• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.510-516
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• 2005

Backgroud : Lung cancer is the leading cause of cancer deaths in Korea and the number of lung cancer deaths is increasing. The higher response rates, decreased toxicity and improved performance status of the first-line treatments have resulted in an increased number of patients becoming candidates for second-line therapy. Several new antineoplastic agents, including gemcitabine, docetaxel and paclitaxel, have recently demonstrated second-line activity. This phase II study evaluated the efficacy and toxicity of gemcitabine and vinorelbine as combination chemotherapy for Korean patients with NSCLC as a second-line treatment. Methods : Sixty response-evaluable patients were enrolled from December 2000 to July 2003. We conducted a phase II study of a combination gemcitabine and vinorelbine chemotherapy for patients with histologically confirmed NSCLC that was stage IIIB and IV disease at the time of diagnosis, and the disease had progressed onward or the patients had relapsed after first-line platinum-based chemotherapy. They were treated with intravenous gemcitabine $1000mg/m^2$ and intravenous vinorelbine $25mg/m^2$ on days 1 and 8. This chemotherapy regimen was repeated every 3 weeks. Results : A total of 215 cycles of treatment were given and the mean number of cycles was 3.6 cycles. All the patients were evaluable for the toxicity profile. The response rate was 10% according to the WHO criteria. The median progression free survival was 3.8 months and the median survival time was 10.1 months. The 1-year survival rate was 32.9%. Grade III and IV neutropenia were seen in 20 (33.3%) and 7 (11.7%) patients, respectively. Conclusion : The combination of gemcitabine and vinorelbine is active and well tolerated as a second-line therapy for patients with advanced nonsmall cell lung carcinoma.

• Radiation Oncology Journal
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• v.12 no.1
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• pp.81-90
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• 1994

Purpose : The aim of this study is to analyze the clinical results of thermo-irradiation treatment for surgically unresectable advanced hepatoma with or without hepatic arterial chemo-embolization (HACE), chemotherapy (CT) and interferon (IFN) therapy. Materials and Methods : Between February 1990 and December 1992, 45 Patients with surgically unresectable advanced hepatomas were treated by thermo-irradiation with or without hepatic arterial chemo-embolization and other treatment modalities. Among them, We analyzed retrospectively 25 patients who received more than three times of hyperthermias. Mean age was 50 years (range : 18-71 years) and male to female ratio was 20 : 5. In the study, treatment was administered as follows : 3 patients received radiation therapy(RT) and hyperthermia (HT). 3 received RT+HT+CT. 3 received RT+HT+HACE. 1 received RT+HT+CT+HACE. 2 received RT+HT+CT+IFN. 10 received RT+HT+HACE+IFN. 3 received RT+HT+CT+HACE+IFN. Radiation therapy was done by a 6 MV linear accelerator Patients were treated with daily fractions of 180 cGy to doses of 11Gy-50Gy (median 30Gy). Local hyperthermia was done by HEH-500C(Omron Co. Japan), 30-45 min/session, 2 sessions/wk and the number of HT sessions ranged from 3 to 17 (median 7 times). 15 patients of 25 were followed by abdominal CT scan or abdominal ultra-sonogram. The following factors were analyzed :Age, histologic grade, sex. number of hyperthermia, total RT dose, hepatic arterial chemo-embolization. Results : Of 25 patients. there were observed tumor regression (partial response and minimal response) in 6 (24$ \% $), no response in 8 (32$ \% $), progression in 1 (4$ \% $) and not evaluable ones in 10 (40$ \% $) radiographically. The over all 1-year survival was 25$ \% $, with a mean survival of 33 weeks. The treatment modes of partial and minimal responsive patients (PR+MR)were as follows : Two were treated with RT+HT+HACE, 2 were done with RT+HT+HACE+IFN Remaining 2 were treated with RT+HT+CT+HACE+IFN. The significant factor affecting the survival rate were RT dose (more than 25 Gy), HACE, number of HT (above 6 times), responsiveness after treatment (PR + MR). Age, sex, histologic differentiation, chemotherapy, interferon therapy were not statistically significant factors affecting the survival rate. Conclusion : Although follow-up duration was short, the thermo-irr3diBtion with/without hepatic arterial chemo-embolization was well tolerated and there were no serious complicatons. In future, it is considered the longer follow up and prospective, well controlled trials should be followed to evaluate the efficacies of survival advantage.

