• 대한한방부인과학회지
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• 제19권1호
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• pp.69-80
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• 2006

Purpose : This study is to evaluate the synergistic cytotoxicity of Rhizoma Rehmanniae(RR), in adriamycin-treated HeLa human cervical carcinoma cells. Methods : We culture HeLa cell which is human metrocarcinoma cell in D-MEM included 10% fetal bovine serum(Hyclone Laboratories) below $37^{\circ}C$, 5% $CO_2$. Then we observed apoptosis of log phage cell which is changed cultivation liquid 24 Hours periodically. Results : The combination of RR and adriamycin synergistically augmented the cytotoxicity of HeLa cells. The apoptotic cell death was accompanied by the activation of caspase-3 and -8 as well as cleavage of poly(ADP- ribose) polymerase (PARP) in HeLa cells. The co-treatment of RR with adriamycin didn't have any effect on either the expression of Bcl-2 or that of Bax. Interestingly, a synergistic increase in apoptosis by the combination of two drugs was accompanied by the enhancement of Pas and Fas ligand (FasL) expression in HeLa cells. Taken together, the combination of RR and adriamycin significantly augmented the apoptotic cytotoxicity of Fas-positive cells, such as HeLa cells. The pathway is not involved in mitochondria-dependent pathway. Conclusion : RR induces apoptosis in HeLa cells via p38 MAPK activation.

• 대한한방부인과학회지
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• 제19권2호
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• pp.34-48
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• 2006

Purpose : This study was conducted to investigate the inhibitory effects of Dangguijakyaksan on cell proliferation in HeLa cells. Methods : Human uterine cervical carcinoma HeLa cells were cultured in the 1%, 5% and 10% concentration of Dangguijakyaksan extract solution for 24 hours, 48 hours and 72 hours for the direct inhibitory effects of Dangguijakyaksan. Afterwards, we executed the analysis of the effect of Dangguijakyaksan extract solution on cell proliferation inhibition using XTT assay, molecular biological method through MAP kinase activity and FACS analysis of caspase activity in the HeLa cells. Results : After 24, 48 and 72 hours cultivation, Dangguijakyaksan extract solution group showed significant decrease of HeLa cells except 1% solution after 24 hours compared with the control group. In the FACS analysis, Dangguijakyaksan extract solution groups showed increase of caspase activity except 1% solution after 48 hours compared with the control group. In the XTT assay, the caspase-3 activities were increased in Dangguijakyaksan extract solution groups except 1% solution after 24 hours in a dose-dependent manner. In the XTT study, cell activities were significantly decreased in 10% Dangguijakyaksan extract solution groups after 48 and 72 hours cultivation compared with the control group. In all Dangguijakyaksan extract solution groups, The activities of MAP kinase were decreased after 24, 48 and 72 hours cultivation compared with the control group. Conclusion : It could be concluded that Dangguijakyaksan is available to the inhibition of proliferation of human cervical carcinoma cell line in vitro.

• 생명과학회지
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• 제23권3호
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• pp.355-360
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• 2013

Withaferin A는 Withania somnifera라는 식물에서 추출한 스테로이드 락톤으로 항염증, 항암, 그리고 면역중재 작용과 같은 다양한 역할을 한다. 그러나, withaferin A에 의한 MMP-9의 발현 및 활성화 조절에 대한 연구는 수행되지 않았다. 본 연구에서 우리는 withaferin A가 인간 자궁경부암세포인 Caski세포에서 PMA 매개의 MMP-9의 발현과 활성화를 조절 할 수 있는지 확인하였다. Withaferin A는 농도의존적으로 PMA유도 MMP-9의 활성을 억제하였고, MMP-9의 promoter assay를 통하여 전사단계에서 조절됨을 확인하였다. 또한, Withaferin A 의한 PMA 유도 MMP-9의 mRNA와 단백질 발현이 억제됨을 확인하였다. 이러한, withaferin A에 의한 MMP-9 발현 조절 전사인자로는 NF-${\kappa}B$가 관여함을 확인하였다. Withaferin A는 PMA에 의한 세포이동을 억제하였는데, 이러한 현상은 MMP-9의 발현 및 활성을 조절함으로써 일어날 수 있음을 확인하였다.

