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OBJECTIVE: Evaluate the detection rates of systematic, targeted and combined cores at biopsy according to tumor positions in biopsy-naïve patients. MATERIAL AND METHODS: A retrospective analysis of a single-center patient cohort (n = 501) that underwent transrectal prostate biopsy between January 2017 and December 2019 was performed. Multi-parametric MRI was executed as a prebiopsy investigation. Biopsy protocol included, for each patient, 12 systematic cores plus 3 to 5 targeted cores per lesion identified at the mpMRI. Pearson and McNemar chi-squared tests were used for statistical analysis to compare tumor location-related detection rates of systematic, targeted and combined (systematic + targeted) cores at biopsy. RESULTS: Median age of patients was 70 years (IQR 62-72), with a median PSA of 8.5 ng/ml (IQR 5.7-15.6). Positive biopsies were obtained in 67.7% of cases. Overall, targeted cores obtained higher detection rates compared to systematic cores (54.3% vs. 43.1%, p < 0.0001). Differences in detection rates were, however, higher for tumors located at the apex (61.1% vs. 26.3%, p < 0.05) and anteriorly (44.4% vs. 19.3%, p < 0.05). Targeted cores similarly obtained higher detection rates in the posterior zone of the prostate gland for clinically significant prostate cancer. A poor agreement was reported between targeted and systematic cores for the apex and anterior zone of the prostate with, respectively κ = 0.028 and κ = -0.018. CONCLUSION: A combined approach of targeted and systematic biopsy delivers the highest detection rate in prostate cancer (PCa). The location of the tumor could however greatly influence overall detection rates, indicating the possibility to omit (as for the base or posterior zone of the gland) or add (as for the apex or anterior zone of the gland) further targeted cores.
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Biopsia Guiada por Imagen , Imágenes de Resonancia Magnética Multiparamétrica , Próstata , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Próstata/patología , Próstata/diagnóstico por imagen , Biopsia Guiada por Imagen/métodos , Biopsia con Aguja Gruesa/métodosRESUMEN
Kidney transplantation offers a longer life expectancy and a better quality of life than dialysis to patients with end-stage kidney disease. Ischemia-reperfusion injury (IRI) is thought to be a cornerstone in delayed or reduced graft function and increases the risk of rejection by triggering the immunogenicity of the organ. IRI is an unavoidable event that happens when the blood supply is temporarily reduced and then restored to an organ. IRI is the result of several biological pathways, such as transcriptional reprogramming, apoptosis and necrosis, innate and adaptive immune responses, and endothelial dysfunction. Tubular cells mostly depend on fatty acid (FA) ß-oxidation for energy production since more ATP molecules are yielded per substrate molecule than glucose oxidation. Upon ischemia-reperfusion damage, the innate and adaptive immune system activates to achieve tissue clearance and repair. Several cells, cytokines, enzymes, receptors, and ligands are known to take part in these events. The complement cascade might start even before organ procurement in deceased donors. However, additional experimental and clinical data are required to better understand the pathogenic events that take place during this complex process.
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Trasplante de Riñón , Daño por Reperfusión , Humanos , Daño por Reperfusión/metabolismo , Trasplante de Riñón/efectos adversos , AnimalesRESUMEN
Renal cell carcinoma (RCC) remains a formidable diagnostic challenge, especially in the context of small renal masses. The quest for non-invasive screening tools and biomarkers has steered research towards liquid biopsy, focusing on microRNAs (miRNAs), exosomes, and circulating tumor cells (CTCs). MiRNAs, small non-coding RNAs, exhibit notable dysregulation in RCC, offering promising avenues for diagnosis and prognosis. Studies underscore their potential across various biofluids, including plasma, serum, and urine, for RCC detection and subtype characterization. Encouraging miRNA signatures show correlations with overall survival, indicative of their future relevance in RCC management. Exosomes, with their diverse molecular cargo, including miRNAs, emerge as enticing biomarkers, while CTCs, emanating from primary tumors into the bloodstream, provide valuable insights into cancer progression. Despite these advancements, clinical translation necessitates further validation and standardization, encompassing larger-scale studies and robust evidence generation. Currently lacking approved diagnostic assays for renal cancer, the potential future applications of liquid biopsy in follow-up care, treatment selection, and outcome prediction in RCC patients are profound. This review aims to discuss and highlight recent advancements in liquid biopsy for RCC, exploring their strengths and weaknesses in the comprehensive management of this disease.
