Katherine E Warren

National Institutes of Health, 베서스다, Maryland, United States

Are you Katherine E Warren?

Claim your profile

Publications (69)323.41 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: NOTCH regulates stem cells during normal development and stemlike cells in cancer, but the roles of NOTCH in the lethal pediatric brain tumor diffuse intrinsic pontine glioma (DIPG) remain unknown. Because DIPGs express stem cell factors such as SOX2 and MYCN, we hypothesized that NOTCH activity would be critical for DIPG growth. We determined that primary DIPGs expressed high levels of NOTCH receptors, ligands, and downstream effectors. Treatment of the DIPG cell lines JHH-DIPG1 and SF7761 with the γ-secretase inhibitor MRK003 suppressed the level of the NOTCH effectors HES1, HES4, and HES5; inhibited DIPG growth by 75%; and caused a 3-fold induction of apoptosis. Short hairpin RNAs targeting the canonical NOTCH pathway caused similar effects. Pretreatment of DIPG cells with MRK003 suppressed clonogenic growth by more than 90% and enhanced the efficacy of radiation therapy. The high level of MYCN in DIPG led us to test sequential therapy with the bromodomain inhibitor JQ1 and MRK003, and we found that JQ1 and MRK003 inhibited DIPG growth and induced apoptosis. Together, these results suggest that dual targeting of NOTCH and MYCN in DIPG may be an effective therapeutic strategy in DIPG and that adding a γ-secretase inhibitor during radiation therapy may be efficacious initially or during reirradiation.
    06/2015; 74(8). DOI:10.1097/NEN.0000000000000216
  • [Show abstract] [Hide abstract]
    ABSTRACT: Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood cancer. We performed a chemical screen in patient-derived DIPG cultures along with RNA-seq analyses and integrated computational modeling to identify potentially effective therapeutic strategies. The multi-histone deacetylase inhibitor panobinostat demonstrated therapeutic efficacy both in vitro and in DIPG orthotopic xenograft models. Combination testing of panobinostat and the histone demethylase inhibitor GSK-J4 revealed that the two had synergistic effects. Together, these data suggest a promising therapeutic strategy for DIPG.
    Nature medicine 05/2015; 21(7). DOI:10.1038/nm.3855 · 27.36 Impact Factor

