SPORE IN LUNG CANCER

Summary

Principal Investigator: Stephen Baylin
Affiliation: Johns Hopkins University
Country: USA
Abstract: DESCRIPTION (provided by applicant): 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

  1. pmc Decoding circulating nucleic acids in human serum using microfluidic single molecule spectroscopy
    Kelvin J Liu
    Biomedical Engineering Department, 3400 North Charles Street, Johns Hopkins University, Baltimore, Maryland 21218, USA
    J Am Chem Soc 132:5793-8. 2010
  2. pmc Itraconazole and arsenic trioxide inhibit Hedgehog pathway activation and tumor growth associated with acquired resistance to smoothened antagonists
    James Kim
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA
    Cancer Cell 23:23-34. 2013
  3. pmc Hedgehog pathway inhibition radiosensitizes non-small cell lung cancers
    Jing Zeng
    Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 2410, USA
    Int J Radiat Oncol Biol Phys 86:143-9. 2013
  4. pmc Loss of LSD1 (lysine-specific demethylase 1) suppresses growth and alters gene expression of human colon cancer cells in a p53- and DNMT1(DNA methyltransferase 1)-independent manner
    Lihua Jin
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Biochem J 449:459-68. 2013
  5. pmc Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer
    Charles M Rudin
    The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA
    Nat Genet 44:1111-6. 2012
  6. pmc Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer
    Rosalyn A Juergens
    Department of Oncology, Johns Hopkins University, Baltimore, Maryland 21231, USA
    Cancer Discov 1:598-607. 2011
  7. pmc Defining a gene promoter methylation signature in sputum for lung cancer risk assessment
    Shuguang Leng
    Lung Cancer Program, Lovelace Respiratory Research Institute, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico 87108, USA
    Clin Cancer Res 18:3387-95. 2012
  8. pmc The TGFβ-miR200-MIG6 Pathway Orchestrates the EMT-Associated Kinase Switch That Induces Resistance to EGFR Inhibitors
    Evgeny Izumchenko
    Authors Affiliations Department of Otolaryngology Head and Neck Surgery, Johns Hopkins University School of Medicine and
    Cancer Res 74:3995-4005. 2014
  9. pmc Itraconazole side chain analogues: structure-activity relationship studies for inhibition of endothelial cell proliferation, vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, and hedgehog signaling
    Wei Shi
    Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, United States
    J Med Chem 54:7363-74. 2011
  10. pmc Invited commentary: the etiology of lung cancer in men compared with women
    Anthony J Alberg
    Hollings Cancer Center, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
    Am J Epidemiol 177:613-6. 2013

Scientific Experts

Detail Information

Publications92

  1. pmc Decoding circulating nucleic acids in human serum using microfluidic single molecule spectroscopy
    Kelvin J Liu
    Biomedical Engineering Department, 3400 North Charles Street, Johns Hopkins University, Baltimore, Maryland 21218, USA
    J Am Chem Soc 132:5793-8. 2010
    ..This demonstrates that microfluidic single molecule spectroscopy can be a rapid, facile, and inexpensive alternative to the established PCR-based methods that have been used near exclusively for CNA analysis...
  2. pmc Itraconazole and arsenic trioxide inhibit Hedgehog pathway activation and tumor growth associated with acquired resistance to smoothened antagonists
    James Kim
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA
    Cancer Cell 23:23-34. 2013
    ..Itraconazole and arsenic trioxide, alone or in combination, inhibit the growth of medulloblastoma and basal cell carcinoma in vivo, and prolong survival of mice with intracranial drug-resistant SMO(D477G) medulloblastoma...
  3. pmc Hedgehog pathway inhibition radiosensitizes non-small cell lung cancers
    Jing Zeng
    Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 2410, USA
    Int J Radiat Oncol Biol Phys 86:143-9. 2013
    ..Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported...
  4. pmc Loss of LSD1 (lysine-specific demethylase 1) suppresses growth and alters gene expression of human colon cancer cells in a p53- and DNMT1(DNA methyltransferase 1)-independent manner
    Lihua Jin
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Biochem J 449:459-68. 2013
    ..The results of the present study suggested that LSD1 is critical in the regulation of cell proliferation, but also indicated that LSD1 is not an absolute requirement for the stabilization of either p53 or DNMT1...
