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BACKGROUND: Lactic acid (LA) can promote the malignant progression of tumors through the crosstalk with the tumor microenvironment (TME). However, the function of long non-coding RNAs (lncRNAs) related to LA metabolism in Wilms tumor (WT) remains unclear. METHODS: Gene expression data and clinical data of WT patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Through the ESTIMATE algorithm and Pearson correlation analysis, lncRNAs related to tumor immunity and LA metabolism were screened. Subsequently, Cox regression analysis and Lasso Cox regression analysis were used to construct a model. Furthermore, candidate genes were identified and a competitive endogenous RNA (ceRNA) network was conducted to explore the specific mechanism of characteristic genes. Finally, based on the strong clinical relevance of UNC5B-AS1, its expression and function were experimentally verified. RESULTS: The immune score and stromal score were found to be closely related to the prognosis of WT. Eventually, a prognostic model (TME-LA-LM) consisting of 6 lncRNAs was successfully identified. The model demonstrated favorable predictive ability and accuracy, with significant variation in immune infiltration and drug susceptibility observed between risk groups. Additionally, the study revealed the involvement of 2 candidate genes and 5 microRNAs (miRNAs) in the tumor's development. Notably, UNC5B-AS1 was highly expressed and found to promote the proliferation and migration of tumor cells. CONCLUSION: This study, for the first time, elucidated the prognostic signatures of WT using lncRNAs related to TME and LA metabolism. The fundings of this research offer valuable insights for future studies on immunotherapy, personalized chemotherapy and mechanism research.
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Regulación Neoplásica de la Expresión Génica , Neoplasias Renales , Ácido Láctico , ARN Largo no Codificante , Microambiente Tumoral , Tumor de Wilms , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Humanos , Tumor de Wilms/genética , Tumor de Wilms/metabolismo , Tumor de Wilms/patología , Microambiente Tumoral/genética , Ácido Láctico/metabolismo , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/metabolismo , Pronóstico , MicroARNs/genética , MicroARNs/metabolismo , Femenino , Redes Reguladoras de Genes , Masculino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismoRESUMEN
Concomitant direct oral anticoagulants (DOACs) and tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (anti-VEGF TKI) have been associated with a higher risk of bleeding. Nevertheless, concomitant administration seems frequent in clinical practice in patients with cancer-associated thrombosis and appears to be safe according to the retrospective study by Boileve A. et al. But the risk of an additional pharmacokinetic interaction between anti-VEGF TKI and DOACs must be considered, in case of P-glycoprotein (P-gp) inhibition by the TKI. We describe a case report with a major bleeding event in a renal metastatic cancer patient treated with cabozantinib and rivaroxaban. This case highlights the difficult therapeutic decision in a complex patient with cancer-associated thrombosis, who refused the anticoagulant subcutaneous route. Accumulation of bleeding risk factors (genito-urinary tumor localization) was additive to several pharmacodynamic interactions (acetylsalicylic acid, venlafaxine) and a potential pharmacokinetic interaction between cabozantinib and rivaroxaban. Indeed, cabozantinib-related P-glycoprotein inhibition could have led to a supratherapeutic level of rivaroxaban, contributing partly to the bleeding event. Before combining an anti-VEGF TKI and DOACs, a multidisciplinary pretherapeutic assessment seems crucial to evaluate the patient's bleeding risk factors, pharmacodynamic interactions, and the risk of pharmacokinetic interactions mediated by P-gp.
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Anticoagulantes , Interacciones Farmacológicas , Piridinas , Rivaroxabán , Humanos , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Estudios Retrospectivos , Piridinas/efectos adversos , Piridinas/administración & dosificación , Piridinas/uso terapéutico , Piridinas/farmacocinética , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Rivaroxabán/farmacocinética , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anilidas/administración & dosificación , Anilidas/efectos adversos , Anilidas/farmacocinética , Hemorragia/inducido químicamente , Neoplasias Renales/tratamiento farmacológico , Masculino , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacocinética , Trombosis/inducido químicamente , Trombosis/etiología , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Administración Oral , AncianoRESUMEN
In recent years, kidney cancer has shown an increased worldwide incidence of more than 400 000 novel cases annually. Although more than half of patients are diagnosed at a localised stage, this disease presents a high-risk of relapse after surgery. Thus, there is a need for adjuvant therapy post-resection to reduce cancer recurrence and prolong disease-free and overall survival. Thorough investigation of adjuvant drugs for renal cell carcinoma (RCC) has shown little promise in the last fifty years, with no recorded overall survival benefits. This was the case until pembrolizumab, an immune checkpoint inhibitor, was introduced into the adjuvant RCC space through the KEYNOTE-564 trial. The adjuvant administration of this novel anti-PD-1 drug demonstrated a significant overall survival benefit which has led to an update in the current treatment guidelines of RCC. This substantial change in the standard of care also caused an investigation of possible treatment combinations and an adoption of innovative predictive biomarkers. In this review, we will present the evolution of past adjuvant ICI trials for the treatment of RCC, the implications of pembrolizumab's overall survival benefits and a discussion of future directions concerning new RCC drug trials and liquid biopsy-based biomarkers.
