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Tamoxifen Resistance and CYP2D6 Copy Numbers in Breast Cancer Patients

  • Motamedi, Sahar;Majidzadeh, Keivan;Mazaheri, Mahta;Anbiaie, Robab;Mortazavizadeh, Seyed Mohammad Reza;Esmaeili, Rezvan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6101-6104
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    • 2012
  • Background: Breast cancer accounts about one million from total annual ten million new diagnosed cases of neoplasia worldwide and is the main cause of death due to cancer in women. Tamoxifen is the most popular selective estrogen receptor modulator used in anti estrogen treatments. Tamoxifen must be converted into its metabolite endoxifen for biologic effects; this conversion process is catalysed by highly polymorphic cytochrome P450 2D6 (CYP2D6). This study surveyed copy number variation of the CYP2D6 gene and its possible correlation with Tamoxifen resistance in breast cancer patients. Methods: This case control study was performed on samples taken from 79 patients with breast cancer who used tamoxifen in Yazd and Tehran Cities, Iran. Real time reactions were conducted for 10 healthy samples using the comparative $C_t$ (Cycles threshold) method, each pair of genes being compared and samples with ratios around 1 were taken as control samples. Proliferation reactions were done by Real-Time PCR ABI Prism 7500. All registered data were transformed into SPSS 15 program and analyzed. Results: Efficiency of PCR for both CYP2D6 and ALB genes was 100%. From all 23 drug resistant patients 21.7% had one copy, 47.8% two copies and 30.4% had three copies. Also from all 56 drug sensitive patients, 26.8% had one copy, 51.8% two copies and 21.4% had three copies. The percentage of patients with one and two copies was similar between two groups but patients with three copies were more likely to belong to the drug resistant group more. Odd ratios for one and two copies were 0.759 and 0.853 respectively, indicating possible protective effects while that for three copies was 1.604. Conclusions: Based on our study there is no significant link between CYP2D6 gene copy numbers and tamoxifen resistance in women with breast cancer. But more studies considering other influencing factors appear warranted.

Trends in Epidemiology, Clinical and Histopathological Characteristics of Breast Cancer in Iran: Results of a 17 Year Study

  • Afsharfard, Aboulfazl;Mozaffar, Mohammad;Orang, Elahe;Tahmasbpour, Eisa
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6905-6911
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    • 2013
  • Background: Breast cancer (BC) is the top cancer among women worldwide and the most frequent malignancy among Iranian women over the past few decades. The increasing trend and high mortality rate of BC in the developing world necessitates studies concentrating on its characteristics in countries in Asia. The current study focused on clinical and histopathological features of BC among Iranian females. Materials and Methods: This retrospective study involved 714 Iranian patients with histopathologically proven BC undergoing resection of primary tumours and axillary clearance. Demographic, clinical and histopathological data were obtained and studied between ten year age groups (${\leq}40$ years, 41-50 years, 51-60 years, 61-70 years, and ${\leq}71$ years) in four chronologic phases from 1994-2009. Results: Mean age of patients was $49.4{\pm}13.1$ years. Most of cases (33.2%) were in 41-50 group. Mean size of primary tumors was $3.94{\pm}2.47$ cm and 87.1% of cases had infiltrative ductal carcinoma. Modified radical mastectomy was the most common method of surgery carried out (48.8%). Some 57.1% of tumors were in pT2 and tumor size decreased significantly during the period (p<0.05). The most common BC stage was llla (27%). Lower BC stages (0 and 1) constituted 13.9% of the diagnosed tumors. Our series of patients aged ${\leq}40$ had larger tumors (mean $4.73{\pm}3.02$ cm) compared to older age groups (p=0.003). Lower stages (0 and I) were more frequent among the oldest patients while nearly 50% of patients aged ${\leq}40$ had tumor stage III. We also observed a significant decreasing trend in the mean LN count (p<0.05) and blood vessel invasion (p=0.023) from younger to older age groups. Conclusions: More aggressive disease for younger age groups, earlier peak incidence age and high rate of advanced BC at the time of diagnosis among Iranian women, were the main findings of this study.

