RESUMO
This study utilized data from 140,294 prostate cancer cases from the Surveillance, Epidemiology, and End Results (SEER) database. Here, 10 different machine learning algorithms were applied to develop treatment options for predicting patients with prostate cancer, differentiating between surgical and non-surgical treatments. The performances of the algorithms were measured using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value. The Shapley Additive Explanations (SHAP) method was employed to investigate the key factors influencing the prediction process. Survival analysis methods were used to compare the survival rates of different treatment options. The CatBoost model yielded the best results (AUC = 0.939, sensitivity = 0.877, accuracy = 0.877). SHAP interpreters revealed that the T stage, cancer stage, age, cores positive percentage, prostate-specific antigen, and Gleason score were the most critical factors in predicting treatment options. The study found that surgery significantly improved survival rates, with patients undergoing surgery experiencing a 20.36% increase in 10-year survival rates compared with those receiving non-surgical treatments. Among surgical options, radical prostatectomy had the highest 10-year survival rate at 89.2%. This study successfully developed a predictive model to guide treatment decisions for prostate cancer. Moreover, the model enhanced the transparency of the decision-making process, providing clinicians with a reference for formulating personalized treatment plans.
RESUMO
Acute promyelocytic leukemia (APL), a distinctive subtype of acute myeloid leukemia (AML), is characterized by the t(15; 17) translocation forming the PML-RARα fusion protein. Recent studies have revealed a crucial role of retinoid X receptor α (RXRα) in PML-RARα's tumorigenesis. This necessitates the development of dual RARα and RXRα targeting compounds for treating APL. Here, we developed a pair of brominated retinoid isomers, 5a and 5b, exhibiting RARα agonistic selectivity among the RAR subtypes and RXRα partial agonistic activities. In the treatment of APL cells, low doses (RARα activation range) of 5a and 5b degrade PML-RARα and strongly induce differentiation, while higher doses (RXRα activation range) induce G2/M arrest and apoptosis in both all-trans retinoic acid (ATRA)-sensitive and resistant cells. We replaced the bromine in 5a with chlorine or iodine to obtain compounds 7 or 8a. Interestingly, the chlorinated compound 7 tends to activate RXRα and induce G2/M arrest and apoptosis, while the iodinated compound 8a tends to activate RARα and induce differentiation. Together, our work underscores several advantages and characteristics of halogens in the rational design of RARα and RXRα ligands, offering three promising drug candidates for treating both ATRA-sensitive and resistant APL.
Assuntos
Antineoplásicos , Leucemia Promielocítica Aguda , Receptor alfa de Ácido Retinoico , Receptor X Retinoide alfa , Retinoides , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/patologia , Leucemia Promielocítica Aguda/metabolismo , Receptor alfa de Ácido Retinoico/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Retinoides/farmacologia , Retinoides/química , Retinoides/síntese química , Receptor X Retinoide alfa/metabolismo , Receptor X Retinoide alfa/antagonistas & inibidores , Relação Estrutura-Atividade , Estrutura Molecular , Relação Dose-Resposta a Droga , Apoptose/efeitos dos fármacos , Halogenação , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular TumoralRESUMO
Background: Numerous studies have substantiated the association between aging and the progression of malignant tumors in humans, notably prostate cancer (PCa). Nevertheless, to the best of our knowledge, no studies have comprehensively elucidated the intricate characteristics of the aging microenvironment (AME) in PCa. Methods: AME regulatory patterns were determined using the NMF algorithm. Then an ageing microenvironment index (AMI) was constructed, with excellent prognostic and immunotherapy prediction ability, and its' clinical relevance was surveyed through spatial transcriptomics. Further, the drug response was analysed using the Genomics of Drug Sensitivity in Cancer (GDSC), the Connectivity Map (CMap) and CellMiner database for patients with PCa. Finally, the AME was studied using in vitro and vivo experiments. Results: Three different AME regulatory patterns were identified across 813 PCa patients, associated with distinct clinical prognosis and physiological pathways. Based on the AMI, patients with PCa were divided into the high-score and low-score subsets. Higher AMI score was significantly infiltrated with more immune cells, higher rate of biochemical recurrence (BCR) and worse response to immunotherapy, antiandrogen therapy and chemotherapy in PCa. In addition, we found that the combination of bicalutamide and embelin was capable of suppressing tumor growth of PCa. Besides, as the main components of AMI, COL1A1 and BGLAP act as oncogenes and were verified via in vivo and in vitro experiments. Conclusions: AME regulation is significantly associated with the diversity and complexity of TME. Quantitative evaluation of the AME regulatory patterns may provide promising novel molecular markers for individualised therapy in PCa.
