This page has only limited features, please log in for full access.
Purpose: 5-hydroxymethylcytosine (5-hmC) is an epigenetic marker of open chromatin and active gene expression. We profiled 5-hmC with Nano-hmC-Seal technology using 10ng of plasma derived cell-free DNA (cfDNA) in blood samples from patients with neuroblastoma to determine its utility as a biomarker. Experimental Design: For the Discovery cohort, one hundred 5-hmC profiles were generated from 34 well children and 32 patients (27 high-risk, 2 intermediate-risk, and 3 low-risk) at various time points during the course of their disease. An independent Validation cohort encompassed 5-hmC cfDNA profiles (n = 29) generated from 21 patients (20 high-risk and 1 intermediate-risk). Metastatic burden was classified as high, moderate, low, or none per Curie Metaiodobenzylguanidine (MIBG) scores and percentage of tumor cells in bone marrow. Genes with differential 5-hmC levels between samples according to metastatic burden were identified using DESeq2. Results: Hierarchical clustering using 5-hmC levels of 347 genes identified from the Discovery cohort defined four clusters of samples that were confirmed in the Validation cohort and corresponded to high, high-moderate, moderate, and low/no metastatic burden. Samples from patients with increased metastatic burden had increased 5-hmC deposition on genes in neuronal stem cell maintenance and epigenetic regulatory pathways. Further, 5-hmC cfDNA profiles generated with 1,242 neuronal pathways genes were associated with subsequent relapse in the cluster of patients with predominantly low or no metastatic burden (sensitivity 65%, specificity 75.6%). Conclusions: cfDNA 5-hmC profiles in children with neuroblastoma correlate with metastatic burden and warrants development as a biomarker of treatment response and outcome.
Mark A Applebaum; Erin Barr; Jason Karpus; Diana West-Szymanski; Meritxell Oliva; Elizabeth A Sokol; Sheng Zhang; Zhou Zhang; Wei Zhang; Alexandre Chlenksi; Helen R. Salwen; Emma Wilkinson; Marija Dobratic; Robert L Grossman; Lucy A Godley; Barbara E Stranger; Chuan He; Susan L Cohn. 5-hydroxymethylcytosine profiles in circulating cell-free DNA associate with disease burden in children with neuroblastoma. Clinical Cancer Research 2019, 26, 1309 -1317.
AMA StyleMark A Applebaum, Erin Barr, Jason Karpus, Diana West-Szymanski, Meritxell Oliva, Elizabeth A Sokol, Sheng Zhang, Zhou Zhang, Wei Zhang, Alexandre Chlenksi, Helen R. Salwen, Emma Wilkinson, Marija Dobratic, Robert L Grossman, Lucy A Godley, Barbara E Stranger, Chuan He, Susan L Cohn. 5-hydroxymethylcytosine profiles in circulating cell-free DNA associate with disease burden in children with neuroblastoma. Clinical Cancer Research. 2019; 26 (6):1309-1317.
Chicago/Turabian StyleMark A Applebaum; Erin Barr; Jason Karpus; Diana West-Szymanski; Meritxell Oliva; Elizabeth A Sokol; Sheng Zhang; Zhou Zhang; Wei Zhang; Alexandre Chlenksi; Helen R. Salwen; Emma Wilkinson; Marija Dobratic; Robert L Grossman; Lucy A Godley; Barbara E Stranger; Chuan He; Susan L Cohn. 2019. "5-hydroxymethylcytosine profiles in circulating cell-free DNA associate with disease burden in children with neuroblastoma." Clinical Cancer Research 26, no. 6: 1309-1317.
Neuroblastoma is a tumor with great clinical heterogeneity. Patients in North America are risk-stratified using a number of features including age at diagnosis, disease stage, tumor histology, MYCN status (amplified versus nonamplified), and tumor cell ploidy. In this paper, we review the evidence for utilizing these features in the risk classification of neuroblastic tumors. Additionally, we review the clinical and biologic criteria used by various cooperative groups to define low, intermediate, and high-risk disease populations in clinical trials, highlighting the differences in risk classification internationally. Finally, we discuss the development of the International Neuroblastoma Risk Group classification system, designed to begin worldwide standardization of neuroblastoma pretreatment risk classification and allow comparison of clinical trials conducted through different cooperative groups.
Elizabeth Sokol; Ami Desai. The Evolution of Risk Classification for Neuroblastoma. Children 2019, 6, 27 .
