• Journal of Microbiology and Biotechnology
• /
• v.11 no.5
• /
• pp.727-738
• /
• 2001

Macrophagal polykaryocytes (MPs) are terminally differentiated multinuclear macrophage cells responsible for remodeling and resorption of bone, foreign body, and tissue deposition in inflammation. MPs are encountered only in bone and cartilagenous tissues, in which they are referred to as osteoclasts, odontoclasts, in which they are referred to as osteoclasts, odontoclasts, and septoclasts. Depending on the disease, the MPs differentiate into many morphological variants that include foreign-body giant cells, Langhans-type cells, and Touton-type cells. Morphological heterogeneity of MPs could Touton-type cells. Morphological heterogeneity of MPs could reflect the giant cell formation from phenotypically different marophage precursors by the process of fusion. At present, many cytokines, adhesion/fusion molecules, and other factors of the microenvironment have been discovered that influence the multinucleation process. Many evidences suggest that conditions in giant cell fibrohistiocytomas, which facilitate MP formation, are similar to the inflammation site of granulomatosis. MPs in the giant cell tumors and granulomatosis foci are formed in response to the factors secreted by mesenchymal cells. It is proposed that one of the first steps in vertebrate evolution could be the organization of skeleton remodeling, in which osteoclasts play a major role. In this step, the same mechanism of regulations served as a basis for the development of both osteoclast and inflammatory forms of MPs.

• Korean Business Review
• /
• v.3
• /
• pp.47-75
• /
• 1990

This study focuses on the ecological and environmental approach for marketing in the attempt to harmonize the objectives and resources of the organizations with the changing environment. This study presents the deductive and nomative method for analyzing recurrent marketing problem and contains seven chapters. The marketing environment is the place the company must start in searching for oportunities and in monitoring threats. It consists of all the actors and forces that affect the company's ability to transact can be divided into two componets-The marketing environment comperies a microenvironment consists of the actors in the company's immediate environment that affect its ability to serve its customers, namely, the company, market channal firms, customers, competitors and publics, the macroenvironment consists of the larger societal forces that affect all the actors in the macroenvironment, nanly, the demographic, economic, natural, technological and cultural forces. Most marketing executives took the phyisical environment for granted. Few consistered it one of the most dynamic elements in the totoal environment of business. However, two development have brought the physical environment to the forefront of business decision. The first has been labeled the ecological crisis-the polution and deterioration of air, water and land, the second is the accelerated depletion of the earth's natural resources. Currently, most product are designed to obtain an optimum combination of customer acceptances and production and distribution efficiencies. If we look to the future, products increasingly will be planned to obtain an optimum combination of market acceptance increasingly, efficiency and environmental protection. The entire ecological cycle of product will have to be considered.

• KSBB Journal
• /
• v.11 no.5
• /
• pp.511-517
• /
• 1996

An amphiphilic phase enzyme reaction was used to synthesize alkyl glucosides from glucose and alkyl alcohol with immobilized ${\beta}$-glucosidase using four glycol ether cosolvents(monoglyme, diglyme, 2-methoxyethanol, and 1,4-dioxane). Monoglyme was shown to be the best cosolvent for the amphiphilic phase medium composed of water/cosolvent/alkyl alcohol admixture. To obtain high yield of alkyl glucoside by amphiphilic phase enzyme reaction, hydrophilicity-hydrophobicity of amphiphilic media and enzyme microenvironment was optimized from the viewpoints of substrate solubility, enzyme activity, water activity, and dynamic equilibrium between glucose alcoholysis and glucoside hydrolysis. Under optimum reaction conditions, the highest concentrations of hexyl, octyl, decyl, and dodecyl glucosides were 18.2, 9.68, 7.27, and 6.03g/L, respectively.

