• 대한기관식도과학회지
• /
• 제4권1호
• /
• pp.73-78
• /
• 1998

The mutation of p53 is the most common genetic alteration found in human cancers and has oncogenic properties. mdm-2 is a recently discoverd that controls the p53 activity by binding of its protein, so negative feedback loop has been suggested in which p53 induces mdm-2 expression. The purpose of this study was to analyze the expression of p53 in leukoplakias, mdm-2 in squamous cell carcinomas, and relationship between p53 and mdm-2 expression in leukoplakias and squamous cell carcinomas. The results were as follows : 1) The p53 was expressed 33.4% in leukoplakias 2) The mdm-2 was expressed 8.3% in leukoplakias and 22.7% in squamous cell carcinomas. 3) The expression rate of p53 was higher in specimens negative for mdm-2 than in specimens positive for mdm-2, but there was not significant relationship between p53 and mdm-2 expression. In conclusion p53 was thought to participate in early phase of oncogenesis, and mdm-2 was thought to have a role as a oncogene in squamous cell carcinoma of head and neck. Though there was not significant relationship between p53 and mdm-2 expression, mdm-2 was thought to inhibit p53 activity.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권7호
• /
• pp.3295-3300
• /
• 2016

Background: Different types of cancer exhibit abnormalities in cell cycle regulators. The murine double minute-2(MDM2) cell cycle regulator is a proto-oncogene that negatively regulates the P53 tumour suppressor gene. Surface epithelial tumours constitute approximately two thirds of ovarian neoplasms. Each histologic type can be classified as benign, borderline and malignant. This study aimed to examine immunohistochemical expression of the MDM2 protein in ovarian serous and mucinous epithelial tumours (benign, borderline and malignant). Materials and Methods: This study included forty five ovarian tumours, subdivided into fifteen cystadenomas (5 serous and 10 mucinous), fifteen borderline tumours (11 serous and 4 mucinous) and fifteen cystadenocarcinomas (9 serous and 6 mucinous). Paraffin sections were stained with haematoxylin and eosin for histopathologic study, and with mouse monoclonal anti-MDM2 antibody for immunohistochemistry. Results: MDM2 positivity was detected in 28.9% of the studied ovarian tumours. All benign tumours were negative and positivity was significantly higher in malignant than borderline tumours (P value of chi-square test =0.000). Significantly, all MDM2 positive mucinous tumours were malignant with no positive mucinous borderline tumours. Malignant tumours showed positive MDM2 expression in 83.3% of mucinous type and in 55.6% of serous type. Borderline serous tumours showed negative MDM2 in 72.7% of cases (P value of Z test =0.04). Conclusions: Alterations in the expression of the cell cycle regulator (MDM2) occur early in the process of tumourigenesis in serous and mucinous ovarian tumours. We suggest that MDM2 may be used in those tumours as a marker for risk stratification and identification of cases with cancer development and progression. We recommend further studies on MDM2 immunohistochemistry, in conjunction with adjuvant methods as DNA ploidy and FISH gene amplification, focusing on the mucinous tumours and differentiating between the three tumour categories, benign, borderline and malignant.

• BMB Reports
• /
• 제50권10호
• /
• pp.485-486
• /
• 2017

Many intrinsically unstructured/unfolded proteins (IUPs) contain transient local secondary structures even though they are "unstructured" in a tertiary sense. These local secondary structures are named "pre-structured motifs (PreSMos)" and in fact are the specificity determinants for IUP-target binding, i.e., the active sites in IUPs. Using high-resolution NMR we have delineated a PreSMo active site in the intrinsically unfolded mid-domain (residues 201-300) of SUMO-specific protease 4 (SUSP4). This 29-residue motif which we termed a p53 rescue motif can protect p53 from mdm2 quenching by binding to the p53-helix binding pocket in mdm2(3-109). Our work demonstrates that the PreSMo approach is quite effective in providing a structural rationale for interactions of p53-mdm2-SUSP4 and opens a novel avenue for designing mdm2-inhibiting anticancer compounds.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권14호
• /
• pp.5767-5772
• /
• 2015

