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1.
Urol Clin North Am ; 47(4): 419-431, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008493

RESUMO

The management of metastatic renal cell carcinoma (RCC) has evolved rapidly in recent years with several immunotherapy-based combinations of strategies approved as first-line therapies. Targeted strategies, including systemic antiangiogenesis agents and immune checkpoint blockade, form the basis of a therapeutic approach. With rising rates of recurrence after first-line treatment, it is increasingly important to not only adopt a personalized treatment plan with minimal adverse events but also develop predictive biomarkers for response. This review discusses currently available first-line and second-line therapies in RCC and their pivotal data, with specific focus on ongoing clinical trials in the adjuvant setting, including those involving novel agents.


Assuntos
Produtos Biológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Imunoterapia/métodos , Neoplasias Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Ensaios Clínicos Fase II como Assunto , Terapia Combinada , Quimioterapia Combinada , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Nefrectomia/métodos , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos
2.
Croat Med J ; 61(4): 326-332, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32881430

RESUMO

AIM: To assess diseases outcomes and tolerability of real-life second-line nivolumab in a series of metastatic renal cell carcinoma (mRCC) patients. METHODS: This retrospective chart review involved prospectively monitored patients (named patient program) treated with second-line nivolumab for mRCC at the University Hospital Centre Zagreb from February 2016 to March 2018. RESULTS: The study enrolled 30 patients, 5 of whom (16.7%) had a complete response. The mean ± standard deviation therapeutic response time to nivolumab treatment was 14.07 ± 8.92 months, with a minimum treatment duration of 2 months and a maximum of 24 months. The median duration of therapy was 17 months (mean: 15.8 months; range: 3-24 months), and 50% (n=15/30) of patients remained alive at the end of follow up. The most common adverse events associated with nivolumab were fatigue (26.67%; n=8/30), anemia (10.0%; n=3/30), adrenal insufficiency (6.67%; n=2/30: G1=1, G2=1), grade 2 pneumonitis (6.67%; n=2/30), grade 2 neuropathy (6.67%; n=2/30), rash (6.67%; n = 2/30: G1=1, G2=1), and hepatitis (3.33%; n=1/30). CONCLUSION: The present study indicates acceptable patient responses and tolerability of nivolumab in mRCC.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
3.
Yonsei Med J ; 61(10): 837-843, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32975057

RESUMO

PURPOSE: The standard schedule for sunitinib treatment is 4 weeks on and 2 weeks off (4/2) in first-line treatment for metastatic renal cell carcinoma (mRCC). Schedule modifications, including 2 weeks on and 1 week off (2/1), appear to reduce the total number of treatment-related adverse events (TRAEs) without compromising efficacy. Even though TRAEs can qualitatively differ from each other, it is not clear as to what effects a 2/1 schedule has on individual TRAEs. MATERIALS AND METHODS: This meta-analysis included one randomized controlled trial (RCT) and four non-randomized controlled studies (non-RCTs) that compared the two schedules in parallel. The primary objective was to estimate risk of individual adverse events (AEs) with a sunitinib 2/1 schedule versus a 4/2 schedule. Seven representative AEs were evaluated as standard data for the RCT and as weighted pooling data of the non-RCTs. Random effects modelling with Review Manager v5.3 was used to pool study-level data using the inverse-variance of each study as the weight. RESULTS: The five selected studies included a total of 484 patients with mRCC. Risk ratios for fatigue for a 2/1 schedule were significantly lower than those for a 4/2 schedule {0.69 [95% confidence intervals (CI), 0.51, 0.95] in the RCT and 0.77 (95% CI, 0.63, 0.94) in the non-RCTs}. Other TRAEs, except diarrhea and anorexia, also tended to decrease in both sets. Efficacy outcomes were comparable between 2/1 and standard schedules. CONCLUSION: This meta-analysis suggests that a 2/1 schedule of sunitinib lowers the risk of fatigue and the occurrence other AEs without compromising efficacy.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Sunitinibe/uso terapêutico , Carcinoma de Células Renais/patologia , Esquema de Medicação , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
4.
Anticancer Res ; 40(10): 5667-5671, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988891

