The Roles of Neutrophil Elastase in Lung Cancer

NCT01360931 | Unknown

• 1 other identifier: HKU_UW_11_085
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Cancer; Chronic Obstructive Pulmonary Diseases

Keywords

Lung cancer; Chronic obstructive pulmonary disease

Outcome Measures

Primary Outcomes (1)

• The protein expression levels of biomarkers related to neutrophil elastase

  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.

  Jan 2011 - June 2013 (30 months)

Secondary Outcomes (1)

• Immunohistochemical staining for NE, IRS-1 and EGFR

  Jan 2011 - June 2013 (30 months)

Study Arms (2)

Lung Cancer group

Subject with histological confirmation of lung cancer

Control group

Subjects with no diagnosis of lung cancer

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects undergoing diagnostic bronchoscopy

You may qualify if:

• All subjects undergoing clinical diagnostic or therapeutic procedures, including:
• Fibreoptic bronchoscopy or pleuroscopy
• Diagnostic or Therapeutic pleurocentesis AND who are mentally fit to give informed consent for donation of clinical specimens

You may not qualify if:

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

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Queen Mary Hospital

Hong Kong, Hong Kong, 0, Hong Kong

RECRUITING

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

MeSH Terms

Conditions

Lung Neoplasms; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• David CL LAM, MBBS, FRCP(Edin), FCCP, FACP

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David CL LAM, MBBS, FRCP(Edin), FCCP, FACP

CONTACT

+852 2255 5814; dcllam@hku.hk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 19, 2011
• First Posted: May 26, 2011
• Study Start: January 1, 2011
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: May 30, 2011

Record last verified: 2011-05

Locations

HK (1)