Giun-Yi Hung - Academia.edu (original) (raw)

Papers by Giun-Yi Hung

Research paper thumbnail of Surgical treatment confers prognostic significance in pediatric malignant mediastinal germ cell tumors

Research paper thumbnail of Effect of c o‐medications and potential risk factors of high‐dose methotrexate‐mediated acute hepatotoxicity in patients with osteosarcoma

Research paper thumbnail of Age-standardized incidence rates (per million person-years) of childhood cancer in patients aged 0–19 years among 22 cities and counties in Taiwan (1995–2009)

Research paper thumbnail of Comparison of infant cancer incidence rates in different countries according to ICCC-3 group

<p>Abbreviations: Both, both sexes; M, male; F, female; CNS, Central Nervous system ICCC-3,... more <p>Abbreviations: Both, both sexes; M, male; F, female; CNS, Central Nervous system ICCC-3, International Classification of Childhood Cancer version 3; NA, data not available; SEER, Surveillance, Epidemiology and End Results Program.</p><p><sup>a</sup>Data include benign brain/CNS tumors.</p><p><sup>b</sup>Data include malignant tumors only.</p><p><sup>c</sup>Mass screening for neuroblastoma initiated in 1984 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0130444#pone.0130444.ref020&quot; target="_blank">20</a>].</p><p>-Statistic could not be calculated. Rate based on less than 16 cases for the time interval [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0130444#pone.0130444.ref017&quot; target="_blank">17</a>].</p><p>Comparison of infant cancer incidence rates in different countries according to ICCC-3 group.</p

Research paper thumbnail of Zebrafish Embryos as an in Vivo Model to Investigate Cisplatin-Induced Oxidative Stress and Apoptosis in Mitochondrion-Rich Ionocytes

Research paper thumbnail of Subcutaneously implanted central venous access device infection in pediatric patients with cancer

Journal of Microbiology Immunology and Infection, Apr 1, 2009

Subcutaneously implanted central venous access devices (SICVADs) are a common route of intravascu... more Subcutaneously implanted central venous access devices (SICVADs) are a common route of intravascular access for pediatric patients with cancer. This study was performed to evaluate the risk for SICVAD-related infection in a large consecutive series of unselected children with cancer in a single medical center. The medical charts of 209 pediatric patients with cancer who received a SICVAD from January 1, 2001 to December 31, 2005 were retrospectively reviewed, and the patients were followed-up until June 30, 2006. The demographics, clinicopathologic features, and infectious complications were collected for analysis. There were 137,924 SICVAD days (median, 660 days; range, 16-1962 days). The rate of SICVAD-related infections was 0.15 episodes/1000 SICVAD days. There were 21 episodes of SICVAD-related infection among 17 patients, 18 were bloodstream infection among 14 patients and the other 3 were local infection among 3 patients. Sixteen SICVADs were removed, 13 were associated with bloodstream infection and 3 with local infection. Young age (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2 years) was associated with a high risk for SICVAD-related infection. Staphylococcal spp. and fungi were the most common pathogens associated with SICVADs. The rate of SICVAD-related infection in children with cancer was low. Children younger than 2 years had a higher risk for SICVAD-related infection than older children. Fungi play an important role in SICVAD-related infection.

Research paper thumbnail of Complete and durable response to immune checkpoint inhibitor in a patient with refractory and metastatic hepatoblastoma

Pediatric Hematology and Oncology, 2021

We herein report the case of a girl with PRETEXT III hepatoblastoma (HB) developing recurrent lun... more We herein report the case of a girl with PRETEXT III hepatoblastoma (HB) developing recurrent lung metastases despite multiple chemotherapy regimens, aggressive tumor excision, multiple lung metastasectomies, and autologous peripheral blood stem cell transplantation. High tumor mutation burden (TMB) was identified through targeted next-generation sequencing, and pembrolizumab was administered post-operatively as a last resort. A complete and sustained response to the immune checkpoint inhibitor was achieved for 22 months. Although the majority of HB have a low TMB, immune checkpoint inhibitor therapy may be useful for patients with refractory HBs with a high TMB.

Research paper thumbnail of Decision-Tree Algorithm Optimize Hematopoietic Progenitor Cell-Based Prediction in Peripheral Blood Stem Cell Mobilization

Blood, 2015

Background and Objectives Enumeration of hematopoietic progenitor cells (HPC) using an automated ... more Background and Objectives Enumeration of hematopoietic progenitor cells (HPC) using an automated hematology analyzer provides rapid, inexpensive, and less technically dependent prediction of peripheral blood stem cell (PBSC) mobilization. This study aimed to incorporate HPC enumeration along with other predictors for optimizing a successful harvest. Materials and Methods Between 2007 and 2012, 189 consecutive patients who proceeded to PBSC harvesting with a preharvest HPC ≥ 20 x 106 /L were recruited. A failed PBSC mobilization was defined as < 2 x 106 CD34+ cells/kg. Variables predicting a successful harvest identified by multivariate logistic regression and correlation analysis were subjected to classification and regression tree (CART) analysis. Results A total of 154 (81.5%) patients successfully achieved mobilization of CD34+ cells (median 8.18 x 106 CD34+ cells/kg). Five independent host predictors including age ≥ 60, a diagnosis of solid tumor, prior chemotherapy cycles ≥ ...