• Analytical Science and Technology
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• v.13 no.4
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• pp.494-503
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• 2000

A 21-residue peptide corresponding to amino acids 84-104 of $p16^{INK4A}$, the tumor suppressor, has been synthesized and its structure was studied by Circular Dichroism, $^1H$ NMR spectroscopy and molecular modeling. A p16-derived peptide (84-104 amino acids) forming stable complex with CDK4 and CDK6 inhibits the ability of CDK4/6 to phosphorylate pRb in vitro, and blocks cell-cycle progression through G1/S phase as shown in the function of the full-length p16. Its NMR spectral data including NOEs, $^3J_{NH-H{\alpha}}$ coupling constants, $C_{\alpha}H$ chemical shift, the average amplitude of amide chemical shift oscillation and temperature coefficients indicate that the secondary structure of a p16-derived peptide is similar to that of the same region of full-length p16, which consists of helix-turn-helix structure. The 3-D distance geometry structure based on NOE-hased distance and torsion angle restraints is characterized by ${\gamma}$-turn conformation between residues $Gly^{89}-Leu^{91}$(${\varphi}_{i+1}=-79.8^{\circ}$, ${\varphi}_{i+1}=60.2^{\circ}$) as evidenced in a single crystal structure for the corresponding region of p18 or p19, but is undefined at both the N and C termini. This compact and rigid ${\gamma}$-turn region is considered to stabilize the structure of p16-derived peptide and serve as a site recognizing cyelin dependent kinase, and this well-defined ${\gamma}$-turn structure could be utilized for the design of anti-cancer drug candidates.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.409-423
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• 1998

Purpose : This retrospective study was tried to evaluate the clinical characteristics of patients, patterns of failure, survival rates, prognostic factors affecting survival, and treatment related toxicities when non-small cell lung cancer patients was treated by definitive radiotherapy alone or combined with chemotherapy. Materials and Methods : We evaluated the treatment results of 70 patients who were treated by definitive radiation therapy for non-small cell lung cancer at the Department of Radiation Oncology, Ewha Womans University Hospital, between March 1982 and April 1996. The number of patients of each stage was 2 in stage I, 6 in stage II, 30 in stage III-A, 29 in stage III-B, 3 in stage IV. Radiation therapy was administered by 6 MV linear accelerator and daily dose was 1.8-2.0 Gy and total radiation dose was ranged from 50.4 Gy to 72.0 Gy with median dose 59.4 Gy. Thirty four patients was treated with combined therapy with neoadjuvant or concurrent chemotherapy and radiotherapy, and most of them were administered with the multi-drug combined chemotherapy including etoposide and cisplatin. The survival rate was calculated with the Kaplan-Meier methods. Results : The overall 1-year, 2-year, and 3-year survival rates were 63$\%$, 29$\%$, and 26$\%$, respectively. The median survival time of all patients was 17 months. The disease-free survival rate for 1-year and 2-year were 23$\%$ and 16$\%$, respectively. The overall 1-year survival rates according to the stage was 100$\%$ for stage I, 80$\%$ for stage II, 61$\%$ for stage III, and 50$\%$ for stage IV. The overall 1-year 2-year, and 3-year survival rates for stage III patients only were 61$\%$, 23$\%$, and 20$\%$, respectively. The median survival time of stage III patients only was 15 months. The complete response rates by radiation therapy was 10$\%$ and partial response rate was 50$\%$. Thirty patients (43$\%$) among 70 patients assessed local control at initial 3 months follow-up duration. Twenty four (80$\%$) of these 30 Patients was possible to evaluate the pattern of failure after achievement of local control. And then, treatment failure occured in 14 patients (58$\%$): local relapse in 6 patients (43$\%$), distant metastasis in 6 patients (43$\%$) and local relapse with distant metastasis in 2 patients (14$\%$). Therefore, 10 patients (23$\%$) were controlled of disease of primary site with or without distant metastases. Twenty three patients (46$\%$) among 50 patients who were possible to follow-up had distant metastasis. The overall 1-year survival rate according to the treatment modalities was 59$\%$ in radiotherapy alone and 66$\%$ in chemoirradiation group. The overall 1-year survival rates for stage III patients only was 51$\%$ in radiotherapy alone and 68$\%$ in chemoirradiation group which was significant different. The significant prognostic factors affecting survival rate were the stage and the achievement of local control for all patients at univariate- analysis. Use of neoadjuvant or concurrent chemotherapy, use of chemotherapy and the achievement of local control for stage III patients only were also prognostic factors. The stage, pretreatment performance status, use of neoadjuvant or concurrent chemotherapy, total radiation dose and the achievement of local control were significant at multivariate analysis. The treatment-related toxicities were esophagitis, radiation pneunonitis, hematologic toxicity and dermatitis, which were spontaneously improved, but 2 patients were died with radiation pneumonitis. Conclusion : The conventional radiation therapy was not sufficient therapy for achievement of long-term survival in locally advanced non-small cell lung cancer. Therefore, aggressive treatment including the addition of appropriate chemotherapeutic drug to decrease distant metastasis and preoperative radiotherapy combined with surgery, hyperfractionation radiotherapy or 3-D conformal radiation therapy for increase local control are needed.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.126-132
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• 2009

