A5048193615- Neuroblastoma Research and Treatments
- Glioma Diagnosis and Treatment
- Sarcoma Diagnosis and Treatment
- Childhood Cancer Survivors' Quality of Life
- Cancer therapeutics and mechanisms
- Chromatin Remodeling and Cancer
- Ocular Oncology and Treatments
- Lymphoma Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- Bone Tumor Diagnosis and Treatments
- Renal and related cancers
- Testicular diseases and treatments
- Brain Metastases and Treatment
- PARP inhibition in cancer therapy
- Cancer, Hypoxia, and Metabolism
- Head and Neck Surgical Oncology
- PI3K/AKT/mTOR signaling in cancer
- Cardiac tumors and thrombi
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Cancer-related Molecular Pathways
- Lung Cancer Research Studies
- Ubiquitin and proteasome pathways
- Lung Cancer Treatments and Mutations
- Neuroendocrine Tumor Research Advances
St. Jude Children's Research Hospital
2016-2025
Bristol-Myers Squibb (Switzerland)
2019
Novartis (Ireland)
2019
Eli Lilly (United States)
2019
Novartis (Switzerland)
2019
Pfizer (United States)
2019
Apexigen (United States)
2019
Merck (Germany)
2019
Children's National
2017-2018
Children's Oncology Group
2018
Abstract Background The Pediatric Preclinical Testing Program (PPTP) is an initiative supported by the National Cancer Institute (NCI) to identify novel therapeutic agents that may have significant activity against childhood cancers. PPTP has established panels of cancer xenografts and cell lines be used for in vivo vitro testing. These include Wilms tumor, sarcomas (rhabdomyosarcoma, Ewing sarcoma, osteosarcoma), neuroblastoma, brain tumors (glioblastoma, ependymoma, medulloblastoma),...
Children with average-risk medulloblastoma (MB) experience survival rates of ≥ 80% at the expense adverse consequences treatment. Efforts to mitigate these effects include deintensification craniospinal irradiation (CSI) dose and volume.ACNS0331 (ClinicalTrials.gov identifier: NCT00085735) randomly assigned patients age 3-21 years MB receive posterior fossa radiation therapy (PFRT) or involved field (IFRT) following CSI. Young children (3-7 years) were also standard-dose CSI (SDCSI; 23.4 Gy)...
Abstract BACKGROUND. Advances in systemic and local therapies have improved outcomes for patients with the Ewing sarcoma family of tumors (ESFT). As new treatments are developed, a critical review data from past treatment eras is needed to identify clinically relevant risk groups. METHODS. The authors reviewed records 220 ESFT who were treated on protocols at St. Jude Children's Research Hospital 1979 2004. Two defined. Factors predictive outcome analyzed distinct RESULTS. median age...
Abstract Background SCH 717454 (19D12) is a fully human antibody directed against the insulin‐like growth factor 1 receptor (IGF‐1R), which implicated in and metastatic phenotype of broad range malignancies. The activity was evaluated vitro vivo panels Pediatric Preclinical Testing Program (PPTP). Procedures tested PPTP panel at concentrations ranging from 0.01 to 100 nM dose 0.5 mg per mouse administered twice weekly for 4 weeks via intraperitoneal injection. Results ineffective retarding...
Abstract Background Rapamycin is a highly specific inhibitor of mTOR, serine/threonine kinase that controls cap‐dependent translation. Here we report the activity rapamycin against in vitro and vivo panels Pediatric Preclinical Testing Program (PPTP). Procedures was tested panel at concentrations from 0.01 to 100 nM tumor by i.p. administration daily × 5 for 6 consecutive weeks dose mg/kg. Results variably inhibited growth cell lines PPTP panel, with maximal inhibition values ranging 19% 85%...
The addition of immunotherapy, including a combination anti-GD2 monoclonal antibody (mAb), ch14.18, and cytokines, improves outcome for patients with high-risk neuroblastoma. However, this therapy is limited by ch14.18-related toxicities that may be partially mediated complement activation. We report the results phase I trial to determine maximum-tolerated dose (MTD), safety profile, pharmacokinetics hu14.18K322A, humanized mAb single point mutation (K322A) reduces complement-dependent...
Carboplatin-induced ototoxicity remains poorly defined but is of potential great consequence in children with retinoblastoma. We retrospectively assessed the incidence and its risk factors retinoblastoma who were treated carboplatin.
Abstract Signaling through the type 1 insulin-like growth factor receptor (IGF-1R) occurs in many human cancers, including childhood sarcomas. As a consequence, targeting IGF-1R has become focus for cancer drug development. We examined antitumor activity of CP-751,871, antibody that blocks ligand binding, alone and combination with rapamycin against sarcoma cell lines vitro xenograft models vivo. In Ewing (EWS) lines, CP751,871 inhibited poorly (<50%), but prevented rapamycin-induced...
BACKGROUND Chemotherapy has improved the outcome of patients with newly diagnosed osteosarcoma, but its role in relapsed disease is unclear. METHODS We reviewed records all who were treated for high‐grade osteosarcoma at our institution between 1970 and 2004. Postrelapse event‐free survival (PREFS) postrelapse (PRS) estimated, comparisons made using an exact log‐rank test. RESULTS The 10‐year PREFS PRS 110 11.8% ± 3.5% 17.0% 4.3%, respectively. Metastasis initial diagnosis (14%), relapse...
