Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.194
Filtrar
1.
Medicine (Baltimore) ; 98(40): e17276, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577719

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer in adults, and patients with advanced ccRCC have a 5-year survival rate of <30%. The poor prognosis of ccRCC is closely related to its lacking of potential therapeutic and prognostic biomarkers. This meta-analysis aimed to elucidate the precise prognostic value of long non-coding RNAs (lncRNAs) in patients with ccRCC. METHODS: A literature search was performed in related databases up to January 31, 2019. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated to explore the relationship between special lncRNAs expression and survival in patients with ccRCC. RESULTS: After literature researching, a total of 16 studies, including 13 lncRNAs were identified. The data from studies that investigated the association between lncRNA expression and survival outcomes in patients with ccRCC were extracted. Results revealed that lncRNAs expression was significantly associated with poor overall survival (OS) outcome in patients with ccRCC (HR = 1.71, 95%CI = 1.40-2.01 in up-regulated subgroup; HR = 0.53, 95% CI = 0.25-0.80 in down-regulated subgroup). The overexpression of PVT1 was significantly associated with poor OS in ccRCC (HR = 1.51, 95% CI = 1.02-2.00). Meanwhile, up-regulation of LUCAT1 was significantly related to worse OS in ccRCC patients (HR = 1.51, 95% CI = 1.01-2.00). CONCLUSIONS: These results suggest that lncRNAs could be used to predict unfavorable prognosis and function as potential prognostic biomarkers in ccRCC.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , RNA Longo não Codificante/genética , Fatores Etários , Biomarcadores Tumorais , Carcinoma de Células Renais/patologia , Proliferação de Células , Ensaios Clínicos como Assunto , Regulação para Baixo , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Fatores Sexuais , Taxa de Sobrevida , Carga Tumoral , Regulação para Cima
2.
Medicine (Baltimore) ; 98(39): e17245, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574838

RESUMO

RATIONALE: Over the past decade, although several new entities of renal tumors have emerged, a form of renal cell carcinoma (RCC) that morphologically resembles epithelial-myoepithelial carcinoma has not been reported thus far. Herein, we describe a case of an unusual renal tumor that remained unclassified under a current RCC subtype, and briefly present its morphologic, immunophenotypic, and genetic features. PATIENT CONCERNS: The patient was an 85-year-old man who presented with hematuria and flank pain. Imaging studies revealed a left renal mass without enlarged lymph nodes. There were no abnormal masses or nodules in other organs. DIAGNOSES: The patient underwent no other treatment except the left radical nephrectomy under a clinical diagnosis of invasive urothelial carcinoma and was discharged on the thirteenth day. Histologically, the renal tumor showed biphasic proliferation of epithelial (strongly cytokeratin-positive; P63, P40, and vimentin-negative) and myoepithelial (strongly vimentin-positive; focal P63 and P40-positive; and weakly cytokeratin-positive) cells arranged in a perivascular pseudorosette-like pattern. No mutations were detected in multiple gene tests. According to the pathological structure, the patient was diagnosed as primary epithelial myoepithelial carcinoma-like renal tumor. INTERVENTIONS: To the best of our knowledge, the present tumor has not been previously described, and thus, this variant has not been integrated into a known form of PCC. Therefore, we cannot diagnose this type of tumor with other types of kidney tumors. OUTCOMES: Three years after primary diagnosis, the patient died of multiple organ failure result from multiple distant metastases. LESSONS: We present the first case of carcinoma of the kidney with EMC-like features and a perivascular pseudorosette-like growth pattern. Clinicians should be aware of the features of this uncommon variant of RCC to avoid diagnostic delays or misdiagnosis and prevent unnecessary or inappropriate treatment.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Mioepitelioma/patologia , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/genética , Evolução Fatal , Humanos , Imunofenotipagem , Rim/patologia , Neoplasias Renais/genética , Masculino , Mioepitelioma/genética , Formação de Roseta
3.
Anticancer Res ; 39(9): 4681-4685, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519567

