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Expression Characteristics of Proteins of the Insulin-like Growth Factor Axis in Non-small Cell Lung Cancer Patients with Preexisting Type 2 Diabetes Mellitus

  • Ding, Jing;Tang, Jie;Chen, Xin;Men, Hai-Tao;Luo, Wu-Xia;Du, Yang;Ge, Jun;Li, Cong;Chen, Ye;Cheng, Ke;Qiu, Meng;Liu, Ji-Yan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5675-5680
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    • 2013
  • Background: Preexisting type 2 diabetes mellitus (T2DM) affects the prognosis and mortality of patients with some cancers. Insulin like growth factor (IGF) and insulin receptor (IR) signaling axes play important roles in both cancer and diabetes development. We aimed to explore the expression characteristics of proteins in IGF/IR axis in non-small cell lung cancer (NSCLC) cases with preexisting T2DM. Methods: Fifty-five NSCLC patients with preexisting T2DM were retrospectively included and matched by 55 NSCLC without diabetes at a 1:1 ratio. The expression of proteins in IGF/IR axis was detected by immunohistochemical staining. Clinicopathological data were collected to analyze their relationship with the protein expression. Results: Both IGF 1 receptor (IGF-1R) and insulin receptor substrate 2 (IRS-2) showed higher expression in the NSCLC with T2DM group, compared with those without T2DM. The high expression of IGF-1R and IRS-2 were found to be negatively associated with lymph node metastases and T staging in the T2DM group, respectively, and IRS-2 expression was also found more in the subgroup whose T2DM duration was more than 4 years. No difference was detected in the expression of IRS-1, IGF-1, IGF-2, IGFBP3, IR and mTOR between groups with or without T2DM. Conclusion: Our study found higher expression of IGF-1R and IRS-2 proteins in NSCLC patients with preexisting T2DM, and that there was an association with early stage NSCLC, which suggested that IGF signaling may play an important early event in development of NSCLC associated with diabetes.

Anti-proliferative Effects of Celastrol, A Quinine Methide Triterpene Extracted from the Perennial Vine Tripterygium wilfordii, on Obesity-related Cancers (미역줄나무 뿌리 추출물인 셀라스트롤의 비만관련 암증식 억제효과)

  • Park, Sunmi;Moon, Hyun-Seuk
    • Journal of Food Hygiene and Safety
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    • v.31 no.1
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    • pp.59-66
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    • 2016
  • It has been generally accepted that obesity and overweight are associated with metabolic diseases and cancer incidence. In fact, obesity increased risks of cancers i.e. breast, liver, pancreatic and prostate. Celastrol is a pentacyclic triterpenoid isolated from Thunder god vine, was used as a Chinese traditional medicine for treatment of inflammatory disorders such as arthritis, lupus erythematosus and Alzheimer's disease. Also, celastrol has various biological properties of chemo-preventive, neuro-protective, and anti-oxidant effects. Recent studies demonstrated that celastrol has anti-proliferation effects in different type of obesity-related cancers and suppresses tumor progression and metastasis. Anticancer effects of celastrol include regulation of $NF-{\kappa}B$, heat shock protein, JNK, VEGF, CXCR4, Akt/mTOR, MMP-9 and so on. For these reasons, celastrol has shown to be a promising anti-tumor agent. In this review, we will address the anticancer activities and multiple mechanisms of celastrol in obesity-related cancers.

Atrial Septal Defect Closure: Comparison of Vertical Axillary Minithoracotomy and Median Sternotomy

