• 제목/요약/키워드: ER-stress

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3-Deoxysappanchalcone Inhibits Cell Growth of Gefitinib-Resistant Lung Cancer Cells by Simultaneous Targeting of EGFR and MET Kinases

  • Jin-Young Lee;Seung-On Lee;Ah-Won Kwak;Seon-Bin Chae;Seung-Sik Cho;Goo Yoon;Ki-Taek Kim;Yung Hyun Choi;Mee-Hyun Lee;Sang Hoon Joo;Jin Woo Park;Jung-Hyun Shim
    • Biomolecules & Therapeutics
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    • 제31권4호
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    • pp.446-455
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    • 2023
  • The mechanistic functions of 3-deoxysappanchalcone (3-DSC), a chalcone compound known to have many pharmacological effects on lung cancer, have not yet been elucidated. In this study, we identified the comprehensive anti-cancer mechanism of 3-DSC, which targets EGFR and MET kinase in drug-resistant lung cancer cells. 3-DSC directly targets both EGFR and MET, thereby inhibiting the growth of drug-resistant lung cancer cells. Mechanistically, 3-DSC induced cell cycle arrest by modulating cell cycle regulatory proteins, including cyclin B1, cdc2, and p27. In addition, concomitant EGFR downstream signaling proteins such as MET, AKT, and ERK were affected by 3-DSC and contributed to the inhibition of cancer cell growth. Furthermore, our results show that 3-DSC increased redox homeostasis disruption, ER stress, mitochondrial depolarization, and caspase activation in gefitinib-resistant lung cancer cells, thereby abrogating cancer cell growth. 3-DSC induced apoptotic cell death which is regulated by Mcl-1, Bax, Apaf-1, and PARP in gefitinib-resistant lung cancer cells. 3-DSC also initiated the activation of caspases, and the pan-caspase inhibitor, Z-VAD-FMK, abrogated 3-DSC induced-apoptosis in lung cancer cells. These data imply that 3-DSC mainly increased mitochondria-associated intrinsic apoptosis in lung cancer cells to reduce lung cancer cell growth. Overall, 3-DSC inhibited the growth of drug-resistant lung cancer cells by simultaneously targeting EGFR and MET, which exerted anti-cancer effects through cell cycle arrest, mitochondrial homeostasis collapse, and increased ROS generation, eventually triggering anti-cancer mechanisms. 3-DSC could potentially be used as an effective anti-cancer strategy to overcome EGFR and MET target drug-resistant lung cancer.

Hsp90 Inhibitor Induces Cell Cycle Arrest and Apoptosis of Early Embryos and Primary Cells in Pigs

