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Genomes and Genes | SPORE IN LUNG CANCERSummaryPrincipal Investigator: Stephen Baylin Affiliation: Johns Hopkins University Country: USA Abstract: The Johns Hopkins Lung Cancer SPORE is in its tenth year and continues to have as its goals, the performance of highly translational research to move ideas from the bench to bedside, and vice versa, to provide new means for the prevention of, risk assessment for, early detection of, gauging prognosis of, and therapy for, lung cancers of all types. In these efforts, extensive formal collaboration with other Lung Cancer SPORE'S is often emphasized. The program uses the flexibility of the SPORE funding mechanism to extend projects that continually evolve higher and higher translational potential and curtail those that do not. There is an emphasis on constantly bringing in new concepts and directions in parallel with fully evolving those areas that are headed for ultimate translational verification and even reaching common clinical practice. In terms of research at the highest translational level, including work at the population level, the SPORE is presently emphasizing the second and third projects (a collaborative venture with the Colorado SPORE), which are testing epigenetic molecular markers which appear to have very high promise for the areas of risk assessment, early detection, and gauging of prognosis of lung cancer. The first project, also aimed at predicting lung cancer risk and prognosis, is taking new approaches to develop genetic markers for these purposes. A fourth project is developing new concepts for lung cancer prevention by taking the concepts through pre-clinical models and initial proof of principle studies in high risk individuals. This work is very complementary with participation of the Hopkins SPORE in the consortium chemoprevention trials (Lung Cancer Biomarker Chemoprevention Consortium-LCBCC) with the other Lung Cancer SPORES and with a collaborative trial of Iloprost in collaboration with the Colorado SPORE. The fifth and sixth projects are both aimed at development of novel therapeutic strategies for lung cancer with one exploiting new insights into these diseases derived from study of molecular pathways guiding early lung development and the other exploring inhibition of fatty acid synthesis as a new approach. Funding Period: 1992-09-30 - 2008-11-30 more information: NIH RePORT Top Publications
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Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft modelJacob E Koskimaki
Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
BMC Cancer 10:29. 2010....- Epigenetic alteration of Wnt pathway antagonists in progressive glandular neoplasia of the lungJulien D F Licchesi
Cancer Biology Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
Carcinogenesis 29:895-904. 2008.... 
Selective inhibition of fatty acid synthase for lung cancer treatmentHajime Orita
Department of Pathology and Johns Hopkins Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
Clin Cancer Res 13:7139-45. 2007..This study investigated pharmacologic inhibition of FAS using C93, a rationally designed molecule that inhibits FAS activity without affecting fatty acid oxidation in preclinical models of lung cancer...- Preclinical evaluation of targeting the Nrf2 pathway by triterpenoids (CDDO-Im and CDDO-Me) for protection from LPS-induced inflammatory response and reactive oxygen species in human peripheral blood mononuclear cells and neutrophilsRajesh K Thimmulappa
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
Antioxid Redox Signal 9:1963-70. 2007.... - WNT10B functional dualism: beta-catenin/Tcf-dependent growth promotion or independent suppression with deregulated expression in cancerHirohide Yoshikawa
Department of Epigenetic Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135 8550, Japan
Mol Biol Cell 18:4292-303. 2007..We suggest that FGF switches WNT10B from a negative to a positive cell growth regulator... - LOXL1 and LOXL4 are epigenetically silenced and can inhibit ras/extracellular signal-regulated kinase signaling pathway in human bladder cancerGuojun Wu
Department of Otolaryngology Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
Cancer Res 67:4123-9. 2007..Thus, our current study suggests for the first time that lysyl oxidase-like genes can act as tumor suppressor genes and exert their functions through the inhibition of the Ras/ERK signaling pathway in human bladder cancer... - Predicting gene promoter methylation in non-small-cell lung cancer by evaluating sputum and serumS A Belinsky
Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr SE, Albuquerque, NM 87108, USA
Br J Cancer 96:1278-83. 2007..These studies demonstrate that sputum can be used effectively as a surrogate for tumour tissue to predict the methylation status of advanced lung cancer where biopsy is not feasible... - FDG-PET for pharmacodynamic assessment of the fatty acid synthase inhibitor C75 in an experimental model of lung cancerJae Sung Lee
Department of Radiology, Johns Hopkins Medical Institutions, 1550 Orleans Street, 492 CRB II, Baltimore, Maryland 21231, USA
Pharm Res 24:1202-7. 2007..The aim of this study was to use positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) to monitor the effects of the FAS inhibitor C75 on tumor glucose metabolism in a rodent model of human A549 lung cancer... - Hedgehog signaling maintains a tumor stem cell compartment in multiple myelomaCraig D Peacock
Sidney Kimmel Comprehensive Cancer Center and Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
Proc Natl Acad Sci U S A 104:4048-53. 2007..The potential existence of similar relationships in other adult cancers may have important biologic and clinical implications for the study of aberrant Hh signaling... - Dual EGFR and mTOR targeting in squamous cell carcinoma models, and development of early markers of efficacyA Jimeno
Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 1M89, Baltimore, MD 21231 1000, USA
Br J Cancer 96:952-9. 2007..In conclusion, an mTOR inhibitor showed antitumor activity in EGFR-resistant SCC cell lines. Marked antitumor effects were associated with dual pathway inhibition, which were detected by early FNA biopsies... 
