Transcript fatty liver
Biomarkers Andrew McNaught BME What is a biomarker? • Gives us the ability to analyze organ function, diagnose diseases in a non-invasive way. • Biomarkers can be any molecule (organic or inorganic) that acts at the test subject while the patient is the host to a biological process. • Biomarkers can be tested from bodily fluids (blood, urine) or from tissues. Importance • Biomarkers give scientists and doctors the ability to ‘work backwards’ and asses organ function. • Cancer biomarkers can identify genetic variations or mutations as well as changes in gene or protein expression that can be linked to a disease state or a response to a medical intervention Definition • A measurement reflecting a biological system and an environmental agent that can be chemical, physical or biological • biomarker of exposure: an exogenous substance or its metabolite or the product of an interaction between a xenobiotic agent and some target molecule or cell that is measured in a compartment within an organism; • **biomarker of effect: a measurable biochemical, physiological, behavioural or other alteration within an organism that, depending upon the magnitude, can be recognized as associated with an established or possible health impairment or disease; ** • biomarker of susceptibility - an indicator of an inherent or acquired ability of an organism to respond to the challenge of exposure to a specific xenobiotic substance. http://www.inchem.org/documents/ehc/ehc/ehc155.htm#SectionNumber:1.1 Uses Biomarkers can be used to: • confirm diagnosis of acute or chronic disease • assess the effectiveness of treatment • evaluate the prognosis of individual cases. Biomarkers in Cancer Detection • The Early Detection Research Network has put growing focus on discovering and validating biomarkers in their use to diagnose cancer in its early stages. • Many patients are diagnosed in late stages of cancer and it may be too late. • Could be a huge breakthrough for science if this non-invasive method can test for cancer. Brain Cancer • National Cancer Institute study on finding improved therapies for adult glioma. (most deadly brain tumor) • This study's purpose is to find molecular features of tumors, immune factors and genetic polymorphisms as biomarkers. • Purpose– Specific therapies are more beneficial to patients that display specific genetic, immunological and tumor characteristics. – University of California San Francisco – Funded amount – $186,000 Serum test • Serum biomarkers are produced by body organs or tumors and they measure the antigens on cells’ surfaces. • When detected in high amounts in the blood, they can be suggestive of tumor activity. • Serum biomarkers are non-specific because organs they can be produced by organ systems as well. PSA • PSA is produced by normal prostate function in small amounts but a large amount is indicative of prostate cancer. • This is one of the most widely used biomarkers in use today. Ovarian cancer • Cancer agent 125 can be a biomarker of ovarian cancer or indicator. • It has low sensitivity and specificity. • Levels of this agent can be high in patients with pancreatic, kidney or liver disease. Carinoembryonic antigen (CEA) • Another biomarker that is elevated in people with breast, lung and pancreatic cancer. • But, it can be elevated by other factors than cancer such as smoking. • After patients have surgery for colon cancer, CEA is an effective way to evaluate how successful surgery was Biomarkers for Parkinsons Disease • Parkinson's disease occurs when a persons brain does not naturally produce enough dopamine to have healthy brain function. – The diminishing amount of dopamine neurotransmission is a biochemical marker for Parkinsons – NIH did a study to show the relationship between purine and dopamine in cerebrospinal fluid. – The ratio between (xanthine/homovanillic acid) should be 13.1 +- 5.5 – In patients with parkinsons, the ratio was raised to 17.4 at the initial check and 19.7 at a second check 24 months later. – The ratio raises as the disease severity raises. • These biomarkers used to detect this ratio can be very beneficial. – Earlier prognosis – Earlier treatment – Treatment depending on how severe it is – Track the disease with more precision – Test the effectiveness of new treatment Predicting Liver Cancer • • • • • • • • • • • • • • • • • • • • • • • • • • • • • Some Proteins which might be used as Liver Biomarkers Lectin-reactive alpha fetoprotein (AFP-L3) Des-gamma-carboxy-prothrombin (DCP) ER6Q Vimentin actin alpha 1 skeletal muscle protein hMFAP 4 tropomyosin PTGES 2 amyloid P component transgelin calponin 1 homo sapiens p20 protein 17 kDa myosin light chain H chain H Igg B12 prolyl 4-hydroxylase beta subunit methylenetetrahydrofolate dehydrogenase 1 PRO2619 aldehyde dehydrogenase 1 fibrinogen alpha chain preproprotein fructose-bisphosphate aldolase B argininosuccinate synthetase Eefla2 AT P 5 Al alpha-2 actin regucalcin serum albumin mitochondrial malate dehydrogenase mitochondrial acetoacetyl-CoA thiolase Liver biomarkers • Vitamin D-binding protein and liver fatty acid binding protein have been identified as biomarkers for liver toxicity. • Using these biomarkers would allow patients to avoid a liver biopsy and assessing 4 common chronic liver diseases. – – – – Hepatitis C Hepatitis B Non alcoholic fatty liver diseases and Alcoholic fatty liver diseases NIH • New biomarker for kidney toxicology that could lead to better and faster diagnosis of kidney injury. • Found nine new gene variants, also known as single nucleotide polymorphisms, associated with an increased risk of myocardial infarction or heart attack • Expression of DNA Repair Genes is Sensitive Marker for Oxidative Stress • Gene-Environment Interaction: Effect of Polymorphisms on Biomarkers in Coal Miners Future • In the future: Biomarkers will be used as a significant prognosis tool to determine if a patient has a disease. Also I see a ‘one test’ suits all- one blood test will determine if someone has any number of diseases. Work cited • http://stm.sciencemag.org/content/3/79/79ps14.abstr act • http://www.liver-products.com/liver-diagnostic/liverbiomarker.html • http://www.niehs.nih.gov/research/supported/sep/20 03/polymorf/ • http://omicsonline.org/jmbdhome.php • http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed &term=%22Cancer%20Epidemiol%20Biomarkers%20Pr ev%20%22[Journal] NIH. "Cancer Biomarkers." Biomarkers (2009): 1-5. Print