Purpose: We wanted to evaluate the prognostic factors for the pathologic N2 non-small cell lung cancer (NSCLC) patients who were treated by postoperative radiotherapy. Materials and Methods: We retrospectively reviewed 112 pN2 NSCLC patients who underwent surgery and postoperative radiotherapy (PORT) From January 1999 to February 2008. Seventy-five (67%) patients received segmentectomy or lobectomy and 37 (33%) patients received pneumonectomy. The resection margin was negative in 94 patients, and it was positive or close in 18 patients. Chemotherapy was administered to 103 (92%) patients. Nine (8%) patients received PORT alone. The median radiation dose was 54 Gy (range, 45 to 66), and the fraction size was 1.8~2 Gy. Results: The 2-year overall survival (OS) rate was 60.2% and the disease free survival (DFS) rate was 44.7% for all the patients. Univariate analysis showed that the patients with multiple-station N2 disease had significantly reduced OS and DFS (p=0.047, p=0.007) and the patients with an advanced T stage ($\geq$T3) had significantly reduced OS and DFS (p<0.001, p=0.025). A large tumor size ($\geq$5 cm) and positive lymphovascular invasion reduced the OS (p=0.035, 0.034). Using multivariate analysis, we found that multiple-station N2 disease and an advanced T stage ($\geq$T3) significantly reduced the OS and DFS. Seventy one patients (63.4%) had recurrence of disease. The patterns of failure were loco-regional in 23 (20.5%) patients, distant failure in 62 (55.4%) and combined loco-regional and distant failure in 14 (12.5%) patients. Conclusion: Multiple involvement of mediastinal nodal stations for the pN2 NSCLC patients with PORT was a poor prognostic factor in this study. A prospective study is necessary to evaluate the N2 subclassification and to optimize the adjuvant treatment.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.233-243
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• 2000

Purpose : First of all, this study was performed to assess the result of curative radiotherapy and to evaluate different possible prognostic factors for squamous cell carcinoma of the supraglottic larynx treated at the Pusan National University Hospital. The second goal of this study was by comparing our data with those of other study groups, to determine the better treatment policy of supraglottic cancer in future. Methods and Material : Thirty-two patients with squamous cell carcinoma of the supraglottic larynx were treated with radiotherapy at Pusan National University Hospital, from August 1985 to December 1996. Minimum follow-up period was 29 months, Twenty-seven patients (84.4$\%$) were followed up over 5 years. Radiotherapy was delivered with 6 MV photons to the primary laryngeal tumor and regional iymphatics with shrinking field technique. Ail patients received radiotherapy under conventional fractionated schedule (once a day). Median total tumor dose was 70.2 Gy (range, 55.8 to 75.6 Gy) on primary or gross tumor lesion. Thirteen patients had Induction chemotherapy with cisplatln and 5-fluorouracil (1-3 cycles). Patient distribution, according to the different stages, were as follows: stage I, 5/32 (15.6$\%$): stage II, 10/32 (31.3$\%$); stage III, 8/32 (25$\%$): stage IV, 9/32 (28.1$\%$). Results :The 5-year overall survival rate of the whole series (32 patients) was 51.7$\%$. The overall survival rate at 5-years was 80$\%$ in stage I, 66.7$\%$ in stage II, 42.9$\%$ in stage III, 25$\%$ in stage IV (p=0.0958). The S-year local control rates after radiotherapy were as fellows: stage I, 100$\%$; stage II, 60$\%$ stage III, 62.5$\%$; stage IV, 44.4$\%$ (p=0.233). Overall vocal preservation rates was 65.6$\%$, 100% In stage I, 70% in stage II, 62.5$\%$ In stage III, 44.4$\%$ in stage IV (p=0.210). There was no statistical significance in survival and local control rate between neoadjuvant chemotherapy followed by radiotherapy group and radiotherapy alone group. Severe laryngeal edema was found in 2 cases after radiotllerapy, emergent tracheostomy was done. Four patients were died from distant metastsis, . three in lung, one in brain. Double primary tumor was found in 2 cases, one in lung (metachronous), another in thyroid (synchronous). Ulcerative lesions were revealed as unfavorable prognostic factor ( p=0.0215), and radiation dose (more or less than 70.2 Gy) was an important factor on survival (p=0.002). Conclusion : The role of radiotherapy treatment of supraglottic carcinoma is to important factor on survival and to preserve the laryngeal function. Based on our data and other studies, early and moderately advanced supragiottic carcinomas could be successfully treated with either consewative surgery or radiotherapy alone. Both modalities showed similar results in survival and vocal preservation. For the advanced cases, radiotherapy alone is Inadequate for curative aim and surgery combined with radiotherapy should be done in operable patients. When patients refuse operation or want to preserve vocal function, or for the patients with inoperable medical conditions, combined chemoradiotherapy (concurrent) or altered fractionated radiotherapy with or without radiosensitizer should be taken into consideration in future.

