|
1
|
Fang JY, Du YQ, Liu WZ, Ren JL, Li YQ, Chen XY, Lv NH, Chen YX, Lv B. Chinese consensus on chronic gastritis (2017, Shanghai). J Dig Dis 2018; 19:182-203. [PMID: 29573173 DOI: 10.1111/1751-2980.12593] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
|
|
2
|
Deregulation of MYC and TP53 through genetic and epigenetic alterations in gallbladder carcinomas. Clin Exp Med 2014; 15:421-6. [PMID: 25200035 DOI: 10.1007/s10238-014-0311-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2014] [Accepted: 08/26/2014] [Indexed: 12/11/2022]
Abstract
Gallbladder cancer is a rare malignancy and presents a poor prognosis. MYC and p53 have been implicated in gallbladder carcinogenesis. However, little is known about the molecular mechanisms involved in their regulation in this neoplasia. Here, we evaluated the MYC and TP53 copy numbers in gallbladder tumors and their possible association with protein expression. We also investigated whether MYC may be controlled by mutations and DNA promoter methylation. In the present study, 15 samples of invasive gallbladder carcinomas and six control samples were analyzed. On the other hand, the expression of MYC and p53 was more frequent in gallbladder carcinomas than in control samples (p = 0.002, p = 0.046, respectively). Gain of copies of the MYC and TP53 genes was detected in 86.7 and 50 % of gallbladder carcinomas, respectively. MYC and TP53 amplifications were associated with immunoreactivity of their protein (p = 0.029, p = 0.001, respectively). MYC hypomethylation was only detected in tumoral samples and was associated with its protein expression (p = 0.029). MYC mutations were detected in 80 % of tumor samples. The G allele at rs117856857 was associated with the presence of gallbladder tumors (p = 0.019) and with MYC expression (p = 0.044). Moreover, two tumors presented a pathogenic mutation in MYC exon 2 (rs28933407). Our study highlights that the gain of MYC and TP53 copies seems to be a frequent finding in gallbladder cancer. In addition, gain of copies, hypomethylation and point mutations at MYC may contribute to overexpression of its protein in this type of cancer.
Collapse
|
|
3
|
Raykov Z, Ivanov V, Raikova E, Galabov A. Folic Acid Role in Mutagenesis, Carcinogenesis, Prevention and Treatment of Cancer. BIOTECHNOL BIOTEC EQ 2014. [DOI: 10.1080/13102818.2004.10817133] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
|
|
4
|
Bae S, Ulrich CM, Bailey LB, Malysheva O, Brown EC, Maneval DR, Neuhouser ML, Cheng TYD, Miller JW, Zheng Y, Xiao L, Hou L, Song X, Buck K, Beresford SAA, Caudill MA. Impact of folic acid fortification on global DNA methylation and one-carbon biomarkers in the Women's Health Initiative Observational Study cohort. Epigenetics 2014; 9:396-403. [PMID: 24300587 PMCID: PMC4053458 DOI: 10.4161/epi.27323] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2013] [Revised: 11/16/2013] [Accepted: 11/22/2013] [Indexed: 12/31/2022] Open
Abstract
DNA methylation is an epigenetic mechanism that regulates gene expression and can be modified by one-carbon nutrients. The objective of this study was to investigate the impact of folic acid (FA) fortification of the US food supply on leukocyte global DNA methylation and the relationship between DNA methylation, red blood cell (RBC) folate, and other one-carbon biomarkers among postmenopausal women enrolled in the Women's Health Initiative Observational Study. We selected 408 women from the highest and lowest tertiles of RBC folate distribution matching on age and timing of the baseline blood draw, which spanned the pre- (1994-1995), peri- (1996-1997), or post-fortification (1998) periods. Global DNA methylation was assessed by liquid chromatography-tandem mass spectrometry and expressed as a percentage of total cytosine. We observed an interaction (P = 0.02) between fortification period and RBC folate in relation to DNA methylation. Women with higher (vs. lower) RBC folate had higher mean DNA methylation (5.12 vs. 4.99%; P = 0.05) in the pre-fortification period, but lower (4.95 vs. 5.16%; P = 0.03) DNA methylation in the post-fortification period. We also observed significant correlations between one-carbon biomarkers and DNA methylation in the pre-fortification period, but not in the peri- or post-fortification period. The correlation between plasma homocysteine and DNA methylation was reversed from an inverse relationship during the pre-fortification period to a positive relationship during the post-fortification period. Our data suggest that (1) during FA fortification, higher RBC folate status is associated with a reduction in leukocyte global DNA methylation among postmenopausal women and; (2) the relationship between one-carbon biomarkers and global DNA methylation is dependent on folate availability.
