Abstract:
BACKGROUND:Malignant peripheral nerve sheath tumor (MPNST) is an aggressive form of soft-tissue sarcoma (STS) in children. Despite intensive therapy, relatively few children with metastatic and unresectable disease survive beyond three years. RAS pathway activation is common in MPNST, suggesting MEK pathway inhibition as a targeted therapy, but the impact on clinical outcome has been small to date. PROCEDURE:We conducted preclinical pharmacokinetic (PK) and pharmacodynamic studies of two MEK inhibitors, trametinib and selumetinib, in two MPNST models and analyzed tumors for intratumor drug levels. We then investigated 3'-deoxy-3'-[18 F]fluorothymidine (18 F-FLT) PET imaging followed by 18 F-FDG PET/CT imaging of MPNST xenografts coupled to short-term or longer-term treatment with selumetinib focusing on PET-based imaging as a biomarker of MEK inhibition. RESULTS:Trametinib decreased pERK expression in MPNST xenografts but did not prolong survival or decrease Ki67 expression. In contrast, selumetinib prolonged survival of animals bearing MPNST xenografts, and this correlated with decreased pERK and Ki67 staining. PK studies revealed a significantly higher fraction of unbound selumetinib within a responsive MPNST xenograft model. Thymidine uptake, assessed by 18 F-FLT PET/CT, positively correlated with Ki67 expression in different xenograft models and in response to selumetinib. CONCLUSION:The ability of MEK inhibitors to control MPNST growth cannot simply be predicted by serum drug levels or drug-induced changes in pERK expression. Tumor cell proliferation assessed by 18 F-FLT PET imaging might be useful as an early response marker to targeted therapies, including MEK inhibition, where a primary effect is cell-cycle arrest.
journal_name
Pediatr Blood Cancerjournal_title
Pediatric blood & cancerauthors
Butler E,Schwettmann B,Geboers S,Hao G,Kim J,Nham K,Sun X,Laetsch TW,Xu L,Williams NS,Skapek SXdoi
10.1002/pbc.28639subject
Has Abstractpub_date
2020-12-01 00:00:00pages
e28639issue
12eissn
1545-5009issn
1545-5017journal_volume
67pub_type
杂志文章abstract:BACKGROUND:Although screening for familial retinoblastoma has been shown to be beneficial we suspected that such screening programs may be less than optimal in developing countries (DC). METHODS:Retrospective cohort study comparing patients with familial retinoblastoma from five centers in DC (Argentina, Brazil, Turke...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.21970
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND:Contemporary descriptions of classical Hodgkin lymphoma (cHL) are lacking from sub-Saharan Africa where human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) are prevalent. METHODS:We describe a prospective cHL cohort in Malawi enrolled from 2013 to 2015. Patients received standardized treatment a...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.26302
更新日期:2017-05-01 00:00:00
abstract:BACKGROUND:(131) I-metaiodobenzylguanidine ((131) I-MIBG) is a targeted radiopharmaceutical for patients with neuroblastoma. Despite its tumor-specific uptake, the treatment with (131) I-MIBG results in whole-body radiation exposure. Our aim was to correlate whole-body radiation dose (WBD) from (131) I-MIBG with tumor ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.25816
更新日期:2016-03-01 00:00:00
abstract:BACKGROUND:A pediatric Phase I trial was performed to determine the maximum-tolerated dose, dose-limiting toxicities (DLTs), and pharmacokinetics (PK) of vorinostat and bortezomib, in patients with solid tumors. PROCEDURE:Oral vorinostat was administered on days 1-5 and 8-12 of a 21-day cycle (starting dose 180 mg/m(2...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.24271
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND:Severe pandemic influenza A (H1N1) infection can lead to acute respiratory failure (ARF) with associated high mortality. Children with malignancy may be at higher risk of H1N1-associated ARF because of underlying primary disease or immunosuppression associated with chemotherapy. PROCEDURE:We describe the cl...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.22973
更新日期:2011-10-01 00:00:00
abstract::Data on prognostic factors in pelvic PNET are minimal. We analyzed patients with pelvic PNET treated between June 2003 and November 2011 for prognostic factors. Forty-eight (13%) of 374 patients with PNET were pelvic PNET with median age 14.5 years (range: 5-33); 31 (65%) had metastases. After median follow-up of 20.4...
