• 제목/요약/키워드: Proliferation resistance

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Emerging Roles of Krüppel-Like Factor 4 in Cancer and Cancer Stem Cells

  • Ding, Bo;Liu, Ping;Liu, Wen;Sun, Ping;Wang, Chun-Ling
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권9호
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    • pp.3629-3633
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    • 2015
  • Cancer stem cells (CSCs) are rare subpopulations within tumors which are recognized as culprits in cancer recurrence, drug resistance and metastasis. However, the molecular mechanisms of how CSCs are regulated remain elusive. Kr$\ddot{u}$ppel-like factors (KLFs) are evolutionarily conserved zinc finger-containing transcription factors with diverse functions in cell differentiation, proliferation, embryogenesis and pluripotency. Recent progress has highlighted the significance of KLFs, especially KLF4, in cancer and CSCs. Therefore, for better therapeutics of cancer disease, it is crucial to develop a deeper understanding of the mechanisms of how KLF4 regulate CSC functions. Herein we summarized the current understanding of the transcriptional regulation of K LF4 in CSCs, and discussed the functional implications of targeting CSCs for potential cancer therapeutics.

균일한 전단응력에 의한 혈관내피세포의 운동성 변화 (EFFECTS OF UNIFORM SHEAR STRESS ON THE MIGRATION OF VASCULAR ENDOTHELIAL CELL)

  • 신현정;송석현
    • 대한기계학회:학술대회논문집
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    • 대한기계학회 2008년도 추계학술대회A
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    • pp.1404-1408
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    • 2008
  • The migration and proliferation of vascular endothelial cells (VEC), which play an important role in vascular remodeling, are known to be regulated by hemodynamic forces in the blood vessels. When shear stresses of 2, 6, 15 dynes/$cm^2$ are applied on mouse micro-VEC in vitro, cells surprisingly migrate against the flow direction at all conditions. While higher flow rate imposes more resistance against the cells, reducing their migration speed, the horizontal component of the velocity parallel to the flow increases with the flow rate, indicating the higher alignment of cells in the direction parallel to the flow at a higher shear stress. In addition, cells exhibit substrate stiffness and calcium dependent migration behavior, which can be explained by polarized remodeling in the mechanosensitive pathway under shear stress.

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원자력 이용개발에서의 기술혁신의 정책방향 고찰

  • 양맹호
    • 한국기술혁신학회:학술대회논문집
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    • 한국기술혁신학회 2001년도 춘계학술대회:발표자료
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    • pp.531-544
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    • 2001
  • The use and development of nuclear energy has a long history more than 5o years and is facing a rapid changing environment in technological innovations in order to meet the requirements of energy supply, environmental conservation and social and political demands. The innovation of nuclear technologies are also necessary continuously in order to contribute for the progress of national economy and industry development, improvement of public health, progress of nation science and technology and furthermore is very important for the survival of nuclear industry and strengthening of competition of nuclear technologies. Major directions of the innovation of nuclear technologies would be the enhance ment of safety and economy of the use of nuclear energy, securing od nuclear proliferation-resistance, safe management of radioactive wastes, technology development for newly emerging markets and improvement of public health.

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The Role of Hippo Pathway in Cancer Stem Cell Biology

  • Park, Jae Hyung;Shin, Ji Eun;Park, Hyun Woo
    • Molecules and Cells
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    • 제41권2호
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    • pp.83-92
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    • 2018
  • The biological significance and deregulation of the Hippo pathway during organ growth and tumorigenesis have received a surge of interest in the past decade. The Hippo pathway core kinases, MST1/2 and LATS1/2, are tumor suppressors that inhibit the oncogenic nuclear function of YAP/TAZ and TEAD. In addition to earlier studies that highlight the role of Hippo pathway in organ size control, cell proliferation, and tumor development, recent evidence demonstrates its critical role in cancer stem cell biology, including EMT, drug resistance, and self-renewal. Here we provide a brief overview of the regulatory mechanisms of the Hippo pathway, its role in cancer stem cell biology, and promising therapeutic interventions.

