• Proceedings of the Korean Journal of Food and Nutrition Conference
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• 1997.06b
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• pp.15-17
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• 1997

암 발생의 원인 중 80% 이상이 식사습관과 환경오염에 있는 것으로 인정되고 있다. 음식물, 담배, 술, 대기오염, 스트레스, 자외선이 그 대표적인 원인물질로 꼽을 수 있으며 그 중에서도 매일 섭취하는 음식물이 가장 중요한 발암요인으로 지적되고 있다. 대장암과 유방암의 발생에 대한 Wynder 등의 역학조사에서도 식사습관이 암 발생에 중요함을 시사 하고 있다. 동물성 단백질과 지방의 다량 섭취가 대장암과 유방암의 발생을 증가 시키고 섬유질이 풍부한 곡류와 야채의 섭취는 대장암 발생을 억제한다는 상관관계가 밝혀졌다. 그러나 우리가 늘 섭취하는 음식물 자체는 대장암과 유방암을 유발하는 기능이 거의 없다. 섭취된 음식물이 암을 일으키려면 장내 부패 미생물의 분해작용에 의하여 발암물질로 변환되는 과정이 필요하다. 그 발암물질들이 장관으로 흡수 자극함으로써 암을 유발할 수 있다. 반대로 일부장내 미생물들은 장내 발암물질들을 무독화 하거나 숙주의 면역기능을 증강 시킴으로써 암 발생을 억제할 수도 있다는 사실을 간과해서는 안 될 것이다. Mitsuoka는 장내 미생물이 암을 유발하는 중요한 요인이라고 강조하였다. Veer 등은 유산균 발효유를 많이 섭취하면 유방암 발생이 억제됨을, 국제암연구위원회는 섬유질을 많이 섭취하고 있는 핀란드 쿠피오의 거주자들에게는 덴마크의 코펜하겐에 거주하는 사람들에 비하여 대장암 발생율이 1/4에 불과하고 분변내 유산간균수는 100배 높은 사실을 역학조사에서 밝혔다. 이 외에 유산균과 발효유제품의 항암효과에 대한 실험결과들이 많이 발표되었다. 여기에서는 유산균의 항암효과에 대한 지금까지의 관련 자료들을 요약, 정리하여 고찰하고자 한다.높은 당 함량을 나타냈으며, T-AS는 70.3%의 당과 7.8%의 단백질로 구성 되었다. GLG 대부분의 분획들은 60~93%의 glucose로 구성된 다당류 이었으며, 주로 $\beta$-glucose로 구성된 다당류 이었다. 아미노산은 Asp 및 Glu의 산성 아미노산과 Ala, Leu 등의 함량이 높게 나타났으며, 비알칼리 추출물에서 Ser과 Thr의 함량이 높게 나타났다. 다당류 T-AS는 평균 분자량이 2,000 kD와 12kD에서 주 peak를 나타냈으며, 수용성 분획의 평균 분자량은 12kD이고 비수용성 분획은 36~2,000 kD의 평균 분자량 분포를 갖는 것으로 나타났다. IR과 NMR 분석 결과 890 cm-1에서 흡수 peak를 나타내어 $\beta$-(1,3)0glucan과 $\beta$-(1,6)-glucan의 구조를 갖는 다당류로 확인 되었다. T-AS 분획은 C:H:O:N의 함량비가 38.9:5.7:49.6:1.84%이며, 이 물질의 융점은 163 $^{\circ}C$로 연한 갈색을 나타낸다. 분리된 GLG의 항암활성 기전 규명을 위해, in vivo 항암실험, 항보체 활성능, 항체 생성능, serum protein 분비능, 대식세포의 탐식능과 활성능 및 세포간 물질 분비 등의 상관관계를 조사하였다. 다당류 GLG 분획물들 가운데 항보체의 활성이 높았던 분획은 sarcome 180에 대한 항암 활성이 높게 나타났다. 다당류 T-AS의 보체 활성화 기작은 classical과 alternative complement pathway의 양 경로를 통해 활성화 되었다.

