Wilms Tumor Research Articles

Predicting the prognosis of Wilms tumor by peripheral blood cells: a real-world study of more than 30years.

Despite established excellent treatment strategies for Wilms tumor (WT), effective prognostic evaluation methods were lacking. This study aims to examine prognostic factors for WT through real-world peripheral blood cell profiling. Basic data and pre-treatment laboratory indices from WT and non-WT children underwent Wilcoxon test analysis. Chi-square tests assessed the correlation between blood cells and the overall survival (OS) and event-free survival (EFS) of WT. Further the Log-rank test and multivariate Cox were used to identify independent prognostic factors for OS. Traditional accepted factors were included in multi-Cox and the nomogram was constructed to further validate the outcome. Blood cells significantly differed between WT and non-WT groups (P < 0.05). Univariate analysis revealed that NLR above 1.380, stage IV, M below 0.325 × 103/μL were linked with lower OS, and PLR below 94.632, LB above 3.570 × 103/μL, stage IV, M above 0.325 × 103/μL,age ≤ 3years were meaningful for higher EFS (P < 0.05). While in the multifactorial COX, only M (HR:0.220, HR95%CI: 0.080 ~ 0.620, P = 0.004 and HR: 0.437, HR95%CI: 0.202 ~ 0.947, P = 0.036, respectively) and stage IV (HR: 7.890, HR95%CI: 1.650 ~ 37.770, P = 0.010 and HR: 3.720, HR95%CI: 1.330 ~ 10.408, P = 0.012, respectively) were independent prognostic factors for OS and EFS. These two variables also were significant after including recognized risk factors, and were demonstrated the predictability via nomogram. OS and EFS were poorer in WT children with M below 0.325 × 103/μL, suggesting the potential as a prognostic predictor for WT.

Abstract A026: A novel ddPCR detects hypermethylated RASSF1A in plasma of patients with pediatric Wilms tumor

Abstract Background: Wilms tumor is the most common pediatric renal cancer. Within the SIOP-Renal Tumor Study Group (SIOP-RTSG), diagnosis is based on imaging and patients receive neo- adjuvant treatment. Final diagnosis is established via histopathological analysis at the timepoint of surgery, which also determines the intensity of adjuvant treatment. Overall, patients with Wilms tumor have a 90% survival rate, but one in five patients will suffer from a relapse, which requires intensive treatment and induces long-term toxicity. It is challenging to identify patients at risk of suffering from relapse at initial diagnosis. Hence the need for additional biomarkers that will optimize risk stratification and minimal residual disease monitoring. RASSF1A is a tumor suppressor gene that is silenced via hypermethylation of its promotor region in multiple adult and pediatric tumors and is reported to represent an aggressive phenotype. We have previously reported on thirteen patients with Wilms tumor where increased hypermethylation of RASSF1A (RASSF1A-M) was observed in plasma cell-free DNA (cfDNA). The aim of this study was to further investigate the levels of RASSF1A-M in a larger cohort. Methods: The presence of RASSF1A-M in plasma cfDNA of patients with Wilms tumor was quantified using a multiplexed droplet digital PCR comprising methylation-specific restriction enzymes. Diagnosis and pre- surgery samples were included to evaluate RASSF1A-M levels during treatment. Results: A total of 49 patients were evaluated. At diagnosis, 37/46 (80.4%) samples were positive for RASSF1A-M. Negative samples were from patients with localized disease (N=6), regressive type regionally advanced Wilms (N=1) or mixed type metastatic Wilms (N=2). RASSF1A-M levels were significantly elevated in regionally advanced and metastatic disease compared to localized disease. Of the 37 positive diagnosis samples, 23 pre-surgical follow-up samples were available. In 7/23, RASSF1A-M was still detectable. These belong to patients with stromal-, regressive- or diffuse anaplastic predominant tumors. Interestingly, an increasing methylation level was seen in one patient with a regressive tumor. Conclusion: RASSF1A-M is a potential biomarker for patients with Wilms tumor, since it was detected in the majority of patients. Furthermore, significantly increased levels were observed in regionally advanced and metastatic disease. In the small number of patients with persisting levels of RASSF1A-M, we did not observe an association with risk groups. In collaboration with SIOP-RTSG, additional follow-up samples will be analyzed to explore the potential of RASSF1A-M as biomarker for relapse detection. Citation Format: Julia Sprokkerieft, Nathalie S.M. Lak, Zeinab van Gestel-Fadaie, Marry M. van den Heuvel-Eibrink, Godelieve A.M. Tytgat. A novel ddPCR detects hypermethylated RASSF1A in plasma of patients with pediatric Wilms tumor [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A026.