RESUMO

BACKGROUND/AIM: S100A8 is a chemoattractant known to be associated with metastatic niche formation. Herein, we evaluated the prognostic value of S100A8 in patients with clear cell renal cell carcinoma (CCRCC). MATERIALS AND METHODS: A total of 152 CCRCC patients who have undergone nephrectomy were enrolled. The expression of S100A8 was assessed immunohistochemically using tissue microarray (TMA) blocks of CCRCC. Using statistical analysis, the relationship between S100A8 expression and clinicopathological factors was evaluated. RESULTS: Among 152 TMA cores, 21 (6.9%) showed higher S100A8 expression. S100A8 expression was significantly increased in cores of patients with higher T stage (≥2, p<0.001) and higher Fuhrman nuclear grade (≥3, p<0.001). Multivariate analysis confirmed that high expression of S100A8 was significantly correlated to poor disease-free survival (hazard ratio, 2.601; 95% confidence interval (CI), 1.020-6.628; p-value=0.045). CONCLUSION: S100A8 expression may have a prognostic value in CCRCC reflecting TNM staging and Fuhrman nuclear grade.


Assuntos
Biomarcadores Tumorais , Calgranulina A/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Expressão Gênica , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Calgranulina A/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico
4.
Anticancer Res ; 39(9): 4737-4742, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519573

RESUMO

BACKGROUND/AIM: There are several unresolved issues regarding the combined treatment with an immune checkpoint inhibitor and anti-angiogenic agent for renal cell carcinoma (RCC) patients. The purpose of this study was to address the inhibitory effects of programmed death-ligand 1 (PD-L1) expression on growth and sensitivity to sunitinib in the mouse RCC RenCa model. MATERIALS AND METHODS: We established RenCa/sh-PD-L1 by transfecting RenCa cells with a plasmid carrying a short hairpin RNA targeted against PD-L1. The growth pattern of RenCa/sh-PD-L1 with or without sunitinib was compared to that of RenCa cells transfected with control plasmid alone (RenCa/Co). RESULTS: No significant difference in growth or sensitivity to sinitinib was noted between RenCa/sh-PD-L1 and RenCa/Co cells in vitro. The tumor volume in mice subcutaneously injected with RenCa/sh-PD-L1 was significantly smaller than that with RenCa/Co. Treatment of mice bearing each tumor with sunitinib resulted in a significant reduction of the RenCa/sh-PD-L1 tumor compared to the RenCa/Co tumor. Moreover, infiltration by CD8+ T cells of RenCa/sh-PD-L1 tumors was significantly higher than that of RenCa/Co tumors, irrespective of treatment with sunitinib. CONCLUSION: Suppressed expression of PD-L1 could increase tumor-infiltrating CD8+ T cells and result in growth inhibition as well as enhanced sensitivity to sunitinib in the RenCa model.


Assuntos
Antineoplásicos/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , RNA Interferente Pequeno/genética , Sunitinibe/farmacologia , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Expressão Gênica , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Camundongos , Carga Tumoral/efeitos dos fármacos
6.
Gene ; 720: 144103, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31491435

RESUMO

Clear cell renal cell carcinoma (ccRCC) is a highly invasive urological malignant tumor that results in shorter patient survival. At present, the mechanism of ccRCC metastasis is not clear. We explored the possible mechanisms of ccRCC metastasis by analyzing the transcriptome of ccRCC patients from the Cancer Genome Atlas (TCGA) database. Comparing the differences in transcriptome in patients with and without metastasis, we found 323 differential genes (|log2FoldChange| > 1 and P < 0.001). KEGG and GO enrichment analyses of differentially expressed genes (DEGs) suggest that the transfer mechanism of ccRCC may be related to complement and coagulation cascades and cholesterol metabolism. To explore the key genes affecting tumor metastasis, we analyzed the association of these genes with patient survival time and found that 16 genes were significantly associated (P < 0.05). We compared the differences in expression of these 16 genes between ccRCC patients and the normal population, and the results showed that TF and B4GALNT1 were overexpressed in patients. Co-expression gene analysis indicated that TF may participate in the metastasis of cancer through the complement system and mucopolysaccharide biosynthesis. B4GALNT1 may affect metastasis through focal adhesion, calcium signaling pathways, and Hippo signaling pathways. Our studies suggest that the complement system and the coagulation cascade, cholesterol metabolism, calcium pathway and iron transport may be associated in the mechanism of metastasis. TF and B4GALNT1 may be the key genes for metastasis, and they may be potential diagnostic markers and therapeutic targets for ccRCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Transcriptoma , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/secundário , Estudos de Casos e Controles , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Prognóstico , Mapas de Interação de Proteínas , Transdução de Sinais , Taxa de Sobrevida
7.
Medicine (Baltimore) ; 98(37): e17172, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517871

