Temozolomide is an active agent in children with recurrent medulloblastoma/primitive neuroectodermal tumor: an Italian multi-institutional phase II trial.

Background: The aim of this study was to assess the objective response rate (ORR) of children and young adults with recurrent medulloblastoma/primitive neuroectodermal tumor (MB/PNET) treated with temozolomide (TMZ). The secondary purpose was to analyze the toxicity profile of TMZ when administered orally for 5 days in 3 divided daily doses every 28 days.

Methods: Forty-two patients with recurrent MB/PNET, aged 21 years and younger, were recruited.

Poor prognosis osteosarcoma: new therapeutic approach.

Over the past 30 years, a significant improvement in the prognosis of localized osteosarcoma of the extremities has been observed. Despite these results, approximately 30-40% of patients will relapse, mostly within the first 3 years from diagnosis. The prognosis of patients with recurrent disease or metastases at diagnosis is poor.

Human mesenchymal stem cell transplantation extends survival, improves motor performance and decreases neuroinflammation in mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a lethal disease affecting motoneurons. In familial ALS, patients bear mutations in the superoxide dismutase gene (SOD1). We transplanted human bone marrow mesenchymal stem cells (hMSCs) into the lumbar spinal cord of asymptomatic SOD1(G93A) mice, an experimental model of ALS.

Interactions between osteosarcoma cell lines and dendritic cells immune function: An in vitro study.

Dendritic cells (DCs) might be partly responsible for the defective immune response in tumor bearing hosts, but no study in osteosarcoma patients is still available. Therefore, we investigated in vitro whether human osteosarcoma cell lines have an inhibitor effect on different types of DCs: CD14+DCs, DC1 and DC2. DCs derived from healthy donors were cultured with osteosarcoma cell lines and appropriate cytokine cocktails and analysed for the expression of co-stimulatory molecules (CD40, CD80, CD83, CD86, HLA-DR).

Osteosarcoma cell line growth inhibition by zoledronate-stimulated effector cells.

Bisphosphonates have a profound effect on bone resorption and are widely used in the treatment of osteoclast-mediated bone diseases. Zoledronic acid (ZA), a third-generation biphosphonate, has a potent antitumor activity and expands gammadelta (gammadelta) T cells endowed of major histocompatibility complex-unrestricted lytic activity. Many solid tumors express tumor-specific antigens on their surface, representing targets for immune effector T cells.

Lymphocyte subsets recovery following allogeneic bone marrow transplantation (BMT): CD4+ cell count and transplant-related mortality.

To assess the kinetics of lymphocyte subset recovery, 758 allografted patients were monitored by surface markers (CD3, CD4, CD8, CD56), with a 5-year follow-up. The donor was a matched sibling donor (MSD) (n=502) or an alternative donor (family mismatched or unrelated, AD) (n=256). The stem cell source was bone marrow for all patients.

Extracorporeal photopheresis for steroid resistant graft versus host disease in pediatric patients: a pilot single institution report.

This study was aimed at ascertaining whether extracorporeal photopheresis (ECP) is an effective treatment for pediatric patients with steroid resistant graft versus host disease (GvHD). Fifteen patients with acute GvHD (aGvHD) and 10 patients with chronic GvHD (cGvHD) were enrolled in the study. At the start of the ECP protocol, aGvHD was staged as II (n=7), III (n=4), and IV (n=4).

Male crickets adjust ejaculate quality with both risk and intensity of sperm competition.

Sperm competition theory predicts that males should increase their expenditure on the ejaculate with increasing risk of sperm competition, but decrease their expenditure with increasing intensity. There is accumulating evidence for sperm competition theory, based on examinations of testes size and/or the numbers of sperm ejaculated. However, recent studies suggest that ejaculate quality can also be subject to selection by sperm competition.

Response to melphalan in up-front investigational window therapy for patients with metastatic Ewing's family tumours.

The aim of the study was to determine the activity and toxicity of melphalan as a single agent given in up-front therapy for patients with newly-diagnosed Ewing's family tumours with bone/bone marrow metastases. Nineteen patients were enrolled from 2001 to 2004. The treatment consisted of up-front therapy with melphalan (two courses of 50 mg/m2, 3 weeks apart).