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Anticuerpos Monoclonales Humanizados , Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Quimioterapia Adyuvante/métodos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéuticoRESUMEN
OBJECTIVE: This study aimed to provide valuable insights into the comparative efficacy of different surgical approaches for nephron-sparing surgery (NSS) and contribute to the existing literature in this field. MATERIALS AND METHODS: This study included patients who underwent NSS for small renal masses between January 2016 and March 2024. A total of 97 patients (41 in the open approach group, 56 in the laparoscopic approach group) with demographic, radiological, intraoperative, renal functional, and oncological follow-up data were included. Three different anatomical scoring systems (R.E.N.A.L. nephrometry score, PADUA score and C-index) were utilised to assess tumour location and estimate proximity to the hilum and collecting system. RESULTS: In the open nephron-sparing surgery (ONSS) and laparoscopic nephron-sparing surgery (LNSS) groups, the mean kidney tumour diameters (SD) were 5.20 ± 2.30 and 4.90 ± 2.10, which were similar in both surgical method groups (p = 0.061). However, tumours treated with ONSS had significantly more adverse morphometric features (p < 0.05). For ONSS and LNSS groups, the mean R.E.N.A.L. nephrometry scores (SD) were 6.15 ± 2.04 and 5.2 ± 1.4 (p = 0.032), respectively; The mean PADUA scores (SD) were 7.46 ± 1.14 and 6.8 ± 1.0 (p = 0.049), respectively; And the mean C-index (SD) scores were 1.39 ± 0.4 and 1.37 ± 0.5 (p = 0.062), respectively. No significant differences were found in the mean tumour diameter (cm) (Inter Quantile Range (IQR)) distribution of both groups (p = 0.058). Despite the slight increase in transfusion rate in the LNSS group, estimated blood loss (EBL), transfusion rates, and length of hospital stay were similar in both groups. CONCLUSIONS: Although LNSS does not appear superior in terms of intraoperative blood loss, length of hospital stay and transfusion rate, it provides comparable long-term outcomes to ONSS. Our study suggests that when matched with nephrometry scores, LNSS can achieve similar outcomes to ONSS.
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Neoplasias Renales , Laparoscopía , Nefrectomía , Nefronas , Tratamientos Conservadores del Órgano , Humanos , Laparoscopía/métodos , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Femenino , Masculino , Tratamientos Conservadores del Órgano/métodos , Persona de Mediana Edad , Nefronas/cirugía , Nefrectomía/métodos , Estudios Retrospectivos , Anciano , Resultado del TratamientoRESUMEN
BACKGROUND: Undergoing surgery for renal cell carcinoma can potentially compromise the mental well-being and overall quality of life of survivors. Long-term psychological education interventions that are delivered remotely through various modalities have shown promise in enhancing the psychological well-being and quality of life of cancer patients. This study investigates the effect of remote multimodal psychoeducational interventions on mental well-being and quality of life of renal cell carcinoma survivors. METHODS: A retrospective study was conducted to compare patients receiving remote psychological interventions (exposure group) with those receiving standard care (control group). Following the interventions, various data sets including general demographic information, and assessments from the Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), the Brief Fatigue Inventory-Chinese version (BFI-C), the Distress Thermometer (DT), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) were gathered and analysed for comparison. RESULTS: This study included 116 renal cell carcinoma survivors, with 52 in the exposure group and 64 in the control group. Baseline characteristics were not significantly different between the two groups (p > 0.05). After the intervention, the exposure group had significantly lower scores than the control group on HAMA (14.63 vs. 16.66, p < 0.001), HAMD (13.63 vs. 16.36, p < 0.001), BFI-C (52.31 vs. 57.65, p < 0.001), and DT (3.94 vs. 4.98, p < 0.001). Additionally, the exposure group had significantly higher total score of EORTC QLQ-C30 (69.22 vs. 65.59, p < 0.001) than the control group. CONCLUSIONS: Remote multimodal psychoeducational interventions demonstrate a notable impact in mitigating adverse emotions, exhaustion, and discomfort experienced by survivors of renal cell carcinoma. Such interventions should be actively promoted in clinical practice.