Collapse
Affiliation(s)
- Sajin Bae
- Division of Nutritional Sciences; Cornell University; Ithaca, NY USA
| | - Cornelia M Ulrich
- Fred Hutchinson Cancer Research Center; Seattle, WA USA
- German Cancer Research Center and National Center for Tumor Diseases; Heidelberg, Germany
| | - Lynn B Bailey
- Department of Foods and Nutrition; University of Georgia; Athens, GA USA
| | - Olga Malysheva
- Division of Nutritional Sciences; Cornell University; Ithaca, NY USA
| | | | - David R Maneval
- Food Science and Human Nutrition Department; University of Florida; Gainesville, FL USA
| | | | | | - Joshua W Miller
- Department of Nutritional Sciences; Rutgers University; New Brunswick, NJ USA
- Department of Medical Pathology and Laboratory Medicine; University of California; Davis, CA USA
| | - Yingye Zheng
- Fred Hutchinson Cancer Research Center; Seattle, WA USA
| | - Liren Xiao
- Fred Hutchinson Cancer Research Center; Seattle, WA USA
| | - Lifang Hou
- Department of Preventive Medicine and Robert H. Lurie Comprehensive Cancer; Northwestern University; Chicago, IL USA
| | - Xiaoling Song
- Fred Hutchinson Cancer Research Center; Seattle, WA USA
| | - Katharina Buck
- German Cancer Research Center and National Center for Tumor Diseases; Heidelberg, Germany
| | | | - Marie A Caudill
- Division of Nutritional Sciences; Cornell University; Ithaca, NY USA
| |
Collapse
|
|
5
|
de Souza CRT, Leal MF, Calcagno DQ, Costa Sozinho EK, Borges BDN, Montenegro RC, Dos Santos AKCR, Dos Santos SEB, Ribeiro HF, Assumpção PP, de Arruda Cardoso Smith M, Burbano RR. MYC deregulation in gastric cancer and its clinicopathological implications. PLoS One 2013; 8:e64420. [PMID: 23717612 PMCID: PMC3661519 DOI: 10.1371/journal.pone.0064420] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2013] [Accepted: 04/12/2013] [Indexed: 12/13/2022] Open
Abstract
Our study investigated the relationship between MYC alterations and clinicopathological features in gastric cancers. We evaluated the effect of MYC mRNA expression and its protein immunoreactivity, as well as copy number variation, promoter DNA methylation, and point mutations, in 125 gastric adenocarcinoma and 67 paried non-neoplastic tissues. We observed that 77% of the tumors presented MYC immunoreactivity which was significantly associated with increased mRNA expression (p<0.05). These observations were associated with deeper tumor extension and the presence of metastasis (p<0.05). MYC protein expression was also more frequently observed in intestinal-type than in diffuse-type tumors (p<0.001). Additionally, MYC mRNA and protein expression were significantly associated with its copy number (p<0.05). The gain of MYC copies was associated with late-onset, intestinal-type, advanced tumor stage, and the presence of distant metastasis (p<0.05). A hypomethylated MYC promoter was detected in 86.4% of tumor samples. MYC hypomethylation was associated with diffuse-type, advanced tumor stage, deeper tumor extension, and the presence of lymph node metastasis (p<0.05). Moreover, eighteen tumor samples presented at least one known mutation. The presence of MYC mutations was associated with diffuse-type tumor (p<0.001). Our results showed that MYC deregulation was mainly associated with poor prognostic features and also reinforced the presence of different pathways involved in intestinal-type and diffuse-type gastric carcinogenesis. Thus, our findings suggest that MYC may be a useful marker for clinical stratification and prognosis.