RESUMO

The aim of the study was to report the experience and outcomes of Xp11.2 translocation renal cell carcinoma (tRCC) patients with tumor thrombus undergoing radical nephrectomy and thrombectomy.Between January 2017 and December 2017, 66 consecutive patients with RCC and venous thrombus involvement received surgical treatment at Peking University Third Hospital. Of which, 5 patients were confirmed of Xp11.2 tRCC, 61 patients were diagnosed of non-tRCC subtypes including 45 ccRCCs, 10 pRCCs, and 6 other subtypes. Demographic, clinical, operation, pathological and follow-up data were extracted for analysis. Prognostic factors were identified by Cox regression analysis.All the patients received radical nephrectomy and thrombectomy successfully. During a median follow-up of 18 months, 5 patients in non-tRCC group and 1 patient in tRCC group died of disease progression. Survival analysis revealed that Xp11.2 tRCC patients experienced shorter DFS than non-tRCC patients, however, there is no significant difference in OS between two groups. Xp11.2 tRCC histological subtype and presence of metastasis at diagnosis were identified as independent negative factors of DFS by multivariate analysis.Radical nephrectomy with thrombectomy provides an acceptable efficacy for tRCC patients with tumor thrombus extending into the venous system. In addition, multimodality treatment should be considered for advanced Xp11.2 RCCs as this subtype was a negative prognostic factor of DFS.


Assuntos
Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/complicações , Neoplasias Renais/cirurgia , Trombose Venosa/complicações , Trombose Venosa/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Feminino , Seguimentos , Humanos , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Nefrectomia , Análise de Sobrevida , Trombectomia , Trombose Venosa/mortalidade , Adulto Jovem
9.
Crit Rev Oncol Hematol ; 142: 141-152, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401421

RESUMO

Knowledge about molecular mechanisms driving development and progression of renal cell carcinoma has been elucidated by different studies. In few years we discovered a large difference between genomic landscapes of clear cell and non-clear cell carcinoma. Moreover, tumor heterogeneity and different acquisition of gene mutations during tumor progression are issues of particular interest. In this review we focalized our attention on principal genomic alterations identified among RCC subtypes. Acquired gene mutations may be an adaptive response to several external pressure including metabolic, treatment, genomic and immune-related external pressure. Thus we correlated and discussed principal genomic alterations adopted by tumor to escape from each external pressures. The aim of the present work is to summarize current knowledge about genomic alterations in RCC with special interest of treatment strategies tailored on the basis of disease mutations assessment.


Assuntos
Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Mutação , Medicina de Precisão , Animais , Carcinoma de Células Renais/genética , Genômica , Humanos , Neoplasias Renais/genética
10.
J Cancer Res Clin Oncol ; 145(9): 2293-2301, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31401673

RESUMO

PURPOSE: Androgen receptors (ARs) are expressed on a variety of cell types, and AR signaling plays an important role in tumor development and progression in several cancers. This in vitro study evaluated the effect of dihydrotestosterone (DHT) on the proliferation of renal cell carcinoma (RCC) cells in relation to AR status. METHODS: Steroid hormone receptor expression was evaluated using RT-PCR and Western blotting. The effect of DHT on cell proliferation and STAT5 phosphorylation was evaluated in RCC cell lines (Caki-2, A498, and SN12C) and primary RCC cells using cell viability assays and Western blotting. ARs and glucocorticoid receptors (GRs) were knocked down with small interfering RNAs before assessing changes in cell proliferation and STAT5 activation. RESULTS: DHT treatment promoted cell proliferation and increased STAT5 phosphorylation regardless of AR status. The AR antagonist bicalutamide reduced kidney cancer cell proliferation, regardless of AR status. AR and GR knockdown blocked STAT5 activation and reduced cell proliferation in all RCC cell lines. In patient-derived primary cells, DHT enhanced cell proliferation and this effect was diminished by treatment with the AR antagonists bicalutamide and enzalutamide and the GR antagonist mifepristone. CONCLUSION: DHT promotes cell proliferation through STAT5 activation in RCC cells, regardless of AR status. DHT appears to utilize the AR and GR pathways to activate STAT5, and the inhibition of AR and GR showed antitumor activity in RCC cells. These data suggest that targeting AR and GR may be a promising new approach to the treatment of RCC.