AMA StyleElizabeth Sokol, Ami Desai. The Evolution of Risk Classification for Neuroblastoma. Children. 2019; 6 (2):27.
Chicago/Turabian StyleElizabeth Sokol; Ami Desai. 2019. "The Evolution of Risk Classification for Neuroblastoma." Children 6, no. 2: 27.
1 Background Radiolabeled metaiodobenzylguanidine (MIBG) is sensitive and specific for detecting neuroblastoma. The extent of MIBG‐avid disease is assessed using Curie scores. Although Curie scoring is prognostic in patients with high‐risk neuroblastoma, there is no standardized method to assess the response of specific sites of disease over time. The goal of this study was to develop approaches for Curie scoring to facilitate the calculation of scores and comparison of specific sites on serial scans. 2 Procedure We designed three semiautomated methods for determining Curie scores, each with increasing degrees of computer assistance. Method A was based on visual assessment and tallying of MIBG‐avid lesions. For method B, scores were tabulated from a schematic that associated anatomic regions to MIBG‐positive lesions. For method C, an anatomic mesh was used to mark MIBG‐positive lesions with automatic assignment and tallying of scores. Five imaging physicians experienced in MIBG interpretation scored 38 scans using each method, and the feasibility and utility of the methods were assessed using surveys. 3 Results There was good reliability between methods and observers. The user‐interface methods required 57 to 110 seconds longer than the visual method. Imaging physicians indicated that it was useful that methods B and C enabled tracking of lesions. Imaging physicians preferred method B to method C because of its efficiency. 4 Conclusions We demonstrate the feasibility of semiautomated approaches for Curie score calculation. Although more time was needed for strategies B and C, the ability to track and document individual MIBG‐positive lesions over time is a strength of these methods.
Elizabeth A. Sokol; Roger Engelmann; Wenjun Kang; Navin Pinto; Adam Starkey; Hollie Lai; Helen Nadel; Barry L. Shulkin; Yonglin Pu; Daniel Appelbaum; Gregory A. Yanik; Susan L. Cohn; Samuel G. Armato; Samuel Volchenboum. Computer‐assisted Curie scoring for metaiodobenzylguanidine (MIBG) scans in patients with neuroblastoma. Pediatric Blood & Cancer 2018, 65, e27417 .
AMA StyleElizabeth A. Sokol, Roger Engelmann, Wenjun Kang, Navin Pinto, Adam Starkey, Hollie Lai, Helen Nadel, Barry L. Shulkin, Yonglin Pu, Daniel Appelbaum, Gregory A. Yanik, Susan L. Cohn, Samuel G. Armato, Samuel Volchenboum. Computer‐assisted Curie scoring for metaiodobenzylguanidine (MIBG) scans in patients with neuroblastoma. Pediatric Blood & Cancer. 2018; 65 (12):e27417.
Chicago/Turabian StyleElizabeth A. Sokol; Roger Engelmann; Wenjun Kang; Navin Pinto; Adam Starkey; Hollie Lai; Helen Nadel; Barry L. Shulkin; Yonglin Pu; Daniel Appelbaum; Gregory A. Yanik; Susan L. Cohn; Samuel G. Armato; Samuel Volchenboum. 2018. "Computer‐assisted Curie scoring for metaiodobenzylguanidine (MIBG) scans in patients with neuroblastoma." Pediatric Blood & Cancer 65, no. 12: e27417.
Survival in pediatric cancer has overall increased significantly over the last several decades. However outcomes for patients with a subset of aggressive pediatric malignancies as well as those with relapsed and refractory cancer remain very poor. New targeted therapies are needed for these diseases. There are fewer mutations found in pediatric cancers than in most adult cancers, and more often, there is a single genetic driver caused by either a translocation or loss of heterozygosity. Here we present an overview of a variety of targeted therapies in various stages of development in pediatrics. Targeting metabolic differences and aberrant signaling is frequently used in standard therapy. Increasingly, targeting cancer cell surface-associated proteins is being utilized as well. Cancer immunotherapy is a rapidly evolving field that utilizes the patient’s immune system in various ways to recognize and attack cancer cells. This includes antibody-dependent cell-mediated cytotoxicity, checkpoint inhibition, chimeric antigen receptor T cells, bispecific T-cell engagers, and other more experimental therapies. Additionally, we discuss several other modalities with unique mechanisms of targeting cancer cells. There is a large amount of work being done to expand the use of targeted therapies in pediatrics. These studies require collaboration between investigators and institutions to broaden the availability of targeted therapies in the future.