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Carcinoma de Células Renales , Neoplasias Renales , MicroARNs , Humanos , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/genética , Medicina de Precisión , Neoplasias Renales/diagnóstico , Neoplasias Renales/genética , MicroARNs/genética , Biopsia Líquida , BiomarcadoresRESUMEN
Sacral neuromodulation (SNM) offers a therapeutic approach to urological patients suffering from idiopathic overactive bladder (OAB) syndrome, with or without incontinence and non-obstructive urinary retention (NOR), who are not responding to or are not compliant with conservative or medical therapies. The exact mechanism of action of SNM is not fully understood but modulation of the spinal cord reflexes and brain networks by peripheral afferents is regarded as the main pathway. Over the years, surgical techniques improved, leading to the development of the modern two-stage implantation technique. The quadripolar lead is positioned percutaneously under fluoroscopy guidance through the third sacral foramen following the trajectory of S3. The procedure can be performed under local or general anesthesia with the patient in prone position. Current applications of sacral neuromodulation in urology are increasing thanks to the recent improvements of the devices that make this a valuable option not only in conditions such as overactive bladder and non-obstructing urinary retention but also neurogenic lower urinary tract dysfunction.
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Terapia por Estimulación Eléctrica , Vejiga Urinaria Hiperactiva , Retención Urinaria , Urología , Humanos , Vejiga Urinaria Hiperactiva/terapia , Retención Urinaria/terapia , Vejiga Urinaria , Terapia por Estimulación Eléctrica/métodos , Resultado del TratamientoRESUMEN
Prostate cancer (PCa) is the most common male malignancy and the fifth leading cause of cancer death in men worldwide. Prostate cancer cells are characterized by a hybrid glycolytic/oxidative phosphorylation phenotype determined by androgen receptor signaling. An increased lipogenesis and cholesterogenesis have been described in PCa cells. Many studies have shown that enzymes involved in these pathways are overexpressed in PCa. Glutamine becomes an essential amino acid for PCa cells, and its metabolism is thought to become an attractive therapeutic target. A crosstalk between cancer and stromal cells occurs in the tumor microenvironment because of the release of different cytokines and growth factors and due to changes in the extracellular matrix. A deeper insight into the metabolic changes may be obtained by a multi-omic approach integrating genomics, transcriptomics, metabolomics, lipidomics, and radiomics data.
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Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/metabolismo , Próstata/patología , Fosforilación Oxidativa , Transducción de Señal , Metabolómica , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Microambiente TumoralRESUMEN
We previously reported the novel finding that ß3-AR is functionally expressed in the renal tubule and shares its cellular localization with the vasopressin receptor AVPR2, whose physiological stimulation triggers antidiuresis by increasing the plasma membrane expression of the water channel AQP2 and the NKCC2 symporter in renal cells. We also showed that pharmacologic stimulation of ß3-AR is capable of triggering antidiuresis and correcting polyuria, in the knockout mice for the AVPR2 receptor, the animal model of human X-linked nephrogenic diabetes insipidus (XNDI), a rare genetic disease still missing a cure. Here, to demonstrate that the same response can be evoked in humans, we evaluated the effect of treatment with the ß3-AR agonist mirabegron on AQP2 and NKCC2 trafficking, by evaluating their urinary excretion in a cohort of patients with overactive bladder syndrome, for the treatment of which the drug is already approved. Compared to baseline, treatment with mirabegron significantly increased AQP2 and NKCC2 excretion for the 12 weeks of treatment. This data is a step forward in corroborating the hypothesis that in patients with XNDI, treatment with mirabegron could bypass the inactivation of AVPR2, trigger antidiuresis and correct the dramatic polyuria which is the main hallmark of this disease.