Assuntos
Carcinoma de Células Renais/patologia , Proliferação de Células/efeitos dos fármacos , Di-Hidrotestosterona/farmacologia , Neoplasias Renais/patologia , Receptores Androgênicos/fisiologia , Receptores de Glucocorticoides/fisiologia , Fator de Transcrição STAT5/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Antagonistas de Receptores de Andrógenos/farmacologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Fator de Transcrição STAT5/genética , Transdução de Sinais/efeitos dos fármacos , Proteínas Supressoras de Tumor/genética
11.
J Clin Pathol ; 72(11): 748-754, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31262952

RESUMO

AIMS: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a newly recognised entity in the WHO 2016 classification defined as the germline mutation of FH gene. Fumaratehydratase-deficient renal cell carcinoma (FH-deficient RCC) is recommended for tumours with FH deficiency but lacking of genetic evidences of FH germline mutation. In this study, we described the clinicopathological and molecular changes of 13 FH-deficient RCCs. METHODS AND RESULTS: Histology features, clinicopathological data, radiology performance and outcomes were collected for each patient. Next-generation sequencing and DNA sequencing of FH gene were performed to examine FH mutations. The patient group included five females and eight males. Different morphological patterns of papillary, nested, adenoid, foam adenoid, cribriform, tubular, tubulocystic, cystic and loose oedema stroma were observed. Except typical big nuclei with or without eosinophilic nucleoli and perinucleolar halos, raisin-like, hobnail-like and even low-grade nuclei were also observed in these tumours. Eleven cases with high-grade nuclei showed disease progression or death, but no disease progression was detected in two cases with low-grade nuclei and eosinophilic cytoplasm. FH expression was absent in tumour cells except for case 11. Next-generation sequencing and DNA sequencing verified seven FH germline mutations and four somatic mutations out of 13 cases. CONCLUSIONS: FH-deficient RCC is a rare renal tumour and has a wide morphological spectrum. Most of the tumours had high-grade nuclei and were aggressive. However, we observed a morphological subtype of FH-deficient RCC with low-grade nuclei and eosinophilic cytoplasm, which might mainly occur in young women and show a relatively good prognosis.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Fumarato Hidratase/genética , Mutação em Linhagem Germinativa , Neoplasias Renais/genética , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/deficiência , Biópsia , Carcinoma de Células Renais/enzimologia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Núcleo Celular/patologia , Citoplasma/patologia , Análise Mutacional de DNA/métodos , Feminino , Fumarato Hidratase/deficiência , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Neoplasias Renais/enzimologia , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Fenótipo
12.
Pathologe ; 40(6): 600-608, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31338565

RESUMO

Pediatric kidney tumors are rare and account for about 6% of all childhood malignancies. By far the most common tumors are nephroblastomas. This review presents rare childhood renal tumors. Mesoblastic nephroma, as tumors of the low risk group, as well as the clear-cell sarcomas of the kidney and malignant rhabdoid tumors, as tumors of the high-risk group, and the so-called anaplastic sarcomas of the kidney will be discussed.Due to the significantly divergent therapy, a correct diagnosis is important. Due to the often overlapping morphology, pathologic diagnosis is often difficult. In addition to the typical morphologic features, the specific immunohistochemical aspects as well as the known molecular changes will be presented.


Assuntos
Neoplasias Renais , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Neoplasias Renais/patologia , Nefroma Mesoblástico/diagnóstico , Nefroma Mesoblástico/genética , Nefroma Mesoblástico/patologia , Tumor Rabdoide/diagnóstico , Tumor Rabdoide/genética , Tumor Rabdoide/patologia , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/patologia , Tumor de Wilms/diagnóstico , Tumor de Wilms/genética , Tumor de Wilms/patologia
13.
Nat Commun ; 10(1): 2977, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278255

RESUMO

Upper tract urothelial carcinoma (UTUC) is characterized by a distinctly aggressive clinical phenotype. To define the biological features driving this phenotype, we performed an integrated analysis of whole-exome and RNA sequencing of UTUC. Here we report several key insights from our molecular dissection of this disease: 1) Most UTUCs are luminal-papillary; 2) UTUC has a T-cell depleted immune contexture; 3) High FGFR3 expression is enriched in UTUC and correlates with its T-cell depleted immune microenvironment; 4) Sporadic UTUC is characterized by a lower total mutational burden than urothelial carcinoma of the bladder. Our findings lay the foundation for a deeper understanding of UTUC biology and provide a rationale for the development of UTUC-specific treatment strategies.


