Liquid biopsy for early detection of lung cancer.

PubMed

Hofman, Paul

2017-01-01

The possibility of complete recovery for a lung cancer patient depends on very early diagnosis, as it allows total surgical resection. Screening for this cancer in a high-risk population can be performed using a radiological approach, but this holds a certain number of limitations. Liquid biopsy could become an alternative and complementary screening approach to chest imaging for early diagnosis of lung cancer. Several circulating biomarkers indicative of lung cancer can be investigated in blood, such as circulating tumor cells, circulating free nucleic acids (RNA and DNA) and proteins. However, none of these biomarkers have yet been adopted in routine clinical practice and studies are ongoing to confirm or not the usefulness and practical interest in routine early diagnosis and screening for lung cancers. Several potential circulating biomarkers for the early detection of lung cancer exist. When coupled to thoracic imaging, these biomarkers must give diagnosis of a totally resectable lung cancer and potentially provide new recommendations for surveillance by imagery of high-risk populations without a detectable nodule. Optimization of the specificity and sensitivity of the detection methods as well as standardization of the techniques is essential before considering for daily practice a liquid biopsy as an early diagnostic tool, or possibly as a predictive test, of lung cancer.

Mig6 Puts the Brakes on Mutant EGFR-Driven Lung Cancer | Center for Cancer Research

Cancer.gov

Lung cancer is the most common cause of cancer-related death worldwide. These cancers are often induced by mutations in the epidermal growth factor receptor (EGFR), resulting in constitutive activation of the protein’s tyrosine kinase domain. Lung cancers expressing these EGFR mutants are initially sensitive to tyrosine kinase inhibitors (TKIs), such as erlotinib, but often

Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach

DTIC Science & Technology

2016-03-01

Award Number: W81XWH-12-1-0323 TITLE: Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach PRINCIPAL...SUBTITLE Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...increasing its sensitivity and specificity through nanotechnology . Hypothesis: Detection of DNA methylation from individuals with cancer can be used to

Lung Cancer

MedlinePlus

Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most lung cancers. The more cigarettes you smoke per day and ...

RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer

PubMed Central

Rao, Shuan; Sigl, Verena; Wimmer, Reiner Alois; Novatchkova, Maria; Jais, Alexander; Wagner, Gabriel; Handschuh, Stephan; Uribesalgo, Iris; Hagelkruys, Astrid; Kozieradzki, Ivona; Tortola, Luigi; Nitsch, Roberto; Cronin, Shane J.; Orthofer, Michael; Branstetter, Daniel; Canon, Jude; Rossi, John; D'Arcangelo, Manolo; Botling, Johan; Micke, Patrick; Fleur, Linnea La; Edlund, Karolina; Bergqvist, Michael; Ekman, Simon; Lendl, Thomas; Popper, Helmut; Takayanagi, Hiroshi; Kenner, Lukas; Hirsch, Fred R.; Dougall, William

2017-01-01

Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRasG12D in mouse lung epithelial cells markedly impairs the progression of KRasG12D-driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRasG12D-driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer. PMID:29118048

RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer.

PubMed

Rao, Shuan; Sigl, Verena; Wimmer, Reiner Alois; Novatchkova, Maria; Jais, Alexander; Wagner, Gabriel; Handschuh, Stephan; Uribesalgo, Iris; Hagelkruys, Astrid; Kozieradzki, Ivona; Tortola, Luigi; Nitsch, Roberto; Cronin, Shane J; Orthofer, Michael; Branstetter, Daniel; Canon, Jude; Rossi, John; D'Arcangelo, Manolo; Botling, Johan; Micke, Patrick; Fleur, Linnea La; Edlund, Karolina; Bergqvist, Michael; Ekman, Simon; Lendl, Thomas; Popper, Helmut; Takayanagi, Hiroshi; Kenner, Lukas; Hirsch, Fred R; Dougall, William; Penninger, Josef M

2017-10-15

Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRas G12D in mouse lung epithelial cells markedly impairs the progression of KRas G12D -driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRas G12D -driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer. © 2017 Rao et al.; Published by Cold Spring Harbor Laboratory Press.

Epidemiology of Lung Cancer

PubMed Central

Brock, Malcolm V.; Ford, Jean G.; Samet, Jonathan M.; Spivack, Simon D.

2013-01-01

Background: Ever since a lung cancer epidemic emerged in the mid-1900s, the epidemiology of lung cancer has been intensively investigated to characterize its causes and patterns of occurrence. This report summarizes the key findings of this research. Methods: A detailed literature search provided the basis for a narrative review, identifying and summarizing key reports on population patterns and factors that affect lung cancer risk. Results: Established environmental risk factors for lung cancer include smoking cigarettes and other tobacco products and exposure to secondhand tobacco smoke, occupational lung carcinogens, radiation, and indoor and outdoor air pollution. Cigarette smoking is the predominant cause of lung cancer and the leading worldwide cause of cancer death. Smoking prevalence in developing nations has increased, starting new lung cancer epidemics in these nations. A positive family history and acquired lung disease are examples of host factors that are clinically useful risk indicators. Risk prediction models based on lung cancer risk factors have been developed, but further refinement is needed to provide clinically useful risk stratification. Promising biomarkers of lung cancer risk and early detection have been identified, but none are ready for broad clinical application. Conclusions: Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world. Further research is needed into the reasons underlying lung cancer disparities, the causes of lung cancer in never smokers, the potential role of HIV in lung carcinogenesis, and the development of biomarkers. PMID:23649439

Lung cancer - small cell

MedlinePlus

Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

Blinded Validation of Breath Biomarkers of Lung Cancer, a Potential Ancillary to Chest CT Screening

PubMed Central

Phillips, Michael; Bauer, Thomas L.; Cataneo, Renee N.; Lebauer, Cassie; Mundada, Mayur; Pass, Harvey I.; Ramakrishna, Naren; Rom, William N.; Vallières, Eric

2015-01-01

Background Breath volatile organic compounds (VOCs) have been reported as biomarkers of lung cancer, but it is not known if biomarkers identified in one group can identify disease in a separate independent cohort. Also, it is not known if combining breath biomarkers with chest CT has the potential to improve the sensitivity and specificity of lung cancer screening. Methods Model-building phase (unblinded): Breath VOCs were analyzed with gas chromatography mass spectrometry in 82 asymptomatic smokers having screening chest CT, 84 symptomatic high-risk subjects with a tissue diagnosis, 100 without a tissue diagnosis, and 35 healthy subjects. Multiple Monte Carlo simulations identified breath VOC mass ions with greater than random diagnostic accuracy for lung cancer, and these were combined in a multivariate predictive algorithm. Model-testing phase (blinded validation): We analyzed breath VOCs in an independent cohort of similar subjects (n = 70, 51, 75 and 19 respectively). The algorithm predicted discriminant function (DF) values in blinded replicate breath VOC samples analyzed independently at two laboratories (A and B). Outcome modeling: We modeled the expected effects of combining breath biomarkers with chest CT on the sensitivity and specificity of lung cancer screening. Results Unblinded model-building phase. The algorithm identified lung cancer with sensitivity 74.0%, specificity 70.7% and C-statistic 0.78. Blinded model-testing phase: The algorithm identified lung cancer at Laboratory A with sensitivity 68.0%, specificity 68.4%, C-statistic 0.71; and at Laboratory B with sensitivity 70.1%, specificity 68.0%, C-statistic 0.70, with linear correlation between replicates (r = 0.88). In a projected outcome model, breath biomarkers increased the sensitivity, specificity, and positive and negative predictive values of chest CT for lung cancer when the tests were combined in series or parallel. Conclusions Breath VOC mass ion biomarkers identified lung cancer in a

Intersections of lung progenitor cells, lung disease and lung cancer.

PubMed

Kim, Carla F

2017-06-30

The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials. Copyright ©ERS 2017.

Caveolin-1 sensitizes cisplatin-induced lung cancer cell apoptosis via superoxide anion-dependent mechanism.

PubMed

Pongjit, Kanittha; Chanvorachote, Pithi

2011-12-01

Caveolin-1 (Cav-1) expression frequently found in lung cancer was linked with disease prognosis and progression. This study reveals for the first time that Cav-1 sensitizes cisplatin-induced lung carcinoma cell death by the mechanism involving oxidative stress modulation. We established stable Cav-1 overexpressed (H460/Cav-1) cells and investigated their cisplatin susceptibility in comparison with control-transfected cells and found that Cav-1 expression significantly enhanced cisplatin-mediated cell death. Results indicated that the different response to cisplatin between these cells was resulted from different level of superoxide anion induced by cisplatin. Inhibitory study revealed that superoxide anion inhibitor MnTBAP could inhibit cisplatin-mediated toxicity only in H460/Cav-1 cells while had no effect on H460 cells. Further, superoxide anion detected by DHE probe indicated that H460/Cav-1 cells generated significantly higher superoxide anion level in response to cisplatin than that of control cells. The role of Cav-1 in regulating cisplatin sensitivity was confirmed in shRNA-mediated Cav-1 down-regulated (H460/shCav-1) cells and the cells exhibited decreased cisplatin susceptibility and superoxide generation. In summary, these findings reveal novel aspects regarding role of Cav-1 in modulating oxidative stress induced by cisplatin, possibly providing new insights for cancer biology and cisplatin-based chemotherapy.

Using a chemiresistor-based alkane sensor to distinguish exhaled breaths of lung cancer patients from subjects with no lung cancer.

PubMed

Tan, Jiunn-Liang; Yong, Zheng-Xin; Liam, Chong-Kin

2016-10-01

Breath alkanes are reported to be able to discriminate lung cancer patients from healthy people. A simple chemiresistor-based sensor was designed to respond to alkanes by a change in resistance measured by a digital multimeter connected to the sensor. In preclinical experiments, the sensor response was found to have a strong positive linear relationship with alkane compounds and not responsive to water. This study aimed to determine the ability of the alkane sensor to distinguish the exhaled breaths of lung cancer patients from that of chronic obstructive pulmonary disease (COPD) patients and control subjects without lung cancer. In this cross-sectional study, 12 treatment-naive patients with lung cancer, 12 ex- or current smokers with COPD and 13 never-smokers without lung disease were asked to exhale through a drinking straw into a prototype breath-in apparatus made from an empty 125 mL Vitagen ® bottle with the chemiresistor sensor attached at its inside bottom to measure the sensor peak output (percentage change of baseline resistance measured before exhalation to peak resistance) and the time taken for the baseline resistance to reach peak resistance. Analysis of multivariate variance and post-hoc Tukey test revealed that the peak output and the time to peak values for the lung cancer patients were statistically different from that for both the COPD patients and the controls without lung disease, Pillai's Trace =0.393, F=3.909, df = (4, 64), P=0.007. A 2.20% sensor peak output and a 90-s time to peak gave 83.3% sensitivity and 88% specificity in diagnosing lung cancer. Tobacco smoking did not affect the diagnostic accuracy of the sensor. The alkane sensor could discriminate patients with lung cancer from COPD patients and people without lung disease. Its potential utility as a simple, cheap and non-invasive test for early lung cancer detection needs further studies.

LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition.

PubMed

Mahoney, C L; Choudhury, B; Davies, H; Edkins, S; Greenman, C; Haaften, G van; Mironenko, T; Santarius, T; Stevens, C; Stratton, M R; Futreal, P A

2009-01-27

LKB1/STK11 is a multitasking tumour suppressor kinase. Germline inactivating mutations of the gene are responsible for the Peutz-Jeghers hereditary cancer syndrome. It is also somatically inactivated in approximately 30% of non-small-cell lung cancer (NSCLC). Here, we report that LKB1/KRAS mutant NSCLC cell lines are sensitive to the MEK inhibitor CI-1040 shown by a dose-dependent reduction in proliferation rate, whereas LKB1 and KRAS mutations alone do not confer similar sensitivity. We show that this subset of NSCLC is also sensitised to the mTOR inhibitor rapamycin. Importantly, the data suggest that LKB1/KRAS mutant NSCLCs are a genetically and functionally distinct subset and further suggest that this subset of lung cancers might afford an opportunity for exploitation of anti-MAPK/mTOR-targeted therapies.

Staging of Lung Cancer

MedlinePlus

... LUNG CANCER MINI-SERIES #2 Staging of Lung Cancer Once your lung cancer is diagnosed, staging tells you and your health care provider about ... at it under a microscope. The stages of lung cancer are listed as I, II, III, and IV ...

Anti-Podocalyxin Monoclonal Antibody 47-mG2a Detects Lung Cancers by Immunohistochemistry.

PubMed

Yamada, Shinji; Itai, Shunsuke; Kaneko, Mika K; Kato, Yukinari

2018-04-01

Lung cancer is one of the leading causes of cancer-related deaths in the world. Regardless of the advances in lung cancer treatments, the prognosis is still poor. Podocalyxin (PODXL) is a highly glycosylated type I transmembrane protein that is expressed in normal tissues, including the heart, pancreas, and breast. It is also found and used as a diagnostic marker in many cancers, such as renal, brain, breast, oral, and lung cancers. We previously developed specific and sensitive anti-PODXL monoclonal antibodies, PcMab-47 (mouse IgG 1 , kappa) and its mouse IgG 2a -type (47-mG 2a ), both of which were suitable for immunohistochemical analyses of oral cancers. In this study, we investigated the utility of PcMab-47 and 47-mG 2a for the immunohistochemical analyses of lung cancers. PcMab-47 stained 51/70 (72.9%) cases of lung cancer, whereas 47-mG 2a stained 59/70 (84.3%) cases, indicating that the latter antibody is more sensitive and is useful for detecting PODXL in lung cancers.

Epidemiology of Lung Cancer.

PubMed

Schwartz, Ann G; Cote, Michele L

2016-01-01

Lung cancer continues to be one of the most common causes of cancer death despite understanding the major cause of the disease: cigarette smoking. Smoking increases lung cancer risk 5- to 10-fold with a clear dose-response relationship. Exposure to environmental tobacco smoke among nonsmokers increases lung cancer risk about 20%. Risks for marijuana and hookah use, and the new e-cigarettes, are yet to be consistently defined and will be important areas for continued research as use of these products increases. Other known environmental risk factors include exposures to radon, asbestos, diesel, and ionizing radiation. Host factors have also been associated with lung cancer risk, including family history of lung cancer, history of chronic obstructive pulmonary disease and infections. Studies to identify genes associated with lung cancer susceptibility have consistently identified chromosomal regions on 15q25, 6p21 and 5p15 associated with lung cancer risk. Risk prediction models for lung cancer typically include age, sex, cigarette smoking intensity and/or duration, medical history, and occupational exposures, however there is not yet a risk prediction model currently recommended for general use. As lung cancer screening becomes more widespread, a validated model will be needed to better define risk groups to inform screening guidelines.

Molecular Imaging and Precision Medicine in Lung Cancer.

PubMed

Zukotynski, Katherine A; Gerbaudo, Victor H

2017-01-01

Precision medicine allows tailoring of preventive or therapeutic interventions to avoid the expense and toxicity of futile treatment given to those who will not respond. Lung cancer is a heterogeneous disease functionally and morphologically. PET is a sensitive molecular imaging technique with a major role in the precision medicine algorithm of patients with lung cancer. It contributes to the precision medicine of lung neoplasia by interrogating tumor heterogeneity throughout the body. It provides anatomofunctional insight during diagnosis, staging, and restaging of the disease. It is a biomarker of tumoral heterogeneity that helps direct selection of the most appropriate treatment, the prediction of early response to cytotoxic and cytostatic therapies, and is a prognostic biomarker in patients with lung cancer. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

A new biomarker panel in bronchoalveolar lavage for an improved lung cancer diagnosis.

PubMed

Uribarri, María; Hormaeche, Itsaso; Zalacain, Rafael; Lopez-Vivanco, Guillermo; Martinez, Antonio; Nagore, Daniel; Ruiz-Argüello, M Begoña

2014-10-01

The enormous biological complexity and high mortality rate of lung cancer highlights the need for new global approaches for the discovery of reliable early diagnostic biomarkers. The study of bronchoalveolar lavage samples by proteomic techniques could identify new lung cancer biomarkers and may provide promising noninvasive diagnostic tools able to enhance the sensitivity of current methods. First, an observational prospective study was designed to assess protein expression differences in bronchoalveolar lavages from patients with (n = 139) and without (n = 49) lung cancer, using two-dimensional gel electrophoresis and subsequent protein identification by mass spectrometry. Second, validation of candidate biomarkers was performed by bead-based immunoassays with a different patient cohort (204 patients, 48 controls). Thirty-two differentially expressed proteins were identified in bronchoalveolar lavages, 10 of which were confirmed by immunoassays. The expression levels of APOA1, CO4A, CRP, GSTP1, and SAMP led to a lung cancer diagnostic panel that reached 95% sensitivity and 81% specificity, and the quantification of STMN1 and GSTP1 proteins allowed the two main lung cancer subtypes to be discriminated with 90% sensitivity and 57% specificity. Bronchoalveolar lavage represents a promising noninvasive source of lung cancer specific protein biomarkers with high diagnostic accuracy. Measurement of APOA1, CO4A, CRP, GSTP1, SAMP, and STMN1 in this fluid may be a useful tool for lung cancer diagnosis, although a further validation in a larger clinical set is required for early stages.

LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition

PubMed Central

Mahoney, C L; Choudhury, B; Davies, H; Edkins, S; Greenman, C; Haaften, G van; Mironenko, T; Santarius, T; Stevens, C; Stratton, M R; Futreal, P A

2009-01-01

LKB1/STK11 is a multitasking tumour suppressor kinase. Germline inactivating mutations of the gene are responsible for the Peutz-Jeghers hereditary cancer syndrome. It is also somatically inactivated in approximately 30% of non-small-cell lung cancer (NSCLC). Here, we report that LKB1/KRAS mutant NSCLC cell lines are sensitive to the MEK inhibitor CI-1040 shown by a dose-dependent reduction in proliferation rate, whereas LKB1 and KRAS mutations alone do not confer similar sensitivity. We show that this subset of NSCLC is also sensitised to the mTOR inhibitor rapamycin. Importantly, the data suggest that LKB1/KRAS mutant NSCLCs are a genetically and functionally distinct subset and further suggest that this subset of lung cancers might afford an opportunity for exploitation of anti-MAPK/mTOR-targeted therapies. PMID:19165201

Interplay between the lung microbiome and lung cancer.

PubMed

Mao, Qixing; Jiang, Feng; Yin, Rong; Wang, Jie; Xia, Wenjie; Dong, Gaochao; Ma, Weidong; Yang, Yao; Xu, Lin; Hu, Jianzhong

2018-02-28

The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. Emerging evidence has suggested that dysbiosis of the microbiota may also play vital roles in carcinogenesis at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. Although the impact of the gut microbiome on the digestive cancer has been widely explored, few studies have investigated the interplay between the microbiome and lung cancer. Some recent studies have shown that certain microbes and microbiota dysbiosis are correlated with development of lung cancer. In this mini-review, we briefly summarize current research findings describing the relationship between the lung microbiome and lung cancer. We further discuss the potential mechanisms through which the lung microbiome may play a role in lung carcinogenesis and impact lung cancer treatment. A better knowledge of the interplay between the lung microbiome and lung cancer may promote the development of innovative strategies for early prevention and personalized treatment in lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Risk prediction models for selection of lung cancer screening candidates: A retrospective validation study

PubMed Central

ten Haaf, Kevin; Tammemägi, Martin C.; Han, Summer S.; Kong, Chung Yin; Plevritis, Sylvia K.; de Koning, Harry J.; Steyerberg, Ewout W.

2017-01-01

Background Selection of candidates for lung cancer screening based on individual risk has been proposed as an alternative to criteria based on age and cumulative smoking exposure (pack-years). Nine previously established risk models were assessed for their ability to identify those most likely to develop or die from lung cancer. All models considered age and various aspects of smoking exposure (smoking status, smoking duration, cigarettes per day, pack-years smoked, time since smoking cessation) as risk predictors. In addition, some models considered factors such as gender, race, ethnicity, education, body mass index, chronic obstructive pulmonary disease, emphysema, personal history of cancer, personal history of pneumonia, and family history of lung cancer. Methods and findings Retrospective analyses were performed on 53,452 National Lung Screening Trial (NLST) participants (1,925 lung cancer cases and 884 lung cancer deaths) and 80,672 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) ever-smoking participants (1,463 lung cancer cases and 915 lung cancer deaths). Six-year lung cancer incidence and mortality risk predictions were assessed for (1) calibration (graphically) by comparing the agreement between the predicted and the observed risks, (2) discrimination (area under the receiver operating characteristic curve [AUC]) between individuals with and without lung cancer (death), and (3) clinical usefulness (net benefit in decision curve analysis) by identifying risk thresholds at which applying risk-based eligibility would improve lung cancer screening efficacy. To further assess performance, risk model sensitivities and specificities in the PLCO were compared to those based on the NLST eligibility criteria. Calibration was satisfactory, but discrimination ranged widely (AUCs from 0.61 to 0.81). The models outperformed the NLST eligibility criteria over a substantial range of risk thresholds in decision curve analysis, with a higher

DNA repair deficiency sensitizes lung cancer cells to NAD+ biosynthesis blockade.

PubMed

Touat, Mehdi; Sourisseau, Tony; Dorvault, Nicolas; Chabanon, Roman M; Garrido, Marlène; Morel, Daphné; Krastev, Dragomir B; Bigot, Ludovic; Adam, Julien; Frankum, Jessica R; Durand, Sylvère; Pontoizeau, Clement; Souquère, Sylvie; Kuo, Mei-Shiue; Sauvaigo, Sylvie; Mardakheh, Faraz; Sarasin, Alain; Olaussen, Ken A; Friboulet, Luc; Bouillaud, Frédéric; Pierron, Gérard; Ashworth, Alan; Lombès, Anne; Lord, Christopher J; Soria, Jean-Charles; Postel-Vinay, Sophie

2018-04-02

Synthetic lethality is an efficient mechanism-based approach to selectively target DNA repair defects. Excision repair cross-complementation group 1 (ERCC1) deficiency is frequently found in non-small-cell lung cancer (NSCLC), making this DNA repair protein an attractive target for exploiting synthetic lethal approaches in the disease. Using unbiased proteomic and metabolic high-throughput profiling on a unique in-house-generated isogenic model of ERCC1 deficiency, we found marked metabolic rewiring of ERCC1-deficient populations, including decreased levels of the metabolite NAD+ and reduced expression of the rate-limiting NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT). We also found reduced NAMPT expression in NSCLC samples with low levels of ERCC1. These metabolic alterations were a primary effect of ERCC1 deficiency, and caused selective exquisite sensitivity to small-molecule NAMPT inhibitors, both in vitro - ERCC1-deficient cells being approximately 1,000 times more sensitive than ERCC1-WT cells - and in vivo. Using transmission electronic microscopy and functional metabolic studies, we found that ERCC1-deficient cells harbor mitochondrial defects. We propose a model where NAD+ acts as a regulator of ERCC1-deficient NSCLC cell fitness. These findings open therapeutic opportunities that exploit a yet-undescribed nuclear-mitochondrial synthetic lethal relationship in NSCLC models, and highlight the potential for targeting DNA repair/metabolic crosstalks for cancer therapy.

American Cancer Society lung cancer screening guidelines.

PubMed

Wender, Richard; Fontham, Elizabeth T H; Barrera, Ermilo; Colditz, Graham A; Church, Timothy R; Ettinger, David S; Etzioni, Ruth; Flowers, Christopher R; Gazelle, G Scott; Kelsey, Douglas K; LaMonte, Samuel J; Michaelson, James S; Oeffinger, Kevin C; Shih, Ya-Chen Tina; Sullivan, Daniel C; Travis, William; Walter, Louise; Wolf, Andrew M D; Brawley, Otis W; Smith, Robert A

2013-01-01

Findings from the National Cancer Institute's National Lung Screening Trial established that lung cancer mortality in specific high-risk groups can be reduced by annual screening with low-dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30-pack-year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision-making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with low-dose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation. Copyright © 2013 American Cancer Society, Inc.

Gene Environment Interactions in Women With Breast and Secondary Lung Cancer

DTIC Science & Technology

2005-07-01

information that may be useful in defining subpopulations sensitive to radiation therapy . 15. SUBJECT TERMS Breast cancer, lung cancer, secondary...risk levels to women choosing a breast cancer therapy . Additionally, this research may provide new data on the susceptibilities of women with...secondary lung cancer risk that increased 2-3 fold for nonsmokers and 30 fold in smokers who receive radiation therapy (4,5). Overall, radiotherapy

Overexpression of TRIM25 in Lung Cancer Regulates Tumor Cell Progression.

PubMed

Qin, Ying; Cui, He; Zhang, Hua

2016-10-01

Lung cancer is one of the most common causes of cancer-related deaths worldwide. Although great efforts and progressions have been made in the study of the lung cancer in the recent decades, the mechanism of lung cancer formation remains elusive. To establish effective therapeutic methods, new targets implied in lung cancer processes have to be identified. Tripartite motif-containing 25 has been associated with ovarian and breast cancer and is thought to positively promote cell growth by targeting the cell cycle. However, whether tripartite motif-containing 25 has a function in lung cancer development remains unknown. In this study, we found that tripartite motif-containing 25 was overexpressed in human lung cancer tissues. Expression of tripartite motif-containing 25 in lung cancer cells is important for cell proliferation and migration. Knockdown of tripartite motif-containing 25 markedly reduced proliferation of lung cancer cells both in vitro and in vivo and reduced migration of lung cancer cells in vitro Meanwhile, tripartite motif-containing 25 silencing also increased the sensitivity of doxorubicin and significantly increased death and apoptosis of lung cancer cells by doxorubicin were achieved with knockdown of tripartite motif-containing 25. We also observed that tripartite motif-containing 25 formed a complex with p53 and mouse double minute 2 homolog (MDM2) in both human lung cancer tissues and in lung cancer cells and tripartite motif-containing 25 silencing increased the expression of p53. These results provide evidence that tripartite motif-containing 25 contributes to the pathogenesis of lung cancer probably by promoting proliferation and migration of lung cancer cells. Therefore, targeting tripartite motif-containing 25 may provide a potential therapeutic intervention for lung cancer. © The Author(s) 2015.

CUL4A overexpression enhances lung tumor growth and sensitizes lung cancer cells to Erlotinib via transcriptional regulation of EGFR

DOE PAGES

Wang, Yunshan; Zhang, Pengju; Liu, Ziming; ...

2014-11-21

CUL4A has been proposed as oncogene in several types of human cancer, but its clinical significance and functional role in human non-small cell lung cancer (NSCLC) remain unclear. Expression level of CUL4A was examined by RT-PCR and Western blot. Forced expression of CUL4A was mediated by retroviruses, and CUL4A silencing by shRNAs expressing lentiviruses. Growth capacity of lung cancer cells was measured by MTT in vitro and tumorigenesis in vivo, respectively. We found that CUL4A was highly expressed in human lung cancer tissues and lung cancer cell lines, and this elevated expression positively correlated with disease progression and prognosis. Overexpressionmore » of CUL4A in human lung cancer cell lines increased cell proliferation, inhibited apoptosis, and subsequently conferred resistance to chemotherapy. On other hand, silencing CUL4A expression in NSCLC cells reduced proliferation, promoted apoptosis and resulted in tumor growth inhibition in cancer xenograft model. Mechanistically, we revealed CUL4A regulated EGFR transcriptional expression and activation, and subsequently activated AKT. Targeted inhibition of EGFR activity blocked these CUL4A induced oncogenic activities. In conclusion, our results highlight the significance of CUL4A in NSCLC and suggest that CUL4A could be a promising therapy target and a potential biomarker for prognosis and EGFR target therapy in NSCLC patients.« less

Using a chemiresistor-based alkane sensor to distinguish exhaled breaths of lung cancer patients from subjects with no lung cancer

PubMed Central

Tan, Jiunn-Liang; Yong, Zheng-Xin

2016-01-01

Background Breath alkanes are reported to be able to discriminate lung cancer patients from healthy people. A simple chemiresistor-based sensor was designed to respond to alkanes by a change in resistance measured by a digital multimeter connected to the sensor. In preclinical experiments, the sensor response was found to have a strong positive linear relationship with alkane compounds and not responsive to water. This study aimed to determine the ability of the alkane sensor to distinguish the exhaled breaths of lung cancer patients from that of chronic obstructive pulmonary disease (COPD) patients and control subjects without lung cancer. Methods In this cross-sectional study, 12 treatment-naive patients with lung cancer, 12 ex- or current smokers with COPD and 13 never-smokers without lung disease were asked to exhale through a drinking straw into a prototype breath-in apparatus made from an empty 125 mL Vitagen® bottle with the chemiresistor sensor attached at its inside bottom to measure the sensor peak output (percentage change of baseline resistance measured before exhalation to peak resistance) and the time taken for the baseline resistance to reach peak resistance. Results Analysis of multivariate variance and post-hoc Tukey test revealed that the peak output and the time to peak values for the lung cancer patients were statistically different from that for both the COPD patients and the controls without lung disease, Pillai’s Trace =0.393, F=3.909, df = (4, 64), P=0.007. A 2.20% sensor peak output and a 90-s time to peak gave 83.3% sensitivity and 88% specificity in diagnosing lung cancer. Tobacco smoking did not affect the diagnostic accuracy of the sensor. Conclusions The alkane sensor could discriminate patients with lung cancer from COPD patients and people without lung disease. Its potential utility as a simple, cheap and non-invasive test for early lung cancer detection needs further studies. PMID:27867553

SFK/FAK Signaling Attenuates Osimertinib Efficacy in Both Drug-Sensitive and Drug-Resistant Models of EGFR-Mutant Lung Cancer.

PubMed

Ichihara, Eiki; Westover, David; Meador, Catherine B; Yan, Yingjun; Bauer, Joshua A; Lu, Pengcheng; Ye, Fei; Kulick, Amanda; de Stanchina, Elisa; McEwen, Robert; Ladanyi, Marc; Cross, Darren; Pao, William; Lovly, Christine M

2017-06-01

Mutant-selective EGFR tyrosine kinase inhibitors (TKI), such as osimertinib, are active agents for the treatment of EGFR -mutant lung cancer. Specifically, these agents can overcome the effects of the T790M mutation, which mediates resistance to first- and second-generation EGFR TKI, and recent clinical trials have documented their efficacy in patients with EGFR -mutant lung cancer. Despite promising results, therapeutic efficacy is limited by the development of acquired resistance. Here we report that Src family kinases (SFK) and focal adhesion kinase (FAK) sustain AKT and MAPK pathway signaling under continuous EGFR inhibition in osimertinib-sensitive cells. Inhibiting either the MAPK pathway or the AKT pathway enhanced the effects of osimertinib. Combined SFK/FAK inhibition exhibited the most potent effects on growth inhibition, induction of apoptosis, and delay of acquired resistance. SFK family member YES1 was amplified in osimertinib-resistant EGFR -mutant tumor cells, the effects of which were overcome by combined treatment with osimertinib and SFK inhibitors. In conclusion, our data suggest that the concomitant inhibition of both SFK/FAK and EGFR may be a promising therapeutic strategy for EGFR -mutant lung cancer. Cancer Res; 77(11); 2990-3000. ©2017 AACR . ©2017 American Association for Cancer Research.

Cypripedin, a phenanthrenequinone from Dendrobium densiflorum, sensitizes non-small cell lung cancer H460 cells to cisplatin-mediated apoptosis.

PubMed

Wattanathamsan, Onsurang; Treesuwan, Surassawadee; Sritularak, Boonchoo; Pongrakhananon, Varisa

2018-03-01

The life-threatening potential of lung cancer has increased over the years due to its acquisition of chemotherapeutic resistance, especially to cisplatin, a first-line therapy. In response to this development, researchers have turned their attention to several compounds derived from natural origins, including cypripedin (CYP), a phenanthrenequinone substance extracted from Dendrobium densiflorum. The aim of the present study was to investigate the ability of CYP to induce apoptosis and enhance cisplatin-mediated death of human lung cancer NCI-H460 cells using cell viability and apoptosis assays. The induction of apoptosis by CYP was observed at a concentration of > 50 μM with the appearance of morphological changes, including DNA condensation and chromatin fragmentation. Together with, CYP was able to activate caspase-3 and downregulate the anti-apoptotic proteins Bcl-2 and Bcl-xL. Also, a non-cytotoxic dose of CYP synergistically potentiated the effect of cisplatin in non-small cell lung cancer line H460 cells, which clearly exhibited the apoptotic phenotype. Western blot analysis revealed that the underlying mechanism involved the downregulation of anti-apoptotic Bcl-xL, whereas the levels of other apoptotic regulatory proteins were not altered. This study provides interesting information on the potent effect of CYP as a chemotherapeutic sensitizer that could be further developed to improve the clinical outcomes of lung cancer patients.

American Cancer Society Lung Cancer Screening Guidelines

PubMed Central

Wender, Richard; Fontham, Elizabeth T. H.; Barrera, Ermilo; Colditz, Graham A.; Church, Timothy R.; Ettinger, David S.; Etzioni, Ruth; Flowers, Christopher R.; Gazelle, G. Scott; Kelsey, Douglas K.; LaMonte, Samuel J.; Michaelson, James S.; Oeffinger, Kevin C.; Shih, Ya-Chen Tina; Sullivan, Daniel C.; Travis, William; Walter, Louise; Wolf, Andrew M. D.; Brawley, Otis W.; Smith, Robert A.

2013-01-01

Findings from the National Cancer Institute’s National Lung Screening Trial established that lung cancer mortality in specific high-risk groups can be reduced by annual screening with low-dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30-pack-year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision-making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with low-dose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation. PMID:23315954

Lung cancer in patients with lung transplants.

PubMed

Espinosa, D; Baamonde, C; Illana, J; Arango, E; Carrasco, G; Moreno, P; Algar, F J; Alvarez, A; Cerezo, F; Santos, F; Vaquero, J M; Redel, J; Salvatierra, A

2012-09-01

The aim of our study was to describe the incidence of lung cancer in patients after lung transplantation (LT). We performed an observational, retrospective, descriptive study based on data from 340 patients undergoing lung transplantation between October 1993 and December 2010. We collected data about the donors, recipients, intra- and postoperative periods, and survivals. We identified 9 (2.6%) patients who developed lung cancer after LT. Their average age was 56 ± 9.3 years (range, 18-63). All cases were men with 8/9 (88.8%) having received a single lung transplant. All cancers developed in the native lung. The indications for transplantation were: emphysema type chronic obstructive pulmonary disease (COPD; n = 5), idiopathic pulmonary fibrosis (n = 3), or cystic fibrosis (n = 1); 77% of them were former smokers. All of the COPD patient were affected. The interval from transplantation to diagnosis was 53.3 ± 12 months (range 24-86). Survival after cancer diagnosis was 49.3 ± 6.3 (range = 0-180) months. LT was associated with a relatively high incidence of lung cancer, particularly in the native lung. In our series, lung cancer was related more to patients with emphysema-type COPD and a history of smoking. We believe that these patients should be closely followed to establish the diagnosis and apply early treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

Combination lung cancer chemotherapy: Design of a pH-sensitive transferrin-PEG-Hz-lipid conjugate for the co-delivery of docetaxel and baicalin.

PubMed

Li, Shuang; Wang, Lin; Li, Na; Liu, Yucai; Su, Hui

2017-11-01

The aim of the present study is to design a novel dual-ligand lipid based nanoparticle system. It is conducted by a specific ligand and pH sensitive lipid conjugate. Docetaxel (DTX) and baicalein (BA) are co-delivered by this system for combination lung cancer chemotherapy. Firstly, transferrin (Tf)-polyethylene glycol (PEG)-hydrazone (hz)-glyceryl monostearate (GMS), Tf-PEG-hz-GMS, was synthesized. Tf decorated DTX and BA loaded solid lipid nanoparticles (Tf-D/B-SLNs) were prepared by emulsification method. The capability of Tf-D/B-SLNs in suppressing lung cancer cells in vitro and in vivo was investigated. The results revealed the better antitumor efficiency of Tf-D/B-SLNs than the non-decorated SLNs and single drug loaded SLNs. Significant synergistic effects were observed in the dual drugs loaded systems. The best tumor inhibition ability and the lowest systemic toxicity also proved the pH-sensitive co-delivery nano-system could be a promising strategy for treatment of lung cancer. Copyright © 2017. Published by Elsevier Masson SAS.

Silencing Receptor EphA2 Enhanced Sensitivity to Lipoplatin™ in Lung Tumor and MPM Cells.

PubMed

Lee, Hung-Yen; Mohammed, Kamal A; Goldberg, Eugene P; Kaye, Frederic; Najmunnisa, Nasreen

2016-08-08

Receptor EphA2 is overexpressed in lung cancer and malignant pleural mesothelioma (MPM) which promote tumorogenesis. Lipoplatin™, a new liposomal cisplatin formulation, is used against resistant tumors. Use of cisplatin-based drugs leads to unacceptable toxicities. To improve the effectiveness of Lipoplatin, enhancing the cellular sensitivity of lung tumor and MPM cells is critical. Therefore, we targeted receptor EphA2 by silencing interference RNA (siRNA) and treated tumor cells with Lipoplatin. The combined effects of siRNA-EphA2 and Lipoplatin were determined. We report that silencing EphA2 significantly enhanced the cellular sensitivity of lung tumor and MPM cells to Lipoplatin and maybe a potential therapy for lung cancer.

Training and Validating a Portable Electronic Nose for Lung Cancer Screening.

PubMed

van de Goor, Rens; van Hooren, Michel; Dingemans, Anne-Marie; Kremer, Bernd; Kross, Kenneth

2018-05-01

Profiling volatile organic compounds in exhaled breath enables the diagnosis of several types of cancer. In this study we investigated whether a portable point-of-care version of an electronic nose (e-nose) (Aeonose, [eNose Company, Zutphen, the Netherlands]) is able to discriminate between patients with lung cancer and healthy controls on the basis of their volatile organic compound pattern. In this study, we used five e-nose devices to collect breath samples from patients with lung cancer and healthy controls. A total of 60 patients with lung cancer and 107 controls exhaled through an e-nose for 5 minutes. Patients were assigned either to a training group for building an artificial neural network model or to a blinded control group for validating this model. For differentiating patients with lung cancer from healthy controls, the results showed a diagnostic accuracy of 83% with a sensitivity of 83%, specificity of 84%, and area under the curve of 0.84. Results for the blinded group showed comparable results, with a sensitivity of 88%, specificity of 86%, and diagnostic accuracy of 86%. This feasibility study showed that this portable e-nose can properly differentiate between patients with lung cancer and healthy controls. This result could have important implications for future lung cancer screening. Further studies with larger cohorts, including also more participants with early-stage tumors, should be performed to increase the robustness of this noninvasive diagnostic tool and to determine its added value in the diagnostic chain for lung cancer. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Liquid biopsy for lung cancer early detection.

PubMed

Santarpia, Mariacarmela; Liguori, Alessia; D'Aveni, Alessandro; Karachaliou, Niki; Gonzalez-Cao, Maria; Daffinà, Maria Grazia; Lazzari, Chiara; Altavilla, Giuseppe; Rosell, Rafael

2018-04-01

Molecularly targeted therapies and immune checkpoint inhibitors have markedly improved the therapeutic management of advanced lung cancer. However, it still remains the leading cause of cancer-related mortality worldwide, with disease stage at diagnosis representing the main prognostic factor. Detection of lung cancer at an earlier stage of disease, potentially susceptible of curative resection, can be critical to improve patients survival. Low-dose computed tomography (LDCT) screening of high-risk patients has been demonstrated to reduce mortality from lung cancer, but can be also associated with high false-positive rate, thus often resulting in unnecessary interventions for patients. Novel sensitive and specific biomarkers for identification of high-risk subjects and early detection that can be used alternatively and/or complement current routine diagnostic procedures are needed. Liquid biopsy has recently demonstrated its clinical usefulness in advanced NSCLC as a surrogate of tissue biopsy for noninvasive assessment of specific genomic alterations, thereby providing prognostic and predictive information. Different biosources from liquid biopsy, including cell free circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes and tumor-educated platelets (TEPs), have also been widely investigated for their potential role in lung cancer diagnosis. This review will provide an overview on the circulating biomarkers being evaluated for lung cancer detection, mainly focusing on results from most recent studies, the techniques developed to perform their assessment in blood and other biologic fluids and challenges in their clinical applications.

Liquid biopsy for lung cancer early detection

PubMed Central

Liguori, Alessia; D’Aveni, Alessandro; Karachaliou, Niki; Gonzalez-Cao, Maria; Daffinà, Maria Grazia; Lazzari, Chiara; Altavilla, Giuseppe; Rosell, Rafael

2018-01-01

Molecularly targeted therapies and immune checkpoint inhibitors have markedly improved the therapeutic management of advanced lung cancer. However, it still remains the leading cause of cancer-related mortality worldwide, with disease stage at diagnosis representing the main prognostic factor. Detection of lung cancer at an earlier stage of disease, potentially susceptible of curative resection, can be critical to improve patients survival. Low-dose computed tomography (LDCT) screening of high-risk patients has been demonstrated to reduce mortality from lung cancer, but can be also associated with high false-positive rate, thus often resulting in unnecessary interventions for patients. Novel sensitive and specific biomarkers for identification of high-risk subjects and early detection that can be used alternatively and/or complement current routine diagnostic procedures are needed. Liquid biopsy has recently demonstrated its clinical usefulness in advanced NSCLC as a surrogate of tissue biopsy for noninvasive assessment of specific genomic alterations, thereby providing prognostic and predictive information. Different biosources from liquid biopsy, including cell free circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes and tumor-educated platelets (TEPs), have also been widely investigated for their potential role in lung cancer diagnosis. This review will provide an overview on the circulating biomarkers being evaluated for lung cancer detection, mainly focusing on results from most recent studies, the techniques developed to perform their assessment in blood and other biologic fluids and challenges in their clinical applications. PMID:29780635

Lung cancer-A global perspective.

PubMed

McIntyre, Amanda; Ganti, Apar Kishor

2017-04-01

Lung cancer is the leading cause of cancer deaths worldwide. While tobacco exposure is responsible for the majority of lung cancers, the incidence of lung cancer in never smokers, especially Asian women, is increasing. There is a global variation in lung cancer biology with EGFR mutations being more common in Asian patients, while Kras mutation is more common in Caucasians. This review will focus on the global variations in lung cancer and its treatment. © 2017 Wiley Periodicals, Inc.

Diagnostic Value of Combining Tumor and Inflammatory Markers in Lung Cancer.