Ifosfamide-Induced Encephalopathy Managed Successfully with Methylene Blue in a Child with Wilms Tumor: A Case Report and Review of the Literature

Introduction: Ifosfamide is a crucial element in various chemotherapy protocols for the treatment of diverse solid tumors in both children and adults. Despite its efficacy, ifosfamide is associated with a rare yet severe adverse effect known as ifosfamide-induced encephalopathy (IIE), with a spectrum of signs and symptoms spanning from mild lethargy to coma or death. While approximately 13% of pediatric patients undergoing ifosfamide treatment experience IIE, consensus regarding its management remains controversial. Case Presentation: We present the case of a 4-year-old girl with stage 4 Wilms tumor and lung metastases who underwent radical nephrectomy followed by UH-1 chemotherapy. Imaging post-chemotherapy initially showed tumor clearance but later revealed relapse and lung metastasis. Following the initiation of the adjusted ICE protocol (ifosfamide, etoposide), the patient developed IIE, which was successfully treated with methylene blue. Conclusions: We strongly advise pediatric oncologists and hematologists to proactively consider the potential occurrence of IIE. Before starting ifosfamide therapy, patients should be assessed for possible risk factors associated with IIE. Considering methylene blue as a prophylactic measure is recommended for patients with significant risk factors. In cases where IIE manifests, using Methylene Blue to alleviate and reverse its signs and symptoms should be considered. Moreover, we highly encourage further research endeavors to validate methylene blue's effectiveness and determine its optimal dosage range, especially concerning pediatric patients.

CT Image Parameters for Predicting Surgical Risk and Outcome in Wilms Tumor

CT Image Parameters for Predicting Surgical Risk and Outcome in Wilms Tumor

Recruitment and polarization typing of tumor-associated macrophages is associated with tumor progression and poor prognosis in Wilms tumor patients.

Tumor-associated macrophages (TAMs) play a crucial role in shaping various tumor microenvironments. However, their recruitment in Wilms tumor (WT), the predominant malignant renal tumor in children, has been inadequately explored. This retrospective cohort study involved the analysis of 148 WT samples to investigate the recruitment and polarization typing of TAMs in WT tissues. WT tissues underwent Western blotting (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence (IF) to measure the expression of TAM markers CD68, CD86, and CD163. Statistically analyze the relationship between TAM recruitment levels and patient clinical characteristics, and use Kaplan-Meier curves and the log-rank test to evaluate the association between TAM levels and survival outcomes. The findings indicated a positive correlation between the recruitment levels of total macrophages (Mtotal) and M2 tumor-associated macrophages (M2 TAM) in both chemotherapy and non-chemotherapy groups with the clinical stage. Elevated recruitment of Mtotal and M2 TAM in tumor tissues was linked to a poorer prognosis. Notably, patients with persistently higher recruitment of M2 TAM following preoperative chemotherapy exhibited the worst prognosis. The recruitment and polarization typing of TAM exhibit significant differences in WT patients with various stages and prognosis outcomes, suggesting a potential avenue for future diagnosis and treatment of WT.

The outcomes of children with primary malignant renal tumors: a 14-year single-center experience.

