Chromene-based compounds as drug candidates for renal and bladder cancer therapy - A systematic review.

Renal (RC) and bladder cancers (BC) are common urological malignancies prevalent in the male population. Incidence and mortality rates are expected to increase in the near future. Drug toxicity and development of drug resistance in both diseases are major obstacles to achieve successful treatments. Chromenes are heterocyclic compounds constituted by a benzene ring fused to a pyran nucleus. Natural and synthetic chromene-based compounds have proven to be promising anticancer agents. Additionally, re-sensitization of cancer cells to classical treatments has also been demonstrated. Thus, the aim of this systematic review is to assess the potential of chromene-based compounds in the treatment of RC and BC. Study collection was performed in six different databases, to compile existing information on preclinical (in vitro and in vivo) and clinical studies developed to date. Overall, multiple chromene-based compounds showed potent anticancer effects, affecting several biological features such as reduction in cell viability, proliferation, migration and invasion in vitro, and induction of cell cycle arrest and cell death. Tumor volume and weight were generally decreased in vivo upon chromene-based treatment. Modest results have been obtained in two clinical trials, with reports of a partial response and two objective responses in RC patients. Thus, the chromene family can be considered an attractive chemical scaffold, harboring promising drug candidates for RC and BC therapeutics.

Sex Differences in Kidney Health and Disease.

BACKGROUND: Sex differences exist in kidney physiology and disease which are underpinned by the biological actions of the sex hormones estrogen, progesterone and testosterone. In this review, we present an up-to-date discussion of the hormonal and molecular signalling pathways implicated in sex differences in kidney health and disease. SUMMARY: Estrogen and progesterone have protective effects on renal blood flow, glomerular filtration rate and nephron ion and water reabsorptive processes, whereas testosterone tends to compromise these functions. The biological effects of estrogen appear to be the most important in reinforcing kidney function and protecting against kidney diseases in females. The actions of estrogen are myriad but all tend to bolster kidney physiology to maintain a steady-state and adaptable extracellular fluid volume (ECFV) and blood pressure. Estrogen safeguards ECFV homeostasis by stimulating renal epithelial sodium channel (ENaC) and water channel (AQP2) expression and transport function. Renal maintenance of ECFV within narrow physiological limits is a first-line of defense against hypertension and lowers the risk of cardiovascular disease in women. The estrogenic and XX chromosome basis for a female advantage are evident in a wide range of kidney diseases including acute kidney injury, chronic kidney disease, end-stage kidney disease, diabetic kidney disease, and polycystic kidney disease. The molecular mechanisms involve estrogen regulation of nephron ion and water transport, genetic immunogenic responses, activation of the protective arm of the renin angiotensin-aldosterone system and XX chromosome reinforcement of immune responses. Kidney disease can also predispose patients to cancer and women are protected in renal cancer with lower incidence, morbidity, and mortality than age-matched men with the disease. KEY MESSAGES: This review underscores the importance of incorporating sex-specific considerations into clinical practice and basic research to bridge the gap in understanding and addressing biological sex disparities in kidney disease and renal cancer.

Stereotactic Body Radiotherapy for Renal Cell Carcinoma-A Review of Use in the Primary, Cytoreductive and Oligometastatic Settings.

Renal cell carcinoma (RCC) has been increasing in incidence by around 1.5% per year for several years. However, the mortality rate has been decreasing by 1.6% per year, and this can be attributed to stage migration and improvements in treatment. One treatment modality that has emerged in recent years is stereotactic body radiotherapy (SBRT), which is an advanced radiotherapy technique that allows the delivery of high-dose radiation to the tumor while minimizing doses to the organs at risk. SBRT has developed a role in the treatment of early-stage, oligometastatic and oligoprogressive RCC. In localized disease, phase II trials and meta-analyses have shown that SBRT provides a very high probability of long-term local control with a low risk of severe late toxicity. In oligometastatic (OMD) RCC, the same level of evidence has similarly shown good local control and minimal toxicity. SBRT could also delay the necessity to start or switch systemic treatments. Medical societies have started to incorporate SBRT in their guidelines in the treatment of localized disease and OMD. A possible future role of SBRT involves cytoreduction. It is theorized that SBRT can lower tumor burden and enhance immune-related response, but it cannot be recommended until the results of the phase II trials are published.

