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MLH1 Polymorphisms and Cancer risk: a Meta-analysis Based on 33 Case-control Studies

  • Xu, Jia-Li;Yin, Zhi-Qiang;Huang, Ming-De;Wang, Xie-Feng;Gao, Wen;Liu, Ling-Xiang;Wang, Rong-Sheng;Huang, Pu-Wen;Yin, Yong-Mei;Liu, Ping;Shu, Yong-Qian
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.3
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    • pp.901-907
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    • 2012
  • Objective: Cumulative evidence suggests that MLH1, the key component in the mismatch pathway, plays an important role in human cancers. Two potential functional polymorphisms (-93G>A and I219V) of MLH1 have been implicated in cancer risk. The aim of this meta-analysis was to summarize the evidence for associations. Methods: Eligible studies were identified by searching the electronic literature PubMed, ScienceDirect and Embase databases for relevant reports and bibliographies. Studies were included if of case-control design investigating MLH1 polymorphisms (-93G>A and I219V) and cancer risk with sufficient raw data for analysis. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to evaluate the strength of associations. Results: Our meta-analysis from 33 published case-control studies showed the variant A allele of -93G>A polymorphism to be associated with increased risk in all genetic models (AA vs. GG: OR = 1.22, 95% CI: 1.03-1.44), especially among non-Asians (AA vs. GG: OR = 1.28, 95% CI: 1.04-1.58). For the I219V polymorphism, however, there was no main effect associated with overall cancer risk in any genetic model. Conclusions: The meta-analysis suggested that the MLH1 -93G>A polymorphism may be a biomarker of cancer susceptibility. Large sample association studies and assessment of gene-to-gene as well as gene-to-environment interactions are required to confirm these findings.

Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese

  • Xu, Jia-Li;Hu, Ling-Min;Huang, Ming-De;Zhao, Wan;Yin, Yong-Mei;Hu, Zhi-Bin;Ma, Hong-Xia;Shen, Hong-Bing;Shu, Yong-Qian
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.3
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    • pp.851-856
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    • 2012
  • Objective: NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. Methods: Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS. Results: Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39). Conclusions: Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.

PDCD4 as a Predictor of Sensitivity to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Patients

  • Dou, Xue;Wang, Ren-Ben;Meng, Xiang-Jiao;Yan, Hong-Jiang;Jiang, Shu-Mei;Zhu, Kun-Li;Xu, Xiao-Qing;Chen, Dong;Song, Xian-Rang;Mu, Dian-Bin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.825-830
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    • 2014
  • Objective: The purpose of this study was to examine the role of programmed cell death 4 (PDCD4) expression in predicting tumor response to neoadjuvant chemoradiotherapy and outcomes for patients with locally advanced rectal cancer. Methods: Clinicopathological factors and expression of PDCD4 were evaluated in 92 patients with LARC treated with nCRT. After the completion of therapy, 4 cases achieved clinical complete response (cCR), and thus the remaining 88 patients underwent a standardized total mesorectal excision procedure. There were 38 patients (41.3%) with a good response (TRG 3-4) and 54 (58.7%) with a poor one (TRG 0-2). Results: Immunohistochemical staining analyses showed that patients with high expression of PDCD4 were more sensitive to nCRT than those with low PDCD4 expression (P=0.02). High PDCD4 expression before nCRT and good response (TRG3-4) were significantly associated with improved 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis demonstrated that the pretreatment PDCD4 expression was an independent prognostic factor. Conclusion: Our study demonstrated that high expression of PDCD4 protein is a useful predictive factor for good tumor response to nCRT and good outcomes in patients with LARC.

Effects of lycopene on number and function of human peripheral blood endothelial progenitor cells cultivated with high glucose

