Current Biomarkers - Volume 6, Issue 2, 2016

Background: Acute kidney injury is a common clinical problem that is associated with substantially increased morbidity and mortality. Biomarkers of AKI can be identified from urine, blood or other samples to aide in early detection, prognostication, and to guide treatment decisions. In addition, biomarkers may represent potential treatment targets for targeted therapy of this syndrome. This is especially important since thus far, only supportive treatment strategies, for example renal replacement therapies, were available for management. Objective: In this update of a previous review article from 2012, a comprehensive but succinct overview over patents issued following the initial article on AKI biomarkers is presented. Methods: The patent review was performed using the United States Patent and Trademark office (uspto.gov) and Google patents. An accompanying literature review was performed using National Library of Medicine's PubMed-MEDLINE database. Due to the sheer number of full patents, with a total of 54 reviewed in this article, and in contrast to the previous article, only full patents were included and patent applications were omitted. Results/Conclusion: The patents in review are summarized in two comprehensive tables, one focused on diagnosis and the other on therapy. A brief assessment of potential future directions and conclusion is formulated at the end of the review.

Background: In many cancers, predictive factors are important for recognition of high-risk patients and amongst individualizing treatment. The understanding of these mechanisms might provide novel and useful approaches for preventing, diagnosing and treating different cancers. Objective: The main objective of this review is to extend the current knowledge on the various tumor biomarkers targeting prognosis and therapies of human cancers. Methods: The present review is based on the extensive churning, analyzing and compilation of the salient information on tumor biomarkers from the authentic published literature available in PubMed and other scientific databases. The information also includes the implicative role of nucleic acids, apolipoproteins, inflammatory biomolecules, receptors, DNA modification, carbohydrate antigens and metabolite signatures as biomarkers for cancer. Results: In this review, we have summarized some tumor biomarkers, which would improve prognostic efficiency and accuracy among patients with cancer particularly for ovarian, lung, breast, melanoma and pancreatic cancer. Conclusion: This review provides in-depth insights of the use and importance of cancer biomarkers in our understanding as well improve knowledge regarding cancer management in clinical practice that will facilitate a more effective prognosis with least undesired systemic toxicity. However, development and evaluation of cancer biomarkers demand a complete understanding of the molecular processes and cellular mechanisms during the onset of cancer; as well how a little modification in regulatory metabolites, proteins or genes can disrupt various kinds of cellular functions and lead to cancer.

Background: Androgens play a major role in the carcinogenesis of prostate cancer (PCa) and the growth of PCa cells is based on the level of androgens. New Gene Expressed in Prostate (NGEP) and LIM-domain-only1 (LMO1) are two proteins that seem to play important roles in prognosis and progress of PCa, respectively. Previous studies reported androgen-dependent NGEP and LMO1 translocation into the nucleus associated with androgen receptor in an androgen-dependent manner. However, the effects of natural androgens such as testosterone on NGEP and LMO1 gene expression have not been investigated and not clear whether androgens can affect NGEP and LMO1 gene expression. Objective: The aim of this study was to investigate the effect of testosterone on NGEP and LMO1 gene expression in PCa cells. Methods: We investigated NGEP, LMO1 and prostate specific antigen (PSA; as positive control) gene expression in LNCaP cells by Real Time RT-PCR in the presence of various testosterone concentrations (5,10, 20 and 50nM) after 24 and 48 hours of incubation. Results: Our results showed that NGEP gene expression was significantly increased in LNCaP cells in the presence of 5mM testosterone after 24 and 48hours, ~4.5 and 3.5 folds respectively in comparison with the control. The LMO1 expression was increased ~ 2.8 folds at 5nM testosterone after 48 hours of with the control. The LMO1 expression was increased ~ 2.8 folds at 5nM testosterone after 48 hours of incubation when compared with the control. Conclusion: Both NGEP and LMO1 up-regulations occurred at a limited range of testosterone concentration. This androgen dependency was relatively lower than that of PSA. Additional studies are required to clearly evaluate the effect of androgens on NGEP and LMO1 protein expression and functions.