• The Korean Journal of Physiology and Pharmacology
• /
• v.14 no.5
• /
• pp.331-336
• /
• 2010

In rapidly growing tumors, hypoxia commonly develops due to the imbalance between $O_2$ consumption and supply. Hypoxia Inducible Factor (HIF)-$1{\alpha}$ is a transcription factor responsible for tumor growth and angiogenesis in the hypoxic microenvironment; thus, its inhibition is regarded as a promising strategy for cancer therapy. Given that CamKII or PARP inhibitors are emerging anticancer agents, we investigated if they have the potential to be developed as new HIF-$1{\alpha}$-targeting drugs. When treating various cancer cells with the inhibitors, we found that a CamKII inhibitor, KN-62, effectively suppressed HIF-$1{\alpha}$ specifically in hepatoma cells. To examine the effect of KN-62 on HIF-$1{\alpha}$-driven gene expression, we analyzed the EPO-enhancer reporter activity and mRNA levels of HIF-$1{\alpha}$ downstream genes, such as EPO, LOX and CA9. Both the reporter activity and the mRNA expression were repressed by KN-62. We also found that KN-62 suppressed HIF-$1{\alpha}$ by impairing synthesis of HIF-$1{\alpha}$ protein. Based on these results, we propose that KN-62 is a candidate as a HIF-$1{\alpha}$-targeting anticancer agent.

• Molecules and Cells
• /
• v.37 no.9
• /
• pp.637-643
• /
• 2014

Wound healing is a complex multi-step process that requires spatial and temporal orchestration of cellular and non-cellular components. Hypoxia is one of the prominent microenvironmental factors in tissue injury and wound healing. Hypoxic responses, mainly mediated by a master transcription factor of oxygen homeostasis, hypoxia-inducible factor-1 (HIF-1), have been shown to be critically involved in virtually all processes of wound healing and remodeling. Yet, mechanisms underlying hypoxic regulation of wound healing are still poorly understood. Better understanding of how the wound healing process is regulated by the hypoxic microenvironment and HIF-1 signaling pathway will provide insight into the development of a novel therapeutic strategy for impaired wound healing conditions such as diabetic wound and fibrosis. In this review, we will discuss recent studies illuminating the roles of HIF-1 in physiologic and pathologic wound repair and further, the therapeutic potentials of HIF-1 stabilization or inhibition.

• Journal of Pharmaceutical Investigation
• /
• v.36 no.4
• /
• pp.231-237
• /
• 2006

Hypoxia in solid tumors is known to contribute to intrinsic chemoresistance. Histocultures are in vitro 3 dimensional cultures of tumor tissues and maintain the characteristic microenvironment of human solid tumors in vivo including hypoxia and multicellular structure. In this study, we evaluated the pharmacodynamics of tirapazamine(TPZ), a hypoxia-selective cytotoxin, in human non small cell lung cancer(NSCLC) cells grown as monolayers and histocultures. Antiproliferative activity of TPZ was determined after various conditions of drug exposure, and cell cycle arrest and apoptosis were also measured using flow cytometry. In monolayers, hypoxia selectivity measured by hypoxic/normoxic cytotoxicity ratio was increased with longer exposure. Lower cytotoxicity of TPZ was observed in histocultures compared to monolayers, however, a similar level of cytotoxicity was obtained with longer exposure of 96 hr. TPZ induced $G_2/M$ arrest and apoptosis in both culture conditions, which were greatly enhanced under hypoxic condition. Our data clearly showed the different pharmacodynamics of TPZ in monolayers and histocultures. Antiproliferative activity of TPZ against human solid tumors can be improved with longer drug exposure by exploiting drug delivery systems or by combining angiogenesis inhibitors to maintain drug concentration in tumor tissues.

• Bulletin of the Korean Chemical Society
• /
• v.25 no.12
• /
• pp.1917-1923
• /
• 2004

