• Title/Summary/Keyword: carcinogenic molecular

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RTN4 3'-UTR Insertion/Deletion Polymorphism and Susceptibility to Non-Small Cell Lung Cancer in Chinese Han Population

  • Lu, De-Yi;Mao, Xu-Hua;Zhou, Ying-Hui;Yan, Xiao-Long;Wang, Wei-Ping;Zheng, Ya-Biao;Xiao, Juan-Juan;Zhang, Ping;Wang, Jian-Guo;Ashwani, Neetika;Ding, Wei-Liang;Jiang, Hua;Shang, Yan;Wang, Ming-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5249-5252
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    • 2014
  • Nogo protein, encoded by gene reticulon-4 (RTN4), includes three major isoforms by different splicing, named Nogo-A Nogo-B and Nogo-C. Nogo proteins play an important role in the apoptosis of cells, especially in tumor cells. RTN4 single nucleotide polymorphisms (SNPs) can influence the efficiency of transcription and translation thus being related with an individual's predisposition to cancer. The CAA insertion/deletion polymorphism (rs34917480) within RTN4 3'-UTR has been reported to be associated with many cancer types. In order to investigate the relationship between this polymorphism and susceptibility to non-small cell lung cancer (NSCLC) in the Chinese population, we conducted the present case-control study including 411 NSCLC patients and 471 unrelated healthy controls. The genotype distributions were significantly different between cases and controls (p=0.014). We found that the del allele could significantly increase NSCLC risk (ins/ins vs ins/del: p=0.007, OR 1.46, 95%CI=1.11-1.93; dominant model: p=0.004, OR 1.47, 95%CI=1.13-1.92 and allele model: p=0.008, OR 1.35, 95%CI=1.08-1.67). This association was stronger in participants over 60 years old, males and smokers. We therefore conclude that the CAA insertion/deletion polymorphism (rs34917480) contributes to non-small cell lung cancer risk in Chinese population. Age, sex and environmental exposure are also related to carcinogenic effects of rs34917480.

Monitoring of Polycyclic Aromatic Hydrocarbons in Sediments and Organisms from Korean Coast

  • Moon Hyo-Bang;Choi Hee-Gu;Kim Sang-Soo;Jeong Seung-Ryul;Lee Pil-Yong;Ok Gon
    • Fisheries and Aquatic Sciences
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    • v.4 no.4
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    • pp.219-228
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    • 2001
  • Surface sediments (0- 5 cm), mussels (Mytilus coruscus and M. edulis) and oysters (Crassostrea gigas) were sampled at 20 stations in Korean coast during a period of February to July 2000. Samples were analyzed for polycyclic aromatic hydrocarbons (PAHs) content using gas chromatography coupled to mass spectrometer detector (GC/MSD). The sediment $\sum PAH$ concentration varied from 7 to 1,214 ng/g dry weight and the level of carcinogenic PAHs of six species ranged from 1 to 563 ng/g dry weight in surface sediments. In organisms, the levels of $\sum PAH$ were in the range of 63-876 ng/g dry weight and the concentrations of carcinogenic PAHs of six species were in the range of 4-582 ng/g dry weight. The highest PAH concentrations in sediments and organisms were in samples from Station 5 in Pohang coast and Station 8 in Jinhae coast, respectively. $\sum PAH$ concentrations in sediments and organisms collected from Korean coast were slightly low or comparable to those in other countries. The contribution of ring aromatic groups to sum of 16 PAHs in sediments and organisms showed a similar pattern for most stations. In sediments, the predominant contributions were four and five ring aromatics like fluoranthene, pyrene, benzo[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene and benzo[a]pyrene. In the organisms, four ring aromatics like fluoranthene, pyrene, benzo[a]anthracene and chrysene were predominant PAH species. Several molecular indices such as phenanthrene/anthracene, fluoranthene/pyrene and LMW/HMW ratio were used to identify the origin of PAH contamination in sediments. The results indicate that PAHs of Korean coast were mainly of pyro1ytic contaminants with slight petrogenic input. A high correlation within individual PAH compound in marine sediments was observed, while correlation in organisms showed a highly significant relationship for heavier molecular weight PAHs.