Research paper thumbnail of Outcomes Following Discontinuation of E. coli- asparaginase upon Severe Allergic Reactions in Children with Acute Lymphoblastic Leukemia

Blood, 2015

Background: Discontinuation of E. coli- asparaginase in patients with acute lymphoblastic leukemi... more Background: Discontinuation of E. coli- asparaginase in patients with acute lymphoblastic leukemia (ALL) upon severe allergic reactions is unavoidable. We aimed to examine the outcomes following E.coli- asparaginase discontinuation upon severe allergic reactions in ALL. Patients and methods : In Taiwan Pediatric Oncology Group (TPOG)-2002-ALL protocol (enrolled 2002-2012), intramuscular E. coli- asparaginase (Kyowa Hakko, Japan) was given at 5000 IU/m2 per dose thrice weekly for 3 weeks during the remission induction therapy of high-risk (HR) and very-high-risk (VHR) groups. During the first 20 weeks of continuation therapy, HR patients received weekly intramuscular E. coli- asparaginase 10,000 IU/m2 per dose every week. They also received two reinduction treatments during which E.coli- asparaginase was given at 5000 IU/m2 per dose thrice weekly for 3 weeks. Patients in VHR groups received one reinduction treatment during which E. coli- asparaginase was given at 5000 IU/m2 per dose ...

Research paper thumbnail of Abstract 1204: Incidences of malignant primary soft-tissue sarcomas regardless of primary site: A nationwide population-based study in Taiwan

Cancer Research, 2018

Population-based studies on soft tissue sarcomas (STS) incidence beyond extremities and trunk wal... more Population-based studies on soft tissue sarcomas (STS) incidence beyond extremities and trunk wall are lacking in Asia. In this study, we aimed to report the incidences of STS arise in any part of the body. The data of primary STS registered in the population-based Taiwan Cancer Registry during 2007 and 2013 was acquired via the Health and Welfare Data Science Center, Taiwan. Histologic subtype-, age-, and gender-specific STS incidence rates of all sites were analyzed. A total of 11393 subjects were identified, with an age-standardized incidence rate of 5.62 (95% CI, 5.51-5.73) per 100,000 person-years. Approximately 30% of STS occurred in soft tissues (ICD-O-3 topography codes of C47, C49), and 70% occurred in all other primary sites (ICD-O-3 topography codes of C00-C80 except C47, C49, C40 and C41). The three most common primary sites other than soft tissues were stomach (15.9%), skin (14.3%) and small intestine (10.5%). Gastrointestinal stromal tumor (GIST) was the most common su...

Research paper thumbnail of CD34+ Selected T-Cell Depleted Peripheral Blood Stem Cell Transplantation from HLA-Haplocompatible Donors for the Treatment of Severe Combined Immunodeficiency Disease

Blood, 2005

We report the results of haplocompatible peripheral blood stem cell transplantation (PBSCT) utili... more We report the results of haplocompatible peripheral blood stem cell transplantation (PBSCT) utilizing CD34+ selection and T-cell depletion for 17 patients with severe combined immunodeficiency disease (SCID). Of these patients, 11 had T−B−NK+, 1 had T−B+NK+, and 5 had T−B+NK− phenotype. A total of 15 cell preparations were processed immediately after collection, in which two were shared between two twin siblings. Total viable nucleated cells (TVNC) in the original cell collections were between 5.9 and 9.13×1010 (median 7.0×1010) with 0.47–2.39% (median 0.9%) CD34+ cells. After Isolex 300i (Baxter Inc., n=14) or CliniMACS System (Miltenyi Biotec Inc., n=1) processing, a median number of 379×106 (89–970×106) TVNC were recovered, with a median viability of 98% (83–100%) and median purity of 96% (89–100%) CD34+ cells. All Isolex processed (n=14) cells were further T-cell depleted with OKT3 monoclonal antibody, yielding a median of 0.09% CD3+ cells (0.008–0.4%). One preparation that util...

