• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10483-10487
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• 2015

Heptaphylline derivatives are carbazoles in Clausena harmandiana, a medicinal plant that is utilized for headache, stomach ache, and other treatments of illness. The present study examined the effects of heptaphylline and 7-methoxyheptaphylline on apoptosis of human colon adenocarcinoma cells (HT-29 cell line). Quantification of cell viability was performed using cell proliferation assay (MTT assay) and of protein expression through immunoblotting. The results showed that only heptaphylline, but not 7-methoxyheptaphylline, significantly significantly activated cleaved of caspase-3 and poly (ADP-ribose) polymerase (PARP-1) which resulted in HT-29 cell death. We found that heptaphylline activated BH3 interacting-domain death agonist (Bid) and Bak, proapoptotic proteins. In contrast, it suppressed X-linked inhibitor-of-apoptosis protein (XIAP), Bcl-xL and survivin, inhibitors of apoptosis. In addition, heptaphylline inhibited activation of NF-${\kappa}B$/p65 (rel), a regulator of apoptotic regulating proteins by suppressing the activation of Akt and $IKK{\alpha}$, upstream regulators of p65. The findings suggested that heptaphylline induces apoptosis in human colon adenocarcinoma cells.

• The Journal of Asian Finance, Economics and Business
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• v.1 no.2
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• pp.15-24
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• 2014

This research investigates the characteristics, principles, advantages, factors and problems of cluster development in Kazakhstan, and identifies the prerequisites, conditions and stages of organizing clusters on the framework of special economic zones. In this research, we used methods, which will allow analyzing of the organization industrial clusters in special economic zones in Kazakhstan. The author studied international experience of cluster development and the efficiency of the use of the model of the "rhombus effect" with account the specific features of interaction between the participants of the cluster, analysis of the legal framework for the formation and development of clusters. These have been identified as the more important or strategically necessary clusters in Kazakhstan: innovation-technological cluster, innovation-education cluster, innovation-petrochemical cluster, innovative-metallurgical cluster, transport and logistics cluster, textile industry cluster, tourism cluster, agro cluster, construction cluster, medical and pharmaceutical cluster. Firstly, the results suggest that the interaction of science, education, business and government in the development and implementation of innovation policy is not sufficiently structured to provide a balanced representation of the interests of the range of various innovative enterprises in Kazakhstan. Secondly, the legal basis of cluster development in Kazakhstan is determined. Need to develop mechanisms for the implementation of promising direction. Thirdly, the clusters can be formed in the existing special economic zones, allowing them to get right to the mass production of high-tech products that are developed.

• Fisheries and Aquatic Sciences
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• v.25 no.7
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• pp.357-379
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• 2022

Increased fisheries products have raised by-products that are discarded due to low economic value. In addition, marine by-products are still rich in protein and nutritional value that have biological activities and give benefits to human health. Meanwhile, there is raised pressure for sustainability practices in marine industries to reduce waste and minimize the detrimental effect on the environment. Thus, valorization by-products through bioactive peptide mining are crucial. This review focus on various ways to obtain bioactive peptides from marine by-products through protein hydrolysis, for instance chemical hydrolysis (acid and based), biochemical hydrolysis (autolysis and enzymatic hydrolysis), microbial fermentation, and subcritical water hydrolysis. Nevertheless, these processes have benefits and drawbacks which need to be considered. This review also addresses various biological activities that are favorable in pharmaceutical industries, including antioxidant, antihypertensive, anticancer, anti-obesity, and other beneficial bioactivities. In addition, some potential marine resources of Indonesia for the marine biopeptide from their by-product or undesired marine commodities would be addressed as well.

• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.163-171
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• 2020

Silibinin exhibits antidiabetic potential by preserving the mass and function of pancreatic β-cells through up-regulation of estrogen receptor-α (ERα) expression. However, the underlying protective mechanism of silibinin in pancreatic β-cells is still unclear. In the current study, we sought to determine whether ERα acts as the target of silibinin for the modulation of antioxidative response in pancreatic β-cells under high glucose and high fat conditions. Our in vivo study revealed that a 4-week oral administration of silibinin (100 mg/kg/day) decreased fasting blood glucose with a concurrent increase in levels of serum insulin in high-fat diet/streptozotocin-induced type 2 diabetic rats. Moreover, expression of ERα, NF-E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in pancreatic β-cells in pancreatic islets was increased by silibinin treatment. Accordingly, silibinin (10 μM) elevated viability, insulin biosynthesis, and insulin secretion of high glucose/palmitate-treated INS-1 cells accompanied by increased expression of ERα, Nrf2, and HO-1 as well as decreased reactive oxygen species production in vitro. Treatment using an ERα antagonist (MPP) in INS-1 cells or silencing ERα expression in INS-1 and NIT-1 cells with siRNA abolished the protective effects of silibinin. Our study suggests that silibinin activates the Nrf2-antioxidative pathways in pancreatic β-cells through regulation of ERα expression.

• Journal of Technology Innovation
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• v.20 no.2
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• pp.135-159
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• 2012

To the analysis and discussion whether to conceptualization between the basis and LCM(Life cycle management) of patentability decisions and evergreening through research on patent application strategies and litigation cases. The Stakeholders have said that the LCM and evergreening strategies are an innovative effort to develop new pharmaceuticals, while others say that it is an effort to block generic pharmaceuticals from entering the market and permanently dominate the market by generic pharmaceuticals manufacturers or health economic perspectives. To achieve the goal of research, to discuss for conceptualization LCM and Evergreening strategies through patent application strategies for 14 pharmaceuticals for APIs and case studies for litigations. As a results, the LCM is getting patent rights for the results of research at the initial R&D stage and as such this shall be regarded as part of an effort for technology innovation. However, Evergreening is granting patent rights for the results by making high permission barrier to prevent the market entry of generic pharmaceuticals in the late development period during the pharmaceuticals development process or after their launch. This may lead to the problem of getting weak in health economic aspects and consumer welfare aspects by lowering the market accessibility of cheap generic pharmaceuticals.

• Journal of Technology Innovation
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• v.22 no.2
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• pp.157-183
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• 2014

This paper examines how the concentration of ownership in firms influences the R&D investment decision and whether the type of a firm's management (i.e, the owner-manager or professional manger) differentiates the relationship between the ownership concentration and R&D investments by using data of Korean pharmaceutical companies between 2004 and 2008. The results show that the share of the largest shareholder and R&D investment have an inverted U-shaped relationship, and whether a CEO is an owner or a professional manager affects the curvature of the inverted U-shaped relationship. Specifically, when a firm's CEO is a professional manager and the share of his stock is small, increase in the CEO's share increases the R&D investment in the larger amount than when a firm's CEO is an owner. This is because the increase in ownership reduces agency cost; However, when the share of his stock is large, the increase in CEO's share decreases R&D investment in the larger amount than when a firm's CEO is an owner. This is because a professional manager gets concerned over excessive risk exposure more than an owner-manager does.

• Asia Marketing Journal
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• v.15 no.3
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• pp.79-95
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• 2013