  • Neuro-Oncology 04/2015; 17(suppl 3):iii13-iii13. DOI:10.1093/neuonc/nov061.51 · 5.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Based on pre-clinical and clinical activity in adult refractory tumors, and absence of significant neuro-, nephro-, or oto-toxicity, we conducted a pediatric phase 1 trial to determine the toxicities, maximum tolerated dose (MTD), and pharmacokinetics of satraplatin, an oral platinum analogue, in children and young adults with refractory solid tumors.ProcedureSatraplatin was administered orally once daily on days 1–5 of a 28-day cycle at dose level (DL) 1 (60 mg/m2/dose), and DL2 (80 mg/m2/dose). Toxicities, responses, satraplatin pharmacokinetics, and pharmacogenomic expression of specific DNA repair genes were evaluated.ResultsNine patients received 1–15 cycles (median = 2). The MTD was exceeded at DL2 with delayed prolonged myelosuppression as dose-limiting toxicity (DLT) in 2/4 patients. At DL1, 0/5 patients had DLTs. Common non-DLTs included myelosuppression, gastrointestinal toxicities, fatigue, headache, liver enzyme elevation, and electrolyte abnormalities. No significant neuro-, nephro-, or oto-toxicity was observed. No objective responses were observed but 2 patients experienced prolonged disease stabilization (­­­6–15 cycles). Satraplatin exposure (day 1 plasma ultrafiltrate area under the curve) was similar at DL1 and DL2. A strong correlation between estimated creatinine clearance and satraplatin pharmacokinetic parameters (clearance, area under the curve, and peak concentration) was observed.Conclusions The MTD of oral satraplatin in children with solid tumors was 60 mg/m2/dose daily ×5 days every 28 days, which is lower than the adult recommended dose of 80–120 mg/m2/dose. The toxicity profile was similar to adults and delayed myelosuppression was the DLT. No significant neuro-, nephro- or oto-toxicities were observed. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 04/2015; 62(4). DOI:10.1002/pbc.25344 · 2.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Central nervous system tumors are histologically and biologically heterogeneous. Standard treatment for malignant tumors includes surgery, radiation and chemotherapy, yet surgical resection is not always an option and chemotherapeutic agents have limited benefit. Recent investigations have focused on molecularly targeted therapies aimed at critical tumorigenic pathways. Several tumor types, including high-grade gliomas and pediatric pontine gliomas, exhibit Akt activation. Perifosine, an orally bioavailable, synthetic alkylphospholipid and potent Akt inhibitor, has demonstrated activity in some preclinical models, but absent activity in a genetically engineered mouse model of pontine glioma. We evaluated the plasma and cerebrospinal fluid pharmacokinetics of orally administered perifosine in a non-human primate model to evaluate CNS penetration. Perifosine was administered orally to three adult rhesus monkeys as a single dose of 7.0 mg/kg perifosine. Serial paired plasma and CSF samples were collected for up to 64 days. Perifosine was quantified with a validated HPLC/tandem mass spectrometry assay. Pharmacokinetic parameters were estimated using non-compartmental methods. CSF penetration was calculated from the areas under the concentration-time curves. Peak plasma concentrations (C max) ranged from 11.7-19.3 µM, and remained >1 µM for >28 days. Time to C max (T max) was 19 h. The median (range) AUCPl was 3148 (2502-4705) µM/h, with a median (range) terminal half-life (t 1/2) of 193 (170-221) h. Plasma clearance was 494 (329-637) mL/h/kg. Peak CSF concentrations were 4.1-10.1 nM (T max 64-235 h). CSF AUCs and t 1/2 were 6358 (2266-7568) nM/h and 277 (146-350) h, respectively. Perifosine concentrations in the CSF remained over nM for >35 days. The mean CSF penetration was 0.16 %. CNS penetration of perifosine after systemic administration is poor. However, levels were measurable in both plasma and CSF for an extended time (>2 months) after a single oral dose.
    Cancer Chemotherapy and Pharmacology 03/2015; 75(5). DOI:10.1007/s00280-015-2711-1 · 2.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rapid, serial, and humane collection of cerebrospinal fluid (CSF) in nonhuman primates (NHP) is an essential element of numerous research studies and is currently accomplished via two different models. The CSF reservoir model (FR) combines a catheter in the 4th ventricle with a flexible silastic reservoir to permit circulating CSF flow. The CSF lateral port model (LP) consists of a lateral ventricular catheter and an IV port that provides static access to CSF and volume restrictions on sample collection. The FR model is associated with an intensive, prolonged recovery and frequent postsurgical hydrocephalus and nonpatency, whereas the LP model is associated with an easier recovery. To maximize the advantages of both systems, we developed the CSF lateral reservoir model (LR), which combines the beneficial features of the 2 previous models but avoids their limitations by using a reservoir for circulating CSF flow combined with catheter placement in the lateral ventricle. Nine adult male rhesus monkeys were utilized in this study. Pre-surgical MRI was performed to determine the coordinates of the lateral ventricle and location of choroid plexus (CP). The coordinates were determined to avoid the CP and major blood vessels. The predetermined coordinates were 100% accurate, according to MRI validation. The LR system functioned successfully in 67% of cases for 221 d, and 44% remain functional at 426 to 510 d postoperatively. Compared with established models, our LR model markedly reduced postoperative complications and recovery time. Development of the LR model was successful in rhesus macaques and is a useful alternative to the FR and LP methods of CSF collection from nonhuman primates.
    Comparative medicine 02/2015; 65(1). · 0.74 Impact Factor

