Recent Patents on Biomarkers - Volume 5, Issue 2, 2015

Preeclampsia is a major cause of maternal and fetal morbidity and mortality and its prediction, diagnosis and management still remain to be challenging. However, recent technological advances in the understanding of its pathophysiology have identified many biomarkers to aid prediction of women at risk of developing preeclampsia (PE). Many etiological factors for PE have been evaluated as biochemical markers in the maternal blood for the prediction and diagnosis of PE such as markers for renal dysfunction, hemolysis, metabolic status, inflammatory markers oxidative stress, placenta-derived factors, and endothelial dysfunction. Pregnancy can be regarded a state of oxidative stress as a result of increased placental metabolic activity and antioxidant defenses. Evaluation of markers of oxidative stress and their molecular pathways may be useful in finding the possible solutions for this disease entity. This article aims to review various oxidative stress biomarkers in preeclampsia and gives an account of cellular responses to oxidative stress at transcript, protein and metabolite level and summarizes the available patents with special emphasis on redox genomics, metabolomics and proteomics applications in maternal-fetal medicine.

Diagnosis of glomerular diseases is based on renal biopsy, an invasive method that offers information about the type and severity of renal damage and predicts renal function outcome. Types of glomerulonephrities differ in etiology, pathogenesis, type of cell involvement, immune reactions, and subsequently in the disease outcome. During evolvement of the disease cytokines, chemokines, growth factors are produced by native of infiltrating kidney cells and excreted in the urine. These molecules may serve as biomarkers and may provide useful information in diagnosis, prognosis and response to treatment. An ideal biomarker should be easily collected and measured and have high sensitivity and specificity. Particular cytokines may have central roles in glomerular diseases. IL-6, MCP-1, IL-1β and EGF urinary excretion can predict renal function outcome in IgA nephropathy. Metaloproteinases, A1 antitrypsin, Tamm-Horsfall protein, MCP-1 and other molecules have been used in the discrimination between focal segmental sclerosis and minimal change disease, in predicting relapse of FSGS after transplantation and response to treatment. Recent patents have established measurement of urinary cytokines in follow up and treatment of renal diseases.

The kidneys control homeostasis by regulating plasma volume and hormone secretion and acid-base balance. These are delicate organs and, sometimes are weakened due to many kidney diseases and use of some toxins and excess drugs. Acute kidney injury (AKI) is an important cause of renal failure. The serum creatinine and blood urea are classical kidney biomarkers. New kidney acute injury biomarkers i.e. acute kidney injury (AKI) biomarkers are early indicators of kidney diseases, which may be used to save the lives of the patients. Therefore, analysis of AKI is essential and urgent issue in urology. The analysis of AKI biomarkers is reviewed. The article describes the-state-of-the art of the analyses of AKI biomarkers in urine, blood and breath samples. The attempts are made to discuss the sample handlings and analyses techniques. The analyses techniques discussed are chromatography, ELISA, NMR, nano technology and others. Some recent patents (2014-2015) have also been reviewed. Most of the patents available used immune assays detections of AKI biomarkers; except few where chromatography was used. Besides, the efforts have also been made to discuss correlation among AKIs biomarkers, serum creatinine and blood urea nitrogen. Additionally, the current and future developments are also highlighted in AKI biomarkers analyses.

Metastasis accounts for 90% of the mortality associated with breast cancer. Upregulated expression of members of the lysyl oxidase (LOX) family of secreted copper amine oxidases catalyzes the crosslinking of collagens and elastin in the extracellular matrix. LOXs are linked to the development and metastatic progression of breast cancers. Accordingly, aberrant expression of LOX-like 2 (LOXL2) is observed in poorly differentiated, high-grade tumors and is predictive of diseases recurrence, and for decreased overall patient survival. Therefore, LOXL2 expression may serve as a biomarker for breast cancer. Mechanistically, hydrogen peroxide is produced as a byproduct of LOXL2 when using an appropriate substrate, lysine. We exploited this chemistry to generate a revolutionary gold-based electrochemical biosensor capable of accurately detecting nanomolar quantities of LOXL2 in mouse blood, and in human blood samples. Two different sources of the blood samples obtained from breast cancer patients were used in this study indicating the applicability of detecting LOXL2 in breast cancers patients. Limited numbers of urine specimens from breast cancer patients were also tested. Collectively, all of these tests show the promise and potential of this biosensor for detecting LOXL2 as a surrogate biomarker of breast cancer. This work is described in patent number WO2014052962 (2014).

Given the diabesity and metabolic syndrome epidemics, fatty liver disease is reaching epidemic proportions. Relatively indolent, this disease is often asymptomatic and the patient is often made aware of its presence only during a routine physical exam. Nevertheless, fatty livers are more susceptible to insult compared to their non-fatty counterparts and persons with fatty livers are at increased risk for morbidity and mortality following consumption of commonly used substances such as alcohol (EtOH) and acetaminophen (APAP). We have developed a rat model of natural diet-induced fatty liver disease and evaluated the effects of two commonly used substances viz. EtOH and APAP in this phenotype. High fat diet (HFD) fed animals exhibited steatosis, liver inflammation and liver fibrosis with an increase in serum aspartate aminotransferase. Bolus administration of EtOH, which was without effect on the livers from standard diet fed animals, had a profound and adverse impact on the HFD fatty liver. Similarly, APAP administration which was without effect on liver function tests in control animals, also provoked an increase in liver enzymes in HFD animals. Treatment with the poly(ADP-ribose) polymerase-1 inhibitor (PARP-1), veliparib, reduced the increase in liver function tests secondary to EtOH and APAP. This model forms the framework for identification of fatty liver disease biomarkers given that this disease is relatively asymptomatic but fraught with risk for acute injury. This model also forms the framework for evaluation of novel drugs for acute injury in fatty livers especially given that current strategies for management of acute liver failure in non-fatty livers are inadequate. Also, relevant patents related to the use of liver biomarkers as diagnostic are discussed.

The aim of this study was to evaluate the diagnostic significance of the bone resorption marker β-Crosslaps for the detection of bone metastases in renal cell cancer patients. β-Crosslaps concentrations were measured in serum samples from 87 renal cell cancer patients. Of these, 35 men, 19 women, and 17 boys showed no bone involvement. 15 men and two women suffered from bone metastases. When comparing women with and without bone metastases by using an optimal cut off value (11.25ng/ml), the sensitivity of β-Crosslaps for detecting bone metastases was 100% and the specificity was 57.89%. Using an optimal cut off value (81.2ng/ml) in men, the sensitivity and specificity for detecting bone metastases was 93.33% and 91.42%, respectively. There was a significant increase (p < 0.01) in β-Crosslaps in patients with renal cell cancer as compared to healthy subjects. This difference existed even in the patients without bone metastases. Furthermore, the β-Crosslaps values increased with the tumor-node-metastases (TNM) system (T-value). β-Crosslaps were suitable as a diagnostic tool for the detection of bone metastases in men with renal cell cancer. In addition, the study showed a significant increase of the β-Crosslaps concentration in renal cell cancer patients without bone metastases, accompanied by an increase as the TNM stage (T-value) increased. β-Crosslaps could be useful as a tumor marker for renal cell cancer. Additionally a review of recent patents on tumor markers is provided.