• 생명과학회지
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• 제22권11호
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• pp.1552-1557
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• 2012

Pipernonaline은 후추나무과에 속하는 필발(Piper longum Linn.)의 유도체로서 전립선 암세포에 대한 항암활성이 보고되고 있다. 하지만 실제 암세포 내에서 생물학적 정보를 가진 수 많은 유전자들에 대한 발현이 어떻게 이루어지고 있는지 알려진 바가 없다. 본 연구에 사용된 microarray 분석은 동시에 수 만개 이상의 유전자 발현양상을 한번에 관찰할 수 있는 기술로서 특정 질병의 유전학적 특성과 기전 연구를 더 광범위하게 연구 할 수 있는 기술이다. 본 연구에서는 전립선 암세포인 PC-3 세포에 pipernonaline을 처리하여 cDNA microarray를 실시하였다. 이후, DAVID database를 이용하여 gene ontology의 Biological Process를 분석하여 세포사멸과 세포주기, 세포성장 및 증식에 관련된 유전자들을 우선적으로 분석하였다. 그 결과, 세포주기관련 256개, 세포사멸관련 197개, 세포성장 및 증식관련에 154개의 유전자가 확인 되었다. 이러한 결과는 pipernonaline은 전립선 암세포 내에 존재하는 생물학적 신호전달체계에 관련된 유전자 발현을 조절함으로써 항암활성을 나타내 것을 알 수 있었고, 이후 이러한 microarray의 추가적인 분석은 암세포 내 새로운 유전자의 탐색 및 메커니즘을 규명하는데 유용하게 사용할 수 있을 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3267-3271
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• 2014

Background: Several studies have investigated the association between methionine synthase reductase (MTRR) A66G polymorphism and breast cancer risk, but controversial results were yielded. Therefore, we performed a meta-analysis to provide a more robust estimate of the effect of this polymorphism on susceptibility to breast cancer. Materials and Methods:Case-control studies investigating the relationship between MTRR A66G polymorphism and breast cancer risk were included by searching PubMed, EMBASE, China National Knowledge Infrastructure and Wanfang Database. Either fixed-effects or random-effects models were applied to calculate odds ratios(ORs) and 95% confidence intervals (CIs) by RevMan5.2 software. Results: A total of 9 studies bearing 7,097 cases and 7,710 controls were included in the meta-analysis. The results were that the combined ORs and 95%CIs of MTRR 66AG, GG, (AG+GG) genotypes were 0.98(0.91-1.05), 1.06(0.97-1.16) and 1.02(0.94-1.10), respectively with p=0.52, 0.19 and 0.65. We also performed subgroup analysis by specific ethnicity. The results of the combined analysis of MTRR 66AG, GG, (AG+GG) genotypes and breast cancer in Asian descent were Z=0.50, 0.53 and 0.21, with p all>0.05; for breast cancer in Caucasian descent, the results were Z=1.14, 1.65 and 0.43, with p all>0.05. Conclusions: Our findings suggested that MTRR A66G polymorphism was not associated with breast cancer susceptibility.

• Genomics & Informatics
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• 제21권4호
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• pp.48.1-48.8
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• 2023

Liver cancer is the fourth leading cause of death worldwide. Well-known risk factors include hepatitis B virus and hepatitis C virus, along with exposure to aflatoxins, excessive alcohol consumption, obesity, and type 2 diabetes. Genomic variants play a crucial role in mediating the associations between these risk factors and liver cancer. However, the specific variants involved in this process remain under-explored. This study utilized a bioinformatics approach to identify genetic variants associated with liver cancer from various continents. Single-nucleotide polymorphisms associated with liver cancer were retrieved from the genome-wide association studies catalog. Prioritization was then performed using functional annotation with HaploReg v4.1 and the Ensembl database. The prevalence and allele frequencies of each variant were evaluated using Pearson correlation coefficients. Two variants, rs2294915 and rs2896019, encoded by the PNPLA3 gene, were found to be highly expressed in the liver tissue, as well as in the skin, cell-cultured fibroblasts, and adipose-subcutaneous tissue, all of which contribute to the risk of liver cancer. We further found that these two SNPs (rs2294915 and rs2896019) were positively correlated with the prevalence rate. Positive associations with the prevalence rate were more frequent in East Asian and African populations. We highlight the utility of this population-specific PNPLA3 genetic variant for genetic association studies and for the early prognosis and treatment of liver cancer. This study highlights the potential of integrating genomic databases with bioinformatic analysis to identify genetic variations involved in the pathogenesis of liver cancer. The genetic variants investigated in this study are likely to predispose to liver cancer and could affect its progression and aggressiveness. We recommend future research prioritizing the validation of these variations in clinical settings.

