• Title/Summary/Keyword: p16 methylation

Search Result 63, Processing Time 0.024 seconds

Relationship between Genetic Polymorphisms in MTHFR (C677T, A1298C and their Haplotypes) and the Incidence Of Breast Cancer among Jordanian Females - Case-Control Study

  • Awwad, Nemah;Yousef, Al-Motassem;Abuhaliema, Ali;Abdalla, Ihab;Yousef, Muhammad
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.12
    • /
    • pp.5007-5011
    • /
    • 2015
  • Background: Breast cancer is a major cause of morbidity and mortality in Jordan and worldwide. Abnormality of DNA methylation is a possible mechanism for the development of cancer. Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA methylation. Our aim was to study the association between genetic polymorphisms of MTHFR at two sites (C677T and A1298C) and their haplotypes and the risk of breast cancer among Jordanian females. Materials and Methods: A case-control study involving 150 breast cancer cases and 150 controls was conducted. Controls were age-matched to cases. Polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) technique and sequencing were conducted to determine the genotypes. Results: There was a significant difference in genotype frequency of C677T in the 41-60 year age category [cases: CC (37.4%), CT (49.5%) and TT (13.2%); controls: CC (56.3%), CT (35.6%) and TT (8%), p= 0.04; $OR_{TT\;vs.\;CC}$: 2.5, 95% CI: (0.9-6.9); $OR_{at\;least\;on\;T$: 2.1, 95%CI: (1.2-3.9)]. There was no significant difference in genotype frequency of A1298C between cases and controls [cases: AA (46.6%), AC (41.8%) and CC (11.6%); controls: AA (43%), AC (47.4%) and CC (9.6%); p= 0.6]. There was a significant difference of MTHFR genetic polymorphism haplotypes among breast cancer cases and controls [cases/control: CA: 38.3/45.4%; CC: 28.9/25.2%; TA: 29.2/21; TC: 3.6/8.3; p value= 0.01; $OR_{TA\;vs.\;CA}=1.6$; 95% CI (1.1-2.5); p= 0.02]. Conclusions: Genetic polymorphism of MTHFR C677T may modulate the risk of breast cancer especially in the 41-60 year age group. Additionally, TA haplotype amends the risk of breast cancer. Future studies with a larger sample size are needed to validate the role of MTHFR genetic polymorphisms in breast cancer.

Fatty Acid Profiles of Various Muscles and Adipose Tissues from Fattening Horses in Comparison with Beef Cattle and Pigs

  • He, M.L.;Ishikawa, S.;Hidari, H.
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.18 no.11
    • /
    • pp.1655-1661
    • /
    • 2005
  • The present studies were designed to provide new information on fatty acid profiles of various muscles and adipose tissues of fattening horses in comparison with beef cattle and pigs. In the first study, the lipids were extracted respectively from subcutaneous, intermuscular adipose tissues, longissimus dorsi and biceps femoris muscles of fattening Breton horses (n = 8) with an average body weight of 1,124 kg. In the second study, the lipids were extracted from subcutaneous, intermuscular adipose tissues and longissimus dorsi muscle of fattening horses (n = 13), Japanese Black beef cattle (n = 5), Holstein steers (n = 5) and fattening pigs (n = 5). The fatty acids in the lipid samples were determined by gas chromatography after methylation by a combined base/acid methylation method. It was found that the lipids from horse subcutaneous and intermuscular adipose tissues contained more (p<0.05) polyunsaturated fatty acids (PUFA) which were mainly composed of linoleic acid (C18:2) and linolenic acid (C18:3) than those in the muscles. The weight percent of conjugated linoleic acids (CLA cis 9, trans 11) in lipids from biceps femoris muscle was 0.22%, which was higher (p<0.05) than that from the other depots. The horse lipids were higher (p<0.05) in PUFA but lower (p<0.05) in SFA and MUFA in comparison with those of the cattle and pigs. The percentage of C18:2 or C18:3 fatty acid in the horse lipids were respectively 2-8 fold or 5-18 fold higher (p<0.05) than those of the cattle and pigs. The percentages of CLA (cis 9, trans 11) in the horse lipids (0.14-0.16%) were very close to those of the pigs (0.18-0.19%) but much lower (p<0.05) than those of the Japanese Black beef cattle (0.55-0.94%) and Holstein steers (0.46-0.71%). The results indicated that the fatty acid profiles of lipids from different muscle and adipose tissues of fattening horses differed significantly. In comparison with that of the beef cattle and pigs, the horse lipids contained more C18:2 and C18:3 but less CLA.

