• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제26권2호
• /
• pp.137-145
• /
• 2000

Carcinogenesis is a multi-stage process that generally consists of at least three steps; initiation, promotion, and progression. If one of these carcinogenic steps were suppressed or delayed, the cancer could be prevented. Cancer chemoprevention is defined to be inhibition or reversal of the carcinogenic process by the specific chemical agents and is a novel approach to cancer management alternative to conventional chemotherapy. Chlorophylln(CHL), a water-soluble derivative of chlorophyll, containing sodium and copper, has been known to be strong antimutagen in several test systems, but its mechanism of antimutagenic action is unknown. In the present experiment, the possibility of CHL as chemopreventive drugs on 7,12-dimethylbenz[a]anthracene(DMBA)-induced hamster buccal pouch carcinogenesis was investigated by mutagenicity test, carcinogenicity test, and frequency or spectrum of H-ras mutations in the both of DMBA-induced and chlorophylln-pretreated-DMBA induced tumor by polymerase chain reaction and non-isotopic restriction fragment length polymorphism. The treatment of CHL reduced the yields and multiplicity of the 0.5% DMBA-induced tumor, 86% to 62.5% and $3.7{\pm}0.6$ to $1.4{\pm}0.3$, respectively. The occurrence of histidine revertant by $20{\mu}mole$ DMBA was inhibited 25.6 to 81.7% by 1 to $5{\mu}M$ CHL in a dose-dependent manner. The mutation rates of H-ras gene in DMBA-induced and CHL-pretreated-DMBA induced tumor were 96%, 94% of which the most mutations were in codon 12/13. These results suggest that CHL inhibits the carcinogenic action of DMBA by the formation of complex between CHL and DMBA or the inhibition of the activation of DMBA in vivo. But CHL did not affect the mutation rates or its spectrum in already formed tumor.

• The Korean Journal of Physiology and Pharmacology
• /
• 제3권5호
• /
• pp.501-505
• /
• 1999

Tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis, is primarily expressed in serotonergic neurons of the raphe nuclei. Simple tandem repeat polymorphisms, typically one to four nucleotides long, are tandemly repeated several times and often characterized by many alleles. To identify the presence of polymorphic repeats, we sequenced the 5'-upstream region of the mouse TPH gene. For the detection of any allelic variants, polymerase chain reaction, nonisotopic single-strand conformation polymophism, and DNA sequencing analyses of the tandem repeat sequences were performed using genomic DNA extracted from 60 ICR mice. Two dinucleotide repeats, $5'-(AC/TG)_{22}-3'$ and $5'-(GT/CA)_{17}3',$ were identified at approximately - 5.7 kb and - 3.4 kb upstream from the transcriptional initiation site of the mouse TPH gene, respectively. Minor allelic variants, $5'-(AC/TG)_{21}-3'$ and $5'-(GT/CA)_{18}-3',$ were observed in heterozygous pairs from 3 of 60 and 1 of 60 ICR mice, respectively. The identification of these microsatellites in the mouse TPH promoter raises the possibility that identical and/or other polymorphic sequences might exist in the upstream region of the human TPH gene.

• Journal of Periodontal and Implant Science
• /
• 제41권4호
• /
• pp.167-175
• /
• 2011

Purpose: Periodontal ligament (PDL) cell differentiation into osteoblasts is important in bone formation. Bone formation is a complex biological process and involves several tightly regulated gene expression patterns of bone-related proteins. The expression patterns of bone related proteins are regulated in a temporal manner both in vivo and in vitro. The aim of this study was to observe the gene expression profile in PDL cell proliferation, differentiation, and mineralization in vitro. Methods: PDL cells were grown until confluence, which were then designated as day 0, and nodule formation was induced by the addition of 50 ${\mu}g$/mL ascorbic acid, 10 mM ${\beta}$-glycerophosphate, and 100 nM dexamethasone to the medium. The dishes were stained with Alizarin Red S on days 1, 7, 14, and 21. Real-time polymerase chain reaction was performed for the detection of various genes on days 0, 1, 7, 14, and 21. Results: On day 0 with a confluent monolayer, in the active proliferative stage, c-myc gene expression was observed at its maximal level. On day 7 with a multilayer, alkaline phosphatase, bone morphogenetic protein (BMP)-2, and BMP-4 gene expression had increased and this was followed by maximal expression of osteocalcin on day 14 with the initiation of nodule mineralization. In relationship to apoptosis, c-fos gene expression peaked on day 21 and was characterized by the post-mineralization stage. Here, various genes were regulated in a temporal manner during PDL fibroblast proliferation, extracellular matrix maturation, and mineralization. The gene expression pattern was similar. Conclusions: We can speculate that the gene expression pattern occurs during PDL cell proliferation, differentiation, and mineralization. On the basis of these results, it might be possible to understand the various factors that influence PDL cell proliferation, extracellular matrix maturation, and mineralization with regard to gene expression patterns.