Beyond Index Conditions: Applying a Multimorbidity Approach to Renal Cancer Nursing.

OBJECTIVE: This article aims to describe the key components of renal cancer nursing and multimorbidity nursing, and reflects on how adopting a multimorbidity approach to renal cancer nursing can help nurses provide holistic patient care. METHODS: This is a discussion paper drawing on relevant evidence and theory. RESULTS: Renal cancer nurses have a highly specialised knowledge base and are able to use this expertise to deliver excellent care to people with cancer. However, lots of people with cancer have other conditions as well. Adopting a multimorbidity approach to nursing care provides a more holistic framework for care delivery. CONCLUSIONS: Cancer nurses are ideally placed to support patients in this way, so they are able to deliver care which accounts for factors such as treatment burden and how this impacts on patients and carers. IMPLICATIONS FOR NURSING PRACTICE: Nurses who care for people with renal cancer should view their patients through the lens of multimorbidity. This involves screening for other chronic conditions, considering polypharmacy, providing emotional support and continuity of care, and coordinating care in a way that accounts for the potentially burdensome nature of the patient's interactions with health care.

T1a renal cancer cryoablation - first experiences in Poland.

Purpose: Cryoablation is one of the methods of treating patients with renal cancer with curative intent. This procedure is not widely available in Poland due to the lack of reimbursement until April 2023. The purpose of this study is to present the results of the first experiences in cryoablation of renal cell carcinoma in Poland. Material and methods: Patients with renal cell carcinoma in T1a stage (up to 4 cm in diameter) were treated with percutaneous cryoablation between December 2020 and December 2023. All patients were disqualified from surgical treatment due to age, comorbidities, or history of nephrectomy. Diagnosis was confirmed by computed tomography (CT)-guided core needle biopsy that was performed 2-4 weeks before cryoablation. Results: Twenty-five patients underwent CT-guided cryoablation of T1a renal cancer. The mean age of the patients was 77 years (43-91 years). The mean diameter of lesions was 27 mm (15-40 mm). None of the patients presented with local or distant recurrence within the mean 12-months of follow-up period (100% progression-free survival). Urine leak treated with a stent was detected in one patient. Four patients died within the follow-up period, but none of the deaths was directly related to the procedure. Conclusions: Cryoablation is an effective and safe procedure and should be available to more patients in Poland.

Intraoperative dexmedetomidine administration and acute kidney injury in patients undergoing unilateral partial nephrectomy: a retrospective study.

Partial nephrectomies are associated with an increased risk of acute kidney injury (AKI), but dexmedetomidine administration may improve renal outcomes. We hypothesized that intraoperative dexmedetomidine administration would be associated with a decrease in AKI development in patients undergoing unilateral partial nephrectomy. In this retrospective study, adult patients who underwent unilateral partial nephrectomy from April 2016 to October 2023 were included. Exclusion criteria were a history of end-stage renal disease, ineligible procedures (i.e., aborted procedure, conversion to radical nephrectomy, surgery on a horseshoe kidney), and reoperation within three days of the initial nephrectomy. Patients were categorized according to whether they received intraoperative dexmedetomidine. The primary outcome was AKI incidence within three days of surgery; AKI was defined according to the Kidney Disease Improving Global Outcomes definition. Propensity score matching (PSM) was conducted to account for potential confounders (age, body mass index, sex, American Society of Anesthesiologists score, final surgical approach, clamping-related ischemia for >15 min). We included 1,632 patients; 214 received dexmedetomidine and 1,418 did not. Before PSM, the AKI rate was 31.2% in patients who received dexmedetomidine and 25.7% in patients who did not (p = 0.081). After PSM, the AKI rate was 31.3% in patients who received dexmedetomidine and 27.6% in those who did not (p = 0.396). The post-PSM odds ratio for AKI following dexmedetomidine administration during unilateral partial nephrectomy was 0.910 (95% CI: 0.585-1.142; p = 0.677). Intraoperative dexmedetomidine was not associated with a reduction in postoperative AKI incidence or severity after unilateral partial nephrectomy.