PubMed

Yoon, Ho Il; Kwon, Oh-Ran; Kang, Kyung Nam; Shin, Yong Sung; Shin, Ho Sang; Yeon, Eun Hee; Kwon, Keon Young; Hwang, Ilseon; Jeon, Yoon Kyung; Kim, Yongdai; Kim, Chul Woo

2016-09-01

Despite major advances in lung cancer treatment, early detection remains the most promising way of improving outcomes. To detect lung cancer in earlier stages, many serum biomarkers have been tested. Unfortunately, no single biomarker can reliably detect lung cancer. We combined a set of 2 tumor markers and 4 inflammatory or metabolic markers and tried to validate the diagnostic performance in lung cancer. We collected serum samples from 355 lung cancer patients and 590 control subjects and divided them into training and validation datasets. After measuring serum levels of 6 biomarkers (human epididymis secretory protein 4 [HE4], carcinoembryonic antigen [CEA], regulated on activation, normal T cell expressed and secreted [RANTES], apolipoprotein A2 [ApoA2], transthyretin [TTR], and secretory vascular cell adhesion molecule-1 [sVCAM-1]), we tested various sets of biomarkers for their diagnostic performance in lung cancer. In a training dataset, the area under the curve (AUC) values were 0.821 for HE4, 0.753 for CEA, 0.858 for RANTES, 0.867 for ApoA2, 0.830 for TTR, and 0.552 for sVCAM-1. A model using all 6 biomarkers and age yielded an AUC value of 0.986 and sensitivity of 93.2% (cutoff at specificity 94%). Applying this model to the validation dataset showed similar results. The AUC value of the model was 0.988, with sensitivity of 93.33% and specificity of 92.00% at the same cutoff point used in the validation dataset. Analyses by stages and histologic subtypes all yielded similar results. Combining multiple tumor and systemic inflammatory markers proved to be a valid strategy in the diagnosis of lung cancer.

Screening for lung cancer: Does MRI have a role?

PubMed

Biederer, Juergen; Ohno, Yoshiharu; Hatabu, Hiroto; Schiebler, Mark L; van Beek, Edwin J R; Vogel-Claussen, Jens; Kauczor, Hans-Ulrich

2017-01-01

While the inauguration of national low dose computed tomographic (LDCT) lung cancer screening programs has started in the USA, other countries remain undecided, awaiting the results of ongoing trials. The continuous technical development achieved by stronger gradients, parallel imaging and shorter echo time has made lung magnetic resonance imaging (MRI) an interesting alternative to CT. For the detection of solid lesions with lung MRI, experimental and clinical studies have shown a threshold size of 3-4mm for nodules, with detection rates of 60-90% for lesions of 5-8mm and close to 100% for lesions of 8mm or larger. From experimental work, the sensitivity for infiltrative, non-solid lesions would be expected to be similarly high as that for solid lesions, but the published data for the MRI detection of lepidic growth type adenocarcinoma is sparse. Moreover, biological features such as a longer T2 time of lung cancer tissue, tissue compliance and a more rapid uptake of contrast material compared to granulomatous diseases, in principle should allow for the multi-parametric characterization of lung pathology. Experience with the clinical use of lung MRI is growing. There are now standardized protocols which are easy to implement on current scanner hardware configurations. The image quality has become more robust and currently ongoing studies will help to further contribute experience with multi-center, multi-vendor and multi-platform implementation of this technology. All of the required prerequisites have now been achieved to allow for a dedicated prospective large scale MRI based lung cancer screening trial to investigate the outcomes from using MRI rather than CT for lung cancer screening. This is driven by the hypothesis that MRI would reach a similarly high sensitivity for the detection of early lung cancer with fewer false positive exams (better specificity) than LDCT. The purpose of this review article is to discuss the potential role of lung MRI for the early

Lung cancer mimicking lung abscess formation on CT images.

PubMed

Taira, Naohiro; Kawabata, Tsutomu; Gabe, Atsushi; Ichi, Takaharu; Kushi, Kazuaki; Yohena, Tomofumi; Kawasaki, Hidenori; Yamashiro, Toshimitsu; Ishikawa, Kiyoshi

2014-01-01

Male, 64 FINAL DIAGNOSIS: Lung pleomorphic carcinoma Symptoms: Cough • fever - Clinical Procedure: - Specialty: Oncology. Unusual clinical course. The diagnosis of lung cancer is often made based on computed tomography (CT) image findings if it cannot be confirmed on pathological examinations, such as bronchoscopy. However, the CT image findings of cancerous lesions are similar to those of abscesses.We herein report a case of lung cancer that resembled a lung abscess on CT. We herein describe the case of 64-year-old male who was diagnosed with lung cancer using surgery. In this case, it was quite difficult to distinguish between the lung cancer and a lung abscess on CT images, and a lung abscess was initially suspected due to symptoms, such as fever and coughing, contrast-enhanced CT image findings showing a ring-enhancing mass in the right upper lobe and the patient's laboratory test results. However, a pathological diagnosis of lung cancer was confirmed according to the results of a rapid frozen section biopsy of the lesion. This case suggests that physicians should not suspect both a lung abscesses and malignancy in cases involving masses presenting as ring-enhancing lesions on contrast-enhanced CT.

Bronchoscopy in the investigation of outpatients with hemoptysis at a lung cancer clinic.

PubMed

Arooj, Parniya; Bredin, Emily; Henry, Michael T; Khan, Kashif A; Plant, Barry J; Murphy, Desmond M; Kennedy, Marcus P

2018-06-01

In the investigation of lung cancer, current practice in many healthcare systems would support bronchoscopy regardless of CT findings in patients with hemoptysis. We sought to identify the cause, the diagnostic yield of CT and bronchoscopy and the requirement for bronchoscopy in at risk patients with hemoptysis with a normal CT scan through our rapid access lung cancer clinic (RALC). Initially, a chart review was performed on all patients with hemoptysis (2011-2012) and thereafter a prospective analysis was performed (2013-2016). Our analysis represents the largest study to date in outpatients with hemoptysis. In our retrospective study, 155 patients reported hemoptysis. Causes were lower respiratory tract infections (RTIs) (47%) and lung cancer (16%). Our prospective study included 182 patients. The causes of hemoptysis were RTIs (50%) and lung cancer (18%). There were no false negative CT-scans for lung cancer. 47/57 present with lung cancer underwent bronchoscopy and 43/47 were positive for lung cancer (92%). Patients with hemoptysis and lung cancer have a higher stage of malignancy with a predominance of squamous cell lung carcinoma. Smoking status, the duration of hemoptysis or description of hemoptysis were not predictive of lung cancer however lung cancer was not identified in patients age <50. One sixth of patients presenting with hemoptysis to our lung cancer clinic had lung cancer. No patient identified with cancer related haemoptysis had a CT negative for lung cancer and a combination of bronchoscopy plus endobronchial ultrasound trans-bronchial needle aspiration (EBUS-TBNA) in those patients with a CT suspicious of lung cancer is 92% sensitive for lung cancer causing hemoptysis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Increased level of annexin A1 in bronchoalveolar lavage fluid as a potential diagnostic indicator for lung cancer.

PubMed

Biaoxue, Rong; Xiguang, Cai; Hua, Liu; Tian, Fu; Wenlong, Gao

2017-03-02

Annexin A1 has been implicated in various tumor types, but few studies have investigated its involvement in lung cancer. The purpose of this investigation was to quantify the annexin A1 level in bronchoalveolar lavage fluid (BALF) and analyze its usefulness in lung cancer diagnosis. Annexin A1 expression was measured by immunohistochemistry and enzyme immunoassay. The sensitivity and specificity of annexin A1 for distinguishing lung cancer were determined by receiver operator characteristic (ROC) curves. Tumor tissues, BALF and serum of patients with lung cancer contained higher levels of annexin A1 than those of the control group of patients with benign lung diseases. Moreover, an increased level of BALF annexin A1 was closely correlated with lymphatic invasion and malignant progression of lung cancer. The sensitivity and specificity of BALF annexin A1 for distinguishing lung cancer were 94.2% and 90.2%, respectively. Increased annexin A1 in BALF was correlated with lymphatic invasion and malignant progression of lung cancer, suggesting that it could be an indicator for discerning lung cancer and predicting outcome.

Lung Cancer Screening.

PubMed

Hoffman, Richard M; Sanchez, Rolando

2017-07-01

Lung cancer is the leading cause of cancer death in the United States. More than 80% of these deaths are attributed to tobacco use, and primary prevention can effectively reduce the cancer burden. The National Lung Screening Trial showed that low-dose computed tomography (LDCT) screening could reduce lung cancer mortality in high-risk patients by 20% compared with chest radiography. The US Preventive Services Task Force recommends annual LDCT screening for persons aged 55 to 80 years with a 30-pack-year smoking history, either currently smoking or having quit within 15 years. Published by Elsevier Inc.

Lung Cancer and Lung Transplantation.

PubMed

Brand, Timothy; Haithcock, Benjamin

2018-02-01

Lung transplantation remains a viable option for patients with endstage pulmonary disease. Despite removing the affected organ and replacing both lungs, the risk of lung malignancies still exists. Regardless of the mode of entry, lung cancer affects the prognosis in these patients and diligence is required. Copyright © 2017 Elsevier Inc. All rights reserved.

Lung Cancer: Glossary

MedlinePlus

... effects of radiation therapy Randomized Clinical Trial: Trial design in which participants are assigned by chance to ... effect caused by treatment. Small Cell Lung Cancer: One of the two main categories of lung cancer; ...

Stages of Small Cell Lung Cancer

MedlinePlus

... Lung Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key ...

Plasma secretory phospholipase A2-IIa as a potential biomarker for lung cancer in patients with solitary pulmonary nodules

PubMed Central

2011-01-01

Background Five-year survival for lung cancer has remained at 16% over last several decades largely due to the fact that over 50% of patients are diagnosed with locally-advanced or metastatic disease. Diagnosis at an earlier and potentially curable stage is crucial. Solitary pulmonary nodules (SPNs) are common, but the difficulty lies in the determination of which SPN is malignant. Currently, there is no convenient and reliable biomarker effective for early diagnosis. Secretory phospholipase A2-IIa (sPLA2-IIa) is secreted into the circulation by cancer cells and may allow for an early detection of lung cancer. Methods Plasma samples from healthy donors, patients with only benign SPN, and patients with lung cancer were analyzed. Expression of sPLA2-IIa protein in lung cancer tissues was also determined. Results We found that the levels of plasma sPLA2-IIa were significantly elevated in lung cancer patients. The receiver operating characteristic curve analysis, comparing lung cancer patients to patients with benign nodules, revealed an optimum cutoff value for plasma sPLA2-IIa of 2.4 ng/ml to predict an early stage cancer with 48% sensitivity and 86% specificity and up to 67% sensitivity for T2 stage lung cancer. Combined sPLA2-IIa, CEA, and Cyfra21.1 tests increased the sensitivity for lung cancer prediction. High level of plasma sPLA2-IIa was associated with a decreased overall cancer survival. sPLA2-IIa was overexpressed in almost all non-small cell lung cancer and in the majority of small cell lung cancer by immunohistochemistry analysis. Conclusion Our finding strongly suggests that plasma sPLA2-IIa is a potential lung biomarker to distinguish benign nodules from lung cancer and to aid lung cancer diagnosis in patients with SPNs. PMID:22151235

Diagnostic Value of Combining Tumor and Inflammatory Markers in Lung Cancer

PubMed Central

Yoon, Ho Il; Kwon, Oh-Ran; Kang, Kyung Nam; Shin, Yong Sung; Shin, Ho Sang; Yeon, Eun Hee; Kwon, Keon Young; Hwang, Ilseon; Jeon, Yoon Kyung; Kim, Yongdai; Kim, Chul Woo

2016-01-01

Background Despite major advances in lung cancer treatment, early detection remains the most promising way of improving outcomes. To detect lung cancer in earlier stages, many serum biomarkers have been tested. Unfortunately, no single biomarker can reliably detect lung cancer. We combined a set of 2 tumor markers and 4 inflammatory or metabolic markers and tried to validate the diagnostic performance in lung cancer. Methods We collected serum samples from 355 lung cancer patients and 590 control subjects and divided them into training and validation datasets. After measuring serum levels of 6 biomarkers (human epididymis secretory protein 4 [HE4], carcinoembryonic antigen [CEA], regulated on activation, normal T cell expressed and secreted [RANTES], apolipoprotein A2 [ApoA2], transthyretin [TTR], and secretory vascular cell adhesion molecule-1 [sVCAM-1]), we tested various sets of biomarkers for their diagnostic performance in lung cancer. Results In a training dataset, the area under the curve (AUC) values were 0.821 for HE4, 0.753 for CEA, 0.858 for RANTES, 0.867 for ApoA2, 0.830 for TTR, and 0.552 for sVCAM-1. A model using all 6 biomarkers and age yielded an AUC value of 0.986 and sensitivity of 93.2% (cutoff at specificity 94%). Applying this model to the validation dataset showed similar results. The AUC value of the model was 0.988, with sensitivity of 93.33% and specificity of 92.00% at the same cutoff point used in the validation dataset. Analyses by stages and histologic subtypes all yielded similar results. Conclusions Combining multiple tumor and systemic inflammatory markers proved to be a valid strategy in the diagnosis of lung cancer. PMID:27722145

Biodistribution and pharmacokinetics of Mad2 siRNA-loaded EGFR-targeted chitosan nanoparticles in cisplatin sensitive and resistant lung cancer models.

PubMed

Nascimento, Ana Vanessa; Gattacceca, Florence; Singh, Amit; Bousbaa, Hassan; Ferreira, Domingos; Sarmento, Bruno; Amiji, Mansoor M

2016-04-01

The present study focuses on biodistribution profile and pharmacokinetic parameters of EGFR-targeted chitosan nanoparticles (TG CS nanoparticles) for siRNA/cisplatin combination therapy of lung cancer. Mad2 siRNA was encapsulated in EGFR targeted and nontargeted (NTG) CS nanoparticles by electrostatic interaction. The biodistribution of the nanoparticles was assessed qualitatively and quantitatively in cisplatin (DDP) sensitive and resistant lung cancer xenograft model. TG nanoparticles showed a consistent and preferential tumor targeting ability with rapid clearance from the plasma to infiltrate and sustain within the tumor up to 96 h. They exhibit a sixfold higher tumor targeting efficiency compared with the NTG nanoparticles. TG nanoparticles present as an attractive drug delivery platform for RNAi therapeutics against NSCLC.

Adaptive Radiation for Lung Cancer

PubMed Central

Gomez, Daniel R.; Chang, Joe Y.

2011-01-01

The challenges of lung cancer radiotherapy are intra/inter-fraction tumor/organ anatomy/motion changes and the need to spare surrounding critical structures. Evolving radiotherapy technologies, such as four-dimensional (4D) image-based motion management, daily on-board imaging and adaptive radiotherapy based on volumetric images over the course of radiotherapy, have enabled us to deliver higher dose to target while minimizing normal tissue toxicities. The image-guided radiotherapy adapted to changes of motion and anatomy has made the radiotherapy more precise and allowed ablative dose delivered to the target using novel treatment approaches such as intensity-modulated radiation therapy, stereotactic body radiation therapy, and proton therapy in lung cancer, techniques used to be considered very sensitive to motion change. Future clinical trials using real time tracking and biological adaptive radiotherapy based on functional images are proposed. PMID:20814539

Evaluation of diagnostic value of four tumor markers in bronchoalveolar lavage fluid of peripheral lung cancer.

PubMed

Li, Jian; Chen, Ping; Mao, Chao-Ming; Tang, Xing-Ping; Zhu, Li-Rong

2014-06-01

The diagnostic role of carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) antigen, Cyfra 21-1 and neuron-specific enolase (NSE) in the bronchoalveolar lavage fluid (BALF) for lung cancer is still controversial. The aim of this study was to evaluate the diagnostic value of these four tumor markers in BALF for peripheral lung cancer. We measured and compared the levels of CEA, SCC, Cyfra21-1 and NSE in BALF in 42 patients with peripheral lung cancer and 22 patients with benign lung disease. In the patients with peripheral lung cancer, the BAL was separately performed in the bronchus of the tumor-bearing lung and in the corresponding bronchus of the opposite healthy lung. The levels of CEA, SCC, Cyfra21-1 and NSE were significantly elevated in BALF from the tumor-bearing lung compared with the opposite healthy lung in the lung cancer patients (P < 0.001) or the benign lung disease patients (P < 0.005). The diagnostic sensitivities of Cyfra21-1 (86 and 76%), with a specificity of 91%, were the highest among the four tumor markers for the tumor-bearing lung versus the opposite healthy lung and benign lung disease. The combination of Cyfra21-1 and CEA increased the sensitivity to 93 and 86 percent, respectively. The assay of these tumor markers in BALF may be used as a diagnostic tool to complement a cytological examination in the diagnosis of peripheral lung cancer. © 2013 Wiley Publishing Asia Pty Ltd.

Mutational analysis of multiple lung cancers: Discrimination between primary and metastatic lung cancers by genomic profile.

PubMed

Goto, Taichiro; Hirotsu, Yosuke; Mochizuki, Hitoshi; Nakagomi, Takahiro; Shikata, Daichi; Yokoyama, Yujiro; Oyama, Toshio; Amemiya, Kenji; Okimoto, Kenichiro; Omata, Masao

2017-05-09

In cases of multiple lung cancers, individual tumors may represent either a primary lung cancer or both primary and metastatic lung cancers. Treatment selection varies depending on such features, and this discrimination is critically important in predicting prognosis. The present study was undertaken to determine the efficacy and validity of mutation analysis as a means of determining whether multiple lung cancers are primary or metastatic in nature. The study involved 12 patients who underwent surgery in our department for multiple lung cancers between July 2014 and March 2016. Tumor cells were collected from formalin-fixed paraffin-embedded tissues of the primary lesions by using laser capture microdissection, and targeted sequencing of 53 lung cancer-related genes was performed. In surgically treated patients with multiple lung cancers, the driver mutation profile differed among the individual tumors. Meanwhile, in a case of a solitary lung tumor that appeared after surgery for double primary lung cancers, gene mutation analysis using a bronchoscopic biopsy sample revealed a gene mutation profile consistent with the surgically resected specimen, thus demonstrating that the tumor in this case was metastatic. In cases of multiple lung cancers, the comparison of driver mutation profiles clarifies the clonal origin of the tumors and enables discrimination between primary and metastatic tumors.

LUNG CANCER AND PULMONARY THROMBOEMBOLISM

PubMed Central

Cukic, Vesna; Ustamujic, Aida

2015-01-01

Introduction: Malignant diseases including lung cancer are the risk for development of pulmonary thromboembolism (PTE). Objective: To show the number of PTE in patients with lung cancer treated in Clinic for pulmonary diseases and TB “Podhrastovi” in three-year period: from 2012-2014. Material and methods: This is the retrospective study in which we present the number of various types of lung cancer treated in three-year period, number and per cent of PTE in different types of lung carcinoma, number and per cent of PTE of all diagnosed PTE in lung carcinoma according to the type of carcinoma. Results: In three-year period (from 2012 to 2014) 1609 patients with lung cancer were treated in Clinic for pulmonary diseases and TB “Podhrastovi” Clinical Centre of Sarajevo University. 42 patients: 25 men middle –aged 64.4 years and 17 women middle- aged 66.7 or 2.61% of all patients with lung cancer had diagnosed PTE. That was the 16. 7% of all patients with PTE treated in Clinic “Podhrastovi “in that three-year period. Of all 42 patients with lung cancer and diagnosed PTE 3 patients (7.14%) had planocellular cancer, 4 patients (9.53%) had squamocellular cancer, 9 (21.43%) had adenocarcinoma, 1 (2.38%) had NSCLC, 3 (7.14 %) had microcellular cancer, 1 (2.38%) had neuroendocrine cancer, 2 (4.76%) had large cell-macrocellular and 19 (45.24%) had histological non-differentiated lung carcinoma. Conclusion: Malignant diseases, including lung cancer, are the risk factor for development of PTE. It is important to consider the including anticoagulant prophylaxis in these patients and so to slow down the course of diseases in these patients. PMID:26622205

Uniform and blinded cause of death verification of the NELSON lung cancer screening participants.

PubMed

Yousaf-Khan, A U; van der Aalst, C M; Aerts, J G J V; den Bakker, M A; de Koning, H J

2017-09-01

Primary outcome of the Dutch-Belgian lung cancer screening trial (NELSON) is lung cancer-specific mortality. Accurate assessment of the cause of death (CoD) is crucial. As death certificates regarding the CoD can be inaccurate, a clinical expert committee (CEC) was formed to assign the CoD. In this study, the medical files of deceased lung cancer patients were reviewed and the outcomes were compared with official death certificates. The first 266 completed medical files of Dutch deceased participants who were diagnosed with lung cancer during the study or of those with lung cancer on the death certificate were selected and blinded towards arms and patients identity. The end product of the review process consisted of six possible categories which defined the graduation of certainty that lung cancer was the primary CoD. The percentage agreement and the Cohen's kappa statistics between the two CEC-memberswere calculated. The sensitivity and specificity of the official death certificates were determined. The results indicated that, the overall concordance and the Cohen's kappa between the CEC-memberswere 86.1% and 0.57(0.45-0.69, p<0.001), respectively. This level increased with the numbers of cases evaluated. The sensitivity and the specificity of the official death certificate were 92.6% and 98.8%; 6.5% cases were reclassified to lung cancer specific death, which is lower than in the National Lung Screening trial(22.0%). Concluding, each death should be reviewed by at least two members. So far, in the NELSON trial, possible biases related to lung cancer death seem relatively small. Copyright © 2017 Elsevier B.V. All rights reserved.

Cross-talk between AMPK and EGFR dependent Signaling in Non-Small Cell Lung Cancer

NASA Astrophysics Data System (ADS)

Praveen, Paurush; Hülsmann, Helen; Sültmann, Holger; Kuner, Ruprecht; Fröhlich, Holger

2016-06-01

Lung cancers globally account for 12% of new cancer cases, 85% of these being Non Small Cell Lung Cancer (NSCLC). Therapies like erlotinib target the key player EGFR, which is mutated in about 10% of lung adenocarcinoma. However, drug insensitivity and resistance caused by second mutations in the EGFR or aberrant bypass signaling have evolved as a major challenge in controlling these tumors. Recently, AMPK activation was proposed to sensitize NSCLC cells against erlotinib treatment. However, the underlying mechanism is largely unknown. In this work we aim to unravel the interplay between 20 proteins that were previously associated with EGFR signaling and erlotinib drug sensitivity. The inferred network shows a high level of agreement with protein-protein interactions reported in STRING and HIPPIE databases. It is further experimentally validated with protein measurements. Moreover, predictions derived from our network model fairly agree with somatic mutations and gene expression data from primary lung adenocarcinoma. Altogether our results support the role of AMPK in EGFR signaling and drug sensitivity.

Cross-talk between AMPK and EGFR dependent Signaling in Non-Small Cell Lung Cancer.

PubMed

Praveen, Paurush; Hülsmann, Helen; Sültmann, Holger; Kuner, Ruprecht; Fröhlich, Holger

2016-06-09

Lung cancers globally account for 12% of new cancer cases, 85% of these being Non Small Cell Lung Cancer (NSCLC). Therapies like erlotinib target the key player EGFR, which is mutated in about 10% of lung adenocarcinoma. However, drug insensitivity and resistance caused by second mutations in the EGFR or aberrant bypass signaling have evolved as a major challenge in controlling these tumors. Recently, AMPK activation was proposed to sensitize NSCLC cells against erlotinib treatment. However, the underlying mechanism is largely unknown. In this work we aim to unravel the interplay between 20 proteins that were previously associated with EGFR signaling and erlotinib drug sensitivity. The inferred network shows a high level of agreement with protein-protein interactions reported in STRING and HIPPIE databases. It is further experimentally validated with protein measurements. Moreover, predictions derived from our network model fairly agree with somatic mutations and gene expression data from primary lung adenocarcinoma. Altogether our results support the role of AMPK in EGFR signaling and drug sensitivity.

Lung Cancer Indicators Recurrence

Cancer.gov

This study describes prognostic factors for lung cancer spread and recurrence, as well as subsequent risk of death from the disease. The investigators observed that regardless of cancer stage, grade, or type of lung cancer, patients in the study were more

Serum Insulin, Glucose, Indices of Insulin Resistance, and Risk of Lung Cancer.

PubMed

Argirion, Ilona; Weinstein, Stephanie J; Männistö, Satu; Albanes, Demetrius; Mondul, Alison M

2017-10-01

Background: Although insulin may increase the risk of some cancers, few studies have examined fasting serum insulin and lung cancer risk. Methods: We examined serum insulin, glucose, and indices of insulin resistance [insulin:glucose molar ratio and homeostasis model assessment of insulin resistance (HOMA-IR)] and lung cancer risk using a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. A total of 196 cases and 395 subcohort members were included. Insulin and glucose were measured in fasting serum collected 5 to 12 years before diagnosis. Cox proportional hazards models were utilized to estimate the relative risk of lung cancer. Results: The average time between blood collection and lung cancer was 9.6 years. Fasting serum insulin levels were 8.7% higher in subcohort members than cases. After multivariable adjustment, men in the fourth quartile of insulin had a significantly higher risk of lung cancer than those in the first quartile [HR = 2.10; 95% confidence interval (CI), 1.12-3.94]. A similar relationship was seen with HOMA-IR (HR = 1.83; 95% CI, 0.99-3.38). Risk was not strongly associated with glucose or the insulin:glucose molar ratio ( P trend = 0.55 and P trend = 0.27, respectively). Conclusions: Higher fasting serum insulin concentrations, as well as the presence of insulin resistance, appear to be associated with an elevated risk of lung cancer development. Impact: Although insulin is hypothesized to increase risk of some cancers, insulin and lung cancer remain understudied. Higher insulin levels and insulin resistance were associated with increased lung cancer risk. Although smoking cessation is the best method of lung cancer prevention, other lifestyle changes that affect insulin concentrations and sensitivity may reduce lung cancer risk. Cancer Epidemiol Biomarkers Prev; 26(10); 1519-24. ©2017 AACR . ©2017 American Association for Cancer Research.

High-depth, high-accuracy microsatellite genotyping enables precision lung cancer risk classification

PubMed Central

Velmurugan, K R; Varghese, R T; Fonville, N C; Garner, H R

2017-01-01

There remains a large discrepancy between the known genetic contributions to cancer and that which can be explained by genomic variants, both inherited and somatic. Recently, understudied repetitive DNA regions called microsatellites have been identified as genetic risk markers for a number of diseases including various cancers (breast, ovarian and brain). In this study, we demonstrate an integrated process for identifying and further evaluating microsatellite-based risk markers for lung cancer using data from the cancer genome atlas and the 1000 genomes project. Comparing whole-exome germline sequencing data from 488 TCGA lung cancer samples to germline exome data from 390 control samples from the 1000 genomes project, we identified 119 potentially informative microsatellite loci. These loci were found to be able to distinguish between cancer and control samples with sensitivity and specificity ratios over 0.8. Then these loci, supplemented with additional loci from other cancers and controls, were evaluated using a target enrichment kit and sample-multiplexed nextgen sequencing. Thirteen of the 119 risk markers were found to be informative in a well powered study (>0.99 for a 0.95 confidence interval) using high-depth (579x±315) nextgen sequencing of 30 lung cancer and 89 control samples, resulting in sensitivity and specificity ratios of 0.90 and 0.94, respectively. When 8 loci harvested from the bioinformatic analysis of other cancers are added to the classifier, then the sensitivity and specificity rise to 0.93 and 0.97, respectively. Analysis of the genes harboring these loci revealed two genes (ARID1B and REL) and two significantly enriched pathways (chromatin organization and cellular stress response) suggesting that the process of lung carcinogenesis is linked to chromatin remodeling, inflammation, and tumor microenvironment restructuring. We illustrate that high-depth sequencing enables a high-precision microsatellite-based risk classifier analysis

High-depth, high-accuracy microsatellite genotyping enables precision lung cancer risk classification.

PubMed

Velmurugan, K R; Varghese, R T; Fonville, N C; Garner, H R

2017-11-16

There remains a large discrepancy between the known genetic contributions to cancer and that which can be explained by genomic variants, both inherited and somatic. Recently, understudied repetitive DNA regions called microsatellites have been identified as genetic risk markers for a number of diseases including various cancers (breast, ovarian and brain). In this study, we demonstrate an integrated process for identifying and further evaluating microsatellite-based risk markers for lung cancer using data from the cancer genome atlas and the 1000 genomes project. Comparing whole-exome germline sequencing data from 488 TCGA lung cancer samples to germline exome data from 390 control samples from the 1000 genomes project, we identified 119 potentially informative microsatellite loci. These loci were found to be able to distinguish between cancer and control samples with sensitivity and specificity ratios over 0.8. Then these loci, supplemented with additional loci from other cancers and controls, were evaluated using a target enrichment kit and sample-multiplexed nextgen sequencing. Thirteen of the 119 risk markers were found to be informative in a well powered study (>0.99 for a 0.95 confidence interval) using high-depth (579x±315) nextgen sequencing of 30 lung cancer and 89 control samples, resulting in sensitivity and specificity ratios of 0.90 and 0.94, respectively. When 8 loci harvested from the bioinformatic analysis of other cancers are added to the classifier, then the sensitivity and specificity rise to 0.93 and 0.97, respectively. Analysis of the genes harboring these loci revealed two genes (ARID1B and REL) and two significantly enriched pathways (chromatin organization and cellular stress response) suggesting that the process of lung carcinogenesis is linked to chromatin remodeling, inflammation, and tumor microenvironment restructuring. We illustrate that high-depth sequencing enables a high-precision microsatellite-based risk classifier analysis

Sensitive detection of EML4-ALK fusion oncoprotein of lung cancer by in situ proximity ligation assay.

PubMed

Rho, Jin Kyung; Lee, Hyangsin; Park, Chan-Sik; Choi, Chang-Min; Lee, Jae Cheol

2013-09-01

EML4-ALK fusion oncogene has emerged as a novel molecular target in non-small cell lung cancer (NSCLC). Although break-apart fluorescent in situ hybridization (FISH) is the standard method for diagnosis, it is expensive, not readily available and sometimes difficult to interpret. In addition, ALK immunohistochemistry (IHC) may miss the diagnosis because of relatively low level of ALK transcription. In situ proximity ligation assay (PLA) originally developed for precise detection and quantification of proteins by dual recognition and amplification process was used for sensitive detection of EML4-ALK fusion oncoprotein in NSCLC cell lines (ALK negative cell: PC-9 and H460, ALK positive cell: H3122 and H2228). EML4-ALK oncogene and protein in lung cancer cells were confirmed by multiplex RT-PCR and Western blots. We detected 117 kDa variant 1 of EML4-ALK in H3122 and 90 kDa variant 3 of EML4-ALK in H2228. These cells were more sensitive to crizotinib, an ALK inhibitor compared with PC-9 and H460 cells without EML4-ALK rearrangement. After fixing on glass slides by cytospin centrifuge, in situ PLA test was performed. Among four cell lines, distinct, tiny spots were visible only in H3122 and H2228 cell lines with ALK rearrangement. The same results were also obtained when paraffin-embedded cell blocks were used. Highly specific and sensitive detection of EML4-ALK fusion oncoprotein is possible by in situ PLA method suggesting its clinical application.

Progressive massive fibrosis in patients with pneumoconiosis: utility of MRI in differentiating from lung cancer.

PubMed

Ogihara, Yukihiro; Ashizawa, Kazuto; Hayashi, Hideyuki; Nagayasu, Takeshi; Hayashi, Tomayoshi; Honda, Sumihisa; Uetani, Masataka

2018-01-01

Background It is occasionally difficult to distinguish progressive massive fibrosis (PMF) from lung cancer on computed tomography (CT) in patients with pneumoconiosis. Purpose To evaluate the magnetic resonance imaging (MRI) features of PMF and to assess its ability to differentiate PMF from lung cancer. Material and Methods Between 2000 and 2014, 40 pulmonary lesions suspected to be lung cancer on the basis of CT in 28 patients with known pneumoconiosis were evaluated. Twenty-four of the 40 lesions were pathologically or clinically diagnosed as PMF. The signal pattern on T2-weighted (T2W) images, post-contrast enhancement pattern on T1-weighted (T1W) images, and the pattern of the time intensity curve (TIC) on contrast-enhanced dynamic studies were evaluated. All images were analyzed independently by two chest radiologists. Results All 24 PMF lesions showed low signal intensity (SI) on T2W images (sensitivity, 100%), while 15 of 16 lung cancer lesions showed intermediate or high SI on T2W images (specificity, 94%) when PMF was regarded as a positive result. Six of 17 PMF lesions showed a homogeneous enhancement pattern (sensitivity, 35%), and 4/9 lung cancer lesions showed an inhomogeneous or a ring-like enhancement pattern (specificity, 44%). Six of 16 PMF lesions showed a gradually increasing enhancement pattern (sensitivity, 38%), and 7/9 lung cancer lesions showed rapid enhancement pattern (specificity, 78%). Conclusion When differentiation between PMF and lung cancer in patients with pneumoconiosis is difficult on CT, an additional MRI study, particularly the T2W imaging sequence, may help differentiate between the two.

Accuracy of FDG-PET to diagnose lung cancer in a region of endemic granulomatous disease.

PubMed

Deppen, Stephen; Putnam, Joe B; Andrade, Gabriela; Speroff, Theodore; Nesbitt, Jonathan C; Lambright, Eric S; Massion, Pierre P; Walker, Ron; Grogan, Eric L

2011-08-01

The 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is used to evaluate suspicious pulmonary lesions due to its diagnostic accuracy. The southeastern United States has a high prevalence of infectious granulomatous lung disease, and the accuracy of FDG-PET may be reduced in this population. We examined the diagnostic accuracy of FDG-PET in patients with known or suspected non-small cell lung cancer treated at our institution. A total of 279 patients, identified through our prospective database, underwent an operation for known or suspected lung cancer. Preoperative FDG-PET in 211 eligible patients was defined by standardized uptake value greater than 2.5 or by description ("moderate" or "intense") as avid. Sensitivity, specificity, positive and negative predictive values, likelihood ratios, and decision diagrams were calculated for FDG-PET in all patients and in patients with indeterminate nodules. In all eligible patients (n=211), sensitivity and specificity of FDG-PET were 92% and 40%, respectively. Positive and negative predictive values were 86% and 55%. Overall FDG-PET accuracy to diagnose lung cancer was 81%. Preoperative positive likelihood ratio for FDG-PET diagnosis of lung cancer in this population was 1.5 compared with previously published values of 7.1. In 113 indeterminate lesions, 65% had lung cancer and the sensitivity and specificity were 89% and 40%, respectively. Twenty-four benign nodules (60%) had false positive FDG-PET scans. Twenty-two of 43 benign nodules (51%) were granulomas. In a region with endemic granulomatous diseases, the specificity of FDG-PET for diagnosis of lung cancer was 40%. Clinical decisions and future clinical predictive models for lung cancer must accommodate regional variation of FDG-PET scan results. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Anti-cancer Effects of Polyphenolic Compounds in Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor-resistant Non-small Cell Lung Cancer

PubMed Central

Jeong, Hyungmin; Phan, Ai N. H.; Choi, Jong-Whan

2017-01-01

Background: Polyphenolic phytochemicals are natural compounds, easily found in fruits and vegetables. Importantly, polyphenols have been intensively studied as excellent antioxidant activity which contributes to anticancer function of the natural compounds. Lung cancer has been reported to mainly account for cancer-related deaths in the world. Moreover, epidermal growth factor receptor tyrosine kinase inhibitor (TKI) resistance is one of the biggest issues in cancer treatment, especially in nonsmall cell lung cancer (NSCLC). Even though several studies both in preclinical and clinical trials have showed promising therapeutic effects of polyphenolic compounds in anticancer therapy, the function of the natural compounds in TKI-resistant (TKIR) lung cancer remains poorly studied. Objective: The aim of this study is to screen polyphenolic compounds as potential anticancer adjuvants which suppress TKIR lung cancer. Materials and Methods: Colony formation and thiazolyl blue tetrazolium blue assay were performed in the pair-matched TKI-sensitive (TKIS) versus TKIR tumor cell lines to investigate the therapeutic effect of polyphenolic compounds in TKIR NSCLC. Results: Our data show that equol, kaempferol, resveratrol, and ellagic acid exhibit strong anticancer effect in HCC827 panel. Moreover, the inhibitory effect of most of tested polyphenolic compounds was highly selective for TKIR lung cancer cell line H1993 while sparing the TKIS one H2073. Conclusion: This study provides an important screening of potential polyphenolic compounds for drug development to overcome TKI resistance in advanced lung cancer. SUMMARY The study provides an important screening of potential polyphenolic compounds for drug development to overcome tyrosine kinase inhibitor (TKI) resistance in advance lung cancerEquol, kaempferol, resveratrol, and ellagic acid show strong anticancer effect in HCC827 panel, including TKI-sensitive (TKIS) and TKI-resistant clonesThe inhibitory effect of polyphenolic

Lung cancer: biology and treatment options

PubMed Central

Hassan, Omer; Yang, Yi-Wei; Buchanan, Petra

2015-01-01

Lung cancer remains the leading cause of cancer mortality in men and women in the U.S. and worldwide. About 90% of lung cancer cases are caused by smoking and the use of tobacco products. However, other factors such as radon gas, asbestos, air pollution exposures, and chronic infections can contribute to lung carcinogenesis. In addition, multiple inherited and acquired mechanisms of susceptibility to lung cancer have been proposed. Lung cancer is divided into two broad histologic classes, which grow and spread differently: small-cell lung carcinomas (SCLC) and non-small cell lung carcinomas (NSCLC). Treatment options for lung cancer include surgery, radiation therapy, chemotherapy, and targeted therapy. Therapeutic-modalities recommendations depend on several factors, including the type and stage of cancer. Despite the improvements in diagnosis and therapy made during the past 25 years, the prognosis for patients with lung cancer is still unsatisfactory. The responses to current standard therapies are poor except for the most localized cancers. However, a better understanding of the biology pertinent to these challenging malignancies, might lead to the development of more efficacious and perhaps more specific drugs. The purpose of this review is to summarize the recent developments in lung cancer biology and its therapeutic strategies, and discuss the latest treatment advances including therapies currently under clinical investigation. PMID:26297204

Lung cancer risk from radon in Ontario, Canada: how many lung cancers can we prevent?

PubMed

Peterson, Emily; Aker, Amira; Kim, JinHee; Li, Ye; Brand, Kevin; Copes, Ray

2013-11-01

To calculate the burden of lung cancer illness due to radon for all thirty-six health units in Ontario and determine the number of radon-attributable lung cancer deaths that could be prevented. We calculated the population attributable risk percent, excess life-time risk ratio, life-years lost, the number of lung cancer deaths due to radon, and the number of deaths that could be prevented if all homes above various cut-points were effectively reduced to background levels. It is estimated that 13.6 % (95 % CI 11.0, 16.7) of lung cancer deaths in Ontario are attributable to radon, corresponding to 847 (95 % CI 686, 1,039) lung cancer deaths each year, approximately 84 % of these in ever-smokers. If all homes above 200 Bq/m(3), the current Canadian guideline, were remediated to background levels, it is estimated that 91 lung cancer deaths could be prevented each year, 233 if remediation was performed at 100 Bq/m(3). There was important variation across health units. Radon is an important contributor to lung cancer deaths in Ontario. A large portion of radon-attributable lung cancer deaths are from exposures below the current Canadian guideline, suggesting interventions that install effective radon-preventive measures into buildings at build may be a good alternative population prevention strategy to testing and remediation. For some health units, testing and remediation may also prevent a portion of radon-related lung cancer deaths. Regional attributable risk estimates can help with local public health resource allocation and decision making.

A reevaluation of CD22 expression in human lung cancer.

PubMed

Pop, Laurentiu M; Barman, Stephen; Shao, Chunli; Poe, Jonathan C; Venturi, Guglielmo M; Shelton, John M; Pop, Iliodora V; Gerber, David E; Girard, Luc; Liu, Xiao-yun; Behrens, Carmen; Rodriguez-Canales, Jaime; Liu, Hui; Wistuba, Ignacio I; Richardson, James A; Minna, John D; Tedder, Thomas F; Vitetta, Ellen S

2014-01-01

CD22 is a transmembrane glycoprotein expressed by mature B cells. It inhibits signal transduction by the B-cell receptor and its coreceptor CD19. Recent reports indicate that most human lung cancer cells and cell lines express CD22, making it an important new therapeutic target for lung cancer. The objective of our studies was to independently validate these results with the goal of testing the efficacy of our CD22 immunotoxins on lung cancer cell lines. As determined by quantitative real-time PCR analysis, we found that levels of CD22 mRNA in a panel of human lung cancer cell lines were 200 to 60,000-fold lower than those observed in the human CD22(+) Burkitt lymphoma cells, Daudi. Using flow cytometry with a panel of CD22 monoclonal antibodies and Western blot analyses, we could not detect surface or intracellular expression of CD22 protein in a panel of lung cancer cell lines. In addition, the in vitro proliferation of the lung tumor cell lines was not affected by either CD22 antibodies or our highly potent anti-CD22 immunotoxin. In contrast, CD22(+) Daudi cells expressed high levels of CD22 mRNA and protein, and were sensitive to our CD22 immunotoxin. Importantly, primary non-small cell lung cancers from more than 250 patient specimens did not express detectable levels of CD22 protein as assessed by immunohistochemistry. We conclude that CD22 is not expressed at measurable levels on the surface of lung cancer cells, and that these cells cannot be killed by anti-CD22 immunotoxins.

Lung cancer in younger patients.

PubMed

Abbasowa, Leda; Madsen, Poul Henning

2016-07-01

Lung cancer remains a leading cause of cancer-related death. The incidence increases with age and the occurrence in young patients is relatively low. The clinicopathological features of lung cancer in younger patients have not been fully explored previously. To assess the age differences in the clinical characteristics of lung cancer, we conducted a retrospective analysis comparing young patients ≤ 65 years of age with an elderly group > 65 years of age. Among 1,232 patients evaluated due to suspicion of lung cancer in our fast-track setting from January-December 2013, 312 newly diagnosed lung cancer patients were included. Patients ≤ 65 years had a significantly higher representation of females (p = 0.0021), more frequent familial cancer aggregation (p = 0.028) and a lower incidence of squamous cell carcinoma (p = 0.0133). When excluding pure carcinoid tumours, a significantly higher proportion of the younger patients presented with advanced stage disease (p = 0.0392). Combined modality therapy was more common in younger patients (p = 0.0009), while chemotherapy appeared less prevalent among the elderly (p = 0.0015). Lung cancer in younger patients comprises a distinct clinicopathological entity with more frequent advanced stage disease and a significantly greater proportion with a family history of cancer. Implementing genetic background assessments and considering lung cancer as a possible diagnosis in younger, symptomatic patients, is of paramount importance. none. The study was approved by the -Danish Data Protection Agency.

Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duan, Lincan; Shen, Hongmei; Zhao, Guangqiang

2014-04-18

Highlights: • Disulfiram and copper synergistically inhibit lung cancer cell proliferation. • Lung cancer cell colony formation ability is inhibited by Disulfiram/copper. • Disulfiram/copper increases the sensitivity of cisplatin to lung cancer cells. • Lung cancer stem cells are specifically targeted by Disulfiram/copper complex. - Abstract: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition ofmore » cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC

Lung cancer in persons with HIV.

