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1.
J Cancer Res Clin Oncol ; 146(1): 261-272, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31677114

RESUMO

PURPOSE: Partial nephrectomy has been persuaded as a widely accepted surgical procedure for T1a (≤ 4 cm) renal tumors. However, when treating T1b (4-7 cm) renal cell carcinoma (RCC), the "optimal" method of surgery is still debatable. The aim of the research is to evaluate the long-term oncological and renal functional outcomes of laparoscopic radical nephrectomy (LRN) versus laparoscopic partial nephrectomy (LPN) for patients with T1b RCC. MATERIALS AND METHODS: From March 1, 2003 to July 1, 2016, 331 patients were included in the current study. Patients presented with unilateral T1b RCC and underwent either LPN (n = 177) or LRN (n = 154). Relevant clinical data including follow-ups were acquired from patients. RESULTS: The operation time of the LPN group patients was longer than that of LRN group (94.3 min vs 88.3 min, p = 0.021) and LPN group patients required shorter stays in hospital (11.5 days vs. 13.4 days, p = 0.009). Contrast to LRN, level of eGFR was superior in LPN at the postoperative time of 1 day, 3 months, 6 months, 12 months and 24 months (all p < 0.001). Kaplan-Meier plots and log-rank tests showed that patients undergoing LPN had a much higher overall survival (OS) (p = 0.007), cancer-specific survival (CSS) (p = 0.006) and metastasis-free survival (MFS) (p = 0.008) than those receiving LRN. In comparison with the LRN group, multivariable Cox analysis indicated that patients of the LPN group had a 1.9-fold OS, 2.9-fold CSS and 2.3-fold MFS. CONCLUSIONS: For patients with T1b RCC, our findings revealed that OS, CSS and MFS are superior in patients receiving LPN than those treated with LRN. With the benefit of preserving renal function of LPN, which leads a less incidence risk of other systematic diseases, LPN may be the preferred option when condition permits for cases involving T1b RCC.


Assuntos
Carcinoma de Células Renais/fisiopatologia , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/fisiopatologia , Neoplasias Renais/cirurgia , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Neoplasias Renais/mortalidade , Laparoscopia/métodos , Laparoscopia/mortalidade , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Nefrectomia/mortalidade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Resultado do Tratamento
2.
Genes Dev ; 33(23-24): 1641-1656, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31727773

RESUMO

Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein homologous to angiopoietins. Previous studies suggest that tumor cell-derived ANGPTL2 has tumor-promoting function. Here, we conducted mechanistic analysis comparing ANGPTL2 function in cancer progression in a murine syngeneic model of melanoma and a mouse model of translocation renal cell carcinoma (tRCC). ANGPTL2 deficiency in tumor cells slowed tRCC progression, supporting a tumor-promoting role. However, systemic ablation of ANGPTL2 accelerated tRCC progression, supporting a tumor-suppressing role. The syngeneic model also demonstrated a tumor-suppressing role of ANGPTL2 in host tumor microenvironmental cells. Furthermore, the syngeneic model showed that PDGFRα+ fibroblasts in the tumor microenvironment express abundant ANGPTL2 and contribute to tumor suppression. Moreover, host ANGPTL2 facilitates CD8+ T-cell cross-priming and enhances anti-tumor immune responses. Importantly, ANGPTL2 activates dendritic cells through PIR-B-NOTCH signaling and enhances tumor vaccine efficacy. Our study provides strong evidence that ANGPTL2 can function in either tumor promotion or suppression, depending on what cell type it is expressed in.


Assuntos
Proteínas Semelhantes a Angiopoietina/genética , Proteínas Semelhantes a Angiopoietina/metabolismo , Linfócitos T CD8-Positivos/imunologia , Carcinoma de Células Renais/fisiopatologia , Progressão da Doença , Melanoma/fisiopatologia , Transdução de Sinais , Proteínas Semelhantes a Angiopoietina/deficiência , Proteínas Semelhantes a Angiopoietina/imunologia , Animais , Vacinas Anticâncer/imunologia , Carcinoma de Células Renais/imunologia , Células Dendríticas/imunologia , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Melanoma/imunologia , Camundongos , Transdução de Sinais/genética , Células Estromais/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
3.
Med Oncol ; 36(10): 88, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31520152

RESUMO

We prospectively validate the efficacy of the frailty discriminant score (FDS) in individuals with urological cancers, as there has been growing importance in evaluating frailty in clinical practice. A prospective, multicenter study was conducted from February 2017 to April 2019. We enrolled 258 patients with urological cancers and 301 community-dwelling participants who were assessed for frailty. Frailty was assessed using FDS that includes ten items, such as physical, mental, and blood biochemical tests. The primary outcome was the non-inferiority (margin 5%) of FDS in discriminating patients with urological cancers from controls (Ctrl). The sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve for each predictive test were calculated. The secondary endpoints included the prediction of overall survival between patients with urological cancer who have high and low FDS. FDS was significantly higher in patients with urological cancers than that in the Ctrl. The AUROC curves for individuals with non-prostate cancers (such as bladder cancer, upper tract urothelial carcinoma, and renal cell carcinoma; 0.942) and those with prostate cancer (0.943) were within the non-inferior margin. The overall survival values were significantly lower in patients with higher FDS score than in those with lower FDS score. The study met its primary and secondary endpoints. The FDS is a reliable and valid tool for assessing frailty and prognosis in patients with urological cancers.


