• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.709-719
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• 1996

Background: Surgical resection is the only way to cure non-small cell lung cancer(NSCLC) and the prognosis of NSCLC in patients who undergo a complete resection is largely influenced by the pathologic stage. After surgical resection, recurrences in distant sites is more common than local recurrences. An effective postoperative adjuvant therapy which can prevent recurrences is necessary to improve long tenn survival Although chemotherapy and radiotherapy are still the mainstay in adjuvant therapy, the benefits of such therapies are still controversial. We initiated this retrospective study to evaluate the effects of adjuvant therapies and analyze the prognostic factors for survival after curative resection. Method: From 1990 to 1995, curative resection was perfomled in 282 NSCLC patients with stage I, II, IIIa, Survival analysis of 282 patients was perfonned by Kaplan-Meier method. The prognostic factors, affecting survival of patients were analyzed by Cox regression model. Results: Squamous cell carcinoma was present in 166 patients(59%) ; adenocarcinoma in 86 pmients(30%) ; adenosquamous carcinoma in II parients(3.9%); and large cell undifferentiated carcinoma in 19 patients(7.1%). By TNM staging system, 93 patients were in stage I; 58 patients in stage II ; and 131 patients in stage rna. There were 139 postoperative recurrences which include 28 local and 111 distant failures(20.1% vs 79.9%). The five year survival rate was 50.1% in stage I ; 31.3% in stage II ; and 24.1% in stage IIIa(p <0.0001). The median survival duration was 55 months in stage I ; 27 months in stage II ; and 16 months in stage rna. Among 131 patients with stage rna, the median survival duration was 19 months for 81 patients who received postoperative adjuvant chemotherapy only or cherne-radiotherapy and 14 months for the other 50 patients who received surgery only or surgery with adjuvant radiotherapy(p=0.2982). Among 131 patients with stage IIIa, the median disease free survival duration was 16 months for 21 patients who received postop. adjuvant chemotherapy only and 4 months for 11 patients who received surgery only(p=0.0494). In 131 patients with stage IIIa, 92 cases were in N2 stage. The five year survival rate of the 92 patients with N2 was 25% and their median survival duration was 15 months. The median survival duration in patients with N2 stage was 18 months for those 62 patients who received adjuvant chemotherapy and 14 months for the other 30 patients who did not(p=0.3988). The median survival duration was 16 months for those 66 patients who received irradiation and 14 months for the other 26 patients who did not(p=0.6588). We performed multivariate analysis to identify the factors affecting prognosis after complete surgical resection, using the Cox multiple regression model. Only age(p=0.0093) and the pathologic stage(p<0.0001) were significam prognostic indicators. Conclusion: The age and pathologic stage of the NSCLC parients are the significant prognostic factors in our study. Disease free survival duration was prolonged with statistical significance in patients who received postoperative adjuvant chemotherapy but overall survival duration was not affected according to adjuvant therapy after surgical resection.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.275-282
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• 1998

