• Radiation Oncology Journal
• /
• v.18 no.2
• /
• pp.85-91
• /
• 2000

Purpose : The aim of this study is to look for the possible efficacy of postoperative external irradiation for incompletely resected meningiomas. Methods and Materials : From August 198: to January 1997, forty-four patients with intracranial meningioma were treated by postoperative external irradiation. Of the 44 meningiomas, 18 transitional, 13 meningotheliomatous, 6 hemangiopericytic, 4 atypical, 2 fibroblastic and 1 malignant meningioma were identified. We classified all patients into two groups by the histology. The benign group was consisted of the meningotheliomatous, transitional and fibroblastic types. The malignant group was consisted of the atypical, hemangiopericytic and malignat types. In the means of surgery, 37 patients were resected incompletely and 7 patients were managed by biopsy only. After surgery, all patients were received postoperative external irradiation. Radiotherapy was deliverd using Co-60 or 4 MV photon beam to a total dose of 50 to 65 Gy (mean dose 57.4 Gy) with a 1.8 to 2 Gy per fraction. The median follow-up was 48 months (range : 21 $\~$ 101 months). Multivariate analysis of the Influence by age, sex, location, histology and radiation dose on local control has been done using Cox's proportional hazard model. Results : 5-year local control rate was 93.8$\%$ for the benign histology and 51.8$\%$ for the malignant histology (p=0.0110) and overall local control rate at 5 years was 87.4$\%$. The analysis of the prognostic factors, such as age, sex, location, and radiation dose were not significant except for the histology. Conclusion : Adjuvant postoperative external irradiation appears to be significantly improved local control in the patients with incompletely resected meningiomas.

• Radiation Oncology Journal
• /
• v.17 no.3
• /
• pp.187-194
• /
• 1999

Purpose : The aim of this study is to look for the possible efficacy of external irradiation for locally advanced papillary thyroid cancers (stage pT4 or Nl ). Methods and Materials : From August 1981 through September 1997, 91 Patients with locally advanced papillary thyroid cancers (stage pT4 or Nl ) have been treated with external irradiation and followed up at our clinic. All of the patients have been treated with surgical resection. After surgery, 23 patients received postoperative external irradiation with or without ablative radioiodine therapy, whereas the other 68 patients were treated with ablative radioiodine therapy alone. Distributions of sex, age, and stage were comparable in both irradiated and nonirradiated groups. Multivariate analysis of the influence by age, sex, stage, ablative radioiodine therapy and external irradiation on local control were peformed by using Cox's proportional hazard model. Results : Overall survival rates at 7 years were of no significant difference in both groups. There were $98.1\%$ for no RT group and $90\%$ for RT group (p=0.506). 5-year local control rates were significantly different, these were $95.2\%$ for RT group and $67.5\%$ for no RT group (p=0.0408). An analysis of the prognostic factors, age, sex, stage, and RAI were not significant variables, except for the external irradiation. Conclusion : Adjuvant postoperative external irradiation did not affect overall survival, but significantly improved local control in the patients with locally advanced papillary thyroid cancers (stage pT4 or lympy node involvement).