Evaluation of the MTHFR C677T Polymorphism as a Risk Factor for Colorectal Cancer in Asian Populations

  • Rai, Vandana
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.18
    • /
    • pp.8093-8100
    • /
    • 2016
  • Background: Genetic and environmental factors play important roles in pathogenesis of digestive tract cancers like those in the esophagus, stomach and colorectum. Folate deficiency and methylenetetrahydrofolate reductase (MTHFR) as an important enzyme of folate and methionine metabolism are considered crucial for DNA synthesis and methylation. MTHFR variants may cause genomic hypomethylation, which may lead to the development of cancer, and MTHFR gene polymorphisms (especially C677T and A1298C) are known to influence predispositions for cancer development. Several case control association studies of MTHFR C677T polymorphisms and colorectal cancer (CRC) have been reported in different populations with contrasting results, possibly reflecting inadequate statistical power. Aim: The present meta-analysis was conducted to investigate the association between the C677T polymorphism and the risk of colorectal cancer. Materials and Methods: A literature search of the PubMed, Google Scholar, Springer link and Elsevier databases was carried out for potential relevant articles. Pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated to assess the association of MTHFR C677T with the susceptibility to CRC. Cochran's Q statistic and the inconsistency index (I2) were used to check study heterogeneity. Egger's test and funnel plots were applied to assess publication bias. All statistical analyses were conducted by with MetaAnalyst and MIX version 1.7. Results: Thirty four case-control studies involving a total of 9,143 cases and 11,357 controls were retrieved according to the inclusion criteria. Overall, no significant association was found between the MTHFR C677T polymorphism and colorectal cancer in Asian populations (for T vs. C: OR=1.03; 95% CI= 0.92-1.5; p= 0.64; for TT vs CC: OR=0.88; 95%CI= 0.74-1.04; p= 0.04; for CT vs. CC: OR = 1.02; 95%CI= 0.93-1.12; p=0.59; for TT+ CT vs. CC: OR=1.07; 95%CI= 0.94-1.22; p=0.87). Conclusions: Evidence from the current meta-analysis indicated that the C677T polymorphism is not associated with CRC risk in Asian populations. Further investigations are needed to offer better insight into any role of this polymorphism in colorectal carcinogenesis.

Epigenetic Regulation of miR-129-2 Leads to Overexpression of PDGFRa and FoxP1 in Glioma Cells

  • Tian, Xiang-Yang;Zhang, Ling;Sun, Lai-Guang;Li, Ming
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.14
    • /
    • pp.6129-6133
    • /
    • 2015
  • miR-129-2 is frequently downregulated in multiple cancers. However, how it is silenced in cancers remains unclear. Here we investigated the expression profile and potential biological function of miR-129-2 in glioblastoma (GBM), the most common and lethal form of brain tumors in adults. We showed that miR-129-2 is lost in GBM patient specimens and cultured cell lines. miR-129-2 expression could be restored upon treatment with a histone deadetylase inhibitor (trichostatin A) but not a DNA methylation inhibitor (5-Aza-2'-deoxycytidine), and more profound effect was observed with the treatment of these two drugs in combination. Furthermore, forced expression of miR-129-2 repressed the expression of major oncogenic genes such as PDGFRa and Foxp1 in GBMs. Consistently, expression of miR-129-2 significantly inhibits GBM cell proliferation in vitro. These results reveal that miR-129-2 is epigenetically regulated and functions as a tumor suppressor gene in GBMs, suggesting it may serve as a potential therapeutic target for GBM treatment.

Synthesis and Characterization of Air Stable σ-Bonded ortho-carborane Manganese Metal Complexes $1-[Mn(CO)_5]-2-R-1,2-closo-(σ-C_2B_{10}H_{10}$ and Their Conversion to the Stable ortho-carborane Substituted Fischer-type Carbene Compexes 1-[(CO

  • 김세진;김유혁;고재정;강상욱
    • Bulletin of the Korean Chemical Society
    • /
    • v.16 no.7
    • /
    • pp.634-641
    • /
    • 1995
  • The metal-carbon σ-bond cluster complexes 1-Mn(CO)5-2-R-1,2-C2B10H10 (R=CH3 Ia, C6H5 Ib) have been prepared in good yields from readily available carboranyl lithium complexes, 1-Li+-2-R-1,2-C2B10H10- (R=CH3, C6H5), by direct reaction with (CO)5MnBr. These manganese metal complexes are rapidly converted to the corresponding manganese metal carbene complexes, 1-[(CO)4Mn=C(OCH3)(CH3)]-2-R-1,2-C2B10H10 (R=CH3 IIIa, C6H5 IIIb), via alkylation with methyllithium followed by O-methylation with CF3SO3CH3. The crystal structure of IIIb was determined by X-ray diffraction. Thus, complex IIIb crystallizes in the orthorhombic space group P212121 with cell parameters a=15.5537(5), b=19.0697(5), c=7.4286(3) Å, V=2203.4(1) Å3, and Z=4. Of the reflections measured a total of 3805 unique reflections with F2>3σ(F2) was used during subsequent structure refinement. Refinement converged to R1=0.053 and R2=0.091. Structural studies showed that the manganese atom had a slightly distorted pseudo-octahedral configuration about the metal center with the carbene and ortho-carborane occupying the equatorial plane cis-orientation to each other.