  • Zeng, Yao-Chi;Mu, Gui-Ping;Huang, Shu-Fen;Zeng, Xue-Hui;Cheng, Hong;Li, Zhong-Xin
    • Nutrition Research and Practice
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    • v.8 no.4
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    • pp.368-376
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    • 2014
  • BACKGROUND/OBJECTIVES: The objectives of this study were to investigate the effects of lycopene on the migration, adhesion, tube formation capacity, and p38 mitogen-activated protein kinase (p38 MAPK) activity of endothelial progenitor cells (EPCs) cultivated with high glucose (HG) and as well as explore the mechanism behind the protective effects of lycopene on peripheral blood EPCs. MATERIALS/METHODS: Mononuclear cells were isolated from human peripheral blood by Ficoll density gradient centrifugation. EPCs were identified after induction of cellular differentiation. Third generation EPCs were incubated with HG (33 mmol/L) or 10, 30, and $50{\mu}g/mL$ of lycopene plus HG. MTT assay and flow cytometry were performed to assess proliferation and apoptosis of EPCs. EPC migration was assessed by MTT assay with a modified boyden chamber. Adhesion assay was performed by replating EPCs on fibronectin-coated dishes, after which adherent cells were counted. In vitro vasculogenesis activity was assayed by Madrigal network formation assay. Western blotting was performed to analyze protein expression of both phosphorylated and non-phosphorylated p38 MAPK. RESULTS: The proliferation, migration, adhesion, and in vitro vasculogenesis capacity of EPCs treated with 10, 30, and $50{\mu}g/mL$ of lycopene plus HG were all significantly higher comapred to the HG group (P < 0.05). Rates of apoptosis were also significantly lower than that of the HG group. Moreover, lycopene blocked phosphorylation of p38 MAPK in EPCs (P < 0.05). To confirm the causal relationship between MAPK inhibition and the protective effects of lycopene against HG-induced cellular injury, we treated cells with SB203580, a phosphorylation inhibitor. The inhibitor significantly inhibited HG-induced EPC injury. CONCLUSIONS: Lycopene promotes proliferation, migration, adhesion, and in vitro vasculogenesis capacity as well as reduces apoptosis of EPCs. Further, the underlying molecular mechanism of the protective effects of lycopene against HG-induced EPC injury may involve the p38 MAPK signal transduction pathway. Specifically, lycopene was shown to inhibit HG-induced EPC injury by inhibiting p38 MAPKs.

Effects of IFN-γ on IL-18 Expression in Pregnant Rats and Pregnancy Outcomes

  • Si, Li-Fang;Zhang, Shou-Yan;Gao, Chun-Sheng;Chen, Shu-Lin;Zhao, Jin;Cheng, Xiang-Chao
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.10
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    • pp.1399-1405
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    • 2013
  • The present study focused on establishing the effects of interferon-gamma (IFN-${\gamma}$) on interleukin-18 (IL-18) expression patterns and pregnancy outcomes in pregnant rats. Pregnant rats at the post-implantation stage were randomized into control, low IFN-${\gamma}$ (L-IFN-${\gamma}$) and high IFN-${\gamma}$ groups (H-IFN-${\gamma}$) that received normal saline, 100 IU/g of IFN-${\gamma}$ and 500 IU/g of IFN-${\gamma}$ vaginal muscular injection, respectively. The effects of IFN-${\gamma}$ on IL-18 expression and pregnancy outcomes were assessed systematically using several methods, including immunohistochemistry streptavidin-perosidase (SP), image pattern analysis, enzyme-linked immune-sorbent assay (ELISA), whole blood count (WBC) count, microscopy and visual observation. IL-18 was detected in the uteri of all pregnant rats, and mainly distributed in the endometrium, decidual cells, vascular endothelium and myometrium. Immunohistochemistry and image pattern analyses revealed significantly lower IL-18 expression in the H-IFN-${\gamma}$ group compared to the L-IFN-${\gamma}$ and control groups (p<0.01), indicating that high doses of IFN-${\gamma}$ induce downregulation of IL-18 in the uterus of pregnant rats. ELISA results disclosed that IL-18 expression in peripheral blood of the H-IFN-${\gamma}$ group was lower than that of the L-IFN-${\gamma}$ group (p<0.05), and significantly reduced compared to the control group (p<0.01). Moreover, the number of peripheral leukocytes in the H-IFN-${\gamma}$ group was significantly higher than those in the control and L-IFN-${\gamma}$ groups (p<0.01). Morphology analysis showed no evident differences between the L-IFN-${\gamma}$ and control groups. However, for the H-IFN-${\gamma}$ group, uterine mucosa bleeding, necrosis and excoriation were observed using microscopy. Visual observation revealed marroon, swelling, crassitude and no embryo in the uterus, which are obvious indicators of abortion. These results indicate that IFN-${\gamma}$ plays a regulatory role in IL-18 expression in the uterus and peripheral blood of pregnant rats at the post-implantation stage. Moreover, high levels (500 IU/g) of IFN-${\gamma}$ influence normal pregnancy at the early stages in rats by downregulating IL-18 expression in the uterus and peripheral blood and increasing the number of peripheral leukocytes, consequently triggering termination of pregnancy.

