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1.
Oxid Med Cell Longev ; 2022: 7560569, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046690

RESUMO

Clear cell renal cell carcinoma (ccRCC), the major histopathological subtype of renal cancer, is sensitive to ferroptosis. MIT-domain containing protein 1 (MITD1) has been reported to play an important role in hepatocellular carcinoma, while it remains unclear whether MITD1 is involved in ccRCC. Based on available data in The Cancer Genome Atlas, we found the expression of MITD1 increased through bioinformatics analysis and high MITD1 expression suggests a poor prognosis. And we validated that MITD1 expressed significantly in ccRCC through Western blot analysis. Then, we further compared the proliferation and migration capacity of ccRCC before and after MITD1 knockdown and further explored the effect of MITD1 knockdown on ferroptosis. The results indicated that MITD1 knockdown inhibited ccRCC cell proliferation and migration and induced ferroptosis in ccRCC. Furthermore, we found and analyzed the key molecule TAZ which was involved in ferroptosis caused by MITD1 knockdown. Subsequent overexpression experiments demonstrated that MITD1 knockdown induced ferroptosis and suppressed tumor growth and migration through the TAZ/SLC7A11 pathway. In summary, our study revealed the role of MITD1 in the ferroptosis of ccRCC and provided a novel target for ccRCC treatment.


Assuntos
Carcinoma de Células Renais , Ferroptose , Neoplasias Renais , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/patologia , Proteínas de Membrana/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional
2.
BMC Urol ; 22(1): 141, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057604

RESUMO

PURPOSE: To develop a system for multi-parametric MRI to differentiate benign from malignant solid renal masses and assess its accuracy compared to the gold standard of histopathological diagnosis. METHODS: This is a retrospective analysis of patients who underwent 3 Tesla mpMRI for further assessment of small renal tumours with specific scanning and reporting protocol incorporating T2 HASTE signal intensity, contrast enhancement ratios, apparent diffusion coefficient and presence of microscopic/macroscopic fat. All MRIs were reported prior to comparison with histopathologic diagnosis and a reporting scheme was developed. 2 × 2 contingency table analysis (sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV)), Fisher Exact test were used to assess the association between suspicion of malignancy on mpMRI and histopathology, and descriptive statistics were performed. RESULTS: 67 patients were included over a 5-year period with a total of 75 renal masses. 70 masses were confirmed on histopathology (five had pathognomonic findings for angiomyolipomas; biopsy was therefore considered unethical, so these were included without histopathology). Three patients were excluded due to a non-diagnostic result, non-standardised imaging and one found to be an organising haematoma rather than a mass. Therefore 72 cases were included in analysis (in 64 patients, with seven patients having multiple tumours). Unless otherwise specified, all further statistics refer to individual tumours rather than patients. 52 (72.2%) were deemed 'suspicious or malignant' and 20 (27.8%) were deemed 'benign' on mpMRI. 51 cases (70.8%) had renal cell carcinoma confirmed. The sensitivity, NPV, specificity and PPV for MRI for detecting malignancy were 96.1%, 90%, 85.7% and 94.2% respectively, Fisher's exact test demonstrated p < 0.0001 for the association between suspicion of malignancy on MRI and histopathology. CONCLUSION: The de Silva St George classification scheme performed well in differentiating benign from malignant solid renal masses, and may be useful in predicting the likelihood of malignancy to determine the need for biopsy/excision. Further validation is required before this reporting system can  be recommended for clinical use.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Imageamento por Ressonância Magnética Multiparamétrica , Carcinoma de Células Renais/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade
3.
Oxid Med Cell Longev ; 2022: 8645830, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36062189

