• Radiation Oncology Journal
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• v.19 no.2
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• pp.100-106
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• 2001

Purpose : We performed a retrospective analysis to compare short term results of induction chemotherapy-radiotherapy versus concurrent chemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma. Materials and Methods : From Oct. 1989 to May 1998, 62 patients with locally advanced nasopharyngeal carcinoma were treated with induction chemotherapy followed by radiotherapy (induction group) or concurrent chemo-radiotherapy (concurrent group). Induction chemotherapy was done for 50 patients, and concurrent chemotherapy for 12 patients. Age, sex, performance status, and pathologic types were evenly distributed between two groups. Stage distribution showed $32\%$ with IIB, $32\%$ with III, and $38\%$ with IV in induction group, and $50\%,\;33.3\%,\;and\;16.7\%$ in concurrent group, respectively. Chemotherapy regimen was CF (cisplatin and 5-FU) in both groups, and drug delivery method also same. Cisplatin $100\;mg/m^2$ was intravenously infused on day 1, and 5-FU $1,000\;mg/m^2$ on day $2\~6$. This was repeated at 3 weeks interval. At the end of radiotherapy, total cycles of chemotherapy were $1\~3$ (median 2) in both groups. Conventionally fractionated radiotherapy with daily fraction size $1.8\~2.0\;Gy$ and 5 fractions/week was done. Total dose was $69.4\~86\;Gy$(median 73.4 Gy) for induction group, and $69.4\~75.4\;Gy$ (median 70.8 Gy) for concurrent group. Follow-up time was $9\~116$ months (median 40.5 months) for induction group, $14\~29$ months (median 21 months) for concurrent group, respectively. Results : Overall 2 year survival rate (2YSR) for all patients was $78.7\%$. According to treatment modality, 2YSR were $77\%$ for induction group, $87\%$ for concurrent group (p>0.05). 2 year disease-free survival rate were $56\%$ and $81\%\;(p>0.05)$, respectively. Complete response to treatment were $75.5\%$ for induction group and $91.7\%$ for concurrent group, but there was no statistical difference. The incidence of grade $3\~4$ hematologic toxicity during radiotherapy was not differ between two groups, but grade 2 leukopenia was more frequent in concurrent group $(18\%\;vs\;66.7\%)$Grade $3\~4$ mucositis was more frequent in concurrent group $(4.0\%\;vs\;33.3\%)$. Overall incidence of grade $3\~4$ acute toxicity during radiotherapy was more frequent in concurrent group $(6.0\%\;vs\;41.7\%,\;p=0.005)$. Conclusion : Concurrent chemo-radiotherapy showed a trend of improvement in short-term survival and in treatment response when compared with induction chemotherapy-radiotherapy in locally advanced nasopharyngeal carcinoma. More controlled randomized trial are needed.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.15 no.2
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• pp.160-167
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• 2004

Objectives : There have been very few studies on the compliance of methylphenidate-immediate releasing form(MPH-IR), which is the most frequently used drug in Korea, in Attention Deficit Hyperactivity Disorder(ADHD). This study was conducted to investigate the compliance rate and the related factors in the one year pharmacotherapy process via OPD for children with ADHD. Method : Total 100 ADHD patients were selected randomly among patients who have been treated with MPH-IR from September in 2002 to December in 2002. All the selected patients were diagnosed with DSM-IV-ADHD criteria and fulfilled the inclusion criteria. In March, 2003(at the time of 6 month treatment), all the patients and parents received the questionnaire for the compliance and satisfaction for MPH-IR treatment. In October 2003(at time of 1 year treatment), we, investigators evaluated the socio-demographic variables, developmental data, medical data, family data, comorbid disorders, treatment variables, and compliance rate. Through these very comprehensive data, The compliance rate at the time of mean 1 year treatment and the related factors were investigated. Result : 1) In the questionnaire for compliance and satisfaction for MPND treatment, the 60% of respondents(parents) reported more than moderate degree of satisfaction in the effectiveness of MPND. Their compliance rate for the morning prescription was 81%, but the rate of afternoon prescription was 43%. 2) In the evaluation at the time of 1 year treatment(October 2003), the 38% of parents were dropped out from the OPD treatment. The mean compliance rate for the 1 year treatment was 62%. the 38% of parents were dropped out from the OPD treatment. The mean compliance rate for the 1year treatment was 62%. 3) Compared with the noncompliant group(drop-out group), compliant group showed higher total, verbal and performance IQ scores. In the treatment variables, higher reposponder rate(clinician rating), higher medication dosage and more compliance rate in afternoon prescription were found in the compliant group compared with the noncompliant group. There were no statistical differences in the demographic variables(age, sex, SES, parental education level), medical data, developmental profiles and academic function. Conclusion : To our knowledge, this is the first report about the compliance rate of the MPH-IR treatment for the children with ADHD. The compliance rate at the time of mean 1year treatment was 62%, which was comparable with other studies performed in foreign countries, especially States. In this study, the compliance related factors were IQ score, clinical treatment response, dosage of MPH-IR, and early compliance for the afternoon prescription. These results suggest that clinician plan the strategies for the promotion of the early compliance for the after prescription and enhancement of overall treatment response.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.16 no.2
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• pp.219-230
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• 2005

