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1.
Hinyokika Kiyo ; 67(10): 471-474, 2021 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-34742173

RESUMO

A 34-year-old man visited our hospital complaining of a small painless left scrotal mass. His serum alpha-fetoprotein and human chorionic gonadotropin-beta levels were normal. Ultrasonography revealed a solitary 14 mm mass. Magnetic resonance imaging revealed a mass with high intensity on T2-weighted imaging. Computed tomography revealed a heterogeneous tumor in the left scrotum. Left high orchiectomy was performed. The histopathological diagnosis was a teratoma without germ cell neoplasia in situ (GCNIS). Fluorescence in situ hybridization analysis showed no appearance of i(12p). The patient was clinically diagnosed as having a prepubertal-type testicular teratoma. Adult teratomas contain GCNIS and are aggressively treated as malignant germ cell tumors. However, a prepubertal-type teratoma is benign and does not relapse. It is essential to validate the appearance of i(12p) to differentiate prepubertal and postpubertal-type teratoma.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Teratoma , Neoplasias Testiculares , Adulto , Humanos , Hibridização in Situ Fluorescente , Masculino , Recidiva Local de Neoplasia , Orquiectomia , Teratoma/diagnóstico por imagem , Teratoma/cirurgia , Neoplasias Testiculares/cirurgia
2.
Cancer Sci ; 111(4): 1392-1406, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31975570

RESUMO

Analysis of microRNA (miRNA) regulatory networks is useful for exploring novel biomarkers and therapeutic targets in cancer cells. The Cancer Genome Atlas dataset shows that low expression of both strands of pre-miR-101 (miR-101-5p and miR-101-3p) significantly predicted poor prognosis in clear cell renal cell carcinoma (ccRCC). The functional significance of miR-101-5p in cancer cells is poorly understood. Here, we focused on miR-101-5p to investigate the antitumor function and its regulatory networks in ccRCC cells. Ectopic expression of mature miRNAs or siRNAs was investigated in cancer cell lines to characterize cell function, ie, proliferation, apoptosis, migration, and invasion. Genome-wide gene expression and in silico database analyses were undertaken to predict miRNA regulatory networks. Expression of miR-101-5p caused cell cycle arrest and apoptosis in ccRCC cells. Downstream neighbor of son (DONSON) was directly regulated by miR-101-5p, and its aberrant expression was significantly associated with shorter survival in propensity score-matched analysis (P = .0001). Knockdown of DONSON attenuated ccRCC cell aggressiveness. Several replisome genes controlled by DONSON and their expression were closely associated with ccRCC pathogenesis. The antitumor miR-101-5p/DONSON axis and its modulated replisome genes might be a novel diagnostic and therapeutic target for ccRCC.


Assuntos
Carcinoma de Células Renais/genética , Proteínas de Ciclo Celular/genética , Proliferação de Células/genética , MicroRNAs/genética , Proteínas Nucleares/genética , Idoso , Apoptose/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Interferência de RNA , Transdução de Sinais/genética
3.
Int J Urol ; 26(4): 506-520, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30818424

RESUMO

OBJECTIVES: To identify oncogenes regulated by micro-ribonucleic acid, miR-199a/b-3p, in metastatic castration-resistant prostate cancer. METHODS: Advanced ribonucleic acid sequencing technologies were applied to construct a micro-ribonucleic acid expression signature using metastatic castration-resistant prostate cancer autopsy specimens. Ectopic expression of mature micro-ribonucleic acids or small-interfering ribonucleic acids were applied to functional assays for cancer cell lines. Genome-wide gene expression and in silico database analyses were carried out to predict micro-ribonucleic acid targets. RESULTS: Ectopic expression of miR-199a/b inhibited cancer cell aggressiveness. The gene coding for non-structural maintenance of chromosomes condensin I complex subunit H was directly regulated by miR-199a/b-3p. High expression of condensin I complex subunit H was significantly associated with poor disease-free survival by The Cancer Genome Atlas database analysis (P < 0.0001). Overexpression of condensin I complex subunit H was detected in hormone-sensitive prostate cancer and castration-resistant prostate cancer specimens, and knockdown assays showed that its expression enhanced cancer cell migration and invasive abilities. CONCLUSIONS: Small ribonucleic acid sequencing of metastatic castration-resistant prostate cancer specimens showed the presence of several antitumor micro-ribonucleic acids whose targets are involved in hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer pathogenesis. Condensin I complex subunit H seems to be a promising diagnostic marker and therapeutic target for this disease. Our approach, based on the roles of anti-tumor micro-ribonucleic acids and their targets, will contribute to an improved understanding of the molecular pathogenesis of hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer.


