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1.
Anticancer Res ; 41(9): 4295-4304, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475049

RESUMO

BACKGROUND/AIM: Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults. The aim of this study was to elucidate the molecular pathogenesis of sporadic RCC in Taiwan. MATERIALS AND METHODS: Fifteen patients with RCC were screened for mutations in the von Hippel-Lindau (VHL) gene by PCR and Sanger sequencing. The methylation status of promoters of 24 tumor suppressor genes by methylation sensitive multiplex ligation-dependent probe amplification analysis was also determined. RESULTS: Inactivation of the VHL gene was observed in 5 cases: three missense somatic mutations, one promoter methylation, and one small deletion. In RCCs, methylation was most frequently observed in APC (100%), CDKN2B (92.9%), CASP8, MLH1_167, and KLLN (85.7.4%), but not in FHIT, MLH1_463, DAPK1, or HIC1 (0%). CONCLUSION: In addition to VHL inactivation, promoter methylation of APC may be a universal pathognomonic event in the tumorigenesis of RCC and a candidate diagnostic and therapeutic biomarker.


Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Carcinoma de Células Renais/diagnóstico , Metilação de DNA , Neoplasias Renais/diagnóstico , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Detecção Precoce de Câncer , Epigênese Genética , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Mutação de Sentido Incorreto , Estadiamento de Neoplasias , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Deleção de Sequência
2.
J Int Med Res ; 49(8): 3000605211033178, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34382464

RESUMO

PURPOSE: To analyze the recurrence in patients with clinic stage T1 renal cell carcinoma (RCC) who were upstaged to stage T3a after partial nephrectomy (PN) using a new sub-classification criterion. METHODS: A retrospective study of pathological characteristics was performed in patients who were upstaged to pT3a on the basis of fat invasion (FI). RESULTS: After analyzing the pathological findings, we proposed the following new sub-classification criteria for pT3a RCC with FI: (1) renal tumor invades the pseudo-capsule and contacts the perinephric adipose tissue directly or the tumor protrudes into the perinephric adipose tissue like a tongue (Type A); and (2) tumor nodules are distributed in perinephric adipose tissues (Type B). A significant difference was observed in the recurrence rate between the two subtypes A and B. For Type B, the recurrence rate after radical nephrectomy (RN) and PN was 15.79% and 63.64%, respectively. The recurrence rates for Types A and B after PN were 11.11% and 63.64%, respectively. CONCLUSIONS: T3a RCC with tumor nodules in perinephric adipose and/or an irregular tumor protruding into the adipose tissues lead to a higher recurrence rate. We recommend that T3a RCC be carefully analyzed and patients be treated on an individual basis.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Nefrectomia , Prognóstico , Estudos Retrospectivos
3.
Nursing ; 51(9): 30-38, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34463651

RESUMO

ABSTRACT: Renal cell carcinoma (RCC) accounts for most renal malignancies. This article, the last in a three-part series, presents treatment options for RCC using the American Joint Committee on Cancer Tumor, Node, and Metastasis staging system as a framework, as well as nursing-care options for patients undergoing partial or radical nephrectomy.


Assuntos
Carcinoma de Células Renais/enfermagem , Neoplasias Renais/enfermagem , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Estadiamento de Neoplasias , Nefrectomia/métodos , Nefrectomia/enfermagem
4.
Medicine (Baltimore) ; 100(31): e26788, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397830

RESUMO

BACKGROUND: In this study, we evaluated the efficacy and safety of histone deacetylase inhibitors (HDACIs) in the treatment of renal cell carcinoma (RCC). METHODS: PubMed, EMBASE, the Cochrane Library, CNKI, and the Wanfang database were searched to retrieve studies describing the use of HDACIs for the treatment of RCC published between January 1, 2009, and January 1, 2021. Relevant studies were selected, and data were extracted. Then, a meta-analysis was performed using R 3.5.2 software. RESULTS: The results showed that the objective response rate (ORR) of HDACIs used to treat RCC was 26% [95% confidence interval (95% CI): 0.19∼0.34] and that the 1-year progression-free survival (PFS) rate was 29% (95% CI: 0.14∼0.59). The ORR and PFS rate of the combination group were better than those of the monotherapy group, and the ORR and PFS rate of the selective HDACI group were better than those of the pan-HDACI group. The incidences of neutropenia and thrombocytopenia were higher and the incidence of fatigue was lower in the selective HDACI group than in the pan-HDACI group. CONCLUSION: This study initially confirmed the efficacy and safety of HDACIs for the treatment of RCC. Due to the limitations of the included studies, more high-quality studies are needed to validate the conclusions.


