• Journal of Life Science
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• v.19 no.1
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• pp.9-14
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• 2009

The prostate cancer is the critical health problem, increasing of its related death in worldwide. Unfortunately present surgery and chemotherapeutic choices seem to be impossible in curing or controlling prostate cancer, because metastasis occasionally advances even after these potentially curative therapies. Therefore, there is immediate need to alternative chemoprevention and chemotherapeutic agents. Over one hundred species of dried medicinal herbs were tested for proliferation inhibitory effects on prostate cancer cell line, PC-3. One of them, Anthriscus sylvestris was selected because of potent anti-proliferation effect. The dried root of A. sylvestris was extracted with 100% methanol for 2-3 days and its extract was fractionated by using ethyl acetate. And ethyl acetate layer was subjected to column chromatographies on silica gel, reverse phase-18 (RP-18) and Sephadex LH-20, in turn. Finally, the pure compound was obtained by crystallization in methanol at $4^{\circ}C$ for overnight and identified as deoxypodophyllotoxin by NMR spedorscopic and physico-chemical analyses. In addition, it was confirmed that deoxypodophyllotoxin clearly inhibits the proliferation of PC-3 cells in a dose and time-dependent manner.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1281-1291
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• 2005

Chungpae-tang is suggested to have the antitumor activity on lung cancer. This study was peformed to investigate apoptotic effect in vitro and antitumor effect and immune response after injection of B16-F10 melanoma cells and Chungpae-tang into a tail vein of C57BL/6 mice and administratition of Chungpae-tang in A549 human lung cancer cell line in vivo, respectively. Experimental studies were obtained by measuring the median survival time and cytokine expression through RT-PCR, and ELISA assay. The results were summarized as follows: 5 mg/ml of Chungpae-tang causing DNA fragmentation, caspase-3 enzyme activation, PARP fragmentation, and cytochrome c release, suggested that Chungpae-tang has in vitro apoptotic effect in A549 human lung cancer cell line in the apoptosis-induced experiment. The median survival time of the Chungpae-tang treated group was 21 days and that of control group was 22 days, suggesting that the median survival time between the Chungpae-tang treated group and the control group was not significant. Cytokine expression between the Chungpae-fang treated group and the control group was noticeable, but was not significant in the RT-PCR. In the ELISA assay, IL-2 productivity in the Chungpae-tang treated group was to increase more than that in the normal group (p<0.05) and was no significant between the Chungpae-tang treated group and the control group. $INF-\gamma$ productivity of the control group decreased more than that of the normal group (p<0.05) and that of the Chungpae-tang-treated group increased more than that of the control group (p<0.05). IL-12 productivity of the control group increased more than that of the normal group (p<0.05) and that of the Chungpae-tang-treated group decreased more than that of the control group (p<0.05) and the normal group. IL-4 productivity of the Chungpae-tang-treated group increased more than that of the normal group and the control group (p<0.05). IL-10 productivity of the Chungpae-tang-treated group increased more than that of the normal group and the control group (p<0.05). Accordingly the results show Chungpae-tang could induce apoptosis in A549 human lung cancer cell line and bring to antitumor effect and immune response against injection of B16-F10 melanoma cells into a tail vein of C57BL/6 mice but it needs more research on the precise mechanism of such effects.

• Tuberculosis and Respiratory Diseases
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• v.62 no.1
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• pp.43-50
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• 2007

Background: Mutated or deregulated expression of C-erbB-2 causes this gene to function as a potent oncogene. Vascular endothelial growth factor (VEGF) is a crucial angiogenic molecule in lung cancer. Both C-erbB-2 and VEGF can promote growth, proliferation and metastasis in non-small cell lung cancer (NSCLC). The purpose of this study was to investigate evaluate the relationship between the expressions of the C-erbB-2 and VEGF genes using immunohistochemistry. Materials and Methods: Ninety-five patients with NSCLC were involved (60 squamous cell carcinoma and 35 adenocarcinoma). The formalin-fixed paraffin embedded specimens were immunohistochemically stained for C-erbB-2 and VEGF using the avidin-biotin complex method. Results: Positive C-erbB-2 expression was observed more often in adenocarcinomas than squamous cell carcinomas (p<0.05). Although the immunohistochemical expressions of C-erbB-2 and VEGF in non-small-cell lung cancer showed increased tendencies at an advanced stage, the correlation between early and advanced cancers was insignificant. In adenocarcinomas, the expressions of VEGF and C-erbB-2 were significantly (p<0.05). Conclusion: The overexpression fo C-erbB-2 was significantly higher in adenocarcinomas than squamous cell carcinomas, and correlated with the expression of VEGF in adenocarcinomas of the lungs.

