• 제목/요약/키워드: cancer biomarkers

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온라인 고체상추출과 LC-MS/MS 기술을 이용한 소변 중 파라벤류 분석 (Determination of 4 Parabens in Human Urine by Online SPE and LC-MS/MS Techniques)

  • 김정환;고영림;김판기;정지연;이은희;이승열;남혜선;이규식
    • 한국환경보건학회지
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    • 제38권6호
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    • pp.561-567
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    • 2012
  • Objectives: Parabens are widely used as antimicrobial agents in pharmaceuticals and cosmetics as well as by the food industry. Parabens have been reported to show weak estrogenic activity and be related to health effects such as allergic reactions and skin and breast cancer. We evaluated an online solid phase extraction (SPE) method coupled with LC-MS/MS technique using free and conjugated parent parabens in human urine for assessing human exposure to parabens. Methods: We employed LC/MS/MS through online solid phase extraction and column-switching techniques and analyzed free and conjugated parabens as biomarkers of human exposure. Four major parabens, methyl-paraben (MP), ethyl-paraben (EP), propyl-paraben (PP) and butyl-paraben (BP), were analyzed. Method validation was performed by sensitivity, accuracy, precision and comparison of the results of online SPE with offline SPE. Results: The limits of detection (LOD) were in the range of 0.2-2 ng/mL, and actual limits of quantification (LOQ) were in the range of 0.7-6 ng/mL urine, depending upon the compound. Accuracy was in the range of 98.3-106.4%, and precision was in the range of 1.3-8.7% (CV) depending upon the compound. We found a good correlation between the results of analysis by online SPE method and that by off-line SPE method. Conclusions: The online SPE method showed proper LOD and validated accuracy, precision and good correlation with the offline method for analyzing parabens in urine.

Lomens-P0 (mixed extracts of Hordeum vulgare and Chrysanthemum zawadskii) regulate the expression of factors affecting premenstrual syndrome symptoms

  • Lee, Yoon Seo;Jeon, Hyelin;Her, Yang-Mi;Lee, Da Eun;Jeong, Yong Joon;Kim, Eun Jeong;Choe, Tae Hwan;Suh, Hee Ju;Shin, Seung-Yeon;Park, Dae Won;Lee, Yeong-Geun;Kang, Se Chan
    • Nutrition Research and Practice
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    • 제15권6호
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    • pp.715-731
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    • 2021
  • BACKGROUND/OBJECTIVES: Premenstrual syndrome (PMS) is a disorder characterized by repeated emotional, behavioral, and physical symptoms before menstruation, and the exact cause and mechanism are uncertain. Hyperprolactinemia interferes with the normal production of estrogen and progesterone, leading to PMS symptoms. Thus, we judged that the inhibition of prolactin hypersecretion could mitigate PMS symptoms. MATERIALS/METHODS: Hordeum vulgare L. extract (HVE), Chrysanthemum zawadskii var. latilobum extract (CZE), and Lomens-P0 the mixture of these extracts were tested in subsequent experiments. The effect of extracts on prolactin secretion at the in vitro level was measured in GH3 cells. Nitric oxide and pro-inflammatory mediator expression were measured in RAW 264.7 cells to confirm the anti-inflammatory effect. Also, the hyperprolactinemic Institute for Cancer Research (ICR) mice model was used to measure extract effects on prolactin and hormone secretion and uterine inflammation. RESULTS: Anti-inflammatory effects of and prolactin secretion suppress by HVE and CZE were confirmed through in vitro experiments (P < 0.05). Treatment with Lomens-P0 inhibited prolactin secretion (P < 0.05) and restored normal sex hormone secretion in the hyperprolactinemia mice model. In addition, extracts significantly inhibited the expression of pro-inflammatory biomarkers, including interleukin-1𝛽, and -6, tumor necrosis factor-𝛼, inducible nitric oxide synthase, and cyclooxygenase-2 (P < 0.01). We used high-performance liquid chromatography analyses to identify tricin and chlorogenic acid as the respective components of HVE and CZE that inhibit prolactin secretion. The Lomens-P0, which includes tricin and chlorogenic acid, is expected to be effective in improving PMS symptoms in the human body. CONCLUSIONS: The Lomens-P0 suppressed the prolactin secretion in hyperprolactinemia mice, normalized the sex hormone imbalance, and significantly suppressed the expression of inflammatory markers in uterine tissue. This study suggests that Lomens-P0 may have the potential to prevent or remedy materials to PMS symptoms.

