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High Expression of Stem Cell Marker ALDH1 is Associated with Reduced BRCA1 in Invasive Breast Carcinomas

  • Madjd, Zahra;Ramezani, Babak;Molanae, Saadat;Asadi-Lari, Mohsen
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2973-2978
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    • 2012
  • Background: Cancer stem cells (CSC) have been described in a variety of malignancies, including breast carcinomas. Among several markers, aldehyde dehydrogenase 1 (ALDH1) has been identified as reliable for breast cancer stem cells. Knockdown of BRCA1 in primary breast epithelial cells leads to an increase in cells expressing ALDH1. Methods: We examined 127 breast carcinomas for expression of ALDH1, using immunohistochemistry and correlated with clinicopathological parameters as well as the BRAC1 status. Results: Comparing the results for both ALDH1 and BRCA1 expression showed a significant inverse association between the two, indicating that reduced BRCA1 was more often seen in breast cancer cells expressing ALDH1 (p-value = 0.044). A total of 24/110 (22%) of tumours displayed the ALDH1 + / BRCA1 -/low phenotype, which showed a trend for a relation with a high grade (p-value= 0.056). Cytoplasmic expression of ALDH1 was not correlated with tumour characteristics. Conclusion: Taken together, our findings suggest that increased ALDH1 is inversely correlated with decreased BRCA1 in a series of unselected breast carcinomas. Therefore, ALDH1 positive (cancer stem) cells with reduced BRCA1 phenotype may indicate a subset of patients for whom specific targeting of the CSC marker ALDH1 and more aggressive adjuvant treatment is appropriate.

Characterization of a Newly Isolated cis-1,2-Dichloroethylene and Aliphatic Compound-Degrading Bacterium, Clostridium sp. Strain KYT-1

  • Kim, Eun-Sook;Nomura, lzumi;Hasegawa, Yuki;Takamizawa, Kazuhiro
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.11 no.6
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    • pp.553-556
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    • 2006
  • A cis-1,2-dichloroethylene (cis-DCE)-degrading anaerobic bacterium, Clostridium sp. strain KYT-1, was isolated from a sediment sample collected from a landfill site in Nanji-do, Seoul, Korea. The KYT-1 strain is a gram-positive, endospore-forming, motile, rod-shaped anaerobic bacterium, of approximately $2.5{\sim}3.0\;{\mu}m$ in length. The degradation of cis-DCE is closely related with the growth of the KYT-1 strain, and it was stopped when the growth of the KYT-1 strain became constant. Although the pathway of cis-DCE degradation by strain KYT-1 remains to be further elucidated, no accumulation of the harmful intermediate, vinyl chloride (VC), was observed during anaerobic cis-DCE degradation. Strain KYT-1 proved able to degrade a variety of volatile organic compounds, including VC, isomers of DCE (1,1-dichloroethylene, trans-1,2-dichloroethylene, and cis-DCE), trichloroethylene, tetrachloroethylene, 1,2-dichloroethane, 1,1,1-trichloroethane, and 1,1,2-trichloroethane. Strain KYT-1 degraded cis-DCE at a range of temperatures from $15\;to\;37^{\circ}C$, with an optimum at $30^{\circ}C$, and at a pH range of 5.5 to 8.5, with an optimum at 7.0.

Association between the Interleukin-17A -197G>A (rs2275913) Polymorphism and Risk of Digestive Cancer

