• 제목/요약/키워드: TP53

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Hereditary Genes and SNPs Associated with Breast Cancer

  • Mahdi, Kooshyar Mohammad;Nassiri, Mohammad Reza;Nasiri, Khadijeh
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권6호
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    • pp.3403-3409
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    • 2013
  • Breast cancer is the most common cancer among women affecting up to one third of tehm during their lifespans. Increased expression of some genes due to polymorphisms increases the risk of breast cancer incidence. Since mutations that are recognized to increase breast cancer risk within families are quite rare, identification of these SNPs is very important. The most important loci which include mutations are; BRCA1, BRCA2, PTEN, ATM, TP53, CHEK2, PPM1D, CDH1, MLH1, MRE11, MSH2, MSH6, MUTYH, NBN, PMS1, PMS2, BRIP1, RAD50, RAD51C, STK11 and BARD1. Presence of SNPs in these genes increases the risk of breast cancer and associated diagnostic markers are among the most reliable for assessing prognosis of breast cancer. In this article we reviewed the hereditary genes of breast cancer and SNPs associated with increasing the risk of breast cancer that were recently were reported from candidate gene, meta-analysis and GWAS studies. SNPs of genes associated with breast cancer can be used as a potential tool for improving cancer diagnosis and treatment planning.

Identification of Marker Genes Related to Cardiovascular Toxicity of Doxorubicin and Daunorubicin in Human Umbilical Vein Endothelial Cells (HUVECs)

  • Kim, Youn-Jung;Lee, Ha-Eun;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • 제3권4호
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    • pp.246-253
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    • 2007
  • Doxorubicin and daunorubicin are excellent chemotherapeutic agents utilized for several types of cancer but the irreversible cardiac damage is the major limitation for its use. The biochemical mechanisms of doxorubicin- and daunorubicin- induced cardiotoxicity remain unclear. There are many reports on toxicity of doxorubicin and doxorubicin in cardiomyocytes, but effects in cardiovascular system by these drugs are almost not reported. In this study, we investigated gene expression profiles in human umbilical vein endothelial cells (HUVECs) to better understand the causes of doxorubicin and doxorubicininduced cardiovascular toxicity and to identify differentially expressed genes (DEGs). Through the clustering analysis of gene expression profiles, we identified 124 up-regulated common genes and 298 down-regulated common genes changed by more than 1.5-fold by all two cardiac toxicants. HUVECs responded to doxorubicin and doxorubicin damage by increasing levels of apoptosis, oxidative stress, EGF and lipid metabolism related genes. By clustering analysis, we identified some genes as potential markers on apoptosis effects of doxorubicin and doxorubicin. Six genes of these, BBC3, APLP1, FAS, TP53INP, BIRC5 and DAPK were the most significantly affected by doxorubicin and doxorubicin. Thus, this study suggests that these differentially expressed genes may play an important role in the cardiovascular toxic effects and have significant potential as novel biomarkers to doxorubicin and doxorubicin exposure.

고랭지 밭의 비점오염부하 저감을 위한 지표피복재와 토양개량제의 효과 (Effects of Surface Cover and Soil Amendments on the NPS load Reduction from Alpine Fields)

  • 원철희;신민환;이수인;금동혁;임경재;최중대
    • 한국농공학회논문집
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    • 제56권3호
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    • pp.47-53
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    • 2014
  • We investigated the effect of straw mat cover and soil amendments on the reduction of runoff, non-point source pollution load and yield of a Chinese cabbage from alpine fields. Two plots on sandy loam soil were prepared. Experimental treatments were control and rice straw mat cover (3,300 kg/ha)+Polyacrylamide (PAM) (5 kg/ha)+Gypsum (1 ton/ha) (SPG). A variety of Chinese cabbage was cultivated and runoff was monitored during a growing season in 2012. Monitoring was conducted to seven times. Runoff rate of SPG plot was lower than those of control plot. The reduction rate of runoff from SPG plot was 29.4 % compared to control plot. The reduction rate of suspended solids (SS), total nitrogen (TN) and total phosphorus (TP) load of SPG plot was 86.5 %, 34.7 % and 39.1 %, respectively. Yield of a Chinese cabbage from SPG plot (39,646 kg/ha) was greater than that of control plots (28,482 kg/ha). It was concluded that the use of SPG on soil surface could not only reduce the NPS pollution loads in receiving waters but also help increase the crop yield.

