• Title/Summary/Keyword: Growth-inhibitor

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Long Term Therapeutic Plan for Patients with Non-Small Cell Lung Cancer Harboring EGFR Mutation

  • Jang, Seung Hun
    • Tuberculosis and Respiratory Diseases
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    • v.76 no.1
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    • pp.8-14
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    • 2014
  • Non-small cell lung cancer harboring epidermal growth factor receptor (EGFR) sensitizing mutations has a distinct disease entity. Patients with this cancer have better prognosis, and frequently achieve long-term survival. EGFR-tyrosine kinase inhibitor (TKI) is the drug of choice for this cancer; but the disease inevitably progresses, after durable response. The tumor is a mixture of EGFR-TKI sensitive clones and resistant clones, regardless of their molecular mechanisms. EGFR-TKI sensitive clones are very susceptible to this drug, but rarely eradicated; so, withdrawal of the drug permits rapid regrowth of drug sensitive clones, possibly causing "disease flare." Re-administration or continuation of EGFR-TKI can effectively suppress the expansion of drug sensitive clones, even when the total tumor volume continuously increases. Chemotherapy can definitely prolong the survival of patients experiencing EGFR-TKI failure. Prospective clinical trials are warranted to compare efficacies of chemotherapeutic agents. A few retrospective studies suggested that a taxanebased regimen may be superior to others. Here, we reviewed therapeutic options and clinical evidence about this unique disease entity.

Isolation of Arthrospira platensis Mutants Producing High Lipid and Phycobiliproteins (지질과 phycobiliproteins 고생산성 Arthrospira platensis 변이주 분리)

  • Kim, Young-Hwa;Lee, Jae-Hwa
    • KSBB Journal
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    • v.27 no.3
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    • pp.172-176
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    • 2012
  • In this study, microalgae Arthrospira platensis (A. platensis) mutants induced by ethyl methane sulfonate (EMS) and further selection for resistance of cerulenin, a potent inhibitor of fatty acid synthase, were characterized. The mutants selected by $2{\mu}M$, $5{\mu}M$ and $10{\mu}M$ of cerulenin were designated EC2, EC5 and EC10, respectively. Under normal growth conditions, the mutants and parental strain exhibited similar growth pattern. The mutants of A. platensis showed enhanced lipid accumulation and phycobiliproteins (phycoerythrin, phycocyanin). The lipid content of mutants EC2 and EC5 was about 4.4 and 4.8-fold higher than wild type. The phycoerythrin and phycocyanin content of mutants EC2 and EC5 was increased about 1.5 and 6.9-fold and 1.4 and 3.8-fold, respectively, compared to the wild type. The chlorophyll and carotenoid content of mutants was slightly increased. The high lipid and pigment contents exhibited by A. platensis mutants would make an excellent candidate for the production of commercially interesting biologically active compounds.

Requirement of EGF Receptor Kinase for Signaling by Calcium-Induced ERK Activation and Neurite Outgrowth in PC12 Cells

  • Park, Jung-Gyu;Jo, Young-Ah;Kim, Yun-Taik;Yoo, Young-Sook
    • BMB Reports
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    • v.31 no.5
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    • pp.468-474
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    • 1998
  • Membrane depolarization in PC12 cells induces calcium influx via an L-type voltage-sensitive calcium channel (L-VSCC) and increases intracellular free calcium, which leads to tyrosine phosphorylation of epidermal growth factor (EGF) receptor and the associated adaptor protein, She. This activated EGF receptor complex then can activate mitogen-activated protein (MAP) kinase, as in nerve growth factor (NGF) receptor activation. In the present study, we investigated the role of EGF receptor in the signaling pathway initiated by membrane depolarization of PC12 cells. Prolonged membrane depolarization induced phosphorylation of extracellular signal-regulated kinase (ERK) within 1 min in undifferentiated PC12 cells. Pretreatment of PC12 cells with the calcium chelator EGTA abolished depolarization-stimulated ERK phosphorylation, but NGF-induced phosphorylation of ERK was not affected. The chronic treatment of phorbol ester, which down-regulated the activity of protein kinase C (PKC), did not affect the phosphorylation of ERK upon depolarization. In the presence of an inhibitor of EGF receptor, neither depolarization nor calcium ionophore increased the level of ERK phosphorylation. These data imply that the EGF receptor is functionally necessary to activate ERK and neurite outgrowth in response to the prolonged depolarization in PC12 cells, and also that PKC is apparently not involved in this signaling pathway.