Ovarian tissue cryostorage and grafting: an option to preserve fertility in pediatric patients with malignancies.

Fertility preservation in childhood cancer has become an important area of investigation due to increasing survival rates after cancer therapy. For these patients with an increased risk of infertility and premature ovarian failure, cryopreservation of ovarian tissue is a promising tool to preserve at least part of the reproductive potential. In recent years significant improvements have been achieved in this area, and 2 live births after autografting of frozen-thawed ovarian tissue have been reported.

Neural differentiation of human mesenchymal stem cells: Evidence for expression of neural markers and eag K+ channel types.

Objective: Mesenchymal stem cells (MSCs) are multipotent cells that can self-renew, proliferate, and exhibit elevated cellular plasticity. To investigate their possible neural fate, we studied human mesenchymal stem cells (hMSCs) in different cell culture conditions from morphological, immunochemical, gene expression, and physiological points of view.

Materials And Methods: We tested hMSCs in three previously reported experimental conditions made of alpha-modified minimum essential medium (alpha-MEM)/1 mM beta-mercaptoethanol (betaME), 10 microM alpha-MEM/retinoic acid (RA) or alpha-MEM/2% dimethylsulfoxide (DMSO) + 200 microM beta-hydroxyanisole (BHA), respectively, and in a new experimental condition with neural progenitor maintenance medium (NPMM).

Diffuse and focal brain stem tumors in childhood: prognostic factors and surgical outcome. Experience in a single institution.

Objective: Brainstem tumors (BSTs) are usually gliomas and are divided into diffuse BSTs (DBSTs) and focal BSTs (FBSTs). The aim of this study is to investigate the different outcomes of these two entities.

Methods: Thirty-one patients with BSTs were admitted to our institution from 1995 to 2003.

Multilineage engraftment of refrozen cord blood hematopoietic progenitors in NOD/SCID mice.

Seven cord blood (CB) units were tested for their capacity to repopulate irradiated NOD/SCID mice after one or two successive cryopreservation procedures. In primary transplants with frozen or refrozen CB cells we observed equivalent human colonies and percentages of human CD45+ cells, with multilineage engraftment. In secondary transplants flow cytometry and polymerase chain reaction for the a satellite region of chromosome 17 showed equivalent levels of human engraftment.

High energy shock waves enhance the cytotoxic effect of doxorubicin and methotrexate to human osteosarcoma cell lines.

Despite recent advances, the prognosis of relapsed osteosarcoma patients remains very poor. Application of high energy shock waves may change the tumour cell growth and increase the cytotoxic effect of in vivo and in vitro chemotherapeutic agents. We studied the effect of their association with doxorubicin or methotrexate on three in vitro osteosarcoma cell lines.

Phase II trial of temozolomide in children with recurrent high-grade glioma.

Purpose: The objective of the study was to evaluate the efficacy and toxicity of Temozolomide (TMZ) administered for 5 consecutive days in three daily dosing in children with recurrent or refractory high-grade glioma.

Patients And Methods: Twenty-four patients with a median age of 10.5 years were enrolled onto this open-label, multicenter, phase II study.

Feasibility of cord blood stem cell manipulation with high-energy shock waves: an in vitro and in vivo study.

Objective: Cord blood CD34+ cells are more uncommitted than their adult counterparts as they can be more easily maintained and expanded in vitro and transduced with lentiviral vectors. The aim of this study was to evaluate whether pretreatment with high-energy shock waves (HESW) could further enhance the expansion of cord blood progenitors and the transduction efficiency with lentiviral vectors.

Methods: Human cord blood CD34+ cells underwent HESW treatment with a wide range of energy and number of shots (from 0.

Expansion of mesenchymal stem cells isolated from pediatric and adult donor bone marrow.

The enormous plasticity of mesenchymal stem cells (MSCs) suggests an improvement of a standard protocol of isolation and ex vivo expansion for experimental and clinical use. We isolated and expanded MSCs from bone marrow (BM) of pediatric and young adult donors, to analyze the growth kinetic, immunophenotype, telomere length, karyotype during ex vivo expansion. Seventeen BM samples were collected from young adult donors and 8 from pediatric donors.

