunoprecipitation, dual-luciferase reporter system assay, etc. Upregulation of lncAPP promoted cell migration and invasion via competitively binding miR218 to facilitate ZEB2/CDH2 expression. In addition, in vivo subcutaneous tumor xenograft models and tail intravenously injection metastatic models were constructed to evaluate lncRNA function. Targeting lncAPP/miR218 axis in cell lines and tumor xenografts restrained tumor progression properties both in vitro and in vivo. These results establish that lncAPP/miR218 axis plays a critical role in PCa progression, and they also suggest new strategies to prevent tumor progression for therapeutic purposes.

5.
Cancer Control ; 26(1): 1073274819887697, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31793344

RESUMO

To evaluate the diagnostic value of α-methylacyl-CoA racemase (AMACR) score in Han Chinese patients with prostate cancer (PCa) through urine sediment analysis. We collected 292 urine sediment samples after digital rectal examination. Levels of AMACR and prostate-specific antigen (PSA) messenger RNA (mRNAs) were evaluated by quantitative real time-polymerase chain reaction. The diagnostic value of AMACR score was assessed by receiver-operating characteristic analysis (ROC), Mann-Whitney test, logistic regression analysis and decision curve analysis. In all patients (n = 292), the area under the curve (AUC) for serum PSA, AMACR score, and a combinative model of these 2 parameters were 0.745 (95% confidence interval [CI]: 0.691-0.794), 0.753 (95% CI: 0.700-0.802), and 0.784 (95% CI: 0.732-0.830). No statistical difference was found between AMACR score and serum PSA (P = .826), while the combinative model was better than AMACR score (Z = 5.222, P < .001). Among patients with serum PSA level of 4 to 10 ng/mL (n = 121), the AMACR score was significantly higher in patients with PCa (P = 0.0002), while serum PSA showed no difference (P = 0.3023). Alpha-methylacyl-CoA racemase score (AUC = 0.712, 95% CI: 0.623-0.790) and a combinative model (AUC = 0.714, 95% CI: 0.626-0.793) showed a better diagnostic value than serum PSA (AUC = 0.559, 95% CI: 0.466-0.649), (P = .048, P = .042). Decision curve analysis showed a biopsy prediction model including AMACR score have a better net benefit when the threshold probability greater than 20%. The diagnostic model combing serum PSA and AMACR score has a better diagnostic value in patients with abnormal PSA level (including PSA level ranging from 4-10 ng/mL), and could reduce unnecessary prostate biopsy in clinical use.

6.
Cell Death Differ ; 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31857702

RESUMO

The treatment of castration-resistant prostate cancer (CRPC) still faces many challenges. Docetaxel is a chemotherapeutic drug commonly used in CRPC patients. However, docetaxel-based chemotherapy usually causes docetaxel resistance, partially due to the resistance of CRPC cells to docetaxel-induced apoptosis. Here, we report that the deubiquitinating enzyme ubiquitin-specific protease 33 (USP33) inhibits docetaxel-induced apoptosis of prostate cancer cells, including androgen-independent prostate cancer cells. USP33 is overexpressed in prostate cancer cells and tissues. We found that knockdown or knockout of USP33 enhanced docetaxel-induced apoptosis of prostate cancer cells, accompanied by increased phosphorylation of the cJUN NH2-terminal kinase (JNK). After blocking docetaxel-induced JNK activation using the JNK inhibitor SP600125 or siRNA targeting JNK, the USP33 knockout-enhanced apoptosis was reversed. Furthermore, we found that USP33 could interact with the phosphatase DUSP1 to negatively regulate the activation of JNK, while USP33 knockdown promoted the proteasomal degradation of DUSP1. Mechanistically, we found that USP33 could inhibit the Lys48 (K48)-linked polyubiquitination of DUSP1. More importantly, DUSP1 overexpression could reverse the USP33 knockdown-induced JNK activation and apoptosis in docetaxel-treated prostate cancer cells. Therefore, USP33 overexpression in prostate cancer may contribute to docetaxel resistance by inhibiting the degradation of its partner DUSP1, leading to impaired JNK activation and apoptosis. Our study suggests that USP33-DUSP1-JNK may be a key signalling module mediating the docetaxel resistance of CRPC, indicating that USP33 is a potential novel therapeutic target in CRPC.

