• Title/Summary/Keyword: PI3K

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Predictive and Prognostic Significance of p27, Akt, PTEN and PI3K Expression in HER2-Positive Metastatic Breast Cancer

  • Okutur, Kerem;Bassulu, Nuray;Dalar, Levent;Aydin, Kubra;Bozkurt, Mustafa;Pilanci, Kezban Nur;Dogusoy, Gulen Bulbul;Tecimer, Coskun;Mandel, Nil Molinas;Demir, Gokhan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2645-2651
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    • 2015
  • Background: The phosphatidylinositol 3'-kinase/Akt (PI3K/Akt) pathway is a key regulator for HER2-overexpressing breast cancer, but data about whether activation of PI3K/Akt is associated with poor prognosis and resistance to trastuzumab therapy is controversial. In this study we investigated predictive and prognostic significance of expression of p27, Akt, PTEN and PI3K, which are components of the PI3K/Akt signaling pathway, in HER2-positive metastatic breast cancer (MBC), retrospectively. Materials and Methods: Fifty-four HER2-positive MBC patients who had received first-line trastuzumab-based therapy were recruited for the study group. All of the patient's breast tissue samples were examined for p27 and Akt expression. In addition, twenty-five patients with sufficient amount of tumor tissue were also examined for PTEN and PI3K expression. p27, Akt, PTEN and PI3K were evaluated by immunohistochemistry and their relationship with patient demographic features, tumor characteristics, response to trastuzumab-based treatment and survival outcomes were analyzed. Results: p27, Akt, PTEN and PI3K were positive in 25.9%, 70.4%, 24% and 96% of the cases, respectively. Nomne were significantly associated with response to trastuzumab and time to progression (TTP). A trend toward statistical significance for longer overall survival (OS) was found for PTEN-positive patients (p=0.058); there was no significant relationship between the other immunohistochemical variables and OS. When we analyzed groups regarding co-expression, the PTEN-negative/Akt-negative group had a significantly lower objective response rate (ORR) (20% vs 80%, p=0.023) and the PTEN-negative/p27-negative and PTEN-negative/Akt-negative groups had significantly lower median OS compared to other patients (26.4 months vs 76.1 months, p=0.005 and 25.6 months vs 52.0 months, p=0.007, respectively). Conclusions: p27, Akt, PTEN and PI3K expression is not statistically significantly associated with ORR, TTP and OS, individually. However, the combined evaluation of p27, Akt and PTEN could be helpful to predict the response to trastuzumab-based therapy and prognosis in HER2-positive MBC.

Studies on HG Type of Heterodera glycines in Korea (국내 콩 씨스트선충의 HG type 분석)

  • Kim, Donggeun;Choi, Insoo;Han, Wonyoung;Ryu, Younghyun;Kim, Myungsik;Bae, Changhwan
    • Research in Plant Disease
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    • v.19 no.1
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    • pp.31-35
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    • 2013
  • Thirteen soybean cyst nematode (SCN) (Heterodera glycines) populations collected in Korea were examined in their HG type by their reproductivity on 7 Plant Introduction indicators for the identification of HG type. Six HG types were identified, HG type 0, 2, 5, 2.5, 1.2.7, and 2.5.7. HG type 2.5 was the most frequent (4 samples, 30.8%), followed by HG type 2.5.7 (3 samples, 23.0%). About 76.9% of SCN populations were reproduced on PI 88788, followed by PI 209332 (61.5%), PI 548316 ('Cloud') (30.8%), and PI 548402 ('Peking') (7.7%). No population could reproduce on PI 90763, PI 437654, thus, they could be used for resistant source for developing SCN resistant soybean in Korea.

THE VERTEX AND EDGE PI INDICES OF GENERALIZED HIERARCHICAL PRODUCT OF GRAPHS

  • Tavakoli, M.;Rahbarnia, F.
    • Journal of applied mathematics & informatics
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    • v.31 no.3_4
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    • pp.469-477
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    • 2013
  • Pattabiraman and Paulraja [K. Pattabiraman, P. Paulraja, Vertex and edge PI indices of the generalized hierarchical product of graphs, Discrete Appl. Math. 160 (2012) 1376- 1384] obtained exact formulas for the vertex and edge PI indices of generalized hierarchical product of graphs. The aim of this note is to improve the main results of this paper.

