• Title/Summary/Keyword: Cdc2

Search Result 313, Processing Time 0.027 seconds

Anti-cancer Effect of Hematopoietic Stem Cell-derived Allogeneic-DC Vaccine in Melanoma Metastasis Model (마우스 동종 줄기세포 유래 수지상 세포를 이용한 백신의 흑색종 폐암 전이 모델에서의 항암 효과 및 기전 연구)

  • Kim, Myoung-Joo;Shon, Hye-Jin;Baek, So-Young;Lee, Kang-Eun;Lee, Young-Joon;Lee, Hyun-Ah
    • IMMUNE NETWORK
    • /
    • v.6 no.3
    • /
    • pp.154-162
    • /
    • 2006
  • Background: Dendritic cell (DC)-based cancer immunotherapy is studied for several years. However, it is mainly derived from autologous PBMC or leukapheresis from patient, which has limitations about yield and ability of DC production according to individual status. In order to solve these problems, inquiries about allogeneic DCs are performed but there are no preclinical trial answers for effect or toxicity of allogeneic DC to use for clinical trial. In this study, we compared the anti-tumor effect of allogeneic and autologous DCs from mouse bone marrow stem cells in mouse metastatic melanoma model. Methods: B16F10 melanoma cells ($5{\times}10^4$/mouse) were injected intravenously into the C57BL/6 mouse. Therapeutic DCs were differentiated from autologous (C57BL/6: CDC) or allogeneic (B6C3F1: BDC) bone marrow stem cells with GM-CSF, SCF and IL-4 for 13days and pulsed with B16F10 tumor cell lysate (Blys) for 18hrs. DC intra-peritoneal injections began on the 8th day after the tumor cell injection by twice with one week interval. Results: Anti-tumor response was observed by DC treatment without any toxicity especially in allogeneic DC treated mice (tumor burden score: $2.667{\pm}0.184,\;2.500{\pm}0.463,\;2.000{\pm}0.286,\;1.500{\pm}0.286,\;1.667 {\pm}0.297$ for saline, CDC/unpulsed-DC: U-DC, CDC/Blys-DC, BDC/U-DC and BDC/Blys-DC, respectively). IFN-${\gamma}$ secretion was significantly increased in allogeneic DC group stimulated with B16F10 cell lysate ($2,643.3{\pm}5,89.7,\;8,561.5{\pm}2,204.9.\;6,901.2{\pm}141.1pg/1{\times}10^6$ cells for saline, BDC/U-DC and BDC/Blys-DC, respectively) with increased NK cell activity. Conclusion: Conclusively, promising data was obtained that allogeneic DC can be used for DC-based cancer immunotherapy.

Hydropneumatic Modeling and Dynamic Characteristic Analysis of a Heavy Truck Semi-active Cabin Air Suspension System (대형 트럭 반능동형 캐빈 공기 현가시스템의 유공압 모델링 및 동특성 해석)

  • Lee, Kwang-Heon;Jeong, Heon-Sul
    • Transactions of the Korean Society of Automotive Engineers
    • /
    • v.19 no.2
    • /
    • pp.57-65
    • /
    • 2011
  • In this paper, a hydropneumatic modeling and dynamic analysis of a heavy truck semi-active cabin air suspension system is presented. Semi-active cabin air suspension system improves driver's ride comfort by controlling the damping characteristics in accordance with driving situation. So it can reduce vibration between truck frame and cabin. Semi-active cabin air suspension system is consist of air spring, leveling valve and CDC shock absorber, and full cabin system are mathematically modelled using AMESim software. Simulation results of components and full cabin system are compared with experimental data of components and test results of a cabin using 6 axis simulation table. It is found that the simulation results are in good agreements with test results, and the hydropneumatic model can be used well to predict dynamic characterics of heavy truck semi-active cabin air suspension system.

