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Biomarker discovery

Qinqin Huang, Fu-Bing Wang, Chun-Hui Yuan, Zhaobo He, Lang Rao, Bo Cai, Bolei Chen, Susu Jiang, Zhiqiang Li, Jincao Chen, Wei Liu, Feng Guo, Zheng Ao, Shi Chen, Xing-Zhong Zhao
Background: Circulating tumor cells (CTCs) are a burgeoning topic in cancer biomarker discovery research with minimal invasive blood draws. CTCs can be used as potential biomarkers for disease prognosis, early cancer diagnosis and pharmacodynamics. However, the extremely low abundance of CTCs limits their clinical utility because of technical challenges such as the isolation and subsequent detailed molecular and functional characterization of rare CTCs from patient blood samples. Methods: In this study, we present a novel density gradient centrifugation method employing biodegradable gelatin nanoparticles coated on silicon beads for the isolation, release, and downstream analysis of CTCs from colorectal and breast cancer patients...
2018: Theranostics
Ibrahim O Alanazi, Sami A AlYahya, Esmaeil Ebrahimie, Manijeh Mohammadi-Dehcheshmeh
Exponentially growing scientific knowledge in scientific publications has resulted in the emergence of a new interdisciplinary science of literature mining. In text mining, the machine reads the published literature and transfers the discovered knowledge to mathematical-like formulas. In an integrative approach in this study, we used text mining in combination with network discovery, pathway analysis, and enrichment analysis of genomic regions for better understanding of biomarkers in lung cancer. Particular attention was paid to non-coding biomarkers...
March 16, 2018: Gene
P Scott Pine, Steven P Lund, Sanford A Stass, Debra Kukuruga, Feng Jiang, Lynn Sorbara, Sudhir Srivastava, Marc Salit
BACKGROUND: We demonstrate the feasibility of creating a pair of reference samples to be used as surrogates for clinical samples measured in either a research or clinical laboratory setting. The reference sample paradigm presented and evaluated here is designed to assess the capability of a measurement process to detect true differences between two biological samples. Cell-based reference samples can be created with a biomarker signature pattern designed in silico. Clinical laboratories working in regulated applications are required to participate in proficiency testing programs; research laboratories doing discovery typically do not...
March 20, 2018: BMC Biotechnology
Chia-Chun Wu, Jen-Der Lin, Jeng-Ting Chen, Chih-Min Chang, Hsiao-Fen Weng, Chuen Hsueh, Hui-Ping Chien, Jau-Song Yu
Thyroid ultrasound and ultrasound-guided fine-needle aspiration (USG/FNA) biopsy are currently used for diagnosing papillary thyroid carcinoma (PTC), but their detection limit could be improved by combining other biomarkers. To discover novel PTC biomarkers, we herein applied a GeLC-MS/MS strategy to analyze the proteome profiles of serum-abundant-protein-depleted FNA cystic fluid from benign and PTC patients, as well as two PTC cell line secretomes. From them, we identified 346, 488, and 2105 proteins, respectively...
February 23, 2018: Oncotarget
Alyssa K Carlson, Rachel A Rawle, Erik Adams, Mark C Greenwood, Brian Bothner, Ronald K June
Osteoarthritis affects over 250 million individuals worldwide. Currently, there are no options for early diagnosis of osteoarthritis, demonstrating the need for biomarker discovery. To find biomarkers of osteoarthritis in human synovial fluid, we used high performance liquid-chromatography mass spectrometry for global metabolomic profiling. Metabolites were extracted from human osteoarthritic (n = 5), rheumatoid arthritic (n = 3), and healthy (n = 5) synovial fluid, and a total of 1233 metabolites were detected...
