Purpose p53 and RAS are multifunctional proteins that are critical to cell cycle regulation, apoptosis, cell survival, gene transcription, response to stress, and DNA repair. We have evaluated the prognostic and predictive value of p53 gene/protein aberrations using tumor samples from JBR.10, a North American phase III intergroup trial that randomly assigned 482 patients with completely resected stage IB and II non–small-cell lung cancer (NSCLC) to receive four cycles of adjuvant cisplatin plus ...
Purpose: MDM2 is a major negative regulator of p53, and a single nucleotide polymorphism in the MDM2 promoter region SNP309 (rs2279744) has been shown to increase the affinity of the transcriptional activator Sp1, resulting in elevated MDM2 transcription and expression in some cancers. There is currently no information about the role of MDM2 polymorphism in renal cell carcinoma (RCC). We investigated polymorphisms in p53-related genes, including MDM2 , and their interactions in renal cancer. Exp...
Purpose MDM2 is a negative regulator of p53. The MDM2 309T/G polymorphism has been associated with differential MDM2 expression levels and inhibition of the p53 pathway. We hypothesized that the MDM2 G/G genotype may be associated with worse survival outcomes in lung cancer, especially in squamous cell cancers where p53 abnormalities are more common. Patients and Methods We evaluated the relationship between MDM2 polymorphism status and overall survival (OS) among patients with early-stage non–s...
#2Fang Zhou(Peking Union Medical College)H-Index: 19
Last. Sen Zhang(Peking Union Medical College)H-Index: 3
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Summary Background Pin1 isomerizes the bonds of molecules important for numerous oncogenic and cell-signaling pathways, including Bcl-2, p53, c-Jun, β-catenin, NF-κB, cyclin D1, c-Myc and Raf-1. This can cause a change in conformation leading to alterations in catalytic activity, protein–protein interactions, subcellular localization and protein stability. These alterations have been shown to be associated with cell transformation and cancer progression. Pin1 is overexpressed in several differen...
7134 Background: To compare the efficacy and toxicity of IP vs. non-platinum-based GV in the treatment of advanced NSCLC, we conducted a randomized phase II trial with planned cross-over to the oth...
#1E Fokkema(UMCG: University Medical Center Groningen)H-Index: 9
#2Wim Timens(UMCG: University Medical Center Groningen)H-Index: 87
Last. Harry J.M. Groen(UMCG: University Medical Center Groningen)H-Index: 84
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Summary Background: Apoptosis related proteins in early staged NSCLC seem to have prognostic value. We studied the value of a combination of eight of those proteins in advanced NSCLC. Patients and methods: Bronchoscopically procured tumor biopsies of NSCLC patients were stained immunohistochemically and rated for expression of eight different cellular proteins. Patients were treated with 60 Gy radiotherapy with or without carboplatin as radiosensitizer. Results: Apoptotic proteins in tumors that...
BACKGROUND Combined chemotherapy with irinotecan and cisplatin (IP) is active in patients with nonsmall cell lung carcinoma (NSCLC). However, the optimal administration schedule needs to be defined to maximize its synergic effect. The authors evaluated the efficacy, toxicity, and pharmacokinetics (PK) of IP chemotherapy given on two administration sequences in chemotherapy-naive patients with NSCLC. METHODS Eighty eligible patients were assigned randomly to receive 1 of 2 irinotecan and cisplati...
Purpose: Recent studies have highlighted that the p53 codon 72 polymorphism plays a crucial role in modulating wild-type p53 apoptotic capacity, and as such may influence the response to chemotherapy. Thus, the purpose of this study was to investigate whether the p53 codon 72 polymorphism might influence pathologic response to neoadjuvant chemotherapy in primary breast cancer. Experimental Design: One hundred and ten operable breast cancer patients received anthracycline-based neoadjuvant chemot...
TP53 is well-recognized as a mutational target in cancers and common variation in the TP53 gene has been investigated as potentially contributing to cancer susceptibility. The codon 72 polymorphism has been proposed to alter the phenotype of TP53 mutations, and TP53 mutations have been reported to occur preferentially on the arginine allele. Using a consecutive case series of non-small cell lung cancer we have investigated whether TP53 mutations occur preferentially on the arginine or proline al...
In a recent article, a candidate pathway approach was taken to try to identify single nucleotide polymorphisms (SNP) that make up the genetic variation, which underlies the phenotypic variation seen between individuals in their susceptibility to cancer and the progression of their disease. The p53 stress response pathway was chosen given its well-documented importance in tumor suppression. A SNP was found which associates with the attenuation of the p53 pathway and the acceleration of tumor form...
