• Clinical and Experimental Pediatrics
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• v.51 no.2
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• pp.214-218
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• 2008

Neuroblastoma is one of the most common extracranial solid tumor of childhood, and treatment of refractory neuroblastoma remains a significant clinical problem. Iodine-131-metaiodobenzylguanidine ($^{131}I-MIBG$) therapy is an alternative approach to treat stage IV neuroblastoma. We report the palliative effect of $^{131}I-MIBG$ in three cases of relapsed neuroblastoma after autologous peripheral blood stem cell transplantation. $^{131}I-MIBG$ is an effective and relatively nontoxic palliative therapy resulting in reduction of pain and prolongation of survival.

• Clinical and Experimental Pediatrics
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• v.45 no.3
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• pp.354-361
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• 2002

Purpose : Selective introduction of genes conferring chemosensitivity into proliferating tumor cells may be used to treat cancer. We first investigated the bystander effect of retrovirus-mediated gene transfer of herpes simplex virus thymidine kinase(HSV-TK) gene to murine neuroblstoma cell line(neuro-2a) in vitro and in vivo. Second, we examined the mechanism and its enhancement of the bystander effect in murine neuroblastoma. Methods : To investigate the bystander effect, we studied tumor growth and survival time after HSV-TK/ganciclovir(GCV) treatment in a syngenic A/J mouse neuroblastoma model by mixing various ratios of HSV-TK-expressing neuro-2a cells with wild type neuro-2a cells followed by GCV treatment. To investigate the mechanism of the bystander effect in murine neuroblastoma, immunohistochemistry using connexin 43, CD4 and CD8-specific monoclonal antibodies was analyzed. We studied whether IL-2-secreting neuro-2a cells(neuro-2a/IL-2) would potentiate the bystander effect. Results : A strong bystander effect was observed in vitro and in vivo. The bystander effect in murine neuroblastoma was dependent on the immune response rather than connexin-mediated gap junction. Neuro-2a/IL-2 treatment enhanced the bystander effect in the HSV-TK/GCV system in murine neuroblastoma model. Conclusion : We conclude that the bystander effect in murine neuroblastoma depends on immune response and is enhanced by neuro-2a/IL-2.

• Journal of the korean academy of Pediatric Dentistry
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• v.37 no.3
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• pp.352-358
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• 2010

Chemotherapy or radiotherapy used for the treatment of pediatric cancer may have many adverse effects on the oral cavity. Oral mucositis, reduced salivary flow, oral infection, hypodontia, microdontia, arrested root development, and enamel hypoplasia are common oral complications. The aim of this study is to evaluate the effects of cancer therapy on dental caries activities. The children who had been treated for neuroblastoma in the department of pediatrics, Samsung Medical Center, were included and healthy children served as controls. The salivary flow rate, salivary buffering capacity, and Streptococcus mutans counts of both groups were evaluated using Dentocult$^{(R)}$ SM and Dentobuff$^{(R)}$ Strip. The dental caries activity related to the age at the start of treatment and the time elapsed since treatment completion were also evaluated. As a result, neuroblastoma patients had significantly lower salivary flow rate than the controls, while there were no significant differences between two groups as for salivary buffering capacity and Streptococcus mutans counts. The dental caries activities related to the age at the start of treatment and the time elapsed since treatment completion were not significantly different.

• Clinical and Experimental Pediatrics
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• v.46 no.7
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• pp.702-709
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• 2003