Collapse
|
|
6
|
Rusiecki JA, Al-Nabhani M, Tarantini L, Chen L, Baccarelli A, Al-Moundhri MS. Global DNA methylation and tumor suppressor gene promoter methylation and gastric cancer risk in an Omani Arab population. Epigenomics 2012; 3:417-29. [PMID: 22126203 DOI: 10.2217/epi.11.65] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
AIM We carried out a case-control study in an Omani Arab population to investigate the association between gastric cancer and peripheral blood leukocyte DNA methylation in LINE-1 and in the tumor suppressor genes CDH1, p16, TP53 and RUNX3. MATERIALS & METHODS We quantified methylation (%5-mC) in DNA extracted from peripheral blood leukocytes via pyrosequencing. We calculated odds ratios (ORs) and 95% CIs using logistic regression. RESULTS We found patterns of global hypomethylation (LINE-1: OR(continuous) = 0.59; 95% CI: 0.42-0.82) and TP53 promoter hypomethylation (OR(continuous) = 0.64; 95% CI: 0.16-0.85) for cases versus controls; p16 promoter region hypomethylation was not statistically significant. Evaluating LINE-1, TP53 and p16 jointly yielded a more pronounced negative association with gastric cancer (OR: 0.24; 95% CI: 0.09-0.66). Age was a significant effect modifier. We found no differences by tumor grade, stage or histology. CONCLUSION We found a pattern of global hypomethylation and promoter region hypomethylation of TP53 and p16 in cases versus controls for this population of Omani Arabs.
Collapse
Affiliation(s)
- Jennifer A Rusiecki
- Department of Preventive Medicine & Biometrics, Uniformed Services University, 4301 Jones Bridge Rd, Bethesda, MD 20814, USA.
| | | | | | | | | | | |
Collapse
|
|
7
|
Abstract
Skin, the largest, most exposed organ of the body, provides a protective interface between humans and the environment. One of its primary roles is protection against exposure to sunlight, a major source of skin damage where the UV radiation (UVR) component functions as a complete carcinogen. Melanin pigmentation and the evolution of dark skin is an adaptive protective mechanism against high levels of UVR exposure. Recently, the hypothesis that skin pigmentation balances folate preservation and Vitamin D production has emerged. Both micronutrients are essential for reproductive success. Photodegradation of bioactive folates suggests a mechanism for the increased tendency of populations of low melanin pigmentation residing in areas of high UV exposure to develop skin cancers. Folate is proposed as a cancer prevention target for its role in providing precursors for DNA repair and replication, as well as its ability to promote genomic integrity through the generation of methyl groups needed for control of gene expression. The cancer prevention potential of folate has been demonstrated by large-scale epidemiological and nutritional studies indicating that decreased folate status increases the risk of developing certain cancers. While folate deficiency has been extensively documented by analysis of human plasma, folate status within skin has not been widely investigated. Nevertheless, inefficient delivery of micronutrients to skin and photolysis of folate argue that documented folate deficiencies will be present if not exacerbated in skin. Our studies indicate a critical role for folate in skin and the potential to protect sun exposed skin by effective topical delivery as a strategy for cancer prevention.
Collapse
Affiliation(s)
- J D Williams
- Division of Medicinal Chemistry, Department of Pharmacology and Toxicology, College of Pharmacy and Arizona Cancer Center, University of Arizona, Tucson, AZ, USA,
| | | | | | | | | |
Collapse
|
|
8
|
Abstract
Methylation of cytosine bases in DNA provides a layer of epigenetic control in many eukaryotes that has important implications for normal biology and disease. DNA methylation is a crucial epigenetic modification of the genome that is involved in regulating many cellular processes. A growing number of human diseases including cancer have been found to be associated with aberrant DNA methylation. Recent advancements in the rapidly evolving field of cancer epigenetics have described extensive reprogramming of every component of the epigenetic machinery in cancer, such as DNA demethylation. In this review, we discuss the current understanding of alterations in DNA methylation composing the epigenetic landscape that occurs in gastric cancer compared with normal cells, the roles of these changes in gastric cancer initiation and progression, and the potential use of this knowledge in designing more effective treatment strategies.