Objectives : This study was designed to compare the demographic data, clinical characteristics, developmental delay, and psychological tests between childhood-onset and adolescent-onset schizophrenic in-patients. Methods Medical records of the 17 childhood-onset (very early onset) Schizophrenia and 16 adolescent-onset (early onset) Schizophrenia in-patients were reviewed. Sex, age, psychiatric past history, prodromal symptoms and period, subtype, co-morbid disease, developmental delay, prescribed drug and dosage, treatment response, intelligence quotient (IQ), and Rorschach test were evaluated. Results : The mean admission age of childhood-onset (very early onset) group and adolescent-onset (early onset) group were 12.69$({\pm}2.34)$ and 15.13$({\pm}1.04)$ years. The mean onset age of childhood-onset(very early onset) group and adolescent-onset (early onset) group were 10.79$({\pm}1.95)$ and 14.46$({\pm}0.82)$ years. The mean prodromal period of childhood-onset (very early onset) group and adolescent-onset (early onset) group were 15.94$({\pm}12.33)$ and 8.06$({\pm}6.10)$ month. The time to remission period of childhood-onset (very early onset) group and adolescent-onset (early onset) group were 50.58$({\pm}24.67)$ and 30.06$({\pm}18.04)$ days. Longer time to remission period in childhood-osnet (very early onset) group was associated with earlier age of onset. The mean of total IQ, performance IQ, verbal IQ were at an average level. Discussion : Childhood-onset (very early onset) group and adolescent-onset (early onset) group Schizophrenia had different clinical and psychological features including prodromal period, and IQ subtests.

• Tuberculosis and Respiratory Diseases
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• v.62 no.5
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• pp.406-416
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• 2007

Background: Single nucleotide polymorphisms (SNPs), which consist of a substitution of a single nucleotide pair, are the most abundant form of genetic variations occurring with a frequency of approximately 1 per 1000 base pairs. SNPs by themselves do not cause disease but can predispose humans to disease, modify the extent or severity of the disease or influence the drug response and treatment efficacy. Single nucleotide polymorphisms (SNPs), particularly those within the regulatory regions of the genes often influence the expression levels and can modify the disease. Studies examining the associations between SNP and the disease outcome have provided valuable insight into the disease etiology and potential therapeutic intervention. Traditionally, the genotyping of SNPs has been carried out using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP), which is a low throughput technique not amenable for use in large-scale SNP studies. Recently, TaqMan real-time PCR chemistry was adapted for use in allelic discrimination assays. This study validated the accuracy and utility of real-time PCR technology for SNPs genotyping Methods: The SNPs in promoter sequence (-37 and -524) of lung cancer suppressor gene, RRM1 (ribonucleotide reductase M1 subunit) with the genomic DNA samples of 89 subjects were genotyped using both real-time PCR and PCR-RFLP. Results: The discordance rates were 2.2% (2 mismatches) in -37 and 16.3% (15 mismatches) in -524. Auto-direct sequencing of all the mismatched samples(17 cases) were in accord with the genotypes read by real-time PCR. In addition, 138 genomic DNAs were genotyped using real-time PCR in a duplicate manner (two separated assays). Ninety-eight percent of the samples showed concordance between the two assays. Conclusion: Real-time PCR allelic discrimination assays are amenable to high-throughput genotyping and overcome many of the problematic features associated with PCR-RFLP.