  • Duan, Yin;Shi, Ji-Nan;Pan, Chi;Chen, Hai-Long;Zhang, Su-Zhan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9295-9300
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    • 2014
  • Interleukin-17A (IL-17A) is a multifunctional cytokine which plays a crucial role in the initiation and progression of cancer. To date, several studies have investigated associations between IL-17A -197G>A (rs2275913) polymorphism and digestive cancer risk, but the results remain conflicting. We here aimed to confirm the role of this single nucleotide polymorphism (SNP) in susceptibility to digestive cancer through a systemic review and meta-analysis. Ten eligible case-control studies were identified by searching electronic databases, involving 3,087 cases and 3,815 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of the association. The results of overall analyses indicated that the variant A allele was associated with an increased risk of digestive cancer (AA vs GG: OR=1.51, 95%CI=1.18-1.93; AA vs GG+GA: OR=1.45, 95%CI=1.12-1.87; A vs G: OR=1.21, 95%CI=1.05-1.39). In subgroup analysis stratified by specific cancer type, elevated risk among studies of gastric cancer was found (AA vs GG: OR=1.68, 95%CI=1.24-2.28; AA vs GG+GA: OR=1.62, 95%CI=1.16-2.26; A vs G: OR=1.23, 95%CI=1.04-1.46). According to ethnicity, there was evidence in the Asian populations for an association between this polymorphism and cancer risk (GA vs GG: OR=1.19, 95%CI=1.05-1.36; AA vs GG: OR=1.56, 95%CI=1.15-2.12; AA+GA vs GG: OR=1.28, 95%CI=1.13-1.44; AA vs GG+GA: OR=1.42, 95%CI=1.01-2.00; A vs G: OR=1.24, 95%CI=1.08-1.44), while in the Caucasian populations an association was found in the recessive model (AA vs GG+GA: OR=1.62, 95%CI=1.17-2.24). In conclusion, the results of this meta-analysis suggest that the IL-17A -197G>A polymorphism contributes to an increased risk of human digestive cancer, both in the Asian and Caucasian populations and especially for gastric cancer.

Helicobacter pylori vacA Mosaicism and New Primers for vacA Signal Sequence Indigenous to Korea (Helicobacter pylori vacA 대립유전자의 Mosaicism과 Signal Sequence의 한국고유 시발체)

  • Ahn, Yeon-Hwa;Kim, Heung-Ryel;Lee, Ji-Eun;Hwang, Tae-Sook;Choe, Yon-Ho
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.4 no.2
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    • pp.155-160
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    • 2001
  • Purpose: Helicobacter pylori has been known to have diverse vacA allelic types. The purpose of the study was to identify vacA diversity in Korea and design new primers for signal sequence alleles indigenous to Korea. Methods: Fifty antral biopsy specimens, which had been proven to be H. pylori-positive, were examined for vacA status; signal sequence and mid-region. After PCR amplification and DNA sequencing, vacA alleles of Korean H. pylori strains were compared with those from other countries. Results: Among Korean H. pylori strains vacA alleles with all combinations of signal sequence and mid-region were found, with the exception of s1b or s2. vacA genotype s1c/m1 was predominant in Korea. We found that GGGAGCGTTR in s1a and GGGGYTATTG in s1c were the indigenous sequences to Korea and constructed the new Korean specific primers for the vacA signal sequence; VASK-F, VASK-R, S1AK-F, and S1CK-F. Conclusion: This study showed that s1c/m1 is the predominant type of vacA allele in Korea. We designed new primers for the vacA signal sequence.

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mPW1PW91 Conformational Study of Di-t-butyl-dinitro-tetramethoxysulfonylcalix[4]arene

  • Choe, Jong-In
    • Bulletin of the Korean Chemical Society
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    • v.32 no.1
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    • pp.100-104
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    • 2011
  • The structures of the conformers for 1,3-di-t-butyl-2,4-dinitro-tetramethoxysulfonylcalix[4]arene (1) and 1,2-di-t-butyl-3,4-dinitro-tetramethoxysulfonylcalix[4]arene (2) were optimized using DFT BLYP and mPW1PW91/6-31G(d,p) (hybrid HF-DF) calculation methods. We have analyzed the total electronic and Gibbs free energies and the differences between the various conformations (cone, partial-cone (PC), 1,2-alternate, and 1,3-alternate) of 1 and 2. For both compounds, the 1,3-alternate (1,3-A) conformers were calculated to be the most stable, which correlate very well with the experimental results. The orderings of the relative stability of 1 and 2 that resulted from the mPW1PW91/6-31G(d,p) calculations are the following: 1: 1,3-A (syn) > PC (syn) > PC (anti) > 1,2-A (anti) > CONE (syn); 2: 1,3-A (anti) > PC (anti) > PC (syn) > 1,2-A (anti) > 1,2-A (syn) > CONE (syn). The BLYP/6-31G(d) calculated IR spectra of the most stable 1,3-A conformers of 1 and 2 are compared.

