32 research outputs found
A Novel Diagnostic Tool for Therapy Stratification of Neuroblastoma: Preoperative Analysis of Tumor Biology Using Circulating Tumor-Released DNA in Serum
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Serum-Based Quantification of MYCN Gene Amplification in Young Patients with Neuroblastoma: Potential Utility as a Surrogate Biomarker for Neuroblastoma
We previously developed a method for determining MYCN gene amplification status using cell-free DNA fragments released from cancer cells into the blood of patients with neuroblastoma (NB). Here, we analyzed the relationship between MYCN amplification (MNA) status and neuroblastoma prognosis. We screened serum samples from 151 patients with NB for MNA, using real-time quantitative PCR, and compared the results with MYCN status determined using paired tumor samples. We additionally investigated whether MNA status correlates with patient survival. When a cut-off value of 5 was used, serum-based MNA analysis was found to show good sensitivity (86%) and very high specificity (95%). The sensitivities for stage 1 and 2 might be acceptable, even though it is not as good as for stage 3 and 4 (67% for stage 1 and 2, 92% for stage 3, and 87% for stage 4). MNA status correlated with overall survival in our cohort of 82 patients, with survival data available (p < 0.01). The hazard ratio of MNA status was 4.98 in patients diagnosed at less than 18 months of age (95% confidence interval, 1.00–24.78), and 1.41 (95% confidence interval, 0.63–3.14) for those diagnosed at 18 months of age or older. Serum-based MNA analysis is rapid and non-invasive compared with tumor-based MNA analysis, and has potential to predict tumor MNA status. There is still a room to improve the sensitivity of the test for tumors of stages 1 and 2, nonetheless this assay might help to determine therapeutic strategies prior to tumor biopsy, especially for patients with a life-threatening condition, as well as for patients of less than 18 months of age whose risk-grouping and treatment allocation depends on their MNA status
CD146 is a potential immunotarget for neuroblastoma
Neuroblastoma, the most common extracranial solid tumor of childhood, is thought to arise from neural crest-derived immature cells. The prognosis of patients with high-risk or recurrent/refractory neuroblastoma remains quite poor despite intensive multimodality therapy; therefore, novel therapeutic interventions are required. We examined the expression of a cell adhesion molecule CD146 (melanoma cell adhesion molecule [MCAM]) by neuroblastoma cell lines and in clinical samples and investigated the anti-tumor effects of CD146-targeting treatment for neuroblastoma cells both in vitro and in vivo. CD146 is expressed by 4 cell lines and by most of primary tumors at any stage. Short hairpin RNA-mediated knockdown of CD146, or treatment with an anti-CD146 polyclonal antibody, effectively inhibited growth of neuroblastoma cells both in vitro and in vivo, principally due to increased apoptosis via the focal adhesion kinase and/or nuclear factor-kappa B signaling pathway. Furthermore, the anti-CD146 polyclonal antibody markedly inhibited tumor growth in immunodeficient mice inoculated with primary neuroblastoma cells. In conclusion, CD146 represents a promising therapeutic target for neuroblastoma
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Bilateral choroid plexus resection in a 9p hexasomy/tetrasomy mosaic patient
Abstract Previous reports have shown that a gain of the chromosome 9 short arm (9p) is associated with choroid plexus hyperplasia (CPH). Furthermore, CPH can lead to communicating hydrocephalus; however, no cases of CPH with 9p gain requiring choroid plexus resection have been reported. Here, we describe the first case in which a 9p hexasomy/tetrasomy mosaic patient required choroid plexus resection for hydrocephalus. This finding suggested that the 9p copy number is correlated with CPH severity
Leukaemic cells expressing ETV6::FRK are sensitive to dasatinib in vivo
Abstract ETV6::Fyn‐related kinase (FRK), which is a Src family tyrosine‐kinase‐related fusion gene and firstly identified in our patient with paediatric high risk B cell precursor acute lymphoblastic leukaemia (B‐ALL), has no evidence of efficacy of tyrosine kinase inhibitor in vivo. We performed functional analysis of ETV6::FRK to establish molecular targeting therapy and determined that dasatinib could abrogate proliferation activity of ETV6::FRK through the repression of FRK‐STAT3/STAT5 pathway in vitro and significantly extended the survival time of the xenografted mice in vivo (p < 0.01). Our data support the potential of dasatinib as a therapeutic option for patients with B‐ALL harboring FRK rearrangements
Diffuse Anterior Retinoblastoma with Sarcoidosis-Like Nodule
Background: Retinoblastomas account for 4% of malignancies in children, 1-2% of which are diffuse infiltrating retinoblastomas. Diffuse anterior retinoblastoma is rare and does not involve the retina. Here, we report on a diffuse anterior retinoblastoma with large sarcoidosis-like nodules on the iris that were responsive to anti-inflammatory therapy. Case: We present a 6-year-old girl who had anterior uveitis with white nodules on the iris and posterior surface of the cornea in her right eye. The nodules initially responded well to anti-inflammatory treatment. However, anterior segment optical coherence tomography (AS-OCT) showed that the nodules gradually grew, shrinking the iris. We then collected the aqueous humor for diagnosis. A biopsy revealed clusters of small cells with a high nuclear-to-cytoplasm ratio with partial rosette formation. Therefore, we diagnosed diffuse anterior retinoblastoma without retinal involvement and performed enucleation of the right eye. The histopathology demonstrated undifferentiated cells similar to those seen on the biopsy, and tumor cells invaded the iris stroma, posterior surface of the cornea, ciliary body, and sclera. After the enucleation, she underwent chemotherapy and remains alive. Conclusion: A differential diagnosis of retinoblastoma should be considered when white nodules refractory to anti-inflammatory therapy occur in the eye, even in the absence of obvious retinal masses. AS-OCT findings are useful in assessing retinoblastoma
Synchronous bilateral lung adenocarcinomas associated with vulvar rhabdomyosarcoma in a 15-year-old girl
Pediatric malignancies are thought to be risk factors of second malignant neoplasms. However, lung cancer associated with rhabdomyosarcoma is extremely rare. When multiple pulmonary lesions are observed in cancer patients, resection is necessary to distinguish them from metastatic lesions. We report an extremely rare case of synchronous bilateral multiple lung cancers showing ground glass nodules (GGNs) associated with rhabdomyosarcoma in a 15-year-old girl with vulvar rhabdomyosarcoma. When we identify GGNs in adolescents with a history of rhabdomyosarcoma, we should consider lung cancer as a differential diagnosis in addition to pulmonary metastasis usually showing solid nodule. In the present case with tiny lesions, surgical resection using lipiodol-marking helped to ensure both an early diagnosis and curative treatment. Keywords: Synchronous bilateral multiple lung cancers, Adolescent, Rhabdomyosarcom