Post-transcriptional and post-translational regulation during mouse oocyte maturation

  • Kang, Min-Kook;Han, Seung-Jin
    • BMB Reports
    • /
    • v.44 no.3
    • /
    • pp.147-157
    • /
    • 2011
  • The meiotic process from the primordial stage to zygote in female germ cells is mainly adjusted by post-transcriptional regulation of pre-existing maternal mRNA and post-translational modification of proteins. Several key proteins such as the cell cycle regulator, Cdk1/cyclin B, are post-translationally modified for precise control of meiotic progression. The second messenger (cAMP), kinases (PKA, Akt, MAPK, Aurora A, CaMK II, etc), phosphatases (Cdc25, Cdc14), and other proteins (G-protein coupled receptor, phosphodiesterase) are directly or indirectly involved in this process. Many proteins, such as CPEB, maskin, eIF4E, eIF4G, 4E-BP, and 4E-T, post-transcriptionally regulate mRNA via binding to the cap structure at the 5' end of mRNA or its 3' untranslated region (UTR) to generate a closed-loop structure. The 3' UTR of the transcript is also implicated in post-transcriptional regulation through an association with proteins such as CPEB, CPSF, GLD-2, PARN, and Dazl to modulate poly(A) tail length. RNA interfering is a new regulatory mechanism of the amount of mRNA in the mouse oocyte. This review summarizes information about post-transcriptional and post-translational regulation during mouse oocyte meiotic maturation.

Increase of Cdk5 and p35 during Retinoic Acid-Induced Neuronal Differentiation of SK-N-BE(2)C cells

  • Lee, Jong-Hee;Kim, Kyung-Tai
    • Proceedings of the Korean Biophysical Society Conference
    • /
    • 2002.06b
    • /
    • pp.46-46
    • /
    • 2002
  • Cdk5, a neuronal Cdc2-like kinase, exhibits a variety of functions in neuronal differentiation and neurocytoskeleton dynamics as well as neuronal degeneration and cell death. However, its role in retinoic acid (RA)-induced differentiation has not been reported yet. We newly found that RA treatment of SK-N-BE(2)C, human neuroblastoma, increased expression of Cdk5 concomitantly with a neuronal specific activator, p35.(omitted)

  • PDF

Silencing of NUF2 Inhibits Tumor Growth and Induces Apoptosis in Human Hepatocellular Carcinomas

  • Liu, Qiang;Dai, She-Jiao;Li, Hong;Dong, Lei;Peng, Yu-Ping
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.20
    • /
    • pp.8623-8629
    • /
    • 2014
  • Background: As an important component of the NDC80 kinetochore complex, NUF2 is essential for kinetochore-microtubule attachment and chromosome segregation. Previous studies also suggested its involvement in development of various kinds of human cancers, however, its expression and functions in human hepatocellular carcinoma (HCC) are still unclear. Materials and Methods: In the present study, we aimed to test the hypothesis that NUF2 is aberrant in human HCCs and associated with cell growth. Results: Our results showed significantly elevated expression of NUF2 in human HCC tissues compared to adjacent normal tissues, and high expression of NUF2 in HCC cell lines. Using lentivirus-mediated silencing of NUF2 in HepG2 human HCC cells, we found that NUF2 depletion markedly suppressed proliferation and colony formation capacity in vitro, and dramatically hampered tumor growth of xenografts in vivo. Moreover, NUF2 silencing could induce cell cycle arrest and trigger cell apoptosis. Additionally, altered levels of cell cycle and apoptosis related proteins including cyclin B1, Cdc25A, Cdc2, Bad and Bax were also observed. Conclusions: In conclusion, these results demonstrate that NUF2 plays a critical role in the regulation of HCC cell proliferation and apoptosis, indicating that NUF2 may serve as a potential molecular target for therapeutic approaches.