  5. pmc Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer
    Charles M Rudin
    The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA
    Nat Genet 44:1111-6. 2012
    ..These data provide an in-depth view of the spectrum of genomic alterations in SCLC and identify several potential targets for therapeutic intervention...
  6. pmc Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer
    Rosalyn A Juergens
    Department of Oncology, Johns Hopkins University, Baltimore, Maryland 21231, USA
    Cancer Discov 1:598-607. 2011
    ..034) and overall survival (P = 0.035). Four of 19 patients had major objective responses to subsequent anticancer therapies given immediately after epigenetic therapy...
  7. pmc Defining a gene promoter methylation signature in sputum for lung cancer risk assessment
    Shuguang Leng
    Lung Cancer Program, Lovelace Respiratory Research Institute, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico 87108, USA
    Clin Cancer Res 18:3387-95. 2012
    ....
  8. pmc The TGFβ-miR200-MIG6 Pathway Orchestrates the EMT-Associated Kinase Switch That Induces Resistance to EGFR Inhibitors
    Evgeny Izumchenko
    Authors Affiliations Department of Otolaryngology Head and Neck Surgery, Johns Hopkins University School of Medicine and
    Cancer Res 74:3995-4005. 2014
    ..Cancer Res; 74(14); 3995-4005. ©2014 AACR. ..
  9. pmc Itraconazole side chain analogues: structure-activity relationship studies for inhibition of endothelial cell proliferation, vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, and hedgehog signaling
    Wei Shi
    Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, United States
    J Med Chem 54:7363-74. 2011
    ..These results also suggest that modification of the sec-butyl side chain can lead to enhancement of the biological activity of itraconazole...
  10. pmc Invited commentary: the etiology of lung cancer in men compared with women
    Anthony J Alberg
    Hollings Cancer Center, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
    Am J Epidemiol 177:613-6. 2013
    ....
  11. pmc Phase 2 study of pemetrexed and itraconazole as second-line therapy for metastatic nonsquamous non-small-cell lung cancer
    Charles M Rudin
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1550 Orleans Street, Baltimore, MD 21231, USA
    J Thorac Oncol 8:619-23. 2013
    ..On the basis of these data, we performed an exploratory clinical study, assessing the efficacy of itraconazole with cytotoxic chemotherapy in the treatment of patients with advanced lung cancer...
  12. doi Epigenetic therapy in non-small-cell lung cancer: targeting DNA methyltransferases and histone deacetylases
    Frank P Vendetti
    Johns Hopkins University, The Sidney Kimmel Comprehensive Cancer Center, David H Koch Cancer Research Building 2, Room 562, 1550 Orleans Street, Baltimore, MD 21231, USA
    Expert Opin Biol Ther 13:1273-85. 2013
    ..Two key levels of aberrant epigenetic control are DNA methylation and histone acetylation. Primary regulators of these epigenetic changes include DNA methyltransferases (DNMTs) and histone deacetylases (HDACs)...
  13. pmc Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers
    Huili Li
    Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
    Oncotarget 5:587-98. 2014
    ..Samples from selected patient biopsies showed upregulation of AIM genes after treatment with epigenetic therapy. These results point to a broad immune stimulatory role for DNA demethylating drugs in multiple cancers. ..
  14. pmc Functional Identification of Cancer-Specific Methylation of CDO1, HOXA9, and TAC1 for the Diagnosis of Lung Cancer
    John Wrangle
    Authors Affiliations The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium MDxHealth Inc, Irvine, California Shinshu University School of Medicine, Asahi, Matsumoto, Nagano, Japan and Lovelace Respiratory Research Institute, Albuquerque, New Mexico
    Clin Cancer Res 20:1856-64. 2014
    ..Hypermethylation of CpG islands is a common and important alteration in the transition from normal tissue to cancer...
