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      • KCI등재

        Survival Benefit of Tamoxifen in Estrogen Receptor-Negative and Progesterone Receptor-Positive Low Grade Breast Cancer Patients

        Li-Heng Yang,Hsin-Shun Tseng,Che Lin,Li-Sheng Chen,Shou-Tung Chen,Shou-Jen Kuo,Dar-Ren Chen 한국유방암학회 2012 Journal of breast cancer Vol.15 No.3

        Purpose: This study aimed to analyze the efficacy and prognostic significance of adjuvant tamoxifen in breast cancer patients with various hormone receptor statuses. Methods: Typically, 1,260 female breast cancer patients were recruited in this study. The correlation between estrogen receptor (ER)/progesterone receptor (PR) phenotypes and clinical characteristics was investigated, and the survival rate was assessed after 5-year follow-up. Results: The 5-year overall survival (85%) was better in women under the age of 50 years. Patients with ER+/PR+ tumors had a better 5-year survival rate (94%); those with ER-/PR- tumors experienced the worst outcome (74% survival rate); whereas singlepositive cases were in between. In 97 out of 128 patients with ER-/PR+ tumors, tamoxifen was given as adjuvant hormonal therapy, and it increased the survival benefit in the lower grade group in terms of overall survival and disease-free survival (p=0.01 and p=0.03, respectively). Conclusion: For high-grade tumors with ER-/PR+, adjuvant tamoxifen therapy may have no survival benefit, whereas for the patients with low-grade ER-/PR+ tumors, adjuvant tamoxifen therapy is highly suggestive.

      • KCI등재

        Springback Nonlinearity of High-strength Titanium Alloy Tube upon Mandrel Bending

        Heng Li,He Yang,Fei-Fei Song,Guang-Jun Li 한국정밀공학회 2013 International Journal of Precision Engineering and Vol. No.

        Taking the stress-relieved Ti-3Al-2.5V tube as the objective, regarding both angular and radius springback, the nonlinear springback behaviors of the high-strength titanium tube (HSTT) upon the universal bending, viz., mandrel bending (rotary draw bending), are clarified. The experiments are conducted to identify the springback and validate the theoretical models, and the deformation theory of plasticity and the explicit/implicit 3D-FE based models are used to reveal the rules and the physical mechanism of the nonlinearity of elastic recovery. The results show that: 1) At early bending stages, the angular springback increases nonlinearly with larger bending angles, then it increases linearly when the bending angle exceeds a critical one; While the radius growth decreases exponentially with the increasing of the bending angles at early stages, then it remains unchanged when the bending angle exceeds another critical value; The springback behaves more nonlinearly under smaller bending radii; Both the critical values for the two springback phenomena become larger with smaller bending radii; The critical angle for radius springback is larger than the one for angular springback. 2) The relationship between the radius springback and angular one is further identified; The radius springback can be estimated by the angular springback of the bending regions of tube; The variation of bending radii has significant effect on angular and radius springback, while it has little influence on the springback angle by the straight regions; The variation of the material properties affects both the springback phenomena much more significantly than the changing of the processing parameters.

      • SPON2 Promotes M1-like Macrophage Recruitment and Inhibits Hepatocellular Carcinoma Metastasis by Distinct Integrin–Rho GTPase–Hippo Pathways

        Zhang, Yan-Li,Li, Qing,Yang, Xiao-Mei,Fang, Fang,Li, Jun,Wang, Ya-Hui,Yang, Qin,Zhu, Lei,Nie, Hui-Zhen,Zhang, Xue-Li,Feng, Ming-Xuan,Jiang, Shu-Heng,Tian, Guang-Ang,Hu, Li-Peng,Lee, Ho-Young,Lee, Su-J American Association for Cancer Research 2018 Cancer research Vol.78 No.9

        <P>Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment.</P><P>Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis. SPON2-α4β1 integrin signaling activated RhoA and Rac1, increased F-actin reorganization, and promoted M1-like macrophage recruitment. F-Actin accumulation also activated the Hippo pathway by suppressing LATS1 phosphorylation, promoting YAP nuclear translocation, and initiating downstream gene expression. However, SPON2-α5β1 integrin signaling inactivated RhoA and prevented F-actin assembly, thereby inhibiting HCC cell migration; the Hippo pathway was not noticeably involved in SPON2-mediated HCC cell migration. In HCC patients, SPON2 levels correlated positively with prognosis. Overall, our findings provide evidence that SPON2 is a critical factor in mediating the immune response against tumor cell growth and migration in HCC.</P><P><B>Significance:</B> Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment.</P><P><B>Graphical Abstract:</B> http://cancerres.aacrjournals.org/content/canres/78/9/2305/F1.large.jpg. <I>Cancer Res; 78(9); 2305–17. ©2018 AACR</I>.</P><P><B>Graphical Abstract</B></P><P> [Figure]</P>