RESUMO

Background: Covalently closed circular RNAs (circRNAs) play critical oncogenic or anticancer roles in various cancers including renal cell carcinoma (RCC), pointing to their regulation as a promising strategy against development of RCC. We, thus, studied the tumor-suppressive role of circ_000829 in RCC through in vitro and in vivo experiments. Methods: The expression of circ_000829 was validated in clinical RCC tissues and RCC cell lines. Based on ectopic expression and knockdown experiments, we examined the interactions among circ_000829, serine and arginine rich splicing factor 1 (SRSF1), and solute carrier family 39 member 14 (SLC39A14, zinc transporter). Then, the effects of circ_000829, SRSF1, and SLC39A14 on cell cycle distribution and proliferation in vitro and on tumor growth in vivo were evaluated in RCC cells. Results: Circ_000829 was poorly expressed in RCC tissues and cells, while SRSF1 was highly expressed. Restoration of circ_000829 reduced the levels of SRSF1 and SLC39A14B, thereby repressing the RCC cell proliferation in vitro and tumor growth in vivo. Meanwhile, overexpression of SRSF1 and SLC39A14B promoted the proliferation and cell cycle entry of RCC cells. Mechanistically, circ_000829 directly bound to SRSF1, and SRSF1 enhanced the expression of SLC39A14B by mediating the alternative splicing of SLC39A14. SLC39A14B upregulation negated the effect of SLC39A14 knockdown on RCC cell proliferation. Conclusion: Hence, this study suggests the antiproliferative role of circ_000829 in RCC growth and further elucidates the underlying mechanism involving the inhibited SRSF1-mediated alternative splicing of SLC39A14 mRNA.


Assuntos
Carcinoma de Células Renais , Proteínas de Transporte de Cátions , Neoplasias Renais , RNA Circular , Fatores de Processamento de Serina-Arginina , Processamento Alternativo , Carcinoma de Células Renais/patologia , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/patologia , RNA Circular/genética , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismo
4.
World J Surg Oncol ; 20(1): 284, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36064369

RESUMO

BACKGROUND: To summarize our clinical experience of cryoablation in renal cell carcinoma (RCC) of Chinese population and to evaluate the long-term outcomes of laparoendoscopic single-site (LESS) cryoablation (LCA) as well as percutaneous CT-guided cryoablation (PCA) for biopsy-proven T1a and T1b RCC. METHODS: This was a multi-center, retrospective study investigating T1 stage RCC patients from 2011 to 2021. The patients were treated by LCA or PCA according to individual situation. Overall survival (OS), cancer-related survival (CSS), and progression-free survival (PFS) were evaluated for oncological outcomes, and kidney function, complications, and hospital stay were used to estimate technical outcomes. RESULTS: A total of 163 consecutive patients were included. Among them, 59 cases were treated by LCA and PCA was performed in 104 cases. All operations were processed successfully. Mean diameter of the mass was (2.9±1.4) cm; median blood volume was 45ml (10~200 ml). The mean operation time was 84.0 ± 24.5 min. The median postoperative hospital stay was 3 days (1~6 days). Compared with LCA, procedure time of PCA was shortened, the volume of bleeding was reduced, and the hospital stay was decreased. The overall adverse events rate was 9.8% (16/163). The mean preoperative and postoperative eGFR of LCA were 77.6±15.3 ml/min and 75.6±17.4 ml/min, respectively. Analogously, the values of PCA were 78.7±12.9 ml/min and 76.7±14.3 ml/min. Mean follow-up time was 64.2 ± 30.2 months (range, 7-127 months). Local recurrence was observed in 13 patients (8.0%), 4 (6.8%) cases of LCA and 9 (8.7%) cases of PCA. PFS at 5 and 10 years were 95.5% and 69.2% for LCA and 96.7% and 62.8% for PCA. In total, 26 patients (16.0%) (11 patients from LCA and 15 from PCA) died throughout the follow-up period. OS at 5 and 10 years were 93.8% and 31.4% for LCA, and 97.4% and 52.7% for PCA. Six patients (3.7%) (3 cases from LCA and 3 from PCA) died of metastatic RCC. CCS for LCA were 98.0% and 82.8% at 5 and 10 years, while the data were 100% and 86.4% for PCA. CONCLUSION: LCA and PCA for T1 stage RCC provides satisfactory long-term oncological and renal function preservation outcomes, with acceptable complication rates.