PubMed

Sigel, Keith; Makinson, Alain; Thaler, Jonathan

2017-01-01

Lung cancer is emerging as a leading cause of death in HIV-infected persons. This review will discuss the latest scientific evidence regarding the mechanisms driving lung cancer risk in HIV infection, the clinical presentation of lung cancer in HIV-infected persons and recent data regarding the outcomes, treatment and prevention of lung cancer in this group. Increased risk of lung cancer in HIV-infected persons is primarily due to higher smoking rates, but emerging evidence also implicates immunosuppression and inflammatory processes. Lung cancer outcomes may be worse in HIV-infected persons in the antiretroviral era, but this may stem, in part, from treatment disparities. Early detection of lung cancer using chest computed tomography (CT) is being increasingly adopted for smokers in the general population, and recent studies suggest that it may be safe and efficacious in HIV-infected smokers. Lung cancer is an important complication associated with chronic HIV infection. It is associated with unique HIV-related causal mechanisms, and may be associated with worse outcomes in some HIV-infected persons. Smoking cessation and early cancer detection with chest CT are likely to benefit HIV-infected smokers.

Scientific Advances in Lung Cancer 2015.

PubMed

Tsao, Anne S; Scagliotti, Giorgio V; Bunn, Paul A; Carbone, David P; Warren, Graham W; Bai, Chunxue; de Koning, Harry J; Yousaf-Khan, A Uraujh; McWilliams, Annette; Tsao, Ming Sound; Adusumilli, Prasad S; Rami-Porta, Ramón; Asamura, Hisao; Van Schil, Paul E; Darling, Gail E; Ramalingam, Suresh S; Gomez, Daniel R; Rosenzweig, Kenneth E; Zimmermann, Stefan; Peters, Solange; Ignatius Ou, Sai-Hong; Reungwetwattana, Thanyanan; Jänne, Pasi A; Mok, Tony S; Wakelee, Heather A; Pirker, Robert; Mazières, Julien; Brahmer, Julie R; Zhou, Yang; Herbst, Roy S; Papadimitrakopoulou, Vassiliki A; Redman, Mary W; Wynes, Murry W; Gandara, David R; Kelly, Ronan J; Hirsch, Fred R; Pass, Harvey I

2016-05-01

Lung cancer continues to be a major global health problem; the disease is diagnosed in more than 1.6 million new patients each year. However, significant progress is underway in both the prevention and treatment of lung cancer. Lung cancer therapy has now emerged as a "role model" for precision cancer medicine, with several important therapeutic breakthroughs occurring during 2015. These advances have occurred primarily in the immunotherapy field and in treatments directed against tumors harboring specific oncogenic drivers. Our knowledge about molecular mechanisms for oncogene-driven tumors and about resistance to targeted therapies has increased quickly over the past year. As a result, several regulatory approvals of new agents that significantly improve survival and quality of life for patients with lung cancer who have advanced disease have occurred. The International Association for the Study of Lung Cancer has gathered experts in different areas of lung cancer research and management to summarize the most significant scientific advancements related to prevention and therapy of lung cancer during the past year. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Targeting DDX3 with a small molecule inhibitor for lung cancer therapy

PubMed Central

Bol, Guus M; Vesuna, Farhad; Xie, Min; Zeng, Jing; Aziz, Khaled; Gandhi, Nishant; Levine, Anne; Irving, Ashley; Korz, Dorian; Tantravedi, Saritha; Heerma van Voss, Marise R; Gabrielson, Kathleen; Bordt, Evan A; Polster, Brian M; Cope, Leslie; van der Groep, Petra; Kondaskar, Atul; Rudek, Michelle A; Hosmane, Ramachandra S; van der Wall, Elsken; van Diest, Paul J; Tran, Phuoc T; Raman, Venu

2015-01-01

Lung cancer is the most common malignancy worldwide and is a focus for developing targeted therapies due to its refractory nature to current treatment. We identified a RNA helicase, DDX3, which is overexpressed in many cancer types including lung cancer and is associated with lower survival in lung cancer patients. We designed a first-in-class small molecule inhibitor, RK-33, which binds to DDX3 and abrogates its activity. Inhibition of DDX3 by RK-33 caused G1 cell cycle arrest, induced apoptosis, and promoted radiation sensitization in DDX3-overexpressing cells. Importantly, RK-33 in combination with radiation induced tumor regression in multiple mouse models of lung cancer. Mechanistically, loss of DDX3 function either by shRNA or by RK-33 impaired Wnt signaling through disruption of the DDX3–β-catenin axis and inhibited non-homologous end joining—the major DNA repair pathway in mammalian somatic cells. Overall, inhibition of DDX3 by RK-33 promotes tumor regression, thus providing a compelling argument to develop DDX3 inhibitors for lung cancer therapy. PMID:25820276

Screening for Lung Cancer

PubMed Central

Mazzone, Peter J.; Naidich, David P.; Bach, Peter B.

2013-01-01

Background: Lung cancer is by far the major cause of cancer deaths largely because in the majority of patients it is at an advanced stage at the time it is discovered, when curative treatment is no longer feasible. This article examines the data regarding the ability of screening to decrease the number of lung cancer deaths. Methods: A systematic review was conducted of controlled studies that address the effectiveness of methods of screening for lung cancer. Results: Several large randomized controlled trials (RCTs), including a recent one, have demonstrated that screening for lung cancer using a chest radiograph does not reduce the number of deaths from lung cancer. One large RCT involving low-dose CT (LDCT) screening demonstrated a significant reduction in lung cancer deaths, with few harms to individuals at elevated risk when done in the context of a structured program of selection, screening, evaluation, and management of the relatively high number of benign abnormalities. Whether other RCTs involving LDCT screening are consistent is unclear because data are limited or not yet mature. Conclusions: Screening is a complex interplay of selection (a population with sufficient risk and few serious comorbidities), the value of the screening test, the interval between screening tests, the availability of effective treatment, the risk of complications or harms as a result of screening, and the degree with which the screened individuals comply with screening and treatment recommendations. Screening with LDCT of appropriate individuals in the context of a structured process is associated with a significant reduction in the number of lung cancer deaths in the screened population. Given the complex interplay of factors inherent in screening, many questions remain on how to effectively implement screening on a broader scale. PMID:23649455

A Pessimistic Explanatory Style is Prognostic for Poor Lung Cancer Survival

PubMed Central

Novotny, Paul; Colligan, Robert C.; Szydlo, Daniel W.; Clark, Matthew M.; Rausch, Sarah; Wampfler, Jason; Sloan, Jeff A.; Yang, Ping

2010-01-01

Background Several studies have demonstrated the importance of personality constructs on health behaviors and health status. Having a pessimistic outlook has been related to negative health behaviors and higher mortality. However, the construct has not been well explored in cancer populations. Methods Survival time of 534 adults, who were diagnosed with lung cancer and had a pessimistic explanatory style, was examined. The patients had completed the Minnesota Multiphasic Personality Inventory (MMPI) approximately 18.2 years prior to receiving their lung cancer diagnosis. MMPI Optimism-Pessimism (PSM) scores were divided into high (60 or more) and low scores (less than 60), and log-rank tests and Kaplan-Meier curves were used to determine survival differences. Multivariate Cox models were used for assessing prognostic values of pessimism along with other known predictors for lung cancer survival outcome. Booting strapping of the survival models was used as a sensitivity analysis. Results At the time of lung cancer diagnosis, patients were on average 67 years old; 48% were female; 85% had non-small cell lung cancer (NSCLC); 15% had small cell lung cancer (SCLC); 30% were stage I; 4% were stage II; 31% were stage III/limited; and 35% were stage IV/extensive. Patients who exhibited a non-pessimistic explanatory style survived approximately six months longer than patients classified as having a pessimistic explanatory style. Conclusion Among lung cancer patients, those having a pessimistic explanatory style experienced less favorable survival outcome, which may be related to cancer treatment decisions. Further research in this area is warranted. PMID:20139778

Cost-effectiveness of Lung Cancer Screening in Canada.

PubMed

Goffin, John R; Flanagan, William M; Miller, Anthony B; Fitzgerald, Natalie R; Memon, Saima; Wolfson, Michael C; Evans, William K

2015-09-01

The US National Lung Screening Trial supports screening for lung cancer among smokers using low-dose computed tomographic (LDCT) scans. The cost-effectiveness of screening in a publically funded health care system remains a concern. To assess the cost-effectiveness of LDCT scan screening for lung cancer within the Canadian health care system. The Cancer Risk Management Model (CRMM) simulated individual lives within the Canadian population from 2014 to 2034, incorporating cancer risk, disease management, outcome, and cost data. Smokers and former smokers eligible for lung cancer screening (30 pack-year smoking history, ages 55-74 years, for the reference scenario) were modeled, and performance parameters were calibrated to the National Lung Screening Trial (NLST). The reference screening scenario assumes annual scans to age 75 years, 60% participation by 10 years, 70% adherence to screening, and unchanged smoking rates. The CRMM outputs are aggregated, and costs (2008 Canadian dollars) and life-years are discounted 3% annually. The incremental cost-effectiveness ratio. Compared with no screening, the reference scenario saved 51,000 quality-adjusted life-years (QALY) and had an incremental cost-effectiveness ratio of CaD $52,000/QALY. If smoking history is modeled for 20 or 40 pack-years, incremental cost-effectiveness ratios of CaD $62,000 and CaD $43,000/QALY, respectively, were generated. Changes in participation rates altered life years saved but not the incremental cost-effectiveness ratio, while the incremental cost-effectiveness ratio is sensitive to changes in adherence. An adjunct smoking cessation program improving the quit rate by 22.5% improves the incremental cost-effectiveness ratio to CaD $24,000/QALY. Lung cancer screening with LDCT appears cost-effective in the publicly funded Canadian health care system. An adjunct smoking cessation program has the potential to improve outcomes.

Detection of Lung Cancer by Sensor Array Analyses of Exhaled Breath

PubMed Central

Machado, Roberto F.; Laskowski, Daniel; Deffenderfer, Olivia; Burch, Timothy; Zheng, Shuo; Mazzone, Peter J.; Mekhail, Tarek; Jennings, Constance; Stoller, James K.; Pyle, Jacqueline; Duncan, Jennifer; Dweik, Raed A.; Erzurum, Serpil C.

2005-01-01

Rationale: Electronic noses are successfully used in commercial applications, including detection and analysis of volatile organic compounds in the food industry. Objectives: We hypothesized that the electronic nose could identify and discriminate between lung diseases, especially bronchogenic carcinoma. Methods: In a discovery and training phase, exhaled breath of 14 individuals with bronchogenic carcinoma and 45 healthy control subjects or control subjects without cancer was analyzed. Principal components and canonic discriminant analysis of the sensor data was used to determine whether exhaled gases could discriminate between cancer and noncancer. Discrimination between classes was performed using Mahalanobis distance. Support vector machine analysis was used to create and apply a cancer prediction model prospectively in a separate group of 76 individuals, 14 with and 62 without cancer. Main Results: Principal components and canonic discriminant analysis demonstrated discrimination between samples from patients with lung cancer and those from other groups. In the validation study, the electronic nose had 71.4% sensitivity and 91.9% specificity for detecting lung cancer; positive and negative predictive values were 66.6 and 93.4%, respectively. In this population with a lung cancer prevalence of 18%, positive and negative predictive values were 66.6 and 94.5%, respectively. Conclusion: The exhaled breath of patients with lung cancer has distinct characteristics that can be identified with an electronic nose. The results provide feasibility to the concept of using the electronic nose for managing and detecting lung cancer. PMID:15750044

Cross-talk between AMPK and EGFR dependent Signaling in Non-Small Cell Lung Cancer

PubMed Central

Praveen, Paurush; Hülsmann, Helen; Sültmann, Holger; Kuner, Ruprecht; Fröhlich, Holger

2016-01-01

Lung cancers globally account for 12% of new cancer cases, 85% of these being Non Small Cell Lung Cancer (NSCLC). Therapies like erlotinib target the key player EGFR, which is mutated in about 10% of lung adenocarcinoma. However, drug insensitivity and resistance caused by second mutations in the EGFR or aberrant bypass signaling have evolved as a major challenge in controlling these tumors. Recently, AMPK activation was proposed to sensitize NSCLC cells against erlotinib treatment. However, the underlying mechanism is largely unknown. In this work we aim to unravel the interplay between 20 proteins that were previously associated with EGFR signaling and erlotinib drug sensitivity. The inferred network shows a high level of agreement with protein-protein interactions reported in STRING and HIPPIE databases. It is further experimentally validated with protein measurements. Moreover, predictions derived from our network model fairly agree with somatic mutations and gene expression data from primary lung adenocarcinoma. Altogether our results support the role of AMPK in EGFR signaling and drug sensitivity. PMID:27279498

Disruption of BASIGIN decreases lactic acid export and sensitizes non-small cell lung cancer to biguanides independently of the LKB1 status.

PubMed

Granja, Sara; Marchiq, Ibtissam; Le Floch, Renaud; Moura, Conceição Souto; Baltazar, Fátima; Pouysségur, Jacques

2015-03-30

Most cancers rely on aerobic glycolysis to generate energy and metabolic intermediates. To maintain a high glycolytic rate, cells must efficiently export lactic acid through the proton-coupled monocarboxylate transporters (MCT1/4). These transporters require a chaperone, CD147/BASIGIN (BSG) for trafficking to the plasma membrane and function.To validate the key role of these transporters in lung cancer, we first analysed the expression of MCT1/4 and BSG in 50 non-small lung cancer (NSCLC) cases. These proteins were specifically upregulated in tumour tissues. We then disrupted BSG in three NSCLC cell lines (A549, H1975 and H292) via 'Zinc-Finger Nucleases'. The three homozygous BSG-/- cell lines displayed a low MCT activity (10- to 5-fold reduction, for MCT1 and MCT4, respectively) compared to wild-type cells. Consequently, the rate of glycolysis, compared to the wild-type counterpart, was reduced by 2.0- to 3.5-fold, whereas the rate of respiration was stimulated in BSG-/- cell lines. Both wild-type and BSG-null cells were extremely sensitive to the mitochondria inhibitor metformin/phenformin in normoxia. However, only BSG-null cells, independently of their LKB1 status, remained sensitive to biguanides in hypoxia in vitro and tumour growth in nude mice. Our results demonstrate that inhibiting glycolysis by targeting lactic acid export sensitizes NSCLC to phenformin.

Disruption of BASIGIN decreases lactic acid export and sensitizes non-small cell lung cancer to biguanides independently of the LKB1 status

PubMed Central

Floch, Renaud Le; Moura, Conceição Souto

2015-01-01

Most cancers rely on aerobic glycolysis to generate energy and metabolic intermediates. To maintain a high glycolytic rate, cells must efficiently export lactic acid through the proton-coupled monocarboxylate transporters (MCT1/4). These transporters require a chaperone, CD147/BASIGIN (BSG) for trafficking to the plasma membrane and function. To validate the key role of these transporters in lung cancer, we first analysed the expression of MCT1/4 and BSG in 50 non-small lung cancer (NSCLC) cases. These proteins were specifically upregulated in tumour tissues. We then disrupted BSG in three NSCLC cell lines (A549, H1975 and H292) via ‘Zinc-Finger Nucleases’. The three homozygous BSG−/− cell lines displayed a low MCT activity (10- to 5-fold reduction, for MCT1 and MCT4, respectively) compared to wild-type cells. Consequently, the rate of glycolysis, compared to the wild-type counterpart, was reduced by 2.0- to 3.5-fold, whereas the rate of respiration was stimulated in BSG−/− cell lines. Both wild-type and BSG-null cells were extremely sensitive to the mitochondria inhibitor metformin/phenformin in normoxia. However, only BSG-null cells, independently of their LKB1 status, remained sensitive to biguanides in hypoxia in vitro and tumour growth in nude mice. Our results demonstrate that inhibiting glycolysis by targeting lactic acid export sensitizes NSCLC to phenformin. PMID:25894929

Association of thymidylate synthase gene 3'-untranslated region polymorphism with sensitivity of non-small cell lung cancer to pemetrexed treatment: TS gene polymorphism and pemetrexed sensitivity in NSCLC.

PubMed

Wang, Xia; Wang, Yadi; Wang, Yue; Cheng, Jian; Wang, Yanyun; Ha, Minwen

2013-01-25

Thymidylate synthase (TS) is a key enzyme responsible for DNA synthesis and repair. Altered expression of TS protein or TS gene polymorphisms has been associated with cancer progression and treatment response. This study investigated the expressions of TS and its gene SNPs in non-small cell lung cancer (NSCLC), and then its association with sensitivity to pemetrexed treatment. Immunohistochemistry and qRT-PCR were performed on 160 resected NSCLC specimens and corresponding normal tissues to assess the expressions of TS protein and TS mRNA, and for associations with clinicopathological data. Blood samples of 106 lung adenocarcinoma patients were examined for polymorphisms of the TS gene 3'-UTR 1494del 6 bp, which was then investigated for associations with responses of the patients to pemetrexed treatment and survival. Expression of both TS protein and its mRNA was elevated in NSCLC tissues compared with matched normal tissues, and significantly higher in lung squamous cell carcinoma than in lung adenocarcinoma. TS expression was associated with poor tumor differentiation. Furthermore, the genotyping data showed that 56% of lung adenocarcinoma patients had the TS gene 3'-UTR 1494 bp (-6 bp/-6 bp) genotype and the rest had TS gene 3'-UTR 1494 bp (-6 bp/+6 bp). There was no TS 3'-UTR 1494 bp (+6 bp/+6 bp) genotype in any patients. Statistical analysis revealed that gender, tumor stage, and TS 3'-UTR 1494del 6 bp polymorphism were significant prognostic factors after short-term pemetrexed treatment. Log-rank analysis revealed that patients with the (-6 bp/-6 bp) genotype had significantly better progression-free and overall survival than patients with (-6 bp/+6 bp). This study showed that TS protein is highly expressed in NSCLC and that polymorphisms of TS 3'-UTR 1494del 6 bp are associated with sensitivity of lung adenocarcinoma patients to pemetrexed treatment. This suggests that TS gene polymorphisms should be further evaluated as prognostic markers for personalized

Inhibition of mTOR enhances radiosensitivity of lung cancer cells and protects normal lung cells against radiation.

PubMed

Zheng, Hang; Wang, Miao; Wu, Jing; Wang, Zhi-Ming; Nan, Hai-Jun; Sun, He

2016-06-01

Radiotherapy has been used for a long time as a standard therapy for cancer; however, there have been no recent research breakthroughs. Radioresistance and various side-effects lead to the unexpected outcomes of radiation therapy. Specific and accurate targeting as well as reduction of radioresistance have been major challenges for irradiation therapy. Recent studies have shown that rapamycin shows promise for inhibiting tumorigenesis by suppressing mammalian target of rapamycin (mTOR). We found that the combination of rapamycin with irradiation significantly diminished cell viability and colony formation, and increased cell apoptosis, as compared with irradiation alone in lung cancer cell line A549, suggesting that rapamycin can enhance the effectiveness of radiation therapy by sensitizing cancer cells to irradiation. Importantly, we observed that the adverse effects of irradiation on a healthy lung cell line (WI-38) were also offset. No enhanced protein expression of mTOR signaling was observed in WI-38 cells, which is normally elevated in lung cancer cells. Moreover, DNA damage was significantly less with the combination therapy than with irradiation therapy alone. Our data suggest that the incorporation of rapamycin during radiation therapy could be a potent way to improve the sensitivity and effectiveness of radiation therapy as well as to protect normal cells from being damaged by irradiation.

On-the-spot lung cancer differential diagnosis by label-free, molecular vibrational imaging and knowledge-based classification

NASA Astrophysics Data System (ADS)

Gao, Liang; Li, Fuhai; Thrall, Michael J.; Yang, Yaliang; Xing, Jiong; Hammoudi, Ahmad A.; Zhao, Hong; Massoud, Yehia; Cagle, Philip T.; Fan, Yubo; Wong, Kelvin K.; Wang, Zhiyong; Wong, Stephen T. C.

2011-09-01

We report the development and application of a knowledge-based coherent anti-Stokes Raman scattering (CARS) microscopy system for label-free imaging, pattern recognition, and classification of cells and tissue structures for differentiating lung cancer from non-neoplastic lung tissues and identifying lung cancer subtypes. A total of 1014 CARS images were acquired from 92 fresh frozen lung tissue samples. The established pathological workup and diagnostic cellular were used as prior knowledge for establishment of a knowledge-based CARS system using a machine learning approach. This system functions to separate normal, non-neoplastic, and subtypes of lung cancer tissues based on extracted quantitative features describing fibrils and cell morphology. The knowledge-based CARS system showed the ability to distinguish lung cancer from normal and non-neoplastic lung tissue with 91% sensitivity and 92% specificity. Small cell carcinomas were distinguished from nonsmall cell carcinomas with 100% sensitivity and specificity. As an adjunct to submitting tissue samples to routine pathology, our novel system recognizes the patterns of fibril and cell morphology, enabling medical practitioners to perform differential diagnosis of lung lesions in mere minutes. The demonstration of the strategy is also a necessary step toward in vivo point-of-care diagnosis of precancerous and cancerous lung lesions with a fiber-based CARS microendoscope.

Induction of autophagy contributes to crizotinib resistance in ALK-positive lung cancer.

PubMed

Ji, Cheng; Zhang, Li; Cheng, Yan; Patel, Raj; Wu, Hao; Zhang, Yi; Wang, Mian; Ji, Shundong; Belani, Chandra P; Yang, Jin-Ming; Ren, Xingcong

2014-05-01

Use of the inhibitor of ALK fusion onco-protein, crizotinib (PF02341066), has achieved impressive clinical efficacy in patients with ALK-positive non-small cell lung cancer. Nevertheless, acquired resistance to this drug occurs inevitably in approximately a year, limiting the therapeutic benefits of this novel targeted therapy. In this study, we found that autophagy was induced in crizonitib-resistant lung cancer cells and contributed to drug resistance. We observed that ALK was downregulated in the crizotinib-resistant lung cancer cell line, H3122CR-1, and this was causally associated with autophagy induction. The degree of crizotinib resistance correlated with autophagic activity. Activation of autophagy in crizotinib-resistant H3122CR-1 cells involved alteration of the Akt/mTOR signaling pathway. Furthermore, we demonstrated that chloroquine, an inhibitor of autophagy, could restore sensitivity of H3122CR-1 to crizotinib and enhance its efficacy against drug-resistant lung cancer. Thus, modulating autophagy may be worth exploring as a new strategy to overcome acquired crizonitib resistance in ALK-positive lung cancer.

Pain management in lung cancer.

PubMed

Nurwidya, Fariz; Syahruddin, Elisna; Yunus, Faisal

2016-01-01

Lung cancer is the leading cause of cancer-related mortality worldwide. Not only burdened by the limited overall survival, lung cancer patient also suffer from various symptoms, such as pain, that implicated in the quality of life. Cancer pain is a complicated and transiently dynamic symptom that results from multiple mechanisms. This review will describe the pathophysiology of cancer pain and general approach in managing a patient with lung cancer pain. The use of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and adjuvant analgesia, as part of the pharmacology therapy along with interventional strategy, will also be discussed.

Lung Cancer Trends

MedlinePlus

... the Biggest Cancer Killer in Both Men and Women” Stay Informed Trends for Other Kinds of Cancer Breast Cervical Colorectal (Colon) Ovarian Prostate Skin Cancer Home Lung Cancer Trends Language: English Español (Spanish) Recommend ...

A deep learning method for early screening of lung cancer

NASA Astrophysics Data System (ADS)

Zhang, Kunpeng; Jiang, Huiqin; Ma, Ling; Gao, Jianbo; Yang, Xiaopeng

2018-04-01

Lung cancer is the leading cause of cancer-related deaths among men. In this paper, we propose a pulmonary nodule detection method for early screening of lung cancer based on the improved AlexNet model. In order to maintain the same image quality as the existing B/S architecture PACS system, we convert the original CT image into JPEG format image by analyzing the DICOM file firstly. Secondly, in view of the large size and complex background of CT chest images, we design the convolution neural network on basis of AlexNet model and sparse convolution structure. At last we train our models on the software named DIGITS which is provided by NVIDIA. The main contribution of this paper is to apply the convolutional neural network for the early screening of lung cancer and improve the screening accuracy by combining the AlexNet model with the sparse convolution structure. We make a series of experiments on the chest CT images using the proposed method, of which the sensitivity and specificity indicates that the method presented in this paper can effectively improve the accuracy of early screening of lung cancer and it has certain clinical significance at the same time.

Curbing the burden of lung cancer.

PubMed

Urman, Alexandra; Hosgood, H Dean

2016-06-01

Lung cancer contributes substantially to the global burden of disease and healthcare costs. New screening modalities using low-dose computerized tomography are promising tools for early detection leading to curative surgery. However, the screening and follow-up diagnostic procedures of these techniques may be costly. Focusing on prevention is an important factor to reduce the burden of screening, treatment, and lung cancer deaths. The International Agency for Research on Cancer has identified several lung carcinogens, which we believe can be considered actionable when developing prevention strategies. To curb the societal burden of lung cancer, healthcare resources need to be focused on early detection and screening and on mitigating exposure(s) of a person to known lung carcinogens, such as active tobacco smoking, household air pollution (HAP), and outdoor air pollution. Evidence has also suggested that these known lung carcinogens may be associated with genetic predispositions, supporting the hypothesis that lung cancers attributed to differing exposures may have developed from unique underlying genetic mechanisms attributed to the exposure of interest. For instance, smokingattributed lung cancer involves novel genetic markers of risk compared with HAP-attributed lung cancer. Therefore, genetic risk markers may be used in risk stratification to identify subpopulations that are at a higher risk for developing lung cancer attributed to a given exposure. Such targeted prevention strategies suggest that precision prevention strategies may be possible in the future; however, much work is needed to determine whether these strategies will be viable.

Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer

ClinicalTrials.gov

2017-08-28

Extensive Stage Small Cell Lung Carcinoma; Lung Adenocarcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

Canine scent detection in the diagnosis of lung cancer: revisiting a puzzling phenomenon.

PubMed

Ehmann, R; Boedeker, E; Friedrich, U; Sagert, J; Dippon, J; Friedel, G; Walles, T

2012-03-01

Patient prognosis in lung cancer largely depends on early diagnosis. The exhaled breath of patients may represent the ideal specimen for future lung cancer screening. However, the clinical applicability of current diagnostic sensor technologies based on signal pattern analysis remains incalculable due to their inability to identify a clear target. To test the robustness of the presence of a so far unknown volatile organic compound in the breath of patients with lung cancer, sniffer dogs were applied. Exhalation samples of 220 volunteers (healthy individuals, confirmed lung cancer or chronic obstructive pulmonary disease (COPD)) were presented to sniffer dogs following a rigid scientific protocol. Patient history, drug administration and clinicopathological data were analysed to identify potential bias or confounders. Lung cancer was identified with an overall sensitivity of 71% and a specificity of 93%. Lung cancer detection was independent from COPD and the presence of tobacco smoke and food odours. Logistic regression identified two drugs as potential confounders. It must be assumed that a robust and specific volatile organic compound (or pattern) is present in the breath of patients with lung cancer. Additional research efforts are required to overcome the current technical limitations of electronic sensor technologies to engineer a clinically applicable screening tool.

Lung tumors with distinct p53 mutations respond similarly to p53 targeted therapy but exhibit genotype-specific statin sensitivity

PubMed Central

Turrell, Frances K.; Kerr, Emma M.; Gao, Meiling; Thorpe, Hannah; Doherty, Gary J.; Cridge, Jake; Shorthouse, David; Speed, Alyson; Samarajiwa, Shamith; Hall, Benjamin A.; Griffiths, Meryl; Martins, Carla P.

2017-01-01

Lung adenocarcinoma accounts for ∼40% of lung cancers, the leading cause of cancer-related death worldwide, and current therapies provide only limited survival benefit. Approximately half of lung adenocarcinomas harbor mutations in TP53 (p53), making these mutants appealing targets for lung cancer therapy. As mutant p53 remains untargetable, mutant p53-dependent phenotypes represent alternative targeting opportunities, but the prevalence and therapeutic relevance of such effects (gain of function and dominant-negative activity) in lung adenocarcinoma are unclear. Through transcriptional and functional analysis of murine KrasG12D-p53null, -p53R172H (conformational), and -p53R270H (contact) mutant lung tumors, we identified genotype-independent and genotype-dependent therapeutic sensitivities. Unexpectedly, we found that wild-type p53 exerts a dominant tumor-suppressive effect on mutant tumors, as all genotypes were similarly sensitive to its restoration in vivo. These data show that the potential of p53 targeted therapies is comparable across all p53-deficient genotypes and may explain the high incidence of p53 loss of heterozygosity in mutant tumors. In contrast, mutant p53 gain of function and their associated vulnerabilities can vary according to mutation type. Notably, we identified a p53R270H-specific sensitivity to simvastatin in lung tumors, and the transcriptional signature that underlies this sensitivity was also present in human lung tumors, indicating that this therapeutic approach may be clinically relevant. PMID:28790158

[Current treatment concepts of lung cancer].

PubMed

Kaiser, F; Engelhardt, M; Rawluk, J; Mertelsmann, R; Passlick, B; Wäsch, R

2011-09-01

Lung cancer occurs with a median age of 69 years. The main cause is cigarette smoking. For both genders lung cancer is the third-most frequent tumor in Germany. While in an operable tumor stage 30-80% of the patients can reach long-term survival, the prognosis in the metastasised stage is unfavourable with a 5-year overall survival rate of 6% for small cell lung cancer (SCLC) and 18% for non-small cell lung cancer (NSCLC). Lung cancer is subject of intense research to improve the outcome. This article gives an overview of current treatment options. © Georg Thieme Verlag KG Stuttgart · New York.

The diagnostic value of narrow-band imaging for early and invasive lung cancer: a meta-analysis.

PubMed

Zhu, Juanjuan; Li, Wei; Zhou, Jihong; Chen, Yuqing; Zhao, Chenling; Zhang, Ting; Peng, Wenjia; Wang, Xiaojing

2017-07-01

This study aimed to compare the ability of narrow-band imaging to detect early and invasive lung cancer with that of conventional pathological analysis and white-light bronchoscopy. We searched the PubMed, EMBASE, Sinomed, and China National Knowledge Infrastructure databases for relevant studies. Meta-disc software was used to perform data analysis, meta-regression analysis, sensitivity analysis, and heterogeneity testing, and STATA software was used to determine if publication bias was present, as well as to calculate the relative risks for the sensitivity and specificity of narrow-band imaging vs those of white-light bronchoscopy for the detection of early and invasive lung cancer. A random-effects model was used to assess the diagnostic efficacy of the above modalities in cases in which a high degree of between-study heterogeneity was noted with respect to their diagnostic efficacies. The database search identified six studies including 578 patients. The pooled sensitivity and specificity of narrow-band imaging were 86% (95% confidence interval: 83-88%) and 81% (95% confidence interval: 77-84%), respectively, and the pooled sensitivity and specificity of white-light bronchoscopy were 70% (95% confidence interval: 66-74%) and 66% (95% confidence interval: 62-70%), respectively. The pooled relative risks for the sensitivity and specificity of narrow-band imaging vs the sensitivity and specificity of white-light bronchoscopy for the detection of early and invasive lung cancer were 1.33 (95% confidence interval: 1.07-1.67) and 1.09 (95% confidence interval: 0.84-1.42), respectively, and sensitivity analysis showed that narrow-band imaging exhibited good diagnostic efficacy with respect to detecting early and invasive lung cancer and that the results of the study were stable. Narrow-band imaging was superior to white light bronchoscopy with respect to detecting early and invasive lung cancer; however, the specificities of the two modalities did not differ

What You Need to Know about Lung Cancer

MedlinePlus

... Publications Reports What You Need To Know About™ Lung Cancer This booklet is about lung cancer. Learning about medical care for your cancer can ... The anatomy of the lungs and basics about lung cancer Treatment for lung cancer, including taking part in ...

Risk factors of Lung Cancer in nonsmoker.

PubMed

Akhtar, Nahid; Bansal, Jeena Gupta

Generally, the cause of lung cancer is attributed to tobacco smoking. But many of the new lung cancer cases have been reported in nonsmokers. Apart from smoking; air pollution, environmental exposure, mutations, and single-nucleotide polymorphisms are known to be associated with lung cancer. Improper diet, alcohol consumption, marijuana smoking, estrogen, infections with human papillomavirus (HPV), HIV, and Epstein-Barr virus are suggested to be linked with lung cancer but clear evidences to ascertain their relation is not available. This article provides a comprehensive review of various risk factors and the underlying molecular mechanisms responsible for increasing the incidence of lung cancer. The pathologic, histologic, and genetic differences exist with lung cancer among smokers and nonsmokers. A better understanding of the risk factors, differences in pathology and molecular features of lung cancer in smokers and nonsmokers and the mode of action of various carcinogens will facilitate the prevention and management of lung cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Stages of Non-Small Cell Lung Cancer

MedlinePlus

... Cancer Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key ...

Targeting DDX3 with a small molecule inhibitor for lung cancer therapy.

PubMed

Bol, Guus M; Vesuna, Farhad; Xie, Min; Zeng, Jing; Aziz, Khaled; Gandhi, Nishant; Levine, Anne; Irving, Ashley; Korz, Dorian; Tantravedi, Saritha; Heerma van Voss, Marise R; Gabrielson, Kathleen; Bordt, Evan A; Polster, Brian M; Cope, Leslie; van der Groep, Petra; Kondaskar, Atul; Rudek, Michelle A; Hosmane, Ramachandra S; van der Wall, Elsken; van Diest, Paul J; Tran, Phuoc T; Raman, Venu

2015-05-01

Lung cancer is the most common malignancy worldwide and is a focus for developing targeted therapies due to its refractory nature to current treatment. We identified a RNA helicase, DDX3, which is overexpressed in many cancer types including lung cancer and is associated with lower survival in lung cancer patients. We designed a first-in-class small molecule inhibitor, RK-33, which binds to DDX3 and abrogates its activity. Inhibition of DDX3 by RK-33 caused G1 cell cycle arrest, induced apoptosis, and promoted radiation sensitization in DDX3-overexpressing cells. Importantly, RK-33 in combination with radiation induced tumor regression in multiple mouse models of lung cancer. Mechanistically, loss of DDX3 function either by shRNA or by RK-33 impaired Wnt signaling through disruption of the DDX3-β-catenin axis and inhibited non-homologous end joining-the major DNA repair pathway in mammalian somatic cells. Overall, inhibition of DDX3 by RK-33 promotes tumor regression, thus providing a compelling argument to develop DDX3 inhibitors for lung cancer therapy. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

A Re-evaluation of CD22 Expression by Human Lung Cancer

PubMed Central

Pop, Laurentiu M.; Barman, Stephen; Shao, Chunli; Poe, Jonathan C.; Venturi, Guglielmo M.; Shelton, John M.; Pop, Iliodora V.; Gerber, David E.; Girard, Luc; Liu, Xiao-yun; Behrens, Carmen; Rodriguez-Canales, Jaime; Liu, Hui; Wistuba, Ignacio I.; Richardson, James A.; Minna, John D.; Tedder, Thomas F.; Vitetta, Ellen S.

2014-01-01

CD22 is a transmembrane glycoprotein expressed by mature B cells. It inhibits signal transduction by the B cell receptor and its co-receptor CD19. Recently it was reported that most human lung cancer cells and cell lines express CD22 making it an important new lung cancer therapeutic target (Can Res 72:5556, 2012). The objective of our studies was to independently validate these results with the goal of testing the efficacy of our CD22 immunotoxins on lung cancer cell lines. As determined by qRT-PCR analysis, we found that levels of CD22 mRNA in a panel of human lung cancer cell lines were 200–60,000- fold lower than those observed in the human CD22+ Burkitt’s lymphoma cells, Daudi. Using flow cytometry with a panel of CD22 monoclonal antibodies and Western blot analyses, we could not detect surface or intracellular expression of CD22 protein in a panel of lung cancer cell lines. In addition, the in vitro proliferation of the lung tumor cell lines was not affected by CD22 antibodies or our highly potent anti-CD22 immunotoxin. By contrast, CD22+ Daudi cells expressed high levels of CD22 mRNA and protein and were sensitive to our CD22 immunotoxin. Importantly, primary non-small cell lung cancers from over 250 patient specimens did not express detectable levels of CD22 protein as assessed by immunohistochemistry. We conclude that CD22 is not expressed at measurable levels on the surface of lung cancer cells and that these cells can not be killed by anti-CD22 immunotoxins. PMID:24395821

Customizing Therapies for Lung Cancer | Center for Cancer Research

Cancer.gov

Lung cancer is the leading cause of cancer-related death in both men and women. Although there have been modest improvements in short-term survival over the last few decades, five-year survival rates for lung cancer remain low at only 16 percent. Treatment for lung cancer depends on the stage of the disease at diagnosis, but generally consists of some combination of surgery,

The Impact of the Cancer Genome Atlas on Lung Cancer

PubMed Central

Chang, Jeremy Tzu-Huai; Lee, Yee-Ming; Huang, R. Stephanie

2015-01-01

The Cancer Genome Atlas (TCGA) has profiled over 10,000 samples derived from 33 types of cancer to date, with the goal of improving our understanding of the molecular basis of cancer and advancing our ability to diagnose, treat, and prevent cancer. This review focuses on lung cancer as it is the leading cause of cancer-related mortality worldwide in both men and women. Particularly, non-small cell lung cancers (including lung adenocarcinoma and lung squamous cell carcinoma) were evaluated. Our goal is to demonstrate the impact of TCGA on lung cancer research under four themes: namely, diagnostic markers, disease progression markers, novel therapeutic targets, and novel tools. Examples were given related to DNA mutation, copy number variation, mRNA, and microRNA expression along with methylation profiling. PMID:26318634

[Occupational lung cancer. A comparison between humans and experimental animals].

PubMed

Adachi, S; Takemoto, K

1987-09-01

Many epidemiological and experimental studies have suggested that the respiratory tract is one of the most sensitive organs to environmental carcinogens. Nevertheless there is little evidence to determine the relationship between a specific environmental carcinogen and a cell type of lung cancer, because the cell types of lung cancer and their relative frequencies are highly complex compared with those of other organs and tissues. In the present paper, occupational lung-cancer characteristics, which are the clearest in the relation between cause and effect in human lung cancers, were reviewed in comparison with the results of animal experiments concerned with occupational lung carcinogens. Through accumulation of histopathological examinations of the lung cancer cases, the following relationships between cause and cell type were conjectured: chromium and squamous cell carcinoma; asbestos and adenocarcinoma; nickel and squamous cell carcinoma; beryllium and small cell carcinoma; bis (chloromethyl) ether and small cell carcinoma; mustard gas and squamous cell or small cell carcinoma; vinyl chloride and large cell or adenocarcinoma; radionuclides and small cell carcinoma. The relation pertaining to arsenic, benzotrichloride and tar could not be conjectured because of insufficient cases and information in the histological diagnosis. On the other hand, the carcinogenicity of these substances in occupational exposure has been confirmed by animal experiments administered intratracheally or by inhalation studies under relatively higher concentration. As a result of recent refinements of inhalation study, all-day and life-span exposure to extremely low concentrations, such as microgram/m3 orders, of certain substances has been possible. The characteristics of lung tumors occurring in these animals are rather different from those of human. For example, in mouse, almost all of the malignant lung tumors developed by carcinogens are adenocarcinomas and it is rare to find the

Knockdown of cullin 4A inhibits growth and increases chemosensitivity in lung cancer cells.

PubMed

Hung, Ming-Szu; Chen, I-Chuan; You, Liang; Jablons, David M; Li, Ya-Chin; Mao, Jian-Hua; Xu, Zhidong; Lung, Jr-Hau; Yang, Cheng-Ta; Liu, Shih-Tung

2016-07-01

Cullin 4A (Cul4A) has been observed to be overexpressed in various cancers. In this study, the role of Cul4A in the growth and chemosensitivity in lung cancer cells were studied. We showed that Cul4A is overexpressed in lung cancer cells and tissues. Knockdown of the Cul4A expression by shRNA in lung cancer cells resulted in decreased cellular proliferation and growth in lung cancer cells. Increased sensitivity to gemcitabine, a chemotherapy drug, was also noted in those Cul4A knockdown lung cancer cells. Moreover, increased expression of p21, transforming growth factor (TGF)-β inducible early gene-1 (TIEG1) and TGF beta-induced (TGFBI) was observed in lung cancer cells after Cul4A knockdown, which may be partially related to increased chemosensitivity to gemcitabine. G0/G1 cell cycle arrest was also noted after Cul4A knockdown. Notably, decreased tumour growth and increased chemosensitivity to gemcitabine were also noted after Cul4A knockdown in lung cancer xenograft nude mice models. In summary, our study showed that targeting Cul4A with RNAi or other techniques may provide a possible insight to the development of lung cancer therapy in the future. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Profile of lung cancer in kuwait.

PubMed

El-Basmy, Amani

2013-01-01

Lung cancer is the most frequent cancer in males and the fourth most frequent site in females, worldwide. This study is the first to explore the profile of lung cancer in Kuwait. Cases of primary lung cancer (Kuwaiti) in Kuwait cancer Registry (KCR) were grouped in 4 periods (10 years each) from 1970-2009. Epidemiological measures; age standardized incidence rate (ASIR) with 95% confidence intervals (CI), Standardized rate ratio (SRR) and Cumulative risk and Forecasting to year 2020-2029 used for analysis. Between years, 2000-2009 lung cancer ranked the 4th and the 9th most frequent cancer in males and females respectively. M:F ratio 1:3. Mean age at diagnosis (95%CI) was 65.2 (63.9-66.4) years. The estimated risk of developing lung cancer before the age of 75 years in males is 1.8% (1/56), and 0.6 (1/167) in females. The ASIR for male cases was 11.7, 17.1, 17.0, 14.0 cases/100,000 population in the seventies, eighties, nineties and in 2000-2009 respectively. Female ASIR was 2.3, 8.4, 5.1, 4.4 cases/100,000 population in the same duration. Lung cancer is the leading cause cancer death in males 168 (14.2%) and the fifth cause of death due to cancer in females accounting for 6.1% of all cancer deaths. The ASMR (95%CI) was 8.1 (6.6-10.0) deaths/100,000 population and 2.8 (1.3-4.3) deaths/100,000 population in males and females respectively. The estimated Mortality to incidence Ratio was 0.6. The incidence of lung cancer between years 2000-2009 is not different from that reported in the seventies. KCR is expecting the number of lung cancer cases to increase.

Lung cancer and air pollution.

