• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.154-161
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• 2024

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder that causes progressive paralysis. L-Citrulline is a nonessential neutral amino acid produced by L-arginine via nitric oxide synthase (NOS). According to previous studies, the pathogenesis of ALS entails glutamate toxicity, oxidative stress, protein misfolding, and neurofilament disruption. In addition, L-citrulline prevents neuronal cell death in brain ischemia; therefore, we investigated the change in the transport of L-citrulline under various pathological conditions in a cell line model of ALS. We examined the uptake of [¹⁴C]L-citrulline in wild-type (hSOD1wt/WT) and mutant NSC-34/ SOD1^G93A (MT) cell lines. The cell viability was determined via MTT assay. A transport study was performed to determine the uptake of [¹⁴C]L-citrulline. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to determine the expression levels of rat large neutral amino acid transported 1 (rLAT1) in ALS cell lines. Nitric oxide (NO) assay was performed using Griess reagent. L-Citrulline had a restorative effect on glutamate induced cell death, and increased [¹⁴C]L-citrulline uptake and mRNA levels of the large neutral amino acid transporter (LAT1) in the glutamate-treated ALS disease model (MT). NO levels increased significantly when MT cells were pretreated with glutamate for 24 h and restored by co-treatment with L-citrulline. Co-treatment of MT cells with L-arginine, an NO donor, increased NO levels. NSC-34 cells exposed to high glucose conditions showed a significant increase in [¹⁴C]L-citrulline uptake and LAT1 mRNA expression levels, which were restored to normal levels upon co-treatment with unlabeled L-citrulline. In contrast, exposure of the MT cell line to tumor necrosis factor alpha, lipopolysaccharides, and hypertonic condition decreased the uptake significantly which was restored to the normal level by co-treating with unlabeled L-citrulline. L-Citrulline can restore NO levels and cellular uptake in ALS-affected cells with glutamate cytotoxicity, pro-inflammatory cytokines, or other pathological states, suggesting that L-citrulline supplementation in ALS may play a key role in providing neuroprotection.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.93-99
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• 2002

Purpose : We intended to decrease late CNS reaction after radical radiotherapy for an intracranial germinoma by using combined neoadjuvant chemotherapy and involved-field radiotherapy. The efficacy in terms of its acute toxicity and short-term relapse patterns was analyzed. Materials and Methods : Eighteen patients were treated with combined neoadjuvant chemotherapy and radiotherapy between 1995 and 2001. The chemotherapy regimen used was the Children's Cancer Group (CCG) 9921A (cisplatin, cyclophosphamide, VP-16, vincristine) for 5 patients younger than 16 years, BEP (bleomycin, VP-16, cisplatin) for 12 patients, and EP (VP-16, cisplatin) for 1 patient. The radiotherapy covered the whole craniospinal axis for 5 patients, the whole brain for 1, and the partial brain (involved field) for 12. the primary lesion received tumour doses between 3,960 and 5,400 cGy. Results : The male to female ratio was 16:2 and the median age was 16 years old. The tumors were located in the pineal gland in 12 patients, in the suprasellar region in 1, in the basal ganglia In 1, in the thalamus in 1. Three patients had multiple lesions and ventricular seedings were shown at MRI. In 3 patients, tumor cells were detected in the cerebrospinal fluid and MRI detected a spinal seeding in 2 patients. The response to neoadjuvant chemotherapy was complete remission in 5 patients, partial remission in 12, and no response in 1. However, after radiotherapy, all except 1 patient experienced complete remission. The toxicity during or after chemotherapy greater than or equal to grade III was remarkable; hematologic toxicity was observed in 11 patients, liver toxicity in none, kidney toxicity in none, and gastrointestinal toxicity in one. One patient suffered from bleomycin-induced pneumonitis. Radiotherapy was therefore stopped and the patient eventually died of respiratory failure. The other 17 are alive without any evidence of disease or relapse during an average of 20 months follow-up. Conclusion : A high response rate and disease control was experienced, which was the same as observed other studies and the morbidity from chemotherapy-induced toxicity was similar. With these results, the results from adjuvant chemotherapy and involved-field radiotherapy cannot be concluded to be equal to those from extended-field radiotherapy. The long term follow-up study on later complications are required in order to draw definite conclusions on the optimal management with minimum side effects.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.100-107
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• 2002

