Effects of bufalin on up-regulating methylation of Wilm's tumor 1 gene in human erythroid leukemic cells / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the effects of bufalin on inhibiting proliferation, up-regulating methylation of Wilm' tumor 1 gene (WT1) as well as its possible mechanisms in human erythroid leukemic (HEL) cells.</p><p><b>METHODS</b>The HEL cells were treated with bufalin at various concentrations to observe cellular morphology, proliferation assay and cell cycle. The mRNA and protein expression levels of WT1 were detected by reverse transcription polymerase chain reaction (RT-PCR), Western blot and immunocytochemistry, DNA methylation of WT1 and protein expression levels of DNA methyltransferase 3a (DNMT3a) and DNMT3b were analyzed by methylation-specific PCR, and Western blot respectively.</p><p><b>RESULTS</b>The bufalin was effective to inhibit proliferation of HEL cells in a dose-dependent manner, their suppression rates were from 23.4%±2.1% to 87.2%±5.4% with an half maximal inhibit concentration (IC) of 0.046 μmol/L. Typical apoptosis morphology was observed in bufalin-treated HEL cells. The proliferation index of cell cycle decreased from 76.4%±1.9% to 49.7%±1.3%. The expression levels of WT1 mRNA and its protein reduced gradually with increasing doses of bufalin, meanwhile, the methylation status of WT1 gene changed from unmethylated into partially or totally methylated. While, the expression levels of DNMT3a and DNMT3b protein gradually increased by bufalin treatment in a dose-dependent manner.</p><p><b>CONCLUSIONS</b>Bufalin can not only significantly inhibit the proliferation of HEL cells and arrest cell cycle at G/Gphase, but also induce cellular apoptosis and down-regulate the expression level of WT1. Our results provide the evidence of bufalin for anti-leukemia, its mechanism may involve in increasing WT1 methylation status which is related to the up-regulation of DNMT3a and DNMT3b proteins in erythroid leukemic HEL cells.</p>

Wilms' tumor with right heart extension: Report of a post-chemotherapeutic fatality.

Wilms' tumor (WT) has a strong propensity to invade the vasculature in the form of tumor-thrombus, into the renal veins, and inferior vena cava and even into the right atrium. This cavo-atrial propagation does not alter the prognosis and pre-operative chemotherapy produces shrinkage to the extent of even disappearance of caval or atrial extensions. We present a case of sudden death due to hemorrhagic expansion of the intra-atrial component of WT, immediately after commencement of chemotherapy, an uncommon incident.

El tumor de Wilms. Un paradigma de heterogeneidad genética: a paradigm of genetic heterogeneity / Wilm's toumor

El Tumor de Wilms constituye el más frecuente de los cánceres renales pediátricos, aparece antes de los 5 años de edad y con igual frecuencia en ambos sexos. El gen causante de la enfermedad está localizado en 11p13, se extiende unas 50 kb con 10 exones y sus alteraciones pueden ser tanto genéticas como epigenéticas. Por diferentes mecanismos se originan al menos 24 productos con funciones diversas. Existen otras regiones cromosómicas, cuyas alteraciones pueden dar lugar a la aparición del tumor. En este sentido, el Tumor de Wilms es un ejemplo sobresaliente de heterogeneidad genética. El presente trabajo hace un análisis de los fundamentos moleculares de la enfermedad y presenta a modo de ilustración una breve reseña de los principales síndromes hereditarios con predisposición a presentar este tumor.

Wilm's tumor is the most frequent cancer of the kidney in childhood with onset before five year old. WT gene was mapped in 11p13 and span 50 kb with 10 exons. WT modifications would be either genetics or epigenetics. The gene code for at least 24 isoforms of protein products. Other chromosomes loci whose alterations may be cause of disease have been identified, so Wilm's tumor is a remarkable paradigm of genetic heterogeneity. In this paper an analysis of the molecular basis of the disease is presented and, also, a brief references on main hereditary syndromes which include Wilm's tumor.