Wilms tumor (WT) is the most common malignant renal tumor in children. This study investigated the clinical features, pathological findings, and outcomes of children with malignant renal tumors in Southern Iran. Factors associated with recurrence and mortality were assessed. Electronic files of children with malignant renal tumors from 2009 to 2023 were reviewed. The 5-year overall survival (OS) and event-free survival (EFS) were reported. Eighty-three patients (44 males) with a median age of 40 months (range: 3-122) were included. WT was the most common pathological variant (94%). Anaplasia was found in 17.3% of patients. Upfront chemotherapy followed by nephrectomy was performed in 54.2% of the patients. Ten patients (12%) experienced relapse, and five patients (6%) died during the 14-year follow-up. The 5-year OS and EFS were 90.75% (95% CI, 78.64-96.16%) and 81.9% (95% CI, 70.10-89.38%), respectively, and were comparable between the two treatment strategies (upfront chemotherapy vs. upfront nephrectomy). Metastasis and residual disease were associated with relapse, whereas tumor recurrence was the only predictive factor of survival. WT is a curable disease with excellent outcomes if diagnosed and treated promptly. The timing of nephrectomy does not affect OS and EFS. Patients with low-stage tumors and those with complete surgical excision are at a lower risk of tumor recurrence. Relapse is the primary risk factor for death.

The accuracy of estimating equations for the evaluation of kidney function in adult survivors of unilateral, nonmetastatic, non-syndromic Wilms tumor: A pilot study from the St. Jude Lifetime Cohort Study.

Adult survivors of unilateral, nonmetastatic, non-syndromic Wilms tumor (WT) treated with whole abdomen radiation therapy (WART) are at risk for impaired kidney function. The impact of bias and accuracy on estimated glomerular filtration rate (eGFR) among adult survivors of WT has not been well documented. We clinically evaluated male and female WT survivors with creatinine and cystatin C, calculated eGFR using the Chronic Kidney Disease-Epidemiology equations with and without cystatin C, and measured 99mTc diethylenetriamine pentaacetic acid (DTPA) plasma clearance. WT survivors treated with unilateral nephrectomy (UN), non-nephrotoxic chemotherapy (NNC) and WART or treated with UN, no radiation therapy, and NNC were enrolled. Correlations between 99mTc DTPA clearance and eGFR were calculated. Bias and the percentage of eGFR calculations that differed from the 99mTc DTPA clearance by 10% or less (P10) or 30% or less (P30) (accuracy) were calculated. Among female WT survivors, none of the eGFR calculations was statistically significantly correlated with 99mTc DTPA clearance. Among both unirradiated and WART-treated male WT survivors, 99mTc DTPA clearance correlated well with eGFR calculations that included creatinine. eGFR calculations that included creatinine were positively biased among female participants compared to 99mTc DTPA clearance, and no P30 was greater than 90% among either irradiated males or females. Among female survivors of unilateral, nonmetastatic, non-syndromic WT who have undergone UN, eGFR is poorly correlated with, is positively biased, and lacks sufficient accuracy, compared to 99mTc DTPA clearance.

Construction of a Wilms tumor risk model based on machine learning and identification of cuproptosis-related clusters

BackgroundCuproptosis, a recently identified type of programmed cell death triggered by copper, has mechanisms in Wilms tumor (WT) that are not yet fully understood. This research focuses on examining the link between WT and Cuproptosis-related genes (CRGs), with the goal of developing a predictive model for WT.MethodsFour gene expression datasets related to WT were sourced from the GEO database. Subsequently, expression profiles of CRGs were extracted for differential analysis and immune infiltration studies. Utilizing 105 WT samples, clusters related to Cuproptosis were identified. This involved analyzing associated immune cell infiltration and conducting functional enrichment analysis. Disease-characteristic genes were pinpointed using weighted gene co-expression network analysis. Finally, the WT risk prediction model was constructed by four machine learning methods: random forest, support vector machine (SVM), generalized linear and extreme gradient strength model. The best-performing machine learning model was chosen, and a nomogram was created. The effectiveness of this predictive model was validated using methods such as the calibration curve, decision curve analysis, and by appiying it to the TARGET-GTEx dataset.ResultsThirteen differentially expressed Cuproptosis-related genes were identified. The infiltration level of CD8 + T cells in WT children was lower than that in Normal tissue (NT) children, and the level of M0 infiltration of macrophages and T follicular helper cells was higher than that in NT children. In addition, two clusters of cuproptosis-related WT were identified. Enrichment analysis results indicated that genes in cluster 2 were primarily involved in cell division, nuclear division regulation, DNA biosynthesis process, ubiquitin-mediated proteolysis. The SVM model was judged to be the optimal model using 5 genes. Its accuracy was confirmed through a calibration curve and decision curve analysis, demonstrating satisfactory performance on the TARGET-GTEx validation dataset. Additional analysis revealed that these five genes exhibited high expression in both the TARGET-GTEx validation dataset and sequencing data.ConclusionThis research established a link between WT and Cuproptosis. It developed a predictive model for assessing the risk of WT and pinpointed five key genes associated with the disease.

