• Biomolecules & Therapeutics
• /
• v.32 no.5
• /
• pp.647-657
• /
• 2024

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat. This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression. Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

• Journal of Life Science
• /
• v.26 no.3
• /
• pp.376-386
• /
• 2016

Apoptosis induction has been proposed as an efficient mechanism by which malignant tumor cells can be removed following chemotherapy. The intrinsic mitochondria-dependent apoptotic pathway is frequently implicated in chemotherapy-induced tumor cell apoptosis. Since DNA-damaging agent (DDA)-induced apoptosis is mainly regulated by the tumor suppressor protein p53, and since more than half of clinical cancers possess inactive p53 mutants, microtubule-damaging agents (MDAs), of which apoptotic effect is mainly exerted via p53-independent routes, can be promising choice for cancer chemotherapy. Recently, we found that the apoptotic signaling pathway induced by MDAs (nocodazole, 17α-estradiol, or 2-methoxyestradiol) commonly proceeded through mitotic spindle defect-mediated prometaphase arrest, prolonged Cdk1 activation, and subsequent phosphorylation of Bcl-2, Mcl-1, and Bim in human acute leukemia Jurkat T cells. These microtubule damage-mediated alterations could render the cellular context susceptible to the onset of mitochondria-dependent apoptosis by triggering Bak activation, Δψm loss, and resultant caspase cascade activation. In contrast, when the MDA-induced Bak activation was inhibited by overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2 or Bcl-xL), the cells in prometaphase arrest failed to induce apoptosis, and instead underwent mitotic slippage and endoreduplication cycle, leading to formation of populations with 8N and 16N DNA content. These data indicate that cellular apoptogenic mechanism is critical for preventing polyploid formation following MDA treatment. Since the formation of polyploid cells, which are genetically unstable, may cause acquisition of therapy resistance and disease relapse, there is a growing interest in developing new combination chemotherapies to prevent polyploidization in tumors after MDA treatment.

• The korean journal of orthodontics
• /
• v.26 no.1 s.54
• /
• pp.83-94
• /
• 1996

Substance P is one of the neuropeptide which presents highly in tension site of periodontal ligament during the orthodontic tooth movement. It has bnn also hon as one of the neuropeptides which cause neurogenic inflammation in various tissues and organs. However, there is no report about the effect of substance P on major extracellular matrix protein, collagen production. The purpose of this study was to evaluate the collagen production by substance P in human periodontal ligament cell. The collagenase-digestion method was used to evaluate collagen production and also used Northern blot hybridization for the evaluation of collagen mRNA level. This study also Included in terms of prostanglandins and gelatinase production with respect to collagen production. For the collagen degradation, zymography was used to estimate denatured collagen degradation. Dose-dependent effect of substance P on noncollagen protein, collagen, and percent collagen was that substance P increased noncollagen protein synthesis, but decreased collagen sytnsis. So the percent collagen, which determined by relative collagen production against total protein production, w3s decreased from $7\%\;to\;3.6\%$. This inhibitory effect of substance P on collagen production was disappeared when cells were treated concomitantly with indomethacin. It means that substance P-induced inhibitory effect on collagen production was due at least in part to the production of prostaglandins. To evaluate whether substance P-induced inhibitory effect on collagen production is correspond to the steady-state levels of procollagen mRNA, Northern blot hybridization was performed and it showed that substance P has no effect on the steady-slate level of ${\alpha}1(I)$ procollagen mRNA. It means that the inhibitory effect of substance P on collagen production was due to the change of a certain mechanism after posttranscription. In this context, gelatinase production by substance P in periodontal ligament cells was evaluated by zymography. Zymogram showed that substance P has no effect on gelatinase production in periodontal ligament cells. To explore wheter substance P-induced inhibitory effect on collagen production is selevtive in periodontal ligament cells or not, MC3T3-E1 cells which originated from mouse calvaria was used. It showed that substance P has no effect on collagen production in MC3T3-E1 cells. Taken together, substance P inhibits collagen production in human periodontal ligament cells. This effect was not due to the change of the steady-state level of procollagen mRNA and gelatinase production, but due at least in part to the change of prostaglandins production.