• Microbiology and Biotechnology Letters
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• v.32 no.1
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• pp.72-77
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• 2004

Previously, we synthesized a novel Cyclin-dependent kinase inhibitor, MCS-5A. Also, we investigated the involvement of cell cycle regulatory events during MCS-5A-mediated apoptosis in HL-60(+p16/-p53) cells with up-regulation of p16 protein expression. In contrast, apoptosis was not observed in A549(-p16/+p53) cells. Therefore we propose that $p16^{INK4A}$ is a key enzyme for inducing apoptosis. In the present studies, we have explored the mechanism of $p16^{INK4A}$ -mediated cytotoxicity and the role of p16.sup INK4A/ overexpression in the induction of apoptosis in human tumor cells. The tumor suppressor gene $p16^{INK4A}$ is known as a cyclin-dependent kinase inhibitor (CKI) and cell cycle regulator. We expressed wild type $p16^{INK4A}$ in pcDNA3.1 vector and then transfected into non-small cell lung cancer (NSCLC) cell expressing different statue of p16$^{INK4A}$, p53 gene〔A549(-p16/+p53), H1299(-p16/-p53) and HeLa(+pl6/+p53) cell line〕. TUNEL assay (including propidium iodide staining following transfection of these cell line with pcDNA3.1-pl6) indicate that p16$^{INK4A}$-mediated cytotoxicity was associated with apoptosis. This is supported by studies demonstrating an induction of caspase 3 cleavage due to the transfection of A549, H1299 and HeLa cells with pcDNA3.1-pl6. These results suggest that p16$^{INK4A}$ has a new function of inducing apoptosis which is not related with the function of tumor suppressor gene p53.

• Journal of Genetic Medicine
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• v.6 no.1
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• pp.1-7
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• 2009

Epigenetic changes represented by promoter CpG island hypermethylation and histone modification are an important carcinogenetic mechanism, which is found in virtually all histologic types of human cancer. About 60-70% of human genes harbor CpG islands in their promoters and 5' exonal sequences, and some of them undergo aberrant promoter CpG island hypermethylation and subsequent downregulation of gene expression. The loss of expression in tumor suppressor or tumor-related genes results in acceleration of tumorigenic processes. In addition to regional CpG island hypermethylation, diffuse genomic hypomethylation represents an important aspect of DNA methylation changes occurring in human cancer cells and contributes to chromosomal instability. These apparently contrasting methylation changes occur not only in human cancer cells, but also in premalignant cells. CpG island hypermethylation has gained attention for not only the tumorigenic mechanistic process, but also its potential utilization as a tumor biomarker. DNA methylation markers are actively investigated for their potential uses as tumor biomarkers for diagnosis of tumors in body fluids, prognostication of cancer patients, or prediction of chemotherapeutic drug response. In this review, these aspects will be discussed in detail.

• Korean Journal of Head & Neck Oncology
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• v.23 no.1
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• pp.21-25
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• 2007

Background：Squamous cell carcinoma(SCC)of the palatine tonsils represents approximately 15-23% of all intraoral SCC. The most frequently reported risk factors for oropharyngeal cancer are smoking and alcohol. In a recent overview of HPV and tonsillar squamous cell carcinoma(TC), 51% contained HPV DNA, and HPV-16 being the most frequent type. We aimed to clarify whether HPV directly effects on the oncogenesis and biologic behavior of TC by comparison with infection prevalence, and physical status of virus. Material and Method：We used HPV genotyping DNA chip(Biocore, Korea, Seoul) arrayed by multiple oligonucleotide probes of L1 sequence of 26 types of HPV and HPV genotypes are identified by fluorescence scanner. The copy numbers of HPV E2 and E6 open reading frames(ORF) were assessed using a TaqMan-based 5'-exonuclease quantitative real-time PCR assay. The ratio of E2 to E6 copy numbers was calculated to determine the physical status of HPV-16 viral gene. Results：We observed a significant difference in HPV prevalence between 52 TCs and 69 CFTs(73.1% vs. 11.6%), and most of the HPVs were type 16(87.2%)and non-episomal(94.1%) state. Conclusions：This study regarding HPV infection prevalence and mechanism in the largest population of palatine tonsillar squamous cell carcinoma with chronic follicular tonsillitis revealed significant difference pf HPV prevalence between TC and CFT. Most of HPV were 16 type and integrated or mixed, HPV-16 integration could be directly related to tonsillar carcinogenesis.

