Abstract:
BACKGROUND:Ispinesib is a highly specific inhibitor of kinesin spindle protein (KSP, HsEg5), a mitotic kinesin required for separation of the spindle poles. Here we report the activity of ispinesib against the in vitro and in vivo panels of the Pediatric Preclinical Testing Program (PPTP). PROCEDURES:Ispinesib was tested against the PPTP in vitro panel cell lines at concentrations from 0.1 nM to 1 microM and against the in vivo tumor panel xenografts by intraperitoneal administration (5 or 10 mg/kg) every 4 days for 3 doses repeated at day 21. RESULTS:Ispinesib was highly potent against the PPTP's in vitro cell lines with a median IC(50) of 4.1 nM. Ispinesib (10 mg/kg) induced unexplained toxicity in mice bearing osteosarcoma xenografts and exceeded the MTD in 12 of 40 non-osteosarcoma xenografts. Ispinesib induced significant tumor growth delay in 88% (23/26) of evaluable xenografts. Using a time to event measure of efficacy, ispinesib had intermediate and high levels of activity against 4 (21%) and 5 (26%) of the 19 evaluable solid tumor xenografts, respectively. Ispinesib induced maintained complete responses (CR) in a rhabdoid tumor, a Wilms tumor and a Ewing sarcoma xenograft. Ispinesib (5 mg/kg) produced 2 complete and 2 partial responses among 6 evaluable xenografts in the ALL panel. The in vivo pattern of activity was distinctive from that previously reported for vincristine. CONCLUSIONS:Ispinesib demonstrated broad in vivo antitumor activity, including maintained complete responses for several xenografts, although with high toxicity rates at the doses studied.
journal_name
Pediatr Blood Cancerjournal_title
Pediatric blood & cancerauthors
Carol H,Lock R,Houghton PJ,Morton CL,Kolb EA,Gorlick R,Reynolds CP,Maris JM,Keir ST,Billups CA,Smith MAdoi
10.1002/pbc.22056subject
Has Abstractpub_date
2009-12-15 00:00:00pages
1255-63issue
7eissn
1545-5009issn
1545-5017journal_volume
53pub_type
杂志文章abstract:BACKGROUND:Wilms tumor is the most common pediatric renal malignancy, but the parameters that are important to its invasion capacity are poorly understood. The aim of this study was to identify new proteins associated with the invasion capacity of Wilms tumor. PROCEDURE:Gene expression profiles for 15 primary Wilms tu...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.23003
更新日期:2011-12-01 00:00:00
abstract:OBJECTIVES:Palliative radiation therapy (pRT) is often used to improve quality of life for pediatric patients. Though palliative doses are generally lower than those for cure, pRT may still introduce undesirable effects. The decision to pursue additional therapy for a child may be challenging and depends on parents' kn...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.28003
更新日期:2020-01-01 00:00:00
abstract:PURPOSE:This pilot study was done to determine the feasibility and accuracy of University of Florida/National Cancer Institute (UF/NCI) phantoms and Monte Carlo (MC) retrospective dosimetry and had two aims: (1) to determine the anatomic accuracy of UF/NCI phantoms by comparing 3D organ doses in National Wilms Tumor St...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.27395
更新日期:2018-12-01 00:00:00
abstract:BACKGROUND:Retinoblastoma (Rb) is the most common intraocular primary malignancy in children. In industrialised countries, the cure rate is about 95%. We present the results of a prospective study on the management of Rb in the paediatric oncology unit of Gabriel Touré Teaching Hospital and African Institute of Tropica...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.27101
更新日期:2018-08-01 00:00:00
abstract::2-Chlorodeoxyadenosine (2-CdA) has been successfully used in children to treat refractory Langerhans cell histiocytosis and juvenile xanthogranuloma (JXG) as salvage therapy. Although 2-CdA is generally well-tolerated, with temporary myelosuppression as the primary dose-limiting toxicity, prolonged myelosuppressive, a...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.23087
更新日期:2012-02-01 00:00:00
abstract:BACKGROUND:Little is known about the clinical significance of coronary artery dilation (CAD) and left ventricular hypertrophy (LVH) in patients with sickle cell disease (SCD). PROCEDURE:In a retrospective cohort, we studied the prevalence of CAD and LVH in 101 children with SCD in comparison to 93 healthy African-Amer...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.25239
更新日期:2015-01-01 00:00:00
abstract::A newborn with unresectable kaposiform hemangioendothelioma associated with Kasabach Merritt phenomenon, unresponsive to vincristine and prednisone, received second-line treatment with propranolol at a dose of 2 mg/kg/day, starting at 2 months of life and continued for 13 months. There was only slight reduction in tum...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.25979
更新日期:2016-07-01 00:00:00