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) is a common urological cancer, and its risk correlates with environmental factors such as obesity, smoking and hypertension. Microarray technology enables analysis of the expression pattern of the whole phosphatome, members of which are involved in many cellular pathways and may act as either tumour suppressors or oncogenes in cancers. MATERIALS AND METHODS: We analysed data for the expression level of 87 out of 107 known protein phosphatase genes included in the Hugo Gene Nomenclature Committee Website for 72 RCC tissues and paired healthy tissues obtained from the GEO Database. RESULTS: Our analysis revealed overexpression of DUSP1, DUSP4, PTP4A3, PTPRC and PTPRE genes at all examined stages of RCC. Moreover, we found overexpression of PTPN12 at stage 2, overexpression of CDKN3 at stages 3 and 4, and overexpression of DUSP10 and PTPN22 at stages 2, 3 and 4. Lower expression of DUSP9, PTPR9 and PTPRO was also observed at all stages. CONCLUSION: Significant changes in expression patterns of protein tyrosine phosphatase genes confirm the involvement of this group in crucial carcinogenesis pathways underlying RCC. Thus, we postulate that protein tyrosine phosphatases play an important role in RCC promotion and progression, and may be considered as potential therapeutic targets.


Assuntos
Carcinoma de Células Renais/genética , Proliferação de Células/genética , Oncogenes/genética , Proteínas Tirosina Fosfatases/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proteínas Inibidoras de Quinase Dependente de Ciclina/genética , Fosfatase 1 de Especificidade Dupla/genética , Fosfatases de Especificidade Dupla/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Antígenos Comuns de Leucócito/genética , Masculino , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/genética , Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/genética , Fatores de Risco , Transdução de Sinais/genética , Fumar/efeitos adversos
5.
Anticancer Res ; 40(10): 5837-5844, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988913

RESUMO

BACKGROUND/AIM: Renal cell carcinoma (RCC) is one of the most common malignancies of the urinary tract. Venous migration, tumor thrombus and metastases are often seen in patients with RCC and are adverse prognostic factors. Intravascular tumor growth along the renal vein into the inferior vena cava occurs in up to 10% of all patients with RCC. Furthermore, extension of the tumor reaching the right atrium is detected in approximately 1% of all patients. Synchronous involvement of pulmonary arteries with tumor emboli is very rare and challenging. Management of metastatic RCC includes surgical resection of renal and metastatic lesions. We present 3 cases of patients with RCC tumor thrombus extending into the inferior vena cava (IVC) and with pulmonary emboli of the tumor thrombus into one of the branches of the main pulmonary artery. All the cases had simultaneous resection of the kidney tumor with the tumor thrombus and pulmonary lobectomy that included the tumor emboli with satisfactory outcome. CASE REPORT: We present a series of cases of RCC with tumor extension into the inferior vena cava (IVC) and with tumor emboli to the pulmonary arteries. Surgical procedure in all cases consisted of radical nephrectomy with IVC tumor thrombus resection, along with a thoracotomy with lung resection including the tumor emboli to one of the branches of the main pulmonary artery. Synchronous metastatic lesions were found on the liver in one case and contiguous extension of renal tumor to the pancreas in another. CONCLUSION: In patients with IVC thrombus with synchronous pulmonary artery tumor embolus, such as the cases presented in this series, a careful multidisciplinary management approach is preferable. Transplant technique used in our open approach minimizes complications, blood loss, and provides excellent visualization for abdominal vascular manipulation of IVC. This provides a potentially curable treatment option with acceptable survival rates.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Pulmonares/cirurgia , Artéria Pulmonar/cirurgia , Veia Cava Inferior/cirurgia , Adulto , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Rim/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Metástase Neoplásica , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Nefrectomia/métodos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/patologia , Veias Renais/diagnóstico por imagem , Veias Renais/patologia , Veias Renais/cirurgia , Trombose/diagnóstico por imagem , Trombose/patologia , Trombose/cirurgia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/patologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/patologia , Trombose Venosa/cirurgia
6.
Nat Commun ; 11(1): 4111, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807776