  • Son, Myeong-Ju;Park, Jin-Mo;Min, Sung-Hun;Hong, Joo-Hee;Park, Hum-Dai;Koo, Deog-Bon
    • Reproductive and Developmental Biology
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    • 제35권1호
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    • pp.33-45
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    • 2011
  • Heat shock protein 90 (Hsp90) is ATPase-directed molecular chaperon and affects survival of cancer cell. Inhibitory effect of Hsp90 by inducing cell cycle arrest and apoptosis in the cancer cell was reported. However, its role during oocyte maturation and early embryo development is very insufficient. In this study, we traced the effects of Hsp90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), on meiotic maturation and early embryonic development in pigs. We also investigated several indicators of developmental potential, including structural integrity, gene expression (Hsp90-, cell cycle-, and apoptosis-related genes), and apoptosis, which are affected by 17-AAG. Then, we examined the roles of Hsp90 inhibitor on viability of primary cells in pigs. Porcine oocytes were cultured in the NCSU-23 medium with or without 17-AAG for 44 h. The proportion of GV arrested oocytes was significantly different between the 17-AAG treated and untreated group (78.2 vs 34.8%, p<0.05). After completion of meiotic maturation, the proportion of MII oocytes was lower in the 17-AAG treated group than in the control group (27.9 vs 71.0%, p<0.05). After IVF, the percentage of penetrated oocytes was significantly lower in the 17-AAG treated group (25.2%), resulting in lower normal pronucleus formation (2PN of 14.6%). Therefore, the inhibition of meiotic progression by Hsp90 inhibitor played a critical role in fertilization status. Porcine embryo were cultured in the PZM-3 medium with or without 17-AAG for 6 days. In result, significant differences in developmental potential were detected between the embryos that were cultured with or without 17-AAG. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) showed that the number of containing fragmented DNA at the blastocyst stage increased in the 17-AAG treated group compared with control (7.5 vs 4.4, respectively). Blastocysts that developed in the 17-AAG treated group had low structural integrity and high apoptotic nuclei than those of the untreated control, resulting in decrease the embryonic qualities of preimplantation porcine blastocysts. The mRNA expressions of cell cycle-related genes were down-regulated in the 17-AAG treated group compared with control. Also, the expression of the pro-apoptotic gene Bax increased in 17-AAG treated group, whereas expression of the anti-apoptotic gene Bel-XL decreased. However, the expression of ER stress-related genes did not changed by 17-AAG. Cultured pESF cells were treated with or without 17-AAG and used for MIT assay. The results showed that viability of pESF cells were decreased by treatment of 17-AAG ($2{\mu}M$) for 24 hr. These results indicated that 17-AAG decreased cell proliferation and increased cell death. Expression patterns Hsp90 complex genes (Hsp70 and p23), cell cycle-related genes (cdc2 and cdc25c) and apoptosis-related genes (Bax and Bcl-XL) were significantly changed by using RT-PCR analysis. The spliced form of pXbp-1 product (pXbp-1s) was detected in the tunicamycin (TM) treated cells, but it is not detected in 17-AAG treated cells. In conclusion, Hsp90 appears to play a direct role in porcine early embryo developmental competence including structural integrity of blastocysts. Also, these results indicate that Hsp90 is closely associated with cell cycle- and apoptosis-related genes expression in developing porcine embryos.

가정간호 서비스 질 평가를 위한 도구개발연구 (A basic research for evaluation of a Home Care Nursing Delivery System)

  • 김모임;조원정;김의숙;김성규;장순복;유호신
    • 가정간호학회지
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    • 제6권
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    • pp.33-45
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    • 1999
  • The purpose of this study was to develop a basic framework and criteria for evaluation of quality care provided to patients with the attributes of disease in the home care nursing field, and to provide measurement tools for home health care in the future. The study design was a developmental study for evaluation of hospital-based HCN(home care nursing) in Korea. The study process was as follows: a home care nursing study team of College of Nursing. Yonsei University reviewed the nursing records of 47 patients who were enrolled at Yonsei University Medical Center Home Care Center in March, 1995. Twenty-five patients were insured at that time, were selected from 47 patients receiving home care service for study feasibility with six disease groups; Caesarean Section (C/S), simple nephrectomy, Liver cirrhosis(LC), chronic obstructive pulmonary disease(COPD), Lung cancer or cerebrovascular accident(CVA). In this study, the following items were selected : First step : Preliminary study 1. Criteria and items were selected on the basis of related literature on each disease area. 2. Items were identified by home care nurses. 3. A physician in charge reviewed the criteria and content of selected items. 4. Items were revised through preliminary study offered to both HCN patients and discharged patients from the home care center. Second step : Pretest 1. To verify the content of the items, a pretest was conducted with 18 patients of which there were three patients in each of the six selected disease groups. Third step : Test of reliability and validity of tools 1. Using the collected data from 25 patients with either cis, Simple nephrectomy, LC, COPD, Lung cancer, or CVA. the final items were revised through a panel discussion among experts in medical care who were researchers, doctors, or nurses. 2. Reliability and validity of the completed tool were verified with both inpatients and HCN patients in each of field for researches. The study results are as follows: 1. Standard for discharge with HCN referral The referral standard for home care, which included criteria for discharge with HCN referral and criteria leaving the hospital were established. These were developed through content analysis from the results of an open-ended questionnaire to related doctors concerning characteristic for discharge with HCN referral for each of the disease groups. The final criteria was decided by discussion among the researchers. 2. Instrument for measurement of health statusPatient health status was measured pre and post home care by direct observation and interview with an open-ended questionnaire which consisted of 61 items based on Gorden's nursing diagnosis classification. These included seven items on health knowledge and health management, eight items on nutrition and metabolism, three items on elimination, five items on activity and exercise, seven items on perception and cognition, three items on sleep and rest, three items on self-perception, three items on role and interpersonal relations, five items on sexuality and reproduction, five items on coping and stress, four items on value and religion, three items on family. and three items on facilities and environment. 3. Instrument for measurement of self-care The instrument for self-care measurement was classified with scales according to the attributes of the disease. Each scale measured understanding level and practice level by a Yes or No scale. Understanding level was measured by interview but practice level was measured by both observation and interview. Items for self-care measurement included 14 for patients with a CVA, five for women who had a cis, ten for patients with lung cancer, 12 for patients with COPD, five for patients with a simple nephrectomy, and 11 for patients with LC. 4. Record for follow-up management This included (1) OPD visit sheet, (2) ER visit form, (3) complications problem form, (4) readmission sheet. and (5) visit note for others medical centers which included visit date, reason for visit, patient name, caregivers, sex, age, time and cost required for visit, and traffic expenses, that is, there were open-end items that investigated OPD visits, emergency room visits, the problem and solution of complications, readmissions and visits to other medical institution to measure health problems and expenditures during the follow up period. 5. Instrument to measure patients satisfaction The satisfaction measurement instrument by Reisseer(1975) was referred to for the development of a tool to measure patient home care satisfaction. The instrument was an open-ended questionnaire which consisted of 11 domains; treatment, nursing care, information, time consumption, accessibility, rapidity, treatment skill, service relevance, attitude, satisfaction factors, dissatisfaction factors, overall satisfaction about nursing care, and others. In conclusion, Five evaluation instruments were developed for home care nursing. These were (1)standard for discharge with HCN referral. (2)instrument for measurement of health status, (3)instrument for measurement of self-care. (4)record for follow-up management, and (5)instrument to measure patient satisfaction. Also, the five instruments can be used to evaluate the effectiveness of the service to assure quality. Further research is needed to increase the reliability and validity of instrument through a community-based HCN evaluation.