Treatment with oral etoposide for childhood recurrent ependymomas.

In this study the authors retrospectively evaluated the feasibility and effectiveness of prolonged oral etoposide therapy in children with recurrent ependymoma. Twelve ependymoma patients with documented recurrent or persistent disease were treated between May 1998 and October 2003. All patients were treated monthly with oral VP-16 administered at a dose of 50 mg/m2/d for 21 days, with a 7-day interval between cycles, for a planned minimum number of six cycles.

Stem cell transplantation as consolidation therapy for children in first-remission AML: a single-center report.

A large number of patients affected by acute myeloid leukemia (AML) achieve complete remission following induction chemotherapy based on high-dose aracytin and anthracyclines. However, a postremission consolidation treatment appears to be essential to maintain the remission status. Sixteen patients with newly diagnosed AML received induction chemotherapy according to the AIEOP LAM 92P/Mod protocol.

Kikuchi-Fujimoto disease is a rare cause of lymphadenopathy and fever of unknown origin in children: report of two cases and review of the literature.

Kikuchi-Fujimoto disease, a benign and unusual self-limiting histiocytic necrotizing lymphadenitis of unknown origin, should be included in the differential diagnosis of lymphadenopathy and fever of unknown origin. This disease mostly affects young Asian women and has rarely been reported in children, thus remaining a poorly recognized entity that is frequently confused with malignant lymphoma. The authors describe two children with Kikuchi-Fujimoto disease, with particular attention to diagnostic approach and clinical and histologic features of the disease.

Outcomes and prognostic factors after recurrence in children and adolescents with nonmetastatic rhabdomyosarcoma.

Background: Although > 90% of children with nonmetastatic rhabdomyosarcoma (RMS) achieve complete remission with current treatment, up to one-third of them experience a recurrence. Survival rates are not always poor in patients who develop recurrences; thus, prognostic factors are needed to tailor salvage treatment.

Methods: The current analysis included 125 children who were affected by localized RMS and were enrolled in 3 consecutive Italian protocols (RMS79, RMS88, and RMS96) who developed recurrences after complete remission.

Two-dimensional and quasi-three-dimensional dosimetry of hadron and photon beams with the Magic Cube and the Pixel Ionization Chamber.

Two detectors for fast two-dimensional (2D) and quasi-three-dimensional (quasi-3D) verification of the dose delivered by radiotherapy beams have been developed at University and Istituto Nazionale di Fisica Nucleare (INFN) of Torino. The Magic Cube is a stack of strip-segmented ionization chambers interleaved with water-equivalent slabs. The parallel plate ionization chambers have a sensitive area of 24 x 24 cm2, and consist of 0.

High-dose thiotepa and etoposide in children with poor-prognosis brain tumors.

Background: Outcome data were analyzed for 27 patients who were affected with recurrent or newly diagnosed high-risk brain tumors and who underwent high-dose chemotherapy with triethylenethiophosphoramide (thiotepa) and etoposide in addition to autologous stem cell transplantation between May 1992 and September 2002.

Methods: Fifteen males and 12 females (median age, 11 years) were included in the study. Twelve patients had newly diagnosed high-risk brain tumors, and 15 patients had recurrent brain tumors.

Hyperfractionated radiotherapy and chemotherapy for childhood ependymoma: final results of the first prospective AIEOP (Associazione Italiana di Ematologia-Oncologia Pediatrica) study.

Purpose: A postsurgical "stage-based" protocol for ependymoma was designed.

Methods And Materials: Children were given: (1) focal hyperfractionated radiotherapy (HFRT) if with no evidence of disease (NED), or (2) 4 courses with VEC followed by HFRT for residual disease (ED). HFRT dose was 70.

Dosimetric characterization of a large area pixel-segmented ionization chamber.

A pixel-segmented ionization chamber has been designed and built by Torino University and INFN. The detector features a 24 x 24 cm2 active area divided in 1024 independent cylindrical ionization chambers and can be read out in 500 micros without introducing dead time; the digital charge quantum can be adjusted between 100 fC and 800 fC. The sensitive volume of each single ionization chamber is 0.