PubMed

Aoki, K; Shimizu, H

1977-12-01

The relationship between incidence of lung cancer and the volume of traffic as indicated by auto exhaust concentration was examined; the results, though suggestive, did not yield consistent evidence of the association between them. Traffic jams in Nagoya began 15 years ago, a period that may not be long enough to provide definitive data on the incidence of lung cancer. The high standardized mortality ratio (SMR) of lung cancer was observed in cities with a population of less than 1 million and guns (rural areas) along the coast, although those in the metropolitan areas with populations of more than 1 million were average. The SMR did not correlate with various socioeconomic conditions and industrial air pollution. Meteorologic or geologic conditions and ocean currents were not associated with SMR of lung cancer by city and gun. The population of a gun or of some cities was not large enough to be statistically significant, and the mortality rate of lung cancer was not always stable.

Did death certificates and a death review process agree on lung cancer cause of death in the National Lung Screening Trial?

PubMed

Marcus, Pamela M; Doria-Rose, Vincent Paul; Gareen, Ilana F; Brewer, Brenda; Clingan, Kathy; Keating, Kristen; Rosenbaum, Jennifer; Rozjabek, Heather M; Rathmell, Joshua; Sicks, JoRean; Miller, Anthony B

2016-08-01

Randomized controlled trials frequently use death review committees to assign a cause of death rather than relying on cause of death information from death certificates. The National Lung Screening Trial, a randomized controlled trial of lung cancer screening with low-dose computed tomography versus chest X-ray for heavy and/or long-term smokers ages 55-74 years at enrollment, used a committee blinded to arm assignment for a subset of deaths to determine whether cause of death was due to lung cancer. Deaths were selected for review using a pre-determined computerized algorithm. The algorithm, which considered cancers diagnosed during the trial, causes and significant conditions listed on the death certificate, and the underlying cause of death derived from death certificate information by trained nosologists, selected deaths that were most likely to represent a death due to lung cancer (either directly or indirectly) and deaths that might have been erroneously assigned lung cancer as the cause of death. The algorithm also selected deaths that might be due to adverse events of diagnostic evaluation for lung cancer. Using the review cause of death as the gold standard and lung cancer cause of death as the outcome of interest (dichotomized as lung cancer versus not lung cancer), we calculated performance measures of the death certificate cause of death. We also recalculated the trial primary endpoint using the death certificate cause of death. In all, 1642 deaths were reviewed and assigned a cause of death (42% of the 3877 National Lung Screening Trial deaths). Sensitivity of death certificate cause of death was 91%; specificity, 97%; positive predictive value, 98%; and negative predictive value, 89%. About 40% of the deaths reclassified to lung cancer cause of death had a death certificate cause of death of a neoplasm other than lung. Using the death certificate cause of death, the lung cancer mortality reduction was 18% (95% confidence interval: 4.2-25.0), as

Lung Cancer: One Disease or Many.

PubMed

O'Brien, Timothy D; Jia, Peilin; Aldrich, Melinda C; Zhao, Zhongming

2018-06-05

Lung cancer is classified as a single entity comprised of multiple histological subtypes. But how similar are these subtypes on a genetic level? This paper aims to address this question through a concise overview of germline and somatic differences between small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma. We reveal the weak overlap found between these 3 lung cancer subtypes using published data from one of the largest germline genetic studies on lung cancer to date and somatic mutation data from Catalogue of Somatic Mutations in Cancer (COSMIC). These data indicate that these 3 subtypes share very little with each other at the genetic level. At the germline SNP level, only 24 independent SNPs from 2 chromosomes were shared across all 3 subtypes. We also demonstrate that only 30 unique cancer-specific mutations overlap the 3 subtypes from COSMIC, and that this is fewer than overlapping mutations chosen at random. Finally, we show that only 3 somatic mutational signatures are shared between these 3 subtypes. This paper highlights that these 3 lung cancer subtypes may be distinct diseases at the genetic level. In the era of precision medicine, we feel that these genomic differences will be of utmost importance in the choice of lung cancer therapy in the future. © 2018 S. Karger AG, Basel.

Evaluation of a Serum Lung Cancer Biomarker Panel.

PubMed

Mazzone, Peter J; Wang, Xiao-Feng; Han, Xiaozhen; Choi, Humberto; Seeley, Meredith; Scherer, Richard; Doseeva, Victoria

2018-01-01

A panel of 3 serum proteins and 1 autoantibody has been developed to assist with the detection of lung cancer. We aimed to validate the accuracy of the biomarker panel in an independent test set and explore the impact of adding a fourth serum protein to the panel, as well as the impact of combining molecular and clinical variables. The training set of serum samples was purchased from commercially available biorepositories. The testing set was from a biorepository at the Cleveland Clinic. All lung cancer and control subjects were >50 years old and had smoked a minimum of 20 pack-years. A panel of biomarkers including CEA (carcinoembryonic antigen), CYFRA21-1 (cytokeratin-19 fragment 21-1), CA125 (carbohydrate antigen 125), HGF (hepatocyte growth factor), and NY-ESO-1 (New York esophageal cancer-1 antibody) was measured using immunoassay techniques. The multiple of the median method, multivariate logistic regression, and random forest modeling was used to analyze the results. The training set consisted of 604 patient samples (268 with lung cancer and 336 controls) and the testing set of 400 patient samples (155 with lung cancer and 245 controls). With a threshold established from the training set, the sensitivity and specificity of both the 4- and 5-biomarker panels on the testing set was 49% and 96%, respectively. Models built on the testing set using only clinical variables had an area under the receiver operating characteristic curve of 0.68, using the biomarker panel 0.81 and by combining clinical and biomarker variables 0.86. This study validates the accuracy of a panel of proteins and an autoantibody in a population relevant to lung cancer detection and suggests a benefit to combining clinical features with the biomarker results.

Evaluation of a Serum Lung Cancer Biomarker Panel

PubMed Central

Mazzone, Peter J; Wang, Xiao-Feng; Han, Xiaozhen; Choi, Humberto; Seeley, Meredith; Scherer, Richard; Doseeva, Victoria

2018-01-01

Background: A panel of 3 serum proteins and 1 autoantibody has been developed to assist with the detection of lung cancer. We aimed to validate the accuracy of the biomarker panel in an independent test set and explore the impact of adding a fourth serum protein to the panel, as well as the impact of combining molecular and clinical variables. Methods: The training set of serum samples was purchased from commercially available biorepositories. The testing set was from a biorepository at the Cleveland Clinic. All lung cancer and control subjects were >50 years old and had smoked a minimum of 20 pack-years. A panel of biomarkers including CEA (carcinoembryonic antigen), CYFRA21-1 (cytokeratin-19 fragment 21-1), CA125 (carbohydrate antigen 125), HGF (hepatocyte growth factor), and NY-ESO-1 (New York esophageal cancer-1 antibody) was measured using immunoassay techniques. The multiple of the median method, multivariate logistic regression, and random forest modeling was used to analyze the results. Results: The training set consisted of 604 patient samples (268 with lung cancer and 336 controls) and the testing set of 400 patient samples (155 with lung cancer and 245 controls). With a threshold established from the training set, the sensitivity and specificity of both the 4- and 5-biomarker panels on the testing set was 49% and 96%, respectively. Models built on the testing set using only clinical variables had an area under the receiver operating characteristic curve of 0.68, using the biomarker panel 0.81 and by combining clinical and biomarker variables 0.86. Conclusions: This study validates the accuracy of a panel of proteins and an autoantibody in a population relevant to lung cancer detection and suggests a benefit to combining clinical features with the biomarker results. PMID:29371783

Bidi smoking and lung cancer.

PubMed

Prasad, Rajendra; Singhal, Sanjay; Garg, Rajiv

2009-04-01

This article discusses the role of bidi smoking as a risk factor for lung cancer. A review of the documented evidence is presented. The literature from Pubmed has been searched using the key words 'beedi smoking', 'bidi smoking' and 'lung cancer'. The bibliographies of all papers found were further searched for additional relevant articles. After this thorough search, eight studies were found. The evidence suggests that bidi smoking poses a higher risk for lung cancer than cigarette smoking and risk further increases with both the length of time and amount of bidi smoking. The focus of tobacco control programs should be expanded to all types of tobacco use, including bidis, to reduce the increasing problem of lung cancer.

1-D grating based SPR biosensor for the detection of lung cancer biomarkers using Vroman effect

NASA Astrophysics Data System (ADS)

Teotia, Pradeep Kumar; Kaler, R. S.

2018-01-01

Grating based surface plasmon resonance waveguide biosensor have been reported for the detection of lung cancer biomarkers using Vroman effect. The proposed grating based multilayered biosensor is designed with high detection accuracy for Epidermal growth factor receptor (EGFR) and also analysed to show high detection accuracy with acceptable sensitivity for both cancer biomarkers. The introduction of periodic grating with multilayer metals generates a good resonance that make it possible for early detection of cancerous cells. Using finite difference time domain method, it is observed wavelength of biosensor get red-shifted on variations of the refractive index due to the presence of both the cancerous bio-markers. The reported detection accuracy and sensitivity of proposed biosensor is quite acceptable for both lung cancer biomarkers i.e. Carcinoembryonic antigen (CEA) and Epidermal growth factor receptor (EGFR) which further offer us label free early detection of lung cancer using these biomarkers.

Treatment Options by Stage (Small Cell Lung Cancer)

MedlinePlus

... Lung Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key ...

The risk of lung cancer among cooking adults: a meta-analysis of 23 observational studies.

PubMed

Jia, Peng-Li; Zhang, Chao; Yu, Jia-Jie; Xu, Chang; Tang, Li; Sun, Xin

2018-02-01

Cooking has been regarded as a potential risk factor for lung cancer. We aim to investigate the evidence of cooking oil fume and risk of lung cancer. Medline and Embase were searched for eligible studies. We conducted a meta-analysis to summarize the evidences of case-control or cohort studies, with subgroup analysis for the potential discrepancy. Sensitivity analysis was employed to test the robustness. We included 23 observational studies, involving 9411 lung cancer cases. Our meta-analysis found that, for cooking female, the pooled OR of cooking oil fume exposure was 1.98 (95% CI 1.54, 2.54, I 2  = 79%, n = 15) among non-smoking population and 2.00 (95% CI 1.46, 2.74, I 2  = 75%, n = 10) among partly smoking population. For cooking males, the pooled OR of lung cancer was 1.15 (95% CI 0.71, 1.87; I 2  = 80%, n = 4). When sub grouped by ventilation condition, the pooled OR for poor ventilation was 1.20 (95% CI 1.10, 1.31, I 2  = 2%) compared to good ventilation. For different cooking methods, our results suggested that stir frying (OR = 1.89, 95% CI 1.23, 2.90; I 2  = 66%) was associated with increased risk of lung cancer while not for deep frying (OR = 1.41, 95% CI 0.87, 2.29; I 2  = 5%). Sensitivity analysis suggested our results were stable. Cooking oil fume is likely to be a risk factor for lung cancer for female, regardless of smoking status. Poor ventilation may increase the risk of lung cancer. Cooking methods may have different effect on lung cancer that deep frying may be healthier than stir frying.

Current questions in HIV-associated lung cancer.

PubMed

Shcherba, Marina; Shuter, Jonathan; Haigentz, Missak

2013-09-01

In this review, we explore current questions regarding risk factors contributing to frequent and early onset of lung cancer among populations with HIV infection, treatment, and outcomes of lung cancer in HIV-infected patients as well as challenges in a newly evolving era of lung cancer screening. Lung cancer, seen in three-fold excess in HIV-infected populations, has become the most common non-AIDS defining malignancy in the highly active antiretroviral therapy era. HIV-associated lung cancer appears to be associated with young age at diagnosis, cigarette smoking, advanced stage at presentation, and a more aggressive clinical course. There is no unified explanation for these observations, and aside from traditional risk factors, HIV-related immunosuppression and biological differences might play a role. In addition to smoking cessation interventions, screening and early cancer detection in HIV-infected populations are of high clinical importance, although evidence supporting lung cancer screening in this particularly high-risk subset is currently lacking, as are prospective studies of lung cancer therapy. There is an urgent need for prospective clinical trials in HIV-associated lung cancer to improve understanding of lung cancer pathogenesis and to optimize patient care. Several clinical trials are in progress to address questions in cancer biology, screening, and treatment for this significant cause of mortality in persons with HIV infection.

[Clinical value of combined determination of serum and pleural effusion level of CEA,CYFRA21-1, TPS in the diagnosis of lung cancer].

PubMed

Huang, Fang; Wang, Xiao-li; Yang, Lian; Yin, Bin-xia; Geng, Yan; Li, Ting-ting

2008-04-01

To study the clinical value of combined determination of carcinoembryonic antigen (CEA), cytokeratin-19-fragments (CYFRA21-1) and tissue polypeptide specific antigen (TPS) levels in both serum and pleural effusion in the diagnosis of lung cancer. The levels of CEA, CYFRA21-1 and TPS in serum and pleural effusion were measured in 78 patients with lung cancer and 45 patients with benign lung disease by using electrochemiluminescence and ELISA methods respectively. The levels of CEA, CYFRA21-1 and TPS in pleural effusion of patients with lung cancer were much higher than those with benign lung disease (P<0.01). The levels of CEA and TPS in serum of patients with lung cancer were much higher than those with benign lung disease (P<0.05, P<0.01). It was also found that the levels of these tumor markers in pleural effusion were higher and more sensitive than those in sera, especially TPS. TPS showed the highest sensitivity in single tumor marker detection, and TPS+CYFRA21-1+ CEA showed the highest sensitivity and accuracy in combined tumor marker detection for diagnosis of lung cancer in pleural effusion. The combined detection of CEA, CYFRA21-1 and TPS in pleural effusion showed higher sensitivity, better accuracy and higher clinical value than those in serum for diagnosis of lung cancer.

Customizing Therapies for Lung Cancer | Center for Cancer Research

Cancer.gov

Lung cancer is the leading cause of cancer-related death in both men and women. Although there have been modest improvements in short-term survival over the last few decades, five-year survival rates for lung cancer remain low at only 16 percent. Treatment for lung cancer depends on the stage of the disease at diagnosis, but generally consists of some combination of surgery, chemotherapy, and radiation therapy. Increasing attention has been paid in recent years to customizing therapies based on the molecular characteristics of patients’ tumors. Some of these targeted regimens have already been integrated into the treatment arsenal for lung cancer and others are still being studied in clinical trials, including several being conducted by researchers at NCI’s Center for Cancer Research.

Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer.

PubMed

Staquicini, Fernanda I; Qian, Ming D; Salameh, Ahmad; Dobroff, Andrey S; Edwards, Julianna K; Cimino, Daniel F; Moeller, Benjamin J; Kelly, Patrick; Nunez, Maria I; Tang, Ximing; Liu, Diane D; Lee, J Jack; Hong, Waun Ki; Ferrara, Fortunato; Bradbury, Andrew R M; Lobb, Roy R; Edelman, Martin J; Sidman, Richard L; Wistuba, Ignacio I; Arap, Wadih; Pasqualini, Renata

2015-03-20

Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. Finally, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lung cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Impacts of Exercise on Prognostic Biomarkers in Lung Cancer Patients

ClinicalTrials.gov

2016-02-18

Extensive Stage Small Cell Lung Cancer; Healthy, no Evidence of Disease; Limited Stage Small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

Cost-effectiveness of an autoantibody test (EarlyCDT-Lung) as an aid to early diagnosis of lung cancer in patients with incidentally detected pulmonary nodules.

PubMed

Edelsberg, John; Weycker, Derek; Atwood, Mark; Hamilton-Fairley, Geoffrey; Jett, James R

2018-01-01

Patients who have incidentally detected pulmonary nodules and an estimated intermediate risk (5-60%) of lung cancer frequently are followed via computed tomography (CT) surveillance to detect nodule growth, despite guidelines for a more aggressive diagnostic strategy. We examined the cost-effectiveness of an autoantibody test (AABT)-Early Cancer Detection Test-Lung (EarlyCDT-LungTM)-as an aid to early diagnosis of lung cancer among such patients. We developed a decision-analytic model to evaluate use of the AABT versus CT surveillance alone. In the model, patients with a positive AABT-because they are at substantially enhanced risk of lung cancer-are assumed to go directly to biopsy, resulting in diagnosis of lung cancer in earlier stages than under current guidelines (a beneficial stage shift). Patients with a negative AABT, and those scheduled for CT surveillance alone, are assumed to have periodic CT screenings to detect rapid growth and thus to have their lung cancers diagnosed-on average-at more advanced stages. Among 1,000 patients who have incidentally detected nodules 8-30 mm, have an intermediate-risk of lung cancer, and are evaluated by CT surveillance alone, 95 (9.5%) are assumed to have lung cancer (local, 73.6%; regional, 22.0%; distant, 4.4%). With use of the AABT set at a sensitivity/specificity of 41%/93% (stage shift = 10.8%), although expected costs would be higher by $949,442 ($949 per person), life years would be higher by 53 (0.05 per person), resulting in a cost per life-year gained of $18,029 and a cost per quality-adjusted life year (QALY) gained of $24,330. With use of the AABT set at a sensitivity/specificity of 28%/98% (stage shift = 7.4%), corresponding cost-effectiveness ratios would be $18,454 and $24,833. Under our base-case assumptions, and reasonable variations thereof, using AABT as an aid in the early diagnosis of lung cancer in patients with incidentally detected pulmonary nodules who are estimated to be at intermediate risk of

Danshen improves survival of patients with advanced lung cancer and targeting the relationship between macrophages and lung cancer cells

PubMed Central

Wu, Ching-Yuan; Cherng, Jong-Yuh; Yang, Yao-Hsu; Lin, Chun-Liang; Kuan, Feng-Che; Lin, Yin-Yin; Lin, Yu-Shih; Shu, Li-Hsin; Cheng, Yu-Ching; Liu, Hung Te; Lu, Ming-Chu; Lung, Jthau; Chen, Pau-Chung; Lin, Hui Kuan; Lee, Kuan-Der; Tsai, Ying-Huang

2017-01-01

In traditional Chinese medicine, Salvia miltiorrhiza Bunge (danshen) is widely used in the treatment of numerous cancers. However, its clinical effort and mechanism in the treatment of advanced lung cancer are unclear. In our study, the in vivo protective effort of danshen in patients with advanced lung cancer were validated using data from the National Health Insurance Research Database in Taiwan. We observed in vitro that dihydroisotanshinone I (DT), a bioactive compound in danshen, exerts anticancer effects through many pathways. First, 10 μM DT substantially inhibited the migration ability of lung cancer cells in both macrophage and macrophage/lung cancer direct mixed coculture media. Second, 10 μM DT repressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3), the protein expression of S-phase kinase associated protein-2 (Skp2), and the mRNA levels of STAT3-related genes, including chemokine (C–C motif) ligand 2 (CCL2). In addition, 10 μM DT suppressed the macrophage recruitment ability of lung cancer cells by reducing CCL2 secretion from both macrophages and lung cancer cells. Third, 20 μM DT induced apoptosis in lung cancer cells. Furthermore, DT treatment significantly inhibited the final tumor volume in a xenograft nude mouse model. In conclusion, danshen exerts protective efforts in patients with advanced lung cancer. These effects can be attributed to DT-mediated interruption of the cross talk between lung cancer cells and macrophages and blocking of lung cancer cell proliferation. PMID:29207614

Expression of pleiotrophin in small cell lung cancer.

PubMed

Wang, H Q; Wang, J

2015-01-01

Pleiotrophin (PTN) is a kind of heparin binding growth factor closely related to tumor progression. This study aimed to discuss the significance of the expression of PTN in benign and malignant lung cancer tissues, especially small cell lung cancer. Lung cancer samples were collected for study and lung tissue samples with benign lesions were taken as controls. The expression of PTN was detected using tissue chip combined with the immunohistochemical method, and the differences of small cell lung cancer with non-small cell lung cancer and benign lesion tissue were compared. It was found that PTN expression was mainly located in the cytoplasm and membrane of cells; PTN expression in the lung cancer group was higher than that in the control group (p < 0.01), and PTN expression in the small cell cancer group was higher than that in the squamous carcinoma group and glandular cancer group (p < 0.05). In addition, PTN expression quantity in patients with lung cancer were in close correlation with TNM staging, pathological type and tumor differentiation degree (p < 0.05). PTN was found to express abnormally high in lung cancer, especially small cell lung cancer tissue. PTN is most likely to be a new tumor marker for diagnosis and prognosis of lung cancer.

Hedgehog Pathway Inhibition Radiosensitizes Non-Small Cell Lung Cancers

PubMed Central

Zeng, Jing; Aziz, Khaled; Chettiar, Sivarajan T.; Aftab, Blake T.; Armour, Michael; Gajula, Rajendra; Gandhi, Nishant; Salih, Tarek; Herman, Joseph M.; Wong, John; Rudin, Charles M.; Tran, Phuoc T.; Hales, Russell K.

2012-01-01

Purpose Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. Methods and Materials We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntag and radiation. In a transgenic mouse model of KrasG12D-induced and Twist1-induced lung adenocarcinoma, we assessed tumor response to radiation and HhAntag by serial micro-computed tomography (CT) scanning. Results In 4 human lung cancer lines in vitro, HhAntag showed little or no effect on radio-sensitivity. By contrast, in both the human tumor xenograft and murine inducible transgenic models, HhAntag enhanced radiation efficacy and delayed tumor growth. By use of the human xenograft model to differentiate tumor and stromal effects, mouse stromal cells, but not human tumor cells, showed significant and consistent downregulation of Hedgehog pathway gene expression. This was associated with increased tumor cell apoptosis. Conclusions Targeted Hedgehog pathway inhibition can increase in vivo radiation efficacy in lung cancer preclinical models. This effect is associated with pathway suppression in tumor-associated stroma. These data support clinical testing of Hedgehog inhibitors as a component of multimodality therapy for locally advanced non-small cell lung cancer. PMID:23182391

TG4010 and Nivolumab in Patients With Lung Cancer

ClinicalTrials.gov

2018-03-01

Recurrent Non-Small Cell Lung Carcinoma; Stage I Non-Small Cell Lung Cancer; Stage II Non-Small Cell Lung Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

Cannabis smoking and lung cancer risk: Pooled analysis in the International Lung Cancer Consortium

PubMed Central

Zhang, Li Rita; Morgenstern, Hal; Greenland, Sander; Chang, Shen-Chih; Lazarus, Philip; Teare, M. Dawn; Woll, Penella J.; Orlow, Irene; Cox, Brian; Brhane, Yonathan; Liu, Geoffrey; Hung, Rayjean J.

2014-01-01

To investigate the association between cannabis smoking and lung cancer risk, data on 2,159 lung cancer cases and 2,985 controls were pooled from 6 case-control studies in the US, Canada, UK, and New Zealand within the International Lung Cancer Consortium. Study-specific associations between cannabis smoking and lung cancer were estimated using unconditional logistic regression adjusting for sociodemographic factors, tobacco smoking status and pack-years; odds-ratio estimates were pooled using random effects models. Subgroup analyses were done for sex, histology and tobacco smoking status. The shapes of dose-response associations were examined using restricted cubic spline regression. The overall pooled OR for habitual versus nonhabitual or never users was 0.96 (95% CI: 0.66–1.38). Compared to nonhabitual or never users, the summary OR was 0.88 (95%CI: 0.63–1.24) for individuals who smoked 1 or more joint-equivalents of cannabis per day and 0.94 (95%CI: 0.67–1.32) for those consumed at least 10 joint-years. For adenocarcinoma cases the ORs were 1.73 (95%CI: 0.75–4.00) and 1.74 (95%CI: 0.85–3.55), respectively. However, no association was found for the squamous cell carcinoma based on small numbers. Weak associations between cannabis smoking and lung cancer were observed in never tobacco smokers. Spline modeling indicated a weak positive monotonic association between cumulative cannabis use and lung cancer, but precision was low at high exposure levels. Results from our pooled analyses provide little evidence for an increased risk of lung cancer among habitual or long-term cannabis smokers, although the possibility of potential adverse effect for heavy consumption cannot be excluded. PMID:24947688

A Bronchial Genomic Classifier for the Diagnostic Evaluation of Lung Cancer.

PubMed

Silvestri, Gerard A; Vachani, Anil; Whitney, Duncan; Elashoff, Michael; Porta Smith, Kate; Ferguson, J Scott; Parsons, Ed; Mitra, Nandita; Brody, Jerome; Lenburg, Marc E; Spira, Avrum

2015-07-16

Bronchoscopy is frequently nondiagnostic in patients with pulmonary lesions suspected to be lung cancer. This often results in additional invasive testing, although many lesions are benign. We sought to validate a bronchial-airway gene-expression classifier that could improve the diagnostic performance of bronchoscopy. Current or former smokers undergoing bronchoscopy for suspected lung cancer were enrolled at 28 centers in two multicenter prospective studies (AEGIS-1 and AEGIS-2). A gene-expression classifier was measured in epithelial cells collected from the normal-appearing mainstem bronchus to assess the probability of lung cancer. A total of 639 patients in AEGIS-1 (298 patients) and AEGIS-2 (341 patients) met the criteria for inclusion. A total of 43% of bronchoscopic examinations were nondiagnostic for lung cancer, and invasive procedures were performed after bronchoscopy in 35% of patients with benign lesions. In AEGIS-1, the classifier had an area under the receiver-operating-characteristic curve (AUC) of 0.78 (95% confidence interval [CI], 0.73 to 0.83), a sensitivity of 88% (95% CI, 83 to 92), and a specificity of 47% (95% CI, 37 to 58). In AEGIS-2, the classifier had an AUC of 0.74 (95% CI, 0.68 to 0.80), a sensitivity of 89% (95% CI, 84 to 92), and a specificity of 47% (95% CI, 36 to 59). The combination of the classifier plus bronchoscopy had a sensitivity of 96% (95% CI, 93 to 98) in AEGIS-1 and 98% (95% CI, 96 to 99) in AEGIS-2, independent of lesion size and location. In 101 patients with an intermediate pretest probability of cancer, the negative predictive value of the classifier was 91% (95% CI, 75 to 98) among patients with a nondiagnostic bronchoscopic examination. The gene-expression classifier improved the diagnostic performance of bronchoscopy for the detection of lung cancer. In intermediate-risk patients with a nondiagnostic bronchoscopic examination, a negative classifier score provides support for a more conservative diagnostic

Racing Against Lung Cancer: Imaging Tools Help Patient in Cancer Fight

MedlinePlus

... Against Lung Cancer Follow us Racing Against Lung Cancer Imaging tools help patient in cancer fight Photo: Courtesy of Ted Simon In early ... primary care doctor. The diagnosis? Stage 4 lung cancer—advanced cancer that had already spread to some ...

Saudi lung cancer management guidelines 2017.

PubMed

Jazieh, Abdul Rahman; Al Kattan, Khaled; Bamousa, Ahmed; Al Olayan, Ashwaq; Abdelwarith, Ahmed; Ansari, Jawaher; Al Twairqi, Abdullah; Al Fayea, Turki; Al Saleh, Khalid; Al Husaini, Hamed; Abdelhafiez, Nafisa; Mahrous, Mervat; Faris, Medhat; Al Omair, Ameen; Hebshi, Adnan; Al Shehri, Salem; Al Dayel, Foad; Bamefleh, Hanaa; Khalbuss, Walid; Al Ghanem, Sarah; Loutfi, Shukri; Khankan, Azzam; Al Rujaib, Meshael; Al Ghamdi, Majed; Ibrahim, Nagwa; Swied, Abdulmonem; Al Kayait, Mohammad; Datario, Marie

2017-01-01

Lung cancer management is getting more complex due to the rapid advances in all aspects of diagnostic and therapeutic options. Developing guidelines is critical to help practitioners provide standard of care. The Saudi Lung Cancer Guidelines Committee (SLCGC) multidisciplinary members from different specialties and from various regions and healthcare sectors of the country reviewed and updated all lung cancer guidelines with appropriate labeling of level of evidence. Supporting documents to help healthcare professionals were developed. Detailed lung cancer management guidelines were finalized with appropriate resources for systemic therapy and short reviews highlighting important issues. Stage based disease management recommendation were included. A summary explanation for complex topics were included in addition to tables of approved systemic therapy. A multidisciplinary lung cancer guidelines was developed and will be disseminated across the country.

Development of a computer-aided detection system for lung cancer diagnosis

NASA Astrophysics Data System (ADS)

Suzuki, Hideo; Inaoka, Noriko; Takabatake, Hirotsugu; Mori, Masaki; Sasaoka, Soichi; Natori, Hiroshi; Suzuki, Akira

1992-06-01

This paper describes a modified system for automatic detection of lung nodules by means of chest x ray image processing techniques. The objective of the system is to help radiologists to improve their accuracy in cancer detection. It is known from retrospective studies of chest x- ray images that radiologists fail to detect about 30 percent of lung cancer cases. A computerized method for detecting lung nodules would be very useful for decreasing the proportion of such oversights. Our proposed system consists of five sub-systems, for image input, lung region determination, nodule detection, rule-based false-positive elimination, and statistical false-positive elimination. In an experiment with the modified system, using 30 lung cancer cases and 78 normal control cases, we obtained figures of 73.3 percent and 89.7 percent for the sensitivity and specificity of the system, respectively. The system has been developed to run on the IBM* PS/55* and IBM RISC System/6000* (RS/6000), and we give the processing time for each platform.

Metformin Sensitizes Non-small Cell Lung Cancer Cells to an Epigallocatechin-3-Gallate (EGCG) Treatment by Suppressing the Nrf2/HO-1 Signaling Pathway.

PubMed

Yu, Chenxiao; Jiao, Yang; Xue, Jiao; Zhang, Qi; Yang, Hongying; Xing, Ligang; Chen, Guangxia; Wu, Jinchang; Zhang, Shuyu; Zhu, Wei; Cao, Jianping

2017-01-01

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. (-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, is widely studied as a cancer chemopreventive agent with potential anti-cancer effects. The NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway is considered to mediate cellular resistance to EGCG. Metformin, a classical antidiabetic drug, has been shown to prevent cancer progression. Researchers have not reported whether metformin potentiates the anti-cancer efficacy of EGCG. In this study, metformin inhibited HO-1 expression and augmented the anti-tumor effect of EGCG. Metformin also enhanced ROS (reactive oxygen species) generation induced by EGCG (100 μM), subsequently resulting in apoptosis. Based on the results of the in vivo study, size of xenografts treated with the combination of metformin and EGCG was smaller than other groups. Mechanistically, metformin modulated the EGCG-activated Nrf2/HO-1 pathway through Sirtuin 1 (SIRT1)-dependent deacetylation of Nrf2. Moreover, metformin upregulated SIRT1 expression partially through the NF-kB pathway. Comparatively, the combination of EGCG and metformin showed little impact on normal lung epithelial BEAS-2B cells. Based on our findings, metformin sensitized NSCLC cells to the EGCG treatment by suppressing the Nrf2/HO-1 signaling pathway.

Lung Cancer Brain Metastases.

PubMed

Goldberg, Sarah B; Contessa, Joseph N; Omay, Sacit B; Chiang, Veronica

2015-01-01

Brain metastases are common among patients with lung cancer and have been associated with significant morbidity and limited survival. However, the treatment of brain metastases has evolved as the field has advanced in terms of central nervous system imaging, surgical technique, and radiotherapy technology. This has allowed patients to receive improved treatment with less toxicity and more durable benefit. In addition, there have been significant advances in systemic therapy for lung cancer in recent years, and several treatments including chemotherapy, targeted therapy, and immunotherapy exhibit activity in the central nervous system. Utilizing systemic therapy for treating brain metastases can avoid or delay local therapy and often allows patients to receive effective treatment for both intracranial and extracranial disease. Determining the appropriate treatment for patients with lung cancer brain metastases therefore requires a clear understanding of intracranial disease burden, tumor histology, molecular characteristics, and overall cancer prognosis. This review provides updates on the current state of surgery and radiotherapy for the treatment of brain metastases, as well as an overview of systemic therapy options that may be effective in select patients with intracranial metastases from lung cancer.

[Radiation-induced modification of human somatic cell chromosome sensitivity to the testing mutagenic exposure of bleomycin in vitro in lung cancer patients in delayed terms following Chernobyl accident].

PubMed

Pilinskaia, M A; Dybskiĭ, S S; Dybskaia, E B; Shvaĭko, L I

2012-01-01

By using modified "G2-bleomycin sensitivity assay" above background level of cytogenetic effect considered as a marker of hidden chromosome instability (HCI) has been investigated in 3 groups--liquidators of Chernobyl accident (occupational group 1), patients with lung cancer who denied conscious contact--with ionizing radiation (group of comparison), liquidators with lung cancer (occupational group 2). Significant interindividual variations of cytogenetic effects induced with bleomycin and the lack of positive correlation between background and above background frequencies of chromosome aberrations have been shown in all observed groups. It had been established that occupational group 2 was the most burdened group by expression of the above background cytogenetic effect and, accordingly, number of persons with HCI. The data obtained permit to suggest the existence of the association between radiation-induced increase of individual sensitivity to testing mutagenic exposure and the realization of cancer in persons exposed to ionizing radiation. The results show acceptability of "G2-bleomycin sensitivity assay" under the cytogenetic examination of irradiated contingents for determining HCI as one of informative markers of predisposition to oncopathology.

A combinatorial strategy for treating KRAS mutant lung cancer

PubMed Central

Manchado, Eusebio; Weissmueller, Susann; Morris, John P.; Chen, Chi-Chao; Wullenkord, Ramona; Lujambio, Amaia; de Stanchina, Elisa; Poirier, John T.; Gainor, Justin F.; Corcoran, Ryan B.; Engelman, Jeffrey A.; Rudin, Charles M.; Rosen, Neal; Lowe, Scott W.

2016-01-01

Therapeutic targeting of KRAS-mutant lung adenocarcinoma represents a major goal of clinical oncology. KRAS itself has proven difficult to inhibit, and the effectiveness of agents that target key KRAS effectors has been thwarted by activation of compensatory or parallel pathways that limit their efficacy as single agents. Here we take a systematic approach towards identifying combination targets for trametinib, an FDA-approved MEK inhibitor that acts downstream of KRAS to suppress signaling through the mitogen-activated protein kinase (MAPK) cascade. Informed by a short-hairpin RNA (shRNA) screen, we show that trametinib provokes a compensatory response involving the fibroblast growth factor receptor 1 (FGFR1) that leads to signaling rebound and adaptive drug resistance. As a consequence, genetic or pharmacologic inhibition of FGFR1 in combination with trametinib enhances tumor cell death in vitro and in vivo. This compensatory response shows distinct specificities – it is dominated by FGFR1 in KRAS mutant lung and pancreatic cancer cells, but is not activated or involves other mechanisms in KRAS wild-type lung and KRAS-mutant colon cancer cells. Importantly, KRAS-mutant lung cancer cells and patient tumors treated with trametinib show an increase in FRS2 phosphorylation, a biomarker of FGFR activation; this increase is abolished by FGFR1 inhibition and correlates with sensitivity to trametinib and FGFR inhibitor combinations. These results demonstrate that FGFR1 can mediate adaptive resistance to trametinib and validate a combinatorial approach for treating KRAS-mutant lung cancer. PMID:27338794

Mig6 Puts the Brakes on Mutant EGFR-Driven Lung Cancer | Center for Cancer Research

Cancer.gov

Lung cancer is the most common cause of cancer-related death worldwide. These cancers are often induced by mutations in the epidermal growth factor receptor (EGFR), resulting in constitutive activation of the protein’s tyrosine kinase domain. Lung cancers expressing these EGFR mutants are initially sensitive to tyrosine kinase inhibitors (TKIs), such as erlotinib, but often become resistant by developing compensatory mutations in EGFR or other growth-promoting pathways. To better understand how mutant EGFR initiates and maintains tumor growth in the hopes of identifying novel targets for drug development, Udayan Guha, M.D., Ph.D., of CCR’s Thoracic and Gastrointestinal Oncology Branch, and his colleagues examined the landscape of proteins phosphorylated in EGFR wild type and mutant cells. One protein hyper-phosphorylated in mutant EGFR cells was Mig6, a putative tumor suppressor.

Maternal lung cancer and testicular cancer risk in the offspring.

PubMed

Kaijser, Magnus; Akre, Olof; Cnattingius, Sven; Ekbom, Anders

2003-07-01

It has been hypothesized that smoking during pregnancy could increase the offspring's risk for testicular cancer. This hypothesis is indirectly supported by both ecological studies and studies of cancer aggregations within families. However, results from analytical epidemiological studies are not consistent, possibly due to methodological difficulties. To further study the association between smoking during pregnancy and testicular cancer, we did a population-based cohort study on cancer risk among offspring of women diagnosed with lung cancer. Through the use of the Swedish Cancer Register and the Swedish Second-Generation Register, we identified 8,430 women who developed lung cancer between 1958 and 1997 and delivered sons between 1941 and 1979. Cancer cases among the male offspring were then identified through the Swedish Cancer Register. Standardized incidence ratios were computed, using 95% confidence intervals. We identified 12,592 male offspring of mothers with a subsequent diagnosis of lung cancer, and there were 40 cases of testicular cancer (standardized incidence ratio, 1.90; 95% confidence interval, 1.35-2.58). The association was independent of maternal lung cancer subtype, and the risk of testicular cancer increased stepwise with decreasing time interval between birth and maternal lung cancer diagnosis. Our results support the hypothesis that exposure to cigarette smoking in utero increases the risk of testicular cancer.

Lung Cancer Precision Medicine Trials

Cancer.gov

Patients with lung cancer are benefiting from the boom in targeted and immune-based therapies. With a series of precision medicine trials, NCI is keeping pace with the rapidly changing treatment landscape for lung cancer.

Saudi lung cancer management guidelines 2017

PubMed Central

Jazieh, Abdul Rahman; Al Kattan, Khaled; Bamousa, Ahmed; Al Olayan, Ashwaq; Abdelwarith, Ahmed; Ansari, Jawaher; Al Twairqi, Abdullah; Al Fayea, Turki; Al Saleh, Khalid; Al Husaini, Hamed; Abdelhafiez, Nafisa; Mahrous, Mervat; Faris, Medhat; Al Omair, Ameen; Hebshi, Adnan; Al Shehri, Salem; Al Dayel, Foad; Bamefleh, Hanaa; Khalbuss, Walid; Al Ghanem, Sarah; Loutfi, Shukri; Khankan, Azzam; Al Rujaib, Meshael; Al Ghamdi, Majed; Ibrahim, Nagwa; Swied, Abdulmonem; Al Kayait, Mohammad; Datario, Marie

2017-01-01

BACKGROUND: Lung cancer management is getting more complex due to the rapid advances in all aspects of diagnostic and therapeutic options. Developing guidelines is critical to help practitioners provide standard of care. METHODS: The Saudi Lung Cancer Guidelines Committee (SLCGC) multidisciplinary members from different specialties and from various regions and healthcare sectors of the country reviewed and updated all lung cancer guidelines with appropriate labeling of level of evidence. Supporting documents to help healthcare professionals were developed. RESULTS: Detailed lung cancer management guidelines were finalized with appropriate resources for systemic therapy and short reviews highlighting important issues. Stage based disease management recommendation were included. A summary explanation for complex topics were included in addition to tables of approved systemic therapy. CONCLUSION: A multidisciplinary lung cancer guidelines was developed and will be disseminated across the country. PMID:29118855

Role of natural killer cells in lung cancer.

PubMed

Aktaş, Ozge Nur; Öztürk, Ayşe Bilge; Erman, Baran; Erus, Suat; Tanju, Serhan; Dilege, Şükrü

2018-06-01

One of the key immune cells involved in the pathogenesis of lung cancer is natural killer (NK) cells and these cells are novel targets for therapeutic applications in lung cancer. The purpose of this review is to summarize the current literature on lung cancer pathogenesis with a focus on the interaction between NK cells and smoking, how these factors are related to the pathogenesis of lung cancer and how NK cell-based immunotherapy effect lung cancer survival. The relevant literature from PubMed and Medline databases is reviewed in this article. The cytolytic potential of NK cells are reduced in lung cancer and increasing evidence suggests that improving NK cell functioning may induce tumor regression. Recent clinical trials on NK cell-based novel therapies such as cytokines including interleukin (IL)-15, IL-12 and IL-2, NK-92 cell lines and allogenic NK cell immunotherapy showed promising results with less adverse effects on the lung cancer survival. The NK cell targeting strategy has not yet been approved for lung cancer treatment. More clinical studies focusing on the role of NK cells in lung cancer pathogenesis are warranted to develop novel NK cell-based therapeutic approaches for the treatment of lung cancer.

Classification of lung cancer patients and controls by chromatography of modified nucleosides in serum

USGS Publications Warehouse

McEntire, John E.; Kuo, Kenneth C.; Smith, Mark E.; Stalling, David L.; Richens, Jack W.; Zumwalt, Robert W.; Gehrke, Charles W.; Papermaster, Ben W.

1989-01-01

A wide spectrum of modified nucleosides has been quantified by high-performance liquid chromatography in serum of 49 male lung cancer patients, 35 patients with other cancers, and 48 patients hospitalized for nonneoplastic diseases. Data for 29 modified nucleoside peaks were normalized to an internal standard and analyzed by discriminant analysis and stepwise discriminant analysis. A model based on peaks selected by a stepwise discriminant procedure correctly classified 79% of the cancer and 75% of the noncancer subjects. It also demonstrated 84% sensitivity and 79% specificity when comparing lung cancer to noncancer subjects, and 80% sensitivity and 55% specificity in comparing lung cancer to other cancers. The nucleoside peaks having the greatest influence on the models varied dependent on the subgroups compared, confirming the importance of quantifying a wide array of nucleosides. These data support and expand previous studies which reported the utility of measuring modified nucleoside levels in serum and show that precise measurement of an array of 29 modified nucleosides in serum by high-performance liquid chromatography with UV scanning with subsequent data modeling may provide a clinically useful approach to patient classification in diagnosis and subsequent therapeutic monitoring.

Molecular understanding of lung cancers-A review

PubMed Central

Singh, Chinnappan Ravinder; Kathiresan, Kandasamy

2014-01-01

Lung cancer is considered to be the most common cancer in the world. The purpose of this paper is to review scientific evidence, particularly epidemiologic evidence of overall lung cancer burden in the world. And molecular understanding of lung cancer at various levels by dominant and suppressor oncogenes. PMID:25183110

Inhibition of SRC-3 enhances sensitivity of human cancer cells to histone deacetylase inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zou, Zhengzhi, E-mail: zouzhengzhi@m.scnu.edu.cn; Luo, Xiaoyong; Nie, Peipei

SRC-3 is widely expressed in multiple tumor types and involved in cancer cell proliferation and apoptosis. Histone deacetylase (HDAC) inhibitors are promising antitumor drugs. However, the poor efficacy of HDAC inhibitors in solid tumors has restricted its further clinical application. Here, we reported the novel finding that depletion of SRC-3 enhanced sensitivity of breast and lung cancer cells to HDAC inhibitors (SAHA and romidepsin). In contrast, overexpression of SRC-3 decreased SAHA-induced cancer cell apoptosis. Furthermore, we found that SRC-3 inhibitor bufalin increased cancer cell apoptosis induced by HDAC inhibitors. The combination of bufalin and SAHA was particular efficient in attenuatingmore » AKT activation and reducing Bcl-2 levels. Taken together, these accumulating data might guide development of new breast and lung cancer therapies. - Highlights: • Depletion of SRC-3 enhanced sensitivity of breast and lung cancer cells to HDAC inhibitors. • Overexpression of SRC-3 enhanced cancer cell resistance to HDAC inhibitors. • SRC-3 inhibitor bufalin increased cancer cell apoptosis induced by HDAC inhibitors. • Bufalin synergized with HDAC inhibitor attenuated AKT activation and reduced Bcl-2 levels in human cancer cell.« less

The evolution of lung cancer screening.

