• Journal of Life Science
• /
• v.27 no.2
• /
• pp.149-154
• /
• 2017

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-hodgkin lymphoma. Advances in the chemotherapeutic treatment of this disease have improved the outcomes of DLBCL; nonetheless, many patients still die of DLBCL, and therefore, a better understanding of this disease and identification of novel therapeutic targets are urgently required. In a recent gene expression profiling study, PDE (phosphodiesterase) 4B was found to be overexpressed in chemotherapy-resistant tumors. The major function of PDE4B is to inactivate the second messenger cyclic 3',5' monophosphate (cAMP) by catalyzing the hydrolysis of cAMP to 5'AMP. It is known that cAMP induces cell cycle arrest and/or apoptosis in B cells, and PDE4B abolishes cAMP's effect on B cells. However, the mechanism by which PDE4B is overexpressed remains unclear. Here, we show that the aberrant expression of miRNA may be associated with the overexpression of this gene. The PDE4B 3' untranslated region (UTR) has three functional binding sites of miR-23b, as confirmed by luciferase reporter assays. Interestingly, miR-23b-binding sites were evolutionarily conserved from humans to lizards, implying the critical role of PDE4B-miR-23b interaction in cellular physiology. The ectopic expression of miR-2 3b repressed PDE4B mRNA levels and enhanced intracellular cAMP concentrations. Additionally, miR-23b expression inhibited cell proliferation and survival of DLBCL cells only in the presence of forskolin, an activator of adenylyl cyclase, suggesting that miR-23b's effect is via the downregulation of PDE4B. These results together suggest that miR-23b could be a therapeutic target for overcoming drug resistance by repressing PDE4B in DLBCL.

• Journal of Life Science
• /
• v.27 no.11
• /
• pp.1245-1255
• /
• 2017

Most cancer cells produce ATP predominantly through glycolysis instead of through mitochondrial oxidative phosphorylation, even in the presence of oxygen. The phenomenon is termed the Warburg effect, or the glycolytic switch, and it is thought to increase the availability of biosynthetic precursors for cell proliferation. EMTs have critical roles in the initiation of the invasion and metastasis of cancer cells. The glycolytic switch and EMT are important for tumor development and progression; however, their correlation with tumor progression is largely unknown. The Snail transcription factor is a major factor involved in EMT. The Snail expression is regulated by distal-less homeobox 2 (Dlx-2), a homeodomain transcription factor that is involved in embryonic and tumor development. The Dlx-2/Snail cascade is involved in Wnt-induced EMTs and the glycolytic switch. This study showed that in response to Wnt signaling, the Dlx-2/Snail cascade induces the expression of PFKFB2, which is a glycolytic enzyme that synthesizes and degrades fructose 2, 6-bisphosphate (F2,6BP). It also showed that PFKFB2 shRNA prevents Wnt-induced EMTs in the breast-tumor cell line MCF-7. The prevention indicated that glycolysis is linked to Wnt-induced EMT. Additionally, this study showed PFKFB2 shRNA suppresses in vivo tumor metastasis and growth. Finally, it showed the PFKFB2 expression is higher in breast, colon and ovarian cancer tissues than in matched normal tissues regardless of the cancers' stages. The results demonstrated that PFKFB2 is an important regulator of EMTs and metastases induced by the Wnt, Dlx-2 and Snail factors.

• Journal of Life Science
• /
• v.23 no.5
• /
• pp.609-615
• /
• 2013

Glyceollin I has gained attention as a useful therapy for various dermatological diseases. However, the binding property of glyceollin I to the mammalian adenylyl cyclase (hereafter mAC), a critical target enzyme for the down-regulation of skin melanogenesis, has not been fully explored. To clarify the action mechanism between glyceollin I and mAC, we first investigated the molecular docking property of glyceollin I to mAC and compared with that of SQ22,536, a well-known mAC inhibitor, to mAC. Glyceollin I showed superiority by forming three hydrogen bonds with Asp 1018, Trp 1020, and Asn 1025, which exist in the catalytic site of mAC. However, SQ22,536 formed only two hydrogen bonds with Asp 1018 and Asn 1025. Secondly, we confirmed that glyceollin I effectively inhibits the formation of forskolin-induced cAMP and the phosphorylation of PKA from a cell-based assay. Long term treatment with glyceollin I had little effect on the cell viability. The findings of the present study also suggest that glyceollin I may be extended to be used as an effective inhibitor of hyperpigmentation.