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The Structural and Functional Role of p53 as a Cancer Therapeutic Target (암 치료 표적으로서 p53의 구조적 및 기능적 역할)

  • Han, Chang Woo;Park, So Young;Jeong, Mi Suk;Jang, Se Bok
    • Journal of Life Science
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    • v.28 no.4
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    • pp.488-495
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    • 2018
  • The p53 gene plays a critical role in the transcriptional regulation of cellular response to stress, DNA damage, hypoxia, and tumor development. Keeping in mind the recently discovered manifold physiological functions of p53, its involvement in the regulation of cancer is not surprising. In about 50% of all human cancers, inactivation of p53's protein function occurs either through mutations in the gene itself or defects in the mechanisms that activate it. This disorder plays a crucial role in tumor evolution by allowing the evasion of a p53-dependent response. Many recent studies have focused on directly targeting p53 mutants by identifying selective, small molecular compounds to deplete them or to restore their tumor-suppressive function. These small molecules should effectively regulate various interactions while maintaining good drug-like properties. Among them, the discovery of the key p53-negative regulator, MDM2, has led to the design of new small molecule inhibitors that block the interaction between p53 and MDM2. Some of these small molecule compounds have now moved from proof-of-concept studies into clinical trials, with prospects for further, more personalized anti-carcinogenic medicines. Here, we review the structural and functional consequences of wild type and mutant p53 as well as the development of therapeutic agents that directly target this gene, and compounds that inhibit the interaction between it and MDM2.

Antiproliferative Properties of Methanolic Extract of Nigella sativa against the MDA-MB-231 Cancer Cell Line

  • Dilshad, Ahmad;Abulkhair, Omalkhair;Nemenqani, Dalal;Tamimi, Waleed
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5839-5842
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    • 2012
  • Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer. Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables. Nigella sativa has been shown to possess anti-carcinogenic activity, inhibiting growth of several cancer cell lines in vitro. However, the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood. Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of $2.5-5{\mu}g/mL$ (P<0.05). Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h. Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.

Antioxidant Activity of Flavonoids in Plant Origin Food (식물성 식품에 존재하는 Flavonoids의 항산화 활성)

  • 김건희;최미희
    • Food Science and Preservation
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    • v.6 no.1
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    • pp.121-135
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    • 1999
  • Effective synthetic antioxidants such as butylated hydroxyanisole(BHA) and butylated hydroxytoluene(BHT) have been widely used in the food industry, but they are suspected to be toxic and carcinogenic effects. Therefore, the development of safely available natural antioxidants such as ascorbic acid, ${\alpha}$-tocopherol, ${\beta}$-carotene, flavonoids and selenium is essential. In particular, flavonoids, 2-phenyl-benzo-${\alpha}$-pyrones, are polyphenolic compounds that occur ubiquitously in food of plant origin. flavonoids occur in foods generally as O-glycosides with sugars bound usually at the C\ulcorner position. And variations in their heterocyclic ring gibes rise to flavones, flavonols, flavanones, flavanols, catechins, anthocyanidins, chalcone and isoflavones. Vegetables, fruits, and beverages are the main dietary sources of the flavonols, primarily as quercetin, kaempferol, and myricetin and the corresponding flavones, apigenin and luteolin. These flavonoids have biological activity such as antioxidant, anti-inflammatory, antithrombotic, antimutagenic, anticarcimogenic antiallergic and antimicrobial activity effects in vitro and in vivo. Flavonoids posses strong antioxidant activities acting as oxygen radicals scavenger, metal chelators and enzyme inhibitor. The antioxidant activity of flavonoids is determined by their molecular structure and more specially, by the position and degree of hydroxylation of the ring structure. All flavonoids with the 3`, 4`-dihydroxy(ortho-dihydroxy) posses marked antioxidant activity. And antioxidant activity increases with the number of hydroxyl groups substituted on the A-and B-rings. There is as yet no certainty about the effect of the presence of a double bond between C\ulcorner and C\ulcorner on the antioxidant activity of flavonoids.