  • Poyrazoglu, Huseyin Hakan;Avsar, Mustafa Kemal;Demir, Serafettin;Karakaya, Zeynep;Guler, Tayfun;Tor, Funda
    • Journal of Chest Surgery
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    • v.46 no.5
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    • pp.340-345
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    • 2013
  • Background: This study aims to evaluate whether or not the method of right vertical axillary minithoracotomy (RVAM) is preferable to and as reliable as conventional sternotomy surgery, and also assesses its cosmetic results. Methods: Thirty-three patients (7 males, 26 females) with atrial septal defect were admitted to the Cardiovascular Surgery Clinic of Cukurova University from December 2005 until January 2010. The patients' ages ranged from 3 to 22. Patients who underwent vertical axillary minithracotomy were assigned to group I, and those undergoing conventional sternotomy, to group II. Group I and group II were compared with regard to the preoperative, perioperative and postoperative variables. Group I included 12 females and 4 males with an average age of $16.5{\pm}9.7$. Group II comprised 14 female and 3 male patients with an average age of $18.5{\pm}9.8$ showing similar features and pathologies. The cases were in Class I-II according to the New York Heart Association (NYHA) Classification, and patients with other cardiac and systemic problems were not included in the study. The ratio of the systemic blood flow to the pulmonary blood flow (Qp/Qs) was $1.8{\pm}0.2$. The average pulmonary artery pressure was $35{\pm}10$ mmHg. Following the diagnosis, performing elective surgery was planned. Results: No significant difference was detected in the average time of the patients' extraportal circulation, cross-clamp and surgery (p>0.05). In the early postoperative period of the cases, the duration of mechanical ventilator support, the drainage volume in the first 24 hours, and the hospitalization time in the intensive care unit were similar (p>0.05). Postoperative pains were evaluated together with narcotic analgesics taken intravenously or orally. While 7 cases (43.7%) in group I needed postoperative analgesics, 12 cases (70.6%) in group II needed them. No mortality or major morbidity has occurred in the patients. The incision style and sizes in all of the patients undergoing RVAM were preserved as they were at the beginning. Furthermore, the patients of group I were mobilized more quickly than the patients of group II. The patients of group I were quite pleased with the psychological and cosmetic results. No residual defects have been found in the early postoperative period and after the end of the follow-up periods. All of the patients achieved functional capacity per NYHA. No deformation of breast growth has been detected during 18 months of follow-up for the group I patients, who underwent RVAM. Conclusion: To conclude, the repair of atrial septal defect by RVAM, apart from the limited working zone for the surgeon in these pathologies as compared to sternotomymay be considered in terms of the outcomes, and early and late complications. And this has accounted for less need of analgesics and better cosmetic results in recent years.

Study on the Source Area of the Stones from Stone-cultural Properties -Geomorphological and Petrological Approach for the Iksan Area- (석조문화재의 석재공급지에 관한 연구 -익산 지역에 대한 지형학적 및 암석학적 접근-)

  • Cho Ki-Man;Jwa Yong-Joo
    • The Journal of the Petrological Society of Korea
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    • v.14 no.1
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    • pp.24-37
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    • 2005
  • In this study we examined the geomorphological and geological characteristics of the granite landforms in the Iksan area. Moreover we investigated the source areas of stones which are used to build the Mieruksaji west stone pagoda. Joint is most identifiable geomorphological and geological structure in the Iksan area. Direction of J1 joint appears to be N71°E∼EW, and that of J2 joint ranges N20°W∼N20°E. Cross-pattern joint is predominant in the study area, and linen.-pattern vertical joint is also observed. Tor and corestone are easily found as geomorphological features in the study area. Corestones forming for are almost 2∼3 m across and 2∼3 m or over 5 m high. Their hardness is mainly of hammer bounce. Tower-type and castle-type of for are characteristic in the Mireuksan granites. Other geomorphological features such as tafoni, gnamma are also observed in the study area. Petrographical and geochemical features of the stones used for the Mireuksaji west stone pagoda are compared with those of the granites cropped out nearby, and indicate that the stones from the Mieruksaji west stone pagoda are quite similar to the Mireuksan granites. In the Mireuksan we can easily find lots of old traces for rock cutting.