Assuntos
Proteínas de Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Proteínas Nucleares/genética , Neoplasias de Próstata Resistentes à Castração/genética , Idoso , Idoso de 80 Anos ou mais , Biópsia com Agulha de Grande Calibre , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Conjuntos de Dados como Assunto , Intervalo Livre de Doença , Regulação para Baixo , Perfilação da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , RNA Interferente Pequeno/metabolismo , Análise de Sequência de RNA , Transfecção
4.
Cancer Sci ; 109(9): 2919-2936, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29968393

RESUMO

In the human genome, miR-451a, miR-144-5p (passenger strand), and miR-144-3p (guide strand) reside in clustered microRNA (miRNA) sequences located within the 17q11.2 region. Low expression of these miRNAs is significantly associated with poor prognosis of patients with renal cell carcinoma (RCC) (miR-451a: P = .00305; miR-144-5p: P = .00128; miR-144-3p: P = 9.45 × 10-5 ). We previously reported that miR-451a acted as an antitumor miRNA in RCC cells. Involvement of the passenger strand of the miR-144 duplex in the pathogenesis of RCC is not well understood. Functional assays showed that miR-144-5p and miR-144-3p significantly reduced cancer cell migration and invasive abilities, suggesting these miRNAs acted as antitumor miRNAs in RCC cells. Analyses of miR-144-5p targets identified a total of 65 putative oncogenic targets in RCC cells. Among them, high expression levels of 9 genes (FAM64A, F2, TRIP13, ANKRD36, CENPF, NCAPG, CLEC2D, SDC3, and SEMA4B) were significantly associated with poor prognosis (P < .001). Among these targets, expression of SDC3 was directly controlled by miR-144-5p, and its expression enhanced cancer cell aggressiveness. We identified genes downstream by SDC3 regulation. Data showed that expression of 10 of the downstream genes (IL18RAP, SDC3, SH2D1A, GZMH, KIF21B, TMC8, GAB3, HLA-DPB2, PLEK, and C1QB) significantly predicted poor prognosis of the patients (P = .0064). These data indicated that the antitumor miR-144-5p/oncogenic SDC3 axis was deeply involved in RCC pathogenesis. Clustered miRNAs (miR-451a, miR-144-5p, and miR-144-3p) acted as antitumor miRNAs, and their targets were intimately involved in RCC pathogenesis.


Assuntos
Carcinoma de Células Renais/patologia , Movimento Celular/genética , Neoplasias Renais/patologia , MicroRNAs/genética , Oncogenes/genética , Sindecana-3/genética , Idoso , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/genética , Sindecana-3/metabolismo
5.
Cancer Sci ; 109(4): 1239-1253, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29417701

RESUMO

Recent analyses of our microRNA (miRNA) expression signatures obtained from several types of cancer have provided novel information on their molecular pathology. In renal cell carcinoma (RCC), expression of microRNA-451a (miR-451a) was significantly downregulated in patient specimens and low expression of miR-451a was significantly associated with poor prognosis of RCC patients (P = .00305) based on data in The Cancer Genome Atlas. The aims of the present study were to investigate the antitumor roles of miR-451a and to identify novel oncogenic networks it regulated in RCC cells. Ectopic expression of miR-451a significantly inhibited cancer cell migration and invasion by RCC cell lines, suggesting that miR-451a had antitumor roles. To identify oncogenes regulated by miR-451a in RCC cells, we analyzed genome-wide gene expression data and examined information in in silico databases. A total of 16 oncogenes and were found to be possible targets of miR-451a regulation. Interestingly, high expression of 9 genes (PMM2, CRELD2, CLEC2D, SPC25, BST2, EVL, TBX15, DPYSL3, and NAMPT) was significantly associated with poor prognosis. In this study, we focused on phosphomannomutase 2 (PMM2), which was the most strongly associated with prognosis. Overexpression of PMM2 was detected in clinical specimens and Spearman's rank test indicated a negative correlation between the expression levels of miR-451a and PMM2 (P = .0409). Knockdown of PMM2 in RCC cells inhibited cancer cell migration and invasion, indicating overexpression of PMM2 could promote malignancy. Analytic strategies based on antitumor miRNAs is an effective tool for identification of novel pathways of cancer.


Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , MicroRNAs/genética , Oncogenes/genética , Idoso , Carcinogênese/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Fosfotransferases (Fosfomutases)/genética , Prognóstico
6.
J Hum Genet ; 63(2): 195-205, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29196733

RESUMO

Our recent determination of a microRNA (miRNA) expression signature in prostate cancer (PCa) revealed that miR-205-5p was significantly reduced in PCa tissues and that it acted as an antitumor miRNA. The aim of this study was to identify oncogenic genes and pathways in PCa cells that were regulated by antitumor miR-205-5p. Genome-wide gene expression analyses and in silico miRNA database searches showed that 37 genes were putative targets of miR-205-5p regulation. Among those genes, elevated expression levels of seven in particular (HMGB3, SPARC, MKI67, CENPF, CDK1, RHOU, and POLR2D) were associated with a shorter disease-free survival in a large number of patients in the The Cancer Genome Atlas (TCGA) database. We focused on high-mobility group box 3 (HMGB3) because it was the most downregulated by ectopic expression of miR-205-5p in PC3 cells and its expression was involved in PCa pathogenesis. Luciferase reporter assays showed that HMGB3 was directly regulated by miR-205-5p in PCa cells. Knockdown studies using si-HMGB3 showed that expression of HMGB3 enhanced PCa cell aggressiveness. Overexpression of HMGB3/HMGB3 was confirmed in naive PCa and castration-resistant PCa (CRPC) clinical specimens. Novel approaches to analysis of antitumor miRNA-regulated RNA networks in PCa cells may provide new insights into the pathogenic mechanisms of the disease.


Assuntos
Genes Supressores de Tumor , Proteína HMGB3/biossíntese , MicroRNAs/biossíntese , Proteínas de Neoplasias/biossíntese , Neoplasias de Próstata Resistentes à Castração , RNA Neoplásico/biossíntese , Linhagem Celular Tumoral , Proteína HMGB3/genética , Humanos , Masculino , MicroRNAs/genética , Proteínas de Neoplasias/genética , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , RNA Neoplásico/genética
7.
Int J Urol ; 25(11): 953-965, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30153702

RESUMO

OBJECTIVES: To identify key oncogenes and proteins that are controlled by the microRNA miR-29 family (miR-29a, miR-29b and miR-29c) in renal cell carcinoma pathogenesis. METHODS: Genome-wide gene expression and in silico database analyses were carried out. The Cancer Genome Atlas database was used to investigate the clinical significance of gene expression data in renal cell carcinoma patients. Loss-of-function assays were applied to investigate the function of target genes. RESULTS: We identified 47 possible target genes that might be regulated by the miR-29 family in renal cell carcinoma cells. Among the targets of the miR-29 family, high expression of 10 genes (ADAMTS14, TRIB13, SERPINH1, FCGR1B, COL1A1, LAIR2, WISP2, TREM1, TNKS1BP1 and GBP2) significantly predicted poor patient prognosis (P < 0.001). SERPINH1 was directly regulated by the miR-29 family, and its overexpression was detected in renal cell carcinoma surgical specimens and tyrosine kinase inhibitor failure autopsy specimens. High expression of SERPINH1 was significantly associated with tumor stage, pathological grade and poor prognosis (P < 0.0001). Knockdown assays showed that its expression enhanced cancer cell migration and invasive abilities. CONCLUSIONS: Genes regulated by the anti-tumor miR-29 family are closely involved in the molecular pathogenesis of renal cell carcinoma. Our approach based on anti-tumor microRNAs might contribute to the development of new diagnostic markers and therapeutic strategies.