  15. pmc Alterations of immune response of Non-Small Cell Lung Cancer with Azacytidine
    John Wrangle
    The Johns Hopkins University, School of Medicine, Oncology Center Hematology Medical Oncology, Baltimore, Maryland
    Oncotarget 4:2067-79. 2013
    ..Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade. ..
  16. pmc MicroRNA 4423 is a primate-specific regulator of airway epithelial cell differentiation and lung carcinogenesis
    Catalina Perdomo
    Division of Computational Biomedicine, Genetics and Genomics Program, and Pulmonary Center, Department of Medicine, Boston University, Boston, MA 02118
    Proc Natl Acad Sci U S A 110:18946-51. 2013
    ..Together, our results indicate that miR-4423 is a regulator of airway epithelium differentiation and that the abrogation of its function contributes to lung carcinogenesis. ..
  17. ncbi Novel methylation biomarker panel for the early detection of pancreatic cancer
    Joo Mi Yi
    Authors Affiliations Departments of Oncology, Surgery, Urology, and Mechanic Engineering, Johns Hopkins University Department of Biomedical Engineering, Johns Hopkins School of Medicine Department of Pathology, The Sol Goldman Pancreatic Research Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland MDxHealth, Ghent, Belgium and Research Institute, Dongnam Institute of Radiological and Medical Sciences DIRAMS, Busan, South Korea
    Clin Cancer Res 19:6544-55. 2013
    ..Here, we identify cancer-specific promoter DNA methylation of BNC1 and ADAMTS1 as a promising biomarker detection strategy meriting investigation in pancreatic cancer...
  18. pmc Aerosolised 5-azacytidine suppresses tumour growth and reprogrammes the epigenome in an orthotopic lung cancer model
    M D Reed
    Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108, USA
    Br J Cancer 109:1775-81. 2013
    ..To mitigate these barriers, an aerosol of 5-azacytidine was generated and characterised...
  19. pmc Transcription factor NRF2 regulates miR-1 and miR-206 to drive tumorigenesis
    Anju Singh
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
    J Clin Invest 123:2921-34. 2013
    ..Our results demonstrate that microRNA-dependent (miRNA-dependent) regulation of the PPP via NRF2 and HDAC4 represents a novel link between miRNA regulation, glucose metabolism, and ROS homeostasis in cancer cells...
  20. pmc Transcriptional regulation of Wnt inhibitory factor-1 by Miz-1/c-Myc
    J D F Licchesi
    Cancer Biology Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
    Oncogene 29:5923-34. 2010
    ..Our data reveal novel insights into c-Myc-mediated DNA methylation-dependent transcriptional silencing, a mechanism that might contribute to the dysregulation of Wnt signaling in cancer...
  21. pmc Expression of ABCG2 (BCRP) is regulated by Nrf2 in cancer cells that confers side population and chemoresistance phenotype
    Anju Singh
    Johns Hopkins University, of Environmental Health Sciences, Bloomberg School of Public Health, E7624, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Mol Cancer Ther 9:2365-76. 2010
    ..Thus, Nrf2-mediated regulation of ABCG2 expression maintains the SP fraction and confers chemoresistance...
  22. pmc Re-expression of CXCL14, a common target for epigenetic silencing in lung cancer, induces tumor necrosis
    M Tessema
    Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA
    Oncogene 29:5159-70. 2010
    ..Together, these findings identify CXCL14 as an important tumor suppressor gene epigenetically silenced during lung carcinogenesis...
  23. pmc Nrf2 and Keap1 abnormalities in non-small cell lung carcinoma and association with clinicopathologic features
    Luisa M Solis
    Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 16:3743-53. 2010
    ....
  24. pmc Long-term survival outcomes by smoking status in surgical and nonsurgical patients with non-small cell lung cancer: comparing never smokers and current smokers
    Robert A Meguid
    Division of Thoracic Surgery, Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA
    Chest 138:500-9. 2010
    ..Survival outcomes of never smokers with non-small cell lung cancer (NSCLC) who undergo surgery are poorly characterized. This investigation compared surgical outcomes of never and current smokers with NSCLC...
