Loss of heterozygosity for chromosomes 16q in Wilms tumors predicts outcomes:A meta-analysis

BACKGROUND The research findings suggest that the prognosis of children with Wilms tumor(WT)is affected by various factors.Some scholars have indicated that loss of heterozygosity(LOH)on chromosome 16q is associated with a poor prognosis in patients with WT.AIM To further elucidate this relationship,we conducted a meta-analysis.METHODS This meta-analysis was registered in INPLASY(INPLASY2023100060).We systematically searched databases including Embase,PubMed,Web of Science,Cochrane,and Google Scholar up to May 31,2020,for randomized trials reporting any intrapartum fetal surveillance approach.The meta-analysis was performed within a frequentist framework,and the quality and network inconsistency of trials were assessed.Odds ratios and 95%CIs were calculated to report the relationship between event-free survival and 16q LOH in patients with WT.RESULTS Eleven cohort studies were included in this meta-analysis to estimate the relationship between event-free survival and 16q LOH in patients with WT(I^(2)=25%,P<0.001).As expected,16q LOH can serve as an effective predictor of eventfree survival in patients with WT(risk ratio=1.95,95%CI:1.52–2.49,P<0.001).CONCLUSION In pediatric patients with WT,there exists a partial correlation between 16q LOH and an unfavorable treatment prognosis.Clinical detection of 16q chromosome LOH warrants increased attention to the patient’s prognosis.

Survival Outcome of Wilms Tumor with Multi-Modality Treatment at Jimma Hospital, Southwest Ethiopia

Background: Wilms’ tumor (WT), the most common malignant neoplasm of the urinary tract of children [1], accounts for 5.9% of childhood cancers and affects one in every 10,000 children worldwide before the age of 15 years. The care of children with Wilm’s tumor in sub-Saharan Africa is compromised due to resource deficiencies that range from inadequate healthcare budgets to paucity of appropriately trained personnel. Childhood Wilms tumor is surging as an important paediatric problem in developing and sub-Saharan Africa countries. The objective of the study is to establish an understanding on the treatment challenges and outcomes of Wilm’s tumor in South West Ethiopia. Results: Forty-three Wilm’s tumor patients who were admitted from January 2017 to December 2021 were included in the study. The most frequent presentation was painless abdominal swelling in 40 (93%) patients. Fourteen patients (32.6%) were hypertensive at the time of diagnosis and the other 13 (30.2%) were normal. In abdominal examination, 31 (72.1%) patients had abdominal mass not crossing the midline and 12 (27.9%) had mass crossing the midline. After multimodal treatment, 37.5% had improvement, 11.6% came back with relapse. Most patients (41.7%) abandoned treatment and 9.3% of the cohort died in the course of treatment. Conclusion: The outcomes in the treatment of Wilms Tumor have been found to be poor in this review. The main reason for poor outcome has been not receiving adequate chemotherapy after surgery. Doses of chemotherapy received after surgery significantly affected treatment outcomes (p = 0.026).

Wilm′s tumor gene1肽疫苗Galinpepimut-S在肿瘤免疫治疗中的应用

目的为Wilm′s tumor gene1(WT1)肽疫苗Galinpepimut-S(GPS)用于肿瘤免疫治疗的后续研究提供参考。方法采用计算机检索中国知网、PubMed等数据库自建库起至2022年12月的肿瘤免疫治疗相关文献,总结GPS在肿瘤免疫治疗中的应用现状。结果GPS能激发自身免疫系统,对WT1抗原产生强烈免疫反应而发挥抗肿瘤作用,在卵巢癌、恶性胸膜间皮瘤、急性髓系白血病、多发性骨髓瘤的治疗中均显示出较好的疗效。结论以GPS为代表的肿瘤疫苗是未来肿瘤治疗的重要方向,需进一步进行临床研究,以获取更多数据。