Assuntos
Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico HSP47/genética , Neoplasias Renais/genética , MicroRNAs/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Bases de Dados Factuais , Feminino , Estudo de Associação Genômica Ampla , Humanos , Japão , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética
8.
Cancer Sci ; 108(10): 2088-2101, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28746769

RESUMO

Analysis of our original microRNA (miRNA) expression signature of patients with advanced renal cell carcinoma (RCC) showed that microRNA-10a-5p (miR-10a-5p) was significantly downregulated in RCC specimens. The aims of the present study were to investigate the antitumor roles of miR-10a-5p and the novel cancer networks regulated by this miRNA in RCC cells. Downregulation of miR-10a-5p was confirmed in RCC tissues and RCC tissues from patients treated with tyrosine kinase inhibitors (TKI). Ectopic expression of miR-10a-5p in RCC cell lines (786-O and A498 cells) inhibited cancer cell migration and invasion. Spindle and kinetochore-associated protein 1 (SKA1) was identified as an antitumor miR-10a-5p target by genome-based approaches, and direct regulation was validated by luciferase reporter assays. Knockdown of SKA1 inhibited cancer cell migration and invasion in RCC cells. Overexpression of SKA1 was observed in RCC tissues and TKI-treated RCC tissues. Moreover, analysis of The Cancer Genome Atlas database demonstrated that low expression of miR-10a-5p and high expression of SKA1 were significantly associated with overall survival in patients with RCC. These findings showed that downregulation of miR-10a-5p and overexpression of the SKA1 axis were highly involved in RCC pathogenesis and resistance to TKI treatment in RCC.


Assuntos
Carcinoma de Células Renais/genética , Proteínas Cromossômicas não Histona/genética , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Renais/genética , MicroRNAs/genética , Regiões 3' não Traduzidas , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Análise de Sobrevida
9.
Br J Cancer ; 117(3): 409-420, 2017 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-28641312

RESUMO

BACKGROUND: Despite recent advancements, metastatic castration-resistant prostate cancer (CRPC) is not considered curative. Novel approaches for identification of therapeutic targets of CRPC are needed. METHODS: Next-generation sequencing revealed 945-1248 miRNAs from each lethal mCRPC sample. We constructed miRNA expression signatures of CRPC by comparing the expression of miRNAs between CRPC and normal prostate tissue or hormone-sensitive prostate cancer (HSPC). Genome-wide gene expression studies and in silico analyses were carried out to predict miRNA regulation and investigate the functional significance and clinical utility of the novel oncogenic pathways regulated by these miRNAs in prostate cancer (PCa). RESULTS: Based on the novel miRNA expression signature of CRPC, miR-145-5p and miR-145-3p were downregulated in CRPC. By focusing on miR-145-3p, which is a passenger strand and has not been well studied in previous reports, we showed that miR-145-3p targeted 4 key molecules, i.e., MELK, NCAPG, BUB1, and CDK1, in CPRC. These 4 genes significantly predicted survival in patients with PCa. CONCLUSIONS: Small RNA sequencing for lethal CRPC and in silico analyses provided novel therapeutic targets for CRPC.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Proteínas Argonautas/genética , Proteína Quinase CDC2 , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Simulação por Computador , Quinases Ciclina-Dependentes/genética , Intervalo Livre de Doença , Regulação para Baixo , Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Proteínas Serina-Treonina Quinases/genética , Complexo de Inativação Induzido por RNA , Análise de Sequência de RNA , Taxa de Sobrevida
10.
J Hum Genet ; 62(1): 25-31, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27278789

RESUMO

Prostate cancer (PCa) is one of the leading causes of cancer-related death in men. PCa is androgen-dependent, and androgen-deprivation therapy is effective for first-line hormonal treatment, but the androgen-independent phenotype of PCa eventually develops, which is difficult to treat and has no effective cure. Recently, microRNAs have been discovered to have important roles in the initiation and progression of PCa, suggesting their use in diagnosis, predicting prognosis and development of treatment for castration-resistant PCa (CRPC). Understanding the networks of microRNAs and their target genes is necessary to ascertain their roles and importance in the development and progression of PCa. This review summarizes the current knowledge about microRNAs regulating PCa progression and elucidates the mechanism of progression to CRPC.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias de Próstata Resistentes à Castração/genética , Transdução de Sinais/genética , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Humanos , Masculino , Modelos Genéticos , Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Androgênicos/genética
11.
Int J Clin Oncol ; 22(2): 353-358, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27744487