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Supervivientes de Cáncer , Carcinoma de Células Renales , Neoplasias Renales , Salud Mental , Educación del Paciente como Asunto , Calidad de Vida , Humanos , Estudios Retrospectivos , Masculino , Neoplasias Renales/psicología , Neoplasias Renales/cirugía , Femenino , Carcinoma de Células Renales/psicología , Carcinoma de Células Renales/cirugía , Persona de Mediana Edad , Supervivientes de Cáncer/psicología , Educación del Paciente como Asunto/métodos , Anciano , AdultoRESUMEN
PURPOSE: To compare outcomes of radical (RN) and partial nephrectomy (PN) in Sarcomatoid Renal Cell Carcinoma (sRCC) utilizing a large national cohort. As RN is the reference standard for localized RCC with clinically aggressive features, PN in sRCC has been seldom studied. METHODS: We performed a retrospective cohort analysis of the National Cancer Database from 2004 to 2019 for patients who underwent PN and RN for sRCC (T1-T3N0-N1M0). We performed multivariable analyses (MVA) to determine factors associated with PN and all-cause mortality (ACM), and Kaplan-Meier Analysis (KMA) for overall survival (OS) in Charlson 0 patients who underwent PN vs. RN according to clinical stage. RESULTS: The cohort consisted of 5,265 patients [RN 4,582 (87.0%)/PN 683 (13.0%)]. Increased odds of receiving PN was associated with papillary RCC (OR = 1.69, p = 0.015); inversely with increasing age (OR = 0.99, p = 0.004), cT2-cT3 (OR = 0.23, p < 0.001), and cN1 (OR = 0.2, p < 0.001). Worsened ACM was associated with positive margins (HR = 1.59, p < 0.001), male (HR = 1.1, p = 0.044), Charlson [Formula: see text]2 (HR = 1.47, p < 0.001), cT2-cT3 (HR 1.17-1.39, p < 0.001-0.035), and cN1 (HR = 1.59, p < 0.001). Improved ACM was noted with PN (HR = 0.64, p < 0.001), increasing household income (HR = 0.77-0.79, p < 0.001), and private insurance (HR = 0.80, p = 0.018). KMA showed PN had improved 5-year OS compared to RN in cT1 (86.5% vs. 63.2%, p < 0.001), and cT3 (61.0% vs. 44.0% p < 0.001), but not cT2 (p = 0.67). CONCLUSION: In select patients, PN with negative margins may not compromise outcomes and may provide benefit when indicated. Patients with private insurance and highest income experienced improved survival suggesting disparity in care.
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Carcinoma de Células Renales , Bases de Datos Factuales , Neoplasias Renales , Nefrectomía , Humanos , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/mortalidad , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Neoplasias Renales/mortalidad , Nefrectomía/métodos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Resultado del Tratamiento , Estados Unidos/epidemiología , Estudios de Cohortes , Tasa de SupervivenciaRESUMEN
This study investigates the intricate mechanisms underlying the correlation between elevated consumption of harmful fats and the onset of kidney malignancies. The rise in global obesity rates has been accompanied by an increased prevalence of renal cancers, prompting an exploration into the molecular pathways and biological processes linking these phenomena. Through an extensive review of current literature and clinical studies, we identify potential key factors contributing to the carcinogenic influence of harmful fats on renal tissues. Our analysis highlights the role of adipose tissue-derived factors, inflammatory mediators, and lipid metabolism dysregulation in fostering a microenvironment conducive to renal tumorigenesis. Furthermore, we delve into the impact of harmful fats on signaling pathways associated with cell proliferation, apoptosis evasion, and angiogenesis within the renal parenchyma. This review underscores the importance of elucidating the molecular intricacies linking lipid metabolism and kidney malignancies, offering a foundation for future research and the development of targeted preventive and therapeutic interventions. The findings discussed herein contribute to our understanding of the complex relationship between lipid mediators and renal cancer, providing a basis for public health strategies aimed at mitigating the impact of harmful fats on kidney health.
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Carcinoma de Células Renales , Neoplasias Renales , Metabolismo de los Lípidos , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Metabolismo de los Lípidos/fisiología , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Animales , Transducción de Señal/fisiología , Reprogramación MetabólicaRESUMEN
Objectives: To identify the cooperation of authors, countries, institutions and explore the hot spots regarding research of renal cell carcinoma with venous tumor thrombus. Methods: Relevant articles were obtained from the Web of Science Core database (WoSC) from 1999 to 2024. CiteSpace was used to perform the analysis and visualization of scientific productivity and emerging trends. Network maps were generated to evaluate the collaborations between different authors, countries, institutions, and keywords. Results: A total of 2180 related articles were identified. We observed an increased enthusiasm in related fields during the past two decades. The USA dominated the field in all countries, and the University of Miami was the core institution. Ciancio G might have a significant influence with more publications and co-citations. Current research hotspots in this field mainly included thrombectomy, tyrosine kinase inhibitors, immune checkpoint inhibitors, vena cava inferior, and microvascular invasion. Thrombectomy complications, thrombectomy survival outcome, and preoperative neoadjuvant immunotherapy represented the frontiers of research in this field, undergoing an explosive phase. Conclusion: This is the first bibliometric study that comprehensively visualize the research trends and status of RCC with VTT. We hope that this work will provide new ideas for advancing the scientific research and clinical application.
