Exosomes in Renal Cell Cancer: Diagnostic and Therapeutic Nanovehicles.

Early diagnosis is crucial for enhancing the survival rate of renal cell cancer patients, and exosomes present potential advantages in this area. Their small size, high mobility, and lipid bilayer structure enable exosomes to cross biological membranes easily, protecting the bioactive cargo within from degradation. Exosomes significantly influence the invasion and metastasis of RCC, and they also contribute to tumor drug resistance and immune evasion.

99mTc-DMSA and 99mTc-DTPA identified renal dysfunction due to microplastic polyethylene in murine model.

In the previous study (Im et al., 2022), we revealed microplastic (MP) was accumulated and cleared through the kidneys via PET imaging. Here, we aimed to identify the renal dysfunction due to polyethylene (PE) MP in the kidney tissue. Mice were exposed to 100 ppm (∼equivalent to 0.1mg/mL) /100 µL of PE for 12 weeks (n =10). PE uptake in the kidney tissues was confirmed using confocal microscopy. QuantSeq analysis was performed to determine gene expression. Renal function assessment was performed using 99mTc-Diethylene triamine penta acetic acid or 99mTc-Dimercaptosuccinic acid. Measurement of creatinine, BUN, and albumin levels in serum and urine samples was also estimated. [18F]-FDG was also acquired. PE increased expression of Myc, CD44, Programmed Death-Ligand 1 (PD-L1), and Hypoxia-Inducible Factor (HIF)-1α, which indicates a potential link to an increased risk of early-onset cancer. An increase in glucose metabolism of [18F]-FDG were observed. We assessed renal failure using 99mTc-Diethylene triamine penta acetic acid and 99mTc-Dimercaptosuccinic acid scintigraphy to determine the renal function. Renal failure was confirmed using serum and urine creatinine, serum blood urea nitrogen levels, serum albumin levels, and urine albumin levels in PE exposed mice, relative to the control. In sum, PE exposure induced renal dysfunction in a murine model.

Renal cancer: signaling pathways and advances in targeted therapies.

Renal cancer is a highlyheterogeneous malignancy characterized by rising global incidence and mortalityrates. The complex interplay and dysregulation of multiple signaling pathways,including von Hippel-Lindau (VHL)/hypoxia-inducible factor (HIF), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), Hippo-yes-associated protein (YAP), Wnt/ß-catenin, cyclic adenosine monophosphate (cAMP), and hepatocyte growth factor (HGF)/c-Met, contribute to theinitiation and progression of renal cancer. Although surgical resection is thestandard treatment for localized renal cancer, recurrence and metastasiscontinue to pose significant challenges. Advanced renal cancer is associatedwith a poor prognosis, and current therapies, such as targeted agents andimmunotherapies, have limitations. This review presents a comprehensiveoverview of the molecular mechanisms underlying aberrant signaling pathways inrenal cancer, emphasizing their intricate crosstalk and synergisticinteractions. We discuss recent advancements in targeted therapies, includingtyrosine kinase inhibitors, and immunotherapies, such as checkpoint inhibitors.Moreover, we underscore the importance of multiomics approaches and networkanalysis in elucidating the complex regulatory networks governing renal cancerpathogenesis. By integrating cutting-edge research and clinical insights, this review contributesto the development of innovative diagnostic and therapeutic strategies, whichhave the potential to improve risk stratification, precision medicine, andultimately, patient outcomes in renal cancer.

Chinese quality control indices for standardized diagnosis and treatment of renal cancer (2022 edition).

Renal cancer is one of the most common malignancies of the urinary system, and the number of deaths continues to increase. The standardized management of the diagnosis and treatment of renal cancer is challenging due to the great differences in the diagnosis and treatment of renal cancer in different regions. The Renal Cancer Expert Committee of the National Cancer Quality Control Center (NCQCC) identified a lack of authoritative quality control standards as an opportunity to utilize its multidisciplinary membership to improve the standardized diagnosis and treatment of renal cancer. The Renal Cancer Expert Committee of the NCQCC aims to promote quality control and national standardization, uniformity, and normalization of renal cancer diagnosis and treatment, which ultimately improved the survival rate and quality of life of renal cancer patients. A panel of experts with renal cancer surgery, renal cancer medicine, medical imaging, pathology and radiotherapy were drawn together and determined the quality control standards for the standardized diagnosis and treatment of renal cancer. The Indices includes 20 items that cover all key areas in the diagnosis and treatment of renal cancer, such as standard diagnosis, surgery treatment, systemic treatment, and prognostic evaluation.

