• Title/Summary/Keyword: p53gene

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No Evidence of Association of the Arg72Pro p53 Gene Polymorphism with Cancer Risk in the Saudi Population: a Meta-Analysis

  • Irshad, Mohammad;Mandal, Raju Kumar;Al-Drees, Abdulmajeed;Khalil, Mahmoud Salah;Abdulghani, Hamza Mohammad
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5663-5667
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    • 2015
  • Background: Earlier studies on the association between p53 codon 72 Arg>Pro polymorphism and cancer risk were inconclusive and conflicting for the Saudi population. Therefore, we performed a meta-analysis to investigate the relationship between the codon 72 Arg>Pro polymorphism and overall cancer risk in Saudi Arabia. Materials and Methods: We searched all eligible published studies and data were pooled together to perform the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for homozygous, heterozygous, dominant and recessive genetic models. Results: A total of five eligible published studies covering 502 cancer cases and 784 healthy controls were included in the meta-analysis. No publication bias was detected in this study. The results suggested that the variant (Pro vs Arg: p=0.960; OR=1.004, 95% CI=0.852-1.183), homozygous (Pro.Pro vs Arg.Arg: p=0.970; OR=1.006, 95% CI=0.729-1.390), heterozygous (Arg.Pro vs Arg.Arg: p=0.473; OR=0.783, 95% CI=0.402-1.527) carriers were not associated with overall cancer risk. Similarly, dominant (Pro.Pro+Pro.Arg vs Arg.Arg: p=0.632; OR=0.886, 95% CI=0.540-1.454) and recessive (Pro.Pro vs Pro.Arg+Arg.Arg: p=0.269; OR=1.163, 95%CI=0.890-1.521) models also did not indicate increased risk of cancer. Conclusions: The current meta-analysis suggests that the codon 72 Arg>Pro polymorphism of the p53 gene might not contribute to cancer susceptibility in Saudi population. Future well designed large case control studies are needed to validate our findings.

Immunohistochemical Detection of p53 Gene Mutation in Urine Samples in the Patients with Bladder Cancer (방광암 환자의 요세포 검사에서 p53 단백 발현의 의의)

  • Lee, Sang-Sook;Bae, Ji-Yeon;Kang, Yu-Na;Cho, Young-Rok;Park, Nam-Jo;Kim, Seun-Young;Kim, Jung-Hi
    • The Korean Journal of Cytopathology
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    • v.7 no.2
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    • pp.144-150
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    • 1996
  • Although bladder cancers are very common, little is known about their molecular pathogenesis. It is known that p53 alteration is found in about 60% of muscle-invasive bladder cancer, necessiating aggressive therapy and poor outcome. We examined the nuclear expression of p53 protein, using D07 monoclonal antibody in the urine samples from 31 patients with transitional cell carcinoma of the bladder to investigate the correlation of p53 overexpression with histologic grades and depth of invasion. The positive rate of p53 protein was 27% in superficial bladder tumor, but increased up to 71% in the invasive bladder carcinomas. The overexpression of p53 protein increased according to Mostofi grading system from 18% in grade I, 45% in grade II, and up to 100% in grade III. The p53 expression tended to be higher in the invasive and high grade bladder cancers than in the superficial and low grade ones(p<0.05). These results suggest that immunohistochemical analysis of the urine specimen in the bladder cancer patients could be a useful method of screening for the presence of p53 mutant protein. The mutant p53 protein expression may be an indicator of bladder cancer with more proliferative potential and/or aggressive biologic behavior.

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Allelic Diversity and Geographical Distribution of the Gene Encoding Plasmodium falciparum Merozoite Surface Protein-3 in Thailand

  • Sawaswong, Vorthon;Simpalipan, Phumin;Siripoon, Napaporn;Harnyuttanakorn, Pongchai;Pattaradilokrat, Sittiporn
    • Parasites, Hosts and Diseases
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    • v.53 no.2
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    • pp.177-187
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    • 2015
  • Merozoite surface proteins (MSPs) of malaria parasites play critical roles during the erythrocyte invasion and so are potential candidates for malaria vaccine development. However, because MSPs are often under strong immune selection, they can exhibit extensive genetic diversity. The gene encoding the merozoite surface protein-3 (MSP-3) of Plasmodium falciparum displays 2 allelic types, K1 and 3D7. In Thailand, the allelic frequency of the P. falciparum msp-3 gene was evaluated in a single P. falciparum population in Tak at the Thailand and Myanmar border. However, no study has yet looked at the extent of genetic diversity of the msp-3 gene in P. falciparum populations in other localities. Here, we genotyped the msp-3 alleles of 63 P. falciparum samples collected from 5 geographical populations along the borders of Thailand with 3 neighboring countries (Myanmar, Laos, and Cambodia). Our study indicated that the K1 and 3D7 alleles co-existed, but at different proportions in different Thai P. falciparum populations. K1 was more prevalent in populations at the Thailand-Myanmar and Thailand-Cambodia borders, whilst 3D7 was more prevalent at the Thailand-Laos border. Global analysis of the msp-3 allele frequencies revealed that proportions of K1 and 3D7 alleles of msp-3 also varied in different continents, suggesting the divergence of malaria parasite populations. In conclusion, the variation in the msp-3 allelic patterns of P. falciparum in Thailand provides fundamental knowledge for inferring the P. falciparum population structure and for the best design of msp-3 based malaria vaccines.