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Bibliometría , Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/terapia , Neoplasias Renales/patología , Neoplasias Renales/terapia , Neoplasias Renales/cirugía , Trombosis de la Vena/patología , Trombosis de la Vena/cirugía , Trombectomía/métodosRESUMEN
Background: Protein information is often replaced by RNA data in studies to understand cancer-related biological processes or molecular functions, and proteins of prognostic significance in Kidney clear cell carcinoma (KIRC) remain to be mined. Methods: The cancer genome atlas program (TCGA) data was utilized to screen for proteins that are prognostically significant in KIRC. Machine learning algorithms were employed to develop protein prognostic models. Additionally, immune infiltration abundance, somatic mutation differences, and immunotherapeutic responses were analyzed in various protein risk subgroups. Ultimately, the validation of protein-coding genes was confirmed by utilizing an online database and implementing quantitative real-time PCR (qRT-PCR). Results: The patients were divided into two risk categories based on prognostic proteins, and notable disparities in both overall survival (OS) and progression free interval (PFI) were observed between the two groups. The OS was more unfavorable in the high-risk group, and there was a noteworthy disparity in the level of immune infiltration observed between the two groups. In addition, the nomogram showed high accuracy in predicting survival in KIRC patients. Conclusion: In this research, we elucidated the core proteins associated with prognosis in terms of survival prediction, immunotherapeutic response, somatic mutation, and immune microenvironment. Additionally, we have developed a reliable prognostic model with excellent predictive capabilities.
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Biomarcadores de Tumor , Carcinoma de Células Renales , Neoplasias Renales , Nomogramas , Proteómica , Transcriptoma , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/inmunología , Neoplasias Renales/genética , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Neoplasias Renales/inmunología , Pronóstico , Proteómica/métodos , Biomarcadores de Tumor/genética , Femenino , Masculino , Transcriptoma/genética , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Regulación Neoplásica de la Expresión Génica , Perfilación de la Expresión Génica , Persona de Mediana Edad , Aprendizaje AutomáticoRESUMEN
Renal cell carcinoma with clear cells (ccRCC) is the most frequent kind; it accounts for almost 70% of all kidney cancers. A primary objective of current research was to find genes that may be used in ccRCC gene therapy to understand better the molecular pathways underlying the disease. Based on PubMed microarray searches and meta-analyses, we compared overall survival and recurrence-free survival rates in ccRCC patients with those in healthy samples. The technique was followed by a KEGG pathway and Gene Ontology (GO) function analyses, both performed in conjunction with the approach. Tumor immune estimate and multi-gene biomarkers validation for clinical outcomes were performed at the molecular and clinical cohort levels. Our analysis included fourteen GEO datasets based on inclusion and exclusion criteria. A meta-analysis procedure, network construction using PPIs, and four significant gene identification standard algorithms indicated that 11 genes had the most important differences. Ten genes were upregulated, and one was downregulated in the study. In order to analyze RFS and OS survival rates, 11 genes expressed in the GEPIA2 database were examined. Nearly nine of eleven significant genes have been found to beinvolved in tumor immunity. Furthermore, it was found that mRNA expression levels of these genes were significantly correlated with experimental literature studies on ccRCCs, which explained these findings. This study identified eleven gene panels associated with ccRCC growth and metastasis, as well as their immune system infiltration.