7.
Exp Ther Med ; 18(4): 3177-3183, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31555390

RESUMO

The aim of the present study was to determine the prognostic value of peroxisome proliferator-activated receptor-γ (PPAR-γ) and phosphatase and tensin homologue deleted on chromosome ten (PTEN) for bladder cancer. Data were collected from The Cancer Genome Atlas (TCGA), a public database, and were analyzed to assess PTEN and PPAR-γ heterogeneity as well as distinct trends in bladder cancers. Furthermore, PPAR-γ and PTEN expression levels and their association with one another were evaluated. Finally, the prognostic significance of PPAR-γ and PTEN for bladder cancer was validated in vivo using clinical samples. Based on the TCGA database, PTEN levels were significantly increased in bladder cancers (P<0.001); whereas PPAR-γ expression was downregulated in the same samples (P<0.05). Furthermore, linear correlation analysis indicated that in bladder cancers, PPAR-γ and PTEN are inversely correlated (P<0.001). The assessment and analysis of clinical samples revealed that PPAR-γ was significantly elevated in tumor tissues (P<0.001); however, PTEN was downregulated in cancer tissues (P<0.001). Furthermore, PPAR-γ expression determined by immunohistochemistry grey level (P=0.002) was also elevated in high-grade and invasive bladder cancers compared with low-grade and superficial tumors, whereas PTEN levels exhibited the opposite in this analysis (P=0.001). In individuals with lymphoid metastasis, PPAR-γ was significantly increased (P<0.001), and PTEN was significantly decreased (P<0.001). Pearson analysis revealed a significant negative correlation between PPAR-γ and PTEN expression (r=-0.604, P<0.05). In conclusion, tissue heterogeneity was observed with respect to PPAR-γ and PTEN expression in bladder cancer. PTEN and PPAR-γ expression are negatively correlated and may be excellent indicators of bladder cancer tumorigenesis and progression.

8.
Biomed Res Int ; 2019: 9306803, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534967

RESUMO

Prostate cancer (PCa) incidence has been rising in Chinese population. Current PSA-based biopsy has limited positive rate. Our research focused on development of serum markers for the diagnosis of PCa in patients with elevated PSA. miRNAs are found to be aberrantly expressed in many types of cancer. They are readily detectable in plasma and serum. Currently, miRNAs are being evaluated as potential prognostic and diagnostic tools for many types of cancer. We first profiled global serum miRNAs in a pilot set of PCa and benign prostatic hyperplasia (BPH) cases undergoing TRUS-guided prostate biopsy due to elevated PSA levels. A total of 20 differentially expressed miRNAs were discovered by high throughput microarray for further testing using qRT-PCR. In the training phase with 78 PCa and 77 BPH cases, miR-365a-3p, miR-4286, miR-424-5p, miR-27a-3p, and miR-29b-3p were found to have potential diagnostic value. The Logistics regression equation was established by 5 parameters including PSA, prostate volume, miR-4286, miR-27a-3p, and miR-29b-3p and ROC analysis of this model was made with AUC up to 0.892 (95% CI: 0.832-0.937, sensitivity 78.95%, and specificity 92.21%). The panel had excellent diagnostic performance and its significance was confirmed in 100 serum samples in the validation cohort. Overall, we found a panel of serum microRNAs that have considerable clinical significance in detecting early-stage prostate cancer. When combined with PSA and prostate volume, these microRNAs exhibit favorable diagnostic potency.