March 15, 2018: Biochemical and Biophysical Research Communications
Szu-Yuan Wu, Nam-Nhut Phan, Shih-Hsin Ho, Yu-Heng Lai, Tsai Chih-Hung, Yang Chung-Han, Kuan-Lun Li, Hang-Gan Yu, Jung-Chieh Wang, Pung-Ling Huang, Yen-Chang Lin
CONTEXT: Arsenic poisoning commonly occurs through exposure to water contaminated with arsenic and causes long-term symptoms. Of all the arsenic derivatives, arsenite is the one of the most toxic compounds. However, the toxicity of arsenite during developmental stages is still unclear. OBJECTIVE: In this study, we performed a metabolomic analysis of arsenite responses in embryonic zebrafish. MATERIALS AND METHODS: Embryonic zebrafish were used as an animal model in this study...
March 15, 2018: Toxicology Letters
S Baleato-González, R García-Figueiras
Recent advances in biology and genetics have accelerated our knowledge about the development, growth, and dissemination of cancer, generating great expectations that these new discoveries will be translated into effective treatments for patients. Imaging techniques play a central role in the care of oncologic patients, since they have become tools capable of evaluating important characteristics of tumors and the response of tumors to different treatments. The objective of this article is to evaluate the different imaging-based criteria for assessing tumor response, discussing their advantages and limitations and illustrating the possible contribution of new imaging techniques as biomarkers of tumor response...
March 13, 2018: Radiología
Daniela Cecconi, Luca Dalle Carbonare, Antonio Mori, Samuele Cheri, Michela Deiana, Jessica Brandi, Vincenzo Degaetano, Valentina Masiero, Giulio Innamorati, Monica Mottes, Giovanni Malerba, Maria Teresa Valenti
Melanoma is an aggressive skin cancer; an early detection of the primary tumor may improve its prognosis. Despite many genes have been shown to be involved in melanoma, the full framework of melanoma transformation has not been completely explored. The characterization of pathways involved in tumor restraint in in vitro models may help to identify oncotarget genes. We therefore aimed to probe novel oncotargets through an integrated approach involving proteomic, gene expression and bioinformatic analysis We investigated molecular modulations in melanoma cells treated with ascorbic acid, which is known to inhibit cancer growth at high concentrations...
February 20, 2018: Oncotarget
Sanjay Tewari, George Renney, John Brewin, Kate Gardner, Fenella Kirkham, Baba Inusa, James E Barrett, Stephan Menzel, Swee Lay Thein, Malcolm Ward, David C Rees
Silent cerebral infarction is the commonest neurological abnormality in children with sickle cell anemia, affecting 30-40% 14 year olds. There are no known biomarkers to identify children with silent cerebral infarcts and the pathological basis is also unknown. We used an unbiased proteomic discovery approach to identify plasma proteins differing in concentration between children with and without silent cerebral infarcts. Clinical parameters and plasma samples were analysed from 51 children (mean age 11.8 years, range 6-18) with sickle cell anemia (HbSS)...
March 15, 2018: Haematologica
Charlotte E Teunissen, Markus Otto, Sebastiaan Engelborghs, Sanna-Kaisa Herukka, Sylvain Lehmann, Piotr Lewczuk, Alberto Lleó, Armand Perret-Liaudet, Hayrettin Tumani, Martin R Turner, Marcel M Verbeek, Jens Wiltfang, Henrik Zetterberg, Lucilla Parnetti, Kaj Blennow
Body fluid biomarkers have great potential for different clinical purposes, including diagnosis, prognosis, patient stratification and treatment effect monitoring. This is exemplified by current use of several excellent biomarkers, such as the Alzheimer's disease cerebrospinal fluid (CSF) biomarkers, anti-neuromyelitis optica antibodies and blood neurofilament light. We still, however, have a strong need for additional biomarkers and several gaps in their development and implementation should be filled. Examples of such gaps are i) limited knowledge of the causes of neurological diseases, and thus hypotheses about the best biomarkers to detect subclinical stages of these diseases; ii) the limited success translating discoveries obtained by e...