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Effects of Polycyclic Aromatic Hydrocarbons on DNA Damage and Plasma Protein Expression in Mouse

  • Oh, Sang-Nam;Oh, Eun-Ha;Im, Ho-Sub;Jo, Gyu-Chan;Sul, Dong-Geun;Kim, Young-Whan;Lee, Eun-Il
    • Molecular & Cellular Toxicology
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    • v.1 no.1
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    • pp.32-39
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    • 2005
  • Polycyclic aromatic hydrocarbons (PAHs) are an important class of environmentally prevalent xenobiotics that exert complex effects on the biological system and characterized as probably carcinogenic materials. Single cell gel electrophoresis assays were performed in order to evaluate DNA damage occurring in the T-and B lymphocytes, spleens (T/B-cell), bone marrow, and livers of mouse exposed to mixture of PAHs (Benzo(a)pyrene, Benzo(e)pyrene, Fluoranthene, Pyrene) at dose of 400, 800, or 1600 mg/kg body weight for 2 days. DNA damage of the cells purified from mice was increased in dose dependent manner. In the blood cells and organs, DNA damage was also discovered to vary directly with PAHs. Especially T-cells had been damaged more than B-cell. Plasma proteomes were separated by 2-dimensional electrophoresis with pH 4-7 ranges of IPG Dry strips and many proteins showed significant up-and -down expressions with the dose dependent manner. Of these, significant 4 spots were identified using matrix-assisted laser desorption/ionization-time of fight (MALDI-TOF) mass spectrometry. Identified proteins were related to energy metabolism and signal transduction.

Fluorescence-Quenched Sensor for Trinitophenol in Aqueous Solution Based on Sulfur Doped Graphitic Carbon Nitride

  • Min, Kyeong Su;Manivannan, Ramalingam;Satheshkumar, Angu;Son, Young-A
    • Textile Coloration and Finishing
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    • v.30 no.2
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    • pp.63-69
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    • 2018
  • In this study, we report on successful attempt towards the synthesis of sulfur self-doped $g-C_3N_4$ by directly heating thiourea in air. The synthesized materials were characterized using UV-vis spectral technique, FT-IR, XRD and TEM analysis. Further, the obtained material shows an excellent detection of carcinogenic TNP(Tri nitro phenol) in the presence of 10-fold excess of various other common interferences. The strong inner filter effect and molecular interactions(electrostatic, ${\pi}-{\pi}$, and hydrogen bonding interactions) between TNP and the $S-g-C_3N_4$ Nano sheets led to the fluorescence quenching of the $S-g-C_3N_4$ Nano sheets with an excellent selectivity and sensitivity towards TNP compared to that of other nitro aromatics under optimal conditions and the detection limit calculated was found to be 6.324 nM for TNP. The synthesized nanocomposite provides a promising platform for the development of sensors with improved reproducibility and stability for ultra-sensitive and selective sensing of TNP.

Assessment of Reliability when Using Diagnostic Binary Ratios of Polycyclic Aromatic Hydrocarbons in Ambient Air PM10