Collapse
|
|
9
|
Al-Moundhri MS, Al-Nabhani M, Tarantini L, Baccarelli A, Rusiecki JA. The prognostic significance of whole blood global and specific DNA methylation levels in gastric adenocarcinoma. PLoS One 2010; 5:e15585. [PMID: 21203466 PMCID: PMC3009731 DOI: 10.1371/journal.pone.0015585] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2010] [Accepted: 11/16/2010] [Indexed: 12/11/2022] Open
Abstract
Background Epigenetics, particularly DNA methylation, has recently been elucidated as important in gastric cancer (GC) initiation and progression. We investigated the clinical and prognostic importance of whole blood global and site-specific DNA methylation in GC. Methods Genomic DNA was extracted from the peripheral blood of 105 Omani GC patients at diagnosis. DNA methylation was quantified by pyrosequencing of global DNA and specific gene promoter regions at 5 CpG sites for CDH1, 7 CpG sites for p16, 4 CpG sites for p53, and 3 CpG sites for RUNX3. DNA methylation levels in patients were categorized into low, medium, and high tertiles. Associations between methylation level category and clinicopathological features were evaluated using χ2 tests. Survival analyses were carried out using the Kaplan-Meier method and log rank test. A backward conditional Cox proportional hazards regression model was used to identify independent predictors of survival. Results Older GC patients had increased methylation levels at specific CpG sites within the CDH1, p53, and RUNX-3 promoters. Male gender was significantly associated with reduced global and increased site-specific DNA methylation levels in CDH1, p16, and p53 promoters. Global DNA low methylation level was associated with better survival on univariate analysis. Patients with high and medium methylation vs. low methylation levels across p16 promoter CpG sites, site 2 in particular, had better survival. Multivariate analysis showed that global DNA hypermethylation was a significant independent predictor of worse survival (hazard ratio (HR) = 2.0, 95% CI: 1.1–3.8; p = 0.02) and high methylation mean values across p16 promoter sites 1–7 were associated with better survival with HR of 0.3 (95% CI, 0.1–0.8; p = 0.02) respectively. Conclusions Analysis of global and site-specific DNA methylation in peripheral blood by pyrosequencing provides quantitative DNA methylation values that may serve as important prognostic indicators.
Collapse
Affiliation(s)
- Mansour S Al-Moundhri
- Medical Oncology Unit, Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Sultanate of Oman.
| | | | | | | | | |
Collapse
|
|
10
|
Calcagno DQ, Leal MF, Assumpção PP, Smith MDAC, Burbano RR. MYC and gastric adenocarcinoma carcinogenesis. World J Gastroenterol 2008; 14:5962-8. [PMID: 18932273 PMCID: PMC2760197 DOI: 10.3748/wjg.14.5962] [Citation(s) in RCA: 89] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
MYC is an oncogene involved in cell cycle regulation, cell growth arrest, cell adhesion, metabolism, ribosome biogenesis, protein synthesis, and mitochondrial function. It has been described as a key element of several carcinogenesis processes in humans. Many studies have shown an association between MYC deregulation and gastric cancer. MYC deregulation is also seen in gastric preneoplastic lesions and thus it may have a role in early gastric carcinogenesis. Several studies have suggested that amplification is the main mechanism of MYC deregulation in gastric cancer. In the present review, we focus on the deregulation of the MYC oncogene in gastric adenocarcinoma carcinogenesis, including its association with Helicobacter pylori (H pylori) and clinical applications.
Collapse
|
|
11
|
Ren H, Du N, Zhang J, Yao J, Shi JS. Variabilities of serum proteomic spectra in patients with gastric cancer before and after operation. Shijie Huaren Xiaohua Zazhi 2008; 16:314-318. [DOI: 10.11569/wcjd.v16.i3.314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the variabilities of serum proteomic spectra in patients with gastric cancer before and after operation in order to detect specific protein markers that can be used in the rapid diagnosis of gastric cancer.
METHODS: Proteomic spectra of 46 serum samples from patients with gastric cancer before and after operation and 40 from normal individuals were generated by IMAC-Cu protein chip and surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS).
RESULTS: Fourteen differentially expressed proteins in serum were screened by analysis of proteomic spectra in preoperative patients and normal individuals. We obtained 4 proteins (heat shock protein 27, glucose-regulated protein, prohibitin, protein disulfide isomerase A3) as markers able to classify gastric cancer patients and normal individuals. The sensitivity and specificity of these markers were 95.7% and 92.5%, respectively. The proteins over-expressed in serum of preoperative patients were obviously down-regulated.