Assuntos
Inibidores de Histona Desacetilases/farmacologia , Antineoplásicos/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Estadiamento de Neoplasias , Resultado do Tratamento
5.
Medicine (Baltimore) ; 100(31): e26838, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397852

RESUMO

RATIONALE: Renal cell carcinoma (RCC) almost metastasizes to every organ, the possibility of adrenal metastasis is relatively low in patients that have undergone radical nephrectomy, only a few cases of bilateral adrenal metastasis are reported on literature. Although surgical treatment of metastases from RCC is preferred and contributes to the rate of survival, it is considered challenging to manage such cases due to the rarity of bilateral metastasis to the adrenal glands. PATIENT CONCERNS: A 64-year-old Manchus female presented with an incidental ultrasonic finding of a left adrenal mass 4 years after radical nephrectomy for left renal cell carcinoma. DIAGNOSIS: Abdominal contrast enhanced CT scan revealed bilateral adrenal masses, suggesting metastatic lesion. Examinations indicated neither local recurrence nor distant metastasis anywhere have been detected by whole body Positron Emission Tomography/Computed Tomography (PET/CT) scan except high radioactive uptake in bilateral adrenal glands. INTERVENTIONS: Metachronous bilateral adrenalectomy was taken and laparoscopic right adrenalectomy was first performed. She was discharged home on third postoperative day. Pathological examination revealed metastatic renal cell carcinoma. Two months later she was performed laparoscopic left adrenalectomy. OUTCOMES: The patient healed without obvious complications and no tumor recurrence. LESSONS: Bilateral metastatic adrenal recurrence from RCC is very rare. Early diagnosis of adrenal metastasis is challenging because they are usually silent both anatomically and functionally. Surgical intervention is a wise option for these patients that may improve survival, and metachronous bilateral adrenalectomy is proved to be safe and effective.


Assuntos
Neoplasias das Glândulas Suprarrenais , Adrenalectomia/métodos , Carcinoma de Células Renais , Neoplasias Renais , Metástase Neoplásica , Nefrectomia/métodos , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/secundário , Neoplasias das Glândulas Suprarrenais/cirurgia , Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/patologia , Glândulas Suprarrenais/cirurgia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico por imagem , Metástase Neoplásica/patologia , Metástase Neoplásica/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Imagem Corporal Total/métodos
6.
Beijing Da Xue Xue Bao Yi Xue Ban ; 53(4): 659-664, 2021 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-34393224

RESUMO

OBJECTIVE: To summarize the clinicoradiological characteristics of clinical T1 renal cell carcinoma patients and to investigate the risk factors of renal sinus invasion in cT1 renal cell carcinoma patients undergoing nephrectomy. METHODS: A retrospective study was conducted in cT1 renal cell carcinoma patients from January 2016 to August 2019 in Department of Urology, Peking University Third Hospital, who underwent partial or radical nephrectomy by analyzing clinicopathological and radiological data. The influencing factors of renal sinus invasion for cT1 renal cell carcinoma were determined by χ2 test, Mann-Whitney U test and Logistic regression analysis. RESULTS: A total of 507 patients were enrolled, including 354 males (69.8%) and 153 females (30.2%). The median age was 59 years and the median body mass index (BMI) was 25.5 kg/m2. Eighteen patients (3.6%) had gross hematuria preoperatively. The median tumor diameter was 3.5 cm. Three hundred twenty-two patients (63.5%) were staged clinical T1a and 165 cases (36.5%) were staged clinical T1b. The median R.E.N.A.L. score was 8. Three hundred fifty-nine patients (70.8%) had regular tumor border and 148 (29.2%) irregular. All the patients underwent surgical treatment, including 186 (36.7%) partial nephrectomy and 321 (63.3%) radical nephrectomy. Postoperative pathology showed seventy-five patients (14.8%) had renal sinus invasion, including 18 in cT1a (5.6%) and 57 in cT1b (30.8%). Univariate analysis showed that age (P=0.020), R.E.N.A.L. score (R value, E value, N value, P < 0.001) and tumor border (P < 0.001) were associated risk factors for cT1 renal cell carcinoma with renal sinus invasion. On multivariate binary Logistic analysis, R.E.N.A.L. score (P≤0.020) and irregular tumor border (P=0.001) were independent risk factors. CONCLUSION: For cT1 renal cell carcinoma patients undergoing nephrectomy, about 15% had renal sinus invasion postoperatively. High R.E.N.A.L. score and irre-gular tumor border help predicting cT1 renal cell carcinoma renal sinus invasion.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nefrectomia , Estudos Retrospectivos , Fatores de Risco
7.
Medicine (Baltimore) ; 100(34): e27025, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449477