Wilms’ Tumor – An Audit

ABSTRACT Background and Aims: Outcome analysis of patients with Wilms’ tumors (WT) is presented. Materials and Methods: A retrospective analysis of 23 children having WT managed by a single surgeon over 3 years (2021–2024) using the International Society of Paediatric Oncology Umbrella protocol was done. Results: The median age at presentation was 36 months; 32 months and 24 months for the unilateral WT (uWT) (n = 19) and bilateral WT (bWT) (n = 4), respectively. M: F ratio was 2.3: 1. WTs were localized in 19 (uWT-16; bWT-3) and metastatic in 4 (uWT-3; bWT-1) patients. Core-needle biopsy was done in 22 patients (26 renal units). Pre-therapy contrast-enhanced computed tomography volumetry (n = 20) showed a median tumor volume of 1023 ml (range: 47–2680 ml). Post-neoadjuvant chemotherapy (NACT) median tumor burden (n = 19) was 612 ml (range 59–3775 ml). Post-NACT, tumor volume decreased in 11/18 patients but increased in seven patients. NACT was avoided in one neonate. Nephroureterectomy (including one with excision of bladder cuff) and nephron-sparing surgery were done in 17 and 10 renal units including 3 with multifocal WT, respectively. Risk stratification was intermediate in 21 and High in 2. Overall staging in 19 uWT included Stage I-7, Stage II-5, Stage III-4, and Stage IV-3 (local staging-stage I in 1 and stage II in 2). Local staging in 8 renal units with bWT was Stage I in 7 and II in 1. One stage IV uWT had bilateral pulmonary metastatectomy. Adjuvant chemotherapy has been completed in 18 patients; two patients are still on adjuvant chemotherapy; flank radiation was administered in six patients. Three patients with synchronous bWT died; two due to acute kidney injury in the immediate postoperative period and one with metastatic disease who had abandoned adjuvant chemotherapy after the 1st cycle. Another patient died of a huge metachronous tumor in the contralateral kidney after a year of completion of therapy. One patient had successful multimodality treatment of local relapse with liver metastasis. 1-year overall and event-free survivals are 84% and 76%, respectively. Conclusions: Excellent short-term results for localized uWT from a center in a low-middle-income country are reported.

Prognostic Value of Preoperative Systemic Immune-Inflammation Index in Non-Metastatic Paediatric Wilms' Tumour Patients Undergoing Upfront Radical Nephrectomy.