• Radiation Oncology Journal
• /
• v.23 no.4
• /
• pp.211-216
• /
• 2005

Purpose: It has been reported that all-trans retinoic acid (ATRA) can inhibit glioma growing in vitro. However, clinical trials with ATRA alone in gliomas revealed modest results. ATRA has been shown to increase radiosensitivity in other tumor types, so combining radiation and ATRA would be one of alternatives to increase therapeutic efficacy in malignant gliomas. Thus, we intended to know the role of catalase, which is induced by ATRA, for radiosensitivity if radiation-reduced reactive oxygen species (ROS) is removed by catalase, the effect of radiation will be reduced. Materials and Methods: A rat glioma cell line (36B10) was used for this study. The change of catalase activity and radiosensitivity by ATRA, with or without 3-amino-1, 2, 4-triazole (ATZ), a chemical inhibitor of catalase were measured. Catalase activity was measured by the decomposition of $H_2O_2$ spectrophotometrically Radiosensitivity was measured with clonogenic assay. Also ROS was measured using a 2, 7-dichlorofluorescein diacetate spectrophotometrically. Results: When 36B10 cells were exposed to 10, 25 and $50{\mu}M$ of ATRA for 48 h, the expression of catalase activity were increased with increasing concentration and incubation time of ATRA. Catalase activity was decreased with increasing the concentration of AT (1, $10{\mu}M$) dose-dependently. ROS was increased with ATRA and it was augmented with the combination of ATRA and radiation. ATZ decreased ROS production and increased cell survival in combination of ATRA and radiation despite the reduction of catalase. Conclusion: The increase of ROS is one of the reasons for the increased radiosensitivity in combination with ATRA. The catalase that is induced by ATRA doesn't decrease ROS production and radiosensitivity.

• Korean Journal of Head & Neck Oncology
• /
• v.14 no.2
• /
• pp.156-163
• /
• 1998

Background & Objectives: Frameless fractionated stereotactic radiotherapy(FFSRT) is a modification of stereotactic radiosurgery(SRS) with radiobiologic advantage of fractionation without losing mechanical accuracy of SRS. Local recurrence of head and neck cancer at or near skull base benefit from reirradiation. Main barrier to successful palliation is dose limitation secondary to normal tissue tolerance. We try to evaluate the efficacy and safety of FFSRT as a new modality of reirradaton in these challenging patients. Materials & Methods: Seven patients with recurrent head & neck cancer involving at or near skull base received FFSRT from September 1995 to November 1997. Six patients with nasopharyngeal cancer had received induction chemotherapy and curative radiation therapy. One patient with maxillary sinus cancer had received total maxillectomy and postoperative radiation therapy as a initial treatment. Follow-up ranged from 11 to 32 months with median of 24 months. Three of 7 patients received hyperfractionated radiation therapy(1.1-1.2Gy/fraction, bid, total 19.8-24Gy) just before FFSRT. All patients received FFSRT(3-5Gy/fraction, total 15-30Gy/5-10fractions). Chemotherapy(cis-platin $100mg/m^2$) were given concurrently with FFSRT in four patients. Second course of FFSRT were given in 4 patients with progression or recurrence after initial FFSRT. Because IF(irregularity factor; ratio of surface area of target to the surface area of sphere with same volume as a target) is too big to use conventional stereotactic RT using multiple arc method for protection of radiation damage to critical normal tissue, all patients received FFSRT with conformal method using irregular static ports. Results: Five of 7 patients showed complete remission in follow-up CT &/or MRI. Three of these five patients who developed marginal, in-field, and out-field recurrences, respectively. Another one of complete responders has been dead of G-I bleeding without evidence of local recurrence. One partial responder who showed progressive disease 15 months after initial FFSRT has received additional FFSRT, and then he is well-being with symptomatic improvement. One minmal responder who showed progression of locoregional disease 9 months after $1^{st}$ FFSRT has received 2nd FFSRT, and then he is alive with stable disease. Five of 7 case had showed direct invasion to skull base and had complaint headache and various symptoms of cranial nerve involvement. Four of these five case showed improvement of neurologic symptoms after FFSRT. No significant neurologic complicaltion related to FFSRT was observed during follow-up periods. Tumor volumes were ranged from 3.9 to 50.7 cc and surface area ranged from 16.1 to $114.9cm^2$. IF ranged from 1.21 to 1.74. The average ratio of volume of prescription isodose shell to target volume was 1.02 that indicated the improvement of target coverage and dose distribution with FFSRT with conformal method compared to target coverage with FFSRT with multiple arc method. Conclusion: Our initial experience suggests that FFSRT with conformal method was relatively effective and safe modality in the treatment of recurrent head and neck cancer involving at or near skull base. Treatment benefit included good palliation of symptoms and reasonable radiographic response. However, more experience and additional follow-up are needed to better assess its ultimate role in treating these challenging patients.