Assuntos
Fragilidade/fisiopatologia , Neoplasias Urológicas/patologia , Neoplasias Urológicas/fisiopatologia , Idoso , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/fisiopatologia , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/fisiopatologia , Estudos de Avaliação como Assunto , Feminino , Idoso Fragilizado , Avaliação Geriátrica/métodos , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/fisiopatologia , Masculino , Prognóstico , Estudos Prospectivos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/fisiopatologia , Curva ROC , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/fisiopatologia
4.
Int J Mol Sci ; 20(19)2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547602

RESUMO

This paper reviews current treatments for renal cell carcinoma/cancer (RCC) with the multikinase inhibitors (MKIs) sorafenib, sunitinib, lenvatinib and axitinib. Furthermore, it compares these drugs regarding progression-free survival, overall survival and adverse effects (AE), with a focus on hypertension. Sorafenib and sunitinib, which are included in international clinical guidelines as first- and second-line therapy in metastatic RCC, are now being challenged by new-generation drugs like lenvatinib and axitinib. These drugs have shown significant clinical benefits for patients with RCC, but all four induce a variety of AEs. Hypertension is one of the most common AEs related to MKI treatment. Comparing sorafenib, sunitinib and lenvatinib revealed that sorafenib and sunitinib had the same efficacy, but sorafenib was safer to use. Lenvatinib showed better efficacy than sorafenib but worse safety. No trials have yet been completed that compare lenvatinib with sunitinib. Although axitinib promotes slightly higher hypertension rates compared to sunitinib, the overall discontinuation rate and cardiovascular complications are favourable. Although the mean rate of patients who develop hypertension is similar for each drug, some trials have shown large differences, which could indicate that lifestyle and/or genetic factors play an additional role.


Assuntos
Axitinibe , Carcinoma de Células Renais , Hipertensão , Neoplasias Renais , Compostos de Fenilureia , Quinolinas , Sorafenibe , Sunitinibe , Axitinibe/efeitos adversos , Axitinibe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/fisiopatologia , Humanos , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/fisiopatologia , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Quinolinas/efeitos adversos , Quinolinas/uso terapêutico , Sorafenibe/efeitos adversos , Sorafenibe/uso terapêutico , Sunitinibe/efeitos adversos , Sunitinibe/uso terapêutico
5.
BMC Cancer ; 19(1): 874, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481081

RESUMO

BACKGROUND: The ubiquitous expressed transcript (UXT) plays a key role in various tumors by regulating transcriptional activity of multiple transcription factors, including androgen receptor (AR). However, the role of UXT in clear cell renal cell carcinoma (ccRCC) is still unknown. METHODS: Yeast two-hybrid screening, GST pull-down and co-immunoprecipitation assays were performed to detect the interacting protein of UXT. Chromatin immunoprecipitation (ChIP) was performed to investigate the levels of histone H3 lysine 27 trimethylation at the HOXA9 promoters. CCK-8 assays, colony formation assays and Transwell assays were performed to detect the proliferation, colony formation, migration and invasion of renal cancer cells. Quantitative PCR analysis was performed to detect the expressions of UXT in human ccRCC samples. RESULTS: The enhancer of zeste homolog 2 (EZH2) is a novel UXT interacting protein and UXT interacts with EZH2 in the nucleus. In addition, UXT interacts with the polycomb repressive complex 2 (PRC2) through directly binding to EZH2 and suppressor of zeste 12 homolog (SUZ12), but not to embryonic ectoderm development (EED). Moreover, the UXT activates EZH2 histone methyltransferase activity by facilitating EZH2 binding with SUZ12. We further provided striking evidences that knockdown of UXT inhibits proliferation, colony formation, migration and invasion of renal cancer cells, in an EZH2-dependent manner. Importantly, the upregulation of UXT expression was observed in clinical ccRCC samples, and the high expression level of UXT was associated with advanced stage, distant metastasis and poor overall survival in patients with ccRCC. CONCLUSION: The UXT is a novel regulator of the PRC2 and acts as a renal cancer oncogene that affects the progression and survival of ccRCC patients.


Assuntos
Carcinoma de Células Renais/genética , Proteínas de Ciclo Celular/metabolismo , Transformação Celular Neoplásica/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Renais/genética , Chaperonas Moleculares/metabolismo , Idoso , Carcinoma de Células Renais/fisiopatologia , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular , Núcleo Celular/metabolismo , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Feminino , Técnicas de Silenciamento de Genes , Células HEK293 , Histonas/metabolismo , Proteínas de Homeodomínio/genética , Humanos , Neoplasias Renais/fisiopatologia , Masculino , Metilação , Pessoa de Meia-Idade , Chaperonas Moleculares/genética , Mutação , Complexo Repressor Polycomb 2/metabolismo , Prognóstico , Ligação Proteica , Análise de Sobrevida
6.
Mol Med Rep ; 20(2): 1212-1220, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173226