Korean Red Ginseng inhibits apoptosis in neuroblastoma cells via estrogen receptor ${\beta}$-mediated phosphatidylinositol-3 kinase/Akt signaling

  • Nguyen, Cuong Thach;Luong, Truc Thanh;Kim, Gyu-Lee;Pyo, Suhkneung;Rhee, Dong-Kwon
    • Journal of Ginseng Research
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    • v.39 no.1
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    • pp.69-75
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    • 2015
  • Background: Ginseng has been shown to exert antistress effects both in vitro and in vivo. However, the effects of ginseng on stress in brain cells are not well understood. This study investigated how Korean Red Ginseng (KRG) controls hydrogen peroxide-induced apoptosis via regulation of phosphatidylinositol-3 kinase (PI3K)/Akt and estrogen receptor (ER)-${\beta}$ signaling. Methods: Human neuroblastoma SK-N-SH cells were pretreated with KRG and subsequently exposed to $H_2O_2$. The ability of KRG to inhibit oxidative stress-induced apoptosis was assessed in MTT cytotoxicity assays. Apoptotic protein expression was examined byWestern blot analysis. The roles of ER-${\beta}$, PI3K, and p-Akt signaling in KRG regulation of apoptosis were studied using small interfering RNAs and/or target antagonists. Results: Pretreating SK-N-SH cells with KRG decreased expression of the proapoptotic proteins p-p53 and caspase-3, but increased expression of the antiapoptotic protein BCL2. KRG pretreatment was also associated with increased ER-${\beta}$, PI3K, and p-Akt expression. Conversely, ER-${\beta}$ inhibition with small interfering RNA or inhibitor treatment increased p-p53 and caspase-3 levels, but decreased BCL2, PI3K, and p-Akt expression. Moreover, inhibition of PI3K/Akt signaling diminished p-p53 and caspase-3 levels, but increased BCL2 expression. Conclusion: Collectively, the data indicate that KRG represses oxidative stress-induced apoptosis by enhancing PI3K/Akt signaling via upregulation of ER-${\beta}$ expression.

Arctigenin Increases Hemeoxygenase-1 Gene Expression by Modulating PI3K/AKT Signaling Pathway in Rat Primary Astrocytes

  • Jeong, Yeon-Hui;Park, Jin-Sun;Kim, Dong-Hyun;Kim, Hee-Sun
    • Biomolecules & Therapeutics
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    • v.22 no.6
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    • pp.497-502
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    • 2014
  • In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat primary astrocytes. Since hemeoxygenase-1 (HO-1) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-1 expression in rat primary astrocytes. We found that arctigenin increased HO-1 mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-Jun to the antioxidant response element (ARE) on HO-1 promoter. In addition, arctigenin increased ARE-mediated transcriptional activities in rat primary astrocytes. Further mechanistic studies revealed that arctigenin increased the phosphorylation of AKT, a downstream substrate of phosphatidylinositol 3-kinase (PI3K). Treatment of cells with a PI3K-specific inhibitor, LY294002, suppressed the HO-1 expression, Nrf2 DNA binding and ARE-mediated transcriptional activities in arctigenin-treated astrocyte cells. The results collectively suggest that PI3K/AKT signaling pathway is at least partly involved in HO-1 expression by arctigenin via modulation of Nrf2/ARE axis in rat primary astrocytes.