Asparagus Polysaccharide and Gum with Hepatic Artery Embolization Induces Tumor Growth and Inhibits Angiogenesis in an Orthotopic Hepatocellular Carcinoma Model

  • Weng, Ling-Ling;Xiang, Jian-Feng;Lin, Jin-Bo;Yi, Shang-Hui;Yang, Li-Tao;Li, Yi-Sheng;Zeng, Hao-Tao;Lin, Sheng-Ming;Xin, Dong-Wei;Zhao, Hai-Liang;Qiu, Shu-Qi;Chen, Tao;Zhang, Min-Guang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10949-10955
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    • 2015
  • Liver cancer is one of leading digestive malignancies with high morbidity and mortality. There is an urgent need for the development of novel therapies for this deadly disease. It has been proven that asparagus polysaccharide, one of the most active derivates from the traditional medicine asparagus, possesses notable antitumor properties. However, little is known about the efficacy of asparagus polysaccharide as an adjuvant for liver cancer chemotherapy. Herein, we reported that asparagus polysaccharide and its embolic agent form, asparagus gum, significantly inhibited liver tumor growth with transcatheter arterial chemoembolization (TACE) therapy in an orthotopic hepatocellular carcinoma (HCC) tumor model, while significantly inhibiting angiogenesis and promoting tumor cell apoptosis. Moreover, asparagine gelatinous possessed immunomodulatory functions and showed little toxicity to the host. These results highlight the chemotherapeutic potential of asparagus polysaccharide and warrant a future focus on development as novel chemotherapeutic agent for liver cancer TACE therapy.

The Concept Analysis of Self-Control (자기통제의 개념 분석)

  • Eun, Young;Lee, In-Sook;Lee, Keung-Sook;Song, Keung-Ja;Choi, Eun-Ok;Shu, Soon-Rim;Yang, Young-Hee;Park, Young-Im;Gu, Mee-Ok;Kim, Sung-Jae;Kim, In-Ja;Lee, Eun-Nam;Park, Song-Ja;Lee, Dong-Suk;Lee, Eun-Ok
    • Journal of Korean Academy of Nursing
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    • v.29 no.4
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    • pp.951-962
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    • 1999
  • Today human needs for health promotion and maintenance are increasing. The nursing profession as a great responsibility to develop the knowledge for helping clients to practice good health behavior under self-control. But there are few studies about the concept of self-control, or the operational definition of self-control. The purpose of this study was to analyze and clarify the meaning of the concept of self-control. This study used Walker and Avant's process of concept analysis. Antecedents of self control consist of 1) perception of the conflict situation to change his or her behavior ; 2) perception of self as the causes of the barrier for a certain behavior ; 3) internal standard or belief such as self-efficacy and learned resourcefulness ; 4) internal motivation for change of behavior. Critical attributes of self-control were 1) goal-orientation ; 2) self-decision ; 3) time sequence ; 4) effort ; 5) possibility of being learned ; 6) individuality ; 7) social desirability. Consequences occurring as a results of self-control consist of 1) achievement of the controlled behavior whose purposes were planned ; 2) enhancement of the internal standard such as self-efficacy and learned resourcefulness ; 3) eventual elevation of physical and emotional wellness. Therefore, this concept is defined as a cognitive behavior which is attempted by his or her decision when one is confronted with the conflict situation, which is characterized by being changed by time, learned by effort and individual characteristics. One is taking such behavior with the perception of self as the causative barrier for a certain behavior, planning a specific objective for a certain behavior which demands self sacrifice, supplies the internal reward, is socially desirable with the internal standard of self-efficacy and learned resourcefulness and environmental factors.

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A study on ${\ulcorner}$HuangDiNeiJing(黃帝內經)${\lrcorner}$ ${\ulcorner}$SanBuJiuHouLun(三部九候論)${\lrcorner}$ ("황제내경(黃帝內經)" 삼부구후론(三部九候論)에 대한 연구)

