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Serum Tumor Marker Levels might have Little Significance in Evaluating Neoadjuvant Treatment Response in Locally Advanced Breast Cancer

  • Wang, Yu-Jie;Huang, Xiao-Yan;Mo, Miao;Li, Jian-Wei;Jia, Xiao-Qing;Shao, Zhi-Min;Shen, Zhen-Zhou;Wu, Jiong;Liu, Guang-Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4603-4608
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    • 2015
  • Background: To determine the potential value of serum tumor markers in predicting pCR (pathological complete response) during neoadjuvant chemotherapy. Materials and Methods: We retrospectively monitored the pro-, mid-, and post-neoadjuvant treatment serum tumor marker concentrations in patients with locally advanced breast cancer (stage II-III) who accepted pre-surgical chemotherapy or chemotherapy in combination with targeted therapy at Fudan University Shanghai Cancer Center between September 2011 and January 2014 and investigated the association of serum tumor marker levels with therapeutic effect. Core needle biopsy samples were assessed using immunohistochemistry (IHC) prior to neoadjuvant treatment to determine hormone receptor, human epidermal growth factor receptor 2(HER2), and proliferation index Ki67 values. In our study, therapeutic response was evaluated by pCR, defined as the disappearance of all invasive cancer cells from excised tissue (including primary lesion and axillary lymph nodes) after completion of chemotherapy. Analysis of variance of repeated measures and receiver operating characteristic (ROC) curves were employed for statistical analysis of the data. Results: A total of 348 patients were recruited in our study after excluding patients with incomplete clinical information. Of these, 106 patients were observed to have acquired pCR status after treatment completion, accounting for approximately 30.5% of study individuals. In addition, 147patients were determined to be Her-2 positive, among whom the pCR rate was 45.6% (69 patients). General linear model analysis (repeated measures analysis of variance) showed that the concentration of cancer antigen (CA) 15-3 increased after neoadjuvant chemotherapy in both pCR and non-pCR groups, and that there were significant differences between the two groups (P=0.008). The areas under the ROC curves (AUCs) of pre-, mid-, and post-treatment CA15-3 concentrations demonstrated low-level predictive value (AUC=0.594, 0.644, 0.621, respectively). No significant differences in carcinoembryonic antigen (CEA) or CA12-5 serum levels were observed between the pCR and non-pCR groups (P=0.196 and 0.693, respectively). No efficient AUC of CEA or CA12-5 concentrations were observed to predict patient response toward neoadjuvant treatment (both less than 0.7), nor were differences between the two groups observed at different time points. We then analyzed the Her-2 positive subset of our cohort. Significant differences in CEA concentrations were identified between the pCR and non-pCR groups (P=0.039), but not in CA15-3 or CA12-5 levels (p=0.092 and 0.89, respectively). None of the ROC curves showed underlying prognostic value, as the AUCs of these three markers were less than 0.7. The ROC-AUCs for the CA12-5 concentrations of inter-and post-neoadjuvant chemotherapy in the estrogen receptor negative HER2 positive subgroup were 0.735 and 0.767, respectively. However, the specificity and sensitivity values were at odds with each other which meant that improving either the sensitivity or specificity would impair the efficiency of the other. Conclusions: Serum tumor markers CA15-3, CA12-5, and CEA might have little clinical significance in predicting neoadjuvant treatment response in locally advanced breast cancer.

Role of Immune Response to Type II Collagen in the Pathogenesis of Rheumatoid Arthritis (류마티스 관절염 병인에서 제2형 콜라겐에 대한 면역반응의 역할)

