NYU Lung Cancer Biomarker Center
Principal Investigator: William N Rom
Abstract: DESCRIPTION (provided by applicant): The NYU Lung Cancer Biomarker Center CVC has recruited 1143 high-risk smokers (SCREENING COHORT) for the early detection of lung cancer. We have evaluated 1047 study subjects in our R/0 LUNG CANCER COHORT in collaboration with Harvey Pass, MD and the Division of Thoracic Surgery. Questionnaires, blood (100ml), spirometry, sputum, and CT-scans are obtained. 52% of the SCREENING COHORT had non-calcified nodules (NCN) with 3771 CT-Scans obtained to assess growth rates. 22 thoracic neoplasms were diagnosed with 18 lung adenocarcinomas. Biomarker collaborations with D, Sidransky Johns Hopkins) identified a panel of genes with promoter hypermethylations in plasma from lung cancer patients. Consistent with this finding, we noted increased plasma S- adenosylmethionine, a key intermediate in the methylation pathway, in lung cancer patients compared to high-risk smokers with NCN. Using set aside funds, we showed a 29-gene expression pattern in PBMC that separated lung cancer from high-risk controls with L, Showe (Wistar, UPenn), M-s Tang and colleagues demonstrated DNA adducts occurred at hot spot mutation sites in p53 and K-ras, and that poor repair contributed to adduct persistence. Exhaled breath predicted lung cancer with high AUC using combinations of alkanes measured in GC/MS. Our research plan is to expand our CVC with 300 new high-risk smokers, 1000 follow-up NCNs, and >250 lung cancers. We will evaluate NCN by CT- scans for early detection. We will determine risk for lung cancer among high-risk smokers by measuring blood acrolein DNA adducts and PBMC DNA repair capacity. We will develop a phase 3 validation case control study of 200 lung cancer cases and 200 matched controls and a phase 4 validation cohorts study of 600 high-risk smokers with >40 incident lung cancers. We will evaluate serum for tumor-associated antigens, auto-antibodies, gene expression patterns in PBMC and pathway control by microRNAs. Importantly, we will cross validate biomarker panels in the same prospective high risk smoker cohorts.
Funding Period: 2000-05-08 - 2015-12-31
more information: NIH RePORT
- Prediction of lung cancer using volatile biomarkers in breathMichael Phillips
Menssana Research Inc, Fort Lee, NJ 07024 6510, USA
Cancer Biomark 3:95-109. 2007..g. alkanes). In patients with lung cancer, induction of high-risk cytochrome p450 genotypes may accelerate catabolism of these VOCs, so that their altered abundance in breath may provide biomarkers of lung cancer...
- Unlocking biomarker discovery: large scale application of aptamer proteomic technology for early detection of lung cancerRachel M Ostroff
SomaLogic, Boulder, Colorado, United States of America
PLoS ONE 5:e15003. 2010..Here we present a comprehensive clinical biomarker study of lung cancer and the first large-scale clinical application of a new aptamer-based proteomic technology to discover blood protein biomarkers in disease...
- Resection of non-small cell lung cancers reverses tumor-induced gene expression changes in the peripheral immune systemAndrew V Kossenkov
The Wistar Institute, Philadelphia, Pennsylvania, USA
Clin Cancer Res 17:5867-77. 2011....
- Pulmonary Nodules: growth rate assessment in patients by using serial CT and three-dimensional volumetryJane P Ko
Department of Radiology, New York University Langone Medical Center, 560 1st Ave, New York, NY 10016, USA
Radiology 262:662-71. 2012..To determine the precision of a three-dimensional (3D) method for measuring the growth rate of solid and subsolid nodules and its ability to detect abnormal growth rates...
- Longitudinal multistage model for lung cancer incidence, mortality, and CT detected indolent and aggressive cancersWilliam D Hazelton
Fred Hutchinson Cancer Research Center, Public Health Sciences Division, 1100 Fairview Avenue North, Box 19024, Seattle, WA 98109, USA
Math Biosci 240:20-34. 2012..Females may have an inherently higher proportion of indolent lung cancers than males, or aggressive lung cancers may be brought into check by the immune system more frequently among females than males...