New product innovation is a process of embodying new knowledge in a product and technology licensing is getting popular as a means to innovations and introduction of new product to the market in today's competitive global market environment. Incumbents often rely on technology licensing to access new product opportunities created by other firms. Prior research has examined various aspects of technology licensing agreements such as specific contract terms of licensing agreements, e.g., distribution of control rights, exclusivity of licensing agreements, cross-licensing, and the scope of licensing agreements. This study aims to provide answers to an important, but under-researched question: why do some incumbents initiate more licensing agreement for exploratory learning while others do it for exploitative learning along the innovation process? We attempt to extend our knowledge of licensing agreements from an organizational learning perspective. Technology licensing as a specific form of interfirm linkages can be initiated with different learning objectives along the process of new product innovation. The exploratory stages of the innovation process such as discovery or research stages involve extensive searches to create new knowledge or capabilities, whereas the exploitative stages of the innovation process such as application or test stages near the commercialization are more focused on developing specific applications or improving their efficiency or reliability. Thus, different stages of the innovation process generate different types of learning and the resulting technological resources. We examine when incumbents as licensees initiate more licensing agreements for exploratory learning objectives and when more for exploitative learning objectives, focusing on two factors that may influence a firm's formation of exploratory and exploitative licensing agreements: 1) its past radical and incremental innovation experience and 2) its internal investments in R&D and marketing. We develop and test our hypotheses regarding the relationship between a firm's radical and incremental new product experience, R&D investment intensity and marketing investment intensity, and the likelihood of engaging in exploratory and exploitive licensing agreements. Using data collected from various secondary sources (Recap database, Compustat database, and FDA website), we analyzed technology licensing agreements initiated in the biotechnology and pharmaceutical industries from 1988 to 2011. The results of this study show that incumbents initiate exploratory rather than exploitative licensing agreements when they have more radical innovation experience and when they invest in R&D activities more intensively; in contrast, they initiate exploitative rather than exploratory licensing agreements when they have more incremental innovation experience and when they invest in marketing activities more intensively. The findings of this study contribute to the licensing and interfirm cooperation studies. First, this study lays a foundation to understand the organizational learning aspect of technology licensing agreements. Second, this study sheds lights on how a firm's internal investments in R&D and marketing are linked to its tendency to initiate licensing agreements along the innovation process. Finally, the findings of this study provide important insight to managers regarding which technologies to gain via licensing agreements. This study suggests that firms need to consider their internal investments in R&D and marketing as well as their past innovation experiences when they initiate licensing agreements along the process of new product innovation.

• Asian Journal of Innovation and Policy
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• v.7 no.3
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• pp.625-645
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• 2018

This paper's objective is to draw a decision guideline to continue research and development (R&D) investments in biotech start-ups facing the "Valley of Death" syndrome - a long negative profit period during a financial crisis. The data include financial indices as Net income, Revenues, Total stockholders' equity, Cash & equivalents, and R&D expenses of 18 major biotech companies (nine in negative profit and nine positive, in FY2008) and 15 major pharmaceutical corporations as benchmarks both in FY2008 and in FY2016 derived from the US SEC Database, EDGAR. A first methodology dealing with real options analysis assumes Total stockholders' equity as a growth option. And a second methodology, Bayesian Markov chain Monte Carlo (MCMC) analysis, is applied to test the probability relationship between the Total stockholders' equity and the R&D expenses in these three groups. This study confirms that Total stockholders' equity can play the role of a call option to support continuing R&D investments even in negative profits.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1169-1173
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• 2015

Background: Paris polyphylla (Chinese name: Chonglou) had been traditionally used for a long time and shown anti-cancer action. Based on the previous study that paris polyphylla steroidal saponins (PPSS) induced cytotoxic effect in human lung cancer A549 cells, this study was designed to further illustrate the mechanisms underlying. Materials and Methods: The mechanisms involved in PPSS-induced A549 cell death were investigated by phase contrast microscopy and fluorescence microscopy, flow cytometry and western blot analysis, respectively. Results: PPSS decreased the proportion of viable A549 cells, and exposure of A549 cells to PPSS led to both apoptosis and autophagy. Apoptosis was due to activations of caspase-8, caspase-3, as well as cleavage of PARP, and autophagy was confirmed by up-regulation of Beclin 1 and the conversion from LC3 I to LC3 II. Conclusions: PPSS was able to induce lung cancer A549 cell apoptosis and autophagy in vitro, the results underlining the possibility that PPSS would be a potential candidate for intervention against lung cancer.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.12 no.7
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• pp.3016-3021
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• 2011

While there is ample information on the investment plans about Korea's selected new growth businesses, it is hard to find any analysis on the valuation of the projects. In this paper, I intend to do a valuation for the three particular technologies, which are solar cell, automotive battery, and bio-pharmaceutical, based on compound option model so that the valuation can capture not only the expected net cash flow but also the value originated from the flexibility of the decision maker. In addition, the real option pricing theory is reviewed and its practical limitations are thoroughly investigated.