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1.
Isr Med Assoc J ; 22(5): 285-288, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32378819

RESUMO

BACKGROUND: Heart transplantation (HT) success rate is limited by a high incidence of cancer post-HT. Data on kidney cancer following solid organ transplantation, especially HT, are limited, and only a few cases have been reported. OBJECTIVES: To report a unique case series of detected kidney cancer following HT. METHODS: Between 1997 and 2018, 265 patients who underwent HT were enrolled and prospectively followed in the HT registry of the Sheba Medical Center. RESULTS: The series included 5 patients, 4 men and a woman (age range 35-50 years at HT). The patients were diagnosed with kidney tumors 6-11 years after HT (age range at diagnosis 40-72 years). Two of the men were identical twin brothers. At HT four patients received induction therapy with anti-thymocyte globulin and all received an initial immunosuppressive regimen based on cyclosporine. All male HT recipients had a history of heavy smoking. Two male patients developed allograft vasculopathy, but all had preserved heart function. The 72-year-old woman developed a kidney tumor of the native kidney 5 years after re-HT and kidney transplantation. Two patients had features of multifocal papillary renal cell carcinoma (RCC) and eventually underwent bilateral nephrectomy, while another patient underwent left partial nephrectomy with preserved renal function. CONCLUSIONS: To the best of our knowledge, this is the first case series study describing kidney tumors following HT. With the improving outcomes and life expectancy of HT patients, a better understanding of the factors that determine cancer risk is of the utmost importance and may have a major impact on the non-cardiac surveillance.


Assuntos
Transplante de Coração , Neoplasias Renais/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
2.
Medicine (Baltimore) ; 99(19): e19943, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384440

RESUMO

RATIONALE: The preoperative diagnosis of massive pulmonary tumor embolism associated with renal neoplasms is relatively rare. In most cases, pulmonary tumor embolism is detected intraoperatively during renal tumor resection. Moreover, primary renal sarcoma is rare, and primary renal sarcoma complicated by pulmonary tumor embolism is extremely rare; accordingly, there is no optimal treatment for such cases. Herein, we report a case of renal sarcoma associated with pulmonary tumor embolism. PATIENT CONCERNS: A 39-year-old man was admitted to the emergency room owing to the sudden onset of dyspnea and palpitation. DIAGNOSIS: Contrast-enhanced computed tomography (CT) revealed a large mass in the right kidney involving the infrahepatic inferior vena cava, with massive pulmonary emboli in both the pulmonary arteries. INTERVENTIONS: Emergency pulmonary embolectomy with radical nephrectomy was performed. OUTCOMES: The patient experienced apparent remission of dyspnea, and resolution of right ventricle dysfunction. However, although remnant emboli were detected in the segmental arteries on postoperative CT, complete resolution of pulmonary embolism was observed after adjuvant chemotherapy. LESSONS: Thus, concomitant cytoreductive nephrectomy with pulmonary embolectomy along with chemotherapy may be effective for patients with renal sarcoma with pulmonary tumor embolism.


Assuntos
Neoplasias Renais/complicações , Neoplasias Pulmonares/complicações , Embolia Pulmonar/etiologia , Sarcoma/complicações , Adulto , Embolectomia/métodos , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Masculino , Nefrectomia/métodos , Artéria Pulmonar/patologia , Embolia Pulmonar/patologia , Embolia Pulmonar/cirurgia , Sarcoma/secundário , Sarcoma/cirurgia , Veia Cava Inferior/patologia
3.
Medicine (Baltimore) ; 99(19): e20071, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384474

RESUMO

Renal cell carcinoma (RCC) is known to be more prevalent in autosomal dominant polycystic kidney disease (ADPKD) patients than in the general population. However, little is known about genetic alterations or changes in signaling pathways in RCC in patients with ADPKD.In the current report, whole-exome and transcriptome sequencing was performed for paired samples of tumor tissue, cyst tissue, and peripheral blood (triple set) from a patient diagnosed with ADPKD and RCC.A 68-year-old man with ADPKD underwent left partial nephrectomy and was diagnosed with RCC. DNA and RNA were extracted from the triple set of the patient. A nonsense mutation in PKD2 (p.Arg742X), which is well known as a pathogenic variant in ADPKD, was identified in the paired triple set. In the tumor sample, a somatic missense mutation of VHL (p.S65L) was found, which is known as a pathogenic mutation in Von Hippel-Lindau syndrome and RCC. Furthermore, loss of chromosome 3p, where VHL is located, was detected. Upregulated VEGFA was found in the analysis of RCC mRNA, which might be caused by the loss of VHL and accelerate angiogenesis in RCC.Proliferation was also expected to be activated by the MAPK signaling pathway, including NRAS and MAPK1 expression.


