Abstract:
BACKGROUND:In lung adenocarcinoma, inactivation of the tumor suppressor p53 may abrogate a safeguard mechanism preventing the development of tumors with activating mutations in EGFR or KRAS. To assess this hypothesis, we analyzed TP53 mutations and downregulation of p14(arf), a negative regulator of p53 activated by oncogenic signals, in a retrospective series of 96 patients with primary adenocarcinoma of the lung. PATIENTS AND METHODS:Mutations in TP53 (exons 4-9), KRAS (exon 1), and EGFR (exons 18-21) were identified by direct sequencing of DNA from formalin-fixed, paraffin-embedded resected tumors. Expression of p14(arf) was semiquantitatively evaluated by immunohistochemical analysis. RESULTS:TP53, KRAS, and EGFR mutations were detected in 42 of 93 (45.2%), 15 of 95 (15.8%), and 31 of 90 (34.4%) cases, respectively. Low p14(arf) expression was observed in 19 of 91 cases (20.9%). Disruption of the p53/p14(arf) pathway (defined as TP53 mutation or decreased p14(arf) expression, or both) was observed in 18 of 31 EGFR-mutated (58.1%) tumors and in 9 of 13 KRAS-mutated (69.2%) tumors. CONCLUSION:Inactivation of the p53/p14(arf) pathway is common but not systematic in EGFR- or KRAS-mutated lung adenocarcinomas. Our work highlights the need to better investigate the association between EGFR and KRAS mutations and alterations in tumor suppressor pathways.
journal_name
Clin Lung Cancerjournal_title
Clinical lung cancerauthors
Cortot AB,Younes M,Martel-Planche G,Guibert B,Isaac S,Souquet PJ,Commo F,Girard P,Fouret P,Brambilla E,Hainaut P,Soria JCdoi
10.1016/j.cllc.2013.08.003subject
Has Abstractpub_date
2014-03-01 00:00:00pages
124-30issue
2eissn
1525-7304issn
1938-0690pii
S1525-7304(13)00180-0journal_volume
15pub_type
杂志文章abstract:BACKGROUND:Programmed cell death 1 (PD-1) inhibitors have become a standard treatment, albeit not completely effective, for patients with advanced non-small-cell lung cancer (NSCLC). Previous studies of advanced melanoma have revealed that the tumor burden predicted the response to PD-1 inhibitors, although this relati...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2020.02.012
更新日期:2020-09-01 00:00:00
abstract:PURPOSE:Lung cancer is an epidemic disease in developing countries. Incorporation of new active drugs in the neoadjuvant treatment of operable patients might lead to improved outcomes. Postchemotherapy mediastinal-based treatment decisions allow for in vivo testing of activity and could help to determine the ideal loca...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/CLC.2007.n.003
更新日期:2007-01-01 00:00:00
abstract::Active tumor immunotherapy may provide hope for patients with non-small-cell lung cancer (NSCLC) because, in more than 20 years, current therapies have yet to change mortality statistics. Creating an efficacious vaccine involves selection of important tumor antigens and formulation of their immunogenic epitopes into a...
journal_title:Clinical lung cancer
pub_type: 杂志文章,评审
doi:10.3816/clc.2008.s.003
更新日期:2008-02-01 00:00:00
abstract:BACKGROUND:Obtaining a tissue diagnosis has traditionally been standard practice before initiating therapy for early-stage non-small-cell lung cancer (NSCLC). In several recent studies from Europe and Asia, a substantial proportion of patients have received stereotactic body radiation therapy (SBRT) based only on the i...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2014.04.001
更新日期:2014-07-01 00:00:00
abstract:BACKGROUND:The purpose of this study was to assess the applicability of an annual low-dose computed tomography (CT) screening program for lung cancer in a single institution in Israel, which has a relatively lower prevalence of lung cancer compared with other Western countries, and to examine stage distribution of dete...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/CLC.2006.n.004
更新日期:2006-01-01 00:00:00
abstract:INTRODUCTION:Continuing tyrosine kinase inhibitor (TKI) therapy may be beneficial when patients with non-small-cell lung cancer and EGFR mutations experience gradual disease progression after initial EGFR-TKI treatment. We aimed to compare the efficacy of simultaneous EGFR-TKI and chemotherapy with that of sequential t...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2020.06.005
更新日期:2020-07-06 00:00:00
abstract:INTRODUCTION:We examined mutational testing of the epidermal growth factor gene (EGFR) and erlotinib treatment among veterans diagnosed with non-small-cell lung cancer in the United States Department of Veterans Affairs (VA). Our objectives were to identify the prevalence of clinically actionable EGFR mutations, to det...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2016.11.018
更新日期:2017-07-01 00:00:00
abstract::This article describes the treatment rationale and study-related procedures for the A Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-Small-Cell Lung Cancer Following Disease Progression after One Prior Platinum-Based Therapy (REVEL) st...