백서 혀에서의 4-nitroquinoline 1-oxide 유도 발암과정에서 Bcl-2 계 유전자의 발현 (Expression of Bcl-2 Family in 4-Nitroquinoline 1-Oxide-Induced Tongue Carcinogenesis of the Rat)

  • 최재욱;정성수;이금숙;김병국;김재형;국은별;장미선;고미경;정권;최홍란;김옥준
    • Journal of Oral Medicine and Pain
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    • 제30권3호
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    • pp.301-317
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    • 2005
  • 전 세계적으로 구강암의 빈도는 점점 증가 추세이며, 특히 한국인의 있어 혀(tongue)는 구강암이 가장 호발하는 장소이다. 구강암은 발암 단계에서부터 과증식 병소(hyperplastic lesion), 이형성(dysplasia) 및 상피내암(carcinoma in situ) 을 거쳐 악성 암종으로 발전하는 다단계 발암과정을 보이며, 분자 생물학적 변이가 구강암을 진행시킴이 널리 알려져 있다. 또한, 구강암은 일반적으로 암세포의 증식 및 고사(apoptosis)의 억제가 중요한 역할을 하고 있다 알려져 있다. 그리고, Bcl-2 family 는 세포 고사에 주요한 역할을 하고 있음이 알려져 있다. 그러나, 이들과 관련한 구강암 발생과정의 변화에 대해서는 널리 연구된 바가 없다. 본 연구는 백서에서 발암 물질인 4-NQO로 구강암을 유도시키고, 구강암 발생 다단계별로 Bcl-2 family의 mRNA 변화를 RT-PCR을 이용해 살펴보았다. Bcl-2 family는 크게 3군, 즉 1) anti-apoptotic, 2) pro-apoptotic, 그리고 3) BH3 only protein으로 분류할 수 있으며, 본 연구에서 anti-apoptotic molecules인 Bcl-w는 모든 군에서 발현이 감소되었으며, Bcl-2는 발현이 증가 되었다. pro-apoptotic molecules에서는 Bad가 제 3군 (편평세포암종)에서 발현이 증가 되었고, 나머지는 감소하였다. BH-3 only protein에서는 Bmf가 제 2군에서, BBC3가 제 3군에서 발현이 증가하였고, 나머지는 모든 군에서 감소하였다. 결론적으로, 4-NQO로 유도된 백서의 발암단계에서, Bcl-2 family의 mRNA 양상은 다양하게 관찰되었으나, Bad 및 BBC3 mRNA가 제 3군에서, Bmf mRNA가 제 2군에서의 발현이 특별함을 알 수 있어, 다단계 발암과정에서의 구강암을 진단하는데 유용하리라 사료된다.