Assuntos
Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/genética , Neoplasias Renais/complicações , Neoplasias Renais/genética , Mutação , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/genética , Idoso , Humanos , Masculino
4.
Aging (Albany NY) ; 12(8): 6518-6535, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32339157

RESUMO

Angiotensin-converting enzyme 2 (ACE2) is a member of the renin-angiotension system, however, the correlation between ACE2 and prognosis in UCEC (Uterine Corpus Endometrial Carcinoma) and KIRP (Kidney Renal Papillary Cell Carcinoma) is not clear. We analyzed the expression levels of ACE2 in the Oncomine and TIMER databases, the correlation between ACE2 and overall survival in the PrognoScan, GEPIA and Kaplan-Meier plotter databases. The correlation between ACE2 and immune infiltration level and the type markers of immune cells was investigated in TIMER database. A prognosis analysis based on the expression levels of ACE2 was further performed in related immune cells subgroup. The ACE2 promoter methylation profile was tested in the UALCAN database. In addition, we used GSE30589 and GSE52920 databases to elucidate the changes of ACE2 expression in vivo and in vitro after SARS-CoV infection. ACE2 was elevated in UCEC and KIRP, and high ACE2 had a favorable prognosis. The expression of ACE2 was positively correlated with the level of immune infiltration of macrophage in KIRP, B cell, CD4+T cell, neutrophil and dendritic cell immune infiltration levels in UCEC. ACE2 was significantly positively correlated with the type markers of B cells and neutrophils, macrophages in UCEC, while ACE2 in KIRP was positively correlated with the type markers of macrophages. High ACE2 expression level had a favorable prognosis in different enriched immune cells subgroups in UCEC and KIRP. And the promoter methylation levels of ACE2 in UCEC and KIRP were significantly reduced. What's more, we found that the expression of ACE2 decreased in vivo and in vitro after SARS-CoV infection. In conclusion, ACE2 expression increased significantly in UCEC and KIRP, elevated ACE2 was positively correlated with immune infiltration and prognosis. Moreover, tumor tissues may be more susceptible to SARS-CoV-2 infection in COVID-19 patients with UCEC and KIRP, which may worsen the prognosis.


Assuntos
Betacoronavirus , Carcinoma de Células Renais , Infecções por Coronavirus , Neoplasias do Endométrio , Imunidade Celular , Neoplasias Renais , Pandemias , Peptidil Dipeptidase A/biossíntese , Pneumonia Viral , Biomarcadores Tumorais , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Prognóstico
5.
G Ital Nefrol ; 37(2)2020 Apr 09.
Artigo em Italiano | MEDLINE | ID: mdl-32281759

RESUMO

Renal cell carcinoma (RCC) is the deadliest of all urogenital tumors, whereas it is the third for incidence after prostate and bladder cancer. An early diagnosis of RCC allows patients affected to be promptly treated with effective therapies, significantly increasing their survival rate. In addition, an early and accurate diagnosis avoids inadequate treatment, helps predict disease progression and establish the most appropriate treatments. Unfortunately, small renal tumors are usually asymptomatic, which results in a late diagnosis and, therefore, a low efficacy of treatment. Sensitive biomarkers are thus essential for early detection of RCC and for monitoring its progression. This review summarizes recent discoveries relating to renal tumor biomarkers, their diagnostic and prognostic values, and clinical feasibility.