An Unusual Case of Oligometastases in a Patient with Renal Cell Carcinoma: Insights from 18F-FDG PET/CT.

Renal cell carcinoma (RCC) is a significant cause of mortality worldwide. To date, many atypical metastatic sites have been observed and reported in patients with RCC. However, to the best of our knowledge, there have been no reported cases of thyroid cartilage metastasis in the context of RCC metastasis. Herein, we present the case of a 68-year-old man who developed left arm pain that led to an RCC diagnosis. First, evaluation by pan-computed tomography (CT) denoted right kidney RCC and identified left humeral metastasis. Subsequently, 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) was performed after right nephrectomy and left humeral lesion excision and fixation. Interestingly, few intramedullary hypermetabolic lesions were observed in addition to a single intensely hypermetabolic thyroid cartilage lesion indicative of oligometastases. This case underscores the importance of 18F-FDG PET/CT in the evaluation of RCC disease for baseline staging and beyond.

Factors associated with surgical refusal and non-surgical candidacy in stage 1 kidney cancer: a National Cancer Database (NCDB) analysis.

INTRODUCTION: We aim to identify factors associated with surgical refusal and non-surgical candidacy in clinical stage I kidney masses and to evaluate their impact on overall survival (OS). MATERIALS AND METHODS: We conducted a retrospective cohort study using the National Cancer Database of patients with clinical stage I kidney cancer between 2004 and 2017. Logistic regression was used to determine baseline sociodemographic-, clinical-, and treatment facility-related factors associated with surgical refusal and non-surgical candidacy. Patients were 1.1 propensity score-matched and Cox regression analysis evaluated the impact of surgical refusal and non-surgical candidacy on OS. RESULTS: Compared to those who underwent surgery, those who refused surgery and those who were non-surgical candidates were more likely to be older, female, non-Hispanic (NH) Black, uninsured, have multiple comorbidities, and traveled a shorter distance to care. Similarly, compared to non-surgical candidates, those who refused surgery were more likely to be younger and have a tumor size ≥ 4.0 cm. Those who refused surgery had significantly lower median survival time and worse OS than those who underwent surgery (HR: 3.18, 95% CI: 2.85, 3.54). Non-surgical candidates had significantly lower median survival time and lower OS than those who had surgery (HR: 4.16, 95% CI: 3.84, 4.51). CONCLUSION: Various socioeconomic, demographic, and clinical factors are associated with patients refusing to undergo surgery, which in turn leads to lower overall survival rates in stage I kidney cancer patients. Recognizing these factors will enable healthcare professionals to address and potentially alleviate these issues, ultimately ensuring that patients receive the most appropriate care.

Innovative strategies in genitourinary cancer: the role of oncolytic viruses.

Urinary tumors pose a significant health threat because of their high prevalence and recurrence rates. Despite the availability of various treatment options, many patients poorly respond to traditional therapies, highlighting the urgent need for alternative approaches. Oncolytic viruses are promising therapeutic agents. These viruses exploit the unique characteristics of cancer cells to specifically target and destroy them, thereby triggering potent antitumor immune responses. This review delves into recent advancements and future prospects of oncolytic viruses, focusing on their application in renal, bladder, and prostate cancers. By discussing practical implications and the potential of different viruses, including the cowpox virus, adenovirus, measles virus, coxsackievirus, and reovirus, we pave the way for further exploration and refinement of this exciting field.

Meta-analysis and systematic review of factors predicting conversion to radical nephrectomy following robotic-assisted partial nephrectomy in renal cancer patients.