journal_title:Clinical lung cancer
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.cllc.2012.06.007
更新日期:2012-11-01 00:00:00
abstract::The therapeutic options for patients with advanced non-small-cell lung cancer (NSCLC) are palliative. Therefore, the quality of life in oncology is considered as an endpoint in clinical trials, and several scales have been accepted for its measurement in parallel with other clinical determinations. However, its use in...
journal_title:Clinical lung cancer
pub_type: 杂志文章,评审
doi:10.3816/CLC.2009.n.010
更新日期:2009-03-01 00:00:00
abstract:BACKGROUND:ROS1 gene fusions cause several cancers by constitutively activating the ROS1 tyrosine kinase receptor. ROS1-targeted inhibitor therapy improves survival in the approximately 1% to 2% of patients with lung adenocarcinoma with ROS1 gene fusions. Although fluorescence in situ hybridization (FISH) is the standa...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2014.10.003
更新日期:2015-03-01 00:00:00
abstract::The standard treatment for early-stage non-small-cell lung cancer is surgical resection. However, many patients are inoperable due to medical comorbidities. Thirty-two medically inoperable patients with early-stage non-small-cell lung cancer were treated with 3-dimensional conformal radiation therapy between January 1...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/clc.2001.n.025
更新日期:2001-11-01 00:00:00
abstract:BACKGROUND:The immune checkpoint proteins programmed death-1/ligand (PD-1/PD-L1) play a critical role in immune escape of tumor cells. In models of epidermal growth factor receptor (EGFR)-driven non-small-cell lung cancer (NSCLC), EGFR signal upregulates PD-1/PD-L1. However, data on the clinical significance of PD1/PD-...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2015.02.002
更新日期:2015-09-01 00:00:00
abstract:BACKGROUND:We investigated the effect of downstaging on OS in LD-SCLC patients treated with first-line treatment. PATIENTS AND METHODS:We retrospectively reviewed 210 LD-SCLC patients who were treated with first-line treatment at Seoul National University Hospital between April 1999 and November 2012. Compared with in...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2013.09.003
更新日期:2014-03-01 00:00:00
abstract::The absolute number of patients with lung cancer is rising as a result of our aging population. Until recently, clinicians have been reluctant to aggressively treat elderly patients with non-small-cell lung cancer (NSCLC) because of a lack of supportive data and concern for potential toxicity. Recently, evidence has e...
journal_title:Clinical lung cancer
pub_type: 杂志文章,评审
doi:10.3816/CLC.2005.n.031
更新日期:2005-11-01 00:00:00
abstract:BACKGROUND:We evaluated the tolerability and efficacy of nimotuzumab, a humanized IgG1 monoclonal anti-epidermal growth factor receptor antibody, with concurrent chemoradiotherapy in patients with unresectable locally advanced non-small-cell lung cancer. PATIENTS AND METHODS:In this multicenter, single-arm, open-label...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2020.12.012
更新日期:2020-12-26 00:00:00
abstract:BACKGROUND:Several studies have assessed the expression of programmed death-ligand 1 (PD-L1) in resected surgical specimens of non-small-cell lung cancer (NSCLC). However, the expression of PD-L1 in smaller biopsy samples of advanced NSCLC has not been reported. PATIENTS AND METHODS:A total of 79 patients with NSCLC a...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2015.03.008
更新日期:2015-09-01 00:00:00
abstract:OBJECTIVE:Uncertainty exists regarding the optimal surveillance imaging schedule following definitive chemoradiation (CRT) for locally advanced non-small-cell lung cancer (LA-NSCLC) with regards to both frequency and modality. We sought to document the clinical impact of frequent (at least every 4 months) surveillance ...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2016.11.010
更新日期:2017-07-01 00:00:00
abstract::Viruses capable of inducing lysis of malignant cells through their replication process are known as "oncolytic" viruses. Clinical trials in oncology have been performed with oncolytic viruses for nearly fifty years. Both systemic and intratumoral routes of administration have been explored. Toxicity has generally been...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/clc.1999.n.003
更新日期:1999-08-01 00:00:00
abstract:BACKGROUND:National costs of lung cancer care exceed $12 billion. We investigate the resource-savings benefit of a single-day thoracic oncology multidisciplinary clinic (MDC) in the diagnostic period prior to non-small-cell lung cancer (NSCLC) treatment. MATERIALS AND METHODS:From July 2007 to January 2015, patients w...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2019.02.010