Background: Polymorphisms in the MDM2 309 (T>G) and TP53 72 (G>C) genes are reported to increase the susceptibility to head and neck cancer (HNC) in various populations. The risk for HNC is also strongly associated with etiologic habits such as smoking, alcohol consumption and/or chewing of betel quid (BQ). In a case-control study, we investigated the significance of the above polymorphisms alone, and upon interaction with one another as well as with various etiologic habits in determining HNC risk in a Northeast Indian population. Materials and Methods: Genotyping at 309 MDM2 and 72 TP53 in 122 HNC patients and 86 cancer free healthy controls was performed by PCR using allele specific primers, and the results were confirmed by DNA sequencing. Results: Individuals with the GG mutant allele of MDM2 showed a higher risk for HNC in comparison to those with the TT wild type allele (OR=1.9, 95%CI: 1.1-3.3) (p=0.022). The risk was further increased in females by ~4-fold (OR=4.6, 95% CI: 1.1-19.4) (P=0.04). TP53 polymorphism did not contribute to HNC risk alone; however, interaction between the TP53 GC and MDM2 GG genotypes resulted in significant risk (OR=4.9, 95% CI: 0.2-105.1) (p=0.04). Smokers, BQ- chewers and alcohol consumers showed statistically significant and dose-dependent increase in HNC risk, irrespective of the MDM2 genotype. Conclusions: MDM2 genotype could serve as an important predictive biomarker for HNC risk in the population of Northeast India.

• 한국식품과학회지
• /
• 제13권3호
• /
• pp.176-180
• /
• 1981

국내의 산란노계와 브로일러로부터 생산(生産)된 수동발골육(HDM) 및 기계발골육(MDM)을 여러가지 비율(比率)로 배합(配合)하여 제조(製造)한 치큰 패티와 프랑크푸르트 소시지의 특성(特性), 보존성(保存性), 기호성(嗜好性)을 평가(評價)하였던 바 다음과 같은 결과(結果)를 얻었다. 1. HDM을 사용한 치큰 패티의 TBA시험에 의한 지방산패도는 냉동저장중 계속 증가하였으나 8주(週)까지는 보존성이 양호(良好)였다. 2. 치큰 패티의 색(色)과 기호성(嗜好性)에 있어 MDM을 50%까지 첨가한 것이 가장 우수하였고 50%까지도 양호(良好)하였으나 70%이상 첨가는 권장할 수 없었다. 3.프랑크푸르트 소시지의 제조에 있어 MDM을 50%까지 첨가한 것의 기호성이나 조직적 특성은 HDM으로만 만든 제품과 비등하게 양호(良好)하였으나 70% 이상 첨가한 것은 불량(不良)하였다. 4. MDM을 함유(含有)한 프랑크푸르트 소시지의 보존성(保存性)은 $4^{\circ}C$에서 4주까지 무난하였으며 저장 기간에 따른 TBA 값의 변화는 거의 없었다. 5. 결론적으로 치큰 패티나 프랑크푸르트 소시지등의 육제품(肉製品) 제조에 있어서 MDM을 총원료육의 $30{\sim}35%$까지 첨가하여도 조직이나 기호성이 우수한 제품을 생산(生産)할 수 있었다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권11호
• /
• pp.6649-6651
• /
• 2013