  • Cancer Research 10/2014; 74(19 Supplement):384-384. DOI:10.1158/1538-7445.AM2014-384 · 9.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: To evaluate tumor structure in children with diffuse intrinsic pontine glioma (DIPG) using histogram analyses of mean diffusivity (MD), determine potential treatment and corticosteroid-related effects on MD, and monitor changes in MD distributions over time. Materials and methods: DTI was performed on a 1.5T GE scanner. Regions of interest included the entire FLAIR-defined tumor. MD data were used to calculate histograms. Patterns in MD distributions were evaluated and fitted using a two-normal mixture model. Treatment-related effects were evaluated using the R (2) statistic for linear mixed models and Cox proportional hazards models. Results: 12 patients with DIPG underwent one or more DTI exams. MD histogram distributions varied among patients. Over time, histogram peaks became shorter and broader (P = 0.0443). Two-normal mixture fitting revealed large lower curve proportions that were not associated with treatment response or outcome. Corticosteroid use affected MD histograms and was strongly associated with larger, sharper peaks (R(2) = 0.51, P = 0.0028). Conclusions: MD histograms of pediatric DIPG show significant interpatient and intratumoral differences and quantifiable changes in tumor structure over time. Corticosteroids greatly affected MD and must be considered a confounding factor when interpreting MD results in the context of treatment response.
    BioMed Research International 06/2014; 2014(1):647356. DOI:10.1155/2014/647356 · 2.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: A phase I trial of veliparib (ABT-888), an oral poly(ADP-ribose) polymerase (PARP) inhibitor, and temozolomide (TMZ) was conducted in children with recurrent brain tumors to (i) estimate the maximum tolerated doses (MTDs) or recommended phase II doses (RP2Ds) of veliparib and TMZ; (ii) describe the toxicities of this regimen; and (iii) evaluate the plasma pharmacokinetic parameters and extent of PARP inhibition in peripheral blood mononuclear cells (PBMCs) following veliparib. Methods: TMZ was given once daily and veliparib twice daily for 5 days every 28 days. Veliparib concentrations and poly(ADP-ribose) (PAR) levels in PBMCs were measured on days 1 and 4. Analysis of pharmacokinetic and PBMC PAR levels were performed twice during study conduct to rationally guide dose modifications and to determine biologically optimal MTD/RP2D. Results: Twenty-nine evaluable patients were enrolled. Myelosuppression (grade 4 neutropenia and thrombocytopenia) were dose limiting. The RP2Ds are veliparib 25 mg/m(2) b.i.d. and TMZ 135 mg/m(2)/d. Only 2 out of 12 patients treated at RP2Ds experienced dose-limiting toxicities. Although no objective response was observed, 4 patients had stable disease >6 months in duration, including 1 with glioblastoma multiforme and 1 with ependymoma. At the RP2D of veliparib, pediatric pharmacokinetic parameters were similar to those in adults. Conclusions: Veliparib and TMZ at the RP2D were well tolerated in children with recurrent brain tumors. A phase I/II trial to evaluate the tolerability and efficacy of veliparib, TMZ, and radiation in children with newly diagnosed brainstem gliomas is in progress.
    Neuro-Oncology 06/2014; 16(12). DOI:10.1093/neuonc/nou103 · 5.