Elizabeth A. Sokol; Navin R. Pinto. Molecular Targeted Therapy of Pediatric Neoplasms. Molecular Pathology Library 2018, 67 -86.
AMA StyleElizabeth A. Sokol, Navin R. Pinto. Molecular Targeted Therapy of Pediatric Neoplasms. Molecular Pathology Library. 2018; ():67-86.
Chicago/Turabian StyleElizabeth A. Sokol; Navin R. Pinto. 2018. "Molecular Targeted Therapy of Pediatric Neoplasms." Molecular Pathology Library , no. : 67-86.
Elizabeth Sokol; Eryong Huang; Peter Pytel; Susan L Cohn; Navin Pinto. Rebound thymic hyperplasia following high dose chemotherapy and stem cell transplant in three neuroblastoma patients. Pediatric Blood & Cancer 2016, 64, e26226 .
AMA StyleElizabeth Sokol, Eryong Huang, Peter Pytel, Susan L Cohn, Navin Pinto. Rebound thymic hyperplasia following high dose chemotherapy and stem cell transplant in three neuroblastoma patients. Pediatric Blood & Cancer. 2016; 64 (3):e26226.
Chicago/Turabian StyleElizabeth Sokol; Eryong Huang; Peter Pytel; Susan L Cohn; Navin Pinto. 2016. "Rebound thymic hyperplasia following high dose chemotherapy and stem cell transplant in three neuroblastoma patients." Pediatric Blood & Cancer 64, no. 3: e26226.
BackgroundThe Infectious Diseases Society of America (IDSA) guidelines recommend collecting blood cultures for the first 3 days of febrile neutropenia (FN) in the clinically stable oncology patient with persistent fevers. Nonetheless, many physicians send daily blood cultures beyond 3 days, and the impact of that practice is uncertain.ProcedureWe reviewed pediatric FN episodes from July 2009 to May 2014 at University of Chicago Comer Children's Hospital. For each positive culture, we determined if it was a pathogen or a contaminant. We reviewed episode and patient demographics to identify risk factors for subsequent positive blood cultures in the setting of an initially negative culture.ResultsWe identified 381 episodes of FN in 162 patients. Of those, 87 had a positive blood culture on day 1 (21.0% incidence of bacteremia). Of 294 episodes with a negative blood culture on day 1, six (2.04%, 95% confidence interval [CI] 0.42–3.67) had a positive culture after day 3. Of those, three were pathogens (1.02%, 95%CI –0.14 to 2.18), and only one was found in a hemodynamically stable patient (0.34%, 95%CI –0.33 to 1.01) with new mucositis. In the other two patients, Escherichia coli was isolated from blood cultures after day 10 in the setting of significant hemodynamic changes. Risk factor analysis performed in stable patients yielded nonsignificant results.ConclusionsOf 294 FN episodes with an initial negative blood culture, only one episode of bacteremia occurred without hemodynamic changes past day 3, supporting the IDSA guidelines to discontinue blood cultures in stable FN patients after day 3.
Lindsay A. Petty; Elizabeth A. Sokol; Allison H. Bartlett; Jennifer L. McNeer; Kenneth A. Alexander; Jennifer Pisano. Repeated Blood Cultures in Pediatric Febrile Neutropenia: Would Following the Guidelines Alter the Outcome? Pediatric Blood & Cancer 2016, 63, 1244 -1249.
AMA StyleLindsay A. Petty, Elizabeth A. Sokol, Allison H. Bartlett, Jennifer L. McNeer, Kenneth A. Alexander, Jennifer Pisano. Repeated Blood Cultures in Pediatric Febrile Neutropenia: Would Following the Guidelines Alter the Outcome? Pediatric Blood & Cancer. 2016; 63 (7):1244-1249.
Chicago/Turabian StyleLindsay A. Petty; Elizabeth A. Sokol; Allison H. Bartlett; Jennifer L. McNeer; Kenneth A. Alexander; Jennifer Pisano. 2016. "Repeated Blood Cultures in Pediatric Febrile Neutropenia: Would Following the Guidelines Alter the Outcome?" Pediatric Blood & Cancer 63, no. 7: 1244-1249.