RESUMO

Mutational inactivation of VHL is the earliest genetic event in the majority of clear cell renal cell carcinomas (ccRCC), leading to accumulation of the HIF-1α and HIF-2α transcription factors. While correlative studies of human ccRCC and functional studies using human ccRCC cell lines have implicated HIF-1α as an inhibitor and HIF-2α as a promoter of aggressive tumour behaviours, their roles in tumour onset have not been functionally addressed. Herein we show using an autochthonous ccRCC model that Hif1a is essential for tumour formation whereas Hif2a deletion has only minor effects on tumour initiation and growth. Both HIF-1α and HIF-2α are required for the clear cell phenotype. Transcriptomic and proteomic analyses reveal that HIF-1α regulates glycolysis while HIF-2α regulates genes associated with lipoprotein metabolism, ribosome biogenesis and E2F and MYC transcriptional activities. HIF-2α-deficient tumours are characterised by increased antigen presentation, interferon signalling and CD8+ T cell infiltration and activation. Single copy loss of HIF1A or high levels of HIF2A mRNA expression correlate with altered immune microenvironments in human ccRCC. These studies reveal an oncogenic role of HIF-1α in ccRCC initiation and suggest that alterations in the balance of HIF-1α and HIF-2α activities can affect different aspects of ccRCC biology and disease aggressiveness.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Células 3T3 , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Western Blotting , Linfócitos T CD8-Positivos/metabolismo , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/fisiologia , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Imuno-Histoquímica , Inflamação/genética , Inflamação/metabolismo , Neoplasias Renais/genética , Espectrometria de Massas , Camundongos , Proteômica/métodos , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNA , Microambiente Tumoral/genética , Microambiente Tumoral/fisiologia
7.
Yakugaku Zasshi ; 140(8): 963-968, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32741869

RESUMO

Metabolome analysis is an approach to investigate cell characteristics from the metabolites that are constantly produced and changed by those cells. We conducted a metabolome analysis of the response of 786-O renal cell carcinoma (RCC) cells to histone deacetylase (HDAC) inhibitors, which are expected to increase anticancer drug sensitivity, and compared the response with that of drug-resistant cells. Trichostatin A (TSA), an HDAC inhibitor, increased the sensitivity of 786-O cells to sunitinib. Moreover, TCA cycle and nucleotide metabolism of the cells were promoted. The findings that acetylated p53 (active form) and early apoptotic cells were increased suggests that the mechanism involved enhancement of mitochondrial metabolism and function. In addition, established sunitinib-resistant RCC cells were exposed to a combination of sunitinib and TSA, resulting in significant growth inhibition. Principal component analysis revealed that the parent and resistant cells were obviously different, but approximately half their fluctuations were illustrated by the same pathways. In summary, it was suggested that TSA reduced sunitinib resistance by triggering intracellular metabolome shifts in energy metabolism. This was the first recognized mechanism of action of TSA as an HDAC inhibitor.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Metaboloma , Metabolômica , Sunitinibe/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Humanos , Mitocôndrias/metabolismo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/metabolismo
8.
Nat Commun ; 11(1): 4168, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32820162

RESUMO

There is conflicting data regarding the role of PBAF complex mutations and response to immune checkpoint blockade (ICB) therapy in clear cell renal cell carcinoma (ccRCC) and other solid tumors. We assess the prevalence of PBAF complex mutations from two large cohorts including the pan-cancer TCGA project (n = 10,359) and the MSK-IMPACT pan-cancer immunotherapy cohort (n = 3700). Across both cohorts, PBAF complex mutations, predominantly PBRM1 mutations, are most common in ccRCC. In multivariate models of ccRCC patients treated with ICB (n = 189), loss-of-function (LOF) mutations in PBRM1 are not associated with overall survival (OS) (HR = 1.24, p = 0.47) or time to treatment failure (HR = 0.85, p = 0.44). In a series of 11 solid tumors (n = 2936), LOF mutations are not associated with improved OS in a stratified multivariate model (HR = 0.9, p = 0.7). In a current series of solid tumors treated with ICB, we are unable to demonstrate favorable response to ICB in patients with PBAF complex mutations.


