What Do We Know about Survival in Skeletally Premature Children Aged 0 to 10 Years with Ewing Sarcoma? A Multicenter 10-Year Follow-Up Study in 60 Patients.

(1) Background: Younger age has been associated with better overall survival (OS) in Ewing sarcoma (ES), especially under the age of 10. The favorable survival in younger patients underlines the need for minimizing treatment burden and late sequelae. Our study aimed at describing clinical characteristics, treatment and outcome of a cohort of ES patients aged 0−10.

Respiratory syncytial virus hospitalization in children in northern Spain.

Objectives: Understanding respiratory syncytial virus (RSV) morbidity may help to plan health care and future vaccine recommendations. We aim to describe the characteristics and temporal distribution of children diagnosed with RSV admitted in a Spanish hospital.

Methods: Descriptive study for which the hospital discharges of children < 5 years of age with RSV infection were analyzed.

[Ionizing radiation received by patients with osteosarcoma during intra-arterial chemotherapy treatment].

Background: Osteosarcoma paediatric patients are usually treated with intra-arterial chemotherapy (QTia) which is admi-nistered directly to the tumour. This procedure exposes patients to ionizing radiation. Paediatric patients are especially sensitive to this exposure.

Adjuvant radiation therapy in resected high-grade localized skeletal osteosarcomas treated with neoadjuvant chemotherapy: Long-term outcomes.

Purpose: To assess long-term outcomes and toxicity of adjuvant radiotherapy in the post-surgical management of patients with resected high-grade skeletal osteosarcomas.

Methods And Materials: Seventy-two patients with primary resected osteosarcomas underwent adjuvant radiotherapy after neoadjuvant chemotherapy from December 1984 to December 2008. Local control (LC), overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan-Meier methods.

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types.

Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.

Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients.

A Genome-Wide Scan Identifies Variants in NFIB Associated with Metastasis in Patients with Osteosarcoma.

Unlabelled: Metastasis is the leading cause of death in patients with osteosarcoma, the most common pediatric bone malignancy. We conducted a multistage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified an SNP, rs7034162, in NFIB significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: P = 1.

Germline TP53 variants and susceptibility to osteosarcoma.

The etiologic contribution of germline genetic variation to sporadic osteosarcoma is not well understood. Osteosarcoma is a sentinel cancer of Li-Fraumeni syndrome (LFS), in which approximately 70% of families meeting the classic criteria have germline TP53 mutations. We sequenced TP53 exons in 765 osteosarcoma cases.

Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis.

The oncolytic adenovirus Δ24-RGD in combination with cisplatin exerts a potent anti-osteosarcoma activity.

Osteosarcoma is the most common malignant bone tumor in children and adolescents. The presence of metastases and the lack of response to conventional treatment are the major adverse prognostic factors. Therefore, there is an urgent need for new treatment strategies that overcome both of these problems.

Genome-wide association study identifies two susceptibility loci for osteosarcoma.

Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. To better understand the genetic etiology of osteosarcoma, we performed a multistage genome-wide association study consisting of 941 individuals with osteosarcoma (cases) and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: a locus in the GRM4 gene at 6p21.

Detectable clonal mosaicism and its relationship to aging and cancer.

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%.

Cortactin (CTTN) overexpression in osteosarcoma correlates with advanced stage and reduced survival.

Background: The cortactin (CTTN) gene has been found, by transcriptomic profiling, to be overexpressed in pediatric osteosarcoma. The location of CTTN at 11q13 and the role of cortactin in cytoskeleton restructuring make CTTN of interest as a potential biomarker for osteosarcoma.

Materials And Methods: Osteoblasts were isolated from 20 high-grade osteosarcomas before chemotherapy, and paired with cell samples from normal tissue, prior to RNA expression analysis on HG-U133A chips (Affymetrix).

Effect of ABCB1 and ABCC3 polymorphisms on osteosarcoma survival after chemotherapy: a pharmacogenetic study.

Background: Standard treatment for osteosarcoma patients consists of a combination of cisplatin, adriamycin, and methotrexate before surgical resection of the primary tumour, followed by postoperative chemotherapy including vincristine and cyclophosphamide. Unfortunately, many patients still relapse or suffer adverse events. We examined whether common germline polymorphisms in chemotherapeutic transporter and metabolic pathway genes of the drugs used in standard osteosarcoma treatment may predict treatment response.

Profiling of chemonaive osteosarcoma and paired-normal cells identifies EBF2 as a mediator of osteoprotegerin inhibition to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis.

Purpose: Osteosarcoma is the most prevalent bone tumor in children and adolescents. At present, the mechanisms of initiation, maintenance, and metastasis are poorly understood. The purpose of this study was to identify relevant molecular targets in the pathogenesis of osteosarcoma.

Proteomic analysis of chemonaive pediatric osteosarcomas and corresponding normal bone reveals multiple altered molecular targets.