DNA methylation markers and early recurrence in stage I lung cancerMalcolm V Brock
Johns Hopkins Hospital, Baltimore, USA
N Engl J Med 358:1118-28. 2008..Despite optimal and early surgical treatment of non-small-cell lung cancer (NSCLC), many patients die of recurrent NSCLC. We investigated the association between gene methylation and recurrence of the tumor...- Inhibiting fatty acid synthase for chemoprevention of chemically induced lung tumorsHajime Orita
Department of Pathology and Johns Hopkins Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
Clin Cancer Res 14:2458-64. 2008..Fatty acid synthase (FAS) is overexpressed in lung cancer, and we have investigated the potential use of FAS inhibitors for chemoprevention of lung cancer... - MS-qFRET: a quantum dot-based method for analysis of DNA methylationVasudev J Bailey
Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA
Genome Res 19:1455-61. 2009..The direct application of MS-qFRET on clinical samples offers great promise for its translational use in early cancer diagnosis, prognostic assessment of tumor behavior, as well as monitoring response to therapeutic agents... - A primary xenograft model of small-cell lung cancer reveals irreversible changes in gene expression imposed by culture in vitroVincent C Daniel
Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
Cancer Res 69:3364-73. 2009..Such changes in gene expression may be a common feature of many cancer cell culture systems, with functional implications for the use of such models for preclinical drug development... - DNA methylation analysis on a droplet-in-oil PCR arrayYi Zhang
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
Lab Chip 9:1059-64. 2009..These results were consistent with standard MSP protocols, yet the simplicity of the droplet-in-oil microfluidic PCR platform provides an easy and efficient tool for DNA methylation analysis in a large-scale arrayed manner... - Nrf2-dependent sulfiredoxin-1 expression protects against cigarette smoke-induced oxidative stress in lungsAnju Singh
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 212045, USA
Free Radic Biol Med 46:376-86. 2009..Thus, Srx1, a key Nrf2-regulated gene, contributes to protection against oxidative injury in the lung... - RNAi-mediated silencing of nuclear factor erythroid-2-related factor 2 gene expression in non-small cell lung cancer inhibits tumor growth and increases efficacy of chemotherapyAnju Singh
Department of Environmental Health Sciences, Division of Toxicology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
Cancer Res 68:7975-84. 2008..Thus, targeting Nrf2 activity in lung cancers, particularly those with Keap1 mutations, could be a promising strategy to inhibit tumor growth and circumvent chemoresistance... - Cancer stem cells and the ontogeny of lung cancerCraig D Peacock
The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 1550 Orleans St, Rm 546, Baltimore, MD 21231, USA
J Clin Oncol 26:2883-9. 2008..This review summarizes our understanding of the cellular and molecular mechanisms operating within the putative cancer-initiating cell at the core of lung neoplasia... - Profiling the expression pattern of GPI transamidase complex subunits in human cancerJatin K Nagpal
Department of Otolaryngology Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
Mod Pathol 21:979-91. 2008..Collectively, our study defines a trend involving the deregulated expression and the functional contribution of the GPIT subunits in various cancers with potential implications in diagnosis, prognosis and therapeutic intervention... - Promoter hypermethylation of hallmark cancer genes in atypical adenomatous hyperplasia of the lungJulien D F Licchesi
Cancer Biology Program at the Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA
Clin Cancer Res 14:2570-8. 2008.... - Ethanol sensitivity: a central role for CREB transcription regulation in the cerebellumGeorge K Acquaah-Mensah
Department of Pharmaceutical Sciences, School of Pharmacy Worcester, Massachusetts College of Pharmacy and Health Sciences, 19 Foster Street, Worcester, MA 01608 1715, USA
