Abstract:
BACKGROUND:Sorafenib is an inhibitor of multiple kinases (e.g., VEGF receptors, PDGFR, FLT3, RET, BRAF, KIT) and is approved by FDA for treatment of two adult cancers. The activity of sorafenib was evaluated against the PPTP's in vitro and in vivo panels. PROCEDURES:Sorafenib was evaluated against the PPTP in vitro panel using 96-hr exposure at concentrations ranging from 1.0 nM to 10.0 µM. It was tested against the PPTP in vivo panels at a dose of 60 mg/kg administered by oral gavage daily for 5 days per week, repeated for 6 weeks. RESULTS:In vitro sorafenib demonstrated cytotoxic activity, with a median IC(50) value of 4.3 µM. Twenty of 23 cell lines had IC(50) values between 1.0 and 10.0 µM. A single cell line (Kasumi-1) with an activating KIT mutation had an IC(50) value < 1.0 µM (IC(50) = 0.02 µM). In vivo sorafenib induced significant differences in event-free survival (EFS) distribution compared to control in 27 of 36 (75%) of the evaluable solid tumor xenografts and in 1 of 8 (12.5%) of the evaluable ALL xenografts. Sorafenib induced tumor growth inhibition meeting criteria for intermediate activity (EFS T/C) in 15 of 34 (44%) evaluable solid tumor xenografts. No xenografts achieved an objective response. CONCLUSIONS:The primary in vitro activity of sorafenib was noted at concentrations above 1 µM, with the exception of a more sensitive cell line with an activating KIT mutation. The primary in vivo effect for sorafenib was tumor growth inhibition, which was observed across multiple histotypes.
journal_name
Pediatr Blood Cancerjournal_title
Pediatric blood & cancerauthors
Keir ST,Maris JM,Lock R,Kolb EA,Gorlick R,Carol H,Morton CL,Reynolds CP,Kang MH,Watkins A,Houghton PJ,Smith MAdoi
10.1002/pbc.22712subject
Has Abstractpub_date
2010-12-01 00:00:00pages
1126-33issue
6eissn
1545-5009issn
1545-5017journal_volume
55pub_type
杂志文章abstract:BACKGROUND:The male excess in childhood cancer incidence is well-established; however, the underlying biologic mechanisms remain unknown. Examining the association between male sex and childhood cancer by single year of age and tumor type may highlight important periods of risk such as variation in growth and hormonal ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.27620
更新日期:2019-06-01 00:00:00
abstract:BACKGROUND:The aim of the study was to investigate factors affecting response to everolimus, a mammalian-target-of-rapamycin (mTOR) inhibitor, of subependymal giant cell astrocytomas (SEGA) in patients with tuberous sclerosis complex (TSC). METHODS:The study group consisted of 15 children with a diagnosis of TSC-relat...