Research paper thumbnail of Marine Antimicrobial Peptide TP4 Exerts Anticancer Effects on Human Synovial Sarcoma Cells via Calcium Overload, Reactive Oxygen Species Production and Mitochondrial Hyperpolarization

Marine Drugs, 2021

Synovial sarcoma is a rare but aggressive soft-tissue sarcoma associated with translocation t(X;1... more Synovial sarcoma is a rare but aggressive soft-tissue sarcoma associated with translocation t(X;18). Metastasis occurs in approximately 50% of all patients, and curative outcomes are difficult to achieve in this group. Since the efficacies of current therapeutic approaches for metastatic synovial sarcoma remain limited, new therapeutic agents are urgently needed. Tilapia piscidin 4 (TP4), a marine antimicrobial peptide, is known to exhibit multiple biological functions, including anti-bacterial, wound-healing, immunomodulatory, and anticancer activities. In the present study, we assessed the anticancer activity of TP4 in human synovial sarcoma cells and determined the underlying mechanisms. We first demonstrated that TP4 can induce necrotic cell death in human synovial sarcoma AsKa-SS and SW982 cells lines. In addition, we saw that TP4 initiates reactive oxygen species (ROS) production and downregulates antioxidant proteins, such as uncoupling protein-2, superoxide dismutase (SOD)-1...

Research paper thumbnail of Subcutaneously implanted central venous access device infection in pediatric patients with cancer

Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi, 2009

BACKGROUND AND PURPOSE Subcutaneously implanted central venous access devices (SICVADs) are a com... more BACKGROUND AND PURPOSE Subcutaneously implanted central venous access devices (SICVADs) are a common route of intravascular access for pediatric patients with cancer. This study was performed to evaluate the risk for SICVAD-related infection in a large consecutive series of unselected children with cancer in a single medical center. METHODS The medical charts of 209 pediatric patients with cancer who received a SICVAD from January 1, 2001 to December 31, 2005 were retrospectively reviewed, and the patients were followed-up until June 30, 2006. The demographics, clinicopathologic features, and infectious complications were collected for analysis. RESULTS There were 137,924 SICVAD days (median, 660 days; range, 16-1962 days). The rate of SICVAD-related infections was 0.15 episodes/1000 SICVAD days. There were 21 episodes of SICVAD-related infection among 17 patients, 18 were bloodstream infection among 14 patients and the other 3 were local infection among 3 patients. Sixteen SICVADs ...

Research paper thumbnail of Differential effects of silver nanoparticles on two types of mitochondrion-rich ionocytes in zebrafish embryos

Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 2022

Silver nanoparticles (AgNPs) are increasingly used in our daily life and have become a potential ... more Silver nanoparticles (AgNPs) are increasingly used in our daily life and have become a potential environmental hazard. However, the toxic effects of AgNPs on the early stages of fish are not fully understood, and little is known about their effects on specific types of ionocytes. Using zebrafish embryos as a model, this study examined the effects (changes in cell number, morphology, NH4+ secretion and gene expression) of sublethal concentrations of AgNPs (0.1, 1, and 3 mg/L) on two major types of ionocytes: H+ pump-rich (HR) ionocytes, and Na+ pump-rich (NaR) ionocytes in the skin of embryos. After exposure to AgNPs for 96 h, the number of HR ionocytes significantly declined by 30% and 41% in the 1 and 3 mg/L AgNP groups, respectively. In addition, the apical opening of HR ionocytes became smaller, suggesting that AgNPs impaired the critical structure for ion transport. NH4+ secretion by HR ionocytes of embryos also declined significantly after AgNP exposure. In contrast, the number of NaR ionocytes increased by 29% and 43% in the 1 and 3 mg/L AgNP groups, respectively, while these cells deformed their shape. AgNPs altered mRNA levels of several ion channel and transporter genes involved in the functions of HR ionocytes and NaR ionocytes, and influenced hormone genes involved in regulating calcium homeostasis. This study shows that AgNPs can cause differential adverse effects on two types of ionocytes and the effects can threaten fish survival.

Research paper thumbnail of Role of Calcium-Sensing Receptor in Mechanotransducer-Channel-Mediated Ca2+ Influx in Hair Cells of Zebrafish Larvae

Frontiers in Physiology, 2018

The calcium-sensing receptor (CaSR) is an extracellular Ca 2+ sensor that plays a critical role i... more The calcium-sensing receptor (CaSR) is an extracellular Ca 2+ sensor that plays a critical role in maintaining Ca 2+ homeostasis in several organs, including the parathyroid gland and kidneys. In this study, through in situ hybridization, the expression of CaSR mRNA was found in the neuromasts of zebrafish larvae. Immunohistochemistry further demonstrated that the CaSR protein was present in neuromast hair cell stereocilia and basolateral membranes. Based on the expression and subcellular localization of the CaSR in hair cells, we hypothesized that the CaSR is expressed in zebrafish lateral-line hair cells to regulate mechanotransducer (MET)-channel-mediated Ca 2+ entry. Using the scanning ion-selective electrode technique, MET-channel-mediated Ca 2+ influx at the stereocilia of hair cells was measured in intact larvae. Ca 2+ influx was suppressed after larvae were pretreated with a CaSR activator (R-568) or high-Ca 2+ (HCa) medium. Gene knockdown by using morpholino oligonucleotides decreased CaSR expression in hair cells and eliminated the effects of R-568 and HCa on Ca 2+ influx. In addition, we found that treatment with R-568 attenuated neomycin-induced hair cell death. This study is the first to demonstrate that the CaSR is involved in mechanotransduction in zebrafish hair cells.