CONCLUSION: Specific proteinic markers of gastric cancer can be detected in serum and used both in the rapid diagnosis of gastric cancer and in the judgment of prognosis. SELDI-TOF-MS is a useful tool for the detection and identification of new protein markers in serum.
Collapse
|
|
12
|
Fang JY, Liu WZ, Shi Y, Ge ZZ, Xiao SD. Consensus on chronic gastritis in China--Second National Consensus Meeting on Chronic Gastritis (14-16 September 2006 Shanghai, China). J Dig Dis 2007; 8:107-19. [PMID: 17532824 DOI: 10.1111/j.1443-9573.2007.00295.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Jing Yuan Fang
- Department of Gastroenterology of Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | | | | | | | | |
Collapse
|
|
13
|
Abstract
Linkages between diet habits and cancer risk have surfaced from a multitude of epidemiological and preclinical studies. Collectively these studies provide rather compelling evidence that dietary components modify the incidence and biological behavior of tumors. While the risk of breast, prostate, colon, lung and liver cancers are frequently associated with dietary patterns, inconsistencies are not uncommon. These inconsistencies likely reflect the multi-factorial and complex nature of cancer and the specificity that individual dietary constituents have in modifying cancer related genetic pathways. The complexity of defining the role of diet is underscored by the numerous and diverse essential and non-essential components that may alter one or more phases of the cancer process. The explosive increase in the recognition of genes and pathways for regulating cell growth and development, and evaluating the response to hormones and other chemicals synthesized by the body, offers exciting opportunities for unraveling the molecular targets by which dietary components influence cancer prevention. It is recognized that all cells have unique ‘signatures’ that are characterized by active and inactive genes and cellular products. It is certainly plausible that bridging knowledge about these unique cellular characteristics with the molecular targets for nutrients can be used to assist in optimizing nutrition and minimizing cancer risk.
Collapse
|
|
14
|
Weng YR, Sun DF, Fang JY, Gu WQ, Zhu HY. Folate levels in mucosal tissue but not methylenetetrahydrofolate reductase polymorphisms are associated with gastric carcinogenesis. World J Gastroenterol 2006; 12:7591-7. [PMID: 17171786 PMCID: PMC4088039 DOI: 10.3748/wjg.v12.i47.7591] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate whether folate levels in mucosal tissue and some common methylenetetrahydrofolate reductase (MTHFR) variants are associated with the risk of gastric cancer through DNA methylation.
METHODS: Real-time PCR was used to study the expression of tumor related genes in 76 mucosal tissue samples from 38 patients with gastric cancer. Samples from the gastroscopic biopsy tissues of 34 patients with chronic superficial gastritis (CSG) were used as controls. Folate concentrations in these tissues were detected by the FOL ACS: 180 automated chemiluminescence system. MTHFR polymorphisms were analyzed by PCR-RFLP, and the promoter methylation of tumor-related genes was determined by methylation-specific PCR (MSP).
RESULTS: Folate concentrations were significantly higher in CSG than in cancerous tissues. Decreased expression and methylation of c-myc accompanied higher folate concentrations. Promoter hypermethylation and loss of p16INK4A in samples with MTHFR 677CC were more frequent than in samples with the 677TT or 677CT genotype. And the promoter hypermethylation and loss of p21WAF1 in samples with MTHFR 677CT were more frequent than when 677CC or 677TT was present. The 677CT genotype showed a non-significant higher risk for gastric cancer as compared with the 677CC genotype.
CONCLUSION: Lower folate levels in gastric mucosal tissue may confer a higher risk of gastric carcinogenesis through hypomethylation and overexpression of c-myc.
Collapse
Affiliation(s)
- Yu-Rong Weng
- Shanghai Institute of Digestive Disease, Shanghai Jiao-Tong University School of Medicine, Renji Hospital, Shanghai 200001, China
| | | | | | | | | |
Collapse
|
|
15
|
Ren H, Du N, Liu G, Hu HT, Tian W, Deng ZP, Shi JS. Analysis of variabilities of serum proteomic spectra in patients with gastric cancer before and after operation. World J Gastroenterol 2006; 12:2789-92. [PMID: 16718772 PMCID: PMC4130994 DOI: 10.3748/wjg.v12.i17.2789] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the variabilities of serum proteomic spectra in patients with gastric cancer before and after operation in order to detect the specific protein markers that can be used for quick diagnosis of gastric cancer.