      • SCISCIESCOPUS

        Prevalence of new psychoactive substances in Northeast Asia from 2007 to 2015

        Lee, Junhui,Yang, Songhee,Kang, Yujin,Han, Eunyoung,Feng, Ling-Yi,Li, Jih-Heng,Chung, Heesun Elsevier Sequoia 2017 Forensic science international Vol.272 No.-

        <P><B>Abstract</B></P> <P>The proliferation of new psychoactive substances (NPS) has been a global trend in drug abuse and its regulation has been a worldwide concern. There is no doubt that it is necessary to share information related to these emerging substances between countries and continents for the effective regulation of NPS. With efforts for the efficient regulation of NPS, many studies and information have been published for the prevalence of NPS in the United States and other countries in Europe and Oceania. However, there is lack of information available for the prevalence of NPS in Asian and African countries. Therefore, this research was focused on the investigation of legal status of certain NPS in Northeast Asian countries, including China, Japan, South Korea and Taiwan, in order to provide information on the prevalence and trend of emerging NPS in these countries. The results showed that a total of 940 NPS was reported in 4 Northeast Asian countries from 2007 to 2015. Among 940 NPS, 882 NPS are legally restricted in at least one country (94%) and 96 substances were not currently under control (6%) in these countries. The number of controlled NPS that are currently controlled in all 4 countries was only 25 (or 28%) out of 882 NPS. Each substance was categorized in 9 groups according to the classification proposed by the United Nations Office on Drugs and Crime (UNODC). In Northeast Asia, the most commonly controlled NPS were synthetic cannabinoids, synthetic cathinones, and phenethylamines. It was found that Japan is the most proactive country in terms of the NPS regulation with 41% of the total number of controlled NPS in Northeast Asia, followed by South Korea (21%), China (28%), Taiwan (10%). Comparing the number of NPS newly regulated in each country every year, NPS has been broadly scheduled in 2011 and the number of scheduled NPS has dramatically increased from 2013 to 2015. It was shown that Northeast Asia is also in danger of these emerging NPS and the effective regulation across countries is important for the prevention of NPS. Also, this study will bring attention to local law enforcement in the construction of local drug crime prevention network sharing information for these controlled substances.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The trend and legal status of NPS in China, Japan, Korea and Taiwan was studied. </LI> <LI> Among total of 940 NPS reported, only 25 are currently controlled in 4 countries. </LI> <LI> Japan is the most proactive country regarding the NPS regulation followed by Korea. </LI> <LI> The information on emerging NPS in four countries was conducted for the first time. </LI> </UL> </P>

      • Increased Serotonin Signaling Contributes to the Warburg Effect in Pancreatic Tumor Cells Under Metabolic Stress and Promotes Growth of Pancreatic Tumors in Mice

        Jiang, Shu-Heng,Li, Jun,Dong, Fang-Yuan,Yang, Jian-Yu,Liu, De-Jun,Yang, Xiao-Mei,Wang, Ya-Hui,Yang, Min-Wei,Fu, Xue-Liang,Zhang, Xiao-Xin,Li, Qing,Pang, Xiu-Feng,Huo, Yan-Miao,Li, Jiao,Zhang, Jun-Feng Elsevier 2017 Gastroenterology Vol.153 No.1

