The Roles of Neutrophil Elastase in Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01360931
Recruitment Status : Unknown
Verified May 2011 by The University of Hong Kong.
Recruitment status was:  Recruiting
First Posted : May 26, 2011
Last Update Posted : May 30, 2011
Information provided by:
The University of Hong Kong

Brief Summary:

Lung cancer is the leading cause of cancer death in Hong Kong. Lung adenocarcinomas is the most common type, accounting for 70% of lung cancer and the molecular target of epidermal growth factor receptor (EGFR) gene mutation at exons 18 - 21 is present in about 50% of lung adenocarcinomas. The v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-ras) mutations are commonly present in the other 50% that are EGFR wildtype. EGFR and K-ras mutations are found to be mutually exclusive in the same tumor. EGFR-tyrosine kinase inhibitor (TKI) can be used as treatment for EGFR mutated tumors while no specific targeted therapy can be recommended for EGFR wildtype tumors and these patients often receive chemoirradiation, which is toxic and clinical response is suboptimal. There is a need to find alternative molecular pathways/targets in EGFR wildtype lung adenocarcinomas.

Even with EGFR mutations, good clinical response to EGFR-TKI is achieved in about 70% of these patients. This would mean suboptimal targeting of the EGFR gene or the presence of alternative pathways mediating tumor progression and susceptibility to therapy. Exploration of molecular pathways in lung cancer may allow for discovery of new molecular targets for therapeutic development.

Neutrophil infiltration is frequently observed in lung cancer. Recognized similarities between neutrophils and cancer cells include (i) ability to circulate as single cells; (ii) target attachment via vascular system; (iii) target invasion. The major difference is that migrated neutrophils will undergo apoptosis while cancer cells can escape apoptosis.

This led to the postulation that neutrophils and cancer cells may share similar inflammatory cascades by secreting a similar panel of proteases, and one of these could be neutrophil elastase (NE). Animal studies demonstrated that NE from neutrophils moves into lung tumor cells and mediates lung tumor growth via degradation of Insulin receptor substrate-1 (IRS-1), leading to activation of intracellular phosphoinositide-3-kinase (PI3k) and the v-akt murine thymoma viral oncogene homolog 1 (Akt) signaling pathways and the intracellular tyrosine kinase of the platelet-derived growth factor receptor (PDGFR).

The aims of this study are to demonstrate NE activities and the subsequent signaling cascades activated in lung cancer cells, and to verify NE and its related pathway activation in clinical lung cancer specimen.

This study will conclude the roles of NE and the therapeutic potential of NE/IRS-1/PI3K/PDGFR pathways in EGFR wildtype lung adenocarinomas.

Condition or disease
Lung Cancer Chronic Obstructive Pulmonary Diseases

  Show Detailed Description

Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Case Control
Time Perspective: Prospective
Official Title: The Roles of Neutrophil Elastase in Lung Cancer
Study Start Date : January 2011
Estimated Primary Completion Date : June 2013
Estimated Study Completion Date : June 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Lung Cancer group
Subject with histological confirmation of lung cancer
Control group
Subjects with no diagnosis of lung cancer

Primary Outcome Measures :
  1. The protein expression levels of biomarkers related to neutrophil elastase [ Time Frame: Jan 2011 - June 2013 (30 months) ]
    The protein expression levels of phosphorylated Akt (pAkt), IRS-1, IRS-2, PDGF, mitogen activated kinase(MAPK) as well as phosphorylated EGFR (pEGFR) and TNF-α and β-actin will be assessed semi-quantitatively on electrophoretic blotting intensity.

Secondary Outcome Measures :
  1. Immunohistochemical staining for NE, IRS-1 and EGFR [ Time Frame: Jan 2011 - June 2013 (30 months) ]
    Fields captured from four different fields from each stained (NE, IRS-1 and EGFR) lung tumor slides will be scored as 0 = absent, 1 = weak, 2 = strong and present. In NE positive cases, concordant and discordant cases of IRS-1 vs PDGF or EGFR staining will be observed. Likelihood ratio tests determining if proportion of discordant cases was significantly larger than half the cases will be presented

Biospecimen Retention:   Samples With DNA
Small bronchial biopsy alongside with the corresponding Bronchoalveolar lavage and bronchial aspirate will be collected in the same one bronchoscopy session

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Subjects undergoing diagnostic bronchoscopy

Inclusion Criteria:

  • All subjects undergoing clinical diagnostic or therapeutic procedures, including:

    1. Fibreoptic bronchoscopy or pleuroscopy
    2. Diagnostic or Therapeutic pleurocentesis AND who are mentally fit to give informed consent for donation of clinical specimens

Exclusion Criteria:

  • Patients who cannot give written informed consent or refuse to give such consent for participation in this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01360931

Contact: David CL LAM, MBBS, FRCP(Edin), FCCP, FACP +852 2255 5814

Hong Kong
Queen Mary Hospital Recruiting
Hong Kong, Hong Kong, 0
Contact: David CL Lam, MBBS, FRCP(Edin), FCCP, FACP    +852 2255 5814   
Sponsors and Collaborators
The University of Hong Kong
Principal Investigator: David CL LAM, MBBS, FRCP(Edin), FCCP, FACP The University of Hong Kong

Responsible Party: Dr Lam Chi Leung David, University of Hong Kong Identifier: NCT01360931     History of Changes
Other Study ID Numbers: HKU_UW_11_085
First Posted: May 26, 2011    Key Record Dates
Last Update Posted: May 30, 2011
Last Verified: May 2011

Keywords provided by The University of Hong Kong:
Lung cancer
Chronic obstructive pulmonary disease

Additional relevant MeSH terms:
Lung Neoplasms
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Respiratory Tract Diseases