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diffuse intrinsic pontine glioma (DIPG) is a malignant pediatric brain tumor associated with dismal outcome. Recent high-throughput molecular studies have shown a high frequency of mutations in histone-encoding genes (H3F3A and HIST1B) and distinctive epigenetic alterations in these tumors. Epigenetic alterations described in DIPG include global DNA hypomethylation. In addition to the generally repressive methylcytosine DNA alteration, 5-hydroxymethylation of cytosine (5hmC) is recognized as an epigenetic mark associated with active chromatin. We hypothesized that in addition to alterations in DNA methylation, that there would be changes in 5hmC. To test this hypothesis, we performed immunohistochemical studies to compare epigenetic alterations in DIPG to extrapontine adult and pediatric glioblastoma (GBM) and normal brain. A total of 124 tumors were scored for histone 3 lysine 27 trimethylation (H3K27me3) and histone 3 lysine 9 trimethylation (H3K9me3) and 104 for 5hmC and 5-methylcytosine (5mC). An H-score was derived by multiplying intensity (0–2) by percentage of positive tumor nuclei (0-100%). We identified decreased H3K27me3 in the DIPG cohort compared to pediatric GBM (p < 0.01), adult GBM (p < 0.0001) and normal brain (p < 0.0001). H3K9me3 was not significantly different between tumor types. Global DNA methylation as measured by 5mC levels were significantly lower in DIPG compared to pediatric GBM (p < 0.001), adult GBM (p < 0.01), and normal brain (p < 0.01). Conversely, 5hmC levels were significantly higher in DIPG compared to pediatric GBM (p < 0.0001) and adult GBM (p < 0.0001). Additionally, in an independent set of DIPG tumor samples, TET1 and TET3 mRNAs were found to be overexpressed relative to matched normal brain. Our findings extend the immunohistochemical study of epigenetic alterations in archival tissue to DIPG specimens. Low H3K27me3, decreased 5mC and increased 5hmC are characteristic of DIPG in comparison with extrapontine GBM. In DIPG, the relative imbalance of 5mC compared to 5hmC may represent an opportunity for therapeutic intervention.
    06/2014; 2(1):59. DOI:10.1186/2051-5960-2-59
  • Prashant Chittiboina · John D Heiss · Katherine E Warren · Russell R Lonser ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Object: Coinfused surrogate imaging tracers can provide direct insight into the properties of convection-enhanced delivery (CED) in the nervous system. To better understand the distributive properties of CED in a clinical circumstance, the authors analyzed the imaging findings in pediatric diffuse intrinsic pontine glioma (DIPG) patients undergoing coinfusion of Gd-DTPA and interleukin-13-Pseudomonas exotoxin (IL13-PE). Methods: Consecutive patients undergoing CED (maximal rates of 5 or 10 μl/minute) of Gd-DTPA (1 or 5 mM) and IL13-PE (0.125 μg/ml or 0.25 μg/ml) for DIPG were included. Real-time MRI was performed during infusions, and imaging results were analyzed. Results: Four patients (2 males, 2 females; mean age at initial infusion 13.0 ± 5.3 years; range 5-17 years) underwent 5 infusions into DIPGs. Brainstem infusions were clearly identified on T1-weighted MR images at 1-mM (1 infusion) and 5-mM (4 infusions) coinfused Gd-DTPA concentrations. While the volume of distribution (Vd) increased progressively with volume of infusion (Vi) (mean volume 2.5 ± 0.9 ml; range 1.1-3.7 ml), final Vd:Vi ratios were significantly reduced with lower Gd-DTPA concentration (Vd:Vi for 1 mM of 1.6 compared with a mean Vd:Vi ratio for 5 mM of 3.3 ± 1.0) (p = 0.04). Similarly, anatomical distribution patterns were affected by preferential flow along parallel axial fiber tracts, into prior infusion cannula tracts and intraparenchymal air pockets, and leak back around the infusion cannula at the highest rate of infusion. Conclusions: Magnetic resonance imaging of a coinfused Gd-DTPA surrogate tracer provided direct insight into the properties of CED in a clinical application. While clinically relevant Vds can be achieved by convective delivery, specific tissue properties can affect distribution volume and pattern, including Gd-DTPA concentration, preferential flow patterns, and infusion rate. Understanding of these properties of CED can enhance its clinical application. Part of clinical trial no. NCT00880061 ( ClinicalTrials.gov ).
    Journal of Neurosurgery Pediatrics 01/2014; 13(3). DOI:10.3171/2013.11.PEDS136 · 1.48 Impact Factor

