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      • KCI등재

        Inhibition of the interaction between Hippo/YAP and Akt signaling with ursolic acid and 3′3-diindolylmethane suppresses esophageal cancer tumorigenesis

        Ruo Yu Meng,Cong Shan Li,Dan Hu,Soon-Gu Kwon,Hua Jin,Ok Hee Chai,Ju-Seog Lee,김수미 대한약리학회 2023 The Korean Journal of Physiology & Pharmacology Vol.27 No.5

        Hippo/YAP signaling hinders cancer progression. Inactivation of this pathway contributes to the development of esophageal cancer by activation of Akt. However, the possible interaction between Akt and Hippo/YAP pathways in esophageal cancer progression is unclear. In this study, we found that ursolic acid (UA) plus 3′3-diindolylmethane (DIM) efficiently suppressed the oncogenic Akt/Gsk-3β signaling pathway while activating the Hippo tumor suppressor pathway in esophageal cancer cells. Moreover, the addition of the Akt inhibitor LY294002 and the PI3K inhibitor 3-methyladenine enhanced the inhibitory effects of UA plus DIM on Akt pathway activation and further stimulated the Hippo pathway, including the suppression of YAP nuclear translocation in esophageal cancer cells. Silencing YAP under UA plus DIM conditions significantly increased the activation of the tumor suppressor PTEN in esophageal cancer cells, while decreasing p-Akt activation, indicating that the Akt signaling pathway could be down-regulated in esophageal cancer cells by targeting PTEN. Furthermore, in a xenograft nude mice model, UA plus DIM treatment effectively diminished esophageal tumors by inactivating the Akt pathway and stimulating the Hippo signaling pathway. Thus, our study highlights a feedback loop between the PI3K/Akt and Hippo signaling pathways in esophageal cancer cells, implying that a low dose of UA plus DIM could serve as a promising chemotherapeutic combination strategy in the treatment of esophageal cancer.

      • KCI등재

        Evaluation of Malignancy Risk of Ampullary Tumors Detected by Endoscopy Using 2-[18F]FDG PET/CT

        Chuang Pei-Ju,Wang Hsiu-Po,Tien Yu-Wen,Chin Wei-Shan,Hsieh Min-Shu,Chen Chieh-Chang,Hong Tzu-Chan,Ko Chi-Lun,Wu Yen-Wen,Cheng Mei-Fang 대한영상의학회 2024 Korean Journal of Radiology Vol.25 No.3

        Objective: We aimed to investigate whether 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) can aid in evaluating the risk of malignancy in ampullary tumors detected by endoscopy. Materials and Methods: This single-center retrospective cohort study analyzed 155 patients (79 male, 76 female; mean age, 65.7 ± 12.7 years) receiving 2-[18F]FDG PET/CT for endoscopy-detected ampullary tumors 5–87 days (median, 7 days) after the diagnostic endoscopy between June 2007 and December 2020. The final diagnosis was made based on histopathological findings. The PET imaging parameters were compared with clinical data and endoscopic features. A model to predict the risk of malignancy, based on PET, endoscopy, and clinical findings, was generated and validated using multivariable logistic regression analysis and an additional bootstrapping method. The final model was compared with standard endoscopy for the diagnosis of ampullary cancer using the DeLong test. Results: The mean tumor size was 17.1 ± 7.7 mm. Sixty-four (41.3%) tumors were benign, and 91 (58.7%) were malignant. Univariable analysis found that ampullary neoplasms with a blood-pool corrected peak standardized uptake value in earlyphase scan (SUVe) ≥ 1.7 were more likely to be malignant (odds ratio [OR], 16.06; 95% confidence interval [CI], 7.13–36.18; P < 0.001). Multivariable analysis identified the presence of jaundice (adjusted OR [aOR], 4.89; 95% CI, 1.80–13.33; P = 0.002), malignant traits in endoscopy (aOR, 6.80; 95% CI, 2.41–19.20; P < 0.001), SUVe ≥ 1.7 in PET (aOR, 5.43; 95% CI, 2.00–14.72; P < 0.001), and PET-detected nodal disease (aOR, 5.03; 95% CI, 1.16–21.86; P = 0.041) as independent predictors of malignancy. The model combining these four factors predicted ampullary cancers better than endoscopic diagnosis alone (area under the curve [AUC] and 95% CI: 0.925 [0.874–0.956] vs. 0.815 [0.732–0.873], P < 0.001). The model demonstrated an AUC of 0.921 (95% CI, 0.816–0.967) in candidates for endoscopic papillectomy. Conclusion: Adding 2-[18F]FDG PET/CT to endoscopy can improve the diagnosis of ampullary cancer and may help refine therapeutic decision-making, particularly when contemplating endoscopic papillectomy.

