• Title/Summary/Keyword: multi-cells

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The Mitochondrial Warburg Effect: A Cancer Enigma

  • Kim, Hans H.;Joo, Hyun;Kim, Tae-Ho;Kim, Eui-Yong;Park, Seok-Ju;Park, Ji-Kyoung;Kim, Han-Jip
    • Interdisciplinary Bio Central
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    • v.1 no.2
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    • pp.7.1-7.7
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    • 2009
  • "To be, or not to be?" This question is not only Hamlet's agony but also the dilemma of mitochondria in a cancer cell. Cancer cells have a high glycolysis rate even in the presence of oxygen. This feature of cancer cells is known as the Warburg effect, named for the first scientist to observe it, Otto Warburg, who assumed that because of mitochondrial malfunction, cancer cells had to depend on anaerobic glycolysis to generate ATP. It was demonstrated, however, that cancer cells with intact mitochondria also showed evidence of the Warburg effect. Thus, an alternative explanation was proposed: the Warburg effect helps cancer cells harness additional ATP to meet the high energy demand required for their extraordinary growth while providing a basic building block of metabolites for their proliferation. A third view suggests that the Warburg effect is a defense mechanism, protecting cancer cells from the higher than usual oxidative environment in which they survive. Interestingly, the latter view does not conflict with the high-energy production view, as increased glucose metabolism enables cancer cells to produce larger amounts of both antioxidants to fight oxidative stress and ATP and metabolites for growth. The combination of these two different hypotheses may explain the Warburg effect, but critical questions at the mechanistic level remain to be explored. Cancer shows complex and multi-faceted behaviors. Previously, there has been no overall plan or systematic approach to integrate and interpret the complex signaling in cancer cells. A new paradigm of collaboration and a well-designed systemic approach will supply answers to fill the gaps in current cancer knowledge and will accelerate the discovery of the connections behind the Warburg mystery. An integrated understanding of cancer complexity and tumorigenesis is necessary to expand the frontiers of cancer cell biology.

A Novel Analysis Of Amorphous/Crystalline Silicon Heterojunction Solar Cells Using Spectroscopic Ellipsometer (Spectroscopic Ellipsometer를 이용한 a-Si:H/c-Si 이종접합 태양전지 박막 분석)

  • Ji, Kwang-Sun;Eo, Young-Ju;Kim, Bum-Sung;Lee, Heon-Min;Lee, Don-Hee
    • New & Renewable Energy
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    • v.4 no.2
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    • pp.68-73
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    • 2008
  • It is very important that constitution of good hetero-junction interface with a high quality amorphous silicon thin films on very cleaned c-Si wafer for making high efficiency hetero-junction solar cells. For achieving the high efficiency solar cells, the inspection and management of c-Si wafer surface conditions are essential subjects. In this experiment, we analyzed the c-Si wafer surface very sensitively using Spectroscopic Ellipsometer for < ${\varepsilon}2$ > and u-PCD for effective carrier life time, so we accomplished < ${\varepsilon}2$ > value 43.02 at 4.25eV by optimizing the cleaning process which is representative of c-Si wafer surface conditions very well. We carried out that the deposition of high quality hydrogenated silicon amorphous thin films by RF-PECVD systems having high density and low crystallinity which are results of effective medium approximation modeling and fitting using spectroscopic ellipsometer. We reached the cell efficiency 12.67% and 14.30% on flat and textured CZ c-Si wafer each under AM1.5G irradiation, adopting the optimized cleaning and deposition conditions that we made. As a result, we confirmed that spectroscopic ellipsometry is very useful analyzing methode for hetero-junction solar cells which need to very thin and high quality multi layer structure.

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Up-regulation of HOXB cluster genes are epigenetically regulated in tamoxifen-resistant MCF7 breast cancer cells