Lack of Association Between the CYP1A1 Ile462Val Polymorphism and Endometrial Cancer Risk: a Meta-analysis

  • Wang, Xi-Wen;Zhong, Tian-Yu;Xiong, Yun-Hui;Lin, Hai-Bo;Liu, Qing-Yi
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3717-3721
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    • 2012
  • Purpose: Any association between the CYP1A1 Ile462Val polymorphism and endometrial cancer risk remains inconclusive. For a more precise estimate, we performed the present meta-analysis. Methods: PUBMED, OVID and EMBASE were searched for the studies which met inclusion criteria. Data in all eligible studies were evaluated and extracted by two authors independently. The meta-analysis estimated pooled odds ratio (OR) with 95% confidence interval (CI) for endometrial cancer risk attributable to the CYP1A1 Ile462Val polymorphism. Results: A total of 7 studies were included in this meta-analysis. The results indicated no association between endometrial cancer risk and the CYP1A1 Ile462Val polymorphism (for Val vs Ile allele model [OR 1.09, 95% CI 0.73-1.62]; for Val.Val vs Ile.Ile genotype model [OR 1.54, 95% CI 0.56-4.23]; for (Ile.Val + Val.Val) vs Ile.Ile genotpye model [OR 1.08, 95% CI 0.71-1.63]; for Val.Val vs (Ile.Ile + Ile.Val) genotype model [OR 1.46, 95% CI 0.53-4.04]). Conclusions: This meta-analysis suggests that there is no association between endometrial cancer risk and the CYP1A1 Ile462Val polymorphism.

COX-inhibitors down-regulate TCDD-induced cyp1a1 activity in C57BL/6 mouse and Hepa- I cells.

  • Bang Syrieo;Jung, Cho-Min;Yhong, Sheen-Yhun
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 2002.10a
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    • pp.173-173
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    • 2002
  • In order to understand the mechanism of action of TCDD, we have examined the effect of COX-inhibitors on cyp1a1 activity. We observed the effect of COX-inhibitor on EROD activity in C57BL/6 mouse in vovo. And we also evaluated the effect of COX-inhibitors on cyp1a1 mRNA, mouse cyp1a1 promoter activity and EROD activity in Hepa cell. When Aspirin were pretreated with 3MC in vivo, the EROD activity that was stimulated by 3MC was inhibited. And Pretreatment of Aspirin, Celecoxib, Nimesulide and other several Cox-inhibitors in vitro, inhibited the TCDD stimulated EROD activity and Luciferase acitivity. In case of cyp1a1 mRNA level, Nimesulide and SB100 were able to decrease cyp1a1 mRNA that was stimulated by TCDD, but other tested COX-inhibitors were not decrease. We don't know this different result exactly. For the action of Cox-inhibitors on the Cyp1a1, it seems to be important to do pretreatment of these chemicals as apposed to TCDD. In this study, thus, we have suggested that COX-inhibitors such as aspirin, celecoxib, Nimesulide and other several Cox-inhibitors decrease the TCDD induced Cyp1a1.

