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International Success the Second Time Around: A Case Study (제이륜국제성공(第二轮国际成功): 일개안례연구(一个案例研究))

  • Colley, Mary Catherine;Gatlin, Brandie
    • Journal of Global Scholars of Marketing Science
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    • v.20 no.2
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    • pp.173-178
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    • 2010
  • A privately held, third generation family owned company, Boom Technologies, Inc. (BTI), a provider of products and services to the electric utility, telecommunications and contractor markets, continues to make progress in exporting. Although export sales only equaled 5% of total revenue in 2008, BTI has an entire export division. Their export division's Managing Director reveals the trial and errors of a privately held company and their quest for success overseas. From its inception, BTI has always believed its greatest asset is its employees. When export sales struggled due to lack of strategy and direction, BTI hired a Managing Director for its export division. With leadership and guidance from BTI's president and from the Managing Director, they utilized the department's skills and knowledge. Structural changes were made to expand their market presence abroad and increase export sales. As a result, export sales increased four-fold, area managers in new countries were added and distribution networks were successfully cultivated. At times, revenue generation was difficult to determine due to the structure of the company. Therefore, in 1996, the export division was restructured as a limited liability company. This allowed the company to improve the tracking of revenue and expenses. Originally, 80% of BTI's export sales came from two countries; therefore, the initial approach to selling overseas was not reaching their anticipated goals of expanding their foreign market presence. However, changes were made and now the company manages the details of selling to over 80 countries. There were three major export expansion challenges noted by the Managing Director: 1. Product and Shipping - The major obstacle for BTI was product assembly. Originally, the majority of the product was assembled in the United States, which increased shipping and packaging costs. With so many parts specified in the order, many times the order would arrive with parts missing. The missing parts could equate to tens of thousands of dollars. Shipping these missing parts separately in another shipment also cost tens of thousands of dollar, plus a delivery delay time of six to eight weeks; all of which came out of the BTI's pockets. 2. Product Adaptation - Safety and product standards varied widely for each of the 80 countries to which BTI exported. Weights, special licenses, product specification requirements, measurement systems, and truck stability can all differ from country to country and can serve as a type of barrier to entry, making it difficult to adapt products accordingly. Technical and safety standards are barriers that serve as a type of protection for the local industry and can stand in the way of successfully pursuing foreign markets. 3. Marketing Challenges - The importance of distribution creates many challenges for BTI as they attempt to determine how each country prefers to operate with regard to their distribution systems. Some countries have competition from a small competitor that only produces one competing product; whereas BTI manufactures over 100 products. Marketing material is another concern for BTI as they attempt to push marketing costs to the distributors. Adapting the marketing material can be costly in terms of translation and cultural differences. In addition, the size of paper in the United States differs from those in some countries, causing many problems when attempting to copy the same layout and With distribution being one of several challenges for BTI, the company claims their distribution network is one of their competitive advantages, as the location and names of their distributors are not revealed. In addition, BTI rotates two offerings yearly: training to their distributors one year and then the next is a distributor's meeting. With a focus on product and shipping, product adaptation, and marketing challenges, the intricacies of selling overseas takes time and patience. Another competitive advantage noted is BTI's cradle to grave strategy, where they follow the product from sale to its final resting place, whether the truck is leased or purchased new or used. They also offer service and maintenance plans with a detailed cost analysis provided to the company prior to purchasing or leasing the product. Expanding abroad will always create challenges for a company. As the Managing Director stated, "If you don't have patience (in the export business), you better do something else." Knowing how to adapt quickly provides BTI with the skills necessary to adjust to the changing needs of each country and its own unique challenges, allowing them to remain competitive.