      • KCI등재

        Potential of a combination of entomopathogenic fungal strains and a non-ionic surfactant to control the fall armyworm (Spodoptera frugiperda)

        Wu Sing-Shan,Tseng Ching-Tzu,Yang Yu-Hung,Liu Yao-Chia,Chang Ju-Chun,Gyawali Purushottam,Li Yi-Hsuan,Yang Tzu-Hao,Tsai Yi-Fang,Tang Li-Cheng,Nai Yu-Shin 한국응용곤충학회 2022 Journal of Asia-Pacific Entomology Vol.25 No.4

        The fall armyworm, Spodoptera frugiperda, is an emerging invasive pest in Taiwan that feeds on a wide range of crops and causes serious damage. Herein, an entomopathogenic fungal library (EFLib) was constructed to identify potential microbes to control FAW. Twenty-eight indigenous entomopathogenic fungi (EPF) were iso lated and investigated for their potential pathogenicity, with Metarhizium pinghaense (Mp-NCHU-124) and Beauveria bassiana (Bb-NCHU-157) exerting dose-dependent effects on the 4th instar FAW larvae. The non-ionic surfactant Silwet L-77 rapidly killed FAW larvae after spraying at a concentration of 300 mg/kg and the toxic effect of Silwet L-77 on FAW larvae was dose-dependent. When the EPF isolates (10 6 conidia/mL) were applied to FAW larvae in combination with the non-ionic surfactant Silwet L-77 (30–90 mg/kg), the mortality rate dramatically increased and the LT 50 reduced, with increased fungal mycosis (Mp-NCHU-124: 38% to 72% and Bb-NCHU-157: 20 to 62%), indicating the high compatibility of EPF with the non-ionic surfactant. Thus, the Silwet L-77+EPF combined formulation has potential for practical field application for FAW pest control and sustainable agriculture in the future.

      • Positive Association Between IL-16 rs11556218 T/G Polymorphism and Cancer Risk: a Meta-analysis

        Mo, Cui-Ju,Peng, Qi-Liu,He, Yu,Wang, Jian,Xie, Li,Li, Tai-Jie,Li, Shan,Qin, Xue Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

        Background: Interleukin-16 (IL-16) is a multifunctional cytokine which plays a key role in inflammatory and autoimmune diseases as well as in cancer. Genetic polymorphisms of IL-16 have been implicated in susceptibility to cancer. However, associations remain inconclusive. The present meta-analysis was therefore carried out to establish a more conclusive association of IL-16 polymorphisms with cancer risk. Materials and Methods: Relevant studies were searched through the PubMed, Embase, Web of Science, Google Scholar and Wan fang electronic databases updated in October 2013. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to assess the association between IL-16 polymorphisms and cancer risk. Results: Eight eligible studies (rs4778889 T/C: 8, rs11556218 T/G: 7, rs4072111 C/T: 6) that met our selection criteria were included. The meta-analysis indicated that rs11556218 T/G was associated with a significant increased risk of cancer (G vs. T, OR=1.321, 95% CI=1.142-1.528, P<0.001; TG vs. TT, OR=1.665, 95% CI=1.448-1.915, P<0.001; GG+TG vs. TT, OR=1.622, 95% CI=1.416-1.858, P<0.001),as well as nasopharyngeal carcinoma and colorectal cancer. Furthermore, in the subgroup of Chinese, significant associations were found between rs11556218 polymorphism and cancer risk. There was no statistically significant association between the other two variants (rs4778889, rs4072111) and risk of cancer. Conclusions: This meta-analysis suggests that the IL-16 rs11556218 polymorphism is associated with increased cancer risk. Large well-designed studies involving various cancer types and different populations are now needed.