  25. pmc Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis
    Deepti Malhotra
    Department of Environmental Health Sciences Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Nucleic Acids Res 38:5718-34. 2010
    ..Results were confirmed in an in vivo stress model of cigarette smoke-exposed mice. This study reveals global circuitry of the Nrf2 stress response emphasizing Nrf2 as a central node in cell survival response...
  26. pmc Transient low doses of DNA-demethylating agents exert durable antitumor effects on hematological and epithelial tumor cells
    Hsing Chen Tsai
    The Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Cancer Cell 21:430-46. 2012
    ..Low-dose decitabine and azacitidine may have broad applicability for cancer management...
  27. pmc Single-tube analysis of DNA methylation with silica superparamagnetic beads
    Vasudev J Bailey
    Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA
    Clin Chem 56:1022-5. 2010
    ..This method includes many disconnected steps with associated losses of material, potentially reducing the analytical sensitivity required for analysis of challenging clinical samples...
  28. pmc The detection of chromosomal aneusomy by fluorescence in situ hybridization in sputum predicts lung cancer incidence
    Marileila Varella-Garcia
    University of Colorado Denver, 12801 East 17th Avenue, Aurora, CO 80045, USA
    Cancer Prev Res (Phila) 3:447-53. 2010
    ..The apparent promise of CA-FISH in sputum for assessing lung cancer risk and/or for lung cancer early detection now needs to be validated in a clinical screening trial...
  29. pmc KEAP1 gene mutations and NRF2 activation are common in pulmonary papillary adenocarcinoma
    Qing Kay Li
    Department of Pathology, The Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA
    J Hum Genet 56:230-4. 2011
    ..Furthermore, this distinctive molecular characteristic supports the recognition of true papillary adenocarcinoma as a diagnostic entity...
  30. pmc Single-molecule analysis enables free solution hydrodynamic separation using yoctomole levels of DNA
    Kelvin J Liu
    Biomedical Engineering Department, Johns Hopkins University, Baltimore, Maryland 21218, USA
    J Am Chem Soc 133:6898-901. 2011
    ..SML-FSHS was used to examine the thermodynamic equilibrium between stochastically open molecular beacon and target-bound molecular beacon in the detection of E. coli 16s rRNA targets...
  31. pmc Novel chalcone derivatives as potent Nrf2 activators in mice and human lung epithelial cells
    Vineet Kumar
    Laboratory of Synthetic Chemistry, SAIC Frederick, Inc, National Cancer Institute at Frederick, Frederick, Maryland 21702, United States
    J Med Chem 54:4147-59. 2011
    ..We have discussed a quantitative structure-activity relationship and proposed a possible mechanism of Nrf2 activation...
  32. pmc Differential epigenetic regulation of TOX subfamily high mobility group box genes in lung and breast cancers
    Mathewos Tessema
    Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America
    PLoS ONE 7:e34850. 2012
    ....
  33. pmc Human immunodeficiency virus infection as a prognostic factor in surgical patients with non-small cell lung cancer
    Craig M Hooker
    Department of Oncology, Johns Hopkins School of Medicine, Johns Hopkins Hospital, Baltimore, Maryland 21287, USA
    Ann Thorac Surg 93:405-12. 2012
    ..The purpose of this study was to assess the effect of human immunodeficiency virus (HIV) infection on postoperative survival among non-small cell lung cancer (NSCLC) patients...
  34. pmc Mapping DNA quantity into electrophoretic mobility through quantum dot nanotethers for high-resolution genetic and epigenetic analysis
    Yi Zhang
    Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    ACS Nano 6:858-64. 2012
    ..Then, QEMSA was used for DNA methylation analysis of the p16/CDK2A tumor suppressor gene, where its ability to detect subtle changes in methylation was shown to be superior to that of qPCR...
  35. pmc Oligoamine analogues in combination with 2-difluoromethylornithine synergistically induce re-expression of aberrantly silenced tumour-suppressor genes
    Yu Wu
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Biochem J 442:693-701. 2012
    ..The treatment-induced re-expression of SFRP2 is associated with increased H3K4me2 (di-methyl H3K4) in the gene promoter. The combination of LSD1-inhibiting oligoamines and DFMO represents a novel approach to epigenetic therapy of cancer...
