Lung Cancer Screening: An Update, Discussion, and Look Ahead

Mazzone, Peter J.

doi:10.1007/s11912-010-0111-6

Cited by 9 publications

(6 citation statements)

References 47 publications

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“…Taken together, the serum CAXII levels should be applicable markers discriminating lung cancer patients from healthy controls. Currently, CT scan or chest X-ray is the main method of lung cancer screening [21]. Mazzone et al suggested that blood and breath tests should also be included for lung cancer screening, because they are both easy to perform and free of risks related to test administration [21], [22].…”

Section: Discussionmentioning

confidence: 99%

“…Currently, CT scan or chest X-ray is the main method of lung cancer screening [21]. Mazzone et al suggested that blood and breath tests should also be included for lung cancer screening, because they are both easy to perform and free of risks related to test administration [21], [22]. In this study, we analyzed CAXII levels in sera from lung cancer patients and healthy controls using monoclonal antibody, and our results suggested that the serum CAXII level was a useful sero-diagnostic marker for lung cancer.…”

Section: Discussionmentioning

confidence: 99%

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CAXII Is a Sero-Diagnostic Marker for Lung Cancer

et al. 2012

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To develop sero-diagnostic markers for lung cancer, we generated monoclonal antibodies using pulmonary adenocarcinoma (AD)-derived A549 cells as antigens by employing the random immunization method. Hybridoma supernatants were immunohistochemically screened for antibodies with AMeX-fixed and paraffin-embedded A549 cell preparations. Positive clones were monocloned twice through limiting dilutions. From the obtained monoclonal antibodies, we selected an antibody designated as KU-Lu-5 which showed intense membrane staining of A549 cells. Based on immunoprecipitation and MADLI TOF/TOF-MS analysis, this antibody was recognized as carbonic anhydrase XII (CAXII). To evaluate the utility of this antibody as a sero-diagnostic marker for lung cancer, we performed dot blot analysis with a training set consisting of sera from 70 lung cancer patients and 30 healthy controls. The CAXII expression levels were significantly higher in lung cancer patients than in healthy controls in the training set (P<0.0001), and the area under the curve of ROC was 0.794, with 70.0% specificity and 82.9% sensitivity. In lung cancers, expression levels of CAXII were significantly higher in patients with squamous cell carcinoma (SCC) than with AD (P = 0.035). Furthermore, CAXII was significantly higher in well- and moderately differentiated SCCs than in poorly differentiated ones (P = 0.027). To further confirm the utility of serum CAXII levels as a sero-diagnostic marker, an additional set consisting of sera from 26 lung cancer patients and 30 healthy controls was also investigated by dot blot analysis as a validation study. Serum CAXII levels were also significantly higher in lung cancer patients than in healthy controls in the validation set (P = 0.030). Thus, the serum CAXII levels should be applicable markers discriminating lung cancer patients from healthy controls. To our knowledge, this is the first report providing evidence that CAXII may be a novel sero-diagnostic marker for lung cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CAXII Is a Sero-Diagnostic Marker for Lung Cancer

et al. 2012

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“…Although repeated scans for the purpose of detecting early stage lung cancer would likely be conducted at lower doses, these scans would likely be coupled to higher-dose diagnostic scans if a lesion were found [51]. In addition, more than 90% of pulmonary nodules observed by CT scan are found to be benign after a biopsy [63]. Transthoracic needle biopsies also carry an additional risk.…”

Section: Implications For Clinical Practicementioning

confidence: 99%

Discovery of BRM Promoter Polymorphisms: Importance in Risk Stratification and Clinical Application

Journal¹,

Marquez²

2014

PDJ

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Lung cancer is the most common cause of all cancer deaths in the United States and worldwide. Despite advances in surgical techniques and therapies, the cure rates for lung cancer have not changed in the last thirty years. Lung cancer typically presents in the advanced stages when the cancer has already spread beyond the chest wall. Therefore, a goal of clinicians is to treat these patients while their lung cancers are at an earlier stage. The screening of smokers and former smokers by computed tomography (CT) is usually the recommended approach in order to detect early-stage lung cancer. However, given that only a small percentage of smokers will get lung cancer, researchers have sought to determine the causes of lung cancer other than tobacco exposure. Throughout the past decade, investigators have attempted to find suitable biomarkers to determine cancer risk so that individuals can be risk-stratified prior to screening. This process would target a much more specific at-risk population and would minimize the risks of CT and other diagnostic modalities in those individuals who are not at the highest risk. The polymorphisms in the promoter of the Brahma (BRM) gene are two candidate biomarkers that have been associated with loss of the tumor susceptibility protein BRM, which in turn is correlated with an increase in cancer risk. Much progress has been made since the initial discovery of these polymorphisms in 2011, and the aim of this commentary is to review the discovery of the BRM polymorphisms and to discuss their pertinence to clinical practice.

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“…Controlled trials of chest x-ray based imaging showed improved survival but not reduced mortality [2]. CT cohort studies showed promising survival data but their design did not allow a mortality outcome to be assessed [3], [4]. These studies also highlighted issues with CT based screening, including the high number of benign lung nodules found requiring additional testing, the potential long-term risk of radiation from CT imaging, and the uncertain cost-effectiveness of a CT based screening program [3]–[5].…”

Section: Introductionmentioning

confidence: 99%

Lung Cancer Screening with Computer Aided Detection Chest Radiography: Design and Results of a Randomized, Controlled Trial

et al. 2013

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IntroductionThe sensitivity of CT based lung cancer screening for the detection of early lung cancer is balanced by the high number of benign lung nodules identified, the unknown consequences of radiation from the test, and the potential costs of a CT based screening program. CAD chest radiography may improve the sensitivity of standard chest radiography while minimizing the risks of CT based screening.MethodsStudy subjects were age 40–75 years with 10+ pack-years of smoking and/or an additional risk for developing lung cancer. Subjects were randomized to receive a PA view chest radiograph or placebo control (went through the process of being imaged but were not imaged). Images were reviewed first without then with the assistance of CAD. Actionable nodules were reported and additional evaluation was tracked. The primary outcome was the rate of developing symptomatic advanced stage lung cancer.Results1,424 subjects were enrolled. 710 received a CAD chest radiograph, 29 of whom were found to have an actionable lung nodule on prevalence screening. Of the 15 subjects who had a chest CT performed for additional evaluation, a lung nodule was confirmed in 4, 2 of which represented lung cancer. Both of the cancers were seen by the radiologist unaided and were identified by the CAD chest radiograph. The cumulative incidence of symptomatic advanced lung cancer was 0.42 cases per 100 person-years in the control arm; there were no events in the screening arm.ConclusionsFurther evaluation is necessary to determine if CAD chest radiography has a role as a lung cancer screening tool.ClinicalTrials.gov identifier NCT01663155

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Lung Cancer Screening: An Update, Discussion, and Look Ahead

Cited by 9 publications

References 47 publications

CAXII Is a Sero-Diagnostic Marker for Lung Cancer

CAXII Is a Sero-Diagnostic Marker for Lung Cancer

Discovery of BRM Promoter Polymorphisms: Importance in Risk Stratification and Clinical Application

Lung Cancer Screening with Computer Aided Detection Chest Radiography: Design and Results of a Randomized, Controlled Trial

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