• 제목/요약/키워드: pRb

검색결과 507건 처리시간 0.031초

Neuroendocrine Differentiation in Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor

  • Chang, Youjin;Kim, Seon Ye;Choi, Yun Jung;So, Kwang Sup;Rho, Jin Kyung;Kim, Woo Sung;Lee, Jae Cheol;Chung, Jin-Haeng;Choi, Chang-Min
    • Tuberculosis and Respiratory Diseases
    • /
    • 제75권3호
    • /
    • pp.95-103
    • /
    • 2013
  • Background: Small cell lung cancer (SCLC) transformation during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer has been suggested as one of possible resistance mechanisms. Methods: We evaluated whether SCLC transformation or neuroendocrine (NE) differentiation can be found in the cell line model. In addition, we also investigated its effect on responses to conventional chemotherapeutic drugs of the SCLC treatment. Results: Resistant cell lines to various kinds of EGFR-TKIs such as gefitinib, erlotinib, CL-387,785 and ZD6474 with A549, PC-9 and HCC827 lung adenocarcinoma cell lines were established. Among them, two resistant cell lines, A549/GR (resistant to gefitinib) and PC-9/ZDR (resistant to ZD6474) showed increased expressions of CD56 while increased synaptophysin, Rb, p16 and poly(ADP-ribose) polymerase were found only in A549/GR in western blotting, suggesting that NE differentiation occurred in A549/GR. A549/GR cells were more sensitive to etoposide and cisplatin, chemotherapeutic drugs for SCLC, compared to parental cells. Treatment with cAMP and IBMX induced synaptophysin and chromogranin A expression in A549 cells, which also made them more sensitive to etoposide and cisplatin than parental cells. Furthermore, we found a tissue sample from a patient which showed increased expressions of CD56 and synaptophysin after development of resistance to erlotinib. Conclusion: NE differentiation can occur during acquisition of resistance to EGFR-TKI, leading to increased chemosensitivity.

천정 거치형 디지털 사이니지 회전 시스템의 BLDC모터 가속수명시험에 관한 연구 (A Study on the Accelerated Life Test of BLDC Motor in Ceiling Mounted Digital Signage Rotating System)

  • 김기홍;권순홍;권순구;박종민;김종순;정성원;최원식
    • 한국산업융합학회 논문집
    • /
    • 제21권3호
    • /
    • pp.141-147
    • /
    • 2018
  • In a time when product development cycles are getting shorter and shorter, many companies are making efforts to develop products with high reliability in a short period of time, accelerated life test is widely used as a method to quickly evaluate reliability. Accelerated life test reduces the test life or the life of the product from the observed data by shortening the lifetime of the product or abruptly lowering the performance under the worse condition than the actual condition in order to shorten the test cost or the test time. In this paper, BL3640A-06P+RB35, DC12V model, which is used in the support device of an automatic rotation type digital signage, which display various information such as textures and images on a display screen in a public place or a commercial space, BLDC motors were subjected to a constant stress test and at the rotational speed of 1rpm, $180^{\circ}$ rotation and reverse rotation under actual use conditions, the stress was imposed on the rotating speed of 2rpm and the weight of the actual installed product from 22.2kgf to 10kgf were installed. The lifetime of the actual use environment condition is 23,545 hours and the rotation speed is accelerated. The life time of the acceleration condition with the additional weight is 1,380 hours. The acceleration factor is calculated as 17.06, the one year guarantee test day is 235 days to 14 days, of the period from 470 days to 28 days, and the third year from 704 days to 42 days. The test date of the BLDC motor was tested on the shortened test date, and the rotational speed and the current value were measured. It is found that there is no defect even if it operates as the test date corresponding to the specified one year warranty period and the 3 year accelerated life test which is experimented. Using the statistical technique of the regression analysis the expected time for the motor to defect to #4 samples was 20 years.