• Radiation Oncology Journal
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• v.19 no.4
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• pp.327-334
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• 2001

Purpose : To find out the role of postoperative adjuvant radiotherapy in the treatment of rectal cancer by comparing survival, pelvic control, complication rate, and any prognostic factor between surgery alone and postoperative radiotherapy group. Materials and methods : From Feb. 1982 to Dec. 1996 total 212 patients were treated by radical surgery with or without postoperative radiotherapy due to rectal carcinoma of modified Astler-Coiler stage $B2\~C3$. Of them, 18 patients had incomplete radiotherapy and so the remaining 194 patients were the database analyzed in this study. One hundred four patients received postoperative radiotherapy and the other 90 patients had surgery only. Radiotherapy was peformed in the range of $39.6\~55.8\;Gy$ (mean: 49.9 Gy) to the whole pelvis and if necessary, tumor bed was boosted by $5.4\~10\;Gy$. Both survival and pelvic control rates were calculated by Kaplan-Meier method and their statistical significance was tested by Log-rank test. Multivariate analysis was peformed by Cox proportional hazards model. Results : 5-year actuarial survival rate (5YSR) and 5-year disease-free survival rate (5YDFSR) of entire patients were $53\%\;and\;49\%$, respectively. 5YSRs of surgery alone group and adjuvant radiotherapy group were $63\%\;vs\;45\%$, respectively (p=0.03). This difference is thought to reflect uneven distribution of stages between two treatment groups (p<0.05 by $\chi^2-test$) with more advanced disease patients in adjuvant radiotherapy group. 5YSRs of surgery alone vs adjuvant radiotherapy group in MAC B2+3, C1, C2+3 were $68\%\;vs\;55\%$ (p=0.09), $100\%\;vs\;100\%$, $40\%\;vs\;33\%$ (p=0.71), respectively. 5YDFSRs of surgery alone vs adjuvant radiotherapy group in above three stages were $65\%\;vs\;49\%$ (p=0.14), $100\%\;vs\;100\%$, $33\%\;vs\;31\%$ (p=0.46), respectively. 5-year pelvic control rate (5YPCR) of entire patients was $72.5\%$. 5YPCRs of surgery alone and adjuvant radiotherapy group were $71\%\;vs\;74\%$, respectively (p=0.41). 5YPCRs of surgery alone vs adjuvant radiotherapy group in B2+3, C1, C2+3 were $79\%\;vs\;75\%$ (p=0.88), $100\%\;vs\;100\%$, $44\%\;vs\;68\%$ (p=0.01), respectively. Multivariate analysis showed that only stage was significant factor affecting overall and disease-free survival in entire patients and also in both treatment groups. In view of pelvic control, stage and operation type were significant in entire patients and only stage in surgery alone group but in adjuvant radiotherapy group, operation type instead of stage was the only significant factor in multivariate analysis as a negative prognostic factor in abdominoperineal resection cases. Conclusion : Our retrospective study showed that postoperative adjuvant radiotherapy could improve the pelvic control in MAC C2+3 group. To improve both pelvic control and survival in all patients with MAC B2 or more, other treatment modality such as concurrent continuous infusion of 5-FU, which is the most standard agent, with radiotherapy should be considered.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.8
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• pp.1137-1143
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• 2015