Preparation of Vitamin E Acetate Nano-emulsion and In Vitro Research Regarding Vitamin E Acetate Transdermal Delivery System which Use Franz Diffusion Cell (Vitamin E Acetate를 함유한 Nano-emulsion 제조와 Franz Diffusion Cell을 이용한 Vitamin E Acetate의 경표피 흡수에 관한 In Vitro 연구)

  • Park, Soo-Nam;Kim, Jai-Hyun;Yang, Hee-Jung;Won, Bo-Ryoung;Ahn, You-Jin;Kang, Myung-Kyu
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.35 no.2
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    • pp.91-101
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    • 2009
  • in the cosmetics and medical supply field as a antioxidant material. The stable nano particle emulsion of skin toner type containing VEA was prepared. To evaluate the skin permeation, experiments on VEA permeation to the skin of the ICR outbred albino mice (12 weeks, about 50 g, female) and on differences of solubility as a function of receptor formulations was performed. The analysis of nano-emulsions containing VEA 0.07 % showed that the higher ethanol contents the larger emulsions were formed, while the higher surfactant contents the size became smaller.In this study, vitamin E acetate (VEA, tocopheryl acetate), a lipid-soluble vitamin which is widely used A certain contents of ethanol in receptor phase increased VEA solubility on the nano-emulsion. When the ethanol contents were 10.0 % and 20.0 %, the VEA solubility was higher than 5.0 % and 40.0 %, respectively. The type of surfactant in receptor solution influenced to VEA solubility. The comparison between three kind surfactants whose chemical structures and HLB values are different, showed that solubility of VEA was increased as order of sorbitan sesquioleate (Arlacel 83; HLB 3.7) > POE (10) hydrogenated castor oil (HCO-10; HLB 6.5) > sorbitan monostearate (Arlacel 60; HLB 4.7). VEA solubility was also shown to be different according to the type of antioxidant. In early time, the solubility of the sample including ascorbic acid was similar to those of other samples including other types of antioxidants. However, the solubility of the sample including ascorbic acid was 2 times higher than others after 24 h. Franz diffusion cell experiment using mouse skin was performed with four nano-emulsion samples which have different VEA contents. The emulsion of 10 wt% ethanol was shown to be the most permeable at the amount of 128.8 ${\mu}g/cm^2$. When the result of 10 % ethanol content was compared with initial input of 220.057 ${\mu}g/cm^2$, the permeated amount was 58.53 % and the permeated amount at 10 % ethanol was higher 45.0 % and 15.0 % than the other results which ethanol contents were 1.0 and 20.0 wt%, respectively. Emulsion particle size used 0.5 % surfactant (HCO-60) was 26.0 nm that is one twentieth time smaller than the size of 0.007 % surfactant (HCO-60) at the same ethanol content. Transepidermal permeation of VEA was 54.848 ${\mu}g/cm^2$ which is smaller than that of particlesize 590.7 nm. Skin permeation of nano-emulsion containing VEA and difference of VEA solubility as a function of receptor phase formulation were determined from the results. Using these results, optimal conditions of transepidermal permeation with VEA were considered to be set up.

Microbiological Hazard Analysis for HACCP System Application to Vinegared Pickle Radishes (식초절임 무의 HACCP 시스템 적용을 위한 미생물학적 위해 분석)