Evaluating the risk factors for the conversion from robotic-assisted partial nephrectomy (RAPN) to radical nephrectomy (RN). Through a comprehensive database search encompassing PubMed, Web of Science, Embase, and the Cochrane Library, we identified pertinent English-language research published by June 2024. We utilized the NOS scale for quality assessment. The aggregate effect was quantified via the odds ratio (OR), alongside a 95% confidence interval (CI). Sensitivity analyses were conducted using both fixed-effects and random-effects models to evaluate reliability. The meta-analytical process was facilitated by the Stata 18 software suite. Our meta-analysis encompassed a total of 8 retrospective studies and 3 prospective studies, totaling 4056 patients. We found that increasing patient age (OR: 1.04; 95% CI 1.00-1.08; P = 0.005), higher American Society of Anesthesiologists (ASA) scores (3 or above) (OR: 2.74; 95% CI 1.52-4.93; P = 0.001), elevated R.E.N.A.L. scores (7 or above) (OR: 2.49; 95% CI 1.57-3.95; P < 0.001), and the use of off-clamp RAPN (OR: 7.21; 95% CI 2.60-19.93; P < 0.001) significantly raised the odds of surgical conversion. On the other hand, male sex (OR: 1.04; 95% CI 0.67-1.62; P = 0.858), the side of the tumor (OR: 0.97; 95% CI 0.48-1.95; P = 0.936), tumor size (OR: 3.43; 95% CI 0.57-20.55; P = 0.177), body mass index (BMI) (OR: 1.03; 95% CI 0.96-1.11; P = 0.426), clinical stage (OR: 3.78; 95% CI 0.46-30.70; P = 0.214), and the use of single-port RAPN (OR: 0.54; 95% CI 0.16-1.78; P = 0.31) did not show a statistically significant link to an increased conversion risk. This meta-analysis elucidates the critical risk factors for the conversion from robotic-assisted partial nephrectomy to radical nephrectomy, providing significant guidance for preoperative risk assessment and clinical decision-making. However, our findings necessitate validation through studies with larger sample sizes.

Highlighting function of Wnt signalling in urological cancers: Molecular interactions, therapeutic strategies, and (nano)strategies.

Cancer is a complex, multistep process characterized by abnormal cell growth and metastasis as well as the capacity of the tumor cells in therapy resistance development. The urological system is particularly susceptible to a group of malignancies known as urological cancers, where an accumulation of genetic alterations drives carcinogenesis. In various human cancers, Wnt singalling is dysregulated; following nuclear transfer of ß-catenin, it promotes tumor progression and affects genes expression. Elevated levels of Wnt have been documented in urological cancers, where its overexpression enhances growth and metastasis. Additionally, increased Wnt singalling contributes to chemoresistance in urological cancers, leading to reduced sensitivity to chemotherapy agents like cisplatin, doxorubicin, and paclitaxel. Wnt upregulation can change radiotherapy response of urological cancers. The regulation of Wnt involves various molecular pathways, including Akt, miRNAs, lncRNAs, and circRNAs, all of which play roles in carcinogenesis. Targeting and silencing Wnt or its associated pathways can mitigate tumorigenesis in urological cancers. Anti-cancer compounds such as curcumin and thymoquinone have shown efficacy in suppressing tumorigenesis through the downregulation of Wnt singalling. Notably, nanoparticles have proven effective in treating urological cancers, with several studies in prostate cancer (PCa) using nanoparticles to downregulate Wnt and suppress tumor growth. Future research should focus on developing small molecules that inhibit Wnt singalling to further suppress tumorigenesis and advance the treatment of urological cancers. Moreover, Wnt can be used as reliable biomarker for the diagnosis and prognosis of urological cancers.

Detection and Validation of Organic Metabolites in Urine for Clear Cell Renal Cell Carcinoma Diagnosis.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) comprises the majority, approximately 70-80%, of renal cancer cases and often remains asymptomatic until incidentally detected during unrelated abdominal imaging or at advanced stages. Currently, standardized screening tests for renal cancer are lacking, which presents challenges in disease management and improving patient outcomes. This study aimed to identify ccRCC-specific volatile organic compounds (VOCs) in the urine of ccRCC-positive patients and develop a urinary VOC-based diagnostic model. METHODS: This study involved 233 pretreatment ccRCC patients and 43 healthy individuals. VOC analysis utilized stir-bar sorptive extraction coupled with thermal desorption gas chromatography/mass spectrometry (SBSE-TD-GC/MS). A ccRCC diagnostic model was established via logistic regression, trained on 163 ccRCC cases versus 31 controls, and validated with 70 ccRCC cases versus 12 controls, resulting in a ccRCC diagnostic model involving 24 VOC markers. RESULTS: The findings demonstrated promising diagnostic efficacy, with an Area Under the Curve (AUC) of 0.94, 86% sensitivity, and 92% specificity. CONCLUSIONS: This study highlights the feasibility of using urine as a reliable biospecimen for identifying VOC biomarkers in ccRCC. While further validation in larger cohorts is necessary, this study's capability to differentiate between ccRCC and control groups, despite sample size limitations, holds significant promise.