Assuntos
Multiômica , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Imunoterapia , Oncogenes , Envelhecimento , Microambiente Tumoral/genéticaRESUMO
The recurrence of prostate cancer (PCa) is intrinsically linked to increased mortality. The goal of this study was to develop an efficient and reliable prognosis prediction signature for PCa patients. The training cohort was acquired from The Cancer Genome Atlas (TCGA) dataset, while the validation cohort was obtained from the Gene Expression Omnibus (GEO) dataset (GSE70769). To explore the Gleason score (GS)-based prediction signature, we screened the differentially expressed genes (DEGs) between low- and high-GS groups, and then univariate Cox regression survival analysis and multiple Cox analyses were performed sequentially using the training cohort. The testing cohort was used to evaluate and validate the prognostic model's effectiveness, accuracy, and clinical practicability. In addition, the correlation analyses between the risk score and clinical features, as well as immune infiltration, were performed. We constructed and optimized a valid and credible model for predicting the prognosis of PCa recurrence using four GS-associated genes (SFRP4, FEV, COL1A1, SULF1). Furthermore, ROC and Kaplan-Meier analysis revealed a higher predictive efficiency for biochemical recurrence (BCR). The results showed that the risk model was an independent prognostic factor. Moreover, the risk score was associated with clinical features and immune infiltration. Finally, the risk model was validated in a testing cohort. Our data support that the GS-based four-gene signature acts as a novel signature for predicting BCR in PCa patients.
RESUMO
BACKGROUND: Aggressive tumor cells can form perfusable networks that mimic normal vasculature and enhance tumor growth and metastasis. A number of molecular players have been implicated in such vasculogenic mimicry, among them the receptor tyrosine kinase EphA2, which is aberrantly expressed in aggressive tumors. Here we study the role and regulation of EphA2 in vasculogenic mimicry in prostate cancer where this phenomenon is still poorly understood. METHODS: Vasculogenic mimicry was characterized by tubules whose cellular lining was negative for the endothelial cell marker CD34 but positive for periodic acid-Schiff staining, and/or contained red blood cells. Vasculogenic mimicry was assessed in 92 clinical samples of prostate cancer and analyzed in more detail in three prostate cancer cell lines kept in three-dimensional culture. Tissue samples and cell lines were also assessed for total and phosphorylated levels of EphA2 and its potential regulator, Phosphoinositide 3-Kinase (PI3K). In addition, the role of EphA2 in vasculogenic mimicry and in cell migration and invasion were investigated by manipulating the levels of EphA2 through specific siRNAs. Furthermore, the role of PI3K in vasculogenic mimicry and in regulating EphA2 was tested by application of an inhibitor, LY294002. RESULTS: Immunohistochemistry of prostate cancers showed a significant correlation between vasculogenic mimicry and high expression levels of EphA2, high Gleason scores, advanced TNM stage, and the presence of lymph node and distant metastases. Likewise, two prostate cancer cell lines (PC3 and DU-145) formed vasculogenic networks on Matrigel and expressed high EphA2 levels, while one line (LNCaP) showed no vasculogenic networks and lower EphA2 levels. Specific silencing of EphA2 in PC3 and DU-145 cells decreased vasculogenic mimicry as well as cell migration and invasion. Furthermore, high expression levels of PI3K and EphA2 phosphorylation at Ser897 significantly correlated with the presence of vasculogenic mimicry and in vitro inhibition of PI3K by LY294002 disrupted vasculogenic mimicry, potentially through a reduction of EphA2 phosphorylation at Ser897. CONCLUSIONS: The expression levels of PI3K and EphA2 are positively correlated with vasculogenic mimicry both in vivo and in vitro. Moreover, phosphorylation levels of EphA2 regulated by PI3K are also significantly associated with vasculogenic mimicry in vivo. Based on its functional implication in vasculogenic mimicry in vitro, EphA2 signaling may be a potential therapeutic target in advanced prostate cancer.