  • Kwon, Sang-Chul
    • Journal of Food Hygiene and Safety
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    • v.28 no.1
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    • pp.69-74
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    • 2013
  • This study has been performed for 150 days from February 1 - June 31, 2012 aiming at analyzing biologically hazardous factors in order to develop HACCP system for the vinegared pickle radishes. A process chart was prepared as shown on Fig. 1 by referring to manufacturing process of manufacturer of general vinegared pickle radishes regarding process of raw agricultural products of vinegared pickle radishes, used water, warehousing of additives and packing material, storage, careful selection, washing, peeling off, cutting, sorting out, stuffing (filling), internal packing, metal detection, external packing, storage and consignment (delivery). As a result of measuring Coliform group, Staphylococcus aureus, Salmonella spp., Bacillus cereus, Listeria Monocytogenes, E. coli O157:H7, Clostridium perfringens, Yeast and Mold before and after washing raw radishes, Bacillus cereus was $5.00{\times}10$ CFU/g before washing but it was not detected after washing and Yeast and Mold was $3.80{\times}10^2$ CFU/g before washing but it was reduced to 10 CFU/g after washing and other pathogenic bacteria was not detected. As a result of testing microorganism variation depending on pH (2-5) of seasoning fluid (condiment), pH 3-4 was determined as pH of seasoning fluid as all the bacteria was not detected in pH3-4. As a result of testing air-borne bacteria (number of general bacteria, colon bacillus, fungus) depending on each workplace, number of microorganism of internal packing room, seasoning fluid processing room, washing room and storage room was detected to be 10 CFU/Plate, 2 CFU/Plate, 60 CFU/Plate and 20 CFU/Plate, respectively. As a result of testing palm condition of workers, as number of general bacteria and colon bacillus was represented to be high as 346 $CFU/Cm^2$ and 23 $CFU/Cm^2$, respectively, an education and training for individual sanitation control was considered to be required. As a result of inspecting surface pollution level of manufacturing facility and devices, colon bacillus was not detected in all the specimen but general bacteria was most dominantly detected in PP Packing machine and Siuping machine (PE Bulk) as $4.2{\times}10^3CFU/Cm^2$, $2.6{\times}10^3CFU/Cm^2$, respectively. As a result of analyzing above hazardous factors, processing process of seasoning fluid where pathogenic bacteria may be prevented, reduced or removed is required to be controlled by CCP-B (Biological) and threshold level (critical control point) was set at pH 3-4. Therefore, it is considered that thorough HACCP control plan including control criteria (point) of seasoning fluid processing process, countermeasures in case of its deviation, its verification method, education/training and record control would be required.

Maternal Vitamin $B_{6}$ Intake and Vitamin $B_{6}$ Level in Maternal, Umbilical Cord Plasma and Placenta (임신부의 비타민 $B_{6}$ 섭취와 모체와 제대혈 및 태반 조직의 비타민 $B_{6}$농도)

  • 안홍석;이금주;정환욱
    • Journal of Nutrition and Health
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    • v.35 no.3
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    • pp.322-331
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    • 2002
  • This study was carried out to evaluate the effect of vitamin $B_{6}$ intake by normal term delivery pregnant women on the concentration of vitamin $B_{6}$ in the material plasma, the umbilical cord plasma, and the placental tissue. Dietary intake data were obtained from a semi-quantitative frequency questionnaire. The daily mean energy and protein intakes were 2189.5 kcal (93.2% of RDA) and 79.3 g (113.3% of RDA), respectively. The average daily vitamin $B_{6}$ intake was 1.7 mg (91.4% of RDA) for the pregnant women. Their main sources of vitamin $B_{6}$ were cereal & starch (50%), and vegetables & fruits (33%). The pyridoxal phosphate (PLP) concentration of the maternal plasma, the umbilical cord plasma, and the placenta were 16.7 $\pm$ 4.1 nmol/1, 61.3 $\pm$ 19.8 nmol/l and 898.6 $\pm$ 159.2 ng/g, respectively. The PLP level was the highest in the placenta. The PLP level of the maternal plasma was significantly lower than the of the umbilical cord plasma (p < 0.001). The PLP level of maternal plasma correlated positively with that of the placenta (p < 0.0001) and the umbilical cord plasma (p < 0.05). Also the PLP level of the placenta correlated positively with that of the umbilical cord plasma (p < 0.05). These findings indicate that the vitamin $B_{6}$ nutritional status of the fetus is affected by placental vitamin $B_{6}$ levels, and that the placental vitamin B$_{6}$ levels reflect the maternal vitamin $B_{6}$ status. The umbilical cord plasma PLP level showed a positive correlation with the gestational length (p < 0.05). A negative association was observed between the PLP level showed of the umbilical cord plasma and the pregnancy weight gain (p < 0.03). The results suggest that the transfer of PLP from maternal plasma to the placental tissue could be an active transport, white the transfer of PLP from the placenta to the fetus is by means of simple diffusion. Thus, neonatal vitamin $B_{6}$ nutrition is influenced by the maternal nutritional status.

