• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.166-179
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• 2000

Background: The main reason for the failure of anti-cancer chemotherapy is the build up of resistance by cancer cells to apoptosis. The activation of NF-${\kappa}B$ in many cancer cell lines is reported to be underlying mechanism behind the build up of resistance of cancer cells to apoptosis. However, this relationship varied depending on the cells used in the experiments. In this study, the role of NF-${\kappa}B$ activation in the TNF-$\alpha$-induced apoptosis in lung cancer cell line was evaluated. Methods: NCI-H157 cells were used in all experiments. Cells were exposed to a high dose of TNF-$\alpha$(20 ng/ml) for 24 or 48 hours with or without blocking NF-${\kappa}B$ activation. TNF-$\alpha$-induced activation of NF-${\kappa}B$ was inhibited either by overexpression of $I{\kappa}B{\alpha}$-super repressor($I{\kappa}B{\alpha}$-SR) or by pre-treatment with proteasome inhibitor. Cell viability and apoptosis were evaluated with MTT assay and Western blot analysis for PARP fragment, respectively. Results: Cell viability of NCI-H157 cells was not affected by TNF-$\alpha$ treatment alone; however, combined treatment with TNF-$\alpha$ and cycloheximide reduced cell viability significantly, indicating that resistance to TNF-$\alpha$ is mediated by the new proteins synthesized after TNF-$\alpha$ stimulation. To evaluate the role of NF-${\kappa}B$ in the transcription of anti-apoptotic proteins. delete NF-${\kappa}B$ activation was inhibited before TNF-$\alpha$ stimulation. as described above. $AD5I{\kappa}B{\alpha}$-SR-transduction inhibited TNF-$\alpha$-induced nuclear translocation of p65. TNF-$\alpha$-induced cell death and apoptosis increased after inhibition of TNF-$\alpha$-induced activation of NF-${\kappa}$ by methods. Conclusion: These results suggest that TNF-$\alpha$-induced activation of NF-${\kappa}B$ may be closely related to the acquisition of the resistance to TNF-$\alpha$-induced apoptosis in lung cancer cells. Therefore. blocking of NF-${\kappa}B$ pathway can be a useful therapeutic modality in the treatment of lung cancer.

• Journal of Chest Surgery
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• v.41 no.5
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• pp.610-618
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• 2008

Background: There are various treatment modalities for atherosclerotic arterial obstructive disease at the lower limbs, for example, conservative physical therapy, medication, operation etc. Yet it has been established that an arterial bypass operation is the most effective treatment. The aim of this study is to evaluate the effect of arterial bypass operation within our experience and to determine the indicators of treatment. Material and Method: Ninety six patients received arterial bypass operation for atherosclerotic arterial obstructive disease from June 2002 to April 2006. We evaluated the feasibility of arterial bypass operation based on the improvement of symptoms and the ankle-brachial index (ABI) and the surgical outcomes, as based on the complications, the amputation rates and the patency rates. We also assessed the possible risk factors such as gender, age, a smoking history, co-morbidities, the anastomotic sites, the graft size and the graft type. We retrospectively reviewed the medical records of the patients. The total mean follow-up period was $29.4{\pm}13.1$ months. Result: The mean age was $65.95{\pm}9.61$ and there were 88 male patients. The most common clinical manifestation was ischemic resting pain in the lower extremities. The underlying combined diseases were hypertension (61%), diabetes (43%), cardiac problems (35%) and smoking (91.7%). The most frequent site of arterial obstruction was the superficial femoral artery (44 cases, 40%). A femoropopliteal artery bypass operation with a Polytetrafluoroethylene(PTFE) synthetic graft was done in 44 cases (40%) and the great saphenous vein graft was used in 11 cases. The postoperative ABI increased significantly from $0.30{\pm}0.11$ preoperatively to $0.63{\pm}0.11$ (p<0.001) postoperatively. In 8 cases, amputations above the ankle level were necessary. The graft patency rates were 86.4% and 68.0% after 1 and 3 years, respectively. There were 29 cases (30.21%) of patency failure; the male gender, smokers and hypertension were significantly more frequent in the failure group. Of these, hypertension was the most powerful risk factor (p=0.042). Conclusion: The arterial bypass operation is an effective treatment modality for controlling the symptoms such as pain and claudication, and for preventing major amputations for the patients with atherosclerotic arterial obstructive disease. This study suggests quitting smoking, strict blood pressure control, selection of an appropriate graft, regular outpatient follow up and proper medication would offer higher patency rates and more favorable outcomes.