POSTNIKOV SECTIONS AND GROUPS OF SELF PAIR HOMOTOPY EQUIVALENCES

  • Lee, Kee-Young
    • Bulletin of the Korean Mathematical Society
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    • v.41 no.3
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    • pp.393-401
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    • 2004
  • In this paper, we apply the concept of the group \ulcorner(X,A) of self pair homotopy equivalences of a CW-pair (X, A) to the Postnikov system. By using a short exact sequence related to the group of self pair homotopy equivalences, we obtain the following result: for any Postnikov section X$\sub$n/ of a CW-complex X, the group \ulcorner(X$\sub$n/, A) of self pair homotopy equivalences on the pair (X$\sub$n/, X) is isomorphic to the group \ulcorner(X) of self homotopy equivalences on X. As a corollary, we have, \ulcorner(K($\pi$, n), M($\pi$, n)) ≡ \ulcorner(M($\pi$, n)) for each n$\pi$1, where K($\pi$,n) is an Eilenberg-Mclane space and M($\pi$,n) is a Moore space.

Novel Erbium(III)-Encapsulated Complexes Based on ${\pi}$-Extended Anthracene Ligands Bearing G3-Aryl-Ether Dendron: Synthesis and Photophysical Studies

  • Baek, Nam-Seob;Kim, Yong-Hee;Roh, Soo-Gyun;Lee, Dong-Hyun;Seo, Kang-Deuk;Kim, Hwan-Kyu
    • Macromolecular Research
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    • v.17 no.9
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    • pp.672-681
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    • 2009
  • A series of inert and photo-stable Er(III)-encapsulated complexes based on ${\pi}$-extended dendritic anthracene ligands bearing G3-aryl-ether dendron ([G3-AnX]-$CO_2H$), which retain different ${\pi}$-bridging systems, such as single (X= S), double (X= D) and triple (X= T) bonds was designed and synthesized to establish the structure-property relationship. The near infrared emission intensities of Er(III)-encapsulated complexes were enhanced dramatically by increasing the ${\pi}$-conjugated extension of anthracene ligands. The time-resolved luminescence spectra show monoexponential decays with a lifetime of $2.0{\sim}2.4ms$ for $Er^{3+}$ ions in thin films, and calculated intrinsic quantum yields of $Er^{3+}$ ions are in the range of $0.025{\sim}0.03%$. As a result, all Er(III)-encapsulated dendrimer complexes exhibit the near IR emission with the following order: $Er^{3+}-[G3-AnD]_3$(terpy) > $Er^{3+}-[G3-AnS]_3$(terpy) ${\approx}$ $Er^{3+}-[G3-AnT]_3$(terpy), because $Er^{3+}-[G3-AnD]_3$(terpy) has a higher relatively spectral overlap J value and energy transfer efficiency. In addition, the lack of detectable phosphorescence and no significant spectral dependence of the ${\pi}$-extended anthracene moieties on the solvent polarity support energy transfer from their singlet state to the central $Er^{3+}$ ion taking place in $Er^{3+}-[G3-AnX]_3$(terpy).

High Expression of HIF-1α, BNIP3 and PI3KC3: Hypoxia-Induced Autophagy Predicts Cholangiocarcinoma Survival and Metastasis

  • Thongchot, Suyanee;Yongvanit, Puangrat;Loilome, Watcharin;Seubwai, Wanchana;Phunicom, Kutcharin;Tassaneeyakul, Wichittra;Pairojkul, Chawalit;Promkotra, Wisuttiphong;Techasen, Anchalee;Namwat, Nisana
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.14
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    • pp.5873-5878
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    • 2014
  • Hypoxia and autophagy are known to facilitate tumor progression. We here aimed to investigate the role of hypoxia-associated autophagy in cholangiocarcinoma (CCA) survival and metastasis. Immunostaining of hypoxic-responsive proteins (HIF-$1{\alpha}$ and BNIP3) and a key regulator of autophagy (PI3KC3) were examined in CCA tissues and their expression levels were compared with clinicopathological parameters. A hypoxia mimicking condition ($CoCl_2$ treatment) was also tested regarding CCA cell functions. Our results showed that HIF-$1{\alpha}$ (66%), BNIP3 (44%) and PI3KC3 (46%) showed strong staining in human CCA tissues. Positive expression of HIF-$1{\alpha}$ (p=0.033), BNIP3 (p=0.040) and PI3KC3 (p=0.037) was significantly correlated with lymph node metastasis. HIF-$1{\alpha}$ was well associated with BNIP3 (r=0.3, p<0.01) and PI3KC3 (r=0.2, p<0.01). The survival rates of patients who were positive with HIF-$1{\alpha}$ (p=0.047) or co-expressed HIF-$1{\alpha}$ and BNIP3 (p=0.032) or HIF-$1{\alpha}$ and PI3KC3 (p=0.043) were significantly greater than in the negative groups. CCA cells treated with $CoCl_2$ showed an increase in HIF-$1{\alpha}$, BNIP3, PI3KC3 and LC3-II, with increased cell migration and pFAK levels. These data suggest that hypoxia associated autophagy enhances CCA metastasis, resulting in a poor prognosis of CCA.

