2,600 research outputs found
Role and regulation of miR-483 in cancer
No full textThe hsa-mir-483 locus is located at chromosome 11p15.5 within intron 2 of the IGF2 locus. Because of its location, de-regulated in Wilms’ tumor and other neoplasia, I hypothesized that this microRNA had a potential role in tumors. By analyzing 19 Wilms’ tumors, I proved that miR-483-3p is indeed over-expressed in 100% of the cases and a co-regulation with the over-expression of IGF2 was found.
However, several other types of common adult cancers exhibit high or even extremely high levels of miR-483-3p expression without IGF2 over-expression. Indeed, independently from IGF2, the expression of the miR-483-3p could also be induced by the oncoprotein β-catenin through a novel interaction with the basic Helix-Loop-Helix protein upstream stimulatory transcription factor 1 (USF1).
I also show that β-catenin itself is a target of miR-483-3p, triggering a negative regulative loop that becomes ineffective in cells harbouring activating mutations of β-catenin pathway.
The potential oncogenic role of miR-483-3p was supported by the findings that its ectopic expression protects cells from apoptosis and, conversely, its inhibition increase the level of apoptosis. To understand the mechanisms of its action, I investigated potential gene targets. Among these, an important pro-apoptotic protein, Puma, were inhibited by miR-483-3p. My results indicate that miR-483-3p functions as an anti-apoptotic oncogene, coordinately over-expressed with IGF2 in Wilms’ tumors or induced by β-catenin activation in other tumor types
Extrarenal testicular Wilms' tumor in a 3-year-old child
No full textWe report an extremely rare case of extrarenal testicular Wilms' tumor in a 3-year-old boy with intrabdominal undescended left testis. The patient was admitted because of pain and vomiting, with evidence of a huge abdominal mass. At surgery a large tumor arising from the intrabdominal testis was found. Histology showed the classical triphasic Wilms' tumor elements: epithelial, mesenchymal and blastemal areas. Extrarenal Wilms' tumors account for only 3 % of all Wilms' tumors and just ~100 cases have been reported in literature. Testicular origin is anecdotic. We present histomorphological, histogenetic, clinical, diagnostic, prognostic and therapeutic features of this rare tumor. © 2013 Springer-Verlag Berlin Heidelberg
Heterogeneity of disease classified as stage III in Wilms tumor: a report from the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).
No full textPURPOSE:
We analyzed whether the prognosis can differ among Wilms tumors (WT) labeled as Stage III according to currently adopted classification systems.
METHODS AND MATERIALS:
Patients with nonanaplastic Stage III WT consecutively registered in two Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) trials (CNR-92, TW-2003) were the subjects in the present analysis. The steady mainstay of therapy was primary nephrectomy, followed by three-drug chemotherapy with vincristine, dactinomycin, doxorubicin, and abdominal radiotherapy (RT).
RESULTS:
Ninety-nine WT patients met the criteria for classification as Stage III according to a revised version of the National Wilms Tumor Study-3 staging system (51 patients in CNR-92, 48 patients in TW-2003). Regional lymph nodes (LN) were not biopsied in 16 patients. After a median follow-up of 66 months, the 4-year disease-free survival (DFS) and overall survival (OS) rates were 85% ± 4% and 92% ± 3%, respectively, for the whole group. For 38 children with positive LN, the 4-year DFS rate was 73% ± 7%, as opposed to 98% ± 2% for the 45 children with Stage III WT according to the other criteria but with negative biopsied LN (p = 0.001). The subgroup with the worst prognosis consisted of children more than 2 years old with positive LN (DFS 67% ± 8%). A delay between surgery and RT > 30 days had an adverse impact on the abdominal tumor relapse rate.
