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1.
Significance of 5-S-Cysteinyldopa as a Marker for Melanoma.
Wakamatsu, K, Fukushima, S, Minagawa, A, Omodaka, T, Hida, T, Hatta, N, Takata, M, Uhara, H, Okuyama, R, Ihn, H
International journal of molecular sciences. 2020;(2)
Abstract
Melanoma is one of the most lethal and malignant cancers and its incidence is increasing worldwide, and Japan is not an exception. Although there are numerous therapeutic options for melanoma, the prognosis is still poor once it has metastasized. The main concern after removal of a primary melanoma is whether it has metastasized, and early detection of metastatic melanoma would be effective in improving the prognosis of patients. Thus, it is very important to identify reliable methods to detect metastases as early as possible. Although many prognostic biomarkers (mainly for metastases) of melanoma have been reported, there are very few effective for an early diagnosis. Serum and urinary biomarkers for melanoma diagnosis have especially received great interest because of the relative ease of sample collection and handling. Several serum and urinary biomarkers appear to have significant potential both as prognostic indicators and as targets for future therapeutic methods, but still there are no efficient serum and urinary biomarkers for early detection, accurate diagnosis and prognosis, efficient monitoring of the disease and reliable prediction of survival and recurrence. Levels of 5-S-cysteinyldopa (5SCD) in the serum or urine as biomarkers of melanoma have been found to be significantly elevated earlier and to reflect melanoma progression better than physical examinations, laboratory tests and imaging techniques, such as scintigraphy and echography. With recent developments in the treatment of melanoma, studies reporting combinations of 5SCD levels and new applications for the treatment of melanoma are gradually increasing. This review summarizes the usefulness of 5SCD, the most widely used and well-known melanoma marker in the serum and urine, compares 5SCD and other useful markers, and finally its application to other fields.
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2.
Insulinoma-associated protein 1 (INSM1): a potential biomarker and therapeutic target for neuroendocrine tumors.
Mahalakshmi, B, Baskaran, R, Shanmugavadivu, M, Nguyen, NT, Velmurugan, BK
Cellular oncology (Dordrecht). 2020;(3):367-376
Abstract
BACKGROUND Insulinoma-associated protein 1 (INSM1), a transcriptional regulator with a zinc-finger DNA-binding domain, has been validated as a cytoplasmic marker for neuroendocrine differentiation of tumor cells. Next to its abundant expression in the fetal pancreas, it is expressed in brain tumors, pheochromocytomas, medullary thyroid carcinomas, insulinomas and pituitary and small-cell lung carcinomas. INSM1 is not expressed in normal adult tissues and/or most non-neuroendocrine tumors. It regulates various downstream signaling pathways, including the Sonic Hedgehog, PI3K/AKT, MEK/ERK1/2, ADK, p53, Wnt, histone acetylation, LSD1, cyclin D1, Ascl1 and N-Myc pathways. Although INSM1 appears to be a subtle and specific biomarker for neuroendocrine tumors, its role in tumor development has remained unclear. CONCLUSIONS Here, we highlight INSMI expression, as well as its diagnostic significance and use as a therapeutic target in various neuroendocrine tumors. Targeting signaling pathways or gene expression alterations associated with INSM1 expression may be instrumental for the design of novel therapeutic strategies for neuroendocrine tumors.
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3.
Prognostic and clinicopathological significance of SR-B1 in solid tumors: A meta-analysis.
Wang, M, Chao, C, Luo, G, Wang, B, Zhan, X, Di, D, Qian, Y, Zhang, X
Pathology, research and practice. 2020;(4):152849
Abstract
BACKGROUND The expression of cell surface receptors is abnormal in malignant tumors. The scavenger receptor class B type I (SR-B1) is an integral membrane glycoprotein receptor that facilitates the selective uptake of cholesterol by malignant cells. Accumulated studies investigated the prognostic role of SR-B1 in many solid tumors, such as breast cancer, lung cancer and so on. However, the conclusions remain undefined. Therefore, we conducted this meta-analysis to obtain more accurate evaluation of prognostic significance of SR-B1 in solid tumors. MATERIALS AND METHODS We searched PubMed, Embase, Web of science and Cochrane library for eligible studies published before November 2018. The included studies investigated the association between the SR-B1 level and clinicopathological features including survival outcomes in solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were adopted to assess the survival outcomes and odds ratio (ORs) with 95% confidence intervals (CIs) were pooled to evaluated the clinicopathological features. RESULTS A total of 10 studies involving 2585 patients were included in this meta-analysis. The results showed that low SR-B1 level was significantly correlated with earlier tumor grade (pooled OR = 2.09, 95%CI = 1.28-3.43, P = 0.001), less nodal involvement (pooled OR = 2.07, 95%CI = 1.43-3.0, P < 0.001), less distant metastasis (OR = 19.8, 95%CI = 2.58-151.65, P = 0.004), smaller tumor size (OR = 2.34, 95%CI = 1.53-3.57, P < 0.001), earlier TNM stage (OR = 3.77, 95%CI = 1.67-8.48, P = 0.001), lower recurrence (HR = 1.98, 95%CI = 1.57-2.49, P = 0.000), and better OS (HR = 1.99, 95%CI = 1.70-2.31, P = 0.000). CONCLUSION The low expression of SR-B1 was significantly associated with better clinicopathological status and longer survival in patients with solid tumors. SR-B1 might act as a promising prognostic biomarker for solid tumors.
