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Association between Laryngeal Squamous Cell Carcinoma and Polymorphisms in Tumor Necrosis Factor Related Apoptosis Induce Ligand (TRAIL), TRAIL Receptor and sTRAIL Levels

  • Verim, Aysegul;Turan, Saime;Farooqi, Ammad Ahmad;Kahraman, Ozlem Timirci;Tepe-Karaca, Cigdem;Yildiz, Yemliha;Naiboglu, Baris;Ozkan, Nazli Ezgi;Ergen, Arzu;Isitmangil, Gulbu Aydinoglu;Yaylim, Ilhan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10697-10703
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    • 2015
  • The laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors occurring in the head and neck. Tumor necrosis factor related apoptosis induce ligand (TRAIL) and TRAIL-receptors (DR4, DR5, DcR1, DcR2) are known as important members of TRAIL-mediated biochemical signaling pathway. Associations between polymorphisms in these genes and clinicopathological characteristics of human laryngeal carcinoma are not well defined. This study therefore aimed to investigate a possible relationship among the TRAIL and TRAIL-DR4 polymorphisms and sTRAIL levels in the risk or progression of LSCC. A total of 99 patients with laryngeal cancer and 120 healthy subjects were enrolled in the study. DR4 C626G and TRAIL 1595 C/T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and sTRAIL levels were measured by ELISA. There were significant differences in the distribution of DR4 C626G genotypes and frequencies of the alleles between laryngeal cancer patients and controls (p<0.001) but not in TRAIL 1595 C/T. We found the increased frequency of the DR4 C626G homozygote CC genotype in patients than in controls (p<0.001). Haplotype analysis revealed that there was also a statistically significant relationship between TRAIL and TRAIL-DR4 polymorphisms and laryngeal cancer. Serum sTRAIL levels in the laryngeal patients with CC genotype who had advanced tumour stage were lower than those of patients with early tumor stage (p=0.014). Our findings suggest that DR4 C626G genotypes and sTRAIL levels might be associated with progression of laryngeal cancer in the Turkish population.

Effects of Rapamycin on Cell Apoptosis in MCF-7 Human Breast Cancer Cells

  • Tengku Din, Tengku Ahmad Damitri Al-Astani;Seeni, Azman;Khairi, Wirdatul-Nur Mohd;Shamsuddin, Shaharum;Jaafar, Hasnan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10659-10663
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    • 2015
  • Background: Rapamycin is an effective anti-angiogenic drug. However, the mode of its action remains unclear. Therefore, in this study, we aimed to elucidate the antitumor mechanism of rapamycin, hypothetically via apoptotic promotion, using MCF-7 breast cancer cells. Materials and Methods: MCF-7 cells were plated at a density of $1{\times}10^5$ cells/well in 6-well plates. After 24h, cells were treated with a series of concentrations of rapamycin while only adding DMEM medium with PEG for the control regiment and grown at $37^{\circ}C$, 5% $CO_2$ and 95% air for 72h. Trypan blue was used to determine the cell viability and proliferation. Untreated and rapamycin-treated MCF-7 cells were also examined for morphological changes with an inverted-phase contrast microscope. Alteration in cell morphology was ascertained, along with a stage in the cell cycle and proliferation. In addition, cytotoxicity testing was performed using normal mouse breast mammary pads. Results: Our results clearly showed that rapamycin exhibited inhibitory activity on MCF-7 cell lines. The $IC_{50}$ value of rapamycin on the MCF-7 cells was determined as $0.4{\mu}g/ml$ (p<0.05). Direct observation by inverted microscopy demonstrated that the MCF-7 cells treated with rapamycin showed characteristic features of apoptosis including cell shrinkage, vascularization and autophagy. Cells underwent early apoptosis up to 24% after 72h. Analysis of the cell cycle showed an increase in the G0G1 phase cell population and a corresponding decrease in the S and G2M phase populations, from 81.5% to 91.3% and 17.3% to 7.9%, respectively. Conclusions: This study demonstrated that rapamycin may potentially act as an anti-cancer agent via the inhibition of growth with some morphological changes of the MCF-7 cancer cells, arrest cell cycle progression at G0/G1 phase and induction of apoptosis in late stage of apoptosis. Further studies are needed to further characterize the mode of action of rapamycin as an anti-cancer agent.