基于高通量RNA测序分析Wilms瘤中关键基因对预后及免疫应答的影响

目的探索肾母细胞瘤(WT)中关键基因及其对预后和免疫应答的潜在影响。方法采用高通量RNA测序技术分析临床肿瘤样本和配对正常组织的mRNA全面表达谱,并鉴定差异表达基因。使用GO、KEGG和GSEA富集分析探索差异表达基因在肾母细胞瘤中的潜在生物学功能和机制。使用STRING数据库鉴定HUB基因。LASSO回归用于构建HUB基因预后模型。基于cBioPortal平台分析关键HUB基因的突变特征并对其免疫治疗效果进行预测。采用qPCR验证关键HUB基因的差异表达。结果本研究筛选出1612个差异表达基因,其中1030个上调,582个下调。GO、KEGG或GSEA富集分析显示,差异基因集与细胞周期和免疫应答有关,一定程度上参与了WT的发生发展。基于STRING数据库构建差异基因的PPI网络,进一步确定了10个HUB基因。其中4个HUB基因(TP53、MED1、CCNB1和EGF)被证实与WT患儿的生存密切相关。通过LASSO回归分析构建WT患者的三基因预后签名,根据该签名将患者分为高危或低危组,生存分析显示显著的预后差异(HR=1.814,Log-rank P=0.002)。该模型的3年、5年和7年生存ROC曲线的AUC值均大于0.7。突变分析显示,关键HUB基因整体突变或TP53/CCNB1的单独突变与较低的生存率密切相关,其中TP53高表达与较差的免疫治疗疗效有关。qPCR结果显示,关键HUB基因在肿瘤组织和细胞中呈现出显著的表达差异。结论TP53基因在WT中发挥重要作用,可能成为新的免疫治疗生物标志物和治疗靶点。

Extrarenal Wilms’ Tumor of the Female Genital System:A Case Report and Literature Review

Extrarenal Wilms’ Tumors (ERWTs) are rare. There have been only 25 cases of ERWT arising from the female genital system reported in the literature. In this paper, we report a 60-year-old woman with a complaint of vaginal bleeding and a polypoid mass in the uterine cavity by sonography that was demonstrated as ERWT by pathology after resection. The pathological characteristics, histological origination,diagnosis, therapy and prognosis of ERWT in female reproductive system are discussed in this paper in the purpose of improving the diagnosis and therapy of this rare tumor.

Wilms tumor with dilated cardiomyopathy: A case report

BACKGROUND Wilms tumor is the most common renal malignancy in childhood. It occurs primarily between the ages of 2 and 5 years. The usual manifestations are abdominal mass, hypertension, and hematuria. The case presented here had an unusual presentation, with dilated cardiomyopathy and hypertension secondary to the Wilms tumor. CASE SUMMARY A 3-year-old boy presented with a 5-d history of irritability, poor appetite, and respiratory distress. His presenting clinical symptoms were dyspnea, tachycardia, hypertension, and a palpable abdominal mass at the left upper quadrant. His troponin T and pro-B-type natriuretic peptide levels were elevated. Echocardiography demonstrated a dilated hypokinetic left ventricle with an ejection fraction of 29%, and a suspected left renal mass. Computed tomography scan revealed a left renal mass and multiple lung nodules. The definitive diagnosis of Wilms tumor was confirmed histologically. The patient was administered neoadjuvant chemotherapy and underwent radical nephrectomy. After surgery, radiotherapy was administered, and the adjuvant chemotherapy was continued. The blood pressure and left ventricular function normalized after the treatments. CONCLUSION Abdominal mass, dilated cardiomyopathy and hypertension can indicate Wilms tumor in pediatric patients. Chemotherapy and tumor removal achieve successful treatment.

Prognostic Impact of HER/2 Expression on Survival of Preoperatively Treated Children with Wilms Tumor at South Egypt

Aim: Wilms tumor (WT) is the most frequent type of pediatric renal tumors. Her/2 is an oncoprotein, its over-expression revealed to play a very vital role in the progress and improvement of certain tumors. This study evaluates the possible role of Her/2 as a prognostic indicator in formerly treated WT. Method: Immunohistochemical expression of Her/2 was studied in paraffin material of 40 WT patients followed SIOP 9 protocol. Patients’ medical records reviewed for clinical, pathological and outcome data and correlated with HER2 expression. Additional 15 samples of normal surrounding kidney tissue specimens were included. Results: Her/2 was often expressed in normal kidney tissue (renal tubules but not glomeruli) and at variable levels in the three elements of WT. At a median of 84 months, 70% of patients are living and under follow-up, surgical stage and pathologic subtypes were the only two factors significantly affect the outcome of our patients (p = 0.000, p = 0.007 & p = 0.004, p = 0.005 for OS (Overall survival) and DFS (Disease Free survival) respectively). Her/2 expression was associated with epithelial differentiation (p < 0.001). There was non-significant effect of Her/2 expression on OS or DFS of studied group. Conclusion: while the major progress in studying biology of WT, stage and pathological subtype continues the only predictive factors of significant value affecting the outcome of patients with WT. There was important association between Her/2 expression and histological differentiation in formerly treated Wilms tumor. Non-conclusive results regarding influence of Her/2 expression on the result of WT patients were found.