• Radiation Oncology Journal
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• v.12 no.3
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• pp.323-329
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• 1994

Purpose: In supraglottic cancer, radiation therapy is used to preserve the laryngeal function but combined surgery and radiation therapy is required in advanced stage. The authors Present the results of radiation therapy alone and combined surgery Plus Postoperative radiation therapy for supraglottic cancer. Methods and Materials: A retrospective analysis was done for 43 patients with squamous cell carcinoma of the supraglottic larynx who were treated from Feburary 1982 to December 1991, in the Department of Radiation Oncology, Korea University Hospital. Patient distribution according to the AJCC staging system was as follows: I, 3($7.0\%$); II, 7($16.3\%$); III, 17($39.5\%$); IV, 16($37.2\%$). Patients' age ranged from 30 to 72 years(median 62). Follow up durations were from 21 to 137 months(median 27). Seventeen patients($39.5\%$) were treated by radiation therapy alone with radiation doses of 6840-7380 cGy and 26 patients($60.5\%$) were treated with surgery plus postoperative irradiation with doses of 5820-6660 cGy. Results: Overall five-year survival rate for all stage was $51.8\%$, with $100\%$ for Stage I and II, $47.3\%$ for Stage III, and $29.2\%$ for Stage III. The difference of the survival rate by stage was statistically significant(p=0.0152). Five-year survival rates were $100\%$ for locally confined tumor in the supraglottic larynx, $37.5\%$ for transglottic extension, $26.7\%$ for hypopharynx extension, and only two of 5 patients with both transglottic and hypopharynx extension were alive(p=0.0033). Five-year survival rates by neck node status were as follows: $55.0\%$ for NO, $64.3\%$ for N1, $50.0\%$ for N2, and all 2 of N3 were died of disease. Overall survival rate for radiation therapy alone group was $42.8\%$, and it was $56.7\%$ for surgery plus postoperative radiation therapy group with no statistically significant difference(p=0.5215). In Stage I and II, all Patients survived. In Stage III and IV, 5-year survival rate for radiation therapy alone group was $28.5\%$ and $43.4\%$ for surgery plus postoperative irradiation group(p=0.5103). Local control rate was $58.8\%$(10/17) for radiation therapy alone group and $73.1\%$ (19/26) for surgery plus postoperative irradiation group. Three patients from surgery plus postoperative radiation therapy group developed distant metastasis in lungs. Conclusion: Treatment results of radiation therapy alone was excellent in early stage supraglottic cancer. In advanced stage, even the difference was statistically not significant, the result of postoperative radiation therapy group was superior compared with radiation therapy alone group. Since 1992, concomitant chemoradiotherapy with hyperfractionated radiotherapy is being used to improve the result of the treatment and preserve the laryngeal function in advanced stage supraglottic cancer.

• Radiation Oncology Journal
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• v.36 no.2
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• pp.147-152
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• 2018

Purpose: To evaluate the treatment outcomes of adjuvant external beam radiation therapy (EBRT) and vaginal brachytherapy (VB) following radical hysterectomy in cervical cancer patients with involved vaginal resection margin (VRM). Materials and Methods: We retrospectively reviewed the medical records of 21 patients treated with postoperative EBRT and VB for positive VRM FIGO stage IB-IIA cervical cancer between 2003 and 2015. Concurrent platinum-based chemotherapy was administered to all patients. Results: The median whole pelvis EBRT dose was 50.4 Gy (range, 45 to 50.4 Gy). In the VB, the median dose per fraction, number of fractions, and total dose delivered were: 4 Gy (range, 3.0 to 4.0 Gy), 4 fractions (range, 3 to 5 fractions), and 16 Gy (range, 12 to 20 Gy), respectively. At a median follow-up of 46 months (range, 9 to 122 months), local recurrence was observed in 2 patients, and distant metastasis was present in 7 patients. All patients with local recurrence subsequently developed distant metastases. The 5-year local control, disease-free survival, and overall survival rates were 89.1%, 65.9%, and 62.9%, respectively. Of the 21 patients, 7 patients (33.3%) reported grade 2 acute toxicity; however, there were no grade 3 or higher acute adverse events. Grade 1-2 late toxicities were observed in 8 patients. Late grade 3 urinary toxicity was reported in 1 patient. Conclusions: Adjuvant EBRT and VB showed excellent local control and low toxicity in cervical cancer patients with positive VRM. Although limited by its retrospective nature, the findings from our study provide evidence supporting the use of additional VB in pathologically involved VRM.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.283-289
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• 1998