RESUMO

Renal cell carcinoma (RCC) is a common malignant tumor globally. The overall survival of patients with RCC is poor; one important factor is tumor heterogeneity. Ubiquitin­conjugating enzyme E2T (UBE2T) has been reported to act as an oncogene in various types of cancer; however, its role in RCC has yet to be investigated. In the present study, UBE2T was demonstrated via reverse transcription­quantitative PCR analysis to be significantly upregulated in RCC samples and cell lines compared with in normal tissue and cells. Additionally, UBE2T expression was significantly associated with late tumor stage and high grade in patients with RCC, and patients with high UBE2T expression exhibited poor prognosis compared with patients with low expression. Following knockdown of UBE2T in 786­O cells using RNA interference technology, the proliferation and colony formation of cells were inhibited as determined by an MTT assay and crystal violet staining, respectively; however, the migration and invasion of 786­O cells were not affected, as determined by wound­healing assay and Transwell assays, respectively. Xenograft RCC tumor growth in vivo was also significantly suppressed. The expression levels of two mesenchymal cell markers, N­cadherin and vimentin, were reduced following UBE2T knockdown, whereas E­cadherin and fibronectin levels were increased as determined by western blotting, indicating that epithelial­mesenchymal transition was suppressed. In addition, the phosphorylation levels of PI3K, Akt and mTOR were notably decreased following UBE2T knockdown, but were increased when UBE2T was overexpressed. Wortmannin, an Akt inhibitor, reversed the UBE2T overexpression­induced increase in the phosphorylation of PI3K, Akt and mTOR. Similarly, the UBE2T overexpression­induced promotion of 786­O cell proliferation was also attenuated by wortmannin. In conclusion, UBE2T promoted the proliferation of RCC cells by regulating PI3K/Akt signaling, suggesting it may be a novel target for the treatment of patients with RCC.


Assuntos
Carcinoma de Células Renais/metabolismo , Proliferação de Células , Neoplasias Renais/metabolismo , Transdução de Sinais , Enzimas de Conjugação de Ubiquitina/metabolismo , Adolescente , Adulto , Animais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/fisiopatologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
7.
Medicina (Kaunas) ; 55(6)2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216752

RESUMO

Background and objective: We investigated the ability of preoperative serum values of red blood cell distribution width (RDW), neutrophil lymphocyte ratio (NLR) and plateletcrit (PCT) to predict Fuhrman grades (FG) and tumor stages of renal cell carcinoma in patients who underwent radical nephrectomy. Materials and methods: Records of 283 patients that underwent radical or partial nephrectomy of renal masses at our clinic between January 2010 and April 2018, whose pathology results indicated renal cell carcinoma (RCC), and who had their FG and T1-4 N0M0 identified were retrospectively evaluated. The patients were divided into two groups based on their FG as low (I-II) and high (III-IV) and their T stages were similarly grouped as limited to kidney (pT1-pT2) and not limited to kidney (pT3-pT4). Results: Mean RDW, NLR, PCT cut-off values of the patients for FG and T stage were 15.65%, 3.54, 0.28% and 14.35%, 2.69, 0.28%, respectively. The RDW and NLR were determined to be statistically significant predictors of a pathologically high FG, whereas the PCT value was not a statistically significant predictor of high FG (p = 0.003, p = 0.006, p = 0.075, respectively). The relationship of RDW, NLR and PCT values with a limited to the kidney pathological T stage revealed statistically significant correlations for all three values. Conclusions: We determined that only RDW and NLR were markers predicting FG, while PCT had no prognostic value. On the other hand, all three of these values were associated with a limited to the kidney pathological T stage in patients who underwent nephrectomy due to renal masses and whose pathologies suggested RCC.


Assuntos
Carcinoma de Células Renais/diagnóstico , Eritrócitos/patologia , Valor Preditivo dos Testes , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carcinoma de Células Renais/fisiopatologia , Feminino , Humanos , Contagem de Linfócitos/métodos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Neutrófilos/fisiologia , Prognóstico , Curva ROC , Estudos Retrospectivos
8.
Medicine (Baltimore) ; 98(17): e15346, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31027111

RESUMO

To assess whether left and right-sided renal cell carcinoma (RCC) carry side-specific outcomes.Surgically treated RCC patients were included from the United States Surveillance, Epidemiology and End Results database (Surveillance, Epidemiology and End Results database [SEER]; 2013 version) and the German Centre for Cancer Registry Data (ZfKD; 2000-2014). Bilateral RCC, those with missing RCC staging, follow-up time, and survival status were excluded. Cancer-specific survival (CSS) according to RCC side was compared using multivariable Cox regression.Seventeen thousand seven hundred nine SEER patients and 41,967 ZfKD patients were included. In both datasets, patients with left-sided RCC had higher T status and more often presented with nodal positive or metastatic disease. In the SEER dataset 1258 (14.33%) patients with left-sided RCC underwent lymphadenectomy (LAD), compared to 908 (10.17%) LADs in right-sided RCC (P <.001). CSS was inferior for left-sided in both datasets after multivariable adjustment (SEER HR = 1.187, 95% CI 1.048-1.345, P = .007, P = .008; ZfKD HR = 1.155, 95% CI 1.046-1.275, P = .004).In the SEER population, site-specific CSS differences were driven by whether or not a LAD was performed. Among SEER patients with LAD no statistically significant differences in laterality were observed (HR 1.096, 95% CI 0.8977-1.337, P = .396) whereas, in absence of LAD, CSS was shorter for individuals with left-sided tumor (HR = 1.176, 95%CI 1.002-1.38, P = .0468).Although the overall survival difference was only marginal, left-sided RCC in surgically treated patients tends to present at more advanced stage and has in general worse CSS, especially in patients without LAD. Site-specific lymphogenic spread patterns might contribute to these findings. Further prospective studies should evaluate, whether side-adapted LAD protocols influence outcomes in RCC patients.


Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/diagnóstico , Neoplasias Renais/mortalidade , Idoso , Carcinoma de Células Renais/fisiopatologia , Feminino , Seguimentos , Humanos , Neoplasias Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Programa de SEER , Análise de Sobrevida
9.
Actas urol. esp ; 43(3): 118-123, abr. 2019. graf
Artigo em Espanhol | IBECS | ID: ibc-181169

RESUMO

Contexto y objetivo: En los últimos años se han producido avances significativos en el conocimiento de la carcinogénesis renal. Hoy en día los tumores renales se clasifican en función de su perfil genético, y además se han desarrollado tratamientos específicos basados en la identificación de dianas terapéuticas. Sin embargo, todavía no se han identificado marcadores pronósticos. El objetivo de esta revisión es analizar la literatura que ha evaluado la expresión de la proteína STAT3 como marcador molecular en el carcinoma renal de célula clara (ccRCC). Adquisición de evidencia: En enero de 2018 se realizó una búsqueda sistemática de la literatura en Pubmed, Cochrane Library y Sciencedirect de las publicaciones realizadas desde 1990. Los términos de búsqueda fueron renal cell carcinoma and STAT3 or STAT-3 and prognostic factor. Se siguieron los principios de la declaración PRISMA y la estrategia de selección PICO, seleccionándose los artículos originales con series de pacientes diagnosticados de ccRCC localizado o metastásico, donde se analiza la actividad de STAT3 como marcador pronóstico. Se identificaron 132 publicaciones de las que finalmente se han revisado 10 por cumplir los criterios de inclusión. Síntesis de evidencia: La activación (fosforilación) de STAT3 (pSTAT3) en el residuo Ser727 es importante en el desarrollo y progresión de ccRCC. La expresión de pSTAT3 parece ser un marcador pronóstico y predictor de resistencia a algunos tratamientos en pacientes con enfermedad diseminada. Existe poca evidencia de su utilidad como un marcador pronóstico en pacientes con enfermedad localizada. Conclusiones: La expresión de pSTAT3(Ser727) en el núcleo de las células del ccRCC puede ser un marcador pronóstico y de respuesta al tratamiento en pacientes con ccRCC. La evidencia científica actual es limitada y son necesarios más estudios que demuestren su utilidad


Context and objective: There have been significant advances in the knowledge of renal carcinogenesis in the last years. Nowadays, renal tumours are classified according to their genetic profile and specific treatments based on the identification of therapeutic targets have also been developed. However, no prognostic markers have yet been identified. The aim of this review is to analyze literature that has evaluated the expression of the STAT3 protein as a molecular marker in clear cell renal carcinoma (ccRCC). Evidence acquisition: In January 2018 a systematic review was conducted in Pubmed, Cochrane library and Sciencedirect databases, from papers published from 1990. Search terms were "renal cell carcinoma" and "STAT3" or "STAT-3" and prognostic factor. Following the principles of the PRISMA declaration and the PICO selection strategy, original articles with series of patients diagnosed with localized or metastatic ccRCC, and where the activity of STAT3 is analyzed as a prognostic marker, were selected. A total of 132 publications were identified, of which 10 were finally revised, for they met the inclusion criteria. Evidence synthesis: STAT3 activation (phosphorylation) through Ser727 is important during ccRCC development and progression. PSTAT3 expression seems to be a prognostic marker and an antiangiogenic-resistance marker in metastatic patients. There is little evidence as prognostic marker in patients with localized disease. Conclusions: STAT3 (Ser 727) expression in the nucleus of the ccRCC cells can be a prognostic marker and an antiangiogenic-resistance marker. Current scientific evidence is limited and more studies are needed to demonstrate its usefulness


Assuntos
Neoplasias Renais/etiologia , Carcinoma de Células Renais/diagnóstico , Fator de Transcrição STAT3/metabolismo , Biomarcadores Tumorais , Carcinoma de Células Renais/fisiopatologia , Prognóstico , Carcinoma de Células Renais/etiologia , Fator de Transcrição STAT3/uso terapêutico
10.
J Surg Oncol ; 119(7): 1016-1023, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30820951