Purpose : The aim of this retrospective study was to assess the treatment results of 30 patients with pineal region tumors who were underwent radiation therapy under the diagnosis by either CT or MRI. There was no histological verification. We analyzed the prognostic factors that have a significant effect on the overall survival (OS) and disease free survival (DFS) rates. Materials and Methods : A total 30 patients with pineal region tumors were treated between March 1983 and August 1995. After a trial radiation therapy of $20\~30\;Gy/2\~3$ weeks, the patients were evaluated for their clinical response and radiological response by either CT or MRI and the final treatment direction was then decided. According to their response to the trial radiation therapy and the involved site, radiation treatment was given in various fields i.e., local, ventricle, whole brain and craniospinal field. The radiation dose ranged from 40.8 to 59.4 Gy (Median 50.4 Gy). The median follow up was 36.5 months $(4\~172\;months)$. Results : An improvement or stability in the clinical symptoms was observed in 28 patients $(93.3\%)$ after the trial RT. Nineteen patients $(63.3\%)$ showed a partial or complete response by CT or MRI. The two-year and five-year survival rates of the patients were $66.7\%$ and $55.1\%$, respectively. No significant difference in the survival rates according to the degree of the radiological response was abserved after the trial RT. The results of univariate analysis showed that age, the primary site, the performance status $(KPS\geq70)$, the degree of response after completing RT and the RT field were significant prognostic factors affecting the survival and disease free survival rates (p<0.05). Conclusion : The clinical and histological characteristics of pineal region tumors are quite complex and diverse. Therefore, it is difficult to predict the histological diagnosis and the possibility of radiocurability only with the initial response to RT. We think that the development of less invasive histological diagnostic techniques and tailored treatment to the histological type of each tumor are needed.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.328-333
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• 2002

Purpose : To analyze the treatment results of concurrent chemoradiation with oral 5-FU plus Gemcitabine or Paclitaxel for unresectable pancreatic cancer. Materials & Methods : The patients, who were diagnosed by imaging modalities or by explo-laparotomy, were treated with concurrent chemoradiation. Radiotherapy was delivered to primary tumor and regional lymph nodes, and the total dose was 45 Gy. Patients received Gemcitabine $1,000\;mg/m^2$ or Paclitaxel $50\;mg/m^2$ weekly and oral 5-FU daily The total number of cycles of chemotherapy ranged from 1 to 39 (median, 11 cycles). The follow-up period ranged from 6 to 36 months, Survival was analyzed using the Kaplan-Meier method. Results : Fifty-four patients between Jan. 1999 to Nov. 2001 were included in this study. Forty-two patients who completed the planned treatment were included in this analysis. The patients' age ranged from 37 to 73 years (median, 50 years) and the male to female ratio was 30:12. Treatment was interrupted for 12 patients due to: disease progression for 6 $(50\%)$, poor performance status for 4 $(33.3\%)$, intercurrent disease for 1 $(8.3\%)$, and refusal for 1 $(8.3\%)$. Response evaluation was possible for 40 patients. One patient gained complete remission and 24 patients gained partial remission, hence the response rate was $59\%$. The survival rates were $46.7\%\;and\;17.0\%$ at 1 year and 2 years, respectively with a median survival time of 12 months. Patients treated with Paclitaxel showed superior outcomes compared to those patients treated with Gemcitabine, in terms of both response rate and survival rate although this difference was not statistically significant. Grade III or IV hematologic toxicity was shown in 8 patients $(19\%)$, while grade III or IV non-hematologic toxicity was shown in 5 patients $(12\%)$. Conclusion : Concurrent chemoradiation with oral 5-FU and Gemcitabine or Paclitaxel improves both the response rate and survival rate in patients with unresectable pancreatic cancer. A prospective study should be investigated in order to improve both the patient selection and the treatment outcome as well as to reduce the toxicity.

• The Journal of Korean Society for Radiation Therapy
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• v.34
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• pp.13-20
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• 2022