• Journal of Global Scholars of Marketing Science
• /
• v.20 no.2
• /
• pp.188-198
• /
• 2010

This study attempts to examine the influence that negative WOM (NWOM) has in an online context. It specifically focuses on the impact of the service failure description and the perceived intention of the communication provider on consumer evaluations of firm competence, attitude toward the firm, positive word of mouth and behavioral intentions. Studies of communication persuasiveness focus on "who says what; to whom; in which channel; with what effect (Chiu 2007)." In this research study, we examine electronic web posting, particularly focusing on two aspects of "what": the level of service failure communicated and perceived intention of the individual posting. It stands to reason electronic NWOM that appears to be trying to damage a product’s or firm's reputation will be viewed as more biased and will thus be considered as less credible. According to attribution theory, people search for the causes of events especially those that are negative and unexpected (Weiner 2006). Hennig-Thurau and Walsh (2003) state "since the reader has only limited knowledge and trust of the author of an online articulation the quality of the contribution could be expected to serve as a potent moderator of the articulation-behavior relationship. We therefore posit the following hypotheses: H1. Subjects exposed to electronic NWOM describing a high level of service failure will provide lower scores on measures of (a) firm competence, (b) attitude toward the firm, (c) positive word of mouth, and (d) behavioral intention than will subjects exposed to electronic NWOM describing a low level of service failure. H2. Subjects exposed to electronic NWOM with a warning intent will provide lower scores on measures of (a) firm competence, (b) attitude toward the firm, (c) positive word of mouth, and (d) behavioral intention than will subjects exposed to electronic NWOM with a vengeful intent. H3. Level of service failure in electronic NWOM will interact with the perceived intention of the electronic NWOM, such that there will be a decrease in mean response on measures of (a) firm competence, (b) attitude toward the firm, (c) positive word of mouth, and (d) behavioral intention from electronic NWOM with a warning intent to a vengeful intent. The main study involved a2 (service failure severity) x2 (NWOM with warning versus vengeful intent) factorial experiment. Stimuli were presented to subjects online using a mock online web posting. The scenario described a service failure associated with non-acceptance of a gift card in a brick-and-mortar retail establishment. A national sample was recruited through an online research firm. A total of 113 subjects participated in the study. A total of 104 surveys were analyzed. The scenario was perceived to be realistic with 92.3% giving the scenario a greater than average response. Manipulations were satisfactory. Measures were pre-tested and validated. Items were analyzed and found reliable and valid. MANOVA results found the multivariate interaction was not significant, allowing our interpretation to proceed to the main effects. Significant main effects were found for post intent and service failure severity. The post intent main effect was attributable to attitude toward the firm, positive word of mouth and behavioral intention. The service failure severity main effect was attributable to all four dependent variables: firm competence, attitude toward the firm, positive word of mouth and behavioral intention. Specifically, firm competence for electronic NWOM describing high severity of service failure was lower than electronic NWOM describing low severity of service failure. Attitude toward the firm for electronic NWOM describing high severity of service failure was lower than electronic NWOM describing low severity of service failure. Positive word of mouth for electronic NWOM describing high severity of service failure was lower than electronic NWOM describing low severity of service failure. Behavioral intention for electronic NWOM describing high severity of service failure was lower for electronic NWOM describing low severity of service failure. Therefore, H1a, H1b, H1c and H1d were all supported. In addition, attitude toward the firm for electronic NWOM with a warning intent was lower than electronic NWOM with a vengeful intent. Positive word of mouth for electronic NWOM with a warning intent was lower than electronic NWOM with a vengeful intent. Behavioral intention for electronic NWOM with a warning intent was lower than electronic NWOM with a vengeful intent. Thus, H2b, H2c and H2d were supported. However, H2a was not supported though results were in the hypothesized direction. Otherwise, there was no significant multivariate service failure severity by post intent interaction, nor was there a significant univariate service failure severity by post intent interaction for any of the three hypothesized variables. Thus, H3 was not supported for any of the four hypothesized variables. This study has research and managerial implications. The findings of this study support prior research that service failure severity impacts consumer perceptions, attitude, positive word of mouth and behavioral intentions (Weun et al. 2004). Of further relevance, this response is evidenced in the online context, suggesting the need for firms to engage in serious focused service recovery efforts. With respect to perceived intention of electronic NWOM, the findings support prior research suggesting reader's attributions of the intentions of a source influence the strength of its impact on perceptions, attitude, positive word of mouth and behavioral intentions. The implication for managers suggests while consumers do find online communications to be credible and influential, not all communications are weighted the same. A benefit of electronic WOM, even when it may be potentially damaging, is it can be monitored for potential problems and additionally offers the possibility of redress.