RESUMO
OBJECTIVES: To determine the prognostic role of vasculogenic mimicry in adrenocortical carcinoma, and to explore its relationship with vascular endothelial growth factor receptor 2 expression. METHODS: A total of 46 samples of adrenocortical carcinoma were collected and reviewed. Vasculogenic mimicry and vascular endothelial growth factor receptor 2 were detected by immunohistochemistry and double staining. Survival analysis was carried out to access pronostic significance. Three-dimensional culture method was applied to test the ability of vasculogenic mimicry formation by adrenocortical carcinoma cell lines SW-13 and H295R. Quantitative polymerase chain reaction and western blotting were used to monitor the expression of vascular endothelial growth factor receptor 2 in SW-13 and H295R. After being treated with specific inhibitor or small interfering ribonucleic acid to downregulate expression of vascular endothelial growth factor receptor 2, vasculogenic mimicry formation and cell prolifration of SW-13 cells were evaluated by 3-D culture and Cell Counting Kit-8 methods. RESULTS: Vasculogenic mimicry was observed in 19 of the 46 (41.30%) adrenocortical carcinoma samples. Both vasculogenic mimicry and vascular endothelial growth factor receptor 2 expressions showed a positive association with Weiss score and TNM stage, whereas vascular endothelial growth factor receptor 2 was also associated with tumor size (all P < 0.05). Vasculogenic mimicry was closely correlated with vascular endothelial growth factor receptor 2 expressions (r = 0.470, P < 0.01). The median overall survival of patients with vasculogenicmimicry-positive or vascular endothelial growth factor receptor 2-positive was shorter than that of patients with vasculogenic mimicry-negative or vascular endothelial growth factor receptor 2-negative (P = 0.001 and 0.028, respectively). The vasculogenic mimicry-forming SW-13 cells expressed higher levels of vascular endothelial growth factor receptor 2 than that of H295R, which was unable to form vasculogenic mimicry on Matrigel. However, downregulation of vascular endothelial growth factor receptor 2 only decreased cell proliferation, but not vasculogenic mimicry formation by SW-13 cells. CONCLUSIONS: Vasculogenic mimicry and overexpression of vascular endothelial growth factor receptor 2 seem to correlate with poor prognostic outcomes in adrenocortical carcinoma. Anti-angiogenesis treatments targeting vascular endothelial growth factor receptor 2 should be combined with therapies targeting vasculogenic mimicry in adrenocortical carcinoma.