• Tuberculosis and Respiratory Diseases
• /
• v.63 no.2
• /
• pp.128-138
• /
• 2007

Backgrounds: Mutations of katG and inhA (ORF and promoter) are known to be related to isoniazid (INH) resistance of Mycobacterium tuberculosis. Because reports on these mutations in Korean isolates are limited (i.e. only the frequency of katG codon 463 was evaluated.), we tried to know the kinds of mutations of two genes and their frequencies in INH resistant Korean M. tuberculosis strains. Methods: PCR was performed to amplify katG (2,223 bp), inhA ORF (-77~897, 975 bp), and inhA promoter (-168~80, 248 bp) from 29 multidrug resistant M. tuberculosis (MDR-TB) DNAs prepared by bead beater-phenol method. Their sequences were determined and analyzed by ABI PRISM 3730 XL Analyzer and MegAlign package program, respectively. Results: All of the isolates had more than one mutation in katG or inhA gene. Twenty seven (93%) of 29 tested strains had katG mutations, which suggests that katG is a critical gene determining INH resistance of M. tuberculosis. Amino acid substitutions, such as Arg463Leu and Ser315Thr, due to point mutations of the katG were the most frequent (62.1% and 55.2%) mutations. In addition, deletion of the katG gene was frequently observed (17.2%). Analyzed Korean MDR-TB isolates also had variable inhA mutations. Point mutation of inhA promoter region, such as -15 ($C{\rightarrow}T$) was frequently found. Substitution of amino acid (Lsy8Asn) due to point mutation ($AAA{\rightarrow}AAC$) of inhA ORF was found in 1 isolate. Interestingly, 14 point mutated types that were not previously reported were newly found. While four types resulted in amino acid change, the others were silent mutations. Conclusions: Although it is not clear that the relationship of these newly found mutations with INH resistance, they show marked diversity in Korean MDR-TB strains. It also suggests their feasibility as a molecular target to supplement determining the INH resistance of clinical isolates because of the possible existence of low-level INH resistant strains.

• Progress in Medical Physics
• /
• v.23 no.4
• /
• pp.219-228
• /
• 2012

The tangential breast intensity modulated radiotherapy (T-B IMRT) technique, which uses the same tangential fields as conventional 3-dimensional conformal radiotherapy (3D-CRT) plans with physical wedges, was analyzed in terms of the calculated dose distribution feature and dosimetric accuracy of beam delivery during treatment. T-B IMRT plans were prepared for 15 patients with breast cancer who were already treated with conventional 3D-CRT. The homogeneity of the dose distribution to the target volume was improved, and the dose delivered to the normal tissues and critical organs was reduced compared with that in 3D-CRT plans. Quality assurance (QA) plans with the appropriate phantoms were used to analyze the dosimetric accuracy of T-B IMRT. An ionization chamber placed at the hole of an acrylic cylindrical phantom was used for the point dose measurement, and the mean error from the calculated dose was $0.7{\pm}1.4%$. The accuracy of the dose distribution was verified with a 2D diode detector array, and the mean pass rate calculated from the gamma evaluation was $97.3{\pm}2.9%$. We confirmed the advantages of a T-B IMRT in the dose distribution and verified the dosimetric accuracy from the QA performance which should still be regarded as an important process even in the simple technique as T-B IMRT in order to maintain a good quality.

• Korean Journal of Poultry Science
• /
• v.42 no.3
• /
• pp.231-238
• /
• 2015

The present study aimed to investigate the effects of lycopene on hepatic metabolic- and immune-related gene expression in laying hens. A total of 48 25-week-old White Leghorn hens were randomly allocated into four groups consisting of four replicates of three birds: control (basal diet), T1 (basal diet + 10 mg/kg of tomato powder-containing lycopene), T2 (basal diet + 10 mg/kg of micelles of tomato powder-containing lycopene), and T3 (basal diet + 10 mg/kg of purified lycopene). Chickens were fed ad libitum for 5 weeks, and then total RNA was extracted from the livers for quantitative RT-PCR analysis. Peroxisome proliferator-activated receptor ${\gamma}$ (PPAR${\gamma}$) expression was decreased in the liver of chickens after lycopene supplementation (P<0.05). Micellar lycopene supplementation decreased the expression of PPAR${\gamma}$ target genes including fatty acid binding protein 4 (FABP4) and fatty acids synthase (FASN) in the T2 group (P<0.05). Sterol regulatory element-binding protein 2 (SREBP2) and C/EBP-${\alpha}$ were also downregulated in hens fed with micellar lycopene (P<0.05). Glucose transporter 8 (GLUT-8) was upregulated in the T2 and T3 groups (P<0.05). However, the expression of carnitine palmitoyltransferase 1 (CPT-1) was not changed by lycopene supplementation. Pro-inflammatory cytokines such as tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) and interleukin 6 (IL-6) were downregulated by lycopene supplementation (P<0.05). These data suggest that the type of lycopene supplementation is critical and that micelles of tomato powder-containing lycopene may play an important role in the modulation of lipid metabolism and immunity in chickens.