Purpose : This study was performed to analyze the efficacy of induction chemotherapy fellowed by radiation therapy in locally advanced non-small cell lung cancer Materials and Methods : Eighty patients with locally advanced non-small cell lung cancer treated from 1989 to 1995 at Pusan Paik hospital were analyzed retrospectively. Twenty-one patients were treated with induction chemotherapy followed by radiation therapy and Fifty-nine Patients were treated with radiation therapy alone. Chemotherapy regimen consisted of cisplatin-based combination (2 or 3 drugs). All patients were treated by Co-60 or 6 MV linear accelerators. Radiation dose ranged from 50 Gy to 80 Gy (median 64.8 Gy). We evaluated response rate, survival rate, and pattern of failure in both treatment groups. Results : Overall response rate in induction chemotherapy group and radiotherapy alone group were 48% and 45%, respectively. Of the 80 patients, 46 patients were evaluable for pattern of failure. Initial failure pattern in induction chemotherapy group was as follows: 8 (67%) at locoregional, 4 (33) in distant metastasis. Radiation alone group was 21 (71%) and 5 (29%), respectively. Results showed no difference of distant failure between induction chemotherapy group and radiation alone group. The 1 and 2 year survival rate in induction chemotherapy group were 43% and 14%, respectively and in radiotherapy alone group, 31% and 7%, respectively (p=0.135). Conclusion : In stage III non-small cell lung cancer, induction chemotherapy and radiation therapy showed increased tendency in survival with no statistical significance Induction chemotherapy seems to have no effect of decreasing distant failure and no survival advantage compared with radiotherapy alone.

• Journal of Gastric Cancer
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• v.8 no.4
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• pp.198-203
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• 2008

Purpose: Multiple early gastric cancer (MEGC) accounts for between 4.5% and 11.7% of all early gastric cancers (EGC). We investigated the treatment of MEGC from the viewpoint of the clinicopathologic features of the disease. Materials and Methods: 2,281 patients with EGC underwent gastric resection at the Department of Surgery, Severance Hospital during the 11 years between January 1994 and December 2004 and we carried out a retrospective analysis of these patients. Results: There were 91 cases of synchronous MEGC (4.0%) according to the diagnostic criteria of Moertel: there were 81 double, 9 triple and 1 quadruple lesions. Of the 102 accessory lesions, 64 (62.7%) were less than 10 mm in diameter and 83 (81.4%) were located in the same region as the main lesion. The most frequent histologic type of main lesion was a well differentiated adenocarcinoma, which was found in 52 cases (57.1%). There were 49 mucosal main lesions and 42 submucosal main lesions. Lymph node metastasis was detected in 6 cases (6.6%): 1 in mucosal lesions and 5 in submucosal main lesions Conclusion: Solitary EGC and MEGC had very similar clinopathological features and a similar prognosis. Therefore, we believe that the general EGC treatment guidelines can be applied for multiple EGC. It is important to evaluate the whole stomach before and during the operation and then after examining the resected specimen.