• Korean Journal of Acupuncture
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• 제41권1호
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• pp.7-15
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• 2024

Objectives : This study aimed to predict the effectiveness and potential of Schizonepeta tenuifolia as an anticancer treatment for non-small cell lung cancer through network-based pharmacology and cellular experiment. Methods : To identify the major bioactive compounds in Schizonepeta tenuifolia, we used the Traditional Chinese Medicine Systems. The target genes for the cancer treatment were selected using the UniProt database and the networked using Cytoscape. We performed functional enrichment analysis based on the Gene Ontology Biological Process and Kyoto Encyclopedia of Genes and Genomes Pathways to predict the mechanisms. To investigate the effect of Schizonepeta tenuifolia on lung cancer cell growth, we treated A549 cells, a lung cancer cell line, with different concentrations of the drug and used the MTT assay for cell viability. Results : Research has shown that the most effective mechanism of active compounds from Schizonepeta tenuifolia is through the pathway of cancer. The results of the network pharmacology analysis indicate that Schizonepeta tenuifolia has potential medicinal value as an adjuvant in anticancer treatment. The concentration-dependent inhibition of cell viability was observed on A549 cells. Furthermore, synergistic anticancer activity with Doxorubicin was also observed. Conclusions : Through a network pharmacological approach, Schizonepeta tenuifolia was predicted to have potential as an anticancer agent, and its efficacy was experimentally demonstrated using A549 cells. These findings suggest that Schizonepeta tenuifolia is a promising candidate for future research.

• Molecules and Cells
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• 제44권3호
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• pp.146-159
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• 2021

DNA methylation, and consequent down-regulation, of tumour suppressor genes occurs in response to epigenetic stimuli during cancer development. Similarly, human oncoviruses, including human papillomavirus (HPV), up-regulate and augment DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activities, thereby decreasing tumour suppressor genes (TSGs) expression. Ubiquitin-like containing PHD and RING finger domain 1 (UHRF1), an epigenetic regulator of DNA methylation, is overexpressed in HPV-induced cervical cancers. Here, we investigated the role of UHRF1 in cervical cancer by knocking down its expression in HeLa cells using lentiviral-encoded short hairpin (sh)RNA and performing cDNA microarrays. We detected significantly elevated expression of thioredoxin-interacting protein (TXNIP), a known TSG, in UHRF1-knockdown cells, and this gene is hypermethylated in cervical cancer tissue and cell lines, as indicated by whole-genome methylation analysis. Up-regulation of UHRF1 and decreased TXNIP were further detected in cervical cancer by western blot and immunohistochemistry and confirmed by Oncomine database analysis. Using chromatin immunoprecipitation, we identified the inverted CCAAT domain-containing UHRF1-binding site in the TXNIP promoter and demonstrated UHRF1 knockdown decreases UHRF1 promoter binding and enhances TXNIP expression through demethylation of this region. TXNIP promoter CpG methylation was further confirmed in cervical cancer tissue by pyrosequencing and methylation-specific polymerase chain reaction. Critically, down-regulation of UHRF1 by siRNA or UHRF1 antagonist (thymoquinone) induces cell cycle arrest and apoptosis, and ubiquitin-specific protease 7 (USP7), which stabilises and promotes UHRF1 function, is increased by HPV viral protein E6/E7 overexpression. These results indicate HPV might induce carcinogenesis through UHRF1-mediated TXNIP promoter methylation, thus suggesting a possible link between CpG methylation and cervical cancer.

• BMB Reports
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• 제55권11호
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• pp.553-558
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• 2022

Hepatocellular carcinoma (HCC) is dangerous cancer that often evades early detection because it is asymptomatic and an effective detection method is lacking. For people with chronic liver inflammation who are at high risk of developing HCC, a sensitive detection method for HCC is needed. In a meta-analysis of The Cancer Genome Atlas pan-cancer methylation database, we identified a CpG island in the USP44 promoter that is methylated specifically in HCC. We developed methylation-sensitive high-resolution melting (MS-HRM) analysis to measure the methylation levels of the USP promoter in cell-free DNA isolated from patients. Our MS-HRM assay correctly identified 40% of patients with early-stage HCC, whereas the α-fetoprotein test, which is currently used to detect HCC, correctly identified only 25% of early-stage HCC patients. These results demonstrate that USP44 MS-HRM analysis is suitable for HCC surveillance.