abstract::High-risk (HR) acute lymphoblastic leukemia (ALL) remains one of the greatest challenges in pediatric oncology. Relapsed ALL is a leading cause of death in young people, and further improvements in outcome will required the development of therapeutic approaches directed against rational therapeutic targets, as escalat...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章,评审
doi:10.1002/pbc.22996
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND:Diamond Blackfan Anemia (DBA) is a rare congenital, bone marrow failure syndrome characterized by normochromic macrocytic anemia, reticulocytopenia and absence or insufficiency of erythroid precursors in normocellular bone marrow, frequently associated with somatic malformations. Here, we present our finding...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.25183
更新日期:2014-12-01 00:00:00
abstract::To assess safety and tolerability, we administered valacyclovir, an oral anti-viral medication that inhibits erythrocyte sickling in vitro, to 14 subjects with sickle-cell anemia for 1 week at a standard dose of 1,000 mg every 8 hr. No clinically significant adverse effects occurred. In 11 subjects in steady state, th...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.22809
更新日期:2011-05-01 00:00:00
abstract:BACKGROUND:Resource-rich countries tend to have a higher incidence of childhood acute lymphoblastic leukemia (ALL), whereas lower rates are seen in more deprived countries. This study describes the incidence of childhood acute leukemia in Brazil, an upper middle-income country, based on data from 16 population-based ca...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.22736
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Children with sickle cell disease (SCD) and abnormal transcranial Doppler (TCD) ultrasonography have a high risk of stroke, but this risk is greatly reduced when chronic transfusion therapy is administered. The change in TCD velocities during chronic transfusion therapy and rate and frequency of normalizatio...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.22951
更新日期:2011-05-01 00:00:00
abstract::Anaphylactic/anaphylactoid reaction to methotrexate (MTX) is uncommon. It may occur with the first dose (non-allergic reactions) or after a previous exposure to the drug (allergic or specific reactions). Desensitization has been shown effective in children with allergic-type reactions permitting the continuation of hi...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.22616
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND:Central venous catheters (CVC) facilitate the management of patients with cancer. Optimal timing for placement of a CVC is controversial. We sought to determine whether early placement in children with acute lymphoblastic leukemia (ALL), a group at high risk for infection and thrombosis, was associated with ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.24010
更新日期:2012-04-01 00:00:00
abstract:BACKGROUND:Primary hemophagocytic lymphohistiocytosis (HLH) represents a group of inherited hyperinflammatory immunodeficiencies, including familial HLH (FHL), Griscelli syndrome type 2 (GS2), and X-linked lymphoproliferative syndrome (XLP). We previously reported an annual incidence of suspected primary HLH in Sweden ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.25308
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND:Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms have been implicated in childhood acute lymphoblastic leukemia (ALL) risk, but previously published studies were inconsistent and recent meta-analyses were not adequate. PROCEDURES:In a meta-analysis of 21 publications with 4,706 cas...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章,meta分析,评审
doi:10.1002/pbc.23137
更新日期:2012-04-01 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::Torsades de Pointes (TdP) is a life-threatening ventricular arrhythmia that can be associated with metabolic abnormalities, exposure to arrhythmogenic medications, and congenital long-QT syndrome. This report describes a patient with ALL and multiple complications of therapy who developed TdP. The patient had no evide...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.20712
更新日期:2007-12-01 00:00:00
abstract::The provision of tele-practice symptom management is often without the provision of evidence-based guidelines. Under the auspices of the Pediatric Oncology Group of Ontario, a nursing task force was established to appraise the evidence and develop guidelines. Promising new efforts to enhance symptom management through...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章,实务指引,评审
doi:10.1002/pbc.22993
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND:The prevalence of nausea and vomiting after receipt of intrathecal methotrexate (IT-MTX) in pediatric oncology patients is unknown. METHODS:Patients (4-18 years) about to receive IT-MTX were eligible to participate in this prospective, observational study. Patients received antiemetics as prescribed by thei...
