Electron spin resonance spectroscopy of serum albumin: a novel new test for cancer diagnosis and monitoring.
ABSTRACT Proteins released by tumor cells can bind to serum albumin, leading to structural and functional modifications. We used electron spin resonance (ESR) spectroscopy to measure these changes in serum albumin and evaluate their utility for the diagnosis and monitoring of cancer.
We used an ESR spectrometer and 16-doxyl stearic acid as spin probe to measure conformational changes in albumin in blood samples from a population of healthy donors and volunteers (n=349), patients with a wide variety of hematologic and nonhematologic malignancy (n=135), and patients with chronic diseases such as gastrointestinal and pulmonary disease, diabetes, and cirrhosis (n=91). We added differing amounts of 16-doxyl stearic acid spin probe in ethanol to 50 microL of serum from each patient to create 3 different aliquots that differed in concentration of spin probe and ethanol, then incubated the aliquots for 10 min at 37 degrees C with continuous shaking. We measured the ESR spectra of each aliquot in triplicate and used proprietary software (MedInnovation GmbH) to evaluate the ESR spectrum for differences between cancer patients and the other groups.
The diagnostic sensitivity and specificity of this test were 87.4% and 95.7%, respectively, for differentiating healthy individuals from cancer patients and 87.4%, and 85.7% for differentiating cancer patients from chronic disease patients. Serial evaluation of albumin conformation changes in several patients followed during the course of their disease showed excellent agreement between the magnitude of abnormality in the ESR spectrum of albumin and clinical and pathologic estimates of disease severity.
ESR spectroscopy of serum albumin is a sensitive and noninvasive technique that clearly demonstrates diagnostic utility in patients with cancer. This test also enables monitoring of the disease course through use of serial measurements.
Article: Alterations in the functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality.[show abstract] [hide abstract]
ABSTRACT: Albumin concentration is diminished in patients with liver failure. Albumin infusion improves survival of cirrhotic patients with spontaneous bacterial peritonitis, and it is hypothesized that this may be due in part to its detoxifying capabilities. The aim of this study was to perform detailed quantitative and qualitative assessment of albumin function in patients with cirrhosis. Healthy controls and patients with acute deterioration of cirrhosis requiring hospital admission (n = 34) were included. Albumin function was assessed using affinity of the fatty acid binding sites using a spin label (16 doxyl-stearate) titration and electron paramagnetic resonance spectroscopy and ischemia-modified albumin (IMA) was measured. Twenty-two patients developed acute-on-chronic liver failure. Twelve were treated with the Molecular Adsorbents Recirculating System (MARS) and 10 with standard medical therapy. For each parameter measured, the patients' albumin had reduced functional ability, which worsened with disease severity. Fifteen patients died, and IMA, expressed as an albumin ratio (IMAR), was significantly higher in nonsurvivors compared with survivors (P < 0.001; area under the receiver operating curve = 0.8). No change in the patients' albumin function was observed following MARS therapy. A significant negative correlation between IMAR and the fatty acid binding coefficients for sites 1 and 2 (P < 0.001 for both) was observed, indicating possible sites of association on the protein. CONCLUSION: The results of this study suggests marked dysfunction of albumin function in advanced cirrhosis and provide further evidence for damage to the circulating albumin, which is not reversed by MARS therapy. IMAR correlates with disease severity and may have prognostic use in acute-on-chronic liver failure.Hepatology 08/2009; 50(2):555-64. · 11.66 Impact Factor
Article: Analysis of albumin fatty acid binding capacity in patients with benign and malignant colorectal diseases using electron spin resonance (ESR) spectroscopy.[show abstract] [hide abstract]
ABSTRACT: In colorectal cancer (CRC), no biological marker is known that could serve both as a marker for detection and prognosis. Electron spin resonance (ESR) spectroscopy of spin-labeled fatty acid (FA) molecules binding to human serum albumin is a suitable method for the detection of conformational changes and alterations of transport function of albumin through changes in its FA binding capabilities. The aim of this study was to examine whether the FA binding to albumin is detectably and significantly altered in CRC patients when compared with patients having benign colorectal diseases. One hundred four patients operatively or endoscopically treated for CRC, sigmoid diverticulitis, or a colorectal adenoma were examined before procedure. Albumin was analyzed by ESR with spin-labeled FA. A determination ratio (DR) was calculated from the measured ESR spectra as ratios of the fraction of FA that is tightly bound vs. the fractions that are loosely interacting with albumin or are unbound. Patients with CRC showed significantly lower DR values (DR, -0.09 +/- 0.98 vs. 0.61 +/- 1.43) than patients with benign colorectal diseases, consistent with a change of conformation and transport function of albumin in CRC. Within the CRC group, with advanced tumor stage, the difference in DR values increased. ESR of FA binding to albumin thus seems to be suitable for detection of patients with CRC. Furthermore, a correlation with advanced tumor stage can be established. These results suggest that a further evaluation of the role of ESR in patients with all stages of CRC should take place. It should also be examined whether ESR might play a role in detecting CRC in a larger panel of patients.International Journal of Colorectal Disease 08/2009; 25(1):119-27. · 2.38 Impact Factor