신경세포 분화에서 세포주기 조절인자로서의 NELL2 유전자의 역할 (NELL2 gene as regulator of cell cycle in neuron differentiation)

  • 정미림;오연미;박우생;박상규
    • Clinical and Experimental Pediatrics
    • /
    • 제49권10호
    • /
    • pp.1100-1105
    • /
    • 2006
  • 목 적 : 신경세포 분화에 있어 NELL2가 세포 주기와 세포자 멸사에 어떤 영향을 미치는지를 규명하고자 하였다. 방 법 : HiB5 세포에 NELL2를 전달감염시켜 배양하여 세포수를 측정하였다. 세포자멸사를 분석하기 위해 DNA 분절검사를 시행하였으며 PI염색으로 DNA양을 측정하였다. 세포주기의 조절에 관여하는 단백질에 대한 NELL2의 효과를 측정하기 위하여 Western blot과 면역염색을 시행하였다. 결 과 : NELL2를 전달감염시킨 군에서 세포수가 의미가 있게 적었고 DNA 분절검사에서 세포자멸사를 확인하였으며 $G_1$ 정지가 증가하였다. Western blot과 면역염색결과 Rb단백, p53, E2F1(KH-95)이 NELL2를 전달감염시킨 군에서 증가하고 cyclin D가 NELL2를 전달감염시킨 군에서 감소하였다. 결 론 : HiB5 세포에서 NELL2에 의하여 일정 수준에서의 세포자멸사가 동반되고 세포 주기에 있어 $G_1$기의 정지가 일어나며 세포주기를 조절하는 단백질의 변화가 발생함을 확인하였다. 따라서 NELL2가 뇌에서 신경세포 분화에 중요한 역할을 할 걸로 생각된다.

Effect of bFGF and fibroblasts combined with hyaluronic acid-based hydrogels on soft tissue augmentation: an experimental study in rats

  • Lee, Su Yeon;Park, Yongdoo;Hwang, Soon Jung
    • Maxillofacial Plastic and Reconstructive Surgery
    • /
    • 제41권
    • /
    • pp.47.1-47.10
    • /
    • 2019
  • Background: Hyaluronic acid (HA) has been applied as a primary biomaterial for temporary soft tissue augmentation and as a carrier for cells and the delivery of growth factors to promote tissue regeneration. Although HA derivatives are the most versatile soft tissue fillers on the market, they are resorbed early, within 3 to 12 months. To overcome their short duration, they can be combined with cells or growth factors. The purpose of this study was to investigate the stimulating effects of human fibroblasts and basic fibroblast growth factors (bFGF) on collagen synthesis during soft tissue augmentation by HA hydrogels and to compare these with the effects of a commercial HA derivative (Restylane®). Methods: The hydrogel group included four conditions. The first condition consisted of hydrogel (H) alone as a negative control, and the other three conditions were bFGF-containing hydrogel (HB), human fibroblast-containing hydrogel (HF), and human fibroblast/bFGF-containing hydrogel (HBF). In the Restylane® group (HGF), the hydrogel was replaced with Restylane® (R, RB, RF, RBF). The gels were implanted subdermally into the back of each nude mouse at four separate sites. Twelve nude mice were used for the hydrogel (n = 6) and Restylane® groups (n = 6). The specimens were harvested 8 weeks after implantation and assessed histomorphometrically, and collagen synthesis was evaluated by RT-PCR. Results: The hydrogel group showed good biocompatibility with the surrounding tissues and stimulated the formation of a fibrous matrix. HBF and HF showed significantly higher soft tissue synthesis compared to H (p < 0.05), and human collagen type I was well expressed in HB, HF, and HBF; HBF showed the strongest expression. The Restylane® filler was surrounded by a fibrous capsule without any soft tissue infiltration from the neighboring tissue, and collagen synthesis within the Restylane® filler could not be observed, even though no inflammatory reactions were observed. Conclusion: This study revealed that HA-based hydrogel alone or hydrogel combined with fibroblasts and/or bFGF can be effectively used for soft tissue augmentation.