  • Yang, Seoyeon;Lee, Ji-Yeon;Hur, Ho;Oh, Ji Hoon;Kim, Myoung Hee
    • BMB Reports
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    • v.51 no.9
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    • pp.450-455
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    • 2018
  • Tamoxifen (TAM) is commonly used to treat estrogen receptor (ER)-positive breast cancer. Despite the remarkable benefits, resistance to TAM presents a serious therapeutic challenge. Since several HOX transcription factors have been proposed as strong candidates in the development of resistance to TAM therapy in breast cancer, we generated an in vitro model of acquired TAM resistance using ER-positive MCF7 breast cancer cells (MCF7-TAMR), and analyzed the expression pattern and epigenetic states of HOX genes. HOXB cluster genes were uniquely up-regulated in MCF7-TAMR cells. Survival analysis of in slico data showed the correlation of high expression of HOXB genes with poor response to TAM in ER-positive breast cancer patients treated with TAM. Gain- and loss-of-function experiments showed that the overexpression of multi HOXB genes in MCF7 renders cancer cells more resistant to TAM, whereas the knockdown restores TAM sensitivity. Furthermore, activation of HOXB genes in MCF7-TAMR was associated with histone modifications, particularly the gain of H3K9ac. These findings imply that the activation of HOXB genes mediate the development of TAM resistance, and represent a target for development of new strategies to prevent or reverse TAM resistance.

Optimization of Expression Conditions for Soluble Protein by Using a Robotic System of Multi-culture Vessels

  • Ahn, Woo-Sung;Ahn, Ji-Young;Jung, Chan-Hun;Hwang, Kwang-Yeon;Kim, Eunice Eun-Kyeong;Kim, Joon;Im, Ha-Na;Kim, Jin-Oh;Yu, Myeong-Hee;Lee, Cheol-Ju
    • Journal of Microbiology and Biotechnology
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    • v.17 no.11
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    • pp.1868-1874
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    • 2007
  • We have developed a robotic system for an automated parallel cell cultivation process that enables screening of induction parameters for the soluble expression of recombinant protein. The system is designed for parallelized and simultaneous cultivation of up to 24 different types of cells or a single type of cell at 24 different conditions. Twenty-four culture vessels of about 200 ml are arranged in four columns${\times}$six rows. The system is equipped with four independent thermostated waterbaths, each of which accommodates six culture vessels. A two-channel liquid handler is attached in order to distribute medium from the reservoir to the culture vessels, to transfer seed or other reagents, and to take an aliquot from the growing cells. Cells in each vessel are agitated and aerated by sparging filtered air. We tested the system by growing Escherichia coli BL21(DE3) cells harboring a plasmid for a model protein, and used it in optimizing protein expression conditions by varying the induction temperature and the inducer concentration. The results revealed the usefulness of our custom-made cell cultivation robot in screening optimal conditions for the expression of soluble proteins.

A Review on Membranes and Catalysts for Anion Exchange Membrane Water Electrolysis Single Cells

  • Cho, Min Kyung;Lim, Ahyoun;Lee, So Young;Kim, Hyoung-Juhn;Yoo, Sung Jong;Sung, Yung-Eun;Park, Hyun S.;Jang, Jong Hyun
    • Journal of Electrochemical Science and Technology
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    • v.8 no.3
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    • pp.183-196
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    • 2017
  • The research efforts directed at advancing water electrolysis technology continue to intensify together with the increasing interest in hydrogen as an alternative source of energy to fossil fuels. Among the various water electrolysis systems reported to date, systems employing a solid polymer electrolyte membrane are known to display both improved safety and efficiency as a result of enhanced separation of products: hydrogen and oxygen. Conducting water electrolysis in an alkaline medium lowers the system cost by allowing non-platinum group metals to be used as catalysts for the complex multi-electron transfer reactions involved in water electrolysis, namely the hydrogen and oxygen evolution reactions (HER and OER, respectively). We briefly review the anion exchange membranes (AEMs) and electrocatalysts developed and applied thus far in alkaline AEM water electrolysis (AEMWE) devices. Testing the developed components in AEMWE cells is a key step in maximizing the device performance since cell performance depends strongly on the structure of the electrodes containing the HER and OER catalysts and the polymer membrane under specific cell operating conditions. In this review, we discuss the properties of reported AEMs that have been used to fabricate membrane-electrode assemblies for AEMWE cells, including membranes based on polysulfone, poly(2,6-dimethyl-p-phylene) oxide, polybenzimidazole, and inorganic composite materials. The activities and stabilities of tertiary metal oxides, metal carbon composites, and ultra-low Pt-loading electrodes toward OER and HER in AEMWE cells are also described.

