• The Journal of Korean Society for Radiation Therapy
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• v.16 no.2
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• pp.1-8
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• 2004

Purpose : What confirm a patient's set-up precisely is an important factor in stereotactic radiosurgery Especially, the tumor is moved by respiration in case of lung cancer. So it is difficult to confirm a exact location by L-gram or EPID. I will verify a exact patient's set-up about this sort of problem by verification system(exactrac 3.0) Materials and Methods : The patient that had lung cancer operated on stereotactic radiosurgery is composed of 6 people. The 5 patients use an ABC tool and 1 patient doesn't use it. I got such a patient's L-gram and EPID image by Body frame(elekta, sweden), compared Ant. image with Lat. one, and then confirmed a set-up. I fused DRR image of CT and X-ray image of Verification system(exactrac 3.0) 3 dimensional, analyzed the coordinate value(vertical, longitudinal, lateral), and then confirmed a difference of existing method. Results : In case of L-gram and EPID, we judge an exact of the patient's set-up subjectively, and on we could treat the patient with radiation. As a result of using Verification system(exactrac 3.0), coordinate value(vertical, longitudinal, lateral) of patient's set-up was comprised within 5mm. We could estimate a difference of the coordinate value visually and objectively. Consequently, Verification system(exactrac 3.0) was useful in judging an exact patient's set-up. Conclusion : In case of Verification system(exactrac 3.0), we can confirm an exact patient's set-up at any time whenever, However, there are several kinds of the demerit. First, it is a complex process of confirmation than the existing process. Second, thickness of CT scan slice is within 3mm. The last, X-ray image has to have shown itself clearly. If we solve this problem. stereotactic radiosurgery will be useful in treating patients why we can confirm an exact patient's positioning easily.

• Journal of Chest Surgery
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• v.40 no.2 s.271
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• pp.114-121
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• 2007

Background: Apoptosis plays a crucial role in carcinogenesis, as well as in development and tissue homeostasis. Terminal deoxyribonucleotidyl transferase mediated neck end labelling (TUNEL) and in situ nick end labelling (ISEL) have been used to investigate the apoptosis in tissues. Since the introduction of the M30 monoclonal antibody to overcome drawbacks of TUNEL and ISEL, the apoptosis in various tumors, with the exception of pulmonary carcinomas, has been studied. In this study, attempts were made to examine the correlation of apoptosis in non-small cell carcinomas, using both M30 and the expression of p53 protein, with the clinicopathological factors. Material and Method: Forty five patients with surgically resected non-small cell carcinomas were included. Immunohistochemical staining with M30 and p53 monoclonal antibody were peformed, and their expressions compared with the clinicopathological features. The overall survival time and recurrence-free survival time were calculated, and the factors influencing the survival time analyzed using a univariate analysis. The effects of the expression stati of M30 and p53 on the risks of cancer related to both death and recurrence were evaluated using a multivariate analysis. Result: The p53 positive group had many more M30 positive cells than the p53 negative group (p53 positive group; $61.7{\pm}26.8$ cells vs. p53 negative group; $45.6{\pm}29.6$ cells, p=0.005) and significantly more p53 positive patients showing at least 10 positive cells (apoptotic index, $Al{\ge}1$) on M30 staining (p53 positive group; 52.4% (11/21) vs. p53 negative group 16,7% (4/24), p=0.025). In the univariate analysis, the survival times in relation to smoking (pack-year), performance status (PS) and Al showed significant differences. The multivariate analysis demonstrated the relative risk (R.R) of cancer death increased almost 7.5-fold (R.R 7.482; 95% Cl $1.886{\sim}29.678$; p=0.004) and the risk of recurrence almost 3,8-fold (R.R 3.795; 95% Cl: $1.184{\sim}12.158$; p=0.025) in the high Al (${\ge}1$) compared to the low Al (<1) group. There was no prognostic effect of p53 expression on the survival time or risk of cancer death and recurrence. Conclusion: In non-small cell lung carcinomas, M30 immunohistochemistry was an excellent method for analyzing apoptosis; the high apoptotic index could be an adverse prognostic predictive factor.