Purpose : The effect of hyperfractionated radiotherapy on locally advanced non-small lung cancer was studied by a retrospective analysis. Materials & Methods : We analyzed sixty one patients of biopsy-confirmed, IIIA and IIIB non-small cell lung cancer. Using the ECOG performance scale, all the patients were scored less than 2. They were treated by curative hyperfractionated radiotherapy alone from Oct. 1992 to Oct. 1995 at the Department of Radiation Oncology. All the patients received 120cGy b.i.d with more than 6 hours interval between each fraction. The total dose of radiation was reached up to 6400-7080 cGy with a mean dose of 6934 cGy. The results were analyzed retrospectively. Results : The overall survival rate was 53 1$\%$ in 1 year, 9.9$\%$ in 2 years with a median survival time (MST) of 13.9 months. The progression free survival (PFS) rate was 37.0$\%$ in 1 year, 8.9$\%$ in 2 years. Twenty two Patients were classified as complete responders to this treatment and their MST was 19.5 months When this was compared with that of partial responders (MST: 11 7months), it was statistically significant (p=0.0003). Twenty nine patients of stage IIIA showed a better overall survival rate (1yr 63.3$\%$, 2yr 16.8$\%$) than IIIB patients (1yr 43.3$\%$, 2yr 3.6$\%$), which was also statistically significant (p=0.003). Patients with adenocarcinoma showed a better survival rate (1yr 64.3$\%$, 2yr 21.4$\%$) than that of squamous cell counterpart (1yr 49.4$\%$, 2yr 7.4$\%$), although this was not significant statistically (p=0.61). Two patients developed fatal radiation-induced pneumonia right after the completion of the treatment which progressed rapidly and they all died within 2 months. One patient developed radiation-induced fibrosis after 13 months. He refused further treatment and died soon after the development of fibrosis. Conclusion : Among locally advanced NSCLC, hyperfractionated radiotherapy was effective on stage IIIA patients by increasing MST with acceptable toxicities. Acute radiation-induced pneumonia should be carefully monitored and must be avoided during or after this treatment.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.100-107
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• 1999

Purpose: This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Materials and Methods Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45~67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in T2, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal Iymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intravenous cis-Platin (100 mg/m$^{2}$) on day 1 and oral Etoposide (50 mg/m$^{2}$/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Results : Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred In 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/l3) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post-operative tumor stagings were pT0 in 3 patients, pTl in 6, and pT2 in 3. Lymph node status findings were pN0 in 8 patients, pN1 in 1, and pN2 in 3. Pathologic tumor down-staging was 61.5% (8/13) including complete response in three patients ($23.7%). Tumor stage was unchanged in four patients (30.8%) and progression was in one (7.7%). Conclusions : Pre-operative concurrent chemoradiotherapy for Stage IIIA (N2) non-small cell lung cancer demonstrated satisfactory results with no increased severe acute complications. This treatment shceme deserves more patinet accrual with long-term follow-up.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.500-518
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• 1996

Background : The solitary pulmonary nodule(SPN) presents a diagnostic dilemma to the physician and the patient. Many clinical characteristics(i.e. age, smoking history, prior history of malignancy) and radiological characteristics( i.e. size, calcification, growth rate, several findings of computed tomography) have been proposed to help to determine whether the SPN was benign or malignant. However, most of these diagnostic guidelines are based on the data collected before computed tomography(CT) has been introduced and lung cancer was not as common as these days. Moreover, it is not well established whether these guidelines from western populations could be applicable to Korean patients. Methods : We had a retrospective analysis of the case records and radiographic findings in 114 patients presenting with SPN from Jan. 1994 to Feb. 1995 in Seoul National University Hospital, a tertiary referral hospital. Results : We observed the following results ; (1) Out of 113 SPNs, the etiology was documented in 94 SP IS. There were 34 benign SP s and 60 malignant SPNs. Among which, 49 SPNs were primary lung cancers and the most common hi stologic type was adenocarcinoma. (2) The average age of patients with benign and malignant SPNs was $49.7{\pm}12.0$ and $58.1{\pm}10.0$ years, respectively( p=0.0004), and the malignant SPNs had a striking linear propensity to increase with age. (3) No significant difference in the hi story of smoking was noted between the patients with benign SPNs($13.0{\pm}17.6$ pack- year) and those with malignant SPNs($18.6{\pm}25.1$ pack-year) (p=0.2108). (4) 9 out of 10 patients with prior history of malignancy had malignant SPNs. 5 were new primary lung cancers with no relation to prior malignancy. (5) The average size of benign SPNs($3.01{\pm}1.20cm$) and malignant SPNs($2.98{\pm}0.97cm$) was not significantly different(p=0.8937). (6) The volume doubling time could be calculated in 22 SPNs. 9 SPNs had the volume doubling time longer than 400 days. Out of these, 6 were malignant SPNs. (7) The CT findings suggesting malignancy included the lobulated or spiculated border, air- bronchogram, pleural tail, and lymphadenopathy. In contrast, calcification, central low attenuation, cavity with even thickness, well-marginated border, and peri nodular micronodules were more suggestive for benign nodule. (8) The diagnostic yield of percutaneous needle aspiration and biopsy was 57.6%(19/33) of benign SPNs and 81.0%(47/58) of malignant SPNs. The diagnostic value of sputum analysis and bronchoscopic evaluations were relatively very low. (9) 42.3%(11/26) of SPNs of undetermined etiology preoperatively turned out to be malignant after surgical resection. Overall, 75.4%(46/61) of surgically resected SPNs were malignant. Conclusions : We conclude that the likelihood of malignant SPN correlates the age of patient, prior history of malignancy, some CT findings including lobulated or spiculated border, air-bronchogram, pleural tail and lymphadenopathy. However, the history of smoking, the size of the nodule, and the volume doubling time are not helpful to determent whether the SPN is benign or malignant, which have been regarded as valuable clinical parameters previously. We suggest that aggressive diagnostic approach including surgical resection is necessary in patient with SPNs.