        <P><B>Background & Aims</B></P> <P>Desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors.</P> <P><B>Methods</B></P> <P>We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras<SUP>G12D/+</SUP>/Trp53<SUP>R172H/+</SUP>/Pdx1-Cre (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples. We also analyzed expression levels of proteins involved in 5-HT synthesis and degradation by immunohistochemical analysis of a tissue microarray containing 311 PDAC specimens, and associated expression levels with patient survival times. 5-HT level in 14 matched PDAC tumor and non-tumor tissues were analyzed by ELISA. PDAC cell lines were incubated with 5-HT and cell survival and apoptosis were measured. We analyzed expression of the 5-HT receptor HTR2B in PDAC cells and effects of receptor agonists and antagonists, as well as HTR2B knockdown with small hairpin RNAs. We determined the effects of 5-HT stimulation on gene expression profiles of BxPC-3 cells. Regulation of glycolysis by 5-HT signaling via HTR2B was assessed by immunofluorescence and immunoprecipitation analyses, as well as by determination of the extracellular acid ratio, glucose consumption, and lactate production. Primary PDACs, with or without exposure to SB204741 (a selective antagonist of HTR2B), were grown as xenograft tumors in mice, and SB204741 was administered to tumor-bearing KPC mice; tumor growth and metabolism were measured by imaging analyses.</P> <P><B>Results</B></P> <P>In immunohistochemical analysis of a tissue microarray of PDAC specimens, increased levels of TPH1 and decreased level of MAOA, which regulate 5-HT synthesis and degradation, correlated with stage and size of PDACs and shorter patient survival time. We found levels of 5-HT to be increased in human PDAC tissues compared with non-tumor pancreatic tissues, and PDAC cell lines compared with non-transformed pancreatic cells. Incubation of PDAC cell lines with 5-HT increased proliferation and prevented apoptosis. Agonists of HTR2B, but not other 5-HT receptors, promoted proliferation and prevented apoptosis of PDAC cells. Knockdown of HTR2B in PDAC cells, or incubation of cells with HTR2B inhibitors, reduced their growth as xenograft tumors in mice. We observed a correlation between 5-HT and glycolytic flux in PDAC cells; levels of metabolic enzymes involved in glycolysis, the phosphate pentose pathway, and hexosamine biosynthesis pathway increased significantly in PDAC cells following 5-HT stimulation. 5-HT stimulation led to formation of the HTR2B–LYN–p85 complex, which increased PI3K–Akt–mTOR signaling and the Warburg effect by increasing protein levels of MYC and HIF1A. Administration of SB204741 to KPC mice slowed growth and metabolism of established pancreatic tumors and prolonged survival of the mice.</P> <P><B>Conclusions</B></P> <P>Human PDACs have increased levels of 5-HT, and PDAC cells increase expression of its receptor, HTR2B. These increases allow for tumor glycolysis under metabolic stress and promote growth of pancreatic tumors and PDAC xenograft tumors in mice.</P>

      • SCISCIESCOPUS

        Recent advances in microfluidic technology for manipulation and analysis of biological cells (2007–2017)

        Alam, Md Kowsar,Koomson, Emmanuel,Zou, Heng,Yi, Changqing,Li, Cheuk-Wing,Xu, Tao,Yang, Mengsu Elsevier Pub. Co 2018 Analytica Chimica Acta Vol. No.

        <P><B>Abstract</B></P> <P>The pivotal role of microfluidic technology in life science and biomedical research is now widely recognized. Indeed, microfluidics as a research tool is unparalleled in terms of its biocompatibility, robustness, efficient reagent consumption, and controlled fluidic, surface, and structure environments. The controlled environments are essential in assessing the complex behavior of cells in response to microenvironmental cues. The strengths of microfluidics also reside in its amenability to integration with other analytical platforms and its capacity for miniaturization, parallelization and automation of biochemical assays. Following previous review on the applications of microfluidic devices for cell-based assays in 2006, we have monitored the progress in the field and summarized the advances in microfluidic technology from 2007 to 2017, with a focus on microfluidics development for applications in cell manipulation, cell capture and detection, and cell treatment and analysis. Moreover, we highlighted novel commercial microfluidic products for biomedical and clinical purposes that were introduced in the review period. Thus, this review provides a comprehensive source for recent developments in microfluidics and presents a snapshot of its remarkable contribution towards basic biomedical research and clinical science. We recognize that although enormous amounts of evidence have reinforced the promise of microfluidic technology across diverse applications, much remains to be done to realize its full potential in mainstream biomedical science and clinical practice.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Advances in microfluidic technology for cell analysis in the last decade were reviewed. </LI> <LI> Microfluidic platforms exhibited superior spatiotemporal resolution for cell manipulation and monitoring of cellular responses.. </LI> <LI> Commercialization of microfluidic technology has gained traction in biomedical research and diagnostic applications. . </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • A Study On Critical Thinning In Thin-walled Tube Bending Of Al-Alloy 5052O Via Coupled Ductile Fracture Criteria

