Search Results (195)

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer subtype and, in most cases, it is incidentally diagnosed, as early-stage disease is often asymptomatic. Therefore, the identification of stable, noninvasive biomarkers is a major unmet clinical need. Urinary microRNAs (miRNAs) have emerged as promising candidates since they are extraordinarily stable in urine and show a close relationship with tumour biology. Methods: In this study, urinary expression levels of five miRNAs (miR-15a, miR-15b, miR-16, miR-210, and miR-let-7b) were analysed in RCC patients before surgery, 5 days after, and one month after surgery, and compared to healthy controls. Results: Non-parametric analyses revealed significant postoperative decreases for miR-15a (p = 0.002), miR-16 (p = 0.025), miR-210 (p = 0.030), and in the overall miRNA Sum (p = 0.002), suggesting that these miRNAs are directly linked to tumour presence. In the comparison between preoperative and one-month postoperative samples, miR-let-7b (p = 0.049) and the global miRNA Sum (p = 0.037) remained significantly reduced after intervention, indicating a partial normalisation of urinary miRNA profiles. Correlation analyses demonstrated positive associations between specific miRNAs and clinical parameters such as age, ischemia time, and surgical time, reinforcing their potential relevance to tumour biology and treatment response. Conclusions: These findings support urinary miRNAs as promising, minimally invasive biomarkers for ccRCC diagnosis and postoperative monitoring. Full article

Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer and is marked by pronounced intra-tumoural heterogeneity that complicates therapeutic response. Patient-derived organoids offer a physiologically relevant model to capture this diversity and evaluate treatment effects. When integrated with spatial transcriptomics, they might enable the mapping of spatially resolved transcriptional and isoform-level changes within the tumour microenvironment. Methods: We established a robust workflow for generating patient-derived ccRCC organoids, that are not passaged and retain original cellular components. These retain key features of the original tumours, including cancer cell, stromal, and immune components. Results: Spatial transcriptomic profiling revealed multiple transcriptionally distinct regions within and across organoids, reflecting the intrinsic heterogeneity of ccRCC. Isoform-level analysis identified spatially variable expression of glutaminase (GLS) isoforms, with heterogeneous distributions of both the GAC and KGA variants. Treatment with NUC-7738, a phosphoramidate derivative of 3′-deoxyadenosine, induced marked transcriptional remodelling of organoids, including alterations in ribosomal and mitochondrial gene expression. Conclusions: This study demonstrates that combining long-read spatial transcriptomics with patient-derived organoid models provides a powerful and scalable approach for dissecting gene and isoform-level heterogeneity in ccRCC and for elucidating spatially resolved transcriptional responses to novel therapeutics. Full article

Introduction: Radiotracer-based nuclear imaging, including positron emission tomography (PET) and single-photon emission computed tomography (SPECT), can complement conventional cross-sectional imaging in renal cell carcinoma (RCC) by providing biological characterisation of tumour metabolism, angiogenesis, hypoxia, and the tumour microenvironment. While computed tomography (CT) and magnetic resonance imaging (MRI) remain the diagnostic standard, accumulating evidence suggests that selected nuclear imaging techniques may offer incremental value in specific clinical scenarios. Methods: A narrative literature review was performed using PubMed, Embase, and Web of Science to identify preclinical, retrospective, and prospective studies evaluating PET and SPECT radiotracers in localised and metastatic RCC. Priority was given to meta-analyses, multicentre prospective trials, and studies with histopathological correlation. Results: [¹⁸F]fluorodeoxyglucose (FDG) PET/CT demonstrates limited sensitivity for primary renal tumours (pooled sensitivity of approximately 60%) but performs substantially better in metastatic and recurrent disease (pooled sensitivity and specificity of approximately 85–90%), where uptake correlates with tumour grade, progression-free survival, and overall survival. [^99mTc]sestamibi SPECT/CT differentiates oncocytoma and hybrid oncocytic/chromophobe tumours from malignant RCC with pooled sensitivity and specificity of around 85–90%, supporting its role in evaluating indeterminate renal masses rather than staging. Prostate-specific membrane antigen (PSMA) PET/CT shows high detection rates in clear-cell RCC, particularly in metastatic disease, with reported sensitivities of approximately 85–90% and management changes in up to 40–50% of selected cohorts. Carbonic anhydrase IX (CAIX)-targeted PET/CT enables the biologically specific visualisation of clear-cell RCC, achieving sensitivities and specificities in the range of 85–90% in prospective phase II and III trials for primary tumour characterisation. Fibroblast activation protein inhibitor (FAPI) PET/CT demonstrates high tumour-to-background uptake in early RCC studies, but evidence remains preliminary, with small cohorts and recognised non-specific uptake in benign inflammatory and fibrotic conditions. Conclusions: Radiotracer-based nuclear imaging provides complementary, biology-driven insights in RCC that extend beyond anatomical assessment. While most modalities remain adjunctive or investigational and are not recommended for routine use, selective application in carefully chosen clinical scenarios may enhance tumour characterisation, prognostication, and personalised treatment planning. Full article