Purpose : IMRT using Tomotherapy during nasopharyngeal cancer radiation therapy irradiate an accurate dose to tumor tissues and is effective to reduce a dose rapidly in normal tissues. However, this has high MU and long Beam On Time. This study aims to analyze differences in tumors, normal tissues and low-dose distributions and the efficiency of Split VMAT after applying Helical IMRT (Tomotherapy), VMAT (Linac : 2Arc) and Split VMAT (Linac : 4Arc) plans. Materials and Methods : This study targeted ten nasopharyngeal cancer patients of this hospital and compared three treatment plans (Helical IMRT, VMAT, Split VMAT). For Helical IMRT planning, Precision^® (Version 1.1.1.1, Accuray, USA) was used, and for VMAT and Split VMAT planning, Pinnacle^3® (Version 9.10, Philips, USA) was used. The total dose applied was 38.4 Gy / 32 Gy (Daily Dose 2.4 Gy (GTV + 0.3 cm) / 2 Gy (CTV + 0.3 cm) 16Fx), and for GTV + 0.3 cm (P_GTV), 95% of V_38.4Gy was prescribed. VMAT with an angle of 360° 2Arc was applied, and for Split VMAT, the field was divided into the right, the left, the top and the bottom and an angle of 360° 4Arc, 6MV was set. For evaluating the quality of the treatment plans, differences in tumors, normal tissues and low-dose area were compared, and Beam On Time was measured to analyze the efficiency. Results : When calculating the mean values of evaluation items of the three treatment plans (Helical IMRT, VMAT, Split VMAT) for the patients, the H.I (Homogeneity Index) of P_GTV was 1.04, 1.11 and 1.1 respectively, and the C.I (Confomity Index) of P_CTV was 1.03, 0.99 and 1.00 respectively. The mean dose of RT Parotid Gland (Gy) was 14.54, 17.06 and 14.76 respectively, the mean dose of LT Parotid Gland (Gy) was 14.32, 17.32 and 15.09 respectively, the maximum dose of P_Cord (Spinal Cord + 0.3 cm) (Gy) was 20.57, 22.59 and 21.06 respectively, and the maximum dose of Brain Stem (Gy) was 22.35, 23.99 and 21.68 respectively. The 50% isodose curve (cc) was 1332, 1132.5 and 1065.2 respectively. Beam On Time (sec) was 373.7, 130.7 and 254.4 respectively. Conclusion : Displaying a similar treatment plan quality to Helical IMRT, which is used a lot for head and neck treatment, Split VMAT reduced the low-dose area and Beam On Time and produced a better result than VMAT. Therefore, it is considered that Split VMAT is effective not only for nasopharyngeal cancer but also for other head and neck cancers.

• Journal of Chest Surgery
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• v.36 no.6
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• pp.397-403
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• 2003

Background: The research sought to identify the clinical features of pleomorphic carcinoma of the lung generally known as a rare subtype in accordance with the lung cancer classification done in 1999 by WHO. Material and Method: 250 cases of surgically resected lung cancers were collected in this hospital from January 1992 to December 2001. This study included 42 cases of pleomorphic carcinoma diagnosed through light microscope and immunohistochemistry. Result: Out of 42 cases, males represented 31, and females 11, the age ranged from 26 to 77. Main clinical symptoms included coughing, hemoptysis, sputum. Diagnoses disclosed the stage as stage la in 3 cases (7%), Ib in 16 (38%), IIa in 1 (2%), IIb in 8 (19%), IIIa in 15 (35%), and IIIb in 1 (2%). Out of these, no lymph node metastasis was represented in 23 cases (54%), while N1 and N2 involving lymph node metastasis was shown 19 cases (46%). A total of 19 patients developed metastasis, comprising the brain in 5 cases (26%), bone in 4 (21%), muscle in 4 (21%), Lymph node in 2 (10%), and 1 liver, ovary, contralateral lung, and adrenal gland, respectively. The size of the tumor ranged from 1 cm to 11 cm, averaging 5.85 cm. Out of the 42 patients, the total two-year and five-year survival rates in accordance with the Kaplan-Meier method represented 26% and 13%, respectively, These figures compared to the corresponding 44% and 34% in cases other than pleomorphic carcinoma from the survey target of 256 cases, proved to be significantly low (p<0.002). No significant difference was found in the survival rates compared between age and tumor size, between stage I and above stage II, and between N0 and above N1. Patients who developed postoperative metastasis all died, and showed significantly low survival rates (p<0.002) compared to those patients without metastasis. Conclusion: With the new diagnosis method of f999 WHO's lung cancer classification applied, pleomorphic carcinoma showed a higher prevalence rate than under previous classifications, their postoperative survival rate was significantly low compared to histologic type of non small cell lung carcinomas.

• Radiation Oncology Journal
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• v.10 no.1
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• pp.7-14
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• 1992