RESUMO

OBJECTIVES: To compare the functional outcomes of open, laparoscopic, and robot-assisted partial nephrectomy (OPN, LPN, and RAPN, respectively) using diethylene triamine penta-acetic acid (DTPA). METHODS: We identified 610 patients who underwent partial nephrectomy for renal cell carcinoma (285 open partial nephrectomy [OPN], 96 laparoscopic partial nephrectomy [LPN], and 229 robot-assisted partial nephrectomy [RAPN]) with preoperative and postoperative DTPA within 1 year. We excluded multiple renal masses and history of immunotherapy or chemotherapy. Predictive factors for glomerular filtration rate (GFR) reduction were assessed using multivariate linear regression. RESULTS: Postoperative complications and disease-free survival were similar in the three groups. Within 1 postoperative year, OPN showed a significantly lower mean ipsilateral GFR than LPN and RAPN (28.9 versus 32.4 versus 32.7 mL/min/1.73 m 2 , respectively; P < 0.001). RAPN was associated with a significantly higher total GFR than OPN within 1 year (76.6 versus 71.2 mL/min/1.73 m 2 , respectively; P = 0.001). On multivariate analysis within 1 year, operation type (OPN versus RAPN: ß = 2.82; 95% confidence interval, 1.17-4.48; P = 0.001) was significantly associated with GFR reduction. CONCLUSION: There was no difference in postoperative complications and disease-free survival among operation types. RAPN could help to promote earlier recovery of ipsilateral GFR than OPN.


Assuntos
Carcinoma de Células Renais/fisiopatologia , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/fisiopatologia , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Carcinoma de Células Renais/diagnóstico por imagem , Intervalo Livre de Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Neoplasias Renais/diagnóstico por imagem , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Ácido Pentético , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Adulto Jovem
11.
J Vasc Interv Radiol ; 30(3): 460-465, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30819494

RESUMO

PURPOSE: To evaluate the influence of percutaneous cryoablation for renal cell carcinoma on function of the affected kidney. MATERIALS AND METHODS: Between June 2016 and September 2017 at our institution, 12 inoperable patients underwent 15 cryoablation sessions for 17 small renal tumors. Of these, 9 patients who underwent 11 sessions of cryoablation were the focus of this study. For those patients, time-dependent changes in postoperative renal function were investigated by a retrospective review of clinical records. Evaluated were the estimated glomerular filtration rate (eGFR) and scintigraphy using 99m technetium-mercaptoacetyltriglycine (99mTc-MAG3) before and 1 week, 1-2 months, and more than 6 months after cryoablation. RESULTS: Mean baseline eGFR was 76.88 ± 29.82 mL/min/1.73 m2 (mean ± standard deviation; range, 23.4-112.5). Mean eGFR 1 week, 1-2 months, and more than 6 months after cryoablation were 74.56 ± 26.68 mL/min/1.73 m2 (21.0-101.1), 69.5 ± 25.28 mL/min/1.73 m2 (24.1-105.6), and 75.08 ± 26.25 mL/min/1.73 m2 (29.0-107.3), respectively. Changes were statistically insignificant (P = .6044, P = .6699, and P = .9038, respectively). Regarding split renal function, the mean baseline contribution of the affected kidney determined by 99mTc-MAG3 was 47.27% ± 6.14 (38.8%-57.0%). Mean contributions of the affected kidney 1 week after, 1-2 months after, and more than 6 months after cryoablation were 44.40% ± 5.37 (38.3%-53.6%), 44.57% ± 6.52 (34.35%-55.0%), and 45.41% ± 7.77 (34.4%-56.5%), respectively. Differences from baseline were significant for the earliest 2 periods (P = .0473 and P = .0334, respectively) but not the later period (P = .2532). CONCLUSIONS: Results suggested that total renal function does not worsen after cryoablation; however, function of the affected kidney worsened after cryoablation but later partially recovered.


Assuntos
Carcinoma de Células Renais/cirurgia , Criocirurgia , Taxa de Filtração Glomerular , Neoplasias Renais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/fisiopatologia , Criocirurgia/efeitos adversos , Feminino , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Neoplasias Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos/administração & dosagem , Recuperação de Função Fisiológica , Estudos Retrospectivos , Tecnécio Tc 99m Mertiatida/administração & dosagem , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral
12.
Cell Mol Biol Lett ; 24: 7, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30675171

RESUMO

Objective: The tumor susceptibility gene 101 (TSG101) is closely associated with various tumor types, but its role in the pathogenesis of renal cell carcinoma (RCC) is still unknown. This study used RNA interference to silence the expression of TSG101 in RCC cell lines and explore the role of TSG101 in RCC. Methods: Immunohistochemistry and western blot were performed to detect the expression of TSG101 in 15 paired renal tumor samples. A small interfering RNA (siRNA) targeting TSG101 was transfected into A498 and 786-O cell lines. The Cell Counting Kit-8 (CCK-8) assay and colony formation assay were used to observe the changes in cell proliferation after transfection. Flow cytometry was used to detect the effect on the cell cycle. Western blot was conducted to study the changes of related functional proteins. Results: The expression of TSG101 was higher in RCC tissues than in adjacent normal tissues. The CCK-8 assay showed that the proliferation and colony formation of the A498 and 786-O cell lines were attenuated after suppression of TSG101. Flow cytometry showed that silencing of TSG101 induced G0/G1 arrest. The western blot results revealed that the levels of cell cycle-related proteins (c-myc, cyclin E1 and cyclin-dependent kinase 2 (CDK2)) were markedly decreased in the siRNA groups. Conclusions: TSG101 promotes proliferation of RCC cells. This positive effect on tumor growth involves activation of c-myc and cyclin E1/CDK2 and their effect on cell cycle distribution.


