Predicting E3 Ubiquitin Ligases as Possible Promising Biomarkers for Brain Tumors
01 Jan 2019-pp 43-72
TL;DR: The chief objective of this current chapter is to understand the critical requirement of new biomarkers, which can early indicate improper cellular proliferation and cancer progression due to the complex defects in various signal transduction mechanisms linked with the promotion and progress of each phase of the cell cycle.
Abstract: Cells perform several post-translational changes in various proteins prior to allow their participation in various intracellular metabolic mechanisms. Ubiquitylation is also a post-translational process for different cellular proteins after which modified proteins contribute their physiological functions in distinct cellular processes. E3 ubiquitin ligases are important components of ubiquitin proteasome system (UPS), which specifically recognize critical substrate proteins (abnormal, over-accumulated & old) for their intracellular elimination. Loss of cell cycle regulation is one of the chief possible causes of deregulated cellular proliferation and cancer progression. How different E3 ubiquitin ligases play essential roles in cell-cycle regulation is still one of the unsolved fundamental questions and potentially stands for the development of early diagnostic methods, which can generate new molecular strategies to treat cancer. In this chapter, our main focus is to understand the functions of E3 Ubiquitin Ligases as setting potential biomarker or targets in various cancers and linked with regulatory roles of cell-cycle transitions. The chief objective of this current chapter is to understand the critical requirement of new biomarkers, which can early indicate improper cellular proliferation and cancer progression due to the complex defects in various signal transduction mechanisms linked with the promotion and progress of each phase of the cell cycle. A better understanding of E3 ubiquitin ligases may result in new insights and therapeutic strategies for the treatment and suppression of the development of cancer.
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01 Jan 2015
TL;DR: In this paper, immunohistochemical detection of BRCA1 and PARP expression in epithelial ovarian cancer (EOC) and their possible prognostic relevance was investigated.
Abstract: BRCA1/2 mutation status in epithelial ovarian cancer (EOC) presently relies on genetic testing which is resource consuming. Immunohistochemistry is cheap, fairly reproducible, and may identify gene product alterations due to both germline and somatic mutations and other defects along the BRCA gene pathway (BRCAness phenomenon), which is important when treatment with poly (adenosine-diphosphate-ribose) polymerase (PARP) inhibitors is considered. The aim of this study was to investigate immunohistochemical detection of BRCA1 and PARP expression in EOC and their possible prognostic relevance. Tumor tissue from 170 patients with EOC was stained immunohistochemically with BRCA1 and PARP antibodies. Semiquantitative analyses were performed to determine loss of, equivocal, and retained BRCA1 and high versus low PARP protein expression. These parameters were analyzed for relation with patient and clinicopathologic characteristics and overall survival. BRCA1 expression was reduced in 21.2 % of the tumors and 36.5% showed high PARP expression. No correlation between the 2 parameters or between PARP and clinicopathologic features was found. Overall survival was significantly increased in the BRCA1-reduced and equivocal groups [median survival 2.4 y (95% CI, 1.6–6.6) and 4.9 y (95 % CI, 2.3–6.7) vs. 1.5 y (95% CI, 1.3–1.9); P=0.0002]. Multivariate analysis confirmed these findings; hazard ratio=0.53 (95% CI, 0.34–0.81; P=0.0037; loss of BRCA1 expression). In conclusion, immunohistochemical BRCA1 expression in EOC holds considerable prognostic information, whereas PARP expression did not influence the outcome. The results call for validation in prospective trials.
22 citations
01 Jan 2022
TL;DR: In this article , the authors summarized the processes for discovery and development of important diagnostic biomarkers with clinical utility, informing clinical monitoring to improve outcomes of patients with cancer, and discussed the potential role of nanotechnology in the development and validation of future prospective cancer biomarkers.
Abstract: The global increase in cancer rates and mortality warrants the identification of biomarkers that are mechanism-and-disease-specific for the detection, diagnosis, disease progression, and development of new regimes for treatment. Cancer biomarkers are biologically active molecules including proteins (enzymes or receptors), nucleic acids (coding and noncoding RNAs), immunoglobulins, or shorter chains of amino acids or peptides. A biomarker can also be used for the detection of modifications in gene expression or protein activity and epigenetic changes or productions of stimuli-induced antibodies by either tumor or healthy cells under normal or pathological conditions. These biomarkers carry a unique and identifiable molecular structure, such as extent and activities of the genome, polypeptides, or epigenetic alterations in circulatory fluids (whole blood, serum, or plasma), excretory fluids (stool, urine, sputum, or milk), and tissues, providing great potential for early diagnosis, monitoring, and selecting a suitable drug for patients with cancer. This chapter underpins the recent findings of cancer biomarkers concerning their expression pattern, molecular and biochemical characterization, diagnostic and therapeutic utilization, and translation into the clinics for the therapeutic intervention of patients with cancer. Several studies have reported various prognostic and predictive cancer biomarkers, although few have been commercialized. However, large multicenter validation studies are required to elucidate their effectiveness and role in translation to the cancer clinics for development into personalized medicines for the management of patients with cancer. Finally, we discuss the potential role of nanotechnology in the development and validation of future prospective cancer biomarkers. In this chapter, we summarize the processes for discovery and development of important diagnostic biomarkers with clinical utility, informing clinical monitoring to improve outcomes of patients with cancer.
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