Mechanistic Analysis of Taxol-induced Multidrug Resistance in an Ovarian Cancer Cell Line

  • Wang, Ning-Ning;Zhao, Li-Jun;Wu, Li-Nan;He, Ming-Feng;Qu, Jun-Wei;Zhao, Yi-Bing;Zhao, Wan-Zhou;Li, Jie-Shou;Wang, Jin-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.4983-4988
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    • 2013
  • Objectives: To establish a taxol-resistant cell line of human ovarian carcinoma (A2780/Taxol) and investigate its biological features. Methods: The drug-resistant cell line (A2780/Taxol) was established by continuous stepwise selection with increasing concentrations of Taxol. Cell morphology was assessed by microscopy and growth curves were generated with in vitro and in vivo tumor xenograft models. With rhodamine123 (Rh123) assays, cell cycle distribution and the apoptotic rate were analyzed by flow cytometry (FCM). Drug resistance-related and signal associated proteins, including P-gp, MRPs, caveolin-1, PKC-${\alpha}$, Akt, ERK1/2, were detected by Western blotting. Results: A2780/Taxol cells were established with stable resistance to taxol. The drug resistance index (RI) was 430.7. Cross-resistance to other drugs was also shown, but there was no significant change to radioresistance. Compared with parental cells, A2780/Taxol cells were significantly heteromorphous, with a significant delay in population doubling time and reduced uptake of Rh123 (p<0.01). In vivo, tumor take by A2780 cells was 80%, and tumor volume increased gradually. In contrast, with A2780/Taxol cells in xenograft models there was no tumor development. FCM analysis revealed that A2780/Taxol cells had a higher percentage of G0/G1 and lower S phase, but no changes of G2 phase and the apoptosis rate. Expression of P-gp, MRP1, MRP2, BCRP, LRP, caveolin-1, PKC-${\alpha}$, Phospho-ERK1/2 and Phospho-JNK protein was significantly up-regulated, while Akt and p38 MARK protein expression was not changed in A2780/Taxol cells. Conclusion: The A2780/Taxol cell line is an ideal model to investigate the mechanism of muti-drug resistance related to overexpression of drug-resistance associated proteins and activation of the PKC-${\alpha}/ERK$ (JNK) signaling pathway.

The effects of music listening, autogenic training, and music-assisted autogenic training on the quality of life, relaxation responses, and daily living of migraine patients

  • Lee, Suyeon
    • Journal of Music and Human Behavior
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    • v.2 no.1
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    • pp.67-85
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    • 2005
  • The purpose of this study was to investigate the effect of music listening, autogenic training, and music-assisted autogenic training on the quality of life, physiological and psychological relaxation responses, and daily living in a population of migraine patients. Forty migraine patients, ranging 20 to 60 years, were referred to the researcher by their physicians and participated in the study. A convenience control-group pretest-posttest design was employed. The participants were randomly assigned to one of four groups: music listening (ML), autogenic training (AT), music-assisted autogenic training (MAT), or a control group participants, with n = 10 participants per group. The participants in experimental groups received four 30-minute sessions with an assigned treatment, once a week during a 4-week experiment period. The participants in the control group continued their regular medical treatment as prescribed by the doctor without receiving any other relaxation treatment. However, they were still aware of the research and their responsibilities for the study. The Migraine Assessment (MIDAS) and Migraine-Specific Quality of Life (MSQOL) questionnaire were used to investigate a migraine patients' quality of life collected before and after the 4-week experiment for all subjects. The physiological and psychological relaxation responses of migraine patients were measured by relaxation levels and forehead temperature recorded before and after each treatment session for the participants in three treatment conditions. The effect of the relaxation treatments on daily living of migraine patients was examined through the frequency and intensity of migraine headaches, and the amount of medication taken for migraine headaches during the 4-week experiment as recorded in participants' diary for all participants. The results found significant differences from pre- to posttest on the MIDAS, MSQOL, and relaxation levels while no significant was found among the groups. The analysis of forehead temperature showed no significant difference from pre- to posttest and among the groups. A one-way ANOVA was performed on the frequency, intensity, and amount of medication taken for migraine headaches during the 4-week experiment period. While results yielded no significant difference among the groups, the data indicate that the participants in the three treatment groups reported fewer migraine headaches, lower degrees of headache intensity, and less medication taken for migraine headaches than participants in the control group. A conclusion drawn from this study is that music listening itself as a relaxation treatment, or as an adjunct to other relaxation techniques can be effective in the treatment of migraine headaches.

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Harmonic Preference of Primary and Secondary School Students Depending on Age and Musical Training (연령과 음악적 배경에 따른 아동 및 청소년의 화음 선호도)

  • Kim, Hye-Kyung
    • Journal of Music and Human Behavior
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    • v.12 no.1
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    • pp.23-42
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    • 2015
  • This study investigated the harmonic preference of children and adolescents depending on age and musical training. A total of 684 primary and secondary school students participated in this study. For this study, a four-measure melody was composed and constructed in four levels of harmonic complexity, determined by the rate of nonharmonic notes used and immediacy of harmonic resolution. Participants rated the degree of their perceived complexity and their preferences after listening to each musical stimulus. Ratings from the participants were analyzed in terms of the effect of age and the length of musical training. The results showed that younger students demonstrated little to no change in their preference regardless of the complexity level. Middle and high school students showed significantly decreased preference with increased harmonic complexity. High school students with more musical instrument training perceived changes in harmonic complexity more sensitively and showd higher level of optimal complexity. Younger students was affected by musical training relatively less than older students. This study presents the baseline data to be considered when determining the appropriate level of harmonic complexity for music appreciation of young population.

