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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.
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
3.
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
4.
Medicine (Baltimore) ; 100(31): e26826, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397846

RESUMO

ABSTRACT: To develop a new prognostic model for the overall survival of patients with clear cell metastatic renal cell carcinoma (mRCC) using Korean Renal Cancer Study Group (KRoCS) database and compared it with 2 renowned prognostic models: the Memorial Sloan Kettering Cancer Center (MSKCC) and the international metastatic renal cell carcinoma database consortium (IMDC) models.Data of 790 patients diagnosed with mRCC and receiving targeted therapy as their first-line treatment were pooled to this study. Data from 4 hospitals (n = 619) were used to develop the new model and those from other 5 hospitals (n = 171) were used for external validation. After detecting prognostic factors in multivariable Cox proportional-hazards regression analysis, patients were classified into 3 risk groups, favorable (0), intermediate (1-2), and poor (3 and more) by the number of prognostic factors.Seven variables such as more than 2 metastasis sites, no prior nephrectomy, Eastern Cooperative Oncology Group performance status ≥2, low hemoglobin, high serum corrected calcium, high neutrophil, high serum alkaline phosphatase were identified as prognostic factors for poor overall survival. Also, risk groups were categorized into 3 groups; median overall survival was 61.1 months in favorable, 26.5 months in intermediate, and 6.8 months in poor group. KRoCS ranked the first in all 3 statistical parameters including akaike information criterion (AIC), concordance index and generalized R2 among other prognostic models.We developed the KRoCS model and validated it externally with demonstrating its superiority over MSKCC and IMDC models. The KRoCS model can provide useful information for counseling patients with clear cell mRCC regarding life-expectancy.


Assuntos
Carcinoma de Células Renais , Expectativa de Vida , Modelos Estatísticos , Terapia de Alvo Molecular/métodos , Planejamento de Assistência ao Paciente/normas , Medição de Risco , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Melhoria de Qualidade , Reprodutibilidade dos Testes , República da Coreia/epidemiologia , Medição de Risco/métodos , Medição de Risco/normas , Fatores de Risco , Análise de Sobrevida
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.
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
8.
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
9.
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
11.
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
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.
Cancer Sci ; 112(9): 3469-3483, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34157192

RESUMO

Renal carcinoma shows a high risk of invasion and metastasis without effective treatment. Herein, we developed a chitosan (CS) nanoparticle-mediated DNA vaccine containing an activated factor L-Myc and a tumor-specific antigen CAIX for renal carcinoma treatment. The subcutaneous tumor models were intramuscularly immunized with CS-pL-Myc/pCAIX or control vaccine, respectively. Compared with single immunization group, the tumor growth was significantly suppressed in CS-pL-Myc/pCAIX co-immunization group. The increased proportion and mature of CD11c+ DCs, CD8+ CD11c+ DCs and CD103+ CD11c+ DCs were observed in the splenocytes from CS-pL-Myc/pCAIX co-immunized mice. Furthermore, the enhanced antigen-specific CD8+ T lymphocyte proliferation, cytotoxic T lymphocyte (CTL) responses, and multi-functional CD8+ T cell induction were detected in CS-pL-Myc/pCAIX co-immunization group compared with CS-pCAIX immunization group. Of note, the depletion of CD8 T cells resulted in the reduction of CD8+ T cells or CD8+ CD11c+ DCs and the loss of anti-tumor efficacy induced by CS-pL-Myc/pCAIX vaccine, suggesting the therapeutic efficacy of the vaccine was required for CD8+ DCs and CD103+ DCs mediated CD8+ T cells responses. Likewise, CS-pL-Myc/pCAIX co-immunization also significantly inhibited the lung metastasis of renal carcinoma models accompanied with the increased induction of multi-functional CD8+ T cell responses. Therefore, these results indicated that CS-pL-Myc/pCAIX vaccine could effectively induce CD8+ DCs and CD103+ DCs mediated tumor-specific multi-functional CD8+ T cell responses and exert the anti-tumor efficacy. This vaccine strategy offers a potential and promising approach for solid or metastatic tumor treatment.


Assuntos
Antígenos CD/metabolismo , Antígenos de Neoplasias/administração & dosagem , Antígenos CD8/metabolismo , Linfócitos T CD8-Positivos/imunologia , Anidrase Carbônica IX/administração & dosagem , Carcinoma de Células Renais/terapia , Quitosana/química , Células Dendríticas/imunologia , Sistemas de Liberação de Medicamentos/métodos , Imunidade , Imunização/métodos , Cadeias alfa de Integrinas/metabolismo , Neoplasias Renais/terapia , Nanopartículas/química , Proteínas Proto-Oncogênicas c-myc/administração & dosagem , Vacinas de DNA/administração & dosagem , Animais , Antígenos de Neoplasias/genética , Anidrase Carbônica IX/genética , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-myc/genética , Resultado do Tratamento , Vacinas de DNA/imunologia
15.
Radiol Med ; 126(9): 1139-1148, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34100169