Assuntos
Carcinoma de Células Renais/terapia , Proteínas Cromossômicas não Histona/genética , Proteínas de Ligação a DNA/genética , Imunoterapia/métodos , Neoplasias Renais/terapia , Mutação , Fatores de Transcrição/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Estudos de Coortes , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/genética , Neoplasias Renais/patologia , Pessoa de Meia-Idade
9.
Am J Med Sci ; 360(3): 279-286, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32829780

RESUMO

BACKGROUND: The essential role of 6-phosphogluconate dehydrogenase (6PGD), the enzyme catalyzing the oxidative pentose phosphate pathway, in tumor growth and metabolism has garnered attention in recent years. In this work, we are the first to demonstrate that aberrant activation of 6PGD is a feature in renal cell carcinoma (RCC) and is critically involved in renal carcinogenesis and chemo- and immuno-resistance. MATERIALS AND METHODS: 6PGD expression and activity were systematically analyzed in normal and malignant renal cells and tissues. The roles of 6PGD and its downstream mechanism were investigated using gain-of-function and loss-of-function approaches. RESULTS: 6PGD expression and enzyme activity were increased in RCC cells and patients' samples. Activation of 6PGD via gain-of-function approach promoted growth of normal kidney but not RCC cells, and alleviated the efficacy of chemotherapeutic (e.g., 5-FU) and immunotherapeutic (e.g., IFN-α) agents. In contrast, 6PGD inhibition using siRNA knockdown and pharmacological inhibitor physcion augmented the inhibitory effects of 5-FU and IFN-α in RCC. Mechanistic studies demonstrated that 6PGD inhibition activated AMPK signaling, leading to ACC1 enzyme inhibition and reduction of lipid synthesis. In addition, 6PGD inhibition disrupted NADPH and NADH homeostasis in RCC cells as shown by the decreased level of NADPH and NADH, and suppressed SIRT-1 activity. AMPK inhibition by siRNA knockdown reversed the inhibitory effects of physcion, demonstrating that the effect of 6PGD inhibition is AMPK activation dependent. CONCLUSIONS: Our work provides preclinical evidence that 6PGD inhibition may represent a potential therapeutic strategy to augment the efficacy of RCC standard of care drugs.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Carcinoma de Células Renais/terapia , Reprogramação Celular/fisiologia , Neoplasias Renais/terapia , Fosfogluconato Desidrogenase/metabolismo , Transdução de Sinais/fisiologia , Proteínas Quinases Ativadas por AMP/genética , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Linhagem Celular , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/fisiologia , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Fluoruracila/uso terapêutico , Técnicas de Silenciamento de Genes , Humanos , Imunoterapia , Interferon-alfa/uso terapêutico , Rim/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , NADP/fisiologia , Fosfogluconato Desidrogenase/antagonistas & inibidores , Fosfogluconato Desidrogenase/genética , RNA Interferente Pequeno , Regulação para Cima
10.
Urol Clin North Am ; 47(3): 271-280, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32600530

