성인여성의 인유두종바이러스와 자궁경부암 예방백신에 대한 지식, 암예방 수행 및 자궁경부암 예방백신 수용도 분석

송갑선,전은미,김주연 대한암예방학회 2013 Journal of cancer prevention Vol.18 No.1

This study was conducted to identify the knowledge of HPV and HPV vaccines and the acceptance of cancer preventive vaccine targeting adult women. The convenience sampling was conducted on subjects of 271 adult women who have visited Gynecologic Clinics residing in the B-city. For data analysis, it conducted the analysis of mean and standard deviation, t-test, ANOVA, and Pearson's Correlation Coefficient. The research results demonstrate that the knowledge about HPV vaccine was higher in less than 40's in their age, subjects over college-graduates, single status in marriage condition, and subjects who have jobs, but the knowledge appeared to be very low with mean score, 5.34 (range 0∼22). In terms of the performance of cancer prevention, subjects of college graduates, those who have religion and were in higher economic level, those who are married, have no job, have a sex-partner and sexually transmitted diseases experience specially made an effort to prevent cancer. Of the subjects, 66.7% responded that they had a will to receive HPV vaccination and 86% subjects wanted to make their children vaccinate. In addition, there was no correlation found between the knowledge of HPV vaccine and the cancer- preventive performance.

Drosophila에서 Genistein의 항돌연변이 효과

윤희선,박건영,이원호 대한암예방학회 2000 Journal of cancer prevention Vol.5 No.3

글루타민 결핍에 의한 LnCap 인체 전립선암세포의 증식억제 현상

신동역,최영현 대한암예방학회 2011 Journal of cancer prevention Vol.16 No.1

While the amino acid L-glutamine, a most abundant amino acid in the blood, is known to play a role in the survival and death of several cell types, the underlying molecular mechanisms are still poorly defined. The purpose of this study is to determine whether glutamine deprivation induces growth inhibition and apoptosis in human prostate carcinoma LnCap cells. Our data indicated that glutamine deprivation triggered a progressive reduction in the cell viability through arresting the cell cycle in the S phase. This process involved the increase of sub-G1 phase DNA contents, however chromatin condensation as well as DNA fragmentation were not detected in cells cultured in the absence of glutamine indicating that glutamine deprivation did not induce apoptosis in LnCap cells. Supporting the data, the several important apoptosis-related gene products such as death receptor-related genes, IAP and Bcl-2 family members, and caspases, were not changed or activated. Moreover, the level poly-(ADP-ribose) polymerase, β-catenin and phospholipase C-γ1 expression, activated caspase-3 target proteins, remained unchanged in response to glutamine deprivation. This study provides biochemical evidence that glutamine deprivation suppresses cell viability without induction of apoptosis in human prostate carcinoma LnCap cells. (Cancer Prev Res 16, 41-50, 2011)

Inhibition of Nuclear Receptor Binding SET Domain 2/ Multiple Myeloma SET Domain by LEM-06 Implication for Epigenetic Cancer Therapies

디 루시오, 에릭 대한암예방학회 2015 Journal of cancer prevention Vol.20 No.2

Background:Multiple myeloma SET domain (MMSET)/nuclear receptor binding SET domain 2 (NSD2) is a lysine histone methyltransferase (HMTase) and bona fideoncoprotein found aberrantly expressed in several cancers, suggesting potential role for novel therapeutic strategies. In particular, MMSET/NSD2 is emerging as a target for therapeutic interventions against multiple myeloma, especially t(4;14) myeloma that is associated with a significantly worse prognosis than other biological subgroups. Multiple myeloma is the secondmost common hematological malignancy in the United States, after non-Hodgkin lymphoma and remains an incurable malignancy. Thus, effective therapeutic strategies are greatly needed. HMTases inhibitors are scarce and no NSDs inhibitors have been isolated. Methods:We used homology modeling, molecular modeling simulations, virtual ligand screening, computational chemistry software for structure-activity relationship and performed in vitro H3K36 histone lysine methylation inhibitory assay using recombinant human NSD2-SET and human H3.1 histone. Results:Here, we report the discovery of LEM-06, a hit small molecule inhibitor of NSD2, with an IC50of 0.8 mM against H3K36 methylation in vitro. Conclusions:We propose LEM-06 as a hit inhibitor that is useful to further optimize for exploring the biology of NSD2. LEM-06 derivatives may pave the way to specific NSD2 inhibitors suitable for therapeutic efforts against malignancies.