journal_title:Pediatric blood & cancer
pub_type: 临床试验,杂志文章
doi:10.1002/pbc.24552
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND:The aims of this study were to define the mRNA expression profiles of MYCN, DDX1, TrkA, and TrkC in biopsy tumor samples from 64 Brazilian patients with neuroblastomas of different risk stages and to correlate altered expression with prognostic values. PROCEDURE:Patients were retrospectively classified into...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.22823
更新日期:2011-05-01 00:00:00
abstract::We report a 10-year-old male with Hb E/Beta thalassemia disease who developed chronic graft-versus-host disease (cGVHD) of antiphospholipid antibody syndrome after successful allogeneic stem cell transplantation (SCT). He exhibited a recurrent ischemic stroke on day 368 post-SCT while on cyclosporine A, azathioprine, ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.23020
更新日期:2011-07-15 00:00:00
abstract:BACKGROUND:Degenerative-like neuro-Langerhans cell histiocytosis (DN-LCH) is a rare complication of LCH marked by progressive cerebellar ataxia. No treatment has so far been shown to slow this progression. PROCEDURE:All-trans retinoic acid (ATRA) was administered orally at a dose of 45 mg/m(2) daily for 6 weeks and th...
journal_title:Pediatric blood & cancer
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1002/pbc.20040
更新日期:2004-07-01 00:00:00
abstract:BACKGROUND:Patients with cancer who receive intensive chemotherapeutic regimens are subject to profound immunosuppression and are susceptible to an extended array of pathogens. PROCEDURE:The infectious causes of symptomatic gastroenteritis as evidenced by diarrhea +/- fever, vomiting, and abdominal colic in children f...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.10394
更新日期:2004-04-01 00:00:00
abstract:PURPOSE:Research using banked tissue is key to advancing risk-stratification and treatment of children with cancer. Knowledge of parental attitudes to ethical issues arising in tissue banking is very limited but essential in obtaining respectful consent. METHODS:One hundred parents of consecutively diagnosed children ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.22716
更新日期:2011-12-15 00:00:00
abstract:BACKGROUND:We sought to determine the prevalence of abnormal pulmonary function tests (PFTs) in a cohort of children who had received whole lung irradiation (WLI) for treatment of metastatic disease. PROCEDURE:This was a retrospective (1988-2003) chart review that included all children treated at our institution with ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.20457
更新日期:2006-02-01 00:00:00
abstract:BACKGROUND:As pegylated asparaginase is becoming the preferred first-line asparaginase preparation in the chemotherapy regimens of childhood acute lymphoblastic leukemia (ALL), there is a need to evaluate this treatment. METHODS:The aim of this study was to evaluate the pharmacokinetics of prolonged upfront biweekly P...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章,随机对照试验
doi:10.1002/pbc.26686
更新日期:2017-12-01 00:00:00
abstract:INTRODUCTION:Understanding factors that affect the decisions of caregivers of African children to enroll their children in clinical trials would lead to more fully informed consent. METHODS:During the NOHARM study (NCT01976416), a placebo-controlled clinical trial of hydroxyurea for Ugandan children with sickle cell a...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.27830
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND:There are no tests to identify critically ill children at high risk of deep venous thrombosis (DVT). In this exploratory study, we aimed to identify proteins that are associated with incident DVT in critically ill adolescents. PROCEDURE:Plasma samples were obtained from critically ill adolescents within 24 ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章,多中心研究
doi:10.1002/pbc.28159
更新日期:2020-04-01 00:00:00
abstract:BACKGROUND:Long-term adverse effects of Imatinib in children with chronic myeloid leukemia (CML) are uncertain. The aim was to study the effect of imatinib on growth in children with CML. PROCEDURE:Children ≤13 years of age at diagnosis were enrolled retrospectively, from 2004 to 2011, from a single center in India. P...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.23389
更新日期:2012-09-01 00:00:00
abstract::Undifferentiated embryonal sarcoma of the liver (UESL) is a rare aggressive mesenchymal pediatric tumor. Previously, reported outcomes have been very poor. Here, we report a single-center experience of five patients with UESL treated with upfront gross total resection and adjuvant chemotherapy. We have a median follow...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.26154
更新日期:2016-12-01 00:00:00
abstract::Treatment with the nucleoside analog cytarabine has been shown to mimic changes in gene expression associated with downregulation of the EWS-FLI1 oncogene in Ewing sarcoma cell lines, selectively inhibit their growth in vitro, and cause tumor regression in athymic nude mice. For this report cytarabine was studied in v...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.22355