RESUMO

Advanced renal cell carcinoma is not uncommon, but necessitates a multidisciplinary approach for optimal treatment. Targeted therapy has increased the likelihood of urologists managing patients in all disease stages. Neoadjuvant therapy is currently experimental. Systemic therapy for metastatic disease demonstrates survival benefits. The role of cytoreductive nephrectomy and adjuvant therapy is dependent on patient selection. Management of advanced renal cell carcinoma involves continued optimization of available agents and biomarker development. This article reviews the role of the urologist in medical and surgical therapies, including prognostication, management of locally advanced and metastatic disease, and provides the most recent clinical trial data.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Papel do Médico , Antineoplásicos/administração & dosagem , Biópsia , Carcinoma de Células Renais/patologia , Terapia Combinada , Humanos , Neoplasias Renais/patologia , Nefrectomia , Prognóstico , Medição de Risco , Urologistas
11.
Urol Clin North Am ; 47(3): 319-327, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32600534

RESUMO

Variant histology renal cell carcinoma (vRCC) encompasses rare non-clear cell subtypes that have long been associated with poor prognosis and minimal response to therapies targeting vascular endothelial growth factor and its receptor. Molecular advances have helped classify vRCC into distinct entities and identify putative targetable driver alterations, such as MET in papillary subtypes. More have since been identified in other vRCC subtypes, including alterations of tumor metabolism, chromatin remodeling genes, cell-cycle genes, and inactivation of tumor suppressors such as TP53 or NF2. New targeted therapies, as well as immune checkpoint inhibitors, have been in development and yielded encouraging results. Collaborative clinical trials will be an essential step toward better implementation of these regimens in clinical practice.


Assuntos
Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Antineoplásicos Imunológicos/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Humanos , Terapia de Alvo Molecular , Nefrectomia
12.
Urol Clin North Am ; 47(3): 329-343, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32600535

RESUMO

There has been strong interest in using neoadjuvant therapy to decrease recurrence rates and facilitate surgical resection in locally advanced renal cell carcinoma. To date, no evidence exists to support improvement in oncologic outcomes with neoadjuvant therapy. Likewise, although targeted therapies have shown efficacy in tumor downsizing, this does not often translate to downstaging. Use of presurgical therapy for the purpose of downstaging inferior vena cava tumor thrombi is currently not supported. Future studies evaluating the benefit of newer immune checkpoint inhibitors will determine if there is a larger role for neoadjuvant therapy in locally advanced renal cell carcinoma.


Assuntos
Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Terapia de Alvo Molecular , Terapia Neoadjuvante
13.
Urol Clin North Am ; 47(3): 345-358, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32600536

RESUMO

This article reviews the use of adjuvant therapies for prevention of recurrence following resection of clinically localized renal cell carcinoma (RCC). Clinical trials evaluating adjuvant therapy for RCC have focused primarily on the use of tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors, which had improved outcome in patients with metastatic disease. However, all but 1 trial found no difference in disease-free survival in the adjuvant setting and none improved overall survival.


Assuntos
Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Carcinoma de Células Renais/patologia , Quimioterapia Adjuvante , Terapia Combinada , Humanos , Imunoterapia , Neoplasias Renais/patologia , Terapia de Alvo Molecular , Nefrectomia
14.
Urol Clin North Am ; 47(3): 371-377, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32600538

RESUMO

The role of lymph node dissection (LND) in the management of renal cell carcinoma (RCC) is controversial. LND serves an indisputable staging role by providing pathologic nodal stage. However, while earlier observational studies had suggested a survival benefit to LND, more recent observational evidence and a randomized trial do not support a survival benefit. The majority of patients with isolated lymph node involvement appear to harbor occult metastatic disease. Still, LND is not associated with increased perioperative morbidity when performed in experienced centers. LND may therefore play a predominantly staging role in patients at increased risk of lymph node metastases.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Excisão de Linfonodo , Carcinoma de Células Renais/terapia , Humanos , Neoplasias Renais/terapia , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Estadiamento de Neoplasias
15.
Urol Clin North Am ; 47(3): 389-397, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32600540