Cyclooxygenase-1 and -2: Molecular Targets for Cervical Neoplasia

김희승,김태훈,김미경,서동훈,정현훈,송용상 대한암예방학회 2013 Journal of cancer prevention Vol.18 No.2

Cyclooxygenase (COX) is a key enzyme responsible for inflammation, converting arachidonic acid to prostaglandin and thromboxane. COX has at least two isoforms, COX-1 and COX-2. While COX-1 is constitutively expressed in most tissues for maintaining physiologic homeostasis, COX-2 is induced by inflammatory stimuli including cytokines and growth factors. Many studies have shown that COX-2 contributes to cancer development and progression in various types of malignancy including cervical cancer. Human papillomavirus, a necessary cause of cervical cancer, induces COX-2 expression via E5, E6 and E7 oncoproteins, which leads to prostaglandin E2 increase and the loss of E-cadherin, promotes cell proliferation and production of vascular endothelial growth factor. It is strongly suggested that COX-2 is associated with cancer development and progression such as lymph node metastasis. Many studies have suggested that non-selective COX-2 inhibitors such as non-steroidal anti-inflammatory drugs (NSAIDs), and selective COX-2 inhibitors might show anti-cancer activity in COX-2 -dependent and -independent manners. Two phase II trials for patients with locally advanced cervical cancer showed that celecoxib increased toxicities associated with radiotherapy. Contrary to these discouraging results, two phase II clinical trials, using rofecoxib and celecoxib, demonstrated the promising chemopreventive effect for patients with cervical intraepithelial neoplasia 2 or 3. However, these agents cause a rare, but serious, cardiovascular complication in spite of gastrointestinal protection in comparison with NSAIDs. Recent pharmacogenomic studies have showed that the new strategy for overcoming the limitation in clinical application of COX-2 inhibitors shed light on the use of them as a chemopreventive method.

Alcohol Intake, Smoking, and Colorectal Adenoma

Yeong Mi Park,조창호,김성희,이정은 대한암예방학회 2014 Journal of cancer prevention Vol.19 No.2

Background: Colorectal cancer is the third most common cancer in Korea. Because colorectal adenoma is a precursor lesion of colorectal cancer, primary prevention of colorectal adenomas may be important for reducing morbidity and mortality from the disease. The aim of this study is to examine the association of alcohol consumption and cigarette smoking in relation with colorectal adenoma in a cross-sectional study of Korean adults. Methods: A total of 366 participants who underwent colonoscopy were included (113 cases and 255 controls) in this study. Information on alcohol intake and cigarette smoking was collected from structured questionnaires. The odds ratio (ORs) and 95% confidence intervals (CIs) were calculated using the multivariate logistic regression models. Results: Alcohol intake was associated with a higher prevalence of colorectal adenoma in men; compared to non-drinkers, ORs (95% CIs) were 11.49 (2.55-51.89) for 10-20 g/day of alcohol intake and 14.15 (3.31-60.59) for > 20 g/day of alcohol intake (P for trend = 0.003). There was a weaker association of alcohol intake for women than men; however, there was a suggestive increase in the prevalence of colorectal cancer in women. Cigarette smoking was not associated with colorectal adenoma, but we cannot rule out the possibility that this was due to low statistical power. Conclusion: Our study provides evidence to suggest that alcohol intake may contribute to colorectal adenoma in the Korean population. Our study results demonstrate that a larger epidemiologic study is needed.

진피 추출물에 의한 인체혈구 암세포의 G2/M 세포주기 억제 유발과 Telomerase 활성 억제

한민호,최영현 대한암예방학회 2012 Journal of cancer prevention Vol.17 No.2

Citrus fruits have been used as edible fruits and traditional medicines since ancient times. In particular, the peels of immature citrus fruits are frequently prescribed in concert with other support herbs for many types of disease including cancer. In this study, in order to investigate the anti-proliferative activity of the peels of Citrus aurantium L. along with their effects on apoptosis, we prepared crude methanol extracts of the peels of C. aurantium L. (CME) and performed experiments using U937 human leukemia cells. The growth of U937 cells was inhibited by CME treatment in a dose- and time-dependent manner, and CME treatment induced G2/M cell cycle arrest, which was associated with inhibition of the expression of cyclin-dependent kinase (pCdc2, pCdc25c and Cdk2) and cyclins (cyclin A and B). Moreover, CME inhibited telomerase activity and the expression of human telomerase reverse transcritase (hTERT). These results, together with previous findings, suggest the cancer therapeutic as well as chemopreventive potential of Citrus fruits.