The Spectrum of Genetic Mutations in Breast Cancer

  • Sheikh, Asfandyar;Hussain, Syed Ather;Ghori, Quratulain;Naeem, Nida;Fazil, Abul;Giri, Smith;Sathian, Brijesh;Mainali, Prajeena;Al Tamimi, Dalal M
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권6호
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    • pp.2177-2185
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    • 2015
  • Breast cancer is the most common malignancy in women around the world. About one in 12 women in the West develop breast cancer at some point in life. It is estimated that 5%-10% of all breast cancer cases in women are linked to hereditary susceptibility due to mutations in autosomal dominant genes. The two key players associated with high breast cancer risk are mutations in BRCA 1 and BRCA 2. Another highly important mutation can occur in TP53 resulting in a triple negative breast cancer. However, the great majority of breast cancer cases are not related to a mutated gene of high penetrance, but to genes of low penetrance such as CHEK2, CDH1, NBS1, RAD50, BRIP1 and PALB2, which are frequently mutated in the general population. In this review, we discuss the entire spectrum of mutations which are associated with breast cancer.

건설현장 탁수제어를 위한 원통형 여과장치의 처리효율 분석 (Analysis of Treatment Efficiency of Cylinder-Shaped Filter for Construction Site Runoff Control)

  • 최종수;공영산;이정민;방기웅
    • 한국물환경학회지
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    • 제30권5호
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    • pp.532-538
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    • 2014
  • A cylinder-shaped filter was developed to manage the runoff from construction sites. Compressed air was used for back-washing and pore sizes of filter were $23{\mu}m$ and $46{\mu}m$. The turbid water was prepared using sediments in construction sites. The grain size analysis showed that grains smaller than $38{\mu}m$ and larger than $335{\mu}m$ in size constituted 34.4 % and 37.6 %, respectively. Removal efficiency of the filter on turbidity, SS, COD, TN and TP showed 25~37%, 20~40%, 50~55%, 23~27% and 14~20%, respectively, whereas their removal efficiecy by using coagulant PAC showed 77~84%, 70~83%, 53~60%, 27~36%, and 59~75%, respectively. The filtration time was determined to be around 10 to 20 minutes. Back-washing for 10 seconds by pressurized air resulted in a satisfactory regeneration efficiency. According to the aforementioned test results, the cylinder-shaped filter is effective in reducing turbidity and would be suitable for practical application in construction sites and farms.

New Lung Cancer Panel for High-Throughput Targeted Resequencing

  • Kim, Eun-Hye;Lee, Sunghoon;Park, Jongsun;Lee, Kyusang;Bhak, Jong;Kim, Byung Chul
    • Genomics & Informatics
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    • 제12권2호
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    • pp.50-57
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    • 2014
  • We present a new next-generation sequencing-based method to identify somatic mutations of lung cancer. It is a comprehensive mutation profiling protocol to detect somatic mutations in 30 genes found frequently in lung adenocarcinoma. The total length of the target regions is 107 kb, and a capture assay was designed to cover 99% of it. This method exhibited about 97% mean coverage at $30{\times}$ sequencing depth and 42% average specificity when sequencing of more than 3.25 Gb was carried out for the normal sample. We discovered 513 variations from targeted exome sequencing of lung cancer cells, which is 3.9-fold higher than in the normal sample. The variations in cancer cells included previously reported somatic mutations in the COSMIC database, such as variations in TP53, KRAS, and STK11 of sample H-23 and in EGFR of sample H-1650, especially with more than $1,000{\times}$ coverage. Among the somatic mutations, up to 91% of single nucleotide polymorphisms from the two cancer samples were validated by DNA microarray-based genotyping. Our results demonstrated the feasibility of high-throughput mutation profiling with lung adenocarcinoma samples, and the profiling method can be used as a robust and effective protocol for somatic variant screening.

Cu를 함유한 HSLA-100강 용접 열영향부의 미세 조직 및 인성 (Microstructure and Toughness of Weld Heat-Affected Zone in Cu-containing HSLA-100 steel)

  • 박태원;심인옥;김영우;강정윤
    • 열처리공학회지
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    • 제8권1호
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    • pp.53-64
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    • 1995
  • A study was made to characterize the microstructures and mechanical properties of the base metal and the heat-affected zone(HAZ) in Cu-bearing HSLA-100 steel. The Gleeble thermal/mechanical simulator was used to simulated the weld HAZ. The relationship between microstructure and toughness of HAZ was studied by impact test, O. M, SEM, TEM, and DSC. The toughness requirement of military specification value was met in all test temperatures for the base metal. The decrease of HAZ toughness comparing to base plate is ascribed to the coarsed-grain and the formation of bainite. Obliquely sectioned Charpy specimens show that secondary crack propagate easily along bainite lath. Improved toughness(240J) at HAZ of $Tp_2=950^{\circ}C$ is due to the fine grain, and reasonable toughness(160~00J) in the intercritical reheated HZA is achieved by the addition of small amount of carbon which affects the formation of "M-A". Cu precipitated during ageing for increasing the strength of base metal is dissolved during single thermal cycle to $1,350^{\circ}C$ and is precipitated little on cooling and heating during subsequent weld thermal cycle. Thus, the decrease of toughness does not occur owing to the precipitation of Cu.