METHODS: Proteomic spectra of 46 serum samples from patients with gastric cancer before and after operation and 40 from normal individuals were generated by IMAC-Cu protein chip and surface-enhanced laser desorption/ ionization time of flight mass spectrometry.
RESULTS: Fourteen differentially expressed proteins in serum were screened by analysis of proteomic spectra of preoperative patients and normal individuals. We obtained 4 proteins (heat shock protein 27, glucose-regulated protein, prohibitin, protein disulfide isomerase A3) making up marker pattern which was able to class the patient-team and normal-team. These marker patterns yielded 95.7% sensitivity and 92.5% specificity, respectively. The proteins over-expressed in serum of preoperative patients were obviously down-regulated.
CONCLUSION: Specific protein markers of gastric cancer can be used for the quick diagnosis of gastric cancer and judgment of prognosis. SELDI-TOF-MS is a useful tool for the detection and identification of new protein markers in serum.
Collapse
Affiliation(s)
- Hong Ren
- Department of Oncosurgery, First Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
| | | | | | | | | | | | | |
Collapse
|
|
16
|
|
|
17
|
Cao DZ, Sun WH, Ou XL, Yu Q, Yu T, Zhang YZ, Wu ZY, Xue QP, Cheng YL. Effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in premalignant gastric lesions. World J Gastroenterol 2005; 11:1571-6. [PMID: 15786529 PMCID: PMC4305933 DOI: 10.3748/wjg.v11.i11.1571] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions.
METHODS: Thirty-eight patients, with premalignant gastric lesions including 18 colonic-type intestinal metaplasia (IM) and 20 mild or moderate dysplasia, were randomly divided into a treatment group (n = 19) receiving folic acid 10 mg thrice daily and a control group (n = 19) receiving sucralfate 1000 mg thrice daily for 3 mo. All patients underwent endoscopies and four biopsies were taken prior to treatment and repeated after concluding therapy. Folate concentrations in gastric mucosa were measured with chemiluminescent enzyme immunoassay. Epithelial apoptosis and the expression of Bcl-2 and p53 protein in gastric mucosa were detected with flow cytometric assay.
RESULTS: The mean of folate concentration in gastric mucosa was 9.03±3.37 μg/g wet wt in the folic acid treatment group, which was significantly higher than 6.83±3.02 μg/g wet wt in the control group. Both the epithelial apoptosis rate and the tumor suppressor p53 expression in gastric mucosa significantly increased after folic acid treatment. In contrast, the expression of Bcl-2 oncogene protein decreased after folic acid therapy.
CONCLUSION: These data indicate that folic acid may play an important role in the chemoprevention of gastric carcinogenesis by enhancing gastric epithelial apoptosis in the patients with premalignant lesions.
Collapse
Affiliation(s)
- Da-Zhong Cao
- Department of Gastroenterology, Zhongda Hospital of Southeast University, Nanjing 210009, Jiangsu Province, China
| | | | | | | | | | | | | | | | | |
Collapse
|
|
18
|
Narayanan S, McConnell J, Little J, Sharp L, Piyathilake CJ, Powers H, Basten G, Duthie SJ. Associations between Two Common Variants C677T and A1298C in the Methylenetetrahydrofolate Reductase Gene and Measures of Folate Metabolism and DNA Stability (Strand Breaks, Misincorporated Uracil, and DNA Methylation Status) in Human Lymphocytes In vivo. Cancer Epidemiol Biomarkers Prev 2004. [DOI: 10.1158/1055-9965.1436.13.9] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Abstract
Objective: Homozygosity for variants of the methylenetetrahydrofolate reductase (MTHFR) gene is associated with decreased risk for colorectal cancer. We have investigated the relationships between two variants of the MTHFR gene (C677T and A1298C) and blood folate, homocysteine, and genomic stability (strand breakage, misincorporated uracil, and global cytosine methylation in lymphocytes) in a study of 199 subjects. Results: The frequencies of homozygosity for the C677T and A1298C variants of the MTHFR gene were 12.6% and 14.6%, respectively. Plasma homocysteine, folate, vitamin B12, 5-methyltetrahydrofolate, and RBC folate were determined in the C677T genotypes. Plasma folate was significantly lower (P < 0.001) in the homozygous variants (6.7 ± 0.6 ng/mL) compared with wild-types (8.8 ± 0.4 ng/mL) and heterozygotes (9.1 ± 0.5 ng/mL). Homocysteine was significantly higher (P < 0.05) in homozygous variants (13.2 ± 1.1 μmol/L) compared with homozygous subjects (10.9 ± 0.4 μmol/L). Homozygous variants had significantly lower (P < 0.05) RBC folate (84.7 ± 6.3 ng/mL) compared with wild-types (112.2 ± 5.2 ng/mL) and heterozygous individuals (125.1 ± 6.6 ng/mL). No significant difference in RBC folate was observed between wild-types and heterozygotes. The A1298C variant did not influence plasma homocysteine, folate, 5-methyltetrahydrofolate, vitamin B12, or RBC folate. Lymphocyte DNA stability biomarkers (strand breaks, misincorporated uracil, and global DNA methylation) were similar for all MTHFR C677T or A1298C variants. Conclusion: Data from this study do not support the hypothesis that polymorphisms in the MTHFR gene increase DNA stability by sequestering 5,10-methylenetetrahydrofolate for thymidine synthesis and reducing uracil misincorporation into DNA.