Although the proteolytic activity of the Cu(II) complex of cyclen (Cyc) is greatly enhanced upon attachment to a cross-linked polystyrene (PS), the Cu(II)Cyc-containing PS derivatives reported previously hydrolyzed only a very limited number of proteins. The PS-based artificial metalloproteases can overcome thermal, mechanical, and chemical instabilities of natural proteases, but the narrow substrate selectivity of the artificial metalloproteases limits their industrial application. In the present study, artificial metalloproteases exhibiting broad substrate selectivity were synthesized by attaching Cu(II)Cyc to a PS derivative using linkers with various structures in an attempt to facilitate the interaction of various protein substrates with the PS surface. The new artificial metalloproteases hydrolyzed all of the four protein substrates (albumin, myoglobin, ${\gamma}$-globulin, and lysozyme) examined, manifesting $k_{cat}/K_m$ values of 28-1500 $h_{-1}M_{-1}$ at 50 $^{\circ}C$. The improvement in substrate selectivity is attributed to steric and/or polar interaction between the bound protein and the PS surface as well as the hydrophobicity of the microenvironment of the catalytic centers.

• BMB Reports
• /
• v.49 no.1
• /
• pp.11-17
• /
• 2016

The gastrointestinal tract forms the largest surface in our body with constantly being exposed to various antigens, which provides unique microenvironment for the immune system in the intestine. Accordingly, the gut epithelium harbors the most T lymphocytes in the body as intraepithelial lymphocytes (IELs), which are phenotypically and functionally heterogeneous populations, distinct from the conventional mature T cells in the periphery. IELs arise either from pre-committed thymic precursors (natural IELs) or from conventional CD4 or CD8αβ T cells in response to peripheral antigens (induced IELs), both of which commonly express CD8α homodimers (CD8αα). Although lineage commitment to either conventional CD4 T helper (Th) or cytotoxic CD8αβ T cells as well as their respective co-receptor expression are mutually exclusive and irreversible process, CD4 T cells can be redirected to the CD8 IELs with high cytolytic activity upon migration to the gut epithelium. Recent reports show that master transcription factors for CD4 and CD8 T cells, ThPOK (Th-inducing BTB/POZ-Kruppel-like factor) and Runx3 (Runt related transcription factor 3), respectively, are the key regulators for re-programming of CD4 T cells to CD8 lineage in the intestinal epithelium. This review will focus on the unique differentiation process of IELs, particularly lineage re-commitment of CD4 IELs. [BMB Reports 2016; 49(1): 11-17]

• BMB Reports
• /
• v.48 no.10
• /
• pp.549-558
• /
• 2015

Cellular senescence is a process by which cells enter a state of permanent cell cycle arrest. It is commonly believed to underlie organismal aging and age-associated diseases. However, the mechanism by which cellular senescence contributes to aging and age-associated pathologies remains unclear. Recent studies showed that senescent cells exert detrimental effects on the tissue microenvironment, generating pathological facilitators or aggravators. The most significant environmental effector resulting from senescent cells is the senescence-associated secretory phenotype (SASP), which is constituted by a strikingly increased expression and secretion of diverse pro-inflammatory cytokines. Careful investigation into the components of SASPs and their mechanism of action, may improve our understanding of the pathological backgrounds of age-associated diseases. In this review, we focus on the differential expression of SASP-related genes, in addition to SASP components, during the progress of senescence. We also provide a perspective on the possible action mechanisms of SASP components, and potential contributions of SASP-expressing senescent cells, to age-associated pathologies.

• BMB Reports
• /
• v.51 no.4
• /
• pp.182-187
• /
• 2018

In carcinoma, cancer-associated fibroblasts participate in force-mediated extracellular matrix (ECM) remodeling, consequently leading to invasion of cancer cells. Likewise, the ECM remodeling actively occurs in glioblastoma (GBM) and the consequent microenvironmental stiffness is strongly linked to migration behavior of GBM cells. However, in GBM the stromal cells responsible for force-mediated ECM remodeling remain unidentified. We show that tumor-associated mesenchymal stem-like cells (tMSLCs) provide a proinvasive matrix condition in GBM by force-mediated ECM remodeling. Importantly, CCL2-mediated Janus kinase 1 (JAK1) activation increased phosphorylation of myosin light chain 2 in tMSLCs and led to collagen assembly and actomyosin contractility. Collectively, our findings implicate tMSLCs as stromal cells providing force-mediated proinvasive ECM remodeling in the GBM microenvironment, and reminiscent of fibroblasts in carcinoma.