Assuntos
Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Biomarcadores Tumorais/análise , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Progressão da Doença , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Prognóstico , Taxa de Sobrevida
6.
Medicine (Baltimore) ; 99(16): e19838, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32312006

RESUMO

Renal cell carcinoma (RCC) has been traditionally thought to be radioresistant. This retrospective cohort study aims to assess the outcomes of patients with spinal metastases from RCC treated with conventionally-fractionated external beam radiation therapy (cEBRT) in our institution.Patients diagnosed with histologically or radiologically-proven RCC who received palliative cEBRT to spinal metastases, using 3-dimensional conformal technique between 2009 and 2018 were reviewed. Local progression-free survival (PFS), overall survival (OS) and common terminology criteria for adverse events version 4.0-graded toxicity were assessed. Univariable and multivariable Cox proportional hazards regression analyses were performed to evaluate for predictors associated with survivals.Thirty-five eligible patients with forty spinal segments were identified, with a median follow-up of 7 months (range, 0-47). The median equivalent dose in 2 Gy fractions (EQD2) was 32.5 Gy 10 (range, 12-39). Thirty-seven percent of patients underwent surgical intervention. At the time of last follow-up, all but 1 patient had died. Seven patients developed local progression, with the median time to local progression of 10.2 months. The median local PFS and OS were 3.3 and 4.8 months. There was no grade 3 or higher toxicity. A higher radiation dose (equivalent dose to 2 Gy fraction <32.5 Gy 10 vs ≥32.5Gy 10) (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.17-3.18; P-value (P) = .68) and spinal surgery (HR, 2.35; 95% CI, 0.53-10.29; P = .26) were not significantly associated with local PFS on univariable analysis. Multivariable analysis showed that higher Tokuhashi score (HR, 0.41; 95% CI, 0.19-0.88; P = .02), lower number of spinal segments irradiated (HR, 1.18; 95% CI, 1.01-1.37; P = .04) and use of targeted therapy (HR, 0.41; 95% CI, 0.18-0.96; P = .04) were independent predictors for improved OS.For an unselected group of patients with RCC, there is no significant association between higher radiation dose and improved local control following cEBRT. This may be due to their short survivals. With the use of more effective systemic therapy, including targeted therapy and immunotherapy, survival will likely be prolonged. A tailored-approach is needed to identify patients with good prognosis who may still benefit from aggressive local treatments.


Assuntos
Carcinoma de Células Renais/complicações , Radiocirurgia/métodos , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunoterapia/métodos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Intervalo Livre de Progressão , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/cirurgia , Coluna Vertebral/patologia , Coluna Vertebral/efeitos da radiação , Resultado do Tratamento
7.
Nat Cell Biol ; 22(4): 476-486, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32231310

RESUMO

SLC7A11-mediated cystine uptake is critical for maintaining redox balance and cell survival. Here we show that this comes at a significant cost for cancer cells with high levels of SLC7A11. Actively importing cystine is potentially toxic due to its low solubility, forcing cancer cells with high levels of SLC7A11 (SLC7A11high) to constitutively reduce cystine to the more soluble cysteine. This presents a significant drain on the cellular NADPH pool and renders such cells dependent on the pentose phosphate pathway. Limiting glucose supply to SLC7A11high cancer cells results in marked accumulation of intracellular cystine, redox system collapse and rapid cell death, which can be rescued by treatments that prevent disulfide accumulation. We further show that inhibitors of glucose transporters selectively kill SLC7A11high cancer cells and suppress SLC7A11high tumour growth. Our results identify a coupling between SLC7A11-associated cystine metabolism and the pentose phosphate pathway, and uncover an accompanying metabolic vulnerability for therapeutic targeting in SLC7A11high cancers.


Assuntos
Sistema y+ de Transporte de Aminoácidos/genética , Carcinoma de Células Renais/genética , Cistina/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Via de Pentose Fosfato/genética , Sistema y+ de Transporte de Aminoácidos/antagonistas & inibidores , Sistema y+ de Transporte de Aminoácidos/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Dissulfetos/metabolismo , Fármacos Gastrointestinais/farmacologia , Glucose/deficiência , Transportador de Glucose Tipo 1/antagonistas & inibidores , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 3/antagonistas & inibidores , Transportador de Glucose Tipo 3/genética , Transportador de Glucose Tipo 3/metabolismo , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Camundongos , Camundongos Nus , Fosfogluconato Desidrogenase/genética , Fosfogluconato Desidrogenase/metabolismo , Pirazóis/farmacologia , Quinolinas/farmacologia , Estresse Fisiológico , Sulfassalazina/farmacologia , Análise de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Medicine (Baltimore) ; 99(16): e19725, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32311963

