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Patients affected by neurofibromatosis type 1 (NF1) are at higher risk of developing soft‐tissue sarcomas (STS) than the general population. The clinical findings and outcome in 43 children and adolescents with NF1 treated for STS in the Italian protocols between 1988 and 2004 are reported.The study included 37 patients with neurogenic sarcomas (36 malignant peripheral nerve sheath tumors [MPNST], 1 triton tumor) and 6 cases of rhabdomyosarcoma (RMS). The prevalence of NF1 observed during the study period was 43% in the MPNST population and 1% in the RMS group.Most patients with neurogenic sarcomas had large, invasive tumors. Five‐year event‐free and overall survival rates were 19% and 28%, respectively. Two of 16 patients with evaluable disease responded to chemotherapy. All 6 RMS patients were ≤3 years old and had embryonal subtype, 5 of 6 arising in the genitourinary tract or pelvis (paravesical); 4 were alive in first remission at the time of the analysis, 1 was alive in second remission after a local recurrence, and 1 died of disease.The occurrence of STS in pediatric patients with NF1 syndrome in Italy is discussed, confirming that NF1 patients have a high risk of developing STS, and particularly MPNST, often with an aggressive clinical presentation and poor outcome. Cases of RMS tended to have particular features (early age, embryonal histotype, genitourinary site) and their outcome seemed to resemble that of the general RMS population. Cancer 2007 © 2007 American Cancer Society. [ABSTRACT FROM AUTHOR]

Previously, we have identified aloe-emodin (AE) as a new type of anticancer agent, with activity that is based on apoptotic cell death promoted by a neuroectodermal tumor-specific drug uptake. We attempt to clarify the intracellular target of AE and the apoptosis-signaling pathway activated by AE in neuroblastoma cell lines. Two-photon excitation microscopy and spectroscopic titrations documented that AE is highly concentrated in susceptible cells and binds to DNA. One of the most important mediators of apoptotic response to genotoxic stimuli, such as anticancer agents, is the p53 tumor suppressor gene. To evaluate the role played by p53 in AE-induced apoptosis a p53 mutant cell line, which lacks transcriptional activity of p53 targeted genes, was tested. AE displayed a reduced growth inhibitory and pro-apoptotic activity in p53 mutant cells (SK-N-BE(2c)) with respect to the p53 wild-type line (SJ-N-KP). This effect was not caused by a reduced drug uptake in the mutant neuroblastoma cell line but was related to a different apoptotic cell phenotype. Whereas SJ-N-KP cells were susceptible to a p53 transcription-dependent pathway of apoptosis, SK-N-BE(2c) cells underwent apoptosis with up-regulation of p53 expression but not of p53-target genes. After AE treatment p53 translocates to the mitochondria inter-membrane space in both neuroblastoma cell lines. Due to its high accumulation in neuroectodermal tumor cells AE could also kill tumor cells harboring p53 mutant genes. This property would further contribute to AE specific anti-tumor activity and might be exploitable in the clinic. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]