• Clinical and Experimental Pediatrics
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• 제46권12호
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• pp.1260-1265
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• 2003

목 적 : 소아기급성림프구성 백혈병의 재발율을 낮추기 위하여 1970년대부터 시작되어 본원에서는 1990년대에 도입된 후기강화 요법의 효과를 평가하기 위하여 본 조사를 시행하였다. 방 법 : 1990년 3월부터 2002년 7월까지 연세대학교 원주의과대학 소아과 및 신촌세브란스병원 소아과에서 치료받은 급성림프구성 백혈병환자 139명을 대상으로 성별, 진단시 나이, 백혈구수, 면역표현형, 후기강화요법 실시여부 및 합병증 등의 기록을 후향적으로 고찰하였다. 후기강화요법은 CCG-1891의 약제를 사용하였으며 Kaplan-Meier 생존곡선을 이용하여 전체생존율 및 재발에 따른 사망을 사건으로 정의한 무병생존추정률을 구하였다. 결 과 : 전체 환아의 정중추적 관찰기간은 39개월(범위 3-237개월)이었으며 5년 생존율은 60%였고, 5년 무병생존추정률은 55%였다. 후기강화요법 시행에 따른 5년 생존율은 1회 시행시 86%, 2회 이상 시행 시 95%였으며 시행하지 않은 경우는 40%였다. 후기강화요법 시행에 따른 5년 무병생존추정률은 1회 시행시 84%, 2회 이상 시행 시 95%였으며 시행하지 않은 경우는 45%였다. 저위험군에서는 후기강화요법 시행 시 5년 생존율이 94%, 시행하지 않은 경우는 58%였고, 5년 무병생존추정률은 시행한 경우는 97%, 시행하지 않은 경우는 52%였다. 결 론 : 급성림프구성 백혈병 소아에서 후기강화요법 시행은 5 년 무병생존추정률 및 5년 생존율을 향상시켰다.

• Journal of Ginseng Research
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• 제42권2호
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• pp.165-174
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• 2018

Background: Extended endoplasmic reticulum (ER) stress may initiate apoptotic pathways in cancer cells, and ER stress has been reported to possibly increase tumor death in cancer therapy. We previously reported that caspase-8 played an important role in compound K-induced apoptosis via activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation in HL-60 human leukemia cells. The mechanisms leading to apoptosis in A549 and SK-MES-1 human lung cancer cells and the role of ER stress have not yet been understood. Methods: The apoptotic effects of compound K were analyzed using flow cytometry, and the changes in protein levels were determined using Western blot analysis. The intracellular calcium levels were monitored by staining with Fura-2/AM and Fluo-3/AM. Results: Compound K-induced ER stress was confirmed through increased phosphorylation of $eIF2{\alpha}$ and protein levels of GRP78/BiP, XBP-1S, and $IRE1{\alpha}$ in human lung cancer cells. Moreover, compound-K led to the accumulation of intracellular calcium and an increase in m-calpain activities that were both significantly inhibited by pretreatment either with BAPTA-AM (an intracellular $Ca^{2+}$ chelator) or dantrolene (an RyR channel antagonist). These results were correlated with the outcome that compound K induced ER stress-related apoptosis through caspase-12, as z-ATAD-fmk (a specific inhibitor of caspase-12) partially ameliorated this effect. Interestingly, 4-PBA (ER stress inhibitor) dramatically improved the compound K-induced apoptosis. Conclusion: Cell survival and intracellular $Ca^{2+}$ homeostasis during ER stress in human lung cancer cells are important factors in the induction of the compound K-induced apoptotic pathway.