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Biomarcadores de Tumor , Carcinoma de Células Renales , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales , Biología de Sistemas , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/mortalidad , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/mortalidad , Biomarcadores de Tumor/genética , Biología de Sistemas/métodos , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes , Ontología de Genes , PronósticoRESUMEN
BACKGROUND: Sunitinib, a newly developed multi-targeted tyrosine kinase inhibitor (TKI), has become a common therapeutic option for managing advanced renal cell carcinoma (RCC). Examining the mechanism underlying the interaction between sunitinib and isavuconazole was the aim of this effort. METHODS: The concentrations of sunitinib and its primary metabolite, N-desethyl sunitinib, were analyzed and quantified using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Our study evaluated the potential interaction between isavuconazole and sunitinib using rat liver microsomes (RLM), human liver microsomes (HLM), and in vivo rat models. For the in vivo study, two groups (n = 5) of Sprague-Dawley (SD) rats were randomly allocated to receive sunitinib either with or without co-administration of isavuconazole. Additionally, the effects of isavuconazole on the metabolic stability of sunitinib and N-desethyl sunitinib were studied in RLM in vitro. RESULTS: Our findings demonstrated that in RLM, isavuconazole exhibited a mixed non-competitive and competitive inhibition mechanism, with an IC50 (half maximal inhibitory concentration) value of 1.33 µM. Meanwhile, in HLM, isavuconazole demonstrated a competitive inhibition mechanism, with an IC50 of 5.30 µM. In vivo studies showed that the presence of isavuconazole significantly increased the pharmacokinetic characteristics of sunitinib, with the AUC(0ât), AUC(0â∞), and Tmax rising to approximately 211.38%, 203.92%, and 288.89%, respectively, in contrast to the control group (5 mg/kg sunitinib alone). The pharmacokinetic characteristics of the metabolite N-desethyl sunitinib in the presence of isavuconazole remained largely unchanged compared to the control group. Furthermore, in vitro metabolic stability experiments revealed that isavuconazole inhibited the metabolic processing of both sunitinib and N-desethyl sunitinib. CONCLUSIONS: Isavuconazole had a major impact on sunitinib metabolism, providing fundamental information for the precise therapeutic administration of sunitinib.
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Interacciones Farmacológicas , Indoles , Microsomas Hepáticos , Nitrilos , Piridinas , Pirroles , Sunitinib , Triazoles , Sunitinib/farmacología , Sunitinib/farmacocinética , Animales , Piridinas/farmacocinética , Piridinas/farmacología , Ratas , Nitrilos/farmacocinética , Nitrilos/farmacología , Humanos , Microsomas Hepáticos/metabolismo , Microsomas Hepáticos/efectos de los fármacos , Pirroles/farmacocinética , Pirroles/farmacología , Triazoles/farmacocinética , Triazoles/farmacología , Indoles/farmacocinética , Indoles/farmacología , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Masculino , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/metabolismo , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/metabolismoRESUMEN
BACKGROUND: Renal epithelioid angiomyolipoma is a rare and unique subtype of classic angiomyolipoma, characterized by the presence of epithelioid cells. It often presents with nonspecific symptoms and can be easily misdiagnosed due to its similarity to renal cell carcinoma and classic angiomyolipoma in clinical and radiological features. This case report is significant for its demonstration of the challenges in diagnosing epithelioid angiomyolipoma and its emphasis on the importance of accurate differentiation from renal cell carcinoma and classic angiomyolipoma. CASE PRESENTATION: A 58-year-old Asian female presented with sudden left flank pain and was initially diagnosed with a malignant renal tumor based on imaging studies. She underwent laparoscopic radical nephrectomy, and postoperative histopathology confirmed the diagnosis of epithelioid angiomyolipoma. The patient recovered well and is currently in good health with regular follow-ups. This case highlights the diagnostic challenges, with a focus on the clinical, radiological, and histopathological features that eventually led to the identification of epithelioid angiomyolipoma. CONCLUSIONS: Epithelioid angiomyolipoma is easily misdiagnosed in clinical work. When dealing with these patients, it is necessary to make a comprehensive diagnosis based on clinical symptoms, imaging manifestations, and pathological characteristics.