RESUMO

RATIONALE: Nephrogenic adenoma (NA) is a rare benign lesion of the urinary tract, which rarely occurs in the renal pelvis. Only 19 cases have been reported in the literature. However, there is no detailed report on the clinicopathological features of NA of the renal pelvis. PATIENT CONCERNS: This case report describes a 46-year-old male patient who was admitted to the hospital for one month because of painless gross hematuria with blood clots. He had a history of hyperuricemia and a family history of gastric cancer. DIAGNOSES: NA of the renal pelvis was diagnosed pathologically and immunohistochemical. INTERVENTIONS: The patient underwent laparoscopic nephroureterectomy. OUTCOMES: The patient recovered well after the operation with no discomfort. In addition, we followed up with the patient regularly post-discharge (approximately 20 months). There were no obvious abnormalities in the results of routine urine culture, computed tomography scan of the abdomen, and cystoscopy during the follow-up period, and the symptoms disappeared completely and did not recur. LESSONS: NA of the renal pelvis is extremely rare in the clinic, which can be easily misdiagnosed and overtreated. However, for pathological diagnosis of this disease, specific immunohistochemical staining for preoperative biopsy was reported to be significant, which should be considered by the urologists and pathologists.


Assuntos
Adenoma/patologia , Neoplasias Renais/patologia , Pelve Renal/patologia , Adenoma/diagnóstico , Adenoma/cirurgia , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/cirurgia , Pelve Renal/cirurgia , Laparoscopia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Nefroureterectomia
8.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445576

RESUMO

CD40 crosslinking plays an important role in regulating cell migration, adhesion and proliferation in renal cell carcinoma (RCC). CD40/CD40L interaction on RCC cells activates different intracellular pathways but the molecular mechanisms leading to cell scattering are not yet clearly defined. Aim of our study was to investigate the main intracellular pathways activated by CD40 ligation and their specific involvement in RCC cell migration. CD40 ligation increased the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH (2)-terminal kinase (JNK) and p38 MAPK. Furthermore, CD40 crosslinking activated different transcriptional factors on RCC cell lines: AP-1, NFkB and some members of the Nuclear Factor of Activated T cells (NFAT) family. Interestingly, the specific inhibition of NFAT factors by cyclosporine A, completely blocked RCC cell motility induced by CD40 ligation. In tumor tissue, we observed a higher expression of NFAT factors and in particular an increased activation and nuclear migration of NFATc4 on RCC tumor tissues belonging to patients that developed metastases when compared to those who did not. Moreover, CD40-CD40L interaction induced a cytoskeleton reorganization and increased the expression of integrin ß1 on RCC cell lines, and this effect was reversed by cyclosporine A and NFAT inhibition. These data suggest that CD40 ligation induces the activation of different intracellular signaling pathways, in particular the NFATs factors, that could represent a potential therapeutic target in the setting of patients with metastatic RCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Antígenos CD40/metabolismo , Ligante de CD40/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/patologia , Fatores de Transcrição NFATC/metabolismo , Idoso , Apoptose , Biomarcadores Tumorais/genética , Antígenos CD40/genética , Ligante de CD40/genética , Movimento Celular , Proliferação de Células , Reagentes para Ligações Cruzadas , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Transcrição NFATC/genética , Metástase Neoplásica , Prognóstico , Células Tumorais Cultivadas
9.
Am J Hum Genet ; 108(9): 1590-1610, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34390653