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Diabetes Insípida Nefrogénica , Diabetes Mellitus , Ratones , Animales , Humanos , Diabetes Insípida Nefrogénica/tratamiento farmacológico , Diabetes Insípida Nefrogénica/genética , Diabetes Insípida Nefrogénica/metabolismo , Acuaporina 2/genética , Acuaporina 2/metabolismo , Poliuria/tratamiento farmacológico , Agonistas Adrenérgicos betaRESUMEN
The term "cancer stem cell" (CSC) refers to a cancer cell with the following features: clonogenic ability, the expression of stem cell markers, differentiation into cells of different lineages, growth in nonadhesive spheroids, and the in vivo ability to generate serially transplantable tumors that reflect the heterogeneity of primary cancers (tumorigenicity). According to this model, CSCs may arise from normal stem cells, progenitor cells, and/or differentiated cells because of striking genetic/epigenetic mutations or from the fusion of tissue-specific stem cells with circulating bone marrow stem cells (BMSCs). CSCs use signaling pathways similar to those controlling cell fate during early embryogenesis (Notch, Wnt, Hedgehog, bone morphogenetic proteins (BMPs), fibroblast growth factors, leukemia inhibitory factor, and transforming growth factor-ß). Recent studies identified a subpopulation of CD133+/CD24+ cells from ccRCC specimens that displayed self-renewal ability and clonogenic multipotency. The development of agents targeting CSC signaling-specific pathways and not only surface proteins may ultimately become of utmost importance for patients with RCC.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Células Madre Neoplásicas , Biomarcadores , Diferenciación CelularRESUMEN
The crosstalk among the complement system, immune cells, and mediators of inflammation provides an efficient mechanism to protect the organism against infections and support the repair of damaged tissues. Alterations in this complex machinery play a role in the pathogenesis of different diseases. Core complement proteins C3 and C5, their activation fragments, their receptors, and their regulators have been shown to be active intracellularly as the complosome. The kidney is particularly vulnerable to complement-induced damage, and emerging findings have revealed the role of complement system dysregulation in a wide range of kidney disorders, including glomerulopathies and ischemia-reperfusion injury during kidney transplantation. Different studies have shown that activation of the complement system is an important component of tumorigenesis and its elements have been proved to be present in the TME of various human malignancies. The role of the complement system in renal cell carcinoma (RCC) has been recently explored. Clear cell and papillary RCC upregulate most of the complement genes relative to normal kidney tissue. The aim of this narrative review is to provide novel insights into the role of complement in kidney disorders.
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Carcinoma de Células Renales , Enfermedades Renales , Neoplasias Renales , Trasplante de Riñón , Daño por Reperfusión , Humanos , Trasplante de Riñón/efectos adversos , Carcinoma de Células Renales/patología , Riñón/metabolismo , Proteínas del Sistema Complemento/metabolismo , Enfermedades Renales/patología , Complemento C3/metabolismo , Daño por Reperfusión/patología , Neoplasias Renales/patología , Activación de ComplementoRESUMEN
Mucin1 (MUC1), a glycoprotein associated with an aggressive cancer phenotype and chemoresistance, is aberrantly overexpressed in a subset of clear cell renal cell carcinoma (ccRCC). Recent studies suggest that MUC1 plays a role in modulating cancer cell metabolism, but its role in regulating immunoflogosis in the tumor microenvironment remains poorly understood. In a previous study, we showed that pentraxin-3 (PTX3) can affect the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system (C1q) and releasing proangiogenic factors (C3a, C5a). In this scenario, we evaluated the PTX3 expression and analyzed the potential role of complement system activation on tumor site and immune microenvironment modulation, stratifying samples in tumors with high (MUC1H) versus tumors with low MUC1 expression (MUC1L). We found that PTX3 tissue expression was significantly higher in MUC1H ccRCC. In addition, C1q deposition and the expressions of CD59, C3aR, and C5aR were extensively present in MUC1H ccRCC tissue samples and colocalized with PTX3. Finally, MUC1 expression was associated with an increased number of infiltrating mast cells, M2-macrophage, and IDO1+ cells, and a reduced number of CD8+ T cells. Taken together, our results suggest that expression of MUC1 can modulate the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system and regulating the immune infiltrate, promoting an immune-silent microenvironment.