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4.
NAA10 as a New Prognostic Marker for Cancer Progression.
Kim, SM, Ha, E, Kim, J, Cho, C, Shin, SJ, Seo, JH
International journal of molecular sciences. 2020;(21)
Abstract
N-α-acetyltransferase 10 (NAA10) is an acetyltransferase that acetylates both N-terminal amino acid and internal lysine residues of proteins. NAA10 is a crucial player to regulate cell proliferation, migration, differentiation, apoptosis, and autophagy. Recently, mounting evidence presented the overexpression of NAA10 in various types of cancer, including liver, bone, lung, breast, colon, and prostate cancers, and demonstrated a correlation of overexpressed NAA10 with vascular invasion and metastasis, thereby affecting overall survival rates of cancer patients and recurrence of diseases. This evidence all points NAA10 toward a promising biomarker for cancer prognosis. Here we summarize the current knowledge regarding the biological functions of NAA10 in cancer progression and provide the potential usage of NAA10 as a prognostic marker for cancer progression.
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5.
Advances in the discovery of novel biomarkers for cancer: spotlight on protein N-glycosylation.
Zhang, W, Yang, Z, Gao, X, Wu, Q
Biomarkers in medicine. 2020;(11):1031-1045
Abstract
Progress on glycosylation and tumor markers has not been extensively reported. Glycosylation plays an important part in post-translational modification. Previous research on glycosylation-modified biomarkers has lagged behind due to insufficient understanding of glycosylation-related regulations. However, some new methods and ideas illustrated in recent research may provide new inspirations in the field. This article aims to review current advances in revealing relationship between tumors and abnormal N-glycosylation and discuss leading-edge applications of N-glycosylation in developing novel tumor biomarkers.
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6.
It's Not All Sunshine: Non-sun-related Melanoma Risk-factors.
Bataille, V
Acta dermato-venereologica. 2020;(11):adv00137
Abstract
There is increasing evidence that the behaviour of naevi and melanoma is under significant genetic and/or epigenetic control. Melanoma tumours behaves similarly all over the world. Many genes have now been implicated in melanoma risk and naevi number. Embryogenesis has also been important in the discovery of links between several neurological diseases and melanoma susceptibility. Telomere biology, which regulates cell senescence, is increasingly relevant in melanoma. Melanoma is often found in the context of family cancer syndromes and the identification of these families is important as screening for cancer will save lives. Melanoma is also one of the most immunogenic cancer as the behaviour of naevi and melanoma differ in patients with vitiligo or eczema. The search for non-sun related melanoma risk factors should continue as it is likely to lead to important discoveries which will, in turn, have an impact on therapeutic targets for this tumour.
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7.
Oncometabolites in renal cancer.
Yong, C, Stewart, GD, Frezza, C
Nature reviews. Nephrology. 2020;(3):156-172
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Abstract
The study of cancer metabolism has evolved vastly beyond the remit of tumour proliferation and survival with the identification of the role of 'oncometabolites' in tumorigenesis. Simply defined, oncometabolites are conventional metabolites that, when aberrantly accumulated, have pro-oncogenic functions. Their discovery has led researchers to revisit the Warburg hypothesis, first postulated in the 1950s, of aberrant metabolism as an aetiological determinant of cancer. As such, the identification of oncometabolites and their utilization in diagnostics and prognostics, as novel therapeutic targets and as biomarkers of disease, are areas of considerable interest in oncology. To date, fumarate, succinate, L-2-hydroxyglutarate (L-2-HG) and D-2-hydroxyglutarate (D-2-HG) have been characterized as bona fide oncometabolites. Extensive metabolic reprogramming occurs during tumour initiation and progression in renal cell carcinoma (RCC) and three oncometabolites - fumarate, succinate and L-2-HG - have been implicated in this disease process. All of these oncometabolites inhibit a superfamily of enzymes known as α-ketoglutarate-dependent dioxygenases, leading to epigenetic dysregulation and induction of pseudohypoxic phenotypes, and also have specific pro-oncogenic capabilities. Oncometabolites could potentially be exploited for the development of novel targeted therapies and as biomarkers of disease.
