• 제목/요약/키워드: TP53

검색결과 164건 처리시간 0.023초

TP53 Codon 72 Polymorphisms and Lung Cancer Risk in the Bangladeshi Population

  • Chowdhury, Miraj Kobad;Moniruzzaman, Md;Al Emran, Abdullah;Mostafa, Mohammad Golam;Kuddus, Ruhul H;Uddin, M Aftab
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권8호
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    • pp.3493-3498
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    • 2015
  • Objective: To assess associations between codon 72 polymorphisms (Pro or B and Arg or b alleles) of the TP53 gene and lung cancer risk among Bangladeshis. Materials and Methods: The distribution of the BB, Bb, and bb genotypes and the frequencies of the B and b alleles were determined by PCR-RFLP method using DNA extracted from leucocytes of 50 confirmed lung cancer patients and 50 age-matched controls and the data were analysed. Results: The ratio of BB, Bb, and bb genotypes were in Hardy-Weinberg equilibrium except for the male patients (${\chi}2=4.6$). The B allele is overrepresented among all patients (OR=2.0, p=0.02) and the female patients (OR=4.1, $p{\leq}0.01$) compared to the controls. The BB/bb ratio was also higher among the patients (OR=3.0, p=0.03). The relative risk of cancer for having BB over bb genotype was 1.8 (p=0.04) but no effect was observed for the Bb genotype. The B allele was overrepresented among patients with adenocarcinomas (OR=2.4, $p{\leq}0.01$) and squamous cell carcinomas (OR=2.7, $p{\leq}0.01$) over the controls but the difference was not significant for those with small cell lung carcinomas (OR=1.1, p=0.66). The B allele was overrepresented among patients age 50 or younger (OR=2.7, $p{\leq}0.01$), but not for older patients (OR=1.7, p=0.07), and among smokers compared to the controls (OR=1.8-10.0, $p{\leq}0.01-0.03$). However, no correlation between increasing pack-years and lung cancer was observed. Conclusions: The Pro/Pro (BB) genotype and the B allele are risk factors for lung cancer among Bangladeshis, particularly for people under age 50, women and smokers.

Polymorphism of p53 Gene Codon 72 in Endometrial Cancer: Correlation with Tumor Grade and Histological Type

  • Kafshdooz, Taiebeh;Tabrizi, Ali Dastranj;Ardabili, Seyyed Mojtaba Mohaddes;Kafshdooz, Leila;Ghojazadeh, Morteza;Gharesouran, Jalal;Abdii, Ali;Alizadeh, Hamideh
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권22호
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    • pp.9603-9606
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    • 2014
  • Background: Endometrial cancer is the fourth most common cancer among women in developed countries. Patients with endometrial cancer may benefit from systemic chemotherapy alone or in combination with targeted therapies if the disease is clinically diagnosed prior to spread and metastasis to other organs. The aim of this study was to evaluate the prognostic role of p53 polymorphism and its correlation with tumor grade in human uterine endometrial carcinomas. Materials and Methods: A total of 75 patients with endometrial carcinomas were studied for possible mutations in exon 4 of the p53 gene using polymerase chain reaction and restricting fragment length polymorphism techniques and sequencing. Results: In recent study, The rate of homozygote genotype of pro/pro or Arg/Arg in high grade group was higher than in comparison with low grade one. In addition samples that were undigested in RFLP, showed mutation in exone 4. Conclusions: Our findings showed that high grade endometrial carcinomas are highly associated with TP53 polymorphisms in comparison with low grades.

돌연변이 p53 단백질의 Silencing에 의한 사람유방암세포의 in vivo 항 종양 효과 (Silencing of Mutant p53 Leads to Suppression of Human Breast Xenograft Tumor Growth in vivo)

  • 박원익;박세라;박현주;배윤희;유현수;장혜옥;배문경;배수경
    • KSBB Journal
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    • 제31권1호
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    • pp.52-57
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    • 2016
  • Mutant p53 (R280K) is highly expressed in MDA-MB-231 triple-negative human breast cancer cells. Currently, we reported the role of mutant p53-R280K in mediating the survival of MDA-MB-231 cells in vitro. The present study was undertaken to determine whether mutant p53-R280K affects breast cancer cell growth in vivo. To this end, we used small interfering RNA to knockdown the level of mutant p53-R280K in MDA-MB-231 cells. Silencing of mutant p53-R280K in MDA-MB-231 cells causes substantial tumor regression of established xenografts in vivo. In xenograft model for breast cancer, silencing of mutant p53-R280K in MDA-MB-231 cells significantly inhibited the tumor growth. Moreover, TUNEL assay showed more occurrence of apoptotic cells in mutant p53-R280K silenced tumors compared to control. Our data indicate that mutant p53-R280K has an important role in mediating tumor growth of MDA-MB-231 cells in vivo. Taken together, this study suggests that endogenous mutant p53-R280K could be used as a therapeutic target for breast cancer cells harboring this TP53 missense mutation.