journal_title:Pediatric blood & cancer
pub_type: 临床试验,杂志文章
doi:10.1002/pbc.25368
更新日期:2015-04-01 00:00:00
abstract:BACKGROUND:Incidence of venous thromboembolism (VTE) in children is reported to be increasing. We examined thrombophilia testing results in children with VTE that presented in inpatient and outpatient settings to explore patterns of thrombophilia testing. PROCEDURE: PATIENTS/METHODS:Children, ages 0-20 years with VTE...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.24846
更新日期:2014-03-01 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:BACKGROUND:The aim was to evaluate self-reported reproductive characteristics and markers of ovarian function in a nationwide cohort of female survivors of childhood acute lymphoblastic leukemia (ALL), because prior investigations have produced conflicting data. PROCEDURE:Self-reported reproductive characteristics wer...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.28894
更新日期:2021-01-18 00:00:00
abstract:BACKGROUND:MYCN amplification marks poor prognosis in neuroblastoma (NB) tumors. In evaluating the mechanisms by which retinoic acid (RA) or nerve growth factor (NGF) decrease cell number in MYCN amplified NB cells, we have identified a number of proteins whose expression either decreases (E2F, CDC2, CDK6, cyclin depen...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.21195
更新日期:2008-02-01 00:00:00
abstract::Twenty-eight patients were maintained on subcutaneous immunoglobulin replacement for persistent B-cell aplasia and agammaglobulinemia following CD19-targeted chimeric antigen receptor T-cell therapy for B-cell lymphoblastic leukemia. Patients were transitioned from intravenous to subcutaneous immunoglobulin replacemen...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.28092
更新日期:2020-03-01 00:00:00
abstract::Pediatric renal cell carcinoma (RCC) is a rare cancer that can be associated with inherited diseases including tuberous sclerosis complex (TSC) caused by germline mutations in TSC1 or TSC2. Somatic mutations in TSC1 and TSC2 have also been reported in adult RCC, which predict response to mTOR inhibitors. Here, we pres...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.26286
更新日期:2017-05-01 00:00:00
abstract::Although awareness of implicit bias and its influence on providers and patients is increasing, the effects of implicit bias on the field of pediatric hematology-oncology are less clear. This Special Report reviews the literature on implicit bias in pediatrics and medical oncology and further provides case examples and...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章,评审
doi:10.1002/pbc.28204
更新日期:2020-05-01 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:BACKGROUND:The purpose of this study was to determine the prevalence of pulmonary dysfunction in pediatric hematopoietic cell transplant (HCT) survivors and to identify associated risk factors. PROCEDURE:In a cross-sectional study, patients surviving at least 5 years after pediatric HCT were requested to undergo pulmo...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.20531
更新日期:2006-10-15 00:00:00
abstract:BACKGROUND:Although maternal thrombocytopenia during pregnancy is common, its effect on neonatal platelets has not yet been fully evaluated. METHODS:We retrospectively evaluated the rate of thrombocytopenia among 767 healthy term neonates (gestational age 37-42 weeks) born to 723 mothers with pregnancy-induced thrombo...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.22514
更新日期:2010-07-15 00:00:00
abstract:BACKGROUND:Transcranial Doppler ultrasound (TCD) has been demonstrated to be a powerful predictor of stroke risk due to sickle cell disease (SCD) in pediatric populations. Little is known about how this healthcare innovation has disseminated into preventive care for SCD. The objective of this study was to determine TCD...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.21677
更新日期:2008-11-01 00:00:00
abstract:BACKGROUND:Information on the epidemiology of pediatric liver tumors in Latin America is limited. PURPOSE:To describe the incidence of liver tumors in a pediatric registry in Argentina according to geographic region, national trends over 16 years, and survival related to stage, age, sex, and care center. METHODS:Newl...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.28583
更新日期:2020-11-01 00:00:00
abstract:BACKGROUND:Outcomes for patients with oncologic disease and/or after hematopoietic stem cell transplant (HSCT) requiring intensive care unit admission have improved, but indications for and outcomes after extracorporeal membrane oxygenation (ECMO) support in this population are poorly characterized. PROCEDURE:We analy...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章,多中心研究
doi:10.1002/pbc.28403
更新日期:2020-10-01 00:00:00
abstract:OBJECTIVE:The objective of this single-center observational study was to determine the clinical and hematologic responses to intravenous ferric carboxymaltose (FCM) in a cohort of pediatric patients with poor response to oral iron therapy. The occurrence of adverse events was systematically recorded for up to 96 hours ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.28614
更新日期:2020-10-01 00:00:00