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Angiomiolipoma , Carcinoma de Células Renales , Errores Diagnósticos , Neoplasias Renales , Nefrectomía , Humanos , Femenino , Angiomiolipoma/diagnóstico , Angiomiolipoma/patología , Angiomiolipoma/diagnóstico por imagen , Persona de Mediana Edad , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Rotura Espontánea , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/diagnóstico por imagen , Hemorragia , Tomografía Computarizada por Rayos X , Diagnóstico Diferencial , Dolor en el Flanco/etiología , LaparoscopíaRESUMEN
BACKGROUND: We discovered a novel human endogenous retrovirus (CT-RCC HERV-E) that was selectively expressed in most clear cell renal cell carcinomas (ccRCC) and served as a source of antigens for T cell-mediated killing. Here, we described the cloning of a novel T cell receptor (TCR) targeting a CT-RCC HERV-E-derived antigen specific to ccRCC and characterized antitumor activity of HERV-E TCR-transduced T cells (HERV-E T cells). METHODS: We isolated a CD8+ T cell clone from a patient with immune-mediated regression of ccRCC post-allogeneic stem cell transplant that recognized the CT-RCC-1 HERV-E-derived peptide in an HLA-A11-restricted manner. We used 5'Rapid Amplification of cDNA Ends (RACE) to clone the full length HERV-E TCR and generated retrovirus encoding this TCR for transduction of T cells. We characterized HERV-E T cells for phenotype and function in vitro and in a murine xenograft model. Lastly, we implemented a good manufacturing practice-compliant method for scalable production of HERV-E T cells. RESULTS: The HLA-A11-restricted HERV-E-reactive TCR exhibited a CD8-dependent phenotype and demonstrated specific recognition of the CT-RCC-1 peptide. CD8+ T cells modified to express HERV-E TCR displayed potent antitumor activity against HLA-A11+ ccRCC cells expressing CT-RCC HERV-E compared with unmodified T cells. Killing by HERV-E T cells was lost when cocultured against HERV-E knockout ccRCC cells. HERV-E T cells induced regression of established ccRCC tumors in a murine model and improved survival of tumor-bearing mice. Large-scale production of HERV-E T cells under good manufacturing practice conditions generated from healthy donors retained specific antigen recognition and cytotoxicity against ccRCC. CONCLUSIONS: This is the first report showing that human ccRCC cells can be selectively recognized and killed by TCR-engineered T cells targeting a HERV-derived antigen. These preclinical findings provided the foundation for evaluating HERV-E TCR-transduced T cell infusions in patients with metastatic ccRCC in a clinical trial (NCT03354390).
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Carcinoma de Células Renales , Retrovirus Endógenos , Neoplasias Renales , Receptores de Antígenos de Linfocitos T , Humanos , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/terapia , Animales , Ratones , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/metabolismo , Neoplasias Renales/inmunología , Neoplasias Renales/terapia , Ensayos Antitumor por Modelo de Xenoinjerto , Línea Celular Tumoral , Linfocitos T CD8-positivos/inmunologíaRESUMEN
Introduction: Kidney cancer (KC) is a significant health burden globally, with over 400,000 new cases estimated in 2020. The prognosis of KC is influenced by various factors, including tumor spread, pathological characteristics, and molecular genetic changes. Recent studies have emphasized the involvement of gut microbiota and the immune system's contribution in the onset of KC. This extensive research endeavor sought to investigate the potential associations between diverse immune cell phenotypes, specific gut microbiota species, and their impact on the risk of developing KC, alongside the examination of circulating inflammatory proteins. Methods: Adhering to the STROBE-MR guidelines, our investigation involved a two-stage Mendelian randomization (2SMR) analysis grounded on three fundamental assumptions: relevance, independence, and exclusion restriction. The exposure data utilized in this study originated from genome-wide association studies (GWAS) specifically designed to explore immune traits, inflammatory proteins, and gut microbiota compositions. Results: Our analysis identified 25 immune phenotypes, 4 circulating inflammatory proteins, and 12 gut microbiota features that exhibited significant causal associations with KC (P < 0.05). 10 immune phenotypes were protective against KC, while 15 were risk factors. Among the inflammatory proteins, CCL28 and IL-2 were protective, whereas FGF-23 and ß-NGF were risk factors. Gut microbiota features associated with reduced KC risk included biosynthetic pathways involving amino acids and specific bacterial genera, whereas others, like Butyrivibrio crossotus and Odoribacter splanchnicus, were risk factors. Conclusion: Immune, inflammatory, and gut microbiota factors impact KC development. Identified factors hint at biomarkers and therapeutic targets. It is very important to understand the relationship between these factors and KC.
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Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Neoplasias Renales , Análisis de la Aleatorización Mendeliana , Humanos , Neoplasias Renales/inmunología , Neoplasias Renales/genética , Neoplasias Renales/microbiología , Microbioma Gastrointestinal/inmunología , Factores de RiesgoRESUMEN
OBJECTIVES: To assess the efficacy and safety of preoperative neoadjuvant everolimus in renal angiomyolipomas (AML) patients with or without Tuberous Sclerosis Complex (TSC). MATERIALS AND METHODS: This multi-institutional retrospective study enrolled renal AML patients who underwent partial nephrectomy (PN) or total nephrectomy after receiving at least 1 month of pre-operative everolimus. Imaging evaluations were collected before and after treatment, along with demographic, surgical, and follow-up information. The primary outcome was tumor volume reduction of ≥25%, with additional outcomes including recurrence, perioperative outcomes, renal function, and safety. RESULTS: From January 2015 to July 2022, 68 renal AML patients were studied-41 with TSC and 27 without. During everolimus treatment, 61.0% (25/41) of TSC patients and 44.4% (12/27) of non-TSC patients achieved tumor reduction of ≥25%. Additionally, 41.5% (17/41) of TSC patients and 18.5% (5/27) of non-TSC patients achieved a ≥ 50% reduction. Three TSC patients and 1 non-TSC patient discontinued treatment due to side-effects. Most patients (92.7% TSC, 85.2% non-TSC) underwent PN. After everolimus treatment, the necessary total nephrectomy decreased to 41.2% (7/17) from baseline. Postoperatively, 1 grade 3 and 3 grade 2 complications occurred, with no grade 4 or 5 complications. After a median follow-up of 24 months, only 1 TSC patient recurred with a diameter >3 cm. Retrospective nature is the major limitation of this study. CONCLUSION: Everolimus was effective and well-tolerated in neoadjuvant treatment for renal AML, especially in TSC patients. This neoadjuvant combination strategy of everolimus and PN could effectively controls recurrence and preserves renal function.