• Asia pacific journal of information systems
• /
• v.24 no.4
• /
• pp.577-610
• /
• 2014

Although service innovation is not a new concept, innovation research in general tends to focus on technological innovation by manufacturing firms. With this view, innovation studies focus on product(e.g., goods) and process(e.g., product systems) innovation, ignoring service innovation and its inherent opportunities. Since major economy has been transformed to service economy, service innovation is considered a new effective way to sustain and gain a competitive advantage. Service innovation is no longer regarded merely as a side activity to product innovation; it has become a main research topic in its own right, accompanied by an increasing focus on services. While the number of service innovation studies has increased dramatically in the past 30 years in international research, few studies have been performed in domestic studies because domestic service innovation research began from the middle of 2000. In addition, there are no comprehensive literature reviews describing the evolution of service innovation research in both international and domestic studies because of the heterogeneities of service industry and multidiscipline characteristics of service innovation studies. To bridge this research gap, the purpose of this paper is to perform an extensive literature review and synthesis to enable a critical review of extant research on service innovation and trace its evolution, which will establish a foundation for further studies. By reviewing 169 articles (136 international papers; 33 domestic papers) published between 2000 and 2014 (in past 15 years), primarily in leading service, innovation and management information systems journals, this study analyzes the progression of service innovation research according to the four aspects such as number of studies, topics, methodologies and target industries. Overall, the view of service innovation has evolved, from a complement of traditional product innovation to a multidimensional, all-encompassing concept that entails several functions, both within and outside the firms. The results showed that domestic research still stays at the formation phase of service innovation studies although international research is in the maturity or multidimensional phase. We found increasing recent activities pertaining to service innovation, resulting from the increasing interest in services innovation across various industries and the links of new topics to the service innovation concept in both international and domestic studies. However, the main focus of service innovation research showed a different propensity between international and domestic studies: the former mainly focuses on a much more diversified pattern, emphasizing the linkages between service innovation and business strategy while the latter mainly focuses on the service innovation process(system) and service design. In addition, there are many case studies in domestic studies while many empirical studies in international studies. Domestic studies should increases the understanding of the interplay between service innovation and product innovation within manufacturing firms. Furthermore, rather than focusing on intrinsic distinctions between service innovation and product innovation, researchers should strive to develop and conceptualize service innovation in domestics studies. The present research also provides useful implications for practitioners. First, this study contributes to expand the current understanding of service innovation research by performing an extensive literature review. Second, tracing and comparing the progression and trends of service innovation research between international and domestic studies, this study showed the similarities and differences between them, which provide practical guidance on future research directions and research agenda. Third, this study performed literature review establishing the analysis system in the initial stage and using them to analyze articles, which is leading to explain the research review of service innovation more systematically and objectively. Finally, this study suggests the domestic researchers their future interests and topics of service innovation research.

• Journal of Distribution Science
• /
• v.10 no.6
• /
• pp.39-53
• /
• 2012

It is widely known that knowledge management plays a facilitating role that contributes to upgrading organizational performance. Knowledge management systems (KMS), especially, support the knowledge management process including the sharing, creating, and using of knowledge within a company, and maximize the value of knowledge resources within an organization. Despite this widely held belief, there are few studies that describe how companies actually develop, share, and practice their knowledge. Companies in the domestic small franchise sector, which are in the early stages in terms of knowledge management, need to improve their KMS to manage their franchisees effectively. From this perspective, this study uses a qualitative approach to explore the actual process of knowledge management implementation. This article presents a case study of PB (Paris Baguette) company, which is the first to build a KMS in the franchise industry. The study was able to confirm the following facts through the analysis of target companies. First, the chief executive's support is a critical success factor and this support can increase the participation of organization members. Second, it is important to build a process and culture that actively creates and leverages information in knowledge management activities. The organizational learning culture should be one where the creation, learning, and sharing of new knowledge is developed continuously. Third, a horizontal network organization is needed in order to make relationships within the organization more close-knit. Fourth, in order to connect the diverse processes such as knowledge acquisition, storage, and utilization of knowledge management activities, information technology (IT) capabilities are essential. Indeed, IT can be a powerful tool for improving the quality of work and maximizing the spread and use of knowledge. However, during the construction of an intranet based KMS, research is required to ensure that the most efficient system is implemented. Finally, proper evaluation and compensation are important success factors. In order to develop knowledge workers, an appropriate program of promotion and compensation should be established. Also, building members' confidence in the benefits of knowledge management should be an ongoing activity. The company developed its original KMS to achieve a flexible and proactive organization, and a new KMS to improve organizational and personal capabilities. The PB case shows that there are differences between participants perceptions and actual performance in managing knowledge; that knowledge management is not a matter of formality but a paradigm that assures the sharing of knowledge; and that IT boosts communication skills, thus creating a mutual relationship to enhance the flow of knowledge and information between people. Knowledge management for building organizational capabilities can be successful when considering its focus and ways to increase its acceptance. This study suggests guidelines for major factors that corporate executives of domestic franchises should consider to improve knowledge management and the higher operating activities that can be used.

