For the most lethal cancers, such as pancreatic adenocarcinoma, the dismal prognosis reflects the inability to detect tumors at early stages, when surgical extirpation and/or chemotherapy can successfully eradicate all malignant cells. Even tumors found at "early" stages have generally spread either regionally or in a distant fashion, and thus recur after removal. Chemotherapy is most effective in a "minimal residual disease"; the lower the volume of disease, the more likely the success. Thus, for such cancers, there is a pressing need for molecular biomarkers that can be detected in body fluids, including blood plasma, other relevant fluids such as saliva, pancreatic juice, bile, cerebrospinal fluid, etc. Such biomarkers promise to enable early diagnosis of tumors at stages when the cancer may be: 1) successfully resected at surgery; 2) sensitive to chemotherapy and/or radiation, 3) would also allow more accurate monitoring of tumor recurrence. Specifically for pancreatic adenocarcinoma we are actively collecting plasma and pancreatic juice from a cohort of patients with pancreatic cancer and control subjects. In addition, we are collecting fluid and blood from patients with premalignant (cystic) lesions of the pancreas. We are profiling the levels of all human microRNAs in these fluids. Preliminary results are promising towards the identification of panels of useful biomarkers. (Collaboration with Dr. Jennifer Tseng, Department of Surgery)
Biomarkers for the early stages of certain neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS), would be of great value for earlier and more accurate diagnosis, as well as for monitoring the efficacy of experimental therapies. The expression of microRNAs in brain is abundant and complex, and changes in microRNA expression in brain tissue has been associated with neurologic and neurodegenerative disease. Much less is known about how microRNA profiles in circulation (plasma and CSF) may provide indicators of neural pathology. We are seeking to identify biomarkers for the status of neurodegenerative disease progression in human patient plasma and CSF samples. We have initial indications that the levels of specific subsets of microRNAs appear to be statistically different between ALS cases and controls. Ongoing efforts are to expand these microRNA profiling efforts to include much larger numbers of subjects and also longitudinal studies of ALS patients over the course of disease progression. (Collaboration with Dr. Robert Brown, Department of Neurology)
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