Assuntos
Carcinoma Adrenocortical/metabolismo , Neovascularização Patológica , Fator A de Crescimento do Endotélio Vascular/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Microvasos/patologia , PrognósticoAssuntos
Carcinoma Adrenocortical/terapia , Antineoplásicos/administração & dosagem , Indóis/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Nódulos Pulmonares Múltiplos/tratamento farmacológico , Pirróis/administração & dosagem , Carcinoma Adrenocortical/patologia , Adulto , Quimioterapia Adjuvante , Feminino , Humanos , Neoplasias Pulmonares/secundário , Mitotano/uso terapêutico , Nódulos Pulmonares Múltiplos/secundário , Nefrectomia/métodos , Sunitinibe , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Vasculogenic mimicry (VM), a new pattern of tumor microcirculation system, has been proved to be important for tumor growth and progression and may be one of the causes of antiangiogenesis resistance. Matrix metalloproteinase-9 (MMP9) was shown to correlate with VM formation in some other cancers. However, the relationship between VM formation and MMP9 in renal cell carcinoma (RCC) has not been determined. METHODS: The VM formation and MMP9 expressions were analyzed by CD34/periodic acid-Schiff dual staining and immunohistochemistry in 119 RCC specimens. We used a well-established 3-dimention culture model to compare VM formation in 786-O, 769-P, and HK-2 cell lines in vitro. MMP9 expressions on either messenger RNA or protein levels were compared among the cell lines by quantitative polymerase chain reaction or Western blot. To determine further the relationship between MMP9 and VM in RCC, 786-O and 769-P were treated with specific MMP9 inhibitor or small interfering RNA. VM formation, cell migration, and invasion were subsequently assessed by 3-dimention culture, wound-healing, and transwell assays. RESULTS: Immunohistochemistry demonstrated both VM formation and MMP9 overexpression were positively associated with clinical staging, pathological grade, and metastasis (P<0.01). VM formation was closely correlated with MMP9 overexpression in RCC (r = 0.602, P<0.01). Lower MMP9 expression level was observed in normal kidney cell line HK-2, which was unable to form VM on Matrigel, whereas higher expression of MMP9 was found in VM-forming cancer cell lines 786-O and 769-P. Inhibition of MMP9 not only disrupted VM formation in 786-O and 769-P but also reduced cell migration and invasion. CONCLUSIONS: These results indicate an intimate relationship between MMP9 overexpression and VM formation in RCC. Treatments targeting VM formation by inhibiting the activity of MMP9 could be beneficial in RCC therapy.
Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Metaloproteinase 9 da Matriz/metabolismo , Neovascularização Patológica/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/enzimologia , Linhagem Celular Tumoral , Criança , Feminino , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/enzimologia , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/enzimologia , Reação em Cadeia da Polimerase , Adulto JovemRESUMO
Obstructive azoospermia (OA) is one of the most common causes of male infertility. Transrectal ultrasound (TRUS) has been used to diagnose OA for many years. From 2009 to 2013, we evaluated a prospective cohort of 1249 patients with suspected OA using TRUS. It was found that dilation of the ejaculatory duct (ED) (29.9%, 374/1249) was the most common cause of OA, followed by seminal vesicle (SV) abnormalities (28.5%, 356/1249). A total of 237 patients were diagnosed with congenital defects (agenesis and/or hypoplasia) of the SV, constituting more than half of the cases of SV disease in OA (19.0%, 237/1249). In contrast to ED, congenital defects of the SV could not be corrected with surgical treatment. Therefore, it is meaningful to compare TRUS and magnetic resonance imaging (MRI) for accurate diagnosis of SV defects. Among our patients, 30 with agenesis or/and hypoplasia of the SV on TRUS were further evaluated using pelvic MRI within 2 years, with the objective of verifying the TRUS results. The concordance rate for diagnosing congenital defects of the SV was 73.3% (22/30). We concluded that TRUS is a reliable and convenient method for diagnosing agenesis or hypoplasia of the SV in OA patients with a high concordance with MRI while MRI is useful in patients with inconclusive TRUS findings.