Gilgyung-tang Inhibits the Migration and Invasion of Human Bladder Cancer 5637 Cells through the Tightening of Tight Junctions and Inhibition of Matrix Metalloproteinase Activity (길경탕의 치밀결합 강화 및 MMPs의 활성 억제를 통한 인체방광암세포의 이동성 및 침윤성의 억제)

  • Hong, Su-hyun;Choi, Yung-hyun
    • The Journal of Internal Korean Medicine
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    • v.37 no.1
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    • pp.16-25
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    • 2016
  • Objectives: Gilgyung-tang (GGT) has been used as one of the main multi-herb formulas to treat “Peo-ong” (lung abscess). In this study, we investigated the inhibitory effects of water extracts of GGT on cell migration and invasion, two critical cellular processes that are often deregulated during metastasis, in human bladder cancer 5637 cells.Methods: Effects on cell viability were quantified using an MTT assay. To analyze the anti-metastatic effects, we conducted a wound healing migration assay, an in vitro invasiveness assay, and a measurement of the transepithelial electrical resistance (TER). The expression of protein and mRNA were measured by Western blotting and real-time polymerase chain reaction (RT-PCR), respectively.Results: GGT markedly inhibited the cell motility and invasiveness of 5637 cells within the concentration range that was not cytotoxic. The inhibitory effects of GGT on cell invasiveness were associated with tightening of the tight junctions (TJs), which was demonstrated by an increase in the TER. The RT-PCR and Western blotting results indicated that GGT decreased the levels of claudin proteins. GGT also inhibited the activity and expression of matrix metalloproteinase (MMP)-2 and -9 and simultaneously increased the levels of tissue inhibitor of metalloproteinase-1 and -2.Conclusions: Our findings suggest that GGT reduces both the migration and the invasion of 5637 cells by modulating the activity of TJs and MMPs.

Expression Patterns of Cancer Stem Cell Markers During Specific Celecoxib Therapy in Multistep Rat Colon Carcinogenesis Bioassays

  • Salim, Elsayed I;Hegazi, Mona M;Kang, Jin Seok;Helmy, Hager M
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1023-1035
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    • 2016
  • The purpose of this study was to investigate the role of colon cancer stem cells (CSCs) during chemically-induced rat multi-step colon carcinogenesis with or without the treatment with a specific cyclooxygenase-2 inhibitor drug (celecoxib). Two experiments were performed, the first, a short term 12 week colon carcinogenesis bioassay in which only surrogate markers for colon cancer, aberrant crypt foci (ACF) lesions, were formed. The other experiment was a medium term colon cancer rat assay in which tumors had developed after 32 weeks. Treatment with celecoxib lowered the numbers of ACF, as well as the tumor volumes and multiplicities after 32 weeks. Immunohistochemical proliferating cell nuclear antigen (PCNA) labeling indexes LI (%) were downregulated after treatment by celecoxib. Also different cell surface antigens known to associate with CSCs such as the epithelial cell adhesion molecule (EpCAM), CD44 and CD133 were compared between the two experiments and showed differential expression patterns depending on the stage of carcinogenesis and treatment with celecoxib. Flow cytometric analysis demonstrated that the numbers of CD133 cells were increased in the colonic epithelium after 12 weeks while those of CD44 but not CD133 cells were increased after 32 weeks. Moreover, aldehyde dehydrogenase-1 activity levels in the colonic epithelium (a known CSC marker) detected by ELISA assay were found down-regulated after 12 weeks, but were up-regulated after 32 weeks. The data have also shown that the protective effect of celecoxib on these specific markers and populations of CSCs and on other molecular processes such as apoptosis targeted by this drug may vary depending on the genetic and phenotypic stages of carcinogenesis. Therefore, uncovering these distinction roles of CSCs during different phases of carcinogenesis and during specific treatment could be useful for targeted therapy.

Targeting Renal Cell Carcinoma with Gambogic Acid in Combination with Sunitinib in Vitro and in Vivo