March 15, 2018: Alzheimer's Research & Therapy
Geny Piro, Carmine Carbone, Raffaela Santoro, Giampaolo Tortora, Davide Melisi
Introduction Esophageal and esophago-gastric junction (EGJ) adenocarcinomas remain a major health problem worldwide with a worryingly increasing incidence. Recent trials indicate survivals benefit for preoperative or perioperative chemoradiotherapy compared to surgery alone. Beside standard chemoradiotherapy regimens, new therapeutic approaches with targeted therapies have been proposed for the treatment of resectable disease. However, clinical outcomes remain extremely poor due to drug resistance phenomena...
March 16, 2018: Expert Review of Molecular Diagnostics
Jian Liu, Fuzhong Ouyang, Zhihao Zhao, Ruifang Gao, Rui Shi, Enhui Wu, Rui Lv, Guoqiang Xu
A dual maleimides (DuMal) tagging method has been developed for both relative and absolute quantitation of cysteine-containing peptides (CCPs) in combination with MALDI-TOF mass spectrometry. We choose a pair of maleimides with the minimal difference in their chemical structures, including N-Methylmaleimide (NMM) and N-Ethylmaleimide (NEM), which allow for tagging CCPs in the Michael Addition reaction with a high efficiency rapidly (~minutes). We have validated that the DuMal Tagging technique is sensitive and reliable in quantitative analysis of CCPs...
March 15, 2018: Chembiochem: a European Journal of Chemical Biology
Margarita Villar, Lourdes Mateos-Hernandez, Jose de la Fuente
BACKGROUND: Why an autoimmune disease that is the main cause of the acute neuromuscular paralysis worldwide has not yet a well-characterized cause or an effective treatment? The existence of different clinical variants for the Guillain-Barré syndrome (GBS) coupled with the fact that a high number of pathogens can cause an infection that sometimes, but not always, precedes the development of the syndrome, confers a high degree of uncertainty for both prognosis and treatment. In the post-genomic era, the development of omics technologies for the high-throughput analysis of biological molecules is allowing the characterization of biological systems in a degree of depth unimaginable before...
March 14, 2018: Current Medicinal Chemistry
Brianna Kim, Robyn Araujo, Marissa Howard, Ruben Magni, Lance A Liotta, Alessandra Luchini
Mass spectrometry (MS) is the premier tool for discovering novel disease-associated protein biomarkers. Unfortunately, when applied to complex body fluid samples, MS has poor sensitivity for the detection of low abundance biomarkers (≪10 ng/mL), derived directly from the diseased tissue cells or pathogens. Areas covered: Herein we discuss the strengths and drawbacks of technologies used to concentrate low abundance analytes in body fluids, with the aim to improve the effective sensitivity for MS discovery...
March 22, 2018: Expert Review of Proteomics
Maurizio Giordano, Kumar Parijat Tripathi, Mario Rosario Guarracino
BACKGROUND: System toxicology aims at understanding the mechanisms used by biological systems to respond to toxicants. Such understanding can be leveraged to assess the risk of chemicals, drugs, and consumer products in living organisms. In system toxicology, machine learning techniques and methodologies are applied to develop prediction models for classification of toxicant exposure of biological systems. Gene expression data (RNA/DNA microarray) are often used to develop such prediction models...
March 8, 2018: BMC Bioinformatics
Ilya Gertsman, Bruce A Barshop
Metabolomics is one of the newer omics fields, and has enabled researchers to complement genomic and protein level analysis of disease with both semi-quantitative and quantitative metabolite levels, which are the chemical mediators that constitute a given phenotype. Over more than a decade, methodologies have advanced for both targeted (quantification of specific analytes) as well as untargeted metabolomics (biomarker discovery and global metabolite profiling). Untargeted metabolomics is especially useful when there is no a priori metabolic hypothesis...
