Search results for "Pediatric Cancer"
showing 10 items of 30 documents
Abstract A02: Neuroblastoma patient-derived orthotopic xenografts: Clinically relevant models for drug testing
2016
Abstract Widespread metastasis is a major problem for the treatment of high-risk neuroblastoma. Relevant neuroblastoma animal models are hence needed to study and target high-risk metastatic neuroblastoma. We developed neuroblastoma patient-derived orthotopic xenografts (PDXs) using viably cryopreserved or fresh patient neuroblastoma fragments which were implanted orthotopically into immunodeficient NSG mice. Immunohistochemistry showed that PDXs retain neuroblastoma markers and a highly infiltrative growth pattern. Importantly, we found distant metastasis to lungs, liver and bone marrow. Single nucleotide polymorphism array analysis confirmed that PDXs maintain patient-specific chromosomal…
CRISPR-Cas9 screen reveals a MYCN-amplified neuroblastoma dependency on EZH2.
2018
Pharmacologically difficult targets, such as MYC transcription factors, represent a major challenge in cancer therapy. For the childhood cancer neuroblastoma, amplification of the oncogene MYCN is associated with high-risk disease and poor prognosis. Here, we deployed genome-scale CRISPR-Cas9 screening of MYCN-amplified neuroblastoma and found a preferential dependency on genes encoding the polycomb repressive complex 2 (PRC2) components EZH2, EED, and SUZ12. Genetic and pharmacological suppression of EZH2 inhibited neuroblastoma growth in vitro and in vivo. Moreover, compared with neuroblastomas without MYCN amplification, MYCN-amplified neuroblastomas expressed higher levels of EZH2. ChIP…
9-ING-41, a small-molecule glycogen synthase kinase-3 inhibitor, is active in neuroblastoma.
2018
Advanced stage neuroblastoma is a very aggressive pediatric cancer with limited treatment options and a high mortality rate. Glycogen Synthase Kinase-3β (GSK-3β) is a potential therapeutic target in neuroblastoma. Using immunohistochemical staining, we observed positive GSK-3β expression in 67% of human neuroblastomas (34 out of 51 cases). Chemically distinct GSK-3 inhibitors (AR-A014418, TDZD8 and 9-ING-41), suppressed the growth of neuroblastoma cells whereas 9-ING-41, a clinically relevant small molecule GSK-3β inhibitor with broad spectrum pre-clinical antitumor activity, being the most potent. Inhibition of GSK-3 resulted in a decreased expression of the antiapoptotic molecule XIAP and…
The genomic landscape of the Ewing Sarcoma family of tumors reveals recurrent STAG2 mutation.
2014
The Ewing sarcoma family of tumors (EFT) is a group of highly malignant small round blue cell tumors occurring in children and young adults. We report here the largest genomic survey to date of 101 EFT (65 tumors and 36 cell lines). Using a combination of whole genome sequencing and targeted sequencing approaches, we discover that EFT has a very low mutational burden (0.15 mutations/Mb) but frequent deleterious mutations in the cohesin complex subunit STAG2 (21.5% tumors, 44.4% cell lines), homozygous deletion of CDKN2A (13.8% and 50%) and mutations of TP53 (6.2% and 71.9%). We additionally note an increased prevalence of the BRCA2 K3326X polymorphism in EFT patient samples (7.3%) compared …
Abstract A42: miR34a: A valuable indicator of differential outcome of Ewing sarcoma patients with complex functions
2014
Abstract The identification of reliable indicators of prognosis, which may allow the stratification of patients according to different risk at diagnosis isan important aspect of translational research in Ewing sarcoma (ES). In this paper, we validated our previous evidence showing how expression of miR34a in ES tumor samples at diagnosis was signficantly associated with tumor progression (Nakatani F. J Pathol 2012). Here we analyzed a different series of speciments derived from very controlled and homogeneously treated non-metastatic ES patients, and we compared evaluation of miR34a by RT-PCR using frozen samples with that obtained by in situ hybridization on paraffin-embedded samples . The…
Evaluación y rehabilitación neuropsicológica en oncología pediátrica.
2003
Objetivo. El presente trabajo tiene como objetivo el estudio de los efectos neuropsicológicos a largo plazo del cáncer infantil y sus tratamientos así como plantear propuestas para la rehabilitación cognitiva. Método. El método ha consistido en una revisión sistemática de los resultados en la literatura científica acerca de los efectos de la quimioterapia y la radioterapia sobre el SNC y en las funciones cognitivas y conductuales detectados a través de estudios de neuroimagen como calcificaciones y cambios en la sustancia blanca. Presentamos, además, el protocolo de evaluación neuropsicológica ejemplificado con un diagnóstico frecuente que presenta deterioro generalizado. Proponemos un prog…
Educational and vocational achievement among long-term survivors of adolescent cancer in Germany
2010
Background Adolescence involves graduating from school and preparing one's professional career. The accomplishment of these tasks may be hampered by the experience of cancer. This study investigates the educational and professional achievements of German long-term survivors of adolescent cancer. Procedure Adult survivors of cancer during adolescence (n = 820, age at onset between 15 and 18 years; M = 15.8, SD = 0.9 years; age at follow-up: M = 30.4, SD = 6.0 years) were recruited through the German Childhood Cancer Registry. They completed self-reports with standard items on their educational and vocational level and their current occupational situation. Outcomes were compared to an age-mat…
Neuropsychological rehabilitation in children with central nervous system tumors and irradiated leukemias
2012
Actualmente la intervención e investigación en psicooncología pediátrica se dirige hacia la evaluación de las consecuencias de la enfermedad y los efectos secundarios de los tratamientos, y a los factores predictivos tanto de desajustes como de aspectos adaptativos a la enfermedad del paciente y de su familia. Las tasas de curación alcanzadas en la actualidad, nos permiten contar con un número considerable de supervivientes de cáncer infantil, susceptibles de ser evaluados y poder determinar así las secuelas a largo plazo de la enfermedad y sus procedimientos terapéuticos. Además de incrementar considerablemente la supervivencia, también se ha mejorado la calidad de vida de los niños, media…
Posttraumatic Growth and Spirituality in Mothers of Children with Pediatric Cancer
2021
A child’s cancer, as a life-threatening illness, is classified as a traumatic event both for the child him-/herself and for his/her relatives. Struggling with a traumatic experience can bring positive consequences for an individual, which is referred to as posttraumatic growth. The aim of this study was to explore the relationship between posttraumatic growth and spirituality understood as a personal resource in mothers of children with pediatric cancer. In total, 55 mothers whose children were in the phase of treatment and who had been staying with them in the hospital filled in a Posttraumatic Growth Inventory, Self-description Questionnaire of Spirituality, and the author’s short questio…
Parental informed consent in pediatric cancer trials: A population-based survey in Germany
2012
In Germany, nearly every child afflicted by a malignant dis-ease or a central nervous system tumor is enrolled in a clinicaltrial during treatment. Many of these children are under the age of5 years when they are first diagnosed [1]. The decision whether ornot to participate in a clinical trial is normally made by theparents on behalf of their child. Therefore, ensuring adequatelyinformed parental consent is essential to ethical practice in pedi-atric oncology.However, many empirical studies have revealed difficultieswith the informed consent process when parents are faced withthe decision to enroll their child in a clinical trial. Previous studyfindings have indicated that recalling signing th…