• The Journal of the Korean bone and joint tumor society
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• v.9 no.1
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• pp.1-11
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• 2003

Purpose: To analysis of the result of the treatment of metastatic diaphyseal fracture of the humerus with closed interlocking intrameduallry nailing. Materials and Methods: Among surgically treated 29 patients with pathologic or impending fracture of diaphysis of the humeurs, 13 patients (16 cases) treated with closed intramedullary interlocking nail were selected for the study. The final result of pain relief and functional recovery was evaluated by modified rating system of Perez et al. Results: Primary cancer was diagnosed after fracture was developed in 2 patients and pathologic or impending fracture was occurred average period of 28.9 months after primary cancer was diagnosed. The main primary malignancies were multiple myeloma, lung cancer and breast cancer. Mean survival after humeral metastasis was 11.7 months. The final result was superior to fair in 13 of 16 cases, and poor in 3 cases with progression of tumor spread or distant dissemination to the ipsilateral fingers. Except the latter 3 patients and other 3 patients, who died before 3 months postoperatively, bony union was achieved in 10 cases. There were no complications related to surgery. Conclusion: Closed interlocking intrameduallry nailing is accomplished with brief operative time, small amount of bleeding and provides immediate stability with resultant early return of function to the arm. Additionally it allows early postoperative irradiation. However, some of our cases shows that intramedullary nailing can accelerate tumor spread and metastases elsewhere, so that serious consideration must be given in planning this treatment. In conclusion, the functional status before fracture, life expectancy, type of tumor and extent of involvement should be carefully considered to decide operative treatment of metastatic disease.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.5
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• pp.921-927
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• 2001

This study was performed to investigated the effects on the cytotoxicity and antigenotoxicity of Cordyceps militaris extracts on the human cancer cell lines. The ethanol extract and five fractions which were hexane, chloroform, ethylacetate, butanol and aqueous were screened for crytotoxicity on human lung carcinoma(A549). human breast adenocarcinoma (MCF-7) human epitheloid carcinoma(HeLa), human fibrosarcoma(HT1080) human hepatocellular carcinoma(Hep3B), human gastric carcinoma(KATOIII) and chronic myelogenous leukemia(K562) cell by SRB and MTT assays. The results showed that growth inhibition rates of the human cancer cell in the presence of Cordyceps militaris were inhibited with increasing concentration of the extract. The ethanol extract from Cordyceps militaris had strong inhibitory effects in1 mg/mL treatment by SRB assay , showing 89.4%, 85.7%, 72.9% and 65.5% inhibition in HT1080, HeLa, Hep3B and A549, respectively. The treatment of 1 mg/mL hexane fraction by SRB assay had the strongest cytotoxicity with 97.0% on HT1080 followed by MCF-7(92.9%) and HeLA(90.3%). The inhibition ration on KATOIII by MTT assay was much higher in the butanol (83.7%) and aqueous (80.4%) than in the ethanol extract (61.5%) And also, K562 showed similar tendency with KATOIII. The effects of Cordyceps militaris extracts on the frequencies of micronucleated polychromatic erythrocytes (MNPCEs) induced by N-methyl-N-nitro-N-nitrosoguanidime(MNNG) were investigated in the bone-marrow cells of ICR male mice. The amount of 10, 20, 40 and 80 mg/kg of each extract were administered to animals immediately after injection of MNNG, and the exposure time was 36 hours. Significant reductions(p<0.05) with 39.7%, 52.7%, 71.4% and 83.9% were observed in the frequencies of MNPCE when 10, 20, 40 and 80 mg/kg of the hexane fraction of Coryceps militarus extracts were given to the mice.