• Investigative Magnetic Resonance Imaging
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• v.13 no.2
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• pp.146-151
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• 2009

Purpose : To evaluate magnetic resonance (MR) imaging features of non-surgically treated tuberculous spondylitis and to evaluate the relationships between these features and clinical outcomes. Materials and Methods : Data from ten patients (male:female=6:4, mean age=45 years) with clinically proven tuberculous spondylitis who were treated nonsurgically over three months were analyzed retrospectively from 2000 to 2007. MRI was performed at least three times for each patient, at baseline, every three or six months, and at the end of treatment. All images were analyzed by two radiologists. Results : The mean follow-up period for the MR examination was 10.1 months (range, 4-17 months). Six patients had clinically complete resolution of tuberculous spondylitis with medication treatment only. Four patients were treated with surgical management alongside medication. All ten patients were divided into two groups by clinical outcome; six patients with complete treatment and four patients with incomplete treatment. In the complete treatment group, follow-up MR findings showed a loss of subligamentous spread of abscesses, decreased size of abscesses, no interval changes in vertebral body heights, and fatty changes in spinal lesions. MR findings in the incomplete treatment group showed bone marrow edema extension to adjacent vertebra, extension of the abscesses, and decreased height of the vertebral bodies. Conclusion : During the nonsurgical management of tuberculous spondylitis, MR imaging may play a role in predicting patient response to antituberculous drug treatment.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.2
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• pp.321-326
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• 2011

The aim of the present study was to investigate antihyperglycemic effect of Gleditschiae Spina (GS) in streptozotocin (STZ)-nicotinamide (NA)-induced type 2 diabetic rats. The rats were divided into four groups: normal control (NC), diabetic control (DC), diabetic rats supplemented with acarbose (AC, 4 mg/kg), and with GS ethanol extracts (GSE, 50 mg/kg). Weekly fasting blood glucose (FBG) for 10 weeks and oral glucose tolerance test (OGTT) at 10th week were monitored using glucose oxidase-peroxidase reactive strips. The FBG level was significantly reduced in AC group after 8 weeks and in GSE group at the end of period. The AUCs for the glucose response from OGTT and blood glucose level after sacrifice were significantly lower in the AC and GSE groups than the DC group. GSE supplementation significantly increased plasma total radical-trapping antioxidant potential (TRAP) in STZ-NA-induced diabetic rats, compared with DC group. The present study indicates that GSE could ameliorate type 2 diabetes and be comparable to acarbose, a standard hypoglycemic drug. Also, we suggest that GSE may possess antioxidant activity against the STZ-NA-induced oxidative stress.

• Korean Journal of Pharmacognosy
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• v.35 no.4 s.139
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• pp.368-374
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• 2004

Cervical cancer is one of the leading causes of female death. Viral oncoproteins E6 and E7 are selectively retained and expressed in carcinoma cells infected with HPV (Human papillomavirus) type 16. The HPV is cooperated in immotalization and transformation of primary keratinocyte. E6 and E7 oncoproteins interfere the functions of tumor suppressor proteins p53 and retinoblasoma protein (pRb), respectively. Among a lots of natural products, Artemisia scoparia Waldstein et Kitamura has inhibitory effects on the binding between E6 oncoprotein and tumor suppressor p53, or the binding between E6 and E6 associated protein (E6AP), an E3 ubiquitin-protein ligase. HPV oncoprotein inhibitors from Artemisia scoparia W. were isolated by solvent partition and column chromatography (Silica gel, RP-18) and the inhibitory compounds were finally purified by HPLC using an ELISA screening system based on the binding between E6 and E6AP. The aim of this study is to identify the structure of inhibitory compounds and to investigate whether these compounds have inhibitory effects on the functions of E6 oncoprotein. We investigated whether 3,5-di-O-caffeoylquinic acid (DCQA) extracted from Artemisia scoparia W. Could inhibit the function of E6 oncoprutein. DCQA inhibited the in vitro binding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53 and also inhibited the proliferation of human cervical cancer cell lines (SiHa and CaSKi) in a dose response manner. These results suggest that DCQA inhibited the function of E6 oncoprotein, suggesting that it can be used as a potential drug for the treatment of cervical cancers infected with HPV.