Background: Mdm2 binds to the amino-terminus of p53 to induce its degradation and a single nucleotide polymorphism in the MDM2 promoter region (T309G) has been reported to increase the risk of several carcinomas, such as gastric cancer. However, the results of published studies to analyze the association between MDM2 T309G and gastric cancer havve often conflicted. Methods: To better illustrate the filiation between MDM2 T309G and gastric cancer, we performed a meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the relationship. The pooled ORs were performed for 4 models, additive, recessive, co-dominant model, and dominant. Results: Nine published case-control studies including 3,225 gastric cancer cases and 4,118 controls were identified. The MDM2 T309G polymorphism was associated with a significantly increased risk of gastric cancer risk when all studies were pooled into the meta-analysis (GG versus TT, OR=1.57; 95%CI=1.57-2.12; p=0.003) and GG versus GT/TT, OR=1.52; 95%CI=1.217-1.90; p<0.001). Furthermore, Egger's test did not show any evidence of publication bias (P = 0.608 for GG versus TT). Conclusion: Our results suggest that the MDM2 T309G polymorphism is indeed associated with a significantly increased risk of gastric cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권3호
• /
• pp.1057-1060
• /
• 2016

Background: The tumor suppressor p53 is as a regulator of cell proliferation, apoptosis and many other biological processes as well as external and internal stress responses. Mdm2 SNIP309 is a negative regulator of 53. Therefore, this study aimed to determine the role of the Mdm2 SNIP 309 polymorphism in the gastric mucosal morphological patterns in patients with Helicobacter pylori associated gastritis. Materials and Methods: A prospective cross-sectional study was carried out from November 2014 through November 2015. Biopsy specimens were obtained from patients and infection was proven by positive histology. Gastric mucosa specimens were sent to the Molecular Genetics Unit, Institute of Medicine, Suranaree University of Technology where they were tested by molecular methods to detect the patterns of Mdm2 SNIP 309 polymorphism using the real-time PCR hybridization probe method. The results were analyzed and correlated with gastric mucosal morphological patterns by using C-NBI endoscopy. Results: A total of 300 infected patients were enrolled and gastric mucosa specimens were collected. In this study the percentage of Mdm2 SNIP 309 T/T homozygous and Mdm2 SNIP309 G/T heterozygous was 78% and 19 % respectively whereas Mdm2 SNIP309 G/G homozygous was 3%. Mdm2 SNIP 309 T/T homozygous and Mdm2 SNIP309 G/T heterozygosity correlated with type 1 to type 3 gastric mucosal morphological patterns (P<0.01) whereas Mdm2 SNIP309 G/G homozygous correlated with type 4 and type 5 (P<0.01). Conclusions: Our study finds the frequency of Mdm2 SNIP309 G/G in a Thai population is very low, and suggests that this can explain ae Thailand enigma. Types 1 to type 3 are the most common gastric mucosal morphological patterns according to the unique genetic polymorphism of MDM2 SNIP 309 in the Thai population.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권17호
• /
• pp.7413-7417
• /
• 2014

Background: Development of gastric cancer (GC) is a multistep process that requires alterations in the expression of oncogenes and tumor suppressor genes, occurring over several decades. The p53 tumor suppressor protein is involved in cell-cycle control, apoptosis and DNA repair. One of the most important regulators of p53 is MDM2, which acts as a negative regulator in the p53 pathway. Based on the key role of p53 and MDM2 in tumor suppression, polymorphisms that cause change in their function might affect cancer risk. We therefore elevated associations of the polymorphisms of p53 (R72P) and MDM2 (SNP309) with GC in Iran. Materials and Methods: A total of 104 patients with gastric cancer and 100 controls were recruited. Genomic DNA was extracted from fresh gastric samples. Genotyping of the p53 and MDM2 genes was performed using allele specific PCR (AS-PCR). Results: There was no significant difference between the p53 codon 72 polymorphism distribution in control and patient groups (p=0.54), but the G allele of MDM2 was found to be over-represented in patients (p=0. 01, Odds Ratio=2. 08, 95% Confidence Interval= 1.37-4.34). Conclusions: The p53 R72P seems not to be a potential risk factor for development of GC among Iranian patients, but our data suggest that MDM2 SNP309 might modify the risk related to GC.