• The Journal of the Korean bone and joint tumor society
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• v.10 no.2
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• pp.96-106
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• 2004

Purpose: To determine the usefulness of limb salvage operation with recycled autogenous bone graft in musculoskeletal malignant tumors. Materials and Methods: Twenty nine cases, who underwent limb salvage operation with recycled autogenous bone graft for the treatment of musculoskeletal malignant tumor between February 1990 and January 2003, were included. There were 18 males and 11 females and the mean age was 33 years (range, 10 to 65 years). The mean follow-up period was 51.8 months (range, 18 to 117 months). The Enneking stage was IIA in 10 cases and IIB in 19 cases. The recycling method of autogenous bone was deep freezing in 6 cases, autoclaving in 11 cases, pasteurization in 7 cases and the composite of autoclaving and vascularized fibular graft in 5 cases. The union of junctional site was evaluated radiologically and the functional results was analyzed by the grading systems of the International Symposium On Limb Salvages (ISOLS). Results: The mean union time was 7.2 months (range, 3 to 15 months). The union took 5.8 months (range, 4 to 8 months) in deep freezing, 9.7 months (range, 6 to 15 months) in autoclaving, 5.9 months (range, 4 to 8 months) in pasteurization, and 5 months (range, 4 to 8 months) in the composite of autoclaving and vascularized fibular graft. The mean functional evaluation percentage was 76.8% (range, 40 to 90%). It was 65.8% (range, 40 to 85%) in deep freezing, 76.6% (range, 40 to 90%) in autoclaving, 81.6% (range, 70 to 90%) in pasteurization, and 83.4% (range, 75 to 90%) in the composite of autoclaving and vascularized fibular graft. There were 6 cases of complications including 1 case of local recurrence, lung metastasis, infection, fracture, respectively and 2 cases of nonunion. Conclusion: The limb salvage operation with recycled autogenous bone graft is a useful treatment method for the musculoskeletal malignant tumors. Particularly, autoclaving is the most reliable sterilization method. The vascularized fibular graft can compensate decreased osteoinductivity and mechanical strength of recycled bone. So, the composite of autoclaving and vascularized bone graft seems to be a favorable treatment method for high grade malignant musculoskeletal tumors.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1981.05a
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• pp.14.2-14
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• 1981

In 1859, Billroth used the term "Zylindrome" to describe a tumor arising in the paranasal sinuses. This neoplasm has been referred to by a variety of terms including cylindroma, basaloma, basaloid adenoma, cribriform adenocarcinoma, and "adenoid cystic carcinoma", now preferred by most authors. It most often arises in the major and minor salivary glands of the head and neck but has been noted in the trachea, lung, breast, skin and elsewhere. The tumors are characterized by a high incidence of local recurrence and ultimate distant metastases after agrressive attempts at surgical excision. Radiation therapy, while not curative, has proved uniformly useful in promoting tumor regression and pain relief as a palliative treatment. The present study was undertaken to review our experience with a group of 44 patients with adenoid cystic carcinoma of the head and neck, diagnosed at the Jeonju Presbyterian Medical Center between 1963 and 1980. The results are as follows: 1. Forty-four cases of adenoid cystic carcinoma represented 40% of the malignant salivary gland tumors during the same interval. 2. The most common primary sites were palate(8 cases) and submandibular gland (8 cases). 3. Thirteen patients (31%) had tumors. that arose in the major salivary glands; 29 (69%), minor salivary glands. 4. Of the 44 patients, there were 21 males. and 23 females. 5. Age at diagnosis ranged from 19 to 78 years; the average age was 50 years. 6. The tumor size was more than 4cm to 6cm in its greatest diamension in 10 patients. Clinically positive cervical lymph nodes were found in 7 patients; distant metastasis in one case at the time of diagnosis. 7. Radical excision was employed in 27 patients, 14 of whom combined with radiotherapy. 8. Of 29 patients available for follow-up the gross and determinate 3-year survival rates were 27.6% and 44.4%, respectively. Among twelve patients who received radical excision, the 3-year survival was 58%. 9. Ten of these 44 patients had local recurrence in an interval of 3 to 88 months. from the initial treatment. Of ten recurrences, 3 occured after 5 years. 10. Distant metastasis was found in 3 of the treated patients. All were pulmonary metastasis.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.441-446
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• 1998

