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Biomarker validation

Xin Chen, Zelan Ma, Yanqi Huang, Lan He, Cuishan Liang, Changzheng Shi, Zhongping Zhang, Changhong Liang, Zaiyi Liu
PURPOSE: To investigate the value of multiparametric magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) for monitoring the ultra-early (within 24 hours) treatment effect of sorafenib in human hepatocellular carcinoma (HCC) xenografts. MATERIALS AND METHODS: With institutional Animal Care and Use Committee approval, 16 BALB/c nude mice bearing subcutaneous HCC xenografts underwent serial Gaussian and non-Gaussian DWI at baseline and 1, 3, 6, 12, and 24 hours posttreatment using a 1...
October 26, 2016: Journal of Magnetic Resonance Imaging: JMRI
Anissa Abi-Dargham, Guillermo Horga
The field of medicine is moving toward the use of biomarkers for the optimization of individualized care. This is a particular challenge for the field of psychiatry, in which diagnosis is based on a descriptive collection of behaviors without the availability of any objective test to stratify patients. Neuroimaging techniques such as molecular imaging with positron-emission tomography (PET) or structural and functional magnetic resonance imaging (MRI) provide an opportunity to bring psychiatry from an era of subjective descriptive classification into objective and tangible brain-based measures...
October 26, 2016: Nature Medicine
Andrea Schmitt, Daniel Martins-de-Souza, Schahram Akbarian, Juliana S Cassoli, Hannelore Ehrenreich, Andre Fischer, Alfred Fonteh, Wagner F Gattaz, Michael Gawlik, Manfred Gerlach, Edna Grünblatt, Tobias Halene, Alkomiet Hasan, Kenij Hashimoto, Yong-Ku Kim, Sophie-Kathrin Kirchner, Johannes Kornhuber, Theo F J Kraus, Berend Malchow, Juliana M Nascimento, Moritz Rossner, Markus Schwarz, Johann Steiner, Leda Talib, Florence Thibaut, Peter Riederer, Peter Falkai
OBJECTIVES: Despite progress in identifying molecular pathophysiological processes in schizophrenia, valid biomarkers are lacking for both the disease and treatment response. METHODS: This comprehensive review summarises recent efforts to identify molecular mechanisms on the level of protein and gene expression and epigenetics, including DNA methylation, histone modifications and micro RNA expression. Furthermore, it summarises recent findings of alterations in lipid mediators and highlights inflammatory processes...
October 26, 2016: World Journal of Biological Psychiatry
Iben Daugaard, Diana Dominguez, Tina E Kjeldsen, Lasse S Kristensen, Henrik Hager, Tomasz K Wojdacz, Lise Lotte Hansen
Lung cancer is the number one cause of cancer-related deaths worldwide. DNA methylation is an epigenetic mechanism that regulates gene expression, and disease-specific methylation changes can be targeted as biomarkers. We have compared the genome-wide methylation pattern in tumor and tumor-adjacent normal lung tissue from four lung adenocarcinoma (LAC) patients using DNA methylation microarrays and identified 74 differentially methylated regions (DMRs). Eighteen DMRs were selected for validation in a cohort comprising primary tumors from 52 LAC patients and tumor-adjacent normal lung tissue from 32 patients by methylation-sensitive high resolution melting (MS-HRM) analysis...
October 26, 2016: Scientific Reports
F Barabé, L Gil, M Celton, A Bergeron, V Lamontagne, É Roques, K Lagacé, A Forest, R Johnson, L Pécheux, J Simard, J Pelloux, A Bellemare-Pelletier, E Gagnon, J Hebert, S Cellot, B T Wilhelm
Acute myeloid leukemias (AML) result from a series of genetic events occurring in a stem or progenitor hematopoietic cell which gives rise to their clonal expansion and an impaired capacity to differentiate. To circumvent the genetic heterogeneity of AML patient cohorts, we have developed a model system, driven by the MLL-AF9 (MA9) oncogene, to generate multiple human leukemias using progenitor cells from a single healthy donor. Through stepwise RNA-sequencing data generated using this model and AML patients, we have identified consistent changes associated with MA9-driven leukemogenesis and demonstrate that no recurrent secondary mutations are required...