Assuntos
Imageamento por Ressonância Magnética/métodos , Glândulas Seminais/diagnóstico por imagem , Adolescente , Adulto , Humanos , Masculino , Reto , Ultrassonografia , Adulto JovemRESUMO
BACKGROUND: Desmocollin 3 (DSC3), a member of the cadherin gene superfamily, is associated with pathogenesis of some cancers, but its role in prostate cancer (PCa) remains largely unknown. METHODS: DSC3 gene expression level in available PCa microarray dataset was examined using the Oncomine database. DSC3 transcript expression in prostate cell line panel and an independent tissue cohort (nâ=â52) was estimated by quantitative PCR (Q-PCR). Epigenetic status of DSC3 gene promoter in PCa was investigated by uploading three dataset (ENCODE Infinium 450K array data and two methylation sequencing) in UCSC genome browser. While pyrosequencing analysis measured promoter DNA methylation, Q-PCR estimates were obtained for DSC3 transcript re-expression after 5-Aza-deoxycytidine (5-Aza) treatment. Clinical relevance of DSC3 expression was studied by Kaplan-Meier survival analysis. Finally, functional studies monitoring cell proliferation, migration and invasion were performed in prostate cell lines after siRNA mediated DSC3 knockdown or following 5-Aza induced re-expression. EMT markers Vimentin and E-cadherin expression was measured by Western Blot. RESULTS: Microarray data analyses revealed a significant decrease in DSC3 transcript expression in PCa, compared to benign samples. Q-PCR analysis of an independent cohort revealed DSC3 transcript down-regulation, both in PCa cell lines and tumor tissues but not in their benign counterpart. Examination of available NGS and Infinium data identified a role for epigenetic regulation DSC3 mRNA reduction in PCa. Pyrosequencing confirmed the increased DSC3 promoter methylation in cancer cell lines and restoration of transcript expression upon 5-Aza treatment further corroborated this epigenetic silencing mechanism. Importantly Kaplan-Meier analysis of an outcome cohort showed an association between loss of DSC3 expression and significantly increased risk of biochemical recurrence. Functional studies indicate a role for epithelial-mesenchymal transition in DSC3 regulated cell migration/invasion. CONCLUSION: Taken together, our data suggests that DNA methylation contributes to down-regulation of DSC3 in prostate cancer, and loss of DSC3 predicts poor clinical outcome.
Assuntos
Metilação de DNA , DNA de Neoplasias/metabolismo , Desmocolinas/biossíntese , Regulação Neoplásica da Expressão Gênica , Regiões Promotoras Genéticas , Neoplasias da Próstata , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Linhagem Celular Tumoral , DNA de Neoplasias/genética , Desmocolinas/genética , Regulação para Baixo/genética , Epigênese Genética/genética , Humanos , Masculino , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , RNA Mensageiro/genética , RNA Neoplásico/genéticaRESUMO
BACKGROUND: Von Hippel-Lindau disease (VHL), a heritable autosomal dominant disease characterized by neoplasia in multiple organ systems, has rarely been reported in Asia. We genetically investigated a unique Chinese family with VHL disease and performed an analysis of the VHL protein stability. METHODS: Genomic deoxyribonucleic acid (DNA) extracted from peripheral blood was amplified by polymerase chain reaction (PCR) to three exons of the VHL gene in 9 members of the Chinese family with VHL disease. PCR products were directly sequenced. We estimated the effects of VHL gene mutation on the stability of pVHL, which is indicated by the free energy difference between the wild-type and the mutant protein (ΔΔG). RESULTS: The Chinese family was classified as VHL type 1. Three family members, including two patients and a carrier, had a T to G heterozygotic missense mutation at nucleotide 515 of the VHL gene exon 1. This missense mutation resulted in the transition from leucine to arginine in amino acid 101 of the VHL protein. There was low stability of the VHL protein (the ΔΔG was 12.71 kcal/mol) caused by this missense mutation. CONCLUSIONS: We first reported a family with this VHL gene mutation in Asia. This missense mutation is predicted to significantly reduce the stability of the VHL protein and contribute to the development of the renal cell carcinoma (RCC) phenotype displayed by this family. The genetic characterization and protein stability analysis of families with VHL disease are important for early diagnosis and prevention of the disease being passed on to their offspring.