• Journal of Distribution Science
• /
• v.9 no.4
• /
• pp.63-73
• /
• 2011

The relationship between buyers and sellers is changing into a long-term relationship. A number of distribution channel researchers have determined that the behavior of distribution channel members can be characterized by relational exchanges. The members of relational distribution channels may be perceived as strategic partners; however, even within these arrangements, member asymmetries may exist, which can create unequal distributions of power and dependence. Thus, as all distribution channel members may not be equal in power, it is possible that a less-dependent channel leader may emerge. Therefore, leadership in distribution channels is a very important variable. Distribution channel leadership can be defined as the activities undertaken by the distribution channel leader to influence the marketing programs and strategies of channel members. A distribution channel's performance is influenced by the leadership style of the channel leader. Although research on channel leadership styles can be broadly categorized, many researchers have dealt with analyzing distribution channel leadership by using the power-influence approach, which includes looking at variables, such as power, power base, and influence strategies. Moreover, they have examined the direct relationship between leadership styles and performance. Many distribution channel scholars have attempted to justify the application of leadership styles identified in alternative leadership theories to the inter-organizational context of distribution channels. They have made suggestions regarding how great the usefulness of leadership style as a strategy is to secure the compliance of distribution channel members and have conceptually and empirically linked it to channel-related phenomena, such as manifest conflict, cooperation, channel efficiency, and effectiveness. However, as few empirical studies have examined the antecedents and consequences of leadership styles, research on leadership style can be considered nascent. Thus, it is required to investigate the antecedents and consequences of the leadership style of a distribution channel leader. This study aims to empirically identify whether there are influences of the antecedents of leadership on two different leadership styles, and to reveal whether these leadership styles induce any consequences. The research subjects were 220 franchisees. Research findings are as follows: First, the results show a positive effect of technological capability on transformational relationships. However, it does not have a significant effect on transactional leadership. Second, innovation-oriented organizational culture has negatively influenced both leaderships. However, task-oriented organizational culture positively and significantly influenced both forms of leadership. Third, the ethics of leaders has influenced both leadership styles positively and significantly. Fourth, regarding consequences, transformational leadership strengthens financial performances, whereas it weakens relational citizenship behaviors. However, transactional leadership positively influences relational citizenship behavior whilst negatively affecting financial performance.

