Recent Patents on Biomarkers (Discontinued) - Volume 5, Issue 1, 2015

Cancer Stem Cells (CSC) comprise a concept proposed in the 1990s in hematopoietic cancers. These cells were considered, by similitude to normal stem cells, to constitute a small pool of self-renewing cells able to maintain a tumor. Due to their quiescence, CSC would be able to avoid chemotherapeutics targeting fast proliferation rates, or radiotherapy, thus being responsible for tumour relapse. Since CSCs have also been implicated in invasion and metastasis and epithelial to mesenchymal transition (EMT) was proposed as a determinant of malignancy in epithelial cancers, the relationship between EMT and CSC is an important issue, which has been increasingly addressed in recent patents on CSC biology. A thorough search for a more accurate identification of these cells, as well as more effective drug search yielded a number of interesting research patents during the last 5 years, several of which are to be detailed in the present review.

The genetic and epigenetic events appear to control the initiation and progression of cancer. The tenuous link between the environmental, lifestyle factors and genetic influences is being actively researched across the world. Epigenetic changes can control gene expression independent of mutations. The current advances in the cancer therapy are targeting on epigenetic mechanisms such as tumor- specificity of genes, DNA methylation, histone modifications, and the role of mi RNAs. The identification of cancer stem cells is a recent promising area in oncological research for a better understanding of tumor genesis. The lack of markers for the identification of cancer stem cells and their therapeutic targets currently has hindered the immediate applications in the clinical and management domain. The recent patents and their application are discussed.

Preeclampsia is a multisystem disorder, pathophysiology of which is still not clear. It is one of the leading causes of maternal and fetal morbidity and mortality. Epigenetic programing is altered during fetal life and postnatal period and after birth, this sceniaro is changed to metabolic disorders of metabolic syndrome complex and this may contribute to future risk of hypertension, DM2, and cardiovascular disease. During (normal and abnormal) gestations, complex physiological changes occur in maternal blood. For studying next generation diagnostic biomarkers for maternal-fetal interface, it is essential to explore the protein changes in maternal serum during healthy gestation. Umbilical cord blood (UCB) is in contact with all the fetal tissues and can reflect both normal physiological as well as pathological states of the fetus. UCB can be compared with adult blood and the diagnostic potential of UCB still remains to be tapped. UCB will be a potential diagnostic medium in future in assessing infant health. Also, UCB can aid in detection and identification of candidate biomarkers for various disease pathways and it can be of help in assessing the existing or future adverse effects. Patents are available for biomarkers in preeclampsia and fewer patents are reported in UCB. Future studies will further uncover the diagnostic value of the umbilical cord blood in human physiology and pathology.

Viruses lack the synthetic machinery, so they hijack the synthetic machinery of host cells to produce proteins; and in this process trigger cancer. Since current therapies are ineffective in dealing with virally induced cancers, a future goal could be to develop vaccines against these tumor viruses. Indeed, a recent patent has demonstrated the utility of host p16 peptide fragments to vaccinate against various HPV induced tumors like penile, anal, cervical, vulvar, vaginal and head and neck cancers. Another patent describes the use of host cell peptide fragments (Rb, Mupp, DLG1 and AP) expressed on surface of virally infected host for vaccinating against the various HPV induced cancers including head and neck cancers. A vaccine has been prepared from peptide antigens derived from HPV L2, to vaccinate against diverse strains of HPV. An HPV assay (RNAscope®) has been recently developed utilizing E6/E7 mRNA to detect high-risk HPV subtypes in head and neck cancer. Another patent deals with the use of two RNAases (ranpirnase and 805 variant of ranpirnase) against HPV infections. We have undertaken this review to summarize and delineate the role of viruses in carcinogenesis in the oral region.

Polycystic kidney disease (PKD) is characterized by the formation and expansion of fluidfilled cysts within the kidneys, painful renal enlargement and declining kidney function. Often, PKD manifests in other organs, including the liver and pancreas. In addition to cyst formation, interstitial collagen deposition is sometimes observed in both the kidney and the liver. While a diagnosis of PKD may be made using ultrasonography coupled with family history, monitoring disease progression is challenging as imaging techniques remain inadequate to track an increasing cystic index over time. Using the PCK rat model of PKD, we have identified a minimally invasive biomarker cluster with high correlative value for renal cystic index. This finding is important in that disease prognosis, patient compliance, interventional decisions and outcomes stand to be improved by regular disease monitoring. Identification of biomarkers of PKD also can better stratify transplant waitlists for kidneys or livers. Furthermore, rather than reliance upon a single biomarker, clinical outcomes may be better predicted from a cluster of disease-relevant biomarkers that correlates strongly with outcome. Clinical trials would also benefit from such biomarkers given the reluctance to invest in trials wherein clinical endpoints could be years away. Moreover, relevant patents are also discussed related to the use of renal biomarkers as diagnostics.

We examined the prognostic performance of measurements of cTnT concentrations at admission compared to discharge, in predicting major cardiovascular events during hospital admission and at six months follow-up. Methods and Results: The study population comprised 1351 patients with AMI and a mean age of 57.5 + 11.4 years, of whom 66% were males. Cardiac TnT was measured on admission, 24 hours, and at discharge using the Elecsys 2010 [Roche Diagnostics]. No significant difference was found in patients who were cTnT negative on admission [n = 345 (26%)] compared to the cTnT positive group [n = 1006 (74%)], with respect to baseline characteristics, infarct pattern, biochemical data, and major cardiac events. In 475 patients [35%], serum cTnT levels were found to be higher on discharge from the CCU compared to admission/24 hour levels. A significantly greater proportion of patients had hypertension [63% vs. 50%, p < 0.001], higher systolic blood pressures [133, IQR 115 -154 vs. 127, IQR 111 -147, p < 0.001], history of previous AMI [17% vs. 9%, p < 0.001], and previous angina [17% vs. 9%, p = 0.001] if the discharge cTnT levels exceeded the admission/24 hour levels. A total of 120 deaths occurred during the study period with a significantly greater number of deaths recorded in patients whose discharge cTnT levels were higher than the admission/24 hour values [54(11%) vs. 66 (8%); p = 0.02, respectively]. Multivariable analysis using logistic regression showed that cardiogenic shock [OR 5.92 {95% CI 2.86 - 12.28}; p < 0.001], cardiac failure [ OR 4.80 {95% CI 2.61 - 8.82}; p < 0.001], cerebrovascular accident [ OR 3.95 {95% CI 1.48 - 10.58}; p = 0.01], complete heart block [ OR 3.50 { 95% CI 1.22 - 10.09}; p = 0.02], increasing age [ OR 1.04 {95% CI 1.02 - 1.01}; p < 0.001], and a greater discharge cTnT value [ OR 1.61 (95%CI 1.01 - 2.56); p = 0.04] conferred a significantly higher odds of mortality. Conclusions: This study shows that, in addition to cardiogenic shock, cardiac failure, cerebrovascular accident, complete heart block, and increasing age, higher cTnT level at discharge is an important independent predictor of mortality in patients with AMI, and could further improve the prognostic accuracy of admission values of cTnT, based on relevant patents.