Assuntos
Carcinoma de Células de Transição/patologia , Neoplasias Renais/patologia , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Linfócitos T/imunologia , Neoplasias Ureterais/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/imunologia , Análise Mutacional de DNA , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/imunologia , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Análise de Sequência de RNA , Transdução de Sinais/genética , Microambiente Tumoral/imunologia , Neoplasias Ureterais/genética , Neoplasias Ureterais/imunologia , Urotélio/patologia , Sequenciamento Completo do Exoma
14.
Int J Oncol ; 55(1): 81-92, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180521

RESUMO

Renal cell carcinoma (RCC) is the most common type of kidney cancer. By analysing The Cancer Genome Atlas (TCGA) database, 16 genes were identified to be consistently highly expressed in RCC tissues compared with the matched para­tumour tissues. Using a high­throughput cell viability screening method, it was found that downregulation of only two genes significantly inhibited the viability of 786­O cells. Among the two genes, pleckstrin homology domain containing O1 (PLEKHO1) has never been studied in RCC, to the best of our knowledge, and its expression level was shown to be associated with the prognosis of patients with RCC in TCGA dataset. The upregulation of PLEKHO1 in RCC was first confirmed in 30 paired tumour and para­tumour tissues. Then, the effect of PLEKHO1 on cell proliferation and apoptosis was assessed in vitro. Additionally, xenograft tumour models were established to investigate the function of PLEKHO1 in vivo. The results showed that PLEKHO1 knockdown significantly inhibited cell viability and facilitated apoptosis in vitro and impaired tumour formation in vivo. Thus, PLEKHO1 is likely to be associated with the viability of RCC cells in vitro and in vivo. Further gene expression microarray and co­expression analyses showed that PLEKHO1 may be involved in the serine/threonine­protein kinase hippo and JNK signalling pathways. Together, the results of the present study suggest that PLEKHO1 may contribute to the development of RCC, and therefore, further study is needed to explore its potential as a therapeutic target.


Assuntos
Carcinoma de Células Renais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Renais/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas Serina-Treonina Quinases/metabolismo , Adulto , Idoso , Animais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Feminino , Técnicas de Silenciamento de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Regulação para Cima
15.
Int J Nanomedicine ; 14: 4091-4103, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239669

RESUMO

Introduction: Curcuma wenyujin is a plant which belongs to the family of Zingiberaceae, found in South Asia and China. C. wenyujin is a major constituent in Chinese traditional medicine and is used to treat liver diseases, blood clots, and is also prescribed as a painkiller. C. wenyujin possesses antioxidant, antiproliferative, and antitumorogenic properties, and many researchers have proved the efficacy of C. wenyujin against various types of cancer. The major drawback of this historical drug is it's low bioavailability. Methods: This study synthesized gold nanoparticles using C. wenyujin and assessed its potency against in vitro renal cancer cells. The biosynthesized C. wenyujin gold nanoparticles (CWAuNPs) were characterized using UV-Spec, DLS, FTIR, SAED, TEM, EDAX, and Atomic Force analysis. The cytotoxicity of CWAuNPs against renal cancer cell lines A498 and SW-156 was assessed with MTT assay. The induction of apoptosis by CWAuNPs in A498 cell was measured using apoptotic staining DAPI, Rhodamine 123, and H2DCFDA. The apoptotic activity of CWAuNPs was further confirmed with flow cytometric analysis. The molecular mechanism of CWAuNPs was analyzed with qPCR and immunoblotting analysis of caspases, proapoptotic, and antiapoptotic proteins. Results: The characterization of results of synthesized CWAuNPs satisfy the distinctive properties of a potent nanodrug. The results of apoptotic staining techniques confirm the induction of CWAuNPs in A498 by increasing the apoptotic Caspase 3,9, Bid, and Bad, and decreasing the antiapoptotic protein Bcl-2, Bcl-xl expressions, which is authentically proven by the qPCR and immunoblotting analysis. Conclusion: In conclusion, these results confirmed that biosynthesized CWAuNPs is a potent anticancer agent which induces apoptosis in the A498 renal carcinoma cell line.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Curcuma/química , Ouro/farmacologia , Neoplasias Renais/tratamento farmacológico , Nanopartículas Metálicas/química , Extratos Vegetais/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Nanopartículas Metálicas/ultraestrutura , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
16.
Urologe A ; 58(7): 768-773, 2019 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-31175376