Research paper thumbnail of Identification of chromosomal aberrations associated with disease progression and a novel 3q13.31 deletion involving LSAMP gene in osteosarcoma

International Journal of Oncology, 2009

Research paper thumbnail of Manipulation Therapy Prior to Diagnosis Induced Primary Osteosarcoma Metastasis—From Clinical to Basic Research

PLoS ONE, 2014

Osteosarcoma (OS) patients who suffer manipulation therapy (MT) prior to diagnosis resulted in po... more Osteosarcoma (OS) patients who suffer manipulation therapy (MT) prior to diagnosis resulted in poor prognosis with increasing metastasis or recurrence rate. The aim of the study is to establish an in vivo model to identify the effects of MT on OS. The enrolled 235 OS patients were followed up in this study. In vivo nude mice model with tibia injection of GFP-labeled human OS cells were randomly allocated into MT(+) that with repeated massage on tumor site twice a week and no treatment as MT(2) group. The five-year survival, metastasis and recurrence rates were recorded in clinical subjects. X-ray plainfilm, micro-PET/CT scan, histopathology, serum metalloproteinase 2 (MMP2), metalloproteinase 9 (MMP9) level and human kinase domain insert receptor (KDR) pattern were assayed in mice model. The results showed that patient with MT decreased 5-year survival and higher recurrence or metastasis rate. Compatible with clinical findings, the decreased body weight (30.560.65 g) and an increased tumor volume (8.361.18 mm 3) in MT(+) mice were observed. The increasing signal intensity over lymph node region of hind limb by micro-PET/CT and the tumor cells were detected in lung and bilateral lymph nodes only in MT(+) group. MMP2 (21469.8 ng/ml) and MMP9 (25.561.81 ng/ml) were higher in MT(+) group than in MT(2) group (16567.8 ng/ml and 16.961.40 ng/ml, individually) as well as KDR expression. Taking clinical observations and in vivo evidence together, MT treatment leads to poor prognosis of primary osteosarcoma; physicians should pay more attention on patients who seek MT before diagnosis.

Research paper thumbnail of Incidence Patterns of Primary Bone Cancer in Taiwan (2003–2010): A Population-Based Study

Annals of Surgical Oncology, 2014

Research paper thumbnail of Treatment outcomes of pediatric acute myeloid leukemia: a retrospective analysis from 1996 to 2019 in Taiwan

Scientific Reports, 2021

Improvement in outcomes of children with acute myeloid leukemia (AML) is attributed to several re... more Improvement in outcomes of children with acute myeloid leukemia (AML) is attributed to several refinements in clinical management. We evaluated treatment outcomes of Taiwanese pediatric AML patients in the past 20 years. Overall, 860 de novo AML patients aged 0–18 years and registered in the Childhood Cancer Foundation of R.O.C during January 1996–December 2019 were included. Survival analysis was performed to identify factors that improved treatment outcomes. Regardless of treatment modalities used, patients during 2008–2019 had better 5-year event-free survival (EFS) and overall survival (OS) rates than patients during 1996–2007. For patients received the TPOG-AML-97A treatment, only 5-year OS rates were significantly different between patients diagnosed before and after 2008. Patients with RUNX1–RUNX1T1 had similar relapse-free survival rates, but 5-year OS rates were better during 2008–2019. However, the survival of patients who received hematopoietic stem-cell transplantations ...

Research paper thumbnail of Ganglioneuroma presenting as an asymptomatic huge posterior mediastinal and retroperitoneal tumor

Journal of the Chinese Medical Association, 2003

Ganglioneuroma is a rare, differentiated, benign and slow-growing tumor that commonly arises from... more Ganglioneuroma is a rare, differentiated, benign and slow-growing tumor that commonly arises from sympathetic ganglion cells. Most of them are asymptomatic and found incidentally. We here report a quite rare case of silent huge ganglioneuroma growing in both posterior mediastinum and retroperitoneum occurring in a 3.5-year-old girl. The patient was relatively well before and incidentally found to have a huge chest mass by chest X-ray film at an episode of respiratory tract infection. Computed tomography showed a huge tumor extending from bilateral posterior mediastinum to the level of the adrenal gland in the retroperitoneum. Initially, neuroblastoma was highly suspected and 24-hour urine vanillyl mandelic acid was slightly elevated. Cytology by bone marrow aspiration revealed no tumor nests or clumps. Biopsy and pathology proved it as ganglioneuroma (GN). Due to too extensive involvement of the tumor and compression of the vital vessels, surgical removal became difficult. The famil...