U-937 세포에서 이온화 방사선의 조사선량에 따른 감수성 유전자들의 발현 변화 (The mRNA Expression of Radio-Sensitive Genes Exposed to Various Dosage of Ionizing Radiation in U-937 Cell)

  • 김종수;임희영;오연경;김인규;강경선;윤병수
    • Toxicological Research
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    • 제20권1호
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    • pp.21-29
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    • 2004
  • We used cDNA microarray to assess gene expression profiles in hematopoetic cell line, U-937, exposed to low doses of ionizing irradiation. The 1,000 DNA elements on this array were PCR-amplified cDNAs selected from named human cancer related genes. According to the strength of irradiation, the levels of some gene expression were increased or decreased as dose-dependent manner. The gene expressions of Tubulin alpha, protein kinase, interferon-alpha, -beta, -omega receptor and ras homolog gene family H were significantly increased. Especially, Tubulin gene was shown 2.5 fold up-regulated manner under stress of 500 rad irradiation than 200 rad. On the other hand, fibroblast growth factor 12 and four and a half LIM domains, etc. were significantly down-regu-lated. Also, tumor protein 53(TP53) related genes that p53 inducible protein, tumor protein 53-binding protein looks of little significance as radiation sensitive manner. The radio-sensitivity of tubulin gene etc. that we proposed could be useful to rapid and correct survey for the bio-damage by exposure to low dose irradiation.

Angiogenesis Markers in Breast Cancer - Potentially Useful Tools for Priority Setting of Anti-Angiogenic Agents

  • Keyhani, Elahe;Muhammadnejad, Ahad;Behjati, Farkhondeh;Sirati, Fereidoon;Khodadadi, Faranak;Karimlou, Masoud;Moghaddam, Fatemeh A.;Pazhoomand, Reza
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권12호
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    • pp.7651-7656
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    • 2013
  • Background: Breast cancer is the most common malignancy among women in both developed and developing countries. The burden is increasing in low-income and middle-income countries (LMCs) and threatens the public health of such societies. Introduction of expensive monoclonal antibodies to cancer treatment regimens poses a real challenge in the health systems of LMCs. Despite controversy of cost-effectiveness of bevacizumab in breast cancer, some studies indicate gain of patients from this drug. The present study aimed to propose a priority setting model for administration of anti-angiogenic agents in breast cancer via assessment of tumor angiogenesis by the microvessel density (MVD) method and associations with clinicopathological characteristics (including simultaneous mutations of TP53 and HER-2 genes). Materials and Methods: Age, axillary lymph nodes status, tumor size, stage and grade, estrogen and progesterone receptors status, HER-2/neu status (by immunohistochemistry and FISH test), TP53 mutation, Ki-67 (for proliferation assay) and CD34 (for angiogenesis assay) were assessed in 111 breast cancer patients. The molecular subtype of each tumor was also determined and correlations of simultaneous mutations of HER-2 and p53 genes with angiogenesis and other clinicopathological characteristics were evaluated. Results: There were significant associations between simultaneous mutations of HER-2 and p53 genes and all other parameters except tumor size. The degree of angiogenesis in the ERBB2 subtype was greater than the others. Younger patients showed a higher angiogenesis rate rather those older than 50 years. Conclusions: Our results demonstrated that patients with simultaneous mutations of HER-2 and p53 genes, those with ERBB2 molecular subtype and also younger women (often triple negative) seem more eligible for obtaining anti-angiogenic agents. These results suggest a model for priority setting of patients with breast cancer for treatment with anti-angiogenic drugs in LMCs.