Clinical study on the comparison of gold and zirconia wear in an implant-supported fixed prosthesis (임플란트 지지 고정성 보철물에서 금과 지르코니아의 마모 비교에 대한 임상 연구)

  • Kim, Jee-Hwan;Yang, Seung-Won;Oh, NamSik
    • Journal of Dental Rehabilitation and Applied Science
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    • v.33 no.4
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    • pp.252-259
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    • 2017
  • Purpose: The purpose of this study was to compare and analyze the wear of a prosthesis for 6 months after restoration with implant-supported fixed dental prosthesis made of either zirconia or gold. Materials and Methods: This study was conducted on patients requiring implant-supported fixed dental prostheses on first or second molar from January, 2015 to January, 2016. A total of 47 prostheses and antagonists were examined. Occlusal surface was recorded by impression of each prosthesis and antagonist 1 week and 6 months after prosthesis delivery. The digital files were created by impression scan. Occlusal shapes of 1 week and 6 months were compared and wear of prostheses and antagonists was analyzed. The Mann-Whitney test was used to analyzed the result data underwent normality test using SPSS (Version 23.0, IBM Corporation) Results: Mann-Whitney test revealed that there was no statistically significant difference in the median amount of mean vertical wear for 6 months in zirconia ($50.84{\mu}m$) and gold ($42.84{\mu}m$) prostheses (P > 0.05). When the opposing teeth were natural, the median amount of mean vertical wear of zirconia and gold prostheses was $47.72{\mu}m$ and $41.97{\mu}m$, respectively, and the median amount of mean vertical wear of enamel was $47.26{\mu}m$ and $44.59{\mu}m$, respectively. Statistical analysis showed no significant difference (P > 0.05). Conclusion: Despite the short study period and the small number of experimental groups, zirconia and gold showed no significant difference in wear during the first 6 months. Opposing natural enamel also showed no significant difference in the wear.

Development of New Device to Improve Sucess Rate of Maze Procedure with Radiofrequency Energy (고주파에너지를 이용한 미로술식의 성적향상을 위한 새로운 기구의 개발)

  • 박남희;유양기;이재원
    • Journal of Chest Surgery
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    • v.37 no.6
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    • pp.467-473
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    • 2004
  • Background: The sinus conversion rate after the maze procedure in chronic atrial fibrillation using radiofrequency energy is lower than with either conventional 'cut and saw' technique or cryothermia. The creation of incomplete transmural lesions due to poor tissue-catheter contact is thought to be the main cause. To address this problem, the current study was aimed to evaluate the effectiveness of a specially constructed compression device designed to enhance tissue catheter contact during unipolar radiofrequency catheter ablation. Material and Method: Circum-ferential right auricular epicardial lesions were created with a linear radiofrequency catheter in 10 anesthetized pigs. A device specially designed to increase contact by compression of the catheter to the atrial wall was used in 5 pigs (study group). This device was not used in the control group (5 pigs). Conduction block across the right auricular lesion was assessed by pacing, and the transmurality of the lesions were confirmed by microscopic examination. Result: Conduction block was observed in a total of 8 pigs; 5 in study group and 3 in control group. Transmural injury was confirmed microscopically by the accumulation of acute inflammatory cells and loss of elastic fibers in the endocardium. In two pigs with failed conduction block, microscopic examination of the endocardium appeared normal. Conclusion: Failed radiofrequency ablation is strongly related to non-transmural energy delivery. The specially constructed compression device in the current study was successful in creating firm tissue-catheter contact and thereby generating transmural lesions during unipolar radiofrequency ablation.

Structural Relationships Among Factors to Adoption of Telehealth Service (원격의료서비스 수용요인의 구조적 관계 실증연구)