The electronic medical records at 2 children’s hospitals were reviewed from June 1, 2011 to May 31, 2013 for all patients with sickle cell disease who presented with fever. Of a total of 390 blood cultures drawn, 11 cultures (2.8%) turned positive with only 1 (0.3%) growing a true pathogen. This culture turned positive in 13 hours. There were 154 patients who received exclusive outpatient management of fever. Fourteen patients (9.1%) completed 1 acute care visit, 16 patients (10.4%) completed 2 acute care visits, and 124 patients (80.5%) completed 3 acute care visits. Of those treated exclusively as outpatients, there was 1 positive culture that was considered a contaminant. Although the overall rate of positivity was low, this study confirms previous findings that pediatric blood cultures become positive with pathogens within 48 hours. Given the high rate of compliance and early time to positivity of true pathogens, we suggest that follow-up for the febrile sickle cell disease patients can be treated on an outpatient basis.
Elizabeth Sokol; Emily Obringer; Brett Palama; Joseph Hageman; Radhika Peddinti. Outpatient Management of Febrile Children With Sickle Cell Disease. Clinical Pediatrics 2015, 55, 268 -271.
AMA StyleElizabeth Sokol, Emily Obringer, Brett Palama, Joseph Hageman, Radhika Peddinti. Outpatient Management of Febrile Children With Sickle Cell Disease. Clinical Pediatrics. 2015; 55 (3):268-271.
Chicago/Turabian StyleElizabeth Sokol; Emily Obringer; Brett Palama; Joseph Hageman; Radhika Peddinti. 2015. "Outpatient Management of Febrile Children With Sickle Cell Disease." Clinical Pediatrics 55, no. 3: 268-271.
CME CME Elizabeth Sokol, MD; Radhika Peddinti, MD Abnormal vaginal bleeding in a postmenarchal adolescent patient is most often related to dysfunctional uterine bleeding. However, there are other potential etiologies, including hematologic disorders, infections, and oncologic problems. We present a 12-year-old girl who presented with prolonged vaginal bleeding and was ultimately diagnosed with rhabdomyosarcoma. In this article, we discuss the approach to a patient with vaginal bleeding along with a more in-depth review of risk stratification in rhabdomyosarcoma, including treatment options such as chemotherapy, surgery, and radiation therapy. [Pediatr Ann.2015;44(7):e164–e167.] Elizabeth Sokol, MD, is a Fellow, Section of Pediatric Hematology/Oncology/Stem Cell Transplant, Comer Children’s Hospital, Pritzker School of Medicine, University of Chicago. Radhika Peddinti, MD, is an Attending Physician, Section of Pediatric Hematology/Oncology/Stem Cell Transplant, Comer Children’s Hospital; and an Assistant Professor of Pediatrics, Pritzker School of Medicine, University of Chicago. Address correspondence to Elizabeth Sokol, MD, University of Chicago Medical Center, 5841 S. Maryland Avenue, MC 4060, Chicago, IL 60637; email: [email protected] Disclosure: The authors have no relevant financial relationships to disclose. 10.3928/00904481-20150710-09 Abnormal vaginal bleeding in a postmenarchal adolescent patient is most often related to dysfunctional uterine bleeding. However, there are other potential etiologies, including hematologic disorders, infections, and oncologic problems. We present a 12-year-old girl who presented with prolonged vaginal bleeding and was ultimately diagnosed with rhabdomyosarcoma. In this article, we discuss the approach to a patient with vaginal bleeding along with a more in-depth review of risk stratification in rhabdomyosarcoma, including treatment options such as chemotherapy, surgery, and radiation therapy. [Pediatr Ann.2015;44(7):e164–e167.] Elizabeth Sokol, MD, is a Fellow, Section of Pediatric Hematology/Oncology/Stem Cell Transplant, Comer Children’s Hospital, Pritzker School of Medicine, University of Chicago. Radhika Peddinti, MD, is an Attending Physician, Section of Pediatric Hematology/Oncology/Stem Cell Transplant, Comer Children’s Hospital; and an Assistant Professor of Pediatrics, Pritzker School of Medicine, University of Chicago. Address correspondence to Elizabeth Sokol, MD, University of Chicago Medical Center, 5841 S. Maryland Avenue, MC 4060, Chicago, IL 60637; email: [email protected] Disclosure: The authors have no relevant financial relationships to disclose.
Elizabeth Sokol; Radhika Peddinti. Causes and Diagnosis of Abnormal Vaginal Bleeding. Pediatric Annals 2015, 44, e164 -e167.
AMA StyleElizabeth Sokol, Radhika Peddinti. Causes and Diagnosis of Abnormal Vaginal Bleeding. Pediatric Annals. 2015; 44 (7):e164-e167.