PubMed

Wilkinson, Neal W; Loewen, Gregory M; Klippenstein, Donald L; Litwin, Alan M; Anderson, Timothy M

2003-12-01

In the 1970s, four trials failed to demonstrate any mortality reduction using a combination of chest X-ray (CXR) and/or sputum cytology. The recent early lung cancer action project (ELCAP) demonstrated that modern screening is capable of detecting Stage I lung cancers. Bronchial epithelial changes leading up to cancers are now being understood to include histologic changes and genetic alterations. Emerging molecular markers detected in sputum and serum show promise in the future of lung cancer screening.

Metachronous Lung Cancer: Clinical Characteristics and Effects of Surgical Treatment.

PubMed

Rzechonek, Adam; Błasiak, Piotr; Muszczyńska-Bernhard, Beata; Pawełczyk, Konrad; Pniewski, Grzegorz; Ornat, Maciej; Grzegrzółka, Jędrzej; Brzecka, Anna

2018-01-01

The occurrence of a second lung tumor after surgical removal of lung cancer usually indicates a lung cancer metastasis, but sometimes a new lesion proves to be a new primary lung cancer, i.e., metachronous lung cancer. The goal of the present study was to conduct a clinical evaluation of patients with metachronous lung cancer and lung cancer metastasis, and to compare the early and distant outcomes of surgical treatment in both cancer types. There were 26 age-matched patients with lung cancer metastases and 23 patients with metachronous lung cancers, who underwent a second lung cancer resection. We evaluated the histological type of a resected cancer, the extent of thoracosurgery, the frequency of early postoperative complications, and the probability of 5-year survival after the second operation. The findings were that metachronous lung cancer was adenocarcinoma in 52% of patients, with a different histopathological pattern from that of the primary lung cancer in 74% of patients. In both cancer groups, mechanical resections were the most common surgery type (76% of all cases), with anatomical resections such as segmentectomy, lobectomy, or pneumectomy being much rarer conducted. The incidence of early postoperative complications in metachronous lung cancer and lung cancer metastasis (30% vs. 31%, respectively) and the probability of 5-year survival after resection of either cancer tumor (60.7% vs. 50.9%, respectively) were comparable. In conclusion, patients undergoing primary lung cancer surgery require a long-term follow-up due to the risk of metastatic or metachronous lung cancer. The likelihood of metachronous lung cancer and pulmonary lung cancer metastases, the incidence of postoperative complications, and the probability of 5-year survival after resection of metachronous lung cancer or lung cancer metastasis are similar.

[Possible Significance of Bronchoalveolar Lavage Cytology at Initial Diagnosis and Follow-up of Lung Cancer].

PubMed

Grünewaldt, A; Hügel, C; Hermann, E; Wagner, T O F

2017-02-01

Bronchoalveolar lavage [BAL] is an important procedure in the diagnosis of a variety of lung diseases. While it has enormous value in the diagnostics of inflammatory parenchymal diseases, its significance in lung cancer is unclear. Keeping in mind that immune therapy (e. g. application of checkpoint inhibitors) is gaining importance in the management of lung carcinoma, it is important to know if there are typical cellular patterns in BAL of lung cancer patients. Methods  In a retrospective proof of principle-study, we analyzed 38 patients who underwent BAL at the initial diagnosis of lung cancer. Results  We observed an elevated level of CD25 lymphocytes as well as an increased expression of DR antigen, both signaling lymphocyte activation. We could not find a typical cytologic pattern of inflammatory cells in lung carcinoma patients. Sensitivity of BAL to malignant cells was rare, thus confirming earlier analysis. Conclusion  We could not demonstrate typical cellular patterns in BAL of lung cancer patients. Evaluation of specific microRNA patterns might play a supporting role in the initial diagnosis as well as follow-up of lung cancer patients. © Georg Thieme Verlag KG Stuttgart · New York.

Lung Cancer Screening (PDQ®)—Health Professional Version

Cancer.gov

Lung cancer screening with low-dose spiral CT scans has been shown to decrease the risk of dying from lung cancer in heavy smokers. Screening with chest x-ray or sputum cytology does not reduce lung cancer mortality. Get detailed information about lung cancer screening in this clinician summary.

HIF1α regulated expression of XPA contributes to cisplatin resistance in lung cancer

PubMed Central

Liu, Yanbin; Bernauer, Amanda M.; Yingling, Christin M.; Belinsky, Steven A.

2012-01-01

Factors regulating nucleotide excision repair probably contribute to the heterogenous response of advanced stage lung cancer patients to drugs such as cisplatin. Studies to identify the genes in the nucleotide excision repair pathway most closely associated with resistance to cisplatin have not been conclusive. We hypothesized that Xeroderma pigmentosum complementation group A (XPA), because of its dual role in sensing and recruiting other DNA repair proteins to the damaged template, would be critical in defining sensitivity to cisplatin. Studies were conducted to identify factors regulating transcription of XPA, to assess its role in modulating sensitivity to cisplatin and its expression in primary lung tumors. Hypoxia-inducible factor 1 alpha (HIF1α) subunit was found to bind with strong affinity to a hypoxia response element sequence in the promoter of XPA. Modulating expression of HIF1α by small interfering RNA or cobalt chloride markedly reduced or increased transcription of XPA in lung cancer cell lines, respectively. Protein levels of XPA were strongly correlated with sensitivity to cisplatin (r = 0.88; P < 0.001) in cell lines and sensitivity could be increased by small interfering RNA depletion of XPA. Expression of XPA determined in 54 primary lung tumors was elevated on average 5.2-fold when compared with normal bronchial epithelial cells and correlated with levels of HIF1α (r = 0.58; P < 0.01). Together, these studies identify XPA as a novel target for regulation by HIF1α whose modulation could impact lung cancer therapy. PMID:22467238

Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer

DOE PAGES

Staquicini, Fernanda I.; Qian, Ming D.; Salameh, Ahmad; ...

2015-03-20

Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. In conclusion, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lungmore » cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications.« less

Lung Cancer Screening (PDQ®)—Patient Version

Cancer.gov

Lung cancer screening with low-dose spiral CT scans has been shown to decrease the risk of dying from lung cancer in heavy smokers. Learn more about tests to detect lung cancer and their potential benefits and harms in this expert-reviewed summary.

Parity and risk of lung cancer in women.

PubMed

Paulus, Jessica K; Asomaning, Kofi; Kraft, Peter; Johnson, Bruce E; Lin, Xihong; Christiani, David C

2010-03-01

Patterns of lung cancer incidence suggest that gender-associated factors may influence lung cancer risk. Given the association of parity with risk of some women's cancers, the authors hypothesized that childbearing history may also be associated with lung cancer. Women enrolled in the Lung Cancer Susceptibility Study at Massachusetts General Hospital (Boston, Massachusetts) between 1992 and 2004 (1,004 cases, 848 controls) were available for analysis of the association between parity and lung cancer risk. Multivariate logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals. After results were controlled for age and smoking history, women with at least 1 child had 0.71 times the odds of lung cancer as women without children (odds ratio = 0.71, 95% confidence interval: 0.52, 0.97). A significant linear trend was found: Lung cancer risk decreased with increasing numbers of children (P < 0.001). This inverse association was stronger in never smokers (P = 0.12) and was limited to women over age 50 years at diagnosis (P = 0.17). Age at first birth was not associated with risk. The authors observed a protective association between childbearing and lung cancer, adding to existing evidence that reproductive factors may moderate lung cancer risk in women.

Contralateral pulmonary metastases in lung cancer

PubMed Central

Onuigbo, Wilson I. B.

1974-01-01

Onuigbo, W. I. B. (1974).Thorax, 29, 132-133. Contralateral pulmonary metastases in lung cancer. It has long been known that lung cancer may attack many organs and yet spare the opposite lung. In 100 cases of this tumour studied at necropsy, only 22 showed contralateral pulmonary spread. Contralateral deposits are generally small and may be related to damaged tissues. Although tissue unsuitability is supposed to underlie the limitation of metastases in recipient organs, this does not apply to the contralateral lung. Since lung tissue is readily accessible to bloodborne cancer cells, research should be directed towards explaining the paradoxical paucity of the metastases. PMID:4825544

MicroRNA-137 inhibits tumor growth and sensitizes chemosensitivity to paclitaxel and cisplatin in lung cancer

PubMed Central

Ge, Xin; Jiang, Cheng-Fei; Shi, Zhu-Mei; Li, Dong-Mei; Liu, Wei-Tao; Yu, Xiaobo; Shu, Yong-Qian

2016-01-01

Chemotherapy resistance frequently drives tumour progression. However, the underlying molecular mechanisms are poorly characterized. In this study, we explored miR-137's role in the chemosensitivity of lung cancer. We found that the expression level of miR-137 is down-regulated in the human lung cancer tissues and the resistant cells strains: A549/paclitaxel(A549/PTX) and A549/cisplatin (A549/CDDP) when compared with lung cancer A549 cells. Moreover, we found that overe-expression of miR-137 inhibited cell proliferation, migration, cell survival and arrest the cell cycle in G1 phase in A549/PTX and A549/CDDP. Furthermore, Repression of miR-137 significantly promoted cell growth, migration, cell survival and cell cycle G1/S transition in A549 cells. We further demonstrated that the tumor suppressive role of miR-137 was mediated by negatively regulating Nuclear casein kinase and cyclin-dependent kinase substrate1(NUCKS1) protein expression. Importantly, miR-137 inhibits A549/PTX, A549/CDDP growth and angiogenesis in vivo. Our study is the first to identify the tumor suppressive role of over-expressed miR-137 in chemosensitivity. Identification of a novel miRNA-mediated pathway that regulates chemosensitivity in lung cancer will facilitate the development of novel therapeutic strategies in the future. PMID:26989074

Do doctors understand the test characteristics of lung cancer screening?

PubMed

Schmidt, Richard; Breyer, Marie; Breyer-Kohansal, Robab; Urban, Matthias; Funk, Georg-Christian

2018-04-01

Screening for lung cancer with a low-dose computed tomography (CT) scan is estimated to prevent 3 deaths per 1000 individuals at high risk; however, false positive results and radiation exposure are relevant harms and deserve careful consideration. Screening candidates can only make an autonomous decision if doctors correctly inform them of the pros and cons of the method; therefore, this study aimed to evaluate whether doctors understand the test characteristics of lung cancer screening. In a randomized trial 556 doctors (members of the Austrian Respiratory Society) were invited to answer questions regarding lung cancer screening based on online case vignettes. Half of the participants were randomized to the group 'solutions provided' and received the correct solutions in advance. The group 'solutions withheld' had to rely on prior knowledge or estimates. The primary endpoint was the between-group difference in the estimated number of deaths preventable by screening. Secondary endpoints were the between-group differences in the prevalence of lung cancer, prevalence of a positive screening results, sensitivity, specificity, positive predictive value, and false negative rate. Estimations were also compared with current data from the literature. The response rate was 29% in both groups. The reduction in the number of deaths due to screening was overestimated six-fold (95% confidence interval CI: 4-8) compared with the actual data, and there was no effect of group allocation. Providing the correct solutions to doctors had no systematic effect on their answers. Doctors poorly understand the test characteristics of lung cancer screening. Providing the correct solutions in advance did not improve the answers. Continuing education regarding lung cancer screening and the interpretation of test characteristics may be a simple remedy. Clinical trial registered with www.clinicaltrials.gov (NCT02542332).

Development of a multiplex methylation specific PCR suitable for (early) detection of non-small cell lung cancer

PubMed Central

Nawaz, Imran; Qiu, Xiaoming; Wu, Heng; Li, Yang; Fan, Yaguang; Hu, Li-Fu; Zhou, Qinghua; Ernberg, Ingemar

2014-01-01

Lung cancer is a worldwide health problem and a leading cause of cancer-related deaths. Silencing of potential tumor suppressor genes (TSGs) by aberrant promoter methylation is an early event in the initiation and development of cancer. Thus, methylated cancer type-specific TSGs in DNA can serve as useful biomarkers for early cancer detection. We have now developed a “Multiplex Methylation Specific PCR” (MMSP) assay for analysis of the methylation status of multiple potential TSGs by a single PCR reaction. This method will be useful for early diagnosis and treatment outcome studies of non-small cell lung cancer (NSCLC). Genome-wide CpG methylation and expression microarrays were performed on lung cancer tissues and matched distant non-cancerous tissues from three NSCLC patients from China. Thirty-eight potential TSGs were selected and analyzed by methylation PCR on bisulfite treated DNA. On the basis of sensitivity and specificity, six marker genes, HOXA9, TBX5, PITX2, CALCA, RASSF1A, and DLEC1, were selected to establish the MMSP assay. This assay was then used to analyze lung cancer tissues and matched distant non-cancerous tissues from 70 patients with NSCLC, as well as 24 patients with benign pulmonary lesion as controls. The sensitivity of the assay was 99% (69/70). HOXA9 and TBX5 were the 2 most sensitive marker genes: 87% (61/70) and 84% (59/70), respectively. RASSF1A and DLEC1 showed the highest specificity at 99% (69/70). Using the criterion of identifying at least any two methylated marker genes, 61/70 cancer samples were positive, corresponding to a sensitivity of 87% and a specificity of 94%. Early stage I or II NSCLC could even be detected with a 100% specificity and 86% sensitivity. In conclusion, MMSP has the potential to be developed into a population-based screening tool and can be useful for early diagnosis of NSCLC. It might also be suitable for monitoring treatment outcome and recurrence. PMID:24937636

DNA Methylation Analysis of the SHOX2 and RASSF1A Panel in Bronchoalveolar Lavage Fluid for Lung Cancer Diagnosis

PubMed Central

Zhang, Chenzi; Yu, Wenjun; Wang, Lin; Zhao, Mingna; Guo, Qiaomei; Lv, Shaogang; Hu, Xiaomeng; Lou, Jiatao

2017-01-01

Introduction: Currently the majority of lung cancer patients are diagnosed as advanced diseases for no sensitive and specific biomarkers exist, noninvasive biomarkers with high sensitivity and specificity are urgently needed in lung cancer diagnosis. Bronchoscopy is a standard procedure of the diagnostic work-up of patients with suspected lung cancer despite of the limited diagnostic accuracy. Besides, epigenetic changes through DNA methylation play an important role in tumorigenesis. Thus, we examined the aberrant methylation of the SHOX2 and RASSF1A in bronchoalveolar lavage fluid (BALF) in comparing with conventional cytology examination and serum CEA in order to evaluate the new diagnostic method. Patients and Methods: BALF and serum samples were collected from 322 patients at the time of diagnosis, 284 of them were pathologically confirmed lung cancer, 35 were benign lung diseases and 3 were malignancies in other systems. For all of the 322 patients, the methylation status of the SHOX2 and RASSF1A gene were detected by a new RT-PCR platform and then confirmed by sanger sequencing. Serum CEA were detected using electrochemiluminescence immunoassay. Results: Profiling data showed the consistency of RT-PCR and sanger sequencing in detecting the methylation of the SHOX2 and RASSF1A. Besides, the combination of SHOX2 and RASSF1A methylation in BALF yielded a diagnostic sensitivity of 81.0% and specificity of 97.4%. When compared with established cytology examination (sensitivity: 68.3%, specificity: 97.4%) and serum biomarker carcinoembryonic antigen (CEA) (sensitivity: 30.6%, specificity: 100.0%), the SHOX2 and RASSF1A methylation panel showed the highest diagnostic efficiency. Notably, the combination of cytology and the SHOX2 and RASSF1A methylation panel could significantly improve the diagnostic efficacy. Conclusion: The methylation analysis of the SHOX2 and RASSF1A panel in BALF with RT-PCR achieved a satisfactory sensitivity and specificity in lung cancer

Peptide hormones and lung cancer.

PubMed

Moody, T W

2006-03-01

Several peptide hormones have been identified which alter the proliferation of lung cancer. Small cell lung cancer (SCLC), which is a neuroendocrine cancer, produces and secretes gastrin releasing peptide (GRP), neurotensin (NT) and adrenomedullin (AM) as autocrine growth factors. GRP, NT and AM bind to G-protein coupled receptors causing phosphatidylinositol turnover or elevated cAMP in SCLC cells. Addition of GRP, NT or AM to SCLC cells causes altered expression of nuclear oncogenes, such as c-fos, and stimulation of growth. Antagonists have been developed for GRP, NT and AM receptors which function as cytostatic agents and inhibit SCLC growth. Growth factor antagonists, such as the NT1 receptor antagonist SR48692, facilitate the ability of chemotherapeutic drugs to kill lung cancer cells. It remains to be determined if GRP, NT and AM receptors will served as molecular targets, for development of new therapies for the treatment of SCLC patients. Non-small cell lung cancer (NSCLC) cells also have a high density of GRP, NT, AM and epidermal growth factor (EGF) receptors. Several NSCLC patients with EGF receptor mutations respond to gefitinib, a tyrosine kinase inhibitor. Gefitinib relieves NSCLC symptoms, maintaining stable disease in patients who are not eligible for systemic chemotherapy. It is important to develop new therapeutic approaches using translational research techniques for the treatment of lung cancer patients.

Thioredoxin reductase 1 knockdown enhances selenazolidine cytotoxicity in human lung cancer cells via mitochondrial dysfunction

PubMed Central

Poerschke, Robyn L.; Moos, Philip J.

2010-01-01

Thioredoxin reductase (TR1) is a selenoprotein that is involved in cellular redox status control and deoxyribonucleotide biosynthesis. Many cancers, including lung, overexpress TR1, making it a potential cancer therapy target. Previous work has shown that TR1 knockdown enhances the sensitivity of cancer cells to anticancer treatments, as well as certain selenocompounds. However, it is unknown if TR1 knockdown produces similar effect on the sensitivity of human lung cancer cells. To further elucidate the role of TR1 in the mechanism of selenocompounds in lung cancer, a lentiviral microRNA delivery system to knockdown TR1 expression in A549 human lung adenocarcinoma cells was utilized. Cell viability was assessed after 48 hr treatment with the selenocysteine prodrug selenazolidines 2-butylselenazolidine-4(R)-carboxylic acid (BSCA) and 2-cyclohexylselenazolidine-4-(R)-carboxylic acid (ChSCA), selenocystine (SECY), methylseleninic acid (MSA), 1,4-phenylenebis(methylene)selenocyanate (p-XSC), and selenomethionine (SEM). TR1 knockdown increased the cytotoxicity of BSCA, ChSCA, and SECY but did not sensitize cells to MSA, SEM, or p-XSC. GSH and TR1 depletion together decreased cell viability, while no change was observed with GSH depletion alone. Reactive oxygen species generation was induced only in TR1 knockdown cells treated with the selenazolidines or SECY. These three compounds also decreased total intracellular glutathione levels and oxidized thioredoxin, but in a TR1 independent manner. TR1 knockdown increased selenazolidine and SECY-induced mitochondrial membrane depolarization, as well as DNA strand breaks and AIF translocation from the mitochondria. These results indicate the ability of TR1 to modulate the cytotoxic effects of BSCA, ChSCA and SECY in human lung cancer cells through mitochondrial dysfunction. PMID:20920480

[Development of the lung cancer diagnostic system].

PubMed

Lv, You-Jiang; Yu, Shou-Yi

2009-07-01

To develop a lung cancer diagnosis system. A retrospective analysis was conducted in 1883 patients with primary lung cancer or benign pulmonary diseases (pneumonia, tuberculosis, or pneumonia pseudotumor). SPSS11.5 software was used for data processing. For the relevant factors, a non-factor Logistic regression analysis was used followed by establishment of the regression model. Microsoft Visual Studio 2005 system development platform and VB.Net corresponding language were used to develop the lung cancer diagnosis system. The non-factor multi-factor regression model showed a goodness-of-fit (R2) of the model of 0.806, with a diagnostic accuracy for benign lung diseases of 92.8%, a diagnostic accuracy for lung cancer of 89.0%, and an overall accuracy of 90.8%. The model system for early clinical diagnosis of lung cancer has been established.

Lung and Upper Aerodigestive Cancer | Division of Cancer Prevention

Cancer.gov

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Role of long non-coding RNA in drug resistance in non-small cell lung cancer.

PubMed

Wang, Leirong; Ma, Leina; Xu, Fei; Zhai, Wenxin; Dong, Shenghua; Yin, Ling; Liu, Jia; Yu, Zhuang

2018-05-03

Lung cancer is the leading cause of cancer-associated death, and non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases. Many drugs have been used to treat NSCLC in order to improve patient prognosis. Platinum-based chemotherapy is the first-line treatment for locally advanced or metastatic patients. For patients with activating EGFR mutations, tyrosine kinase inhibitors are the best treatment choice. NSCLC initially exhibits an excellent response to treatment; however, acquired resistance has been observed in many patients, leading to ineffective treatment. Clinical resistance is an impediment in the treatment of patients with advanced NSCLC. Many sequencing technologies have shown that long non-coding RNA (lncRNA) is expressed differently between drug-resistant and drug-sensitive lung cancer cells. We review the literature on lncRNA in drug resistance of NSCLC. The aim of this review is to gain insight into the molecular mechanisms of drug resistance, mainly focusing on the role of lncRNA in NSCLC. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Immunotherapy in lung cancer.

PubMed Central

Al-Moundhri, M.; O'Brien, M.; Souberbielle, B. E.

1998-01-01

More research and new treatment options are needed in all stages of lung cancer. To this end immunotherapy needs a revival in view of recent improved technologies and greater understanding of the underlying biology. In this review we discuss mechanisms of tumour immunotherapy, non-specific, specific and adoptive, with particular reference to a direct therapeutic action on all subtypes of lung cancer. PMID:9703271

Lung Cancer in HIV Infection

PubMed Central

Mani, Deepthi; Haigentz, Missak; Aboulafia, David M

2011-01-01

Lung cancer is the most prevalent non-AIDS-defining malignancy in the HAART era. Smoking plays a significant role in the development of HIV-associated lung cancer, but the cancer risk is 2–4 times greater in HIV-infected persons than in the general population, even after adjusting for smoking intensity and duration. Lung cancer is typically diagnosed a decade or more earlier among HIV-infected persons (mean age, 46 years) compared to those without HIV infection. Adenocarcinoma is the commonest histological subtype, and the majority of patients are diagnosed with locally advanced or metastatic carcinoma. Since pulmonary infections are common among HIV-infected individuals, clinicians may not suspect lung cancer in this younger patient population. Surgery with curative intent remains the treatment of choice for early stage disease. Although there is increasing experience in using radiation and chemotherapy for HIV-infected patients who do not have surgical options, there is a need for prospective studies for this population frequently excluded from participating in cancer trials. Evidence-based treatments for smoking-cessation with demonstrated efficacy in the general population must be routinely incorporated into the care of HIV-positive smokers. PMID:21802373

[Concurrent chemoradiation in lung cancer].

PubMed

Girard, Nicolas; Mornex, Françoise

2005-12-01

Concurrent chemoradiation has become for the 15 last years the standard treatment for locally advanced non-small cell lung cancer, either as a definite therapy in non resectable tumors, or in a neoadjuvant setting in potentially resectable tumors. Associating sequential and concurrent schedules, by administering chemotherapy before or after concurrent chemoradiation, has been recently investigated, but the best sequence remains a matter of controversy. Increasing local control and survival after definite chemoradiation seems possible not only by using optimized radiation fractionation schedules and escalated total doses, but also by associating more convenient and less toxic chemotherapy agents at the right cytotoxic or radio-sensitizing dose. Moreover, recent data have suggested that surgery following induction chemoradiation is feasible and effective in selected patients without mediastinal nodes involvement, if a complete resection can be performed. In patients with localized small cell lung cancer, early concurrent chemoradiation with platinium and etoposide has been recognized as the state-of-the-art treatment. The increasing number of ongoing trials including modern radiation schedules combined with newer chemotherapy agents shows that chemoradiation is one of the most promising therapeutic strategies in thoracic oncology.

[Comparison of TPS, CEA, CYFRA21-1 and STNFR in diagnosis of lung cancer].

PubMed

Liao, Qiulin; Li, Lianhua; Chen, Mingsheng

2005-08-20

In recent years, new progress has been made in research of tumor markers. And namely tissue polypeptide specific antigen (TPS), cytokeratin 19-fragments (CYFRA21-1) and soluble tumor necrosis factor receptor (STNFR) are new tumor markers that have been used in clinical application. The aim of this study is to determine and compare the diagnostic value of 4 kinds of tumor markers, TPS, carcinoembryonic antigen (CEA), CYFRA21-1 and STNFR in patients with lung cancer. The serum levels of TPS, CEA, CYFRA21-1 and STNFR were determined in 72 patients with lung cancer, 54 patients with pulmonary benign diseases and 32 healthy adults by enzyme-linked immunosorbent assay (ELISA). The levels of the four tumor markers in lung cancer group were significantly higher than those in benign disease group (P < 0.005) and healthy control group (P < 0.001). Among the four markers, STNFR had the highest sensitivity (81.9%), CYFRA21-1 had the highest specificity (91.5%) and TPS had the highest accuracy (83.5%). TPS, CYFRA21-1 and STNFR can be used as very useful and sensitive tumor markers in the diagnosis of lung cancer, in which CYFRA21-1 may be the most useful tumor marker for clinical application.

Enhanced expression of PKM2 associates with the biological properties of cancer stem cells from A549 human lung cancer cells.

PubMed

Guo, Chang-Ying; Yan, Chen; Luo, Lan; Goto, Shinji; Urata, Yoshishige; Xu, Jian-Jun; Wen, Xiao-Ming; Kuang, Yu-Kang; Tou, Fang-Fang; Li, Tao-Sheng

2017-04-01

Cancer cells express the M2 isoform of glycolytic enzyme pyruvate kinase (PKM2) for favoring the survival under a hypoxic condition. Considering the relative low oxygen microenvironment in stem cell niche, we hypothesized that an enhanced PKM2 expression associates with the biological properties of cancer stem cells. We used A549 human lung cancer cell line and surgical resected lung cancer tissue samples from patients for experiments. We confirmed the co-localization of PKM2 and CD44, a popular marker for cancer stem cells in lung cancer tissue samples from patients. The expression of PKM2 was clearly observed in approximately 80% of the A549 human lung cancer cells. Remarkably, enhanced expression of PKM2 was specially observed in these cells that also positively expressed CD44. Downregulation of PKM2 in CD44+ cancer stem cells by siRNA significantly impaired the potency for spheroid formation, decreased the cell survival under fetal bovine serum deprivation and hypoxic conditions, but increased their sensitivity to anti-cancer drug of cisplatin and γ-ray. The enhanced expression of PKM2 seems to associate with the biological properties of cancer stem cells from A549 human lung cancer cells. Selective targeting of PKM2 may provide a new strategy for cancer therapy, especially for patients with therapeutic resistance.

Proteomic biomarkers in lung cancer.

PubMed

Pastor, M D; Nogal, A; Molina-Pinelo, S; Carnero, A; Paz-Ares, L

2013-09-01

The correct understanding of tumour development relies on the comprehensive study of proteins. They are the main orchestrators of vital processes, such as signalling pathways, which drive the carcinogenic process. Proteomic technologies can be applied to cancer research to detect differential protein expression and to assess different responses to treatment. Lung cancer is the number one cause of cancer-related death in the world. Mostly diagnosed at late stages of the disease, lung cancer has one of the lowest 5-year survival rates at 15 %. The use of different proteomic techniques such as two-dimensional gel electrophoresis (2D-PAGE), isotope labelling (ICAT, SILAC, iTRAQ) and mass spectrometry may yield new knowledge on the underlying biology of lung cancer and also allow the development of new early detection tests and the identification of changes in the cancer protein network that are associated with prognosis and drug resistance.

Radiation-induced heart disease in lung cancer radiotherapy

PubMed Central

Ming, Xin; Feng, Yuanming; Yang, Chengwen; Wang, Wei; Wang, Ping; Deng, Jun

2016-01-01

Abstract Background: Radiation-induced heart disease (RIHD), which affects the patients’ prognosis with both acute and late side effects, has been published extensively in the radiotherapy of breast cancer, lymphoma and other benign diseases. Studies on RIHD in lung cancer radiotherapy, however, are less extensive and clear even though the patients with lung cancer are delivered with higher doses to the heart during radiation treatment. Methods: In this article, after extensive literature search and analysis, we reviewed the current evidence on RIHD in lung cancer patients after their radiation treatments and investigated the potential risk factors for RIHD as compared to other types of cancers. Result: Cardiac toxicity has been found highly relevant in lung cancer radiotherapy. So far, the crude incidence of cardiac complications in the lung cancer patients after radiotherapy has been up to 33%. Conclusion: The dose to the heart, the lobar location of tumor, the treatment modality, the history of heart and pulmonary disease and smoking were considered as potential risk factors for RIHD in lung cancer radiotherapy. As treatment techniques improve over the time with better prognosis for lung cancer survivors, an improved prediction model can be established to further reduce the cardiac toxicity in lung cancer radiotherapy. PMID:27741117

Occupational lung cancer in US women, 1984-1998.

PubMed

Robinson, Cynthia F; Sullivan, Patricia A; Li, Jia; Walker, James T

2011-02-01

Lung cancer is the leading cause of cancer death in US women, accounting for 72,130 deaths in 2006. In addition to smoking cessation, further reduction of the burden of lung cancer mortality can be made by preventing exposure to occupational lung carcinogens. Data for occupational exposures and health outcomes of US working women are limited. Population-based mortality data for 4,570,711 women who died between 1984 and 1998 in 27 US States were used to evaluate lung cancer proportionate mortality over time by the usual occupation and industry reported on death certificates. Lung cancer proportionate mortality ratios were adjusted for smoking, using data from the National Health Interview Survey (NHIS) and the American Cancer Society's Cancer Prevention Study II. Analyses revealed that 194,382 white, 18,225 Black and 1,515 Hispanic women died 1984-1998 with lung cancer reported as the underlying cause of death. Following adjustment for smoking, significant excess proportionate lung cancer mortality was observed among US women working in the US manufacturing; transportation; retail trade; agriculture, forestry, and fishing; and nursing/personal care industries. Women employed in precision production, technical, managerial, professional specialty, and administrative occupations experienced some of the highest significantly excess proportionate lung cancer mortality during 1984-1998. The results of our study point to significantly elevated risks for lung cancer after adjustment for smoking among women in several occupations and industries. Because 6-17% of lung cancer in US males is attributable to known exposures to occupational carcinogens, and since synergistic interactions between cigarette smoke and other occupational lung carcinogens have been noted, it is important to continue research into the effects of occupational exposures on working men and women. Copyright © 2010 Wiley-Liss, Inc.

Molecular profiling of single circulating tumor cells from lung cancer patients.

PubMed

Park, Seung-Min; Wong, Dawson J; Ooi, Chin Chun; Kurtz, David M; Vermesh, Ophir; Aalipour, Amin; Suh, Susie; Pian, Kelsey L; Chabon, Jacob J; Lee, Sang Hun; Jamali, Mehran; Say, Carmen; Carter, Justin N; Lee, Luke P; Kuschner, Ware G; Schwartz, Erich J; Shrager, Joseph B; Neal, Joel W; Wakelee, Heather A; Diehn, Maximilian; Nair, Viswam S; Wang, Shan X; Gambhir, Sanjiv S

2016-12-27

Circulating tumor cells (CTCs) are established cancer biomarkers for the "liquid biopsy" of tumors. Molecular analysis of single CTCs, which recapitulate primary and metastatic tumor biology, remains challenging because current platforms have limited throughput, are expensive, and are not easily translatable to the clinic. Here, we report a massively parallel, multigene-profiling nanoplatform to compartmentalize and analyze hundreds of single CTCs. After high-efficiency magnetic collection of CTC from blood, a single-cell nanowell array performs CTC mutation profiling using modular gene panels. Using this approach, we demonstrated multigene expression profiling of individual CTCs from non-small-cell lung cancer (NSCLC) patients with remarkable sensitivity. Thus, we report a high-throughput, multiplexed strategy for single-cell mutation profiling of individual lung cancer CTCs toward minimally invasive cancer therapy prediction and disease monitoring.

Concerns About Lung Cancer Among Prisoners.

PubMed

Renault, Luc; Perrot, Emmanuel; Pradat, Eric; Bartoli, Christophe; Greillier, Laurent; Remacle-Bonnet, Anne; Telmon, Norbert; Mazières, Julien; Molinier, Laurent; Couraud, Sébastien

2018-02-01

Few studies have looked at lung cancer in prisoners, despite this population is possibly at increased risk of malignancy. In a previous study, we found an early onset of lung cancer in prisoners. Thus, the present CARCAN study was aimed at assessing the epidemiological characteristics, management, prognosis, and incidence of lung cancer in prisoners compared to a sample of non-prisoner patients. We performed a multi-center observational case-control study. Cases were prisoners diagnosed with lung cancer from 2005 to 2013. Controls were non-prisoner lung cancer patients selected from hospital databases and randomly matched to cases (targeted case-control ratio: 1:3). Incidence rates in both groups were calculated using national statistics. Seventy-two cases and 170 controls met inclusion criteria. Cases were mainly men (99%). Mean age at diagnosis was 52.9 (± 11.0) in cases and 64.3 (± 10.1) in controls (p < 0.0001). More case patients were current smokers compared to control patients (83% vs 53%; p < 0.0001). We found no significant differences between the two groups as concerns histologic types, TNM stages at diagnosis, initially-employed treatments, times to management or survival. Incidence rates (2008-2012) in male prisoners were higher than those in the general population in all concerned age groups. There is a shift of lung cancer toward young people in prisons. However, the presentation, management, and prognosis of lung cancer are similar between prisoners and non-prisoners. These finding could justify a specific screening policy for the incarcerated populations.

Drug delivery and nanodetection in lung cancer.

PubMed

Badrzadeh, Fariba; Rahmati-Yamchi, Mohammad; Badrzadeh, Kazem; Valizadeh, Alireza; Zarghami, Nosratollah; Farkhani, Samad Mussa; Akbarzadeh, Abolfazl

2016-01-01

Lung carcinoma is the most widespread type of cancer worldwide, and is responsible for more deaths than other types of cancer. Lung cancer remains the chief cause of cancer-related deaths in both men and women worldwide, and is increasingly common in women. Each year, the number of deaths from lung cancer is greater than the number due to breast and colorectal cancer combined. Lung cancer accounted for 13% (1.6 million) of the total cases and 18% (1.4 million) of the deaths in 2008. In Iran, lung cancer is one of the five leading tumors. Among females, it was the fourth most commonly diagnosed cancer, and the second leading cause of cancer death. Nanotechnology can be defined as the science and engineering involved in the design, characterization, and application of materials and devices whose smallest functional organization in at least one dimension is on the nanometer scale, i.e. one billionth of a meter. It is an exciting multidisciplinary field that involves the design and engineering of nano objects or nanotools with diameters less than 500 nanometers (nm), and it is one of the most interesting fields of the 21st century. Nanotechnology also offers the ability to detect diseases, such as tumors, much earlier than ever imaginable. This article presents nano devices for lung cancer detection and drug delivery systems.

[Survey and analysis of awareness of lung cancer prevention and control in a LDCT lung cancer screening project in Tianjin Dagang Oilfield of China].

PubMed

Ren, Guanhua; Ye, Jianfei; Fan, Yaguang; Wang, Jing; Sun, Zhijuan; Jia, Hui; Du, Xinxin; Hou, Chaohua; Wang, Ying; Zhao, Yongcheng; Zhou, Qinghua

2014-02-01

It has been proven that increase of the awareness level of lung cancer prevention and control could enhance participation of lung cancer screening of lung cancer high risk group. The aim of this study is to investigate the awareness level of lung cancer prevention and control and the effect of individual characteristics on lung cancer awareness, and to provide evidence for comprehensive lung cancer prevention in high risk areas of lung cancer. Staffs of Tianjin Dagang Oil Field who participate low dose CT (LDCT) lung cancer screening by cluster sampling or according to voluntary principle were surveyed, data of lung cancer awareness were collected by questionnaire. A total of 1,633 valid questionnaires were collected. The average age of respondents was 60.08±6.58. Most participants were males (82.2%) while female only accounted for 17.8%. The proportions of awareness about lung cancer in China, risk factors, screening methods and the knowledge of health examination were 64.5%, 77.1%, 43.7%, 49.6% respectively. Result of multiple logistic regression analysis showed that education level, smoking (pack-year), age, prior tuberculosis were the influencing factors of lung cancer awareness with adjusted Ors for education and age level as of 0.567 (95%CI: 0.439-0.733) and 1.373 (95%CI: 1.084-1.739) respectively. 80.3% of the participants can accept health examination once a year, while the ability to pay the medical expenses was not high. The influencing factors of health examination willingness were gender, age, income, the knowledge of lung cancer. Education level and smoking affect the awareness of lung cancer prevention and control, health education for lung cancer should be conducted especially in population with low education level. Comprehensive lung cancer control in high risk areas should combined lung cancer screening, tobacco control and health education.

Lung cancer among women in north-east China.

PubMed Central

Wu-Williams, A. H.; Dai, X. D.; Blot, W.; Xu, Z. Y.; Sun, X. W.; Xiao, H. P.; Stone, B. J.; Yu, S. F.; Feng, Y. P.; Ershow, A. G.

1990-01-01

A case-control study of lung cancer involving interviews with 965 female patients and 959 controls in Shenyang and Harbin, two industrial cities which have among the highest rates of lung cancer in China, revealed that cigarette smoking is the main causal factor and accounted for about 35% of the tumours among women. Although the amount smoked was low (the cases averaged eight cigarettes per day), the percentage of smokers among women over age 50 in these cities was nearly double the national average. Air pollution from coal burning stoves was implicated, as risks of lung cancer increased in proportion to years of exposure to 'Kang' and other heating devices indigenous to the region. In addition, the number of meals cooked by deep frying and the frequency of smokiness during cooking were associated with risk of lung cancer. More cases than controls reported workplace exposures to coal dust and to smoke from burning fuel. Elevated risks were observed for smelter workers and decreased risks for textile workers. Prior chronic bronchitis/emphysema, pneumonia, and recent tuberculosis contributed significantly to lung cancer risk, as did a history of tuberculosis and lung cancer in family members. Higher intake of carotene-rich vegetables was not protective against lung cancer in this population. The findings were qualitatively similar across the major cell types of lung cancer, except that the associations with smoking and previous lung diseases were stronger for squamous/oat cell cancers than for adenocarcinoma of the lung. PMID:2257230

Cell-surface marker discovery for lung cancer

PubMed Central

Cohen, Allison S.; Khalil, Farah K.; Welsh, Eric A.; Schabath, Matthew B.; Enkemann, Steven A.; Davis, Andrea; Zhou, Jun-Min; Boulware, David C.; Kim, Jongphil; Haura, Eric B.; Morse, David L.

2017-01-01

Lung cancer is the leading cause of cancer deaths in the United States. Novel lung cancer targeted therapeutic and molecular imaging agents are needed to improve outcomes and enable personalized care. Since these agents typically cannot cross the plasma membrane while carrying cytotoxic payload or imaging contrast, discovery of cell-surface targets is a necessary initial step. Herein, we report the discovery and characterization of lung cancer cell-surface markers for use in development of targeted agents. To identify putative cell-surface markers, existing microarray gene expression data from patient specimens were analyzed to select markers with differential expression in lung cancer compared to normal lung. Greater than 200 putative cell-surface markers were identified as being overexpressed in lung cancers. Ten cell-surface markers (CA9, CA12, CXorf61, DSG3, FAT2, GPR87, KISS1R, LYPD3, SLC7A11 and TMPRSS4) were selected based on differential mRNA expression in lung tumors vs. non-neoplastic lung samples and other normal tissues, and other considerations involving known biology and targeting moieties. Protein expression was confirmed by immunohistochemistry (IHC) staining and scoring of patient tumor and normal tissue samples. As further validation, marker expression was determined in lung cancer cell lines using microarray data and Kaplan–Meier survival analyses were performed for each of the markers using patient clinical data. High expression for six of the markers (CA9, CA12, CXorf61, GPR87, LYPD3, and SLC7A11) was significantly associated with worse survival. These markers should be useful for the development of novel targeted imaging probes or therapeutics for use in personalized care of lung cancer patients. PMID:29371917

Paraneoplastic syndromes associated with lung cancer

PubMed Central

Kanaji, Nobuhiro; Watanabe, Naoki; Kita, Nobuyuki; Bandoh, Shuji; Tadokoro, Akira; Ishii, Tomoya; Dobashi, Hiroaki; Matsunaga, Takuya

2014-01-01

Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy (Trousseau’s syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cytokines, and antibodies. Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer. PMID:25114839

HIV Infection in the Etiology of Lung Cancer

PubMed Central

Kirk, Gregory D.; Merlo, Christian A.

2011-01-01

Persons infected with HIV have an elevated risk of lung cancer, but whether the increase simply reflects a higher smoking prevalence continues to be debated. This review summarizes existing data on the association of HIV infection and lung cancer, with particular attention to study design and adjustment for cigarette smoking. Potential mechanisms by which HIV infection may lead to lung cancer are discussed. Finally, irrespective of causality and mechanisms, lung cancer represents an important and growing problem confronting HIV-infected patients and their providers. Substantial efforts are needed to promote smoking cessation and to control lung cancer among HIV-infected populations. PMID:21653536

Lung Cancer and Lung Injury: The Dual Role of Ceramide

PubMed Central

Goldkorn, Tzipora; Chung, Samuel; Filosto, Simone

2015-01-01

Sphingolipids play key roles in cancer, yet our current understanding of sphingolipid function in lung cancer is limited to a few key players. The best characterized of these are sphingosine-1-phoshate and ceramide which are described for their opposing roles in cell fate. However, because sphingolipids as a whole are readily interconverted by a complex enzymatic machinery, no single sphingolipid appears to have exactly one role. Instead, the roles of specific sphingolipids appear to be context specific as demonstrated by findings that ceramide-1-phosphate has both proliferative and apoptotic effects depending on its concentration. Therefore, we present herein several years of research on ceramide, a sphingolipid linked to apoptotic signaling, that is emerging in cancer research for its potential roles in proliferation and cell-to-cell communication via exosomes. Ceramide is a well-studied sphingolipid in both normal and pathological conditions ranging from skin development to lung cancer. Interestingly, several groups have previously reported its increased levels in emphysema patients who are smokers, a patient subpopulation greatly susceptible to lung cancer. However, the molecular mechanisms through which cigarette smoke (CS) and ceramide accumulation lead to lung cancer, non-small cell lung cancer (NSCLC) specifically, are unknown. Interestingly, recent studies clearly establish that two signaling pathways are activated during CS exposure in the lung airway. One centers on the activation of neutral sphingomyelinase2 (nSMase2), an enzyme that hydrolyzes sphingomyelin to ceramide. The other pathway focuses on the oncogenic EGF receptor (EGFR), which becomes aberrantly activated but not degraded, leading to prolonged proliferative signaling. Recent studies show that these two signaling pathways may actually converge and integrate. Specifically, Goldkorn et al. demonstrated that during CS exposure, EGFR is favorably co-localized in ceramide-enriched regions of the

An updated review of case-control studies of lung cancer and indoor radon-Is indoor radon the risk factor for lung cancer?