Research paper thumbnail of Surgical treatment confers prognostic significance in pediatric malignant mediastinal germ cell tumors

Research paper thumbnail of Effect of c o‐medications and potential risk factors of high‐dose methotrexate‐mediated acute hepatotoxicity in patients with osteosarcoma

Research paper thumbnail of Age-standardized incidence rates (per million person-years) of childhood cancer in patients aged 0–19 years among 22 cities and counties in Taiwan (1995–2009)

Research paper thumbnail of Comparison of infant cancer incidence rates in different countries according to ICCC-3 group

<p>Abbreviations: Both, both sexes; M, male; F, female; CNS, Central Nervous system ICCC-3,... more <p>Abbreviations: Both, both sexes; M, male; F, female; CNS, Central Nervous system ICCC-3, International Classification of Childhood Cancer version 3; NA, data not available; SEER, Surveillance, Epidemiology and End Results Program.</p><p><sup>a</sup>Data include benign brain/CNS tumors.</p><p><sup>b</sup>Data include malignant tumors only.</p><p><sup>c</sup>Mass screening for neuroblastoma initiated in 1984 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0130444#pone.0130444.ref020&quot; target="_blank">20</a>].</p><p>-Statistic could not be calculated. Rate based on less than 16 cases for the time interval [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0130444#pone.0130444.ref017&quot; target="_blank">17</a>].</p><p>Comparison of infant cancer incidence rates in different countries according to ICCC-3 group.</p

Research paper thumbnail of Zebrafish Embryos as an in Vivo Model to Investigate Cisplatin-Induced Oxidative Stress and Apoptosis in Mitochondrion-Rich Ionocytes

Research paper thumbnail of Subcutaneously implanted central venous access device infection in pediatric patients with cancer

Journal of Microbiology Immunology and Infection, Apr 1, 2009

Subcutaneously implanted central venous access devices (SICVADs) are a common route of intravascu... more Subcutaneously implanted central venous access devices (SICVADs) are a common route of intravascular access for pediatric patients with cancer. This study was performed to evaluate the risk for SICVAD-related infection in a large consecutive series of unselected children with cancer in a single medical center. The medical charts of 209 pediatric patients with cancer who received a SICVAD from January 1, 2001 to December 31, 2005 were retrospectively reviewed, and the patients were followed-up until June 30, 2006. The demographics, clinicopathologic features, and infectious complications were collected for analysis. There were 137,924 SICVAD days (median, 660 days; range, 16-1962 days). The rate of SICVAD-related infections was 0.15 episodes/1000 SICVAD days. There were 21 episodes of SICVAD-related infection among 17 patients, 18 were bloodstream infection among 14 patients and the other 3 were local infection among 3 patients. Sixteen SICVADs were removed, 13 were associated with bloodstream infection and 3 with local infection. Young age (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2 years) was associated with a high risk for SICVAD-related infection. Staphylococcal spp. and fungi were the most common pathogens associated with SICVADs. The rate of SICVAD-related infection in children with cancer was low. Children younger than 2 years had a higher risk for SICVAD-related infection than older children. Fungi play an important role in SICVAD-related infection.

Research paper thumbnail of Complete and durable response to immune checkpoint inhibitor in a patient with refractory and metastatic hepatoblastoma

Pediatric Hematology and Oncology, 2021

We herein report the case of a girl with PRETEXT III hepatoblastoma (HB) developing recurrent lun... more We herein report the case of a girl with PRETEXT III hepatoblastoma (HB) developing recurrent lung metastases despite multiple chemotherapy regimens, aggressive tumor excision, multiple lung metastasectomies, and autologous peripheral blood stem cell transplantation. High tumor mutation burden (TMB) was identified through targeted next-generation sequencing, and pembrolizumab was administered post-operatively as a last resort. A complete and sustained response to the immune checkpoint inhibitor was achieved for 22 months. Although the majority of HB have a low TMB, immune checkpoint inhibitor therapy may be useful for patients with refractory HBs with a high TMB.

Research paper thumbnail of Decision-Tree Algorithm Optimize Hematopoietic Progenitor Cell-Based Prediction in Peripheral Blood Stem Cell Mobilization

Blood, 2015

Background and Objectives Enumeration of hematopoietic progenitor cells (HPC) using an automated ... more Background and Objectives Enumeration of hematopoietic progenitor cells (HPC) using an automated hematology analyzer provides rapid, inexpensive, and less technically dependent prediction of peripheral blood stem cell (PBSC) mobilization. This study aimed to incorporate HPC enumeration along with other predictors for optimizing a successful harvest. Materials and Methods Between 2007 and 2012, 189 consecutive patients who proceeded to PBSC harvesting with a preharvest HPC ≥ 20 x 106 /L were recruited. A failed PBSC mobilization was defined as < 2 x 106 CD34+ cells/kg. Variables predicting a successful harvest identified by multivariate logistic regression and correlation analysis were subjected to classification and regression tree (CART) analysis. Results A total of 154 (81.5%) patients successfully achieved mobilization of CD34+ cells (median 8.18 x 106 CD34+ cells/kg). Five independent host predictors including age ≥ 60, a diagnosis of solid tumor, prior chemotherapy cycles ≥ ...