9.
World J Urol ; 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31292732

RESUMO

OBJECTIVES: To evaluate the feasibility and safety of the application of robotic enucleation of adrenal masses (REAM). METHODS: Thirteen patients at Shanghai Changhai Hospital who underwent robotic enucleation of adrenal mass from February 2017 to March 2018 were reviewed. After mobilizing the adrenal gland and clamping the feeding blood vessels, the tumor was enucleated and reconstruction was performed. Relevant clinical data were recorded including baseline patient and tumor characteristics, and perioperative outcomes (operating time, ischemic time, estimated blood loss, complications, and so on). RESULTS: All cases were successfully completed without conversion to total adrenalectomy or open surgery. The mean operative time was 75 min (range 60-95), with a mean warm ischemia time of 12 min (range 8-17). The estimated blood loss was 20 mL (range 10-50). No intraoperative complications were observed, and no steroid replacement was given post-operatively. After a median follow-up period of 12 months (range 9-15), no evidence of disease recurrence was detected. CONCLUSIONS: Robotic enucleation of adrenal masses is a safe and feasible procedure with excellent short-term functional and oncologic outcomes. Steroid supplementation is not necessary and recurrence is not usual with limited follow-up. Long-term follow-up and larger studies should be conducted to further evaluate outcomes of this robotic adrenal-sparing approach.

10.
Asian J Androl ; 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31210145

RESUMO

Fusion between the transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG fusion) is a common genetic alteration in prostate cancer among Western populations and has been suggested as playing a role in tumorigenesis and progression of prostate cancer. However, the prevalence of TMPRSS2-ERG fusion differs among different ethnic groups, and contradictory results have been reported in Asian patients. We aim to evaluate the prevalence and significance of TMPRSS2-ERG fusion as a molecular subtyping and prognosis indicator of prostate cancer in Asians. We identified the fusion status in 669 samples from prostate biopsy and radical prostatectomy by fluorescence in situ hybridization and/or immunohistochemistry in China. We examined the association of TMPRSS2-ERG fusion with clinicopathological characteristics and biochemical recurrence by Chi-square test and Kaplan-Meier analysis. Finally, a systematic review was performed to investigate the positive rate of the fusion in Asian prostate cancer patients. McNemar's test was employed to compare the positive rates of TMPRSS2-ERG fusion detected using different methods. The positive rates of TMPRSS2-ERG fusion were 16% in our samples and 27% in Asian patients. In our samples, 9.4% and 19.3% of cases were recognized as fusion positive by fluorescence in situ hybridization and immunohistochemistry, respectively. No significant association between the fusion and clinical parameters was observed. TMPRSS2-ERG fusion is not a frequent genomic alteration among Asian prostate cancer patients and has limited significance in clinical practices in China. Besides ethnic difference, detection methods potentially influence the results showing a positive rate of TMPRSS2-ERG fusion.

11.
Dis Markers ; 2019: 7090545, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30809318

RESUMO

Objective: To characterize the disease progression and median survival of patients with prostate cancer (PCa) according to the prostatic-specific acid phosphatase (PAP) analysis in a population-based study from the Surveillance, Epidemiology, and End Results (SEER) database. Materials and Methods: Prostate cancer patients with completed PAP results were identified using the SEER database of the National Cancer Institute. The Mann-Whitney Sum test was utilized to compare the statistical significance for measurement data and ranked data. Data were stratified by ages, races, TNM Classification of Malignant Tumors (TNM), pathological grades, number of tumors, PAP, and survival duration. Multivariable logistic analysis was performed to identify predictors of the presence of invasion and metastases. Cox regression was analyzed for the factors associated with all-cause mortality and prostate cancer-specific mortality. Moreover, survival curve was used to detect the survival months. The unknown data were excluded from these tests. Results: In total, there are 5184 PAP+ patients and 3161 PAP- patients involved. The Mann-Whitney Sum test showed that slightly greater tumor size (P = 0.03), elevated lymphatic (P = 0.005) and distant (P < 0.001) metastasis rate, higher pathological grade (P < 0.001), localized tumor number (P < 0.001), and shortened survival months (P < 0.001) were observed in the PAP+ group compared with the PAP- group. In the multivariable logistic regression, invasion and metastasis Hazard Ratio (HR) were elevated significantly (P < 0.001) in the PAP+ individuals. In the survival analysis, PAP- patients experienced the prolonged median survival. In the postsurgical patients, the survival months were still longer in PAP+ patients compared with the negative ones (P < 0.001), though surgery prolonged the survival months of both groups. Survival months stratified by localized, invasion, and metastasis situations were analyzed. In the three stratified subgroups, the survival duration is significantly decreased in the PAP+ individuals in the localized PCa group (P < 0.001) and the metastasis group (P = 0.013). Conclusions: The findings of this study provide population-based estimates of the PCa progress and prognosis for patients with different PAP results, which may suggest a renewed period for the PAP.