Collapse
Affiliation(s)
- Sabrina Narayanan
- 1Division of Cellular Integrity, Rowett Research Institute, Aberdeen, United Kingdom
| | - Josie McConnell
- 1Division of Cellular Integrity, Rowett Research Institute, Aberdeen, United Kingdom
| | - Julian Little
- 2Epidemiology Group, Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, United Kingdom
| | - Linda Sharp
- 2Epidemiology Group, Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, United Kingdom
| | - Chandrika J. Piyathilake
- 3Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama; and
| | - Hilary Powers
- 4Centre for Human Nutrition, University of Sheffield, Sheffield, United Kingdom
| | - Graham Basten
- 4Centre for Human Nutrition, University of Sheffield, Sheffield, United Kingdom
| | - Susan J. Duthie
- 1Division of Cellular Integrity, Rowett Research Institute, Aberdeen, United Kingdom
| |
Collapse
|
|
19
|
N/A. N/A. Shijie Huaren Xiaohua Zazhi 2003; 11:846-848. [DOI: 10.11569/wcjd.v11.i6.846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
|
|
20
|
Niculescu MD, Zeisel SH. Diet, methyl donors and DNA methylation: interactions between dietary folate, methionine and choline. J Nutr 2002; 132:2333S-2335S. [PMID: 12163687 DOI: 10.1093/jn/132.8.2333s] [Citation(s) in RCA: 343] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
DNA methylation influences the expression of some genes and depends upon the availability of methyl groups from S-adenosylmethionine (SAM). Dietary methyl groups derive from foods that contain methionine, one-carbon units and choline (or the choline metabolite betaine). Humans ingest approximately 50 mmol of methyl groups per day; 60% of them are derived from choline. Transmethylation metabolic pathways closely interconnect choline, methionine, methyltetrahydrofolate (methyl-THF) and vitamins B-6 and B-12. The pathways intersect at the formation of methionine from homocysteine. Perturbing the metabolism of one of these pathways results in compensatory changes in the others. For example, methionine can be formed from homocysteine using methyl groups from methyl-THF, or using methyl groups from betaine that are derived from choline. Similarly, methyl-THF can be formed from one-carbon units derived from serine or from the methyl groups of choline via dimethylglycine, and choline can be synthesized de novo using methyl groups derived from methionine (via SAM). When animals and humans are deprived of choline, they use more methyl-THF to remethylate homocysteine in the liver and increase dietary folate requirements. Conversely, when they are deprived of folate, they use more methyl groups from choline, increasing the dietary requirement for choline. The availability of transgenic and knockout mice has made possible additional studies that demonstrate the interrelationship of these methyl sources. In summary, as we consider dietary requirements and possible effects on DNA methylation, it is important to realize that methionine, methyl-THF and choline can be fungible sources of methyl groups, and the design of our studies should reflect this.