RESUMO

The aim of this study was to discriminate malignant and benign clinical T1 renal masses on routinely acquired computed tomography (CT) images using radiomics and machine learning techniques.Adult patients undergoing surgical resection and histopathological analysis of clinical T1 renal masses were included. Preoperative CT studies in venous phase from multiple referring centers were included, without restriction to specific CT scanners, slice thickness, or degrees of artifacts. Renal masses were segmented and 120 standardized radiomic features extracted. Machine learning algorithms were used to predict malignancy of renal masses using radiomics features and cross-validation. Diagnostic accuracy of machine learning models and assessment by independent blinded radiologists were compared based on the gold standard of histopathologic diagnosis.A total of 94 patients met inclusion criteria (benign renal masses: n = 18; malignant: n = 76). CT studies from 18 different scanners were assessed with median slice thickness of 2.5 mm and artifacts in 15 cases (15.9%).Area under the receiver-operating-characteristics curve (AUC) of random forest (random forest [RF], AUC = 0.83) was significantly higher compared to the radiologists (AUC = 0.68, P = .047). Sensitivity was significantly higher for RF versus radiologists (0.88 vs 0.80, P = .045), whereas specificity was numerically higher for RF (0.67 vs 0.50, P = .083).Although limited by an overall small sample size and few benign renal tumors, a radiomic features and machine learning approach suggests a high diagnostic accuracy for discrimination of malignant and benign clinical T1 renal masses on venous phase CT. The presented algorithm robustly outperforms human readers in a real-life scenario with nonstandardized imaging studies from various referring centers.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Aprendizado de Máquina , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
9.
Zhonghua Yi Xue Za Zhi ; 100(14): 1068-1071, 2020 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-32294868

RESUMO

Objective: To determine the status of bone metastasis (BM) and prognosis factors of patients with renal cell carcinoma (RCC) in our center. Methods: The clinical and medical records of RCC patients with BM, who were admitted to the Department of Urology, Bone Oncology and Spine Surgery, Beijing Jishuitan Hospital from August 2009 to August 2017 were collected. The gender, age, time of BM, location of BM, numbers of BM, presence or absence of visceral metastasis, pathological types of BM were investigated. The patients were followed up regularly, and the survival curves were analyzed by Kaplan-Meier method. Cox proportional hazard regression model was used to estimate the prognostic factors. Results: A total of 51 RCC patients with bone metastasis were collected. The age of patients ranged from 38 to 76 (58.6±8.2) years old, including 39 males (76.5%) and 12 females (23.5%). The ratio of male to female was 3.25∶1. The patients were followed up for 8 to 109 months, with a median follow-up time of 30 months. The follow-up rate was 90.2%. Thirty-one (60.8%) patients died at the last follow-up, with a median overall survival (OS) time of 25 months. The median OS was 38 months and 20 months in the solitary BM group (26 cases, 51.0%) and BM ≥ 2 group (25 cases, 49.0%), respectively. The difference between the two groups was statistically significant (P=0.021). The median OS was 30 months, 69 months and 17 months in the axis BM group (22 cases, 43.1%), appendicular BM group (19 cases, 37.3%) and both the axis and appendicular BM group (10 cases, 19.6%), respectively. The difference between the groups was statistically significant (P=0.012). The median OS was 22 months and 38 months in the patients with (15 cases, 29.4%) and without (36 cases, 70.6%) visceral metastases groups, respectively. The difference between the two groups was statistically significant (P=0.007). Univariate and multivariate Cox regression analysis showed that the numbers of BM (HR=3.130, 95%CI: 1.502-6.520, P=0.035) and visceral metastasis (HR=4.699, 95%CI: 1.810-9.545, P=0.001) were independent prognostic factors for RCC with BM. Conclusions: Solitary BM, no visceral metastasis are good prognostic factors for RCC with BM. For these patients, radical resection of BM is feasible to improve survival rate.


Assuntos
Neoplasias Ósseas , Carcinoma de Células Renais , Neoplasias Renais , Adulto , Idoso , Neoplasias Ósseas/secundário , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
10.
Zhonghua Bing Li Xue Za Zhi ; 49(4): 324-328, 2020 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-32268668