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Perspective of breaking stagnation of soybean yield under monsoon climate

  • Shiraiwa, Tatsuhiko
    • 한국작물학회:학술대회논문집
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    • 한국작물학회 2017년도 9th Asian Crop Science Association conference
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    • pp.8-9
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    • 2017
  • Soybean yield has been low and unstable in Japan and other areas in East Asia, despite long history of cultivation. This is contrasting with consistent increase of yield in North and South America. This presentation tries to describe perspective of breaking stagnation of soybean yield in East Asia, considering the factors of the different yields between regions. Large amount of rainfall with occasional dry-spell in the summer is a nature of monsoon climate and as frequently stated excess water is the factor of low and unstable soybean yield. For example, there exists a great deal of field-to-field variation in yield of 'Tanbaguro' soybean, which is reputed for high market value and thus cultivated intensively and this results in low average yield. According to our field survey, a major portion of yield variation occurs in early growth period. Soybean production on drained paddy fields is also vulnerable to drought stress after flowering. An analysis at the above study site demonstrated a substantial field-to-field variation of canopy transpiration activity in the mid-summer, but the variation of pod-set was not as large as that of early growth. As frequently mentioned by the contest winners of good practice farming, avoidance of excess water problem in the early growth period is of greatest importance. A series of technological development took place in Japan in crop management for stable crop establishment and growth, that includes seed-bed preparation with ridge and/or chisel ploughing, adjustment of seed moisture content, seed treatment with mancozeb+metalaxyl and the water table control system, FOEAS. A unique success is seen in the tidal swamp area in South Sumatra with the Saturated Soil Culture (SSC), which is for managing acidity problem of pyrite soils. In 2016, an average yield of $2.4tha^{-1}$ was recorded for a 450 ha area with SSC (Ghulamahdi 2017, personal communication). This is a sort of raised bed culture and thus the moisture condition is kept markedly stable during growth period. For genetic control, too, many attempts are on-going for better emergence and plant growth after emergence under excess water. There seems to exist two aspects of excess water resistance, one related to phytophthora resistance and the other with better growth under excess water. The improvement for the latter is particularly challenging and genomic approach is expected to be effectively utilized. The crop model simulation would estimate/evaluate the impact of environmental and genetic factors. But comprehensive crop models for soybean are mainly for cultivations on upland fields and crop response to excess water is not fully accounted for. A soybean model for production on drained paddy fields under monsoon climate is demanded to coordinate technological development under changing climate. We recently recognized that the yield potential of recent US cultivars is greater than that of Japanese cultivars and this also may be responsible for different yield trends. Cultivar comparisons proved that higher yields are associated with greater biomass production specifically during early seed filling, in which high and well sustained activity of leaf gas exchange is related. In fact, the leaf stomatal conductance is considered to have been improved during last a couple of decades in the USA through selections for high yield in several crop species. It is suspected that priority to product quality of soybean as food crop, especially large seed size in Japan, did not allow efficient improvement of productivity. We also recently found a substantial variation of yielding performance under an environment of Indonesia among divergent cultivars from tropical and temperate regions through in a part biomass productivity. Gas exchange activity again seems to be involved. Unlike in North America where transpiration adjustment is considered necessary to avoid terminal drought, under the monsoon climate with wet summer plants with higher activity of gas exchange than current level might be advantageous. In order to explore higher or better-adjusted canopy function, the methodological development is demanded for canopy-level evaluation of transpiration activity. The stagnation of soybean yield would be broken through controlling variable water environment and breeding efforts to improve the quality-oriented cultivars for stable and high yield.