  • Pongpiachan, Siwatt
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8605-8611
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    • 2016
  • The reliability of using diagnostic binary ratios of particulate carcinogenic polycyclic aromatic hydrocarbons (PAHs) as chemical tracers for source characterisation was assessed by collecting PM10 samples from various air quality observatory sites in Thailand. The major objectives of this research were to evaluate the effects of day and night on the alterations of six different PAH diagnostic binary ratios: An/(An + Phe), Fluo/(Fluo + Pyr), B[a]A/(B[a]A + Chry), B[a]P/(B[a]P + B[e]P), Ind/(Ind + B[g,h,i]P), and B[k]F/Ind, and to investigate the impacts of site-specific conditions on the alterations of PAH diagnostic binary ratios by applying the concept of the coefficient of divergence (COD). No significant differences between day and night were found for any of the diagnostic binary ratios of PAHs, which indicates that the photodecomposition process is of minor importance in terms of PAH reduction. Interestingly, comparatively high values of COD for An/(An + Phe) in PM10 collected from sites with heavy traffic and in residential zones underline the influence of heterogeneous reactions triggered by oxidising gaseous species from vehicular exhausts. Therefore, special attention must be paid when interpreting the data of these diagnostic binary ratios, particularly for cases of low-molecular-weight PAHs.

Elucidation of Anti-Tumor Initiator and Promoter Derived from Seaweed-4: Desmutagenic Principles of Ecklonia stolonifera Extracts against Carcinogenic Heterocyclic Amines (해조류 중의 Anti-Tumor Initiator 및 Promoter의 해석-4: 발암성 Heterocyclic Amine에 대한 곰피 추출물 중의 돌연변이원성 억제인자)

  • 김선봉;박영범;안종관;유승재;박덕천;김인수;박영호
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.27 no.3
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    • pp.537-542
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    • 1998
  • The present study was performed to elucidate desmutagenic principles from Ecklonia stolonifera extracts against 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine(PhIP) and 2-amino-3,8-dime-thylimidazo[4,5-f]duinoxaline(MeIQx) with Salmonella/mammalian-microsome mutagenicity test. Alginate, phenols, chlorophyll and carotenoids from Ecklonia stolonifera were extracted and their desmutagenicities were assayed. Alginate hydroysates showed desmutagenic activities against PhIP and MeIQx at high level dose. Phenol fractions and bromophenol showed desmutagenic activity of about MeIQx at high level dose. Phenol fractions and bromophenol showed desmutagenic activity of about 90% per 0.5mg against PhIP and MeIQx. Chlorophyllin among chlorophyll derivatives exhibited remarkable desmutagenic activities of 92.9% and 82.7% at 20uM against PhIP and MeIQx, respectively. Carotenoids, such as lutein and $\alpha$-cryptoxanthin isolated from Ecklonia stolonifera exerted also high desmutagenic activity. Major desmutagenic substances from Ecklonia stolonifera are considered to be chlorophyllin, phenols, lutein, $\alpha$-cryptoxanthin and low molecular alginates.

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The Effect of Benzene on the Activity of Adenosine Deaminase in Tissues of Rats

  • Turhan, Ali;Dere, Egemen
    • BMB Reports
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    • v.40 no.3
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    • pp.295-301
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    • 2007
  • Swiss Albino (Rat rattus norvegicus) rats were intraperitoneally injected with a 100 mg $kg^{-1}$ dosage of benzene, a toxic and carcinogenic agent widely used for industrial purposes. Changes in the adenosine deaminase (ADA) activity in the liver, kidney and serum of rats were investigated at 0, 2, 4, 8, 16, 32 and 64 h following injection. Serum physiological was administered to each control group. Enzyme activities were measured spectrophotometrically. Our purpose was to further investigations of some diseases caused by benzene, and present evidence of variations in the activity of ADA enzyme effected by benzene. While benzene caused significant inhibitions in ADA activity in the liver at 16 and 32 h and at 0.05 probability level, no significant inhibition or activation occurred at other test periods (hours). ADA activity did not present any significant variation in the kidneys. It was observed that ADA activity displayed similar patterns in the control groups. Comparisons of ADA activities in the two groups showed a statistically significant decrease between $4^{th}$ and $64^{th}$ hours (p< 0.05), demonstrating a direct correlation between benzene and its effects on ADA enzymes.