Clinical analysis of six cases of nephroblastomatosis combined with Wilm's tumor / 中华泌尿外科杂志

Objective To investigate the diagnosis,treatment and prognosis of nephroblastomatosis (Nbm) combined with Wilms'tumor (WT). Methods Clinical data of six patients treated for WT combined with Nbm in Beijing Children's Hospital from 2006 to 2010 were reviewed retrospectively.The patients'ages ranged from five to 14 months.Two of the patients were female and four were male.The WTs were left-sided in four cases and right-sided in two cases.The Nbms were ipsilateral with WT in three cases,contralateral in two cases and bilateral in one case. The Nbms were single In three cases and multiple in three cases.WTs were all single and the maximum diameter was 3,4,8,10,11,and 12 cm respectively.Two paitents underwent nephrectomy.Nephron sparing surgery and upper and lower pole nodule biopsy was conducted in two cases,Nephrectomy and contralateral nephron sparing surgery was conducted in an additional two cases.Adjuvant chemotherapy included vincristine,actinomycin and doxorubicin. Results One patient had tumor recurrence 33 months after a 15 month regimen of postoperative chemotherapy. One patient had tumor recurrence and died after nephron sparing surgery 5 months after a 11 month regimen of chemotherapy.Four patients underwent 6 months of chemotherapy,and it was 9,12,and 21 months respectively after stop of chemotherapy.Another patient was still in chemotherapy. Conclusions Nbm is a pre-neoplastic proliferative process with high risk of developing WT.Chemotherapy may reduce the rate of Nbm malignancy.If Nbm is malignant or chemotherapy is invalid,nephron sparing surgery is recommended.

Wilm’s Tumor Ten Year Experience at Kanti Children’s Hospital.

Introduction: Wilm's tumor is the second most common abdominal tumor in children. It arises from the kidney. The survival of children with Wilm's tumor has improved over the past 25 years. Objectives: To study the clinical presentation of Wilm’s tumor and evaluate the ten year survival. Materials and Methods: A retrospective hospital based study was conducted at Kanti Children's Hospital from March 1998 to February 2008. A total of 60 histopathologically diagnosed children below 14 yr of age were included in the study. Results: About 2/3rd (66.5%) presented with abdominal swelling followed by abdominal pain (16.5%) and fever (13.5%). A few children manifested with red colored urine (3.5%). The age of children ranged from one month to 13 years with the mean age of 36 months. Males were affected more than the females (M:F=3:1). Most affected age group was 2 to 5 yrs (41.5%) followed by 1 to 2 yrs (25.0%). Most of the cases were in stage III (36.5%) followed by stage II (33.5%). SIOP protocol was used to treat these children and overall 10 year survival rate was 50.0%. One fifth (20%) of the cases died, 16.5% relapsed and 13.5% lost to follow up. Conclusion: Despite severe resource limitations, paediatric oncology unit at Kanti Children’s Hospital has been successfully treating Wilm's tumor with the success rate of 50.0%.

Effect to the expression of VEGF in K562 cells by down-regulation of WT1 / 肿瘤研究与临床

Objective To investigate the effect to the expression of VEGF in human leukemic cell line by WT1gene silencing.MethodsK562 cells were transfected with WT1shRNA Plasmid.Transfection efficiency was detected by flow cytometIy,and the succeed transfered cells Were sorted.WT1 and VEGF mRNA variation were measured by fluorescence RT-PCR.VEGF concentrations in the cell growth medium were detected by ELISA.Results 48 hours after transfection,the transfection efficiency was 65％±4.5％.WT1shRNA positive cells were sorted by flow cytometry.Both the mRNA level of WT1 and VEGF and VEGF concentrations in cell growth medium were significantly decreased than the control group.ConclusionWT1 gene silence can down-regulate the expression of VEGF in K562 cells which suggest that WT1 gene may take part in leukemia angiogenesis through up-regulation of VEGF.

Neuroblastoma intrarenal mimetizando tumor de Wilms / Intrarenal neuroblatoma mimics Wilms' tumor

No presente trabalho, os autores relatam o caso de uma criança com neuroblastoma intrarenal, que foi, inicialmente,diagnosticado como tumor de Wilms. Pré-escolar, sexo feminino, com um ano e três meses, apresentava uma tumoração endurecida que ocupava o hipocôndrio esquerdo e se estendia até a região do mesogástrio, acompanhada de febre e palidez. O ultra-som do abdome total revelou massa intrarenal. A biópsia por agulha fina, em vários pontos de acesso tumoral, revelou um tumor de Wilms. Entretanto, não foi possível naquele momento realizar a imunohistoquímica (IHQ), face à escassez de material. Diante da gravidade da paciente, foi iniciado o protocolo SIOP por quatro semanas. Como não houve resposta clínica, foi indicada uma laparotomia exploradora, com ressecção parcial do tumor, sendo também, nesse momento, realizada punção aspirativa de medula óssea (MO). O exame histopatológico revelou neoplasia maligna de pequenas células mal diferenciadas. A IHQ foi negativa para WT-1 e positiva para NB-84, cromogranina e sinaptofisina. A biologia molecular revelou amplificação de N-myc. O mielograma identificou infiltração medular por pequenas células redondas. O neuroblastoma intrarenal é um tumor raro que se assemelha clínica e radiologicamente ao tumor de Wilms. Esse trabalho procura enfatizar a importância do emprego de análises imunohistoquímica e moleculares para o diagnóstico do neuroblastoma intrarenal.