Background: There is high risk of left ventricular hypertrophy (LVH) in hemodialysis patients and attention is required to address this problem. Till date most of the proteomics studies in Chronic Kidney Disease (CKD) have been carried out in urine samples and have revealed some important protein biomarkers. Objective: The current study was undertaken to evaluate the serum proteomic profile in hemodialysis patients with LVH. Methods: The study comprised of 12 hemodialysis patients with evidence of LVH and 12 normal healthy individuals. The serum samples pooled from cases and normal healthy individuals were subjected to 2D-DIGE followed by gel analysis. Fifteen spots were selected based on folds of increase or decrease and uniqueness of the protein spot for further mass spectrum (MS) analysis. The 3D structures of proteins were predicted using Prime from Schrodinger software. From the MS data, the 1D structure of protein was assessed through which 2D structure and 3D structure were predicted using in silico tools. Protein structure validation was done using PROCHECK and ERRAT and further protein interaction was studied using STRING analysis. Results: The results data suggest that plasma inflammatory proteins (like Monoclonal antibody CH89 heavy chain (partial), Immunoglobin heavy chain variable region, IgM heavy chain VH1 region precursor), nuclear related proteins (such as zinc finger protein 224, lethal malignant brain tumor like protein, mitotic check point) were differentially expressed. Conclusion: The assessment of serum proteomics in hemodialysis with LVH provides an altered protein pattern, which may serve as a potential biomarker for monitoring the course of the disease.

Background: Peripheral blood stem cells (PBSCs) are now established curative treatment for patients with various hematologic malignancies and are proposed to be superior to other cell sources for cell based therapy. Aims: The aims are to characterize the PBSCs by constructing proteome using 2D-gel electrophoresis and analyze the kinetic parameters of pirarubicin transport of PBSCs compared with peripheral blood mononuclear cells (PBMCs), and erythromyelogenous leukemic (K562 and K562/adr) cells. Methods: Whole cell proteomes of PBMCs, PBSCs and erythromyelogenous leukemic cells were separated by 2D-gel electrophoresis and analyzed by multivariate and principle component analysis. The parallel series of experiments were measured by pirarubicin transport parameters by the cells using spectrofluorometer. Results: The PBSCs were initially found in 1% in the fraction of PBMCs and majority of them were found in the culture after 14 days. Multivariate and principle component analysis revealed the proteins that might be considered as biomarkers of PBSCs (4 proteins), PBMCs (9 proteins), K562 (4 proteins) and K562/adr (9 proteins) cells. The analysis of transport of pirarubicin by these cell models indicated that PBSCs and PBMCs possessed exocytotic pathway by which the mean rate constant was equal to 0.056 + 0.001 and 0.56 + 0.01 pL.cell-1.sec-1, respectively. While the two cancer lines showed the lack of the exocytosis activity. Conclusion: The overall results suggested that both whole cell proteome and kinetic parameter of exocytosis should be considered as characteristics of PBSCs, PBMCs, K562 and K562/adr cells.

Background: Inflammatory cytokines play a major role in pathophysiology, prognosis and progression in HIV infection. Studies on pre-ART levels of different pro-inflammatory and coagulation markers have shown predictive role on progression and mortality in HIV. IL-6, CRP has also been shown to be correlated with HIV-RNA levels as disease progresses. Objective: Biomarkers of inflammation are of increasing interest as predictors of morbidity and mortality in HIV infected patients. Though India is a major contributor to HIV-related mortality in Asia and Pacific zone, studies on inflammatory markers predictive of progression of HIV disease, on population from the Indian sub-continent are few. In this study, we observed the baseline levels of inflammatory cytokines among treatment naïve HIV positive subjects in respect to healthy volunteers. Materials and Methods: Serum levels of IL-6, TNF-α and CRP in 130 antiretroviral naive, HIVpositive individuals were estimated using sandwich ELISA, along with routine CD4 cell count, plasma HIV-1 viral load and biochemical tests for clinical assessment. Cytokine levels between ‘study’ and ‘control’ arms (30 age & gender matched HIV-negative healthy volunteers) were compared. Independent unpaired t-test was done using Graph Pad Prism 6.0 to analyze differences statistically. Results: Baseline cytokine levels were significantly high (p ≤ 0.05) in ARV naive HIV-positive subjects compared to healthy controls. Cytokine levels among treatment naive patients also correlated with severity of immunosuppression. Conclusion: Biomarkers of inflammation (IL-6, TNF-α) and CRP were found to be high in ARV naïve HIV-positive subjects, enrolled at an Eastern Indian tertiary hospital. Extensive studies on baseline inflammatory profile of patients may be predictive of disease progression, treatment response and mortality.