MAGE A1-A6 RT-PCR and MAGE A3 and p16 methylation analysis in induced sputum from patients with lung cancer and non-malignant lung diseases

Shin, Kyeong‐Cheol; Lee, Kwan-Ho; Lee, Chaehun; Shin, Im-Hee; Suh, Hun-Suk; Jeon, Chang‐Ho

doi:10.3892/or.2011.1566

Cited by 15 publications

(12 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The median frequency of gene hypermethylation was higher in tumour than in sputum samples: 48% (interquartile range 36–64%) vs 38% (interquartile range 31–57%), respectively. A meta-analysis on exact data (Kersting et al , 2000; Liu et al , 2003; Wang et al , 2003; Olaussen et al , 2005; Shivapurkar et al , 2007; Shin et al , 2012) showed that this observed tendency was not significant ( P =0.09; Durkalski et al , 2003). Median concordance of methylation between tumour and matched sputum, calculated from the same studies, is 78% (interquartile range 73–91%), indicating that the use of sputum as non-invasive biological fluid for detection of aberrant methylation is representative of the methylation status of primary tumour tissue.…”

Section: Molecular Analysis Of Sputummentioning

confidence: 96%

“…Concerning p16 gene, five studies (Belinsky et al , 1998; Destro et al , 2004; Olaussen et al , 2005; Cirincione et al , 2006; Shivapurkar et al , 2007) with ⩽55 PCR cycles and nine studies with >55 PCR cycles (Kersting et al , 2000; Palmisano et al , 2000; Konno et al , 2004; Belinsky et al , 2006; Hsu et al , 2007; Liu et al , 2008; Guzmán et al , 2012; Leng et al , 2012; Shin et al , 2012) with sensitivity and specificity data were available for bivariate analysis (Reitsma et al , 2005). Interestingly, mean specificity was shown to be significantly lower in the group of studies with >55 PCR cycles (74% vs 87%, P <0.001), whereas sensitivity was higher, but not significantly different (49% vs 33%, P =0.13).…”

Section: Molecular Analysis Of Sputummentioning

confidence: 99%

See 1 more Smart Citation

Molecular sputum analysis for the diagnosis of lung cancer

et al. 2013

View full text Add to dashboard Cite

Lung cancer is the leading cause of cancer mortality rate worldwide, mainly because of the presence of metastatic disease at the time of diagnosis. Early detection of lung cancer improves prognosis, and towards this end, large screening trials in high-risk individuals have been conducted since the past century. Despite all efforts, the need for novel (complementary) lung cancer diagnostic and screening methods still exists. In this review, we focus on the assessment of lung cancer-related biomarkers in sputum in the past decennium. Besides cytology, mutation and microRNA analysis, special attention has been paid to DNA promoter hypermethylation, of which all available literature is summarised without time restriction. A model is proposed to aid in the distinction between diagnostic and risk markers. Research on the use of sputum for non-invasive detection of early-stage lung cancer has brought new insights and advanced molecular techniques. The sputum shows a promising potential for routine diagnostic and possibly screening purposes.

show abstract

Section: Molecular Analysis Of Sputummentioning

confidence: 96%

Section: Molecular Analysis Of Sputummentioning

confidence: 99%

Molecular sputum analysis for the diagnosis of lung cancer

et al. 2013

View full text Add to dashboard Cite

show abstract

“…INK4a was identified in plasma and sputum samples of patients with early lung cancer, as well as in lung cancer tissue samples (27,28). These studies indicated that p16…”

Section: Discussionmentioning

confidence: 98%

Effect of combined 5-aza-2′deoxycytidine and cisplatin treatment on the P15 lung adenocarcinoma cell line