October 26, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Hyerim Ha, Ah-Rong Nam, Ju-Hee Bang, Ji-Eun Park, Tae-Yong Kim, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang, Do-Youn Oh
Programmed death-ligand 1 (PD-L1) expression in tumor tissue is under investigation as a candidate biomarker in immuno-oncology dug development. The soluble form of PD-L1 (sPDL1) is suggested to have immunosuppressive activity. In this study, we measured the serum level of sPDL1 and evaluated its prognostic implication in biliary tract cancer (BTC). Blood was collected from 158 advanced BTC patients (68 intrahepatic cholangiocarcinoma, 56 gallbladder cancer, 22 extrahepatic cholangiocarcinoma and 12 ampulla of vater cancer) before initiation of palliative chemotherapy...
October 21, 2016: Oncotarget
Lichao Sun, Chunguang Guo, Joseph Burnett, Zhihua Yang, Yuliang Ran, Duxin Sun
Hepatic metastasis is the most critical prognostic factor for colorectal cancer (CRC), and early detection of CRC liver metastasis can significantly improve cancer patient outcomes. In this study, we examined the levels of CPA4 in CRC samples, and assessed the potential of serum CPA4 as a biomarker for predicting CRC liver metastasis. CPA4 positivity was observed in 68.4% (130/190) colorectal cancer tissues, and significantly correlated with Depth of invasion, Lymph node metastasis, Distant metastasis and Stage...
October 21, 2016: Oncotarget
Yao-Jie Pan, Ying Zhuang, Jun-Nian Zheng, Dong-Sheng Pei
MicroRNAs (miRNAs), which are characterized by highly conserved and small non-coding RNAs, have been a hot spot regarding biological processes such as cellular proliferation, apoptosis and metabolism as well as cellular differentiation, signal transduction and carcinogenesis. MiRNA-106a (miR-106a), a member of the miR-17 family, has been validated to be aberrantly regulated in the diversity of tumors. The purpose of this review is supposed to deliver an intricate overview of miR-106a, including its role in cell proliferation, apoptosis, cell cycle, invasion and metastasis, involvement in drug resistance as well as its interactions with the target proteins and signaling pathways involved...
October 15, 2016: Bioorganic & Medicinal Chemistry Letters
Mindi Zhao, Jianqiang Wu, Youhe Gao
Urine, reflecting many changes in the body, is a better source than blood for biomarker discovery. However, even under physiological conditions, the urine proteome often varies. Understanding how various regulating factors affect urine proteome helps link changes to urine proteome with urinary biomarkers of physiological conditions as well as corresponding diseases. To evaluate the possible impact of α1-adrenergic receptor on urine proteome, this study investigated effects of the specific inhibitor prazosin on the urine proteome in a rat model by using tandem mass tagging and two-dimensional liquid chromatography-tandem mass spectrometry...
2016: PloS One
Aodhán Hickey, Eleanor Gunn, Lisa Alcock, Silvia Del Din, Alan Godfrey, Lynn Rochester, Brook Galna
Biomarkers are required to track disease progression and measure the effectiveness of interventions for people with spinocerebellar ataxia type-6 (SCA6). Gait is a potential biomarker that is sensitive to SCA6 which can be measured using wearable technology, reducing the need for expensive specialist facilities. However, algorithms used to calculate gait using data from wearables have not been validated in SCA6. This study sought to examine the validity of a single wearable for deriving 14 spatio-temporal gait characteristics in SCA6 and control cohorts...