To analyse the relationship between the preoperative systemic immune-inflammation index (SII) and the relapse-free survival (RFS) of paediatric patients with Wilms' tumour (WT) after radical surgery, and to establish and validate a prognostic survival model. Observational study. Place and Duration of the Study: Department of Oncologic Surgery, Anhui Children's Hospital of Fudan University, Hefei, China, from January 2013 to August 2023. A retrospective analysis was conducted on 79 WT patients treated with radical resection, with their preoperative SII values computed. The best cut-off for SII was determined through the ROC curve, categorising patients into high and low SII groups. The Kaplan-Meier method and Cox-regression were used for survival analysis. A survival prognostic model was constructed and its predictive capability gauged (AUC of the ROC). The study included 79 WT patients with a median RFS of 65 months and an average of 75.5 ± 3.4 months. The optimal cut-off value for SII was 534.95. The low SII group had a higher RFS (Log-rank: χ2 = 9.380, p = 0.002). Preoperative SII (HR = 3.277, 95% CI: 1.167 - 9.200, p = 0.024), clinical staging (HR = 8.408, 95% CI: 2.604 - 27.147, p <0.001), and tissue differentiation (HR = 2.237, 95% CI: 1.043 - 5.828, p = 0.039) were independent risk factors for RFS. The model's diagnostic performance was 0.749 (95% CI: 0.636 - 0.861). Internal validation showed an AUC of 0.723 (95% CI: 0.608 - 0.838). Lower preoperative SII suggests a more favourable prognosis. The SII-based nomogram efficiently forecasts post-radical surgery prognosis for WT. Wilms' Tumour, Systemic immune-inflammation index, Relapse-free survival, Nomogram.

Prognostic Value of Preoperative Systemic Immune-Inflammation Index in Non-Metastatic Paediatric Wilms' Tumour Patients Undergoing Upfront Radical Nephrectomy.

To analyse the relationship between the preoperative systemic immune-inflammation index (SII) and the relapse-free survival (RFS) of paediatric patients with Wilms' tumour (WT) after radical surgery, and to establish and validate a prognostic survival model. Observational study. Place and Duration of the Study: Department of Oncologic Surgery, Anhui Children's Hospital of Fudan University, Hefei, China, from January 2013 to August 2023. A retrospective analysis was conducted on 79 WT patients treated with radical resection, with their preoperative SII values computed. The best cut-off for SII was determined through the ROC curve, categorising patients into high and low SII groups. The Kaplan-Meier method and Cox-regression were used for survival analysis. A survival prognostic model was constructed and its predictive capability gauged (AUC of the ROC). The study included 79 WT patients with a median RFS of 65 months and an average of 75.5 ± 3.4 months. The optimal cut-off value for SII was 534.95. The low SII group had a higher RFS (Log-rank: χ2 = 9.380, p = 0.002). Preoperative SII (HR = 3.277, 95% CI: 1.167 - 9.200, p = 0.024), clinical staging (HR = 8.408, 95% CI: 2.604 - 27.147, p <0.001), and tissue differentiation (HR = 2.237, 95% CI: 1.043 - 5.828, p = 0.039) were independent risk factors for RFS. The model's diagnostic performance was 0.749 (95% CI: 0.636 - 0.861). Internal validation showed an AUC of 0.723 (95% CI: 0.608 - 0.838). Lower preoperative SII suggests a more favourable prognosis. The SII-based nomogram efficiently forecasts post-radical surgery prognosis for WT. Wilms' Tumour, Systemic immune-inflammation index, Relapse-free survival, Nomogram.

Survival and Toxicity Outcomes with Radiotherapy Technique and Timing in the Management of Wilms Tumor: a Systematic Review to Inform a National Clinical Practice Guideline Development

Purpose: Wilms tumor (WT) management has evolved into a multimodality paradigm that includes radiotherapy (RT), usually as an adjuvant or consolidative modality. Protocols are refined to maximize cure and compliance while minimizing acute toxicity and long-term effects. RT technique and timing are two factors that could improve these outcomes. We reviewed the evidence on survival and toxicity outcomes among WT patients with conventional versus advanced RT techniques and early versus delayed RT to inform a Department of Health (DOH) commissioned guideline. Materials and Methods: We systematically searched PubMed, EuropePMC, EBSCOHost, HERDIN, systematic review and clinical trial registries and official websites of scientific societies for relevant publications and grey literature. Eligibility screening, risk-of-bias assessment and data extraction were performed using a single-reviewer approach. Given the study and data heterogeneity, only a qualitative synthesis was performed. Certainty of evidence assessment was done using the GRADE approach. Results: We screened 314 studies and included seven in the review, including a phase 1/2 trial and six retrospective studies, all from first-world countries (US, France, Netherlands), except one from a newly industrialized country (Brazil). The certainty of evidence on the survival and toxicity outcomes with advanced RT techniques was very low. Moderate-certainty evidence supports that giving RT &gt;14 days after surgery leads to increased mortality. Conclusion: Current evidence does not support the routine use of advanced RT techniques; proper contextualization is necessary. Tertiary centers managing WT should strive to administer RT within 14 days after surgery whenever possible. Keywords: Wilms tumor, nephroblastoma, radiotherapy, intensity-modulated radiotherapy, survival, toxicity

