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Carcinoma Microsatellite Instability Status as a Predictor of Benefit from Fluorouracil-Based Adjuvant Chemotherapy for Stage II Rectal Cancer

  • Yang, Liu;Sun, Yan;Huang, Xin-En;Yu, Dong-Sheng;Zhou, Jian-Nong;Zhou, Xin;Li, Dong-Zheng;Guan, Xin
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.4
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    • pp.1545-1551
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    • 2015
  • Purpose: Rectal cancers with high microsatellite-instable have clinical and pathological features that differentiate them from microsatellite-stable or low-frequency carcinomas, which was studied rarely in stage II rectal cancer, promoting the present investigation of the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II rectal cancer. Patients and Methods: Data of 460 patients who underwent primary anterior resection with a double stapling technique for rectal carcinoma at a single institution from 2008 to 2012 were retrospectively collected. All patients experienced a total mesorectal excision (TME) operation. Survival analysis were analyzed using the Cox regression method. Results: Five-year rate of disease-free survival (DFS) was noted in 390 (84.8%) of 460 patients with stage II rectal cancer. Of 460 tissue specimens, 97 (21.1%) exhibited high-frequency microsatellite instability. Median age of the patients was 65 (50-71) and 185 (40.2%) were male. After univariate and multivariate analysis, microsatellite instability (p= 0.001), female sex (p<0.05) and fluorouracil-based adjuvant chemotherapy (p<0.001), the 3 factors were attributed to a favorable survival status independently. Among 201 patients who did not receive adjuvant chemotherapy, those cancers displaying high-frequency microsatellite instability had a better 5-year rate of DFS than tumors exhibiting microsatellite stability or low-frequency instability (HR, 13.61 [95% CI, 1.88 to 99.28]; p= 0.010), while in 259 patients who received adjuvant chemotherapy, there was no DFS difference between the two groups (p= 0.145). Furthermore, patients exhibiting microsatellite stability or low-frequency instability who received adjuvant chemotherapy had a better 5-year rate of DFS than patients did not (HR, 5.16 [95% CI, 2.90 to 9.18]; p<0.001), while patients exhibiting high-frequency microsatellite instability were not connected with increased DFS (p= 0.696). It was implied that female patients had better survival than male. Conclusion: Survival status after anterior resection of rectal carcinoma is related to the microsatellite instability status, adjuvant chemotherapy and gender. Fluorouracil-based adjuvant chemotherapy benefits patients of stage II rectal cancer with microsatellite-stable or low microsatellite-instable, but not those with high microsatellite-instable. Additionally, free of adjuvant chemotherapy, carcinomas with high microsatellite-instable have a better 5-year rate of DFS than those with microsatellite-stable or low microsatellite-instable, and female patients have a better survival as well.

Risk Factors for Clinical Metastasis in Men Undergoing Radical Prostatectomy and Immediate Adjuvant Androgen Deprivation Therapy

  • Taguchi, Satoru;Fukuhara, Hiroshi;Kakutani, Shigenori;Takeshima, Yuta;Miyazaki, Hideyo;Suzuki, Motofumi;Fujimura, Tetsuya;Nakagawa, Tohru;Igawa, Yasuhiko;Kume, Haruki;Homma, Yukio
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10729-10733
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    • 2015
  • Background: Adjuvant androgen deprivation therapy (ADT) is a treatment option for prostate cancer (PC) patients after radical prostatectomy (RP). Although it can achieve a good progression-free survival rate, some patients still develop clinical metastasis. We here investigated risk factors of clinical metastasis in post-prostatectomy patients who received immediate adjuvant ADT. Materials and Methods: We identified 197 patients with non-metastatic PC who underwent RP at our institution between 2000 and 2012, followed by adjuvant ADT. The associations of various clinicopathologic factors with clinical metastasis (primary endpoint) and cancer-specific survival (secondary endpoint) were assessed. Multivariate analysis was conducted using a Cox proportional hazards model. Median follow-up was 87 months after RP. Results: Nine (4.6%) patients developed clinical metastasis and six (3.0%) died from PC. Eight of nine metastatic patients had a pathologic Gleason score (GS) 9 and developed bone metastasis, while the remaining one had pathologic GS 7 and developed metastasis only to para-aortic lymph nodes. On multivariate analyses, pathologic GS ${\geq}9$ and regional lymph node metastasis (pN1) were independent predictors of clinical metastasis and pathologic GS ${\geq}9$ was an independent predictor of cancer-specific death. Conclusions: Pathologic GS ${\geq}9$ and pN1 were independent predictors of clinical metastasis in post-prostatectomy patients who received immediate adjuvant ADT. Furthermore, pathologic GS ${\geq}9$ was an indispensable condition for bone metastasis, which may imply that patients with GS ${\leq}8$ on adjuvant ADT are unlikely to develop bone metastasis.