Research paper thumbnail of Outcomes Following Discontinuation of E. coli- asparaginase upon Severe Allergic Reactions in Children with Acute Lymphoblastic Leukemia

Blood, 2015

Background: Discontinuation of E. coli- asparaginase in patients with acute lymphoblastic leukemi... more Background: Discontinuation of E. coli- asparaginase in patients with acute lymphoblastic leukemia (ALL) upon severe allergic reactions is unavoidable. We aimed to examine the outcomes following E.coli- asparaginase discontinuation upon severe allergic reactions in ALL. Patients and methods : In Taiwan Pediatric Oncology Group (TPOG)-2002-ALL protocol (enrolled 2002-2012), intramuscular E. coli- asparaginase (Kyowa Hakko, Japan) was given at 5000 IU/m2 per dose thrice weekly for 3 weeks during the remission induction therapy of high-risk (HR) and very-high-risk (VHR) groups. During the first 20 weeks of continuation therapy, HR patients received weekly intramuscular E. coli- asparaginase 10,000 IU/m2 per dose every week. They also received two reinduction treatments during which E.coli- asparaginase was given at 5000 IU/m2 per dose thrice weekly for 3 weeks. Patients in VHR groups received one reinduction treatment during which E. coli- asparaginase was given at 5000 IU/m2 per dose ...

Research paper thumbnail of Abstract 1204: Incidences of malignant primary soft-tissue sarcomas regardless of primary site: A nationwide population-based study in Taiwan

Cancer Research, 2018

Population-based studies on soft tissue sarcomas (STS) incidence beyond extremities and trunk wal... more Population-based studies on soft tissue sarcomas (STS) incidence beyond extremities and trunk wall are lacking in Asia. In this study, we aimed to report the incidences of STS arise in any part of the body. The data of primary STS registered in the population-based Taiwan Cancer Registry during 2007 and 2013 was acquired via the Health and Welfare Data Science Center, Taiwan. Histologic subtype-, age-, and gender-specific STS incidence rates of all sites were analyzed. A total of 11393 subjects were identified, with an age-standardized incidence rate of 5.62 (95% CI, 5.51-5.73) per 100,000 person-years. Approximately 30% of STS occurred in soft tissues (ICD-O-3 topography codes of C47, C49), and 70% occurred in all other primary sites (ICD-O-3 topography codes of C00-C80 except C47, C49, C40 and C41). The three most common primary sites other than soft tissues were stomach (15.9%), skin (14.3%) and small intestine (10.5%). Gastrointestinal stromal tumor (GIST) was the most common su...

Research paper thumbnail of CD34+ Selected T-Cell Depleted Peripheral Blood Stem Cell Transplantation from HLA-Haplocompatible Donors for the Treatment of Severe Combined Immunodeficiency Disease

Blood, 2005

We report the results of haplocompatible peripheral blood stem cell transplantation (PBSCT) utili... more We report the results of haplocompatible peripheral blood stem cell transplantation (PBSCT) utilizing CD34+ selection and T-cell depletion for 17 patients with severe combined immunodeficiency disease (SCID). Of these patients, 11 had T−B−NK+, 1 had T−B+NK+, and 5 had T−B+NK− phenotype. A total of 15 cell preparations were processed immediately after collection, in which two were shared between two twin siblings. Total viable nucleated cells (TVNC) in the original cell collections were between 5.9 and 9.13×1010 (median 7.0×1010) with 0.47–2.39% (median 0.9%) CD34+ cells. After Isolex 300i (Baxter Inc., n=14) or CliniMACS System (Miltenyi Biotec Inc., n=1) processing, a median number of 379×106 (89–970×106) TVNC were recovered, with a median viability of 98% (83–100%) and median purity of 96% (89–100%) CD34+ cells. All Isolex processed (n=14) cells were further T-cell depleted with OKT3 monoclonal antibody, yielding a median of 0.09% CD3+ cells (0.008–0.4%). One preparation that util...