  • Jiang, Xiao-Liang;Zhang, Yao;Luo, Chun-Li;Wu, Xiao-Hou
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6463-6468
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    • 2012
  • Purpose: To evaluated the effect of the gambogic acid (GA), one of the effective components of Garcinia, in combination with a new multi-targeted oral medication, sunitinib (SU) on renal cancer cell proliferation in vitro and on tumor growth in vivo. Methods: After treatment with GA or SU, either alone or in combination, MTT and FACS analysis were used to examine cell viability and cycle distribution of the renal carcinoma cell lines 786-0 and Caki-1. Western blotting was employed to examine the expression of proteins related to the cell cycle and vascular formation. Furthermore, a xenograft model was applied to study the antitumor efficacy of SU or GA alone or in combination, with immunohistochemistry to detect expression of proteins related to xenograft growth and angiogenesis. Western blotting was used to examine NF-${\kappa}B$ signaling pathway elements in xenografts. Results: Treatment of 786-0 and Caki-1 cells with GA or SU resulted in decreased tumor cell proliferation, especially with joint use. Cells accumulated more strongly in the sub-G1 phase after joint treatment with GA and SU than treatment of GA and SU alone. Western blotting arrays showed 1 protein significantly upregulated, 2 proteins downregulated, and 2 proteins unchanged. Moreover, combined use of GA and SU inhibited the growth and angiogenesis of xenografts generated from Caki-1 significantly. Immunohistochemistry arrays showed downregulation of the expression of proteins promoting xenograft growth and angiogenesis, and Western blotting showed inhibition of the NF-${\kappa}B$ signaling pathway after treatment by GA alone and in combination with SU in xenografts. Conclusions: Our results show that the joint use of GA and SU can provide greater antitumor efficacy compared to either drug alone and thus may offer a new treatment strategy for renal cell carcinoma.

Anticancer Effect of COX-2 Inhibitor DuP-697 Alone and in Combination with Tyrosine Kinase Inhibitor (E7080) on Colon Cancer Cell Lines

  • Altun, Ahmet;Turgut, Nergiz Hacer;Kaya, Tijen Temiz
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3113-3121
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    • 2014
  • Colorectal cancer remains one of the most common types of cancer and a leading cause of cancer death worldwide. In this study, we aimed to investigate effects of DuP-697, an irreversible selective inhibitor of COX-2 on colorectal cancer cells alone and in combination with a promising new multi-targeted kinase inhibitor E7080. The HT29 colorectal cancer cell line was used. Real time cell analysis (xCELLigence system) was conducted to determine effects on colorectal cell proliferation, angiogenesis was assessed with a chorioallantoic membrane model and apoptosis was determined with annexin V staining. We found that DuP-697 alone exerted antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. For the antiproliferative effect the half maximum inhibition concentration ($IC_{50}$) was $4.28{\times}10^{-8}mol/L$. Antiangiogenic scores were 1.2, 0.8 and 0.5 for 100, 10 and 1 nmol/L DuP-697 concentrations, respectively. We detected apoptosis in 52% of HT29 colorectal cancer cells after administration of 100 nmol/L DuP-697. Also in combination with the thyrosine kinase inhibitor E7080 strong antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells were observed. This study indicates that DuP-697 may be a promising agent in the treatment of colorectal cancer. Additionally the increased effects observed in the combination with thyrosine kinase inhibitor give the possibility to use lower doses of DuP-697 and E7080 which can avoid and/or minimize side effects.

Intracellular Electrical Stimulation on PC-12 Cells through Vertical Nanowire Electrode

  • Kim, Hyungsuk;Kim, Ilsoo;Lee, Jaehyung;Lee, Hye-young;Lee, Eungjang;Jeong, Du-Won;Kim, Ju-Jin;Choi, Heon-Jin
    • Proceedings of the Korean Vacuum Society Conference
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    • 2014.02a
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    • pp.407-407
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    • 2014
  • Nanotechnology, especially vertically grown silicon nanowires, has gotten great attentions in biology due to characteristics of one dimensional nanostructure; controllable synthetic structure such as lengths, diameters, densities. Silicon nanowires are promising materials as nanoelectrodes due to their highly complementary metal-oxide-semiconductor (CMOS) - and bio-compatibility. Silicon nanowires are so intoxicated that are effective for bio molecular delivery and electrical stimulation. Vertical nanowires with integrated Au tips were fabricated for electrical intracellular interfacing with PC-12 cells. We have made synthesized two types of nanowire devices; one is multi-nanowires electrode for bio molecular sensing and electrical stimulation, and the other is single-nanowires electrode respectively. Here, we demonstrate that differentiation of Nerve Growth Factor (NGF) treated PC-12 cells can be promoted depending on different magnitudes of electrical stimulation and density of Si NWs. It was fabricated by both bottom-up and top-down approaches using low pressure chemical vapor deposition (LPCVD) with high vacuuming environment to electrically stimulate PC-12 cells. The effects of electrical stimulation with NGF on the morphological differentiation are observed by Scanning Electron Microscopy (SEM), and it induces neural outgrowth. Moreover, the cell cytosol can be dyed selectively depending on the degree of differentiation along with fluorescence microscopy measurement. Vertically grown silicon nanowires have further expected advantages in case of single nanowire fabrication, and will be able to expand its characteristics to diverse applications.

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