  36. pmc The redox-sensitive transcription factor Nrf2 regulates murine hematopoietic stem cell survival independently of ROS levels
    Akil A Merchant
    Division of Hematology, Department of Medicine, School of Medicine, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
    Blood 118:6572-9. 2011
    ..These findings demonstrate a critical role for Nrf2 in hematopoiesis and stem cell survival that is independent of ROS levels...
  37. pmc Denitrosylation of HDAC2 by targeting Nrf2 restores glucocorticosteroid sensitivity in macrophages from COPD patients
    Deepti Malhotra
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
    J Clin Invest 121:4289-302. 2011
    ..These effects of sulforaphane were glutathione dependent. We conclude that NRF2 is a novel drug target for reversing corticosteroid resistance in COPD and other corticosteroid-resistant inflammatory diseases...
  38. pmc Itraconazole inhibits angiogenesis and tumor growth in non-small cell lung cancer
    Blake T Aftab
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA
    Cancer Res 71:6764-72. 2011
    ..Based on these observations, we have initiated a randomized phase II study comparing the efficacy of standard cytotoxic therapy with or without daily oral itraconazole in patients with recurrent metastatic NSCLC...
  39. pmc Prevalence of the alternative lengthening of telomeres telomere maintenance mechanism in human cancer subtypes
    Christopher M Heaphy
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Am J Pathol 179:1608-15. 2011
    ..These findings may have therapeutic consequences, because ALT-positive cancers are predicted to be resistant to anti-telomerase therapies...
  40. pmc Nuclear factor-kappaB (NF-kappaB) mediates a protective response in cancer cells treated with inhibitors of fatty acid synthase
    Colleen R M Lemmon
    Department of Pathology and Johns Hopkins Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    J Biol Chem 286:31457-65. 2011
    ..These results suggest a link between PKC and NF-κB in protecting cancer cells from metabolic stress induced by inhibiting FAS...
  41. pmc Loss of Kelch-like ECH-associated protein 1 function in prostate cancer cells causes chemoresistance and radioresistance and promotes tumor growth
    Ping Zhang
    Division of Toxicology, Bloomberg School of Public Health, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA
    Mol Cancer Ther 9:336-46. 2010
    ..Thus, targeting the Nrf2 pathway in prostate cancer cells may provide a novel strategy to enhance chemotherapy and radiotherapy responsiveness and ameliorate the growth and tumorigenicity, leading to improved clinical outcomes...
  42. pmc High levels of the Mps1 checkpoint protein are protective of aneuploidy in breast cancer cells
    JEWEL DANIEL
    Department of Pathology and Johns Hopkins Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Proc Natl Acad Sci U S A 108:5384-9. 2011
    ..Thus, high levels of Mps1 in breast cancer cells likely contribute to these cells tolerating aneuploidy...
  43. pmc Progressive chromatin repression and promoter methylation of CTNNA1 associated with advanced myeloid malignancies
    Ying Ye
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Cancer Res 69:8482-90. 2009
    ....
  44. pmc Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis
    Rajesh 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...
  45. ncbi Hypermethylation of ASC/TMS1 is a sputum marker for late-stage lung cancer
    Emi 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...
  46. pmc Glutathione peroxidase 2, the major cigarette smoke-inducible isoform of GPX in lungs, is regulated by Nrf2
    Anju 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...
  47. ncbi LKB1/STK11 suppresses cyclooxygenase-2 induction and cellular invasion through PEA3 in lung cancer
    Sunil 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...
  48. ncbi Delayed diagnosis and elevated mortality in an urban population with HIV and lung cancer: implications for patient care
    Malcolm 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...
  49. pmc Nrf2 regulates an adaptive response protecting against oxidative damage following diquat-mediated formation of superoxide anion
    William 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...
  50. ncbi Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway
    Thomas 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...
  51. pmc Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer
    Anju 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...
  52. ncbi 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 cancer
    Guojun 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...
  53. ncbi Elevated incidence of lung cancer among HIV-infected individuals
    Eric 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...