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두경부암의 최신 표적치료 (What's New in Molecular Targeted Therapies for Head and Neck Cancer?)

  • 이서영;김혜련
    • 대한두경부종양학회지
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    • 제37권2호
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    • pp.11-17
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    • 2021
  • Head and neck cancer is the 6th most frequently diagnosed solid tumor in the world. Alcohol consumption, smoking, and HPV infection are associated with the incidence of head and neck squamous cell carcinoma (HNSCC). Although a multidisciplinary approach is a key strategy for the treatment of locally advanced HNSCC, systemic therapy is the mainstream of recurrent or metastatic HNSCC treatment. Stage IV HNSCC has a relatively poor prognosis with median overall survival of around one year. There have been many clinical trials to investigate the efficacy of target agents in the treatment of HNSCC. In the HPV-negative HNSCC, TP53 and CDKN2A are the most commonly mutated genes. In the HPV-positive HNSCC, the PI3K pathway is frequently altered. EGFR, PI3K, cell cycle pathway, MET, HRAS, and IL6/JAK/STAT pathway are explored targets in HNSCC. In this study, we review the target pathways and agents under research. We also introduce here umbrella trials of recurrent or metastatic HNSCC conducted by the Korea Cancer Study Group. The combination of target agents with immune checkpoint inhibitors or cytotoxic chemotherapies would be a future step in the precision medicine of HNSCC treatment.

논 생태 증진을 위해 설치된 둠벙의 물리.화학적 및 생물학적 특성 (Physicochemical and Biological Properties of Constructed Small-scale Ponds for Ecological Improvement in Paddy Fields)

  • 김재옥;신현상;유지현;이승헌;장규상;김범철
    • 생태와환경
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    • 제44권3호
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    • pp.253-263
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    • 2011
  • 본 연구는 인공 조성된 둠벙의 물리 화학적 및 생물학적 특성을 분석하여 둠벙의 복원 및 관리를 위한 기초 자료를 얻고자 수행한 연구로 다음과 같은 결론을 도출하였다. 연구대상지 둠벙의 면적은 4.6~14.1 $m^2$였으며 모양은 원형과 사각형 모양이 대부분이었다. 조사 둠벙 중 가장 자리에 석축이나 목축을 두르지 않은 둠벙들은 주변 둑이 매몰되어 수심이 얕아져 둠벙의 기능을 잃을 수 있다. 따라서 지속적인 둠벙 기능 유지를 위해서는 주변에 석축이나 목축 등을 둘러 매몰되는 것을 방지할 필요가 있다. 연구대상지의 수질환경은 COD, TN, TP의 경우 농업용수 기준을 초과한 수질등급을 보였으며 특히 TN의 농도는 평균 8.03 mg $L-1$로 농업용수 수질기준을 약 8.0배를 초과하는 농도분포를 보였다. 조사지역 둠벙의 질소농도가 높은 원인으로는 홍성지역의 높은 축산 밀도, 농경지 주변 산재해 있는 축사 시설과 축산폐수를 이용한 저장 액비 사용에 의한 것으로 판단된다. 오히려 농촌지역에서 둠벙과 같은 작은 저류지가 하천으로 유출되는 영양물질을 저감시켜 주는 소규모 침전지 역할도 할 수 있을 것으로 사료된다. 연구대상지 둠벙의 평균적인 모래함량, 유기물 함량, 유효인산 함량은 각각 53.4${\pm}$16.6%, 21.8${\pm}$9.74 g $kg^{-1}$, 12.8${\pm}$7.59 mg $kg^{-1}$로 나타났다. 둠벙의 토양 특성 조사결과 모래함량과 유효인산 농도는 둠벙 안정화를 위한 식생정착에 적합한 농도분포였으나 신규로 조성된 5곳의 둠벙에서는 유기물 함량이 높지 않아 식생 정착에 다소 시간이 소요될 것으로 판단된다. 연구 대상지 둠벙의 어류상은 붕어, 미꾸리, 미꾸라지, 드렁허리 4종이 출현하였으며 군집구조 분석결과 군집 안정도와 다양도 지수가 불량하게 나타났다. 이와 같이 단순한 어류상 구조는 둠벙이 주변 하천과 고립된 구조를 가지고 있기 때문에 논과 정수지역, 농수로 등 연중 수위와 환경변화가 큰 환경에 적응한 어종들만이 서식할 수 있기 때문으로 판단된다. 요인분석에서 도출된 요인점수(Facter score)를 바탕으로 조사한 둠벙을 구분한 결과, 요인점수 1에서 양의 값을 보이는 둠벙은 다른 둠벙에 비해 둠벙의 크기가 큰 것들로 구성되었으며 (Group I), 요인점수 2에서 양의 값을 보인 Group III은 다른 둠벙에 비해 유기물 농도가 높은 둠벙들로(S5, S6) 구성되었다(Fig. 4). 본 연구를 바탕으로 향후 농촌지역 둠벙의 복원 및 효율적 관리를 위해서는 둠벙과 주변하천과의 연계성, 둠벙의 크기를 비롯한 구조적 특성을 잘 고려해야 할 것으로 판단된다. 본 연구에서 거론하지 못한 둠벙 용수의 유 출입량, 둠벙 수체내 먹이 연쇄 구조 등 세부적인 부분에 대한 연구를 추가적으로 진행해야 할 것으로 판단된다.