BMC Genomics 7:308. 2006..In this report, the extent to which CREB signalling impacts the differential expression of genes in ILS and ISS mouse cerebella is examined... - Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-ImidazolideRajesh K Thimmulappa
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
Biochem Biophys Res Commun 351:883-9. 2006..Activation of Nrf2-dependent compensatory antioxidative pathways by CDDO-Im protects from LPS induced inflammatory response and mortality... - Role of lung maintenance program in the heterogeneity of lung destruction in emphysemaRubin M Tuder
Division of Cardiopulmonary Pathology, Department of Pathology, Ross Research Building, Room 519, 720 Rutland Avenue, Baltimore, MD 21205, USA
Proc Am Thorac Soc 3:673-9. 2006..As injury prevails during the course of this chronic disease, it leads to a more homogeneous pattern of lung disease... - C-fos assessment as a marker of anti-epidermal growth factor receptor effectAntonio Jimeno
The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231-1000, USA
Cancer Res 66:2385-90. 2006..In summary, variations in c-fos expression reflect the pharmacologic actions of EGFR inhibitors in in vitro and in vivo models... - Nested multigene MSP/DHPLC method for analyzing promoter hypermethylation status in clinical samplesKevin K Divine
Lovelace Respiratory Research Institute, Albuquerque, NM 87108-5127, USA
Biotechniques 40:40, 42, 44 passim. 2006 - Can we improve the cytologic examination of malignant pleural effusions using molecular analysis?Malcolm V Brock
Division of Thoracic Surgery, Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
Ann Thorac Surg 80:1241-7. 2005..Deoxyribonucleic acid (DNA) methylation is a robust strategy for detecting cancer early in tissue. We hypothesized that DNA methylation would be more sensitive in diagnosing patients with malignant pleural effusions than cytology... - Somatic mutation and gain of copy number of PIK3CA in human breast cancerGuojun Wu
Department of Otolaryngology Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Breast Cancer Res 7:R609-16. 2005..Even though PIK3CA amplification and somatic mutation have been reported previously in various kinds of human cancers, the genetic change in PIK3CA in human breast cancer has not been clearly identified... - Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in miceTirumalai Rangasamy
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
J Exp Med 202:47-59. 2005..Our studies suggest that the responsiveness of Nrf2-directed antioxidant pathways may act as a major determinant of susceptibility to allergen-mediated asthma... - Colorimetric approach to high-throughput mutation analysisNicole E Benoit
Johns Hopkins University School of Medicine, Baltimore MD 21205, USA
Biotechniques 38:635-9. 2005..This assay is straightforward, accurate, inexpensive, and allows for rapid, high-throughput analysis of samples, making it ideal for genomic mutation or polymorphism screening studies in both clinical and research settings... - Enhanced autoantigen expression in regenerating muscle cells in idiopathic inflammatory myopathyLivia Casciola-Rosen
Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
J Exp Med 201:591-601. 2005..Regulating pathways of antigen expression may provide unrecognized therapeutic opportunities in autoimmune diseases... - DeltaNp63alpha up-regulates the Hsp70 gene in human cancerGuojun Wu
Department of Otolaryngology-Head and Neck Surgery, Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205-2196, USA
Cancer Res 65:758-66. 2005..Our study provides strong evidence for the physiologic association between DeltaNp63alpha and hsp70 in human cancer, thus further supporting the oncogenic potential of DeltaNp63alpha... - Silencing of genes by promoter hypermethylation: key event in rodent and human lung cancerSteven A Belinsky
Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108, USA
Carcinogenesis 26:1481-7. 2005.... - Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohortSteven A Belinsky
Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA
Cancer Res 66:3338-44. 2006.... - Elevated incidence of lung cancer among HIV-infected individualsEric A Engels
Johns Hopkins Hospital, Baltimore, MD, USA