• 대한본초학회지
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• 제30권4호
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• pp.37-44
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• 2015

Objectives : The present study was designed to evaluate the anti-inflammatory and anti-oxidative stress activities through regulation of Nrf2-mediated genes by Rhei rhizoma and Glycyrrhiza rhizoma combined extract (RGE) in reflux esophagitis.Methods : The antioxidant activity of RGE in vitro was measured in terms of radical scavenging capacity such as DPPH and ABTS. RGE was administered at 350 mg/kg body weight prior to induction of reflux esophagitis. Reflux esophagitis was induced that tied the pylorus and the transitional junction between the forestomach and the corpus in Sprague-Dawley rats.Results : RGE scavenged DPPH and ABTS effectively and IC₅₀of RGE each were 4.9 μg/ml and 45.6 μg/ml. Our results show that RGE administration markedly ameliorated mucosal damage upon histological evaluation. In serum and esophagus tissue, RGE significantly suppressed the oxidative stress biomarkers. Reflux esophagitis induced rats exhibited down-regulation of antioxidant-related proteins in the esophagus; however, the levels with treatment of RGE were significantly higher than those of vehicle reflux esophagitis rats. RGE treatment caused significant reductions in activation of NF-κB transcription factor. Thus, RGE significantly exhibited potent anti-inflammatory activities by suppressing the protein expression levels of pro-inflammatory proteins such as COX-2 and iNOS and inflammatory cytokines such as TNF-αin the esophagus tissue.Conclusions : Reflux esophagitis caused considerable levels of oxidative stress in the esophageal mucosa and the administration of RGE reduced the esophageal mucosa damage through the regulation of Nrf2 and NF-κB pathways. Our findings can considered as supplementary therapy in the prevention or treatment of reflux esophagitis.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.627-633
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• 2015

Background: To study the effect of parecoxib, a novel cyclooxygenase-2 selective inhibitor, on the radiation response of colorectal cancer (CRC) cells and its underlying mechanisms. Materials and Methods: Both in vitro colony formation and apoptosis assays as well as in vivo mouse xenograft experiments were used to explore the radiosensitizing effects of parecoxib in human HCT116 and HT29 CRC cells. Results: Parecoxib sensitized CRC cells to radiation in vitro with a sensitivity enhancement ratio of 1.32 for HCT116 cells and 1.15 for HT29 cells at a surviving fraction of 0.37. This effect was partially attributable to enhanced apoptosis induction by parecoxib combined with radiation, as illustrated using an in vitro apoptosis assays. Parecoxib augmented the tumor response of HCT116 xenografts to radiation, achieving growth delay more than 20 days and an enhancement factor of 1.53. In accordance with the in vitro results, parecoxib combined with radiation resulted in less proliferation and more apoptosis in tumors than radiation alone. Radiation monotherapy decreased microvessel density (MVD) and microvessel intensity (MVI), but increased the hypoxia level in xenografts. Parecoxib did not affect MVD, but it increased MVI and attenuated hypoxia. Conclusions: Parecoxib can effectively enhance radiation sensitivity in CRC cells through direct effects on tumor cells and indirect effects on tumor vasculature.

• 한국식품영양과학회지
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• 제33권1호
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• pp.1-6
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• 2004

$\beta$-Sitosterol은 과일과 야채 등을 포함한 대부분의 고등식물에 존재하는 중요한 phytosterol의 하나로서, 인체 암의 예방과 치료에 매우 유효한 것으로 보고되어져 오고 있다. 본 연구에서는 $\beta$-sitosterol의 암세포 증식억제 기전의 해석을 시도하기 위하여 인체 대장암세포 HCT116의 증식에 미치는 $\beta$-sitosterol의 영향을 조사하였다. $\beta$-Sitosterol의 처리로 HCT116 암세포의 증식은 처리 농도 의존적으로 감소되었으며, 특히 7.5 $\mu$M 이상 처리에서는 급격한 성장억제 효과가 있었다. 또한 5.0 $\mu$M 처리군에서부터 apoptotic body의 형성이 관찰되었고, $\beta$-catenin 단백질의 분해 현상과 연관성이 있었다. 그리고 $\beta$-sitosterol이 처리된 암세포에서는 종양억제유전자 p53 및 Cdk inhibitor p21의 발현이 전사 및 번역 수준에서 모두 증가되었다. 본 결과는 그동안 연구가 거의 진행되어져 있지 않았던 $\beta$-sitosterol에 의한 암세포주기 조절 해석을 위한 주요한 자료로 활용될 것이다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6651-6661
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• 2015