RESUMO

Our study investigated the underlying mechanism for the 14q24 renal cell carcinoma (RCC) susceptibility risk locus identified by a genome-wide association study (GWAS). The sentinel single-nucleotide polymorphism (SNP), rs4903064, at 14q24 confers an allele-specific effect on expression of the double PHD fingers 3 (DPF3) of the BAF SWI/SNF complex as assessed by massively parallel reporter assay, confirmatory luciferase assays, and eQTL analyses. Overexpression of DPF3 in renal cell lines increases growth rates and alters chromatin accessibility and gene expression, leading to inhibition of apoptosis and activation of oncogenic pathways. siRNA interference of multiple DPF3-deregulated genes reduces growth. Our results indicate that germline variation in DPF3, a component of the BAF complex, part of the SWI/SNF complexes, can lead to reduced apoptosis and activation of the STAT3 pathway, both critical in RCC carcinogenesis. In addition, we show that altered DPF3 expression in the 14q24 RCC locus could influence the effectiveness of immunotherapy treatment for RCC by regulating tumor cytokine secretion and immune cell activation.


Assuntos
Carcinoma de Células Renais/genética , Cromossomos Humanos Par 14 , Proteínas de Ligação a DNA/genética , Loci Gênicos , Neoplasias Renais/genética , Fator de Transcrição STAT3/genética , Fatores de Transcrição/genética , Carcinogênese/genética , Carcinogênese/imunologia , Carcinogênese/patologia , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Linhagem Celular Tumoral , Cromatina/química , Cromatina/imunologia , Montagem e Desmontagem da Cromatina/imunologia , Citocinas/genética , Citocinas/imunologia , Proteínas de Ligação a DNA/imunologia , Regulação da Expressão Gênica , Predisposição Genética para Doença , Genoma Humano , Estudo de Associação Genômica Ampla , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunoterapia/métodos , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Polimorfismo de Nucleotídeo Único , Fator de Transcrição STAT3/imunologia , Linfócitos T Citotóxicos , Fatores de Transcrição/imunologia
10.
Medicine (Baltimore) ; 100(33): e26886, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414942

RESUMO

ABSTRACT: Renal cell carcinoma is one common type of urologic cancers. It has tendencies to invade into the inferior vena cava (IVC) and usually requires an open surgery procedure. High rates of operative complications and mortality are usually associated with an open surgery procedure. The recently emerged robot-assisted laparoscopic radical nephrectomy (RAL-RN) and IVC tumor thrombectomy have shown to reduce operative related complications in patients with renal cell carcinoma.This case series study aimed to summarize technical utilization, perioperative outcomes, and efficacies of RAL-RN and IVC tumor thrombectomy in our hospital. A retrospective analysis was performed on clinical data from 20 patients who underwent RAL-RN and IVC tumor thrombectomy from January 2017 to December 2019 in our department.Patients had a median age of 59 years (interquartile range [IQR], 46-68). Four patients had renal neoplasm on left side and 16 on right side. Nineteen patients underwent RAL-RN (level 0: n = 2) or RAL-RN with IVC thrombectomy (n = 17) (level I: n = 3; level II: n = 12; and level III: n = 3) and 1 patient was converted into an open surgery. The median operative time was 328 minutes (IQR, 221-453). The estimated median blood loss was 500 mL (IQR, 200-1200). The median size of removed renal carcinoma was 67 cm2 (IQR, 40-91); the length of IVC tumor thrombus was 5 cm (IQR, 3-7). The postsurgery hospital length of stay was 6 days (IQR, 5-7). The complications included intestinal obstruction (n = 1), lymphatic fistula (n = 1), heart failure (n = 1), and low hemoglobin level (n = 1). The outcomes for patients after 16 months (IQR, 11-21) follow-up were tumor-free (n = 10), tumor progression (n = 4), loss of contact (n = 1), and death (n = 5).We concluded that RAL-RN and IVC thrombectomy renders good safety profiles including minimal invasiveness, low estimated median blood loss, short hospitalization, low morbidity, and quick renal function recovery. The long-term efficacy needs a further investigation.