      • Association of XRCC3 Thr241Met Polymorphisms and Gliomas Risk: Evidence from a Meta-analysis

        Liang, Hong-Jie,Yan, Yu-Lan,Liu, Zhi-Ming,Chen, Xu,Peng, Qi-Liu,Wang, Jian,Mo, Cui-Ju,Sui, Jing-Zhe,Wu, Jun-Rong,Zhai, Li-Min,Yang, Shi,Li, Tai-Jie,Li, Ruo-Lin,Li, Shan,Qin, Xue Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

        The relationship between the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and gliomas remains inclusive or controversial. For better understanding of the effect of XRCC3 Thr241Met polymorphism on glioma risk, a meta-analysis was performed. All eligible studies were identified through a search of PubMed, Elsevier Science Direct, Excerpta Medica Database (Embase) and Chinese Biomedical Literature Database (CBM) before May 2013. The association between the XRCC3 Thr241Met polymorphism and gliomas risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of nine case-control studies including 3,533 cases and 4,696 controls were eventually collected. Overall, we found that XRCC3 Thr241Met polymorphism was significantly associated with the risk of gliomas (T vs. C: OR=1.10, 95%CI=1.01-1.20, P=0.034; TT vs. CC: OR=1.30, 95%CI=1.03-1.65, P=0.027; TT vs. TC/CC: OR=1.29, 95%CI=1.01-1.64, P=0.039). In the subgroup analysis based on ethnicity, the significant association was found in Asian under four models (T vs. C: OR=1.17, 95%CI=1.07-1.28, P=0.00; TT vs. CC: OR=1.79, 95%CI=1.36-2.36, P=0.00; TT vs. TC/CC: OR=1.75, 95%CI=1.32-2.32, P=0.00; TT/TC vs. CC: OR=1.11,95% CI=1.02-1.20). This meta-analysis suggested that the XRCC3 Thr241Met polymorphism is a risk factor for gliomas, especially for Asians. Considering the limited sample size and ethnicities included in the meta-analysis, further large scale and well-designed studies are needed to confirm our results.

      • Association between Dietary Factors and Breast Cancer Risk among Chinese Females: Systematic Review and Meta-analysis

        Liu, Xue-Ou,Huang, Yu-Bei,Gao, Ying,Chen, Chuan,Yan, Ye,Dai, Hong-Ji,Song, Feng-Ju,Wang, Yao-Gang,Wang, Pei-Shan,Chen, Ke-Xin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.3

        Background: Evidence for associations between dietary factors and breast cancer risk is inconclusive among Chinese females. To evaluate this question, we conducted a systematic review of relevant case-control and cohort studies. Methods: Studies were systematically searched among 5 English databases (PudMed, ScienceDirect, Wiley, Clinicaltrials.gov, and Cochrane) and 3 Chinese databases (CNKI, WanFang, and VIP) until November 2012. Random effects models were used to estimate summary odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Results: Thirty one case-control studies and two cohort studies involving 9,299 cases and 11,413 controls were included. Consumption of both soy and fruit was significantly associated with decreased risk of breast cancer, with summary ORs of 0.65 (95% CIs: 0.43-0.99; I2=88.9%, P<0.001; N=13) and 0.66 (95% CIs: 0.47-0.91; $I^2$=76.7%, P<0.001; N=7), respectively. Consumption of fat was significantly associated with increased risk of breast cancer (OR=1.36; 95% CIs: 1.13-1.63; $I^2$=47.9%, P=0.088; N=6). There was nonsignificant association between consumption of vegetables and breast cancer risk (OR=0.72; 95% CIs: 0.51-1.02; $I^2$= 74.4%, P<0.001; N=9). However, sensitivity analysis based on adjusted ORs showed decreased risk of breast cancer was also associated with consumption of vegetables (OR=0.49; 95% CIs: 0.30-0.67). Conclusion: Both soy food and fruit are significantly associated with decreased risk of breast cancer among Chinese females, and vegetables also seems to be protective while dietary fatexerts a promoting influence.