Breast cancer is a global health concern and is a major cause of death among women. In Oman, it is the most common cancer in women, with an incidence rate of 15.6 per 100,000 Omani females. Various anticancer remedies have been discovered from natural products in the past and the search is continuing for additional examples. Cytotoxic natural compounds may have a major role in cancer therapy either in potentiating the effect of chemotherapy or reducing its harmful effects. Recently, a few studies have reported advantages of using crude camel milk in treating some forms of cancer. However, no adequate data are available on the lyophilised camel's milk responsibility for triggering apoptosis and oxidative stress associated with human breast cancer. The present study aimed to address the role of the lyophilised camel's milk in inducing proliferation repression of BT-474 and HEp-2 cells compared with the non-cancer HCC1937 BL cell line. Lyophilized camel's milk fundamentally repressed BT-474 cells growth and proliferation through the initiation of either the intrinsic and extrinsic apoptotic pathways as indicated by both caspase-3 mRNA and its action level, and induction of death receptors in BT-474 but not the HEp-2 cell line. In addition, lyophilised camel's milk enhanced the expression of oxidative stress markers, heme-oxygenase-1 and reactive oxygen species production in BT-474 cells. Increase in caspase-3 mRNA levels by the lyophilised camel's milk was completely prevented by the actinomycin D, a transcriptional inhibitor. This suggests that lyophilized camel's milk increased newly synthesized RNA. Interestingly,it significantly (p<0.003) repressed the growth of HEp-2 cells and BT-474 cells after treatment for 72 hours while 24 hours treatment repressed BT-474 cells alone. This finding suggests that the lyophilised camel's milk might instigate apoptosis through initiation of an alternative apoptotic pathway.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.6007-6012
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• 2013

ANXA2, a member of the annexin family, is overexpressed and plays important roles in tumor development. However, the significance of ANXA2 expression in gastric carcinoma has not been clarified.To elucidate its roles in growth of gastric cancer, ANXA2 expression in SGC-7901 cells was inhibited with a designated siRNA, then cell proliferation, cell cycling, apoptosis and motility were determined by MTT assay, flow cytometry, Hoechst 33342 staining and wound healing assay, respectively. To further assess the behavior of ANXA2 deleted SGC-7901 cells, changes of microstructures were observed under fluorescence microscopy, laser scanning confocal microscopy and electron microscopy. We found that inhibition of ANXA2 expression caused cell proliferation to decrease significantly with G1 arrest, motility to be reduced with changes in pseudopodia/filopodia structure and F-actin and ${\beta}$-tubulin expression, and apoptosis to be enhanced albeit without significance. At the same time, ANXA2 deletion resulted in fewer pseudopodia/filopodia, non-stained areas were increased, contact inhibition among cells reappeared, and expression of F-actin and ${\beta}$-tubulin was decreased, with induction of polymerized disassembled forms. Taken together, these data suggest that ANXA2 overexpression is important to maintain the malignancy of cancer cells, and this member of the annexin family has potential to be considered as a target for the gene therapy of gastric carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5989-5993
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• 2013

Background: Radiation therapy is the mainstay of treatment for nasopharyngeal carcinoma. Importance of tumor coverage and challenges posed by its unique and critical location are well evident. Therefore we aimed to evaluate our radiation treatment plan through dose volume histograms (DVHs) to find planning target volume (PTV) dose coverage and factors affecting it. Materials and Methods: This retrospective study covered 45 histologically proven nasopharyngeal cancer patients who were treated with definitive 3D-CRT and chemotherapy between Feb 2006 to March 2013 at the Department of Oncology, Section Radiation Oncology, Aga Khan University Hospital, Karachi, Pakistan. DVH was evaluated to find numbers of shrinking field (phases), PTV volume in different phases and its coverage by the 95% isodose lines, along with influencing factors. Results: There were 36 males (80%) and 9 females (20%) in the age range of 12-84 years. Stage IVA (46.7%) was the most common stage followed by stage III (31.1). Eighty six point six-percent received induction, 95.5% received concurrent and 22.2% received adjuvant chemotherapy. The prescribed median radiation dose was 70Gy to primary, 60Gy to clinically positive neck nodes and 50Gy to clinically negative neck regions. Mean dose to spinal cord was 44.2Gy and to optic chiasma was 52Gy. Thirty seven point eight-percent patients completed their treatment in three phases while 62.2% required four to five phases. Mean volume for PTV3 was $247.8cm^3$ (50-644.3), PTV4 $173.8cm^3$ (26.5-345.1) and PTV5 $119.6cm^3$ (18.9-246.1) and PTV volume coverage by 95% isodose lines were 74.4%, 85.7% and 100% respectively. Advanced T stage, intracranial extension and tumor volume > $200cm^3$ were found to be important factors associated with decreased PTV coverage by 95% isodose line. Conclusions: 3D CRT results in adequate PTV dose coverage by 95% isodose line. However advanced T stage, intracranial extension and large target volume require more advanced techniques like IMRT for appropriate PTV coverage.