  • Jung, Young Ok;Hong, Seung-Jae;Kim, Ho-Youn
    • IMMUNE NETWORK
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    • v.3 no.1
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    • pp.1-7
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    • 2003
  • Type II collagen (CII), major component of hyaline cartilage, has been considered as an auto-antigen in rheumatoid arthritis (RA). However, the clinical and biological significances with regard to the CII autoimmunity need to be clarified in human RA. The presence of antibodies to CII has been identified in sera, synovial fluid, and cartilage of patients with RA. In our study, the increased titer of IgG anti-CII in sera was well correlated with C-reactive protein, suggesting that this antibody may reflect the inflammatory status of RA. The titer of anti-CII antibodies (anti-CII Abs) tended to be higher in early stages of diseases. In our extending study, among 997 patients with RA, 269 (27.0%) were positive for circulatory IgG antibody to CII, those levels were fluctuated over time. It is hard to assess the significant amount of T cell responses to CII and CII (255~274) in RA. By using a sensitive method of antigen specific mixed lymphocyte culture, we can detect the presence of CII-reactive T cells in peripheral blood mononuclear cells of RA patients. Sixty seven (46.9%) of 143 patients showed positive CII reactive T cell responses to CII or CII (255~274). The frequencies of CII reactive T cells were more prominent in inflamed synovial fluid (SF) than in peripheral blood. These T cells could be clonally expanded after consecutive stimulation of CII with feeding of autologous irradiated antigen presenting cells (APC). Moreover, the production of Th1-related cytokine, such as IFN-${\gamma}$, was strongly up-regulated by CII reactive T cells. These data suggest that T cells responding to CII, which are probably presenting the IFN-${\gamma}$ producing cells, may play an important role in the perpetuation of inflammatory process in RA. To evaluate the effector function of CII reactive T cells, we investigated the effect of CII reactive T cells and fibroblasts-like synoviocytes (FLS) interaction on the production of pro-inflammatory cytokines. When the CII reactive T cells were co-cultured with FLS, the production of IL-15 and TNF-${\alpha}$ from FLS were significantly increased (2 to 3 fold increase) and this increase was clearly presented in accord to the expansion of CII reactive T cells. In addition, the production of IFN-${\gamma}$ and IL-17, T cell derived cytokines, were also increased by the co-incubation of CII reactive T cells with FLS. We also examined the impact of CII reactive T cells on chemokines production. When FLS were co-cultured with CII stimulated T cells, the production of IL-8, MCP-1, and MIP-1${\alpha}$ were significantly enhanced. The increased production of these chemokines was strongly correlated with increase the frequency of CII reactive T cells. Conclusively, immune response to CII was frequently found in RA. Activated T cells in response to CII contributed to increase the production of proinflammatory cytokines and chemokines, which were critical for inflammatory responses in RA. The interaction of CII-reactive T cells with FLS further augmented this phenomenon. Taken together, our recent studies have suggested that autoimmunity to CII could play a crucial role not only in the initiation but amplification/perpetuation of inflammatory process in human RA.

Estimation and assessment of baseflow at an ungauged watershed according to landuse change (토지이용변화에 따른 미계측 유역의 기저유출량 산정 및 평가)

  • Lee, Ji Min;Shin, Yongchun;Park, Youn Shik;Kum, Donghyuk;Lim, Kyoung Jae;Lee, Seung Oh;Kim, Hungsoo;Jung, Younghun
    • Journal of Wetlands Research
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    • v.16 no.4
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    • pp.303-318
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    • 2014
  • Baseflow gives a significant contribution to stream function in the regions where climatic characteristics are seasonally distinct. In this regard, variable baseflow can make it difficult to maintain a stable water supply, as well as causing disruption to the stream ecosystem. Changes in land use can affect both the direct flow and baseflow of a stream, and consequently, most other components of the hydrologic cycle. Baseflow estimation depends on the observed streamflow in gauge watersheds, but accurate predictions of streamflow through modeling can be useful in determining baseflow data for ungauged watersheds. Accordingly, the objectives of this study are to 1) improve predictions of SWAT by applying the alpha factor estimated using RECESS for calibration; 2) estimate baseflow in an ungauged watershed using the WHAT system; and 3) evaluate the effects of changes in land use on baseflow characteristics. These objectives were implemented in the Gapcheon watershed, as an ungauged watershed in South Korea. The results show that the alpha factor estimated using RECESS in SWAT calibration improves the prediction for streamflow, and, in particular, recessions in the baseflow. Also, the changes in land use in the Gapcheon watershed leads to no significant difference in annual baseflow between comparable periods, regardless of precipitation, but does lead to differences in the seasonal characteristics observed for the temporal distribution of baseflow. Therefore, the Guem River, into which the stream from the Gapcheon watershed flows, requires strategic seasonal variability predictions of baseflow due to changes in land use within the region.