• Journal of Life Science
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• v.32 no.4
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• pp.271-278
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• 2022

The detailed mechanism by which cancer upregulated gene 2 (CUG2) overexpression induces cancer stem cell-like phenotypes is not fully understood. The downregulation of FBXW7 E3 ligase, a tumor suppressor known for its proteolytic regulation of oncogenic proteins such as cyclin E, c-Myc, Notch, and Yap1, has been frequently reported in several types of tumor tissues, including those in the large intestine, cervix, and stomach. Therefore, we investigated whether FBXW7 is involved in CUG2-induced oncogenesis. In this study, the decreased expression of FBXW7 was examined in human lung adenocarcinoma A549 (A549-CUG2) and human bronchial BEAS-2B cells (BEAS-CUG2) overexpressing CUG2 and compared with control cells stably expressing an empty vector (A549-Vec or BEAS-Vec). Treatment with MG132 (a proteosome inhibitor) prevented the degradation of FBXW7 and Yap1 proteins, which are substrates of the FBXW7 E3 ligase. To address the role of Fbxw7 in the development of cancer stem cell (CSC) phenotypes, we suppressed Fbxw7 protein levels using its siRNA. We observed that decreased levels of FBXW7 enhanced cell migration, invasion, and spheroid size and number in A549-Vec and BEAS-Vec cells. The enforced expression of FBXW7 produced the opposite results in A549-CUG2 and BEAS-CUG2 cells. Furthermore, the downregulation of FBXW7 elevated the activities of EGFR, Akt, and ERK1/2 and upregulated β-catenin, Yap1, and NEK2, while the enforced expression of FBXW7 generated the opposite results. We thus propose that FBXW7 downregulation induced by CUG2 confers CSC-like phenotypes through the upregulation of both the EGFR-ERK1/2 and β-catenin-Yap1-NEK2 signaling pathways.

• Food Science and Preservation
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• v.11 no.4
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• pp.550-556
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• 2004

In the present study, we investigated the antimutagenic and cytotoxic effects of Acer ginnala Max. bark extract on S. typhimurium TA98, TA100 and cancer cell lines with Ames test and SRB assay, respectively. They were extracted with methanol and then fractionated using hexane, chloroform, ethyl acetate, butanol, and water to obtain the fractions. The inhibition rate of methanol ($200\;{\mu}g/plate$) of Acer ginnala Max. bark extract in the Salmonella typhimurium TA100 strain showed $83.3\%$ against the mutagenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In addition, the suppression of methanol extract with same concentration of in the Salmonella typhimurium TA98 and TA100 strains showed $80.3\%\;and\;92.7\%$ inhibition against 3-amino-1,4-dimethyl-5H-pyrido-(4,3-b)indol (Trp-P-1), respectively. The cytotoxicity effects of Acer ginnala Max. bark extract against the cell lines with human lung carcinoma (A549), human gastric carcinoma (AGS), human hepatocellular carcinoma (Hep3B) and human breast adenocarcinoma (MCF-7) were inhibited with the increase of the extract concentration. The treatment of 1.0 mg/mL Acer ginnala Max. bark methanol extract of methanol showed strong cytotoxicities of $77.3\%,\;90.4\%,\;88.9\%,\;and\;83.7\%$ against A549, AGS, Hep3B and MCF-7, respectively.