• 한국의학물리학회지:의학물리
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• 제32권4호
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• pp.130-136
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• 2021

Purpose: The Halcyon radiotherapy platform at Groote Schuur Hospital was delivered with a factory-configured analytical anisotropic algorithm (AAA) beam model for dose calculation. In a recent system upgrade, the Acuros XB (AXB) algorithm was installed. Both algorithms adopt fundamentally different approaches to dose calculation. This study aimed to compare the dose distributions of cervical carcinoma RapidArc plans calculated using both algorithms. Methods: A total of 15 plans previously calculated using the AAA were retrieved and recalculated using the AXB algorithm. Comparisons were performed using the planning target volume (PTV) maximum (max) and minimum (min) doses, D95%, D98%, D50%, D2%, homogeneity index (HI), and conformity index (CI). The mean and max doses and D2% were compared for the bladder, bowel, and femoral heads. Results: The AAA calculated slightly higher targets, D98%, D95%, D50%, and CI, than the AXB algorithm (44.49 Gy vs. 44.32 Gy, P=0.129; 44.87 Gy vs. 44.70 Gy, P=0.089; 46.00 Gy vs. 45.98 Gy, P=0.154; and 0.51 vs. 0.50, P=0.200, respectively). For target min dose, D2%, max dose, and HI, the AAA scored lower than the AXB algorithm (41.24 Gy vs. 41.30 Gy, P=0.902; 47.34 Gy vs. 47.75 Gy, P<0.001; 48.62 Gy vs. 50.14 Gy, P<0.001; and 0.06 vs. 0.07, P=0.002, respectively). For bladder, bowel, and left and right femurs, the AAA calculated higher mean and max doses. Conclusions: Statistically significant differences were observed for PTV D2%, max dose, HI, and bowel max dose (P>0.05).

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2947-2951
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• 2015

Background: The phenomenon of occult carcinoma maybe observed in patients with clinically unilateral papillary thyroid microcarcinoma (PTMC). Although many studies have reported that the $BRAF^{T1799A}$ mutation is associated with aggressive PTMC, the relationship between $BRAF^{T1799A}$ mutation and occult carcinoma is unclear. The aim of this study was to investigate the risk factors, including $BRAF^{T1799A}$ mutation, for occult contralateral carcinoma in clinically unilateral PTMC accompanied by benign nodules in the contralateral lobe. Materials and Methods: From January 2011 to December 2013, we prospectively enrolled 89 consecutive PTMC patients with clinically unilateral carcinoma accompanied by benign nodules in the contralateral lobe who received a total thyroidectomy and cervical lymph node dissection. $BRAF^{T1799A}$ mutation was tested by pyrosequencing on postoperative paraffin specimens. The frequency and predictive factors for occult contralateral carcinoma were analyzed with respect to the following variables: age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or $BRAF^{T1799A}$ mutation. Results: A total of 36 patients (40.4%) had occult PTMC in the contralateral lobe. The median diameter of the occult tumors was $0.33{\pm}0.21cm$. The $BRAF^{T1799A}$ mutation was found in 38 cases (42.7%). According to the univariate analysis, there were no significant differences between the presence of occult contralateral carcinoma and age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or $BRAF^{T1799A}$ mutation. Conclusions: Using current methods, it is difficult to preoperatively identify patients with PTMC, and further research is needed to determine predictive factors for the presence of occult contralateral carcinoma in patients with unilateral PTMC.

• Radiation Oncology Journal
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• 제19권3호
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• pp.224-229
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• 2001