Cloning and Characterization of Directly Amplified Antiviral Gene Interferon Alpha-2b (HulFN$\{alpha}$-2b) from Human Leukocytes Chromosomal DNA

  • Behravan, Javad;Ahmadpour, Hassan
    • Archives of Pharmacal Research
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    • 제27권7호
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    • pp.776-780
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    • 2004
  • Interferons are cytokines that confer resistance to viral infection and inhibit cellular proliferation. The interferon alpha gene from human blood samples was amplified, cloned and expressed in E. coli (BL21). Leukocyte chromosomal DNA was used as a source of template DNA. Using specific primers, the gene for HulFN$\{alpha}$-2b was amplified and inserted into the E. coli vector, pET21b, by ligation of the HindIII and BamHI linkers of the vector and insert. The insert was further analyzed by PCR, DNA restriction mapping and sequencing, and expressed in a suitable E. coli strain. The production of this important cellular protein in the laboratory has significant applications in production of the recombinant pharmaceutical proteins.

Antibacterial compounds in green microalgae from extreme environments: a review

  • Little, Shannon M.;Senhorinho, Gerusa N.A.;Saleh, Mazen;Basiliko, Nathan;Scott, John A.
    • ALGAE
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    • 제36권1호
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    • pp.61-72
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    • 2021
  • Increased proliferation of bacterial resistance to antibiotics is a critical issue that has increased the demand for novel antibacterial compounds. Antibacterial activities have been evaluated in extracts from photosynthetic green microalgae, with varying levels of subsequent potential for development based on the strain of algae, strain of bacterial pathogen, and solvent used to extract the metabolites. Green microalgae from extreme environmental conditions have had to adapt to conditions that exclude many other organisms. The production of antibacterial compounds aids directly or indirectly in the survival of green microalgae in these extreme environments, as well as potentially serve other roles. This review investigates antibacterial activities of green microalgae from both extreme in-situ environmental conditions and induced extreme laboratory conditions and highlights.

Identification of inhibitors against ROS1 targeting NSCLC by In- Silico approach

  • Bavya, Chandrasekhar
    • 통합자연과학논문집
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    • 제15권4호
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    • pp.171-177
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    • 2022
  • ROS1 (c-ros oncogene) is one of the gene with mutation in NSCLC (non-small cell lung cancer). The increased expression of ROS1 is leading to the increase proliferation of cell, cell migration and survival. Crizotinib and Entrectinib are the drugs that have been approved by FDA against ROS1 protein, but recently patients started to develop resistance against Crizotinib and there is a need of new drug that could act as an effective drug against ROS1 for NSCLC. In this study, we have performed virtual screening, where compounds are taken from Zinc 15 dataset and molecular docking was performed. The top compounds were taken based upon their binding affinity and their interactions with the residues. The compounds stability and chemical reactivity was also studied through Density Functional theory and their properties. Further study of these compounds could reveal the required information of ROS1-inhibitor complex and in the discovery of potent inhibitors.

레스베라트롤에 의한 인간 암세포주, A549와 SKOV3의 p53의존적 Apoptosis 유발 (Induction of p53-dependent Apoptosis by Resveratrol in Human Cancer Cells, A549 and SKOV3)

  • 이슬기;남주옥
    • 한국미생물·생명공학회지
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    • 제44권2호
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    • pp.194-200
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    • 2016
  • Resveratrol은 포도, 오디, 땅콩과 같은 많은 과일과 채소에 존재하는 폴리페놀 화합물로써 다양한 생물학적 효과를 가진다고 보고되어있다. 그러나, resveratrol이 A549 폐암세포에서 유도하는 apoptosis에 관여하는 분자적 기전 및 anoikis에 관해서는 명백하게 밝혀지지 않았다. 본 연구에서, 우리는 정상적인 p53 유전자를 갖는 A549 세포에서 resveratrol의 효과를 조사하고, p53 유전자가 결실된 SKOV3 난소암 세포와 그 효과를 비교했다. Resveratrol은 확실하게 SKOV3 세포에 비해 농도, 시간의존적으로 A549 세포의 생존과 증식을 억제했다. 또한 resveratrol은 A549 세포의 apoptosis를 유도했지만 세포의 anoikis 저항성에는 영향을 미치지 않았다. 더불어, p53 유전자 기능이 불완전 소실된(knock-down) A549 세포의 생존과 증식은 resveratrol에 의해 변하지 않았다. 그러므로, 본 연구의 결과는 resveratrol의 항암 효과가 기능을 하는 p53 유전자의 존재에 의존한다는 것을 보여준다. 결론적으로, 우리는 resveratrol이 p53 유전자에 의존적으로 A549 세포에 대해 항암효과를 가진다는 것을 입증했다.