• 대한임상검사과학회지
• /
• 제44권2호
• /
• pp.81-85
• /
• 2012

This study was undertaken to evaluate phenotypic and genotypic methods for detection of Metallo-Beta-Lactamases (MBLs) among nosocomial Pseudomonas aeruginosa. Of the 50 P. aeruginosa isolates from clinical specimens, 20 were evaluated for carbapenem resistance and screened for MBL by double-disk synergy test and combined-disk test. Nineteen strains (95%) were found to be MBL producers among the 20 P. aeruginosa. MBL positives were further confirmed by Polymerase Chain Reaction (PCR). For the IMP and VIM types of MBLs, PCR analysis was performed on 19 of the 20, and 10 were positive for VIM MBL type. This study reports the validation of a simple and accurate MBL detection method that can be easily incorporated into the daily routine of a clinical laboratory. Early detection of MBL-carrying organisms, including those with susceptibility to carbapenems, is of paramount clinical importance, as it allows rapid initiation of strict infection control practices as well as therapeutic guidance for confirmed infection.Key Words : Hepatitis A virus (HAV), Anti-HAV, Hospital workers, Prevalence, Vaccination

• 통합자연과학논문집
• /
• 제2권1호
• /
• pp.18-23
• /
• 2009

This minireview provides the chosen examples of our recent discoveries in the polymerization of hydrosilanes, dihydrosilole, lactones, and vinyl derivatives using various catalysts. Hydrosilanes and lactones copolymerize to give poly(lactone-co-silane)s with $Cp_2MCl_2$/Red-Al (M = Ti, Zr, Hf) catalyst. Hydrosilanes (including dihydrosilole) reduce noble metal complexes (e.g., $AgNO_3$, $Ag_2SO_4$, $HAuCl_4$, $H_2PtCl_6$) to give nanoparticles along with silicon polymers such as polysilanes, polysilole, polysiloxanes (and silicas) depending on the reaction conditions. Interestingly, phenylsilane dehydrocoupled to polyphenylsilane in the inert nitrogen atmosphere while phenylsilane dehydrocoupled to silica in the ambient air atmosphere. $Cp_2M/CX_4$ (M = Fe, Co, Ni; X = Cl, Br, I) combination initiate the polymerization of vinyl monomers. In the photopolymerization of vinyl monomers using $Cp_2M/CCl_4$ (M = Fe, Co, Ni), the photopolymerization of MMA initiated by $Cp_2M/CCl_4$ (M = Fe, Co, Ni) shows while the polymerization yield decreases in the order $Cp_2Fe$ > $Cp_2Ni$ > $Cp_2Co$, the molecular weight decreases in the order $Cp_2Co$ > $Cp_2Ni$ > $Cp_2Fe$. For the photohomopolymerization and photocopolymerization of MA and AA, the similar trends were observed. The photopolymerizations are not living. Many exciting possibilities remain to be examined and some of them are demonstrated in the body of the minireview.