• Journal of Life Science
• /
• v.25 no.7
• /
• pp.801-809
• /
• 2015

Homotypic cell adhesion (homotypic aggregation) in activated monocytes plays a central role in physiological and pathological processes including inflammatory responses, differentiation and migration. The extract of the Prunus mume Sieb. et Zucc. fruit (Maesil) has potential benefits to human health; such as anti-viral, anti-microbial, and anti-cancer activities. Indeed, Maesil extract may modulate inflammatory responses via interference with homotypic aggregation in monocytes. In the present study, the molecular mechanisms underpinning the therapeutic efficacy of Maesil extract in inflammatory diseases were investigated. It was found that Maesil extract inhibited homotypic aggregation in lipopolysaccharide (LPS)-activated monocytes. This was mediated by reduction of nitric oxide (NO) production, partly via inhibition of inducible nitric oxide synthase (iNOS) expression in LPS-activated THP-1 cells. It was confirmed that NO inhibition is a key mechanism in Maesil induced blockade of monocyte aggregation through identification of reversal of this inhibitory effect by the NO-producing agent S-nitroso-N-acetyl penicillamine (SNAP). In addition, Maesil extract significantly attenuated LPS-induced IκB-α phosphorylation and NF-κB translocation into the nucleus. In conclusion, Maesil extract exerts anti-inflammatory effects via inhibition of homotypic aggregation of LPS-activated monocytes through mechanisms involving the suppression of NO production and NF-κB activity, suggesting Maesil extract as a potential therapeutic candidate for the prevention and treatment of chronic inflammatory diseases.

• Tuberculosis and Respiratory Diseases
• /
• v.62 no.2
• /
• pp.113-118
• /
• 2007

Background: Paraquat is known to induce oxidant injury that results in multiorgan failure and lung fibrosis. Iron has been considered to play a key role in paraquat-induced oxidant lung injury. This study examined the effect of deferoxamine, an iron-chelating agent, in the treatment of paraquat poisoning. Methods: From September, 2001 to April, 2005, 28 patients with paraquat poisoning who were admitted at a medical intensive care unit of a University-affiliated hospital, were enrolled in this study. Sixteen patients were treated according to the paraquat poisoning treatment guidelines and 12 received an intravenous infusion of deferoxamine in addition to the treatment guidelines. Results: There were no differences between the two groups in terms of age, gender, severity of paraquat poisoning, and the time elapsed from ingestion to presentation at hospital. There was no difference in overall mortality between the two groups but the incidence of respiratory failure in the deferoxamine group was higher than in the conventional group(4/7 versus 0/9, p=0.019). Conclusion: Deferoxamine seems to have no clinical benefit compared with the conventional treatment.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.28 no.5
• /
• pp.375-395
• /
• 2006