siRNA Silencing EZH2 Reverses Cisplatin-resistance of Human Non-small Cell Lung and Gastric Cancer Cells

  • Zhou, Wen;Wang, Jian;Man, Wang-Ying;Zhang, Qing-Wei;Xu, Wen-Gui
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.6
    • /
    • pp.2425-2430
    • /
    • 2015
  • Clinical resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. EHZ2 is involved in drug resistance and is overexpressed in drug-resistant cancer cell lines. In this study, we investigated the effects of EHZ2 on cisplatin -resistance in A549/DDP and AGS/DDP cells. EHZ2 mRNA and protein were found to be significantly overexpressed in A549/DDP and AGS/DDP cells, compared to parental cells. EHZ2 siRNA successfully silenced EHZ2 mRNA and protein expression. Proliferation was inhibited and drug resistance to cisplatin was improved. Flow cytometry showed that silencing of EHZ2 arrested A549/DDP and AGS/DDP cells in the G0/G1 phase, increasing apoptosis, rh-123 fluorescence intensity and caspase-3/8 activities. Silencing of EHZ2 also significantly reduced the mRNA and protein expression levels of cyclin D1 and MDR1,while up-regulating p15, p21, p27 and miR-218 in A549/DPP cells. Furthermore, silencing of EHZ2 also significantly increased the expression level of tumor suppressor factor miR-218. We also found down-regulating EHZ2 expression increased methylation in A549/DDP and AGS/DDP cells. This study demonstrates that drug resistance can be effectively reversed in human cisplatin-resistant lung and gastric cancer cells through delivery of siRNAs targeting EHZ2.

Optimal Conditions and Substrate Specificity for Trehalose Production by Resting Cells of Arthrobacter crystallopoietes N-08

  • Seo, Yi-Seul;Shin, Kwang-Soon
    • Preventive Nutrition and Food Science
    • /
    • v.16 no.4
    • /
    • pp.357-363
    • /
    • 2011
  • Recently, we found that Arthrobacter crystallopoietes N-08 isolated from soil directly produces trehalose from maltose by a resting cell reaction. In this study, the optimal set of conditions and substrate specificity for the trehalose production using resting cells was investigated. Optimum temperature and pH of the resting cell reaction were $55^{\circ}C$ and pH 5.5, respectively, and the reaction was stable for two hours at $37{\sim}55^{\circ}C$ and for one hour at the wide pH ranges of 3~9. Various disaccharide substrates with different glycosidic linkages, such as maltose, isomaltose, cellobiose, nigerose, sophorose, and laminaribiose, were converted into trehalose-like spots in thin layer chromatography (TLC). These results indicated broad substrate specificity of this reaction and the possibility that cellobiose could be converted into other trehalose anomers such as ${\alpha},{\beta}$- and ${\beta},{\beta}$-trehalose. Therefore, the product after the resting cell reaction with cellobiose was purified by ${\beta}$-glucosidase treatment and Dowex-1 ($OH^-$) column chromatography and its structure was analyzed. Component sugar and methylation analyses indicated that this cellobiose-conversion product was composed of only non-reducing terminal glucopyranoside. MALDI-TOF and ESI-MS/MS analyses suggested that this oligosaccharide contained a non-reducing disaccharide unit with a 1,1-glucosidic linkage. When this disaccharide was analyzed by $^1H$-NMR and $^{13}C$-NMR, it gave the same signals with ${\alpha}$-D-glucopyranosyl-(1,1)-${\alpha}$-D-glucopyranoside. These results suggest that cellobiose can be converted to ${\alpha},{\alpha}$-trehalose by the resting cells of A. crystallopoietes N-08.