Assuntos
Mutação de Sentido Incorreto , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau/genética , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estabilidade Proteica , Proteína Supressora de Tumor Von Hippel-Lindau/químicaRESUMO
BACKGROUND: ZEB2 has been reportedly shown to mediate the epithelial-to-mesenchymal transition (EMT) and disease aggressiveness in human tumors. However, the expression status of ZEB2 in renal cell carcinoma (RCC) and ZEB2's clinicopathologic/prognostic significance are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, tissue microarray, immunohistochemistry (IHC) and western blot analyses were utilized to investigate the ZEB2 expression status in RCC and adjacent renal tissue samples. In our study, samples from 116 RCC patients treated with radical nephrectomy were used as a training set to generate a ZEB2 optimal cut-point for patient outcome by receiver operating characteristic (ROC) analysis. For validation, the correlation of ZEB2 expression with the clinical characteristics and patient outcomes in another set (including 113 patients) was analyzed to validate the obtained cut-point. In the training and validation sets, high expression of ZEB2, defined by ROC analysis, predicted a poorer overall survival and progression-free survival, as evidenced by the univariate and multivariate analyses. In different subsets of overall patients, ZEB2 expression was also a prognostic indicator in patients with stage I/II, stage III/IV, grade 1/2 and grade 3/4 disease (P<0.05). Downregulation of ZEB2 by shRNA decreased the migration and invasion ability of 769-P cells in vitro. Furthermore, high ZEB2 expression was positively correlated with vimentin expression and inversely linked to E-cadherin expression in RCC. CONCLUSIONS/SIGNIFICANCE: Our findings provide a basis for the concept that high ZEB2 expression in RCC may be important in the acquisition of an aggressive phenotype. This evidence suggests that ZEB2 overexpression (examined by IHC) is an independent biomarker for the poor prognosis of patients with RCC.
Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Biomarcadores Tumorais/deficiência , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Movimento Celular , Transição Epitelial-Mesenquimal , Feminino , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , RNA Interferente Pequeno/genética , Proteínas Repressoras/deficiência , Análise de Sobrevida , Homeobox 2 de Ligação a E-box com Dedos de ZincoRESUMO
BACKGROUND: Multiple recurrences are common in non-muscle invasive bladder cancer, but the risk of multiple recurrences has not been fully described. Identifying patients at high risk of multiple recurrences will help to select an optimal therapeutic strategy and to improve prognosis. This study was conducted to identify the risk factors for multiple recurrences of non-muscle invasive bladder cancer. METHODS: We reviewed the clinical data of all patients with non-muscle invasive bladder cancer in our hospital between January 2003 and February 2010. Patients with at least one recurrence were included. Multivariate analysis was performed for theorized risk factors (age, gender, tumor stage, grade, size, location, number of lesions, adjuvant intra-vesical chemotherapy after transurethral resection, and recurrence-free survival after each resection) to clarify risk factors for multiple recurrences of non-muscle invasive bladder cancer. RESULTS: Of the 278 patients with non-muscle invasive bladder cancer, 84 were with at least one recurrence and a total of 222 recurrences among them were followed up for 6 - 70 months (mean, 36.1 months). Recurrence-free survival after initial resection predicted the overall frequency of bladder cancer recurrence (risk ratio (RR) = 37.83, 95% confidence interval (CI) = 3.45 - 396.13, P = 0.001) and second recurrence (RR = 6.15, 95%CI = 1.28 - 29.57, P = 0.023). Similarly, recurrence-free survival after a second resection was the only significant risk factor for third recurrence (RR = 31.08, 95%CI = 2.53 - 381.47, P = 0.007). Moreover, recurrence-free survival after initial resection was the only significant factor to predict later progression to muscle invasive bladder cancer (RR = 8.62, 95%CI = 1.47 - 58.34, P = 0.001). CONCLUSIONS: Recurrence-free survival after resection is an independent predictor of multiple recurrences of non-muscle invasive bladder cancer. The shorter the period between resection and recurrence is, the higher the risk of multiple recurrences.