Impact of a kidney-adjusted ERAS® protocol on postoperative outcomes in patients undergoing partial nephrectomy.

PURPOSE: Evaluation of a kidney-adjusted enhanced recovery after surgery (ERAS®) protocol (kERAS) in patients undergoing nephron-sparing surgery (PN). METHODS: The kERAS protocol is a multidimensional protocol focusing on optimized perioperative fluid and nutrition management as well as strict intraoperative and postoperative blood pressure limits. It was applied in a prospective cohort (n = 147) of patients undergoing open or robotic PN. Patients were analyzed for the development of acute postoperative renal failure (AKI), achievement of TRIFECTA criteria, upstaging or new onset of chronic kidney disease (CKD) and length of hospital stay (LOS) and compared to a retrospective cohort (n = 162) without application of the protocol. RESULTS: Cox regression analyses could not confirm a protective effect of kERAS on the development of AKI post-surgery. A positive effect was observed on TRIFECTA achievement (OR 2.2, 95% CI 1.0-4.5, p = 0.0374). Patients treated with the kERAS protocol showed less long-term CKD upstaging compared to those treated with the standard protocol (p = 0.0033). There was no significant effect on LOS and new onset of CKD. CONCLUSION: The implementation of a kERAS protocol can have a positive influence on long-term renal function in patients undergoing PN. It can be used safely without promoting AKI. Furthermore, it can be realized with a manageable amount of additional effort.

Hereditary and Familial Traits in Urological Cancers and Their Underlying Genes.

Early recognition of hereditary urological cancers may influence diagnostic and therapeutic decision-making, and potentially alter the fate of patients and family members. Here, we introduce readers to the current knowledge on germline genetic testing and clinical practice in prostate, bladder, renal, and testicular carcinoma. Considering all urological cancer patients, routine inquiries about familial cancer history should become a standard practice in clinical settings. If suspicion arises, patients can opt for two avenues: referral to genetic counseling or undergoing genetic tests after consultation with the treating urologist. Patient summary: Tumors of the urogenital tract (prostate, kidney, bladder, and testes) can sometimes be related to genetic mutations that are present in all the cells of the body. Such mutations can be inherited and run in families. Therefore, it is relevant to obtain information on the incidence of all cancers in the family history. The information obtained may initiate genetic testing, leading to the identification of mutations that are related to cancer in the current or next generation. In addition, these mutations may offer alternative treatment options for patients.

The Detrimental Effect of Metabolic Syndrome on Long-term Renal Function in Patients Undergoing Elective Partial Nephrectomy for Small Renal Masses.

Background and objective: Metabolic syndrome (MetS) is a clinical condition associated with higher rates of overall and cardiovascular mortality. There is scarce evidence regarding the impact of MetS on surgical and functional outcomes for patients undergoing partial nephrectomy (PN) for clinically localized small renal masses (SRMs). Methods: We analyzed data from a prospectively maintained institutional database for 690 patients with cT1a renal cancer undergoing PN between 2000 and 2023 at a tertiary referral center. MetS was defined according to international guidelines. Cumulative incidence curves were used to estimate the 5-yr risk of stage IIIB-V chronic kidney disease (CKD) stage and other-cause mortality (OCM). Multivariable regression models were used to analyze the impact of MetS on the risk of complications, acute kidney injury (AKI), stage IIIB-V CKD, and OCM. Key findings and limitations: Overall, 10% of the PN cohort had MetS. The MetS group was older (median age 70 yr, interquartile range [IQR] 65-74 vs 61 yr, IQR 50-69; p < 0.001) and had worse preoperative kidney function (median estimated glomerular filtration rate 65 [IQR 62-81] vs 88 [IQR 69-98] ml/min/1.73 m2; p < 0.001) than the group without MetS. The MetS group had higher incidence of complications (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.05-3.08; p = 0.03) and postoperative AKI (OR 3.17, 95% CI 1.54-6.41; p = 0.001). The 5-yr risk of stage IIIB-V CKD (45% vs 7.2%; hazard ratio [HR] 2.34, 95% CI 1.27-4.30; p = 0.006) and OCM (14% vs 3.5%; HR 3.00, 95% CI 1.06-8.55; p = 0.039) were also higher in the MetS group. The main limitations are the extended accrual time and unmeasured confounders that could potentially affect outcomes. Conclusions and clinical implications: Patients with MetS had worse postoperative, functional, and survival outcomes after SRM surgery in comparison to patients without MetS. Multidisciplinary care could help in reducing the preoperative metabolic burden in these patients. Further research should explore if alternative approaches (eg, surveillance or focal therapy) could minimize postoperative comorbidities and protect long-term renal function in this population. Patient summary: Patients with a condition called metabolic syndrome who have part of their kidney removed for small kidney tumors are at higher risk of complications and long-term kidney issues. Patient care from a multidisciplinary team could help in reducing the metabolic burden before surgery. Further research is needed to explore if less invasive treatment options could reduce these risks.