Osteopathia striata with cranial sclerosis, Wilms' tumor and the WTX gene

Osteopathia striata with cranial sclerosis(OSCS, OMIM#300373) is an X-linked dominant sclerosing bone dysplasia that shows a distinct phenotype in females and males. In 2009, Zandra Jenkins et al found that germline mutations in the FAM123 B /WTX /AMER1 gene, mapped to chromosome Xq11.2, cause both the familial and sporadic forms of OSCS. Intriguingly, the WTX gene was already known as a putative tumor suppressor gene, since in 2007 Rivera et al had reported inactivating WTX mutations in Wilms' tumor(WT), the most frequent renal tumor of childhood. Here we review the heterogeneous clinical presentation of OSCS patients and the involvement of WTX anomalies in OSCS and in WT.

Identification of a constitutional mutation in the WT1 gene in Taiwan Residents patients with Wilms tumor

The overall frequency of WT1 gene alterations in Wilms tumor is still unclear in Taiwan. Here we conducted molecular genetic analysis of the WT1 gene in Taiwan Residents patients with Wilms tumor. Polymerase chain reaction and direct sequencing were performed on DNA samples from blood and paraffin-embedded tumor specimens. A constitutional mutation in the WT1 gene was found in one DNA sample from peripheral blood lymphocytes. The remaining DNA samples from peripheral blood lymphocytes and paraffin-embedded tumor specimens were tested negative for both constitutional mutations and somatic mutations. Thus, mutations at other Wilms tumor loci may play an important role in Wilms tumor development.

儿童肾脏原发非Wilms瘤恶性肿瘤的临床特点

目的:探讨儿童肾脏原发非Wilms瘤恶性肿瘤的临床特点及预后。方法:回顾性分析我院血液肿瘤科2015年1月至2020年12月收治的22例儿童肾脏原发非Wilms瘤恶性肿瘤的临床资料。结果:本组共22例儿童肾脏原发非Wilms瘤恶性肿瘤,男性12例,女性10例,中位发病年龄42.5月(4月~173月),肾透明细胞肉瘤10例,肾恶性横纹肌样瘤5例,肾细胞癌4例,神经母细胞瘤2例,尤文肉瘤1例,临床表现以肉眼血尿和体格检查发现腹部包块最常见,临床分期:Ⅰ期2例,Ⅱ期3例,Ⅲ期11例,Ⅳ期6例,21例患者行根治性肿瘤切除术,随访时间23月(4~80月),2年和5年OS分别为81.3%和69.7%,临床分期Ⅳ期OS和EFS较临床分期Ⅰ+Ⅱ+Ⅲ期患者低,差异有统计学意义(P<0.05)。结论:儿童肾脏原发非Wilms瘤恶性肿瘤临床罕见,不同类型肿瘤的诊断主要依据免疫组化及分子诊断,临床分期Ⅳ期与预后不良相关,早期发现、早期多学科联合诊治有助于改善预后。

CT鉴别诊断儿童TFE3重排肾细胞癌与Wilms瘤

目的观察CT鉴别诊断儿童TFE3重排肾细胞癌(TFE3 RCC)与Wilms瘤(WT)的价值。方法回顾性分析经手术病理证实的10例单发TFE3 RCC(TFE3 RCC组)及20例单发WT(WT组)患儿的术前腹盆腔CT资料。对比组间病灶CT表现差异;针对差异有统计学意义的参数绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC),评估其鉴别儿童TFE3 RCC与WT的效能。结果组间CT所示病灶最大径、平扫CT净值、边界清晰与否、有无病灶内钙化、动脉期和静脉期强化CT值、强化程度差异均有统计学意义(P均<0.05),上述各项指标鉴别诊断TFE3 RCC与WT的AUC分别为0.82、0.97、0.80、0.75、0.91、0.83及0.93。结论CT可有效鉴别诊断儿童TFE3 RCC与WT。