RESUMO

The introduction of molecular targeted agents has fundamentally changed the treatment of metastatic renal cell carcinoma. A first wave of development was based on the improved understanding of tumor biology since the discovery of the importance of the von Hippel-Lindau gene as the key driver of the disease and paved the way for antiangiogenic agents. Of relevance is the overexpression of proangiogenic and proliferation-promoting factors (VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor) as well as an overactivation of the PI3K-Akt signaling pathway: the target structure is the "mammalian target of rapamycin" (mTOR) molecule, which is involved in the regulation of cell proliferative processes. VEGF-, PDGF-, and mTOR-signals and signaling pathways are central targets of current targeted substances. A second wave is certainly to be seen in the development of therapeutic approaches with the targeted activation and modulation of the immune system, which has brought "immunotherapy" back into the focus of interest. Central development is the application of immune-checkpoint inhibitors, with the help of which (re-)activation of the cellular defense, especially of T cells, takes place, which per se holds the potential of a cytoreductive therapy by killing the tumor cells. Even though the prognosis has improved significantly due to the rapid development of recent years, treatment remains challenging as most patients experience progress, and long-term survival is only achieved in about 20% of cases because some patients are primarily refractory or do not respond. The more intensive interlocking of molecular biology, pathology, clinical research, and interdisciplinary uro-oncology, as is the claim of molecular tumor boards, can contribute to the individual selection of a suitable therapy strategy and, thus, establish the latest findings and developments for the benefit of patients in the clinic.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Terapia de Alvo Molecular , Neoplasias/genética , Fator A de Crescimento do Endotélio Vascular , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fosfatidilinositol 3-Quinases , Fator de Crescimento Derivado de Plaquetas/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais , Serina-Treonina Quinases TOR , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Oncology ; 97(3): 164-172, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31195398

RESUMO

BACKGROUND: MicroRNAs are a class of small noncoding RNAs that play an important role in progression and drug resistance in cancer. Several reports have shown that miR-130b modulates cell growth and drug resistance in some cancers. However, the expression and biological role of miR-130b in renal cell carcinoma (RCC) remain poorly understood. This study aimed to examine the expression and functional role of miR-130b and to analyze the association between miR-130b and sunitinib resistance in RCC. METHODS: The expression of miR-130b in 32 RCC tissues and their corresponding normal kidney tissues was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We performed a 4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay in RCC cell lines transfected with miR-130b inhibitor or miR-130b mimics. We evaluated the relationship between miR-130b and PTEN and also analyzed the effect of miR-130b on sunitinib resistance. RESULTS: qRT-PCR analysis showed that the expression of miR-130b was higher in RCC tissues than in corresponding normal kidney tissues. The MTT assay revealed that miR-130b modulated cell growth. qRT-PCR revealed an inverse correlation between miR-130b and PTEN in RCC. Western blotting demonstrated that miR-130b regulated the expression of PTEN in the RCC cell line. Additionally, miR-130b was associated with sunitinib resistance through regulation of PTEN. We established the sunitinib-resistant Caki-1 (Caki-1-SR) cells and observed that the expression of miR-130b was elevated in Caki-1-SR cells compared with parental Caki-1 cells. Knockdown of miR-130b improved sunitinib resistance in Caki-1-SR cells. CONCLUSION: The expression of miR-130b was upregulated in RCC. miR-130b promoted cell growth and was associated with sunitinib resistance through regulating PTEN expression. Collectively, these results suggest that miR-130b may play an oncogenic role and be a promising therapeutic target.


Assuntos
Carcinoma de Células Renais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Sunitinibe/farmacologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Feminino , Técnicas de Inativação de Genes , Humanos , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , PTEN Fosfo-Hidrolase/metabolismo
18.
BMC Cancer ; 19(1): 581, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200666