Research paper thumbnail of Marine Antimicrobial Peptide TP4 Exerts Anticancer Effects on Human Synovial Sarcoma Cells via Calcium Overload, Reactive Oxygen Species Production and Mitochondrial Hyperpolarization

Marine Drugs, 2021

Synovial sarcoma is a rare but aggressive soft-tissue sarcoma associated with translocation t(X;1... more Synovial sarcoma is a rare but aggressive soft-tissue sarcoma associated with translocation t(X;18). Metastasis occurs in approximately 50% of all patients, and curative outcomes are difficult to achieve in this group. Since the efficacies of current therapeutic approaches for metastatic synovial sarcoma remain limited, new therapeutic agents are urgently needed. Tilapia piscidin 4 (TP4), a marine antimicrobial peptide, is known to exhibit multiple biological functions, including anti-bacterial, wound-healing, immunomodulatory, and anticancer activities. In the present study, we assessed the anticancer activity of TP4 in human synovial sarcoma cells and determined the underlying mechanisms. We first demonstrated that TP4 can induce necrotic cell death in human synovial sarcoma AsKa-SS and SW982 cells lines. In addition, we saw that TP4 initiates reactive oxygen species (ROS) production and downregulates antioxidant proteins, such as uncoupling protein-2, superoxide dismutase (SOD)-1...

Research paper thumbnail of Subcutaneously implanted central venous access device infection in pediatric patients with cancer

Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi, 2009

BACKGROUND AND PURPOSE Subcutaneously implanted central venous access devices (SICVADs) are a com... more BACKGROUND AND PURPOSE Subcutaneously implanted central venous access devices (SICVADs) are a common route of intravascular access for pediatric patients with cancer. This study was performed to evaluate the risk for SICVAD-related infection in a large consecutive series of unselected children with cancer in a single medical center. METHODS The medical charts of 209 pediatric patients with cancer who received a SICVAD from January 1, 2001 to December 31, 2005 were retrospectively reviewed, and the patients were followed-up until June 30, 2006. The demographics, clinicopathologic features, and infectious complications were collected for analysis. RESULTS There were 137,924 SICVAD days (median, 660 days; range, 16-1962 days). The rate of SICVAD-related infections was 0.15 episodes/1000 SICVAD days. There were 21 episodes of SICVAD-related infection among 17 patients, 18 were bloodstream infection among 14 patients and the other 3 were local infection among 3 patients. Sixteen SICVADs ...

Research paper thumbnail of Differential effects of silver nanoparticles on two types of mitochondrion-rich ionocytes in zebrafish embryos

Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 2022

Silver nanoparticles (AgNPs) are increasingly used in our daily life and have become a potential ... more Silver nanoparticles (AgNPs) are increasingly used in our daily life and have become a potential environmental hazard. However, the toxic effects of AgNPs on the early stages of fish are not fully understood, and little is known about their effects on specific types of ionocytes. Using zebrafish embryos as a model, this study examined the effects (changes in cell number, morphology, NH4+ secretion and gene expression) of sublethal concentrations of AgNPs (0.1, 1, and 3 mg/L) on two major types of ionocytes: H+ pump-rich (HR) ionocytes, and Na+ pump-rich (NaR) ionocytes in the skin of embryos. After exposure to AgNPs for 96 h, the number of HR ionocytes significantly declined by 30% and 41% in the 1 and 3 mg/L AgNP groups, respectively. In addition, the apical opening of HR ionocytes became smaller, suggesting that AgNPs impaired the critical structure for ion transport. NH4+ secretion by HR ionocytes of embryos also declined significantly after AgNP exposure. In contrast, the number of NaR ionocytes increased by 29% and 43% in the 1 and 3 mg/L AgNP groups, respectively, while these cells deformed their shape. AgNPs altered mRNA levels of several ion channel and transporter genes involved in the functions of HR ionocytes and NaR ionocytes, and influenced hormone genes involved in regulating calcium homeostasis. This study shows that AgNPs can cause differential adverse effects on two types of ionocytes and the effects can threaten fish survival.

Research paper thumbnail of Role of Calcium-Sensing Receptor in Mechanotransducer-Channel-Mediated Ca2+ Influx in Hair Cells of Zebrafish Larvae

Frontiers in Physiology, 2018

The calcium-sensing receptor (CaSR) is an extracellular Ca 2+ sensor that plays a critical role i... more The calcium-sensing receptor (CaSR) is an extracellular Ca 2+ sensor that plays a critical role in maintaining Ca 2+ homeostasis in several organs, including the parathyroid gland and kidneys. In this study, through in situ hybridization, the expression of CaSR mRNA was found in the neuromasts of zebrafish larvae. Immunohistochemistry further demonstrated that the CaSR protein was present in neuromast hair cell stereocilia and basolateral membranes. Based on the expression and subcellular localization of the CaSR in hair cells, we hypothesized that the CaSR is expressed in zebrafish lateral-line hair cells to regulate mechanotransducer (MET)-channel-mediated Ca 2+ entry. Using the scanning ion-selective electrode technique, MET-channel-mediated Ca 2+ influx at the stereocilia of hair cells was measured in intact larvae. Ca 2+ influx was suppressed after larvae were pretreated with a CaSR activator (R-568) or high-Ca 2+ (HCa) medium. Gene knockdown by using morpholino oligonucleotides decreased CaSR expression in hair cells and eliminated the effects of R-568 and HCa on Ca 2+ influx. In addition, we found that treatment with R-568 attenuated neomycin-induced hair cell death. This study is the first to demonstrate that the CaSR is involved in mechanotransduction in zebrafish hair cells.