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

  • 조성래;변정훈;김종인;이봉근;천봉권
    • Journal of Chest Surgery
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    • 제39권11호
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    • pp.828-837
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    • 2006
  • 배경: 악성종양에서 신생혈관 생성 및 당분해의 증가는 저산소 상태의 미세환경을 나타내며, 이는 종양의 침습성, 전이 및 환자의 예후와 관련이 있는 것으로 알려져 있다. Hypoxia-inducible factor 1(HIF-1)는 당원 수송체, 당분해 효소, 혈관내피세포 성장인자 등의 유전자의 전사를 활성화한다고 알려져 있다. 그리고 HIF-1의 전사 활성도는 HIF-$1{\alpha}$ 아단위의 표현이 조절되는 정도에 의존한다. 비소세포 폐암에서 HIF-$1{\alpha}$의 발현이 혈관 생성능, 종양세포 증식능 및 이상형 p53의 축적 등 종양의 생물학적 특성에 미치는 영향과 환자의 수술 후 예후와의 관계를 규명하고자 한다. 대상 및 방법: 1997년부터 1999년까지 비소세포 폐암으로 진단받고 전폐절제술 혹은 폐엽절제술을 시행 받은 59명의 폐암 환자들에서 얻어진 파라핀 조직 블록을 대상으로 하였다. ABC(avidin-biotin complex) 방법에 기초한 면역조직화학검사를 이용하여 암조직과 정상조직에서 HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), p53 단백의 발현을 조사하고, Ki-67의 발현을 이용한 증식지수를 측정하였다. HIF-$1{\alpha}$ 발현과 환자의 생존기간을 포함한 임상적-병리학적 변수들과의 상관관계, VEGF, p53의 발현과 증식지수와의 상관관계를 분석하였다. 결과: HIF-$1{\alpha}$의 과발현은 40.7%(24예/59예)였다. HIF-$1{\alpha}$의 과발현은 병리학적 TNM병기(p=0.004), T병기(p=0.020), N병기(p=0.004), 림프관/혈관 침범(p=0.019) 등과 관련이 있었다. 또 혈관내피세포 성장인자의 발현(p<0.001) 및 이상형의 p53의 발현(p=0.040)과 관련성이 있었다. Kaplan-Meier 생존분석에서 HIF-$1{\alpha}$의 과발현이 있는 환자의 5년 생존울은 22%로 HIF-$1{\alpha}$의 저발현 환자의 5년 생존율 61%에 비해 불량한 생존율을 보였고, 단변량분석과 다변량분석에서 HIF-$1{\alpha}$의 발현은 불량한 예후를 나타내는 인자로 관찰되었다. 결론: 이상의 결과로 비소세포 폐암 환자에서 HIF-$1{\alpha}$의 과발현은 종양내 신생혈관의 생성과 림프절 전이와 관련이 있는 표지자로 여겨지며, 수술 후 불량한 예후를 나타내었다.

파월국군장병의 고엽제 위해에 관한 예비적 역학조사 (A Preliminary Epidemiologic Study on Korean Veterans Exposed to Herbicides in Vietnam War)

  • 김정순;임현술;이홍복;이원영;박영주;김성수
    • Journal of Preventive Medicine and Public Health
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    • 제27권4호
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    • pp.711-734
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    • 1994
  • Among chemical agents in herbicides, dioxin (2, 3, 7, 8-tetrachloro dibenzo-$\rho$-dioxin : TCDD), a chemical contaminant in herbicides sprayed during the Vietnam War has been known to be the major agent causing toxic effects. Approximately 320,000 korean soldiers participated the Vietnam War from 1964 to 1974. Although the potential hazards of the herbicides among Korean veterans exposed were implicated, the problem had not been a public issue until 1991 when Korean veterans were informed U.S. companies, the herbicides manufacturer payed fund, from which a trust fund for New Zealand and Australian Class members were established in 1985. After a series of appeals and demonstration by the Korean Veterans demanding medical care and compensation for their serious health damages, a bill of medical care and compensation for herbicides victims was promulgated in March 1993 and become effective from May 1993, This study was carried out with two major objectives : the first to understand the health problems caused from the herbicides by reviewing literatures published, and the second to examine the nature and extent of health impacts among Korean veterans exposed and to develop valid study methods for the major study by interviewing and reviewing records on a part of veterans (638 persons) registered and completed medical examination in Seoul Veterans Administration Hospital from June to October 1993. The results obtained are as followings: 1. The literature review of 107 papers revealed that 1) Dioxin is teratogenic, carcinogenic and affects almost all organs including nervous, endocrine, and reproductive systems in animal experiments. 2) The diseases showing evidence of causal association were Hodgkin's disease, non-Hodgkin's disease, lung cancer, lymphoma, soft tissue sarcoma, chloroacne and polyneuropathy when judged on the basis of consistency in study results and biological plausibility. 2. Interview and medical record review study on 638 veterans, though limited validity owing to lack of control group, crude estimates of dioxin exposure levels (no biomarkers measurable), and uncertainty of diagnosis, showed that: 1) Most of the study subject's were in their 40's of age and had been dispatched to Vietnam during the period from $1965{\sim}1970$ around one year. 2) Most frequently complained symptoms in medical examination were motor weakness (32%), sensory abnormalities in extremities (23%), skin diseases (22%), and pain in extremities (20%) whereas in Interview they were more frequent in order of skin problem (44%), motor weakness (38%), sensory abnormalities and pain in extremities(17% and 19% each). Kappa indices on the same category of complaints between two sources of information were variable and relatively low. 3) On medical examination, only a part of the 638 subjects had initial impression (442 pts) and final diagnosis (218 pts) suggesting decision making on diagnosis appeared to be difficult even with all available modern medical technologies: in initial impression disorders from peripheral and central neuropathy were predominant whereas in final diagnosis various types of skin disorder were most frequent 4) When dose-response relationship between several conditions (from questionnaire) and arbitrary exposure scores were examined by CMH linear trend test, spontaneous abortion, sexual problems and health problem of offsprings showed statistically significant linear trends. However, pregnancy, accident and suicidal attempts did not show any relationship in this study capacity. 5) Among complaints, psychosis and neurosis (anxiety, phobia) in interview study, and memory disorder and psychosis in medical record study revealed linear trend. 6) Skin disorder was the only condition showing linear trend in initial impression and none in final diagnosis on medical examination. Even though objective to select out dioxin-related disease or group of diseases from this study was not achieved the research experiences provided firm basis for developing various methodological approaches. 3. From this preliminary study we concluded that a larger scale major epidemiologic study on health impacts of herbicides among Korean veterans exposed is not only Indispensible but also well designed study with more valid exposure information and diagnosis may be able to establish causal relationship between certain groups of diseases and exposure to the herbicides among Korean veterans.