J Clin Oncol 24:1383-8. 2006..We sought to characterize lung cancer incidence among HIV-infected individuals, examine whether cancer risk was related to HIV-induced immunosuppression, and assess whether the high prevalence of smoking explained elevated risk... - Overexpression of glycosylphosphatidylinositol (GPI) transamidase subunits phosphatidylinositol glycan class T and/or GPI anchor attachment 1 induces tumorigenesis and contributes to invasion in human breast cancerGuojun Wu
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
Cancer Res 66:9829-36. 2006..This aberrant growth is mediated, at least partially, by phosphorylation of paxillin, contributing to invasion and progression of breast cancer... - Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancerAnju Singh
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America
PLoS Med 3:e420. 2006..Increased expression of cellular antioxidants and xenobiotic detoxification enzymes has been implicated in resistance of tumor cells against chemotherapeutic drugs... - Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathwayThomas W Kensler
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
Annu Rev Pharmacol Toxicol 47:89-116. 2007..This review highlights the key elements in this adaptive response to protection against acute and chronic cell injury provoked by environmental stresses... - Nrf2 regulates an adaptive response protecting against oxidative damage following diquat-mediated formation of superoxide anionWilliam O Osburn
Johns Hopkins University Bloomberg School of Public Health, Department of Environmental Health Sciences, Baltimore, MD, USA
Arch Biochem Biophys 454:7-15. 2006..Thus the enhanced sensitivity of N0 cells does not reflect basal differences in antioxidative capacity, but rather an impaired ability to mount an adaptive response to sustained oxidative stress... - Delayed diagnosis and elevated mortality in an urban population with HIV and lung cancer: implications for patient careMalcolm V Brock
Johns Hopkins Hospital, and Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21287, USA
J Acquir Immune Defic Syndr 43:47-55. 2006..Lung cancer is more common in HIV-infected patients than in the general population. We examined how effectively lung cancer was being diagnosed in our HIV-infected patients... - LKB1/STK11 suppresses cyclooxygenase-2 induction and cellular invasion through PEA3 in lung cancerSunil Upadhyay
Department of Otolaryngology Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 2196, USA
Cancer Res 66:7870-9. 2006..These results suggest that PEA3 stabilization due to LKB1 inactivation could lead to epithelial/mesenchymal transition and greater lung cancer invasion potential... - Glutathione peroxidase 2, the major cigarette smoke-inducible isoform of GPX in lungs, is regulated by Nrf2Anju Singh
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Am J Respir Cell Mol Biol 35:639-50. 2006..This study shows that GPX2 is the major oxidative stress-inducible cellular GPX isoform in the lungs, and that its basal as well as inducible expression is dependent on Nrf2... - Hypermethylation of ASC/TMS1 is a sputum marker for late-stage lung cancerEmi Ota Machida
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
Cancer Res 66:6210-8. 2006..Thus, hypermethylation of ASC/TMS1 is a marker for late-stage lung cancer and, in sputum, could predict prognosis in patients resected for early-stage disease... - Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsisRajesh K Thimmulappa
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
J Clin Invest 116:984-95. 2006..Our study reveals Nrf2 as a novel modifier gene of sepsis that determines survival by mounting an appropriate innate immune response... - Surgical resection of limited disease small cell lung cancer in the new era of platinum chemotherapy: Its time has comeMalcolm V Brock
Division of Thoracic Surgery, Department of Surgery, The Johns Hopkinds Medical Institutions, Baltimore, MD, USA
J Thorac Cardiovasc Surg 129:64-72. 2005..Although resection is not the standard of care in treating small cell lung cancer, new platinum drugs and modern staging have allowed the role of surgery to be reevaluated...