RESUMO

BACKGROUND: A retrospective, multi-institutional collaborative study was conducted to evaluate the impact of second transurethral resection (TUR) on the clinical outcome of non-muscle invasive high-grade bladder cancer and to identify predictors of invasion to the lamina propria (pT1) or deeper and residual tumor at the second TUR. METHODS: The clinical and pathological features of 198 patients with non-muscle invasive high-grade bladder cancer treated in five medical institutions from April 1990 to March 2013 were reviewed retrospectively. All patients underwent a second TUR within a mean of 1.5 months after the first resection. Clinicopathological findings of the first and second TURs were compared. Cancer-specific survival and recurrence-free survival were evaluated. Univariate and multivariate analyses for predictors of residual cancer at the second TUR were performed using a logistic regression model. RESULTS: At the second TUR, no tumor was found in 111 (56 %) patients, and 87 (44 %) had residual cancer. At the first TUR, five pT1 patients (3 %) were upstaged to pT2, one pTa patient (1 %) was upstaged to pT1, and 12 G2 patients (6 %) had their tumor upgraded to G3. Patients the group with less than stage pT1 cancer at the second TUR had significantly better survival than those in the group with stage pT1 or deeper cancer. Tumor multiplicity at the first resection was an independent risk factor for pT1 or deeper tumor at the second TUR. CONCLUSION: A second TUR is a valuable diagnostic procedure for accurate staging of non-muscle invasive high-grade bladder cancer. Tumor multiplicity at the first TUR was a significant independent predictor of pT1 or deeper tumor at the second TUR.


Assuntos
Recidiva Local de Neoplasia/patologia , Neoplasia Residual/patologia , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasia Residual/cirurgia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/cirurgia
12.
Int J Mol Sci ; 18(9)2017 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-28902136

RESUMO

Our recent studies revealed that dual strands of certain pre-microRNAs, e.g., pre-miR-144, pre-miR-145, and pre-miR-150, act as antitumor microRNAs (miRNAs) in several cancers. The involvement of passenger strands of miRNAs in cancer pathogenesis is a novel concept in miRNA research. The analysis of a miRNA expression signature in clear cell renal cell carcinoma (ccRCC) has revealed that the guide strand of pre-miR-149 is significantly downregulated in cancer tissues. The aims of this study were to investigate the functional significance of miR-149's guide strand (miR-149-5p) and passenger strand (miR-149-3p), and to identify the oncogenic genes regulated by these miRNAs in ccRCC cells. The ectopic expression of these miRNAs significantly inhibited cancer cell migration and invasion in ccRCC cells. Forkhead box protein M1 (FOXM1) was directly regulated by miR-149-5p and miR-149-3p in ccRCC cells. Knockdown studies using si-FOXM1 showed that the expression of FOXM1 enhanced RCC cell aggressiveness. Interestingly, the analysis of a large number of patients in the The Cancer Genome Atlas (TCGA) database (n = 260) demonstrated that patients with high FOXM1 expression had significantly shorter survival than did those with low FOXM1 expression (p = 1.5 × 10⁻6). Taken together, dual strands of pre-miR-149 (miR-149-5p and miR-149-3p) acted as antitumor miRNAs through the targeting of FOXM1 in ccRCC cells.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Proteína Forkhead Box M1/antagonistas & inibidores , Neoplasias Renais/tratamento farmacológico , MicroRNAs/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação para Baixo , Feminino , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica
13.
Br J Cancer ; 113(7): 1055-65, 2015 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-26325107

RESUMO

BACKGROUND: Our present study of the microRNA (miRNA) expression signature in castration-resistant prostate cancer (CRPC) revealed that the clustered miRNAs microRNA-221 (miR-221) and microRNA-222 (miR-222) are significantly downregulated in cancer tissues. The aim of this study was to investigate the functional roles of miR-221 and miR-222 in prostate cancer (PCa) cells. METHODS: A CRPC miRNA signature was constructed by PCR-based array methods. Functional studies of differentially expressed miRNAs were analysed using PCa cells. The association between miRNA expression and overall survival was estimated by the Kaplan-Meier method. In silico database and genome-wide gene expression analyses were performed to identify molecular targets regulated by the miR-221/222 cluster. RESULTS: miR-221 and miR-222 were significantly downregulated in PCa and CRPC specimens. Kaplan-Meier survival curves showed that low expression of miR-222 predicted a short duration of progression to CRPC. Restoration of miR-221 or miR-222 in cancer cells revealed that both miRNAs significantly inhibited cancer cell migration and invasion. Ecm29 was directly regulated by the miR-221/222 cluster in PCa cells. CONCLUSIONS: Loss of the tumour-suppressive miR-221/222 cluster enhanced migration and invasion in PCa cells. Our data describing targets regulated by the tumour-suppressive miR-221/222 cluster provide insights into the mechanisms of PCa and CRPC progression.