RESUMO

Despite advances in systemic therapy and immunotherapy, surgery continues to have a role in management of advanced renal cell carcinoma (aRCC). Minimally invasive surgery (MIS) is considered standard of care for smaller, localized tumors due to faster recovery without compromising oncologic outcomes. There are concerns about MIS for aRCC due to a potential risk of inferior oncologic outcomes and unusual patterns of disease recurrence. Recent studies, however, suggest that in properly selected patients with aRCC, MIS can provide improved peri-operative outcomes without compromising oncologic control.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Carcinoma de Células Renais/patologia , Procedimentos Cirúrgicos de Citorredução , Humanos , Neoplasias Renais/patologia , Laparoscopia , Excisão de Linfonodo , Procedimentos Cirúrgicos Minimamente Invasivos , Seleção de Pacientes , Veias Renais/cirurgia , Procedimentos Cirúrgicos Robóticos , Veia Cava Inferior/cirurgia
16.
Urol Clin North Am ; 47(3): 399-411, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32600541

RESUMO

Stereotactic radiosurgery and stereotactic body radiation therapy (SBRT) have led to a resurgence of the use of radiotherapy in the management of advanced renal cell carcinoma (RCC). These techniques provide excellent local control and palliation of metastatic sites of disease with minimal toxicity. Additionally, SBRT to the primary tumor may be efficacious and well tolerated in select patients that are not surgical candidates. Emerging data suggest that SBRT may potentiate the immune response, and current and future study will evaluate if SBRT can improve survival outcomes in patients with metastatic RCC.


Assuntos
Carcinoma de Células Renais/radioterapia , Neoplasias Renais/radioterapia , Radiocirurgia/métodos , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/terapia
17.
Medicine (Baltimore) ; 99(27): e20986, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629713

RESUMO

RATIONALE: Cerebral carbon dioxide embolism (CCDE) is a rare cause of stroke and is a recognized life-threatening complication.CCDE may result from direct intravascular CO2 insufflation during surgery. Due to the lack of typical clinical manifestations, the disease is often missed or mistaken for another condition. The clinical signs and symptoms depend on the speed and volume of embolized gas entering the blood and the patient's condition. In particular, patent foramen ovale has been found to be associated, in rare cases, with the intraoperative entry of gas into the arterial system. PATIENT CONCERNS: In this report, we present the case of a 35-year-old woman with kidney cancer who underwent laparoscopic right partial nephrectomy. DIAGNOSIS: After the laparoscopic surgery, the patient was initially diagnosed with acute cerebral infarction. INTERVENTIONS: The patient was treated according to the standard method for treatment of acute cerebrovascular disease. OUTCOMES: Three days after the laparoscopic procedure, the patient gained consciousness, and she was discharged without any neurologic sequelae on postoperative day 12. LESSONS SUBSECTIONS AS PER STYLE: Due to the low incidence and sudden occurrence of CCDE, there is a strong likelihood of missed diagnosis or misdiagnosis, and it is; therefore, important to be aware of the risk. The findings from this report would be highly useful as a reference to clinicians in the future.


Assuntos
Dióxido de Carbono/efeitos adversos , Embolia Aérea/etiologia , Insuflação/efeitos adversos , Embolia Intracraniana/etiologia , Laparoscopia/efeitos adversos , Adulto , Dióxido de Carbono/sangue , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Embolia Intracraniana/diagnóstico por imagem , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Nefrectomia/efeitos adversos
18.
Anticancer Res ; 40(7): 4087-4093, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620657

RESUMO

BACKGROUND/AIM: Hypertension is a risk factor for occurrence of renal cell carcinoma; however, it remains unclear whether hypertension affects development and prognosis of renal cell carcinoma. This study evaluated the impact of hypertension on the progression of renal cell carcinoma. PATIENTS AND METHODS: Renal cell carcinoma patients who were treated from October 2007 to December 2018 at our Institution were retrospectively analyzed. RESULTS: Of 462 patients, the number of patients with and without hypertension was 234 (including 227 treated with anti-hypertensive agents) and 228, respectively. The tumor size was significantly smaller in the hypertension group than in the non-hypertension group (median 32 and 45 mm, respectively, p=0.010). The 5-year cancer-specific and metastasis-free survival in the hypertension group were significantly better than those in the non-hypertension group (93.6% and 80.4%, and 84.6% and 73.0%, respectively, p=0.021 and p=0.017). Propensity score matching revealed significantly better metastatic-free survival in the hypertension group than the non-hypertension group (p=0.022). CONCLUSION: Renal cell carcinoma patients with hypertension show better prognosis with low metastasis possibility.