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

  • 양일종;김종인;이해영;천봉권;조성래
    • Journal of Chest Surgery
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    • 제37권8호
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    • pp.691-701
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    • 2004
  • 배경: 악성종양에서 신생혈관 생성 및 당분해의 증가는 저산소 상태의 미세환경을 나타내며, 이는 종양의 침습성, 전이 등으로 환자의 예후와 관련이 있는 것으로 알려져 있다. Hypoxia-inducible factor 1(HIF-1)는 당원 수송체, 당분해 효소, 혈관내피세포 성장인자 등의 유전자의 전사를 활성화한다고 알려져 있다. 그리고 HIF-1의 전사 활성도는 HIF-1 a subunit의 표현이 조절되는 정도에 의존한다. 그러나 식도암에서 HIF-1의 발현과 혈관 생성능 및 종양세포 증식능과의 관계 및 예후에 관한 연구는 전무하다. 대상 및 방법: 고신대학교 의과대학 흉부외과학교실에서 1995년부터 2000년까지 수술치험한 77예의 식도 편평세포암 환자의 조직에서 채취한 정상 편평상피와 암조직에서 면역조직화학검사를 이용하여 HIF-1 a의 발현을 조사하고 혈관생성인자, 증식지수, p53 단백과의 상관관계, 임상-병리학적인 인자 및 생존율과의 상관관계를 분석하였다. 결과: HIF-1 a의 고발현율은 42.9% (33예/77예)였다. HIF-1 a의 고발현은 조직학적 등급(p=0.032), 병리학적 병기(p=0.002), 종양 침윤의 깊이(p=0.022), 주위 림프절 전이(p=0.002), 원격전이(p=0.049), 림프관 침윤(p=0.004)과 관련이 있었다. HIF-1 a의 고발현은 혈관내피세포 성장인자의 발현, Ki-67 증식지수와 관련이 있었으나, 미세혈관수와는 관련이 없었고, p53의 발현과는 관련이 있는 경향을 보였다. 단변량분석과 다변량분석에서 HIF-1 a의 고발현은 불량한 예후를 나타내는 인자로 보였다. 결론: 식도 편평세포암 조직에서 HIF-1 a의 발현은 종양조직내 신생혈관의 생성과 관련이 있는 것으로 나타났고, 고발현 된 경우는 림프절 전이와 수술 후 불량한 예후를 나타내었으므로 보다 강화된 치료전략이 필요할 것으로 사료된다.