With a view to identify the proteins involved in transformation, metastasis or chemoresistance in pediatric osteosarcoma, we carried out a new experimental approach based on comparison of the proteomic profile of paired samples of osteosarcoma and normal bone tissues from the same patient. The proteomic profiles of five pairs of cell lines (normal vs tumoral) were obtained by two-dimensional difference gel electrophoresis. We detected 56 differential protein spots (t test, p < 0.

Prognostic factors and outcomes for osteosarcoma: an international collaboration.

We aimed to evaluate the prognostic significance of traditional clinical predictors in osteosarcoma through an international collaboration of 10 teams of investigators (2680 patients) who participated. In multivariate models the mortality risk increased with older age, presence of metastatic disease at diagnosis, development of local recurrence when the patient was first seen, use of amputation instead of limb salvage/wide resection, employment of unusual treatments, use of chemotherapeutic regimens other than anthracycline and platinum and use of methotrexate. It was also influenced by the site of the tumour.

Methotrexate in pediatric osteosarcoma: response and toxicity in relation to genetic polymorphisms and dihydrofolate reductase and reduced folate carrier 1 expression.

Objective: To determine the influence of the genotype and the level of expression of different enzymes involved in folate metabolism on the response to and toxicity of high-dose methotrexate treatment in pediatric osteosarcomas.

Study Design: DHFR and Reduced folate carrier 1 (RFC1) semiquantitative expression was analyzed in 34 primary and metastatic osteosarcoma tissues by real-time polymerase chain reaction. The following polymorphisms were also analyzed in peripheral blood from 96 children with osteosarcoma and 110 control subjects: C677T, A1298C (MTHFR), G80A (RFC1), A2756G (MTR), C1420T (SHMT), the 28bp-repeat polymorphism, and 1494del6 of the TYMS gene.

CDH11 expression is associated with survival in patients with osteosarcoma.

Previous studies have shown that cadherin-11 (CDH11) may be involved in the metastatic process of osteosarcoma. The correlation of the expression levels of CDH11 in osteosarcoma samples with the risk of disease progression and metastasis was examined. Real time qRT-PCR was used to quantify CDH11 expression in a set of newly established osteosarcoma cell lines, 11 primaries and five metastases, compared to the levels in 12 normal osteoblast cell lines established from healthy bone, and also in a set of 10 snap-frozen osteosarcoma samples.

Limb salvage in Ewing's sarcoma of the distal lower extremity.

Background: Ewing's sarcoma (ES) of the foot and ankle is a rare condition whose treatment is controversial. There are no large series covering this issue. Some authors advise amputation as the "gold standard" treatment.

Effects of benzopyrene-7,8-diol-9,10-epoxide (BPDE) in vitro and of maternal smoking in vivo on micronuclei frequencies in fetal cord blood.

Up to 20% of pregnant women smoke and there is indirect evidence that certain tobacco-specific metabolites can cross the placental barrier and are genotoxic to the fetus. The presence of micronuclei results from chromosome damage and reflects the degree of underlying genetic instability. Fetal blood was obtained from the cord blood of 143 newborns (102 from nonsmoking mothers and 41 from mothers smoking >10 cigarettes/d during pregnancy).

Bone mineral density and bone metabolism in children treated for bone sarcomas.

In adolescent bone sarcoma patients, bone mass acquisition is potentially compromised at a time in which it should be at a maximum. To evaluate the problem we measured bone mineral density (BMD) and serum markers of bone formation and resorption in a series of pediatric patients with bone tumors. BMD was measured by dual-energy x-ray absorptiometry, at clinical remission, for lumbar spine and the neck of the femur in 38 osteosarcoma and 25 Ewing's sarcoma patients.

Use of brachytherapy in children with cancer: the search for an uncomplicated cure.

Brachytherapy is a sophisticated radiation method in which radioisotopes are placed inside or at a short distance from the tumour. The volume of tissue that receives the prescribed dose of radiotherapy is therefore fairly small compared with that used in standard radiotherapy techniques. In paediatric oncology, this method of radiation delivery can have a favourable effect on several undesirable long-term side-effects that sometimes develop in children who receive radiotherapy, such as growth retardation and development of second primary tumours.

TNF-alpha promoter gene polymorphisms in Spanish children with persistent oligoarticular and systemic-onset juvenile idiopathic arthritis.

Objective: To explore the possible association/s of the first reported tumour necrosis factor (TNF-alphaTNF-) alpha promoter gene polymorphisms -308, -238, -376 and -163 (G-->A) with systemic (SoJIA) and oligoarticular subtypes of juvenile idiopathic arthritis (JIA); and to test the association between these polymorphisms and the class I/class II HLA alleles in our population.

Methods: The patient group comprised 29 oligoarticular and 26 systemic Caucasian Spanish children with JIA; 68 healthy volunteers from the same ethnic group and geographical region served as controls. HLA alleles were determined using low-resolution polymerase chain reaction (PCR).