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Effect of buprofezin on the formation and reversion of protoplast from mycelia of Pleurotus ostreatus and P. sajor-caju (Buprofezin이 느타리버섯속의 원형질체 나출 및 재생에 미치는 영향)

  • Shin, Gwan Chull;Whang, Ewi Ill;Seo, Geon Sik
    • Korean Journal of Agricultural Science
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    • v.17 no.2
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    • pp.77-81
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    • 1990
  • Effects of buprofezin, an inhibitor of chitin synthesis, on mycelial growth, protoplast formation and reversion of Pleurotus ostreatus and P. sajor-caju were investigated. The mycelial growth of Pleurotus ostreatus and P. sajor-caju was the inhibited by buprofezin treatment, and the inhibition rate was severer as the concentration of the buprofezin increased. Aerial mycelium formation was increased by buprofezin treatment, but mycelial morphology was not changed. Protoplast formation of Pleurotus ostreatus and P. sajor-caju. was significantly increased when buprofezin was added to the culture medium at the concentration of 200~500 ppm and the protoplast reversion of the mushrooms was also increased by the treatment of the buprofezin.

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Potential Interaction of Plasmodium falciparum Hsp60 and Calpain

  • Yeo, Seon-Ju;Liu, Dong-Xu;Park, Hyun
    • Parasites, Hosts and Diseases
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    • v.53 no.6
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    • pp.665-673
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    • 2015
  • After invasion of red blood cells, malaria matures within the cell by degrading hemoglobin avidly. For enormous protein breakdown in trophozoite stage, many efficient and ordered proteolysis networks have been postulated and exploited. In this study, a potential interaction of a 60-kDa Plasmodium falciparum (Pf)-heat shock protein (Hsp60) and Pf-calpain, a cysteine protease, was explored. Pf-infected RBC was isolated and the endogenous Pf-Hsp60 and Pf-calpain were determined by western blot analysis and similar antigenicity of GroEL and Pf-Hsp60 was determined with anti-Pf-Hsp60. Potential interaction of Pf-calpain and Pf-Hsp60 was determined by immunoprecipitation and immunofluorescence assay. Mizoribine, a well-known inhibitor of Hsp60, attenuated both Pf-calpain enzyme activity as well as P. falciparum growth. The presented data suggest that the Pf-Hsp60 may function on Pf-calpain in a part of networks during malaria growth.

HQSAR Study of Tricyclic Azepine Derivatives as an EGFR (Epidermal Growth Factor Receptor) Inhibitors

  • Chung, Hwan-Won;Lee, Kyu-Whan;Oh, Jung-Soo;Cho, Seung-Joo
    • Molecular & Cellular Toxicology
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    • v.3 no.3
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    • pp.159-164
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    • 2007
  • Stimulation of epidermal growth factor receptor (EGFR) is essential in signaling pathway of tumor cells. Thus, EGFR has intensely studied as an anticancer target. We developed hologram quantitative structure activity relationship (HQSAR) models for data set which consists of tricyclic azepine derivatives showing inhibitory activities for EGFR. The optimal HQSAR model was generated with fragment size of 6 to 7 while differentiating fragments having different atom and connectivity. The model showed cross-validated $q^2$ value of 0.61 and non-cross-validated $r^2$ value of 0.93. When the model was validated with an external set excluding one outlier, it gave predictive $r^2$ value of 0.43. The contribution maps generated from this model were used to interpret the atomic contribution of each atom to the overall inhibition activity. This can be used to find more efficient EGFR inhibitors.

Insulin Promotes Proliferation and Migration of Breast Cancer Cells through the Extracellular Regulated Kinase Pathway

  • Pan, Feng;Hong, Li-Quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6349-6352
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    • 2014
  • The present study was undertaken to determine the roles of insulin in the growth of transplanted breast cancer in nude mice, and the proliferation and migration of MCF-7 human breast cancer cells and assess its influence on downstream signaling pathways. In a xenograft mouse model with injection of MCF-7 human breast cancer cells, tumor size was measured every other day. The insulin level and insulin receptor (IR) were increased in the breast cancer patient tissues. Insulin injected subcutaneously around the tumor site in mice caused increase in the size and weight of tumor masses, and promoted proliferation and migration of MCF-7 cells. The effects of insulin on the increase in the proliferation and migration of MCF-7 human breast cancer cells were abolished by pretreatment with the extracellular regulated kinase (ERK) inhibitor PD98059. Insulin increased the phosphorylation of ERK in the MCF-7 cells. These results indicate that insulin promotes the growth of breast cancer in nude mice, and increases the proliferation and migration of MCF-7 human breast cancer cells via the ERK pathway.