Assuntos
Biomarcadores Tumorais/genética , MicroRNAs/genética , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Família Multigênica , Prognóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Análise de Sobrevida
14.
World J Surg ; 39(12): 2935-40, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26296835

RESUMO

BACKGROUND: Many patients with primary aldosteronism (PA) show a significant decline in kidney function after adrenalectomy. Thus, PA patients who undergo surgery are at greater risk of both postoperative renal damage and new-onset metabolic events associated with renal insufficiency. The aim of this study was to explore postoperative changes in serum lipid levels and to identify risk factors associated with postoperative new-onset dyslipidemia in PA patients. METHODS: The records of 57 Japanese patients who underwent unilateral laparoscopic adrenalectomy for PA were retrospectively surveyed. Clinical and biochemical data were evaluated at baseline and 12 months after surgery. Preoperative and postoperative estimated glomerular filtration (eGFR) and serum lipid profile, including triglycerides, high-density lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol levels, were compared. Furthermore, uni- and multivariate analyses were performed to determine the predictors for postoperative new-onset dyslipidemia. RESULTS: A significant decrease in eGFR and deterioration of serum lipid levels was identified postoperatively in most patients. Of the 39 patients without pre-existing dyslipidemia, 18 developed new-onset dyslipidemia postoperatively. Multivariate analysis identified preoperative lower eGFR and higher body mass index as independent predictors for new-onset dyslipidemia after surgery. On univariate analyses, additional factors associated with new-onset dyslipidemia included older age, male sex, higher LDL-cholesterol, and higher LDL/HDL ratio. CONCLUSIONS: PA patients had a higher risk of postoperative new-onset or progressive dyslipidemia. Clinicians should pay attention to not only follow-up of renal impairment but also total management of new-onset metabolic events associated with renal insufficiency in PA patients.


Assuntos
Adrenalectomia/efeitos adversos , Dislipidemias/etiologia , Hiperaldosteronismo/cirurgia , Insuficiência Renal/etiologia , Adulto , Idoso , Índice de Massa Corporal , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Triglicerídeos/sangue , Adulto Jovem
15.
Int J Urol ; 22(9): 867-77, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26059417

RESUMO

OBJECTIVES: To investigate the functional roles of microRNA-205 in the modulation of novel cancer pathways in prostate cancer cells. METHODS: Functional studies of microRNA-205 were carried out to investigate cell proliferation, migration and invasion in prostate cancer cell lines (PC3 and DU145) by restoration of mature microRNA. In silico database and genome-wide gene expression analyses were carried out to identify molecular targets and pathways mediated by microRNA-205. Loss-of-function studies were applied to microRNA-205 target genes. RESULTS: Restoration of microRNA-205 in cancer cell lines significantly inhibited cancer cell migration and invasion. Our data showed that the centromere protein F gene was overexpressed in prostate cancer clinical specimens and was a direct target of microRNA-205 regulation. Silencing of centromere protein F significantly inhibited cancer cell migration and invasion. Furthermore, MCM7, an oncogenic gene functioning downstream of centromere protein F, was identified by si-centromere protein F transfectants in prostate cancer cells. CONCLUSIONS: Loss of tumor-suppressive microRNA-205 seems to enhance cancer cell migration and invasion in prostate cancer through direct regulation of centromere protein F. Our data describing pathways regulated by tumor-suppressive microRNA-205 provide new insights into the potential mechanisms of prostate cancer oncogenesis and metastasis.