목적 : 방사선단독으로 치료했던 자궁경부암에서 치료실패 양상과 치료실패에 대한 위험인자를 확인하여 동시항암 화학방사선요법의 적용기준을 마련하고자 본 연구를 시행하였다. 대상 및 방법 : 1989년 4월부터 1997년 12월까지 경상대학교병원 치료방사선과에서 자궁경부암으로 방사선치료를 시행받은 환자중 외부방사선조사와 강내조사를 계획대로 완료한 154명을 대상으로 후향적 분석을 시행하였다. FIGO에 의한 병기별 분포는 Ib 12명, IIa 24명, IIb 98명, IIIa 1명, IIIb 17명, IVa 2명이었다. 생존율은 Kaplan-Meyer 법을 이용하여 구하였고, 생존율의 비교는 Log-rank test로, 다변량분석은 Cox proportional hazard model을 이용하였다. 국소 또는 원격실패에 대한 단변량, 다변량분석은 logistic regression model을 사용하였다. 방광 및 직장의 합병증 평가는 RTOG/EORTC에서 제안하여 사용하고 있는 SOMA scale을 적용하였다. 결과 : 전체 154명 가운데 완전 관해를 보인 경우는 130명으로 완전관해율은 $84.4\%$였다. 완전관해자 가운데 6명이 국소재발, 25명이 원격전이, 10명이 국소재발 및 원격전이를 보여 완전관해자 가운데 $31.5\%$가 치료에 실패하였다. 연구대상 전체의 치료실패양상을 보면 국소실패가 25명, 원격실패가 25명, 국소 및 원격실패가 15명으로 전체환자의 치료실패율은 $42.1\%$ (65/154)였고, 국소실패율(국소단독실패와 국소, 원격 이중실패를 합한 것) 및 원격실패율(원격단독실패와 국소, 원격 이중실패를 합한 것)은 각각 $25.9\%$ (40/154), $25.9\%$ (40/154)였다. 국소실패의 위험인자로서는 단변량, 다변량분석 모두에서 종양의 크기가 유의하였고 원격실패의 위험인자로서는 단변량분석에서는 병리, 종양의 크기, 골반임파절전이, 치료전 혈색소 수치가 유의하였으나, 다변량분석에서는 종양의 크기, 골반임파절전이가 유의하였다. 5년 생존율은 $FIGO\;Ib\;74\%,\;IIa\;67\%,\;IIb\;63\%,\;IIb\;45\%$. 결론 : 종양의 크기가 4 cm 이상인 경우 방사선치료만으로는 국소 및 원격실패의 가능성이 높고 생존율 역시 낮다. 크기가 4 cm 이상이거나 골반임파절전이가 있는 경우 대동맥임파절 전이 가능성이 높다. 따라서 크기가 4 cm 이상이거나 골반임파절 전이가 있는 경우 국소제어율을 높이고 원격전이를 줄이기 위해 동시방사선항암화학요법을 시행하여야 한다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4363-4368
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• 2015

Background: The tumor-stroma ratio (TSR) represents the percentage of neoplastic cell components compared to the combined area of neoplastic cells and the surrounding tumor-induced stroma. A low TSR (predomination of stromal component) has been demonstrated to be an independent adverse prognostic factor in cancers of several organs. In cervical carcinoma patients, TSR has been evaluated in only one previous study with different histological types. The present study aimed to assess the prognostic value of TSR in early stage cervical cancer patients with adenocarcinoma histology only. Materials and Methods: Histological slides of patients with early stage (IB-IIA) cervical adenocarcinoma who underwent surgical treatment between January 2003 and December 2011 were reviewed. Patients who had received preoperative chemotherapy were excluded. TSR was categorized as low (<50%) and high (${\geq}50%$). Correlations between TSR and clinicopathological variables were evaluated. Prognostic values of TSR and other variables were estimated using Cox's regression. Results: Of 131 patients; 38 (29.0%) had low TSR and 93 (71.0%) had high TSR. The patients with low TSR had significantly higher proportions of deep cervical stromal invasion (outer third of wall, p=0.011; residual stroma less than 3 mm, p=0.008) and parametrial involvement (p=0.026). Compared to the patients with high TSR, those with low TSR tended to have lower 5-year disease-free survival rate (83.8% versus 88.9%) and overall survival rate (85.6% versus 90.3%), although the differences were not statistically significant. Low TSR was significantly associated with decreased overall survival in univariate analysis (HR 2.7; 95% CI 1.0-7.0; p=0.041), but not in multivariate analysis. TSR was not significantly associated with decreased disease-free survival. Conclusions: Low TSR is associated with decreased overall survival in patients with early stage cervical adenocarcinoma treated by surgery. However, it was not found to be an independent prognostic predictor in this study.