Assuntos
Carcinoma de Células Renais , Criocirurgia , Neoplasias Renais , Laparoscopia , Biópsia , Carcinoma de Células Renais/cirurgia , Criocirurgia/efeitos adversos , Criocirurgia/métodos , Humanos , Neoplasias Renais/patologia , Laparoscopia/efeitos adversos , Estudos Retrospectivos
7.
Clin Nucl Med ; 47(10): 885-887, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36067086

RESUMO

ABSTRACT: Intraventricular metastasis from extracranial tumor is rare. We describe MRI and 68Ga-FAPI-04 PET/CT findings in a case of histologically proved solitary choroid plexus metastasis from clear cell renal cell carcinoma. The tumor showed remarkable enhancement on MRI and increased FAPI uptake with high tumor-to-background activity ratio on PET/CT. This case indicates FAPI PET may be useful for detection of intraventricular metastasis from renal cell carcinoma.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Plexo Corióideo/patologia , Fluordesoxiglucose F18 , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Quinolinas
8.
J Immunol Res ; 2022: 6378567, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046723

RESUMO

Although substantial progress has been made in the immunotherapy of kidney cancer, its efficacy varies from patient to patient, with many responding suboptimally or even developing metastases. Thus, research on the tumour immune microenvironment and immune cell heterogeneity is essential for kidney cancer treatment. In this study, natural killer (NK) cell populations were isolated using signature genes from the single-cell sequencing data of clear cell renal cell carcinoma (ccRCC) and normal kidney tissues and divided into three subpopulations according to the differences in gene expression profiles: NK(GZMH), NK(EGR1), and NK(CAPG). Gene set enrichment analysis revealed that NK(EGR1) and NK(CAPG) were closely related to tumour metastasis, as shown by kidney cancer metastasis to Hodgkin lymphoma, T-cell leukaemia, and Ki-1+ anaplastic large cell lymphoma. Thus, these two NK cell subpopulations are promising targets for inhibiting metastasis in ccRCC. Our findings revealed heterogeneity in the infiltrating NK cells of kidney cancer, which can serve as a reference for the mechanisms underlying metastasis in kidney cancer.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/patologia , Humanos , Imunoterapia , Neoplasias Renais/patologia , Células Matadoras Naturais , Microambiente Tumoral
10.
Rev Esp Patol ; 55 Suppl 1: S69-S73, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36075667

RESUMO

Regression of primary renal cell carcinoma (RCC) is a rare phenomenon and for several reasons many of the reported cases have been questioned. We present a case that can be considered a true spontaneous and complete regression of a primary RCC. A 79-year-old female underwent nephrectomy because a renal tumor. At the time of surgery image studies showed a small para-aortic lymph node. The tumor measured 3cm and was analyzed completely. Histology showed a fibro-inflammatory lesion with necrosis, foamy macrophages and inflammatory cells. No neoplastic cells were observed and the lesion was interpreted as a localized type of xanthogranulomatous pyelonephritis. One year later a CT control scan, showed that the para-aortic lymph node had increased in size to 4cm. Fine needle aspiration revealed features of clear RCC. Metastatic dissemination was limited so surgical removal of the para-aortic lymph node was performed and the cytologic diagnosis confirmed.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Idoso , Biópsia por Agulha Fina , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Linfonodos/patologia , Nefrectomia/efeitos adversos , Nefrectomia/métodos
11.
Mol Cancer ; 21(1): 181, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36117171

RESUMO

BACKGROUND: Although, micropeptides encoded by non-coding RNA have been shown to have an important role in a variety of tumors processes, there have been no reports on micropeptide in renal cell carcinoma (RCC). Based on the micropeptide MIAC (micropeptide inhibiting actin cytoskeleton) discovered and named in the previous work, this study screened its tumor spectrum, and explored its mechanism of action and potential diagnosis and treatment value in the occurrence and development of renal carcinoma. METHODS: The clinical significance of MIAC in RCC was explored by bioinformatics analysis through high-throughput RNA-seq data from 530 patients with kidney renal clear cell carcinoma (KIRC) in the TCGA database, and the detection of clinical samples of 70 cases of kidney cancer. In vitro and in vivo experiments to determine the role of MIAC in renal carcinoma cell growth and metastasis; High-throughput transcriptomics, western blotting, immunoprecipitation, molecular docking, affinity experiments, and Streptavidin pulldown experiments identify MIAC direct binding protein and key regulatory pathways. RESULTS: The analysis of 600 renal carcinoma samples from different sources revealed that the expression level of MIAC is significantly decreased, and corelated with the prognosis and clinical stage of tumors in patients with renal carcinoma. Overexpression of MIAC in renal carcinoma cells can significantly inhibit the proliferation and migration ability, promote apoptosis of renal carcinoma cells, and affect the distribution of cells at various stages. After knocking down MIAC, the trend is reversed. In vivo experiments have found that MIAC overexpression inhibit the growth and metastasis of RCC, while the synthetized MIAC peptides can significantly inhibit the occurrence and development of RCC in vitro and in vivo. Further mechanistic studies have demonstrated that MIAC directly bind to AQP2 protein, inhibit EREG/EGFR expression and activate downstream pathways PI3K/AKT and MAPK to achieve anti-tumor effects. CONCLUSIONS: This study revealed for the first time the tumor suppressor potential of the lncRNA-encoded micropeptide MIAC in RCC, which inhibits the activation of the EREG/EGFR signaling pathway by direct binding to AQP2 protein, thereby inhibiting renal carcinoma progression and metastasis. This result emphasizes that the micropeptide MIAC can provide a new strategy for the diagnosis and treatment of RCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , RNA Longo não Codificante , Aquaporina 2/genética , Aquaporina 2/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Epirregulina , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/patologia , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais , Estreptavidina/genética , Estreptavidina/metabolismo , Estreptavidina/uso terapêutico
13.
Dis Markers ; 2022: 6062236, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072902