A Study on the Characteristics and Utilization Measures of Rock Formations in the Romantic Road in the Eastern Coast of Korea (동해안 낭만가도의 바위지형경관 특성과 활용방안)

  • Kwon, Dong Hi
    • Journal of the Korean Geographical Society
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    • v.48 no.6
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    • pp.803-818
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    • 2013
  • In this study, a total of 80 rock formations in the romantic road(Nangmangado) were investigated and analyzed and the results are as follows. The area in where the rock formations landscape is seen the most is Yangyang(43 formations), and the formations are most densely concentrated in Jukdo beach when seen from the site group. The most observed landform is weathering landform(61%) and the rest is comprised of coastal landform(24%) and structural landform(15%). For weathering landform, Tafoni takes up the largest portion (33%) and is followed by Corestone(27%), Tor(22%), Gnamma(10%), Groove(4%) and Exfoliation(4%). Considering academic value, rarity and accessibility overall, the 35 landforms are expected to have high utility value as tourism resources and topography filed course. And out of these 35 landforms, 11 are concentrated in Dongsan beach in Yangyang. Therefore, it seems worthy to consider developing Dongsan beach under the name of "Dongsan Coast Rock Park(Tentative Name)" to be actively utilized as tourism resources. The landforms which are evaluated as highly valuable for geomorphology filed course are a total of 16 areas including Fan rock and Op rock formations. In these areas, typical weathering landforms are concentrated in one spot and two or three other types of landform can also be additionally observed, allowing the place to be highly efficient for field education.

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Strutural Change of Root Surface Following $CO_2$ Laser Treatment (($CO_2$)레이저 치료에 의한 치근표면의 구조적 변화)

  • Kim, Do-Young;Han, Soo-Boo;Ko, Jae-Sung;Park, Sung-Hyun;Kye, Seung-Beom;Hwang, Kwang-Se;Kim, Woo-Sung
    • Journal of Periodontal and Implant Science
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    • v.27 no.3
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    • pp.469-478
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    • 1997
  • The purpose of this study was to evaluate the structural change of root surface and the occlusion of dentinal tubule following $CO_2$ laser treatment. Seven extracted healthy human premolar werw curetted, sectioned, and four specimens were randomly assigned to each of 6 different treatment groups : 1) untreated EDTA etched control: 2) root plande only: 3) $CO_2$ laser treated with 2W mode 6(10msec/pulse, 20pps) for 1 minute: 4) $CO_2$ laser treated with 2W mode 6(lOmsec/pulse, 20pps) for 2 minutes: 5) $CO_2$ laser treated with 2W mode 7(20msec/pulse, 20pps) for 1 minute: 6) $CO_2$ laser treated with 2W mode 7(20msec/pulse, 20pps) for 2 minutes. Following the prescribed treatment, the specimens were prepared for SEM evaluation. Results showed that $CO_2$ laser may be effective to occlude dentinal tubules tor dentin sensitivity treatment. The effect of dentinal tubule occlusion was enhanced with increasing the total energy level lased to specimen regardless of lasing mode. The structural changes of root surfaces were restricted to superficies, and these changes included fissuring, charring, crater formation over the smooth lava like texture. The charring and crater formation implying root damage was observed in the case of the longer duration of a pulse. The results of the present study suggests that the pulsed $CO_2$ laser with shorter pulse duration and longer exposure time can be used effectively in order to obtain the optimal dentinal tubule occlusion with minimal root damage.

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Geoheritage Values and Geotourism of the Igidae-Oryukdo Geosites in the Busan National Geopark, Korea (부산국가지질공원 이기대·오륙도 지질명소에 분포하는 지질유산의 가치평가와 이를 활용한 지오투어리즘)

  • Kim, Sunwoong;Kang, Karyoung;Son, Moon;Paik, Insung;Lim, Hyounsoo;Kim, Jinseop
    • The Journal of the Petrological Society of Korea
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    • v.26 no.2
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    • pp.99-112
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    • 2017
  • Geoheritage is designated to preserve geodiversity of geological and geomorphological cases. Geotourism is an extensive activity that aims at the understanding of geology and earth's history for the geoheritage and for developing regions through preserving the geodiveristy of geoheritage. Igidae-Oryukdo is geosite of Busan National Geopark and its visitors are expected to grow rapidly. Accordingly, for the effective use of the geosites, The development and application of geotourism is required. This study suggests that tuffacious sedimentary rocks, hornblende megacrysts-bearing dike, copper mine, marine potholes should designated as the central points for advanced learning stage; volcanic breccia, sea caves, sea cliffs, wavecut platform, tor and islands as the central points for basic learning stage. Based on this central points, this study established concepts for getourism in this study area at basic and expert level for individual and family tourists, and also small or large groups such as school students.