Evaluation of Flexural Properties of Indirect Gum-Shade Composite Resin for Esthetic Improvement (심미성 향상을 위한 간접수복용 Gum-Shade 복합레진의 굽힘 특성 평가)

  • Im, Yong-Woon;Hwang, Seong-Sig
    • Journal of dental hygiene science
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    • v.15 no.4
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    • pp.407-412
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    • 2015
  • This study investigated flexural properties of indirect Gum-shade composite resins for esthetic improvement. The material utilized in this study was Crea.lign, Twiny flow and Twiny paste (TP). Ten specimens were fabricated with a dimension of $25{\times}2{\times}2mm$ according to the ISO 4049. After fabrications, specimens were stored in the distilled water for 24 hours at the temperature of $37^{\circ}C$. Three-point bending test was performed in universal testing machine (Instron 3344; Instron, USA) at a crosshead speed of 1 mm/min until the failure occurred. TP exhibited a higher flexural strength (FS) and flexural modulus (FM) compared to the flowable materials. There were significant differences among the three materials in FS and FM. However, there was no significant difference in work of fracture (WOF) in all tested materials (p>0.05). In Weibull analysis, TP showed the greatest Weibull modulus which means a higher reliability of the materials. Also, Gum-shade composite resins revealed a strong correlation in all flexural properties. There was a positive correlation in FS-FM ($r^2=0.99$) and a negative correlation between FS-WOF and FM-WOF ($r^2>0.97$). Therefore, this confirmed that flexural property was important for mechanical behavior evaluation and useful information. To addition, this improved among mechanical properties correlation of materials as important factor.

Preclinical Study of DA-5018, a Non-narcotic Analgesic Agent

  • Kim, Soon-Hoe
    • Proceedings of the PSK Conference
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    • 2000.04a
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    • pp.70-81
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    • 2000
  • DA-5018 is a synthetic capsaicin derivative under development as a non-narcotic a analgesic ag$\varepsilon$nt. DA-50 18 showed a potent analgesic activity against acute and chronic pain m model(Tablel, 2.), but it had a narrow margin of safety. DA-5018 did not bind to opioid(${\kappa}, {\delta}, {\mu}$), NKl, CGRP receptors in vitro and its analgesic effect was not antagonized by naloxone, a and it did not develop analgesic tolerance. In addition DA-5018 had no inhibitory effects against c cyclooxygenase and 5-lipooxygenase activities. DA-5018 significantly increased the relcase of substance P from the slices of the rat spinal cord. These results suggest that DA-50 18 is not a narcotic nor aspirin-like analgesic and the release of substance P is one of analgesic mechanism of action of DA-5018. We found that DA-5018 was almost ten times more potent and was at l least IOO-times less irritable compared to capsaicin. Accordingly development of topical formula was adopted. Topical formula was desiged and screened by flux test of DA-5018 using hairless mouse skin and several formulas were selected. With these topical formulas we a assessed the analgesic efficacy and carried out the toxicity, skin irritation and pharmacokinetic studies. In streptozotocin-induced hyperalgesic rat and 50 % galactose-fed hyperalgesic rat as diabetic pain models, DA-5018 cream increased the pain thresh이ds up to 77.0% and 24.4% respectively, while Zostrix-HP(capsaicin cream) incr$\varepsilon$as cd by 65.9% and 21.0%. DA-5018 c cream showed a good analgesic effect as welI in FCA-induced arthritic rat. DA-5018 cream did not show any toxicological signs in acute and chronic toxicity test and had little skin irritation in car swclIing and scratching t$\varepsilon$st. Pharmacokinetics of DA-50 18 were studied after topical application of ${14}^C$-Iabelled or unlabelIed DA-5018 cream. Plasma and skin concentrations c except applied skin wcre below the dctection limit and after 7-day cummulative application, plasma concentrations were also below detection limit DA-50 18 may have an advantag$\varepsilon$ ov$\varepsilon$r c capsaicin and is now being developed as a topical agent for the treatment of pains. DA-50 18 cream was approved for Korean IND and is now under a Phase II clinical study for arthritic pain a after finising Phase I study. DA-50 18 was also liscensed out to Stiefel Company in America in

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Screening for Anti-inflammatory Activities in Extracts from Korean Herb Medicines (국산 생약 추출물의 항염증 활성 스크리닝)