Assuntos
Movimento Celular/genética , Proteínas Cromossômicas não Histona/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas dos Microfilamentos/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Idoso , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas Cromossômicas não Histona/metabolismo , Expressão Gênica , Perfilação da Expressão Gênica , Inativação Gênica , Humanos , Masculino , MicroRNAs/metabolismo , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Dados de Sequência Molecular , Invasividade Neoplásica/genética , Próstata/metabolismo , Transdução de Sinais/genética , Transfecção
16.
Minim Invasive Ther Allied Technol ; 24(3): 141-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25273605

RESUMO

INTRODUCTION: Transurethral surgery is widely accepted as standard therapy for male urethral obstruction. The present study was undertaken to identify and select lesions to be managed by processing endoscopic images of the urethra for assisting less invasive therapy in patients with voiding dysfunction. MATERIAL AND METHODS: Cystourethroscopic video files of 25 patients with lower urinary tract symptoms were recorded before and after administration of alpha-1 adrenoceptor antagonists. Each video frame was restored and tagged with information indicating the position in the panoramic image of the urethra. A three-dimensional virtual urethra was created to indicate critical lesions for voiding dysfunction, together with fluid dynamics simulation of urine flow. RESULTS: The urine stream was depicted in the virtual urethras in 19 patients. Before therapy, 17 patients showed vortex formation that was diminished after therapy in nine patients with a significant relationship in improvement of relative energy loss of flow (p=0.025). The narrowing points proximal to the vortex, candidate of lesions, were identified in the panoramic image and linked to the endoscopic image. DISCUSSION: Therapeutic designing for endoscopic management was possible in patients with voiding dysfunction based on computational fluid dynamics, and would be promising as "focal" therapy for aging males.


Assuntos
Endoscopia do Sistema Digestório/métodos , Imageamento Tridimensional , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Ressecção Transuretral da Próstata/métodos , Obstrução Uretral/cirurgia , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Humanos , Masculino , Hiperplasia Prostática/complicações , Obstrução Uretral/etiologia
17.
Cancer Sci ; 105(7): 802-11, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24815849

RESUMO

Our recent studies of the microRNA (miRNA) expression signature in prostate cancer (PCa) indicated that miRNA-218 (miR-218) was significantly downregulated in clinical specimens, suggesting that miR-218 might act as a tumor-suppressive miRNA in PCa. The aim of the present study was to investigate the functional significance of miR-218 in PCa and to identify novel miR-218-regulated cancer pathways and target genes involved in PCa oncogenesis and metastasis. Restoration of miR-218 in PCa cell lines (PC3 and DU145) revealed that this miRNA significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that LIM and SH3 protein 1 (LASP1) is a potential target of miR-218 regulation. LASP1 is a cytoskeletal scaffold protein that plays critical roles in cytoskeletal organization and cell migration. Luciferase reporter assays showed that miR-218 directly regulated expression of LASP1. Moreover, downregulating the LASP1 gene significantly inhibited cell migration and invasion in cancer cells, and the expression of LASP1 was upregulated in cancer tissues. We conclude that loss of tumor-suppressive miR-218 enhanced cancer cell migration and invasion in PCa through direct regulation of LASP1. Our data on pathways regulated by tumor-suppressive miR-218 provide new insight into the potential mechanisms of PCa oncogenesis and metastasis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas do Citoesqueleto/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas com Domínio LIM/metabolismo , MicroRNAs/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Idoso , Movimento Celular/genética , Proliferação de Células , Proteínas do Citoesqueleto/genética , Humanos , Proteínas com Domínio LIM/genética , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Células Tumorais Cultivadas
18.
J Hum Genet ; 59(2): 78-87, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24284362

RESUMO

Our recent study of microRNA (miRNA) expression signature of prostate cancer (PCa) has revealed that the microRNA-143/145 (miR-143/145) cluster is significantly downregulated in cancer tissues, suggesting that these cluster miRNAs are candidate tumor suppressors. The aim of this study was to investigate the functional significance of the miR-143/145 cluster in PCa cells and to identify novel targets regulated by these cluster miRNAs in PCa. Restoration of miR-143 or miR-145 in PCa cell lines (PC3 and DU145) revealed that these miRNAs significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that Golgi membrane protein 1 (GOLM1) resembling a type II golgi transmembrane protein was a potential target of miR-143/145 cluster target gene. Gene expression studies and luciferase reporter assays showed that GOLM1 was directly regulated by the miR-143/145 cluster. Silencing of GOLM1 resulted in significant inhibition of cell migration and invasion in PCa cells. Furthermore, the expression of GOLM1 was upregulated in cancer tissues by immunohistochemistry. Loss of the tumor-suppressive miR-143/145 cluster enhanced cancer cell migration and invasion in PCa through directly regulating GOLM1. Our data on target genes regulated by the tumor-suppressive miR-143/145 cluster provide new insights into the potential mechanisms of PCa oncogenesis and metastasis.