• Journal of Gastric Cancer
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• 제20권3호
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• pp.313-327
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• 2020

Purpose: Nodal downstaging after preoperative therapy for gastric cancer has been shown to impart excellent prognosis, but this has not been validated in a national cohort. The role of neoadjuvant chemoradiation (NACR) in nodal downstaging remains unclear when compared with that of neoadjuvant chemotherapy alone (NAC). Furthermore, it is unknown whether the prognostic implications of nodal downstaging differ by preoperative regimen. Materials and Methods: Using the National Cancer Database, overall survival (OS) duration was compared among natural N0 (cN0/ypN0), downstaged N0 (cN+/ypN0), and nodepositive (ypN+) gastric cancer patients treated with NACR or NAC. Factors associated with nodal downstaging were examined in a propensity score-matched cohort of cN+ patients, matched 1:1 by receipt of NACR or NAC. Results: Of 7,426 patients (natural N0 [n=1,858, 25.4%], downstaged N0 [n=1,813, 24.4%], node-positive [n=3,755, 50.4%]), 58.2% received NACR, and 41.9% received NAC. The median OS durations of downstaged N0 (5.1 years) and natural N0 (5.6 years) patients were similar to one another and longer than that of node-positive patients (2.1 years) (P<0.001). In the matched cohort of cN+ patients, more recent diagnosis (2010-2015 vs. 2004-2009) (odds ratio [OR], 2.57; P<0.001) and NACR (OR, 2.02; P<0.001) were independently associated with nodal downstaging. The 5-year OS rate of downstaged N0 patients was significantly lower after NACR (46.4%) than after NAC (57.7%) (P=0.003). Conclusions: Downstaged N0 patients have the same prognosis as natural N0 patients. Nodal downstaging occurred more frequently after NACR; however, the survival benefit of nodal downstaging after NACR may be less than that when such is achieved by NAC.

• Nutrition Research and Practice
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• 제15권6호
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• pp.773-788
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• 2021

BACKGROUND/OBJECTIVES: Due to the rapid increase of global cancer incidence and mortality and a high level of interest in cancer prevention, a systematic review of garlic intake and cancer risk is needed. SUBJECTS/METHODS: We implemented a systematic review to examine the effects of varying levels of garlic intake on cancer. We conducted comprehensive literature searches in three electronic databases (MEDLINE, Embase, and Web of Science) for studies published between database inception and July or September of 2018. Two investigators independently screened abstracts and full-texts, extracted data, and assessed risk of bias (RoB). A total of one medium-quality randomized controlled trial (RCT) and 13 cohort studies graded as high RoB were included. RESULTS: The 1-year follow-up results from a RCT showed that a significant decrease in the number and size of colorectal adenomas among participants with colorectal adenomas who received high-dose aged garlic extract (AGE) compared with those who received low-dose AGE (P < 0.05). The results of prospective observational studies provided inconsistent associations of colorectal cancer risk with garlic supplements and garlic intake as food. CONCLUSIONS: In summary, the AGE was effective in reducing the number and magnitude of colorectal adenomas in one RCT, but there were inconsistent associations between garlic intake and colorectal cancer in cohort studies. Therefore, we could not draw a firm conclusion regarding the effects of garlic on cancer, because the current strength of evidence is inadequate due to a lack of number of high-quality RCTs.

• Journal of Gastric Cancer
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• 제23권1호
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• pp.3-106
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• 2023

Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7117-7120
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• 2013

Background: This study hypothesized living in a poor neighborhood decreased the cause specific survival in individuals suffering from carcinoid carcinomas. Surveillance, Epidemiology and End Results (SEER) carcinoid carcinoma data were used to identify potential socioeconomic disparities in outcome. Materials and Methods: This study analyzed socioeconomic, staging and treatment factors available in the SEER database for carcinoid carcinomas. The Kaplan-Meier method was used to analyze time to events and the Kolmogorov-Smirnov test to compare survival curves. The Cox proportional hazard method was employed for multivariate analysis. Areas under the receiver operating characteristic curves (ROCs) were computed to screen the predictors for further analysis. Results: There were 38,546 patients diagnosed from 1973 to 2009 included in this study. The mean follow up time (S.D.) was 68.1 (70.7) months. SEER stage was the most predictive factor of outcome (ROC area of 0.79). 16.4% of patients were un-staged. Race/ethnicity, rural urban residence and county level family income were significant predictors of cause specific survival on multivariate analysis, these accounting for about 5% of the difference in actuarial cause specific survival at 20 years of follow up. Conclusions: This study found poorer cause specific survival of carcinoid carcinomas of individuals living in poor and rural neighborhoods.