Oocyte Maturation Process of Zebrafish (Danio rerio), an Emerging Animal Model (새로운 실험 동물 모델인 제브라피쉬(Danio rerio)의 난자 성숙 기작)

  • Han, Seung Jin
    • Journal of Life Science
    • /
    • v.25 no.10
    • /
    • pp.1184-1195
    • /
    • 2015
  • The zebrafish is an emerging vertebrate model organism in reproductive biology. The oocyte maturation of zebrafish is triggered by maturation inducing hormone (MIH, 17α,20β-Dihydroxy-4-pregnen-3-one). In almost all animals, the oocyte maturation is governed by activation of pre-MPF which consists of cyclinB and inactive Cdk1. In the oocyte of Xenopus and mice, the activity of Cdk1 is regulated in two ways, one is the interaction with cyclinB and the other is phosphorylation/dephosphorylation of T14/Y15 residues on the Cdk1 by Wee1 and Cdc25. Unlike Xenopus and mice that have a sufficient amount of pre-MPF, pre-MPF is absent in GV oocyte of most teleost including zebrafish. Therefore, the activation of MPF during zebrafish oocyte maturation might totally depend on de novo synthesis of cyclinB proteins. It is reported that the translation of maternal mRNA is regulated by combination of several RNA binding proteins such as CPEB, Dazl, Pum1/Pum2, and insulin-like growth factor2 mRNA-binding protein 3 in the zebrafish oocytes. However, the definitive mechanism of these proteins to regulate the translation of stored maternal mRNAs remains to be elucidated. Therefore, the investigation of the maturation process of the zebrafish oocyte will provide new information that can help identify the role of translational control in early vertebrate oocyte maturation.

Effect of Arresting MCF-7 Human Breast Carcinoma Cell at G2/M Phase of Trichosanthes Kirilowii (천화분이 MCF-7 유방암 세포주의 G2/M 세포주기 억제에 미치는 영향)

  • Jeong, Seung-Min;Jeong, Mi-Kyung;Ko, Seong-Gyu;Choi, You-Kyung;Park, Jong-Hyeong;Jun, Chan-Yong
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.25 no.5
    • /
    • pp.857-862
    • /
    • 2011
  • The purpose of this study is to investigate the anti-proliferative mechanism by Trichosanthes kirilowii (TCK) in MCF-7 human breast carcinoma cell. In this study, we used human breast cancer cell line, Michigan cancer foundation-7 cells (MCF-7 cells). They were co-incubated with 30~200 ${\mu}g$/ml TCK for 48 hours, and cell viability was measured by Water-soluble tetrazolium salt-1 (WST-1) assay. After MCF-7 cells were exposed to 60 ${\mu}g$/ml of TCK for 0, 3, 6, 12, 24, 48 hours, We performed flow analysis cytometry sorting(FACS) and western blot analysis. We investigated the effect of dose-dependent cell growth inhibition by TCK, which could be proved by WST-1 assay. Also, flow cytometry analysis showed that TCK increased percentage of subG1 phase and G2/M phase cell cycle. In addition, TCK induced apoptosis through the expression of caspase-9, -3 and poly(ADP-ribose) polymerase(PARP) activation. Moreover, we showed that ATM-dependent G2/M phase arrest by DNA damage and phosphorylation of chk2, cdc25C, cdc2(Tyr15). Taken together, these results suggest that by G2/M phase arrest through DNA damage and inducing of apoptosis through intrinsic pathway, TCK may have potential tumor suppressor in breast cancer.