Abstract Purpose: Inhibitors of PARP, an enzyme involved in base excision repair, have demonstrated single-agent activity against tumors deficient homologous repair processes. Ewing sarcoma cells are also sensitive to PARP inhibitors, although the mechanism is not understood. Here, we evaluated stereo-selective inhibitor, talazoparib (BMN 673), combined with temozolomide or topotecan. Experimental Design: Talazoparib was tested vitro combination (0.3–1,000 μmol/L) topotecan (0.03–100 nmol/L)...
<h3>Importance</h3> Brain tumors are the leading cause of disease-related death in children. Medulloblastoma is most common malignant embryonal brain tumor, and strategies to increase survival needed. <h3>Objective</h3> To evaluate therapy intensification with carboplatin as a radiosensitizer isotretinoin proapoptotic agent children high-risk medulloblastoma randomized clinical trial and, correlative biology study, facilitate planned subgroup analysis according World Health Organization...
Purpose Children with histologically diagnosed high-risk medulloblastoma, supratentorial primitive neuroectodermal tumor of the CNS (CNS-PNET), and pineoblastoma (PBL) have had poor survival despite intensive treatment. We included these patients in this Children’s Oncology Group trial. Molecular profiling later revealed heterogeneity that was not detectable at protocol inception. Enrollment CNS-PNET/PBL subsequently discontinued, outcomes for part study are reported here. Patients Methods...
Abstract Background A Pediatric Brain Tumor Consortium (PBTC) phase I/II trial of veliparib and radiation followed by temozolomide (TMZ) was conducted in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). The objectives were to: (i) estimate the recommended II dose (RP2D) concurrent radiation; (ii) evaluate pharmacokinetic parameters during (iii) feasibility intrapatient TMZ escalation; (iv) describe toxicities protocol therapy; (v) overall survival distribution compared...
We sought to investigate clinical outcomes of relapsed medulloblastoma and compare molecular features between patient-matched diagnostic tumors.Children infants enrolled on either SJMB03 (NCT00085202) or SJYC07 (NCT00602667) trials who experienced relapse were analyzed for outcomes, including anatomic temporal patterns postrelapse survival. A largely independent, paired cohort was by DNA methylation array next-generation sequencing.A total 72 329 (22%) 52 79 (66%) patients with significant...
To evaluate the efficacy of chemoreduction using vincristine and carboplatin in preventing or delaying external-beam radiotherapy (EBRT) enucleation patients with intraocular retinoblastoma.Twenty-five (43 eyes) newly diagnosed retinoblastoma received primary treatment eight courses carboplatin. Focal treatments were delayed until documentation disease progression. Outcome measures for each eye length time to progression, avoidance delay EBRT, globe survival. Event-free survival was defined...
Abstract BACKGROUND Despite improved therapies, 30–40% of patients with Ewing tumors (ET) experience recurrence and have a poor prognosis. The authors analyzed factors prognostic survival in recurrent ET. METHODS assessed the relation between postrecurrence (PRS) demographic, disease, treatment 71 who experienced ET after on one three consecutive institutional protocols. RESULTS Thirty‐four (47.9%) had distant recurrence, 25 (35.2%) local 12 (16.9%) both at median 1.7 years diagnosis....
PURPOSE: To describe the clinical features, response to therapy, and outcome of pediatric patients with initially unresected nonmetastatic nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). PATIENTS AND METHODS: We retrospectively reviewed presenting features tumor characteristics all 40 NRSTS who were seen at our institution between March 1962 December 1996. A subset 27 for whom complete treatment information was available analyzed determine whether therapy associated local disease control...
More than 90% of children with favorable-risk Hodgkin lymphoma can achieve long-term survival, yet many will experience toxic effects from radiation therapy. Pediatric oncologists strive for maintaining excellent cure rates while minimizing effects.To evaluate the efficacy 4 cycles vinblastine, Adriamycin (doxorubicin), methotrexate, and prednisone (VAMP) in patients who a complete response after 2 do not receive radiotherapy.Multi-institutional, unblinded, nonrandomized single group phase...
AZD6244 (ARRY-142886) is a potent small molecule inhibitor of MEK1/2 that in phase 2 clinical development.AZD6244 was tested against the Pediatric Preclinical Testing Program (PPTP) vitro panel (1 nM-10 microM). In vivo at dose 100 mg/kg administered orally twice daily 5 days per week for 6 weeks. Subsequently, evaluated two juvenile pilocytic astrocytoma (JPA) xenografts using once and dosing schedules. Phosphorylation ERK1/2 used as surrogate inhibition determined by immunoblotting.At...
Abstract BACKGROUND: The objective of this study was to prospectively evaluate dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) as an early indicator tumor histologic response preoperative chemotherapy and a possible prognostic factor for event‐free survival (EFS) overall in pediatric patients with newly diagnosed, nonmetastatic osteosarcoma who were treated on single, multi‐institutional phase 2 trial. METHODS: Three serial DCE‐MRI examinations at week 0 (before treatment), 9,...