• The Journal of Korean Society for Radiation Therapy
• /
• v.30 no.1_2
• /
• pp.129-138
• /
• 2018

Purpose : An aim of this study was to compare the effect of multi leaf collimator(MLC) types for high dimension radiotherapy in treatment sites used clinically. Material and Method : 70 patients with lung cancer, spine cancer, prostate cancer, whole pelvis, head and neck, breast cancer were included in this study. High definition(HD) MLC of TrueBeam STx (Varian Medical system, Palo Alto, CA) and millenium(M) MLC of VitalBeam (Varian Medical system, Palo Alto, CA) were used. Radiotherapy plans were performed for each patient under same treatment goals with Eclipse (Version 13.7, Varian Palo Alto USA, CA). To compare the indicators of the radiotherapy plans, planning target volume(PTV) coverage, conformity index(CI), homogeneity index(HI), and clinical indicators for each treatment sites in normal tissues were evaluated. To evaluate low dose distribution, $V_{30%}$ values were compared according to MLC types. Additionally, length and volume of targets for each treatment sites were investigated. Result : In stereotatictic body radiotherapy(SBRT) plan for lung, the average value of PTV coverage was reduced by 0.52 % with HD MLC. With SBRT plan using HD MLC for spine, the average value of PTV coverage decreased by 0.63 % and maximum dose decreased by 1.13 %. In the test of CI and HI, the values in SBRT plan with HD MLC for spine were 1.144, 1.079 and the values using M MLC were 1.160, 1.092 in SBRT plan for lung, The dose evaluation of critical organ was reduced by 1.48 % in the ipsilateral lung mean dose with HD MLC. In prostate cancer volumetric modulated arc therapy(VMAT) with HD MLC, the mean dose and the $V_{30}$ of bladder and the mean dose and the $V_{25}$ of rectum were reduced by 0.53 %, 1.42 %, 0.97 %, and 0.69 %, respectively (p<0.05). The average value of heart mean dose was reduced by 0.83 % in breast cancer VMAT with M MLC. Other assessment indices for treatment sites showed no significant difference between treatment plans with two types of MLC. Conclusion : Using HD MLC had a positive impact on the PTV coverage and normal tissue sparing in usually short or small targets such as lung and spine SBRT and prostate VMAT. But, there was no significant difference in targets with long and large such as lung, head and neck, and whole pelvis for VMAT.

• Asia-Pacific Journal of Business Venturing and Entrepreneurship
• /
• v.17 no.2
• /
• pp.65-80
• /
• 2022

Despite the uncertainty and risky factors of startups, the special and critical role of accelerators in carrying out professional nurturing and investment for them is becoming increasingly significant in the startup social-system. However, academic research on investment determinants that have a profound impact on the survival of accelerators is lacking, and there are only a few empirical studies on the classification and importance of factors, and they do not enjoy the benefits of theoretical studies. This study proposes a business model innovation framework based on the business model innovation theory that reflects the nature and properties of startups that are investment targets of accelerators and derives 12 investment decision factors. The framework defines that the target, direction, and performable force of startup innovation are a business model, strategy, and dynamic capability. Besides, the framework analyzes the investment decision factors of the existing accelerators based on the business model innovation framework to verify the suitability and sufficiency of the composition. As a result of the analysis, first, most of the items were faithfully composed from a static point of view of business model innovation, but it was found that the factors related to the core activities to evaluate the activity and customer relationship were insufficient. Second, from the strategic point of view, the necessity of developing factors that can encompass the definition and content of core resources, which are internal strategic factors, was raised. Third, from the dynamic point of view, it was found that many of the investment determinants of accelerators were concentrated on the lower level of dynamic competencies. This can be judged as a result of reflecting the characteristics of a startup that needs to develop a solution with few resources and a small number of team members. In addition, the roles and interrelationships between each factor are not clear, thus it was found as a limiting point for startups to view and evaluate the direction and process in which startups dynamically innovate their business models. This study is considerably differentiated in that it provides a business model innovation framework and offers a theoretical basis for investment determinants by deriving the investment determinants of accelerators based on the framework and design the foundation for subsequent research. The business model innovation framework presented in this study has great implications in that it contributes to the achievement of startups, accelerators, and startup support organizations.