006. Wilm’s Tumor with Obstructive Ileus in A Newborn

Background: Wilms' tumor is the most common kidney malignancy in the pediatric population. Wilms' tumor can spread to other organs, pressing on surrounding organs, and causing kidney damage and high blood pressure. This case report aims to report on neonatal patients with Wilms' tumor which complicate into obstructive ileus. This study aims to explore the effect of wilm’s tumor on causing obstructive ileus which can be detrimental to a newborn. Methods: A 21-day-old baby boy was brought in with complaints of a lump in the left abdomen that had been felt since birth. The lump was felt to be growing rapidly and feels hard. Physical examination revealed sunken eyes, dry lips, holosystolic murmur on parasternal line intercostal II-IV, and a solid mass sized 5x4 cm in the left hypochondrium up to left iliac region. Abdominal ultrasound and CT scan confirmed a renal mass. Results: The patient was diagnosed with partial obstructive ileus due to left kidney tumor suppression, suspected Wilms tumor and low intake malnutrition with moderate to severe dehydration. The patient was managed with laparotomy and left nephrectomy. The procedure alleviated all symptoms and upon 1 month follow up, the patient was healthy with good nutrition status. Conclusion: The presence of large abdominal mass in neonates can be a sign of Wilms tumor. This disease can lead to obstructive ileus and can be treated with laparotomy and nephrectomy.

ZSTK474 targeting PIK3R3 inhibits the Wilms' tumor through G0 / G1 phase arrest.

Wilms' tumor (WT), also known as nephroblastoma, is the predominant form of primary malignant renal cancer. The unfavorable prognoses linked to anaplastic nephroblastoma and recurrent nephroblastoma emphasize the crucial requirement for the exploration of innovative treatment modalities for WT. Our study conducted one-way Cox regression and Kaplan-Meier analyses using TARGET-WT nephroblastoma data to identify differentially expressed genes in nephroblastoma and evaluate their prognostic relevance. Utilizing the Connectivity Map database, ZSTK474 emerged as a viable therapeutic option for WT. The effect of ZSTK474 on WT and related underlying mechanisms were further investigated through in vitro and in vivo investigations. The in vivo experiment results indicated that ZSTK474 effectively inhibited subcutaneous tumor growth in WT mice. CCK-8 assays revealed two nephroblastoma cell lines exhibited half-inhibitory concentrations of 2μM and 2.51μM for ZSTK474, respectively. ZSTK474 was shown to inhibit the migration and invasion capabilities of WT cells in both Transwell and wound healing assays. Flow cytometry apoptosis and TUNEL assays demonstrated that ZSTK474 induced apoptosis in WT cells. Cell cycle analysis revealed that ZSTK474 led to the induction of G0/G1 phase arrest. Sequencing of ZSTK474-treated WiT49 cells suggested that the impact of ZSTK474 on WT might be mediated by the PI3K/Akt pathway, specifically by inhibiting PIK3R3. Knock-down of PIK3R3 confirmed that ZSTK474 downregulated PIK3R3, reducing Akt phosphorylation, cyclin D and CDK4 levels and elevating P21 expression in nephroblastoma cells. However, current research has limitations, including a lack of understanding of the long-term effects and potential resistance mechanisms of new therapies. This research provides insight into the potential of ZSTK474 and other PI3K inhibitors for treating nephroblastoma.