RESUMO

BACKGROUND: Discrimination of low grade (grade 1-2) renal tumors from high grade (grade 3-4) ones carries crucial importance in terms of the management of these patients and also in the decision-making of appropriate treatment strategies. Our aim was to investigate whether contrast-enhanced multidetector computed tomography (MDCT) and T2 weighted fast spin echo (FSE) magnetic resonance imaging (MRI) could play a specific role in the discrimination of low grade versus high grade tumors in clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) patients. METHODS: In this study, we retrospectively evaluated 66 RCC patients based on histopathologic findings who had underwent either partial or total nephrectomies. Our cohort consisted of 52 ccRCC and 14 pRCC patients, of whom 50 were male (%76) and 16 were female (%24). Among the 52 ccRCC patients, 18 had both cortico-medullary phase contrast-enhanced CT and MRI, 15 had only cortico-medullary phase CT and 19 had only MRI examination. In the pRCC group, 8 patients had both cortico-medullary phase contrast-enhanced CT and MRI, 3 had only cortico-medullary phase CT and 3 had only MRI. We both calculated mean tumor attenuation values on cortico-medullary phase MDCT images as HU (hounsfield unit) and also tumor mean signal intensity values on FSE T2 weighted MR images, using both region of interest and whole lesion measurements including normal renal cortex. The obtained values were compared with the grading results of the ccRCC and pRCC tumors according to the WHO/International Society of Urological Pathology grading system. RESULTS: A significant positive correlation was found between the mean attenuation values of both tumor subtypes on cortico-medullary phase contrast-enhanced CT and their grades (p < 0.001). High grade tumors exhibited higher mean attenuation values (74.3 ± 22.3 HU) than the low grade tumors (55.2 ± 23.7 HU) in both subtypes. However, a statistically significant correlation was not found between the mean signal intensity values of the two tumor subtypes on FSE T2 weighted MR images and their grades (p > 0.05). Low grade tumors had a mean signal intensity value of 408.9 ± 44.6, while high grade tumors showed a value of 382.1 ± 44.2. The analysis of the ccRCC group patients, yielded a statistically significant correlation between the mean signal intensity values on T2 weighted images and tumor grading (p < 0.001). Low grade (grade 1-2) ccRCC patients exhibited higher mean signal intensity values (475.7 ± 51.3), as compared to those of high grade (grade 3-4) (418.5 ± 45.7) tumors. On the other hand, analysis of the pRCC group patients revealed that there was a significant correlation between the mean attenuation values of tumors on cortico-medullary phase contrast-enhanced CT and their grades (p < 0.001). High grade papillary subtype tumors (54.2 ± 25.2) showed higher mean attenuation values than the low grade (35.5 ± 18.8) ones. CONCLUSIONS: Contrast-enhanced MDCT and T2 weighted FSE MRI can play a considerable role in the discrimination of low grade versus high grade tumors of both subtype RCC patients. Thus, these non-invasive evaluation techniques may have positive impact on the determination of the management and treatment strategies of these patients.


Assuntos
Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada Multidetectores/métodos , Gradação de Tumores/métodos , Idoso , Carcinoma Papilar/diagnóstico por imagem , Carcinoma de Células Renais/diagnóstico por imagem , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Rim/patologia , Neoplasias Renais/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Medicine (Baltimore) ; 100(23): e26292, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34115033

RESUMO

ABSTRACT: Minute clear cell renal cell carcinoma (MccRCC) has a diameter of <1.5 cm and can be diagnosed using multi-slice spiral CT (MSCT). Recently, the role of the neutrophil-lymphocyte ratio (NLR) in the development of MccRCC has attracted attention. This study aimed to further explore the relationship between the NLR and MccRCC.This was a prospective study of 100 patients who were diagnosed with MccRCC using MSCT at Urumqi Friendship Hospital, China. The study investigated a series of pretreatment factors, including NLR and patients' general clinical data. Statistical methods employed included Pearson's chi-square test, Spearman-rho correlation test, Cox regression analysis, and receiver operator characteristic curve analysis.Based on Pearson's χ2, Spearman-rho test, and univariate/multivariate Cox regression analysis, the overall survival of patients with MccRCC was shown to be significantly related to NLR (P < .001). NLR (hazard ratio = 50.676, 95%CI, 17.543-146.390, P < .001) is a significant independent risk-factor for MccRCC. A receiver operator characteristic curve was plotted to examine specificity and sensitivity between NLR and MccRCC (area under curve = 0.958, P < .001).The level of the NLR plays a crucial role in the survival of patients with MccRCC, as diagnosed with MSCT. The higher the NLR, the worse the prognosis for patients with MccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Linfócitos/imunologia , Neutrófilos/imunologia , Tomografia Computadorizada Espiral/métodos , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , China , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/sangue , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Contagem de Leucócitos/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Sensibilidade e Especificidade
17.
Cancer Sci ; 112(8): 3136-3149, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34091990