Assuntos
Cistectomia/métodos , Recidiva Local de Neoplasia/etiologia , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Uretra , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologiaRESUMO
After androgen ablation therapy (AAT), advanced prostate cancer (Pca) eventually progresses to castration-resistant Pca (CRPC); however, the biomarkers that are used to predict its prognosis are limited. In this study, serum samples from four patients with advanced Pca were collected at the time of the initial diagnosis and 3 months after AAT. Proteomic changes were analyzed with two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Altogether, nine proteins were differentially expressed in the samples collected at diagnosis and in the samples collected after AAT. Among them, the expression of transthyretin (TTR) was 1.58-fold lower and clusterin (CLU) was 1.51-fold higher in the sera of post-AAT patients compared with those in the sera from pre-AAT patients. The significant changes in serum TTR and CLU in post-AAT patients were further confirmed by a large-scale ELISA. Immunohistochemistical staining revealed that the expression levels of TTR and CLU were significantly higher in Pca tissue than in normal and benign prostate hyperplasia tissue. The expression levels of TTR and CLU in Pca tissue were found to be associated with the grade and stage of Pca. Overall, this study indicated that TTR and CLU might be used to monitor the efficacy of AAT therapy and serve as biomarkers for the prognosis of Pca.
RESUMO
Percutaneous ultrasound-guided radiofrequency ablation is increasingly being studied in the treatment of renal tumors. Because percutaneous ultrasound-guided radiofrequency ablation is a minimally invasive and nephron-sparing procedure, it is ideally suited for patients with a single kidney, multiple tumors, or contraindications to conventional surgery. We report on a patient with Von Hippel-Lindau (VHL) disease who had multicentric tumors in the single kidney that was successfully treated with percutaneous ultrasound-guided radiofrequncy ablation. The one-year follow-up showed that there was no local recurrence or metastasis. And genetic testing showed the patient had a T to G heterozygotic missense mutation at nucleotide 515 of VHL gene exon 1.
Assuntos
Técnicas de Ablação/métodos , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Cirurgia Assistida por Computador/métodos , Ultrassonografia/métodos , Doença de von Hippel-Lindau/genética , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Histocitoquímica , Humanos , Neoplasias Renais/complicações , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Tomografia Computadorizada por Raios X , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau/complicaçõesRESUMO
Several studies have proved transrectal ultrasonography (TRUS) is efficient in the evaluation of patients with hematospermia, but the numbers of patients were less than 60 in each of the previous reports. Herein, a total of 270 patients with hematospermia were evaluated by TRUS to assess its efficacy in the etiologic diagnosis of hematospermia. The age of patients ranged from 15 to 75 years (x, 41.2 years), and the duration of symptoms was 1 day to 8 years (x, 3.4 months). Abnormalities were revealed by TRUS in 256 patients (94.8%). The percentages of pathological conditions located in the seminal vesicles, in the ejaculatory ducts, in the prostate, and in the bladder were 46.3% (125 cases), 29.6% (80 cases), 55.2% (149 cases), and 0.4% (1 case), respectively. The number of patients older than 40 years old and 40 years old or younger were 126 and 144, respectively. Our results show significantly higher percentages for malignant diseases, prostatic calcification and benign prostatic hyperplasia in the group of patients more than 40 years old compared with the group of patients 40 years old or less. Eight of 270 patients (3.0%) had malignant tumors, and all of the 8 malignancies occurred in patients more than 40 years old. TRUS is a noninvasive, reliable tool for the investigation of causes of hematospermia. Hematospermia is generally a benign symptom in younger patients. Special attention should be paid to elderly patients to exclude malignancy.