Shigella R Plasmid의 분자적 특성 (Molecular Characteristics of R Plasmids in Shigella)

  • 이유철;설성용;조동택;전도기
    • 대한미생물학회지
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    • 제22권1호
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    • pp.35-53
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    • 1987
  • Multiply resistant Shigella strains isolated in Taegu area were subjected for the characterization of R plasmids. All strains isolated in 1984 and 1985 were susceptible to gentamicin, amikacin, and cephalothin, and most strains were susceptible to kanamycin (Km) and rifampin by agar dilution antimicrobial susceptibility test. The resistance frequency of S. flexneri against ampicillin (Ap) was higher than that of S. sonnei. The strains resistant to sulfisomidine (Su) and trimethoprim (Tp) were found at higher frequency in S. sonnei than in S. flexneri. The most prevalent resistance pattern of S. flexneri was chloramphenicol (Cm) tetracycline (Tc) streptomycin (Sm) Ap, followed by the pattern of CmTcSmSuApTp, CmTcSmSuApTp nalidixic acid, and CmTcSmSuAp in the decreasing order. The antibiogram of CmTcSmSuTp was found to be the most frequent pattern in S. sonnei. The ratio of conjugal transfer of S. flexneri was 47% and 75% of S. sonnei. The average number of plasmid harboring in Shigella was 4 and the size of plasmid ranged 1.3 to 134 megadalton (Mdal). Most S. flexneri carried plasmids of 2 to 3 Mdal and S. sonnei carried those of 3 to 4 Mdal size. The sizes of conjugative plasmids ranged 40-90 Mdal. The incompatibility group (Inc) F II plasmids (54-59 Mdal) were most frequent and rare Inc B plasmids (60 Mdal) of isolates in 1979 and 1980 and Inc FI (87 Mdal) of 1983 isolates were able to be classified by the colony test with standard reference plasmids. The R plasmids of known Inc group were tested for the restriction endonuclease analysis. The pattern of plasmids digested by EcoRl were apparently different by the Inc group but there was no significant difference between species or by the resistance patterns. Nonconjugative plasmids and their phenotypes were identified by transformation test. The transformants were resistant to less than two drugs. Colicin producing transformants carried the Col plasmid of 3.7 or 3.9 Mdal size. $Ap^r$ plasmids derived from S. sonnei were found to be mobilized by transfer factor RT641 to E. coli #CS100. $Ap^r$ plasm ids of same size shared by S. flexneri, S. sonnei, and E. coli were digested with Pstl. All of them showed two restriction fragments of 2.8 kilobase(kb) and 0.7kb. Other plasmids ($Sm^r\;Su^r$) derived from S. flexneri, S. boydii, and S. sonnei were digested with Pstl and they showed same restriction fragment patterns of 3.1kb and 2.9kb. The plasmid profiles of three strains of S. sonnei producing colicin and showing same resistance pattern of CmTcSmSuApTpKm appeared to be similar. Restriction patterns by EcoRl and the behavior of plasmids in conjugation or transformation process were also similar between those plasmids. The restriction patterns were significantly different between the plasmids of Inc FI group and those of unclassified Inc group.

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U937 세포에서 발암관련 유전자들로 구성된 DNA chip을 이용한 방사선 감수성 유전자들의 선발 (Identification of Radiation-Sensitive Gene in U937 Cell by using cDNA-Chip Composed of Human Cancer Related Gene)

  • 김종수;김인규;강경선;윤병수
    • 한국환경성돌연변이발암원학회지
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    • 제22권1호
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    • pp.54-59
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    • 2002
  • We have used cDNA microarray hybridization to identify gene regulated in response to gamma-irradiation in U-937 cell. The cDNA-chip was composed entirely of 1,000 human cancer related gene including apoptosis and angiogenesis etc. In gamma-irradiated U-937 cell, highly charged protein, ribosomal protein L32, four and a half LIM domains 3, lipocalin 2 (oncogene 24p3) and interleukin 15, ataxia telangiectasia mutated (includes complementation groups A, C and D) genes showed increased level of its transcription, and cell division cycle 25A, dihydrofolate reductase, topoisomerase (DNA) II beta(180kD), kinase suppressor of ras and strarigin genes showed reduced level of its transcription compared to untreated U-937 cell. The significant change of level of transcription was not found in well-known ionizing radiation(IR)-responsive gene, such as transcription factor TP53 and p53 related gene, except ataxia telangiectasia mutated gene.