• Radiation Oncology Journal
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• v.13 no.4
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• pp.331-338
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• 1995

Purpose : To evaluate our clinical experience with the combination of teletherapy and intraluminal brachytherapy in patients with unresectable or inoperable esophageal cancers. Materials and Methods : From Nov 1989 to Mar 1993, twenty patients with esophageal cancer were treated with radical radiotherapy and intraluminal brachytherapy at Yonsei Cancer Center. All patients had squamous histolgy and stage distribution was as follows: stage II, 4($20{\%}$)patients; III, 15 ($75{\%}$)patients; IV, 1($5{\%}$)patients. A dose of S-12Gy/1-3weeks with intraluminal brachytherapy (3-5Gy/fraction) to 5mm from the outside of the esophageal tube using high dose rate Iridium-192 remotely afterloading brachytherapy machine was given 2 weeks after a total dose of 59-64Gy with external radiotherapy. Induction chemotherapy using cisplatin and 5-FU was performed in 13 patients with median 3 cycles(1-6 cycles), Response rate, local control rate, survival and complications were analysed retrospectively. Results : Two-year overall survival rate and median survival were $15.8{\%}$ and 13.5 months. Response rates were as follows complete remission(CR) 5($25{\%}$): partial remission a(PRa) 7($35{\%}$): partial remission b(PRb) 7($35{\%}$), no response(NR) 1($5{\%}$). Patterns of failure were as follows; local failure 13($65{\%}$), local and distant failure 3($15{\%}$), distant failure 0($0{\%}$). Ultimate local control rate was $20{\%}$. Treatment related complications included esophageal ulcer in two patients and esophageal stricture in one. Conclusion : Though poor local conrol rate, median survival was improved as compared with previous results of radiation therapy alone(8months) and chemoradiation combined treatment(11 months) in Yonsei Cancer Center High-dose-rate intraluminal brachytherapy following external irradiation is an effective treatment modality with acceptable toxicity in esophageal cancer.

• Radiation Oncology Journal
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• v.14 no.3
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• pp.201-209
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• 1996

Purpose : To assess the efficacy of high dose rate - intracavitary radio-therapy (HDR-ICR) in the radiotherapy of FIGO stage IB squamous cell carcinoma of uterine cervix and to determine the optimum dose combination scheme of external radiotherapy and ICR to achieve acceptable local control without severe complication. Materials and Methods : One hundred and sixty two patients with FIGO stage Ib squamous cell carcinoma of uterine cervix who received definitive radiotherapy between May 1979 and December 1990 were retrospectively analyzed. All the patients received external radiotherapy combined with HDR-ICR. External dose of 40-46 Gy in 4.5-5 weeks was given to whole pelvis(median 45 Gy) and ICR dose of 30-39 Gy in 10-13 times was given to the point A. Midline shielding was done after 20-45 Gy of external radiotherapy(median 40 Gy) Summation of external dose Plus ICR dose to the point A range were 64.20-95.00 Gy. and mean was 83.94 Gy. We analyzed the local control rate, survival rate, and late complication rate. Rusults : Initial complete response rate was $99.4\%$ for all patients. Overall 5-year survival rate was $91.1\%$ and 5-year disease free survival rate was $90.9\%$. Local failure rate was $4.9\%$ and distant failure rate was $4.3\%$. Tumor size was the only significant prognostic factor. When tumor size greater than 3cm, 5-rear survival rate was $92.6\%$ and less than 3cm, that was $79.6\%$. Late complication rate was $23.5\%$ with $18.5\%$ of rectal complication and $4.9\%$ of bladder complication. Mean rectal dose summation of external midline dose plus ICR rectal point dose was lower in the patients without rectal complication(74.88 Gr) than those with rectal complication (78.87 Gy). Complication rate was increased with low rate of improvement of survival rate when summation of external midline dose plus point A or point R dose by ICR was greater than 70-75 Gy. Conclusion : The definitive radiation therapy using high dose rate ICR in FIGO stage IB uterine cervical cancer is effective treatment modality with good local control and survival rate without severe complication.

• Radiation Oncology Journal
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• v.21 no.4
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• pp.299-305
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• 2003