  • [Show abstract] [Hide abstract]
    ABSTRACT: Research has suggested that autopsy in pediatrics is a valued way for parents to better understand and process their child's death, yet physicians often express hesitancy in discussing this topic with parents. To better assist clinicians with initiating discussion about this often sensitive topic, the current study examined bereaved parents' preferences about the timing and content of the autopsy discussion as well as reasons for considering autopsy. This study explored the views of 30 parents who lost a child to a variety of malignancies between 6 months and 6 years ago. Results showed that 36.7% of parents recalled having a discussion about autopsy, and the vast majority of those who did not recall a discussion (89.5%) would have considered an autopsy if it had been discussed. The majority of participants in this study indicated their preference to have the first conversation about autopsy when it becomes clear that cure is no longer possible. Findings suggest that educating parents about the clinical, emotional, and potential research benefits of autopsy and tissue procurement will ultimately help them make informed decisions and understand the importance of autopsy in medical progress. The future research and clinical implications of these findings are discussed.
    Journal of Pediatric Hematology/Oncology 12/2013; 36(6). DOI:10.1097/MPH.0000000000000078 · 0.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The incidence and spectrum of acute toxicities related to the use of bevacizumab (BVZ)-containing regimens in children are largely unknown. This report describes the adverse events in a recently completed large phase 2 trial of BVZ plus irinotecan (CPT-11) in children with recurrent central nervous system tumors. Pediatric Brain Tumor Consortium trial-022 evaluated the efficacy and toxicity of BVZ (10 mg/kg administered intravenously) as a single agent for 2 doses given 2 weeks apart and then combined with CPT-11 every 2 weeks (1 course = 4 weeks) in children with recurrent central nervous system tumors. Children were treated until they experienced progressive disease, unacceptable toxicity or completed up to a maximum of 2 years of therapy. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Patients who received at least 1 dose of BVZ were included for toxicity assessment. Between October 2006 and June 2010, 92 patients evaluable for toxicity were enrolled and received 687 treatment courses. The most common toxicities attributable to BVZ included grade I-III hypertension (38% of patients), grade I-III fatigue (30%), grade I-II epistaxis (24%), and grade I-IV proteinuria (22%). Twenty-two patients (24%) stopped therapy due to toxicity. The combination of BVZ and CPT-11 was fairly well-tolerated, and most severe BVZ-related toxicities were rare, self-limiting, and manageable. Cancer 2013;. © 2013 American Cancer Society.
    Cancer 12/2013; 119(23). DOI:10.1002/cncr.28343 · 4.89 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pediatric diffuse intrinsic pontine gliomas are aggressive brainstem tumors that fail to respond to treatment. We hypothesize that the protective features of the pons may hinder chemotherapeutic agents from entering pontine tissue compared with cortical brain tissue. To test this hypothesis, we developed a unique nonhuman primate model using microdialysis, a continuous in vivo extracellular sampling technique, to compare drug exposure concurrently in pontine tissue, cortical tissue, CSF, and plasma after intravenous administration of chemotherapeutic agents. The surgical coordinates and approach for microdialysis cannula-probe placement were determined in 5 adult male rhesus monkeys (Macaca mulatta) by using MRI. Microdialysis cannulas-probes were implanted stereotactically in the brain, retrodialysis was performed to measure relative recovery, and a 1-h intravenous infusion of temozolomide was administered. Continuous microdialysis samples were collected from the pons and cortex over 4 h with concurrent serial plasma and CSF samples. Postsurgical verification of microdialysis cannula-probe placement was obtained via MRI in 3 macaques and by gross pathology in all 5 animals. The MRI-determined coordinates and surgical methodologies resulted in accurate microdialysis probe placement in the pons and cortex in 4 of the 5 macaques. Histologic examination from these 4 animals revealed negligible tissue damage to the pontine and cortical tissue from microdialysis. One macaque was maintained for 8 wk and had no deficits attributed to the procedure. This animal model allows for the determination of differences in CNS penetration of chemotherapeutic agents in the pons, cortex, and CSF after systemic drug administration.