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캐나다의 동계한냉지역에 있어서 초지개발과 조사료 공급의 활성화에 필요한 요인 (Factors Required to Sustain Pastoral Farming Systems and Forage Supply In Winter-Cold Zones in Canada)

  • Kunelius, H.T.;Fraser, Joanna
    • 한국초지조사료학회지
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    • 제12권3호
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    • pp.3-12
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    • 1992
  • 캐나다에서 화본과와 두과목초 및 사료작물은 가축사양에 있어서 주된 에너지 공급원이다 캐나다에 는 약 1,100만 ha의 개량초지와 조사료 생산은 가능하지만 환경조건이 다소 불량한 방대한 면적의 아직 개발되지 않은 3,000만 ha가 넘는 일반초지가 있다. 캐나다는 약 1,240만우의 육우와 약 150만두 의 젖소를 가지고 있다.캐나다 남부지역에서는 짧은 생육기간이 초지농업을 제한한다. 겨울은 길며, 대부분 지역은 저온, 결벙, 해벙 및 질병 등으로 사초의 월동은 큰 피해를 입고 있다 따라서 적응력 높은 품종의 개발은 양호한 초생유지를 위해 펼수적이며, 특히 생육기간이 짧은 불량 환경지대에서 그러하다. 건물생산은 초여름의 높은 생육에 비해 늦여름과 가을의 낮은 건물축적 양상으로 계절성을 나타낸다. 이러한 불균형적 생산형태를 극복하고 방목기간을 효과적으로 연장시키기 위해서는 혁신적인 관리 기술과 재생력이 우수한 품종개발이 필요하다. 초지의 생산성증대는 가축사육에 있어서 생산비를 절감 시키고 경쟁력을 갖추기 위한 중요한 부문을 차지한다. 유용한 기술의 적용은 초지의 생산성을 증진시키고 사내에서의 저장사료 사양의존도를 낮추며 소규모 농가들을 경제적으로 유리하게 해준다. 수확과 저장 및 사양과정에서 영양분 손실의 방지는 생산효율을 높이는데 펼수적이다. 사일리지 조제시에 도 생산비 절감과 생력관리기숭 개발은 조사료 위주 낙농엽의 생산효율을 높이고 순수익을 높이는데 큰 역할을 하고 있다. 축산업은 저지방이나 저콜레스테롤 식풍 같은 소비자의 가호성을 충족시키는 데에 지속적인 관심을 기울여야 하며, 연구와 교육 및 농민지도에 있어서 많은 어려움은 있으나 협력과 공동연구를 확대시켜 조사료 위주의 축산업을 발전시켜야 한다

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