RESUMO

Objective: To describe our experiences in application of the 2019 revision of "CCCG-WT-2016" for the diagnosis of Wilms tumors. Methods: Ninety-one cases of Wilms tumor diagnosed at Shanghai Children's Medical Center from January 2015 to December 2018 were collected. All cases were reviewed by two senior pathologists, including one from China and the other from Singapore, according to the 2019 revision of "CCCG-WT-2016." Results: The specimens were obtained by core biopsy (n=21), primary nephrectomy (n=41), post-chemotherapy nephrectomy/resection (n=18), or biopsy/resection of metastatic/relapse/post-chemotherapy metastatic lesion(s) (n=11). The specimens of core biopsy and primary nephrectomy (n=62) all had favorable histology.Twelve post-chemotherapy nephrectomy cases were subdivided into three risk groups: low risk (n=0), intermediate risk (n=10) and high risk (n=2). Six post-chemotherapy resection cases were subdivided into 3 risk groups:low risk (n=0), intermediate risk (n=5) and high risk (n=1). The remaining 11 cases were comprised of metastatic, relapse, and post-chemotherapy metastatic lesions. The concordance rate of the two senior pathologists was 100%(91/91). Conclusions: The 2019 revision of "CCCG-WT-2016" is clearly written and easy to use. It can serve as the basis of accurate classification for clinical treatment.


Assuntos
Neoplasias Renais , Tumor de Wilms , Quimioterapia Adjuvante , China , Humanos , Neoplasias Renais/terapia , Estadiamento de Neoplasias , Nefrectomia , Tumor de Wilms/terapia
11.
13.
Isr Med Assoc J ; 22(4): 244-248, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32286029

RESUMO

BACKGROUND: Pancreatic injuries during nephrectomy are rare, despite the relatively close anatomic relation between the kidneys and the pancreas. The data regarding the incidence and outcome of pancreatic injuries are scarce. OBJECTIVES: To assess the frequency and the clinical significance of pancreatic injuries during nephrectomy. METHODS: A retrospective analysis was conducted of all patients who underwent nephrectomy over a period of 30 years (1987-2016) in a large tertiary medical center. Demographic, clinical, and surgical data were collected and analyzed. RESULTS: A total of 1674 patients underwent nephrectomy during the study period. Of those, 553 (33%) and 294 patients (17.5%) underwent left nephrectomy and radical left nephrectomy, respectively. Among those, four patients (0.2% of the total group, 0.7% of the left nephrectomy group, and 1.36% of the radical left nephrectomy) experienced iatrogenic injuries to the pancreas. None of the injuries were recognized intraoperatively. All patients were treated with drains in an attempt to control the pancreatic leak and one patient required additional surgical interventions. Average length of stay was 65 days (range 15-190 days). Mean follow-up was 23.3 months (range 7.7-115 months). CONCLUSIONS: Pancreatic injuries during nephrectomy are rare and carry a significant risk for postoperative morbidity.


Assuntos
Carcinoma de Células Renais/cirurgia , Doença Iatrogênica , Neoplasias Renais/cirurgia , Nefrectomia/efeitos adversos , Pâncreas/lesões , Pancreatopatias/etiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Estudos de Coortes , Tratamento Conservador/métodos , Feminino , Seguimentos , Humanos , Israel , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Pancreatopatias/mortalidade , Pancreatopatias/terapia , Reoperação/métodos , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Taxa de Sobrevida , Centros de Atenção Terciária
14.
Wiad Lek ; 73(1): 12-16, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32124799

RESUMO

OBJECTIVE: The aim: to study the association between rs1899663-polymorphic variant of HOTAIR gene and clear cell renal cell carcinoma (CCRCC) development in Ukrainian population. PATIENTS AND METHODS: Materials and methods: whole venous blood from 101 Ukrainians with CCRCC (42 females and 59 males) and 100 control subjects (34 females and 66 males) were enrolled in the study. DNA extraction was performed using GeneJET Whole Blood Genomic DNA Purification Mini Kit (Thermo Fisher Scientific, USA). Polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) was used for HOTAIR rs1899663 genotyping. The Statistical Package for Social Science software (SPSS, version 17.0, Chicago, IL, USA) was used for all calculations. RESULTS: Results: It was found the lack of association between HOTAIR rs1899663 single nucleotide polymorphism and CCRCC emergence as well as tumor metastasis property in dominant, recessive, over-dominant and additive crude models of inheritance, as well after the adjustment for age, sex, smoking and excessive alcohol consumption (P > 0.05). CONCLUSION: Conclusions: No association was found between HOTAIR rs1899663-polymorphic variant and CCRCC development in Ukrainian population. Further studies with extended samples are required to validate these results.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino
15.
Harefuah ; 159(3): 170-174, 2020 Mar.
Artigo em Hebraico | MEDLINE | ID: mdl-32186786