• Tuberculosis and Respiratory Diseases
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• v.47 no.1
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• pp.77-89
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• 1999

Background: High-dose chemotherapy is increasingly employed in many refractory malignant diseases. This therapy has been reported to increase response rate and survival benefits but it is also associated with higher treatment-related morbidity and mortality. We evaluated clinical characteristics and course of the pulmonary toxicity following high-dose chemotherapy with peripheral blood stem cell transplantation. Methods: Ninety-seven patients who had received high-dose chemotherapy with peripheral blood stem cell transplantation were evaluated. Five patients who developed lung lesions which were not related to infection nor primary malignant disease underwent transbronchial lung biopsy. The patients' clinical characteristics, treatments, and prognosis were reviewed retrospectively. Results: Five patients(5.1%) developed idiopathic pneumonia syndrome. The high dose chemotherapy regimens employed were cyclophosphamide, BCNU, and cisplatin in 3 cases, one case of BCNU, etoposide, Ara-C, and cyclophosphamide combination, and a regimen consisting of BCNU, etoposide, Ara-C, and melphalan. The total dose of BCNU used was 300-400 mg/$m^2$ and that of cyclophosphsmide was 6,000 mg/$m^2$. All of 5 patients received radiation therapy before this treatment. After an average duration of 14 weeks (4-26 weeks) of high-dose chemotherapy, patients developed cough, dyspnea and fever. The chest X-rays showed bilateral diffuse infiltration in 3 cases and the focal infiltration in the other 2 cases. All the patients received corticosteroid therapy as a treatment for the lung lesions. Two of them progressed to acute respiratory distress syndrome and died. Three patients recovered without residual lung lesion but one of them died of dilated cardiomyopathy. Conclusion: High-dose chemotherapy with peripheral blood stem cell transplantation especially which containing BCNU regimen may develop idiopathic pneumonia syndrome related to pulmonary toxicity and corticosteroid therapy may be bel1eficial in some cases.

• Journal of Korean Neurosurgical Society
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• v.30 no.5
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• pp.553-560
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• 2001

Objective : The objective of this study was to determine the photodynamic therapeutic response of U-87 human glioma cell in vitro as well as in the nude rat xenograft model using photofrin as photosensitizer. Material and Method : U-87 cells were cultured on 96-well culture plates, photofrin(Quadralogic Technologies Inc., Vancouver, Canada) was added into the cell culture medium at concentration of $1{\mu}g/ml$, $2.5{\mu}g/ml$, $5{\mu}g/ml$, $10{\mu}g/ml$ and $20{\mu}g/ml$. 24 hour after drug treatment, cells were treated with optical(632nm) irradiation of $100mJ/cm^2$, $200mJ/cm^2$ and $400mJ/cm^2$. Photofrin(12.5mg/kg, i.p.) was administered to 28 nude rats containing intracerebral U-87 human glioma as well as 26 normal nude rats. 48 hours after administration, animals were treated with optical irradiation(632nm) of $35J/cm^2$, $140J/cm^2$ and $280J/cm^2$ to exposed tumor and normal brain. The photofrin concentration was measured in tumor and normal brain in a separate population of animals. Results : By MTT assay, there was 100% cytotoxicity at any dose of photofrin with optical irradiation of $200mJ/cm^2$ and $400mJ/cm^2$. But at the optical irradiation of $100mJ/cm^2$ cells were killed in dose dependent manner 28.5%, 49.1%, 54.4%, 78.2%, and 84.6% at concentration of $1{\mu}g/ml$, $2.5{\mu}g/ml$, $5{\mu}g/ml$, $10{\mu}g/ml$ and $20{\mu}g/ml$, respectively. Dose dependent PDT lesions in both tumor and normal brain were observed. In the tumor lesion, only superficial tissue damage was found with optical irradiation of $35J/cm^2$. However, in the optical irradiation group of $140J/cm^2$ and $280J/cm^2$ the volume of lesions was measured of $7.2mm^3$ and $14.0mm^3$ for treatment at $140J/cm^2$ and $280J/cm^2$, respectively. The U-87 bearing rats showed a photofrin concentration in tumor tissue of $6.53{\pm}2.16{\mu}g/g$, 23 times higher than that found in the contralateral hemisphere of $0.28{\pm}0.15{\mu}g/g$. Conclusion : Our data indicate that the U-87 human glioma in vitro and in the xenografted rats is responsive to PDT. At these doses, a reproducible injury can be delivered to human glioma in this model. Strategies to spare the normal brain collateral damage are being studied.