Purpose : The incidence of esophageal carcinoma is increasing. Radical surgery is the treatment of choice, but large proportion of the esophageal cancer patients are with unresectable disease at the time of initial diagnosis, so radiation therapy has been the major treatment modality. We carried out retrospective analysis to see the outcome and prognostic factors of radiation therapy alone for esophageal carcinoma. Methods and Materials : From June of 1979 through December 1992, 289 patients with esophageal carcinoma were treated with radiation therapy alone at Department of Therapeutic Radiology, Seoul National University Hospital. Of these patients, 84 patients were excluded as they were ineligible for the current analyses. Twenty-two patients had distant metastasis other than supraclavicular lymph node metastasis, 52 patients received less than 45 Gy, and 10 patient were lost from follow-up. Therefore 205 patients constituted the base population of this study. According to AJCC s1aging system, there were 2 patients with stage 1, 104 with stage IIA, 26 with stage IIB, 48 with stage III, and 25 with stage IV Radiation dose ranged from 4500 cGy to 6980 cGy with median dose of 5940 cGy. Follow-up period of the alive patients ranged from 77 to 180 months. Results : The Median survival period of all the patients was II months and the 2-, 5-, and 10-year overall survival rates were 22.4$\%$, 10.2$\%$ and 5.3$\%$, respectively. Most of the failures were local recurrences. Of 169 failures, 134 had local failure as a component and 111 had local recurrence only. The Lymph node was most common distant metastatic site and the next was the lung. The stage, T-stage, N-stage, functional status, tumor size, and aim of treatment were statistically significant prognostic factors for survival by univariate analyses. But only tumor size and N-stage were significant by multivariate analyses. Conclusion : We could get 10.2$\%$ of 5 year survival rate and 5.3$\%$ of 10 year survival rate with radiation therapy alone. The size of tumor and N-stage were statistically significant prognostic factors for survival on multivariate analyses.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.465-484
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• 2004

Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.

• The Korean Journal of Nuclear Medicine
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• v.35 no.3
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• pp.168-184
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• 2001

Purpose: KR-30035 (KR), a new MDR reversing agent, has been found to produce a similar degree of increased Tc-99m MIBI uptake in cultured tumor cells over-expressing mdr1 mRNA compared to verapamil (VP), with less cardiovascular effects. We assessed the MDR-reversing ability of KR in vivo, and effects of various doses of KR on MIBI uptake un nude mice hearing P-glycoprotein (P-gp) positive (+) and P-gp negative (-) human tumor xenografts. Methods: P-gp (+) HCT15/CL02 colorectal and P-gp (-) A549 non-small cell cancer cells were inoculated in each flank of 120 nude mice (20 mice ${\times}$ 6 groups). Group 1 (Gr1) mice received 10mg/kg KR i.p. 3 times $({\times}3)$; Gr2, 10mg/kg VP i.p. ${\times}3$; Gr3, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.p. ${\times}1$; Gr4, 10mg/kg KR i.p. ${\times}2$ + 50mg/kg i.p. ${\times}1$; Gr5, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.v. ${\times}1$, GrC, controls. The mice were then injected with Tc-99m MIBI and sacrificed after 10 min, 30 min, 90 min and 240 min. Tumor uptake of MIBI (TU) in each group was compared. Results: TU in P-gp (+) and (-) tumors were both higher in Gr1 than Gr2. Washout rate between the 10 min and 4 hours was lower in Gr5 of P-gp (+) cell(0.93) than the control. Percentage increases in TU were higher in P-gp (+) than P-gp (-) tumors with all KR doses. Pgp (+) TU were highest at 10 mon (173% of GrC) and persisted up to 240 min (144%) in Gr3. Larger doses of KR resulted in a lesser degree of increase in P-gp (+) TU at 10 min (130% in Gr4 and 117% un Gr5) and 30 min (178%, 129%), but TU increased by time up to 240 min (177%, 196%). Heart and lung uptakes were markedly increased in Gr4 and Gr5 at 10 and 30 min, likely due to cardiovascular effects. No mice died. Conclusion: These data further suggest that KR that has significantly lower cardiovascular toxicity than verapamil can be used as an active inhibitor of MDR. Even a relatively low dose of KR significantly increased Tc-99m MIBI uptake in P-gp (+) tumors in vivo.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.295-301
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• 1993