  • An, Sang Mi;Kim, Hyoung Gun;Choi, Eun Jung;Hwang, Hyoung Hoon;Lee, Eunseok;Baek, Ji Hwoon;Boo, Yong Chool;Koh, Jae Sook
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.40 no.1
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    • pp.95-108
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    • 2014
  • Cosmetics are products used over long periods by the public, and their safety is very important. Contact dermatitis induced by cosmetics is the result of an inflammatory response of the skin to direct irritancy. The initial event that this inflammatory response is observed is the release of pro-inflammatory cytokines. In this study, the anti-inflammatory activities of extracts from Korean herb medicines were investigated using RAW264.7 macrophage. Among the fifty one extracts tested, the ethanol extracts from Biotae Orientalis Folium, Biotae Orientalis Folium (roasted), Cyperi Rhizoma, Nepetae Spica, Benincasae Semen, Dioscoreae Rhizoma, Dioscoreae Rhizoma (roasted), Mori Ramulus, Pini Ramulus and Alismatis Rhizoma reduced the cytotoxicity and inhibited the productions of Nitric oxide (NO) and cytokines such as interleukin (IL)-1${\beta}$, IL-6 and tumor necrosis factor (TNF)-${\alpha}$n lipopolysaccharide (LPS)-induced RAW264.7 macrophage. Additionally, they didn't induce the skin irritation when tested the human patch test. Overall, the result of this study suggests that the extracts of the ten Korean herb medicines are useful cosmetic agents for preventing the skin irritation.

INTONATION OF TAIWANESE: A COMPARATIVE OF THE INTONATION PATTERNS IN LI, IL, AND L2

  • Chin Chin Tseng
    • Proceedings of the KSPS conference
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    • 1996.10a
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    • pp.574-575
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    • 1996
  • The theme of the current study is to study intonation of Taiwanese(Tw.) by comparing the intonation patterns in native language (Ll), target language (L2), and interlanguage (IL). Studies on interlanguage have dealt primarily with segments. Though there were studies which addressed to the issues of interlanguage intonation, more often than not, they didn't offer evidence for the statement, and the hypotheses were mainly based on impression. Therefore, a formal description of interlanguage intonation is necessary for further development in this field. The basic assumption of this study is that native speakers of one language perceive and produce a second language in ways closely related to the patterns of their first language. Several studies on interlanguage prosody have suggested that prosodic structure and rules are more subject to transfer than certain other phonological phenomena, given their abstract structural nature and generality(Vogel 1991). Broselow(1988) also shows that interlanguage may provide evidence for particular analyses of the native language grammar, which may not be available from the study of the native language alone. Several research questions will be addressed in the current study: A. How does duration vary among native and nominative utterances\ulcorner The results shows that there is a significant difference in duration between the beginning English learners, and the native speakers of American English for all the eleven English sentences. The mean duration shows that the beginning English learners take almost twice as much time (1.70sec.), as Americans (O.97sec.) to produce English sentences. The results also show that American speakers take significant longer time to speak all ten Taiwanese utterances. The mean duration shows that Americans take almost twice as much time (2.24sec.) as adult Taiwanese (1.14sec.) to produce Taiwanese sentences. B. Does proficiency level influence the performance of interlanguage intonation\ulcorner Can native intonation patterns be achieved by a non-native speaker\ulcorner Wenk(1986) considers proficiency level might be a variable which related to the extent of Ll influence. His study showed that beginners do transfer rhythmic features of the Ll and advanced learners can and do succeed in overcoming mother-tongue influence. The current study shows that proficiency level does play a role in the acquisition of English intonation by Taiwanese speakers. The duration and pitch range of the advanced learners are much closer to those of the native American English speakers than the beginners, but even advanced learners still cannot achieve native-like intonation patterns. C. Do Taiwanese have a narrower pitch range in comparison with American English speakers\ulcorner Ross et. al.(1986) suggests that the presence of tone in a language significantly inhibits the unrestricted manipulation of three acoustical measures of prosody which are involved in producing local pitch changes in the fundamental frequency contour during affective signaling. Will the presence of tone in a language inhibit the ability of speakers to modulate intonation\ulcorner The results do show that Taiwanese have a narrower pitch range in comparison with American English speakers. Both advanced (84Hz) and beginning learners (58Hz) of English show a significant narrower FO range than that of Americans' (112Hz), and the difference is greater between the beginning learners' group and native American English speakers.