RF 반응성 스펏터링으로 제조한 $Ta_{2}O_{5}$ 막의 특성 (Characteristics of $Ta_{2}O_{5}$ Films by RF Reactive Sputtering)

  • 박욱동;금동열;김기완;최규만
    • 센서학회지
    • /
    • 제1권2호
    • /
    • pp.173-181
    • /
    • 1992
  • RP 반응성 스펏터링으로서 P형 실리콘 웨이퍼위에 $Ta_{2}O_{5}$막을 제조하였다. 시편의 구조 및 조성은 XRD와 AES로 조사하였다. 산소의 혼합비가 10%일 때 C-V 특성으로부터 구한 $Ta_{2}O_{5}$막의 비유전률은 10-12이었다. AES와 RBS로 측정한 $Ta_{2}O_{5}$막의 Ta : O의 비는 각각 1 : 2와 1 : 2.49로 나타났으며, 산소분위기에서 $700^{\circ}C$의 열처리 온도에서 결정성장이 시작되었다. 산소분위기에서 $1000^{\circ}C$로 열처리한 $Ta_{2}O_{5}$막의 비유전률값은 20.5였으며, 질소분위기에서 열처리한 경우의 비유전률값은 23으로 나타났다. 이 때 가육방전계(pseudo hexagonal ${\delta}-Ta_{2}O_{5}$)의 결정구조를 나타내었다. 시편의 ${\Delta}V_{FB}$와 누설전류밀도는 산소의 혼합비가 증가함에 따라 감소하였다. 그리고 최대절연파괴전장은 산소가 10% 혼합되었을 때 2.4MV/cm로 나타났다. 이러한 $Ta_{2}O_{5}$막은 수소이온 감지막 및 기억용소자의 게이트 절연막 등에 응용될 수 있을 것이다.

  • PDF

5,8-Dimethoxy-2-Nonylamino-Naphthalene-1,4-Dione Inhibits Vascular Smooth Muscle Cell Proliferation by Blocking Autophosphorylation of PDGF-Receptor ${\beta}$

  • Kim, Yohan;Lee, Jung-Jin;Lee, Sang-Gil;Jung, Sang-Hyuk;Han, Joo-Hui;Yang, So Young;Yun, Eunju;Song, Gyu-Yong;Myung, Chang-Seon
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제17권3호
    • /
    • pp.203-208
    • /
    • 2013
  • As the abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a critical role in the development of atherosclerosis and vascular restenosis, a candidate drug with antiproliferative properties is needed. We investigated the antiproliferative action and underlying mechanism of a newly synthesized naphthoquinone derivative, 5,8-dimethoxy-2-nonylamino-naphthalene-1,4-dione (2-nonylamino-DMNQ), using VSMCs treated with platelet-derived growth factor (PDGF). 2-Nonylamino-DMNQ inhibited proliferation and cell number of VSMCs induced by PDGF, but not epidermal growth factor (EGF), in a concentration-dependent manner without any cytotoxicity. This derivative suppressed PDGF-induced $[^3H]$-thymidine incorporation, cell cycle progression from $G_0/G_1$ to S phase, and the phosphorylation of phosphor-retinoblastoma protein (pRb) as well as the expression of cyclin E/D, cyclin-dependent kinase (CDK) 2/4, and proliferating cell nuclear antigen (PCNA). Importantly, 2-nonylamino-DMNQ inhibited the phosphorylation of PDGF receptor${\beta}$(PDGF-$R{\beta}$) enhanced by PDGF at $Tyr^{579}$, $Tyr^{716}$, $Tyr^{751}$, and $Tyr^{1021}$ residues. Subsequently, 2-nonylamino-DMNQ inhibited PDGF-induced phosphorylation of STAT3, ERK1/2, Akt, and $PLC{\gamma}1$. Therefore, our results indicate that 2-nonylamino-DMNQ inhibits PDGF-induced VSMC proliferation by blocking PDGF-$R{\beta}$ autophosphorylation, and subsequently PDGF-$R{\beta}$-mediated downstream signaling pathways.