Assuntos
Movimento Celular , Regulação da Expressão Gênica , Proteínas de Membrana/biossíntese , MicroRNAs/metabolismo , Família Multigênica , Proteínas de Neoplasias/biossíntese , Neoplasias da Próstata/metabolismo , RNA Neoplásico/metabolismo , Idoso , Linhagem Celular Tumoral , Humanos , Masculino , Proteínas de Membrana/genética , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , RNA Neoplásico/genética
19.
World J Surg ; 38(10): 2640-4, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24831672

RESUMO

BACKGROUND: Primary aldosteronism is the most common curable cause of secondary hypertension. Despite resection, however, many patients with primary aldosteronism continue to require antihypertensive drugs to control their blood pressure. Although many patients with primary aldosteronism want to know the postoperative probability of hypertension cure before surgery, there are no predictive models calculating its probability. We therefore developed a nomogram to predict hypertension cure in patients with primary aldosteronism after laparoscopic adrenalectomy. METHODS: We retrospectively surveyed 132 Japanese patients with primary aldosteronism who were treated by unilateral laparoscopic adrenalectomy. Hypertension cure was defined as normal blood pressure (<140/90 mmHg) without antihypertensive drugs 6 months postoperatively. We developed a novel nomogram that postoperatively predicted cured hypertension in 105 (80 %) randomly selected patients and validated it with the remaining 27 (20 %). RESULTS: At 6 months, blood pressure had normalized in 42 % of patients without antihypertensive drugs. Duration of hypertension, preoperative number of antihypertensive drug classes, age, and sex were incorporated into a novel nomogram as independent predictors of hypertension cure. The value of the area under the receiver operating characteristics curve for this nomogram was 0.83-which was significantly higher than that of the Aldosteronoma Resolution Score-on internal validation. CONCLUSIONS: We developed the first nomogram that can accurately predict postoperative hypertension cure in patients with primary aldosteronism. This nomogram can help clinicians calculate the probability of postoperative hypertension cure in patients with primary aldosteronism and objectively inform them of their hypertension outcome before laparoscopic adrenalectomy.


Assuntos
Hiperaldosteronismo/cirurgia , Hipertensão/cirurgia , Nomogramas , Adrenalectomia , Adulto , Idoso , Área Sob a Curva , Pressão Sanguínea , Feminino , Humanos , Hiperaldosteronismo/complicações , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Japão , Laparoscopia , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Resultado do Tratamento
20.
Int J Clin Oncol ; 19(1): 157-64, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23299278

RESUMO

BACKGROUND: The aim of this study was to retrospectively investigate clinical outcomes by relative dose and dose intensity of docetaxel (DOC) as chemotherapy for Japanese patients with castration-resistant prostate cancer (CRPC). METHODS: A total of 145 CRPC patients who received more than 4 courses of DOC chemotherapy at 14 hospitals between 2005 and 2011 were enrolled. Patients were divided into two groups--those receiving a higher or lower dose (mg/m(2)) or dose intensity (mg/m(2)/week). Differences between the groups regarding treatment outcomes and adverse events (AEs) were determined. Additionally, prognostic factors predictive of cancer-specific survival (CSS) in these patients were identified by both univariate and multivariate analysis. RESULTS: The total patient group underwent a mean of 11.2 ± 7.4 DOC cycles, and the mean CSS after therapy was 15.6 ± 10.1 months. The higher-dose group had a better prostate-specific antigen (PSA) response than the lower-dose group. However, there was no significant difference between the groups in prognosis after DOC chemotherapy. Leukopenia and neutropenia were observed more frequently in the higher-dose group. Serum biomarkers (including PSA, lactate dehydrogenase and alkaline phosphatase), hemoglobin levels and presence of pain at initiation of chemotherapy, as well as the PSA nadir level on first-line hormone therapy, all were significant predictors of CSS. CONCLUSIONS: In the Japanese population, relatively low-dose DOC chemotherapy had no deleterious effect on the CSS of CRPC patients, and a lower incidence of AEs occurred, in spite of a diminished PSA response compared with those receiving a higher dose.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Docetaxel , Relação Dose-Resposta a Droga , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Taxoides/efeitos adversos , Resultado do Tratamento
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