Luteolin이 인간의 대장암세포인 HT-29 세포의 ErbB3 Signaling Pathway에 미치는 영향

임도영,조한진,박소영,이기원,윤정한 대한암예방학회 2011 Journal of cancer prevention Vol.16 No.2

Luteolin is 3’,4’,5,7-tetrahydroxyflavone found in various kind of fruits and vegetables. We have previously shown that luteolin decreased HT-29 cell growth by inducing apoptosis and cell cycle arrest. The present study examined whether luteolin downregulates ErbB3 signaling pathway in HT-29 cells. Cells were cultured with or without 60μmol/L of luteolin and/or heregulin (HRG)-β. HRG-β induced proliferation of HT-29 cells and luteolin abrogated this induction. Luteolin decreased both protein and mRNA levels of EGFR, ErbB3 and ErbB2 in HT-29 cells. Immunoprecipitation/Western blot analyses revealed that luteolin decreased HRG-β-induced tyrosine phosphorylation of ErbB3, recruitment of the p85 subunit of PI3K to ErbB3, and ErbB3-associated PI3K activity. Furthermore luteolin decreased HRG-β-stimulated phosphorylation of Akt. Luteolin also decreased extracellular signal-regulated kinase (ERK)1/2. The present results demonstrate that luteolin down-regulates the ErbB3 signaling pathway,which may one of the mechanisms responsible for the growth inhibitory effect on HT-29 cells. (Cancer Prev Res 16, 134-140, 2011)

Histologic Findings and Inflammatory Reactions After Long-term Colonization of Helicobacter felis in C57BL/6 Mice

이주엽,김나영,최윤정,남령희,최윤진,권용환,Kichul Yoon,서지형,Seon Min Lee,이혜승,이동호 대한암예방학회 2014 Journal of cancer prevention Vol.19 No.3

Background: The Helicobacter felis (H. felis) mouse model has been developed for the research regarding pathogenesis of chronic gastritis and gastric cancer. The aim of this study was to investigate long-term H. felis colonization in the stomachs of C57BL/6 mice and subsequent histologic findings and inflammatory reactions including pro-inflammatory cytokines. Methods: Twenty-three female C57BL/6 mice at 4 weeks of age were gavaged with H. felis, and 13 control mice served as vehicle only. The mice were sacrificed at 4, 24, and 52 weeks after inoculation. The infection status and degree of inflammation were determined by culture and histopathology. The level of gastric mucosal myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-α), and interleukin-1beta (IL-1β) were measured by ELISA. Results: The overall infection rate was 100%, as determined by the culture and histology. At 4, 24, and 52 weeks, the neutrophil and monocyte scores were significantly higher in infected mice than in control mice. At 24 weeks after inoculation, most of the infected mice showed mucosal atrophy with or without metaplasia, and a few showed focal dysplasia. Adenocarcinoma was observed in one mouse at 52 week post-infection. Gastric mucosal MPO and IL-1 levels were significantly higher in infected mice than those in control mice at 24 and 52 weeks. However, the expression of gastric mucosal TNF-α was not significantly different between the infected and control mice at any time-point. Conclusions: Long-term H. felis-infection in C57BL/6 mice provoked a severe inflammatory reaction and it progressed into atrophy, metaplasia, dysplasia and cancer. IL-1β might play an important role in the inflammatory response of mice to Helicobacter species.

Interactions Between Ataxia Telangiectasia Mutated Kinase Inhibition, Poly(ADP-ribose) Polymerase-1 Inhibition and BRCA1 Status in Breast Cancer Cells

Józefa Węsierska-Gądek,Sarah Heinzl 대한암예방학회 2014 Journal of cancer prevention Vol.19 No.2

Background: Cells harboring BRCA1/BRCA2 mutations are hypersensitive to inhibition of poly(ADP-ribose) polymerase-1 (PARP-1). We recently showed that interference with PARP-1 activity by NU1025 is strongly cytotoxic for BRCA1-positive BT-20 cells but not BRCA1-deficient SKBr-3 cells. These unexpected observations prompted speculation that other PARP-1 inhibitor(s) may be more cytotoxic towards SKBr-3 cells. In addition, interference with the DNA damage signaling pathway via (for instance) Ataxia telangiectasia mutated (ATM) kinase inhibition may induce synthetic lethality in DNA repair-deficient breast cancer cells and pharmacological interference with ATM activity may sensitize breast cancer cells to PARP-1 inactivation. Methods: We determined drug cytotoxicity in human MCF-7 and SKBr-3 breast cancer cells using the CellTiterGLO Luminescent cell viability assay and a Tecan multi-label, multitask plate counter to measure generated luminescence. Changes in cell cycle progression were monitored by flow cytometric measurement of DNA content in cells stained with propidium iodide. Results: Unlike NU1025, AZD2461, a new PARP-1 inhibitor, markedly reduced the numbers of living MCF-7 and SKBr-3 cells. ATM kinase inhibition (CP466722) was also cytotoxic for both MCF-7 and SKBr-3 cells. Furthermore, AZD2461 enhanced the cytotoxicity of CP466722 in both cell lines by inducing apoptosis, and concurrent inhibition of ATM and PARP-1 reduced cell proliferation more strongly than either single treatment. Conclusions: Our data show that inhibition of PARP-1 by AZD2461 is synthetically lethal for NU1025-resistant MCF-7 and SKBr-3 breast cancer cells. They also indicate that DNA damage signaling is essential for survival of both SKBr-3 and MCF-7 cells, especially after inactivation of PARP-1.