• Title, Summary, Keyword: ALDH1A1

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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.

Prognostic Value of ALDH1A3 Promoter Methylation in Gliob;astoma: A Single Center Experience in Western China

  • Ni, Wei;Luo, Lin;Ping, Zuo;Yuan, Hong-Ping;Zhao, Xu-Dong;Xu, Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.591-594
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    • 2015
  • Background: Aberrations in gene methylation patterns play important roles in gliomagenesis. However, whether the ALDH1A3 promoter methylation is related to prognoses of primary glioblastomas (GBMs) in Western China remains unclear. Materials and Methods: Methylation levels of ALDH1A3 CpG island in 36 GBMs were identified by pyrophosphate sequencing, while ALDH1A3 expression was assessed with matched paraffin section immunohistochemistry. Survival curves were analysed by Kaplan-Meier. Results: The hypermethylation status of ALDH1A3 promoter predicted a better prognosis accompanied with low expression of ALDH1A3 protein. Conclusions: Our results indicate ALDH1A3 promoter methylation correlates with prognosis in primary GBMs.

Clinicopathological Significance of CD133 and ALDH1 Cancer Stem Cell Marker Expression in Invasive Ductal Breast Carcinoma

  • Mansour, Sahar F;Atwa, Maha M
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7491-7496
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    • 2015
  • Background: Biomarkers in breast neoplasms provide invaluable information regarding prognosis and help determining the optimal treatment. We investigated the possible correlation between cancer stem cell (CSC) markers (CD133, and ALDH1) in invasive ductal breast carcinomas with some clinicopathological parameters. Aim: To assess the correlation between expression of cancer stem cell (CSC) markers (CD133, and ALDH1) and clinicopathological parameters of invasive ductal breast carcinomas. Materials and Methods: Immunohistochemical analysis of CD133 and ALDH1 was performed on a series of 120 modified radical mastectomy (MRM) specimens diagnosed as invasive ductal breast carcinoma. Results: Expression of both CD133 and ALDH1 was significantly changed and related to tumor size, tumor stage (TNM), and lymph node metastasis. A negative correlation between CD133 and ALDH1 was found. Conclusions: Detecting the expression of CD133 and ALDH1 in invasive ductal breast carcinomas may be of help in more accurately predicting the aggressive properties and determining the optimal treatment.

ALDH and CYP2E1 Single Nucleotide Polymorphism Distribution in Korean

  • Han, Dong-Hoon;Kim, Jeong-Hee
    • International Journal of Oral Biology
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    • v.31 no.3
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    • pp.107-112
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    • 2006
  • Aldehyde dehydrogenase (ALDH) plays an important role in alcohol metabolism; ALDH is responsible for the oxidation of acetaldehyde generated during alcohol oxidation. ALDH is also known to oxidize various other endogenous and exogenous aldehydes. Cytochrome P-450 2E1 (CYP2E1), a liver microsomal enzyme, also metabolizes acetaldehyde and ethanol and can be induced by other inducers including acetone and ethanol. We examined single nucleotide polymorphisms (SNP) of ALDH and CYP2E1 genotypes in Korean. Restriction fragment length polymorphism (RFLP) method was used to determine ALDH and CYP2E1 SNP. Mutation in ALDH was 60% (heterozygote 46.7% and homozygote 13.3%) among 15 cases. CYP2E1 mutation was 52.7% (heterozygote 47.4% and homozygote 5.3%) among 19 cases.

ALDH1 in Combination with CD44 as Putative Cancer Stem Cell Markers are Correlated with Poor Prognosis in Urothelial Carcinoma of the Urinary Bladder

  • Keymoosi, Hossein;Gheytanchi, Elmira;Asgari, Mojgan;Shariftabrizi, Ahmad;Madjd, Zahra
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2013-2020
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    • 2014
  • Background: The aldehyde dehydrogenase 1 family member A1 (ALDH1A1) is one of the promising markers for identifying cancer stem cells in many cancer types, along with other markers including CD44. The aim of the present study was to evaluate the expression and clinical significance of putative cancer stem cell markers, CD44 and ALDH1A1, in a series of urothelial carcinomas of urinary bladder (UCUB) by tissue microarray (TMA). Materials and Methods: A total of 159 Urothelial Carcinomas (UC) including 96 (60%) low grade and 63 (40%) high grade carcinomas were immunohistochemically examined for the expression of CD44 and ALDH1A1. Correlations of the relative expression of these markers with clinicopathological parameters were also assessed. Results: High level expression of ALDH1A1 was found in 16% (25/159) of bladder UC which was significantly correlated with increased tumor size (p value=0.002), high grade (p value<0.001), pathologic stage (T1, p value=0.007 and T2, p value<0.001) and increased rate of recurrence (p value=0.013). A high level of CD44 expression was found in 43% (68/159) of cases, being positively correlated with histologic grade (p value=0.032) and recurrence (p value=0.039). Conclusions: Taken together, our results showed that ALDH1 was concurrently expressed in a fraction of CD44+ tumors and its expression correlated with poor prognosis in UCs. ALDH1A1 could be an ideal marker for targeted therapy of UCs in combination with conventional therapies, particularly in patients with high grade carcinomas. These findings indicate that cells expressing ALDH1A1 along with CD44 can be a potential therapeutic target in bladder carcinomas.