Purpose: In order to develop the national guide-lines for the standardization of radiotherapy we are planning to establish a web-based, on-line data-base system for laryngeal cancer. As a first step this study was performed to accumulate the basic clinical information of laryngeal cancer and to determine the items needed for the data-base system. Materials and Methods: We analyzed the clinical data on patients who were treated under the diagnosis of laryngeal cancer from January 1998 through December 1999 In the South-west area of Korea. Eligiblity criteria of the patients are as follows: 18 years or older, currently diagnosed with primary epithelial carcinoma of larynx, and no history of previous treatments for another cancers and the other laryngeal diseases. The items were developed and filled out by radiation oncologlst who are members of forean Southwest Radiation Oncology Group. SPSS vl0.0 software was used for statistical analysis. Results: Data of forty-five patients were collected. Age distribution of patients ranged from 28 to 88 years(median, 61). Laryngeal cancer occurred predominantly In males (10 : 1 sex ratio). Twenty-eight patients (62$\%$) had primary cancers in the glottis and 17 (38$\%$) in the supraglottis. Most of them were diagnosed pathologically as squamous cell carcinoma (44/45, 98$\%$). Twenty-four of 28 glottic cancer patients (86$\%$) had AJCC (American Joint Committee on Cancer) stage I/II, but 50$\%$ (8/16) had In supraglottic cancer patients (p=0.02). Most patients(89$\%$) had the symptom of hoarseness. indirect laryngoscopy was done in all patients and direct laryngoscopy was peformed in 43 (98$\%$) patients. Twenty-one of 28 (75$\%$) glottic cancer cases and 6 of 17 (35$\%$) supraglottic cancer cases were treated with radiation alone, respectively. The combined treatment of surgery and radiation was used in 5 (18$\%$) glottic and 8 (47$\%$) supraglottic patients. Chemotherapy and radiation was used in 2 (7$\%$) glottic and 3 (18$\%$) supraglottic patients. There was no statistically significant difference in the use of combined modality treatments between glottic and supraglottic cancers (p=0.20). In all patients, 6 MV X-ray was used with conventional fractionation. The iraction size was 2 Gy In 80$\%$ of glottic cancer patients compared with 1.8 Gy in 59$\%$ of the patients with supraglottic cancers. The mean total dose delivered to primary lesions were 65.98 ey and 70.15 Gy in glottic and supraglottic patients treated, respectively, with radiation alone. Based on the collected data, 12 modules with 90 items were developed or the study of the patterns of care In laryngeal cancer. Conclusion: The study Items for laryngeal cancer were developed. In the near future, a web system will be established based on the Items Investigated, and then a nation-wide analysis on laryngeal cancer will be processed for the standardization and optimization of radlotherapy.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.237-244
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• 2001

Purpose : To assess the tolerance, complete response rate, bladder preservation rate and survival rate in patients with muscle-invading bladder cancer treated with selective bladder preservation protocol. Method and Materials : From October 1990 to June 1998, twenty six patients with muscle-invading bladder cancer (clinical stage T2-4, N0-3, M0) were enrolled for the treatment protocol of bladder preservation. They were treated with maximal TURBT (transurethral resection of bladder tumor) and 2 cycles of MCV chemotherapy (methotrexate, crisplatin, and vinblastine) followed by $39.6\~45\;Gy$ pelvic irradiation with concomitant cisplatin. After complete urologic evaluation (biopsy or cytology), the patients who achieved complete response were planed for bladder preservation treatment and treated with consolidation cisplatin and radiotherapy (19.8 Gy). The patients who had incomplete response were planed to immediate radical cystectomy. If they refused radical cystectomy, they were treated either with TURBT followed by MCV or cisplatin chemotherapy and radiotherapy. The median follow-up duration is 49.5 months. Results : The Patients with stage T2-3a and T3b-4a underwent complete removal of tumor or gross tumor removal by TURBT, respectively. Twenty one out of 26 patients $(81\%)$ successfully completed the protocol of the planned chemo-radiotherapy. Seven patients had documented complete response. Six of them were treated with additional consolidation cisplatin and radiotherapy. One patient was treated with 2 cycles of MCV chemotherapy due to refusal of chemo-radiotherapy. Five of 7 complete responders had functioning tumor-free bladder. Fourteen patients of incomplete responders were further treated with one of the followings : radical cystectomy (1 patient), or TURBT and 2 cycles of MCV chemotherapy (3 patients), or cisplatin and radiotherapy (10 patients). Thirteen patients of them were not treated with planned radical cystectomy due to patients' refusal (9 patients) or underlying medical problems (4 patients). Among twenty one patients, 12 patients $(58\%)$ were alive with their preserved bladder, 8 patients died with the disease, 1 patient died of intercurrent disease. The 5 years actuarial survival rates according to CR and PR after MCV chemotherapy and cisplatin chemoradiotherapy were $80\%\;and\;14\%$, respectively (u=0.001). Conclusion : In selected patients with muscle-invading bladder cancer, the bladder preservation could be achieved by MCV chemotherapy and cisplatin chemo-radiotherapy. All patients tolerated well this bladder preservation protoco. The availability of complete TURBT and the responsibility of neoadjuvant chemotherapy and chemoradiotherapy were important predictors for bladder preservation and survival. The patients who had not achieved complete response after neoadjuvant chemotherapy and chemoradiotherapy should be immediate radical cystectomy. A randomized prospective trial might be essential to determine more accurate indications between cystectomy or bladder preservation.