Expression Profiling of MLO Family Genes under Podosphaera xanthii Infection and Exogenous Application of Phytohormones in Cucumis melo L. (멜론 흰가루병균 및 식물 호르몬 처리하에서 MLO 유전자군의 발현검정)

  • Howlader, Jewel;Kim, Hoy-Taek;Park, Jong-In;Ahmed, Nasar Uddin;Robin, Arif Hasan Khan;Jung, Hee-Jeong;Nou, III-Sup
    • Journal of Life Science
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    • v.26 no.4
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    • pp.419-430
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    • 2016
  • Powdery mildew disease caused by Podosphaera xanthii is a major concern for Cucumis melo production worldwide. Knowledge on genetic behavior of the related genes and their modulating phytohormones often offer the most efficient approach to develop resistance against different diseases. Mildew Resistance Locus O (MLO) genes encode proteins with seven transmembrane domains that have significant function in plant resistance to powdery mildew fungus. We collected 14 MLO genes from ‘Melonomics’ database. Multiple sequence analysis of MLO proteins revealed the existence of both evolutionary conserved cysteine and proline residues. Moreover, natural genetic variation in conserved amino acids and their replacement by other amino acids are also observed. Real-time quantitative PCR expression analysis was conducted for the leaf samples of P. xanthii infected and phyto-hormones (methyl jasmonate and salicylic acid) treated plants in melon ‘SCNU1154’ line. Upon P. xanthii infection using 7 different races, the melon line showed variable disease reactions with respect to spread of infection symptoms and disease severity. Three out of 14 CmMLO genes were up-regulated and 7 were down-regulated in leaf samples in response to all races. The up- or down-regulation of the other 4 CmMLO genes was race-specific. The expression of 14 CmMLO genes under methyl jasmonate and salicylic acid application was also variable. Eleven CmMLO genes were up-regulated under salicylic acid treatment, and 7 were up-regulated under methyl jasmonate treatments in C. melo L. Taken together, these stress-responsive CmMLO genes might be useful resources for the development of powdery mildew disease resistant C. melo L.

The Role of Plant Fatty Acids in Regulation of the Adaptation of Organisms to the Cold Climate in Cryolithic Zone of Yakutia (야쿠티아의 동토지역에 서식하는 생물의 추운기후-순화의 조절에서 식물 지방산의 역할)

  • Petrov, Klim Alekseevich;Dudareva, Lyubov Vissarionovna;Nokhsorov, Vasilii Vasilevich;Perk, Aleksandr Aleksandrovich;Chepalov, Valentin Azotovich;Sophronova, Valentina Egorovna;Voinikov, Victor Kirillovich;Zulfugarov, Ismayil S.;Lee, Choon-Hwan
    • Journal of Life Science
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    • v.26 no.5
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    • pp.519-530
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    • 2016
  • Vegetative plants in Yakutia are naturally frozen when they are covered with snow in the fall, and they function as green cryo-fodder that is a source of biologically active substances and nutrients for herbivorous animals. We observed a considerable increase in the total fatty acid content in the leaves of Avena sativa, Elytrigia rеpens, Equisetum variegatum and Equisetum scirpoides during the fall period. However, the degree of unsaturation of fatty acids was not higher in the frozen plants covered with snow than in the summer plants, with the exception of E. scirpoides, a dwarf horsetail found in the Pole of Cold in the northern hemisphere. In the internal adipose tissue of the Yakut horse (young horse meat), 18 fatty acids were found, including 10 saturated ones. Monounsaturated oleic С18:1 (n-9) acid and polyunsaturated α-linolenic С18:3 (n-3) acid were equally prevalent among the unsaturated fatty acids, accounting for 70% of the total unsaturated fatty acids. This composition of polyenoic fatty acids in the internal adipose tissue indicates that the Yakut horse actively feeds on the fall vegetation and the wintergreen sedge-grass. We believe that the high plant-specific free fatty acid content in the tissue of Yakut horses may play an important role in the regulation of their resistance to long-term low-temperature stress.

Study on the Characteristics of EEG in Resting State on Visuo-Spatial Working Memory Performance (시공간 작업기억 수행능력에 따른 안정상태에서의 뇌파 특성 연구)

  • Jung, Chul-Woo;Lee, Hyeob-Eui;Wi, Hyun-Wook;Choi, Nam-Sook;Park, Pyong-Woon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.17 no.4
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    • pp.351-360
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    • 2016
  • The purpose of this study is to predict visual-spatial working memory performance through the characteristics of an electroencephalogram (EEG) in the resting state. The 31 study participants, middle school students with various to academic performance, were underwent visual-spatial working memory test in the Comprehensive Attention Test (CAT) on December in 2014. Each 7 and 6 participants were divided into an Excellent Working Memory (EWM) group and Poor Working Memory (PWM) group depending on the forward/backward working memory scores. The EEG measurements and analysis of the data from a Brain Function Tester were performed by the two groups. A Mann-Whitney Test was used to examine the statistical differences between them. The activation of high beta (${\beta}H$) at the Fp1 and Fp2 sites in the left and right hemisphere, and that of the low beta (${\beta}L$) in the right hemisphere in the EWM group was significantly higher than that in the PWM group. In conclusion, there is a correlation between the visual-spatial working memory performance and the activation of ${\beta}H$ and ${\beta}L$ in the resting state and a close correlation that of ${\beta}L$ in the right hemisphere in terms of mental activity and faculty. Therefore, the visual-spatial working memory performance can be predicted by the activation of ${\beta}H$ and ${\beta}L$ in the resting state. The activation of EEG can be applied as an assessment tool and provide basis data for visual-spatial working memory performance.