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총인부하량을 이용한 인공호의 부영양화 평가 (The evaluation of the eutrophication for the lakes by phosphorus loading)

  • 김재윤
    • 한국환경과학회지
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    • 제12권7호
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    • pp.689-695
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    • 2003
  • The purpose of this study is to evaluate and to predict of eutrophication in lakes by using Vollenweider-OECD model and total phosphorus concentration and inflow rate which were measured in 1993∼2001. The results of study were as follows. The annual total phosphorus loading from the watershed was calculated to be 55∼195tP/yr at lake Soyang, 221∼466tP/yr at lake Taechong, 123∼278tP/yr at lake Andong, 57∼109tP/yr at lake Seomjin. These are discharged, far the most parts, from population and fishfarm facility. TP loading on the surface area at lake Soyang was 3.01gP/㎡/yr, 2.82gP/㎡/yr, 2.84gP/㎡/yr, 3.03gP/㎡/yr, 2.34gP/㎡/yr, 1.78gP/㎡/yr, 0.91gP/㎡/yr, 0.89gP/㎡/yr, 0.86gP/㎡/yr, lake Taechong was 6.71gP/㎡/yr, 7.25gP/㎡/yr, 7.24gP/㎡/yr, 6.53gP/㎡/yr, 6.50gP/㎡/yr, 7.06gP/㎡/yr, 7.04gP/㎡/yr, 4.05gP/㎡/yr, 3.44gP/㎡/yr and TP loading on the surface area of lake Andong, lake Soemjin were 5.39gP/㎡/yr, 4.47gP/㎡/yr, 4.56gP/㎡/yr, 4.45gP/㎡/yr, 3.33gP/㎡/yr, 2.38gP/㎡/yr, 2.53gP/㎡/yr, 2.46gP/㎡/yr, 2.54gP/㎡/yr, 4.09gP/㎡/yr, 4.10gP/㎡/yr, 3.98gP/㎡/yr, 3.73gP/㎡/yr, 2.80gP/㎡/yr, 3.46gP/㎡/yr, 3.22gP/㎡/yr, 2.19gP/㎡/yr, 2.13gP/㎡/yr respectively. The tropic states of four lakes can be assessed as eutrophy because phosphorus leading exceeds the critical phosphorus loading by Vollenweider-OECD model.

Mutational Analysis of Extranodal NK/T-Cell Lymphoma Using Targeted Sequencing with a Comprehensive Cancer Panel

  • Choi, Seungkyu;Go, Jai Hyang;Kim, Eun Kyung;Lee, Hojung;Lee, Won Mi;Cho, Chun-Sung;Han, Kyudong
    • Genomics & Informatics
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    • 제14권3호
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    • pp.78-84
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    • 2016
  • Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples. The sequencing analysis detected 25 mutations in 21 genes. Among them, KMT2D, a histone modification-related gene, was the most frequently mutated gene (four of the five cases). This result was consistent with recent NGS studies that have suggested KMT2D as a novel driver gene in NKTCL. Mutations were also found in ARID1A, a chromatin remodeling gene, and TP53, which also recurred in recent NGS studies. We also found mutations in 18 novel candidate genes, with molecular functions that were potentially implicated in cancer development. We suggest that these genes may result in multiple oncogenic events and may be used as potential bio-markers of NKTCL in the future.

주요우울장애 환자에서 생애초기스트레스와 연관된 심박변이도의 특성 (Characteristics in Heart Rate Variability associated with Early Life Stress in Patients with Major Depressive Disorder)

  • 이치헌;김민경;최선우;박해인;석정호
    • 우울조울병
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    • 제15권3호
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    • pp.117-122
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    • 2017
  • Objectives : Early life stress (ELS) may have impact on functions of the autonomic nervous system. Heart rate variability (HRV) is a reliable psychophysiological marker for functions of the autonomic nervous system. The purpose of this study was to investigate characteristics of HRV associated with ELS in patients with major depressive disorder (MDD). Methods : We compared HRV measures of MDD patients with ELS and without ELS in a 5-minute resting-state electrocardiogram recoding. Forty subjects participated in the study (25 with ELS, 15 without ELS). The Mann-Whitney test was conducted to identify group differences. Results : We found significant group differences in standard deviation of the NN interval (SDNN) and total power (TP). SDNN was lower in the ELS group (M=38.80 ms, SD=13.05 ms) than in the Non-ELS group (M=53.53 ms, SD=19.47 ms). TP was lower in the ELS group ($M=7.07ms^2$, $SD=0.69ms^2$) than in the Non-ELS group ($M=7.72ms^2$, $SD=0.77ms^2$). Conclusion : ELS may have a negative impact on the autonomic nervous system function in patients with MDD. ELS and dysfunction of autonomic nervous system should be considered in treatment for patients with MDD.