et al. 2015

View full text Add to dashboard Cite

Abstract. Aberrant promoter hypermethylation resulting in the epigenetic silencing of apoptosis-associated genes is a key process in the chemotherapeutic treatment of cancer. The nucleoside analog, 5-aza-2'deoxycytidine (DAC), inhibits the activity of DNA methyltransferase enzymes and is able to restore the expression levels of genes that have been silenced by aberrant DNA methylation. The aim of the present study was to investigate the effect of combined treatment with DAC and cisplatin (CDDP) on the lung adenocarcinoma cell line, P15. Growth inhibition was examined using a clone formation assay and growth inhibitory activities by cell counting during treatment with DAC alone, CDDP alone or DAC followed by CDDP. In addition, changes in the mRNA expression levels of various apoptosis-associated genes following treatment with increasing concentrations of DAC were determined using reverse transcription-polymerase chain reaction. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis was used to detect the number of apoptotic P15 tumor cells following treatment with DAC and/or CDDP. The results indicated that DAC treatment alone restored the mRNA expression levels of p73, p16INK4a , B-cell lymphoma (Bcl)-2-associated agonist of cell death and Bcl-2-associated X protein. In addition, combined therapy with DAC and CDDP was found to significantly suppress the growth of P15 tumor cells compared with DAC or CDDP treatment alone. In conclusion, DAC may enhance the chemosensitivity of the P15 cell line to treatment with CDDP. IntroductionLung cancer is a leading cause of cancer-associated mortality worldwide and the most common type is non-small cell lung cancer (NSCLC) (1). Despite progress in the development of molecular-targeted therapeutic agents and surgical approaches, chemotherapy remains an important strategy for the treatment of NSCLC. A combination of a next-generation cytotoxic agents and a platinum compound is the standard treatment regimen for patients with advanced NSCLC (2,3). The cytotoxicity of cisplatin (CDDP), a platinum compound used in chemotherapy, is predominantly due to its interaction with DNA, forming DNA adducts that result in the activation of a number of apoptosis signaling pathways (4). However, the resistance of NSCLC cells to CDDP, which is currently a barrier in the treatment of patients with NSCLC, is associated with inactivation of these apoptosis signaling pathways (5,6).In tumor cells, numerous apoptosis-associated genes appear to have methylated CpG islands. DNA methylation is a crucial regulator in various biological processes; however, aberrant CpG island hypermethylation in gene promoter regions may impact the cell cycle, proliferation, apoptosis, metastasis, drug resistance and intracellular signaling. Therefore, the occurrence of this aberrant hypermethylation is important in carcinogenesis and cancer treatment. DNA hypermethylation is an epigenetic modification that leads to the transcriptional silencing of regulatory genes in various...

show abstract

“…Shin et al collected sputum from 133 patients with lung diseases (65 lung cancers and 68 benign lung diseases) and showed methylation abnormalities in patients with MAGE-positive sputum (in both malignant and benign diseases). Thus, MAGE expression in the sputum suggests the presence of lung cancer cells or pre-cancerous cells (51). …”

Section: Prognostic and Predictive Value Of Epigenetic Changesmentioning

confidence: 99%

Targeting the Epigenome in Lung Cancer: Expanding Approaches to Epigenetic Therapy

et al. 2013

View full text Add to dashboard Cite

Epigenetic aberrations offer dynamic and reversible targets for cancer therapy; increasingly, alteration via overexpression, mutation, or rearrangement is found in genes that control the epigenome. Such alterations suggest a fundamental role in carcinogenesis. Here, we consider three epigenetic mechanisms: DNA methylation, histone tail modification and non-coding, microRNA regulation. Evidence for each of these in lung cancer origin or progression has been gathered, along with evidence that epigenetic alterations might be useful in early detection. DNA hypermethylation of tumor suppressor promoters has been observed, along with global hypomethylation and hypoacetylation, suggesting an important role for tumor suppressor gene silencing. These features have been linked as prognostic markers with poor outcome in lung cancer. Several lines of evidence have also suggested a role for miRNA in carcinogenesis and in outcome. Cigarette smoke downregulates miR-487b, which targets both RAS and MYC; RAS is also a target of miR-let-7, again downregulated in lung cancer. Together the evidence implicates epigenetic aberration in lung cancer and suggests that targeting these aberrations should be carefully explored. To date, DNA methyltransferase and histone deacetylase inhibitors have had minimal clinical activity. Explanations include the possibility that the agents are not sufficiently potent to invoke epigenetic reversion to a more normal state; that insufficient time elapses in most clinical trials to observe true epigenetic reversion; and that doses often used may provoke off-target effects such as DNA damage that prevent epigenetic reversion. Combinations of epigenetic therapies may address those problems. When epigenetic agents are used in combination with chemotherapy or targeted therapy it is hoped that downstream biological effects will provoke synergistic cytotoxicity. This review evaluates the challenges of exploiting the epigenome in the treatment of lung cancer.

show abstract

MAGE A1-A6 RT-PCR and MAGE A3 and p16 methylation analysis in induced sputum from patients with lung cancer and non-malignant lung diseases

Cited by 15 publications

References 23 publications

Molecular sputum analysis for the diagnosis of lung cancer

Molecular sputum analysis for the diagnosis of lung cancer

Effect of combined 5-aza-2′deoxycytidine and cisplatin treatment on the P15 lung adenocarcinoma cell line

Targeting the Epigenome in Lung Cancer: Expanding Approaches to Epigenetic Therapy

Contact Info

Product

Resources

About