• Journal of Chest Surgery
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• 제41권2호
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• pp.253-259
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• 2008

배경: 경부식도암은 흉부식도암에 비해 발생 빈도가 상대적으로 낮고 방사선치료나 항암 약물치료의 역할이 흉부식도암에서보다 상대적으로 높다. 따라서 경부식도암에 대한 수술적 치료의 역할이 흉부식도암에 비해 상대적으로 제한적이다. 저자들은 경부식도암에 대한 수술적 치료의 결과를 알아보기 위해 본 연구를 시행하였다. 대상 및 방법: 1989년 1월부터 2002년 12월까지 경부식도암(경흉부식도 암 포함 )으로 수술을 시행 받은 환자 43명의 결과를 후향적으로 분석하였다. 모든 환자에서 추적이 가능하였으며, 최종 추적일은 2004년 2월 28일이었다. 결과: 대상 환자의 평균 나이는 60세$(43{\sim}77)$였고, 남녀 비는 40:3이었다. 조직학적으로 편평상피세포암이 42명, 악성 흑색종이 1명이었다. 식도 재건 방법은 gastric pull-up 32명, 유리 공장 이식 7명, colon interposition 4명이었다. 전체 43명 중 31명(72%)의 환자에서 합병증이 발생하였고, 수술 사망자는 7명(16%)이었다. 수술 후 최종 병기는 I 3명, IIa 14 명, IIb 1명, III 19명, IVa 6명이었다. 수술 사망자를 제외한 36 명 중 16명(44%)에서 종양이 재발하였고, 수술 후 3년, 5년 생존율은 29.3% 와 20.9%이었다. 결론: 경부식도암에 대한 수술은 수술 사망률, 합병증 발생률, 재발률이 높고, 장기 생존율이 낮지만, 방사선치료나 항암약물치료 만으로는 연하곤란의 완전한 해소 및 종양의 완치가 어려우므로 수술이 포함되는 다방법 병합치료가 필요하다고 생각한다.

• 동의생리병리학회지
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• 제27권1호
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• pp.63-77
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• 2013

The object of this study was to observe anticancer and related immunomodulatory and anticachexic effects of Insamyangyoung-tang aqueous extracts (ISYYTe) on non-small cell lung carcinoma (squamous epithelial carcinoma), NCI-H520, xenograft Balb/c nu-nu nude mice. Changes on the tumor volume and weights, lymphatic organ(spleen and popliteal lymph node), serum interferon (IFN)-${\gamma}$ levels, splenocytes and peritoneal macrophage activities (NK cell activity), splenic tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-10 contents, splenic T-lymphocyte subsets (CD3+, CD4+ and CD8+) and TNF-${\alpha}+$ cells were observed with tumor mass and lymphatic organ histopathology to detect anticancer and immunomodulatory effects. In addition, changes on the body weights, epididymal fat weights and serum IL-6 levels were also detected with the thicknesses of deposited cervical brown adipose tissue and their mean diameters to monitor the tumor-related anticachexic effects. The results obtained in this study suggest that over 50 mg/kg of ISYYTe showed favorable anticancer effects on the NCI-H520 cell xenograft with immunomodulatory and anticachexic effects. However, detail mechanism studies should be conducted in future with the screening of the biological active compounds in this herb.

• International Journal of Oral Biology
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• 제41권4호
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• pp.183-190
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• 2016

Anthricin (Deoxypodophyllotoxin), a naturally occurring flavolignan, has well known anti-cancer properties in several cancer cells, such as prostate cancer, cervical carcinoma and pancreatic cancer. However, the effects of Anthricin are currently unknown in oral cancer. We examined the anticancer effect and mechanism of action of Anthricin in human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that Anthricin inhibits cell viability in a dose- and time-dependent manner ($IC_{50}$ 50 nM) in the MTT assay and Live & Dead assay. In addition, Anthricin treated FaDu cells showed marked apoptosis by DAPI stain and FACS. Furthermore, Anthricin activates anti-apoptotic factors such as caspase-3, -9 and poly (ADP-ribose) polymerase (PARP), suggesting that caspase-mediated pathways are involved in Anthricin- induced apoptosis. Anthricin treatment also leads to accumulation of the pro-apoptotic factor Bax, followed by inhibition of cell growth. Taken together, these results indicate that Anthricn-induced cell death of human FaDu hypopharyngeal squamous carcinoma cells is mediated by mitochondrial-dependent apoptotic pathway. In summary, our findings provide a framework for further exploration on Anthricin as a novel chemotherapeutic drug for human oral cancer.