• Journal of Life Science
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• v.19 no.9
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• pp.1289-1293
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• 2009

Proto-oncogene human cervical cancer oncogene (HCCR) functions as a negative regulator of p53 and contributes to tumorigenesis in various human tissues. However, it is unknown how HCCR contributes to the cellular and biochemical mechanisms of human tumorigenesis. In this study, we showed how the expression of HCCR is modulated. The luciferase activity assay indicated that the HCCR 5'-flanking region at positions -370 to -406 plays an important role in the promoter activity. Computational analysis of this region identified one consensus sequence for the TG-interacting factor (TGIF) located at -390 to -366 (TG). Mobility shift assays (EMSA) revealed that nuclear proteins from K562 bind to the TG site, but not to the mutated TG site. The reporter activity assay with promoter constructs carrying mutated TGIF sequences pGL3-mTGIF significantly increased reporter activities compared to wild type constructs pGL3-$406{\sim}+30$. In this study, we characterized the HCCR promoter and found that HCCR expression was partially regulated by the transcription repressor TGIF, which bound the promoter at positions -390 to -366.

• Korean Journal of Head & Neck Oncology
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• v.25 no.1
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• pp.28-32
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• 2009

Background : The most frequently reported risk factors for head and neck suamous cell carcinoma are smoking and alcohol. But in a recent overview, human papilloma virus(HPV) infection was revealed the important carcinogenic factor in oropharyngeal cancer. We aimed to clarify whether HPV directly effects on the oncogenesis and biologic behavior of hean and neck squamous cell carcinoma by comparison with infection prevalence, and physical status of virus. Material and Method : We used HPV genotyping DNA chip(Biocore, Korea, Seoul) arrayed by multiple oligonucleotide probes of L1 sequence of 26 types of HPV and HPV genotypes are identified by fluorescence scanner. The copy numbers of HPV E2 and E6 open reading frames(ORF) were assessed using a TaqMan-based 5'-exonuclease quantitative real-time PCR assay. The ratio of E2 to E6 copy numbers was calculated to determine the physical status of HPV-16 viral gene. Results : We observed a significant difference in HPV prevalence between tonsillar cancer group and control group(73.1% vs. 11.6%), and most of the HPVs were type 16(87.2%) and integrated(94.1%) state. In terms of oral tongue cancer, we demonstrate that 30.5% has integrated HPV-16 in cancer tissue. But Glottic cancer only 1% is related to HPV-16 integration. Conclusion : This study revealed significant relationship of HPV prevalence with oropharyngeal and oral tongue squamous cell carcinoma. Most of HPV were 16 type and integrated or mixed, HPV-16 integration could be directly related to the carcinogenesis.

• The Korean Journal of Food And Nutrition
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• v.28 no.4
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• pp.579-585
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• 2015

Rutin is a well-known flavonoid found in buckwheat. Recent studies have demonstrated that the biological actions of rutin include anti-inflammatory and anti-cancer effects, but the underlying molecular mechanisms of these actions are not yet fully understood. Neoplastic cell transformation is considered a major event that contributes to carcinogenesis, and the present study aimed to determine whether rutin would exert anti-tumor effects via the results suggest that rutin exerted a potent inhibitory influence on the molecular activity of the MEK/ERK and MKK4/JNK pathways and strongly attenuated EGF-induced neoplastic cell transformation. These findings provide insight into the biological actions of rutin and the molecular basis for the development of new chemoprotective agents.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.5
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• pp.782-787
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• 2002