Successful treatment of eosinophilia associated with dialysis-related renal cancer with radical nephrectomy.

Introduction: Secondary eosinophilia due to solid tumors is a rare case. This is the first study to report secondary eosinophilia due to renal cancer in a patient on dialysis. Case presentation: A 70-year-old man, on long-term hemodialysis was incidentally detected with right renal cancer, and workup performed revealed eosinophilia. Allergic symptoms caused by hemodialysis were initially considered; however, treatment did not lead to any improvement in eosinophilia. Therefore, nephrectomy for renal cancer was performed. The resolution of symptoms and eosinophilia after surgery suggested renal cancer as the cause of eosinophilia. Conclusion: As demonstrated in this patient with dialysis-related renal cancer, eosinophilia associated with solid tumors may be addressed by treating the tumor.

Internist's tumour into thyroid: A case report.

Renal cell carcinoma (RCC) is well known for its unpredictable and diverse behaviour, with tendency to cause synchronous or metachronous metastasis to unusual site, which is why it is called the "internist's tumour."Although thyroid gland is an infrequent site for metastasis of different primary malignancies, metastatic RCC is one of the most common secondary thyroid malignancies. Diagnosis relies on a high index of suspicion in patients with prior RCC, combined with cross-sectional imaging and biopsy. A case of secondary thyroid neoplasm from RCC after 13 years of radical nephrectomy is described with clinicopathological features and literature review.

Contemporary review of papillary renal cell carcinoma-current state and future directions.

Historically, papillary renal cell carcinoma (PRCC) was divided into two types, type 1 and type 2, based solely on morphology. However, it is apparent that PRCC is far more complex and represents a histological, clinical, and molecular spectrum. There has been a significant evolution in our understanding of PRCC, highlighted by the recognition of new and molecularly defined entities that were previously included in PRCC type 2. This contemporary review addresses the evolving concepts regarding the PRCC, including why it is no longer needed to subtype PRCC, the current molecular landscape, prognostic parameters, and PRCC variants, including biphasic PRCC, papillary renal neoplasm with reverse polarity, and Warthin-like PRCC. Pathologists should also be aware of the potential mimickers of both low-grade and high-grade PRCCs as well as some new and emerging entities that may show papillary growth that should be excluded in the diagnostic workup. The evolving knowledge of PRCC biomarkers, morphologic patterns, and PRCC variants could also have important implications for clinical management. Lastly, the heterogeneity within the PRCC spectrum needs to be further studied, aiming to better stratify PRCC for appropriate clinical management and systemic therapy.

Image-Guided Ablation of Renal Masses: Challenges to Produce High-Quality Evidence and Future Directions.

Image-guided ablation (IGA) is a rapidly developing field in interventional oncology. There is some evidence suggesting IGA's non-inferiority compared with partial or radical nephrectomy for the treatment of small renal masses (SRM). However, these are mostly limited to retrospective cohort studies. This review article outlines the evidence comparing IGA to partial nephrectomy by collating the different survival measures and evaluates the challenges of producing clinical trials and high-quality evidence. The main challenges are due to the heterogeneity of SRM, patient selection bias, unstandardized endpoint and outcomes, and the lack of global practice standards. Despite the evidence thus far demonstrating that IGA stands as a non-inferior treatment modality for SRMs, exhibiting favorable short- and long-term outcomes, further robust research is needed to integrate ablation techniques into routine clinical practice with a multidisciplinary approach. There is emerging evidence that suggests randomized controlled trial in SRMs is possible, and technologies such as histotripsy as well as artificial intelligence are used in IGA.

Advancements in Radiogenomics for Clear Cell Renal Cell Carcinoma: Understanding the Impact of BAP1 Mutation.

Recent advancements in understanding clear cell renal cell carcinoma (ccRCC) have underscored the critical role of the BAP1 gene in its pathogenesis and prognosis. While the von Hippel-Lindau (VHL) mutation has been extensively studied, emerging evidence suggests that mutations in BAP1 and other genes significantly impact patient outcomes. Radiogenomics with and without texture analysis based on CT imaging holds promise in predicting BAP1 mutation status and overall survival outcomes. However, prospective studies with larger cohorts and standardized imaging protocols are needed to validate these findings and translate them into clinical practice effectively, paving the way for personalized treatment strategies in ccRCC. This review aims to summarize the current knowledge on the role of BAP1 mutation in ccRCC pathogenesis and prognosis, as well as the potential of radiogenomics in predicting mutation status and clinical outcomes.

Failure of the PD-1 Blocking Agent Pembrolizumab to Benefit a Patient with Renal Squamous Cell Cancer.