Assuntos
Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Laparoscopia , Células Neoplásicas Circulantes , Nefrectomia/métodos , Procedimentos Cirúrgicos Robóticos , Trombectomia/métodos , Veia Cava Inferior , Idoso , Feminino , Humanos , Masculino , Registros Médicos , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208157

RESUMO

Advanced imaging techniques for diagnosis have increased awareness on the benefits of brain screening, facilitated effective control of extracranial disease, and prolonged life expectancy of metastatic renal cell carcinoma (mRCC) patients. Brain metastasis (BM) in patients with mRCC (RCC-BM) is associated with grave prognoses, a high degree of morbidity, dedicated assessment, and unresponsiveness to conventional systemic therapeutics. The therapeutic landscape of RCC-BM is rapidly changing; however, survival outcomes remain poor despite standard surgery and radiation, highlighting the unmet medical needs and the requisite for advancement in systemic therapies. Immune checkpoint inhibitors (ICIs) are one of the most promising strategies to treat RCC-BM. Understanding the role of brain-specific tumor immune microenvironment (TIME) is important for developing rationale-driven ICI-based combination strategies that circumvent tumor intrinsic and extrinsic factors and complex positive feedback loops associated with resistance to ICIs in RCC-BM via combination with ICIs involving other immunological pathways, anti-antiangiogenic multiple tyrosine kinase inhibitors, and radiotherapy; therefore, novel combination approaches are being developed for synergistic potential against RCC-BM; however, further prospective investigations with longer follow-up periods are required to improve the efficacy and safety of combination treatments and to elucidate dynamic predictive biomarkers depending on the interactions in the brain TIME.


Assuntos
Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Carcinoma de Células Renais/patologia , Imunoterapia , Neoplasias Renais/patologia , Humanos , Imunossupressão , Microambiente Tumoral
13.
Anticancer Res ; 41(8): 3809-3813, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281840

RESUMO

BACKGROUND/AIM: Renal cell carcinoma (RCC) comprises a variety of pathological entities. Many RCCs are aggressive, demanding efficient targeted and immunetherapeutic strategies. Programmed cell death ligand-1 (PD-L1) is expressed mainly in hematopoietic cells and also in epithelial cells. The aim of this study was to correlate PD-L1 protein expression in a series of RCC tissues with their histo-pathological features. MATERIALS AND METHODS: One hundred (n=100) archival, formalin-fixed and paraffin-embedded RCC tissue specimens were analysed by immunohistochemistry. Conventional tumor proportion score (TPS) qualitative assay was applied for evaluating protein expression levels. RESULTS: Based on the TPS evaluation, 8 (8%) cases were characterized as positive, and the rest of them (n=92; 92%) as negative. A progressive increase in PD-L1 positivity was significantly associated with the differentiation grade of the examined malignancies (p=0.001). CONCLUSION: Although PD-L1 over-expression is detected in low rates in RCCs, its correlation with differentiation grade should be considered as a factor for discriminating sub-groups of patients with specific histo-pathological features eligible for targeted anti-PD-L1 immunotherapy strategies.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Carcinoma de Células Renais/metabolismo , Diferenciação Celular , Feminino , Humanos , Neoplasias Renais/metabolismo , Masculino
14.
Int J Mol Sci ; 22(12)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207825

RESUMO

Non-clear cell renal cell carcinomas are a miscellaneous group of tumors that include different histological subtypes, each one characterized by peculiarity in terms of genetic alteration, clinical behavior, prognosis, and treatment response. Because of their low incidence and poor enrollment in clinical trials, alongside their heterogeneity, additional efforts are required to better unveil the pathogenetic mechanisms and, consequently, to improve the treatment algorithm. Nowadays, tyrosine kinase inhibitors, mTOR and MET inhibitors, and even cisplatin-based chemotherapy and immunotherapy are potential weapons that are still under evaluation in this setting. Various biomarkers have been evaluated for detecting progression and monitoring renal cell carcinoma, but more studies are necessary to improve this field. In this review, we provide an overview on the molecular characteristics of this group of tumors and the recently published trials, giving an insight into what might become the future therapeutic standard in this complex world of non-clear cell kidney cancers.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais , Neoplasias Renais , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-met , Serina-Treonina Quinases TOR , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-met/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo
15.
Nat Commun ; 12(1): 4245, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253722

