De Kock L.,Jewish General Hospital |
Sabbaghian N.,Jewish General Hospital |
Soglio D.B.-D.,University of Montréal |
Guillerman R.P.,Baylor College of Medicine |
And 5 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014
Context: Carriers of germline DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 syndrome. Thyroid abnormalities are a common finding in DICER1 syndrome with multinodular goiter frequently present in many families in which a germline DICER1 mutation is segregating. Differentiated thyroid carcinoma (DTC) is infrequently seen in such pedigrees. In addition to germline DICER1 mutations, specific somatic mutations have been identified in the DICER1 ribonuclease IIIb catalytic domain in several tumor types. Objective: We aimed to determine whether such characteristic somatic DICER1 mutations are present in DTCs that arise within germline DICER1 mutation carriers. Design and Setting: The study involved an opportunistic collection of 3 cases of DTC arising in individuals suspected to have DICER1 syndrome and hospital-based ascertainment and testing was implemented. Results: We identified somatic DICER1 mutations in 3 DTCs arising in unrelated germline DICER1 mutation carriers, all of whom had been diagnosed in infancy with pleuropulmonary blastoma (PPB), were treated with chemotherapy, exposed frequently to diagnostic radiation, and subsequently developed DTC. The somatic mutations occurred within the DICER1 ribonuclease IIIb domain, affecting highly conserved amino acid residues central to the catalytic activity of the domain. Conclusion: This report of somatic DICER1 mutations in DTC strengthens the association between DTC and the DICER1 syndrome. The possible association between germline DICER1 mutations, PPB treatment, and the risk of subsequent DTC must be considered by clinicians when treating PPB. © 2014 by the Endocrine Society.
Park E.S.,Gyeongsang National University |
Sung K.W.,Sungkyunkwan University |
Baek H.J.,Chonnam National University |
Park K.D.,Seoul National University |
And 4 more authors.
Journal of Korean Medical Science | Year: 2012
The feasibility and effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) were evaluated in children younger than 3 yr of age with atypical teratoid/rhabdoid tumors (ATRT). Tandem HDCT/autoSCT was administered following six cycles of induction chemotherapy. Radiotherapy (RT) was administered if the tumor relapsed or progressed, otherwise, it was administered after 3 yr of age. Tumors relapsed or progressed during induction chemotherapy in 5 of 9 patients enrolled; 3 of these 5 received tandem HDCT/autoSCT as a salvage treatment. One patient died from sepsis during induction chemotherapy. The remaining 3 patients proceeded to tandem HDCT/autoSCT; however, 2 of these patients showed tumor relapse/progression after tandem HDCT/autoSCT. All 7 relapses/progressions occurred at primary sites even in patients with leptomeningeal seeding. Toxicities during tandem HDCT/autoSCT were manageable. A total of 5 patients were alive with a median follow-up of 20 (range 16-70) months from diagnosis. Four of 5 patients who received RT after relapse/progression are alive. The probability of overall survival at 3 yr from diagnosis was 53.3% ± 17.3%. Our tandem HDCT/autoSCT is feasible; however, early administration of RT prior to tandem HDCT/autoSCT should be considered to improve the outcome after tandem HDCT/autoSCT. © 2012 The Korean Academy of Medical Sciences.
PubMed | Center for Pediatric Oncology, Korea University, University of Ulsan, Korea Cancer Center Hospital and 7 more.
Type: Journal Article | Journal: Journal of Korean medical science | Year: 2016
This retrospective study investigated the clinical characteristics and outcomes of second malignant neoplasms (SMNs) in survivors of childhood cancer from multiple institutions in Korea. A total of 102 patients from 11 institutions who developed SMN after childhood cancer treatment between 1998 and 2011 were retrospectively enrolled. The most common primary malignant neoplasms (PMNs) were central nervous system (CNS) tumors (n = 17), followed by acute lymphoblastic leukemia (n = 16), non-Hodgkin lymphoma (n = 13), and osteosarcoma (n = 12). The most common SMNs were therapy-related myeloid neoplasms (t-MNs; acute myeloid leukemia [AML], 29 cases; myelodysplastic syndrome [MDS], 12 cases), followed by thyroid carcinomas (n = 15) and CNS tumors (n = 10). The median latency period was 4.9 years (range, 0.5-18.5 years). Among 45 patients with solid tumors defined as an SMN, 15 (33%) developed the lesion in a field previously subjected to radiation. The 5-year overall survival (OS) rate of patients with an SMN was 45% with a median follow-up time of 8.6 years. Patients with AML, MDS, and CNS tumors exhibited the poorest outcomes with 5-year OS rates of 18%, 33%, and 32%, respectively, whereas those with second osteosarcoma showed comparable outcomes (64%) to patients with primary counterpart and those with second thyroid carcinoma had a 100% OS rate. Further therapeutic efforts are recommended to improve the survival outcomes in patients with SMNs, especially in cases with t-MNs and CNS tumors.