• The Journal of the Korean Society for Microbiology
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• v.21 no.3
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• pp.311-329
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• 1986

The experimental exposure of animals to sources of ultraviolet radiation (UVR) which emit their energy primarily in the UVB region (280-320nm) is known to result in a number of well-described changes in the recipient's immune competence. Two such changes include a depressed capacity to effectively respond immunologically to transplants of syngeneic UVR tumors and a markedly reduced responsiveness to known inducers of delayedtype (DTH) and contact hypersensitivity (CH) reactions. The results of experiments that were designed to elucidate the mechanisms responsible for UVR-induced immunomodulation have implicated: 1) an altered pattern of lymphocyte recirculation, 2) suppressor T cells(Ts), 3) deviations in systemic antigen presenting cell (APC) potential. 4) changes in the production of interleukin-1-like molecules, and 5) the functional inactivation of epidermal Langerhans cells in this process. The exposure of skin to UVR, therefore, causes a number of both local and systemic alterations to the normal host immune system. In spite of this seeming complexity and diversity of responses, our recent studies have established that each of the UVR-mediated changes is probably of equal importance to creating the UVR-induced immunocompromised state. Normal animals were exposed to low dose UVR radiation on their dorsal surfaces under conditions where a $3.0\;cm^2$ area of skin was physically protected from the light energy. Contact sensitization of these animals with DNFB, to either the irradiated or protected back skin, resulted in markedly reduced CH responses. This was observed in spite of a normal responsiveness following the skin sensitization to ventral surfaces of the UVR-exposed animals. Systemic treatment of the low dose UVR recipients with the drug indomethacin (1-3 micrograms/day) during the UVR exposures resulted in a complete reversal of the depressions observed following DNFB sensitization to "protected" dorsal skin while the altered responsiveness found in the group exposed to the skin reactive chemical through directly UVR-exposed sites was maintained. These studies implicate the importance of EC as effective APC in the skin and also suggest that some of the systemic influences caused by UVR exposure involve the production of prostaglandins. This concept was further supported by finding that indomethacin treatment was also capable of totally reversing the systemic depressions in CH responsiveness caused by high dose UVR exposure (30K joules/$m^2$) of mice. Attempts to analyze the cellular mechanisms responsible established that the spleens of all animals which demonstrated altered CH responses, regardless of whether sensitization was through a normal or an irradiated skin site, contained suppressor cells. Interestingly, we also found normal levels of T effector cells in the peripheral lymph nodes of the UVR-exposed mice that were contact sensitized through normal skin. No effector cells were found when skin sensitization took place through irradiated skin sites. In spite of such an apparent paradox, insight into the probable mechanisms responsible for these observations was provided by establishing that UVR exposure of skin results in a striking and dose-dependent blockade of the efferent lymphatic vessels in all peripheral lymph nodes. Therefore, the afferent phases of immune responses can apparently take place normally in UVR exposed animals when antigen is applied to normal skin. The final effector responses, however, appear to be inhibited in the UVR-exposed animals by an apparent block of effector cell mobility. This contrasts with findings in the normal animals. Following contact sensitization, normal animals were also found to simultaneously contain both antigen specific suppressor T cells and lymph node effector cells. However, these normal animals were fully capable of mobilizing their effector cells into the systemic circulation, thereby allowing a localization of these cells to peripheral sites of antigen challenge. Our results suggest that UVR is probably not a significant inducer of suppressor T-cell activity to topically applied antigens. Rather, UVR exposure appears to modify the normal relationship which exists between effector and regulatory immune responses in vivo. It does so by either causing a direct reduction in the skin's APC function, a situation which results in an absence of effector cell generation to antigens applied to UVR-exposed skin sites, inhibiting the capacity of effector cells to gain access to skin sites of antigen challenge or by sequestering the lymphocytes with effector cell potential into the draining peripheral lymph nodes. Each of these situations result in a similar effect on the UVR-exposed host, that being a reduced capacity to elicit a CH response. We hypothesize that altered DTH responses, altered alloresponses, and altered graft-versus-host responses, all of which have been observed in UVR exposed animals, may result from similar mechanisms.