The Role of Radiation Therapy in Adenocarcinoma of Endometrium (자궁 체부암의 방사선 치료)

  • Yun Hyong Geun;Ha Sung Whan;kang Soon Beom;Lee Hyo Pyo
    • Radiation Oncology Journal
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    • v.8 no.1
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    • pp.95-102
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    • 1990
  • From May, 1979 to October,1987, 38 patients with endometrial carcinoma were treated with radiotherapy at Seoul National University Hospital. Of these, 32 patients received radiotherapy Postoperatively, one received radiotherapy preoperatively, and five received radiotherapy only. Relative frequencies of obesity, nulliparity, late menopause, diabetes mellitus, and hypertension were all higher than those reported in normal women in Korea, and those of obesity, diabetes mellitus, and nulliparity were significantly high. The overall actuarial five-year survival rate was $75.6\%$. The overall actuarial five year survival rates of stage I (22 cases), stage II (six cases), and stage III (10 cases) were $90.0\%,\;80.0\%,\;and\;44.4\%$, respectively, and were significantly different from each other. Among various factors, stage only proved to be prognostic by multivariate analysis. There were two local failures, three local failures combined with distant metastasis, and three distant metastasis. Stages I and II could be adequately controlled by local modalities without severe complications, stage III endometrial carcinoma might need more aggressive treatment for better survival.

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Anti-inflammatory and anti-allergic effect of soybean extracts produced by organic cultivation (유기농 대두 추출물의 항염증 및 항알레르기 효과)

  • Chung, Eun-Kyung;Seo, Eun-Hye;Park, Jun-Ho;Kim, Young-Nam;Kim, Kyung-Hee;Lee, Byung-Ryong
    • Proceedings of the Korean Society of Organic Agriculture Conference
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    • 2009.12a
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    • pp.103-113
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    • 2009
  • This present study was carried out to investigate the biological effects of soybean extracts comparing organic and conventional cultivation. Cellular and molecular analysis was performed to determine anti-oxidative, anti-inflammatory, anti-apoptotic, and anti-inflammatory effects of both soybean extracts. First, we obtained various solvent extracts of soybeans such as water, ethanol, and methanol. Molecular and cellular analysis were performed with 0.1 mg/ml concentration of each solvent extracts. The results of anti-oxidative, anti-inflammatory and anti-apoptotic effects of organic cultivated soybean extracts were prominent than conventional cultivated soybean extracts. However, discrepancy between organic and conventional cultivated soybean extracts was not observed in anti-allergic effects determined by releasing histamine from rat mast cell line, RBL-2H3. Conclusively, organic cultivated soybeans have stronger effects than conventional cultivated soybeans in suppression of inflammation. In addition, organic soybeans could be applied as a functional food ingredient for treatment of chronic inflammation, asthma, and atopic dermatitis with enhanced anti-inflammatory activities.

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Cigarette Smoking and Gastric Cancer Risk in a Community-based Cohort Study in Korea (흡연과 위암 발생의 관련성에 관한 지역사회 기반의 코호트 연구)

  • Kim, Yeon-Ju;Shin, Ae-Sun;Gwack, Jin;Jun, Jae-Kwan;Park, Sue-Kyung;Kang, Dae-Hee;Shin, Hai-Rim;Chang, Soung-Hoon;Yoo, Keun-Young
    • Journal of Preventive Medicine and Public Health
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    • v.40 no.6
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    • pp.467-474
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    • 2007
  • Objectives : Gastric cancer is the most common incident cancer in Korea. Although Helicobacter pylori infection is the most important risk factor for the development of gastric cancer, cigarette smoking has also been suggested to play an important role in the development of gastric cancer. The objective of this study is to evaluate the relationship between cigarette smoking and gastric cancer risk in a Korean population. Methods : The study population consisted of 13,785 subjects who had been enrolled in the Korean Multi-Center Career Cohort between 1993 and 2002. As of December 2002, 139 incident gastric cancer cases were ascertained through the Korea Central Cancer Registry and the National Death Certificate Database. Relative risks (RR) and 95% confidence intervals (CI) for gastric cancer were estimated using Cox#s proportional hazard model adjusted for age, education, alcohol drinking status and history of gastritis or ulcer. Results : Significant dose-response relationships were observed between the duration of smoking and the risk of gastric cancer among the male subjects in comparison to non-smokers: men who smoked for 20-39 years had a 2.09-fold (95% CI 1.00-4.38) increase, and those who smoked for more than 40 years had a 3.13-fold (95% CI 1.59-6.17) increase in the risk of gastric cancer ($P_{trend}<0.01$). Conclusions : This study suggests that a longer duration of cigarette smoking may increase the risk of gastric cancer development in a dose-response manner in Korean men. The association between smoking and gastric cancer risk in women should be verified in future studies with a larger number of cases.