News Article | December 20, 2016
In the third week of PLOS Medicine's ongoing special issue on cancer genomics, principal investigator Jules Meijerink of the Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands and colleagues seek to identify mechanisms underlying treatment resistance in children with T-cell acute lymphoblastic leukemia (T-ALL) by combining genomic DNA sequencing and chromosomal copy-number analyses, and suggest a new approach to therapy. Treatment of childhood leukemia has improved markedly in recent decades, with long-term cure achieved in most patients who have access to modern, highly intensive treatment regimens. However, some patients develop resistance to the steroid drugs which are a key part of combination chemotherapy treatments, which results in poor clinical outcomes. As described in their Research Article, Meijerink and colleagues studied genetic changes in leukemic cells from pediatric T-ALL patients before treatment. The researchers found specific gene mutations affecting signaling inside cells, involving the interleukin 7 receptor and downstream molecules, that were associated with steroid resistance and adverse clinical outcome. Drugs designed to target individual signaling proteins were able to restore steroid sensitivity to primary leukemic cells from patients. Discussing the research in an accompanying Perspective article, Steven Goossens and Pieter Van Vlierberghe conclude that "inhibition of MEK-ERK or PI3K/AKT/mTOR signaling could enhance steroid sensitivity in T-ALL and potentially improve patient outcomes, a notion that warrants investigation in future prospective clinical trials." Funding: YL was funded by Stichting Kinderen Kankervrij (https:/ ; KiKa-2010-082). KC-B and WKS were funded by Stichting Kinderen Kankervrij (https:/ ; KiKa-2008-029, KiKa-2013-116). EMV was funded by KWF Kanker Bestrijding (https:/ ; EMCR-KWF-2010-4691). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: RCB and GJRZ are founders and shareholders of Netherlands Translational Research Center B.V. The other authors have declared that no competing interests exist. Citation: Li Y, Buijs-Gladdines JGCAM, Canté-Barrett K, Stubbs AP, Vroegindeweij EM, Smits WK, et al. (2016) IL-7 Receptor Mutations and Steroid Resistance in Pediatric T cell Acute Lymphoblastic Leukemia: A Genome Sequencing Study. PLoS Med 13(12): e1002200. doi:10.1371/journal.pmed.1002200 Author Affiliations: Department of Pediatric Oncology/Hematology, Erasmus Medical Center/Sophia Children's Hospital, Rotterdam, The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands Department of Bioinformatics, Erasmus Medical Center, Rotterdam, The Netherlands Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands Research Institute Children's Cancer Center Hamburg, Hamburg, Germany Clinic of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Co-operative Study Group for Childhood Acute Lymphoblastic Leukemia, Hamburg, Germany Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands Netherlands Translational Research Center, Oss, The Netherlands IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER: http://journals. Funding: The authors received no funding for this work. Competing Interests: The authors have declared that no competing interests exist. IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER: http://journals.
Kim S.J.,Center for Pediatric Oncology |
Sohn Y.B.,Sungkyunkwan University |
Park S.W.,Sungkyunkwan University |
Jin D.-K.,Sungkyunkwan University |
Paik K.H.,Sungkyunkwan University
Pediatric Nephrology | Year: 2011
Residual renal function (RRF) is an important parameter in the management of patients on chronic dialysis. The aim of this cross-sectional study was to determine the efficacy of serum cystatin C (CysC) for RRF estimation in 20 children (16 boys, 4 girls; median age 13.4 years) undergoing peritoneal dialysis (PD). For studies of correlation with serum CysC, the average of creatinine clearance rate (Ccr) and urea clearance rate (C urea), Kt/Vurea, and weekly Ccr were evaluated as parameters reflecting RRF. The serum CysC level was found to be negatively correlated with urine volume (r∈=∈-0.717, P∈<∈0.001), average of Ccr and Curea(r∈=∈-0.851, P∈<∈0.001), total and renal weekly Ccr (r∈=∈-0.795, P∈<∈0.001; r∈=∈-0.845, P∈<∈0.001, respectively), and renal Kt/Vurea (r∈=∈-0.793, P∈<∈0.001) and positively correlated with peritoneal weekly Ccr (r∈=∈0.738, P∈<∈0.001) and peritoneal Kt/Vurea (r∈=∈0.785, P∈<∈0.001) . There was no significant association with total Kt/Vurea (r∈=∈-0.335, P∈=∈0.148). In non-anuric group of patients, serum CysC had no link to peritoneal Kt/Vurea (r∈=∈0.573, P∈=∈0.066), but was negatively correlated with renal Kt/V urea (r∈=∈-0.609, P∈=∈0.047). In the multiple regression analysis, renal Kt/Vurea significantly contributed to log CysC concentration rather than peritoneal Kt/Vurea. The results of this study suggest that serum CysC could be an appropriate marker for RRF, independent of total and peritoneal Kt/Vurea. © 2010 IPNA.