        Heng Li,He Yang,Mei Zhan 한국소성가공학회 2010 기타자료 Vol.2010 No.6

        Thin-walled tube bending(TWTB) method of Al-alloy tube has attracted wide applications in aerospace, aviation and automobile,etc. While, under in-plane double tensile stress states at the extrados of bending tube, the overthinning induced ductile fracture is one dominant defect in Al-alloy tube bending. The main objective of this study is to predict the critical wall-thinning of Al-alloy tube bending by coupling two ductile fracture criteria(DFCs) into FE simulation. The DFCs include Continuum Damage Mechanics(CDM)-based model and GTN porous model. Through the uniaxial tensile test of the curved specimen, the basic material properties of the Al-alloy 5052O tube is obtained; via the inverse problem solution, the damage parameters of both the two fracture criteria are interatively determined. Thus the application study of the above DFCs in the TWTB is performed, and the more reasonable one is selected to obtain the critical thinning of Al-alloy tube in bending. The virtual damage initiation and evolution (when and where the ductile fracture occurs) in TWTB are investigated, and the fracture mechanisms of the voided Al-alloy tube in tube bending are consequently discussed.

      • New Insights into Autonomic Nerve Preservation in High Ligation of the Inferior Mesenteric Artery in Laparoscopic Surgery for Colorectal Cancer

        Yang, Xiao-Fei,Li, Guo-Xin,Luo, Guang-Heng,Zhong, Shi-Zhen,Ding, Zi-Hai Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

        Aim: To take a deeper insight into the relationship between the root of the inferior mesenteric artery (IMA) and the autonomic nerve plexuses around it by cadaveric anatomy and explore anatomical evidence of autonomic nerve preservation in high ligation of the IMA in laparoscopic surgery for colorectal cancer. Methods: Anatomical dissection was performed on 11 formalin-fixed cadavers and 12 fresh cadavers. Anatomical evidence-based autonomic nerve preservation in high ligation of the IMA was performed in 22 laparoscopic curative resections of colorectal cancer. Results: As the upward continuation of the presacral nerves, the bilateral trunks of SHP had close but different relationships with the root of the IMA. The right trunk of SHP ran relatively far away from the root of IMA. When the apical lymph nodes were dissected close to the root of the IMA along the fascia space in front of the anterior renal fascia, the right trunk of SHP could be kept in suit under the anterior renal fascia. The left descending branches to SHP constituted a natural and constant anatomical landmark of the relationship between the root of IMA and the left autonomic nerves. Proximal to this, the left autonomic nerves surrounded the root of the IMA. Distally, the left trunk of the SHP departed from the root of IMA under the anterior renal fascia. When high ligation of the IMA was performed distal to it, the left trunk of SHP could be preserved. The distance between the left descending branches to SHP and the origin of IMA varied widely from 1.3 cm to 2.3 cm. Conclusions: The divergences of the bilateral autonomic nerve preservation around the root of the IMA may contribute to provide anatomical evidence for more precise evaluation of the optimal position of high ligation of the IMA in the future.

      • KCI등재

        Effects of spin-casting speed on solar cell performances and corresponding films morphology and optical properties using 2D perovskite of PEA2MA2Pb3I10

        Yang Zhang,Zeyang Wang,Ting Liu,Bo Yang,Shu Hu,Heng Li,ChuanXiang Sheng 대한금속·재료학회 2022 ELECTRONIC MATERIALS LETTERS Vol.18 No.3

        On hot substrates with a temperature of 100 °C, the qualities of two-dimensional perovskite PEA2MA2Pb3I10(PEA = phenethylammonium,MA = methylammonium) films have been explored which are constructed with different spin-casting speeds. These films are performed at the speed of 1000, 2000, 4000, and 6000 revolution per minute (RPM). Below 4000 r, a higherRPM results in higher crystalline quality with more uniform morphology. Correspondingly, 4000 r devices show better performanceon average (4.3% power conversion efficiency) and less hysteresis in the J-V curve than 1000 r (3.6%) and 2000 rdevices (3.4%). However, for devices that were fabricated at 6000 r, inferior performance (2.8% on average) may not bepredicted simply by the morphology characterization or optical measurement results at room temperature; instead, carriertrapping states can occur that result in thermally activated PL below 200 K with an activation energy of 18 meV, which donot occur in the 1000 r, 2000 r, and 4000 r films. Our results suggest that for evaluating 2D perovskite films prior to fabricatingoptimal devices, multiple morphology characterizations and optical measurements, including of low-temperature PL,will be helpful.

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