• Radiation Oncology Journal
• /
• 제25권4호
• /
• pp.193-200
• /
• 2007

목적: 식도암에서 동시적 항암화학방사선치료 전 MDM2, p53, pRb 발현양상이 치료반응 및 생존율 등 치료결과와 연관성이 있는지 알아보고자 하였다. 대상 및 방법: AJCC 병기 $I{\sim}IVa$로 근치적 목적의 동시적 항암화학방사선요법을 받은 51명의 환자를 대상으로 하였다. 방사선치료는 일일 $1.8{\sim}2.0$ Gy씩 원발병소에 중앙값 54 Gy를 시행하였고 항암화학요법은 CDDP/5-FU를 4주 간격으로 4회 시행하고 첫 2회는 방사선치료와 동시에 시행하였다. MDM2, p53, pRb 발현의 검출은 치료 전 내시경하 조직생검을 이용하여 면역조직화학 염색방법을 이용하였다. 단백발현 양성종양세포가 50%이상인 경우를 고발현군으로 정의하였다. 전체 환자의 중앙 추적관찰기간은 26개월이었다. MDM2, p53, pRb 고발현군은 각각 19.6%, 27.5%, 66.7% 이었다. 그러나 이들의 발현 정도와 치료반응, 종양특이 생존율, 전체 생존율 등 모두 유의한 연관성은 없었다. 연령(65세 이하 vs. 초과), 종양의 위치(상부, 중앙부, 하부),종양의 길이(5 cm이하 vs. 초과). 병기($I{\sim}II$ vs. $III{\sim}IVa$), MDM2 (저발현 vs. 고발현), p53 (저발현 vs. 고발현), pRb (저발현 vs. 고발현), 병리학적 완전관해여부, 임상적 완전관해여부 등 9개 요인들을 대상으로 종양특성 생존율에 대한 다변량 분석에서 병리학적 완전관해여부(RR 12.100, p<0.001)와 병기(RR 3.300, p=0.028) 만이 유의한 인자들이었다. 결 론: 본 연구에서 MDM2, p53, pRb의 치료 전 발현양상과 치료결과와 의미있는 연관성은 발견할 수 없었다. 향후 상기 발현인자들을 포함하여 잠재적인 예후인자로서 새로운 다른 발현인자들을 발굴하고 보다 많은 증례 수를 대상으로 추적기간을 보강하여 이들을 재평가하는 연구가 요망된다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권9호
• /
• pp.5415-5420
• /
• 2013

Background: Cell cycle deregulation is a major component of carcinogenesis. The p53 tumor suppressor gene plays an important role in regulating cell cycle arrest, and mouse double minute 2 (MDM2) is a key regulator of p53 activity and degradation. Abnormal expression of p53 and MDM2 occurs in various cancers including lung cancer. Methods: We investigated the distribution of the p53 Arg72Pro (rs1042522) and MDM2 SNP309 (rs2279744) genotypes in patients and healthy control subjects to assess whether these single nucleotide polymorphisms (SNPs) are associated with an increased risk of lung adenocarcinomas in Chinese female non-smokers. Genotypes of 764 patients and 983 healthy controls were determined using the TaqMan SNP genotyping assay. Results: The p53 Pro/Pro genotype (adjusted OR = 1.55, 95% CI = 1.17-2.06) significantly correlated with an increased risk of lung adenocarcinoma, compared with the Arg/Arg genotype. An increased risk was also noted for MDM2 GG genotype (adjusted OR = 1.68, 95% CI = 1.27-2.21) compared with the TT genotype. Combined p53 Pro/Pro and MDM2 GG genotypes (adjusted OR = 2.66, 95% CI = 1.54-4.60) had a supermultiplicative interaction with respect to lung adenocarcinoma risk. We also found that cooking oil fumes, fuel smoke, and passive smoking may increase the risk of lung adenocarcinomas in Chinese female non-smokers who carry p53 or MDM2 mutant alleles. Conclusions: P53 Arg72Pro and MDM2 SNP309 polymorphisms, either alone or in combination, are associated with an increased lung adenocarcinoma risk in Chinese female non-smokers.