CONCLUSIONS:
This study provides further evidence that Stage III tumors with LN metastases might be distinguished from WTs meeting the other criteria for classification as Stage III. The worse outcome of the former may warrant a prospective study on the effects of intensified therapy. A subclassification of Stage III tumors is discussed
Origins of DNA methylation defects in Wilms tumors
No full textWilms tumor is an embryonic renal cancer that typically presents in early childhood and accounts for 7% of all paediatric cancers. Different genetic alterations have been described in this malignancy, however, only a few of them are associated with a majority of Wilms tumors. Alterations in DNA methylation, in contrast, are frequent molecular defects observed in most cases of Wilms tumors. How these epimutations are established in this tumor is not yet completely clear. The recent identification of the molecular actors required for the epigenetic reprogramming during embryogenesis suggests novel possible mechanisms responsible for the DNA methylation defects in Wilms tumor. Here, we provide an overview of the DNA methylation alterations observed in this malignancy and discuss the distinct molecular mechanisms by which these epimutations can arise
LOSS OF HETEROZYGOSITY ANALYSIS AT DIFFERENT CHROMOSOME REGIONS IN WILMS TUMOR CONFIRMS 1P ALLELIC LOSS AS A MARKER OF WORSE PROGNOSIS: A STUDY FROM THE ITALIAN ASSOCIATION OF PEDIATRIC HEMATOLOGY AND ONCOLOGY
No full textPURPOSE: The specific aims of the AIEOP-TW-2003 protocol included prospectively investigating a possible association of tumor loss of heterozygosity with outcomes in children treated for Wilms tumor.
MATERIALS AND METHODS: We analyzed 125 unilateral favorable histology Wilms tumors registered between 2003 and 2008 in the Italian cooperative protocol for microsatellite markers mapped to chromosomes 1p, 7p, 11q, 16q and 22q.
RESULTS: The 3-year disease-free survival and overall survival probabilities were 0.87 (95% CI 0.81-0.93) and 0.98 (95% CI 0.96-1.0), respectively. Loss of heterozygosity at 1p was significantly associated with a worse disease-free survival (probability 0.67 for patients with and 0.92 for those without 1p loss of heterozygosity, p = 0.0009), as confirmed also by multivariate analysis adjusting for tumor stage and patient age at diagnosis. There was no difference in disease-free survival probability among children with loss of heterozygosity in the other chromosomal regions tested. The worse outlook for children older than 2 years at diagnosis did not seem to be influenced by the loss of heterozygosity patterns considered.
CONCLUSIONS: Chromosome 1p loss of heterozygosity seems to be a risk factor for nonanaplastic Wilms tumor, possibly regardless of other clinical factors. Our findings were uninformative regarding loss of heterozygosity in the other chromosomal regions tested
Faithful expression of a tagged Fugu WT1 protein from a genomic transgene in zebrafish:efficient splicing of pufferfish genes in zebrafish but not mice
No full textThe teleost fish are widely used as model organisms in vertebrate biology. The compact genome of the pufferfish, Fugu rubripes, has proven a valuable tool in comparative genome analyses, aiding the annotation of mammalian genomes and the identification of conserved regulatory elements, whilst the zebrafish is particularly suited to genetic and developmental studies. We demonstrate that a pufferfish WT1 transgene can be expressed and spliced appropriately in transgenic zebrafish, contrasting with the situation in transgenic mice. By creating both transgenic mice and transgenic zebrafish with the same construct, we show that Fugu RNA is processed correctly in zebrafish but not in mice. Furthermore, we show for the first time that a Fugu genomic construct can produce protein in transgenic zebrafish: a full-length Fugu WT1 transgene with a C-terminal beta-galactosidase fusion is spliced and translated correctly in zebrafish, mimicking the expression of the endogenous WT1 gene. These data demonstrate that the zebrafish:Fugu system is a powerful and convenient tool for dissecting both vertebrate gene regulation and gene function in vivo
Factors associated with survival in patient with Wilms tumor