Assuntos
Fosfatase Ácida/sangue , Biomarcadores Tumorais/sangue , Neoplasias da Próstata/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia
12.
Cancer Med ; 8(3): 1004-1012, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30693666

RESUMO

The neutrophil-to-lymphocyte ratio (NLR) has been reported to be a prognostic marker in prostate cancer. In this study, we assessed the association between preoperative NLR and the clinicopathological characteristics, biomolecular features and prognosis of patients with localized prostate cancer treated with radical prostatectomy. A total of 994 subjects were retrospectively enrolled, and the histological specimens of 210 patients were retrieved for constructing a tissue microarray. Immunohistochemistry was then performed to assess the expression of AR, ERG, PTEN, p-AKT, Bcl-2, Beclin-1, Ki-67, CD3, CD4, CD8, IFN-γ and TNF-α. No significant differences in the NLR distributions among clinicopathological variables were observed (P > 0.05) when the original NLR data were utilized. When we dichotomized the NLR value into the high-NLR group (NLR ≥ 2) and low-NLR group (NLR < 2), we found that the patients in the high-NLR group had more prostate capsule invasion (P = 0.047). Additionally, no significant correlation was found between the NLR and infiltrating CD3+ cells, the CD4/CD8 ratio, AR, ERG, PTEN, p-AKT, Bcl-2, Beclin-1, Ki-67, IFN-γ or TNF-α (P > 0.05). When we analyzed the data of patients without postoperative adjuvant hormone therapy or radiotherapy, univariate and multivariate survival analysis indicated that a high NLR was a predictor of better BCR-free survival (P < 0.05). When analyzing the entire cohort, univariate survival analysis showed that the high-NLR group had significantly poorer overall survival (P < 0.05). In conclusion, NLR cannot reflect prostate cancer characteristics or the local immune microenvironment, but a high NLR can serve as an independent predictor of better BCR.

13.
J Endourol ; 33(8): 641-646, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30565487

RESUMO

Purpose: To evaluate the feasibility and effectiveness of the navigation of intelligent/interactive qualitative and quantitative analysis (IQQA) three-dimensional (3D) reconstruction technique in laparoscopic or robotic assisted partial nephrectomy (LPN or RAPN) for renal hilar tumors. Patients and Methods: The study retrospectively reviewed 26 patients with hilar tumors from February 2016 to February 2018. IQQA 3D reconstruction technique was applied for the purpose of navigation and resection of the tumors. Relevant clinical parameters and surgical outcomes were recorded. Results: All 26 LPN or RAPN were effectively completed without conversion to a hand-assisted or an open approach. Under the navigation of IQQA, all tumors were found precisely at the first time during surgeries. The mean operative time was 142 minutes (142 ± 35), with a mean warm ischemia time of 24.3 minutes (24.3 ± 9.5). The estimated blood loss was 156 mL (156 ± 112). No intraoperative complications occurred. Two patients suffered from postoperative complications. All patients had negative margins on the final pathological examination. At a mean follow-up period of 3 months, the mean glomerular filtration rate is 22.5 mL/min (22.5 ± 7.1) without tumor recurrence. Conclusions: With peculiar features, such as accurate location, complete resection, and fewer perioperative complications, the navigation of IQQA 3D reconstruction technique in partial nephrectomy represents a safe and effective procedure for hilar tumors.

