Clinical Research Directory

Cytochrome P450 Epoxygenase Pathway Regulation of Macrophage Function

Background: Respiratory diseases affect more than 1 billion people worldwide. They are a growing public health concern. The lungs are constantly exposed to environmental factors such as dust, fumes, microbes, and pollutants. But much is still not known about how these pollutants lead to respiratory illnesses. Researchers want to collect samples from lungs and blood to see how genetics and environmental pollutants affect cellular responses or functioning. Objectives: To study how cytochrome P450 epoxygenase pathway enzymes affect macrophage function in the lungs and inflammatory responses. Eligibility: Adults ages 18 65 who can have a bronchoscopy. Design: All study visits will take place at the NIEHS Clinical Research Unit in Research Triangle Park, NC. At study visit 1, participants will be screened with medical history and physical exam. They will have blood and urine tests. They will take tests that measure their lung function. They will answer questionnaires. Before the visit, they will be given a list of medicines they cannot take. They also must not have caffeine on the day of their visit. The visit will last about 3 hours. At study visit 2, participants will give blood samples. They will undergo bronchoscopy. For this, they will get an intravenous line in a vein to get sedatives. Their airways will be numbed. Cells will be collected from their lungs. They will fast for 8 hours before the visit. They must have someone else drive them home from the visit. The visit will last about 3-4 hours. Participants will get a follow-up phone call about 1 day after study visit 2.

Study of the Impact of VEGF Polymorphism on the Development of Renal Carcinoma in Renal Transplant Patients

Renal transplant patients have on average 3-5 times more risk of developing cancer than the general population. This rate can be increased up to 10 to 15 times in some type of cancer like kidney cancer. Among the identified risk factors, immunosuppressants and, in particular, calcineurin inhibitors (ciclosporin and tacrolimus) play a major role in increasing cancers apart from their depressant effects on the immune system. Calcineurin inhibitors (CCN) are the basis of immunosuppressive therapy in renal transplantation. Several mechanisms have been implicated to explain their pro-oncogenic properties. One related to an increase in VEGF expression seems particularly interesting in the study of renal cell carcinoma in the transplanted patient. Indeed, the physiopathology of kidney cancer has clearly been associated with an increase in the production of VEGF. Furthermore, some polymorphisms of the gene encoding VEGF have already been associated with the survival of patients with renal carcinoma and the circulating level of VEGF in the general population. The search for an association between the polymorphisms of the VEGF gene and renal carcinoma in renal transplant patients could thus identify patients whose risk of renal cell carcinoma (cRCC) post-transplantation is increased. If the involvement of certain polymorphisms in the development of cRCC was confirmed in this population, their research before the introduction of the immunosuppressive treatment would make it possible to direct the choice of treatment towards molecules without pro-oncogenic property in the Patients such as mTOR protein inhibitors (sirolimus, everolimus). This research project is therefore in line with the desire to move towards a more "personalized" medicine that could be beneficial for the patient.