PubMed

Sheen, Seungsoo; Lee, Keu Sung; Chung, Wou Young; Nam, Saeil; Kang, Dae Ryong

2016-01-01

Lung cancer is a leading cause of cancer-related death in the world. Smoking is definitely the most important risk factor for lung cancer. Radon ((222)Rn) is a natural gas produced from radium ((226)Ra) in the decay series of uranium ((238)U). Radon exposure is the second most common cause of lung cancer and the first risk factor for lung cancer in never-smokers. Case-control studies have provided epidemiological evidence of the causative relationship between indoor radon exposure and lung cancer. Twenty-four case-control study papers were found by our search strategy from the PubMed database. Among them, seven studies showed that indoor radon has a statistically significant association with lung cancer. The studies performed in radon-prone areas showed a more positive association between radon and lung cancer. Reviewed papers had inconsistent results on the dose-response relationship between indoor radon and lung cancer risk. Further refined case-control studies will be required to evaluate the relationship between radon and lung cancer. Sufficient study sample size, proper interview methods, valid and precise indoor radon measurement, wide range of indoor radon, and appropriate control of confounders such as smoking status should be considered in further case-control studies.

Molecular pathways and therapeutic targets in lung cancer

PubMed Central

Shtivelman, Emma; Hensing, Thomas; Simon, George R.; Dennis, Phillip A.; Otterson, Gregory A.; Bueno, Raphael; Salgia, Ravi

2014-01-01

Lung cancer is still the leading cause of cancer death worldwide. Both histologically and molecularly lung cancer is heterogeneous. This review summarizes the current knowledge of the pathways involved in the various types of lung cancer with an emphasis on the clinical implications of the increasing number of actionable molecular targets. It describes the major pathways and molecular alterations implicated in the development and progression of non-small cell lung cancer (adenocarcinoma and squamous cancer), and of small cell carcinoma, emphasizing the molecular alterations comprising the specific blueprints in each group. The approved and investigational targeted therapies as well as the immune therapies, and clinical trials exploring the variety of targeted approaches to treatment of lung cancer are the main focus of this review. PMID:24722523

Prevention and management of lung cancer in China.

PubMed

Hong, Qun-Ying; Wu, Guo-Ming; Qian, Gui-Sheng; Hu, Cheng-Ping; Zhou, Jian-Ying; Chen, Liang-An; Li, Wei-Min; Li, Shi-Yue; Wang, Kai; Wang, Qi; Zhang, Xiao-Ju; Li, Jing; Gong, Xin; Bai, Chun-Xue

2015-09-01

Lung cancer is the leading cause of cancer-related death worldwide. In China, the incidence of lung cancer has grown rapidly, resulting in a large social and economic burden. Several researchers have devoted their studies to lung cancer and have demonstrated that there are many risk factors for lung cancer in China, including tobacco use, environmental pollution, food, genetics, and chronic obstructive pulmonary disease. However, the lung cancer incidence is still growing rapidly in China, and there is an even higher incidence among the younger generation. One explanation may be the triple-neglect situation, in which medical policies that neglect prevention, diagnosis, and supportive care have increased patients' mortality and reduced their quality of life. Therefore, it is necessary to enhance the efficiency of prevention and early diagnosis not only by focusing more attention on treatment but also by drawing more attention to supportive care for patients with lung cancer. © 2015 American Cancer Society.

USP7 promotes cell proliferation through the stabilization of Ki-67 protein in non-small cell lung cancer cells.

PubMed

Zhang, Chao; Lu, Jing; Zhang, Quan-Wu; Zhao, Wei; Guo, Jia-Hui; Liu, Shan-Ling; Wu, Ying-Li; Jiang, Bin; Gao, Feng-Hou

2016-10-01

The Ki-67 antigen (Ki-67) is the most reliable immunohistochemical marker for evaluation of cell proliferation in non-small cell lung cancer. However, the mechanisms underlying the regulation of protein levels of Ki-67 in non-small cell lung cancer have remained elusive. In this study, we found that Ki-67 and ubiquitin-specific processing protease 7 (USP7) protein were highly expressed in the nucleus of non-small cell lung cancer cells. Furthermore, statistical analysis uncovered the existence of a strong correlation between Ki-67 and USP7 levels. We could also show that the protein levels of Ki-67 in non-small cell lung cancer cells significantly decreased after treatment with P22077, a selective chemical inhibitor of USP7, while the Ki-67 mRNA levels were unperturbed. Similar results were obtained by knocking down USP7 using short hairpin RNA (shRNA) in lung cancer cells. Interestingly, we noticed that ubiquitination levels of Ki-67 increased dramatically in USP7-silenced cells. The tests in vitro and vivo showed a significant delay in tumor cell growth upon knockdown of USP7. Additionally, drug sensitivity tests indicated that USP7-silenced A549 cells had enhanced sensitivity to paclitaxel and docetaxel, while there was no significant change in sensitivity toward carboplatin and cisplatin. Taken together, these data strongly suggest that the overexpression of USP7 might promote cell proliferation by deubiquitinating Ki-67 protein, thereby maintaining its high levels in the non-small cell lung cancer. Our study also hints potential for the development of deubiquitinase-based therapies, especially those targeting USP7 to improve the condition of patients diagnosed with non-small cell lung cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dilemmas in Lung Cancer Staging.

PubMed

Vlahos, Ioannis

2018-05-01

The advent of the 8th edition of the lung cancer staging system reflects a further meticulous evidence-based advance in the stratification of the survival of patients with lung cancer. Although addressing many limitations of earlier staging systems, several limitations in staging remain. This article reviews from a radiological perspective the limitations of the current staging system, highlighting the process of TNM restructuring, the residual issues with regards to the assignment of T, N, M descriptors, and their associated stage groupings and how these dilemmas impact guidance of multidisciplinary teams taking care of patients with lung cancer. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Multilevel Opportunities to Address Lung Cancer Stigma across the Cancer Control Continuum.

PubMed

Hamann, Heidi A; Ver Hoeve, Elizabeth S; Carter-Harris, Lisa; Studts, Jamie L; Ostroff, Jamie S

2018-05-22

The public health imperative to reduce the burden of lung cancer has seen unprecedented progress in recent years. Realizing fully the advances in lung cancer treatment and control requires attention to potential barriers in their momentum and implementation. In this analysis, we present and evaluate the argument that stigma is a highly significant barrier to fulfilling the clinical promise of advanced care and reduced lung cancer burden. This evaluation of lung cancer stigma is based on a multilevel perspective that incorporates the individual, persons in their immediate environment, the healthcare system, and the larger societal structure which shapes perceptions and decisions. We also consider current interventions and interventional needs within and across aspects of the lung cancer continuum, including prevention, screening, diagnosis, treatment, and survivorship. Current evidence suggests that stigma detrimentally impacts psychosocial, communication, and behavioral outcomes over the entire lung cancer control continuum and across multiple levels. Interventional efforts to alleviate stigma in the context of lung cancer show promise, yet more work is needed to evaluate their impact. Understanding and addressing the multi-level role of stigma is a crucial area for future study in order to realize the full benefits offered by lung cancer prevention, control, and treatment. Coordinated, interdisciplinary, and well-conceptualized efforts have the potential to reduce the barrier of stigma in the context of lung cancer and facilitate demonstrable improvements in clinical care and quality of life. Copyright © 2018. Published by Elsevier Inc.

Immune-Modulation by Epidermal Growth Factor Receptor Inhibitors: Implication on Anti-Tumor Immunity in Lung Cancer

PubMed Central

Herrmann, Amanda C.; Bernatchez, Chantale; Haymaker, Cara; Molldrem, Jeffrey J.; Hong, Waun Ki; Perez-Soler, Roman

2016-01-01

Skin toxicity is the most common toxicity caused by Epidermal Growth Factor Receptor (EGFR) inhibitors, and has been associated with clinical efficacy. As EGFR inhibitors enhance the expression of antigen presenting molecules in affected skin keratinocytes, they may concurrently facilitate neo-antigen presentation in lung cancer tumor cells contributing to anti-tumor immunity. Here, we investigated the modulatory effect of the EGFR inhibitor, erlotinib on antigen presenting molecules and PD-L1, prominent immune checkpoint protein, of skin keratinocytes and lung cancer cell lines to delineate the link between EGFR signaling pathway inhibition and potential anti-tumor immunity. Erlotinib up-regulated MHC-I and MHC-II proteins on IFNγ treated keratinocytes but abrogated IFNγ-induced expression of PD-L1, suggesting the potential role of infiltrating autoreactive T cells in the damage of keratinocytes in affected skin. Interestingly, the surface expression of MHC-I, MHC-II, and PD-L1 was up-regulated in response to IFNγ more often in lung cancer cell lines sensitive to erlotinib, but only expression of PD-L1 was inhibited by erlotinib. Further, erlotinib significantly increased T cell mediated cytotoxicity on lung cancer cells. Lastly, the analysis of gene expression dataset of 186 lung cancer cell lines from Cancer Cell Line Encyclopedia demonstrated that overexpression of PD-L1 was associated with sensitivity to erlotinib and higher expression of genes related to antigen presenting pathways and IFNγ signaling pathway. Our findings suggest that the EGFR inhibitors can facilitate anti-tumor adaptive immune responses by breaking tolerance especially in EGFR driven lung cancer that are associated with overexpression of PD-L1 and genes related to antigen presentation and inflammation. PMID:27467256

Exhaled breath analysis for lung cancer

PubMed Central

Sutedja, Tom G.; Zimmerman, Paul V.

2013-01-01

Early diagnosis of lung cancer results in improved survival compared to diagnosis with more advanced disease. Early disease is not reliably indicated by symptoms. Because investigations such as bronchoscopy and needle biopsy have associated risks and substantial costs, they are not suitable for population screening. Hence new easily applicable tests, which can be used to screen individuals at risk, are required. Biomarker testing in exhaled breath samples is a simple, relatively inexpensive, non-invasive approach. Exhaled breath contains volatile and non-volatile organic compounds produced as end-products of metabolic processes and the composition of such compounds varies between healthy subjects and subjects with lung cancer. Many studies have analysed the patterns of these compounds in exhaled breath. In addition studies have also reported that the exhaled breath condensate (EBC) can reveal gene mutations or DNA abnormalities in patients with lung cancer. This review has summarised the scientific evidence demonstrating that lung cancer has distinct chemical profiles in exhaled breath and characteristic genetic changes in EBC. It is not yet possible to accurately identify individuals with lung cancer in at risk populations by any of these techniques. However, analysis of both volatile organic compounds in exhaled breath and of EBC have great potential to become clinically useful diagnostic and screening tools for early stage lung cancer detection. PMID:24163746

Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO)

PubMed Central

Kim, Claire H; Lee, Yuan-Chin Amy; Hung, Rayjean J; McNallan, Sheila R; Cote, Michele L; Lim, Wei-Yen; Chang, Shen-Chih; Kim, Jin Hee; Ugolini, Donatella; Chen, Ying; Liloglou, Triantafillos; Andrew, Angeline S; Onega, Tracy; Duell, Eric J; Field, John K; Lazarus, Philip; Le Marchand, Loic; Neri, Monica; Vineis, Paolo; Kiyohara, Chikako; Hong, Yun-Chul; Morgenstern, Hal; Matsuo, Keitaro; Tajima, Kazuo; Christiani, David C; McLaughlin, John R; Bencko, Vladimir; Holcatova, Ivana; Boffetta, Paolo; Brennan, Paul; Fabianova, Eleonora; Foretova, Lenka; Janout, Vladimir; Lissowska, Jolanta; Mates, Dana; Rudnai, Peter; Szeszenia-Dabrowska, Neonila; Mukeria, Anush; Zaridze, David; Seow, Adeline; Schwartz, Ann G; Yang, Ping; Zhang, Zuo-Feng

2014-01-01

While the association between exposure to secondhand smoke and lung cancer risk is well established, few studies with sufficient power have examined the association by histological type. In this study, we evaluated the secondhand smoke-lung cancer relationship by histological type based on pooled data from 18 case-control studies in the International Lung Cancer Consortium (ILCCO), including 2,504 cases and 7,276 controls who were never smokers and 10,184 cases and 7,176 controls who were ever smokers. We used multivariable logistic regression, adjusting for age, sex, race/ethnicity, smoking status, pack-years of smoking, and study. Among never smokers, the odds ratios (OR) comparing those ever exposed to secondhand smoke with those never exposed were 1.31 (95% CI: 1.17–1.45) for all histological types combined, 1.26 (95% CI: 1.10–1.44) for adenocarcinoma, 1.41 (95% CI: 0.99–1.99) for squamous cell carcinoma, 1.48 (95% CI: 0.89–2.45) for large cell lung cancer, and 3.09 (95% CI: 1.62–5.89) for small cell lung cancer. The estimated association with secondhand smoke exposure was greater for small cell lung cancer than for non-small cell lung cancers (OR=2.11, 95% CI: 1.11–4.04). This analysis is the largest to date investigating the relation between exposure to secondhand smoke and lung cancer. Our study provides more precise estimates of the impact of secondhand smoke on the major histological types of lung cancer, indicates the association with secondhand smoke is stronger for small cell lung cancer than for the other histological types, and suggests the importance of intervention against exposure to secondhand smoke in lung cancer prevention. PMID:24615328

Radon exposure and cancers other than lung cancer in Swedish iron miners.

PubMed Central

Darby, S C; Radford, E P; Whitley, E

1995-01-01

Data are presented on the risks of cancers other than lung cancer in a cohort of iron miners from northern Sweden occupationally exposed to elevated levels of the radioactive gas radon. Compared with rates for the four northernmost counties of Sweden, mortality was increased for all cancers other than lung cancer (ratio of observed to expected deaths 1.21, 95% confidence interval 1.03-1.41), stomach cancer (ratio of observed to expected deaths 1.45, 95% confidence interval 1.04-1.98), and rectal cancer (ratio of observed to expected deaths 1.94, 95% confidence interval 1.03-3.31). Despite these overall increases, mortality was not significantly associated with cumulative exposure to radon, either for all cancers other than lung cancer or for any site of cancer other than lung cancer individually. However, the data from this cohort on its own have limited power; and for several sites of cancer the data in this study would be consistent with a radon-related increase. Further study of cancers other than lung cancer in populations exposed to radon is required. PMID:7614946

Curcumin sensitizes human lung cancer cells to apoptosis and metastasis synergistically combined with carboplatin

PubMed Central

Kang, Ji Ho; Kang, Hye Seon; Kim, In Kyoung; Lee, Hwa Young; Ha, Jick Hwan; Yeo, Chang Dong; Kang, Hyun Hui; Moon, Hwa Sik

2015-01-01

Although carboplatin is one of the standard chemotherapeutic agents for non-small cell lung cancer (NSCLC), it has limited therapeutic efficacy due to activation of a survival signaling pathway and the induction of multidrug resistance. Curcumin, a natural compound isolated from the plant Curcuma longa, is known to sensitize tumors to different chemotherapeutic agents. The aim of this study is to evaluate whether curcumin can chemosensitize lung cancer cells to carboplatin and to analyze the signaling pathway underlying this synergism. We investigated the synergistic effect of both agents on cell proliferation, apoptosis, invasion, migration, and expression of related signaling proteins using the human NSCLC cell line, A549. A549 cell was treated with different concentrations of curcumin and carboplatin alone and in combination. Combined treatment with curcumin and carboplatin inhibited tumor cell growth, migration, and invasion compared with either drug alone. Matrix metalloproteinase (MMP)-2 and MMP-9 were more efficiently downregulated by co-treatment than by each treatment alone. mRNA and protein expression of caspase-3 and caspase-9 and proapoptotic genes was increased in cells treated with a combination of curcumin and carboplatin, whereas expression of the antiapoptotic Bcl-2 gene was suppressed. Co-treatment of both agents substantially suppressed NF-κB activation and increased expression of p53. Phosphorylation of Akt, a protein upstream of NF-κB, was reduced, resulting in inhibition of the degradation of inhibitor of κB(IκBα), whereas the activity of extracellular signal-regulated kinase (ERK1/2) was enhanced. Our study demonstrated that the synergistic antitumor activity of curcumin combined with carboplatin is mediated by multiple mechanisms involving suppression of NF-κB via inhibition of the Akt/IKKα pathway and enhanced ERK1/2 activity. Based on this mechanism, curcumin has potential as a chemosensitizer for carboplatin in the treatment of

Regular aspirin use and lung cancer risk.

PubMed

Moysich, Kirsten B; Menezes, Ravi J; Ronsani, Adrienne; Swede, Helen; Reid, Mary E; Cummings, K Michael; Falkner, Karen L; Loewen, Gregory M; Bepler, Gerold

2002-11-26

Although a large number of epidemiological studies have examined the role of aspirin in the chemoprevention of colon cancer and other solid tumors, there is a limited body of research focusing on the association between aspirin and lung cancer risk. We conducted a hospital-based case-control study to evaluate the role of regular aspirin use in lung cancer etiology. Study participants included 868 cases with primary, incident lung cancer and 935 hospital controls with non-neoplastic conditions who completed a comprehensive epidemiological questionnaire. Participants were classified as regular aspirin users if they had taken the drug at least once a week for at least one year. Results indicated that lung cancer risk was significantly lower for aspirin users compared to non-users (adjusted OR = 0.57; 95% CI 0.41-0.78). Although there was no clear evidence of a dose-response relationship, we observed risk reductions associated with greater frequency of use. Similarly, prolonged duration of use and increasing tablet years (tablets per day x years of use) was associated with reduced lung cancer risk. Risk reductions were observed in both sexes, but significant dose response relationships were only seen among male participants. When the analyses were restricted to former and current smokers, participants with the lowest cigarette exposure tended to benefit most from the potential chemopreventive effect of aspirin. After stratification by histology, regular aspirin use was significantly associated with reduced risk of small cell lung cancer and non-small cell lung cancer. Overall, results from this hospital-based case-control study suggest that regular aspirin use may be associated with reduced risk of lung cancer.

Regular aspirin use and lung cancer risk

PubMed Central

Moysich, Kirsten B; Menezes, Ravi J; Ronsani, Adrienne; Swede, Helen; Reid, Mary E; Cummings, K Michael; Falkner, Karen L; Loewen, Gregory M; Bepler, Gerold

2002-01-01

Background Although a large number of epidemiological studies have examined the role of aspirin in the chemoprevention of colon cancer and other solid tumors, there is a limited body of research focusing on the association between aspirin and lung cancer risk. Methods We conducted a hospital-based case-control study to evaluate the role of regular aspirin use in lung cancer etiology. Study participants included 868 cases with primary, incident lung cancer and 935 hospital controls with non-neoplastic conditions who completed a comprehensive epidemiological questionnaire. Participants were classified as regular aspirin users if they had taken the drug at least once a week for at least one year. Results Results indicated that lung cancer risk was significantly lower for aspirin users compared to non-users (adjusted OR = 0.57; 95% CI 0.41–0.78). Although there was no clear evidence of a dose-response relationship, we observed risk reductions associated with greater frequency of use. Similarly, prolonged duration of use and increasing tablet years (tablets per day × years of use) was associated with reduced lung cancer risk. Risk reductions were observed in both sexes, but significant dose response relationships were only seen among male participants. When the analyses were restricted to former and current smokers, participants with the lowest cigarette exposure tended to benefit most from the potential chemopreventive effect of aspirin. After stratification by histology, regular aspirin use was significantly associated with reduced risk of small cell lung cancer and non-small cell lung cancer. Conclusions Overall, results from this hospital-based case-control study suggest that regular aspirin use may be associated with reduced risk of lung cancer. PMID:12453317

Hepatocyte growth factor induces resistance to anti-epidermal growth factor receptor antibody in lung cancer.

PubMed

Yamada, Tadaaki; Takeuchi, Shinji; Kita, Kenji; Bando, Hideaki; Nakamura, Takahiro; Matsumoto, Kunio; Yano, Seiji

2012-02-01

Epidermal growth factor receptor (EGFR) is an attractive drug target in lung cancer, with several anti-EGFR antibodies and small-molecule inhibitors showing efficacy in lung cancer patients. Patients, however, may develop resistance to EGFR inhibitors. We demonstrated previously that hepatocyte growth factor (HGF) induced resistance to EGFR tyrosine kinase inhibitors in lung cancers harboring EGFR mutations. We therefore determined whether HGF could induce resistance to the anti-EGFR antibody (EGFR Ab) cetuximab in lung cancer cells, regardless of EGFR gene status. Cetuximab sensitivity and signal transduction in lung cancer cells were examined in the presence or absence of HGF, HGF-producing fibroblasts, and cells tranfected with the HGF gene in vitro and in vivo. HGF induced resistance to cetuximab in H292 (EGFR wild) and Ma-1(EGFR mutant) cells. Western blotting showed that HGF-induced resistance was mediated by the Met/Gab1/Akt signaling pathway. Resistance of H292 and Ma-1 cells to cetuximab was also induced by coculture with lung fibroblasts producing high levels of HGF and by cells stably transfected with the HGF gene. This resistance was abrogated by treatment with anti-HGF neutralizing antibody. HGF-mediated resistance is a novel mechanism of resistance to EGFR Ab in lung cancers, with fibroblast-derived HGF inducing cetuximab resistance in H292 tumors in vivo. The involvement of HGF-Met-mediated signaling should be assessed in acquired resistance to EGFR Ab in lung cancer, regardless of EGFR gene status.

Lung cancer in HIV Infection.

PubMed

Mani, Deepthi; Haigentz, Missak; Aboulafia, David M

2012-01-01

Lung cancer is the most prevalent non-AIDS-defining malignancy in the highly active antiretroviral therapy era. Smoking plays a significant role in the development of HIV-associated lung cancer, but the cancer risk is two to four times greater in HIV-infected persons than in the general population, even after adjusting for smoking intensity and duration. Lung cancer is typically diagnosed a decade or more earlier among HIV-infected persons (mean age, 46 years) compared to those without HIV infection. Adenocarcinoma is the most common histological subtype, and the majority of patients are diagnosed with locally advanced or metastatic carcinoma. Because pulmonary infections are common among HIV-infected individuals, clinicians may not suspect lung cancer in this younger patient population. Surgery with curative intent remains the treatment of choice for early-stage disease. Although there is increasing experience in using radiation and chemotherapy for HIV-infected patients who do not have surgical options, there is a need for prospective studies because this population is frequently excluded from participating in cancer trials. Evidence-based treatments for smoking-cessation with demonstrated efficacy in the general population must be routinely incorporated into the care of HIV-positive smokers. Copyright © 2012 Elsevier Inc. All rights reserved.

Expanded Circulating Tumor Cells from a Patient with ALK-Positive Lung Cancer Present with EML4-ALK Rearrangement Along with Resistance Mutation and Enable Drug Sensitivity Testing: A Case Study.

PubMed

Zhang, Zhuo; Shiratsuchi, Hiroe; Palanisamy, Nallasivam; Nagrath, Sunitha; Ramnath, Nithya

2017-02-01

The emergence of liquid biopsy using circulating tumor cells (CTCs) as a resource to identify genomic alterations in cancer presents new opportunities for diagnosis, therapy, and surveillance. We identified EML4-ALK gene rearrangement in expanded CTCs from a patient with ALK-positive lung adenocarcinoma. At the time of radiographic progression, CTCs obtained from the patient revealed a drug resistance mutation (i.e., L1196M on the ALK gene). CTCs were expanded ex vivo and drug sensitivity testing was performed using two ALK inhibitors, crizotinib and ceritinib. The half maximal inhibitory concentration of ceritinib was 1664 nM compared with crizotinib (2268 nM), showing that ceritinib was a more potent ALK inhibitor. We show that it is feasible to detect serial genetic alterations in expanded CTCs and perform in vitro drug screening. These findings support the clinical utility of CTCs not only for diagnosis, but also a potential tool for drug sensitivity testing in distinct subsets of lung cancer and for personalized precision medicine. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

The liquid biopsy in lung cancer.

PubMed

Ansari, Junaid; Yun, Jungmi W; Kompelli, Anvesh R; Moufarrej, Youmna E; Alexander, Jonathan S; Herrera, Guillermo A; Shackelford, Rodney E

2016-11-01

The incidence of lung cancer has significantly increased over the last century, largely due to smoking, and remains the most common cause of cancer deaths worldwide. This is often due to lung cancer first presenting at late stages and a lack of curative therapeutic options at these later stages. Delayed diagnoses, inadequate tumor sampling, and lung cancer misdiagnoses are also not uncommon due to the limitations of the tissue biopsy. Our better understanding of the tumor microenvironment and the systemic actions of tumors, combined with the recent advent of the liquid biopsy, may allow molecular diagnostics to be done on circulating tumor markers, particularly circulating tumor DNA. Multiple liquid biopsy molecular methods are presently being examined to determine their efficacy as surrogates to the tumor tissue biopsy. This review will focus on new liquid biopsy technologies and how they may assist in lung cancer detection, diagnosis, and treatment.

Lung cancer disparities and African-Americans.

PubMed

Sin, Mo-Kyung

2017-07-01

African-Americans, as historically disadvantaged minorities, have more advanced stages of cancer when diagnosed, lower survival rates, and lower rates of accessing timely care than do Caucasians. Lung cancer incidence and mortality, in particular, are high among African-Americans. The U.S. Preventive Services Task Force recently released an evidence-based lung cancer screening technology called low-dose computerized tomography. High-risk African-Americans might benefit greatly from such screening but not many are aware of this technology. Public health nurses can play a key role in increasing awareness of the technology among African-American communities and encouraging qualified African-Americans to obtain screening. This study discusses issues with lung cancer and smoking among African-Americans, a recently released evidence-based lung cancer screening technology, and implications for public health nurses to enhance uptake of the new screening technology among high-risk African-Americans. © 2017 Wiley Periodicals, Inc.

Angiogenin and vascular endothelial growth factor expression in lungs of lung cancer patients.

PubMed

Rozman, Ales; Silar, Mira; Kosnik, Mitja

2012-12-01

BACKGROUND.: Lung cancer is the leading cause of cancer deaths. Angiogenesis is crucial process in cancer growth and progression. This prospective study evaluated expression of two central regulatory molecules: angiogenin and vascular endothelial growth factor (VEGF) in patients with lung cancer. PATIENTS AND METHODS.: Clinical data, blood samples and broncho-alveolar lavage (BAL) from 23 patients with primary lung carcinoma were collected. BAL fluid was taken from part of the lung with malignancy, and from corresponding healthy side of the lung. VEGF and angiogenin concentrations were analysed by an enzyme-linked immunosorbent assay. Dilution of bronchial secretions in the BAL fluid was calculated from urea concentration ratio between serum and BAL fluid. RESULTS.: We found no statistical correlation between angiogenin concentrations in serum and in bronchial secretions from both parts of the lung. VEGF concentrations were greater in bronchial secretions in the affected side of the lung than on healthy side. Both concentrations were greater than serum VEGF concentration. VEGF concentration in serum was in positive correlation with tumour size (p = 0,003) and with metastatic stage of disease (p = 0,041). There was correlation between VEGF and angiogenin concentrations in bronchial secretions from healthy side of the lung and between VEGF and angiogenin concentrations in bronchial secretions from part of the lung with malignancy. CONCLUSION.: Angiogenin and VEGF concentrations in systemic, background and local samples of patients with lung cancer are affected by different mechanisms. Pro-angiogenic activity of lung cancer has an important influence on the levels of angiogenin and VEGF.

Angiogenin and vascular endothelial growth factor expression in lungs of lung cancer patients

PubMed Central

Rozman, Ales; Silar, Mira; Kosnik, Mitja

2012-01-01

Background. Lung cancer is the leading cause of cancer deaths. Angiogenesis is crucial process in cancer growth and progression. This prospective study evaluated expression of two central regulatory molecules: angiogenin and vascular endothelial growth factor (VEGF) in patients with lung cancer. Patients and methods. Clinical data, blood samples and broncho-alveolar lavage (BAL) from 23 patients with primary lung carcinoma were collected. BAL fluid was taken from part of the lung with malignancy, and from corresponding healthy side of the lung. VEGF and angiogenin concentrations were analysed by an enzyme-linked immunosorbent assay. Dilution of bronchial secretions in the BAL fluid was calculated from urea concentration ratio between serum and BAL fluid. Results. We found no statistical correlation between angiogenin concentrations in serum and in bronchial secretions from both parts of the lung. VEGF concentrations were greater in bronchial secretions in the affected side of the lung than on healthy side. Both concentrations were greater than serum VEGF concentration. VEGF concentration in serum was in positive correlation with tumour size (p = 0,003) and with metastatic stage of disease (p = 0,041). There was correlation between VEGF and angiogenin concentrations in bronchial secretions from healthy side of the lung and between VEGF and angiogenin concentrations in bronchial secretions from part of the lung with malignancy. Conclusion. Angiogenin and VEGF concentrations in systemic, background and local samples of patients with lung cancer are affected by different mechanisms. Pro-angiogenic activity of lung cancer has an important influence on the levels of angiogenin and VEGF. PMID:23412843

Treatment Options by Stage (Non-Small Cell Lung Cancer)

MedlinePlus

... Cancer Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key ...

Survival in patients with metachronous second primary lung cancer.

PubMed

Ha, Duc; Choi, Humberto; Chevalier, Cory; Zell, Katrina; Wang, Xiao-Feng; Mazzone, Peter J

2015-01-01

Four to 10% of patients with non-small cell lung cancer subsequently develop a metachronous second primary lung cancer. The decision to perform surveillance or screening imaging for patients with potentially cured lung cancer must take into account the outcomes expected when detecting metachronous second primaries. To assess potential survival differences between patients with metachronous second primary lung cancer compared to matched patients with first primary lung cancer. We retrospectively reviewed patients diagnosed with lung cancer at the Cleveland Clinic (2006-2010). Metachronous second primary lung cancer was defined as lung cancer diagnosed after a 4-year, disease-free interval from the first lung cancer, or if there were two different histologic subtypes diagnosed at different times. Patients with first primary lung cancer diagnosed in the same time period served as control subjects. Propensity score matching was performed using age, sex, smoking history, histologic subtype, and collaborative stage, with a 1:3 case-control ratio. Survival analyses were performed by Cox proportional hazards modeling and Kaplan-Meier estimates. Forty-four patients met criteria for having a metachronous second primary lung cancer. There were no statistically significant differences between case subjects and control subjects in prognostic variables. The median survival time and 2-year overall survival rate for the metachronous second primary group, compared with control subjects, were as follows: 11.8 versus 18.4 months (P = 0.18) and 31.0 versus 40.9% (P = 0.28). The survival difference was largest in those with stage I metachronous second primaries (median survival time, 26.8 vs. 60.4 mo, P = 0.09; 2-year overall survival, 56.3 vs. 71.2%, P = 0.28). Patients with stage I metachronous second primary lung cancer may have worse survival than those who present with a first primary lung cancer. This could influence the benefit-risk balance of screening the high-risk cohort with

Comparative assessment of the diagnostic value of transbronchial lung biopsy and bronchoalveolar lavage fluid cytology in lung cancer.

PubMed

Binesh, Fariba; Pirdehghan, Azar; Mirjalili, Mohammad Reza; Samet, Mohammad; Majomerd, Zahra Amini; Akhavan, Ali

2015-01-01

This study was designed to determine the accuracy of bronchoalveolar lavage fluid cytology (BAL) using histopathologic examination of transbronchial biopsy specimens as the gold standard in diagnosis of lung carcinoma at our center. A retrospective study was conducted to investigate a total of 388 patients who were suspected of having lung cancer and had undergone fiberoptic bronchoscopy in Shahid Sadoughi hospital from 2006 to 2011. Lung masses were proven to be malignant by histology. Transbronchial lung biopsy (TBLB) identified malignancy in 183 of the 388 cases, including 48 cases (26.2%) with adenocarcinoma, 4(2.1%) with bronchioloalveolar carcinoma, 47(25.6%)with squamous cell carcinoma, 34(18.5%) with well-diffentiated neuroendocrine carcinoma, 35(19.1%) with small cell carcinoma, 14 (7.6%) with non-small cell carcinoma, and 1 (0.54%) with large cell carcinoma. A total of 205 cases were correctly classified as negative. BAL was also performed in 388 patients; 86/103 cases were consistent with the final diagnosis of lung cancer and 188/285 cases were correctly classified as negative. The sensitivity of BAL was 46.9%(CI:41.9%, 51.8%)) and its specificity was 91.6%(CI:88.8%, 94.3%). BAL had a positive predictive value (PPV) of 83.4%(CI:79.7%, 87.1%) and a negative predictive value (NPV) of 65.8%(CI:61%, 70.5%). The overall accuracy of BAL was 70.5% and the exact concordance was 39%. Our findings suggest that BAL cytology is not sensitive but is a specific test for diagnosis of lung carcinoma. If transbronchial lung biopsy is combined with bronchoalveolar lavage, the positive diagnostic rate will be further elevated.

Reactive oxygen species modulator 1 (Romo1) as a novel diagnostic marker for lung cancer-related malignant effusion

PubMed Central

Lee, Seung Hyeun; Park, Myung Jae; Choi, Sue In; Lee, Eun Joo; Lee, Sang Yeub; In, Kwang Ho

2017-01-01

Abstract Reactive oxygen species modulator 1 (Romo1) is a novel protein that plays an important role in intracellular reactive oxygen species generation. Recently, Romo1 has been suggested to have diagnostic and prognostic potential in lung cancer. However, there is no data on the diagnostic value of Romo1 level in malignant pleural effusion. We evaluated the clinical usefulness of Romo1 in pleural fluid for the diagnosis of malignant effusion in lung cancer patients. Pleural fluid Romo1 level was measured using enzyme-linked immunosorbent assay and compared between lung cancer-associated malignant effusion (n = 53; 29 adenocarcinomas and 24 squamous cell carcinomas) and benign pleural effusions (n = 91; 31 tuberculous pleurisy, 30 parapneumonic effusion, and 30 transudate). The discriminative power of Romo1 for lung cancer-associated malignant effusion was determined using receiver operating characteristic (ROC) curve analysis and compared with those of other tumor markers. Median Romo1 level in lung cancer-associated malignant effusion was 99.3 ng/mL, which was significantly higher than that in benign pleural effusions (P < 0.001). The optimal cutoff value of Romo1 to discriminate lung cancer-associated malignant effusion from benign effusions was 67.0 ng/mL with a sensitivity of 73.8% and a specificity of 84.1%. The area under the curve was 0.837 (95% confidence interval [CI]: 0.750–0.886), which was significantly better than that of cytokeratin 19 fragments (P < 0.001). Pleural fluid Romo1 could discriminate lung cancer from benign diseases with considerable sensitivity and specificity. Our findings suggest a diagnostic potential of Romo1 for lung cancer-associated malignant effusion. PMID:28121949

Missed lung cancer: when, where, and why?

PubMed Central

del Ciello, Annemilia; Franchi, Paola; Contegiacomo, Andrea; Cicchetti, Giuseppe; Bonomo, Lorenzo; Larici, Anna Rita

2017-01-01

Missed lung cancer is a source of concern among radiologists and an important medicolegal challenge. In 90% of the cases, errors in diagnosis of lung cancer occur on chest radiographs. It may be challenging for radiologists to distinguish a lung lesion from bones, pulmonary vessels, mediastinal structures, and other complex anatomical structures on chest radiographs. Nevertheless, lung cancer can also be overlooked on computed tomography (CT) scans, regardless of the context, either if a clinical or radiologic suspect exists or for other reasons. Awareness of the possible causes of overlooking a pulmonary lesion can give radiologists a chance to reduce the occurrence of this eventuality. Various factors contribute to a misdiagnosis of lung cancer on chest radiographs and on CT, often very similar in nature to each other. Observer error is the most significant one and comprises scanning error, recognition error, decision-making error, and satisfaction of search. Tumor characteristics such as lesion size, conspicuity, and location are also crucial in this context. Even technical aspects can contribute to the probability of skipping lung cancer, including image quality and patient positioning and movement. Albeit it is hard to remove missed lung cancer completely, strategies to reduce observer error and methods to improve technique and automated detection may be valuable in reducing its likelihood. PMID:28206951

Improved Classification of Lung Cancer Using Radial Basis Function Neural Network with Affine Transforms of Voss Representation.

PubMed

Adetiba, Emmanuel; Olugbara, Oludayo O

2015-01-01

Lung cancer is one of the diseases responsible for a large number of cancer related death cases worldwide. The recommended standard for screening and early detection of lung cancer is the low dose computed tomography. However, many patients diagnosed die within one year, which makes it essential to find alternative approaches for screening and early detection of lung cancer. We present computational methods that can be implemented in a functional multi-genomic system for classification, screening and early detection of lung cancer victims. Samples of top ten biomarker genes previously reported to have the highest frequency of lung cancer mutations and sequences of normal biomarker genes were respectively collected from the COSMIC and NCBI databases to validate the computational methods. Experiments were performed based on the combinations of Z-curve and tetrahedron affine transforms, Histogram of Oriented Gradient (HOG), Multilayer perceptron and Gaussian Radial Basis Function (RBF) neural networks to obtain an appropriate combination of computational methods to achieve improved classification of lung cancer biomarker genes. Results show that a combination of affine transforms of Voss representation, HOG genomic features and Gaussian RBF neural network perceptibly improves classification accuracy, specificity and sensitivity of lung cancer biomarker genes as well as achieving low mean square error.

Lung cancer: diagnosis, treatment principles, and screening.

PubMed

Latimer, Kelly M; Mott, Timothy F

2015-02-15

Lung cancer is classified histologically into small cell and non-small cell lung cancers. The most common symptoms of lung cancer are cough, dyspnea, hemoptysis, and systemic symptoms such as weight loss and anorexia. High-risk patients who present with symptoms should undergo chest radiography. If a likely alternative diagnosis is not identified, computed tomography and possibly positron emission tomography should be performed. If suspicion for lung cancer is high, a diagnostic evaluation is warranted. The diagnostic evaluation has three simultaneous steps (tissue diagnosis, staging, and functional evaluation), all of which affect treatment planning and determination of prognosis. The least invasive method possible should be used. The diagnostic evaluation and treatment of a patient with lung cancer require a team of specialists, including a pulmonologist, medical oncologist, radiation oncologist, pathologist, radiologist, and thoracic surgeon. Non-small cell lung cancer specimens are tested for various mutations, which, if present, can be treated with new targeted molecular therapies. The family physician should remain involved in the patient's care to ensure that the values and wishes of the patient and family are considered and, if necessary, to coordinate end-of-life care. Early palliative care improves quality of life and may prolong survival. Family physicians should concentrate on early recognition of lung cancer, as well as prevention by encouraging tobacco cessation at every visit. The U.S. Preventive Services Task Force recommends lung cancer screening using low-dose computed tomography in high-risk patients. However, the American Academy of Family Physicians concludes that the evidence is insufficient to recommend for or against screening. Whether to screen high-risk patients should be a shared decision between the physician and patient.

Contemporary management of voice and swallowing disorders in patients with advanced lung cancer.

PubMed

Brady, Grainne C; Carding, Paul N; Bhosle, Jaishree; Roe, Justin W G

2015-06-01

Advanced lung cancer can cause changes to swallowing and communication function. Direct tumour invasion, dyspnoea and deconditioning can all impact on swallowing function and communication. Cancer treatment, if administered, may cause or compound symptoms. In this study, the nature of swallowing and communication difficulties in patients with advanced lung cancer will be discussed, and management options including medical management, speech and language therapy (SLT) intervention, and surgical interventions will be considered. Advanced lung cancer can result in voice and swallowing difficulties, which can increase symptom burden and significantly impact on quality of life (QOL). There is a growing evidence base to support the use of injection laryngoplasty under local anaesthetic to offer immediate improvement in voice, swallowing and overall QOL. There is limited literature on the nature and extent of voice and swallowing impairment in patients with lung cancer. Well designed studies with robust and sensitive multidimensional dysphagia and dysphonia assessments are required. Outcome studies examining interventions with clearly defined treatment goals are required. These studies should include both functional and patient-reported outcome measures to develop the evidence base and to ensure that interventions are both timely and appropriate.

Osimertinib making a breakthrough in lung cancer targeted therapy

PubMed Central

Zhang, Haijun

2016-01-01

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the evidence-based first-line treatment for advanced non-small-cell lung cancer that harbors sensitizing EGFR mutations (EGFRm+) such as exon 19 deletions and L858R substitutions in exon 21. However, acquired resistance to EGFR TKIs is mostly driven by a second-site EGFR T790M mutation, which negates their inhibitory activity. Osimertinib (AZD9291, Tagrisso™), an oral, third-generation EGFR TKI, has been designed to target the EGFR T790M mutation, while sparing wild-type EGFR. In this up-to-date review, focus is not only on the structure, mechanisms, and pharmacokinetics of osimertinib but also on summarizing clinical trials and making recommendations of osimertinib for patients with non-small-cell lung cancer. PMID:27660466

Immunotherapy for lung cancer: advances and prospects.

PubMed

Yang, Li; Wang, Liping; Zhang, Yi

2016-01-01

Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths worldwide. To date, surgery is the first choice treatment, but most clinically diagnosed cases are inoperable. While chemotherapy and/or radiotherapy are the next considered options for such cases, these treatment modalities have adverse effects and are sometimes lethal to patients. Thus, new effective strategies with minimal side effects are urgently needed. Cancer immunotherapy provides either active or passive immunity to target tumors. Multiple immunotherapy agents have been proposed and tested for potential therapeutic benefit against lung cancer, and some pose fewer side effects as compared to conventional chemotherapy and radiotherapy. In this article, we discuss studies focusing on interactions between lung cancer and the immune system, and we place an emphasis on outcome evidence in order to create a knowledge base well-grounded in clinical reality. Overall, this review highlights the need for new lung cancer treatment options, with much ground to be paved for future advances in the field. We believe that immunotherapy agents alone or with other forms of treatment can be recognized as next modality of lung cancer treatment.

JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors

PubMed Central

Gao, Sizhi P.; Chang, Qing; Mao, Ninghui; Daly, Laura A.; Vogel, Robert; Chan, Tyler; Liu, Shu Hui; Bournazou, Eirini; Schori, Erez; Zhang, Haiying; Brewer, Monica Red; Pao, William; Morris, Luc; Ladanyi, Marc; Arcila, Maria; Manova-Todorova, Katia; de Stanchina, Elisa; Norton, Larry; Levine, Ross L.; Altan-Bonnet, Gregoire; Solit, David; Zinda, Michael; Huszar, Dennis; Lyden, David; Bromberg, Jacqueline F.

2016-01-01

Lung adenocarcinomas with mutant epidermal growth factor receptor (EGFR) respond to EGFR-targeted tyrosine kinase inhibitors (TKIs), but resistance invariably occurs. We found that the Janus kinase (JAK)/signal transduction and activator of transcription 3 (STAT3) signaling pathway was aberrantly increased in TKI-resistant EGFR-mutant non–small cell lung cancer (NSCLC) cells. JAK2 inhibition restored sensitivity to the EGFR inhibitor erlotinib in TKI-resistant cell lines and xenograft models of EGFR-mutant TKI-resistant lung cancer. JAK2 inhibition uncoupled EGFR from its negative regulator, suppressor of cytokine signaling 5 (SOCS5), consequently increasing EGFR abundance and restoring the tumor cells’ dependence on EGFR signaling. Furthermore, JAK2 inhibition led to heterodimerization of mutant and wild-type EGFR subunits, the activity of which was then blocked by TKIs. Our results reveal a mechanism whereby JAK2 inhibition overcomes acquired resistance to EGFR inhibitors and support the use of combination therapy with JAK and EGFR inhibitors for the treatment of EGFR-dependent NSCLC. PMID:27025877

Fludeoxyglucose F-18-PET in Planning Lung Cancer Radiation Therapy

ClinicalTrials.gov

2018-04-19

Stage I Lung Cancer; Stage I Non-Small Cell Lung Cancer AJCC v7; Stage IA Non-Small Cell Lung Carcinoma AJCC v7; Stage IB Non-Small Cell Lung Carcinoma AJCC v7; Stage II Lung Cancer; Stage II Non-Small Cell Lung Cancer AJCC v7; Stage IIA Non-Small Cell Lung Carcinoma AJCC v7; Stage IIB Non-Small Cell Lung Carcinoma AJCC v7

Collagen gel droplet-embedded culture drug sensitivity test for adjuvant chemotherapy after complete resection of non-small-cell lung cancer.

PubMed

Inoue, Masayoshi; Maeda, Hajime; Takeuchi, Yukiyasu; Fukuhara, Kenjiro; Shintani, Yasushi; Funakoshi, Yasunobu; Funaki, Soichiro; Nojiri, Takashi; Kusu, Takashi; Kusumoto, Hidenori; Kimura, Toru; Okumura, Meinoshin

2018-04-01

We conducted a prospective clinical study to individualize adjuvant chemotherapy after complete resection of non-small-cell lung cancer (NSCLC), based on the drug sensitivity test. Patients with resectable c-stage IB-IIIA NSCLC were registered between 2005 and 2010. We performed the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) on a fresh surgical specimen to assess in vitro chemosensitivity and evaluated the prognostic outcome after adjuvant chemotherapy with carboplatin/paclitaxel based on the CD-DST. Among 92 registered patients, 87 were eligible for inclusion in the analysis. The success rate of CD-DST was 86% and chemosensitivity to carboplatin and/or paclitaxel was evident in 57 (76%) of the 75 patients. Adjuvant chemotherapy was completed in 22 (73%) of 30 patients. The 5-year overall survival rates were 71, 73, and 75% for all, CD-DST success, and chemosensitive patients, respectively. The 5-year disease-free survival and overall survival rates of the chemosensitive patients who completed adjuvant chemotherapy using carboplatin/paclitaxel were 68 and 82%, respectively. The 5-year disease-free survival and overall survival rates of the patients with stage II-IIIA chemosensitive NSCLC were 58 and 75%, respectively. Comparative analyses of the chemosensitive and non-chemosensitive/CD-DST failure groups showed no significant survival difference. CD-DST can be used to evaluate chemosensitivity after lung cancer surgery; however, its clinical efficacy for assessing individualized treatment remains uncertain.

Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology

NASA Astrophysics Data System (ADS)

Wendel, Marco; Bazhenova, Lyudmila; Boshuizen, Rogier; Kolatkar, Anand; Honnatti, Meghana; Cho, Edward H.; Marrinucci, Dena; Sandhu, Ajay; Perricone, Anthony; Thistlethwaite, Patricia; Bethel, Kelly; Nieva, Jorge; van den Heuvel, Michel; Kuhn, Peter

2012-02-01

Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL-1 (range 0-515.6) and a mean of 44.7 (±95.2) HD-CTCs mL-1. No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0-178.2), stage III (n = 34, range 0-515.6) and stages I/II (n = 13, range 0-442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and surveillance in

The European initiative for quality management in lung cancer care.

PubMed

Blum, Torsten G; Rich, Anna; Baldwin, David; Beckett, Paul; De Ruysscher, Dirk; Faivre-Finn, Corinne; Gaga, Mina; Gamarra, Fernando; Grigoriu, Bogdan; Hansen, Niels C G; Hubbard, Richard; Huber, Rudolf Maria; Jakobsen, Erik; Jovanovic, Dragana; Konsoulova, Assia; Kollmeier, Jens; Massard, Gilbert; McPhelim, John; Meert, Anne-Pascale; Milroy, Robert; Paesmans, Marianne; Peake, Mick; Putora, Paul-Martin; Scherpereel, Arnaud; Schönfeld, Nicolas; Sitter, Helmut; Skaug, Knut; Spiro, Stephen; Strand, Trond-Eirik; Taright, Samya; Thomas, Michael; van Schil, Paul E; Vansteenkiste, Johan F; Wiewrodt, Rainer; Sculier, Jean-Paul

2014-05-01

Lung cancer is the commonest cause of cancer-related death worldwide and poses a significant respiratory disease burden. Little is known about the provision of lung cancer care across Europe. The overall aim of the Task Force was to investigate current practice in lung cancer care across Europe. The Task Force undertook four projects: 1) a narrative literature search on quality management of lung cancer; 2) a survey of national and local infrastructure for lung cancer care in Europe; 3) a benchmarking project on the quality of (inter)national lung cancer guidelines in Europe; and 4) a feasibility study of prospective data collection in a pan-European setting. There is little peer-reviewed literature on quality management in lung cancer care. The survey revealed important differences in the infrastructure of lung cancer care in Europe. The European guidelines that were assessed displayed wide variation in content and scope, as well as methodological quality but at the same time there was relevant duplication. The feasibility study demonstrated that it is, in principle, feasible to collect prospective demographic and clinical data on patients with lung cancer. Legal obligations vary among countries. The European Initiative for Quality Management in Lung Cancer Care has provided the first comprehensive snapshot of lung cancer care in Europe.

The ALCHEMIST Lung Cancer Trials

Cancer.gov

A collection of material about the ALCHEMIST lung cancer trials that will examine tumor tissue from patients with certain types of early-stage, completely resected non-small cell lung cancer for gene mutations in the EGFR and ALK genes, and assign patients with these gene mutations to treatment trials testing post-surgical use of drugs targeted against these mutations.

Metabolic Signaling and Therapy of Lung Cancer

DTIC Science & Technology

2013-09-01

this grant is to decipher molecular mechanisms by which glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) promotes lung cancer cell metabolism and...PGAM1 in regulation of lung cancer metabolism; molecular mechanisms underlying PGAM1 activation in lung cancer; PGAM1 inhibitor as novel therapy to...leukemia cells from human patients with minimal toxicity. Therefore, the current funded proposal focuses to decipher molecular mechanisms by which

[The Clinical Application of Video Mediastinoscopy and CT in the N Staging of Preoperative Lung Cancer.].

PubMed

Wang, Zhiheng; Qi, Weibo; Zhu, Yong; Lin, Ruobai

2009-10-20

Preoperative lung cancer with mediastinal lymph nodes metastasis can be diagnosed by vedio mediastinoscopy (VM) and CT. This study was to explore the value of VM and CT in the diagnosis of N staging of preoperative lung cancer, and to discuss the difference between the two methods. Forty-eight cases diagnosed of lung cancer by CT or PET-CT were examined by VM. The sensitivity, specificity, validity, positive predictive value and negative predictive value of VM and CT were speculated according to the postoperative pathological reports, and the difference between VM and CT in the diagnosis of lung cancer with mediastinal lymph nodes metastasis was discussed. (1)Under the examination of VM, 31 patients with the negative outcome received the direct operation; 14 patients with N2 received 2 courses of neoadjuvant chemotherapy before operation; 3 patients with N3 received chemotherapy and/or radiotherapy. (2)Forty-one cases with final diagnosis of lung cancer were used as samples to speculate the sensitivity, specificity, validity, positive predictive value and negative predictive value of VM. They were 93.3%, 100%, 97.6%, 100%, 96.3%, which of CT were 66.7%, 53.8%, 58.5%, 45.5%, 73.7% (Chi-square=4.083, P=0.039), the difference between VM and CT was statistically significant. (3)In this group, the complications of VM incidence rate was 2.08% (1/48), and the case was pneumothorax. VM is superior to CT in the diagnosis of N staging of preoperative lung cancer; Due to its safety and effectiveness, VM will be wildly used in the field of thoracic surgery.

Inflammatory Gene Polymorphisms in Lung Cancer Susceptibility.

PubMed

Eaton, Keith D; Romine, Perrin E; Goodman, Gary E; Thornquist, Mark D; Barnett, Matt J; Petersdorf, Effie W

2018-05-01

Chronic inflammation has been implicated in carcinogenesis, with increasing evidence of its role in lung cancer. We aimed to evaluate the role of genetic polymorphisms in inflammation-related genes in the risk for development of lung cancer. A nested case-control study design was used, and 625 cases and 625 well-matched controls were selected from participants in the β-Carotene and Retinol Efficacy Trial, which is a large, prospective lung cancer chemoprevention trial. The association between lung cancer incidence and survival and 23 polymorphisms descriptive of 11 inflammation-related genes (interferon gamma gene [IFNG], interleukin 10 gene [IL10], interleukin 1 alpha gene [IL1A], interleukin 1 beta gene [IL1B], interleukin 2 gene [IL2], interleukin 4 receptor gene [IL4R], interleukin 4 gene [IL4], interleukin 6 gene [IL6], prostaglandin-endoperoxide synthase 2 gene [PTGS2] (also known as COX2), transforming growth factor beta 1 gene [TGFB1], and tumor necrosis factor alpha gene [TNFA]) was evaluated. Of the 23 polymorphisms, two were associated with risk for lung cancer. Compared with individuals with the wild-type (CC) variant, individuals carrying the minor allele variants of the IL-1β-511C>T promoter polymorphism (rs16944) (CT and TT) had decreased odds of lung cancer (OR = 0.74, [95% confidence interval (CI): 0.58-0.94] and OR = 0.71 [95% CI: 0.50-1.01], respectively, p = 0.03). Similar results were observed for the IL-1β-1464 C>G promoter polymorphism (rs1143623), with presence of the minor variants CG and CC having decreased odds of lung cancer (OR = 0.75 [95% CI: 0.59-0.95] and OR = 0.69 [95% CI: 0.46-1.03], respectively, p = 0.03). Survival was not influenced by genotype. This study provides further evidence that IL1B promoter polymorphisms may modulate the risk for development of lung cancer. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Whole blood FPR1 mRNA expression predicts both non‐small cell and small cell lung cancer

PubMed Central

Vachani, Anil; Pass, Harvey I.; Rom, William N.; Ryden, Kirk; Weiss, Glen J.; Hogarth, D. K.; Runger, George; Richards, Donald; Shelton, Troy; Mallery, David W.

2018-01-01

While long‐term survival rates for early‐stage lung cancer are high, most cases are diagnosed in later stages that can negatively impact survival rates. We aim to design a simple, single biomarker blood test for early‐stage lung cancer that is robust to preclinical variables and can be readily implemented in the clinic. Whole blood was collected in PAXgene tubes from a training set of 29 patients, and a validation set of 260 patients, of which samples from 58 patients were prospectively collected in a clinical trial specifically for our study. After RNA was extracted, the expressions of FPR1 and a reference gene were quantified by an automated one‐step Taqman RT‐PCR assay. Elevated levels of FPR1 mRNA in whole blood predicted lung cancer status with a sensitivity of 55% and a specificity of 87% on all validation specimens. The prospectively collected specimens had a significantly higher 68% sensitivity and 89% specificity. Results from patients with benign nodules were similar to healthy volunteers. No meaningful correlation was present between our test results and any clinical characteristic other than lung cancer diagnosis. FPR1 mRNA levels in whole blood can predict the presence of lung cancer. Using this as a reflex test for positive lung cancer screening computed tomography scans has the potential to increase the positive predictive value. This marker can be easily measured in an automated process utilizing off‐the‐shelf equipment and reagents. Further work is justified to explain the source of this biomarker. PMID:29313979

Components Necessary for High-Quality Lung Cancer Screening

PubMed Central

Powell, Charles A.; Arenberg, Douglas; Detterbeck, Frank; Gould, Michael K.; Jaklitsch, Michael T.; Jett, James; Naidich, David; Vachani, Anil; Wiener, Renda Soylemez; Silvestri, Gerard

2015-01-01

Lung cancer screening with a low-dose chest CT scan can result in more benefit than harm when performed in settings committed to developing and maintaining high-quality programs. This project aimed to identify the components of screening that should be a part of all lung cancer screening programs. To do so, committees with expertise in lung cancer screening were assembled by the Thoracic Oncology Network of the American College of Chest Physicians (CHEST) and the Thoracic Oncology Assembly of the American Thoracic Society (ATS). Lung cancer program components were derived from evidence-based reviews of lung cancer screening and supplemented by expert opinion. This statement was developed and modified based on iterative feedback of the committees. Nine essential components of a lung cancer screening program were identified. Within these components 21 Policy Statements were developed and translated into criteria that could be used to assess the qualification of a program as a screening facility. Two additional Policy Statements related to the need for multisociety governance of lung cancer screening were developed. High-quality lung cancer screening programs can be developed within the presented framework of nine essential program components outlined by our committees. The statement was developed, reviewed, and formally approved by the leadership of CHEST and the ATS. It was subsequently endorsed by the American Association of Throacic Surgery, American Cancer Society, and the American Society of Preventive Oncology. PMID:25356819

Thyroid function in lung cancer

PubMed Central

Ratcliffe, J G; Stack, B H R; Burt, R W; Ratcliffe, W A; Spilg, W G S; Cuthbert, J; Kennedy, R S

1978-01-01

Thyroid function was assessed at the time of initial diagnosis in 204 patients with lung cancer and compared with that of age and sex-matched patients with non-malignant lung disease. Abnormalities in thyroid function were found in 67 patients (33%). The most prevalent abnormality was a low T3 concentration; this was not associated with other clinical or biochemical evidence of hypothyroidism, but the short-term prognosis of these patients was worse than that of matched patients with lung cancer having normal T3 concentrations. Primary hypothyroidism occurred in three patients, low T4 concentrations and free thyroxine index (FTI) with normal thyrotrophin (TSH) concentrations in four patients, and moderately raised TSH with normal thyroid hormone concentrations in six patients; nine patients had a raised FTI with or without raised T4 concentration as the sole abnormality. Overall, the pattern of thyroid hormone metabolism in lung cancer was a tendency towards reduced T3 concentrations with significantly increased T4/T3 ratios and modestly increased 3,3′,5′-triiodothyronine (rT3) concentrations. The altered T4/T3 ratio was particularly noticeable in patients with anaplastic tumours of small (“oat cell”) and large cell types, but was not apparently related to detectable extrathoracic metastases. These data suggest that thyroid hormone metabolism is altered in patients with lung cancer by decreased 5′-monodeiodination of T4. The resulting low T3 concentrations and altered T4/T3 ratio may be partly responsible for the reduced ratio of androsterone to aetiocholanolone observed in lung cancer, which is known to be a poor prognostic sign. PMID:620266

Practical use of advanced mouse models for lung cancer.

PubMed

Safari, Roghaiyeh; Meuwissen, Ralph

2015-01-01

To date a variety of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) mouse models have been developed that mimic human lung cancer. Chemically induced or spontaneous lung cancer in susceptible inbred strains has been widely used, but the more recent genetically engineered somatic mouse models recapitulate much better the genotype-phenotype correlations found in human lung cancer. Additionally, improved orthotopic transplantation of primary human cancer tissue fragments or cells into lungs of immune-compromised mice can be valuable tools for preclinical research such as antitumor drug tests. Here we give a short overview of most somatic mouse models for lung cancer that are currently in use. We accompany each different model with a description of its practical use and application for all major lung tumor types, as well as the intratracheal injection or direct injection of fresh or freeze-thawed tumor cells or tumor cell lines into lung parenchyma of recipient mice. All here presented somatic mouse models are based on the ability to (in) activate specific alleles at a time, and in a tissue-specific cell type, of choice. This spatial-temporal controlled induction of genetic lesions allows the selective introduction of main genetic lesions in an adult mouse lung as found in human lung cancer. The resulting conditional somatic mouse models can be used as versatile powerful tools in basic lung cancer research and preclinical translational studies alike. These distinctively advanced lung cancer models permit us to investigate initiation (cell of origin) and progression of lung cancer, along with response and resistance to drug therapy. Cre/lox or FLP/frt recombinase-mediated methods are now well-used techniques to develop tissue-restricted lung cancer in mice with tumor-suppressor gene and/or oncogene (in)activation. Intranasal or intratracheal administration of engineered adenovirus-Cre or lentivirus-Cre has been optimized for introducing Cre

Primary lung cancer coexisting with active pulmonary tuberculosis.

PubMed

Varol, Y; Varol, U; Unlu, M; Kayaalp, I; Ayranci, A; Dereli, M S; Guclu, S Z

2014-09-01

Lung cancer and pulmonary tuberculosis (TB) comorbidity is a clinical problem that presents a challenge for the diagnosis and treatment of both diseases. To clarify the clinical and survival characteristics of cases with both lung cancer and active pulmonary TB. From 2008 to 2013, 3350 TB patients admitted to the TB Department of the Chest Diseases Hospital of Izmir, Turkey, were evaluated. In 38 (1.1%) male patients, lung cancer and TB were found to coexist. Almost all of the patients were diagnosed at Stage III (n = 14, 36.8%) or IV (n = 17, 44.7%) lung cancer, whereas four (10.6%) had Stage II and three (7.9%) had Stage I disease. Squamous cell lung cancer was the predominant histology (n = 23, 60.7%). The median overall survival among patients was 13.4 months (95%CI 8.09-18.8). One-year survival rates for patients with Stages I, II, III and IV were respectively 100%, 75%, 57% and 40%. The present study demonstrates that lung cancer combined with active pulmonary TB most frequently presents as squamous cell carcinoma, with a male predominance. The overall survival of lung cancer patients did not change even with concomitant active TB.

Outcomes in Lung Cancer: 9-Year Experience From a Tertiary Cancer Center in India

PubMed Central

Murali, Aditya Navile; Ganesan, Trivadi S.; Rajendranath, Rejiv; Ganesan, Prasanth; Selvaluxmy, Ganesarajah; Swaminathan, Rajaraman; Sundersingh, Shirley; Krishnamurthy, Arvind; Sagar, Tenali Gnana

2017-01-01

Purpose Lung cancer is the most common cause of cancer mortality in the world. There are limited studies on survival outcomes of lung cancer in developing countries such as India. This study analyzed the outcomes of patients with lung cancer who underwent treatment at Cancer Institute (WIA), Chennai, India, between 2006 and 2015 to determine survival outcomes and identify prognostic factors. Patients and Methods In all, 678 patients with lung cancer underwent treatment. Median age was 58 years, and 91% of patients had non–small-cell lung cancer (NSCLC). Testing for epidermal growth factor receptor mutation was performed in 132 of 347 patients and 61 (46%) were positive. Results Median progression-free survival was 6.9 months and overall survival (OS) was 7.6 months for patients with NSCLC. Median progression-free survival was 6 months and OS was 7.2 months for patients with small-cell lung cancer. On multivariable analysis, the factors found to be significantly associated with inferior OS in NSCLC included nonadenocarcinoma histology, performance status more than 2, and stage. In small-cell lung cancer, younger age and earlier stage at presentation showed significantly better survival. Conclusion Our study highlights the challenges faced in treating lung cancer in India. Although median survival in advanced-stage lung cancer is still poor, strategies such as personalized medicine and use of second-line and maintenance chemotherapy may significantly improve the survival in patients with advanced-stage lung cancer in developing countries. PMID:29094084

Involvement of MicroRNAs in Lung Cancer Biology and Therapy

PubMed Central

Liu, Xi; Sempere, Lorenzo F.; Guo, Yongli; Korc, Murray; Kauppinen, Sakari; Freemantle, Sarah J.; Dmitrovsky, Ethan

2011-01-01

MicroRNAs (miRNAs) are a class of small RNAs that regulate gene expression. Expression profiles of specific miRNAs have improved cancer diagnosis and classification and even provided prognostic information in many human cancers, including lung cancer. Tumor suppressive and oncogenic miRNAs were uncovered in lung carcinogenesis. The biological functions of these miRNAs in lung cancer were recently validated in well characterized cellular, murine transgenic as well as transplantable lung cancer models and in human paired normal-malignant lung tissue banks and tissue arrays. Tumor suppressive and oncogenic miRNAs that were identified in lung cancer will be reviewed here. Emphasis is placed on highlighting those functionally validated miRNAs that are not only biomarkers of lung carcinogenesis, but also candidate pharmacologic targets. How these miRNA findings advance an understanding of lung cancer biology and could improve lung cancer therapy are discussed in this article. PMID:21420030

[A test of screening to predict lung cancer among dust-exposed tin miners with sputum imaging cytometry].

PubMed

Liu, Yue-wei; Chen, Jing-qiong; Sun, Xiao-rong; Yang, Jian; Liu, Yong; Chen, Wei-hong

2008-04-01

To evaluate efficacy of sputum imaging cytometry in early diagnosis on lung cancer among tin miners exposed to dust and analyze possible risk factors related to lung cancer among tin miners. From a cohort of tin miners in Guangxi Province, a total of 345 male tin miners higher than 45 years old and with high exposure to crystalline silica dust were randomly selected as the objects. Imaging cytometry was used to implement the sputum analysis for the screening on lung cancer according to the experience diagnostic standard. All objects were then followed up to the end of 2006. Clinical diagnosis of lung cancer was used as the golden standard to evaluate the efficacy of screening. From 1998 to 2006, 11 new cases were diagnosed as clinical lung cancer. Except of age and exposure to occupational hazards, smoking status (P = 0.0384) and mean smoking dose (P = 0.0078) were significantly associated with lung cancer, and the adjusted odds ratio of high level to the low was 18.21 (2.15 approximately 154.39). The sensitivity, specificity and Youden's index of the sputum imaging cytometry for the experience diagnosis were 27.3%, 83.9% and 11.2% respectively. According to the ROC curve analysis, area under ROC Curve (AUC) of C2.5 (the percentage when the DNA index ranged from 1.25 to 2.50) was 0.647 (0.525 approximately 0.768), with the optimal operating point (OOP) of 1.70%. Sensitivity, specificity, agreement rate, positive predictive value, negative predictive value and Youden's index for predicting lung cancers in high-exposure tin miners were found to be 72.7%, 62.3%, 62.6%, 6.0%, 98.6% and 35.0% respectively. Smoking is confirmed as an important risk factor of lung cancer in tin miners. The diagnostic efficiency can be improved if the diagnostic point of C2.5 is adjusted to 1.70%.

Electrochemical treatment of lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xin, Y.L.; Xue, F.Z.; Ge, B.S.

1997-03-01

A pilot study of electrochemical treatment (ECT) as a therapy for 386 patients with nonsmall cell lung cancer was undertaken. There were 103 stage 2 cases, 89 stage 3a cases, 122 stage 3b cases, and 72 stage 4 cases. Two ECT methods were used. For peripherally located lung cancer, platinum electrodes were inserted transcutaneously into the tumor under x-ray or CT guidance. For central type lung cancer or for those inoperable during thoracotomy, electrodes were inserted intraoperatively directly into the cancer. Voltage was 6--8 V, current was 40--100 mA, and electric charge was 100 coulombs per cm of tumor diameter.more » The number of electrodes was determined from the size of cancer mass, because the diameter of effective area around each electrode is approximately 3 cm. The short-term (6 months after ECT) results of the 386 lung cancer cases were: complete response (CR), 25.6% (99/386); partial response (PR), 46.4% (179/386); no change (NC), 15.3% (59/386); and progressive disease (PD), 12.7% (49/386). The total effective rate (CR + PR) was 72% (278/386). The 1, 3, and 5 year overall survival rates were 86.3% (333/386), 58.8% (227/386), and 29.5% (114/386), respectively. The main complication was traumatic pneumothorax, with an incidence rate of 14.8% (57/386). These clinical results show that ECT is simple, safe, effective, and minimally traumatic. ECT provides an alternative method for treating lung cancers that are conventionally inoperable, that are not responsive to chemotherapy or radiotherapy, or that cannot be resected after thoracotomy. Long-term survival rates suggest that ECT warrants further investigation.« less

Lung Cancer Risk Models for Screening (R package: lcrisks)

Cancer.gov

In both the absence and presence of screening, the R package lcrisks, calculates individual risks of lung cancer and lung cancer death based on covariates: age, education, sex, race, smoking intensity/duration/quit-years, Body Mass Index, family history of lung-cancer, and self-reported emphysema. In the presence of CT screening akin to the NLST (3 yearly screens, 5 years of follow-up), it uses the covariates to estimate risk of false-positive CT screen as well as the reduction in risk of lung cancer death and increase in risk of lung cancer screening.

Hsp27 Inhibition with OGX-427 Sensitizes Non-Small Cell Lung Cancer Cells to Erlotinib and Chemotherapy.

PubMed

Lelj-Garolla, Barbara; Kumano, Masafumi; Beraldi, Eliana; Nappi, Lucia; Rocchi, Palma; Ionescu, Diana N; Fazli, Ladan; Zoubeidi, Amina; Gleave, Martin E

2015-05-01

Non-small cell lung cancer (NSCLC) is the most frequent cause of death from cancer worldwide. Despite the availability of active chemotherapy regimens and EGFR tyrosine kinase inhibitors, all advanced patients develop recurrent disease after first-line therapy. Although Hsp27 is a stress-induced chaperone that promotes acquired resistance in several cancers, its relationship to treatment resistance in NSCLC has not been defined. Understanding adaptive responses of acquired resistance will help guide new strategies to control NSCLC. Hsp27 levels were evaluated in an HCC827 erlotinib-resistant-derived cell line (HCC-827Resistant), and sensitivity to erlotinib was examined in Hsp27-overexpressing A549 cells. The role of Hsp27 in both erlotinib and cytotoxic treatment resistance was evaluated in HCC-827 and A549 NSCLC cells using the Hsp27 antisense drug OGX-427. The effect of OGX-427 in combination with erlotinib was also assessed in mice bearing A549 xenografts. Hsp27 is induced by erlotinib and protects NSCLC cells from treatment-induced apoptosis, whereas OGX-427 sensitizes NSCLC cells to erlotinib. Interestingly, increased resistance to erlotinib was observed when Hsp27 was increased either in HCC827 erlotinib-resistant or overexpressing A549 cells. Combining OGX-427 with erlotinib significantly enhanced antitumor effects in vitro and delayed A549 xenograft growth in vivo. OGX-427 also significantly enhanced the activity of cytotoxic drugs used for NSCLC. These data indicate that treatment-induced Hsp27 contributes to the development of resistance, and provides preclinical proof-of-principle that inhibition of stress adaptive pathways mediated by Hsp27 enhances the activity of erlotinib and chemotherapeutics. ©2015 American Association for Cancer Research.

Dinaciclib Induces Anaphase Catastrophe in Lung Cancer Cells via Inhibition of Cyclin-Dependent Kinases 1 and 2.

PubMed

Danilov, Alexey V; Hu, Shanhu; Orr, Bernardo; Godek, Kristina; Mustachio, Lisa Maria; Sekula, David; Liu, Xi; Kawakami, Masanori; Johnson, Faye M; Compton, Duane A; Freemantle, Sarah J; Dmitrovsky, Ethan

2016-11-01

Despite advances in targeted therapy, lung cancer remains the most common cause of cancer-related mortality in the United States. Chromosomal instability is a prominent feature in lung cancer and, because it rarely occurs in normal cells, it represents a potential therapeutic target. Our prior work discovered that lung cancer cells undergo anaphase catastrophe in response to inhibition of cyclin-dependent kinase 2 (CDK2), followed by apoptosis and reduced growth. In this study, the effects and mechanisms of the multi-CDK inhibitor dinaciclib on lung cancer cells were investigated. We sought to determine the specificity of CDK-dependent induction of anaphase catastrophe. Live cell imaging provided direct evidence that dinaciclib caused multipolar cell divisions resulting in extensive chromosome missegregation. Genetic knockdown of dinaciclib CDK targets revealed that repression of CDK2 and CDK1, but not CDK5 or CDK9, triggered anaphase catastrophe in lung cancer cells. Overexpression of CP110, which is a mediator of CDK2 inhibitor-induced anaphase catastrophe (and a CDK1 and 2 phosphorylation substrate), antagonized anaphase catastrophe and apoptosis following dinaciclib treatment. Consistent with our previous findings, acquisition of activated KRAS sensitized lung cancer cells to dinaciclib-mediated anaphase catastrophe and cell death. Combining dinaciclib with the mitotic inhibitor taxol augmented anaphase catastrophe induction and reduced cell viability of lung cancer cells. Thus, the multi-CDK inhibitor dinaciclib causes anaphase catastrophe in lung cancer cells and should be investigated as a potential therapeutic for wild-type and KRAS-mutant lung cancer, individually or in combination with taxanes. Mol Cancer Ther; 15(11); 2758-66. ©2016 AACR. ©2016 American Association for Cancer Research.

Is cancer history really an exclusion criterion for clinical trial of lung cancer? Influence of gastrointestinal tract cancer history on the outcomes of lung cancer surgery.

PubMed

Aokage, Keiju; Okada, Morihito; Suzuki, Kenji; Nomura, Shogo; Suzuki, Shigeki; Tsubokawa, Norifumi; Mimae, Takahiro; Hattori, Aritoshi; Hishida, Tomoyuki; Yoshida, Junji; Tsuboi, Masahiro

2017-02-15

Exclusion of patients with a history of other cancer treatment except in situ situation has been considered to be inevitable for clinical trials investigating survival outcome. However, there have been few reports confirming these influences on surgical outcome of lung cancer patients ever. Multi-institutional, individual data from patients with non–small cell lung cancer resected between 2000 and 2013 were collected. The patients were divided into two groups: those with a history of gastrointestinal tract cancer (GI group) and those without any history (non-GI group). We compared the outcomes with well-matched groups using propensity scoring to minimize bias related to the nonrandomness. The influence of gastrointestinal tract cancer stage, disease-free interval, and treatment method for gastrointestinal tract cancer on the surgical outcome of non–small cell lung cancer was examined. We analyzed 196 patients in the GI group and 3732 in the non-GI group. In unmatched cohort, multivariate analyses showed that a history of gastrointestinal tract cancer did not affect overall survival or recurrence-free survival. Independent predictors of poor prognosis included older age, male sex, high carcinoembryonic antigen levels and advanced clinical stage of non–small cell lung cancer. The two groups in the matched cohort demonstrated equivalent overall survival and recurrence-free survival, even in patients with clinical stage I. Gastrointestinal tract cancer stage, disease-free interval and treatment method for gastrointestinal tract cancer were not associated with outcomes. History of early gastrointestinal tract cancer completely resected is not always necessary for exclusion criteria in clinical trial of lung cancer.

Factors affecting 30-month survival in lung cancer patients.

PubMed

Mahesh, P A; Archana, S; Jayaraj, B S; Patil, Shekar; Chaya, S K; Shashidhar, H P; Sunitha, B S; Prabhakar, A K

2012-10-01

Age adjusted incidence rate of lung cancer in India ranges from 7.4 to 13.1 per 100,000 among males and 3.9 to 5.8 per 100,000 among females. The factors affecting survival in lung cancer patients in India are not fully understood. The current study was undertaken to evaluate the factors affecting survival in patients diagnosed with lung cancer attending a tertiary care cancer institute in Bangalore, Karnataka, India. Consecutive patients with primary lung cancer attending Bangalore Institute of Oncology, a tertiary care centre at Bangalore, between 2006 and 2009 were included. Demographic, clinical, radiological data were collected retrospectively from the medical records. A total of 170 consecutive subjects (128 males, 42 females) diagnosed to have lung cancer; 151 non-small cell lung cancer (NSCLC) and 19 small cell lung cancer (SCLC) were included. A higher proportion of never-smokers (54.1%) were observed, mostly presenting below the age of 60 yr. Most subjects were in stage IV and III at the time of diagnosis. More than 50 per cent of patients presented with late stage lung cancer even though the duration of symptoms is less than 2 months. The 30-month overall survival rates for smokers and never-smokers were 32 and 49 per cent, respectively. No significant differences were observed in 30 month survival based on age at presentation, gender and type of lung cancer. Cox proportional hazards model identified never-smokers and duration of symptoms less than 1 month as factors adversely affecting survival. Our results showed that lung cancer in Indians involved younger subjects and associated with poorer survival as compared to other ethnic population. Studies on large sample need to be done to evaluate risk factors in lung cancer patients.

Factors affecting 30-month survival in lung cancer patients

PubMed Central

Mahesh, P.A.; Archana, S.; Jayaraj, B.S.; Patil, Shekar; Chaya, S.K.; Shashidhar, H.P.; Sunitha, B.S.; Prabhakar, A.K.

2012-01-01

Background & objectives: Age adjusted incidence rate of lung cancer in India ranges from 7.4 to 13.1 per 100,000 among males and 3.9 to 5.8 per 100,000 among females. The factors affecting survival in lung cancer patients in India are not fully understood. The current study was undertaken to evaluate the factors affecting survival in patients diagnosed with lung cancer attending a tertiary care cancer institute in Bangalore, Karnataka, India. Methods: Consecutive patients with primary lung cancer attending Bangalore Institute of Oncology, a tertiary care centre at Bangalore, between 2006 and 2009 were included. Demographic, clinical, radiological data were collected retrospectively from the medical records. Results: A total of 170 consecutive subjects (128 males, 42 females) diagnosed to have lung cancer; 151 non-small cell lung cancer (NSCLC) and 19 small cell lung cancer (SCLC) were included. A higher proportion of never-smokers (54.1%) were observed, mostly presenting below the age of 60 yr. Most subjects were in stage IV and III at the time of diagnosis. More than 50 per cent of patients presented with late stage lung cancer even though the duration of symptoms is less than 2 months. The 30-month overall survival rates for smokers and never-smokers were 32 and 49 per cent, respectively. No significant differences were observed in 30 month survival based on age at presentation, gender and type of lung cancer. Cox proportional hazards model identified never-smokers and duration of symptoms less than 1 month as factors adversely affecting survival. Interpretation & conclusions: Our results showed that lung cancer in Indians involved younger subjects and associated with poorer survival as compared to other ethnic population. Studies on large sample need to be done to evaluate risk factors in lung cancer patients. PMID:23168702

The relationship between J waves and contact of lung cancer with the heart.

PubMed

Hayashi, Hideki; Wu, Qi; Horie, Minoru

2017-09-01

J waves result mainly from an increased density of transient outward current (I to ). Mechanical stretch to the heart activates multiple signal transduction pathways, in which I to may be involved. The purpose of this study was to test the hypothesis that mechanical contact of lung cancer with the heart may manifest J waves. We reviewed 12-lead electrocardiograms to examine whether J waves were associated with contact of lung cancer with the heart. J waves were defied as an elevation of ≥0.1 mV at the junction between QRS complex and ST segment with either notching or slurring morphology. The locational interaction between lung cancer and the heart was determined by computed tomography image. A total of 264 patients (176 men; mean 68.5 ± 10.7 years) with lung cancer were evaluated. The prevalence of J waves was 25.4% in the total population. J waves were present in 40 of 44 (90.9%) patients with the contact. In contrast, J waves were present in 25 of 220 (11.4%) patients without the contact. The sensitivity and specificity of the contact for J waves were 90.9% and 88.6%, respectively. The odds ratio of the contact with the heart to the presence of J waves was 78 (95% confidence interval 25.7-236.4). The appearance of J waves that coincided with the development of lung cancer was observed in 12 patients. The presence of J waves was associated with the contact of lung cancer with the heart. © 2017 Wiley Periodicals, Inc.

Lung Cancer Rates by State

MedlinePlus

... the Biggest Cancer Killer in Both Men and Women” Stay Informed Rates by State for Other Kinds of Cancer All Cancers Combined Breast Cervical Colorectal (Colon) HPV-Associated Ovarian Prostate Skin Uterine Cancer Home Lung Cancer Rates by State Language: English (US) ...

The Cost-Effectiveness of High-Risk Lung Cancer Screening and Drivers of Program Efficiency.

PubMed

Cressman, Sonya; Peacock, Stuart J; Tammemägi, Martin C; Evans, William K; Leighl, Natasha B; Goffin, John R; Tremblay, Alain; Liu, Geoffrey; Manos, Daria; MacEachern, Paul; Bhatia, Rick; Puksa, Serge; Nicholas, Garth; McWilliams, Annette; Mayo, John R; Yee, John; English, John C; Pataky, Reka; McPherson, Emily; Atkar-Khattra, Sukhinder; Johnston, Michael R; Schmidt, Heidi; Shepherd, Frances A; Soghrati, Kam; Amjadi, Kayvan; Burrowes, Paul; Couture, Christian; Sekhon, Harmanjatinder S; Yasufuku, Kazuhiro; Goss, Glenwood; Ionescu, Diana N; Hwang, David M; Martel, Simon; Sin, Don D; Tan, Wan C; Urbanski, Stefan; Xu, Zhaolin; Tsao, Ming-Sound; Lam, Stephen

2017-08-01

Lung cancer risk prediction models have the potential to make programs more affordable; however, the economic evidence is limited. Participants in the National Lung Cancer Screening Trial (NLST) were retrospectively identified with the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The high-risk subgroup was assessed for lung cancer incidence and demographic characteristics compared with those in the low-risk subgroup and the Pan-Canadian Early Detection of Lung Cancer Study (PanCan), which is an observational study that was high-risk-selected in Canada. A comparison of high-risk screening versus standard care was made with a decision-analytic model using data from the NLST with Canadian cost data from screening and treatment in the PanCan study. Probabilistic and deterministic sensitivity analyses were undertaken to assess uncertainty and identify drivers of program efficiency. Use of the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial with a threshold set at 2% over 6 years would have reduced the number of individuals who needed to be screened in the NLST by 81%. High-risk screening participants in the NLST had more adverse demographic characteristics than their counterparts in the PanCan study. High-risk screening would cost $20,724 (in 2015 Canadian dollars) per quality-adjusted life-year gained and would be considered cost-effective at a willingness-to-pay threshold of $100,000 in Canadian dollars per quality-adjusted life-year gained with a probability of 0.62. Cost-effectiveness was driven primarily by non-lung cancer outcomes. Higher noncurative drug costs or current costs for immunotherapy and targeted therapies in the United States would render lung cancer screening a cost-saving intervention. Non-lung cancer outcomes drive screening efficiency in diverse, tobacco-exposed populations. Use of risk selection can reduce the budget impact, and

Overall environmental quality and lung cancer survival

EPA Science Inventory

Lung cancer is one of the most prevalent and lethal cancers in the United States. While individual environmental exposures have been associated with lung cancer incidence, the impact of cumulative environmental exposures on survival is not understood. We used the U.S. Environment...

A Multiplexed Serum Biomarker Immunoassay Panel Discriminates Clinical Lung Cancer Patients from High-Risk Individuals Found to be Cancer-Free by CT Screening

PubMed Central

Bigbee, William L.; Gopalakrishnan, Vanathi; Weissfeld, Joel L.; Wilson, David O.; Dacic, Sanja; Lokshin, Anna E.; Siegfried, Jill M.

2012-01-01

Introduction Clinical decision-making in the setting of CT screening could benefit from accessible biomarkers that help predict the level of lung cancer risk in high-risk individuals with indeterminate pulmonary nodules. Methods To identify candidate serum biomarkers, we measured 70 cancer-related proteins by Luminex xMAP® multiplexed immunoassays in a training set of sera from 56 patients with biopsy-proven primary non small cell lung cancer and 56 age-, sex- and smoking-matched CT-screened controls. Results We identified a panel of 10 serum biomarkers – prolactin, transthyretin, thrombospondin-1, E-selectin, C-C motif chemokine 5, macrophage migration inhibitory factor, plasminogen activator inhibitor, receptor tyrosine-protein kinase, Cyfra 21.1, and serum amyloid A – that distinguished lung cancer from controls with an estimated balanced accuracy (average of sensitivity and specificity) of 76.0%±3.8% from 20-fold internal cross-validation. We then iteratively evaluated this model in independent test and verification case/control studies confirming the initial classification performance of the panel. The classification performance of the 10-biomarker panel was also analytically validated using ELISAs in a second independent case/control population further validating the robustness of the panel. Conclusions The performance of this 10-biomarker panel based model was 77.1% sensitivity/76.2% specificity in cross-validation in the expanded training set, 73.3% sensitivity/93.3% specificity (balanced accuracy 83.3%) in the blinded verification set with the best discriminative performance in Stage I/II cases: 85% sensitivity (balanced accuracy 89.2%). Importantly, the rate of misclassification of CT-screened controls was not different in most control subgroups with or without airflow obstruction or emphysema or pulmonary nodules. These biomarkers have potential to aid in the early detection of lung cancer and more accurate interpretation of indeterminate pulmonary

Mind-mapping for lung cancer: Towards a personalized therapeutics approach

PubMed Central

Mollberg, N; Surati, M; Demchuk, C; Fathi, R; Salama, AK; Husain, AN; Hensing, T; Salgia, R

2011-01-01

There will be over 220,000 people diagnosed with lung cancer and over 160,000 dying of lung cancer this year alone in the United States. In order to arrive at better control, prevention, diagnosis, and therapeutics for lung cancer, we must be able to personalize the approach towards lung cancer. Mind-mapping has existed for centuries for physicians to properly think about various “flows” of personalized medicine. We include here the epidemiology, diagnosis, histology, and treatment of lung cancer—specifically, non-small cell lung cancer. As we have new molecular signatures for lung cancer, this is further detailed. This review is not meant to be a comprehensive review, but rather its purpose is to highlight important aspects of lung cancer diagnosis, management, and personalized treatment options. PMID:21337123

Current and Prospective Protein Biomarkers of Lung Cancer

PubMed Central

Zamay, Tatiana N.; Zamay, Galina S.; Kolovskaya, Olga S.; Zukov, Ruslan A.; Petrova, Marina M.; Gargaun, Ana; Berezovski, Maxim V.