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Angiomiolipoma , Everolimus , Neoplasias Renales , Terapia Neoadyuvante , Nefrectomía , Esclerosis Tuberosa , Humanos , Everolimus/uso terapéutico , Everolimus/administración & dosificación , Everolimus/efectos adversos , Angiomiolipoma/tratamiento farmacológico , Angiomiolipoma/patología , Femenino , Masculino , Estudios Retrospectivos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/tratamiento farmacológico , Adulto , Resultado del Tratamiento , AncianoRESUMEN
BACKGROUND: The population diagnosed with renal cell carcinoma, especially in Asia, represents 36.6% of global cases, with the incidence rate of renal cell carcinoma in Korea steadily increasing annually. However, treatment options for renal cell carcinoma are diverse, depending on clinical stage and histologic characteristics. Hence, this study aims to develop a machine learning based clinical decision-support system that recommends personalized treatment tailored to the individual health condition of each patient. RESULTS: We reviewed the real-world medical data of 1,867 participants diagnosed with renal cell carcinoma between November 2008 and June 2021 at the Pusan National University Yangsan Hospital in South Korea. Data were manually divided into a follow-up group where the patients did not undergo surgery or chemotherapy (Surveillance), a group where the patients underwent surgery (Surgery), and a group where the patients received chemotherapy before or after surgery (Chemotherapy). Feature selection was conducted to identify the significant clinical factors influencing renal cell carcinoma treatment decisions from 2,058 features. These features included subsets of 20, 50, 75, 100, and 150, as well as the complete set and an additional 50 expert-selected features. We applied representative machine learning algorithms, namely Decision Tree, Random Forest, and Gradient Boosting Machine (GBM). We analyzed the performance of three applied machine learning algorithms, among which the GBM algorithm achieved an accuracy score of 95% (95% CI, 92-98%) for the 100 and 150 feature sets. The GBM algorithm using 100 and 150 features achieved better performance than the algorithm using features selected by clinical experts (93%, 95% CI 89-97%). CONCLUSIONS: We developed a preliminary personalized treatment decision-support system (TDSS) called "RCC-Supporter" by applying machine learning (ML) algorithms to determine personalized treatment for the various clinical situations of RCC patients. Our results demonstrate the feasibility of using machine learning-based clinical decision support systems for treatment decisions in real clinical settings.
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Carcinoma de Células Renales , Sistemas de Apoyo a Decisiones Clínicas , Neoplasias Renales , Aprendizaje Automático , Humanos , Carcinoma de Células Renales/terapia , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/terapia , Neoplasias Renales/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , República de Corea , Toma de Decisiones Clínicas , Anciano , AdultoRESUMEN
PURPOSE: We aimed to develop and externally validate a CT-based deep learning radiomics model for predicting overall survival (OS) in clear cell renal cell carcinoma (ccRCC) patients, and investigate the association of radiomics with tumor heterogeneity and microenvironment. METHODS: The clinicopathological data and contrast-enhanced CT images of 512 ccRCC patients from three institutions were collected. A total of 3566 deep learning radiomics features were extracted from 3D regions of interest. We generated the deep learning radiomics score (DLRS), and validated this score using an external cohort from TCIA. Patients were divided into high and low-score groups by the DLRS. Sequencing data from the corresponding TCGA cohort were used to reveal the differences of tumor heterogeneity and microenvironment between different radiomics score groups. What's more, univariate and multivariate Cox regression were used to identify independent risk factors of poor OS after operation. A combined model was developed by incorporating the DLRS and clinicopathological features. The SHapley Additive exPlanation method was used for interpretation of predictive results. RESULTS: At multivariate Cox regression analysis, the DLRS was identified as an independent risk factor of poor OS. The genomic landscape of different radiomics score groups was investigated. The heterogeneity of tumor cell and tumor microenvironment significantly varied between both groups. In the test cohort, the combined model had a great predictive performance, with AUCs (95%CI) for 1, 3 and 5-year OS of 0.879(0.868-0.931), 0.854(0.819-0.899) and 0.831(0.813-0.868), respectively. There was a significant difference in survival time between different groups stratified by the combined model. This model showed great discrimination and calibration, outperforming the existing prognostic models (all p values < 0.05). CONCLUSION: The combined model allowed for the prognostic prediction of ccRCC patients by incorporating the DLRS and significant clinicopathologic features. The radiomics features could reflect the tumor heterogeneity and microenvironment.