Purpose: Lingual nerve (LN) damage may be caused by either tumor resection or injury such as wisdom tooth extraction, Although autologous nerve graft is sometimes used to repair the damaged nerve, it has the disadvantage of necessity of another operation for nerve harvesting. Moreover, the results of nerve grafting is not satisfactory. The nerve growth factor (NGF) is well-known to play a critical role in peripheral nerve regeneration and its local delivery to the injured nerve has been continuously tried to enhance nerve regeneration. However, its application has limitations like repeated administration due to short half life of 30 minutes and an in vivo delivery model must allow for direct and local delivery. The aim of this study was to construct a well-functioning $rhNGF-{\beta}$ adenovirus for the ultimate development of improved method to promote peripheral nerve regeneration with enhanced and extended secretion of hNGF from the injured nerve by injecting $rhNGF-{\beta}$ gene directly into crush-injured LN in rat model. Materials and Methods: $hNGF-{\beta}$ gene was prepared from fetal brain cDNA library and cloned into E1/E3 deleted adenoviral vector which contains green fluorescence protein (GFP) gene as a reporter. After large scale production and purification of $rhNGF-{\beta}$ adenovirus, transfection efficiency and its expression at various cells (primary cultured Schwann cells, HEK293 cells, Schwann cell lines, NIH3T3 and CRH cells) were evaluated by fluorescent microscopy, RT-PCR, ELISA, immunocytochemistry. Furthermore, the function of rhNGF-beta, which was secreted from various cells infected with $rhNGF-{\beta}$ adenovirus, was evaluated using neuritogenesis of PC-12 cells. For in vivo evaluation of efficacy of $rhNGF-{\beta}$ adenovirus, the LNs of 8-week old rats were exposed and crush-injured with a small hemostat for 10 seconds. After the injury, $rhNGF-{\beta}$ adenovirus($2{\mu}l,\;1.5{\times}10^{11}pfu$) or saline was administered into the crushed site in the experimental (n=24) and the control group (n=24), respectively. Sham operation of another group of rats (n=9) was performed without administration of either saline or adenovirus. The taste recovery and the change of fungiform papilla were studied at 1, 2, 3 and 4 weeks. Each of the 6 animals was tested with different solutions (0.1M NaCl, 0.1M sucrose, 0.01M QHCl, or 0.01M HCl) by two-bottle test paradigm and the number of papilla was counted using SEM picture of tongue dorsum. LN was explored at the same interval as taste study and evaluated electro-physiologically (peak voltage and nerve conduction velocity) and histomorphometrically (axon count, myelin thickness). Results: The recombinant adenovirus vector carrying $rhNGF-{\beta}$ was constructed and confirmed by restriction endonuclease analysis and DNA sequence analysis. GFP expression was observed in 90% of $rhNGF-{\beta}$ adenovirus infected cells compared with uninfected cells. Total mRNA isolated from $rhNGF-{\beta}$ adenovirus infected cells showed strong RT-PCR band, however uninfected or LacZ recombinant adenovirus infected cells did not. NGF quantification by ELISA showed a maximal release of $18865.4{\pm}310.9pg/ml$ NGF at the 4th day and stably continued till 14 days by $rhNGF-{\beta}$ adenovirus infected Schwann cells. PC-12 cells exposed to media with $rhNGF-{\beta}$ adenovirus infected Schwann cell revealed at the same level of neurite-extension as the commercial NGF did. $rhNGF-{\beta}$ adenovirus injected experimental groups in comparison to the control group exhibited different taste preference ratio. Salty, sweet and sour taste preference ratio were significantly different after 2 weeks from the beginning of the experiment, which were similar to the sham group, but not to the control group.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
• /
• v.14 no.1
• /
• pp.12-25
• /
• 2003

Objectives：As increasing number of new antidepressants have been being introduced in clinical practice, pharmacological understanding has been broadened. These changes mandate new information and theories to be incorporated into the treatment process of children with depressive disorders. In light of newly coming knowledge, this review intended to recapitulate the characteristics of new antidepressants and to consider the pivotal issues to develope guidelines for the treatment of depression in childhood and adolescence. Methods：Searching the Pub-Med online database for the articles with the key words of 'new', 'antidepressants' and 'children' ninety-seven headings of review articles were obtained. The author selected the articles of pertinent subjects in terms of either treatment guideline or psychopharmacology of new antidepressants. When required, articles about the clinical effectiveness of individual antidepressants were separatedly searched. In addition, the safety information of new antidepressants was acquired by browsing the official sites of the United States Food and Drugs Administration and Department of Health and Human Services. Results：1) For the clinical course, treatment phase, and treatment outcome, the reviews or treatment guidelines adopted the information from adult treatment guidelines. 2) Systematic and critical reviews unambiguously concluded that selective serotonin reuptake inhibitors(SSRIs) excelled tricyclic antidepressants( TCAs) for both efficacy and side effect profiles, and were recommend for the first-line choice for the treatment of children with depressive disorders. 3) New antidepressants generally lacked treatment experiences and randomized controlled clinical trials. 4) SSRIs and other new antidepressants, when used together, might result in pharmacokinetic and/or pharmacodynamic drug-to-drug interaction. 5) The difference of the clinical effectiveness of antidepressants between children and adults should be addressed from developmental aspects, which required further evidence. Conclusion：Treatment guidelines for the pharmacological treatment of childhood and adolescence depression could be constructed on the basis of clinical trial findings and practical experiences. Treatment guidelines are to best serve as the frame of reference for a clinician to make reasonable decisions for a particular therapeutic situation. In order to fulfill this role, guidelines should be updated as soon as new research data become available.