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Tracking of low disease burden in multiple myeloma: Using mass spectrometry assays in peripheral blood.
Chapman, JR, Thoren, KL
Best practice & research. Clinical haematology. 2020;(1):101142
Abstract
Efforts over the last 5 years have demonstrated that it is technically feasible to detect low levels of monoclonal proteins in peripheral blood using mass spectrometry. These methods are based on the fact that an M-protein has a specific amino acid sequence, and therefore, a specific mass. This mass can be tracked over time and can serve as a surrogate marker of the presence of clonal plasma cells. This review describes the use of mass spectrometry to detect M-proteins in multiple myeloma to date, identifies the challenges of using this biomarker, and describes potential strategies to overcome these challenges. We discuss the work that must be done for these techniques to be incorporated into clinical practice for tracking of low disease burden in multiple myeloma.
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Glioblastoma: Is There Any Blood Biomarker with True Clinical Relevance?
Linhares, P, Carvalho, B, Vaz, R, Costa, BM
International journal of molecular sciences. 2020;(16)
Abstract
Glioblastoma (GBM) is the most frequent malignant primary brain tumor in adults, characterized by a highly aggressive, inflammatory and angiogenic phenotype. It is a remarkably heterogeneous tumor at several levels, including histopathologically, radiographically and genetically. The 2016 update of the WHO Classification of Tumours of the Central Nervous System highlighted molecular parameters as paramount features for the diagnosis, namely IDH1/2 mutations that distinguish primary and secondary GBM. An ideal biomarker is a molecule that can be detected/quantified through simple non- or minimally invasive methods with the potential to assess cancer risk; promote early diagnosis; increase grading accuracy; and monitor disease evolution and treatment response, as well as fundamentally being restricted to one aspect. Blood-based biomarkers are particularly attractive due to their easy access and have been widely used for various cancer types. A number of serum biomarkers with multiple utilities for glioma have been reported that could classify glioma grades more precisely and provide prognostic value among these patients. At present, screening for gliomas has no clinical relevance. This is because of the low incidence, the lack of sensitive biomarkers in plasma, and the observation that gliomas may develop apparently de novo within few weeks or months. To the best of our knowledge, there is no routine use of a serum biomarker for clinical follow-up. The purpose of this paper is to review the serum biomarkers described in the literature related to glioblastoma and their possible relationship with clinical features.
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10.
Approaches to PET Imaging of Glioblastoma.
Drake, LR, Hillmer, AT, Cai, Z
Molecules (Basel, Switzerland). 2020;(3)
Abstract
Glioblastoma multiforme (GBM) is the deadliest type of brain tumor, affecting approximately three in 100,000 adults annually. Positron emission tomography (PET) imaging provides an important non-invasive method of measuring biochemically specific targets at GBM lesions. These powerful data can characterize tumors, predict treatment effectiveness, and monitor treatment. This review will discuss the PET imaging agents that have already been evaluated in GBM patients so far, and new imaging targets with promise for future use. Previously used PET imaging agents include the tracers for markers of proliferation ([11C]methionine; [18F]fluoro-ethyl-L-tyrosine, [18F]Fluorodopa,[18F]fluoro-thymidine, and [18F]clofarabine), hypoxia sensing ([18F]FMISO, [18F]FET-NIM, [18F]EF5, [18F]HX4, and [64Cu]ATSM), and ligands for inflammation. As cancer therapeutics evolve toward personalized medicine and therapies centered on tumor biomarkers, the development of complimentary selective PET agents can dramatically enhance these efforts. Newer biomarkers for GBM PET imaging are discussed, with some already in use for PET imaging other cancers and neurological disorders. These targets include Sigma 1, Sigma 2, programmed death ligand 1, poly-ADP-ribose polymerase, and isocitrate dehydrogenase. For GBM, these imaging agents come with additional considerations such as blood-brain barrier penetration, quantitative modeling approaches, and nonspecific binding.