Assuntos
Carcinoma de Células Renais/genética , Proliferação de Células , Proteínas de Ligação a DNA/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Pontos de Checagem da Fase G1 do Ciclo Celular , Neoplasias Renais/genética , Fatores de Transcrição/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/fisiopatologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/fisiopatologia
13.
J Agric Food Chem ; 67(6): 1691-1701, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30658530

RESUMO

In recent years, various studies have confirmed the role of natural products as effective cancer prevention and treatment drugs. The present study demonstrated that chitosan oligosaccharide (COS) from shells of shrimp and crab caused an inhibitory effect on the proliferation of human renal carcinoma in vitro and in vivo. First, the in vivo biodistribution of COS was investigated by the synthesis of cyanine-7-labeled COS (COS-Cy7) following tail vein injection. The kidney was found to be a major target organ. Then, the impacts on renal carcinoma cell proliferation, apoptosis, and reactive oxygen species (ROS) production were observed in vitro, and an orthotopic xenograft tumor model was designed to evaluate the antitumor efficacy of COS in vivo. In renal carcinoma cells, COS induced G2/M phase arrest and apoptosis in a ROS-dependent fashion. COS significantly promoted mRNA expression of nuclear factor erythroid 2-related factor (Nrf2) and Nrf2 target genes, such as heme oxygenase 1, modifier subunit of glutamate cysteine ligase, and solute carrier family 7 member 11. Additionally, COS significantly upregulated the protein expression of glucose-regulated protein 78, protein RNA-like endoplasmic reticulum (ER) kinase, eukaryotic initiation factor 2α, activating transcription factor 4, C/EBP homologous protein, and cytochrome c, which justified the activation of the ER stress signaling pathway. In vivo, COS repressed tumor growth and induced apoptosis and ROS accumulation, consistent with the in vitro results. Taken together, COS repressed human renal carcinoma growth and induced apoptosis both in vitro and in vivo, mainly via ROS-dependent ER stress pathways.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Quitosana/administração & dosagem , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Neoplasias Renais/tratamento farmacológico , Oligossacarídeos/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose/efeitos dos fármacos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/fisiopatologia , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/fisiopatologia , Camundongos Nus , Fator 2 Relacionado a NF-E2 , Fator de Transcrição CHOP
14.
J Robot Surg ; 13(3): 401-405, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30171484

RESUMO

Mannitol is routinely used during partial nephrectomies due to its renoprotective properties. With minimally invasive techniques, the need for mannitol has been questioned. Robotic-assisted laparoscopic partial nephrectomy (RALPN) has been shown to decrease warm ischemia time, which may potentially minimize the benefit of mannitol. To date, no prospective, randomized, controlled trials have investigated the use of mannitol in only robotic procedures. We hypothesize that the intraoperative mannitol use during RALPN provides no statistically significant benefit for post-operative renal function outcomes. We conducted a randomized, controlled, double-blinded, single surgeon, prospective study to assess renal function after RALPN. Patients were randomized into a control group with intravenous normal saline infusion prior to clamping of the vessels or to an experimental group with an infusion of mannitol. Estimated glomerular filtration rate (eGFR) were obtained prior to the surgery as well as post operatively at 24 h, 1 week, and 30 days. Preoperative eGFR showed no statistical differences between the groups and evaluation of median percent change in eGFR after surgery did not indicate a statistical difference between the groups after RALPN. After prospective analysis of the change in post-operative renal function of randomized groups who received 12 g of mannitol following RALPN, we determined that infusion of mannitol does not provide significant improvement of maintenance of renal functions after RALPN. Based on our results, we recommend discontinuing routine use of mannitol during RALPN.


Assuntos
Carcinoma de Células Renais/fisiopatologia , Carcinoma de Células Renais/cirurgia , Taxa de Filtração Glomerular , Cuidados Intraoperatórios , Neoplasias Renais/fisiopatologia , Neoplasias Renais/cirurgia , Laparoscopia/métodos , Manitol/administração & dosagem , Nefrectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Período Pós-Operatório , Estudos Prospectivos , Resultado do Tratamento
15.
Urol J ; 16(1): 44-49, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30120758

RESUMO

PURPOSE: It remains unclear whether laparoscopic radiofrequency ablation (RFA) for primary treatment of small renal masses is similar to partial nephrectomy (PN) in terms of long-term oncological and renal function outcomes. We reviewed the long-term outcomes for patients with T1a renal masses treated with either laparoscopic RFA orPN. MATERIALS AND METHODS: This retrospective single-center study on 115 patients who were treated by laparoscopic RFA or PN for small (<4 cm) renal masses between January 2005 and October 2014 at Chungnam National University Hospital. Estimated glomerular filtration rate (eGFR) was measured before and 1-2 weeks after surgery and at last follow-up. The laparoscopic RFA and PN groups were compared in terms of clinical characteristics data and change in eGFR after surgery using the Chi-squared test or Student's t-test. Survival data were analyzed using theKaplan-Meier method and the log-rank test. RESULTS: Of the 115 patients, 62 and 53 underwent laparoscopic RFA and PN, respectively. Their mean (range) follow-up duration was 60 (30-104) and 68 (30-149) months, respectively (P = 0.092). The RFA patients were older (P = 0.023) and had smaller tumors (P = 0.000). RFA associated with shorter operation and hospitalization times and less perioperative blood loss (all P<0.001). The groups did not differ in terms of change in eGFR 1-2 weeks after surgery (P = 0.252) or at the last follow-up (P = 0.395) or 5 year survival rates (P = 0.360). CONCLUSION: Laparoscopic RFA for small renal masses was comparable to PN in terms of oncological and functional outcomes and associated with shorter operative and hospitalization times and less perioperative bleeding.


