Biomarkers to Detect Wilms Tumors in Pediatric Patients: Where are We Now?

Charlton, Jocelyn; Pavasovic, Vesna; Pritchard‐Jones, Kathy

doi:10.2217/fon.15.136

Cited by 19 publications

(16 citation statements)

References 53 publications

(80 reference statements)

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“…to confirm whether the mutation is homozygous. This was visualized by the Sanger sequencing method, to determine if it originated from the two mutated alleles or because only one allele was sequenced since the other allele was lost by deletion and gave the false impression of homozygous [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

HPV positive, wild type TP53, and p16 overexpression correlate with the absence of residual tumors after chemoradiotherapy in anal squamous cell carcinoma

et al. 2018

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BackgroundAnal residual tumors are consensually identified within six months of chemoradiotherapy and represent a persistent lesion that may have prognostic value for overall survival. The aim of this study was to evaluate the association of HPV and HIV status, p16 expression level and TP53 mutations with the absence of residual tumors (local response) in Squamous Cell Carcinoma (SCC) of the anal canal after chemoradiotherapy.MethodsWe performed a study on 78 patients with SCC of the anal canal who submitted to chemoradiotherapy and were followed for a six-month period to identify the absence or presence of residual tumors. HPV DNA was identified by polymerase chain reaction and direct sequencing, HIV RNA was detected by TaqMan amplification, p16 expression was detected by western blotting, and the mutational analysis of TP53 was performed by direct sequencing; additionally, samples carrying mutations underwent fluorescent in sit hybridization. The evaluation of the tumor response to treatment was conducted six months after the conclusion of chemoradiotherapy. The following classifications were used to evaluate the outcomes: a) no response (presence of residual tumor) and b) complete response (absence of residual tumor).ResultsThe significant variables associated with the absence of residual tumors were HPV positive, p16 overexpressed, wild-type TP53, female gender, and stages I and II. Only the presence of HPV was independently correlated with the clinical response; this variable increased the chances of a response within six months by 31-fold.ConclusionsThe presence of HPV in tumor cells was correlated with the absence of a residual tumor. This correlation is valuable and can direct future therapeutic approaches in the anal canal.

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Section: Discussionmentioning

confidence: 99%

HPV positive, wild type TP53, and p16 overexpression correlate with the absence of residual tumors after chemoradiotherapy in anal squamous cell carcinoma

et al. 2018

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“…This heterogeneity is also reflected in gene expression profiles [45] and genomic alterations [44] with impact in risk stratification and treatment response [46]. The studies in WT have tried to define the groups of patients of high and low risk, independently of the morphology and staging, using molecular markers [47][48][49]. The identified biomarkers have failed to give the consistent predictive information in regard to the clinical outcome of WT; however, data from NMR are scarce.…”

Section: Nephroblastoma or Wilms Tumor (Wt)mentioning

confidence: 99%

Insights into the Chemical Biology of Childhood Embryonal Solid Tumors by NMR-Based Metabolomics

et al. 2019

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Most childhood cancers occur as isolated cases and show very different biological behavior when compared with cancers in adults. There are some solid tumors that occur almost exclusively in children among which stand out the embryonal solid tumors. These cancers main types are neuroblastoma, nephroblastoma (Wilms tumors), retinoblastoma and hepatoblastomas and tumors of the central nervous system (CNS). Embryonal solid tumors represent a heterogeneous group of cancers supposedly derived from undifferentiated cells, with histological features that resemble tissues of origin during embryogenesis. This key observation suggests that tumorigenesis might begin during early fetal or child life due to the errors in growth or pathways differentiation. There are not many literature data on genomic, transcriptomic, epigenetic, proteomic, or metabolomic differences in these types of cancers when compared to the omics- used in adult cancer research. Still, metabolomics by nuclear magnetic resonance (NMR) in childhood embryonal solid tumors research can contribute greatly to understand better metabolic pathways alterations and biology of the embryonal solid tumors and potential to be used in clinical applications. Different types of samples, such as tissues, cells, biofluids, mostly blood plasma and serum, can be analyzed by NMR to detect and identify cancer metabolic signatures and validated biomarkers using enlarged group of samples. The literature search for biomarkers points to around 20–30 compounds that could be associated with pediatric cancer as well as metastasis.

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“…Wilms tumor is the most common pediatric renal tumor with a prevalence of ~1 in 10,000 children ( 1 ). Although combination therapy has improved the prognosis for most patients, ~10% of patients with Wilms tumors experience poor survival due to metastasis and recurrence ( 2 – 5 ).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑92a‑3p inhibits the cell proliferation, migration and invasion of Wilms tumor by targeting NOTCH1

Zhu

Zhang

et al. 2018

Oncol Rep

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Dysregulation of miR-92a-3p has been shown to contribute to many tumorigenic processes, and is correlated with tumor progression and prognosis. However, the association between miR-92a-3p and the clinicopathological features of Wilms tumorand its regulatory mechanism remain unknown. In the present study, we demonstrated that miR-92a-3p was downregulated in Wilms tumor tissues and was significantly correlated with the lung metastasis of patients with Wilms tumor. Furthermore, miR-92a-3p mimics suppressed Wilms tumor cell proliferation, migration and invasion by in vitro assays. In addition, miR-92a-3p knockdown promoted tumor progression. Moreover, miR-92a-3p was shown to target directly the 3′-UTR of NOTCH1 mRNA by Dual-Luciferase reporter assays in Wilm's tumor cells. miR-92a-3p mimics decreased the expression of mRNA and protein of NOTCH1. miR-92a-3p inhibitor enhanced NOTCH1 expression by using western blotting and qPCR. In Wilms tumor tissues, NOTCH1 was highly expressed when compared with that in adjacent non-tumor tissues. NOTCH1 expression was found to be negatively correlated with miR-92a-3p in tumor tissues. Knockdown of NOTCH1 expression reversed the promotive effect of miR-92a-3p inhibitor on the cell proliferation, migration and invasion in Wilms tumor. In conclusion, miR-92a-3p blocks the progression of Wilms tumor by targeting NOTCH1.

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Biomarkers to Detect Wilms Tumors in Pediatric Patients: Where are We Now?

Cited by 19 publications

References 53 publications

HPV positive, wild type TP53, and p16 overexpression correlate with the absence of residual tumors after chemoradiotherapy in anal squamous cell carcinoma

HPV positive, wild type TP53, and p16 overexpression correlate with the absence of residual tumors after chemoradiotherapy in anal squamous cell carcinoma

Insights into the Chemical Biology of Childhood Embryonal Solid Tumors by NMR-Based Metabolomics

MicroRNA‑92a‑3p inhibits the cell proliferation, migration and invasion of Wilms tumor by targeting NOTCH1

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