Introduction: Renal squamous cell carcinoma (SCC) is a neoplasm with an extremely rare occurrence compared to other renal malignancies. The classic presentation includes a palpable mass and flank pain; however, the presentation is seldom non-specific. Our study describes the significance of programmed death ligand-1 (PD-L1) expression in renal cancer and its association with clinical outcomes, alongside available treatment options. Case description: An 80-year-old female with a history of hypertension and cerebral aneurysm presented with right flank pain and blood in urine and was diagnosed with pyelonephritis and left renal mass/phlegmon. A biopsy revealed SCC of the kidney with metastasis to the lung and aortocaval lymph node. Positron emission tomography (PET) scan confirmed malignancy in the kidney and lung. Treatment with pemrolizumab and carboplatin plus paclitaxel was initiated but poorly tolerated as the haemoglobin dropped rapidly. Conclusion: SCC poses a diagnostic challenge due to its rarity and non-specific symptoms, often leading to advanced stage diagnosis. PD-L1 expression is pivotal in assessing tumour aggressiveness and prognosis. PD-L1 inhibitors offer promise, but their efficacy in renal SCC warrants further investigation. Radical nephrectomy and systemic chemotherapy show potential in advanced cases, necessitating vigilant management of treatment-related side effects. This case emphasises the need for ongoing research to refine therapeutic approaches and enhance outcomes in renal SCC patients. LEARNING POINTS: PD-L1 expression is pivotal in assessing tumour aggressiveness and prognosis of renal cell carcinoma.PD-L1 inhibitors hold promise as a therapeutic intervention in renal squamous cancer.Radical nephrectomy and systemic chemotherapy show potential in managing advanced renal cancer.

UCHL5 is a putative prognostic marker in renal cell carcinoma: a study of UCHL family.

A macroscopic perspective is indispensable for understanding the intricate relationship between deubiquitinases and tumorigenesis. Proteomics has been proposed as a viable approach for elucidating the complex role of deubiquitylation in cellular progression. Instead of studying the function of a single ubiquitinase, research on a deubiquitinase family with similar catalytic core(s) may provide a new perspective for the pathological understanding of cancer. The Ubiquitin C-terminal hydrolase L (UCHL) family consists of four members: UCHL1, UCHL3, UCHL5, and BRAC1 associated protein-1 (BAP1), and they have been implicated in tumorigenesis and metastasis. Some members are considered hallmarks of intracranial lesions, colon cancer, chromatin remodeling, and histone stability. The present study uncovered an unknown correlation between the UCHL family and renal cancer. We discovered that UCHLs exhibit diverse regulatory effects in renal cancer, establishing connections between the renal cancer and truncated gene mutations, mitochondrial energetic metastasis, immune cell infiltration, and chromosomal stability of UCHLs family. Notably, we found that the increase of UCHL5 expression in renal cancer cells decreases the antigen processing and presentation of RCC tumor-infiltrating B cells. Further research identified that the expression of UCHL5 in RCC tumors is correlated with transport proteins, which led us to find that the abundance of UCHL5 in the blood of late-stage renal cell cancer patients is upregulated from 18 ng/L to 500 ng/L. Therefore, we propose that the abundance of UCHL5 in patients' blood can be a possible indicator of poor prognosis for renal cell cancer.

The role of tissue persistent organic pollutants and genetic polymorphisms in patients with benign and malignant kidney tumors.

This study aimed to explore whether there is an association between environmental exposure to POPs and kidney tumor induction, and whether blood POP concentrations reflect kidney tissue concentrations. POP derivatives were determined in blood, tumor tissue, tumor surrounding tissue, and perirenal fat tissue samples taken from patients who underwent surgery for renal tumors. A voluntary control group was recruited for blood and urine samples as well. Urinary excretions of o,o'-dityrosine, chlorotyrosine, nitrotyrosine, and 8-OHdG were measured in the same patients. The possible role of genetic polymorphisms in CYP1A1, GST isozymes P, M, and T, and hOGG1 genes on the predisposition to renal cancer was investigated. Some POPs have been found to be associated with kidney cancer, as evidenced by their significantly high ORs. 8-OHdG levels were significantly higher compared to the control group. The GSTT1 null polymorphism can be a risk factor for malignant but not for benign kidney tumors.

Dose-response relationship between arsenic in drinking water and mortality of urinary cancers in Taiwan.