  54. ncbi Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort
    Steven A Belinsky
    Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA
    Cancer Res 66:3338-44. 2006
    ....
  55. ncbi C-fos assessment as a marker of anti-epidermal growth factor receptor effect
    Antonio 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...
  56. ncbi Surgical resection of limited disease small cell lung cancer in the new era of platinum chemotherapy: Its time has come
    Malcolm 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...
  57. ncbi Silencing of genes by promoter hypermethylation: key event in rodent and human lung cancer
    Steven A Belinsky
    Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108, USA
    Carcinogenesis 26:1481-7. 2005
    ....
  58. ncbi DeltaNp63alpha up-regulates the Hsp70 gene in human cancer
    Guojun 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...
  59. pmc Enhanced autoantigen expression in regenerating muscle cells in idiopathic inflammatory myopathy
    Livia 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...
  60. ncbi Colorimetric approach to high-throughput mutation analysis
    Nicole 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...
  61. pmc Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice
    Tirumalai 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...
  62. pmc Somatic mutation and gain of copy number of PIK3CA in human breast cancer
    Guojun 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...
  63. ncbi 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...
  64. ncbi Nested multigene MSP/DHPLC method for analyzing promoter hypermethylation status in clinical samples
    Kevin K Divine
    Lovelace Respiratory Research Institute, Albuquerque, NM 87108 5127, USA
    Biotechniques 40:40, 42, 44 passim. 2006
  65. pmc Role of lung maintenance program in the heterogeneity of lung destruction in emphysema
    Rubin 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...
  66. pmc Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide
    Rajesh 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...
  67. pmc Ethanol sensitivity: a central role for CREB transcription regulation in the cerebellum
    George 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...
  68. doi Inhibiting fatty acid synthase for chemoprevention of chemically induced lung tumors
    Hajime 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...
  69. pmc Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model
    Jacob E Koskimaki
    Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
    BMC Cancer 10:29. 2010
    ....
  70. pmc Profiling the expression pattern of GPI transamidase complex subunits in human cancer
    Jatin 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...
  71. pmc Cancer stem cells and the ontogeny of lung cancer
    Craig 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...
  72. pmc 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 chemotherapy
    Anju 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...
  73. pmc Nrf2-dependent sulfiredoxin-1 expression protects against cigarette smoke-induced oxidative stress in lungs
    Anju 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...
  74. pmc DNA methylation analysis on a droplet-in-oil PCR array
    Yi 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...
  75. pmc A primary xenograft model of small-cell lung cancer reveals irreversible changes in gene expression imposed by culture in vitro
    Vincent 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...
  76. pmc MS-qFRET: a quantum dot-based method for analysis of DNA methylation
    Vasudev 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...
  77. ncbi Promoter hypermethylation of hallmark cancer genes in atypical adenomatous hyperplasia of the lung
    Julien 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
    ....
  78. doi DNA methylation markers and early recurrence in stage I lung cancer
    Malcolm 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...
  79. pmc Dual EGFR and mTOR targeting in squamous cell carcinoma models, and development of early markers of efficacy
    A 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...
  80. pmc Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma
    Craig 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...
  81. ncbi FDG-PET for pharmacodynamic assessment of the fatty acid synthase inhibitor C75 in an experimental model of lung cancer
    Jae 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...
  82. pmc Predicting gene promoter methylation in non-small-cell lung cancer by evaluating sputum and serum
    S 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...
  83. ncbi LOXL1 and LOXL4 are epigenetically silenced and can inhibit ras/extracellular signal-regulated kinase signaling pathway in human bladder cancer
    Guojun 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...
  84. pmc WNT10B functional dualism: beta-catenin/Tcf-dependent growth promotion or independent suppression with deregulated expression in cancer
    Hirohide 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...
  85. pmc 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 neutrophils
    Rajesh 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
    ....
  86. ncbi Selective inhibition of fatty acid synthase for lung cancer treatment
    Hajime 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...
  87. pmc Epigenetic alteration of Wnt pathway antagonists in progressive glandular neoplasia of the lung
    Julien D F Licchesi
    Cancer Biology Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
    Carcinogenesis 29:895-904. 2008
    ....