RESUMO

INTRODUCTION: Until recently, radical nephroureterectomy was considered the gold standard treatment for upper tract urothelial carcinoma (UTUC). Post-operative complications, long-term adverse effects of nephrectomy as well as the risk of contralateral recurrence have led to the development of nephron-sparing techniques. OBJECTIVES: To evaluate the safety, complication rate, and oncologic outcomes of ureteroscopic nephron-sparing treatment for low-grade UTUC utilizing a hybrid laser system that incorporates two types of lasers: Nd:YAG and Ho:YAG. METHODS: We reviewed the files of patients who underwent ureteroscopic treatment for UTUC with the hybrid laser system between the years 2014-2018. Only cases of low-grade UTUC and follow-up time of at least 6 months were included in the present study. The following were analyzed: demographic data, tumor histologic characteristics, peri-operative complications, histologic upgrade, oncologic outcomes (i.e: local recurrence, local spread, metastatic progression). RESULTS: A total of 38 patients, who underwent 74 ureteroscopies, met inclusion criteria. Mean tumor size was 16.2 mm. No intra-operative complications were recorded. Two post-operative complications were recorded in one patient - hematuria and retroperitoneal bleeding - both had been treated conservatively. Mean follow-up time was 21.8 months. Local recurrence rate was 73%. Histologic upgrade has been observed in two patients. Four patients (10.5%) were referred to radical nephroureterectomy. There were no cases of local spread, distant metastases or death during the follow-up period. DISCUSSION: Endoscopic dual-laser treatment for low-grade UTUC is safe, surgically feasible and associated with good short-term oncologic outcome. Patient selection and strict follow-up are mandatory.


Assuntos
Carcinoma de Células de Transição/diagnóstico , Terapia a Laser , Neoplasias Urológicas/diagnóstico , Carcinoma de Células de Transição/terapia , Endoscopia , Humanos , Neoplasias Renais , Recidiva Local de Neoplasia , Nefrectomia , Estudos Retrospectivos , Ureteroscopia , Neoplasias Urológicas/terapia
16.
Nat Cell Biol ; 22(4): 465-475, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32203421

RESUMO

Advanced clear cell renal cell carcinoma (ccRCC) frequently causes systemic inflammation. Recent studies have shown that cancer cells reshape the immune landscape by secreting cytokines or chemokines. This phenotype, called cancer-cell-intrinsic inflammation, triggers a metastatic cascade. Here, we identified the functional role and regulatory mechanism of inflammation driven by advanced ccRCC cells. The inflammatory nature of advanced ccRCC was recapitulated in a preclinical model of ccRCC. Amplification of cancer-cell-intrinsic inflammation during ccRCC progression triggered neutrophil-dependent lung metastasis. Massive expression of inflammation-related genes was transcriptionally activated by epigenetic remodelling through mechanisms such as DNA demethylation and super-enhancer formation. A bromodomain and extra-terminal motif inhibitor synchronously suppressed C-X-C-type chemokines in ccRCC cells and decreased neutrophil-dependent lung metastasis. Overall, our findings provide insight into the nature of inflammatory ccRCC, which triggers metastatic cascades, and suggest a potential therapeutic strategy.


Assuntos
Carcinoma de Células Renais/genética , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , Animais , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Linhagem Celular Tumoral , Quimiocinas CXC/genética , Quimiocinas CXC/metabolismo , Progressão da Doença , Perfilação da Expressão Gênica , Humanos , Inflamação , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Proteínas de Neoplasias/metabolismo , Neutrófilos/metabolismo , Neutrófilos/patologia , Prognóstico , Análise de Sobrevida , Microambiente Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Zhonghua Bing Li Xue Za Zhi ; 49(3): 244-249, 2020 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-32187896