Depletion of the Pre-RC Proteins Induces Chk1/Chk2 Independent Checkpoint Responses and Apoptotic Cell Death in HeLa Cells

  • Im, Jun-Sub;Lee, Joon-Kyu
    • Animal cells and systems
    • /
    • v.11 no.2
    • /
    • pp.129-134
    • /
    • 2007
  • The initiation of eukaryotic DNA replication requires assembly of the pre-replicative complex (Pre-RC) through the concerted action of Orc, Cdc6, Cdt1 and Mcm2-7 complex during G1 phase. The pre-RC assembly licenses individual replication origins for the initiation of DNA replication and sufficient number of the pre-RC is essential for proper progression of S phase. However, it is not well known how cells recognize the completion of the pre-RC assembly before G1-S transition. In order to understand the cellular responses to the defects in pre-RC assembly, we depleted the known components of pre-RC proteins using the small interference RNAs in HeLa cells. Although the defects of pre-RC assembly by the depletion of the pre-RC proteins such as Orc2, Cdt1, Mcm2 & Mcm10 did not elicit the activation of Chk1- or Chk2-dependent checkpoint pathways, these cells still showed significant decrease in the cellular level of Cdc25A proteins. These results suggests that a novel checkpoint pathway exist in HeLa cells, which is not dependent upon Chk1 or Chk2 proteins and play essential roles in the cellular responses to the defects in the pre-RC assembly. Also, among those four proteins tested in this study, the depletion of Mcm10 and Cdt1 proteins significantly increased the apoptotic cell death in HeLa cells, suggesting that these proteins not only play roles in the pre-RC assembly, but also are involved in the checkpoint responses to the defects in the pre-RC assembly.

Measurement of Fast Neutron Spectrum and Flux in Central Thimble of TRIGA MARK-II Reactor

  • Kim, Dong-Hoon;Kim, Hong-Sik;Yang, Jae-Choon
    • Nuclear Engineering and Technology
    • /
    • v.2 no.2
    • /
    • pp.67-72
    • /
    • 1970
  • The measurements of the fast neutron flux and its spectrum have been carried out by the threshold detectors in the central thimble of TRIGA Mark-II reactor operating at 250 KW. The following reactions have been employed for these measurements, viz : Ni$^{58}$ (n, p) Co$^{58}$$Mg^{24}$ (n, p) Na$^{24}$$Al^{27}$ (n, $\alpha$) Na$^{24}$ . From the activation data the fast neutron spectrum were calculated by CDC-3600 computer making use of two semi-empirical methods. It has been verified that the validity of assumption of a fission spectrum in the central thimble exists only above 1 to 2 Mev energy level. With this spectrum, a fast neutron flux in the range of 1 $\times$ 10$^{12}$ n/$\textrm{cm}^2$-sec above the energy of 2.6 Mev was observed in the central thimble of TRIGA MARK-II reactor.

  • PDF

Ribosomal protein S3 is phosphorylated by Cdk1/cdc2 during G2/M phase

  • Yoon, In-Soo;Chung, Ji-Hyung;Hahm, Soo-Hyun;Park, Min-Ju;Lee, You-Ri;Ko, Sung-Il;Kang, Lin-Woo;Kim, Tae-Sung;Kim, Joon;Han, Ye-Sun
    • BMB Reports
    • /
    • v.44 no.8
    • /
    • pp.529-534
    • /
    • 2011
  • Ribosomal protein S3 (rpS3) is a multifunctional protein involved in translation, DNA repair, and apoptosis. The relationship between rpS3 and cyclin-dependent kinases (Cdks) involved in cell cycle regulation is not yet known. Here, we show that rpS3 is phosphorylated by Cdk1 in G2/M phase. Co-immunoprecipitation and GST pull-down assays revealed that Cdk1 interacted with rpS3. An in vitro kinase assay showed that Cdk1 phosphorylated rpS3 protein. Phosphorylation of rpS3 increased in nocodazole-arrested mitotic cells; however, treatment with Cdk1 inhibitor or Cdk1 siRNA significantly attenuated this phosphorylation event. The phosphorylation of a mutant form of rpS3, T221A, was significantly reduced compared with wild-type rpS3. Decreased phosphorylation and nuclear accumulation of T221A was much more pronounced in G2/M phase. These results suggest that the phosphorylation of rpS3 by Cdk1 occurs at Thr221 during G2/M phase and, moreover, that this event is important for nuclear accumulation of rpS3.