14.
J BUON ; 24(6): 2531-2538, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31983129

RESUMO

PURPOSE: To explore the effects of Transmembrane-4-L-six-family-1 (TM4SF1) in prostate cancer (PCa), and the related underlying mechanisms. METHODS: PCa tissues were obtained from 78 patients. PCa cell lines DU145 and RWPE-2 were purchased from American Type Culture Collection (ATCC). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were conducted to analyze the expression of TM4SF1 in PCa tissues and DU145 cells. Plasmid containing over-expressed TM4SF1 was achieved by plasmid transfection. Transwell assay and wound-healing assay were designed to examine the invasion and migration of DU145 cells, whereas colony formation assay and 5-Ethynyl-2'- deoxyuridine (EdU) staining assay were performed to study the proliferation ability of DU145 cells. RESULTS: TM4SF1 was found over-expressed in PCa tissues and DU145 cells. Over-expression of TM4SF1 significantly activated the extracellular regulated protein kinases (ERK)1/2 signaling pathway, increased the epithelial-mesenchymal transition (EMT) expression, and enhanced the invasion, migration and proliferation of DU145 cells. Further studies revealed that suppression of ERK1/2 signaling pathway nearly resisted the positive effects on DU145 cells induced by TM4SF1 over-expression. CONCLUSIONS: The present study demonstrated that TM4SF1 enhanced the invasion, migration and proliferation of DU145 cells by activating ERK1/2 signaling pathway.

15.
Urology ; 120: 120-124, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30036616

RESUMO

OBJECTIVE: To describe a novel technique of laparoscopic partial nephrectomy (LPN) with direct lateral access (DLA) to renal artery and to report our early outcomes with this technique. MATERIALS AND METHODS: A retrospective review of 135 cases of transperitoneal LPN done by a single surgeon at our tertiary care institution from August 2014 to December 2016 was performed. Standard LPN (n = 73) or DLA-LPN (n = 62) was performed. Relevant clinical data were recorded including baseline patient and tumor characteristics, and surgical outcomes (operative time, artery mobilization time, warm ischemia time, estimated blood loss, complications, and so on). A comparative analysis between standard LPN cases and DLA-LPN was performed. RESULTS: The use of DLA technique had shorter operative time (P <.001), which was mainly due to a shorter artery mobilization time (18.1 vs 25.6 minutes; P <.001). This time difference was more significant in case of "complex" renal vasculature (2 or more arteries, P <.001). There was no difference in terms of perioperative complications between the 2 techniques. CONCLUSION: DLA to renal artery is safe and feasible, and it may translate into a shorter operative time. This can represent a useful trick to facilitate a challenging step of the LPN procedure, especially in case of complex vascular anatomy.


Assuntos
Neoplasias Renais/cirurgia , Laparoscopia/métodos , Nefrectomia/métodos , Artéria Renal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Rim/cirurgia , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nefrectomia/efeitos adversos , Duração da Cirurgia , Peritônio/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento
16.
Int J Cancer ; 143(2): 396-407, 2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-29441565