journal_title:Pediatric blood & cancer
pub_type: 评论,杂志文章
doi:10.1002/pbc.26603
更新日期:2017-10-01 00:00:00
abstract::Diffuse intrinsic pontine glioma (DIPG) is characterized by a short history of brainstem symptoms and well-known magnetic resonance imaging features with a fatal outcome. However, we report three unusual cases of brainstem tumors with an initial indolent and protracted course, which subsequently developed the classica...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.28102
更新日期:2020-03-01 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: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:Thiotepa and carboplatin are known to be active in central nervous system tumors. Topotecan potentiates the anti-cancer effects of alkylators and crosses the blood-brain barrier. We present ten patients with recurrent or progressive central nervous system malignancies treated on a myeloablative regimen using...
journal_title:Pediatric blood & cancer
pub_type: 临床试验,杂志文章
doi:10.1002/pbc.22347
更新日期:2010-04-01 00:00:00
abstract:BACKGROUND:Positron emission tomography (PET) and gallium scans facilitate diagnosis and staging, evaluation of response to therapy, and monitoring for relapse in Hodgkin lymphoma (HL), but have not been compared in pediatric HL. PROCEDURE:We performed concurrent PET and gallium scans on 44 pediatric HL patients at di...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.21574
更新日期:2008-08-01 00:00:00
abstract:BACKGROUND:The Kids ITP Tools (KIT) is a disease-specific measure of health-related quality of life for children with immune thrombocytopenia (ITP). To facilitate use in international trials it has been cross-culturally adapted for France, Germany, the United Kingdom and Uruguay. This study assessed the validity and re...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.24257
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Chronic myeloid leukemia (CML) is a rare disease in children and represents approximately 2% of all childhood leukemia. This results in difficulty creating large cohorts of patients for pediatric CML research. The Glivec International Patient Assistance Program (GIPAP) is a patient-access program sponsored b...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.25120
更新日期:2014-10-01 00:00:00
abstract:BACKGROUND:Alveolar soft part sarcomas (ASPS) are generally chemo- and radio-resistant mesenchymal tumours, with no standardized treatment guidelines. We describe the clinical behaviour of paediatric ASPS and compare these features to previously reported adult series. PATIENTS AND METHODS:The clinical data of 51 child...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.24683
更新日期:2013-11-01 00:00:00
abstract:BACKGROUND:Iron overload is well documented in patients with β-thalassemia major, and patients who have undergone hematopoietic stem cell transplantation (HSCT) remain at risk as a result of pre- and immediate post-HSCT transfusions. PROCEDURE:This is a prospective, randomized, 1-year clinical trial that compares the ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章,随机对照试验
doi:10.1002/pbc.26213
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Fever and neutropenia (F&N) is a pediatric oncology emergency due to the risk of disseminated infection. Quality improvement (QI) efforts to improve time to antibiotics for F&N in the emergency department have been documented, but the issue has not been studied in the established inpatient setting. PROCEDUR...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.25712
更新日期:2016-01-01 00:00:00