• Journal of Ginseng Research
• /
• 제39권3호
• /
• pp.230-237
• /
• 2015

Background: Colorectal cancer (CRC) is a leading cause of death worldwide. Chronic gut inflammation is recognized as a risk factor for tumor development, including CRC. American ginseng is a very commonly used ginseng species in the West. Methods: A genetically engineered $Apc^{Min/+}$ mouse model was used in this study. We analyzed the saponin composition of American ginseng used in this project, and evaluated its effects on the progression of high-fat-diet-enhanced CRC carcinogenesis. Results: After oral ginseng administration (10-20 mg/kg/d for up to 32 wk), experimental data showed that, compared with the untreated mice, ginseng very significantly reduced tumor initiation and progression in both the small intestine (including the proximal end, middle end, and distal end) and the colon (all p < 0.01). This tumor number reduction was more obvious in those mice treated with a low dose of ginseng. The tumor multiplicity data were supported by body weight changes and gut tissue histology examinations. In addition, quantitative real-time polymerase chain reaction analysis showed that compared with the untreated group, ginseng very significantly reduced the gene expression of inflammatory cytokines, including interleukin-$1{\alpha}$ (IL-$1{\alpha}$), IL-$1{\beta}$, IL-6, tumor necrosis factor-${\alpha}$, granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor in both the small intestine and the colon (all p < 0.01). Conclusion: Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention.

• 한국발생생물학회지:발생과생식
• /
• 제4권1호
• /
• pp.101-108
• /
• 2000

자궁내막증은 흔한 부인과적 질병이며 여성 불임의 한 원인이 되나 그 발생 원인에 대하여서는 아직 논란의 여지가 많다. 최근 월경혈의 역류에 의하여 자궁내막증이 생긴다는 가설이 가장 유력한데 자궁내막증 환자가 정상여성에서보다 역류되는 월경혈의 양이 많거나 침습성이 강한 것이 자궁내막증의 발생원인이 될 수 있다는 이론들이 소개되었다. Pleitrophin (PTN)이나 midkine(MK)은 성장 및 분화에 관여하는 인자로서 여러 종류의 악성 종양에서 그 발현이 보고되어있으며 종양화 (carcinogenensis), 맥관형성 (angiogenesis), plasminogen activator의 활성화 증가 등에 관여한다고 보고된 바 있다. 이에 자궁내막증 환자의 자궁 내막과 대조군의 자궁내막에서 PTN과 MK mRNA의 발현의 차이를 quantitative competitive RT PCR로 비교하였다. 그 결과 자궁내막증 환자의 황체기 자궁내막에서 대조군의 자궁내막에 비하여 PTN과 MK의 발현이 높게 나타났다. 이러한 PTN과 MK의 발현의 증가로 자궁내막증 환자의 자궁내막이 복강 내에서 더욱 쉽게 맥관형성을 하고 성장이 촉진되어 자궁내막증이 발생될 것으로 생각되어 PTN과 MK가 자궁내막증의 초기 발생과정에 관여할 가능성이 있다.

• 생명과학회지
• /
• 제28권6호
• /
• pp.733-737
• /
• 2018

박과 작물에 함유되어 있는 tetracyclic triterpene 성분 중 하나인 쿠쿠르비타신(cucurbitacin)-I는 대장암, 유방암, 간암세포에서의 항종양 활성이 밝혀져 있으나 난소암에서의 쿠쿠르비타신-I의 역할은 보고된 바 없다. CD44는 세포막에 존재하는 당단백질로 생체 내 리간드인 glycosaminoglycan hyaluronic acid를 통해 세포 외부 매트릭스와 다른 세포와의 접촉을 매개한다. 최근 연구에 의해 CD44의 발현이 난소암세포의 증식 및 세포 부착과 침윤을 증가시키는 주요 원인이라는 것이 보고되었다. 이러한 결과는 CD44의 발현을 억제함으로써 난소암의 진행을 조절할 수 있음을 시사하고 있다. 본 연구에서는 쿠쿠르비타신-I가 난소암세포의 CD44의 발현을 억제할 수 있는 지의 여부를 조사하였다. 인간의 난소암 세포인 SKOV-3를 이용한 MTS assay를 수행한 결과, 쿠쿠르비타신-I는 100 nM이상의 농도에서 세포독성을 나타내었다. 세포독성을 나타내지 않는 농도의 쿠쿠르비타신-I를 SKOV-3 세포에 처리하여 Western blot 분석과 qRT-PCR을 수행한 결과, 쿠쿠르비타신-I에 의해 CD44의 단백질과 mRNA의 발현이 유의적으로 감소되는 것을 확인하였다. 또한 쿠쿠르비타신-I에 의한 CD44의 발현 억제가 $NF-{\kappa}B$와 AP-1의 인산화 감소에 기인하고 있음을 밝혔다. 이러한 결과는 쿠쿠르비타신-I가 CD44 발현을 억제하는 기능을 가지며, 이는 난소암 치료에 도움을 줄 수 있는 제재로서 쿠쿠르비타신-I의 가능성을 제시하는 것이다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권2호
• /
• pp.541-549
• /
• 2015