Assuntos
Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Nefrectomia , Ablação por Radiofrequência , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Carcinoma de Células Renais/fisiopatologia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Neoplasias Renais/fisiopatologia , Laparoscopia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Duração da Cirurgia , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
16.
BMC Cancer ; 18(1): 1030, 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30352550

RESUMO

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a non-invasive alternative to surgery to control primary renal cell cancer (RCC) in patients that are medically inoperable or at high-risk of post-surgical dialysis. The objective of the FASTRACK II clinical trial is to investigate the efficacy of SABR for primary RCC. METHODS: FASTRACK II is a single arm, multi-institutional phase II study. Seventy patients will be recruited over 3 years and followed for a total of 5 years. Eligible patients must have a biopsy confirmed diagnosis of primary RCC with a single lesion within a kidney, have ECOG performance ≤2 and be medically inoperable, high risk or decline surgery. Radiotherapy treatment planning is undertaken using four dimensional CT scanning to incorporate the impact of respiratory motion. Treatment must be delivered using a conformal or intensity modulated technique including IMRT, VMAT, Cyberknife or Tomotherapy. The trial includes two alternate fractionation schedules based on tumour size: for tumours ≤4 cm in maximum diameter a single fraction of 26Gy is delivered; and for tumours > 4 cm in maximum diameter 42Gy in three fractions is delivered. The primary outcome of the study is to estimate the efficacy of SABR for primary RCC. Secondary objectives include estimating tolerability, characterising overall survival and cancer specific survival, estimating the distant failure rate, describing toxicity and renal function changes after SABR, and assessment of cost-effectiveness of SABR compared with current therapies. DISCUSSION: The present study design allows for multicentre prospective validation of the efficacy of SABR for primary RCC that has been observed from prior single institutional and retrospective series. The study also allows assessment of treatment related toxicity, overall survival, cancer specific survival, freedom from distant failure and renal function post therapy. TRIAL REGISTRATION: Clinicaltrials.gov NCT02613819 , registered Nov 25th 2015.


Assuntos
Carcinoma de Células Renais/radioterapia , Neoplasias Renais/radioterapia , Radiocirurgia/efeitos adversos , Adulto , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/fisiopatologia , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/fisiopatologia , Estudos Multicêntricos como Assunto , Resultado do Tratamento
17.
Curr Med Sci ; 38(5): 834-839, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30341517

RESUMO

This study was designed to explore the safety and feasibility of robotic-assisted laparoscopic nephrectomy with vein thrombectomy (RAL-NVT) for the treatment of renal cell carcinoma (RCC) with venous tumor thrombus (VTT). Clinical data of 6 patients treated with RAL-NVT between July 2016 and November 2017 in our hospital were retrospectively collected and analyzed. There were 5 males and 1 female with their age ranging from 48 years to 68 years. Five renal tumors were right-sided and one left-sided. Three cases fell in level 0 VTT, one in level I and two in level II. Preoperative imaging revealed lymph node involvement in 1 case and distant metastasis in 2 cases. For RCC with level 0 VTT, the renal vein of the affected side was adequately and carefully dissected around the thrombus to the proximity of inferior vena cava (IVC) and was ligated with Hem-o-loks without cross-clamping the IVC. For level I and II VTT, the IVC was crossclamped cephalically and caudally around the tumor thrombus and all tributaries were sequentially blocked to ensure the safe retrieval of VTT. All operations were successfully completed without conversion to open operation. The mean operative time was 150 (115-230) min. Cross-clamping of the IVC happened in 3 cases, and the blocking time was 14, 19 and 20 min, respectively. The mean estimated blood loss during the operation was 400 (200-580) mL. The peritoneal drainage tube was removed 5 to 9 days after the operation, and all patients were postoperatively discharged at 6 to 11 days. Postoperative pathological analysis confirmed that the RCCs were comprised of 4 clear cell RCCs, 1 papillary cell RCC, and 1 medullary cell RCC; 2 cases were Fuhrman grade II, 3 cases grade III, and 1 case undefined grade. No recurrence or progression was observed during the follow-up of 4.2 (3-6) months. We concluded that RAL-NVT is highly challenging but safe and feasible for the treatment of RCC with VTT.