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Carcinoma de Células Renales , Neoplasias Renales , Mucina-1 , Microambiente Tumoral , Humanos , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/patología , Activación de Complemento , Complemento C1q/metabolismo , Neoplasias Renales/inmunología , Neoplasias Renales/patología , Macrófagos/inmunología , Mucina-1/metabolismo , Microambiente Tumoral/inmunologíaRESUMEN
Renal cancer management is challenging from diagnosis to treatment and follow-up. In cases of small renal masses and cystic lesions the differential diagnosis of benign or malignant tissues has potential pitfalls when imaging or even renal biopsy is applied. The recent artificial intelligence, imaging techniques, and genomics advancements have the ability to help clinicians set the stratification risk, treatment selection, follow-up strategy, and prognosis of the disease. The combination of radiomics features and genomics data has achieved good results but is currently limited by the retrospective design and the small number of patients included in clinical trials. The road ahead for radiogenomics is open to new, well-designed prospective studies, with large cohorts of patients required to validate previously obtained results and enter clinical practice.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Inteligencia Artificial , Estudios Retrospectivos , Estudios ProspectivosRESUMEN
MicroRNAs (miRNAs) are emerging as biomarkers for the detection and prognosis of cancers due to their inherent stability and resilience. To summarize the evidence regarding the role of urinary miRNAs (umiRNAs) in the detection, prognosis, and therapy of genitourinary cancers, we performed a systematic review of the most important scientific databases using the following keywords: (urinary miRNA) AND (prostate cancer); (urinary miRNA) AND (bladder cancer); (urinary miRNA) AND (renal cancer); (urinary miRNA) AND (testicular cancer); (urinary miRNA) AND (urothelial cancer). Of all, 1364 articles were screened. Only original studies in the English language on human specimens were considered for inclusion in our systematic review. Thus, a convenient sample of 60 original articles was identified. UmiRNAs are up- or downregulated in prostate cancer and may serve as potential non-invasive molecular biomarkers. Several umiRNAs have been identified as diagnostic biomarkers of urothelial carcinoma and bladder cancer (BC), allowing us to discriminate malignant from nonmalignant forms of hematuria. UmiRNAs could serve as therapeutic targets or recurrence markers of non-muscle-invasive BC and could predict the aggressivity and prognosis of muscle-invasive BC. In renal cell carcinoma, miRNAs have been identified as predictors of tumor detection, aggressiveness, and progression to metastasis. UmiRNAs could play an important role in the diagnosis, prognosis, and therapy of urological cancers.
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Carcinoma de Células Renales , Carcinoma de Células Transicionales , Neoplasias Renales , MicroARNs , Neoplasias de la Próstata , Neoplasias Testiculares , Neoplasias de la Vejiga Urinaria , Neoplasias Urológicas , Masculino , Humanos , MicroARNs/genética , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/terapia , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/genética , Neoplasias Renales/genética , Carcinoma de Células Renales/genética , Neoplasias de la Próstata/genética , Biomarcadores de Tumor/genéticaRESUMEN
Background and Objectives: In recent years, the prevalence of pediatric urolithiasis has increased in North America and Western countries, though it is endemic in developing countries. The aim of this study is to describe the experience of a tertiary pediatric referral center in the surgical management of pediatric urolithiasis. Materials and Methods: We retrospectively reviewed the experience of patients ≤ 16 years old affected by urinary stones who underwent surgery. Results: From April 2021 to September 2023, 31 pediatric patients underwent surgical procedures for stone diseases at our department: 13 preschool-aged (1-5 years) and 18 school-aged (6-16 years) children. During this period, 12 URSs, 17 RIRSs, and 2 PCNLs were recorded. Five patients had residual fragments at first, so three of them underwent a second endourological lithotripsy (2 RIRSs and 1 URS). Complete clearance was finally achieved in 27 patients. The stone composition was evaluated in 25 cases. Conclusions: Numerous innovations in the surgical treatment of pediatric urolithiasis have resulted from the development of smaller devices and new technology. Our results show how, in experienced centers, retrograde and percutaneous lithotripsy are safe and effective procedures for use in pediatric populations.
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Ureteroscopía , Urolitiasis , Preescolar , Niño , Humanos , Adolescente , Estudios Retrospectivos , Centros de Atención Terciaria , Urolitiasis/epidemiología , Urolitiasis/cirugía , ItaliaRESUMEN
INTRODUCTION: The association between obesity and clinically significant prostate cancer (PCa) is still a matter of debate. In this study, we evaluated the effect of body mass index (BMI) on the prediction of pathological unfavorable disease (UD), positive surgical margins (PSMs), and biochemical recurrence (BCR) in patients with clinically localized (≤cT2c) International Society of Urological Pathology (ISUP) grade group 1 PCa at biopsy. METHODS: 427 patients with ISUP grade group 1 PCa who have undergone radical prostatectomy and BMI evaluation were included. The outcome of interest was the presence of UD (defined as ISUP grade group ≥3 and pT ≥3a), PSM, and BCR. RESULTS: Statistically significant differences resulted in comparing BMI with prostate-specific antigen (PSA) and serum testosterone levels (both p < 0.0001). Patients with UD and PSM had higher BMI values (p < 0.0001 and p = 0.006, respectively). BCR-free survival was significantly decreased in patients with higher BMI values (p < 0.0001). BMI was an independent risk factor for BCR and PSM. Receiver-operating characteristic analysis testing PSA accuracy in different BMI groups, showed that PSA had a reduced predictive value (area under the curve [AUC] = 0.535; 95% confidence interval [CI] = 0.422-0.646), in obese men compared to overweight (AUC = 0.664; 95% CI = 0.598-0.725) and normal weight patients (AUC = 0.721; 95% CI = 0.660-0.777). CONCLUSION: Our findings show that increased BMI is a significant predictor of UD and PSM at RP in patients with preoperative low-to intermediate-risk diseases, suggesting that BMI evaluation may be useful in a clinical setting to identify patients with favorable preoperative disease characteristics harboring high-risk PCa.