Ingested arsenic is carcinogenic to the human urinary tract, but uncertainties remain regarding the dose-response relationship. To assess dose-response relationships between arsenic ingestion and urinary cancers, we evaluated the associations between the arsenic level in drinking water and mortality of cancers of the bladder, kidney, and prostate in Taiwan. We utilized the 1971-2000 Taiwan death registry data and calculated the age-standardized mortality rates (ASMRs) using the 1976 world standard population as the reference group. We used the data from a 1974-1976 census survey of wells on the arsenic levels in drinking water conducted by the government to assess exposure levels, which had been divided into three categories: below 0.05 ppm, 0.05-0.35 ppm, and above 0.35 ppm. The data were analyzed using multiple linear regression models and geographical information system. We found no increase in ASMR for all, or any, of the urinary cancers at exposure levels of 0.05-0.35 ppm arsenic, but at exposure levels > 0.35 ppm arsenic was associated with increased ASMR in both males and females for bladder cancer, kidney cancer, and all urinary cancers combined. There was no increased ASMR associated with prostate cancer observed for either exposure category.

[Peculiarities of angiogenesis in clear cell renal cancer]. / Osobennosti angiogeneza pri svetlokletochnom rake pochki.

A literature search was conducted to review papers on the results of studies of clear cell renal cancer (CCRC) vascularization. Numerous data on the relationship between tumor pathogenesis and its vascularization have been revealed, which indicates the multifactorial nature of CCRC development and the significant role of angiogenesis in this process. It should be taken into account that patients with CCRC may have impaired vessel formation even before tumor development. To evaluate normal and pathologic angiogenesis, a pathohistologic study using immunohistochemistry is certainly necessary. Due to the significant role of angiogenesis in the development and course of CCRC, the use of drugs that suppress the formation of the vascular network in the tumor is relevant and advisable. To date, many drugs have been developed and introduced into clinical practice to inhibit angiogenesis. However, such drugs have not lived up to the expectations placed due to the frequent and rapidly developing drug resistance. Timely detection of pre-tumor and tumor processes, as well as effective treatment of cancer, including CCRC, is possible only with close cooperation between pathomorphologists and oncologists.

Identification of miRNAs and Their Target Genes Associated with Sunitinib Resistance in Clear Cell Renal Cell Carcinoma Patients.

Sunitinib has greatly improved the survival of clear cell renal cell carcinoma (ccRCC) patients in recent years. However, 20-30% of treated patients do not respond. To identify miRNAs and genes associated with a response, comparisons were made between biopsies from responder and non-responder ccRCC patients. Using integrated transcriptomic analyses, we identified 37 miRNAs and 60 respective target genes, which were significantly associated with the NF-kappa B, PI3K-Akt and MAPK pathways. We validated expression of the miRNAs (miR-223, miR-155, miR-200b, miR-130b) and target genes (FLT1, PRDM1 and SAV1) in 35 ccRCC patients. High levels of miR-223 and low levels of FLT1, SAV1 and PRDM1 were associated with worse overall survival (OS), and combined miR-223 + SAV1 levels distinguished responders from non-responders (AUC = 0.92). Using immunohistochemical staining of 170 ccRCC patients, VEGFR1 (FLT1) expression was associated with treatment response, histological grade and RECIST (Response Evaluation Criteria in Solid Tumors) score, whereas SAV1 and BLIMP1 (PRDM1) were associated with metachronous metastatic disease. Using in situ hybridisation (ISH) to detect miR-155 we observed higher tumoural cell expression in non-responders, and non-tumoural cell expression with increased histological grade. In summary, our preliminary analysis using integrated miRNA-target gene analyses identified several novel biomarkers in ccRCC patients that surely warrant further investigation.

Understanding symptom contribution to sex inequality in bladder and renal cancer stage at diagnosis.

Background: Understanding sex-specific factors contributing to advanced-stage diagnosis can guide interventions to reduce sex inequality in patients with urological cancers. Method: We used linked primary care and cancer registry data to examine associations between symptoms and advanced-stage in 1151 bladder cancer and 440 renal cancer patients diagnosed between January 2012 and December 2015 in England. We performed logistic regression, adjusting for sex, age, deprivation and routes to diagnosis, including interaction terms between symptoms and sex and symptoms and age. Results: Female sex (OR vs. men 1.89 [1.28-2.79]; p = 0.001) and patients presenting with urinary tract infections (OR 2.22 [1.34-3.69]) and abdominal symptoms (OR 2.19 [1.30-3.70]) were associated with increased odds of advanced-stage bladder cancer (vs. haematuria, p = 0.016 for both). Women with haematuria and men with abdominal symptoms (compared with the opposite sex with the same presenting symptom) were more likely to have advanced-stage bladder cancer. Neither sex nor symptom associations were observed for renal cancer. Conclusion: Non-haematuria symptoms are associated with higher risk of advanced-stage bladder cancer. Greater risk of advanced-stage bladder cancer in women may reflect biological differences in haematuria onset and sex differences during diagnostic process. Identifying higher risk women with haematuria may reduce sex inequalities in bladder cancer outcomes.