• 대한의생명과학회지
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• 제3권1호
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• pp.11-20
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• 1997

신경아세포종 세포 분화의 조절에 대한 연구는 아직 초기 단계에 불과하나 신경아세포종양의 임상적인 치료에 매우 중요한 기초가 된다. 본 연구는 신경아세포종 세포의 분화를 유도 할 수 있는 유용한 시약을 찾아내고자 하는 노력의 일환으로, 잘 알려진 DNA 합성 억제제가 신경 아세포종의 분화를 유도할 수 있는지를 살펴보고자 신경아세포종양 세포의 형태적, 생화학적 및 유전자 발현에 미치는 효과를 살펴보았다. 신경아세포종양으로부터 수립된 세포주, IMR-32 세포에 DNA 합성 억제제인 sodium butyrate, hydroxyurea, cytosine arabinoside를 각각 처리한 결과 처리하지 않은 대조군과는 달리 정상신경 세포 분화시 볼 수 있는 신경 돌기의 성장이 유도됨을 관찰할 수 있었으며 ,신경 전달 물질인 acetylcholine의 합성 효소인 choline acetyltransferase의 활성도가 현저히 증가되었다. 또한DNA합성 억제제를 처리하지 않은 IMR-32세포에서 탐지되지 않았던 c-myc 유전자의 발현이 시약 처리시 확연히 탐지됨을 관찰할 수 있었다. 이러한 실험 결과들은 DNA합성 억제제가 IMR-32세포의 성장을 억제하고 분화를 유도했음을 보여준 것이며, 어린 아이 시기에 많이 발병되는 신경아세포종양의 급속한 악성화나 전이의 억제기전을 제시해 줄 수 있으리라 생각한다.

• Journal of Plant Biotechnology
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• 제38권1호
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• pp.62-68
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• 2011

원예작물의 생육을 저하시키는 각종 병충해로 인한 과도한 농약과 화학비료의 사용은 환경오염뿐만 아니라 작물의 생산량에도 큰 영향을 미치고 있다. 식물생명공학기술을 이용하여 농약이나 화학비료 사용량을 획기적으로 줄일 수 있는 식물체의 개발, 즉 형질전환을 이용한 분자 육종기술은 병충해 내성 농작물을 개발하여 과도한 화학비료의 사용에 따르는 여러가지 문제점들을 극복할 수 있는 대안으로 대두되고 있다. 본 연구에서는 모델식물인 애기장대에서 분리한 식물생체방어 신호전달에 관련된 AtCBP63 유전자를 감자에 과발현시켰고, 이러한 형질 전환 감자에서 병저항성에 관여하는 유전자인 PR-2, PR-3, PR-5 유전자들의 발현이 증가되어 지속적으로 식물 방어 기작이 활성화되어 있음을 확인하였다. 또한, 감자에서 무름병 (soft rot disease)을 일으켜 막대한 피해를 유발하는 병원성 세균인 Erwinia carotovora subsp. Carotovora (Ecc)를 이용하여 AtCBP63 유전자를 과발현한 감자에 감염시켰을 때, 병 저항성이 증가한다는 사실을 검증하였다. 앞으로, 다양한 곰팡이 균에 대응하여 AtCBP63 유전자를 과발현한 감자에 저항성을 검증하고자 한다.