- CT scan screening for lung cancer: risk factors for nodules and malignancy in a high-risk urban cohortAlissa K Greenberg
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, New York, USA
PLoS ONE 7:e39403. 2012..We hypothesized that by reviewing demographic, clinical and nodule characteristics, we could identify risk factors associated with the presence of nodules on screening CT, and with the probability that a NCN was malignant...
- Effect of CpG methylation at different sequence context on acrolein- and BPDE-DNA binding and mutagenesisHsiang Tsui Wang
Department of Environmental Medicine, Pathology and Medicine, New York University School of Medicine, Tuxedo Park, New York 10987, USA
Carcinogenesis 34:220-7. 2013..These results indicate that both CpG sequence context and the chemical nature of the carcinogens are crucial factors for determining the effect of CpG methylation on mutagenesis...
- Variant Ciz1 is a circulating biomarker for early-stage lung cancerGillian Higgins
Cizzle Biotech, University of York, Yorkshire YO10 5DD, United Kingdom
Proc Natl Acad Sci U S A 109:E3128-35. 2012..The data show that variant Ciz1 is a strong candidate for a cancer-specific single marker capable of identifying early-stage lung cancer within at-risk groups without resort to invasive procedures...
- Aryl hydrocarbon receptor and lung cancerJunchieh J Tsay
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, NY, USA
Anticancer Res 33:1247-56. 2013..In this review article we summarize the current understanding of AhR and its role in the development of lung cancer, including its influence on cell proliferation, angiogenesis, inflammation, and apoptosis...
- Plasma osteopontin velocity differentiates lung cancers from controls in a CT screening populationSasha Joseph
Thoracic Oncology Laboratory, Department of Cardiothoracic Surgery, NYU School of Medicine, New York, NY 10016, USA
Cancer Biomark 12:177-84. 2012..We hypothesize that changes in plasma OPN over time (i.e., OPN velocity [OPNV]) can differentiate NSCLC patients from those without cancer in a CT screening population...
- Experimental human exposure to air pollutants is essential to understand adverse health effectsWilliam N Rom
1 Division of Pulmonary, Critical Care, and Sleep Medicine, and
Am J Respir Cell Mol Biol 49:691-6. 2013..We find that these studies appear to have been done with proper approval of institutional review boards, were done with informed consent from the participants, and have rarely been associated with serious adverse events...
- Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screeningHemant K Roy
Department of Medicine, NorthShore University HealthSystem Biomedical Engineering Department, Northwestern University, Evanston, Illinois, USA
Cancer Res 70:7748-54. 2010..Our results offer proof of concept that buccal PWS may potentially herald a minimally intrusive prescreening test that could be integral to the success of lung cancer population screening programs...
- S-adenosylmethionine as a biomarker for the early detection of lung cancerAlissa K Greenberg
Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA
Chest 132:1247-52. 2007..We hypothesized that AdoMet levels were elevated in patients with lung cancer and may prove useful as a biomarker for early lung cancer...
- In vitro mechanisms of lovastatin on lung cancer cell lines as a potential chemopreventive agentElena Maksimova
Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA
Lung 186:45-54. 2008..g., reversing ground glass opacities detected on CT scans or resolving airway preneoplasias detected by bronchoscopy before they progress to malignant transformation...
- Gene profiling of normal human bronchial epithelial cells in response to asbestos and benzo(a)pyrene diol epoxide (BPDE)Ilana Belitskaya-Levy
Division of Biostatistics, Department of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
J Environ Pathol Toxicol Oncol 26:281-94. 2007..These in vitro findings in NHBE cells model environment-gene interaction for asbestos and BPDE, highlighting effects of inflammation, fibrosis, proliferation, and DNA damage recognition and repair...
- Detection of lung cancer using weighted digital analysis of breath biomarkersMichael Phillips
Menssana Research Inc, Fort Lee, NJ 07024 6510, United States
Clin Chim Acta 393:76-84. 2008..We developed a non-linear method of multivariate analysis, weighted digital analysis (WDA), and evaluated its ability to predict lung cancer employing volatile biomarkers in the breath...