RESUMO

Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, resulting in hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1). Transcription factor EB (TFEB), a master regulator of lysosome biogenesis, is negatively regulated by mTORC1 through a RAG GTPase-dependent phosphorylation. Here we show that lysosomal biogenesis is increased in TSC-associated renal tumors, pulmonary lymphangioleiomyomatosis, kidneys from Tsc2+/- mice, and TSC1/2-deficient cells via a TFEB-dependent mechanism. Interestingly, in TSC1/2-deficient cells, TFEB is hypo-phosphorylated at mTORC1-dependent sites, indicating that mTORC1 is unable to phosphorylate TFEB in the absence of the TSC1/2 complex. Importantly, overexpression of folliculin (FLCN), a GTPase activating protein for RAGC, increases TFEB phosphorylation at the mTORC1 sites in TSC2-deficient cells. Overexpression of constitutively active RAGC is sufficient to relocalize TFEB to the cytoplasm. These findings establish the TSC proteins as critical regulators of lysosomal biogenesis via TFEB and RAGC and identify TFEB as a driver of the proliferation of TSC2-deficient cells.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Lisossomos/metabolismo , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Biogênese de Organelas , Proteína 2 do Complexo Esclerose Tuberosa/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Carcinoma de Células Renais/patologia , Núcleo Celular/metabolismo , Proliferação de Células , Feminino , Regulação da Expressão Gênica , Células HEK293 , Células HeLa , Humanos , Neoplasias Renais/patologia , Lisossomos/ultraestrutura , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Fosforilação , Fosfosserina/metabolismo , Transporte Proteico , Proteínas Proto-Oncogênicas/metabolismo , Transcrição Genética , Proteína 2 do Complexo Esclerose Tuberosa/deficiência , Proteínas Supressoras de Tumor/metabolismo
16.
Medicine (Baltimore) ; 100(26): e26581, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190202

RESUMO

BACKGROUND: To investigate the clinical application and effect of laparoscopic partial nephrectomy with renal artery branch occlusion in the treatment of early renal tumors. METHODS: A retrospective analysis was conducted on the clinical data of 15 cases of renal tumor patients who underwent partial nephrectomy by laparoscopic selective renal artery branch occlusion in our department from January 2017 to January 2018. Nine male patients and 6 female patients were aged 46 to 65 years, with an average age of 54.3 ±â€Š7.2 years. The diameters of tumors were 2.2 to 4.0 cm, with an average of 3.3 ±â€Š0.7 cm. There are 10 tumors locating on the left side and 5 on the right side. Preoperative renal glomerular filtration rate (GFR) were 77.3 to 61.9 mL/min with an average of 47.6 ±â€Š7.5 mL/min. All patients' diseased kidneys underwent renal computer tomography angiography examination before surgery. And the diseased kidney underwent reexamination of renal GFR. The operation time, renal artery branch occlusion time, intraoperative blood loss, postoperative hospital stay, changes of renal function, and complications were evaluated. RESULTS: All surgery were completed successfully, the surgery time was 136.7 ±â€Š15.2 min, intraoperative renal artery branch occlusion time was 21.3 ±â€Š4.5 min, the intraoperative blood loss was 223.3 ±â€Š69.5 mL, the postoperative hospital stay was 6.5 ±â€Š1.7 days, and the postoperative 1-month GFR was 49.5 ±â€Š6.6 mL/min. There was no significant difference between the renal GFR before and after surgery (P > .05). There was no blood transfusion and transfer open surgery cases. The patients were followed up for 3 to 15 months without complications. CONCLUSIONS: Partial nephrectomy with selective renal artery branch occlusion by laparoscopy is a safe, feasible, and effective method for the treatment of early renal cancer. It makes good use of the technical advantages of clear operation field and fine operation of laparoscopic surgery, avoids the heat ischemia process of the whole kidney, and can better protect the renal function.