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher metastatic rate and both local and systemic recurrence compared to non-TNBC. The generation of reactive oxygen species (ROS) secondary to oxidative stress is associated with DNA damage, chromosomal degradation and alterations of both hypermethylation and hypomethylation of DNA. This study concerns differential methylation of promoter regions in specific groups of genes in TNBC and non-TNBC Saudi females in an effort to understand whether epigenetic events might be involved in breast carcinogenesis, and whether they might be used as markers for Saudi BCs. Methylation of glutathione S-transferase P1 (GSTP1), T-cadherin (CDH13), Paired box protein 5 (PAX5), death associated protein kinase (DAPK), twist-related protein (TWIST), DNA-binding protein inhibitor (ID4), High In Normal-1 (HIN-1), cyclin-dependent kinase inhibitor 2A (p16), cyclin D2 and retinoic acid receptor-${\beta}$ ($RAR{\beta}1$) genes was analyzed by methylation specific polymerase chain reaction (MSP) in 200 archival formalin-fixed paraffin embedded BC tissues divided into 3 groups; benign breast tissues (20), TNBC (80) and non-TNBC (100). The relationships between methylation status, and clinical and pathological characteristics of patients and tumors were assessed. Higher frequencies of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 hypermethylation were found in TNBC than in non-TNBC. Hypermethylation of GSTP1, CDH13, ID4, DAPK, HIN-1 and PAX5 increased with tumor grade increasing. Other statistically significant correlations were identified with studied genes. Data from this study suggest that increased hypermethylation of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 genes in TNBC than in non-TNBC can act as useful biomarker for BCs in the Saudi population. The higher frequency of specific hypermethylated genes paralleling tumor grade, size and lymph node involvement suggests contributions to breast cancer initiation and progression.

• Natural Product Sciences
• /
• 제18권1호
• /
• pp.60-66
• /
• 2012

Human skin is the first line of defense for the protection of the internal organs of the body from different stimuli. Ultraviolet B (UVB) irradiation induces skin damage and inflammation through the secretion of various cytokines, which are immune regulators produced by cells. To prevent the initiation of skin inflammation, keratinocytes that have been irreversibly damaged by radiation must be removed through the apoptotic mechanism. Ixeris dentata (family: Asteraceae) is a perennial medicinal herb indigenous to Korea. It has been used in Korea, China, and Japan to treat in digestion, pneumonia, diabetes, hepatitis, and tumors. To gain insight into the anti-inflammatory effects of I. dentata, we examined its influence on UVB-induced pro-inflammatory cytokine production in human keratinocytes (HaCaT cells), by observing cells that were stimulated with UVB in the presence or absence of I. dentata. In the present study, pro-inflammatory cytokine production was determined by performing enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and western blot analysis to measure the activation of mitogen-activated protein kinase (MAPKs). I. dentata inhibited UVBinduced production of the pro-inflammatory cytokine interleukin (IL)-6 in a dose-dependent manner. Further, I. dentata inhibited the UVB-induced expression of cyclooxygenase (COX)-2. Furthermore, I. dentata inhibited the phosphorylation of c-Jun NH2-terminal kinase and p38 MAPKs, suggesting that it inhibits the secretion of the pro-inflammatory cytokines IL-6 and IL-8, and COX-2 expression, by blocking MAPK phosphorylation. These results suggest that I. dentate can potentially protect against UVB-induced skin inflammation.