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Carcinoma de Células Renales , Neoplasias Renales , Tomografía Computarizada por Rayos X , Microambiente Tumoral , Humanos , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/mortalidad , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/mortalidad , Femenino , Masculino , Persona de Mediana Edad , Pronóstico , Tomografía Computarizada por Rayos X/métodos , Aprendizaje Profundo , Anciano , Estudios Retrospectivos , RadiómicaRESUMEN
BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the predominate histological type of renal cell carcinoma (RCC), has been extensively studied, with poor prognosis as the stage increases. Research findings consistently indicated that the PI3K-Akt pathway is commonly dysregulated across various cancer types, including ccRCC. Targeting the PI3K-Akt pathway held promise as a potential therapeutic approach for treating ccRCC. Development and validation of PI3K-Akt pathway-related genes related biomarkers can enhance healthcare management of patients with ccRCC. PURPOSE: This study aimed to identify the key genes in the PI3K-Akt pathway associated with the diagnosis and prognosis of CCRCC using data mining from the Cancer Genome Atlas (TCGA) and Gene Expression Synthesis (GEO) datasets. METHODS: The purpose of this study is to use bioinformatics methods to screen data sets and clinicopathological characteristics associated with ccRCC patients. The exhibited significantly differential expressed genes (DEGs) associated with the PI3K-Akt pathway were examined by KEGG. In addition, Kaplan-Meier (KM) analysis used to estimate the survival function of the differential genes by using the UALCAN database and graphPad Prism 9.0. And exploring the association between the expression levels of the selected genes and the survival status and time of patients with ccRCC based on SPSS22.0. Finally, a multigene prognostic model was constructed to assess the prognostic risk of ccRCC patients. RESULTS: A total of 911 genes with common highly expressed were selected based on the GEO and TCGA databases. According to the KEGG pathway analysis, there were 42 genes enriched in PI3K-Akt signalling pathway. And seven of highly expressed genes were linked to a poor prognosis in ccRCC. And a multigene prognostic model was established based on IL2RG, EFNA3, and MTCP1 synergistic expression might be utilized to predict the survival of ccRCC patients. CONCLUSIONS: Three PI3K-Akt pathway-related genes may be helpful to identify the prognosis and molecular characteristics of ccRCC patients and to improve therapeutic regimens, and these risk characteristics might be further applied in the clinic.
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Biomarcadores de Tumor , Carcinoma de Células Renales , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/mortalidad , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pronóstico , Neoplasias Renales/genética , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Biomarcadores de Tumor/genética , Transducción de Señal/genética , Masculino , Femenino , Biología Computacional , Perfilación de la Expresión Génica , Bases de Datos Genéticas , Persona de Mediana Edad , Estimación de Kaplan-MeierRESUMEN
Objectives: Renal cell carcinoma (RCC) is a leading urological malignancy with an age-standardised incidence rate of 2.5 per 100,000 per year in Oman. Experts are inclined towards the early detection and use of minimally invasive technology for the treatment of RCC. This study aimed report the shifting trend in the clinical presentation and management of RCC in Oman, comparing the outcomes of laparoscopic and open nephrectomy. Methods: This retrospective study included adult RCC patients from Sultan Qaboos University Hospital, Muscat, Oman, diagnosed from 2011-2022. Patient biodata, mode of presentation, diagnostic modality, final histopathology and details of treatment received including the perioperative outcomes were analysed. Results: A total of 56 patients that underwent surgical treatment for RCC, 34 underwent laparoscopic nephrectomy (LN) and 22 underwent open nephrectomy (ON). The mean ages in the LN and ON groups were 53.82 ± 13.44 years and 56.22 ± 15.00 years (P = 0.53), respectively. There were 47 patients of Omani descent and 9 patients were expatiates. The patients' mean tumour size was 6.25 ± 3.16 cm and 9.23 ± 5.20 cm for the LN and ON groups, respectively; 55.35% of the RCC cases were incidentally diagnosed. A trend towards LN was observed. Conclusion: This study found a trend towards early diagnosis of RCC in Oman, with the majority of cancers being discovered incidentally in the studied period. LN is more commonly used in the surgical management of RCC with acceptable morbidity. These trends remain aligned with those found in the global literature on RCC.