Renal cell carcinoma (RCC) is a biologically heterogeneous malignancy accounting for 3% of adult cancers globally. Despite advances in immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor (VEGF)-targeted therapies, durable disease control remains elusive for many patients. Increasing evidence implicates the acidic tumour microenvironment (TME) as a critical mediator of RCC progression, immune evasion, and therapeutic resistance. Solid tumours, including RCC, exhibit reversed pH gradients, characterised by acidic extracellular (pH 6.2–6.9) and alkaline intracellular conditions. This dysregulation arises from enhanced glycolysis, hypoxia-driven lactate accumulation, and the overexpression of pH-regulating enzymes such as carbonic anhydrase (CA9). Acidic TMEs impair cytotoxic T-cell and NK-cell activity, promote tumour-associated macrophage (TAM) polarisation towards an immunosuppressive phenotype, and upregulate alternative immune checkpoints. These mechanisms collectively undermine ICI efficacy and contribute to primary and secondary treatment resistance. Proton-sensing G-protein-coupled receptors (GPCRs), notably GPR65, have emerged as pivotal mediators linking extracellular acidosis to immune dysfunction. Preclinical studies demonstrate that GPR65 antagonists restore anti-tumour immune activity by reversing acidosis-driven immunosuppression and enhancing antigen processing. In RCC models, selective GPR65 inhibitors have shown the ability to reduce immunosuppressive cytokine IL-10 production, induce immunoproteasome activation, and synergise with anti-PD-1 therapy. The first-in-class GPR65 inhibitor, PTT-4256, is now under evaluation in the Phase I/II RAISIC-1 trial (NCT06634849) in solid tumours, including RCC. Targeting acid-sensing pathways represents a novel and promising therapeutic strategy in RCC, aiming to remodel the TME and overcome ICI resistance. Integrating GPR65 inhibition with existing immunotherapies may define the next era of RCC management, warranting continued translational and clinical investigation. Full article

Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that has become central to prostate cancer (PCa) diagnostics and treatment. Beyond its enzymatic role in folate and glutamate metabolism, PSMA is upregulated in advanced PCa, where it contributes to angiogenesis, tumour progression, and therapeutic resistance. This review integrates current understanding of PSMA biology with an emphasis on the role of PSMA expression and the hallmarks of cancer-proliferative signalling, metabolic adaptation, and evasion of cell death. While PSMA has revolutionised theranostic strategies in PCa, its utility as a sole biomarker is limited in select cases such as neuroendocrine differentiation and discordant disease biology. To address these challenges, we highlight emerging biomarkers and novel imaging markers that complement PSMA, including genomic alterations, circulating tumour markers, and exosomal microRNAs. Advances in radiomics and dual-tracer positron emission tomography (PET) further refine patient selection by capturing aggressive low-PSMA phenotypes. Furthermore, PSMA-PET is showing promise in other malignancies, including renal cell carcinoma (RCC) and glioblastoma multiforme (GBM), where neovasculature expression may extend its theranostic applications beyond PCa. By situating PSMA within this broader biomarker landscape, we outline opportunities for theranostic integration, including predictive models, combination therapies and expansion into non-prostate malignancies. Understanding the biology of PSMA in conjunction with novel biomarkers provides a framework for optimising theranostic applications and advancing personalised cancer care. Full article