Expression of Mutant p53 and MAGE-3 Gene Products in Esophageal Squamous Cell Carcinoma (식도 편평세포암종에서 변형 p53 단백과 MAGE-3 유전자 산물의 발현)

  • 조성래;양일종;이충석;전도환;장희경
    • Journal of Chest Surgery
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    • v.34 no.1
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    • pp.64-71
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    • 2001
  • 배경: 최근 치료법의 진보에도 불구하고 진행성 식도암의 예후는 5년 생존율이 10% 이하로매우 불량하기 때문에 식도암에 대한 새로운 치료방법의 하나로 암면역 치료가 대두되고 있다. 암면역 치료를 위해서 MAGE 등 종양 특이항원이 연구의 대상이 되고 있으나 국내에서는 아직 이에 대한 연구가 없다. 대상 및 방법: 1995년 1월부터 1998년 12월까지 고신대학교 복음병원 흉부외과에서 수술 치험한 125례의 식도암중 병리조직 보관상태가 양호한 편평세포암 79례를 병기에 따라(1병기 19례, IIa병기 19례, IIb병기 10례, III병기 21례, IV병기 10례) 무작위로 추출하고 대조군으로 평활근종 20례와 정상 식도점막 20례를 대조군으로 하여 DO7 단클론 항체와 항 MAGE-3 단클론 항체 57B를 이용하여 면역조직화학검사를 시행하여 변형 p53 단백과 MAGE-3 유전자 산물의 발현율을 조사하고 식도암 조직에서 질병의 진행도를 반영하는 병기에 따른 발현율 및 변형 p53 단백과 MAGE-3 유전자 산물의 발현율간의 상관관계를 조사하였다. 결과: 식도암조직에서 변형 p53 단백과 MAGE-3 유전자 산물의 발현율은 각각 51.9%, 60.8%의 발현율을 보였으나 식도평활근종과 정상 식도점막에서는 한례도 발현되지 않아 변형 p53 단백과 MAGE-3 유전자 산물은 대조군에 비해 식도암 조직에서 의미있게 발현되었다(p<0.001). 변형 p53 단백과 MAGE-3 유전자 산물의 발현은 I병기에서 68.4%, 52.6%, IIa병기에서 57.9%, 47.6%, IIb병기에서 60%, 70%, III병기에서 33.3%, 71.4%, IV병기에서 40%, 70% 각각 발현되어 병기에 따른 발현율의 차이는 없었다(p=0.193, p=0.452). 식도암 조직내에서 변형 p53 단백과 MAGE-3 유전자 산물의 발현간에는 상관관계가 없는 것으로 나타났다(p=0.679). 결론: 이상의 결과로 변형 p53 단백과 MAGE-3 유전자 산물의 발현은 식도암에서 예후인자로서의 역할은 할수 없으나 식도 편평세포 암조직에서만 특이하게 높은 빈도로 발현됨으로써 식도암도 면역치료의 대상이 될 수 있음을 확인하였다.

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Protective effects of Camellia sinensis fruit and fruit peels against oxidative DNA damage

  • Ahn, Joung-Jwa;Jang, Tae-Won;Park, Jae-Ho
    • Journal of Applied Biological Chemistry
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    • v.64 no.3
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    • pp.237-244
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    • 2021
  • Camellia sinensis, Green tea, contains phenolic compounds that act to scavenge reactive oxygen species (ROS), such as catechin, epicatechin, etc. In contrast with the tea leaf, the bioactivity of its fruit and the fruit peels remains still unclear. This study focused on the effects of fruit and fruit peels of C. sinensis (FC and PC) against oxidative DNA damage in NIH/3T3 cells. The scavenging effects of FC and PC on ROS were assessed using 1,1-diphenyl-2-picryl hydrazyl or 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radicals. The measurement of ROS in cellular levels was conducted by DCFDA reagent and the protein expression of γ-H2AX, H2AX, cleaved caspase-3, p53, and, p-p53 was analyzed by immunoblotting. The gene expressions of p53 and H2AX were assessed using polymerase chain reaction techniques. The major metabolites of FC and PC were quantitatively measured analyzed and the amounts of phenolic compounds and flavonoids in PC were greater than those in FC. Further, PC suppressed ROS production, which protects the oxidative stress-induced DNA damage through reducing H2AX, p53, and caspase-3 phosphorylation. These results refer that the protective effects of FC and PC are mediated by inhibition of p53 signaling pathways, probably via the bioactivity of phenolic compounds. Thus, FC and PC can serve as a potential antioxidant in DNA damage-associated diseases.