Dietary Exposure Assessment of Arsenic in Korean Adults (한국 성인에 있어서 식이를 통한 비소 노출 평가)

  • Im, Ruth;Youm, Hyun-Cher;Kim, Dong-Won;Bae, Hye-Sun;Ahn, Su-Ju;Ryu, Doug-Young;Choi, Byung-Sun;Park, Jung-Duck
    • Environmental Analysis Health and Toxicology
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    • v.25 no.4
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    • pp.307-314
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    • 2010
  • Objectives : Arsenic (As) is ubiquitously distributed in the environment and has been known as a human carcinogen. The main source of arsenic exposure in general population is an oral route through As-contaminated water and foods. This study was performed to estimate the daily intake of As from diet and associated factors in Korean adults. Methods : We investigated 590 adults, 249 males and 341 females, with age of 20 years and older, who had not been exposed to the As occupationally. Study subjects were interviewed for demographic characteristics, lifestyles and diets during the last 24 hours. The estimation of As intake daily was based on amount of food consumption and As concentration in each food by using database of As concentrations in 117 food species. Results : Daily As intake was estimated as $56.46\;{\mu}g$/day, $56.60\;{\mu}g$/day in male and $56.36\;{\mu}g$/day in female. As intake was not significant from sex, age group, smoking and alcoholic habits, while was by occupation with the most intake of As in fishery. The daily As intakes was positively correlated with the total food consumption, specifically related with fishes and shellfishes, seaweeds, oils, grains and flavors. About 75% of As intake from diet was contributed by seafoods, such as $32.07\;{\mu}g$/day from fishes & shellfishes and $10.05\;{\mu}g$/day from seaweeds. However, it is necessary to evaluate if the dietary As intake affects on the levels of As in the body. Conclusions : The amount of As intake daily in Korean adults was estimated as $56.46\;{\mu}g$/day, and is determined mainly by diet behavior. The seafoods, such as fishes & shellfishes and seaweeds, is major source of As exposure from diet in Korean.

A Study on Unconstitutionality of Insurance Premium Rating System in Accordance with National Health Insurance Act. - Focused on Age and Gender in Premium Rating Standards Activity Rate and Living Standards of the Local Insured - (국민건강보험법상 보험료부과체계에 관한 법적 고찰 -지역가입자 생활수준 및 경제활동 참가율 부과기준 중 성과 연령을 중심으로 -)

  • Song, Kimin;Jeong, Jeong-Ile
    • The Korean Society of Law and Medicine
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    • v.15 no.1
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    • pp.185-209
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    • 2014
  • While the local health insurance and the employment-based insurance were integrated in July 2000, the insured is divided into employment-based insured and the local insured and the relevant premium has been applied to both groups. The health insurance premium having the feature of social solidarity has to be determined depending on income, that is, the ability to pay in accordance with the principles of social insurance. While employment-based insurance premium has been determined depending on the earned income, the local insurance premium for the local insured has been determined by scoring gross income(evaluated income), property and possession of automobiles. A variety of improvement approaches has been implemented including introduction of the employment-based insurance premium ceiling system (2002) and the change of property scoring system for the local insured (2006). However, the health insurance system which was merged in 2000 has been implemented up to now without significant change even though there were lots of socio-demographic change including increase of income level and the population structure such as low birth and aging. In other words, it is required to implement the premium rating system securing the income-based equity. Nevertheless, it was inevitable to apply the diverse rating standards in the early stage because it was very difficult to verify the income of the self-employed. Although the income verification rate was significantly increased from 23% in 1989 to 44% in 2010, the irrational standards including property, automobiles, living standard and activity rate have been still applied to the local insured because it is difficult to secure the validity of insurance premium rating system and it severely lacks of security. This paper investigated whether the current insurance premium rating system for the local insured imposing the premium on the basis of 'gender' and 'age' complies with the basic human rights secured by the current Constitution of the Republic of Korea with respect to the practical and theoretic irrationality of insurance premium rating system and standards for he local insured. In accordance with the analysis results, this paper proposed the approach to improve the system.