Assuntos
Embolização Terapêutica/métodos , Neoplasias Renais , Laparoscopia , Nefrectomia , Artéria Renal , China/epidemiologia , Angiografia por Tomografia Computadorizada/métodos , Intervenção Médica Precoce/métodos , Feminino , Humanos , Testes de Função Renal/métodos , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde , Cuidados Pós-Operatórios/métodos , Artéria Renal/diagnóstico por imagem , Artéria Renal/cirurgia , Carga Tumoral
17.
Lancet Oncol ; 22(7): 946-958, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34143969

RESUMO

BACKGROUND: Despite advances in the first-line treatment of metastatic renal cell carcinoma (RCC), there is an unmet need for options to address disease progression during or after treatment with immune checkpoint inhibitors (ICIs). Pembrolizumab and lenvatinib are active as monotherapies in RCC; thus, we aimed to evaluate the combination of lenvatinib plus pembrolizumab in these patients. METHODS: We report results of the metastatic RCC cohort from an open-label phase 1b/2 study of lenvatinib plus pembrolizumab in patients aged at least 18 years with selected solid tumours and an Eastern Cooperative Oncology Group performance status of 0-1. Oral lenvatinib at 20 mg was given once daily along with intravenous pembrolizumab at 200 mg once every 3 weeks. Patients remained on study drug treatment until disease progression, development of unacceptable toxicity, or withdrawal of consent. Efficacy was analysed in patients with clear cell metastatic RCC receiving study drug by previous therapy grouping: treatment naive, previously treated ICI naive (previously treated with at least one line of therapy but not with an anti-PD-1 or anti-PD-L1 ICI), and ICI pretreated (ie, anti-PD-1 or anti-PD-L1) patients. Safety was analysed in all enrolled and treated patients. The primary endpoint was the objective response rate at week 24 per immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) by investigator assessment. This trial is registered with ClinicalTrials.gov (NCT02501096) and with the EU Clinical Trials Register (EudraCT2017-000300-26), and is closed to new participants. FINDINGS: Between July 21, 2015, and Oct 16, 2019, 145 patients were enrolled in the study. Two patients had non-clear cell RCC and were excluded from the efficacy analysis (one in the treatment-naive group and one in the ICI-pretreated group); thus, the population evaluated for efficacy comprised 143 patients (n=22 in the treatment-naive group, n=17 in the previously treated ICI-naive group, and n=104 in the ICI-pretreated group). All 145 enrolled patients were included in the safety analysis. The median follow-up was 19·8 months (IQR 14·3-28·4). The number of patients with an objective response at week 24 by irRECIST was 16 (72·7%, 95% CI 49·8-89·3) of 22 treatment-naive patients, seven (41·2%, 18·4-67·1) of 17 previously treated ICI-naive patients, and 58 (55·8%, 45·7-65·5) of 104 ICI-pretreated patients. Of 145 patients, 82 (57%) had grade 3 treatment-related adverse events and ten (7%) had grade 4 treatment-related adverse events. The most common grade 3 treatment-related adverse event was hypertension (30 [21%] of 145 patients). Treatment-related serious adverse events occurred in 36 (25%) patients, and there were three treatment-related deaths (upper gastrointestinal haemorrhage, sudden death, and pneumonia). INTERPRETATION: Lenvatinib plus pembrolizumab showed encouraging antitumour activity and a manageable safety profile and might be an option for post-ICI treatment of metastatic RCC. FUNDING: Eisai and Merck Sharp & Dohme.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/secundário , Europa (Continente) , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
18.
J Urol ; 206(2): 209-218, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34115531