RESUMO

IMPLICATION: By understanding Matrix Metalloprotease (MMP) dysregulation from a pan-cancer perspective, this study sheds light on the diagnostic potentials of MMPs across multiple neoplasms. BACKGROUND: MMPs are intriguing genes related to cancer disease progression, functional promotion of angiogenesis, invasion, metastasis, and avoidance of immune surveillance. Many studies have noted these genes are frequently upregulated in cancer. However, expression patterns of all MMPs and their diagnostic and prognostic potential have not been investigated in a pan-cancer perspective. METHODS: The Cancer Genome Atlas (TCGA) data were used to evaluate diagnostic and prognostic potential of 24 MMPs in fifteen different cancer types. Gene expression measured by RNA-seq was analyzed by differential expression, hierarchical clustering, and ROC analysis for individual genes and in combination. RESULTS: MMP1, MMP9, MMP10, MMP11, and MMP13 were almost universally upregulated across all cancers, with significant (p < 0.05) fold change (FC > 2) in ten of fifteen cancers. MMP3, MMP7, MMP12 and MMP14) are significantly up-regulated in at least 10 cancer types. Interestingly, MMP2, MMP7, MMP23B, MMP27 and MMP28) are significantly down-regulated in seven to nine cancer types. Multiple MMPs possess AUC's > 0.9 in more than one cancer. However, survival analyses suggest that the prognostic value of MMPs is limited to clear cell renal carcinoma. CONCLUSIONS: Most MMPs have consistently increased gene expression across cancers, while several MMPs have consistently decreased expression in several cancer types. Many MMPs have diagnostic value individually or in combination, while the prognostic value of MMPs is restricted to one subtype of kidney cancer.


Assuntos
Metaloproteinases da Matriz/metabolismo , Neoplasias/enzimologia , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Metaloproteinase 11 da Matriz/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Análise em Microsséries , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/mortalidade , Prognóstico , RNA Mensageiro/genética , Transcriptoma , Regulação para Cima
19.
BMC Bioinformatics ; 20(Suppl 11): 282, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31167637

RESUMO

BACKGROUND: Intra-tumor heterogeneity is known to contribute to cancer complexity and drug resistance. Understanding the number of distinct subclones and the evolutionary relationships between them is scientifically and clinically very important and still a challenging problem. RESULTS: In this paper, we present BAMSE (BAyesian Model Selection for tumor Evolution), a new probabilistic method for inferring subclonal history and lineage tree reconstruction of heterogeneous tumor samples. BAMSE uses somatic mutation read counts as input and can leverage multiple tumor samples accurately and efficiently. In the first step, possible clusterings of mutations into subclones are scored and a user defined number are selected for further analysis. In the next step, for each of these candidates, a list of trees describing the evolutionary relationships between the subclones is generated. These trees are sorted by their posterior probability. The posterior probability is calculated using a Bayesian model that integrates prior belief about the number of subclones, the composition of the tumor and the process of subclonal evolution. BAMSE also takes the sequencing error into account. We benchmarked BAMSE against state of the art software using simulated datasets. CONCLUSIONS: In this work we developed a flexible and fast software to reconstruct the history of a tumor's subclonal evolution using somatic mutation read counts across multiple samples. BAMSE software is implemented in Python and is available open source under GNU GLPv3 at https://github.com/HoseinT/BAMSE .


Assuntos
Biologia Computacional/métodos , Neoplasias/classificação , Filogenia , Algoritmos , Teorema de Bayes , Carcinoma de Células Renais/genética , Simulação por Computador , Humanos , Neoplasias Renais/genética , Modelos Biológicos , Mutação/genética , Neoplasias/genética , Software
20.
Anticancer Res ; 39(6): 2757-2765, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177111

RESUMO

BACKGROUND/AIM: Clear cell renal cell carcinoma (ccRCC) shows variable chromosomal abnormalities. The aim of this study was to assess the prognostic role of ccRCC chromosomal abnormalities in a single-center cohort with an extended follow-up. MATERIALS AND METHODS: A systematic cytogenetic analysis was performed in 283 consecutive surgically-treated patients for renal masses between 1997 and 2002. Kaplan-Meier and multivariable Cox regression (MCR) models were used to calculate cancer specific survival (CSS). RESULTS: Among 174 ccRCC patients, the most common abnormality was deletion in chromosome 3 (54.6%). At a median follow-up of 119 months, 38 patients (21.8%) died from RCC. At MCR models, worse CSS was independently predicted by deletions in chromosomes 2, 19, 20 or 22 and insertions in chromosome 18. CONCLUSION: Specific ccRCC chromosomal abnormalities are independently associated with worse CSS. Cytogenetic evaluation may direct further genetic analysis for personalized prognostic stratification.


Assuntos
Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/cirurgia , Aberrações Cromossômicas , Cromossomos Humanos/genética , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Idoso , Carcinoma de Células Renais/genética , Deleção Cromossômica , Citogenética , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/genética , Masculino , Pessoa de Meia-Idade , Mutagênese Insercional , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA