Efficacy and safety of deferasirox compared with deferoxamine in sickle cell disease: two-year results including pharmacokinetics and concomitant hydroxyurea.

We report a prospective, randomized, Phase II study of deferasirox and deferoxamine (DFO) in sickle cell disease patients with transfusional iron overload, with all patients continuing on deferasirox after 24 weeks, for up to 2 years. The primary objective was to evaluate deferasirox safety compared with DFO; long-term efficacy and safety of deferasirox was also assessed. We also report, for the first time, the safety and pharmacokinetics of deferasirox in patients concomitantly receiving hydroxyurea.

A t(17;22)(q21;q12) with partial ETV4 deletion in a soft tissue Ewing sarcoma.

Cytogenetic analysis of a lumbar soft tissue Ewing sarcoma (ES) in a 7-month-old female child showed a t(17;22)(q21;q12), a rare translocation leading to an EWSR1-ETV4 chimeric transcript. These findings were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) techniques. The breakpoints were characterized by direct sequencing of the chimeric fusion gene.

High level of apoptosis and low AKT activation in mass screening as opposed to standard neuroblastoma.

Aims: Neuroblastoma is a paediatric solid tumour with a poor outcome except in children <1 year old. Based on catecholamine urinary excretion, mass screening (MS) programmes have been organized but failed to decrease the mortality of this tumour. To test the hypotheses of a spontaneous maturation/differentiation or regression, the levels of poly (ADP-ribose) polymerase (PARP)-1, an early apoptosis marker, of PhosphoAKT, a major apoptosis inhibitor, and of maturation/differentiation were compared in standard and in MS neuroblastomas.

Identification of membrane-type 1 matrix metalloproteinase tyrosine phosphorylation in association with neuroblastoma progression.

Background: Neuroblastoma is a pediatric tumor of neural crest cells that is clinically characterized by its variable evolution, from spontaneous regression to malignancy. Despite many advances in neuroblastoma research, 60% of neuroblastoma, which are essentially metastatic cases, are associated with poor clinical outcome due to the lack of effectiveness of current therapeutic strategies. Membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP-14), an enzyme involved in several steps in tumor progression, has previously been shown to be associated with poor clinical outcome for neuroblastoma.

SNP genotyping of a sclerosing rhabdomyosarcoma: reveals highly aneuploid profile and a specific MDM2/HMGA2 amplification.

Since the first description of sclerosing rhabdomyosarcoma in 2000, 19 pediatric cases have been reported in the literature. However, it is debated whether sclerosing rhabdomyosarcoma represents a specific rhabdomyosarcoma entity or a variant of embryonal or alveolar rhabdomyosarcoma. To date, 6 sclerosing rhabdomyosarcoma karyotypes and 1 sclerosing rhabdomyosarcoma comparative genomic hybridization profile have been reported.

Beta-catenin mutation does not seem to have an effect on the tumorigenesis of pediatric rhabdomyosarcomas.

Involvement of the Wnt signal transduction pathway has been shown in different pediatric embryonal tumors, such as hepatoblastoma, nephroblastoma, pancreatoblastoma, and medulloblastoma. There are few data available on the status of beta-catenin in rhabdomyosarcoma (RMS), another pediatric embryonal tumor. The aims of this study were 1st to verify the status of the exon 3 of CTNNB1 and 2nd to assess the usefulness of beta-catenin immunostaining in a small series of 8 embryonal RMS, 3 alveolar RMS, and 1 sclerosing RMS (SRMS).

Delphinidin, a dietary anthocyanidin, inhibits platelet-derived growth factor ligand/receptor (PDGF/PDGFR) signaling.

Most cancers are dependent on the growth of tumor blood vessels and inhibition of tumor angiogenesis may thus provide an efficient strategy to retard or block tumor growth. Recently, tumor vascular targeting has expanded to include not only endothelial cells (ECs) but also smooth muscle cells (SMCs), which contribute to a mature and functional vasculature. We have reported previously that delphinidin, a major biologically active constituent of berries, inhibits the vascular endothelial growth factor-induced phosphorylation of vascular endothelial growth factor receptor-2 and blocks angiogenesis in vitro and in vivo.