Prognostic factors and treatment impact on overall survival in patients with renal neuroendocrine tumour.

Background: Renal neuroendocrine neoplasms (R-NEN) are exceptionally rare tumours characterized by high mortality rates. Objective: The objective of this study is to analyse prognostic factors and treatment impact on overall survival in patients with R-NEN. Design setting and participants: We identified all patients with R-NEN in the National Cancer Database (NCDB) from 2004 to 2019 and identified prognostic factors for improved survival. Results and limitations: Of 542 R-NEN cases, 166 (31%) were neuroendocrine tumour grade 1 (NET-G1), 14 (3%) were neuroendocrine tumour grade 2 (NET-G2), 169 (31%) were neuroendocrine carcinoma (NEC-NOS), 18 (3%) were large cell neuroendocrine carcinoma (LC-NEC) and 175 (32%) were small cell neuroendocrine carcinoma (SC-NEC). Median overall survival for all patients in the study was 44.88 months (SE, 4.265; 95% CI, 27.57-62.19). Median overall survival was 7.89 months (SE 0.67; 95% CI, 6.58-9.20) for patients without surgical intervention and 136.61 months (SE 16.44; 95% CI, 104.38-168.84, p < 0.001) for patients who underwent surgery. Increased age (HR, 1.05; 95% CI, 1.03-1.06; p < 0.001), T4 stage disease (HR, 3.17; 95% CI, 1.96-5.1; p < 0.001), NEC-NOS histology (HR, 2.82; 95% CI, 1.64-4.86; p < 0.001), LC-NEC histology (HR, 2.73; 95% CI, 1.04-7.17; p = 0.041) and SC-NEC histology (HR, 5.17; 95% CI, 2.95-9.05; p < 0.001) were all positive predictors of worsening overall survival. The main limitation of the study is its retrospective design. Conclusion: R-NEN is an aggressive tumour characterized by high mortality rates. Surgery continues to be the mainstay of treatment and has shown to provide a survival benefit for most patients. Patient Summary: R-NEN is composed of several tumour histologies that differ based on their aggressiveness with NEC-NOS and SC-NEC being the most lethal. Surgery, predominantly through minimally invasive approaches, is the mainstay of treatment and has a clear survival benefit.

A 23-year bibliometric analysis of the development of global research on hereditary renal carcinoma.

Objectives: Medical research continues to be extensively devoted to investigating the pathogenesis and treatment approaches of hereditary renal cancer. By aspect including researchers, institutions, countries, journals, and keywords, we conduct a bibliometric analysis of the literature pertaining to hereditary renal cancer over the last 23 years. Methods: From the Web of Science Core Collection, we conducted a search for publications published between January 1, 2000 and November 28, 2023. Reviews and original articles were included. Results: A cumulative count of 2,194 publications met the specified criteria for inclusion. The studies of the included articles involved a collective of 2,402 institutions representing 80 countries. Notably, the United States exhibited the highest number of published documents, constituting approximately 45.49% of the total. The preeminent institution in this discipline is the National Cancer Institute (NCI), which maintains a publication volume of 8.98%. In addition to being the most prolific author (125 publications), Linehan WM's works received the highest number of citations (11,985). In a comprehensive count, 803 journals have published related articles. In the top 10 most recent occurrences were the terms "hereditary leiomyomatosis" and "fumarate hydratase." Conclusion: This is the first bibliometric analysis of the literature on hereditary renal cancer. This article offers a thorough examination of the present status of investigations concerning hereditary renal cancer during the previous 23 years.

The role of metabolic reprogramming in kidney cancer.

Metabolic reprogramming is a cellular process in which cells modify their metabolic patterns to meet energy requirements, promote proliferation, and enhance resistance to external stressors. This process also introduces new functionalities to the cells. The 'Warburg effect' is a well-studied example of metabolic reprogramming observed during tumorigenesis. Recent studies have shown that kidney cells undergo various forms of metabolic reprogramming following injury. Moreover, metabolic reprogramming plays a crucial role in the progression, prognosis, and treatment of kidney cancer. This review offers a comprehensive examination of renal cancer, metabolic reprogramming, and its implications in kidney cancer. It also discusses recent advancements in the diagnosis and treatment of renal cancer.