Novosphingobium ginsenosidimutans sp. nov., with the Ability to Convert Ginsenoside

  • Kim, Jin-Kwang;He, Dan;Liu, Qing-Mei;Park, Hye-Yoon;Jung, Mi-Sun;Yoon, Min-Ho;Kim, Sun-Chang;Im, Wan-Taek
    • Journal of Microbiology and Biotechnology
    • /
    • 제23권4호
    • /
    • pp.444-450
    • /
    • 2013
  • A Gram-negative, strictly aerobic, non-motile, non-spore-forming, and rod-shaped bacterial strain designated FW-$6^T$ was isolated from a freshwater sample and its taxonomic position was investigated by using a polyphasic approach. Strain FW-$6^T$ grew optimally at $10-42^{\circ}C$ and at pH 7.0 on nutrient and R2A agar. Strain FW-$6^T$ displayed ${\beta}$-glucosidase activity that was responsible for its ability to transform ginsenoside $Rb_1$ (one of the dominant active components of ginseng) to Rd. On the basis of 16S rRNA gene sequence similarity, strain FW-$6^T$ was shown to belong to the family Sphingomonadaceae and was related to Novosphingobium aromaticivorans DSM $12444^T$ (98.1% sequence similarity) and N. subterraneum IFO $16086^T$ (98.0%). The G+C content of the genomic DNA was 64.4%. The major menaquinone was Q-10 and the major fatty acids were summed feature 7 (comprising $C_{18:1}{\omega}9c/{\omega}12t/{\omega}7c$), summed feature 4 (comprising $C_{16:1}{\omega}7c/iso-C_{15:0}2OH$), $C_{16:0}$, and $C_{14:0}$ 2OH. DNA and chemotaxonomic data supported the affiliation of strain FW-$6^T$ to the genus Novosphingobium. Strain FW-$6^T$ could be differentiated genotypically and phenotypically from the recognized species of the genus Novosphingobium. The isolate that has ginsenoside converting ability therefore represents a novel species, for which the name Novosphingobium ginsenosidimutans sp. nov. is proposed, with the type strain FW-$6^T$ (= KACC $16615^T$ = JCM $18202^T$).

호박류의 조리방법에 따른 무기질 성분의 변화 (Effect of Cooking Methods on Elemental Composition of Pumpkin (Cucurbitaceae spp.))

  • 홍영신;김경수
    • 한국식품영양과학회지
    • /
    • 제46권10호
    • /
    • pp.1195-1204
    • /
    • 2017
  • 본 연구는 애호박, 쥬키니, 단호박 및 늙은호박 조리방법에 따른 무기성분 변화를 확인하고자 하였다. 조리방법은 데치기, 전자레인지 및 찌기를 이용하였으며, 조리시간은 3분, 5분 및 10분으로 설정하였다. 설정된 시간에 따라 3가지 조리방법을 이용하여 조리한 후 건조하였다. 건조된 시료는 분쇄 후 microwave법을 이용하여 분해하였으며, 다량 무기성분은 ICP-OES로, 미량 무기성분은 ICP-MS를 이용하여 분석하였다. 4종의 호박에 함유된 다량 무기성분은 칼륨, 인, 칼슘, 마그네슘, 황, 철, 아연, 나트륨 순으로 확인되었으며, 미량 무기성분은 망간, 구리, 루비듐, 바륨, 니켈, 크롬, 갈륨, 코발트, 리튬, 바나듐, 셀레늄 순으로 검출되었다. 4종의 호박에 함유된 무기성분은 데치기, 전자레인지 조리 및 찌기에서 모두 감소하였으며, 데치는 조리에서 가장 많은 감소를 보였다. 조리시간에 따른 무기성분의 함량 변화는 조리시간이 증가할수록 낮은 함량을 보였으며, 5분과 10분에서 큰 차이를 확인하였다. 미량 무기성분의 함량은 조리방법과 조리시간에 따른 큰 변화를 확인할 수 없었다. 호박의 종류에 따른 무기성분의 조성은 비슷하였으며, 무기성분의 함량은 약간의 차이를 나타내었다. 애호박과 늙은호박의 무기성분은 찌는 조리법에서 높은 잔존율을 보였으며, 쥬키니와 단호박은 전자레인지 조리 시 가장 높은 잔존율을 나타내었다. 결과적으로 조리방법과 시간은 호박의 무기성분 잔존량에 영향을 주는 것으로 확인되었다.