Incidence of neuroblastoma after a screening program.

Purpose: A significant increase in the incidence of neuroblastoma occurred among a 5-year birth cohort (May 1989 to April 1994) during an active urinary screening program for its early detection. We examined the postscreening incidence of neuroblastoma in the subsequent 5-year birth cohort (May 1994 to April 1999), with follow-up to 2002, to determine whether the incidence remained increased.

Patients And Methods: We reviewed institutional records of patients diagnosed with neuroblastoma during the period from 1994 to 2002 who were born in 1994 to 1999 in the province of Quebec, as well as in the state of Minnesota and the province of Ontario, regions that had served as controls during the screening interval.

Complications of apheresis in children.

Background: Although the frequency of complications in adults undergoing therapeutic apheresis is low, there are little data in children.

Study Design And Methods: A retrospective study of 186 children who had undergone a total of 1632 apheresis procedures between 1994 and 2002 was conducted. Adverse reactions were prospectively documented.

Inhibition of cancer cell proliferation and suppression of TNF-induced activation of NFkappaB by edible berry juice.

Background: Berries contain several phytochemicals, such as phenolic acids, proanthocyanidins, anthocyanins and other flavonoids. There has been growing interest in a variety of potential chemopreventive activities of edible berries. The potential chemopreventive activity of a variety of small berries cultivated or collected in the province of Québec, Canada were evaluated here.

Anthocyanidins inhibit migration of glioblastoma cells: structure-activity relationship and involvement of the plasminolytic system.

Complete resection of malignant glioblastomas is usually impossible because of diffuse and widespread invasion of tumor cells, and complementary approaches need to be developed in order to improve the efficacy of current treatments. Consumption of fruits and berries has been associated with decreased risk of developing cancer and there is great interest in the use of molecules from dietary origin to improve anticancer therapies. In this work, we report that the aglycons of the most abundant anthocyanins in fruits, cyanidin (Cy), delphinidin (Dp), and petunidin (Pt), act as potent inhibitors of glioblastoma cell migration.

Treatment complications in children diagnosed with neuroblastoma during a screening program.

Purpose: The Québec Neuroblastoma Screening Program was put in place to investigate the possibility of decreasing mortality from high-risk neuroblastoma through early screening. We assess treatment complications in the patients diagnosed during this screening program.

Patients And Methods: A total of 476,603 patients born during the screening period were eligible.

Delphinidin, a dietary anthocyanidin, inhibits vascular endothelial growth factor receptor-2 phosphorylation.

Epidemiological studies have shown that a diet rich in fruits and vegetables has a beneficial preventive effect on cardiovascular diseases and cancer by mechanisms that have not yet been elucidated. In this work, we investigated the antiangiogenic activities of anthocyanidins, a class of polyphenols present at high levels in fruits. Among the tested anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin and petunidin), delphinidin was the most potent angiogenic inhibitor.

Second induction in pediatric patients with recurrent acute lymphoid leukemia using DFCI-ALL protocols.

Between 15% and 30% of children with acute lymphoblastic leukemia (ALL) experience disease recurrence. With the possible exception of patients presenting with late isolated extramedullary relapse, induction of second complete remission (CR) is employed as a stepping stone to allogeneic hematopoietic stem cell transplantation (HSCT). The authors report their institutional experience in the management of children with recurrent ALL using the Dana Farber Cancer Institute (DFCI) ALL protocol in patients treated initially with that same protocol.

Matrix metalloproteinase regulation of sphingosine-1-phosphate-induced angiogenic properties of bone marrow stromal cells.

Objective: Bone marrow-derived stromal cells (MSC) are able to acquire histological and immunophenotypic characteristics consistent with endothelial cells (EC). In this study we examined the effect of sphingosine-1-phosphate (S1P), a platelet-derived bioactive lysophospholipid that is believed to specifically stimulate EC migration and tube formation, on the angiogenic properties of MSC.

Methods: MSC were isolated from murine bone marrow and cultured in the presence of diverse angiogenic growth factors.