      • KCI등재

        Characteristics and Impact Factors of Renal Threshold for Glucose Excretion in Patients with Type 2 Diabetes Mellitus

        Xiao-Dan Yue,Jing-Yu Wang,Xin-Rong Zhang,Ju-Hong Yang,Chun-Yan Shan,Miao-Yan Zheng,Hui-Zhu Ren,Yi Zhang,Shao-Hua Yang,Zhen-Hong Guo,Bai Chang,Bao-Cheng Chang 대한의학회 2017 Journal of Korean medical science Vol.32 No.4

        Sodium glucose co-transporter 2 (SGLT-2) inhibitors are newly developed but promising medicine for type 2 diabetes. However, patients with a different renal threshold for glucose excretion (RTG) may have a different reaction to this medicine. Therefore, the objective of this study was to investigate the characteristics of RTG and its impact factors in patients with type 2 diabetes mellitus (T2DM). The clinical and laboratory data of 36 healthy individuals and 168 in-hospital patients with T2DM were collected and analyzed, RTG was calculated using blood glucose (BG) measured by dynamic BG monitoring, urinary glucose excretion (UGE) and estimated glomerular filtration rate (eGFR). The characteristics of RTG were investigated. The risk factors for high RTG were analyzed using non-conditional logistic regression analysis. Our results found that RTG of the T2DM group was higher than that of the healthy individuals (P < 0.05); and 22.22% from the healthy individuals group but 58.33% from the T2DM group had high RTG. Age, duration of diabetes, body mass index (BMI), and homeostasis model assessment insulin resistance index (HOMA-IR) were independently associated with high RTG (P < 0.05). Further stratified analysis revealed that RTG in T2DM patients increased with age, duration of diabetes, and BMI. In conclusion, RTG is increased in patients with T2DM, especially in those with longer diabetic duration, higher BMI, and those who are older. Therefore, these patients may be more sensitive to SGLT-2 inhibitors.

      • KCI등재

        Identification of a Novel Mutation and Polymorphic Change in the NIPBL Gene of Subjects with Cornelia de Lange Syndrome

        Pen Hua Su,Ju Shan Yu,Suh Jen Chen,Jia Yuh Chen 한국유전학회 2008 Genes & Genomics Vol.30 No.3

        Cornelia de Lange syndrome (CdLS) is a multisystem congenital anomaly disorder characterized by distinctive facial dysmorphism, including low anterior hairline, synophrys, anteverted nares, maxillary prognathism, long philtrum, and carp mouth; prenatal and postnatal growth retardation; mental retardation; limb anomalies; and multiple organ defects. The disease is caused by mutations in the NIPBL gene located at 5p13.1. To date, a variety of NIPBL mutations have been identified and shown to be associated with CdLS symptoms. Here, three Taiwanese subjects exhibiting multiple features of CdLS were analyzed in this study. One of the subjects characterized by classic CdLS symptoms had a novel frameshift mutation (C.3196delT) in exon11 of the NIPBL gene complex followed by a premature termination codon four amino acids downstream, whereas the two other subjects characterized by less pronounced CdLS symptoms had no detectable mutations in that part of thethe NIPBL gene complex that was analyzed herein. However, the former two subjects had a novel and unreported polymorphism in exon 33 that was also detected in the corresponding allele of 77 of 200 healthy Taiwanese control subjects. In conclusion, we report a novel NIPBL mutation likely associated with CdLS and one new polymorphism that is likely not related to CdLS. These observations suggest that truncating mutations were generally associated with a more severe phenotype. Additional studies using an expanded population of CdLS patients are being performed to enhance our understanding of the role of NIPBL in CdLS pathogenesis.

      • KCI등재

        Identification of a Novel Frameshift Mutation in the ARSE Gene of a Newborn Boy Diagnosed with Chondrodysplasia Punctata 1 (CDPX1)

        Pen Hua Su,Jia Yuh Chen,Ju Shan Yu,Suh Jen Chen,Jui Ming Hu,Jia Min Yang 한국유전학회 2007 Genes & Genomics Vol.29 No.3

        X-linked chondrodysplasia punctata (CDPX 1) is a congenital disorder characterized by abnormalities in cartilage and bone development. Here, we examined a young, male subject diagnosed with chondrodysplasia punctata presented by typical radiologic findings of calcific stippling at the vertebrae as well as in the sacral area. CDPX 1 has long been thought to be a hereditary disease of generalized skeletal dysplasia. We discovered a de novo frame shift mutation in the arylsulphatase gene, ARSE, which generated an early stop codon. Remarkably, the mother of the newborn subject consumed Chinese herbs, cnidiir rhizome, during the entire pregnancy period. To the best of our knowledge, this is the first report of chondrodysplasia punctata that is correlated with mutations in exon 9 of the ARSE gene. Furthermore, we postulated that consuming specific herbs during prolonged periods while pregnant could be directly or indirectly related to the occurrence of mutation in the ARSE gene and may as a consequence lead to drug embryopathy.

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