Theoretical Investigation for the Adsorption of Various Gases (COx, NOx, SOx) on the BN and AlN Sheets (N과 AlN 시트에 다양한 기체(COx, NOx, SOx)의 흡착에 관한 이론 연구)

  • Kim, Sung-Hyun;Kim, Baek-Jin;Shin, Chang-Ho;Kim, Seung-Joon
    • Journal of the Korean Chemical Society
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    • v.61 no.1
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    • pp.16-24
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    • 2017
  • The adsorption of various atmospheric harmful gases ($CO_x$, $NO_x$, $SO_x$) on graphene-like boron nitride(BN) and aluminum nitride(AlN) sheets was theoretically investigated using density functional theory (DFT) and MP2 methods. The structures were fully optimized at the $B3LYP/6-31G^{**}$ and $CAM-B3LYP/6-31G^{**}$ levels of theory and confirmed to be a local minimum by the calculation of the harmonic vibrational frequencies. The MP2 single-point binding energies were computed at the $CAM-B3LYP/6-31G^{**}$ optimized geometries. Also the zero-point vibrational energy (ZPVE) and 50%-basis set superposition error (BSSE) corrections were included. The adsorptions of gases on the BN sheet were predicted to be a physisorption process and the adsorptions of gases on the AlN sheet were predicted to be a physisorption process for $CO_x$ and $NO_x$ but to be a chemisorption process for $SO_x$.

Apoptotic Effects of Curcumin and EGCG via Akt-p53 Signaling Pathway in HCT116 Colon Cancer Cells (HCT116 대장암 세포에서 Akt-p53 신호경로를 통한 커큐민과 EGCG의 apoptosis 효과)

  • Park, Song-Yi;Lee, Sol-Hwa;Park, Ock-Jin;Kim, Young-Min
    • Journal of Life Science
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    • v.21 no.1
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    • pp.89-95
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    • 2011
  • p53 is tumor suppressor gene that regulates apoptosis such as caspase-dependent and p21-mediated signaling pathways. PI3K/Akt is known to be over-activated in cancer cells. Akt activates many survival-related signals such as mTOR and COX-2. Inactivation of Akt would result in non-inhibition of p53 as well as induced apoptosis. In this study, we showed that curcumin and EGCG activate p53 via inhibition of the Akt signaling pathway. Treatments using curcumin and EGCG in different concentrations for 24 hr and 48 hr inhibited proliferation of HCT116 colon cancer cells and increased apoptotic cell death. Also, our data showed that curcumin and EGCG increased the p53 expression and decreased the p-Akt. Treatment of LY294002 (Akt inhibitor) resulted in decreased cell proliferation of cancer cells, while LY294002 treated with curcumin or EGCG showed a greater decrease of cell proliferation. In addition, inhibition of Akt induced p53 activation in HCT116 colon cancer cells. These results suggest that curcumin and EGCG induce apoptosis by inhibiting Akt and increase p53 in HCT116 colon cancer cells.

Efficacy of First-Line Targeted Therapy in Real-World Korean Patients with Metastatic Renal Cell Carcinoma: Focus on Sunitinib and Pazopanib