March 13, 2018: Journal of Inherited Metabolic Disease
Brunella Costanza, Andrei Turtoi, Akeila Bellahcène, Touko Hirano, Olivier Peulen, Arnaud Blomme, Vincent Hennequière, Eugene Mutijima, Jacques Boniver, Marie-Alice Meuwis, Claire Josse, Benjamin Koopmansch, Karin Segers, Takehiko Yokobori, Karim Fahmy, Marc Thiry, Carla Coimbra, Nancy Garbacki, Alain Colige, Dominique Baiwir, Vincent Bours, Edouard Louis, Olivier Detry, Philippe Delvenne, Masahiko Nishiyama, Vincent Castronovo
The identification of diagnostic and prognostic biomarkers from early lesions, measurable in liquid biopsies remains a major challenge, particularly in oncology. Fresh human material of high quality is required for biomarker discovery but is often not available when it is totally required for clinical pathology investigation. Hence, all OMICs studies are done on residual and less clinically relevant biological samples. Here after, we present an innovative, simple, and non-destructive, procedure named EXPEL that uses rapid, pressure-assisted, interstitial fluid extrusion, preserving the specimen for full routine clinical pathology investigation...
February 13, 2018: Oncotarget
Nathalie Harder, Maria Athelogou, Harald Hessel, Nicolas Brieu, Mehmet Yigitsoy, Johannes Zimmermann, Martin Baatz, Alexander Buchner, Christian G Stief, Thomas Kirchner, Gerd Binnig, Günter Schmidt, Ralf Huss
Tissue Phenomics is the discipline of mining tissue images to identify patterns that are related to clinical outcome providing potential prognostic and predictive value. This involves the discovery process from assay development, image analysis, and data mining to the final interpretation and validation of the findings. Importantly, this process is not linear but allows backward steps and optimization loops over multiple sub-processes. We provide a detailed description of the Tissue Phenomics methodology while exemplifying each step on the application of prostate cancer recurrence prediction...
March 13, 2018: Scientific Reports
Patrick Kwok-Shing Ng, Jun Li, Kang Jin Jeong, Shan Shao, Hu Chen, Yiu Huen Tsang, Sohini Sengupta, Zixing Wang, Venkata Hemanjani Bhavana, Richard Tran, Stephanie Soewito, Darlan Conterno Minussi, Daniela Moreno, Kathleen Kong, Turgut Dogruluk, Hengyu Lu, Jianjiong Gao, Collin Tokheim, Daniel Cui Zhou, Amber M Johnson, Jia Zeng, Carman Ka Man Ip, Zhenlin Ju, Matthew Wester, Shuangxing Yu, Yongsheng Li, Christopher P Vellano, Nikolaus Schultz, Rachel Karchin, Li Ding, Yiling Lu, Lydia Wai Ting Cheung, Ken Chen, Kenna R Shaw, Funda Meric-Bernstam, Kenneth L Scott, Song Yi, Nidhi Sahni, Han Liang, Gordon B Mills
The functional impact of the vast majority of cancer somatic mutations remains unknown, representing a critical knowledge gap for implementing precision oncology. Here, we report the development of a moderate-throughput functional genomic platform consisting of efficient mutant generation, sensitive viability assays using two growth factor-dependent cell models, and functional proteomic profiling of signaling effects for select aberrations. We apply the platform to annotate >1,000 genomic aberrations, including gene amplifications, point mutations, indels, and gene fusions, potentially doubling the number of driver mutations characterized in clinically actionable genes...
March 12, 2018: Cancer Cell
Guangde Zhang, Haoran Sun, Yawei Zhang, Hengqiang Zhao, Wenjing Fan, Jianfei Li, Yingli Lv, Qiong Song, Jiayao Li, Mingyu Zhang, Hongbo Shi
Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play important roles in initiation and development of human diseases. However, the mechanism of ceRNA regulated by lncRNA in myocardial infarction (MI) remained unclear. In this study, we performed a multi-step computational method to construct dysregulated lncRNA-mRNA networks for MI occurrence (DLMN_MI_OC) and recurrence (DLMN_MI_Re) based on "ceRNA hypothesis". We systematically integrated lncRNA and mRNA expression profiles and miRNA-target regulatory interactions...
December 2018: Cell Death Discovery
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