• Journal of Intelligence and Information Systems
• /
• v.21 no.2
• /
• pp.19-47
• /
• 2015

In this era of knowledge economy, a variety of virtual communities are proliferating for the purpose of knowledge creation and utilization. Since the voluntary contributions of members are the essential source of knowledge, member turnover can have significant implications on the survival and success of virtual communities. However, there is a dearth of research on the effect of membership turnover and even the method of measurement for membership turnover is left unclear in virtual communities. In a traditional context, membership turnover is calculated as the ratio of the number of departing members to the average number of members for a given time period. In virtual communities, while the influx of newcomers can be clearly measured, the magnitude of departure is elusive since explicit withdrawals are seldom executed. In addition, there doesn't exist a common way to determine the average number of community members who return and contribute intermittently at will. This study initially examines the limitations in applying the concept of traditional turnover to virtual communities, and proposes five membership fluidity measures based on a preliminary analysis of editing behaviors of 2,978 featured articles in English Wikipedia. Subsequently, this work investigates the relationships between three selected membership fluidity measures and group collaboration performance, reflecting a moderating effect dependent on work characteristic. We obtained the following results: First, membership turnover relates to collaboration efficiency in a right-shortened U-shaped manner, with a moderating effect from work characteristic; given the same turnover rate, the promotion likelihood for a more professional task is lower than that for a less professional task, and the likelihood difference diminishes as the turnover rate increases. Second, contribution period relates to collaboration efficiency in a left-shortened U-shaped manner, with a moderating effect from work characteristic; the marginal performance change per unit change of contribution period is greater for a less professional task. Third, the number of new participants per month relates to collaboration efficiency in a left-shortened reversed U-shaped manner, for which the moderating effect from work characteristic appears to be insignificant.

• Korean Journal of Social Welfare
• /
• v.57 no.2
• /
• pp.5-40
• /
• 2005

Social welfare centers and residential care facilities where provide the socially disadvantaged with proper social services, face financial difficulties. This is because not only of the lack of governmental support, but also of social welfare centers and residential care facilities' lack of skills in developing abundant resources from the private sector. In this context, this study tried to find factors affecting resource mobilization of the social welfare facilities to devise policies in resource development. Mail survey was conducted with the structured questionnaire. Employees in charge of community resource development were asked to answer the questionnaire. The study population were welfare centers and residential care facilities. A total of 293 community welfare centers and 632 residential care facilities responded to the survey. The response rate was about 62%. The dependent variables of the study were the amount of resource mobilization in the year 2001 which was measured as the number of donors, the total amount of donation, and estimated amount of gift-in-kind. Three types models were constructed per each welfare institution. Independent variables were selected based on the previous research findings: community environment factor, structural factor, and resource development factor. Multiple regression was utilized to analyze the data. The resource development factor turned out to be significant variable in various models. In the models of donors, the amount of donation, and the amount of gift-in-kind (except for the welfare center model), at least one out of six variables of the resource development factors was significant welfare center. Welfare centers which establish the resource development department or hire employees to take care of resource development, utilize computer softwares to file donors, and utilize donor management programs, have more donors and/or donations than their counterparts. In addition, residential care facilities located in urban area have more donors and donations, and among residential facilities those for the disables, those with longer history and more employees, receive more donations than their counterparts. As for the gift-in-kind model, the welfare centers located in high income area and residential care facilities for the elderly, children and mentally retarded receive less gift-in-kind than their counterparts Based on the above findings, this study suggested that to mobilize resources the welfare centers as well residential care facilities need to have community resource development department or resource development staffs, adopt computer software to systematically organize donors, and utilize donor mobilizing and maintaining programs.

• Asia pacific journal of information systems
• /
• v.19 no.2
• /
• pp.195-221
• /
• 2009