RESUMO

Renal cell carcinoma (RCC) is one of the most common urological malignancies with high incidence and metastatic relapse. Clear cell RCC (ccRCC) comprises nearly 70% of all RCC cases and is responsible for the majority of morbidity and mortality of RCC. Due to the poor diagnosis strategy and unsatisfactory clinical intervention, ccRCC causes a huge economic burden and poor patient quality of life; therefore, novel diagnostic or therapeutic targets for ccRCC are urgently needed. This study investigated the biological role of circFOXO3 in ccRCC development, showing that circFOXO3 is highly expressed in RCC cells and tissues and inhibits the viability of ccRCC cells. circFOXO3 dysregulation regulates NK cell cytotoxicity towards RCC cells by directly sponging miR-29a-3p and miR-122-5p. Overexpression of miR-29a-3p or miR-122-5p attenuated NK cell toxicity towards RCC cells and the transcriptional factor Kruppel-Like Factor 16 (KLF16) regulates circFOXO3 expression in RCC cells. In conclusion, this study has partially elucidated the function of circFOXO3 in ccRCC development, providing potential novel therapeutic targets for ccRCC.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Proteína Forkhead Box O3 , Neoplasias Renais , MicroRNAs , RNA Circular , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Proteína Forkhead Box O3/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Células Matadoras Naturais/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , MicroRNAs/genética , Recidiva Local de Neoplasia , Qualidade de Vida , RNA Circular/genética
17.
Oxid Med Cell Longev ; 2022: 1727575, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052158

RESUMO

Background: Accumulating evidence substantiated that the immune cells were intricately intertwined with the prognosis and therapy of clear cell renal cell carcinoma (ccRCC). We aimed to construct an immune cell signatures (ICS) score model to predict the prognosis of ccRCC patients and furnish guidance for finding appropriate treatment strategies. Methods: Based on The Cancer Genome Atlas (TCGA) database, the normalized enrichment score (NES) of 184 ICSf was calculated using single-sample gene set enrichment analysis (ssGSEA). An ICS score model was generated in light of univariate Cox regression and Least absolute shrinkage and selection operator (Lasso)-Cox regression, which was independently validated in ArrayExpress database. In addition, we appraised the predictive power of the model via Kaplan-Meier (K-M) curves and time-dependent receiver operating characteristic (ROC) curves. Eventually, immune infiltration, genomic alterations and immunotherapy were analyzed between high and low ICS score groups. Results: Initially, we screened 11 ICS with prognostic impact based on 515 ccRCC patients. K-M curves presented that the high ICS score group experienced a poorer prognosis (P < 0.001). In parallel, ROC curves revealed a satisfactory reliability of model to predict individual survival at 1, 3, and 5 years, with area under the curves (AUCs) of 0.744, 0.713, and 0.742, respectively. In addition, we revealed that the high ICS score group was characterized by increased infiltration of immune cells, strengthened BAP1 mutation frequency, and enhanced expression of immune checkpoint genes. Conclusion: The ICS score model has higher predictive power for patients' prognosis and can instruct ccRCC patients in seeking suitable treatment.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/patologia , Prognóstico , Reprodutibilidade dos Testes
19.
Int J Mol Sci ; 23(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36077297