Lee E.J.,Comparative Biomedicine Research Branch |
Yun U.-J.,Comparative Biomedicine Research Branch |
Koo K.H.,Comparative Biomedicine Research Branch |
Sung J.Y.,Center for Pediatric Oncology |
And 4 more authors.
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2014
Lipid rafts, plasma membrane microdomains, are important for cell survival signaling and cholesterol is a critical lipid component for lipid raft integrity and function. DHA is known to have poor affinity for cholesterol and it influences lipid rafts. Here, we investigated a mechanism underlying the anti-cancer effects of DHA using a human breast cancer cell line, MDA-MB-231. We found that DHA decreased cell surface levels of lipid rafts via their internalization, which was partially reversed by cholesterol addition. With DHA treatment, caveolin-1, a marker for rafts, and EGFR were colocalized with LAMP-1, a lysosomal marker, in a cholesterol-dependent manner, indicating that DHA induces raft fusion with lysosomes. DHA not only displaced several raft-associated onco-proteins, including EGFR, Hsp90, Akt, and Src, from the rafts but also decreased total levels of those proteins via multiple pathways, including the proteasomal and lysosomal pathways, thereby decreasing their activities. Hsp90 overexpression maintained its client proteins, EGFR and Akt, and attenuated DHA-induced cell death. In addition, overexpression of Akt or constitutively active Akt attenuated DHA-induced apoptosis. All these data indicate that the anti-proliferative effect of DHA is mediated by targeting of lipid rafts via decreasing cell surface lipid rafts by their internalization, thereby decreasing raft-associated onco-proteins via proteasomal and lysosomal pathways and decreasing Hsp90 chaperone function. © 2013 Elsevier B.V.
PubMed | Center for Pediatric Oncology, Seoul National University and National Cancer Center
Type: Journal Article | Journal: Cancer research and treatment : official journal of Korean Cancer Association | Year: 2016
An epidemiologic study of childhood cancer would provide useful information on cancer etiology and development of management guidelines.Data from the Korea National Cancer Incidence Database were used to examine the incidence and survival of cancer in patients aged 0-14 years. Patients were grouped according to the International Classification of Childhood Cancer, 3rd edition. Age-specific and age-standardized incidences per million and estimated annual percentage change (APC) were calculated by sex and age. Five-year relative survival was calculated for four periods from 1993 to 2011.The study comprised 15,113 patients with malignant neoplasms. Age-standardized incidence rates for all cancers were 134.9 per million children in 1999-2011 and 144.0 and 124.9 per million for males and females, respectively (M/F ratio, 1.2; p < 0.05). The highest incidences were observed for leukemias, myeloproliferative diseases, and myelodysplastic diseases (group I) (46.4), central nervous system neoplasms (group III) (18.3), and lymphomas and reticuloendothelial neoplasms (group II) (13.4). Age-standardized incidence increased from 117.9 in 1999 to 155.3 in 2011, with an APC of 2.4% (95% confidence interval, 2.1 to 2.7). There was a significant increase of APC in neuroblastoma and other peripheral nervous cell tumors (group IV) (5.6%) and other malignant epithelial neoplasms and malignant melanomas (group XI) (5.6%). The 5-year relative survival rate for all childhood cancers improved significantly from 56.2% (1993-1995) to 78.2% (2007-2011) (males, 56.7% to 77.7%; females, 55.5% to 78.8%).This study provides reliable information on incidence and survival trends for childhood cancer in Korea.
PubMed | Center for Pediatric Oncology, Chung - Ang University and Seoul National University
Type: Journal Article | Journal: Transplant infectious disease : an official journal of the Transplantation Society | Year: 2016
Ganciclovir (GCV) has been widely used as preemptive therapy after hematopoietic stem cell transplantation (HSCT), although bone marrow suppression is a known accompaniment, with secondary infection or bleeding as potential complications. Our aim was to evaluate clinical outcomes in pediatric patients with low cytomegalovirus (CMV) antigenemia levels using half the dosage of GCV generally given preemptively.Patients received half doses of intravenous GCV (5 mg/kg once daily, 6 days/week) at CMV antigenemia levels <10/200,000 cells. At higher levels of CMV antigenemia, conventional doses of GCV (5 mg/kg every 12 h) were administered.A total of 130 patients were evaluated, detecting CMV antigenemia in 87 (66.9%). Of these patients, 74 (85.1%) were treated preemptively with half-dose GCV, which proved effective as sole therapy in 51 (68.9%). CMV retinitis developed in 4 patients, 2 of whom initially were given half-dose GCV. All infections resolved successfully, with no CMV-related deaths. CMV seropositivity in recipients was the only significant risk factor for positive CMV antigenemia (hazard ratio [HR] = 10.05, P = 0.046). Compared with half-dose GCV administration, conventional GCV dosing resulted in a higher rate of severe neutropenia, defined as absolute neutrophil count <0.5 10(9) /L (HR = 4.30, P = 0.015).Half-dose GCV therapy at CMV antigenemia levels <10/200,000 cells is an effective and safe means of preemptively treating pediatric CMV infection after HSCT.