Between August 1988 and December 1991, 24 patients with intracranial tumors were treated with stereotactic radiosurgery(RS) using a 10 MV linear accelerator at Severance Hospital, Yonsei University College of Medicine. There were 5 meningiomas, 3 craniopharyngiomas, 9 glial tumors, 2 solitary metastases, 2 acoustic neurinomas, 2 pineal tumors, and 1 non-Hodgkin's lymphoma. Ten patients were treated as primary treatment after diagnosis with stereotactic biopsy or neuroimaging study. Nine patients underwent RS for post-op. residual tumors and three patients as a salvage treatment for recurrence after external irradiation. Two patients received RS as a boost followed by fractionated conventional radiotherapy. Among sixteen patients who were followed more than 6 months with neuroimage, seven patients (2 meningiomas, 4 benign glial tumors, one non-Hodgkin's lymphoma) showed complete response on neuroimage after RS and nine patients showed decreased tumor size. There was no acute treatment related side reaction. Late complications include three patients with symptomatic peritumoral brain edema and one craniopharyngioma with optic chiasmal injury. Through this early experience, we conclude that stereotactically directed single high doses of irradiation to the small intracranial tumors is effective for tumor control. However, in order to define the role of radiosurgery in the management of intracraniai tumors, we should get the long-term results available to demonstrate the benefits versus potential complications of this therapeutic modality.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.219-223
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• 1990

This is a retrospective review of 33 patients with large cell lung carcinoma treated at Yonsei University Cancer Center between Jan.1985 and Dec.1989. Of the thirty-three patients, twenty eight were men and five women. Median age was 59 years. Large cell undifferentiated carcinoma was the most common pathologic type, $78.8\%$. Twenty one of thirty three patients had far advanced diseases, stage IIIB-IV at the time of initial diagnosis. Pleural effusion was initially presented in 12 patients, and SVC syndrome appeared in 5 patients. As to location of the primary tumor,19($57.6\%$) appeared in the right lung and 14 ($42.4\%$) in the left. Patients with a centrally located primary tumor mass were nearly the same as those peripherally located (17 vs.16). Fifteen of thirty three patients developed metastasis involving not only bone, brain, the opposite lung, adrenal gland but also soft tissue, skin, pancreas and appendix. Treatment was individualized with 19 treated radically and 14 palliatively. After treatment, only two patients showed a complete response. Long term survival was observed in 4 patients: 1 (24 mo.),2 (41 mo.) and 1 (54 mo.). The overall 2 year survival rate was $14.3\%$ while the median survival time was 6.0 months. Through the analysis of the various factors affecting survival, we observed that pleural effusion-absent group and complete response group had a statistical significant better survival rate (p<0.01).

• Radiation Oncology Journal
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• v.15 no.4
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• pp.287-296
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• 1997

Purpose : This is study of whether 3-D conformal radiotherapy for carcino-mas of the ethmoid sinus were better than those treated with conventional 2-D plan, Materials and Methods : The 3-D conformal treatment Plans were compared with conventional 2-D plans in 4 patients with malignancy of the ethmoid sinus. Isodose distribution, dose statistics, and dose volume histogram of the planning target volume were used to evaluate differences between 2-D and 3-D plans. In addition. the risk of radiation exposure of surrounding normal critical organs are evaluated by means of point dose calculation and dose volume histogram. Results : 3-D conformal treatment plans for each patient that the better tumor coverages by the planning target volume with improved dose homo-geneity, compared to 2-D conventional treatment Plans in the same Patient. On the other hand, the radiation dose distributions to the surrounding nor-mal tissue organs, such as the orbit and optic nerves are not significantly reduced with our technique, but a substantial sparing in the brain stem and optic chiasm for each patient. Conclusion : Our findings represented the potential advantage of 3-D treatment planning for dose homogeniety as well as sparing of the normal tissue surrounding the tumor. However, further investigational studies are required to define the clinical benefit.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.2 no.2
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• pp.204-210
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• 1999

Purpose: We assessed the nutritional status and the alterations of oral diets during anti-cancer chemotherapy in pediatric oncology patients. Methods: Twenty children with malignancy were evaluated from day 0 until day 21 of post-chemotherapy. Nutritional status was assessed by body weight and biochemical parameters. The amount and calories of oral diets were assessed and food preference before and during chemotherapy were analysed by questionnelle. Results: 1) The underlying diseases of 20 patients were 11 acute lymphoblastic lekemia, 2 non-Hodgkin's lymphoma, 2 Langerhans cell histiocytosis, 2 Wilm's tumor, 2 brain tumor, 1 rhabdomyosarcoma. 2) There were weight loss during chemotherapy in 8 patients (40.0%), weigt gain in 5 patients (25.0%), and no significant changes in 7 patients (35.0%). 3) Biochemical parameters showed no significant interval changes during chemotherapy except elevation of serum ALT level. 4) The daily caloric intakes of oral diets during chemotherapy were 310~600 Kcal which was much lower than average of daily recommended calory for Korean children. 5) The most favorate food was altered by chemotherapy, from meats to carbonated beverages and unfavorate food was not altered as vegetables. Conclusion: The periodic assessment of nutritional status and dietary supplements according to preferred foods of patients will be required for the optimal nutrition care in cancer patients.