    Comparative medicine 11/2013; 63(4):355-60. · 0.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Treatment of pediatric diffuse intrinsic pontine glioma (DIPG) remains challenging, and reliable biomarkers of response are lacking. Radiographic response is a primary endpoint in many investigational studies of brain tumors, but there is no standard method of tumor measurement for DIPG, significant inter-observer variability exists given the invasive nature of these tumors, and tumor measurements are not predictive of outcome. Because DIPGs involve a significant portion of the pons, we evaluated the reliability and prognostic value of one-dimensional (1D) and two-dimensional (2D) pons measurements using anatomical landmarks rather than tumor boundaries. Patients with DIPG (n = 75) were evaluated longitudinally at our institution using MRI. Four readers independently performed 1D and 2D measurements of the pons using FLAIR images. Agreement and inter-reader variability were evaluated using differences among the six reader pairs and the coefficient of variation (CV). Prognostic value of pons measurements was calculated using Cox proportional hazards models, where relative hazard (RH) represents risk of death. Readers evaluated 384 exams. Agreement of readers' 1D and 2D measurements was strong (median difference between reader pairs 3.1 and 5.4 %, respectively), with low inter-reader variability (median CV = 3.1 % and median CV = 4.8 %, respectively). Increases in 1D and 2D pons measurements over time indicated poorer prognosis (RH = 2.29, p = 0.0025 and RH = 1.13, p = 0.0016, respectively), with shorter overall survival. Pons measurements had low inter-reader variability compared to previously reported tumor measurement techniques and correlated with outcome in children with DIPG. Measurements of the pons (as opposed to direct measurements of tumor) are a viable in vivo biomarker for DIPG.
    Journal of Neuro-Oncology 10/2013; 116(1). DOI:10.1007/s11060-013-1266-4 · 3.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Criteria for new drug approval include demonstration of efficacy. In neuro-oncology, this is determined radiographically utilizing tumor measurements on MRI scans. Limitations of this method have been identified where drug activity is not reflected in decreased tumor size. The RANO (Response Assessment in Neuro-Oncology) working group was established to address limitations in defining endpoints for clinical trials in adult neuro-oncology and to develop standardized response criteria. RAPNO was subsequently established to address unique issues in pediatric neuro-oncology. The aim of this paper is to delineate response criteria issues in pediatric clinical trials as a basis for subsequent recommendations. Pediatr Blood Cancer 2013;9999:XX-XX. © 2013 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 09/2013; 60(9). DOI:10.1002/pbc.24562 · 2.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tumors of the central nervous system are the second most common malignancy in children. In particular, diffuse intrinsic pontine gliomas (DIPGs) are aggressive tumors with poor prognosis and account for 10% to 25% of pediatric brain tumors. The majority of DIPGs are astrocytic, infiltrative, and localized to the pons. Studies have shown median survival times of less than a year, with 90% of children dying within 2 years. We built multitissue arrays with 24 postmortem DIPG samples and analyzed the morphology and expression of several proteins (p53, EGFR, GFAP, MIB1, BMI1, β-catenin, p16, Nanog, Nestin, OCT4, OLIG2, SOX2) with the goal of identifying potential treatment targets and improving our understanding of the biology of these tumors. The majority of DIPGs were high-grade gliomas (22), with 18 cases having features of glioblastoma (World Health Organization [WHO] grade IV) and 4 cases with high-grade features consistent with anaplastic astrocytoma (WHO grade III). One case was low grade (WHO grade II), and 1 case showed intermediate features between a grade II and grade III glioma (low mitotic rate but increased cellularity and cell atypia), being difficult to grade precisely. The majority of the tumors were positive for GFAP (24/24), MIB1 (23/24), OLIG2 (22/24), p16 (20/24), p53 (20/24), SOX2 (19/24), EGFR (16/24), and BMI1 (9/24). Our results suggest that dysregulation of EGFR and p53 may play an important role in the development of DIPGs. The majority of DIPGs express stem cell markers such as SOX2 and OLIG2, consistent with a role for tumor stem cells in the origin and maintenance of these tumors. Targeted therapies against these proteins could be beneficial in treatment.
    The American journal of surgical pathology 09/2013; 37(9):1357-64. DOI:10.1097/PAS.0b013e318294e817 · 5.15 Impact Factor

  • Cancer Research 08/2013; 73(8 Supplement):3374-3374. DOI:10.1158/1538-7445.AM2013-3374 · 9.33 Impact Factor

  • Cancer Research 08/2013; 73(8 Supplement):5049-5049. DOI:10.1158/1538-7445.AM2013-5049 · 9.33 Impact Factor

Publication Stats

744 Citations
323.41 Total Impact Points


  • 2008-2015
    • National Institutes of Health
      • Branch of Pediatric Oncology
      베서스다, Maryland, United States
  • 2000-2015
    • National Cancer Institute (USA)
      • • Pediatric Oncology Branch
      • • Neuro-Oncology Branch
      베서스다, Maryland, United States
  • 2000-2014
    • NCI-Frederick
      Фредерик, Maryland, United States
  • 2008-2012
    • National Cancer Institute
      Μπογκοτά, Bogota D.C., Colombia