생기액(生肌液)의 세포독성 및 자궁경부암 바이러스 (HPV 16 type) 암 유발인자 E6와 E7의 작용에 미치는 효과 (The Effects of Somatid on the Cytotoxicity of Cancer Cells and Human Papillomavirus Type 16 E6 and E7 Oncogenes)

  • 정옥;조영식;조정원;이경애;심정현;조민철;이홍수;염영일;김상범;박순희;윤도영
    • 약학회지
    • /
    • 제44권4호
    • /
    • pp.340-346
    • /
    • 2000
  • Cervical cancer is one of the leading causes of female death from cancer worldwide with about 500,000 deaths per year. A strong association between certain human papilloma viruses (HPV types 16 and 18) and cervical cancer has been well known. An extract of natural products, named as Somatid, has been used to investigate whether this agent has the ability of inhibiting the oncogenes E6 and E7 of HPV type 16. This Somatid inhibited the proliferation of human cervical cancer cell lines (C-33A, SiHa, CaSki) and HaCaT keratinocytes in a dose response manner, In vitro binding assay and ELISA showed that Somatid inhibited the in vitro biding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53. In addition, Somatid inhibited the in vitro binding of E7 and Rb which is essential tumor suppressor for the control of cell cycle. The levels of mRNA for E6 and E7 were also decreased by Somatid. Our data suggested that Somatid inhibited the oncogenecity of E6 and E7 of HPV 16 type, thus can be used as a putative anti-HPV agent for the treatment of cervical carcinomas caused by HPV.

  • PDF

삼광 금-은광산 일대의 하상퇴적물과 토양내 함유된 독성원소의 지구화학적 부화와 이동 (Geochemical Enrichment and Migration of Environmental Toxic Elements in Stream Sediments and Soils from the Samkwang Au-Ag Mine Area, Korea)

  • 이찬희;이현구;유봉철;조애란
    • 자원환경지질
    • /
    • 제31권2호
    • /
    • pp.111-125
    • /
    • 1998
  • Dispersion, migration and enrichment of environmental toxic elements from the Samkwang Au-Ag mine area were investigated based upon major, minor and rare earth element geochemistry. The Samkwang mine area composed mainly of Precambrian granitic gneiss. The mine had been mined for gold and silver, but closed in 1996. According to the X-ray powder diffraction, mineral composition of stream sediments and soils were partly variable mineralogy, which are composed of quartz, orthoclase, plagioclase, amphibole, muscovite, biotite and chlorite, respectively. Major element variations of the host granitic gneiss, stream sediments and soils of mining and non-mining drainage, indicate that those compositions are decrese $Al_2O_3$, $Fe_2O_3$, MgO, $TiO_2$, $P_2O_5$ and LOI with increasing $SiO_2$ respectively. Average compositional ranges (ppm) of minor and/or environmental toxic elements within those samples are revealed as As=<2-4500, Cd=<1-24, Cu=6-117, Sb=1-29, Pb=17-1377 and Zn=32-938, which are extremely high concentrations of sediments from the mining drainage (As=2006, Cd=l1, Cu=71, Pb=587 and Zn=481 ppm, respectively) than concentrations of the other samples and host granitic gneiss. Major elements (average enrichment index=6.53) in all samples are mostly enriched, excepting $SiO_2$, $Na_2O$ and $K_2O$, normalized by composition of host granitic gneiss. Rare earth element (average enrichment index=2.34) are enriched with the sediments from the mining drainage. Minor and/or environmental toxic elements within all samples on the basis of host rock were strongly enriched of all elements (especially As, Br, Cu, Pb and Zn), excepting Ba, Cr, Rb and Sr. Average enrichment index of trace elements in all samples is 15.55 (sediments of mining drainage=37.33). Potentially toxic elements (As, Cd, Cr, Cu, Ni, Pb, and Zn) of the samples revealed that average enrichment index is 46.10 (sediments of mining drainage=80.20, sediments of nonmining drainage=5.35, sediments of confluent drainage=20.22, subsurface soils of mining drainage=7.97 and subsurface soils of non-mining drainage=4.15). Sediments and soils of highly concentrated toxic elements are contained some pyrite, arsenopyrite, sphalerite, galena and goethite.

  • PDF