  • Kim, Sung-Soo;Ryu, See-Won
    • Asia pacific journal of information systems
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    • v.21 no.3
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    • pp.71-96
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    • 2011
  • Within the traditional medical delivery system, patients residing in medically vulnerable areas, those with body movement difficulties, and nursing facility residents have had limited access to good healthcare services. However, Information and Communication Technology (ICT) provides us with a convenient and useful means of overcoming distance and time constraints. ICT is integrated with biomedical science and technology in a way that offers a new high-quality medical service. As a result, rapid technological advancement is expected to play a pivotal role bringing about innovation in a wide range of medical service areas, such as medical management, testing, diagnosis, and treatment; offering new and improved healthcare services; and effecting dramatic changes in current medical services. The increase in aging population and chronic diseases has caused an increase in medical expenses. In response to the increasing demand for efficient healthcare services, a telehealth service based on ICT is being emphasized on a global level. Telehealth services have been implemented especially in pilot projects and system development and technological research. With the service about to be implemented in earnest, it is necessary to study its overall acceptance by consumers, which is expected to contribute to the development and activation of a variety of services. In this sense, the study aims at positively examining the structural relationship among the acceptance factors for telehealth services based on the Technology Acceptance Model (TAM). Data were collected by showing audiovisual material on telehealth services to online panels and requesting them to respond to a structured questionnaire sheet, which is known as the information acceleration method. Among the 1,165 adult respondents, 608 valid samples were finally chosen, while the remaining were excluded because of incomplete answers or allotted time overrun. In order to test the reliability and validity of the assessment scale items, we carried out reliability and factor analyses, and in order to explore the causal relation among potential variables, we conducted a structural equation modeling analysis using AMOS 7.0 and SPSS 17.0. The research outcomes are as follows. First, service quality, innovativeness of medical technology, and social influence were shown to affect perceived ease of use and perceived usefulness of the telehealth service, which was statistically significant, and the two factors had a positive impact on willingness to accept the telehealth service. In addition, social influence had a direct, significant effect on intention to use, which is paralleled by the TAM used in previous research on technology acceptance. This shows that the research model proposed in the study effectively explains the acceptance of the telehealth service. Second, the research model reveals that information privacy concerns had a insignificant impact on perceived ease of use of the telehealth service. From this, it can be gathered that the concerns over information protection and security are reduced further due to advancements in information technology compared to the initial period in the information technology industry, and thus the improvement in quality of medical services appeared to ensure that information privacy concerns did not act as a prohibiting factor in the acceptance of the telehealth service. Thus, if other factors have an enormous impact on ease of use and usefulness, concerns over these results in the initial period of technology acceptance may become irrelevant. However, it is clear that users' information privacy concerns, as other studies have revealed, is a major factor affecting technology acceptance. Thus, caution must be exercised while interpreting the result, and further study is required on the issue. Numerous information technologies with outstanding performance and innovativeness often attract few consumers. A revised bill for those urgently in need of telehealth services is about to be approved in the national assembly. As telemedicine is implemented between doctors and patients, a wide range of systems that will improve the quality of healthcare services will be designed. In this sense, the study on the consumer acceptance of telehealth services is meaningful and offers strong academic evidence. Based on the implications, it can be expected to contribute to the activation of telehealth services. Further study is needed to assess the acceptance factors for telehealth services, such as motivation to remain healthy, health care involvement, knowledge on health, and control of health-related behavior, in order to develop unique services according to the categorization of customers based on health factors. In addition, further study may focus on various theoretical cognitive behavior models other than the TAM, such as the health belief model.

A Study on the Knowledge and Attitude about Sex in One Commercial Girls' High school in Seoul (서울지역 일 여자 상업고등학교의 성에 대한 지식 및 태도에 관한 연구)