RESUMO

Sunitinib and pazopanib are tyrosine kinase inhibitors (TKIs) used as first-line therapy for metastatic renal cell carcinoma (RCC). Although these TKIs are associated with similar survival outcomes, some differences have been reported in their safety profiles. In this work, traditional toxicological endpoints (cell viability and growth, oxidative stress, and nuclear morphology) and 1H NMR spectroscopy-based metabolomics analysis were used to provide new insights into the cytotoxicity and metabolic mechanisms underlying sunitinib and pazopanib treatments. Tumoral (Caki-1) and non-tumoral (HK-2) human renal cells were exposed to clinically relevant concentrations of sunitinib (2 µM) or pazopanib (50 µM). Sunitinib showed selectivity for cancer cells, inhibiting proliferation, and inducing apoptotic death of Caki-1 cells, whereas pazopanib had a similar cytotoxic effect in both tumoral and non-tumoral cells. 1H-NMR metabolomics unveiled a higher impact of sunitinib on the levels of intracellular metabolites of Caki-1 cells (seven dysregulated metabolites), suggesting dysregulations on amino acid, glutathione and glycerophospholipid metabolisms. In contrast, pazopanib had a higher impact on the levels of extracellular metabolites of Caki-1 cells (seven dysregulated metabolites in culture medium), unveiling alterations on amino acid and energetic metabolisms. In HK-2 cells, sunitinib caused only a minor increase in intracellular isoleucine levels, whereas pazopanib induced several alterations on the intracellular (three dysregulated metabolites) and extracellular (three dysregulated metabolites) compartments suggesting changes on amino acid, glycerophospholipid, and energy metabolisms. Our results demonstrate that these TKIs elicit distinct cellular and metabolic responses, with sunitinib showing better in vitro efficacy against target RCC cells and lesser nephrotoxic potential than pazopanib.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Aminoácidos , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Glicerofosfolipídeos , Humanos , Indazóis , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Pirimidinas , Pirróis/efeitos adversos , Sulfonamidas , Sunitinibe/uso terapêutico
20.
BMJ Open ; 12(9): e058396, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104138

RESUMO

OBJECTIVES: The non-randomised, open-label, phase IIIb/IV multicohort CheckMate 920 trial explored the safety and efficacy with a less frequent, but continual nivolumab plus ipilimumab (NIVO+IPI) dosing regimen (cohort 1) to determine whether this modification could potentially retain efficacy benefits while improving on the manageable safety profile previously observed with this combination in patients with advanced renal cell carcinoma (aRCC). SETTING: Patients were enrolled from 48 largely community-based sites in the USA. PARTICIPANTS: 106 patients with previously untreated, predominantly clear cell aRCC received treatment. INTERVENTIONS: Patients received NIVO 6 mg/kg plus IPI 1 mg/kg on day 1 of the first week of each 8-week cycle; the combination alternated with NIVO 480 mg monotherapy on day 1 of the fifth week of each 8-week cycle. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or study end. The maximum treatment duration was 2 years. The primary endpoint was the incidence of high-grade (grade 3/4 and grade 5) immune-mediated adverse events (IMAEs) within 100 days of the last dose. Select secondary endpoints included time to onset and resolution of high-grade IMAEs, progression-free survival (PFS) and objective response rate (ORR). The incidence of treatment-related adverse events and the overall survival (OS) were the exploratory endpoints. RESULTS: The most common grade 3/4 IMAEs were diarrhoea/colitis (7.5%) and rash (6.6%) and no grade 5 IMAEs occurred, with a minimum follow-up of 28.5 months. The median PFS was 4.8 (95% CI 3.0 to 8.3) months, the ORR in evaluable patients (n=96) was 34.4% (95% CI 25.0 to 44.8), and the median OS was not reached (95% CI 24.8 months to not estimable). CONCLUSIONS: While no new safety signals were reported with less frequent, but continual NIVO+IPI dosing in CheckMate 920, the modified regimen was not associated with clinical benefits relative to the approved NIVO+IPI dose. These results support the continued use of the currently approved NIVO+IPI combination dosing schedule for patients with aRCC. TRIAL REGISTRATION NUMBER: NCT02982954.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Humanos , Ipilimumab/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Nivolumabe/efeitos adversos
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