  • Park, Hyun-Kook;Kim, Ki-Wook
    • Journal of Korean Medical classics
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    • v.19 no.1 s.32
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    • pp.26-40
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    • 2006
  • It is generally understood that San Bu Jiu Hou is the pulse form at CunGuanChi(寸關尺) as in ${\ulcorner}$NanJing(難經)${\lrcorner}$. However, it is totally different in ${\ulcorner}$HuangDiNeiJing${\lrcorner}$. This only appears in tew chapters of ${\ulcorner}$SuWen(素問)${\lrcorner}$ and does not appear in ${\ulcorner}$LingShu(靈樞)${\lrcorner}$. SanBu in ${\ulcorner}$SuWen SanBuJiuHouLun${\lrcorner}$ refers to top, middle, bottom and each part is divided into 3 parts, Tian(天), Di(地), Ren(人) to form JiuHou, and through Jiu Hou, not only does it diagnose ShenZang(神臟) and XingZang(形臟), but also goes on to form a diagnostic system by fusing diagnostic skill and treatment into one. ${\ulcorner}$JiuZhenShiErYuan(九針十二原)${\lrcorner}$ discusses detailed shapes and functions of nine types of acupuncture, and the ${\ulcorner}$GuanZhen(官針)${\lrcorner}$ explains how to manipulate Jiu Zhen adequately, but there is more to it than just shape and function in techniques of acupuncture. It is because it fuses (or merges) pathology, diagnostics, treatment etc to form a single diagnosis system. ${\ulcorner}$JinFu(禁服)${\lrcorner}$ discusses about nine types of acupuncture of pulse form and effect, which are treatment means based on RenYingCunKouMaiFa(人迎寸口脈法). Various pulse daignosises exist in ${\ulcorner}$HuangDiNeiJing${\lrcorner}$, but those influence of future generations can be divided into SanBuJiuHouMaiFa(三部九候脈法) and RenYingCunKouMaiFa(人迎寸口脈法), and which medical ideologies this kind of pulse daignosis originates from should be discusssed. We will finally expolre and report the process its development into 寸尺脈(Cun Chi Mai).

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Posttranscriptional deregulation of Src due to aberrant miR34a and miR203 contributes to gastric cancer development

  • Hao, Qiang;Lu, Xiaozhao;Liu, Nannan;Xue, Xiaochang;Li, Meng;Zhang, Cun;Qin, Xin;Li, Weina;Shu, Zhen;Song, Bin;Wang, Qing;Song, Liqiang;Zhang, Wei;Zhang, Yingqi
    • BMB Reports
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    • v.46 no.6
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    • pp.316-321
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    • 2013
  • Gastric cancer remains the main cause of cancer death all around the world, and upregulated activation of the nonreceptor tyrosine kinase c-SRC (SRC) is a key player in the development. In this study, we found that expression of Src is also increased in clinical gastric cancer samples, with the protein level increased more significantly than that at the RNA level. Further study revealed that miR34a and miR203, two tumor suppressive miRNAs, inversely correlate with the expression of Src. Restoration of miR34a and miR203 decreased Src expression in gastric cancer cell lines, which in turn inhibited cell growth and cell migration. In summary, our study here revealed that posttranscriptional regulation of Src contributes to the deregulated cell growth and metastasis in gastric cancer, and targeting Src by miR34a or miR203 mimics would be a promising strategy in therapy.

Synthesis of Enantiopure Epoxide Compounds Using Dimeric Chiral Salen Catalyst (이량체구조를 갖는 키랄 살렌 촉매를 이용한 고 광학순도의 에폭사이드 화합물 합성)

  • Kim, Geon-Joong;Kim, Seong-Jin;Li, Wenji;Chen, Shu-Wei;Shin, Chang-Kyo;Thakur, Santosh S.
    • Korean Chemical Engineering Research
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    • v.43 no.6
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    • pp.647-661
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    • 2005
  • The stereoselective synthesis of chiral terminal epoxide is of immense academic and industrial interest due to their utility as versatile starting materials as well as chiral intermediates. In this review, we investigate the research and development trend in the asymmetric ring opening reactions using cobalt salen catalysts. Hydrolytic kinetic resolution (HKR) technology is the very prominent way to prepare optically pure terminal epoxides among available methods. We have synthesized homogeneous and heterogeneous chiral dinuclear salen complexes and demonstrated their catalytic activity and selectivity for the asymmetric ring opening of terminal epoxides with variety of nucleophiles and for asymmetric cyclization to prepare optically pure terminal epoxides in one step. The resolved ring opened product combined with ring closing in the presence of base and catalyst afforded the enantioriched terminal epoxides in quantitaive yield. Potentially, these catalysts are using on an industrial scale to produce chiral intermediates. The experimental results of HKR technology applied to the synthesis of various chiral compounds are presented in this paper.