CD147在儿童Wilms瘤中的表达及意义

目的 探索CD147在儿童Wilms瘤中的表达及其临床意义。方法 选取48例Wilms瘤患者作为研究对象,并选取非肾脏肿瘤儿童48例作为对照,采用免疫组织化学法检测CD147在受试患者中的表达情况,分析其临床意义。结果 CD147在Wilms瘤患者中的表达水平显著高于非肾脏肿瘤儿童(P<0.05)。CD147表达与Wilms瘤患者的性别、年龄、肿瘤转移不相关(P>0.05),但与肿瘤危险度分级、肿瘤长、肿瘤宽、临床分期、病理类型具有相关性(P<0.01)。结论 Wilms瘤患者中CD147呈现高水平表达,可以此辅助诊断儿童Wilms瘤。

Spontaneous xenogeneic GvHD in Wilms'tumor Patient-Derived xenograft models and potential solutions

Severely immunocompromised NOD.Cg-PrkdcIl2rg(NOG)mice are among the ideal animal recipients for generation of human cancer models.Transplantation of human solid tumors having abundant tumor-i nfiltrating lymphocytes(TILs)can induce xenogeneic graft-versus-host disease(xGvHD)following engraftment and expansion of the TILs inside the animal body.Wilms’tumor(WT)has not been recognized as a lymphocyte-predominant tumor.However,3 consecutive generations of NOG mice bearing WT patient-derived xenografts(PDX)xenotransplanted from a single donor showed different degrees of inflammatory symptoms after transplantation before any therapeutic intervention.In the initial generation,dermatitis,auto-amputation of digits,weight loss,lymphadenopathy,hepatitis,and interstitial pneumonitis were observed.Despite antibiotic treatment,no response was noticed,and thus the animals were prematurely euthanized(day 47 posttransplantation).Laboratory and histopathologic evaluations revealed lymphoid infiltrates positively immunostained with anti-human CD3 and CD8 antibodies in the xenografts and primary tumor,whereas no microbial infection or lymphoproliferative disorder was found.Mice of the next generation that lived longer(91 days)developed sclerotic skin changes and more severe pneumonitis.Cutaneous symptoms were milder in the last generation.The xenografts of the last 2 generations also contained TILs,and lacked lymphoproliferative transformation.The systemic immunoinflammatory syndrome in the absence of microbial infection and posttransplant lymphoproliferative disorder was suggestive of xGvHD.While there are few reports of xGvHD in severely immunodeficient mice xenotransplanted from lymphodominant tumor xenografts,this report for the first time documented serial xGvHD in consecutive passages of WT PDX-bearing models and discussed potential solutions to prevent such an undesired complication.