  • Kim, Eun Hee
    • Journal of the Korean Society of School Health
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    • v.4 no.2
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    • pp.100-118
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    • 1991
  • This study was conducted in order to grasp the condition of the student's knowledge and attitude about sex. And to offer the basic materials for sex education of school health service. The objects were comprised of 464 volunteered students who study in commercial girls' high school. The material of this study was the questionaire suited to the purposed of this research which has been made through studying references. All the questionaire written by students. The self reported questionaires were collected immediately without explanation on supervision of school nurse. The data was collected from 28th to 30th of June on 1990. Analysis of the data was done utilizing SPSS for percentage, mean, ANOVA and Pearson Correlation Coefficients. The Results are as follows; 1. General features of the objects of study School grade distribution was similar. Fathers of 41-50 years were the highest(58.3%), mothers of 41-50 years were the highest(64.3%), family of living together were the highest(87.5%), fathers of graduated high school were highest(60.7%), mothers of graduated middle school were the highest(43.0%) and neuclear families were highest(91.5%). 2. The Conditions of Knowledge about sex When 5 Point was given to "Well known" and 1 point was given to "Never known", the total average was 2.97, Especially the mean of Female physiology was shown 3.93, 73.4% of students have known. But the mean of male physiology was shown 2.23, 17.2% of students only. And Family planning item was 3.54, hymen item was 3.38, female genitalia item was 3.35, abortion item was 3.25, Intercourse and pregnancy item was 3.24, Ovulation item was 3.02, Contraception item was 2.97, Veneral disease and masturbation item was 2.82, maintenance of pregnancy item was 2.76, Anatomical differences between male and female item was 2.59, male genitalia item was 2.31, ejaculation item was 2.27. 3. The conditions of attitude about Sex When 5 point was given to "Very affirming" and 1 point was given to "Very deny" the total average was 3.20. Especially the mean of social intercourse between other sex was shown 3.92, 73.4% of students have affirmed. But the mean of psychic response on menstruation was shown 2.24, 8.8% of students only. And baby birth item was 3.72, the fact that I am a woman item was 3.53, marriage item was 3.49. Secondary body change item was 3.38, puberty item was 3.31, delivery and sexual intercourse item was 3.05, pregenancy item was 3.02, psychic condition on menarche item was 2.50. Also present counsellors about sex were teachers in charge (44.9%), friends(21.6%), mothers(20.6%), elder sisters (10.6%), mass-communications (1.5%), fathers (0.4%), school nurses and elder brother(0.2%). In addition to, future counsellors about sex were friends (37.7%), mothers(30.6%), elder sister (18.4%), school nurses (4.6%), mass communication (3.8%), teachers in charge (2.5%), elder brothers (1.4%) and fathers(1.0%). 4. Correlation between the general features and knowledge variables School grade and knowledge condition has relationship to female genitalia(P<0.05), female physiology (P<0.00), male physiology (P<0.05),ovulation (P<0.00), and femily planning (P<0.005). Fathers age and knowledge condition has relationship to male physiology(P<0.05), and abortion (P<0.05). Marrital status and knowledge condition has relationship to female physiology (P<0.01), masturbation (P<0.05). Fathers educational background and knowledge condition has relationship to masturbation (P<0.00). Mothers age and knowledge condition has relationship to family planning (P<0.05). 5. Correlation between the general futures and attituded variables Fathers age and attitude condition has relationship to psychic response on menstruation (P<0.05). Mothers age and attitude condition has relationship to fact that I am a woman (P<0.00). Mothers educational background and attitude condition has relationship to social intercourse between other sex (P<0.05). Type of family and attitude condition has relationship to puberty (P<0.01). 6. Correlation between knowledge condition and attitude condition Those who had more knowledge about sex have more affirmative response (P<0.001).

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Expression of Hypoxia-inducible Factor-1 $\alpha$ in Esophageal Squamous Cell Carcinoma: Relationship to Prognosis and Tumor Biomarkers (식도 편평세포암에시 Hypoxia-inducible Factor-1 $\alpha$의 발현: 예후와 종양표지자와의 상관성)

  • 양일종;김종인;이해영;천봉권;조성래
    • Journal of Chest Surgery
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    • v.37 no.8
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    • pp.691-701
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    • 2004
  • Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.

Expression of Hypoxia-inducible Factor-$1{\alpha}$ in Non-small Cell Lung Cancer: Relationship to Prognosis and Tumor Biomarkers (비소세포 폐암에서 HIF-$1{\alpha}$의 발현: 예후 및 종양표지자와의 관련성)

  • Cho, Sung-Rae;Byun, Joung-Hun;Kim, Jong-In;Lee, Bong-Geun;Chun, Bong-Kwon
    • Journal of Chest Surgery
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    • v.39 no.11 s.268
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    • pp.828-837
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    • 2006
  • Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.