This study investigated the free radical-scavenging and antitumor activities of hot water, water, acetone, ethanol, ethyl acetate, chloroform, and hexane extracts of fruits and leaves from Prunus mume. The various extracts were evaluated for their total polyphenol, flavonoid, and tannin contents, scavenging activities by DPPH and ABTS analyses, reducing power, protective effects against oxidative stress in L-132 cells, and antitumor activities against A549, HeLa, and U87 cancer cells. Ethanol extracts of fruits and leaves showed the highest total polyphenol content (336.41 and 523 mg GAE/100 g, respectively). DPPH and ABTS radical-scavenging activities increased according to concentration of fruit. DPPH radical-scavenging activity of ethanol extracts from leaves was 65.48% at $200{\mu}g/mL$. All extract fractions of leaves showed high ABTS radical-scavenging activities. The reducing power activities increased according to increasing concentration of fruits and leaves. All extracts of leaves performed better than extracts of fruits in terms of protective effects against oxidative stress in L-132 cells. Ethyl acetate, chloroform, hexane, ethanol extracts of fruits and leaves showed anticancer activities against A549, HeLa, and U87 cancer cells. However, ethanol extracts of fruits and leaves showed no toxicity in normal cells (BNLCL2). This study suggests that antioxidant activities of fruits and leaves from P. mume depend on polyphenol contents. Thus, fruits and leaves from P. mume can be useful as natural antioxidant compounds.

• Journal of Applied Biological Chemistry
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• v.60 no.2
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• pp.161-171
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• 2017

This study was aimed to evaluate and compare the proximate composition, antioxidant and antiproliferative activities of Sageretia thea (Osbeck) M.C.Johnst (S. thea) fruit and blueberry. The calorific value, crude protein, crude fat, crude ash, and carbohydrate were higher in S. thea fruit than in blueberry. S. thea fruit and blueberry have different profile of free sugars, in which amounts of fructose, glucose, and maltose were much higher in S. thea fruit than in blueberry. The methanol extracts of S. thea fruit contain higher amounts of total polyphenol and anthocyanin compared to those of blueberry extracts. In additions, 2,2-diphenyl-1-picrylhydrazyl (DPPH), alkyl, and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging activities are greater in S. thea fruit extracts. Ethyl acetate fractions and n-butanol fractions of S. thea fruit and blueberry show the most potent scavenging activity in DPPH-, alkyl-, and ABTS-radical scavenging assay. The ethyl acetate fractions of S. thea fruit and blueberry are the richest fraction in polyphenol contents while the n-butanol fractions of those are the highest fraction in anthocyanin contents. Furthermore, both S. thea fruit and blueberry extracts protect human dermal fibroblast cells against a $H_2O_2$-induced oxidative stress. The antiproliferative activities of n-hexane and chloroform fraction from S. thea fruit and blueberry were observed in AGS human gastric cancer and MDA-MB-231 human breast cancer cells. Therefore, our results suggest for the first time that the antioxidant and antiproliferative activities of S. thea fruit is comparable to that of blueberry and the nutritional value of the former is even superior to that of the latter.

• Progress in Medical Physics
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• v.19 no.1
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• pp.14-20
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• 2008

Accounting for tumor motion in treatment planning and delivery is one of the most recent and significant challenges facing radiotherapy. The purpose of this study was to investigate the correlation and clarified the relationship between the motion of an external marker using the Real-Time Position Management (RPM) System and an internal organ motion signal obtained fluoroscope. We enrolled 10 patients with locally advanced lung cancer and liver cancer, retrospectively. The external marker was a plastic box, which is part of the RPM used to track the patient's respiration. We investigated the quantitatively correlation between the motions of an external marker with RPM and internal motion with fluoroscope. The internal fiducial motion is predominant in the caraniocaudal direction, with a range of $1.3{\sim}3.5cm$ with fluoroscopic unit. The external fiducial motion is predominant in the caraniocaudal direction, with a range of $0.43{\sim}2.19cm$ with RPM gating. The two measurements ratio is from 1.31 to 5.56. When the regularization guided standard deviation is from 0.08 to 0.87, mean 0.204 cm, except only for patients #3 separated by a mean 0.13 cm, maximum of 0.23 cm. This result is a good correlation between internal tumor motion imaged by fluoroscopic unit and external marker motion with RPM during expiration within 0.23 cm. We have demonstrated that gating may be best performed but special attention should be paid to gating for patients whose fiducials do not move in synchrony, because targeting on the correct phase difference alone would not guarantee that the entire tumor volume is within the treatment field.