RESUMO

Objective: To investigate the clinicopathological features,diagnosis and differential diagnosis of renal angiomyolipoma with epithelial cysts(AMLEC). Methods: Four cases of renal AMLEC diagnosed between January 2014 and June 2019 at the Department of Pathology,Zhejiang Provincial People's Hospital were subjected to clinicopathological, histological and immunohistochemistry analyses along with a literature review. Results: All the four patients were females and aged from 19 to 52 years (mean 34.5 years). Three cases were accidentally discovered by physical examination, and the medical history was 1 to 6 years. The preoperative imaging Bosniak classification was grade Ⅲ in 3 and grade Ⅳ in 1 case. The maximum diameter of the tumor ranged from 2.5 to 9.0 cm (average 5.0 cm). Histologically, all of the 4 tumors showed three histological components: (1) simple epithelial cysts lined by a layer of cuboidal/low-columnar to occasionally, hobnailcells; (2) a thin, compact subepithelial "cambium-like" layer of cellular, mullerian-like short spindle cell stromas with prominent admixedchronic inflammation; (3) a outermost layer of thick, long-fascicles of smooth muscle-like stromas, often surrounded by dysplastic, tortuous thick-walled blood vessels. There was often a prominent lymphatic channel network in the smooth muscle component forming slit like branched and curvilinear spaces. None of the 4 tumors had fat content.Immunohistochemically, the epithelial cells lining the cysts strongly expressed PAX8 and CK7. The subepithelial "cambium-like" stromas strongly expressed melanocytic markers (HMB45, Melan A, Cathspin K, MiTF) and mullerian markers (ER,PR,CD10), and were negative for smooth-muscle markers(SMA,desmin,calponin). The outermost layer of smooth muscle-like stromas strongly expressed smooth-muscle markers, and were only focally positive for melanocytic and mullerian markers. Follow-up information was obtained in 3 cases, among which no evidence of tumor recurrence or metastasis was found at 3, 5, and 66 months of follow-up, respectively. Conclusions: Renal AMLEC is a rare histological subtype of angiomyolipoma with benign biological behavior, and has characteristic histological and immunophenotypic characteristics.Pathologists should be familiar with the clinicopathological appearances of AMLEC and include it in the differential diagnostic spectrums of renal tumors with biphasic epithelial and mesenchymal features.


Assuntos
Angiomiolipoma , Cistos , Neoplasias Renais , Adulto , Biomarcadores Tumorais , Feminino , Humanos , Imuno-Histoquímica , Antígeno MART-1 , Pessoa de Meia-Idade , Adulto Jovem
19.
Crit Rev Oncol Hematol ; 149: 102921, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32172222

RESUMO

Patients diagnosed with non-clear renal cell carcinoma have often been excluded from clinical trials due to the shortage of treatments available, the low incidence of tumours with non-clear histology, and the corresponding diversity of intrinsic molecular features. This approach led to a knowledge gap in finding the optimal treatment for patients diagnosed with non-clear cell renal carcinoma. Cabozantinib, a potent multiple tyrosine kinase receptor inhibitor, has been recently investigated in patients with non-clear cell histologies of renal cell cancer. In this review, we have summarized available data on the use of cabozantinib in non-clear renal cell carcinoma.


Assuntos
Anilidas/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Piridinas/uso terapêutico , Intervalo Livre de Doença , Humanos , Inibidores de Proteínas Quinases
20.
Mol Genet Genomics ; 295(3): 807-824, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32185457

RESUMO

Patterns of DNA methylation are significantly altered in cancers. Interpreting the functional consequences of DNA methylation requires the integration of multiple forms of data. The recent advancement in the next-generation sequencing can help to decode this relationship and in biomarker discovery. In this study, we investigated the methylation patterns of papillary renal cell carcinoma (PRCC) and its relationship with the gene expression using The Cancer Genome Atlas (TCGA) multi-omics data. We found that the promoter and body of tumor suppressor genes, microRNAs and gene clusters and families, including cadherins, protocadherins, claudins and collagens, are hypermethylated in PRCC. Hypomethylated genes in PRCC are associated with the immune function. The gene expression of several novel candidate genes, including interleukin receptor IL17RE and immune checkpoint genes HHLA2, SIRPA and HAVCR2, shows a significant correlation with DNA methylation. We also developed machine learning models using features extracted from single and multi-omics data to distinguish early and late stages of PRCC. A comparative study of different feature selection algorithms, predictive models, data integration techniques and representations of methylation data was performed. Integration of both gene expression and DNA methylation features improved the performance of models in distinguishing tumor stages. In summary, our study identifies PRCC driver genes and proposes predictive models based on both DNA methylation and gene expression. These results on PRCC will aid in targeted experiments and provide a strategy to improve the classification accuracy of tumor stages.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Metilação de DNA , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/patologia , Carcinoma Papilar/genética , Carcinoma de Células Renais/genética , Estudos de Casos e Controles , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Renais/genética , Regiões Promotoras Genéticas , Transcriptoma
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