G1 Arrest of the Cell Cycle by Onchungeum in Human Hepatocarcinoma Cells (온청음(溫淸飮)이 인체 간암세포의 세포주기 G1 Arrest에 미치는 영향)

  • Goo, In-Moo;Shin, Heung-Mook
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.4
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    • pp.821-828
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    • 2008
  • Onchungeum, a herbal formula, which has been used for treatment of anemia due to bleeding, discharging blood and skin disease. In the present study, it was examined the effects of extract of Onchungeum (OCE) on the growth of human hepatocarcinoma cell lines Hep3B (p53 null type) and HepG2 (p53 wild type) in order to investigate the anti-proliferative mechanism by OCE. Treatment of Hep3B and HepG2 cells to OCE resulted in the growth inhibition in a dose-dependent manner, however Hep3B cell line exhibited a relatively strong anti-proliferative activity to OEC. Flow cytometric analysis revealed that OCE treatment in Hep3B cells caused G1 phase arrest of the cell cycle, which was associated with various morphological changes in a dose-dependent fashion. RT-PCR and immunoblotting data revealed that treatment of OCE caused the down-regulation of cyclin D1 expression, however the levels of cyclin E expression were not changed by OCE. The G1 arrest of the cell cycle was also associated with the induction of Cdk inhibitor p27 by OCE. Because the p53 gene is null in Hep3B cells, it is most likely that the induction of p21 is mediated through a p53-independent pathway. Moreover, p27 detected in anti-Cdk4 and anti-Cdk2 immunoprecipitates from the OCE-treated cells, suggesting that OCE-induced p27 protein blocks Cdk kinase activities by directing binding to the cyclin/Cdk complexes. Furthermore, OCE treatment potently suppresses the phosphorylation of retinoblastoma proteins and the levels of the transcription factor E2F-1 expression. Taken together, these results indicated that the growth inhibitory effect of OCE in Hep3B hepatoma cells was associated with the induction of G1 arrest of the cell cycle through regulation of several major growth regulatory gene products.

The Significance of p53 Expression in Serum and Tissue from Patients with Lung Cancer (원발성 폐암환자의 혈청 및 조직에서의 p53단백 표현)

  • Chang, Jung-Hyun;Sung, Sun-Hee
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.2
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    • pp.333-340
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    • 1998
  • Background: Lung cancer is the leading cause of cancer over the world. P53 alteration is by far the most common genetic defect in lung cancer. The mutation of p53 protein involves the loss of inhibitory function of p53 related tumor suppressor gene and resultant oncogenesis. The analysis of p53 alterations consists of immunohistochemical stain, PCR based assay, or serologic ELISA (enzyme-linked immunosorbent assay). Methods : Serum levels of p53 mutant protein were measured in 69 cases of lung cancer (adenocarcinoma n=29, epidermoid n=16, small cell n=13, large cell n=1, undifferentiated n=1, undetermined n=9) and 42 controls of respiratory disorders using ELISA. Immunohistochemical stain in tissue was performed using monoclonal antibody of p53 in lung cancer subjects. Results: Both serum p53s in nonsmall cell cancer ($0.28{\pm}0.44ng/ml$) and in small cell cancer ($0.20{\pm}0.14ng/ml$) were not different from controls ($0.34{\pm}0.20ng/ml$). Also there was no significant difference in serum p53 according to tumor stages. P53 immunohistochemical stain showed 50% positivity overall in lung cancer. There were no close correlation between serologic level and positivity of immunohistochemical stain. Conclusion: The serologic determination of p53 mutant protein is thought to have no diagnostic role in lung cancer. Immunohistochemical stain in lung cancer specimen shows 50% positivity.

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Clinical Significance of the Expression of Oncosuppressor Gene Protein and Epidermal Growth Factor Receptor in Squamous Cell Carcinomas of Larynx (후두 편평세포암에서 암억제유전자 단백 및 상피성장인자 수용체 발현의 임상적 의의)

  • 정광윤;최종욱
    • Proceedings of the KOR-BRONCHOESO Conference
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    • 1993.05a
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    • pp.85-85
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    • 1993
  • The clinical staging system for laryngeal cancers is not sufficient for prognosticator due to different biologic characteristics and their microenvironment according to primary sites. For determining the prognosticators, the authors peformed immunohistochemical staining to EGFR, p53 protein, and pRB in 40 cases of surgically treated squamous cell carcinomas of larynx in our institute during the past 5 years. The results are as followings; 1. The positive expression rate of p53 protein and negative expression rate of pRB showed correlations with clinical parameters. 2. The three-year survival rate for p53 protein positive cases was worse than the p53 protein negative cases. 3. Expression rate of EGFR was not correlated with the clinical parameters. As a conclusion, expression rates of p53 protein and pRB not only reflect well the biologic behavior of laryngeal cancer, but correlate closely with the tumor factors. Therefore they may be useful as the prognosticator to predict the malignant potency of laryngeal squamous cell carcinomas.

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