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Índice de Masa Corporal , Prostatectomía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Anciano , Biopsia/métodos , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Prostatectomía/métodos , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
An altered metabolism is involved in the development of clear cell renal carcinoma (ccRCC). MUC1 overexpression has been found to be associated with advanced disease and poor prognosis. In this study, we evaluated the metabolomic profile of human ccRCC, according to MUC1 expression, and integrated it with transcriptomic data. Moreover, we analyzed the role of MUC1 in sustaining ccRCC aggressiveness and the prognostic value of its soluble form CA15-3. Integrated metabolomic and transcriptomic analysis showed that MUC1-expressing ccRCC was characterized by metabolic reprogramming involving the glucose and lipid metabolism pathway. In addition, primary renal cancer cells treated with a small interfering RNA targeting MUC1 (siMUC1) migrated and proliferated at a slower rate than untreated cancer cells. After cisplatin treatment, the death rate of cancer cells treated with siMUC1 was significantly greater than that of untreated cells. Kaplan-Meier curves showed significant differences in CSS and PFS among groups of patients with high versus low levels of CA15-3. In a multivariate analysis, CA15-3 was an independent adverse prognostic factor for cancer-specific and progression-free survival. In conclusion, MUC1 expressing ccRCC is characterized by a particular metabolic reprogramming. The inhibition of MUC1 expression decreases cell motility and viability and improves cisplatin susceptibility, suggesting that this pathway can regulate de novo chemotherapy resistance in ccRCC.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Cisplatino/farmacología , Cisplatino/uso terapéutico , Mucina-1/genética , Neoplasias Renales/genética , MetabolomaRESUMEN
Clear cell renal cell carcinoma (ccRCC) is the most frequent histological kidney cancer subtype. Over the last decade, significant progress has been made in identifying the genetic and metabolic alterations driving ccRCC development. In particular, an integrated approach using transcriptomics, metabolomics, and lipidomics has led to a better understanding of ccRCC as a metabolic disease. The metabolic profiling of this cancer could help define and predict its behavior in terms of aggressiveness, prognosis, and therapeutic responsiveness, and would be an innovative strategy for choosing the optimal therapy for a specific patient. This review article describes the current state-of-the-art in research on ccRCC metabolic pathways and potential therapeutic applications. In addition, the clinical implication of pharmacometabolomic intervention is analyzed, which represents a new field for novel stage-related and patient-tailored strategies according to the specific susceptibility to new classes of drugs.
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Carcinoma de Células Renales , Neoplasias Renales , Enfermedades Metabólicas , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Biomarcadores , MetabolómicaRESUMEN
Metabolomic analysis has proven to be a useful tool in biomarker discovery and the molecular classification of cancers. In order to find new biomarkers, and to better understand its pathological behavior, bladder cancer also has been studied using a metabolomics approach. In this article, we review the literature on metabolomic studies of bladder cancer, focusing on the different available samples (urine, blood, tissue samples) used to perform the studies and their relative findings. Moreover, the multi-omic approach in bladder cancer research has found novel insights into its metabolic behavior, providing excellent start-points for new diagnostic and therapeutic strategies. Metabolomics data analysis can lead to the discovery of a "signature pathway" associated with the progression of bladder cancer; this aspect could be potentially valuable in predictions of clinical outcomes and the introduction of new treatments. However, further studies are needed to give stronger evidence and to make these tools feasible for use in clinical practice.
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Neoplasias de la Vejiga Urinaria , Biomarcadores , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Masculino , Metabolómica/métodos , Enfermedades Raras , Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.