광양만으로 유입되는 질소, 인의 점원 오염부하 특성 (The Characteristic of Point Source Loads for Nitrogen and Phosphorus to Gwangyang Bay, Korea)

  • 김도희;조현서;이영식
    • 한국해양환경ㆍ에너지학회지
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    • 제8권1호
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    • pp.1-8
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    • 2005
  • 2003년 4월부터 12월까지 광양만으로 유입되는 33개 하천과 공장에서 유입되는 질소와 인의 유입 부하랑을 조사하였다. 전체 담수 유입량 중 섬진강, 동천, 주교천, 서천 및 심금교천에서 96% 이상을 차지하며, 섬진강이 51-76%나 차지하고 있었다. DIN유입부하는 7월에 311,173 kg/월로 최대였고, 4월에 61,131 kg/월로 최소로 유입되고 있었다. 하천별로는 DIN의 전체 유입량 중 섬진강이 46-66%를 차지하고 있었다. 다음으로 동천이 1-20%, 덕양천이 12%, 길호천이 4%, 주교천이 5-6%를 차지하고 있었다. 그 외 하천에서는 1% 미만으로 유입되고 있었다. TN의 유입토 7월에 417,733 kg/월로 최대였고, 12월에 119.710 kg/월로 가장 낮게 유입되고 있었으며, 하천별로는 섬진강에서 36-64%로 동천과 함께 7, 8월에 높은 유입 율을 보였으며, 길호천과 덕양천에서는 4, 5월에 높은 유입 비율을 보였다. DIP의 유입은 7월에 」0,533 kg/월로 최대였고, 10월에 1,53 9kg/월로 최소를 보였다. 하천별 DIP의 유입비운은 섬진강이 2-55%로 강우기에 높은 비율을 보인 대신 비강우기에는 생활하수인 남수천에서 8-23 %, 덕양천에서 1-23%, 길호천에서 5-33%로 높은 비율을 보였다. TP의 유입부하는 166,279 kg/월로 7월에 최대였고, 12월에 4,837 kg/월로 최소를 보였으며, 하천별로는 섬진강에서 12-67%로 강우기에 높은 비율을 보였고, 비강우기에는 덕양천과 남수천, 길호천에서 높은 비율을 보였다. 이상의 결과로부터 광양만의 질소와 인의 유입부하를 제어하기 위해서는 먼저 남수천, 덕양천, 길호천의 유입을 그리고 동천과 주교천 및 공장폐수를 제어하는 것이 효과적일 것으로 판단되었다. 유입 하천수 중의 DIN/DIP 원소비는 강우기인 7, 8월에 약 18정도로 낮았고, 비강우피에는 16보다 헐씬 높은 DIN/DIP비를 보였다. 한편, TN/TP 원소비도 7, 8월에 일시적으로 7정도로 낮았고, 비강우기에는 16를 헐씬 상회하는 값을 대부분 보여 질소 보다는 유입수중의 인이 광앙만 해역의 식물플랑크톤의 성장을 제한할 것으로 추정되었다.

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