RESUMO

PURPOSE: This AUA Guideline focuses on active surveillance (AS) and follow-up after intervention for adult patients with clinically-localized renal masses suspicious for cancer, including solid enhancing tumors and Bosniak 3/4 complex cystic lesions. MATERIALS AND METHODS: In January 2021, the Renal Mass and Localized Renal Cancer guideline underwent additional amendment based on a current literature-search. This literature search retrieved additional studies published between July 2016 to October 2020 using the same Key Questions and search criteria from the Renal Mass and Localized Renal Cancer guideline. When sufficient evidence existed, the body of evidence was assigned strength-rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). RESULTS: AS with potential delayed intervention should be considered for patients with solid, enhancing renal masses <2cm or Bosniak 3-4 lesions that are predominantly-cystic. Shared decision-making about AS should consider risks of intervention/competing mortality versus the potential oncologic benefits of intervention. Recommendations for renal mass biopsy and considerations for periodic clinical/imaging-based surveillance are discussed. After intervention, risk-based surveillance protocols are defined incorporating clinical/laboratory evaluation and abdominal/chest imaging designed to detect local/systemic recurrences and possible treatment-related sequelae, such as progressive renal-insufficiency. CONCLUSION: AS is a potential management strategy for some patients with clinically-localized renal masses that requires careful risk-assessment, shared decision-making and periodic-reassessment. Follow-up after intervention is designed to identify local/systemic recurrences and potential treatment-related sequelae. A risk-based approach should be prioritized with selective use of laboratory/imaging resources.


Assuntos
Continuidade da Assistência ao Paciente , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Tomada de Decisão Clínica , Humanos , Medição de Risco , Conduta Expectante
19.
J Urol ; 206(2): 199-208, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34115547

RESUMO

PURPOSE: This AUA Guideline focuses on evaluation/counseling/management of adult patients with clinically-localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions. MATERIALS/METHODS: The Renal Mass and Localized Renal Cancer guideline underwent an update literature review which resulted in the 2021 amendment. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). RESULTS: Great progress has been made regarding the evaluation/management of clinically-localized renal masses. These guidelines provide updated, evidence-based recommendations regarding evaluation/counseling including the evolving role of renal-mass-biopsy (RMB). Given great variability of clinical/oncologic/functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Options for intervention (partial-nephrectomy (PN), radical-nephrectomy (RN), and thermal-ablation (TA)) are reviewed including recent data about comparative-effectiveness/potential morbidities. Oncologic issues are prioritized while recognizing the importance of functional-outcomes for survivorship. Granular criteria for RN are provided to help reduce overutilization of RN while also avoiding imprudent PN. Priority for PN is recommended for clinical T1a lesions, along with selective utilization of TA, which has good efficacy for tumors≤3.0 cm. Recommendations for genetic-counseling have been revised and considerations for adjuvant-therapies are addressed. Active-surveillance and follow-up after intervention are discussed in an adjunctive article. CONCLUSION: Several factors require consideration during counseling/management of patients with clinically-localized renal masses including general health/comorbidities, oncologic-considerations, functional-consequences, and relative efficacy/potential morbidities of various management-strategies.


Assuntos
Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Técnicas de Ablação , Antineoplásicos/uso terapêutico , Aconselhamento , Medicina Baseada em Evidências , Humanos , Neoplasias Renais/patologia , Nefrectomia
20.
BMJ Case Rep ; 14(6)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34158333

RESUMO

While half of the metastatic clear cell renal cell carcinomas (ccRCCs) involve the lungs, metastatic lesions have been described in various other organs, including glandular tissues such as the pancreas. Recent evidence suggests that ccRCC lesions affecting the pancreas are poorly responsive to immune checkpoint inhibition (ICI) but show superior responses to tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) signalling pathway. However, this has yet to be explored in ccRCC spreading to other glandular tissues. Here we present two cases of ccRCC with glandular metastases, the first to the pancreas and the second to the parotid gland. In both patients, ICI-based immunotherapy offered minimal clinical benefit, but both had durable responses to angiogenesis inhibitors. Given the anatomic similarity between the pancreas and parotid glands, ccRCC with involvement of the parotid gland may also benefit from VEGF-targeting TKIs as opposed to ICIs.


Assuntos
Carcinoma de Células Renais , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais , Neoplasias Pancreáticas/secundário , Neoplasias Parotídeas/secundário , Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Fator A de Crescimento do Endotélio Vascular
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