According to an industry report, a large number of organizations have invested in Organizational Information System(OIS) in the past few years. Several research results indicate that successful investments in OIS lead to productivity enhancement, while failed ones result in undesirable consequences such as financial losses and dissatisfaction among employees. In spite of huge investments, however, many organizations have failed in achieving the hoped-for returns from OIS. Thus, understanding user acceptance, adoption, and usage of new IS(Information Systems) is an important issue for IS practitioners. Indeed, study of the user acceptance of new information system has been one of the most important research topics in the contemporary IS literature. Several theoretical models are tested to examine 'user acceptance' and 'usage behavior' in IS context. While many research models incorporate 'ease of use' or 'usefulness' as important factors in explaining user acceptance, Technology Acceptance Model(TAM) has been one of the most widely applied models in user acceptance and usage behavior. Even in recent IS studies that employ theories of innovation diffusion in the area of IS implementation, a major focus has been on the user's perception of information technologies. In this research, we study 'voluntariness' as an important factor in IS acceptance by users. Voluntariness is defined as "the degree to which the use of the innovation is perceived as being voluntary, or of free will" When examining the diffusion of accepting OIS, a thoughtful consideration should be given to 'perceived voluntariness.' Current article has following research questions: 1) What models are appropriate to explain the success of OIS? and 2) How does the 'voluntariness' affect the success of OIS? In order to answer these questions, a research model is proposed to describe the detailed nature of association among three independent variables (IT usage level, task interdependency, and organizational support), a mediating variable (IS usage), a dependent variable (perceived performance), and a moderating variable(perceived voluntariness). The central claim of this article is that organizations hardly realize expected returns from OIS investments unless perceived voluntariness is effectively managed after operating OIS. As an example of OIS in this study we have selected the Intranet of Republic of Korea Air Force (ROKAF). ROKAF has implemented the Intranet in an attempt to improve communication and coordination within the organization. To test our research model and hypotheses, survey questionnaires were first sent out to 400 Intranet users. With the assistance of ROKAF, Intranet users were initially identified among its members, and subjects were randomly drawn from the pool. 377 survey responses were finally returned. The unit of measurement and analysis in this research is a personal level. Path analysis based on structural equation modeling was used to test research hypotheses. Construct validity represents accordance between the theoretical base concept of constructs and its measurement items. Tests for the reliability and discriminant validity are accepted, thus verifying our survey instrument. In this research, we have proposed a conceptual framework to highlight the importance of perceived voluntariness after organization deploys OIS. The results of our analysis present several key finding. First, all three independent variables (IT usage level, task interdependency, and organizational support) have significant effects on IS usage, which will eventually improve performance. Thus, IS usage plays a mediating role between antecedent variables (IT usage level. task interdependency, and organizational support) and performance improvement. Second, the effect of the task dependency was the highest for IS usage among the three antecedent variables. This is highly plausible since one of the Intranet's major capabilities is to facilitate communication among members within an organization. Accordingly, we conclude that the higher the task dependency, the higher Intranet usage. The effect of user's IT usage level was the second, while the effect of the organizational support was the third. Finally, the perceived voluntariness plays a pivotal role in enhancing perceived performance in personal level after launching the Intranet. Relationships among investigated variables were significantly different between groups with a high level and a low level of voluntariness. The impact of the Intranet usage on the performance was greater in the higher level voluntariness group than in the lower one. For the lower level voluntariness group, the user's IT usage had the highest effect on the Intranet usage among the three antecedent variables. In short, our study suggests that the higher the perceived voluntariness is the more IS usage will be. Perceived voluntariness was found to have a moderating effect on the relationships among user IT usage level, task interdependency, IS usage, and perceived performance, supporting all the hypotheses on the moderating effect. Most of all, user IT usage level has the strongest influence on IS usage, indicating that users with superior IT usage are more likely to enjoy a high level of perceived performance.

• Journal of Korean Society of Forest Science
• /
• v.80 no.3
• /
• pp.257-264
• /
• 1991