RESUMO

Intratumoral heterogeneity, including in clear cell renal cell carcinoma, is a potential cause of drug resistance and metastatic cancer progression. We specified the heterogeneous population marked by endoglin (also known as CD105) in a preclinical model of clear cell renal cell carcinoma progression. Highly malignant derivatives of human clear cell renal cell carcinoma OS-RC-2 cells were established as OS5Ks by serial orthotopic inoculation in our previous study. Expression of both ENG (encoding endoglin) mRNA and protein were heterogeneously upregulated in OS5Ks, and the endoglin-positive (ENG+ ) population exhibited growth dependency on endoglin in anchorage-independent cultures. Despite the function of endoglin as a type III receptor, transforming growth factor ß and bone morphogenetic protein-9 signaling were unlikely to contribute to the proliferative phenotype. Although endoglin has been proposed as a marker for renal cancer-initiating cells, the OS5K-3 ENG+ population did not enrich other reported cancer-initiating cell markers or differentiate into the ENG- population. Mouse tumor inoculation models revealed that the tumor-forming capabilities of OS5K-3 ENG+ and ENG- cells in vivo were highly dependent on the microenvironment, with the renal microenvironment most preferable to ENG+ cells. In conclusion, the renal microenvironment, rather than the hypothesized ENG+ cell-centered hierarchy, maintains cellular heterogeneity in clear cell renal cell carcinoma. Therefore, the effect of the microenvironment should be considered when evaluating the proliferative capability of renal cancer cells in the experimental settings.


Assuntos
Carcinoma de Células Renais/patologia , Endoglina/genética , Endoglina/metabolismo , Neoplasias Renais/patologia , Regulação para Cima , Animais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Heterogeneidade Genética , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Masculino , Camundongos , Transplante de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Microambiente Tumoral
18.
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
19.
Acta Biochim Biophys Sin (Shanghai) ; 53(8): 988-996, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34133712

RESUMO

The ubiquitin-proteasome system (UPS) plays a central role in regulating protein homeostasis in tumor progression. The proteasome subunit Rpn10 is associated with the progression of several tumor types. However, little is known regarding the role of Rpn10 in clear cell renal cell carcinoma (ccRCC). In this study, we found that overexpression of Rpn10 increased ccRCC cell proliferation, migration, and invasion. Silencing Rpn10 expression resulted in decreased cell proli-feration, migration, and invasion in ccRCC cells. Knockdown of Rpn10 inhibits tumor growth and cell proliferation in vivo. Furthermore, we demonstrated that Rpn10 increased cell proliferation, migration, and invasion via regulation of the nuclear factor kappa B (NF-κB) pathway. Rpn10 directly promoted inhibitor of nuclear factor-kappa B alpha (IκBα) degradation through the UPS. Moreover, we observed that upregulation of Rpn10 or downregulation of IκBα in ccRCC was associated with poor prognosis. We found that the combination of these two parameters was a more powerful predictor of poor prognosis than either parameter alone. Collectively, these findings provide evidence that Rpn10 promotes the progression of ccRCC by regulation of the NF-κB pathways and is a prognostic indicator for patients with ccRCC.


Assuntos
Carcinoma de Células Renais/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/metabolismo , NF-kappa B/metabolismo , Proteínas de Ligação a RNA/biossíntese , Transdução de Sinais , Regulação para Cima , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Células HEK293 , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , NF-kappa B/genética , Proteínas de Ligação a RNA/genética
20.
Cancer Imaging ; 21(1): 42, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162442

RESUMO

BACKGROUND: The aim of the study is to compare the diagnostic value of models that based on a set of CT texture and non-texture features for differentiating clear cell renal cell carcinomas(ccRCCs) from non-clear cell renal cell carcinomas(non-ccRCCs). METHODS: A total of 197 pathologically proven renal tumors were divided into ccRCC(n = 143) and non-ccRCC (n = 54) groups. The 43 non-texture features and 296 texture features that extracted from the 3D volume tumor tissue were assessed for each tumor at both Non-contrast Phase, NCP; Corticomedullary Phase, CMP; Nephrographic Phase, NP and Excretory Phase, EP. Texture-score were calculated by the Least Absolute Shrinkage and Selection Operator (LASSO) to screen the most valuable texture features. Model 1 contains the three most distinctive non-texture features with p < 0.001, Model 2 contains texture scores, and Model 3 contains the above two types of features. RESULTS: The three models shown good discrimination of the ccRCC from non-ccRCC in NCP, CMP, NP, and EP. The area under receiver operating characteristic curve (AUC)values of the Model 1, Model 2, and Model 3 in differentiating the two groups were 0.748-0.823, 0.776-0.887 and 0.864-0.900, respectively. The difference in AUC between every two of the three Models was statistically significant (p < 0.001). CONCLUSIONS: The predictive efficacy of ccRCC was significantly improved by combining non-texture features and texture features to construct a combined diagnostic model, which could provide a reliable basis for clinical treatment options.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Radiometria/métodos , Tomografia Computadorizada por Raios X/métodos , Carcinoma de Células Renais/patologia , Diferenciação Celular , Humanos , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos
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