Response of Ground Beetles (Coleoptera: Carabidae) to Vegetation Structure in Wildlife Crossings (생태통로 내부 식생구조에 대한 지표성 딱정벌레류(딱정벌레목: 딱정벌레과)의 반응)

  • Jung, Jong-Kook;Park, Yujeong;Lee, Sun Kyung;Lee, Hyoseok;Park, Young-gyun;Lee, Joon-Ho;Choi, Tae Young;Woo, Donggul
    • Korean Journal of Environment and Ecology
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    • v.30 no.2
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    • pp.185-198
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    • 2016
  • Korea has put in significant efforts to increase the number of wildlife crossings between fragmented habitats to prevent loss of biodiversity and to encourage the habitat connectivity in Korea. However, there is a lack of biological data on the effect of vegetation structure in these wildlife crossings and guidelines for design and management of wildlife crossing structures in Korea. Therefore, we selected ground beetle assemblages as model organisms to compare the effect of vegetation structure in wildlife crossings, i.e. bare ground- and shrub-type corridors, in agro-forested landscapes. For this study, 4,207 ground beetles belonging to 33 species were collected through pitfall trapping along the northern forest-corridor-southern forest transects from late April to early September in 2015. Dominant species, abundance, and species richness of ground beetles were significantly higher in the shrub-type corridors than the bare ground-type corridors. Also, the species composition of bare ground-type corridor was significantly different compared to the other habitats such as shrub-type corridor and forests. Similarly, environmental variables were also influenced by vegetation management regimes or trap locations. Collectively, our study clearly indicates that the movement of forest associated ground beetles between forest patches can increase as the vegetation in wildlife crossings becomes complex. Although further studies are needed to verify this, there are indications that the current wildlife crossings that comply with the guidelines may be unfriendly to the movement of ground dwelling arthropods as well as ground beetles. To enhance the ecological function of wildlife crossings, the guidelines need to be rectified as follows: 1) Shrubs or trees should be planted along the corridor verges to provide refuge or movement paths for small mammals and ground dwelling arthropods, and 2) Open spaces should be provided in the middle of the corridors to be used as a path for the movement of large mammals.

Monitoring for Rheological Properties of Black Jam Produced by Black Ginseng and Black Garlic (흑삼 및 흑마늘을 이용한 블랙잼 유동특성 모니터링)

  • Lee, Gee-Dong
    • Journal of the Korean Applied Science and Technology
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    • v.37 no.2
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    • pp.183-191
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    • 2020
  • This study monitored the rheological properties of jams manufactured using the black ginseng and black garlic. The conditions for mixing black jam were black ginseng (X1, 30-54 g), black garlic (X2, 75-135 g), pectin 4.5 g, apple paste 270 g, and fructo-oligosaccharide 360 g. The response surface analysis was performed with springiness, cohesiveness, chewiness, brittleness and gumminess. The R2s of the regression equation for springiness, cohesiveness, chewiness, brittleness and gumminess were recognized at a significant level of 5 to 10 %, with 0.8948, 0.9103, 0.9032, 0.9097, and 0.8561, respectively. The combination conditions of black ginseng and black garlic with the highest springiness of black jam were found to be 194.39% (springiness) with black ginseng 54.00 g and black garlic 105.83 g, while the conditions of black ginseng and black garlic mixing with the lowest springiness were found to be 164.11% with black ginseng 31.48 g and black garlic 119.43 g. The mixing conditions of black ginseng and black garlic with the highest cohesiveness of black jam and its consistency were 40.96% (cohesiveness) with black ginseng 48.85 g and black garlic 129.62 g, while black ginseng and black garlic combination conditions with the lowest cohesiveness were found to be 32.96% with black ginseng 50.06 g and black garlic 82.77 g. Black ginseng and black garlic mixing conditions, which have the highest chewiness of black jam, was 43.19 g (chewiness) from black ginseng 42.95 g and black garlic 106.83 g. Black ginseng and black garlic mixing conditions and their brittleness were found to be the highest in black ginseng 32.10 g and black garlic 88.04 g to 16,874 g. Black ginseng and black garlic mixing conditions and their brittleness were found to be 678 g from black ginseng 50.53 g and black garlic 83.91 g. Black ginseng and black garlic mixing conditions and their gumminess were 14.06 g with black ginseng content of 32.91 g and black garlic content of 124.60 g. By examining the relationship between black ginseng/black garlic ratio and the rheological property of black jam from above results, it is believed that black jam can be produced for anyone to enjoy using health function material.

Ameliorative effect of onion (Allium Cepa L.) flesh and peel on amyloid-β-induced cognitive dysfunction via mitochondrial activation (미토콘드리아 활성화를 통한 양파(Allium Cepa L.) 과육 및 과피의 Amyloid-β 유도성 인지손상에 대한 개선효과)

  • Park, Seon Kyeong;Lee, Uk;Kang, Jin Yong;Kim, Jong Min;Shin, Eun Jin;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.52 no.3
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    • pp.263-273
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    • 2020
  • In this study, in order to confirm the ameliorative effects of onion (Allium cepa L.) flesh and peel on amyloidbeta (Aβ)-induced cognitive dysfunction, we evaluated their in vitro neuroprotection and in vivo cognitive functions. As the result of in vitro neuroprotection, the protective effect of the ethyl acetate fraction of onion flesh (EOF) on Aβ-induced cytotoxicity was similar to that of the ethyl acetate fraction of onion peel (EOP). In the behavioral tests, the EOF and EOP effectively improved the Aβ-induced learning and memory impairments. For this reason, it could be concluded that the EOF and EOP improved the antioxidant activities (superoxide dismutase, oxidized glutathione/total glutathione, and malondialdehyde) in brain tissue. In addition, the EOF and EOP effectively activated mitochondrial functions by protecting the mitochondrial membrane potential, ATP, mitochondria-mediated protein (BAX and cytochrome c), and caspase 3/7 activities. The EOF and EOP also improved the cholinergic system (acetylcholinesterase and acetylcholine). Therefore, we suggest that onion could be used for management of Aβ-induced cognitive dysfunction.

Investigation of O4 Air Mass Factor Sensitivity to Aerosol Peak Height Using UV-VIS Hyperspectral Synthetic Radiance in Various Measurement Conditions (UV-VIS 초분광 위성센서 모의복사휘도를 활용한 다양한 관측환경에서의 에어로솔 유효고도에 대한 O4 대기질량인자 민감도 조사)

  • Choi, Wonei;Lee, Hanlim;Choi, Chuluong;Lee, Yangwon;Noh, Youngmin
    • Korean Journal of Remote Sensing
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    • v.36 no.2_1
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    • pp.155-165
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    • 2020
  • In this present study, the sensitivity of O4 Air Mass Factor (AMF) to Aerosol Peak Height (APH) has been investigated using radiative transfer model according to various parameters(wavelength (340 nm and 477 nm), aerosol type (smoke, dust, sulfate), aerosol optical depth (AOD), surface reflectance, solar zenith angle, and viewing zenith angle). In general, it was found that O4 AMF at 477 nm is more sensitive to APH than that at 340 nm and is stably retrieved with low spectral fitting error in Differential Optical Absorption Spectroscopy (DOAS) analysis. In high AOD condition, sensitivity of O4 AMF on APH tends to increase. O4 AMF at 340 nm decreased with increasing solar zenith angle. This dependency isthought to be induced by the decrease in length of the light path where O4 absorption occurs due to the shielding effect caused by Rayleigh and Mie scattering at high solar zenith angles above 40°. At 477 nm, as the solar zenith angle increased, multiple scattering caused by Rayleigh and Mie scattering partly leads to the increase of O4 AMF in nonlinear function. Based on synthetic radiance, APHs have been retrieved using O4 AMF. Additionally, the effect of AOD uncertainty on APH retrieval error has been investigated. Among three aerosol types, APH retrieval for sulfate type is found to have the largest APH retrieval error due to uncertainty of AOD. In the case of dust aerosol, it was found that the influence of AOD uncertainty is negligible. It indicates that aerosol types affect APH retrieval error since absorption scattering characteristics of each aerosol type are various.