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Association between CYP1A1 Expression and Childhood Asthma (CYP1A1 유전자발현과 소아천식의 상관)

  • Yang Mihi
    • Environmental Analysis Health and Toxicology
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    • v.20 no.3 s.50
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    • pp.209-213
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    • 2005
  • Due to steady increase of childhood asthma, exposure to air toxics including PAHs have been thought as an etiology for the asthma. PAHs -involvement in airway inflammation, such as IgE production, is the potential mechanism of the PAHs-induced asthma. Cytochrome P450s (CYPs), particularly CYP1A1 is known enzyme to metabolite PAHs and to be induced by PAHs. The CYP1A1 expression has been emphasized as an biomarker for PAHs - exposure. The present study was performed to clarify the etiology of childhood asthma with PAHs-exposure using mRNA expression of CYP1A1 . The study Objects were Korean children who were asthma patients (cases) or other hospital controls (N=20; age,3 $\~$ 16; boys,56$\%$). As result, we detected expression of the CYP1A1 in all peripheral blood specimens which were collected from the subjects. Moreover, we found approx. 300 fold-higher expression of the CYP1A1 in the cases than that in the controls (p(<)0.01). When we considered age which was related to Asthma, the above significant trend was somewhat diluted, however, the relation between asthma and the Cypih i expression waL stronger than that between asthma and age (chi square,7.99 vs. 3.34). Therefore, our study supports that PAHs induce or worse childhood asthma and suggests application of expression of the CYP1A1 as an initiation or progress biomarker for PAHs - induced childhood asthma.

The effect of CYP1A2 gene polymorphisms on Theophylline metabolism and chronic obstructive pulmonary disease in Turkish patients

  • Uslu, Ahmet;Ogus, Candan;Ozdemir, Tulay;Bilgen, Turker;Tosun, Ozgur;Keser, Ibrahim
    • BMB Reports
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    • v.43 no.8
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    • pp.530-534
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    • 2010
  • Cytochrome P450 (CYP) 1A2 gene polymorphisms are thought to be involved in the metabolism of theophylline (TP). We aimed to investigate the effect of CYP1A2*1C, CYP1A2*1D, CYP1A2*1E, and CYP1A2*1F polymorphisms of the CYP1A2 on TP metabolism by PCR-RFLP in 100 Turkish patients with chronic obstructive pulmonary disease (COPD) receiving TP. One hundred and one healthy volunteers were included as control group. The genotype frequencies of the CYP1A2*1D and CYP1A2*1F were found to be significantly different in the patients compared to the controls. The "T" allele at -2467 delT and the "C" allele at -163 C > A in the CYP1A2 displayed association with a significantly increased risk for COPD. "T" allele at -2467 delT was also associated with a high risk of disease severity in COPD. In conclusion, our data suggest that genetic alterations in CYP1A2 may play a role both in the pharmacogenetics of TP and in the development of COPD.

Effects of SULT1A1 Copy Number Variation on Estrogen Concentration and Tamoxifen-Associated Adverse Drug Reactions in Premenopausal Thai Breast Cancer Patients: A Preliminary Study

  • Charoenchokthavee, Wanaporn;Ayudhya, Duangchit Panomvana Na;Sriuranpong, Virote;Areepium, Nutthada
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.1851-1855
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    • 2016
  • Tamoxifen is a pharmacological estrogen inhibitor that binds to the estrogen receptor (ER) in breast cells. However, it shows an estrogenic effect in other organs, which causes adverse drug reactions (ADRs). The sulfotransferase 1A1 (SULT1A1) enzyme encoded by the SULT1A1 gene is involved in estrogen metabolism. Previous research has suggested that the SULT1A1 copy number is linked with the plasma estradiol (E2) concentration. Here, a total of 34 premenopausal breast cancer patients, selected from the Thai Tamoxifen (TTAM) Project, were screened for their SULT1A1 copy number, plasma E2 concentration and ADRs. The mean age was $44.3{\pm}11.1years$, and they were subtyped as ER+/progesterone receptor (PR)+ (28 patients), ER+/PR- (5 patients) and ER-/PR- (1 patient). Three patients reported ADRs, which were irregular menstruation (2 patients) and vaginal discharge (1 patient). Most (33) patients had two SULT1A1 copies, with one patient having three copies. The median plasma E2 concentration was 1,575.6 (IQR 865.4) pg/ml. Patients with ADRs had significantly higher plasma E2 concentrations than those patients without ADRs (p = 0.014). The plasma E2 concentration was numerically higher in the patient with three SULT1A1 copies, but this lacked statistical significance.