RESUMO

Genetic alterations drive metabolic reprograming to meet increased biosynthetic precursor and energy demands for cancer cell proliferation and survival in unfavorable environments. A systematic study of gene-metabolite regulatory networks and metabolic dysregulation should reveal the molecular mechanisms underlying prostate cancer (PCa) pathogenesis. Herein, we performed gas chromatography-mass spectrometry (GC-MS)-based metabolomics and RNA-seq analyses in prostate tumors and matched adjacent normal tissues (ANTs) to elucidate the molecular alterations and potential underlying regulatory mechanisms in PCa. Significant accumulation of metabolic intermediates and enrichment of genes in the tricarboxylic acid (TCA) cycle were observed in tumor tissues, indicating TCA cycle hyperactivation in PCa tissues. In addition, the levels of fumarate and malate were highly correlated with the Gleason score, tumor stage and expression of genes encoding related enzymes and were significantly related to the expression of genes involved in branched chain amino acid degradation. Using an integrated omics approach, we further revealed the potential anaplerotic routes from pyruvate, glutamine catabolism and branched chain amino acid (BCAA) degradation contributing to replenishing metabolites for TCA cycle. Integrated omics techniques enable the performance of network-based analyses to gain a comprehensive and in-depth understanding of PCa pathophysiology and may facilitate the development of new and effective therapeutic strategies.


Assuntos
Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Metabolômica/métodos , Neoplasias da Próstata/patologia , Ciclo do Ácido Cítrico , Fumaratos/análise , Cromatografia Gasosa-Espectrometria de Massas , Regulação Neoplásica da Expressão Gênica , Humanos , Malatos/análise , Masculino , Gradação de Tumores , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Análise de Sequência de RNA
17.
FASEB J ; 32(2): 654-668, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28970251

RESUMO

Administration of exosomes derived from mesenchymal stromal cells (MSCs) could improve some neurologic conditions by transferring functional biomolecules to recipient cells. Furthermore, exosomes from hypoxic progenitor cells exerted better therapeutic effects in organ injury through specific cargoes. However, there are no related reports about whether exosomes derived from MSCs or hypoxia-preconditioned MSCs (PC-MSCs) could prevent memory deficits in Alzheimer disease (AD). In this study, the exosomes derived from MSCs or PC-MSCs were systemically administered to transgenic APP/PS1 mice. The expression of miR-21 in MSCs was significantly increased after hypoxic treatment. Injection of exosomes from normoxic MSCs could rescue cognition and memory impairment according to results of the Morris water maze test, reduced plaque deposition, and Aß levels in the brain; could decrease the activation of astrocytes and microglia; could down-regulate proinflammatory cytokines (TNF-α and IL-1ß); and could up-regulate anti-inflammatory cytokines (IL-4 and -10) in AD mice, as well as reduce the activation of signal transducer and activator of transcription 3 (STAT3) and NF-κB. Compared to the group administered exosomes from normoxic MSCs, in the group administered exosomes from PC-MSCs, learning and memory capabilities were significantly improved; the plaque deposition and Aß levels were lower, and expression of growth-associated protein 43, synapsin 1, and IL-10 was increased; and the levels of glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, TNF-α, IL-1ß, and activation of STAT3 and NF-κB were sharply decreased. More importantly, exosomes from PC-MSCs effectively increased the level of miR-21 in the brain of AD mice. Additionally, replenishment of miR-21 restored the cognitive deficits in APP/PS1 mice and prevented pathologic features. Taken together, these findings suggest that exosomes from PC-MSCs could improve the learning and memory capabilities of APP/PS1 mice, and that the underlying mechanism may lie in the restoration of synaptic dysfunction and regulation of inflammatory responses through regulation of miR-21.-Cui, G.-H., Wu, J., Mou, F.-F., Xie, W.-H., Wang, F.-B., Wang, Q.-L., Fang, J., Xu, Y.-W., Dong, Y.-R., Liu, J.-R., Guo, H.-D. Exosomes derived from hypoxia-preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP/PS1 mice.


Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Exossomos/metabolismo , Precondicionamento Isquêmico , Células-Tronco Mesenquimais/metabolismo , Sinapses/metabolismo , Doença de Alzheimer/patologia , Animais , Encéfalo/patologia , Disfunção Cognitiva/patologia , Citocinas/metabolismo , Exossomos/patologia , Células-Tronco Mesenquimais/patologia , Camundongos , Camundongos Transgênicos , Sinapses/patologia
18.
Cancer Cell ; 31(3): 368-382, 2017 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-28292438

RESUMO

Metastasis is a predominant cause of death for prostate cancer (PCa) patients; however, the underlying mechanisms are poorly understood. We report that monoamine oxidase A (MAOA) is a clinically and functionally important mediator of PCa bone and visceral metastases, activating paracrine Shh signaling in tumor-stromal interactions. MAOA provides tumor cell growth advantages in the bone microenvironment by stimulating interleukin-6 (IL6) release from osteoblasts, and triggers skeletal colonization by activating osteoclastogenesis through osteoblast production of RANKL and IL6. MAOA inhibitor treatment effectively reduces metastasis and prolongs mouse survival by disengaging the Shh-IL6-RANKL signaling network in stromal cells in the tumor microenvironment. These findings provide a rationale for targeting MAOA and its associated molecules to treat PCa metastasis.


Assuntos
Comunicação Celular , Proteínas Hedgehog/fisiologia , Interleucina-6/fisiologia , Monoaminoxidase/fisiologia , Neoplasias da Próstata/patologia , Ligante RANK/fisiologia , Transdução de Sinais/fisiologia , Animais , Neoplasias Ósseas/secundário , Humanos , Masculino , Camundongos , Camundongos SCID , Monoaminoxidase/análise , Osteoblastos/fisiologia , Células Estromais/fisiologia , Microambiente Tumoral
19.
Asian J Androl ; 19(2): 238-243, 2017.
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
20.
Urol Oncol ; 34(9): 416.e1-7, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27185342

RESUMO

OBJECTIVE: Substantial differences exist in the relationship of prostate cancer (PCa) detection rate and prostate-specific antigen (PSA) level between Western and Asian populations. Classic Western risk calculators, European Randomized Study for Screening of Prostate Cancer Risk Calculator, and Prostate Cancer Prevention Trial Risk Calculator, were shown to be not applicable in Asian populations. We aimed to develop and validate a risk calculator for predicting the probability of PCa and high-grade PCa (defined as Gleason Score sum 7 or higher) at initial prostate biopsy in Chinese men. MATERIALS AND METHODS: Urology outpatients who underwent initial prostate biopsy according to the inclusion criteria were included. The multivariate logistic regression-based Chinese Prostate Cancer Consortium Risk Calculator (CPCC-RC) was constructed with cases from 2 hospitals in Shanghai. Discriminative ability, calibration and decision curve analysis were externally validated in 3 CPCC member hospitals. RESULTS: Of the 1,835 patients involved, PCa was identified in 338/924 (36.6%) and 294/911 (32.3%) men in the development and validation cohort, respectively. Multivariate logistic regression analyses showed that 5 predictors (age, logPSA, logPV, free PSA ratio, and digital rectal examination) were associated with PCa (Model 1) or high-grade PCa (Model 2), respectively. The area under the curve of Model 1 and Model 2 was 0.801 (95% CI: 0.771-0.831) and 0.826 (95% CI: 0.796-0.857), respectively. Both models illustrated good calibration and substantial improvement in decision curve analyses than any single predictors at all threshold probabilities. Higher predicting accuracy, better calibration, and greater clinical benefit were achieved by CPCC-RC, compared with European Randomized Study for Screening of Prostate Cancer Risk Calculator and Prostate Cancer Prevention Trial Risk Calculator in predicting PCa. CONCLUSIONS: CPCC-RC performed well in discrimination and calibration and decision curve analysis in external validation compared with Western risk calculators. CPCC-RC may aid in decision-making of prostate biopsy in Chinese or in other Asian populations with similar genetic and environmental backgrounds.


Assuntos
Biópsia , Neoplasias da Próstata/diagnóstico , Idoso , Grupo com Ancestrais do Continente Asiático , China , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/patologia , Medição de Risco
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