Assuntos
Carcinoma de Células Renais/epidemiologia , Hipertensão/epidemiologia , Neoplasias Renais/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Carcinoma de Células Renais/patologia , Progressão da Doença , Feminino , Humanos , Hipertensão/tratamento farmacológico , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Carga Tumoral , Adulto Jovem
19.
PLoS One ; 15(7): e0236119, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32667929

RESUMO

The alcohol-abuse drug disulfiram has antitumor effects against diverse cancer types via inhibition of the ubiquitin-proteasome protein nuclear protein localization protein 4 (NPL4). However, the antitumor effects of NPL4 and disulfiram in clear cell renal cell carcinoma (ccRCC) are unclear. Here, we evaluated the therapeutic potential of targeting the ubiquitin-proteasome pathway using disulfiram and RNA interference and investigated the mechanisms underlying disulfiram in ccRCC. According to data from The Cancer Genome Atlas, NPL4 mRNA expression was significantly upregulated in clinical ccRCC samples compared with that in normal kidney samples, and patients with high NPL4 expression had poor overall survival compared with patients with low NPL4 expression. Disulfiram and NPL4 siRNA inhibited ccRCC cell proliferation in vitro, and disulfiram inhibited ccRCC tumor growth in a xenograft model. Synergistic antiproliferative effects were observed for combination treatment with disulfiram and sunitinib in vitro and in vivo. In RCC cells from mice treated with disulfiram and/or sunitinib, several genes associated with serine biosynthesis and aldose reductase were downregulated in cells treated with disulfiram or sunitinib alone and further downregulated in cells treated with both disulfiram and sunitinib. These findings provided insights into the mechanisms of disulfiram and suggested novel therapeutic strategies for RCC treatment.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Dissulfiram/farmacologia , Reposicionamento de Medicamentos/métodos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Renais/tratamento farmacológico , Proteínas Nucleares/antagonistas & inibidores , Inibidores de Acetaldeído Desidrogenases/farmacologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Prognóstico , RNA Interferente Pequeno/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
20.
DNA Cell Biol ; 39(10): 1799-1812, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32716214

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most prevalent renal malignancy in adults with generally poor prognosis. This study aimed to establish a DNA methylation-driven gene-based prognostic model for ccRCC. We collected DNA methylation and gene expression profiles of over 1500 ccRCC samples from The Cancer Genome Atlas (TCGA) dataset, four Gene Expression Omnibus (GEO) datasets, the Genotype-Tissue Expression (GTEx) dataset, and cancer cell lines from Cancer Cell Line Encyclopedia database and performed comprehensive bioinformatics analysis. As a result, a total of 31 differentially expressed methylation-driven genes (DEMDGs) were identified. After univariate Cox regression, least absolute shrinkage and selection operator, and multivariate Cox regression analyses, four (NFE2L3, HHLA2, IFI16, and ZNF582) were finally selected to construct a risk score prognostic model. The high-risk group demonstrated significantly poor prognosis than the low-risk group did in TCGA training (hazard ratio [HR] = 3.533, p < 0.001), TCGA internal, and GEO external validation datasets. Furthermore, the nomogram, including the prognostic model and clinical factors, showed promising prognostic value (HR = 5.756, p < 0.001, and area under the curve at 1 year = 0.856). In addition, the model was found to be significantly associated with drug sensitivity of eight targeted agents. These findings provided a novel and reliable four DEMDG-based prognostic model for ccRCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Metilação de DNA , Neoplasias Renais/genética , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
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