• Tuberculosis and Respiratory Diseases
• /
• v.44 no.3
• /
• pp.547-558
• /
• 1997

Background : Tumor necrosis factor(TNF) has been considered as an important candidate for cancer gene therapy based on its potent anti-tumor activity. However, since the efficiency of current techniques of gene transfer is not satisfactory, the majorities of current protocols is aiming the in vitro gene transfer to cancer cells and re-introducing genetically modified cancer cells to hoot. In previous study, it was shown that TNF-sensitive cancer cells transfected with TNF-$\alpha$ cDNA would become highly resistant to TNF. Understanding the mechanisms of TNF-resistance in TNF-$\alpha$ gene transfected cancer cells would be an important step for improving the efficacy of cancer gene therapy as well as for better understandings of tumor biology. This study was designed to evaluate the role of new protective protein synthesis in the acquired resistance to TNF of TNF-$\alpha$ gene transfected cancer cells. Method : We transfected TNF-$\alpha$ c-DNA to WEHI164, a murine fibrosarcoma cell line, using retroviral vector(pLT12SN(TNF)) and confirm the expression of TNF with PCR, ELISA, MIT assay. Then we determined the TNF resistance of TNF gene transfected cells(WEHI164-TNF) and the changes of TNF sensitivities after treatments with actinomycin D(transcription inhibitor) and cycloheximide ( translation inhibitor). Results : WEHI164 which was sensitive to TNF became resistant to TNF after being transfected with TNF-$\alpha$ gene and the resistance to TNF was partially reversed after treatment with actinomycin D, but not with cycloheximide. Conclusion : The acquired resistance to TNF after TNF-$\alpha$ gene transfection may be associated with synthesis of some protective proteins.

• Journal of Chest Surgery
• /
• v.31 no.4
• /
• pp.339-345
• /
• 1998

Arrhythmias are common after cardiac surgery and are multifactorial. Intravenous magnesium administration reduces the frequency of ventricular arrhythmias in patient with symptomatic heart failure or acute myocardial infarction. This study was designed to evaluate the role of magnesium in preventing PVCs(premature ventricular contractions) occurred frequently after coronary artery bypass graft(CABG). 50 consecutive patients were prospectively entered into a randomized trial to determine the efficacy of postoperative magnesium therapy on the incidence of cardiac arrhythmias after elective coronary artery bypass graft. The patients underwent coronary angiography, echocardiography, electrocardiography and clinical laboratory study preoperatively. Continuous electrocardiographic monitoring was done and magnesium level was checked 0, 3, 6, 12, 18, 24, 36, 48, 60 and 72 hours postoperatively. Study group of 25 patients were given 4g of magnesium continuously over the first 24 hours and then 2g/24hours from 25 to 72 hours. The clinical characteristics of both groups were similar(p<0.05). The preoperative mean serum magnesium concentration was similar in both study group, 1.59mg/dl and control group, 1.71mg/dl. The mean postoperative serum magnesium concentration in study group elevated significantly over postoperative 12hours through 36hours(p<0.05). The postoperative mean serum magnesium concentration in control group declined and remained significantly depressed over immediate postoperation through 72hours. The mean serum magnesium concentration was significantly greater in the study group compared with the control group over postoperative 3hours through 72hours(p<0.05). There was a significant decrease in the incidence of arrhythmias such as PVCs(p<0.01) which might jeopardize hemodynamics. There were no recognized adverse effects of magnesium Administration. In conclusion, prophylactic magnesium administration seems to lessen the incidence and severity of rrhythmias after coponary artery bypass graft.