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Fosfatidilinositol 3-Quinasas , Neoplasias de la Próstata , Apoptosis , Autofagia/genética , Línea Celular Tumoral , Humanos , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
IgA nephropathy (IgAN) is a frequent cause of chronic kidney disease (CKD) and progressive renal impairment. A native renal biopsy diagnosis of IgAN is a predictor of graft loss, with a relative risk of 47% but it is difficult to predict graft survival and progressive allograft dysfunction in these patients. Deletion of complement factor H-related genes 1 and 3 (delCFHR3-1) has been associated with a decreased risk of developing IgAN on native kidneys, but the impact on the graft in IgAN-transplanted patients is unknown. We hypothesized that delCFHR3-1 is also associated with the processes that influence graft survival in transplant recipients with IgAN and tested whether cellular senescence is involved in mediating graft damage. We found that patients carrying two copies of CFHR1-3 had a worse outcome (P = .000321) and presented increased FHR1 deposits at glomerular and tubulointerstitial level associated with higher expression of the senescence marker p16INK4a (P = .001) and tubulointerstitial fibrosis (P = .005). Interestingly, FHR1 deposits were associated with increased complement activation as demonstrated by C5b-9 deposits. These data support both the role of FHR1 in mediating complement activation and tubular senescence, and suggest the possibility of genotyping delCFHR3-1 to predict graft survival in IgAN-transplanted patients.
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Glomerulonefritis por IGA , Trasplante de Riñón , Senescencia Celular , Supervivencia de Injerto , Humanos , Riñón , Trasplante de Riñón/efectos adversosRESUMEN
The adipocyte-like morphology of clear cell renal cell carcinoma (ccRCC) cells results from a grade-dependent neutral lipid accumulation; however, the molecular mechanism and role in renal cancer progression have yet to be clarified. ccRCC shows a gene expression signature consistent with adipogenesis, and the phospholipid-binding protein annexin A3 (AnxA3), a negative regulator of adipocyte differentiation, is down-regulated in RCC and shows a differential expression pattern for two isoforms of 36 and 33 kDa. Using primary cell cultures and cell lines, we investigated the involvement of AnxA3 isoforms in lipid storage modulation of ccRCC cells. We found that the increased accumulation of lipids into ccRCC cells correlated with a decrease of the 36/33 isoform ratio. Treatment with adipogenic medium induced a significant increment of lipid storage in ccRCC cells that had a low 36-kDa AnxA3 expression and 36/33 ratio. The 36-kDa AnxA3 silencing in ccRCC cells increased lipid storage induced by adipogenic medium. These data suggest that 36-kDa AnxA3 negatively modulates the response to adipogenic treatment and may act as negative regulator of lipid storage in ccRCC cells. The subcellular distribution of AnxA3 in the cellular endocytic compartment suggests its involvement in modulation of vesicular trafficking, and it might serve as a putative mechanism of lipid storage regulation in ccRCC cells, opening novel translational outcomes.
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Anexina A3/metabolismo , Carcinoma de Células Renales/metabolismo , Neoplasias Renales/metabolismo , Metabolismo de los Lípidos , Proteínas de Neoplasias/metabolismo , Anciano , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Femenino , Humanos , Isoenzimas/metabolismo , Neoplasias Renales/patología , MasculinoRESUMEN
PURPOSE: To provide a systematic analysis of the comparative outcomes of robot-assisted radical prostatectomy (RARP) versus laparoscopic radical prostatectomy (LRP) in the treatment of prostate cancer based on the best currently available evidence. METHODS: An independent systematic review of the literature was performed up to February 2021, using MEDLINE®, EMBASE®, and Web of Science® databases. Preferred reporting items for systematic review and meta-analysis (PRISMA) recommendations were followed to design search strategies, selection criteria, and evidence reports. The quality of the included studies was determined using the Newcastle-Ottawa scale for non-randomized controlled trials. Demographics and clinical characteristics, surgical, pathological, and functional outcomes were collected. RESULTS: Twenty-six studies were identified. Only 16 "high-quality" (RCTs and Newcastle-Ottawa scale 8-9) studies were included in the meta-analysis. Among the 13,752 patients included, 6135 (44.6%) and 7617 (55.4%) were RARP and LRP, respectively. There was no difference between groups in terms of demographics and clinical characteristics. Overall and major complication (Clavien-Dindo ≥ III) rates were similar in LRP than RARP group. The biochemical recurrence (BCR) rate at 12months was significantly lower for RARP (OR: 0.52; 95% CI 0.43-0.63; p < 0.00001). RARP reported lower urinary incontinence rate at 12months (OR: 0.38; 95% CI 0.18-0.8; p = 0.01). The erectile function recovery rate at 12months was higher for RARP (OR: 2.16; 95% CI 1.23-3.78; p = 0.007). CONCLUSION: Current evidence shows that RARP offers favorable outcomes compared with LRP, including higher potency and continence rates, and less likelihood of BCR. An assessment of longer-term outcomes is lacking, and higher cost remains a concern of robotic versus laparoscopic prostate cancer surgery.