This study was done to investigate the effects of Korean mistletoe water extract and lectin on the apoptosis and preneoplastic lesion in chemically induced rat hepatocarcinogenesis. To attain the above objectives, weanling Sprague-Dawley male rats were fed modified AIN-76 diets containing 10% corn oil for 9 weeks. One week after feeding starts, rats were intraperitoneally injected twice with a dose of diethylnitrosamine (DEN, 50 mg/kg body weight (BW). Rats were provided with 0.05% phenobarbital (PB) in drinking water from one week after DEN treatment until the end of experiment. During the period of PB treatment, rats were injected with mistletoe extract (100 $\mu\textrm{g}$/kg BW) and lectin (10 $\mu\textrm{g}$/kg BW) twice a week. At the end of 9th week, rats were sacrificed and the formation of hepatic glutathione S-transferase placental form positive (GST-P$^{+}$) foci, apoptosis, DNA fragmentation and apoptosis related proteins were determined respectively. The formation of GST-P$^{+}$foci was significantly decreased by mistletoe extract or lectin treatment. Although there was no effect on apoptosis and DNA fragmentation in hepatic tissue by mistletoe extract or lectin treatment, caspase-9 and fas-L were increased. These results suggest that Korean mistletoe extract and lectin have a potential to inhibit hepatocarcinogenesis by increasing apoptosis.sis.

• Journal of Environmental Health Sciences
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• v.36 no.1
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• pp.1-13
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• 2010

Evidences supporting gene-environment interaction are accumulating in terms of environmental exposure including lifestyle factors and related genetic variants. One form of defense mechanism against cancer development involves a series of genes whose role is to metabolize (activation/detoxification) and excrete potentially toxic compounds and to repair subtle mistakes in DNA. The purpose of this article is to provide a brief review of the notion of gene-environment interaction, environmental/occupational carcinogens and related cancers, and previous studies of gene-environment interaction on cancers caused by exposure to carcinogenesis. With a number of studies on the interaction between lifestyle factors (e.g., smoking and diet) and genetic polymorphisms in genes involved in xenobiotic metabolism and DNA repair excluded, only several studies have been conducted on the interactive effects between polymorphisms of CYPs, GSTs, ERCCs, XRCCs and environmental/occupational carcinogens such as vinyl chloride, benzo[a]pyrene, and chloroform on carcinogenesis or genotoxicity. Future studies may need to be conducted with sufficient number of subjects and based on occupational cohorts to provide useful information in terms of advanced risk assessment and regulation of exposure level.

• Environmental Analysis Health and Toxicology
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• v.20 no.4 s.51
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• pp.327-332
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• 2005

장기간 노출 시 발암 등 인체 유해성을 갖는 환경유래 내분비장애물질(endocrine disrupting chemicals, EDCs)에 대한 선택적이고 민감한 노출지표를 개발하기 위하여 본 연구에서는 DNA microarray를 이용하였다. 피험자는 아직 특별한 질환을 갖지 않는 18세 이상 연령, 성을 맞춘 EDCs고농도 노출군(N = 16)과 저농도군(N = 16)으로 구성되었다. 노출정도 구분은 10년 이상 거주지가 K산업폐기물 소각장과 2.5 km 반경 내, 외 인지에 따라 고노출군,저노출군으로 구분하였다. 피험자의 말초혈에서 total RNA를 분리, 각 군당 B인씩 pool로 cDNA를 합성하여 oligonucleotide DNA 칩에 적용하였다. 유전자발현의 차이를 GenePixPro 4.0 software를 이용하여 분석하였다. 총 3장의 칩을 이용하여 공통적으로 저노출군보다 고노출군에서 2배 이상 발현의 증가를 보인 유전자는 plasminogen activator(PLAT)등 12종이 관찰되었고, l/2이하로 발현의 감소를 보인 유전자는 kallikrein 3 (KLK3)등 29종이었다. 이 들 유전자는 PLAT등 면역계 반응에 관여하는 유전자 및 apoptosis, transport, G protein, chromatin, 암화, 발생 (development), 대사 등에 관여하는 유전자들이었다. 그러므로 KLK3등 본 연구에서 발굴한 유전자는 향후 확대된 인구에서 본 연구 결과의 확인을 통하여 EDCs특이적 노출지표로써, 나아가 암 등 EDCs관련 질병의 기전 및 병인학을 구명하는데 이용가치가 높다고 사료된다.