• Radiation Oncology Journal
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• v.26 no.3
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• pp.149-159
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• 2008

Purpose: To evaluate the results and prognostic factors for postoperative adjuvant radiation therapy in patients at stages I and II of endometrial cancer. Materials and Methods: Between January 1991 and December 2006, 35 patients with FIGO stages I and II disease, who received adjuvant radiation therapy following surgery for endometrial cancer at Ewha Womans University Hospital, were enrolled in this study. A total of 17 patients received postoperative pelvic external beam radiation therapy; whereas, 12 patients received vaginal brachytherapy alone, and 6 patients received both pelvic radiation therapy and vaginal brachytherapy. Results: The median follow-up period for all patients was 54 months. The 5-yr overall survival and disease-free survival rates for all patients were 91.4% and 81.7%, respectively. The 5-yr overall survival rates for low-risk, intermediate-risk, and high-risk groups were 100%, 100% and 55.6%, respectively. In addition, the 5-yr disease-free survival rates were 100%, 70.0%, and 45.7%, respectively. Although no locoregional relapses were identified, distant metastases were observed in 5 patients (14%). The most common site of distant metastases was the lung, followed by bone, liver, adrenal gland, and peritoneum. A univariate analysis revealed a significant correlation between distant metastases and risk-group (p=0.018), pathology type (p=0.001), and grade (p=0.019). A multivariate analysis also revealed that distant metastases were correlated with pathology type (p=0.009). Papillary, serous and clear cell carcinoma cases demonstrated a poor patient survival rate compared to cases of endometrioid adenocarcinoma or adenosquamous carcinoma. The most common complication of pelvic external beam radiation therapy was enteritis (30%), followed by proctitis, leucopenia, and lymphedema. All these complications were of RTOG grades 1 and 2; no grades 3 and 4 were observed. Conclusion: For the low-risk and intermediate-risk groups (stages 1 and 2) endometrial cancer, pelvic control, and overall survival rate was free of severe toxicity when pelvic radiation therapy or vaginal brachytherapy was performed. In the high-risk group, pelvic control rate was excellent, but the survival rate was poor due to distant metastases, in spite of the pelvic radiation therapy. The combined modality of chemotherapy and radiation therapy is recommended for high-risk groups. For the intermediate-risk group, a prospective randomized study is required to compare the efficacy between whole pelvic radiation therapy and vaginal brachytherapy.

• Korean Journal of Food Science and Technology
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• v.41 no.5
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• pp.552-559
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• 2009

In this study, the anticancer activity of the water extract at $100^{\circ}C$ was compared to that of the callus extracts via a ultrasonification extraction process. All the extracts were utilized to evaluate cytotoxicity, antioxidant and immune activities. The callus extracted via ultrasonification extraction showed relatively low cytotoxicity on normal human cell lines, HEK293 and HEL299, showing 13.17% and 21.78%, respectively. The callus extract has 59.82% which was similar to 61.70% for water extracts. It was also found that callus extract yielded higher nitric oxide secretion form macrophage than other extracts. The growths of both human stomach adenocarcinoma (AGS) cell and human lung carcinoma (A549) were inhibited up to 70% by adding 1.0 mg/mL of the callus extracts with ultrasonification extraction. This inhibition ratio (70%) was almost close to that of water extract. Human hepatoma carcinoma (HEP3B) cell growth was most significantly inhibited up to 75% by adding 1.0 mg/mL of callus extracts, and its selectivity was highest compared to other extracts. It indicates that the callus extracts could selectively inhibit growth of digestive system-related cancer cells. It can be also concluded from the results of this study that the callus extracts associated with ultrasonification extraction process have the potential for anticancer activity.