Assuntos
Doenças dos Genitais Masculinos/diagnóstico por imagem , Genitália Masculina/diagnóstico por imagem , Hemospermia/diagnóstico por imagem , Adolescente , Adulto , Fatores Etários , Idoso , Biópsia , Distribuição de Qui-Quadrado , Doenças dos Genitais Masculinos/complicações , Hemospermia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Ultrassonografia , Adulto JovemRESUMO
OBJECTIVE: To assess the role of transrectal ultrasonography (TRUS) in the etiological diagnosis of male obstructive azoospermia. METHODS: We retrospectively analyzed the clinical data and TRUS findings of 695 patients with obstructive azoospermia from January 2007 to May 2009. RESULTS: Concerning the etiology of obstructive azoospermia, the main TRUS findings included ejaculatory duct abnormality (29.2%), seminal vesicle abnormality (25.4%) and prostate midline cyst (18.5%). TRUS revealed 203 cases of ejaculatory duct dilation, 177 cases of seminal vesicle abnormality (including 108 with absence or agenesis and 51 with dilation of the seminal vesicle), and 128 cases of prostate midline cyst (including 75 with ejaculatory duct cyst and 39 with Müllerian cyst). Calcification of the verumontanum or ejaculatory duct was suspected to be the causes of obstructive azoospermia in 34 cases. However, no significant etiological abnormality was found in 153 cases. Obvious etiology was shown by TRUS in 78.0% of the patients. CONCLUSION: TRUS can clearly display the structural abnormality of the ejaculatory duct and seminal vesicle, and provide important information on the etiology of male obstructive azoospermia.
Assuntos
Azoospermia/diagnóstico por imagem , Azoospermia/etiologia , Reto/diagnóstico por imagem , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , UltrassonografiaRESUMO
INTRODUCTION: Men frequently develop diabetic erectile dysfunction (DMED), as a result of endothelial dysfunction. DMED patients often have reduced efficacy with phosphodiesterase type 5 inhibitors therapy. AIM: To determine whether chronic sildenafil administration can modify the impaired vascular endothelial growth factor (VEGF) system and improve the erectile function in rats with diabetic erectile dysfunction. METHODS: A group of Sprague Dawley rats (n = 30) with DMED were induced by intraperitoneal injection of streptozotocin (40 mg/kg) and screened by subcutaneous injection of Apomorphine (100 mg/kg). They were then exposed to either vehicle or sildenafil (prescribed in our hospital, 5 mg/kg and 10 mg/kg, respectively) for 10 weeks. An additional nondiabetic and age-matched control group (n = 10) was also allocated and given the routine diet for the same period. Assessments were performed to both groups at 36 hours after the last dose of sildenafil. Penile intracavernous pressure (ICP), mean arterial pressure (MAP), penile tissue morphology, immunohistologic analysis, and Western blot analysis of VEGF, VEGFR1, and eNOS were determined. MAIN OUTCOME MEASURE: Functional, morphological, and proteomical changes on penile structures by the chronic Sildenafil (5 mg/kg and 10 mg/kg, respectively) administration were determined. RESULTS: A significant increase of ICP, ICP/MAP ratio, and area under the curve were observed in the both groups treated by sildenafil (5 mg/kg and 10 mg/kg, respectively), compared with the DMED rats without receiving Sildenafil. Immunohistochemical staining of their penile tissue showed a decrease in VEGF, VEGFR1, and eNOS staining in the controlled group compared with an improvement in the chronic sildenafil administration group. Western blot analysis demonstrated exactly the same results. CONCLUSION: We demonstrated that daily sildenafil administration can restore the impaired VEGF system in the penis of DMED rats and progressively improve both erectile function and endothelial function, suggesting a potential general mechanism of improved signaling through the VEGF/eNOS signaling cascade.
Assuntos
Disfunção Erétil/tratamento farmacológico , Pênis/metabolismo , Inibidores da Fosfodiesterase 5/farmacologia , Piperazinas/farmacologia , Sulfonas/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Western Blotting , Diabetes Mellitus Experimental , Esquema de Medicação , Estimulação Elétrica , Disfunção Erétil/etiologia , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Pênis/inervação , Purinas/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Citrato de Sildenafila , Coloração e Rotulagem , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacosRESUMO
Ureteral triplication is one of the rarest malformations of the upper urinary tract. We report the case of a 12-year-old girl with right ureteral triplication combined with renal ectopia and ureteral cyst with stenosis at the junction of the ureteral cyst and distal ureter. The ureteral cyst was tailored and tubularized, and the tight junction was removed, as in Hynes-Anderson ureteropyeloplasty; on reevaluation almost 4 years later, kidney function was normal and computed tomography showed a normal kidney and ureter.