Update on surveillance guidelines in emerging Wilms tumor predisposition syndromes.

Wilms tumors are commonly associated with predisposition syndromes. Many of these syndromes are associated with specific phenotypic features and are discussed in the related paper from the AACR Pediatric Cancer Working Group. Guidelines for surveillance in this population were published in 2017 but since then several studies have identified new genes with recurrent pathogenic variants associated with increased risk for Wilms tumor development. In general, variants in these genes are less likely to be associated with other phenotypic features. Recently, members of the AACR Pediatric Cancer Working Group met to update surveillance guidelines for patients with a predisposition to Wilms tumors with a review of recently published evidence and risk estimates. Risk estimates for Wilms tumor for the more recently described genes are discussed here along with suggested surveillance guidelines for these populations. Several other emerging clinical scenarios associated with Wilms tumor predisposition are also discussed including patients with family histories of Wilms tumor and no identified causative gene, patients with bilateral tumors, and patients with somatic mosaicism for chromosome 11p15.5 alterations. This perspective serves to update pediatric oncologists, geneticists, radiologists, counselors and other healthcare professionals on emerging evidence and harmonize updated surveillance recommendations in the North American and Australian context for patients with emerging forms of Wilms tumor predisposition.

001. Large Wilms Tumor in A 3-Year-Old Child at Abdoel Wahab Sjahranie Hospital: A Case Report

Background: Wilms tumor (WT) is the most common primary renal tumor in children, typically diagnosed between ages of 1 and 5, with peak incidence at 3 years. Imaging modalities like ultrasound, CT, and MRI can predict WT in up to 95% of cases, but histological subtypes necessitate tissue examination. Management usually involves surgery, chemotherapy, and sometimes radiation therapy. This report aims to present and analyze the clinical presentation, diagnostic approach, and management of an unusually large Wilms tumor in a 3-year-old child at our hospital, highlighting the challenges and treatment strategies for such rare case. Case: A 3-year-old girl with hematuria for two weeks and an abdominal mass that had been present for years but had enlarged in the last 2-3 months. Physical examination revealed a palpable mass in the left hypochondrium. Abdominal CT showed grade II/III left hydronephrosis with a cystic and solid lesion measuring 10.3 x 8.1 cm and enlarged right para-aortic glands. Conclusion: This case underscores the importance of a multidisciplinary approach involving surgery and chemotherapy to effectively manage WT and highlights the positive prognosis associated with timely treatment

WTAP Promotes the Excessive Proliferation of Airway Smooth Muscle Cells in Asthma by Enhancing AXIN1 Levels Through the Recognition of YTHDF2.

Asthma is a common chronic respiratory disease in children, the incidence rate of which has increased in recent years. Wilms tumour 1-associated protein (WTAP) is an N6-methyladenosine (m6A) methyltransferase. The purpose of this study was to explore the specific mechanism of WTAP in asthma progression, and clarify the intricate interplay between m6A modifications, WTAP, AXIN1, and their collective impact on airway smooth muscle cells (ASMCs) proliferation in asthma. Platelet-derived growth factor-BB (PDGF-BB)-treated ASMCs were used to establish an asthma model in vitro. The cell phenotype was tested using CCK-8, transwell, and wound healing assays. The expression of the Wnt signalling pathway was detected by western blotting. In addition, the relationship between WTAP/YTDHF2 and AXIN1 was assessed by a double luciferase reporter assay. Actinomycin D treatment and RT‒qPCR assays were performed to determine the mRNA stability of AXIN1. We found that WTAP was significantly increased in PDGF-BB-treated ASMCs. Knockdown of WTAP inhibited the excessive cell viability and migration of ASMCs induced by PDGF-BB. Furthermore, WTAP knockdown increased AXIN1 levels and inhibited the Wnt signalling pathway. Furthermore, WTAP knockdown decreased the m6A levels and enhanced the mRNA stability of AXIN1. WTAP overexpression showed the opposite effect. In addition, YTHDF2 was demonstrated to be the reader that recognizes the WTAP-mediated m6A modification of AXIN1. YTHDF2 knockdown enhanced the mRNA stability of AXIN1 and reversed the effect of WTAP overexpression on PDGF-BB-treated ASMCs. WTAP knockdown inhibited the excessive cell viability and migration of ASMCs by enhancing the m6A levels of AXIN1, which was further recognized by YTHDF2. The upregulation of AXIN1 mediated by the WTAP/YTHDF2 axis further inhibited the Wnt signalling pathway. Our study provides a new method for the treatment of asthma. This work not only deepens our understanding of the molecular underpinnings of asthma but also identifies potential therapeutic targets for the development of novel treatments aimed at inhibiting ASMC proliferation and alleviating asthma symptoms.