Ferroptosis in Renal Cancer Therapy: A Narrative Review of Drug Candidates.

Renal cancer is a common and serious malignant tumor of the urinary system. While surgery effectively treats early-stage renal cancer, advanced cases pose a significant challenge due to poor treatment outcomes and chemotherapy resistance. Therefore, there is an urgent need to develop alternative therapeutic strategies. Ferroptosis is a newly defined form of programmed cell death characterized by the accumulation of iron-dependent lipid peroxides, which plays a critical role in tumor progression and drug resistance. Recent studies have shown that ferroptosis is involved in the occurrence and development of renal cancer, and ferroptosis-related genes can induce cell apoptosis and can be used as potential biomarkers for early diagnosis of renal cancer and participate in drug resistance of renal cancer chemotherapy. With the continuous improvement of the mechanism of ferroptosis, drugs targeting ferroptosis for the treatment of renal cancer are emerging in an endless stream. Based on the theoretical basis of the occurrence of ferroptosis, this paper reviewed drug-induced ferroptosis in renal cancer cells from the aspects of herbal medicine, natural compounds, drug resistance mechanisms, and nanomaterials, and delves into the clinical application potential of ferroptosis-related drugs in the treatment of renal cancer.

JAK/STAT Signaling Pathway Mediates Anti-Tumor Immunity of CD8+ T Cells in Renal Cancer.

Background: CD8+ T cells play a crucial role in immune responses, and have significant potential in tumor immunotherapy. The JAK/STAT pathway is essential for cytokine signal transduction and is linked to immune escape. However, its role in mediating CD8+ T cell anti-tumor immunity in renal cancer is not fully understood. Objective: To study the mechanisms underlying CD8+ T cell-mediated anti-tumor immunity and propose new possibilities for immunotherapy in patients with renal cancer. Methods: CD8+ T cells from mouse spleens were sorted using immunomagnetic beads, and their purity was confirmed by flow cytometry. Proliferation was analyzed using CCK-8 and CFSE assays. Activation of CD8+ T cells was assessed through ELISA and Western blotting. The malignant properties of Renca cells were evaluated through flow cytometry, Calcein-AM/PI staining, wound healing, Transwell, Western blot, and immunofluorescence. A subcutaneous tumor model in nude mice was used to examine the role of JAK1/STAT1 pathway in vivo. Results: Inhibitors of JAK1 and STAT1 significantly reduced the proliferation and activation of CD8+ T cell. Co-culture with CD8+ T cells increased apoptosis and inhibited the proliferation, migration, and invasion of Renca cells. The effects were diminished by JAK1 and STAT1 inhibitors, confirming that CD8+ T cells exert antitumor effects through the JAK1/STAT1 pathway. In vivo, inhibition of this pathway reduced the anti-tumor effects of CD8+ T cells. Conclusion: Inhibitors of JAK1 and STAT1 weakened the antitumor effects of CD8+ T cells, suggesting that targeting this pathway could enhance CD8+ T cell-mediated immunity in renal cancer.

CCL5 promotes the epithelial-mesenchymal transition of circulating tumor cells in renal cancer.