This work reports the case history of a child with intrarenal neuroblastoma, initially diagnosed as Wilms' tumor.The patient, a one year and three months old girl, presented a hard abdominal mass on the left flank that extended to the mesogastric region, plus fever and paleness. The ultrasound of the entire abdomen revealed an intrarenal mass. Biopsy with fine needle in many points of the tumor revealed Wilms' tumor. The scarcety of the material, however, made immunohistoquemistry impossible at that moment. Because of the child's severe condition the SIOP protocol was started. As no clinical response was observed, an exploratory laparatomy was indicated with partial resection of the tumor and bone marrow aspiration (MO). The histopathologic study revealed a malignant neoplasia of small cells, poorly differentiated. IHQ was negative for WT-1 and positive for NB-84, synaptofisin, cromogranine. N-myc amplification was observed by molecular biology. The bone marrow aspiration identified matastatic small round cells infiltration. Intrarenal neuroblastoma is a rare entity that clinically and radiographicallyresembles Wilms' tumor. The objective of this case report is to show the importance of immunohistochemical andmolecular analysis in the diagnosis of intrarenal neuroblastoma.

Clinical evaluation of urinary interventional therapy in children / 介入放射学杂志

Objective To evaluate the role of interventional therapy in Wilm's tumor, renal vascular lesions and ureter stricture in children. Methods Thirty-eight cases were analysed, including 18 cases of Wilm's tumor treated with preprocedural chemotherapy and embolization through renal artery, and 13 cases of unknown-reason hypertension with selective renal arterial angiography for venous blood renin including undergone some patients PTA. Six cases of ureter stricture were dilated with balloon and 1 with hematurea by small aerial embolization. Results After embolization, Wilm's tumors showed reduction in vascularization and reduction in size too. The surrounding tissue of the tumor had a clear demarcation with the normal tissue, decreasing the dissemination to blood and distal metastasis. Renal vascular hypertension was clearly diagnosed and treated, and the increase of renin was helpful to the diagnosis of unknown-reason hypertension. And the obstruction of ureter was improved. Conclusions Interventional therapy is feasible in the application of urinary system diseases with great significance clinically.

Wilms' Tumor in an Adult: Report of a case

Wilm's tumor, which is the most mommon renal tumor in childhood, has rarely been reported in adult. Diagnosis of Wilm's tumor in an adult is more apt to be accidental and is almost never suspected in the adult until discovered at operation or necropsy. Recently, we experienced a caseof Wilm's tumor in 20-year-old female patient with chief complaints of right flank pain and he maturia for two months. Renal angiogram revealed a huge renal mass replacing the upper portion of the right kidney. Nephrectomy was done under the impression of renal tumor. Grossly, the tumor was rather soft and relatively well circumscribed, measuring 13 x 8.3 cm in dimension with adhesion to renal capsule and perirenal adipose tissue. The cut surfaces revealed grayish brown in color with areas of multifocal necrosis and hemorrhage. Histologically, the tumor was composed of mainly ovoid or polygonal shaped undifferentiated blastemal cells with large areas of necrosis.

A Case of Wilms' Tumor / 대한비뇨기과학회지

Wilms's tumor is a malignant renal parenchymal neoplasm. This tumor is most frequently discovered by palpable abdominal mass, while only total gross hematuria is not common in subjective symptom. We have experienced a four year-old girl complaining total gross hematuria and could not define preoperative diagnosis by clinical, radiological and laboratory findings. After operation, Wilms's tumor was confirmed on pathology.

Wilms's Tumor: Three Cases / 대한비뇨기과학회지

Three cases of Wilms's tumor observed during the period from January, 1969 to October, 1969 are presented and related literature reviewed.