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.

Raloxifene Induces Autophagy-Dependent Cell Death in Breast Cancer Cells via the Activation of AMP-Activated Protein Kinase

  • Kim, Dong Eun;Kim, Yunha;Cho, Dong-Hyung;Jeong, Seong-Yun;Kim, Sung-Bae;Suh, Nayoung;Lee, Jung Shin;Choi, Eun Kyung;Koh, Jae-Young;Hwang, Jung Jin;Kim, Choung-Soo
    • Molecules and Cells
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    • v.38 no.2
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    • pp.138-144
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    • 2015
  • Raloxifene is a selective estrogen receptor modulator (SERM) that binds to the estrogen receptor (ER), and exhibits potent anti-tumor and autophagy-inducing effects in breast cancer cells. However, the mechanism of raloxifene-induced cell death and autophagy is not well-established. So, we analyzed mechanism underlying death and autophagy induced by raloxifene in MCF-7 breast cancer cells. Treatment with raloxifene significantly induced death in MCF-7 cells. Raloxifene accumulated GFP-LC3 puncta and increased the level of autophagic marker proteins, such as LC3-II, BECN1, and ATG12-ATG5 conjugates, indicating activated autophagy. Raloxifene also increased autophagic flux indicators, the cleavage of GFP from GFP-LC3 and only red fluorescence-positive puncta in mRFP-GFP-LC3-expressing cells. An autophagy inhibitor, 3-methyladenine (3-MA), suppressed the level of LC3-II and blocked the formation of GFP-LC3 puncta. Moreover, siRNA targeting BECN1 markedly reversed cell death and the level of LC3-II increased by raloxifene. Besides, raloxifene-induced cell death was not related to cleavage of caspases-7, -9, and PARP. These results indicate that raloxifene activates autophagy-dependent cell death but not apoptosis. Interestingly, raloxifene decreased the level of intracellular adenosine triphosphate (ATP) and activated the AMPK/ULK1 pathway. However it was not suppressed the AKT/mTOR pathway. Addition of ATP decreased the phosphorylation of AMPK as well as the accumulation of LC3-II, finally attenuating raloxifene-induced cell death. Our current study demonstrates that raloxifene induces autophagy via the activation of AMPK by sensing decreases in ATP, and that the overactivation of autophagy promotes cell death and thereby mediates the anti-cancer effects of raloxifene in breast cancer cells.

Study on the 2G High Temperature Superconducting Coil for Large Scale Superconducting Magnetic Energy Storage Systems (대용량 에너지 저장장치용 2세대 고온 초전도 코일의 특성해석)

  • Lee, Ji-Young;Lee, Seyeon;Kim, Yungil;Park, Sang Ho;Choi, Kyeongdal;Lee, Ji-Kwang;Kim, Woo-Seok
    • KEPCO Journal on Electric Power and Energy
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    • v.1 no.1
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    • pp.157-162
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    • 2015
  • Large scale superconducting magnetic energy storage (SMES) system requires very high magnetic energy density in its superconducting coils to enhance the energy capacity and efficiency of the system. The recent high temperature superconducting (HTS) conductors, so called 2G conductors, show very good performance under very high magnetic field so that they seem to be perfect materials for the large scale SMES coils. A general shape of the coil system with the 2G HTS conductor has been a tor oid, because the magnetic field applied perpendicularly to the surface of the 2G HTS conductor could be minimized in this shape of coil. However, a toroid coil requires a 3-dimensional computation to acquire the characteristics of its critical current density - magnetic field relations which needs very complicated numerical calculation, very high computer specification, and long calculation time. In this paper, we suggested an analytic and statistical calculation method to acquire the maximum magnetic flux density applied perpendicularly to the surface of the 2G HTS conductor and the stored energy in the toroid coil system. Although the result with this method includes some errors but we could reduce these errors within 5 percent to get a reasonable estimation of the important parameters for design process of the HTS toroid coil system. As a result, the calculation time by the suggested method could be reduced to 0.1 percent of that by the 3-dimensional numerical calculation.