Korea has accomplished the afforestation of its forest land in the early 1980's. To meet the increasing demand for forest products and forest recreation, a development of scientific forest management system is needed as a whole. For this purpose the development of efficient forestfire management system is essential. In this context, the purpose of this study is to develop a theoretical foundation of forestfire danger rating system. In this study, it is hypothesized that the degree of forestfire risk is affected by Weather Factor and Man-Caused Risk Factor. (1) To accommodate the Weather Factor, a statistical model was estimated in which weather variables such as humidity, temperature, precipitation, wind velocity, duration of sunshine were included as independent variables and the probability of forestfire occurrence as dependent variable. (2) To account man-caused risk, historical data of forestfire occurrence was investigated. The contribution of man's activities make to risk was evaluated from three inputs. The first, potential risk class is a semipermanent number which ranks the man-caused fire potential of the individual protection unit relative to that of the other protection units. The second, the risk sources ratio, is that portion of the potential man-caused fire problem which can be charged to a specific cause. The third, daily activity level is that the fire control officer's estimate of how active each of these sources is, For each risk sources, evaluate its daily activity level ; the resulting number is the partial risk factor. Sum up the partial risk factors, one for each source, to get the unnormalized Man-Caused Risk. To make up the Man-Caused Risk, the partial risk factor and the unit's potential risk class were considered together. (3) At last, Fire occurrence index was formed fire danger rating estimation by the Weather Factors and the Man-Caused Risk Index were integrated to form the final Fire Occurrence Index.

• Asia pacific journal of information systems
• /
• v.20 no.1
• /
• pp.127-140
• /
• 2010

The benefit that a consumer derives from the use of a good often depends on the number of other consumers purchasing the same goods or other compatible items. This property, which is known as network externality, is significant in many IT related industries. Over the past few decades, network externalities have been recognized in the context of physical networks such as the telephone and railroad industries. Today, as many products are provided as a form of system that consists of compatible components, the appreciation of network externality is becoming increasingly important. Network externalities have been extensively studied among economists who have been seeking to explain new phenomena resulting from rapid advancements in ICT (Information and Communication Technology). As a result of these efforts, a new body of theories for 'New Economy' has been proposed. The theoretical bottom-line argument of such theories is that technologies subject to network effects exhibit multiple equilibriums and will finally lock into a monopoly with one standard cornering the entire market. They emphasize that such "tippiness" is a typical characteristic in such networked markets, describing that multiple incompatible technologies rarely coexist and that the switch to a single, leading standard occurs suddenly. Moreover, it is argued that this standardization process is path dependent, and the ultimate outcome is unpredictable. With incomplete information about other actors' preferences, there can be excess inertia, as consumers only moderately favor the change, and hence are themselves insufficiently motivated to start the bandwagon rolling, but would get on it once it did start to roll. This startup problem can prevent the adoption of any standard at all, even if it is preferred by everyone. Conversely, excess momentum is another possible outcome, for example, if a sponsoring firm uses low prices during early periods of diffusion. The aim of this paper is to analyze the dynamics of the adoption process in markets exhibiting network effects by focusing on two factors; switching and agent heterogeneity. Switching is an important factor that should be considered in analyzing the adoption process. An agent's switching invokes switching by other adopters, which brings about a positive feedback process that can significantly complicate the adoption process. Agent heterogeneity also plays a important role in shaping the early development of the adoption process, which has a significant impact on the later development of the process. The effects of these two factors are analyzed by developing an agent-based simulation model. ABM is a computer-based simulation methodology that can offer many advantages over traditional analytical approaches. The model is designed such that agents have diverse preferences regarding technology and are allowed to switch their previous choice. The simulation results showed that the adoption processes in a market exhibiting networks effects are significantly affected by the distribution of agents and the occurrence of switching. In particular, it is found that both weak heterogeneity and strong network effects cause agents to start to switch early and this plays a role of expediting the emergence of 'lock-in.' When network effects are strong, agents are easily affected by changes in early market shares. This causes agents to switch earlier and in turn speeds up the market's tipping. The same effect is found in the case of highly homogeneous agents. When agents are highly homogeneous, the market starts to tip toward one technology rapidly, and its choice is not always consistent with the populations' initial inclination. Increased volatility and faster lock-in increase the possibility that the market will reach an unexpected outcome. The primary contribution of this study is the elucidation of the role of parameters characterizing the market in the development of the lock-in process, and identification of conditions where such unexpected outcomes happen.