Background and Objectives: Multiple myeloma (MM) remains an incurable plasma cell malignancy with heterogeneous clinical outcomes. Although current prognostic systems integrate biochemical and cytogenetic parameters, they do not fully capture disease complexity. Adipocytes within the bone marrow microenvironment secrete adipokines that regulate inflammation, metabolism, and immune interactions and may influence disease progression. This study aimed to assess circulating adipokines and related microenvironmental mediators as potential biomarkers of disease activity and treatment response in MM. Materials and Methods: In this case–control, cross-sectional study, the serum levels of eight adipokine-related molecules—adiponectin, leptin, resistin, chemerin, adipsin, thrombospondin-1 (TSP-1), paraoxonase-1 (PON-1), and myeloperoxidase (MPO)—were measured in 40 MM patients and 38 age- and sex-matched healthy controls. Enzyme-linked immunosorbent assays (ELISA) and bead-based multiplex immunoassays were used. Associations with prognostic markers (serum β₂-microglobulin (sB2M), LDH, albumin, hemoglobin, renal function) and treatment response were analyzed using correlation and non-parametric statistical methods. Results: Compared to the controls, MM patients exhibited significantly higher circulating levels of adiponectin, resistin, chemerin, adipsin, TSP-1, and MPO, while leptin was decreased. Among clinical correlations, chemerin and PON-1 correlated positively with sB2M, TSP-1 correlated with LDH, and MPO correlated with M-protein and albumin. Resistin was lower in patients with renal impairment and an advanced disease stage. Adiponectin and TSP-1 were significantly lower in progressive disease compared to complete remission, suggesting their potential association with treatment response. Conclusions: This study demonstrates that multiple adipokines are dysregulated in MM and exhibit distinct associations with disease burden, renal function, and therapeutic response. Novel associations identified for TSP-1, PON-1, and adipsin highlight previously unrecognized microenvironmental pathways in MM biology. Adipokine profiling may complement established prognostic markers and provide new insights into the tumour microenvironment in MM. Full article

Background and Objectives: Robotic-assisted partial nephrectomy (RAPN) is a preferred minimally invasive option for renal tumours, but its use in highly complex cases (RENAL score ≥ 9) remains underexplored. Only four Asian countries, India, China, South Korea, and Japan, have published studies on RAPN for complex kidney tumours, highlighting limited evidence. The aim of this study is to assess the perioperative, functional, and oncological effects of RAPN for complex renal tumours at a single tertiary centre in Malaysia. Materials and Methods: Patient demographics, tumour characteristics, perioperative parameters, and postoperative results were collected through a retrospective review that was conducted on 35 patients who had undergone RAPN between January 2023 and June 2024. The outcomes were analyzed using descriptive statistics, correlation analysis, and comparative tests between surgical approaches (transperitoneal vs. retroperitoneal). Results: Of the 35 patients, all had high-complexity tumours. RAPN achieved a “trifecta” outcome in 88.6% of patients. Significantly lower intraoperative blood loss is associated with the retroperitoneal approach in comparison with the transperitoneal approach, whereas other perioperative parameters, which include warm ischaemia time, did not show any significant differences. No positive surgical margins were observed, and no local recurrences or port-site metastases were detected during a mean follow-up of 11.31 ± 5.78 months. Postoperative changes in renal function were negligible, with a mean creatinine change of 5.69 ± 20.39 µmol/L. Conclusions: RAPN is a safe and effective option for complex renal tumours, offering excellent functional and oncological outcomes. The choice between transperitoneal and retroperitoneal approaches should be tailored to tumour characteristics for optimal surgical outcomes. This single-centre Malaysian study contributes to the limited Southeast Asian literature on RAPN for complex renal tumours. Full article

Robotic-assisted surgery has gradually established its role in uro-oncological cases that demand a high level of precision, optimising surgeon ergonomics and decreasing fatigue whilst maintaining optimal clinical outcomes. With the novel Hinotori surgical robot (Medicaroid Corporation (Kobe, Hyogo, Japan)) launched in Japan back in 2019, it has now demonstrated its use case across various clinical series of different surgeries. We sought to narratively synthesise the initial feasibility of the Hinotori robotic system in urology. A systematic, comprehensive literature search was conducted across various databases from September 2024 to October 2024. Relevant keywords within the scope of this study were generated for a more accurate search. After exclusion and removal of duplicates, a total of nine articles were included for review. Among the included studies, one study reported data solely on radical prostatectomy for prostate cancer, two studies reported on robotic-assisted nephroureterectomy for renal tumours, two studies reported on partial nephrectomy performed for renal masses, two studies reported on radical nephrectomy carried out for renal malignancies and one study reported on robotic-assisted adrenalectomy for adrenal cancer. Lastly, one study collectively reported on outcomes pertaining to partial nephrectomy, partial nephrectomy, vesicourethral anastomosis and pelvic lymph node dissection in a porcine model, as well as partial nephrectomy, radical prostatectomy and pelvic lymph node dissection in cadavers. The current literature supports its non-inferiority to the well-established Da Vinci system, with no major drawbacks or concerns identified when comparing parameters such as intraoperative time, estimated blood loss (EBL), perioperative events (transfusions, conversion to open surgery), length of hospital stay and major postoperative complications. Future studies involving larger cohorts and more complex surgical cases are essential to further evaluate the efficacy and safety of the Hinotori system. The new Hinotori robotic system offers unique three-dimensional features as a non-inferior robotic platform alternative that has proven clinically safe thus far in its use. Larger scale studies and randomised trials are eagerly awaited to assess and validate more holistically its clinical utility. Full article