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Characteristics of Rural Amenity Resources for Anmyeon-island (안면도의 농촌어메니티자원 특성 분석)

  • Son, Jae-Gwon;Choi, Jin-Kyu;Goh, Nam-Young
    • Journal of Korean Society of Rural Planning
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    • v.17 no.1
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    • pp.67-77
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    • 2011
  • This survey is focused on analyzing amenity resources for the purpose of offering basic sources for balanced development and the activation of sightseeing in Anmyen-island which has superior landscape resources and the result follows as this. 1. As a result of selecting "Amenities characterized in isles" and comparing their applications in order to choose amenity resource surveying method which is suitable for the isle districts where beaches, tidelands, fishing villages and so on are formed, it was considered that the surveying method of the rural amenity resource in the Korean Society of Rural Planning could be properly used. 2. In spite of a variety of amenity resources besides ten beaches, Anmyeon-island has been developed only focused on beaches. Therefore, it is highly recommended to develop new sightseeing courses which connect beaches with adjacent amenity resources such as theme programs. 3. It proved that compared with Anmyeoneup, Gonammyeon has superior landscape resources and higher special product rates, which is caused by the fact that it doesn't have various kinds of amenities. As diverse fish inhabit the sea and tidelands in Gonammyeon, it is beneficial for activating sightseeing tours to develop fishing village experiencing programs including going fishing. 4. Anmyen-island can be divided into East district and West distict by the national road no,77 and two districts have different distributional features of sightseeing amenity resources. In the west district, amenity resources such as coastal sightseeing routes, large event halls, and resorts have been activated in addition to fourteen beaches which have already been developed while the amenity resources in the east like fishing villages, tidelands, and salt fields have not been activated. Accordingly, for activating balanced sightseeing development in Amyeon-island, it is required to make plans which can incorporate the east amenity resources of sea sightseeing and the west amenity resources of fishing village experiencing programs. As a way, constructing sightseeing routes connecting the west and the east district or making a detour lane connecting beaches in the west, Anmyeon pine trees in the center, and fishing villages in the east.

Field Comparison of Korean Diffusive Sampler and Charcoal Tube Methods for Determination of Organic Vapors (공기중 유기용제 농도 측정에 있어서 국산 확산포집기와 활성탄관의 비교연구)

  • Cho, Sook Ja;Paik, Nam Won
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.7 no.1
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    • pp.33-48
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    • 1997
  • Korean diffusive sampler (KDS) and charcoal tube (CT) were used for sampling n-hexane, trichloroethylene and toluene in air KDS was made by Department of Environmental Health, SNU-SPH in 1995. Surveys were conducted at ten industrial plants with organic solvents. The relationship between two sampling methods was examined by linear regression analysis, and concentrations by two sampling methods were compared using paired t-test. The results are as follows: 1. The geometric means by CT and KDS methods were 3.26ppm and 3.32ppm for n-hexane, 5.07ppm and 6.34ppm for toluene, and 7.18ppm and 7.90ppm for toluene, respectively. There was no significant difference between results by CT and KDS methods in three organic vapors (p>0.05). When linear regression analysis was performed, two sampling methods were highly related ; correlation coefficients were 0.98, 0.90 and 0.96 for n-hexane, toluene and trichloroethylene, respectively. 2. Airborne concentrations of n-hexane (n=21) were below 0.5 TLV level. The GM by two methods were almost same (3.09 ppm). And there was no significant difference between results by two methods (p>0.05). 3. Since toluene and trichloroethylene concentrations showed several levels, appropriate sampling rates were applied for each level. The GM of toluene concentrations by two methods at 0.5 TLV level were 3.75ppm and 5.48ppm. The KDS method overestimated the toluene concentrations at 0.5 TLV level (p<0.05). The GM values of toluene concentrations at 1 TLV level were 31.80ppm and 25.38ppm and at 2 TLV level were 64.13 ppm and 51.37 ppm. The KDS method underestimated concentration at both level (p<0.05). For trichloroethylene, the GM at 0.5 TLV level were 4.97 ppm and 7.11ppm. The KDS method overestimated the concentration of trichloroethylene (p<0.05). In conclusion, concentrations of three organic vapors measured by CT and KDS were not significantly different and results by two methods were highly related. But at contain concentrations, the levels by method were significantly different. Therefore, it is suggested that sampling rate of KDS should be studied simultaneously using CT method for organic vapors.