A Study of JUN’s Promoter Region and Its Regulators in Chickens

Background: The Jun proto-oncogene (JUN), also referred to as C-JUN, is an integral component of the JNK signaling pathway, which is crucial for the formation and differentiation of spermatogonial stem cells (SSCs). Investigations into the transcriptional regulation of chicken JUN can offer a molecular foundation for elucidating its mechanistic role in SSCs. Methods: In this study, we successfully cloned a 2000 bp upstream sequence of the JUN transcription start site and constructed a series of pGL3 recombinant vectors containing JUN promoters of varying lengths. Results: We verified the promoter activity of the 2000 bp upstream sequence by assessing the fluorescence intensity of DF-1 and identified the promoter activities of different regions via dual-luciferase assays. The transcription of JUN and its promoter region spanning −700 to 0 bp was modulated by an activator of the JNK signaling pathway. Bioinformatics analysis revealed that this −700 to 0 bp region was highly conserved among avian species and predicted the presence of binding sites for Wilms tumor 1 (WT1) and CCAAT/enhancer binding protein alpha (CEBPA). The JNK signaling pathway activator was found to upregulate the expression of these transcription factors in DF-1 cells. Through the deletion of binding sites and the overexpression of WT1 and CEBPA, we demonstrated that WT1 inhibited the transcription of JUN, while CEBPA promoted it. Conclusions: In conclusion, the −700 to 0 bp region is the key region of the JUN promoter, with WT1 inhibiting JUN transcription. The results of the study not only provide ideas for exploring the regulatory mechanism of JUN in chicken SSCs, but also lay an important foundation for the study of avian SSCs.

Retraction Note: Wilms tumor-suppressing peptide inhibits proliferation and induces apoptosis of Wilms tumor cells in vitro and in vivo

Retraction Note: Wilms tumor-suppressing peptide inhibits proliferation and induces apoptosis of Wilms tumor cells in vitro and in vivo

Pathological Insights into Non-Neoplastic Renal Parenchyma in Wilms Tumor: Implications for Nephron-Sparing Surgery.

This study aimed to evaluate the non-neoplastic renal parenchyma in Wilms tumor (WT) and investigate its impact on nephron-sparing surgery (NSS). The non-neoplastic renal parenchyma of WT patients was prospectively collected for pathological examination. The histology of non-neoplastic renal parenchyma was assessed from two perspectives: nephrogenic rests (NRs) and nephrons. A total of 46 non-neoplastic renal parenchyma specimens were collected from 42 WT patients. The surgeons assessed the median proportion of non-neoplastic renal parenchyma as 30%, whereas using ellipsoid volume, it was calculated to be 27%. The Youden index of surgeons' assessment peaked at a 15% proportion of non-neoplastic renal parenchyma. The bilateral WT (BWT) group and NSS group exhibited significant differences compared with the unilateral WT group and radical nephrectomy group, respectively, with the BWT group showing a tendency toward thickened basement membrane. The presence of NRs and endogenous nephron alternations should be given due attention in WT. The probability of abnormalities is low when the proportion of non-neoplastic renal parenchyma exceeds 15%, providing pathological support for expanding the adaptation of NSS.