Epidermal Growth Factor Receptor Gene Polymorphisms and Gastric Cancer in Iran

  • Abediankenari, Saeid;Jeivad, Fereshteh
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3187-3190
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    • 2013
  • Background: Epidermal growth factor receptor (EGFR) is a transmembrane receptor which contributes to many processes involved in cell survival, proliferation and inhibits apoptosis, that may lead to cancer development. Gastric cancer is one of the most common diseases of digestive system that has low 5-year-survival. The aim of this research was to determine the significance of EGFR tyrosine kinase domain gene polymorphisms in gastric cancer in Iran. Materials and Methods: In the present study, 83 patients with gastric cancer and 40 normal subjects were investigated for EGFR gene polymorphisms in exons 18-21 by PCR-SSCP. Then, DNA sequencing was conducted for different mobility shift bands. Finally the data were statistically analyzed using the chi-2 test and the SPSSver.16 program. Results: Exon 18 of EGFR gene showed three different bands in SSCP pattern and DNA sequencing displayed one mutation. SSCP pattern of Exons 19 and 21 did not show different migration bands. Exon 20 of EGFR gene revealed multiple migrate bands in SSCP pattern. DNA sequencing displayed 2 mutations in this exon: one mutation was caused amino acid change and another mutation was silent. Conclusion: It may be that EGFR tyrosine kinase gene polymorphisms differ between populations and screening could be useful in gastric cancer patients who might benefit from tyrosine kinase inhibitor therapy.

Calpeptin Prevents Malignant Pleural Mesothelioma Cell Proliferation via the Angiopoietin-1/Tie-2 System

  • Tabata, Chiharu;Tabata, Rie;Nakano, Takashi
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3405-3409
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    • 2016
  • Malignant pleural mesothelioma (MPM), an aggressive malignant tumor of mesothelial origin associated with asbestos exposure, shows a limited response to conventional chemotherapy and radiotherapy. Therefore, the overall survival of MPM patients remains very poor. Progress in the development of therapeutic strategies for MPM has been limited. We recently reported that the calpain inhibitor, calpeptin exerted inhibitory effects on pulmonary fibrosis by inhibiting the proliferation of lung fibroblasts. In the present study, we examined the preventive effects of calpeptin on the cell growth of MPM, the origin of which is mesenchymal cells, similar to lung fibroblasts. Calpeptin inhibited the proliferation of MPM cells, but not mesothelial cells. It also prevented 1) the expression of angiopoietin (Ang)-1 and Tie-2 mRNA in MPM cells, but not mesothelial cells and 2) the Ang-1-induced proliferation of MPM cells through an NF-kB dependent pathway, which may be the mechanism underlying the preventive effects of calpeptin on the growth of MPM cells. These results suggest potential clinical use of calpeptin for the treatment of MPM.

Preparation of High density YIG ferrite by conventional solid-state sintering (고상합성법에 의한 고밀토 YIG 자성체 제조)

  • Kim, Dong-Young;Jun, Dong-Suk;Lee, Hong-Yeol;Lee, Sang-Seok
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 2003.07a
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    • pp.533-536
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    • 2003
  • YIG(Yttrium Iron Garnet) is one of the most widely used ferrites for microwave telecommunication. It used as a passive devices such as isolators and circulators. In order to reduce the insertion losses of these passive devices, it is very important to reduce magnetic loss of the ferrites. In general, the magnetic losses of ferrites is closely related to the microstructure of the ceramics. In the sintering of YIG, pores are easily trapped in grains and grain boundaries. These pores cause to increase magnetic losses of the sinterted bodies. In this paper, the effect of the $SiO_2$ addition on the microstructure was discussed. Increasing the $SiO_2$ addition, the grain size was reduced, which means that added acts as a grain-growth inhibitor. During the sintering, $SiO_2$ settled down on the grain boundaries, and drag the grain growth. Therefore, there is enough time for pores to move out. The relative density of YIG sintered at $1350^{\circ}C$ with 1 mol% $SiO_2$ addition was 99.6%. $\Delta$H of these samples was under 50 Oe.

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