abstract::Hyperglycemia during induction chemotherapy for childhood acute lymphoblastic leukemia (ALL) has been inconsistently associated with risk of infection. We investigated the incidence of hyperglycemia during induction for childhood ALL in a retrospective cohort study of 144 patients treated on a single national protocol...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.24689
更新日期:2013-12-01 00:00:00
abstract::We report on an acute myeloid leukemia in a neonate whose mother was exposed to diethylstilboestrol in utero. The newborn presented with leukemia cutis, hemorrhagic skin lesions, hyperleucocytosis and disseminated intravascular coagulation. A bone marrow examination confirmed the diagnosis of acute monocytic leukemia ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.22040
更新日期:2009-08-01 00:00:00
abstract::Optic pathway gliomas represent approximately 5% of all pediatric intracranial tumors. While these tumors are most frequently low grade astrocytomas, they follow a highly variable clinical course, and accordingly, there is much debate regarding their optimal management. Their propensity to occur in very young children...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章,评审
doi:10.1002/pbc.20655
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND:Few studies have evaluated social determinants of outcomes disparities for children with acute lymphoblastic leukemia (ALL). We investigated the association of area deprivation index (ADI), a measure of neighborhood socioeconomic disadvantage, with overall survival (OS) among children and adolescents with AL...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.28525
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:Glucocorticoids and asparaginase, used to treat acute lymphoblastic leukemia (ALL), can cause hypertriglyceridemia. We compared triglyceride levels, risk factors, and associated toxicities in two ALL trials at St. Jude Children's Research Hospital with identical glucocorticoid regimens, but different asparag...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.28040
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Abandonment of treatment is one of the toughest challenges to deal with in pediatric oncology. It leads to unnecessary mortality and morbidity in patients from low- and middle-income countries. PROCEDURE:The objective of our retrospective study was to determine the prevalence and predictors for abandonment ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.26818
更新日期:2018-02-01 00:00:00
abstract::Enrollment of patients in sickle cell intervention trials has been challenging due to difficulty in obtaining consent from a legal guardian and lack of collaboration between emergency medicine and hematology. We utilized education and preconsent in a pediatric multisite sickle cell intervention trial to overcome these...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章,多中心研究
doi:10.1002/pbc.26013
更新日期:2016-09-01 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::Male breast cancer (MBC) is unusual, especially in young adults. Most cases of MBC as a secondary malignancy relate to the previous treatment with ionizing radiation. MBC can be associated with mutations in hereditary cancer predisposition syndrome genes (i.e., BRCA2); however, no such association has been reported in...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.25796
更新日期:2016-03-01 00:00:00
abstract:INTRODUCTION:Our objectives were to design and validate methods to identify relapse and hematopoietic stem cell transplantation (HSCT) in children with acute lymphoblastic leukemia (ALL) using administrative data representing hospitalizations at US pediatric institutions. METHODS:We developed daily billing and ICD-9 c...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.28315
更新日期:2020-05-11 00:00:00
abstract::We describe an African American family with Hoyeraal-Hreidarrson syndrome (HHS) in which 2 TERT mutations (causing P530L and A880T amino acid changes) and two in the DKC1 variants (G486R and A487A) were segregating. Both genes are associated with dyskeratosis congenita and HHS. It was important to determine the import...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.24389
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:The level of minimal residual disease (MRD) prior to allogeneic hematopoietic stem cell transplantation (HSCT) has been shown to be an independent prognostic factor for outcome of pediatric patients with high-risk acute lymphoblastic leukemia (ALL). Retrospective studies which used (semi-) quantitation of cl...
journal_title:Pediatric blood & cancer
pub_type: 临床试验,杂志文章
doi:10.1002/pbc.20794
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Cisplatin (CDDP) ototoxicity is a significant side effect of the current treatment of medulloblastoma (MB). Cumulative dose of CDDP and age are recognized risk factors for hearing loss, but inter-individual susceptibility limits our ability to identify patients at risk for hearing loss. We describe the kinet...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.24307
更新日期:2013-02-01 00:00:00
abstract:BACKGROUND:Pediatric venous thromboembolism (VTE) is an increasingly common problem. We hypothesized that VTE occurs most commonly in tertiary care settings and that the pattern of associated illnesses may have changed from earlier reports. METHODS:The Kids' Inpatient Database 2006 was utilized to identify children ≤ ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.23388
更新日期:2012-08-01 00:00:00