• Journal of Gastric Cancer
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• v.19 no.3
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• pp.329-343
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• 2019

Purpose: Gastric cancer with lymph node metastasis (LNM) more than 15 (N3b) was defined as stage IV until the 6th AJCC system. However, it has been reclassified as a localized disease (stage IIb or III) since the 7th system. The aim of this study is to demonstrate that the survival of N3b is comparable to cytology-only positive (CY1-only) stage IV and to propose a new TNM system interpreting N3b as an eligibility criterion for receiving more intensive chemotherapy regimens. Materials and Methods: 1,430 patients who underwent gastric cancer surgery at Seoul National University Hospital from 2007 to 2012 were retrospectively analyzed. The 5-year survival rate (5YSR) and 3-year recurrence-free survival (RFS) were evaluated according to the 7th and 8th systems, as well as a new categorization based on N-classification; N0-2 (LNM<7), N3a (LNM 7-15), or N3b (LNM>15). Results: The survival of N3b is comparable to that of CY1-only stage IV (log rank test, P=0.671) and is distinct from that of grossly stage IV (log rank test, P<0.001). The survival of the remaining stage IIIc (T4bN3a) was comparable to those of N3b and CY1-only stage IV. Most N3b patients had significantly shorter 3-year RFS and mean RFS than those with IIb-IIIc, as if N3b itself was a higher TNM stage. Conclusions: In terms of survival, T4bN3a, N3b, and CY1-only stage IV were unified as stage IVa, while grossly stage IV was defined as stage IVb. N3b can be regarded as an eligibility criterion for undergoing more intensive chemotherapy regimens.

• Journal of Life Science
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• v.33 no.6
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• pp.523-529
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• 2023

Ubiquitination is a post-translational modification that is involved in the quality control of proteins and responsible for modulating a variety of cellular physiological processes. Protein ubiquitination and deubiquitination are reversible processes that regulate the stability of target substrates. The ubiquitin proteasome system (UPS) helps regulate tumor-promoting processes, such as DNA repair, cell cycle, apoptosis, metastasis, and angiogenesis. The UPS comprises a combination of ubiquitin, ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin-ligase enzymes (E3), which complete the degradation of target proteins. Ubiquitin-conjugating enzymes (UBE2s) play an inter-mediate role in the UPS process by moving activated ubiquitin to target proteins through E3 ligases. UBE2s consist of 40 members and are classified according to conserved catalytic ubiquitin-conjugating (UBC) domain-flanking extensions in humans. Since UBE2s have specificity to substrates like E3 ligase, the significance of UBE2 has been accentuated in tumorigenesis. The dysregulation of multiple E2 enzymes and their critical roles in modulating oncogenic signaling pathways have been reported in several types of cancer. The elevation of UBE2 expression is correlated with a worse prognosis in cancer patients. In this review, we summarize the basic functions and regulatory mechanisms of UBE2s and suggest the possibility of their use as therapeutic targets for cancer.

• Journal of Digestive Cancer Research
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• v.5 no.1
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• pp.44-49
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• 2017

Background: Recently, endoscopic submucosal dissection (ESD) with laparoscopic sentinel lymph node dissection, named ESN or endoscopic full-thickness gastric resection with laparoscopic sentinel lymph node dissection, named Hybrid-natural orifice transluminal endoscopic surgery (NOTES) was suggested the possibility of minimally invasive treatment for patients with early gastric cancer (EGC) who were beyond the indication of ESD. This study aimed to evaluate the outcomes of ESN or Hybrid-NOTES. Methods: We retrospectively analyzed patients treated with these therapies from January 2009 to May 2013 in terms of short- and long-term outcomes. Each patient was diagnosed with EGC but was not included in ESD indications and had the high risk of lymph node metastasis (LNM). Results: A total of 42 patients with EGC treated by ESN or Hybrid-NOTES. Of the 21 patients who underwent ESN, a total of 4 patients underwent additional gastrectomy, 1 with LNM, 1 with surgical complication, and 2 with noncurative resection. Of the 21 patients who underwent Hybrid-NOTES, a total of 5 patients underwent additional surgery, 1 with LNM, 2 with surgical complication, and 2 with noncurative resection. Overall survival was 100% over a mean follow-up of 75 months, but 3 patients underwent ESD or gastrectomy with metachronous lesion. And 1 patient who had received ESN was found to have a metastatic lymph node and undergo palliative chemotherapy. Conclusion: ESN or Hybrid-NOTES showed favorable short-and long-term outcomes. These methods may be utilized as a bridge between ESD and gastrectomy in the case of EGC which is more likely to have LNM beyond the ESD indications.