Wilms瘤基因1、B7家族成员H3及自然杀伤细胞表面受体在多发性骨髓瘤和淋巴瘤中的表达及临床意义

目的探讨Wilms瘤基因1(WT1)、B7家族成员H3(B7H3)及自然杀伤(NK)细胞表面受体在多发性骨髓瘤和淋巴瘤中的表达及临床意义。方法选取56例多发性骨髓瘤患者和50例淋巴瘤患者,分别作为骨髓瘤组和淋巴瘤组,采用流式细胞仪检测两组患者NK细胞占有核细胞比例,采用荧光定量聚合酶链反应(PCR)检测两组患者WT1、B7H3 mRNA相对表达量以及NK细胞表面受体NKG2D、CD69、程序性死亡受体1(PD-1)mRNA的相对表达量。随访1年,比较不同预后情况多发性骨髓瘤和淋巴瘤患者WT1、B7H3 mRNA相对表达量及NK细胞占有核细胞比例。绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC),评估各指标对多发性骨髓瘤患者和淋巴瘤患者预后的预测价值。结果骨髓瘤组患者B7H3 mRNA相对表达量低于淋巴瘤组,PD-1、NKG2D mRNA相对表达量及NK细胞占有核细胞比例均高于淋巴瘤组,差异均有统计学意义(P﹤0.05)。随访结束,56例多发性骨髓瘤患者中,预后不良15例,预后良好41例,预后良好的多发性骨髓瘤患者B7H3 mRNA相对表达量明显低于预后不良患者,差异有统计学意义(P﹤0.01)。B7H3预测多发性骨髓瘤患者预后的AUC为0.748(95%CI:0.605~0.891),cut-off值为3.29,此时的灵敏度为0.867,特异度为0.659。随访结束,淋巴瘤组患者中,预后不良19例,预后良好31例,预后良好淋巴瘤患者B7H3 mRNA相对表达量低于预后不良患者,NK细胞占有核细胞比例高于预后不良患者,差异均有统计学意义(P﹤0.05)。B7H3、NK细胞占有核细胞比例联合检测预测淋巴瘤患者预后的AUC为0.852(95%CI:0.731~0.973),灵敏度为0.871,特异度为0.737。结论B7H3及NK细胞受体在多发性骨髓瘤和淋巴瘤患者中的表达水平存在差异,但WT1水平的差异不明显,B7H3及NK细胞占有核细胞比例对多发性骨髓瘤及淋巴瘤患者的预后有一定的预测意义。

Expression and significance of p53,nm23 and p16 in Wilms' tumor of children

We studied 22 Wilms’tumors of children immunohistochemically.We’ve found that the positive rate of p53 in slices was 31.8％ (7),of nm23 was 50％ (11),and of p16 was 86.4％ (19).It suggested that mutation rate of p53 was high in tumors,expression of nm23 in favorite histology(FH)was higher than that in unfavorite histology(UFH) group,and p16 showed very high positive rate in tumors.All of the three showed no relation with sex,age,or pathological type.So each one may be useful in clinic to evaluate pathogenesis and prognosis.

YTE-17 inhibits colonic carcinogenesis by resetting antitumor immune response via Wnt5a/JNK mediated metabolic signaling

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical b-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with b-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.

Juvenile myelo-monocytic leukemia (JMML): No effect of granulocyte monocyte-colony stimulating factor (GM-CSF) on Wilms Tumor gene (<i>WT</i>1) by nested Polymerase Chain Reaction (nPCR) and flow cytometry

This study was to determine whether GM-CSF induced WT1 gene expression and to establish an association with markers of proliferation CD71+CD34+ using nPCR and flow cytometry respectively, in samples obtained from 5 newly diagnosed JMML patients. Overtime (day 0 to day 14) there was an insignificant difference in WT1 gene expression and CD71+CD34+ in JMML samples when compared to peripheral blood of normal volunteers (n = 3). Our study suggests that there is a correlation between WT1 gene expression and cellular proliferation and that GMCSF in vitro does not create a significant difference in JMML samples.

Unilateral Ptosis in a Child with Wilm’s Tumor Induced by Vincristine

Vincristine is a chemotherapy drug belonging to the group of Vinca alkaloids which also includes vinblastine and vindesine. It is used in hematological malignancies and solid tumors. The Vinca alkaloids are neurotoxic, usually causing peripheral neuropathy, and rarely cranial neuropathies. We report a case of a 33-month-old male child diagnosed with Wilms’ tumor, who had an isolated unilateral right ptosis following vincristine, with a good improvement after stopping it.

Fine needle aspiration cytology of Wilms' tumor:a case report

Wilms' tumor is extremely rare.In this article,we reported one case diagnosed by fine needle aspiration cytology(FNAC) and pathology.A three and a half-year-old boy was admitted to hospital with abdominal pain for two days.CT scan showed a large mass in the region of the left kidney of the boy.FNAC was performed on the mass,and the cytologic specimen showed malignant cells suggestive of a Wilms' tumor.Histologic examination of the operative specimen after the left nephrectomy also revealed Wilms' tumor.

Diagnosis and treatment of Wilms tumor

We collected a medical record of“Wilms’tumor”in the Department of Urology at the Third Affiliated Hospital of Inner Mongolia Medical University,and discussed the diagnosis,auxiliary examination and treatment of the disease.We hope to expand clinical thinking,improve our diagnosis and treatment of the disease through data analysis.