Assuntos
Carcinoma de Células Renais/cirurgia , Nefrectomia/métodos , Procedimentos Cirúrgicos Robóticos , Trombectomia/métodos , Trombose Venosa/cirurgia , Adulto , Idoso , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/fisiopatologia , Feminino , Humanos , Rim/fisiopatologia , Rim/cirurgia , Laparoscopia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Veias Renais/fisiopatologia , Veias Renais/cirurgia , Veia Cava Inferior/fisiopatologia , Veia Cava Inferior/cirurgia , Trombose Venosa/complicações , Trombose Venosa/fisiopatologia
18.
J Cell Biochem ; 119(12): 9974-9985, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30171729

RESUMO

Although emerging evidence has revealed that microRNAs (miRNAs) dysregulation contribute to carcinogenesis, the mechanism underlying their roles in renal cell carcinoma (RCC) is unclear. The purpose of the current study was to analyze the association of miR-200a-3p expression with RCC and to understand potential novel target genes, functions and mechanisms of miR-200a-3p in RCC. MiR-200a-3p expression levels were first measured by quantitative real-time polymerase chain reaction and in situ hybridization in pairs of RCC tissue samples. Next, the potential miR-200a-3p target gene was analyzed using a combination of computer-aided algorithms, luciferase reporter assays and Western blot analysis. Finally, the biological roles of miR-200a-3p in RCC tumorigenesis were investigated both in vitro by 5-ethynyl-20-deoxyuridine, apoptosis assay and transwell assay, as well as in vivo using a xenograft mouse model. Our results demonstrated that miR-200a-3p was remarkably downregulated in RCC tissues compared with normal adjacent tissue, and CBL is a direct target of miR-200a-3p. An inverse correlation between miR-200a-3p and CBL was observed in RCC tissue samples. Mechanistic investigations revealed that ectopic expression of miR-200a-3p in RCC cell lines suppressed cell proliferation and migration and enforced cell apoptosis by directly inhibiting CBL in vitro and in vivo, whereas silencing miR-200a-3p resulted in the opposite effects. Additionally, overexpressing CBL abolished the effects induced by miR-200a-3p overexpression. Taken together, our results show that the miR-200a-3p/CBL regulation axis is a novel mechanism underlying RCC pathogenesis and may serve as a candidate biomarker and therapeutic target in RCC.


Assuntos
Carcinoma de Células Renais/genética , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , MicroRNAs/genética , Animais , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/fisiopatologia , Linhagem Celular Tumoral , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/fisiopatologia , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-cbl/genética , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Cell Physiol Biochem ; 49(5): 1755-1765, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30231239

RESUMO

BACKGROUND/AIMS: Increasing evidence has shown that miR-216b plays an important role in human cancer progression. However, little is known about the function of miR-216b in renal cell carcinoma. METHODS: The expression levels of miR-216b in renal cell carcinoma tissues and cell lines were examined by qRT-PCR. The biological role of miR-216b in renal cell carcinoma proliferation and/or metastasis was examined in vitro and in vivo. The target of miR-216b was identified by a dual-luciferase reporter assay. The expression level of KRAS protein was measured by western blotting. RESULTS: The expression of miR-216b was downregulated in clear cell renal cell carcinoma (ccRCC) cell lines and specimens compared to the adjacent normal tissues. Furthermore, miR-216b can bind to the 3'untranslated region (UTR) of KRAS and inhibit the expression of KRAS through translational repression. The in vitro study revealed that miR-216b attenuated ccRCC cell proliferation and invasion. Furthermore, in vivo study also showed that miR-216b suppressed tumor growth. MiR-216b exerted its tumor suppressor function through inhibiting the KRAS-related MAPK/ERK and PI3K/AKT pathways. CONCLUSION: Our findings provide, for the first time, significant clues regarding the role of miR-216b as a tumor suppressor by targeting KRAS in ccRCC.


Assuntos
Carcinoma de Células Renais/fisiopatologia , Regulação para Baixo , Neoplasias Renais/fisiopatologia , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/uso terapêutico , Transdução de Sinais
20.
Rev Sci Instrum ; 89(7): 075107, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30068108

RESUMO

Noninvasive in vivo imaging technologies enable researchers and clinicians to detect the presence of disease and longitudinally study its progression. By revealing anatomical, functional, or molecular changes, imaging tools can provide a near real-time assessment of important biological events. At the preclinical research level, imaging plays an important role by allowing disease mechanisms and potential therapies to be evaluated noninvasively. Because functional and molecular changes often precede gross anatomical changes, there has been a significant amount of research exploring the ability of different imaging modalities to track these aspects of various diseases. Herein, we present a novel robotic preclinical contrast-enhanced ultrasound system and demonstrate its use in evaluating tumors in a rodent model. By leveraging recent advances in ultrasound, this system favorably compares with other modalities, as it can perform anatomical, functional, and molecular imaging and is cost-effective, portable, and high throughput, without using ionizing radiation. Furthermore, this system circumvents many of the limitations of conventional preclinical ultrasound systems, including a limited field-of-view, low throughput, and large user variability.


Assuntos
Imagem Tridimensional/instrumentação , Roedores , Ultrassonografia/instrumentação , Animais , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/fisiopatologia , Linhagem Celular Tumoral , Meios de Contraste , Progressão da Doença , Desenho de Equipamento , Feminino , Hemangiossarcoma/diagnóstico por imagem , Hemangiossarcoma/fisiopatologia , Humanos , Estudos Longitudinais , Microbolhas , Transplante de Neoplasias , Variações Dependentes do Observador , Projetos Piloto , Reprodutibilidade dos Testes , Robótica , Software
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