  • Kim, Myung Soo;Chung, Ho Seok;Hwang, Eu Chang;Jung, Seung Il;Kwon, Dong Deuk;Hwang, Jun Eul;Bae, Woo Kyun;Park, Jae Young;Jeong, Chang Wook;Kwak, Cheol;Song, Cheryn;Seo, Seong Il;Byun, Seok-Soo;Hong, Sung-Hoo;Chung, Jinsoo
    • Journal of Korean Medical Science
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    • v.33 no.51
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    • pp.325.1-325.10
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    • 2018
  • Background: To evaluate survival outcomes and prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who received sunitinib (SU) and pazopanib (PZ) as first-line therapy in real-world Korean clinical practice. Methods: Data of 554 patients with mRCC who received SU or PZ at eight institutions between 2012 and 2016 were retrospectively reviewed. Based on the targeted therapy, the patients were divided into SU (n = 293) or PZ (n = 261) groups, and the clinicopathological variables and survival rates of the two groups were compared. A multivariable Cox proportional hazard model was used to determine the prognostic factors for OS. Results: The median follow-up was 16.4 months (interquartile range, 8.3-31.3). Patients in the PZ group were older, and no significant difference was observed in the performance status (PS) between the two groups. In the SU group, the dose reduction rate was higher and the incidence of grade 3 toxicity was more frequent. The objective response rates were comparable between the two groups (SU, 32.1% vs. PZ, 36.4%). OS did not differ significantly between the two groups (SU, 36.5 months vs. PZ, 40.2 months; log-rank, P = 0.955). Body mass index, Eastern Cooperative Oncology Group PS > 2, synchronous metastasis, poor Heng risk criteria, and liver and bone metastases were associated with a shorter OS. Conclusion: Our real-world data of Korean patients with mRCC suggested that SU and PZ had similar efficacies as first-line therapy for mRCC. However, PZ was better tolerated than SU in Korean patients.

Anti-atopic Effect of Zizyphus jujuba var. spinosa Composite oil(ZjJ-C_oil) and Aralia cordata var. continentalis Composite oil(ARC-C_oil) in DNCB-induced Atopic Dermatitis-like Skin Lesions NC/Nga Mice (천연물 유래 산조인 복합오일 (Zizyphus jujuba var. spinosa Composite oil, ZjJ-C_oil) 및 독활 복합오일 (Aralia cordata var. continentalis Composite oil, ARC-C_oil)의 DNCB로 유도된 NC/Nga 생쥐의 아토피에 미치는 효과 연구)

  • Kwak, Jin-young;Choir, Hee-Jeong;Park, Jung-mi;Park, Jung-hwan;Kho, Young-mee;Jang, Tae-soo;Ahn, Teakwon
    • Journal of Sasang Constitutional Medicine
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    • v.29 no.4
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    • pp.347-368
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    • 2017
  • The aim of this study is to investigate the effect of Zizyphus jujuba var. spinosa Composite oil(ZjJ-C_oil) and Aralia cordata var. continentalis Composite oil(ARC-C_oil) to NC/Nga mice induced in Atopic dermatitis-like skin lesions by DNCB. NC/Nga mice which have been induced to Atopic dermatitis-like skin lesions by DNCB are divided into 4 groups, the first is the mice which have been spread with izyphus jujuba var. spinosa Composite oil(ZjJ-C_oil), the second is the mice which have been spread with Aralia cordata var. continentalis Composite oil(ARC-C_oil), the third is which have been spread with dexamethasone (Dexa.) 0.5% on their Atopic lesion, the last is the control group. Then We analyzed skin clinical score, blood sample of each group of measure state of the dorsal skin, the number of immunocytes, and resect the skin lesion to anlayze the state of cells. There are meaningful results of measuring the number of IgE, IL-4, IL-13, $IFN-{\gamma}$, IL-5, the total cells in ALN, dorsal skin, CD4+ Th, CD11b+/Gr-1+ in PBMCs, CD4+ Th, B220+/CD23+ in ALN, $CD4^+$, $CD8^+$ Th in dorsal skin, the level of COX-2, $TNF-{\alpha}$, $TGF-{\beta}1$, IL-4, IL-13 mRNA, the state of the skin lesion and cells in the group with ZjJ-C_oil, ARC-C_oil cream in comprarison with the control group.

Anti-inflammatory activity of indigenous Tuber himalayense in Korea (자생 Tuber himalayense 자실체 추출물의 항염증 활성)

  • Kim, Minkyeong;Hong, Hyehyun;Kim, Jung-Hwan;Kim, Seung-Young;Kim, Changmu
    • Journal of Mushroom
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    • v.19 no.3
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    • pp.176-183
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    • 2021
  • In this study, the anti-inflammatory activity of an extract of the fruiting body of the Tuber himalayense (TH) truffle collected from oak growing areas in Korea was investigated. The extract was not cytotoxic at concentrations below 100 ㎍/mL in an experiment evaluating inflammation inhibitory effect in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production was inhibited by the extract in a concentration-dependent manner. Western blot assay results indicated that the anti-inflammatory activity of TH extract was likely caused by the reduced production of NO and PGE2 via suppression of induced NO synthase and cyclooxygenase-2 gene expression. In addition, TH extract effectively inhibited the production of interleukin (IL)-1β and IL-6 by macrophages. Thus, TH extract effectively inhibits the overexpression of various inflammatory mediators and could be valuable in formulating anti-inflammatory foods and medicines that target these components.