Development of antibodies after foot and mouth disease vaccination in pigs (돼지에서 구제역 백신 접종 후 항체가 변화 조사)

  • Ahn, Gil-Ho;Bae, Jin-Gyu;Jung, Kwang;Wang, Young-Il;Jung, Jun-Yong;Kang, Soon-Keun;Kwon, Hyuk-Moo
    • Korean Journal of Veterinary Service
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    • v.36 no.1
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    • pp.15-21
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    • 2013
  • Three serotypes (O+A+Asia1 type) of the foot-and-mouth disease (FMD) vaccine were injected into cloven-hoofed animals in Korea after the nationwide spread of FMD at the end of 2010. This study was conducted to investigate FMD antibody development after FMD vaccination, and to determine whether there was a significant correlation between the antibody titer of the sow and the antibody titer of the growing pigs. The antibody titer (percentage inhibition [PI] titer) of the sow (gilt) after FMD vaccination was maintained at a level higher than 50 (P<0.05) for 5 months. A higher PI titer for the 1-month-old growing pigs corresponded with greater inhibition of the PI titer of the vaccinated growing pigs (P<0.05). A negative correlation (P<0.05) between the PI titer of the 1-month-old growing pigs and the PI titer of 3-month-old growing pigs, 4-month-old growing pigs after FMD vaccination at 2 months, 3months was identified, with a coefficient of determination ($R^2$) of 0.274. Thus the PI titer of the growing pigs was inhibited to a greater degree when vaccination was performed at 2 months of age than at 3 months. However, many other factors likely influence growing pigs' PI titer in addition to the PI titer of the sow and age at vaccination, given that the coefficient of determination was somewhat lower.

THEMIS Pi2 observations near dawn and dusk sectors in the inner magnetosphere

  • Kwon, Hyuck-Jin;Kim, Khan-Hyuk;Lee, Dong-Hun;Takahashi, K.;Park, Young-Deuk;Bonnell, J.W.
    • Bulletin of the Korean Space Science Society
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    • 2010.04a
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    • pp.40.3-40.3
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    • 2010
  • The most frequently suggested source for Pi2 pulsations in the inner magnetosphere (L < 4) is standing fast-mode waves trapped in the plasmasphere (i.e., plasmaspheric resonances). They have been considered as the source of low-latitude Pi2 pulsations. The plasmaspheric resonance model suggests that compressional fast-mode waves can be detected at all local times inside the plasmasphere provided reflection of the wave energy is efficient. Until now, however, there are no reports about compressional Pi2s observed in the dayside inner magnetosphere. That is, there is longitudinal limit of inner magnetosphere. In February 2008, THEMIS probes were near dawn and/or dusk sides, which are the transition regions between the nightside and dayside, in the inner magnetosphere (L = 2-4) when low-altitude Pi2s were identified at Bohyun (L = 1.35) station in Korea. Using the THEMIS electric field data, we examined if Pi2s are excited by longitudinally localized disturbances. We found that compressional Pi2s having high coherence with a low-latitude Pi2 pulsation occur on dawnside. However, any compressional pulsations in the Pi2 frequency band were not detected on duskside. This indicates that compressional Pi2s disappear near the duskside. Our observations are discussed with spatial plasmaspheric structure and possible Pi2 mechanisms.

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