크롬에 의해 유발된 백서 임파구 DNA-Protein Crosslinks의 복구 (Repair of Chromate induced DNA-Protein Crosslinks in Rat Lymphocyte)

  • 이훈재;이관희;홍윤철
    • Journal of Preventive Medicine and Public Health
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    • 제29권3호
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    • pp.597-607
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    • 1996
  • Genotoxic agents can induce various DNA lesions. DNA-Protein Crosslinks(DPCs) were known as the important DNA lesions which could impair gene expression because DPCs had a high probability of resisting repair and persisting through cell cycle. This repair resistance of DPCs could have biological significance but had not been evaluated clearly yet. Most of the studies that have evaluated the repair of DPCs only compared the extent of DPCs repair with other DNA lesions. We injected $K_2CrO_4$, a genotoxic agent, into Sprague-Dawley rats intraperitoneally(5mg/kg) and isolated blood lymphocytes 12 hours later. These lymphocytes were cultured in the mitogen added growth media and mitogen free media separately. The degree of the repair of DPCs was monitored for 4 days by the K-SDS assay. 4 days later, the amount of DPCs decreased by 4.6% in the mitogen added media high increased by 10.9% in the mitogen free media. These results showed that DPCs induced by $K_2CrO_4$ were not repaired easily and the DPCs were biologically significant DNA lesions. We thought the decrease of DPCs in the mitogen added media was not due to the repair of DPCs, but from the increase of normal cell proliferation. Therefore, it is very important to consider the proliferation of normal cells when estimating the repair of DPCs.

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Enhanced Sensitivity to Gefitinib after Radiation in Non-Small Cell Lung Cancer Cells

  • Choi, Yun-Jung;Rho, Jin-Kyung;Back, Dae-Hyun;Kim, Hye-Ryoun;Lee, Jae-Cheol;Kim, Cheol-Hyeon
    • Tuberculosis and Respiratory Diseases
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    • 제71권4호
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    • pp.259-265
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    • 2011
  • Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, are effective therapies for non-small cell lung cancer (NSCLC) patients whose tumors harbor somatic mutations in EGFR. The mutations are, however, only found in about 30% of Asian NSCLC patients and all patients ultimately develop resistance to these agents. Ionizing radiation has been shown to induce autophosphorylation of EGFR and activate its downstream signaling pathways. In the present study, we have tested whether the effect of gefitinib treatment can be enhanced after ionizing radiation. Methods: We compared the PC-9 and A549 cell line with its radiation-resistant derivatives after gefitinib treatment with cell proliferation and apoptosis assay. We also analyzed the effect of gefitinib after ionizing radiation in PC-9, A549, and NCI-H460 cells. Cell proliferation was determined by MTT assay and induction of apoptosis was evaluated by flow cytometry. Caspase 3 activation and PARP cleavage were evaluated by western blot analysis. Results: PC-9 cells having mutated EGFR and their radiation-resistant cells showed no significant difference in cell viability. However, radiation-resistant A549 cells were more sensitive to gefitinib than were their parental cells. This was attributable to an increased induction of apoptosis. Gefitinib-induced apoptosis increased significantly after radiation in cells with wild type EGFR including A549 and NCI-H460, but not in PC-9 cells with mutated EGFR. Caspase 3 activation and PARP cleavage accompanied these findings. Conclusion: The data suggest that gefitinib-induced apoptosis could increase after radiation in cells with wild type EGFR, but not in cells with mutated EGFR.