October 25, 2016: Physiological Measurement
Youngwoo Kim, Sonu K Bae, Tianming Cheng, Cheng Tao, Yinghui Ge, Arlene B Chapman, Vincente E Torres, Alan S L Yu, Michal Mrug, William M Bennett, Michael F Flessner, Doug P Landsittel, Kyongtae T Bae
Liver and liver cyst volume measurements are important quantitative imaging biomarkers for assessment of disease progression in autosomal dominant polycystic kidney disease (ADPKD) and polycystic liver disease (PLD). To date, no study has presented automated segmentation and volumetric computation of liver and liver cysts in these populations. In this paper, we proposed an automated segmentation framework for liver and liver cysts from bounded abdominal MR images in patients with ADPKD. To model the shape and variations in ADPKD livers, the spatial prior probability map (SPPM) of liver location and the tissue prior probability maps (TPPMs) of liver parenchymal tissue intensity and cyst morphology were generated...
November 21, 2016: Physics in Medicine and Biology
Daniel Shu Wei Ting, Kara-Anne Tan, Val Phua, Gavin Siew Wei Tan, Chee Wai Wong, Tien Yin Wong
Diabetic retinopathy (DR), a leading cause of acquired vision loss, is a microvascular complication of diabetes. While traditional risk factors for diabetic retinopathy including longer duration of diabetes, poor blood glucose control, and dyslipidemia are helpful in stratifying patient's risk for developing retinopathy, many patients without these traditional risk factors develop DR; furthermore, there are persons with long diabetes duration who do not develop DR. Thus, identifying biomarkers to predict DR or to determine therapeutic response is important...
December 2016: Current Diabetes Reports
Rintaro Saito, Anaïs Rocanin-Arjo, Young-Hyun You, Manjula Darshi, Benjamin Van Espen, Satoshi Miyamoto, Jessica Pham, Minya Pu, Simone Romoli, Loki Natarajan, Wenjun Ju, Matthias Kretzler, Robert Nelson, Keiichiro Ono, Dana Thomasova, Shrikant R Mulay, Trey Ideker, Vivette D'Agati, Ergin Beyret, Juan Carlos Izpisua Belmonte, Hans Joachim Anders, Kumar Sharma
To derive new insights in diabetic complications, we integrated publicly available human protein-protein interaction (PPI) networks with global metabolic networks using metabolomic data from patients with diabetic nephropathy. We focused on the participating proteins in the network that were computationally predicted to connect the urine metabolites. MDM2 had the highest significant number of PPI connections. As validation, significant downregulation of MDM2 gene expression was found in both glomerular and tubulointerstitial compartments of kidney biopsy tissue from 2 independent cohorts of patients with diabetic nephropathy...
October 20, 2016: JCI Insight
Ana Isabel Sánchez-Fructuoso, Isabel Pérez-Flores, Rosalia Valero, Maria Angeles Moreno, Miguel Fernandez-Arquero, Elena Urcelay, Cristina Fernández-Pérez, Jose Luis Santiago
The -308G/A SNP of tumor necrosis factor-alpha (TNF-α) gene affects TNF-α production. As its impact on transplant outcome remains open to debate, we decided to genotype it in a cohort of transplant subjects. A retrospective analysis of 439 first kidney recipients randomly divided into two subgroups (discovery and validation cohorts) was performed to identify the best predictors of acute rejection (AR). The effect on transplant outcome was analyzed by an adjusted logistic regression model. Carriers of the A allele, associated with elevated TNF-α production, presented a higher risk of AR (OR = 2...
2016: Journal of Immunology Research
Yun Su, HongBin Fang, Feng Jiang
BACKGROUND: Abnormal microRNA (miRNA) expressions and promoter methylation of genes detected in sputum may provide biomarkers for non-small lung cancer (NSCLC). Here, we evaluate the individual and combined analysis of the two classes of sputum molecular biomarkers for NSCLC detection. RESULTS: We analyze expression of 3 miRNAs (miR-21, miR-31, and miR-210) and methylation of 3 genes (RASSF1A, PRDM14, and 3OST2), which were previously identified as potential biomarkers for NSCLC, in sputum of a set of 117 stage I NSCLC patients and 174 cancer-free smokers...