- Performance of mitochondrial DNA mutations detecting early stage cancerJohn P Jakupciak
Biochemical Science Division, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, USA
BMC Cancer 8:285. 2008..The detection of mtDNA mutations in body fluids using resequencing microarrays, which are more sensitive than other sequencing methods, could provide a strategy to measure mutation loads in remote anatomical sites...
- Wnt pathway in pulmonary fibrosis in the bleomycin mouse modelLi Liu
Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA
J Environ Pathol Toxicol Oncol 28:99-108. 2009..The Wnt/beta-catenin signaling pathway plays an important role in regulating cellular differentiation, proliferation, and polarity...
- Gene expression profiles in peripheral blood mononuclear cells can distinguish patients with non-small cell lung cancer from patients with nonmalignant lung diseaseMichael K Showe
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
Cancer Res 69:9202-10. 2009..Our results show the feasibility of using peripheral blood gene expression signatures to identify early-stage NSCLC in at-risk populations...
- Emerging exposures and respiratory health: World Trade Center dustWilliam N Rom
MPH, Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, 550 1st Ave, New York, NY 10016, USA
Proc Am Thorac Soc 7:142-5. 2010....
- Identification of an autoantibody panel to separate lung cancer from smokers and nonsmokersWilliam N Rom
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Radiology, Thoracic Surgery, and Environmental Medicine, New York University School of Medicine, New York, NY 10016, USA
BMC Cancer 10:234. 2010..Sera from lung cancer patients contain autoantibodies that react with tumor associated antigens (TAAs) that reflect genetic over-expression, mutation, or other anomalies of cell cycle, growth, signaling, and metabolism pathways...
- Molecular analysis of plasma DNA for the early detection of lung cancer by quantitative methylation-specific PCRKimberly Laskie Ostrow
Department of Otolaryngology Head and Neck Cancer Research Division, Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA
Clin Cancer Res 16:3463-72. 2010..We investigated the likelihood of detecting aberrant DNA methylation of tumor suppressor genes in plasma samples of patients with abnormalities of the lung detected upon computed tomography (CT) scan...
- Lung microbiome for clinicians. New discoveries about bugs in healthy and diseased lungsLeopoldo N Segal
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, NYU Human Microbiome Program, New York University School of Medicine, New York, New York
Ann Am Thorac Soc 11:108-16. 2014..Future investigations with longitudinal follow-up to understand the dynamics of the lung microbiome may lead to the development of new therapeutic targets. ..
- Genome Wide Association Study of Head and Neck CancerSanjay Shete; Fiscal Year: 2013....
- The Emphysematous Microenvironment Promotes Lung Tumorigenesis and ProgressionJohn J Reilly; Fiscal Year: 2013....
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- Epigenetic Changes Link COPD and Lung CancerYohannes Tesfaigzi; Fiscal Year: 2013..Together, the integrated results from these studies will provide novel insights into mechanisms that connect COPD to the development of lung cancer. ..
- Biosynthesis and Function of Lactosaminyl Glycans in HematopoiesisRobert Sackstein; Fiscal Year: 2013..This research effort should yield new treatments to improve marrow function in such conditions. (End of Abstract) ..
- Early detection of lung cancer in veteransFeng Jiang; Fiscal Year: 2013..The use of the biomarkers that can identify NSCLC at its early stage will offer the best opportunity for effective treatments of the malignancy, and therefore will provide the best health care for Veterans diagnosed with lung cancer. ..
- Identifying non-coding RNAs for early detection and prevention of lung cancerHarvey Ira Pass; Fiscal Year: 2013....
- Frontotemporal Dementias: Genotypes and PhenotypesVirginia M Lee; Fiscal Year: 2013..elegans and transgenic mouse models. The proposed studies will provide important insights into mechanisms of FTLD and the diagnosis and treatment of these disorders. ..
- Benefits and Harms of Lung Cancer Screening in HIV InfectionJuan P Wisnivesky; Fiscal Year: 2013....