Renal cell carcinoma (RCC) has a well-established propensity to form grossly visible tumour thrombi; however a comprehensive understanding of the underlying mechanisms is still lacking. The epithelial–mesenchymal transition (EMT) has been implicated in the progression of many carcinomas, including RCC; however, its exact role in the formation of venous tumour thrombi remains unclear. This study aims to explore the involvement of the EMT in venous invasion in RCC. In 14 patients with WHO/ISUP grade 2/3 clear cell RCC with venous invasion, the expression of main EMT markers (the miR-200 family, miR-205, SNAI1/2, TWIST1, ZEB2, and CDH1) was analyzed by qPCR in the selected tumour regions—the tumour centre (TC), the tumour periphery (TP), the venous tumour thrombus (VTT)—and compared to the corresponding non-neoplastic kidney tissue (N). Expression of E-cadherin, N-cadherin, and ZEB2 was analyzed immunohistochemically. The miR-200 family was downregulated in all areas examined compared to the corresponding N. When comparing the VTT with the TC, upregulation of miR-200c and miR-429 was observed. CDH1 was downregulated when the TP was compared with N, while SNAI2 was downregulated in all tumour regions. There was a strong correlation between the expression of all members of the miR-200 family. Our results demonstrate the presence of distinct molecular signatures between the selected ccRCC regions. The upregulation of two miRNAs in the VTT compared to the TC and their correlation with CDH1 expression could indicate a reversal of the EMT towards a more epithelial cell state in the VTT. Full article

Renal cell carcinoma (RCC) is a major global health issue with an increasing incidence and mortality rate. Current diagnostic methods are either invasive or limited in their ability to accurately differentiate between benign and malignant tumours and to predict early treatment response. This can lead to incorrect diagnosis, delayed treatment, patient anxiety, and suboptimal outcomes. RCC subtypes are known to exhibit distinct metabolic alterations, for example in glucose metabolism. These metabolic phenotypes offer potential targets for non-invasive imaging techniques to improve diagnosis and treatment, but current clinically available metabolic imaging tools such as ¹⁸F-FDG-PET and ^99mTc-sestamibi SPECT have limitations. Therefore, new approaches are required to assess this metabolism, and novel metabolic MRI techniques including hyperpolarised [1-¹³C]pyruvate MRI and deuterium metabolic imaging offer promising alternatives. These techniques are non-radioactive, demonstrate spatial metabolic heterogeneity, and can probe metabolic flux beyond tracer uptake. This review aims to explore the potential of metabolic MRI in the clinical management of RCC by (1) summarising current clinical guidelines; (2) reviewing metabolic heterogeneity across RCC subtypes; (3) discussing the potential of metabolic MRI to advance the understanding of in vivo metabolism; (4) and finally suggesting future directions for research in this field. Full article

During the 70 years since the Balkan endemic nephropathy was recognised, failure to make a universal diagnostic cause continues for some critical researchers. Claims for cause by toxic molecules from microorganisms and/or plants are difficult to verify experimentally in retrospect, partly because no lifetime human experimentation is possible and partly since no experimental source is a convincing model. Apoptosis as a primary step in human nuclear decline has been a source of experiments for many years. Now, one has been used, which employs the detection of abnormal nuclear hydroxyls by using an Abcam histology protocol. Recent access to a few human tissues diagnosed for the Balkan nephropathy has enabled preliminary exploration to publish some positive human manifestations of apoptosis. Parallel use and positive findings have also now illustrated applications to experimental rats’ kidneys after daily dietary exposure to ochratoxin A in lifetime experiments. Focus on renal cortical nephrons and their nuclei reveals a TUNEL-stained pattern with intensity linked to many months of the sub-clinical ochratoxin dietary exposure. The pattern survives long after exposure, but where experimental rats have internally developed cancer did not arise outside the kidney. Our experimental rat findings could not attribute the mechanism for the very different human urothelial tumours to traces of dietary ochratoxin A, but the present study encourages the exploration of more archived Balkan nephropathy renal cases to predict the focal urothelial origin of early tumours. Full article