BACKGROUND: Circulating tumor cells (CTCs) are pivotal in tumor metastasis across cancers, yet their specific role in renal cancer remains unclear. METHODS: This study investigated C-C motif chemokine ligand 5 (CCL5)'s tumorigenic impact on renal cancer cells and CTCs using bioinformatics, in vivo, and in vitro experiments. It also assessed renal cancer patients' CTCs prognostic value through Lasso regression and Kaplan-Meier survival curves. RESULTS: Bioinformatics analysis revealed differential genes focusing on cellular adhesion and migration between CTCs and tumor cells. CCL5 exhibited high expression in various CTCs, correlating with poor prognosis in renal cancer. In 786-O-CTCs, CCL5 enhanced malignancy, while in renal cell carcinoma cell line CAKI-2 and 786-O, it promoted epithelial-mesenchymal transition (EMT) via smad2/3, influencing cellular characteristics. The nude mouse model suggested CCL5 increased CTCs and intensified EMT, enhancing lung metastasis. Clinical results shown varying prognostic values for different EMT-typed CTCs, with mesenchymal CTCs having the highest value. CONCLUSIONS: In summary, CCL5 promoted EMT in renal cancer cells and CTCs through smad2/3, enhancing the malignant phenotype and facilitating lung metastasis. Mesenchymal-type CTC-related factors can construct a risk model for renal cancer patients, allowing personalized treatment based on metastatic risk prediction.

Targeting the Adenosine A2A Receptor as a Novel Therapeutic Approach for Renal Cell Carcinoma: Mechanisms and Clinical Trial Review.

Renal cell carcinoma (RCC) accounts for nearly 2% of cancers diagnosed worldwide. For metastatic RCC, targeted therapy is one of the most common treatment methods. It can include approaches that target vascular endothelial growth factor (VEGFR) or rely on immune checkpoint inhibitors or mTOR inhibitors. Adenosine A2A receptor (A2AR) is a type of widely distributed G-protein-coupled receptor (GPCR). Recently, an increasing number of studies suggest that the activation of A2AR can downregulate anti-tumor immune responses and prevent tumor growth. Currently, the data on A2AR antagonists in RCC treatment are still limited. Therefore, in this article, we further investigate the clinical trials investigating A2AR drugs in RCC. We also describe the epidemiology and current treatment of RCC, along with the physiological role of A2AR, and the types of A2AR drugs that are associated with tumor treatment.

Trends in Stage-Specific Kidney Cancer Incidence in Kazakhstan, 2005-2019.

OBJECTIVE: The aim is to analyze the incidence of kidney cancer over a 15-year period, considering factors such as stage, age, sex, and morphological verification in the regional context in Kazakhstan. METHODS: The retrospective study was done using descriptive and analytical methods of oncoepidemiology. The extensive, crude and age-specific incidence rates are determined according to the generally accepted methodology used in sanitary statistics. The data were used to calculate the average percentage change (APС) using the Joinpoint regression analysis to determine the trend over the study period. RESULTS: Among the meticulously documented 15,277 cases, a conspicuous male predominance was noted, comprising 53.7% of cases compared to 46.3% in females, with peak incidences observed within the 50-69 age cohorts. The average age at diagnosis exhibited a progressive rise over the study period, with discernible variations observed in age-specific incidence rates, particularly pronounced within the 60-84 age brackets. Noteworthy temporal trends indicated a consistent uptick in crude incidence rates, with distinct regional disparities manifesting higher rates in northern regions relative to their southern and western counterparts. Stratification by cancer stage unveiled a significant surge in stages I-II cases alongside a concomitant decrement in stage III incidences, complemented by reductions in stage IV occurrences and instances of unspecified disease stages. Morphological verification rates displayed regional variations, with an overarching ascending trajectory across most regions, albeit exceptions noted, notably in the Kyzylorda region. CONCLUSION: Our study identified a rise in kidney cancer incidence in Kazakhstan, likely reflecting global trends driven by increased risk factor exposure and incidental imaging findings. Regional disparities and varied stage distributions highlight the complexity of kidney cancer epidemiology. Despite advancements in early detection, delayed diagnosis persists, necessitating improved surveillance and diagnostic practices.