Structural and Physiological Characteristics of Rhamnogalacturonan II from Fruit Wines

  • Park, So-Yeon;Shin, Kwang-Soon
    • Food Science and Biotechnology
    • /
    • v.16 no.2
    • /
    • pp.270-274
    • /
    • 2007
  • To characterize the polysaccharides which exist as soluble forms in fruit wines, crude polysaccharides were isolated from red, white, raspberry, wild grape, and pear wine, respectively. Among them, the crude polysaccharide (RW-0) in red wine showed the highest yield and considerable amounts of thiobarbituric acid (TBA)-positive materials. The pectic polysaccharide RW-2 was purified to homogeneity from RW-0 by subsequent size-exclusion chromatography using Sephadex G-75 and its structure was characterized. RW-2 consisted of 14 different monosaccharides which included rarely observed sugars in general polysaccharides, such as 2-O-methyl-fucose, 2-O-methyl-xylose, apiose (Api), 3-C-carboxy-5-deoxy-L-xylose (aceric acid, AceA), 3-deoxy-D-manno-2-octulosonic acid (Kdo), and 3-deoxy-D-lyxo-2-heptulosaric acid (Dha). Methylation analysis indicated that RW-2 comprised at least 20 different glycosyl linkages such as 3,4-linked fucose, 2,3,4-linked rhamnose, 3'-linked apiose, and 2,3,3'-linked apiose, being characteristic in rhamnogalacturonan II (RG-II). High performance size-exclusion chromatography indicated that RW-2 mainly comprised RG-II of higher molecular weight (12,000), and that the changes of molecular weight to apparent 7,000 under less than pH 2.0 were observed. These analyses indicated that the higher molecular weight polysaccharide in RW-2 was mainly present as a RG-II dimer.

Synthesis and Cation Binding Properties of Triester Calix[4]arenes and Calix[4]quinones

  • 남계천;강성옥;전종철
    • Bulletin of the Korean Chemical Society
    • /
    • v.18 no.10
    • /
    • pp.1050-1052
    • /
    • 1997
  • The complexes M(CO)4-1,2-(PPh2)2-1,2-C2B10H10 (M=Cr 2a, Mo 2b, W 2c) have been prepared in good yields from readily available bis-diphenylphosphino-o-carboranyl ligand, closo-1,2-(PPh2)2-1,2-C2B10H10 (1), by direct reaction with Group Ⅵ metal carbonyls. The infrared spectra of the complexes indicate that there is an octahedral disposition of chelate bis-diphenylphosphino-o-carboranyl ligand around the metal atom. The crystal structure of 2a was determined by X-ray diffraction. Complex 2a crystallizes in the monoclinic space group P21/n with cell parameters a = 12.2360(7), b = 17.156(1), c = 16.2040(6) Å, V = 3354.1(3) Å3, and Z =4. Of the reflections measured a total of 2514 unique reflections with F2 > 3σ(F2) was used during subsequent structure refinement. Refinement converged to R1 = 0.066 and R2 = 0.071. Structural studies showed that the chromium atom had a slightly distorted pseudo-octahedral configuration about the metal center with two phosphine groups of o-carborane occupying the equatorial plane cis-orientation to each other. These metal carbonyl complexes are rapidly converted to the corresponding metal carbene complexes, [(CO)3M=C(OCH3)(CH3)]-1,2-(PPh2)2-1,2-C2B10H10 (M= Cr 3a, Mo 3b, W 3c), via alkylation with methyllithium followed by O-methylation with CF3SO3CH3.

High-Level Production of Low-Branched Levan from Pseudomonas aurantiaca S-4380 for the Production of $di-\beta-D-Fructofuranose$ Dianhydride IV

  • JANG KI-HYO;JANG EUN-KYUNG;KIM SEUNG-HWAN;KIM IN-HWAN;KANG SOON AH;KOH ISSAC;PARK YOUNG-IL;KIM YOUNG-JUN;HA SANG-DO;KIM CHUL HO
    • Journal of Microbiology and Biotechnology
    • /
    • v.16 no.1
    • /
    • pp.102-108
    • /
    • 2006
  • The IscA gene, encoding a levansucrase of 424 amino acids (aa) residues, was cloned from the genomic DNA of Pseudomonas aurantiaca S-4380, and overexpressed in Escherichia coli. The recombinant levansucrase overexpressed in E. coli was then used to produce levan from sucrose. Levan crystals with 98% purity could be obtained from the reaction mixture with $62\%$ yield using an alcohol precipitation method. The molecular weight of the levan was $7\times10^5$ daltons. Methylation studies showed that the levan was branched: main linkage C-2,6; branched linkage C-2,1; and degree of branching $6\%$. Three bacterial levans from different strains were incubated with levan fructotransferase (LFTase) from Arthrobacter ureafaciens K2032, which produced $di-\beta-D-fructofuranose$ dianhydride IV (DFA IV); final conversion yields from the levans to DFA IV were $39\%$ in Zymomonas mobilis, $53\%$ in Serratia levanicum, and $59\%$ in P. aurantiaca S-4380 levansucrase. The levan from P. aurantiaca S-4380 levansucrase gave the highest conversion yield of levan to DFAIV so far reported.