Chicago/Turabian StyleElizabeth Sokol; Radhika Peddinti. 2015. "Causes and Diagnosis of Abnormal Vaginal Bleeding." Pediatric Annals 44, no. 7: e164-e167.
Outcome for the vast majority of high‐risk neuroblastoma patients with refractory or relapsed disease is dismal. We report two high‐risk patients who remain progression‐free for more than 113 and 18 months following the diagnosis of refractory/relapsed disease who were treated with surgery alone. Complete resolution of a refractory thoracic mass and relapsed liver nodules was observed in one patient. The refractory/relapsed disease in the second patient has remained stable. In both cases, the tumor showed histologic evidence of neuroblastoma maturation. These cases demonstrate that refractory/relapsed neuroblastoma is clinically heterogeneous and highlight the need for better biomarkers to optimize patient care. Pediatr Blood Cancer 2013; 60: 512–514.
Elizabeth Sokol; Paul R. Haut; Yasmin Gosiengfiao; Kate Feinstein; Peter Pytel; Susan L. Cohn. Progression-free survival of two cases of high-risk neuroblastoma with refractory/relapsed disease following surgery alone. Pediatric Blood & Cancer 2012, 60, 512 -514.
AMA StyleElizabeth Sokol, Paul R. Haut, Yasmin Gosiengfiao, Kate Feinstein, Peter Pytel, Susan L. Cohn. Progression-free survival of two cases of high-risk neuroblastoma with refractory/relapsed disease following surgery alone. Pediatric Blood & Cancer. 2012; 60 (3):512-514.
Chicago/Turabian StyleElizabeth Sokol; Paul R. Haut; Yasmin Gosiengfiao; Kate Feinstein; Peter Pytel; Susan L. Cohn. 2012. "Progression-free survival of two cases of high-risk neuroblastoma with refractory/relapsed disease following surgery alone." Pediatric Blood & Cancer 60, no. 3: 512-514.
The adsorption of three- and four-atom Ag and Pd clusters on the alpha-Al(2)O(3) (0001) surface is explored with density functional theory. Within each adsorbed cluster, two different cluster-surface interactions are present. We find that clusters simultaneously form both ionic bonds with surface oxygen and intermetallic bonds with surface aluminum. The simultaneous formation of disparate electronic structure motifs within a single metal nanoparticle is termed a "dipolar nanocluster". This coexistence is ascribed to a balance of geometric constraints and metal electronic structure, and its importance for nanoparticle catalysis is highlighted.
Sara E. Mason; Elizabeth Sokol; Valentino Cooper; Andrew M. Rappe. Spontaneous Formation of Dipolar Metal Nanoclusters. The Journal of Physical Chemistry A 2009, 113, 4134 -4137.
AMA StyleSara E. Mason, Elizabeth Sokol, Valentino Cooper, Andrew M. Rappe. Spontaneous Formation of Dipolar Metal Nanoclusters. The Journal of Physical Chemistry A. 2009; 113 (16):4134-4137.
Chicago/Turabian StyleSara E. Mason; Elizabeth Sokol; Valentino Cooper; Andrew M. Rappe. 2009. "Spontaneous Formation of Dipolar Metal Nanoclusters." The Journal of Physical Chemistry A 113, no. 16: 4134-4137.
The adsorption of Ag$_3$ and Ag$_4$ clusters on the $\alpha$-Al$_2$O$_3$(0001) surface is explored with density functional theory. Within each adsorbed cluster, two different cluster-surface interactions are present. We find that silver clusters simultaneously form both ionic bonds with surface oxygen and intermetallic bonds with surface aluminum. The simultaneous formation of disparate electronic structure motifs within a single metal nanoparticle is termed a "dipolar nanocluster". This coexistence is ascribed to the similar bond enthalpies of Ag--Al and Ag--O bonds, and its importance for nanoparticle catalysis is highlighted.
Elizabeth A. Sokol; Sara E. Mason; Valentino R. Cooper; Andrew M. Rappe. Spontaneous Formation of Dipolar Metal Nanoclusters. 2006, 1 .
AMA StyleElizabeth A. Sokol, Sara E. Mason, Valentino R. Cooper, Andrew M. Rappe. Spontaneous Formation of Dipolar Metal Nanoclusters. . 2006; ():1.
Chicago/Turabian StyleElizabeth A. Sokol; Sara E. Mason; Valentino R. Cooper; Andrew M. Rappe. 2006. "Spontaneous Formation of Dipolar Metal Nanoclusters." , no. : 1.