2016: Clinical Epigenetics
Chao-Jun Hu, Jian-Bo Pan, Guang Song, Xiao-Ting Wen, Zi-Yan Wu, Si Chen, Wen-Xiu Mo, Feng-Chun Zhang, Jiang Qian, Heng Zhu, Yong-Zhe Li
Behcet disease (BD) is a chronic systemic vasculitis and considered as an autoimmune disease. Although rare, BD can be fatal due to ruptured vascular aneurysms or severe neurological complications. To date, no known biomarker has been reported for this disease, making it difficult to diagnosis in the clinics. To undertake this challenge, we employed the HuProt arrays, each comprised of~20,000 unique human proteins, to identify BD-specific autoantibodies using a Two-Phase strategy established previously. In Phase I, we profiled the autoimmunity on the HuProt arrays with 75 serum samples collected from 40 BD patients, 15 diagnosed autoimmune patients who suffer from Takayasu arteritis (TA; N=5)), ANCA associated vasculitis(AAV; N=5), and Sjogren's syndrome(SS; N=5), and 20 healthy subjects, and identified 20 candidate autoantigens that were significantly associated with BD...
October 24, 2016: Molecular & Cellular Proteomics: MCP
Barry C Jones, Helen Rollison, Susanne A Johansson, Kajsa P Kanebratt, Craig Lambert, Karthick Vishwanathan, Tommy B Andersson
Induction of cytochrome P450 (CYP) can impact the efficacy and safety of a drug molecule upon multiple dosing of co-administered drugs. This strategy is focused on CYP3A since the majority of clinically relevant cases of CYP induction are related to this enzyme. However, the in vitro evaluation of induction is applicable to other CYP enzymes but the in vivo relevance cannot be assessed because the scarcity of relevant clinical data. In the pre-clinical phase, compounds are screened using PXR reporter gene assay and, if necessary, structure-activity relationships (SAR) are developed...
October 24, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Graziano Colombo, Marco Clerici, Alessandra Altomare, Francesco Rusconi, Daniela Giustarini, Nicola Portinaro, Maria Lisa Garavaglia, Ranieri Rossi, Isabella Dalle-Donne, Aldo Milzani
: In this study, we assessed the oxidative damage occurring in plasma proteins when human blood was exposed to inflammatory concentrations of hypochlorous acid (HOCl). We used specific thiol labelling and Western blot analyses to determine protein thiol oxidation, as well as analytical gel filtration HPLC coupled to fluorescence detection to explore formation of high molecular weight (HMW) protein aggregates. Thiol-containing proteins oxidized by HOCl were identified by redox proteomics...
October 21, 2016: Journal of Proteomics
Elijah Mak, Silvy Gabel, Habib Mirette, Li Su, Guy B Williams, Adam Waldman, Katie Wells, Karen Ritchie, Craig Ritchie, John O'Brien
The last decade has witnessed a proliferation of neuroimaging studies characterising brain changes associated with Alzheimer's disease (AD), where both widespread atrophy and 'signature' brain regions have been implicated. In parallel, a prolonged latency period has been established in AD, with abnormal cerebral changes beginning many years before symptom onset. This raises the possibility of early therapeutic intervention, even before symptoms, when treatments could have the greatest effect on disease-course modification...
October 21, 2016: Ageing Research Reviews
Lourdes Mateos-Hernández, Margarita Villar, Ernesto Doncel-Pérez, Marco Trevisan-Herraz, Ángel García-Forcada, Francisco Romero Ganuza, Jesús Vázquez, José de la Fuente
Guillain-Barré syndrome (GBS) is an autoimmune-mediated peripheral neuropathy of unknown cause. However, about a quarter of GBS patients have suffered a recent bacterial or viral infection, and axonal forms of the disease are especially common in these patients. Proteomics is a good methodological approach for the discovery of disease biomarkers. Until recently, most proteomics studies of GBS and other neurodegenerative diseases have focused on the analysis of the cerebrospinal fluid (CSF). However, serum represents an attractive alternative to CSF because it is easier to sample and has potential for biomarker discovery...
October 20, 2016: Oncotarget
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