Expression and Functional Role of ALDH1 in Cervical Carcinoma Cells

  • Rao, Qun-Xian;Yao, Ting-Ting;Zhang, Bing-Zhong;Lin, Rong-Chun;Chen, Zhi-Liao;Zhou, Hui;Wang, Li-Juan;Lu, Huai-Wu;Chen, Qin;Di, Na;Lin, Zhong-Qiu
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1325-1331
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    • 2012
  • Tumor formation and growth is dictated by a very small number of tumor cells, called cancer stem cells, which are capable of self-renewal. The genesis of cancer stem cells and their resistance to conventional chemotherapy and radiotherapy via mechanisms such as multidrug resistance, quiescence, enhanced DNA repair abilities and anti-apoptotic mechanisms, make it imperative to develop methods to identify and use these cells as diagnostic or therapeutic targets. Aldehyde dehydrogenase 1 (ALDH1) is used as a cancer stem cell marker. In this study, we evaluated ALDH1 expression in CaSki, HeLa and SiHa cervical cancer cells using the Aldefluor method to isolate ALDH1-positive cells. We showed that higher ALDH1 expression correlated with significantly higher rates of cell proliferation, microsphere formation and migration. We also could demonstrate that SiHa-ALDH1-positive cells were significantly more tumorigenic compared to SiHa-ALDH1-negative cells. Similarly, SiHa cells overexpressing ALDH1 were significantly more tumorigenic and showed higher rates of cell proliferation and migration compared to SiHa cells where ALDH1 expression was knocked down using a lentivirus vector. Our data suggested that ALDH1 is a marker of cervical cancer stem cells and expand our understanding of its functional role.

Acute Alcohol Responses and Personality Traits by Aldehyde Dehydrogenase 2 Genotype Variances in Patients with Alcohol Dependence (알코올의존 환자의 Aldehyde Dehydrogenase 2 유전자 변이에 따른 음주 후 반응 및 성격특성)

  • Lee, Jong-Il;Lee, Jung-Sik;Cho, Sung Nam;Chai, Young-Gyu;Nam, Jung Hyun;Yang, Byung Hwan;Choi, Ihn-Geun;Kim, Seok Hyeon;Roh, Sungwon
    • Korean Journal of Biological Psychiatry
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    • v.12 no.2
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    • pp.196-206
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    • 2005
  • Objectives:The purpose of this study is to evaluate the pathophysiology of alcoholics by investigating the differences in frequency of Aldehyde Dehydrogenase 2(ALDH2) genotypes and ALDH2 alleles between patients with alcohol dependence and controls, and the differences of drinking and personality traits in Korean male alcoholics with ALDH2 genotype variances. Methods:The authors selected 98 patients with alcohol dependence and 53 controls. Self-report questionnaires for acute reponses after alcohol ingestion, the AUI(Alcohol Use Inventory), and the NEO-PI-R(NEO Personality Inventory Revised) were given to all patients with alcohol dependence. ALDH2 genotypes were typed with MboII RFLP(Restriction Fragment Length Polymorphism) method in 53 controls and 98 patients with alcohol dependence. The authors divided alcoholic patients into two groups according to the presence of variant $ALDH2^2$ allele;normal ALDH2 alcoholics(N=87) and variant ALDH2 alcoholics(N=11). Results:1) The genotypic frequencies of subjects with $ALDH2^{1/1}$ were higher and those with $ALDH2^{1/2}$ and $ALDH2^{2/2}$ were lower in patients than in controls. 2) Alcohol dependence could be found in $ALDH2^{2/2}$ homozygote individuals. 3) Variant ALDH2 alcoholics had more family problems in the AUI than normal ALDH2 alcoholics. 4) Variant ALDH2 alcoholics experienced more flushing and cardiovascular responses after alcohol ingestion than normal ALDH2 alcoholics. 5) Variant ALDH2 alcoholics had less altruistic personality traits in the NEO-PI-R than normal ALDH2 alcoholics. 6) Variant ALDH2 alcoholics tended to have more tolerance to alcohol than normal ALDH2 alcoholics. Conclusion:Variant $ALDH2^2$ allele might play a protective role in the pathogenesis of alcohol dependence and there were several significant differences of drinking and personality traits in Korean male alcoholics with ALDH2 genotype variances.