Collapse
Affiliation(s)
- Mihai D Niculescu
- Department of Nutrition, School of Public Health, School of Medicine, University of North Carolina, Chapel Hill 27599-7400, USA
| | | |
Collapse
|
|
21
|
Milner J, McDonald S, Anderson D, Greenwald P. Molecular Targets for Nutrients Involved with Cancer Prevention. Nutr Cancer 2001. [DOI: 10.1207/s15327914nc41-1&2_1] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
|
|
22
|
Abstract
DNA methylation is the main epigenetic modification in humans. The methylation of promoter inhibits the transcription in most genes. In normal tissues, isolated CpG dinucleotides in bulk chromatin are often methylated, whereas cytosines in CpG islands are unmethylated. In neoplasms including gastrointestinal cancer, this pattern of methylation is commonly reversed. The alteration of DNA methylation plays a key role in the process of carcinogenesis. The gastrointestinal carcinogenesis is suggested to be associated with the decrease of total genomic DNA methylation; hypomethylation of certain specific oncogenes such as c-myc, c-Ha-ras, c-fos and alpha-fetoprotein; and hypermethylation of the promoter of some tumor suppressor genes containing p16(INK4A), E-cadherin and hMLH1 genes. This review focuses on the analysis methods for methylation, studies for aberrant DNA methylation in gastrointestinal carcinogenesis, and the intervention changing methylation, including the treatment of 5-azacytidine, supplement of folate and gene therapy.
Collapse
Affiliation(s)
- J Y Fang
- Shanghai Institute of Digestive Disease, Shanghai Second Medical University, Shanghai, People's Republic of China.
| | | |
Collapse
|
|
23
|
Jacob RA. The role of micronutrients in DNA synthesis and maintenance. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2000; 472:101-13. [PMID: 10736620 DOI: 10.1007/978-1-4757-3230-6_10] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- R A Jacob
- Western Human Nutrition Research Center, U.S. Department of Agriculture, University of California, Davis 95616, USA
| |
Collapse
|
|
24
|
Duthie SJ, Hawdon A. DNA instability (strand breakage, uracil misincorporation, and defective repair) is increased by folic acid depletion in human lymphocytes
in vitro. FASEB J 1998. [DOI: 10.1096/fasebj.12.14.1491] [Citation(s) in RCA: 198] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- S. J. Duthie
- Rowett Research Institute Bucksburn, Aberdeen AB21 9SB United Kingdom
| | - A. Hawdon
- Rowett Research Institute Bucksburn, Aberdeen AB21 9SB United Kingdom
| |
Collapse
|
|
25
|
Jacob RA, Gretz DM, Taylor PC, James SJ, Pogribny IP, Miller BJ, Henning SM, Swendseid ME. Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women. J Nutr 1998; 128:1204-12. [PMID: 9649607 DOI: 10.1093/jn/128.7.1204] [Citation(s) in RCA: 324] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
To determine the human folate requirement on the basis of changes in biochemical pathways, we studied the effect of controlled folate intakes on plasma homocysteine and lymphocyte DNA methylation and deoxynucleotide content in healthy postmenopausal women. Eight women (49-63 y of age) were housed in a metabolic unit and fed a low folate diet containing 56 microg/d of folate for 91 d. Folate intake was varied by supplementing 55-460 microg/d of folic acid (pteroylglutamic acid) to the diet to provide total folate intake periods of 5 wk at 56 microg/d, 4 wk at 111 microg/d and 3 wk at 286-516 microg/d. A subclinical folate deficiency with decreased plasma folate was created during the first two periods. This resulted in significantly elevated plasma homocysteine and urinary malondialdehyde, and lymphocyte DNA hypomethylation. The folate depletion also resulted in an increased ratio of dUTP/dTTP in mitogen-stimulated lymphocyte DNA and decreased lymphocyte NAD, changes suggesting misincorporation of uracil into DNA and increased DNA repair activity. The DNA hypomethylation was reversed with 286-516 microg/d of folate repletion, whereas the elevated homocysteine decreased with 516 but not 286 microg/d of folate. The results indicate that marginal folate deficiency may alter DNA composition and that the current RDA of 180 microg/d may not be sufficient to maintain low plasma homocysteine concentrations of some postmenopausal women.
Collapse
Affiliation(s)
- R A Jacob
- Western Human Nutrition Research Center, U.S. Department of Agriculture, Agricultural Research Service, Presidio of San Francisco, CA 94129, USA
| | | | | | | | | | | | | | | |
Collapse
|