更新日期:2019-07-01 00:00:00
abstract:INTRODUCTION:Clinical manifestation of non-small-cell lung cancer (NSCLC) mainly occurs at advanced stages. Thus, the scientific community is evaluating different screening programs in high-risk patients to detect NSCLC at an earlier stage to improve survival. However, up to now patient selection and modalities have be...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2015.08.006
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:The primary objective of this study was to evaluate the association between radiation sensitivity of the lungs and candidate single nucleotide polymorphisms (SNP) in genes implicated in radiation-induced toxicity. METHODS:Patients with lung cancer who received radiation therapy (RT) had pre-RT and serial po...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2012.10.006
更新日期:2013-05-01 00:00:00
abstract:BACKGROUND:In advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients whose disease has progressed during treatment with first- and second-generation tyrosine kinase inhibitors (TKIs), liquid biopsy (LB) is routinely used to evaluate the presence of EGFR T790M as an acquired...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2020.02.021
更新日期:2020-09-01 00:00:00
abstract::Lung cancer remains the number one cause of cancer-based mortality in men and women. The importance of proper lung cancer care outside of major academic centers cannot be overemphasized because the vast majority of lung cancer care occurs in community hospital settings. We have had the opportunity to develop a highly ...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/CLC.2009.n.032
更新日期:2009-07-01 00:00:00
abstract::Epidermal growth factor receptor (EGFR) inhibitors are associated with unique and dramatic dermatologic side effects. Skin rash is the dose-limiting factor for all EGFR inhibitors and is usually dose related and reversible. Microbiologic stains and cultures from skin rash usually do not show an infectious cause. We re...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/CLC.2008.n.010
更新日期:2008-01-01 00:00:00
abstract::Lung cancer is the leading cause of cancer deaths worldwide, with the majority of patients presenting with advanced disease. Despite the introduction of newer therapeutic agents and modest survival improvement, the overall prognosis for these patients is poor. The goals of therapy should therefore include improvement ...
journal_title:Clinical lung cancer
pub_type: 杂志文章,评审
doi:10.3816/CLC.2003.n.018
更新日期:2003-07-01 00:00:00
abstract:BACKGROUND:It is unclear what proportion of VTE events in lung cancer patients are incidentally discovered and whether incidental events affect mortality. PATIENTS AND METHODS:We conducted a retrospective cohort study of lung cancer patients seen at the University of Rochester between January 1, 2006 and December 31, ...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2013.06.003
更新日期:2013-11-01 00:00:00
abstract:INTRODUCTION:Maintenance therapy is a new treatment paradigm for advanced non-small-cell lung cancer (NSCLC). We conducted a meta-analysis to evaluate its clinical efficacy in NSCLC and compared the efficacy of chemotherapy, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), and other treatment ap...
journal_title:Clinical lung cancer
pub_type: 杂志文章,meta分析
doi:10.1016/j.cllc.2015.01.002
更新日期:2015-09-01 00:00:00
abstract:INTRODUCTION:Pneumonitis is one of the immune-related adverse events of programmed death 1 (PD-1) inhibitors that sometimes cause lethal outcomes. Although some recent reports have described PD-1 inhibitors as more effective in non-small-cell lung cancer (NSCLC) patients with immune-related adverse events than in those...
journal_title:Clinical lung cancer
pub_type: 杂志文章,多中心研究
doi:10.1016/j.cllc.2019.07.006
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND:The programmed death 1/programmed death-ligand 1 (PD-L1) pathway reportedly is as an important factor determining effects of immunotherapy; however, its prognostic impact is controversial, and its association with the surrounding immune microenvironment has not yet been elucidated. PATIENTS AND METHODS:We r...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2020.01.013
更新日期:2020-07-01 00:00:00
abstract:INTRODUCTION:Small-cell lung cancer is an aggressive disease for which the mainstay of treatment is chemotherapy. Despite good initial responses most patients will relapse. Some will receive second-line therapy with clinical benefit, but for third-line chemotherapy there is little evidence to guide treatment decisions ...
journal_title:Clinical lung cancer
pub_type: 杂志文章,多中心研究
doi:10.1016/j.cllc.2013.11.003
更新日期:2014-03-01 00:00:00