Purpose : $IFN{\gamma}$ sentitizes many tumor cells to $TNF{\alpha}$ and FASL-mediated apoptosis by enhancing the expression of TNF or FAS/CD95 receptor and modulating the activation of caspase and Bcl-2 family. It has been reported that $IFN{\gamma}$ and $TNF{\alpha}$ synergistically caused differentiation and growth inhibition of neuroblastoma cells. Even though some neuroblastoma cell express FASR/FASL on the cell surface, they could not induce apoptosis by ligation of the FAS/CD95 receptor. But the treatment of $IFN{\gamma}$ is reported to induce apoptosis in some neuroblastoma cell lines through the CD95/CD95L autocrine circuit. In this study, we examined whether $IFN{\gamma}$ could affect $TNF{\alpha}$ and agonistic FAS/CD95 antibody(CH-11)-induced apoptosis against neuroblastoma cell lines that had shown diverse drug sensitivity and resistance. Methods : CHLA-15, CHLA-90 and LA-N-2 neuroblastoma cells were cultured in IMDM and treated with recombinant $IFN{\gamma}$, $TNF{\alpha}$ and CH-11 antibody. Cell viability was measured by DIMSCAN with a fluorescent calcein-AM. Apoptosis was analyzed through flow cytometry using Annexin V-PE and 7-ADD staining and confirmed by pancaspase and caspase-8 blocking experiments. The expression of TNF RI and FAS/CD95 receptor was evaluated by flow cytometry using the corresponding antibody and PE-conjugated secondary antibody. Results : $IFN{\gamma}$ or $TNF{\alpha}$ alone had no demonstrable cytotoxic effects, whereas both cytokines in combination induced apoptosis synergistically in CHLA-15 and CHLA-90 cells. Although there was no cytotoxicity with the ligation of CH-11 alone in CHLA-90 cells, pretreatment of $IFN{\gamma}$ increased the sensitivity of CH-11-mediated apoptosis. The expression of TNFRI and FAS/CD95R were non-specifically enhanced after treatment of $IFN{\gamma}$ without relation to sensitivity to $TNF{\alpha}$ and CH-11. This finding suggest up-regulation of both receptors may contribute to sensitization of $TNF{\alpha}$ and CH-11-mediated apoptosis by $IFN{\gamma}$ in only sensitive cell lines. Conclusion : $IFN{\gamma}$ induced sensitization of $TNF{\alpha}$ and agonistic FAS/CD95 antibody-mediated apoptosis on some neuroblastoma cells through up-regulation of TNFRI and FAS/CD95 receptor.

• Clinical and Experimental Pediatrics
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• v.46 no.12
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• pp.1279-1282
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• 2003

Neuroblastoma is the most common intraabdominal malignant tumor of childhood, with 40% arising from the adrenal gland. Bilateral adrenal involvement from synchronous development or metastatic spread of tumor is rarely seen in children with neuroblastoma. The patient was born with a spontaneous vaginal delivery. Birth weight was 3,200 g. Fetal ultrasonography showed a left adrenal cystic mass. At two weeks of age, she was admitted due to a massive abdominal distension and tachypnea. Percutaneous ultrasonography guided biopsy of the left adrenal mass was performed. The result of the biopsy was neuroblastoma. Vincristine and cyclophosphamide were administerd intravenously and 450 cGy of irradiation was added. Left adrenalectomy was accomplished and postoperative course was uneventful. The patient received cancer chemotherapy with a combination of carboplatin, ifosfamide and VP-16 and is now being followed up for three months. We have experienced a case of congenital bilateral neuroblastoma and report the case with brief review of related literatures.

• Clinical and Experimental Pediatrics
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• v.49 no.4
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• pp.439-445
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• 2006

Purpose : ${\alpha}$-Galactosylceramide (${\alpha}$-GalCer)-stimulated human $V{\alpha}24$ natural killer T (NKT) cells exert antitumor activity against some leukemia in a CD1d dependent and TCR-mediated manner, but could not kill CD1d - negative neuroblastoma (NB) cells. There are few reports about the direct antitumor effect of highly secreted cytokines by these cells on activation. In this study, using a cell-free supernatant (SPN) collected from plate bound hCD1d/${\alpha}$ GalCer tetramers-stimulated NKT cells, we examined whether they could be helpful in the immunotherapeutic treatment of NB. Methods : Cells were cultured in IMDM. The cytokines produced by NKT cells were measured with Cytometric Bead Array (CBA) analysis. Cell viability was evaluated by calcein-AM fluorescence with digital image microscopy scanning (DIMSCAN). The percentage of specific apoptosis was calculated by flow cytometric detection of apoptosis using annexin V and 7-AAD. Results : The activated NKT cells secreted high levels of IL-2, INF-${\gamma}$, TNF-${\alpha}$. The SPN was significantly cytotoxic against four out of eight tested NB cell lines, through mainly apoptosis as evidenced by annexin-V staining and inhibition with the pretreatment of pancaspase blocker. This apoptosis was significantly inhibited when anti-TNF-${\alpha}$ and anti-IFN-${\gamma}$ neutralizing mAbs were used separately and it was completely abolished when the two mAbs were combined. Conclusion : IFN-${\gamma}$ and TNF-${\alpha}$ produced by NKT cells could exert synergistically direct antitumor activity through apoptosis on some NB cell lines.