Approximately 5% to 8% of patients with Wilms tumour have bilateral disease. The prevalence of bilateral Wilms tumour (BWT) is higher in individuals with genetic predisposition syndromes than in those without. The goal of therapy is to preserve as much renal tissue as possible without compromising the overall oncological outcomes, utilising neoadjuvant chemotherapy followed by nephron sparing surgery (NSS) if possible. The Children’s Oncology Group (COG) in North America and the International Society of Paediatric Oncology (SIOP) in Europe have developed the main protocols for the treatment of BWT. Both protocols are similar: initial biopsies are not indicated, and they both recommend surgical resection at week 6 or no later than week 12. Chemotherapy includes the use of vincristine and actinomycin-D in both protocols, but the COG approach also includes the use of doxorubicin, which is a cardiotoxic drug with important long-term effects on the cardiac function of childhood cancer survivors. What doxorubicin adds to patients with BWT in terms of radiological tumour response, resectability, long-term renal function and overall survival, is still not very well described and it may be variable depending on the tumour biology. This article describes the current approach for BWT in North America and Europe, focusing on the potential effect that doxorubicin may have on patient outcomes. Full article

Mammary tumours are the most common neoplasia in adult female dogs. Mastectomy leads to moderate to severe pain. Effective pain management is crucial in veterinary medicine. This review outlines analgesic techniques for managing perioperative pain in dogs undergoing mastectomy. A literature search on dog mastectomy analgesia was conducted from January 2001 to January 2025. Pre-emptive meloxicam reduces postoperative cardiovascular changes without affecting renal function. When combined with gabapentin, it lowers the need for rescue analgesic opioids, similar to robenacoxib. With regard to tramadol, it offers contrasting analgesia in the studies considered when used alone, while its effect appears enhanced when used in combination with meloxicam/dipyrone. However, methadone provides superior pain control, especially when given preoperatively or intraoperatively. The combination of ketamine, lidocaine, and maropitant enhances pain management, while fentanyl, alone or with lidocaine and ketamine, is effective for intraoperative pain control. Local infiltration with lidocaine/bupivacaine provides effective pain control, and devices like Comfont-in^® or WSC facilitate this process. Tumescent anaesthesia using lidocaine/ropivacaine allows for extensive infiltration of the mammary gland. Epidural analgesia, paravertebral blocks, and TAP blocks are beneficial in multimodal protocols. Transdermal patches containing fentanyl/buprenorphine offer prolonged analgesia, while electroacupuncture can help reduce the need for rescue analgesics. Multimodal analgesic protocols are crucial for effective pain management in dog mastectomy surgeries, minimising the need for rescue opioids. Full article

Kidney injury molecule-1 (KIM-1) is a transmembrane protein that is significantly upregulated in renal cells following injury. It has considerable potential as a biomarker for diagnosing and monitoring renal cell carcinoma (RCC). This review examines KIM-1 expression across multiple biological sources—including tissue, blood, and urine—and highlights its strong association with RCC risk. Clinical studies have shown that KIM-1 levels decline within weeks after nephrectomy, underscoring its utility in assessing therapeutic response. Additionally, urinary KIM-1 levels correlate with histopathological outcomes following cisplatin treatment, supporting its role as a non-invasive marker for treatment effectiveness. Despite these promising findings, several challenges remain. These include variability in assay performance and the modulatory effects of the tumour microenvironment on KIM-1 expression. Overcoming these technical limitations is crucial for integrating KIM-1 into clinical workflows. Furthermore, its potential role in guiding combination therapies—such as tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and mTOR inhibitors—could enhance therapeutic precision while minimizing toxicity. Continued research is essential to validate these applications and facilitate the routine clinical use of KIM-1 in RCC management. Full article

Background/Objectives: This investigation compared the therapeutic efficacy of extracellular microvesicles (MVs) derived from murine L929 sarcoma cells and murine mesenchymal stem cells (MSCs). Methods: A mouse model of acute kidney injury (AKI) was used. Results: Both MVs from L929 cells (L929-MVs) and MSCs (MSC-MVs), unlike those obtained from murine peripheral blood mononuclear cells (PBMCs), enhanced survival rates in AKI mice and significantly improved kidney function. This was indicated by decreased levels of urine albumin and serum creatinine. Furthermore, treatment with L929-MVs and MSC-MVs elevated the proportions of CD4+CD25+FOXP3+ regulatory T cells while reducing the presence of pro-inflammatory CD4+CD44+ T cells in the spleens of AKI mice. Conclusions: the results highlight the potential of tumour-derived MVs to facilitate organ repair and exert cytoprotective immunomodulatory effects. Full article