Last. Yearul Kabir(DU: University of Dhaka)H-Index: 16
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BACKGROUND Tumor suppressor gene (TP53) is considered as the most frequently mutated gene in almost all forms of human cancer. Moreover, genetic variations in the XPD gene affect the DNA repair capacity increasing cancer susceptibility. Polymorphisms within these genes can play a major role in determining individual lung cancer susceptibility. However, several studies have investigated this possibility; but reported conflicting results. Therefore, the objective of this study was to investigate t...
Last. M Aftab Uddin(DU: University of Dhaka)H-Index: 1
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BACKGROUND/AIMS: Bangladesh is a densely populated country with an increased incidence of lung cancer, mostly due to smoking. Therefore, elucidating the association of mouse double minute 2 homolog (MDM2) single nucleotide polymorphism (SNP) 309 (rs2279744) with lung cancer risk from smoking in Bangladeshi population has become necessary. METHODS: DNA was extracted from blood samples of 126 lung cancer patient and 133 healthy controls. The MDM2 SNP309 was genotyped by polymerase chain reaction- ...
#2Reza Aghabozorgi(Arak University of Medical Sciences)H-Index: 2
Last. Zoha Khademi(Arak University of Medical Sciences)H-Index: 2
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BACKGROUND: The nucleotide changes in different genetic loci increased the incidence risk of breast cancer. AIM: The aim of present study was to investigate genotype distribution at codon 72 of the TP53 gene (rs1042522) in breast cancer patients to achieve a potential diagnostic marker related to some demographic feathers. METHODS: In our case-control study, blood samples were collected from a total of 34 patients harboured breast cancer. DNA was extracted, and nested-PCR was performed. Products...
BACKGROUND: Breast cancer (BC) is the most common neoplasm in women, with 5%-10% patients showing a familial predisposition, where germline mutations in BRCA1/BRCA2 genes are found in -20% of cases. Next-generation sequencing (NGS) is among the best available options for genetic screening, providing several benefits that include enhanced sensitivity and unbiased mutation detection. PALB2 (partner and localizer of BRCA2) is a cancer predisposing gene recently described that encodes a protein part...
The TP53 gene remains the most frequently altered gene in human cancer, of which variants are associated with cancer risk, therapy resistance, and poor prognosis in several tumor types. To determin...
Last. Somayeh Jalilvand(Tehran University of Medical Sciences)H-Index: 14
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A single-nucleotide polymorphism (SNP) in the promoter region of MDM2 (SNP309T>G, rs2279744) has been shown to increase the expression of the MDM2 protein in various cancer types. However, only one study has analyzed the role of the MDM2 polymorphism in the development of Kaposi’s sarcoma (KS). The association of MDM2 SNP309 with classic KS risk was evaluated in 79 Iranian patients with classic KS and 123 healthy controls. The MDM2 SNP309 was genotyped using PCR and restriction fragment length p...
The increased prevalence and severity of periodontal disease have long been associated with aging, such that this oral condition affects the majority of the adult population over 50 years of age. Although the immune system is a critical component for maintaining health, aging can be characterized by quantitative and qualitative modifications of the immune system. This process, termed ‘immunosenescence’, is a progressive modification of the immune system that leads to greater susceptibility to in...
p53 helps in maintaining genomic stability by undergoing cellular arrest, DNA repair or cellular apoptosis during DNA damage. So, as to find the association of p53Arg 72 Pro towards lung carcinogenesis and overall survival of North Indian lung cancer patients, single nucleotide polymorphic variant (rs1042522) was analyzed. 840 subjects including 420 cases and 420 controls were recruited and genotyped using PCR-RFLP technique for p53Arg 72 Pro polymorphic site. Association was analyzed using adju...
The MDM2 protein plays an important role in the regulation of cell proliferation and apoptosis via ubiquitination and proteasome-mediated degradation of p53. The genetic polymorphism rs2279744 (c.309T>G) of the MDM2 gene is reportedly associated with susceptibility and/or prognosis in various cancers. In this study, we investigated the risk factors for worse survival in patients with lung adenocarcinoma (AC). We examined the association between c.309T>G and the prognosis of lung cancer by retros...
Abstract The p53 pathway has been extensively studied for its role in carcinogenesis. Disruption of the pathway occurs in more than half of all cancers, often leading to a worse prognosis for the patient. In recent years several compounds have been successfully developed to target and restore the p53 pathway, either by blocking the MDM2-p53 interaction, restoring wild type conformation of mutant p53, or exploiting the presence of mutant p53 by blocking DNA damage repair pathways. In this review ...