2017-01-01

Lung cancer is a malignant lung tumor with various histological variants that arise from different cell types, such as bronchial epithelium, bronchioles, alveoli, or bronchial mucous glands. The clinical course and treatment efficacy of lung cancer depends on the histological variant of the tumor. Therefore, accurate identification of the histological type of cancer and respective protein biomarkers is crucial for adequate therapy. Due to the great diversity in the molecular-biological features of lung cancer histological types, detection is impossible without knowledge of the nature and origin of malignant cells, which release certain protein biomarkers into the bloodstream. To date, different panels of biomarkers are used for screening. Unfortunately, a uniform serum biomarker composition capable of distinguishing lung cancer types is yet to be discovered. As such, histological analyses of tumor biopsies and immunohistochemistry are the most frequently used methods for establishing correct diagnoses. Here, we discuss the recent advances in conventional and prospective aptamer based strategies for biomarker discovery. Aptamers like artificial antibodies can serve as molecular recognition elements for isolation detection and search of novel tumor-associated markers. Here we will describe how these small synthetic single stranded oligonucleotides can be used for lung cancer biomarker discovery and utilized for accurate diagnosis and targeted therapy. Furthermore, we describe the most frequently used in-clinic and novel lung cancer biomarkers, which suggest to have the ability of differentiating between histological types of lung cancer and defining metastasis rate. PMID:29137182

[Lung cancer and rheumatoid arthritis. An interdisciplinary challenge].

PubMed

Rubbert-Roth, A; Zander, T; Kneitz, C; Baerwald, C; Wirtz, H; Witt, C

2016-02-01

Lung cancer is a frequently occurring disease, particularly in the elderly; however, within the last 10 years the pharmaceutical treatment of lung cancer has been significantly improved. Due to a better understanding of the pathophysiological events and the identification of molecular subgroups of lung tumors, new therapeutic drugs have been developed that significantly prolong survival of patients with the respective molecular pattern. In particular immunotherapeutic agents, such as programmed death-ligand 1 (PD-L1) and programmed death 1 (PD1) antibodies have shown promising clinical results in a subgroup of lung cancer patients. Due to the high incidence of both lung cancer and rheumatic diseases they often occur together, which necessitates an interdisciplinary management. The success of improved therapy of lung cancer has led to a greater focus on the treatment of comorbidities; however, interventions into the immune system by immune checkpoint inhibitors can lead to new challenges when an autoimmune disease is simultaneously present. The possibility of an effective screening for lung cancer in the future also presents the prospect of an improvement in mortality, which raises the question of the optimal monitoring of patients with rheumatoid arthritis (RA) under immunosuppressive therapy. The aim of this review is to discuss the interaction between lung cancer and RA with respect to the currently available data.

Lung cancer in patients with idiopathic pulmonary fibrosis.

PubMed

Karampitsakos, Theodoros; Tzilas, Vasilios; Tringidou, Rodoula; Steiropoulos, Paschalis; Aidinis, Vasilis; Papiris, Spyros A; Bouros, Demosthenes; Tzouvelekis, Argyris

2017-08-01

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease of unknown etiology. With a gradually increasing worldwide prevalence and a mortality rate exceeding that of many cancers, IPF diagnosis and management are critically important and require a comprehensive multidisciplinary approach. This approach also involves assessment of comorbid conditions, such as lung cancer, that exerts a dramatic impact on disease survival. Emerging evidence suggests that progressive lung scarring in the context of IPF represents a risk factor for lung carcinogenesis. Both disease entities present with major similarities in terms of pathogenetic pathways, as well as potential causative factors, such as smoking and viral infections. Besides disease pathogenesis, anti-cancer agents, including nintedanib, have been successfully applied in the treatment of patients with IPF while an oncologic approach with a cocktail of several pleiotropic anti-fibrotic agents is currently in the therapeutic pipeline of IPF. Nevertheless, epidemiologic association between IPF and lung cancer does not prove causality. Currently there is significant lack of knowledge supporting a direct association between lung fibrosis and cancer reflecting to disappointing therapeutic algorithms. An optimal therapeutic strategy for patients with both IPF and lung cancer represents an amenable need. This review article synthesizes the current state of knowledge regarding pathogenetic commonalities between IPF and lung cancer and focuses on clinical and therapeutic data that involve both disease entities. Copyright © 2017. Published by Elsevier Ltd.

Vaccine Therapy in Treating Patients With Colon, Pancreatic, or Lung Cancer

ClinicalTrials.gov

2015-04-27

Recurrent Colon Cancer; Extensive Stage Small Cell Lung Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Limited Stage Small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Stage III Non-small Cell Lung Cancer; Stage I Pancreatic Cancer; Stage II Non-small Cell Lung Cancer; Stage IVB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage IVA Pancreatic Cancer

Lung cancer in shipbuilding and related industries in Louisiana.

PubMed

Gottlieb, M S; Stedman, R B

1979-09-01

The relationship between shipbuilding and related industries and risk of fatal lung cancer (1960-1975) is described for selected Louisiana parishes. Deaths from lung cancer were matched to deaths not caused by cancer. Shipbuilders had a significantly increased risk (greater than twofold) of dying of lung cancer as compared with other causes. The risk of dying of lung cancer in related occupations (seamen and longshoremen) was also increased. Information on laterality of lung cancer was not supportive of particulate substances contributing to causality due to the large number of unspecified cases. The preponderance of deaths appears to be occurring in men with a greater number of years of exposure to this industry and in those aged 20 to 34 years in 1940. These common occupations in Louisiana could contribute to the high rate of lung cancer.

Surgical and survival outcomes of lung cancer patients with intratumoral lung abscesses.

PubMed

Yamanashi, Keiji; Okumura, Norihito; Takahashi, Ayuko; Nakashima, Takashi; Matsuoka, Tomoaki

2017-05-26

Intratumoral lung abscess is a secondary lung abscess that is considered to be fatal. Therefore, surgical procedures, although high-risk, have sometimes been performed for intratumoral lung abscesses. However, no studies have examined the surgical outcomes of non-small cell lung cancer patients with intratumoral lung abscesses. The aim of this study was to investigate the surgical and survival outcomes of non-small cell lung cancer patients with intratumoral lung abscesses. Eleven consecutive non-small cell lung cancer patients with intratumoral lung abscesses, who had undergone pulmonary resection at our institution between January 2007 and December 2015, were retrospectively analysed. The post-operative prognoses were investigated and prognostic factors were evaluated. Ten of 11 patients were male and one patient was female. The median age was 64 (range, 52-80) years. Histopathologically, 4 patients had Stage IIA, 2 patients had Stage IIB, 2 patients had Stage IIIA, and 3 patients had Stage IV tumors. The median operative time was 346 min and the median amount of bleeding was 1327 mL. The post-operative morbidity and mortality rates were 63.6% and 0.0%, respectively. Recurrence of respiratory infections, including lung abscesses, was not observed in all patients. The median post-operative observation period was 16.1 (range, 1.3-114.5) months. The 5-year overall survival rate was 43.3%. No pre-operative, intra-operative, or post-operative prognostic factors were identified in the univariate analyses. Surgical procedures for advanced-stage non-small cell lung cancer patients with intratumoral lung abscesses, although high-risk, led to satisfactory post-operative mortality rates and acceptable prognoses.

Relationships between lung cancer incidences and air pollutants.

PubMed

Yue, Shihong; Wang, Yaru; Wang, Jianpei; Chen, Jun

2017-07-20

Statistics on lung cancer incidences and air pollutants show a strong correlation between air pollutant concentrations and pulmonary diseases. And environmental effects on lung cancer incidences remain highly unknown and uncertain in China. This study aims to measure the relationships between different air pollutants and lung cancer incidences in Tianjin. One thusand five hundred patients across 27 districts in Tianjin were studied for lung cancer incidences. The patients had come into contact with various air pollutants such as PM2.5, PM10, SO2, NO2, CO, and O3. These pollutants were measured daily and were published via a Geographic Information System across the 27 districts of Tianjin. The air pollutant compositions of environments the patients lived in were determined using the nearest air monitoring station to the patient. And we used rough set theory to measure the relationships between different air pollutants and lung cancer incidences. Different air pollutants and combinations of pollutants impacted lung cancer incidences differently across different districts, sexes, and lung cancer types in Tianjin. Based on data analysis and interpretation, rough set theory provided data relationships that were objective and interpretable. The method is simple, general, and efficient, and lays the foundation for further applications in other cities.

Lung Cancer Assistant: a hybrid clinical decision support application for lung cancer care.

PubMed

Sesen, M Berkan; Peake, Michael D; Banares-Alcantara, Rene; Tse, Donald; Kadir, Timor; Stanley, Roz; Gleeson, Fergus; Brady, Michael

2014-09-06

Multidisciplinary team (MDT) meetings are becoming the model of care for cancer patients worldwide. While MDTs have improved the quality of cancer care, the meetings impose substantial time pressure on the members, who generally attend several such MDTs. We describe Lung Cancer Assistant (LCA), a clinical decision support (CDS) prototype designed to assist the experts in the treatment selection decisions in the lung cancer MDTs. A novel feature of LCA is its ability to provide rule-based and probabilistic decision support within a single platform. The guideline-based CDS is based on clinical guideline rules, while the probabilistic CDS is based on a Bayesian network trained on the English Lung Cancer Audit Database (LUCADA). We assess rule-based and probabilistic recommendations based on their concordances with the treatments recorded in LUCADA. Our results reveal that the guideline rule-based recommendations perform well in simulating the recorded treatments with exact and partial concordance rates of 0.57 and 0.79, respectively. On the other hand, the exact and partial concordance rates achieved with probabilistic results are relatively poorer with 0.27 and 0.76. However, probabilistic decision support fulfils a complementary role in providing accurate survival estimations. Compared to recorded treatments, both CDS approaches promote higher resection rates and multimodality treatments.

Pulmonary Rehabilitation in Improving Lung Function in Patients With Locally Advanced Non-Small Cell Lung Cancer Undergoing Chemoradiation

ClinicalTrials.gov

2017-04-12

Cachexia; Fatigue; Pulmonary Complications; Radiation Toxicity; Recurrent Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

In vivo imaging models of bone and brain metastases and pleural carcinomatosis with a novel human EML4-ALK lung cancer cell line.

PubMed

Nanjo, Shigeki; Nakagawa, Takayuki; Takeuchi, Shinji; Kita, Kenji; Fukuda, Koji; Nakada, Mitsutoshi; Uehara, Hisanori; Nishihara, Hiroshi; Hara, Eiji; Uramoto, Hidetaka; Tanaka, Fumihiro; Yano, Seiji

2015-03-01

EML4-ALK lung cancer accounts for approximately 3-7% of non-small-cell lung cancer cases. To investigate the molecular mechanism underlying tumor progression and targeted drug sensitivity/resistance in EML4-ALK lung cancer, clinically relevant animal models are indispensable. In this study, we found that the lung adenocarcinoma cell line A925L expresses an EML4-ALK gene fusion (variant 5a, E2:A20) and is sensitive to the ALK inhibitors crizotinib and alectinib. We further established highly tumorigenic A925LPE3 cells, which also have the EML4-ALK gene fusion (variant 5a) and are sensitive to ALK inhibitors. By using A925LPE3 cells with luciferase gene transfection, we established in vivo imaging models for pleural carcinomatosis, bone metastasis, and brain metastasis, all of which are significant clinical concerns of advanced EML4-ALK lung cancer. Interestingly, crizotinib caused tumors to shrink in the pleural carcinomatosis model, but not in bone and brain metastasis models, whereas alectinib showed remarkable efficacy in all three models, indicative of the clinical efficacy of these ALK inhibitors. Our in vivo imaging models of multiple organ sites may provide useful resources to analyze further the pathogenesis of EML4-ALK lung cancer and its response and resistance to ALK inhibitors in various organ microenvironments. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Preferential elevation of Prx I and Trx expression in lung cancer cells following hypoxia and in human lung cancer tissues.

PubMed

Kim, H J; Chae, H Z; Kim, Y J; Kim, Y H; Hwangs, T S; Park, E M; Park, Y M

2003-10-01

Transient/chronic microenvironmental hypoxia that exists within a majority of solid tumors has been suggested to have a profound influence on tumor growth and therapeutic outcome. Since the functions of novel antioxidant proteins, peroxiredoxin I (Prx I) and II, have been implicated in regulating cell proliferation, differentiation, and apoptosis, it was of our special interest to probe a possible role of Prx I and II in the context of hypoxic tumor microenvironment. Since both Prx I and II use thioredoxin (Trx) as an electron donor and Trx is a substrate for thioredoxin reductase (TrxR), we investigated the regulation of Trx and TrxR as well as Prx expression following hypoxia. Here we show a dynamic change of glutathione homeostasis in lung cancer A549 cells and an up-regulation of Prx I and Trx following hypoxia. Western blot analysis of 10 human lung cancer and paired normal lung tissues also revealed an elevated expression of Prx I and Trx proteins in lung cancer tissues. Immunohistochemical analysis of the lung cancer tissues confirmed an augmented Prx I and Trx expression in cancer cells with respect to the parenchymal cells in adjacent normal lung tissue. Based on these results, we suggest that the redox changes in lung tumor microenvironment could have acted as a trigger for the up-regulation of Prx I and Trx in lung cancer cells. Although the clinical significance of our finding awaits more rigorous future study, preferential augmentation of the Prx I and Trx in lung cancer cells may well represent an attempt of cancer cells to manipulate a dynamic redox change in tumor microenvironment in a manner that is beneficial for their proliferation and malignant progression.

Viral colonization in exhaled breath condensate of lung cancer patients: Possible role of EBV and CMV.

PubMed

Carpagnano, Giovanna E; Lacedonia, Donato; Natalicchio, Maria Iole; Cotugno, Grazia; Zoppo, Luigi; Martinelli, Domenico; Antonetti, Raffaele; Foschino-Barbaro, Maria Pia

2018-02-01

Today, an increasing interest is being addressed to the viral etiology of lung tumors. As a consequence, research efforts are currently being directed to the identification of the new viruses involved in lung carcinogenesis toward which the screening programs could be directed. The aim of this study was to investigate the airways colonization by the Epstein-Barr virus (EBV) and Citomegalovirus (CMV) in patients affected by lung cancer using, as a respiratory non-invasive sample, the exhaled breath condensate (EBC). About 70 lung-cancer patients and 40 controls were enrolled. All subjects underwent bronchial brushing and EBC collection. EBV-DNA and CMV-DNA were evaluated in both samples by real-time PCR assay. They were able to detect EBV and CMV in the EBC. An increase of the EBV positivity in non-small cell lung cancer (NSCLC) patients compared with controls and of the CMV in advanced stages of lung cancer were observed. The association of the positivity of the cytology and the CMV test (in EBC or brushing) slightly increased the sensitivity of malignant diagnosis. EBV and CMV resulted detectable in the EBC. In consideration of the potential involvement of these viruses in lung cancer, which was confirmed in this study, future studies in this direction were supported. © 2016 John Wiley & Sons Ltd.

28 CFR 79.64 - Proof of primary lung cancer.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by medical...

28 CFR 79.45 - Proof of primary lung cancer.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.54 - Proof of primary lung cancer.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.64 - Proof of primary lung cancer.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by medical...

28 CFR 79.54 - Proof of primary lung cancer.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.45 - Proof of primary lung cancer.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.45 - Proof of primary lung cancer.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.45 - Proof of primary lung cancer.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.64 - Proof of primary lung cancer.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by medical...

28 CFR 79.54 - Proof of primary lung cancer.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.54 - Proof of primary lung cancer.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.45 - Proof of primary lung cancer.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.54 - Proof of primary lung cancer.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.64 - Proof of primary lung cancer.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by medical...

28 CFR 79.64 - Proof of primary lung cancer.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by medical...

Cost-Effectiveness Analysis of a Capitated Patient Navigation Program for Medicare Beneficiaries with Lung Cancer.

PubMed

Shih, Ya-Chen Tina; Chien, Chun-Ru; Moguel, Rocio; Hernandez, Mike; Hajek, Richard A; Jones, Lovell A

2016-04-01

To assess the cost-effectiveness of implementing a patient navigation (PN) program with capitated payment for Medicare beneficiaries diagnosed with lung cancer. Cost-effectiveness analysis. A Markov model to capture the disease progression of lung cancer and characterize clinical benefits of PN services as timeliness of treatment and care coordination. Taking a payer's perspective, we estimated the lifetime costs, life years (LYs), and quality-adjusted life years (QALYs) and addressed uncertainties in one-way and probabilistic sensitivity analyses. Model inputs were extracted from the literature, supplemented with data from a Centers for Medicare and Medicaid Services demonstration project. Compared to usual care, PN services incurred higher costs but also yielded better outcomes. The incremental cost and effectiveness was $9,145 and 0.47 QALYs, respectively, resulting in an incremental cost-effectiveness ratio of $19,312/QALY. One-way sensitivity analysis indicated that findings were most sensitive to a parameter capturing PN survival benefit for local-stage patients. CE-acceptability curve showed the probability that the PN program was cost-effective was 0.80 and 0.91 at a societal willingness-to-pay of $50,000 and $100,000/QALY, respectively. Instituting a capitated PN program is cost-effective for lung cancer patients in Medicare. Future research should evaluate whether the same conclusion holds in other cancers. © Health Research and Educational Trust.

Lung Cancer Prevention (PDQ®)—Patient Version

Cancer.gov

Lung cancer prevention approaches include avoiding exposure to risk factors like tobacco smoke, radon, radiation, asbestos, and other substances. Learn more about preventing lung cancer in this expert-reviewed summary.

Anatomical thoracoscopic segmentectomy for lung cancer.

PubMed

Ohtaki, Yoichi; Shimizu, Kimihiro

2014-10-01

Minimally invasive surgery for lung cancer has seen considerable progress. A segmentectomy is less invasive than a lobectomy as it preserves lung parenchyma. The preservation of pulmonary function can reduce complications. The combination of a thoracoscopic approach with a segmentectomy should be less invasive, and retrospective studies have shown that the thoracoscopic approach is safe and feasible due to the lower postoperative mortality and complication rates as compared to an open thoracotomy. The validity of a segmentectomy for ground-glass-opacity-type lung cancer has been demonstrated, and it has also been evaluated for small, predominantly solid, lung cancers. Two prospective studies of segmentectomy versus lobectomy for ≤2-cm non-small-cell lung cancer are now underway (CALGB 140503 and JCOG0802/WJTOG4607L) and should clarify the role of segmentectomy. Regarding thoracoscopic segmentectomy, few retrospective studies have reported the oncological outcome for lung cancer and there is inadequate evidence regarding the long-term oncological outcome, although the perioperative complication rate and duration of hospital stay seem to be non-inferior to those of an open approach. For preoperative simulation, three-dimensional multidetector computed tomography (3D-CT) is essential for performing an atypical thoracoscopic segmentectomy safely. Preoperative 3D-CT angiography and bronchography (3D-CTAB) enable accurate identification of the venous branches in the affected segment and the intersegmental vein. This review describes the surgical and oncological outcomes, utility of 3D-CTAB, and surgical techniques and procedure used for a thoracoscopic segmentectomy.

Linking the generation of DNA adducts to lung cancer.

PubMed

Ceppi, Marcello; Munnia, Armelle; Cellai, Filippo; Bruzzone, Marco; Peluso, Marco E M

2017-09-01

Worldwide, lung cancer is the leading cause of cancer death. DNA adducts are considered a reliable biomarker that reflects carcinogen exposure to tobacco smoke, but the central question is what is the relationship of DNA adducts and cancer? Therefore, we investigated this relationship by a meta-analysis of twenty-two studies with bronchial adducts for a total of 1091 subjects, 887 lung cancer cases and 204 apparently healthy individuals with no evidence of lung cancer. Our study shows that these adducts are significantly associated to increase lung cancer risk. The value of Mean Ratio lung-cancer (MR) of bronchial adducts resulting from the random effects model was 2.64, 95% C.I. 2.00-3.50, in overall lung cancer cases as compared to controls. The significant difference, with lung cancer patients having significant higher levels of bronchial adducts than controls, persisted after stratification for smoking habits. The MR lung-cancer value between lung cancer patients and controls for smokers was 2.03, 95% C.I. 1.42-2.91, for ex-smokers 3.27, 95% C.I. 1.49-7.18, and for non-smokers was 3.81, 95% C.I. 1.85-7.85. Next, we found that the generation of bronchial adducts is significantly related to inhalation exposure to tobacco smoke carcinogens confirming its association with volatile carcinogens. The MR smoking estimate of bronchial adducts resulting from meta-regression was 2.28, 95% Confidence Interval (C.I.) 1.10-4.73, in overall smokers in respect to non-smokers. The present work provides strengthening of the hypothesis that bronchial adducts are not simply relate to exposure, but are a cause of chemical-induced lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer

ClinicalTrials.gov

2014-08-04

Adenocarcinoma of the Lung; Bronchoalveolar Cell Lung Cancer; Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

PPARGC1A is upregulated and facilitates lung cancer metastasis.

PubMed

Li, Jin-Dong; Feng, Qing-Chuan; Qi, Yu; Cui, Guanghui; Zhao, Song

2017-10-15

Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence it is imperative to determine reliable biomarkers for lung cancer prognosis. We performed quantitative real-time PCR (qRT-PCR) analysis to explore epithelial-mesenchymal transition (EMT) inducers that regulate EMT process in three patients with advanced lung cancer disease. Peroxisome proliferator-activated receptor gamma (PPARGC1A) was uniformly the topmost overexpressed gene in all three human non-small cell lung cancer (NSCLC) patient samples. Further evaluation in human normal lung and metastatic lung cancer cell lines revealed that the expression of PPARGC1A was upregulated in metastatic lung cancer cell lines. Metagenomic analysis revealed direct correlation among PPARGC1A, zinc-finger transcription factor snail homolog 1 (SNAI1), and metastatic lung disease. Upregulation of PPARGC1A transcript expression was independent of a differential upregulation of the upstream AMP-dependent protein kinase (AMPK) activation or steady state expression of the silent mating type information regulation 2 homolog 1 (SIRT1). Xenograft tail vein colonization assays proved that the high expression of PPARGC1A was a prerequisite for metastatic progression of lung cancer to brain. Our results indicate that PPARGC1A might be a potential biomarker for lung cancer prognosis. Copyright © 2017. Published by Elsevier Inc.

Increased risk of lung cancer in individuals with a family history of the disease: a pooled analysis from the International Lung Cancer Consortium.

PubMed

Coté, Michele L; Liu, Mei; Bonassi, Stefano; Neri, Monica; Schwartz, Ann G; Christiani, David C; Spitz, Margaret R; Muscat, Joshua E; Rennert, Gad; Aben, Katja K; Andrew, Angeline S; Bencko, Vladimir; Bickeböller, Heike; Boffetta, Paolo; Brennan, Paul; Brenner, Hermann; Duell, Eric J; Fabianova, Eleonora; Field, John K; Foretova, Lenka; Friis, Søren; Harris, Curtis C; Holcatova, Ivana; Hong, Yun-Chul; Isla, Dolores; Janout, Vladimir; Kiemeney, Lambertus A; Kiyohara, Chikako; Lan, Qing; Lazarus, Philip; Lissowska, Jolanta; Le Marchand, Loic; Mates, Dana; Matsuo, Keitaro; Mayordomo, Jose I; McLaughlin, John R; Morgenstern, Hal; Müeller, Heiko; Orlow, Irene; Park, Bernard J; Pinchev, Mila; Raji, Olaide Y; Rennert, Hedy S; Rudnai, Peter; Seow, Adeline; Stucker, Isabelle; Szeszenia-Dabrowska, Neonila; Dawn Teare, M; Tjønnelan, Anne; Ugolini, Donatella; van der Heijden, Henricus F M; Wichmann, Erich; Wiencke, John K; Woll, Penella J; Yang, Ping; Zaridze, David; Zhang, Zuo-Feng; Etzel, Carol J; Hung, Rayjean J

2012-09-01

Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analysed. Unconditional logistic regression models and generalised estimating equations were used to estimate odds ratios and 95% confidence intervals. Individuals with a first-degree relative with lung cancer had a 1.51-fold increase in the risk of lung cancer, after adjustment for smoking and other potential confounders (95% CI: 1.39, 1.63). The association was strongest for those with a family history in a sibling, after adjustment (odds ratios (OR) = 1.82, 95% CI: 1.62, 2.05). No modifying effect by histologic type was found. Never smokers showed a lower association with positive familial history of lung cancer (OR = 1.25, 95% CI: 1.03, 1.52), slightly stronger for those with an affected sibling (OR = 1.44, 95% CI: 1.07, 1.93), after adjustment. The occurrence of lung cancer among never smokers and similar magnitudes of the effect of family history on lung cancer risk across histological types suggests familial aggregation of lung cancer is independent of those risks associated with cigarette smoking. While the role of genetic variation in the aetiology of lung cancer remains to be fully characterised, family history assessment is immediately available and those with a positive history represent a higher risk group. Copyright © 2012 Elsevier Ltd. All rights reserved.

Preanalytics in lung cancer.

PubMed

Warth, Arne; Muley, Thomas; Meister, Michael; Weichert, Wilko

2015-01-01

Preanalytic sampling techniques and preparation of tissue specimens strongly influence analytical results in lung tissue diagnostics both on the morphological but also on the molecular level. However, in contrast to analytics where tremendous achievements in the last decade have led to a whole new portfolio of test methods, developments in preanalytics have been minimal. This is specifically unfortunate in lung cancer, where usually only small amounts of tissue are at hand and optimization in all processing steps is mandatory in order to increase the diagnostic yield. In the following, we provide a comprehensive overview on some aspects of preanalytics in lung cancer from the method of sampling over tissue processing to its impact on analytical test results. We specifically discuss the role of preanalytics in novel technologies like next-generation sequencing and in the state-of the-art cytology preparations. In addition, we point out specific problems in preanalytics which hamper further developments in the field of lung tissue diagnostics.

A Cost-Utility Analysis of Lung Cancer Screening and the Additional Benefits of Incorporating Smoking Cessation Interventions

PubMed Central

Villanti, Andrea C.; Jiang, Yiding; Abrams, David B.; Pyenson, Bruce S.

2013-01-01

Background A 2011 report from the National Lung Screening Trial indicates that three annual low-dose computed tomography (LDCT) screenings for lung cancer reduced lung cancer mortality by 20% compared to chest X-ray among older individuals at high risk for lung cancer. Discussion has shifted from clinical proof to financial feasibility. The goal of this study was to determine whether LDCT screening for lung cancer in a commercially-insured population (aged 50–64) at high risk for lung cancer is cost-effective and to quantify the additional benefits of incorporating smoking cessation interventions in a lung cancer screening program. Methods and Findings The current study builds upon a previous simulation model to estimate the cost-utility of annual, repeated LDCT screenings over 15 years in a high risk hypothetical cohort of 18 million adults between age 50 and 64 with 30+ pack-years of smoking history. In the base case, the lung cancer screening intervention cost $27.8 billion over 15 years and yielded 985,284 quality-adjusted life years (QALYs) gained for a cost-utility ratio of $28,240 per QALY gained. Adding smoking cessation to these annual screenings resulted in increases in both the costs and QALYs saved, reflected in cost-utility ratios ranging from $16,198 per QALY gained to $23,185 per QALY gained. Annual LDCT lung cancer screening in this high risk population remained cost-effective across all sensitivity analyses. Conclusions The findings of this study indicate that repeat annual lung cancer screening in a high risk cohort of adults aged 50–64 is highly cost-effective. Offering smoking cessation interventions with the annual screening program improved the cost-effectiveness of lung cancer screening between 20% and 45%. The cost-utility ratios estimated in this study were in line with other accepted cancer screening interventions and support inclusion of annual LDCT screening for lung cancer in a high risk population in clinical recommendations. PMID

The regional association between bronchiectasis and lung cancer in chest CT.

PubMed

Kim, Yeon Wook; Lee, Chang-Hoon; Jin, Kwang-Nam; Lee, Jung-Kyu; Heo, Eun Young; Park, Sung Soo; Chung, Hee Soon; Kim, Deog Kyeom

2016-11-15

Limited studies have examined the association between lung cancer and bronchiectasis (BE). This study evaluated the regional association between BE and lung cancer by analyzing the lobar location of lung cancer in patients with underlying BE. This clustered multi-level study enrolled patients who had underlying BE and were newly diagnosed with lung cancer between January 1, 2010 and May 30, 2013 in two referral hospitals in South Korea. By analyzing the presence of lung cancer and underlying BE as event variables at the level of lung lobes on chest computed tomography (CT), we evaluated the association of BE and lung cancer by the locations of the diseases. Eighty-one patients with BE and combined lung cancer were enrolled. Within 486 lung lobes of the patients, combined BE and lung cancer in the same lobe was found in 11 lobes (2.3 %). Using the general estimating equation assuming BE as a risk factor of lung cancer, the results indicated that the prevalence of lung cancer was significantly lower in the lobes with pre-existing BE (β = -1.09, p-value = 0.001). Regionally, pre-existing BE was associated with a lower risk of the occurrence of lung cancer in the same lobe.

Impact of Prior Cancer on Eligibility for Lung Cancer Clinical Trials

PubMed Central

Laccetti, Andrew L.; Xuan, Lei; Halm, Ethan A.; Pruitt, Sandi L.

2014-01-01

Background In oncology clinical trials, the assumption that a prior cancer diagnosis could interfere with study conduct or outcomes results in frequent exclusion of such patients. We determined the prevalence and characteristics of this practice in lung cancer clinical trials and estimated impact on trial accrual. Methods We reviewed lung cancer clinical trials sponsored or endorsed by the Eastern Oncology Cooperative Group for exclusion criteria related to a prior cancer diagnosis. We estimated prevalence of prior primary cancer diagnoses among lung cancer patients using Surveillance Epidemiology and End Results (SEER)-Medicare linked data. We assessed the association between trial characteristics and prior cancer exclusion using chi-square analysis. All statistical tests were two-sided. Results Fifty-one clinical trials (target enrollment 13072 patients) were included. Forty-one (80%) excluded patients with a prior cancer diagnosis as follows: any prior (14%), within five years (43%), within two or three years (7%), or active cancer (16%). In SEER-Medicare data (n = 210509), 56% of prior cancers were diagnosed within five years before the lung cancer diagnosis. Across trials, the estimated number and proportion of patients excluded because of prior cancer ranged from 0–207 and 0%-18%. Prior cancer was excluded in 94% of trials with survival primary endpoints and 73% of trials with nonsurvival primary endpoints (P = .06). Conclusions A substantial proportion of patients are reflexively excluded from lung cancer clinical trials because of prior cancer. This inclusion criterion is applied widely across studies, including more than two-thirds of trials with nonsurvival endpoints. More research is needed to understand the basis and ramifications of this exclusion policy. PMID:25253615

Retrospective analysis of icotinib neoadjuvant therapy of 63 lung cancer patients.

PubMed

Wang, T; Liu, Y; Zhou, B; Hao, S; Wang, Z; Liang, N; Liu, J; Wang, S

2017-01-01

This study aims to explore the feasibility of icotinib neoadjuvant therapy for nonsmall cell lung cancer (NSCLC). This was a retrospective analysis of the clinical data for 63 NSCLC patients (61 cases of adenocarcinoma and two cases of squamous cell carcinoma) receiving surgical resection of lung lesions after oral intake of icotinib from December 2011 to November 2013 in the PLA General Hospital. Preoperative oral intake of the patients was icotinib 125 mg tid, drug side effects were evaluated according to the American National Cancer Institute Common Toxicity Criteria Version 4.0; computed tomography scan was done on the day taking medicine and 2 weeks later to determine tumor changes. After oral intake of Icotinib for 2 to 22 weeks (5 cases for 2 weeks,13 cases for 3 to 22 weeks), all patients receive surgical resection of lung cancer lesions, and testing of removed tumor to evaluate the epidermal growth factor receptor (EGFR) gene mutation status was performed by fluorescence polymerase chain reaction. The patients with sensitive EGFR mutations receive Icotinib as postoperative adjuvant therapy. Side effects of medication within 2 weeks included rash (44.4%, 28/63), dry skin (34.9%, 22/63), diarrhea (14.3%, 9/63), and oral ulcer (1.6%, 1/63); there were no icotinib-associated thoracic surgery complications during the perioperational period. 71.4% patients (45/63) achieve an average reduction of 23.5% ±10.7%(10%-53.5%) after 2 weeks medication of Icotinib(regressive tumor[RT]) .28.6% patients(18/63) achieve stable tumor(ST),enlargement of 8.7% to reduction of 8.7% of the maximum diameter of lung cancer after 2 weeks medication of Icotinib. Of the RT group, 68.9% (31/45) of the tumors were detected with EGFR-sensitive mutation (exon 19 or 21 mutation), 24.4% (11/45) with wild-type EGFR, and three cases of exon 20 mutation. Of the ST group, 77.8% (14/18) were detected with wild-type EGFR, three cases of exon 20 mutation, and one case of exon 19 deletion mutation

Postoperative Management of Multiple Primary Cancers Associated with Non-small Cell Lung Cancer.

PubMed

Shoji, Fumihiro; Yamazaki, Koji; Miura, Naoko; Katsura, Masakazu; Oku, Yuka; Takeo, Sadanori; Maehara, Yoshihiko

2018-06-01

Modern treatment for primary cancers has improved survival. Therefore, increased numbers of patients with multiple primary cancers (MPC) associated with lung cancer may be expected. The aim of the present study was to report MPC associated with lung cancer and discuss patients' characteristics and postoperative management. Overall, 973 consecutive patients who underwent surgery for non-small cell lung cancer (NSCLC) were retrospectively studied. NSCLC with MPC was observed in 148 patients (15.2%). MPC comprised 24 synchronous (2.5%) and 124 metachronous (12.7%) diseases. Of the 124 metachronous patients, NSCLC was detected before cancers were detected in other organs (lung cancer first (LCF)) in 25 (20.2%) patients and subsequently in other organs after treatment (other organs, primary cancer-first (OCF)) in 99 (79.8%) patients. MPC was significantly associated with advanced age (p<0.0001) and chronic obstructive pulmonary disease (COPD) (p=0.0040). The leading sites of MPC in patients with synchronous tumors and those with OCF were the digestive organs. In contrast, the leading site of MPC in patients with LCF was the lung. In the latter, at least two primary lung cancers were detected within 5 years as well as 5 years after surgery for the treatment of the first detected lung cancer, while primary cancers of other organs were detected within 5 years. Advanced age and COPD may represent a high-risk of MPCs. Therefore, we recommend careful follow-up to detect MPC in the lung as well as the digestive organs beyond 5 years after treatment of the first cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Resonance Raman Spectroscopy of human brain metastasis of lung cancer analyzed by blind source separation

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-Hui; Pu, Yang; Cheng, Gangge; Yu, Xinguang; Zhou, Lixin; Lin, Dongmei; Zhu, Ke; Alfano, Robert R.

2017-02-01

Resonance Raman (RR) spectroscopy offers a novel Optical Biopsy method in cancer discrimination by a means of enhancement in Raman scattering. It is widely acknowledged that the RR spectrum of tissue is a superposition of spectra of various key building block molecules. In this study, the Resonance Raman (RR) spectra of human metastasis of lung cancerous and normal brain tissues excited by a visible selected wavelength at 532 nm are used to explore spectral changes caused by the tumor evolution. The potential application of RR spectra human brain metastasis of lung cancer was investigated by Blind Source Separation such as Principal Component Analysis (PCA). PCA is a statistical procedure that uses an orthogonal transformation to convert a set of observations of possibly correlated variables into a set of values of linearly uncorrelated variables called principal components (PCs). The results show significant RR spectra difference between human metastasis of lung cancerous and normal brain tissues analyzed by PCA. To evaluate the efficacy of for cancer detection, a linear discriminant analysis (LDA) classifier is utilized to calculate the sensitivity, and specificity and the receiver operating characteristic (ROC) curves are used to evaluate the performance of this criterion. Excellent sensitivity of 0.97, specificity (close to 1.00) and the Area Under ROC Curve (AUC) of 0.99 values are achieved under best optimal circumstance. This research demonstrates that RR spectroscopy is effective for detecting changes of tissues due to the development of brain metastasis of lung cancer. RR spectroscopy analyzed by blind source separation may have potential to be a new armamentarium.

Lung cancer in railroad workers exposed to diesel exhaust.

PubMed

Garshick, Eric; Laden, Francine; Hart, Jaime E; Rosner, Bernard; Smith, Thomas J; Dockery, Douglas W; Speizer, Frank E

2004-11-01

Diesel exhaust has been suspected to be a lung carcinogen. The assessment of this lung cancer risk has been limited by lack of studies of exposed workers followed for many years. In this study, we assessed lung cancer mortality in 54,973 U.S. railroad workers between 1959 and 1996 (38 years). By 1959, the U.S. railroad industry had largely converted from coal-fired to diesel-powered locomotives. We obtained work histories from the U.S. Railroad Retirement Board, and ascertained mortality using Railroad Retirement Board, Social Security, and Health Care Financing Administration records. Cause of death was obtained from the National Death Index and death certificates. There were 43,593 total deaths including 4,351 lung cancer deaths. Adjusting for a healthy worker survivor effect and age, railroad workers in jobs associated with operating trains had a relative risk of lung cancer mortality of 1.40 (95% confidence interval, 1.30-1.51). Lung cancer mortality did not increase with increasing years of work in these jobs. Lung cancer mortality was elevated in jobs associated with work on trains powered by diesel locomotives. Although a contribution from exposure to coal combustion products before 1959 cannot be excluded, these results suggest that exposure to diesel exhaust contributed to lung cancer mortality in this cohort. Key words: diesel exhaust, lung cancer, occupational exposure.

Prognostic impact of EGFR mutation in non-small-cell lung cancer patients with family history of lung cancer.

PubMed

Kim, Jung Soo; Cho, Min Seong; Nam, Jong Hyeon; Kim, Hyun-Jung; Choi, Kyeng-Won; Ryu, Jeong-Seon

2017-01-01

A family history can be a valuable tool in the era of precision medicine. Although a few studies have described an association of family history of lung cancer with EGFR activating mutation, their impact on survival of lung cancer patients is unclear. The study included consecutive 829 non-small-cell lung cancer patients who received analysis of EGFR mutation in a prospective lung cancer cohort. Family history of lung cancer was obtained by face-to-face interviews at the time of diagnosis. An association of EGFR activating mutation with a family history of lung cancer in first-degree relatives was evaluated with multivariate logistic regression analysis, and its association with survival was estimated with Cox's proportional hazards model. Seventy five (9.0%) patients had family history of lung cancer. The EGFR mutation was commonly observed in patients with positive family history compared to those with no family history (46.7% v 31.3%, χ2 p = 0.007). The family history was significantly associated with the EGFR mutation (aOR and 95% CI: 2.01 and 1.18-3.60, p = 0.011). Patients with the positive family history survived longer compared to those without (MST, 17.9 v 13.0 months, log-rank p = 0.037). The presence of the EGFR mutation was associated with better survival in patients without the family history (aHR and 95% CI: 0.72 and 0.57-0.90, p = 0.005). However, this prognostic impact was not observed in patients with the positive family history (aHR and 95% CI: 1.01 and 0.50-2.36, p = 0.832). In comparison to patients without the family history, EGFR activating mutation was common, and it did not affect prognosis in patients with positive family history.

[Lung abscess which needed to be distinguished from lung cancer; report of a case].

PubMed

Kamiya, Kazunori; Yoshizu, Akira; Misumi, Yuki; Hida, Naoya; Okamoto, Hiroaki; Yoshida, Sachiko

2011-12-01

Differential diagnosis of lung abscess from lung cancer is sometimes difficult. In February 2009, a 57-year-old man consulted our hospital complaining of bloody sputum. Chest computed tomography (CT) demonstrated a 2.5 cm nodule with pleural indentation, spicula and vascular involvement in the right S(3). Bronchofiberscope could not establish a definitive diagnosis. Blood test showed no abnormality. Three months later, progression of the nodule to the adjacent middle lobe was demonstrated by follow-up CT, and F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) showed isotope accumulation in the nodule and hilar lymph node. A diagnosis of lung cancer was suspected and surgery was performed. The diagnosis of possible lung cancer was made by needle biopsy, and the patient underwent right upper lobectomy and partial resection of middle lobe with standard nodal dissection. The final pathological diagnosis was lung abscess. Lung abscess must be kept in mind as a possible differential diagnosis when abnormal shadow suspected of lung cancer is observed.

Validation of Protein Markers for Lung Cancer Using CARET Sera and Proteomics Techniques — EDRN Public Portal

Cancer.gov

1.1 To validate the finding from pilot studies with CARET sera of autoantibodies to annexins I and II and PGP9.5 as potential biomarkers for lung cancers before the clinical diagnosis, evaluating sensitivity and specificity by time before diagnosis, treatment arm, gender, histologic type, and smoking status. 1.2 To determine whether a pattern of occurrence of autoantibodies in lung cancer sera may be diagnostic of lung cancer that is not dependent on the occurrence of any particular autoantibody. 1.3 To compare the findings for individual biomarker candidates and combinations of biomarker candidates in participants who were current smokers versus former smokers.

[Strategies for lung cancer with ischemic heart disease].

PubMed

Miyamoto, Nobuhiro; Kishimoto, Koji; Suehiro, Shouichi; Oda, Teiji; Tanabe, Kazuaki

2015-04-01

For lung cancer surgery which merged ischemic heart disease to need coronary artery treatments, the strategy is demanded on the timing of each treatment. Our department conforms to American College of Chest Physicians( ACCP) guideline and treatment strategies are decided as follows. 1) If right heart load has already occurred, we choose limited surgery for lung cancer. 2) Two-stage surgery is performed with principle. Coronary artery treatment is given priority to against left main trunk disease and unstable angina. 3) Simultaneous surgery is chosen for lung cancer more than stage II or lung cancer pressing neighboring organ and vessel not to be able to wait coronary artery treatments. Since 2007, we performed 4 simultaneous surgeries and experienced 3 pneumonia cases, 1 patient died in 5 months. We must decide a strategy in consideration of progress of the lung cancer and cardiac urgency.

Historical Perspectives of the Causation of Lung Cancer

PubMed Central

2015-01-01

Lung cancer is the leading cause of cancer deaths worldwide. Less-known forces are involved in the etiology of lung cancer and have relevant implications for providers in ameliorating care. The purpose of this article is to discuss theories of causation of lung cancer using historical analyses of the evolution of the disease and incorporating related explanations integrating the relationships of science, nursing, medicine, and society. Literature from 160 years was searched and Thagard’s model of causation networks was used to exhibit how nursing and medicine were significant influences in lung cancer causation theory. Disease causation interfaces with sociological norms of behavior to form habits and rates of health behavior. Historically, nursing was detrimentally manipulated by the tobacco industry, engaging in harmful smoking behaviors, thus negatively affecting patient care. Understanding the underlying history behind lung cancer causation may empower nurses to play an active role in a patient’s health. PMID:28462309