Since Jan. 1991 a prospective randomized study for Stage III unresectable non small cell lung cancer (NSCLC) has been conducted to evaluate the response rate and tolerance of induction chemotherapy with MVP followed by hyperfractionated radiotherapy and evaluate the efficacy of maintenance chemotherapy in Asan Medical Center. All patients in this study were treated with hyperfractionated radiotherapy (120 cGy/fx BID, 6480 cGy/54 fx) following 3 cycles of induction chemotherapy, MVP (Mitomycin C 6 $mg/m^2,$ Vinblastin 6 $mg/m^2,$ Cisplatin 60 $mg/m^2$) and then the partial and complete responders from induction chemotherapy were randomized to 3 cycles of adjuvant MVP chemotherapy group and observation group. 48 patients were registered to this study until December 1992; among 48 patients 3 refused further treatment after induction chemotherapy and 6 received incomplete radiation therapy because of patient's refusal, 39 completed planned therapy. Twenty-three $(58\%)$ patients including 2 complete responders showed response from induction chemotherapy. Among the 21 patients who achieved a partial response after induction chemotherapy,1 patient rendered complete clearance of disease and 10 patients showed further regression of tumor following hyperfractionated radiotherapy. Remaining 10 patients showed stable disease or progression after radiotherapy. Of the sixteen patients judged to have stable disease or progression after induction chemotherapy, seven showed more than partial remission after radiotherapy but nine showed no response in spite of radiotherapy. Of the 39 patients who completed induction chemotherapy and radiotherapy, 25 patients $(64\%)$ including 3 complete responders showed more than partial remission. Nineteen patients were randomized after radio-therapy. Nine Patients were allocated to adjuvant chemotherapy group and 4/9 showed further regression of tumor after adjuvant chemotherapy. For the time being, there is no suggestion of a difference between the adjuvant chemotherapy group and observation group in distant metastasis rate and survival. Median survival time was 13 months. Actuarial survival rates at 6,12 and 18 months of 39 patients who completed this study were $84.6\%,\;53.7\%\;and\;40.3\%,$ respectively. The partial and complete responders from induction chemotherapy showed significantly better survival than non-responders (p=0.028). Incidence of radiation pneumonitis in this study group was less than that in historical control group inspite of induction chemotherapy. All patients tolerated hypertractionated radiotherapy without definite increase of acute complications compared with conventional radiotherapy group. The longer follow up is needed to evaluate the efficacies of induction and maintenance chemotherapy and survival advantage by hyperfractionated radiotherapy but authors are encouraged with an excellent tolerance, higher response rate and improvement of one year survival rate in patients of this study.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.339-353
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• 1994

Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.

• Herbal Formula Science
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• v.15 no.1
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• pp.163-173
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• 2007

Jeungaektang (JAT) is the herbal formula, has the effect of moistening the dryness by activating lung Qi and by nourishing Yin, has being used for dryness syndromes. Generally the herbal formulae for moistening dryness are used for exogenous or endogenous dryness syndromes. JAT has been clinically used for the treatment of endogenous dryness syndromes. It is composed of Scrophulariae Radix. Rehmanniae Radix and Liriopis Tuber. Recent studies showed that JAT has a protective effect against $CCl_{4}-induced$ hepatotoxicity and anti-inflammatory effects against ear swelling of mouse induced by Crotonis Fructus. However, the effect of JAT on the immunological activity was rarely studied. Therefore, this study evaluated the effects of JAT the regulatory mechanism of nitric oxide (NO) and cytokines in the lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. After the treatment of JAT water extract, cell viability was measured by MTT assay, NO production was monitored by measuring the nitrite content in culture medium. Cyclooxygenase-2 (COX -2) and inducible nitric oxide synthase (iNOS) were determined by immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. Results provided evidence that JAT inhibited the production of nitrite and nitrate ($0.1{\sim}1.0$ mg/ml), iNOS ($0.1{\sim}1.0$ mg/ml), $interleukin-1{\beta}$ ( $0.1{\sim}1.0$ mg/ml) and tumor necrosis $factor-{\alpha}$ ($0.1{\sim}1.0$ mg/ml) in RAW 264.7 cells activated with LPS. Furthermore, JAT inhibited the expression of COX-2 expression and production of prostagladin E2 ($0.1{\sim}1.0$ mg/ml). These findings suggest that JAT can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections.