Clinical Trial: Detection of Genetic Markers of Lung Cancer

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Detection of Genetic Markers of Lung Cancer Initiation and Progression

Brief Summary: The purpose of the intended genetic research is to improve the diagnosis and prognosis of lung cancer patients as well as to identify genetic risk factors that may predict lung cancer risk.

Detailed Summary:

The multistage theory of carcinogenesis includes the development of multiple activating genetic changes due to exposure to carcinogens, either primarily, or superimposed upon pre-existing mutations in the genome. These changes result in activation of protooncogenes, lack of expression of tumor suppressor genes, or combinations of the above, the sum of which results in malignant transformation. Detailed analyses of chromosomal lesions in bronchogenic lung cancer reveal several recurring abnormalities, including deletions, duplications or polysomy of chromosomes 1, 3, 7 and 20. Aberrations in the short arm of chromosome 3, in particular, are found in many small cell and non-small cell lung cancers, and polysomy 7 is a frequent finding in non-small cell lung cancers. Many of these abnormalities have no identified significance, however the application of current and evolving techniques of molecular biology have revealed specific genomic changes leading to malignant phenotypes in several tumors, for example, the application of polymerase chain reaction amplification techniques has revealed a striking incidence of mutations in the h- and k-ras protooncogenes have been discovered, associated with over-expression of growth factors or receptors, for example epidermal growth factor receptor.

As all epithelial cells are exposed to similar environmental conditions, it seems likely that many cells undergo mutagenesis simultaneously. Clinically, this is frequently apparent, as 10-20% of patients with lung cancer have another epithelial cancer arise, either concurrently, or at some later time in their course. The predisposition for development of second malignancies also affects other epithelial surfaces, for example, there is a strong tendency for patients with cancer of the head and neck to develop a second malignancy (bronchogenic lung cancer) in the aerodigestive tract. Despite decr
Sponsor: University of Pittsburgh

Current Primary Outcome:

  • To detect genetic markers of lung cancer initiation and progression in tissue obtained during bronchoscopy. [ Time Frame: No specific time frame ]
  • To identify genetic risk factors that may predict lung cancer risk. [ Time Frame: No specific time frame ]


Original Primary Outcome:

  • To detect genetic markers of lung cancer initiation and progression in tissue obtained during bronchoscopy.
  • To identify genetic risk factors that may predict lung cancer risk.


Current Secondary Outcome:

  • To obtain/maintain in cell culture "normal" bronchial epithelial cells(NBECs) and tumors from subjects undergoing resection for cure of bronchogenic non-small cell lung cancer(NSCLC). [ Time Frame: No specific time frame ]
  • To harvest NBEC and lung tumors for evaluation of genetic abnormalities; this will be obtained at the time of bronchoscopy and lung resection. [ Time Frame: No specific time frame ]
  • To perform polymerase chain reaction(PCR) amplification of DNA harvested from NBECs,tumors,adjacent & normal lung, & white blood cells as a control for evaluation for mutations in the K-ras & p53 protooncogenes,& other candidate lung cancer genes. [ Time Frame: No specific time frame ]
  • To look for mutations and alterations of expression of Fas, Fas ligand, and FADD, three molecules which mediate programmed cell death and have recently been shown to be expressed on multiple tumor cells including lung cancer. [ Time Frame: No specific time frame ]
  • To analyze cytokines present in lavage fluid, tumors, and lung tissues; this will be obtained at the time of bronchoscopy. [ Time Frame: No specific time frame ]
  • To produce T cell cultures from cells present in tumor-draining lymph nodes. [ Time Frame: No specific time frame ]
  • To use these cultures to identify carcinoembryonic antigen(CEA), cytokeratin-19, hepatocyte growth factor, gastrin-releasing peptide(GRP)receptor, and the neuromedin-B(NMB) receptor as potential for evidence of micrometastases. [ Time Frame: No specific time frame ]
  • To detect metastatic tumor in bone marrow extracted from discarded rib resection material which is sometimes removed for access during resection of the lung. [ Time Frame: No specific time frame ]


Original Secondary Outcome:

  • To obtain/maintain in cell culture "normal" bronchial epithelial cells(NBECs) and tumors from subjects undergoing resection for cure of bronchogenic non-small cell lung cancer(NSCLC).
  • To harvest NBEC and lung tumors for evaluation of genetic abnormalities; this will be obtained at the time of bronchoscopy and lung resection.
  • To perform polymerase chain reaction(PCR) amplification of DNA harvested from NBECs,tumors,adjacent & normal lung, & white blood cells as a control for evaluation for mutations in the K-ras & p53 protooncogenes,& other candidate lung cancer genes.
  • To look for mutations and alterations of expression of Fas, Fas ligand, and FADD, three molecules which mediate programmed cell death and have recently been shown to be expressed on multiple tumor cells including lung cancer.
  • To analyze cytokines present in lavage fluid, tumors, and lung tissues; this will be obtained at the time of bronchoscopy.
  • To produce T cell cultures from cells present in tumor-draining lymph nodes.
  • To use these cultures to identify carcinoembryonic antigen(CEA), cytokeratin-19, hepatocyte growth factor, gastrin-releasing peptide(GRP)receptor, and the neuromedin-B(NMB) receptor as potential for evidence of micrometastases.
  • To detect metastatic tumor in bone marrow extracted from discarded rib resection material which is sometimes removed for access during resection of the lung.


Information By: University of Pittsburgh

Dates:
Date Received: January 18, 2006
Date Started: June 1996
Date Completion: December 2050
Last Updated: December 1, 2015
Last Verified: December 2015