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Toxoplasma gondii B1 Gene Detection in Feces of Stray Cats around Seoul, Korea and Genotype Analysis of Two Laboratory-Passaged Isolates

  • Jung, Bong-Kwang;Lee, Sang-Eun;Lim, Hyemi;Cho, Jaeeun;Kim, Deok-Gyu;Song, Hyemi;Kim, Min-Jae;Shin, Eun-Hee;Chai, Jong-Yil
    • Parasites, Hosts and Diseases
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    • v.53 no.3
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    • pp.259-263
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    • 2015
  • The increasing prevalence of Toxoplasma gondii infection in the human population in the Republic of Korea (= Korea) is due to various reasons such as an increase in meat consumption. However, the importance of cats in transmitting T. gondii infection through oocysts to humans has seldom been assessed. A total of 300 fecal samples of stray cats captured around Seoul from June to August 2013 were examined for T. gondii B1 gene (indicating the presence of oocysts) using nested-PCR. Fourteen (4.7%) of 300 cats examined were positive for B1 gene. Female cats (7.5%) showed a higher prevalence than male cats (1.4%). Cats younger than 3 months (5.5%) showed a higher prevalence than cats (1.5%) older than 3 months. For laboratory passage of the positive samples, the fecal suspension (0.2 ml) of B1 gene positive cats was orally inoculated into experimental mice. Brain tissues of the mice were obtained after 40 days and examined for the presence of tissue cysts. Two isolates were successfully passaged (designated KNIH-1 and KNIH-2) and were molecularly analyzed using the SAG5D and SAG5E gene sequences. The SAG5D and SAG5E gene sequences showed high homologies with the ME49 strain (less virulent strain). The results indicated the importance of stray cats in transmitting T. gondii to humans in Korea, as revealed by detection of B1 gene in fecal samples. T. gondii isolates from cats were successfully passaged in the laboratory for the first time in Korea.

A Case with Perinatal Hypophosphatasia Caused by the ALPL Mutations (ALPL 유전자의 돌연변이를 가진 양성 주산기 저인산증 1례)

  • Kim, Joonil;Kang, Eungu;Kim, Yoon-Myung;Lee, Beom Hee;Kim, Gu-Hwan;Yoo, Han-Wook
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.16 no.3
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    • pp.141-147
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    • 2016
  • Hypophosphatasia is caused by the mutations in ALPL, which encodes tissue-nonspecific alkaline phosphatase (TNSALP). It can be inherited either in an autosomal dominant or recessive manner. Clinically, hypophophosphatasia is characterized by skeletal findings similar to those in rickets or osteomalacia, but serum alkaline phosphatase levels are decreased in the affected patients. Hypophosphatasia can be classified into six clinical forms according to age at diagnosis and severity of symptoms: perinatal lethal, infantile, childhood, adult, odontohypophosphatasia, and perinatal benign. As being a very rare disease, only one case has been reported in Korean population. Here we describe a case with perinatal benign hypophosphatasia with recessive ALPL mutations. Bowing of lower legs was detected in prenatal period and low serum alkaline phosphatase level was noted after birth. During the follow-up evaluation for 4.5 years, bone mineralization and legs bowing were improved but the growth retardation was persistent. As the recombinant bone-targeted human TNSALP became available, the clinical improvement of the affected patients is expected including the case described here with this treatment. More efforts are needed to identify the cases affected by hypophosphatasia.

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Water Quality Improvement of Pocheon Stream Using Freshwater Bivalves: Development and Operation of Continuous Removal of Organic Matter in Streams (S-CROM) (포천천 수질개선을 위한 패류의 이용 하천형 유기물 제어(S-CROM) 기술의 적용)

  • Kim, Baik-Ho;Lee, Ju-Hwan;Kim, Yong-Jae;Hwang, Su-Ok;Hwang, Soon-Jin
    • Korean Journal of Ecology and Environment
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    • v.42 no.3
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    • pp.317-330
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    • 2009
  • To diminish the levels of organic matters, a novel S-CROM (continuous removal of organic matters in the stream system using freshwater bivalve), was developed and applied to the polluted stream discharging from the wastewater treatment plant, Pocheon stream, Pocheon city (Korea). Major pollutants of the stream were human population and industrial wastewaters. The study was conducted at a small dam constructed within the stream, often called 'bo', and designed with four tanks; no mussels and no sediment (negative control), no mussels and sediment (positive control), 30 mussels and sediment (D1), and 60 mussels and sediment (D2). Physicochemical and biological parameters were measured at 12 hours interval (day and night) after mussel stocking. Results indicated that Anodonta woodiana Lea (D2) clearly removed approximately 72% of chl-$\alpha$ and 57% of suspended solids on second day, however, there were no differences in removal activities between animal densities (P>0.5). Dislike a laboratory CROM system, which previously developed, there were no huge release of nutrient ($NH_3$-N and SRP), due perhaps to the higher flow rate and the lower animal density. Therefore, we may suggest that if we can determine the relevant current and the animal density considering the stream state, an S-CROM system has a strong potential to water quality improvement of eutrophic streams. Some characteristics on both CROM and S-CROM were compared.