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The Effect of Saponins of Panax ginseng C.A. Meyer on Brain Aldehyde Dehydrogenase Activity of Ethanol Administered Rat (인삼사포인 성분이 에탄올을 투여한 쥐의 뇌 Aldehyde Dehydrogenase 활성에 미치는 영향)

  • 이영돈;주충노
    • Journal of Ginseng Research
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    • v.18 no.1
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    • pp.1-9
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    • 1994
  • Sprague-Dawley rats were given freely with 15% ethanol (control) and 15% ethanol containing (1) 0.1% ginseng saponin, (2) 0.02% ginsenoside $Rb_1$, and (3) $Rg_1$ (tests) instead of water for 7 days and aldehyde dehydrogenase (ALDH) and monoamine oxidase (MAO) activity in different regions of brain were examined. In control group, total ALDH activity with indoleacetaldehyde and acetaldehyde as substrate in all different regions was lower than that of normal group except in the hippocampus. The inhibitory effect on the activity was prominent in the corpus striatum and was not in the hippocampus. However, low-$K_m$ ALDH activity in all different regions was much lower than that of normal group. A considerable decrease in mitochondria ALDH activity in cerebellum and striatum was also observed in control group. In test groups total, low-$K_m$, and mitochondria AkDH activities in all different regions were higher than those in control group. Although ALDH activity in the striatum of test group was higher than control group, it was relatively depressed as compared with normal. There was not found a remarkable difference in extent of stimulating effect on the AkDH activity according to the ginseng saponin components. When biogenic aldehydes were used as substrate, ALDH activity with 3,4-dihydroxy-phenylacetaldehyde (DOPAL) in all brain regions of control group was lower than that using 5-hydroxy-indoleacetaldehyde (HIAL) and 3,4-dihydroxyphenylglycolaldehyde (NORAL) as substrate. In control group, ALDH activity with biogenic aldehydes above mentioned was markedly inhibited in the striatum contrary to other regions. The higher ALDH activity with biogenic aldehydes in test group than in control was found in the striatum, cerebrum, and cerebellum. MAO activity in the cerebellum was inhibited in control group and slightly increased in test group. The results of present study suggest that the corpus striatum is significantly affected by ethanol exposure while the hippocampus is not and that ginseng saponin fraction and ginsenosid es might have a preventive effect against depression of brain ALDH activity by chronic administration of ethanol.

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The Influence of ADH1B, ALDH2 Activities and Their Combination on Drinking Behaviors of Korean Young Adults (ADH1B와 ALDH2 활성 조합이 젊은 한국인의 음주 행동에 미치는 영향)

  • Park, Jae-Young;Kim, Sie-Kyeong;Lee, Sang-Ick
    • Korean Journal of Biological Psychiatry
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    • v.17 no.1
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    • pp.26-36
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    • 2010
  • Objectives : It is well-known that Korean people show distinctive drinking behaviors depending on the gene polymorphisms of alcohol metabolizing enzymes. This study examined the gene polymorphisms of ALDH2 and ADH1B and their combination on the drinking behaviors of Korean young adults. Methods : Through a follow-up survey performed for a cohort consisting of 551 university freshmen for six years, the authors attempted to identify genetic factors affecting drinking behaviors. In 2000, drinking behaviors and scores of CAGE questionnaires were assessed and ALDH2 gene polymorphism was determined with PCR-RFLP. In 2006(n= 150), AUDIT-K was assessed in addition to the above and gene polymorphism of ADH1B was determined through SNaPshot$^{TM}$ method. Results : While ALDH2*2 allele was associated with increased degree of drinking in 2000 and 2006. When both enzymes were active, the possibility to be classified into the risk group for alcohol dependence such as AUDIT-K(>12), and CAGE(>2) was high. Conclusion : The ALDH2 genotype had a significant effect on drinking behavior and degree of drinking during early adulthood. However, the combination of the active form of ADH1B and the active form of ALDH2 can be risk factor for problem drinking.

A Study on the analysis of constitutional genes (체질유전자 분석에 관한 연구)

  • Han, Sung-Kyu;Chi, Sang-Eun;Choi, Sun-Mi
    • Journal of Sasang Constitutional Medicine
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    • v.15 no.1
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    • pp.109-117
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    • 2003
  • There have been several the reports that the mechanism of Sasang consititution might be understood in the level of genes. Previous study of the authors showed that HLA types and constitutional information had significant relationships. One hundred subjects who showed Taeum characteristics were selected in the present study. HLA-A, HLA-B, HLA-DRB1, ACE, ${\beta}-IIAR$, ${\beta}-IIIAR$, UCP-1, and ALDH2 polymorphisms were analyzed. Also, ACE, ${\beta}-IIAR$, ${\beta}-IIIAR$, UCP-1, and ALDH2 analyses were performed on the 100 samples of previous study who showed Taeyang characteristics. Despite of several significant differences of HLA allele frequencies between Taeum-inclined group and normal control group, this significance level was not sufficient ro support the association between constitution and HLA genes, because of the raised alpha error rate. The polymorphisrns of ACE, ${\beta}-IIAR$, ${\beta}-IIIAR$, UCP-1, and ALDH2 genes did not show relationship between Taeyang-inclined and Taeum-inclined groups, whereas BMI showed difference between Taeyang-inclined and Taeum-inclined groups. ALDH2 in Taeyang-inclined group confirmed the protective role of ALDH2*2 allele against alcoholism.

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