No full textIntroducción. El tumor de Wilms es el segundo tumor abdominal más frecuente en la edad pediátrica y responde por más del 90 % de los tumores renales en pediatría. A pesar de que la sobrevida descrita es mayor del 90 %, en nuestro medio encontramos que solo alcanza al 70 %, por lo que deseamos evaluar cuáles son los factores asociados con dichos resultados desfavorables, con el fin de implementar medidas para mejorar la sobrevida de nuestros pacientes.Métodos. Se realizó un estudio observacional, transversal, en dos centros de alto nivel de atención, que incluyó una muestra de 84 pacientes menores de 15 años, con diagnóstico de tumor de Wilms.Resultados. Los factores que se asociaron significativamente con un aumento en la probabilidad de morir fueron: no completar el protocolo de quimioterapia, (OR 34; IC95% 3,7-312; p 0,000) y presentar recidiva tumoral (OR 35,7; IC95% 6,9-184; p 0,000). Otros factores que aumentaron esta probabilidad sin alcanzar a ser significativos, pero mostrando una evidente tendencia fueron: presentación bilateral (OR 4,1; IC95% 0,6-5,5; p 0,147), complicaciones quirúrgicas (OR 3,2; IC95% 0,7-14,6; p 0,136), compromiso de ganglios linfáticos en tomografía (OR 2,4; IC95% 0,7-8,4; p 0,139) y las metástasis a distancia (OR 2,5; IC95% 0,7-9; p 0,143). Discusión. La sobrevida de nuestros niños con tumor de Wilms es menor que la reportada en la literatura mundial, siendo la falla en terminar la quimioterapia, la recidiva y la necesidad de cirugía bilateral, los factores asociados con este desenlace. Palabras clave: tumor de Wilms; nefroblastoma; cirugía; urología; oncología quirúrgica; supervivientes de cáncer.Introduction. Wilms tumor is the second most frequent abdominal tumor in pediatric age, and it accounts for more than 90% of kidney tumors in pediatrics. Although the described survival is greater than 90%, in our set-ting we find that it only reaches 70%. Our objective was to evaluate the factors associated with these unfavorable results, in order to implement measures to improve the survival of our patients.Methods. An observational, cross-sectional study was conducted in two tertiary medical centers, which included a sample of 84 patients under 15 years of age with a diagnosis of Wilms tumor.Results. The factors that were significantly associated with an increase in the probability of dying were not com-pleting the chemotherapy protocol (OR 34; 95%CI 3.7-312; p 0.000) and presenting tumor recurrence (OR 35.7; 95%CI 6.9-184; p 0.000). Other factors that increased this probability without being significant, but showing an evident trend were: bilateral presentation (OR 4.1; 95%CI 0.6-5.5; p 0.147), surgical complications (OR 3.2; 95%CI 0.7-14.6; p 0.136), lymph node involvement in tomography (OR 2.4; 95%CI 0.7-8.4; p 0.139) and distant metastases (OR 2.5; 95%CI 0.7-9; p 0.143).Discussion. The survival of the children with Wilms tumor in our study was lower than that reported in the world literature, with failure to complete chemotherapy, recurrence and the need for bilateral surgery being the factors associated with this outcome.Keywords:Wilms tumor; nephroblastoma; surgery; urology; surgical oncology; cancer survivors
Mapping of a putative tumor suppressor locus to proximal 7p in Wilms tumors
No full textDifferent findings suggest that alterations of chromosome 7 genes play a role in the development of Wilms tumors. To define the positions of these genes, we have accomplished a combined cytogenetic and molecular study on 11 sporadic Wilms tumors. In one case, where both chromosomes 7 were rearranged, the karyotypic picture was consistent with the presence of a tumor suppressor gene at 7p15. To test this hypothesis, a loss of heterozygosity analysis was performed using microsatellite markers. This revealed a common region of allele losses mapped to the proximal short arm of chromosome 7 and defined the position of the gene(s) involved in Wilms tumors within an interval of approximately 25 cM
Adult Wilms’ tumour in pregnancy
No full textWilms’ tumor (nephroblastoma) is the most common primary renal malignancy in children, with a peak presentation in the ages 3-4 years. Wilms’ tumor is extremely rare in adults with around 300 cases described in literature. This presents both a diagnostic and treatment challenge in adults due to lack of standard protocols. Herein, we report a case of a 28-year-old primigravida who underwent nephrectomy postpartum for presumed renal cell carcinoma that was diagnosed as Wilms’ tumor at histology. This case is being reported on account of its peculiar presentation, and its presentation in pregnancy, to provoke further research and thus improve management in the adult patient
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