更新日期:2010-12-01 00:00:00
abstract::Chronic hypoxemia is a common manifestation among patients with sickle cell anemia (SCA) who develop chronic lung disease. We report the beneficial effect of hydroxyurea on chronic hypoxemia in three pediatric patients with SCA and recurrent episodes of acute chest syndrome (ACS). All three patients improved rapidly a...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.21480
更新日期:2008-06-01 00:00:00
abstract::Surgery plays an important role as part of the treatment plan in most children with malignant solid tumors in regards to initial biopsy, upfront resection, and delayed resection. Surgeons also play a critical role in the treatment of surgical complications that may arise during medical treatment. The pediatric surgica...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.26618
更新日期:2017-10-01 00:00:00
abstract::Children with cancer are at risk of malnutrition, which can impair critical childhood processes of growth and development and contribute to poor health outcomes. Enteral nutrition can effectively ameliorate malnutrition or weight loss in children with cancer; however, published nutrition support algorithms contain min...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.27702
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND:In low- and middle-income countries, therapeutic options for advanced, refractory, or relapsing malignancies are limited due to local constraints such as cost of drugs, distance from oncology centers, and lack of availability of new anticancer drugs. Metronomics, which combines metronomic chemotherapy (MC) a...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.28508
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:Although genetic and environmental factors are considered to be the main causes of acute lymphoblastic leukemia, the associations between maternal factors during pregnancy and the childhood ALL is still unclear. PROCEDURE:In this study, meta-analysis was used. Medline, PubMed, and Web of Science were search...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章,meta分析
doi:10.1002/pbc.25443
更新日期:2015-07-01 00:00:00
abstract:BACKGROUND:Extramedullary infiltration (EMI) is an occasional clinical symptom in childhood acute myelogenous leukemia (AML), but there is considerable controversy regarding the prognostic significance of EMI in AML. PROCEDURE:We evaluated the frequency and prognostic significance of EMI at diagnosis of AML in childre...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.20824
更新日期:2007-04-01 00:00:00
abstract::We evaluated the effects of body mass index (BMI) on the risk of thromboembolism (TE) in children (<18 years) with hematological malignancies during the period 1990-2009 (n = 359). Obesity was prevalent in 12% of patients: 6% versus 17% prior to and after the year 2000 (P = 0.02). Sixty-one (17%) patients developed TE...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.23355
更新日期:2012-08-01 00:00:00
abstract::We report two second malignant neoplasms (SMNs) of the parotid gland. Patient 1 was initially diagnosed with precursor B-cell lymphoblastic lymphoma of the scalp. Eight years after her initial diagnosis she presented with a small, painless mass in the region of her parotid gland. Patient 2 was diagnosed with pre-B-cel...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.20306
更新日期:2005-12-01 00:00:00
abstract::Embryonal rhabdomyosarcoma (ERMS) is the most common childhood sarcoma and is a component of the familial pleuropulmonary blastoma (PPB)-predisposition syndrome. Using the PPB model, we hypothesized that DICER1 mutations would be found in familial and sporadic forms of ERMS. Blood samples from four children with famil...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.24020
更新日期:2012-09-01 00:00:00
abstract::Hospital-based home care (HBHC) is widely applied in Pediatric Oncology. We reviewed the potential effect of HBHC on children's physical health and risk of adverse events, parental and child satisfaction, quality of life of children and their parents, and costs. A search of PubMed, CINAHL, and EMBASE led to identifica...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章,评审
doi:10.1002/pbc.23047
更新日期:2011-09-01 00:00:00
abstract::The molecular detection of minimal residual disease (MRD) is standard of care in acute lymphoblastic leukemia to personalize the stratification of patients to appropriate intensity chemotherapy regimens. High-throughput sequencing (HTS) techniques are driving changes to MRD methodologies. Our study demonstrates HTS ca...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.27787
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:Irinotecan is highly active against rhabdomyosarcoma (RMS), yet its tolerability and efficacy in combination with radiation is unknown. We examined local control and toxicities in RMS patients treated with radiotherapy (RT) in combination with radiosensitizing agents irinotecan + carboplatin (I + C). PROCED...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.24205
更新日期:2013-02-01 00:00:00