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The development and validation of a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) procedure for the determination of fluoroquinolones residues in chicken muscle using modified QuEChERS (quick, easy, cheap, effective, rugged and safe) method

  • Park, Sunjin;Kim, Hyobi;Choi, Byungkook;Hong, Chung-Oui;Lee, Seon-Young;Jeon, Inhae;Lee, Su-Young;Kwak, Pilhee;Park, Sung-Won;Kim, Yong-Sang;Lee, Kwang-jick
    • Korean Journal of Veterinary Service
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    • v.42 no.4
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    • pp.289-296
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    • 2019
  • A novel rapid procedure with liquid chromatography tandem mass spectrometry (LC-MS/MS) detection has been developed by changing various conditions including sample preparation such as QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) methodology. This work has been involved the optimization and validation of detection method for fluoroquinolones which are widespread used in livestock especially in the chicken. Five grams of homogenized chicken muscle were extracted with QuEChERS EN and acetonitrile containing 5% formic acid and cleaned with anhydrous magnesium sulfate and C18 sorbent. The separation was performed on Acquity UPLC HSS T3 (2.1 mm×100 mm, 1.8 ㎛) column. The mobile phase A and B were composed of water containing 0.1% formic acid and acetonitrile containing 0.1% formic acid, respectively. Flow rate was 0.25 mL/min and column temperate was 40℃. LC-MS/MS with multiple reaction monitoring has been optimized for ten fluoroquinolones (ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, marbofloxacin, norfloxacin, ofloxacin, orbifloxacin, pefloxacin and sarafloxacin). The method developed in this study has been presented good linearity with correlation coefficient (R2) of 0.9971~0.9998. LOD and LOQ values ranged from 0.09 to 0.76 ppb and from 0.26 to 2.29 ppb, respectively. The average recoveries were from 77.46 to 111.83% at spiked levels of 10.0 and 20.0 ㎍/kg. Relative standard deviation (%) ranged 1.28~11.90% on intra-day and 3.10~8.38 % on inter-day, respectively. This analysis method was applicable to the livestock residue laboratories and was expected to be satisfactory for the residue surveillance system.

Evaluation of the Dressed Soil applied in Mountainous Agricultural Land (산지농경지에 투입되는 모재성토의 특성과 농업환경에 미치는영향)

  • Joo, Jin-Ho;Park, Chol-Soo;Jung, Yeong-Sang;Yang, Jae-E;Choi, Joong-Dae;Lee, Won-Jung;Kim, Sung-Il
    • Korean Journal of Soil Science and Fertilizer
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    • v.37 no.4
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    • pp.245-250
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    • 2004
  • Farmers typically apply the dressed soil (coarse saprolite) for various reasons in the sloped upland with high altitude in Kangwon province. However, little researches on the impacts of application of dressed soil in uplands were conducted. Therefore, it is necessary to assess soil quality in this area and to study adverse effects on soil and water due to application of dressed soil. Coarse saprolite itself showed signiScantly poor chemical properties, Particularly P and organic matter contents were not enough for crops to grow. With respect to biological qualities such as enzyme activity and microbial population, coarse saprolite itself showed poor qualities. For example, bacterial population in coarse saprolite contains six times or ten times smaller populations. Based on survey at Jawoon-ri in Hongchon-gun, this region is susceptible for soil erosion due to massive amounts of coarse saprolite application, undesirably long slope length, etc. When weestimated soil loss, more than 40% of farming field in this region exceeded $11.2MT\;ha^{-1}\;yr^{-1}$. According to experiment by installing sediment basins. the sediment basin with up-down tillage and application with dressed soil had the highest soil loss and runofT, while the sediment basin with contour tillage and without soil dressing showed the lowest soil erosion and runoff.