Research paper thumbnail of Identification of chromosomal aberrations associated with disease progression and a novel 3q13.31 deletion involving LSAMP gene in osteosarcoma

International Journal of Oncology, 2009

Research paper thumbnail of Manipulation Therapy Prior to Diagnosis Induced Primary Osteosarcoma Metastasis—From Clinical to Basic Research

PLoS ONE, 2014

Osteosarcoma (OS) patients who suffer manipulation therapy (MT) prior to diagnosis resulted in po... more Osteosarcoma (OS) patients who suffer manipulation therapy (MT) prior to diagnosis resulted in poor prognosis with increasing metastasis or recurrence rate. The aim of the study is to establish an in vivo model to identify the effects of MT on OS. The enrolled 235 OS patients were followed up in this study. In vivo nude mice model with tibia injection of GFP-labeled human OS cells were randomly allocated into MT(+) that with repeated massage on tumor site twice a week and no treatment as MT(2) group. The five-year survival, metastasis and recurrence rates were recorded in clinical subjects. X-ray plainfilm, micro-PET/CT scan, histopathology, serum metalloproteinase 2 (MMP2), metalloproteinase 9 (MMP9) level and human kinase domain insert receptor (KDR) pattern were assayed in mice model. The results showed that patient with MT decreased 5-year survival and higher recurrence or metastasis rate. Compatible with clinical findings, the decreased body weight (30.560.65 g) and an increased tumor volume (8.361.18 mm 3) in MT(+) mice were observed. The increasing signal intensity over lymph node region of hind limb by micro-PET/CT and the tumor cells were detected in lung and bilateral lymph nodes only in MT(+) group. MMP2 (21469.8 ng/ml) and MMP9 (25.561.81 ng/ml) were higher in MT(+) group than in MT(2) group (16567.8 ng/ml and 16.961.40 ng/ml, individually) as well as KDR expression. Taking clinical observations and in vivo evidence together, MT treatment leads to poor prognosis of primary osteosarcoma; physicians should pay more attention on patients who seek MT before diagnosis.

Research paper thumbnail of Incidence Patterns of Primary Bone Cancer in Taiwan (2003–2010): A Population-Based Study

Annals of Surgical Oncology, 2014

Research paper thumbnail of Treatment outcomes of pediatric acute myeloid leukemia: a retrospective analysis from 1996 to 2019 in Taiwan

Scientific Reports, 2021

Improvement in outcomes of children with acute myeloid leukemia (AML) is attributed to several re... more Improvement in outcomes of children with acute myeloid leukemia (AML) is attributed to several refinements in clinical management. We evaluated treatment outcomes of Taiwanese pediatric AML patients in the past 20 years. Overall, 860 de novo AML patients aged 0–18 years and registered in the Childhood Cancer Foundation of R.O.C during January 1996–December 2019 were included. Survival analysis was performed to identify factors that improved treatment outcomes. Regardless of treatment modalities used, patients during 2008–2019 had better 5-year event-free survival (EFS) and overall survival (OS) rates than patients during 1996–2007. For patients received the TPOG-AML-97A treatment, only 5-year OS rates were significantly different between patients diagnosed before and after 2008. Patients with RUNX1–RUNX1T1 had similar relapse-free survival rates, but 5-year OS rates were better during 2008–2019. However, the survival of patients who received hematopoietic stem-cell transplantations ...

Research paper thumbnail of Ganglioneuroma presenting as an asymptomatic huge posterior mediastinal and retroperitoneal tumor

Journal of the Chinese Medical Association, 2003

Ganglioneuroma is a rare, differentiated, benign and slow-growing tumor that commonly arises from... more Ganglioneuroma is a rare, differentiated, benign and slow-growing tumor that commonly arises from sympathetic ganglion cells. Most of them are asymptomatic and found incidentally. We here report a quite rare case of silent huge ganglioneuroma growing in both posterior mediastinum and retroperitoneum occurring in a 3.5-year-old girl. The patient was relatively well before and incidentally found to have a huge chest mass by chest X-ray film at an episode of respiratory tract infection. Computed tomography showed a huge tumor extending from bilateral posterior mediastinum to the level of the adrenal gland in the retroperitoneum. Initially, neuroblastoma was highly suspected and 24-hour urine vanillyl mandelic acid was slightly elevated. Cytology by bone marrow aspiration revealed no tumor nests or clumps. Biopsy and pathology proved it as ganglioneuroma (GN). Due to too extensive involvement of the tumor and compression of the vital vessels, surgical removal became difficult. The famil...