• Clinical and Experimental Pediatrics
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• v.46 no.11
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• pp.1128-1130
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• 2003

Retinoic acid has been used successfully as a differentiating agent in acute promyelocytic leukemia and neuroblastoma. However, some adverse effects have been recognized, such as headaches, dry skin and retinoic acid syndrome, a life threatening acute cardiorespiratory disorder. Acute pancreatitis with hyperlipidemia has rarely been reported. We experienced a case of acute pancreatitis with hyperlipidemia in a neuroblastoma patient after retinoic acid therapy for 21 months. Although the patient was ordered nothing by mouth and total parenteral nutrition was administrated, she died of disseminated intravascular coagulopathy and pulmonary hemorrhage, possibly because of oral intake during her recovery period.

• Clinical and Experimental Pediatrics
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• v.46 no.11
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• pp.1107-1111
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• 2003

Purpose : Neuroblastoma is a malignant neoplasm which arises from primitive sympathetic neuroblasts, and occasionally can matured from a malignant neuroblastoma into a benign ganglioneuroma. It has the highest rate of spontaneous regression of any pediatric tumor. We performed a retrospective study of pathologic features after combination therapy in advanced neuroblastoma. Prognostic effects of the individual morphologic feature and prognostic groupings according to modified Shimada classification systems were analyzed. Methods : The treatment results for six patients with neuroblastoma seen at Keimyung University from Jan. 1991 to June 2000 were analyzed. Patients were treated with a combination of chemotherapy, radiation therapy, and surgery, and classified by two major prognostic criteria based on morphological features of neuroblastoma, such as modified Shimada classification and histologic grading. Results : Three cases were classified to a good histologic group; among them, two cases survived, but one case was lost in follow-up. There were three cases classified in a poor histologic group. All of these patients expired due to sepsis and hemorrhagic pancreatitis. Conclusion : Prognostic classification due to pathologic findings had significant value in evaluating the survival rate of neuroblastoma patients.

• Clinical and Experimental Pediatrics
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• v.52 no.1
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• pp.93-98
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• 2009

Purpose : The purpose of this study was to evaluate the clinical characteristics and outcomes of patients with neuroblastoma aged less than 1 year. Methods : From January 1997 to December 2007, 41 patients aged less than 1 year were diagnosed with neuroblastoma. Patients were divided into 3 risk groups according to the stage of the disease and N-myc amplification. Low-risk patients underwent surgery with (stage 2) or without (stage 1) short-term chemotherapy. Intermediate-risk patients underwent chemotherapy and surgery with or without local radiation therapy. High-risk patients underwent chemotherapy, surgery, radiation therapy, and high-dose chemotherapy/autologous stem cell rescue (HDCT/ASCR). Results : While tumor relapse occurred in only 1 patient, 7 patients died of treatment-related toxicities. Causes of treatment- related death included infection during conventional chemotherapy in 5 patients and acute myocarditis during HDCT/ASCR in 2 patients. The overall 5-year survival (${\pm}$ standard error) and 5-year event-free survival (EFS) rates after diagnosis for all 41 patients were $82.8{\pm}5.9%$ and $80.0{\pm}$6.3%$, respectively, with a median follow-up of 58 (9-137) months. The 5-year EFS rates for low-risk, intermediate-risk, and high-risk patients were 100%, $68.4{\pm}10.8%$, and $66.7{\pm}19.3%$, respectively. Conclusion : Increased efforts to reduce infection-associated toxicity deaths during conventional chemotherapy are needed to further improve the survival of patients with neuroblastoma aged less than 1 year.

• 대한핵의학회:학술대회논문집
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• 2005.11a
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• pp.325.1-325.1
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• 2005