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Biomarker Research

Marte Karen Brattås, Kyrre Lilleeng, Randi Hovland, Ingvild Jenssen Lægreid, Marta Vorland, Friedemann Leh, Øystein Bruserud, Bjørn Tore Gjertsen, Håkon Reikvam
Background: A feature of myeloproliferative neoplasia is transforming to more aggressive and malignant myeloid neoplasia, including acute myeloid leukemia. Different pathogenesis mechanisms participate in transformation, including transformation of existing potential preleukemic clones, since JAK2 -mutant myeloproliferative neoplasms often transform to JAK2 wild-type acute myeloid leukemia. Case presentation: Here, we present an 80 year old man with a JAK2 -V617F mutant primary myelofibrosis...
2018: Biomarker Research
Runxia Gu, Xue Yang, Hui Wei
For decades, genetic aberrations including chromosome and molecular abnormalities are important diagnostic and prognostic factors in acute myeloid leukemia (AML). ATRA and imatinib have been successfully used in AML and chronic myelogenous leukemia, which proved that targeted therapy by identifying molecular lesions could improve leukemia outcomes. Recent advances in next generation sequencing have revealed molecular landscape of AML, presenting us with many molecular abnormalities. The individual prognostic information derived from a specific mutation could be modified by other molecular lesions...
2018: Biomarker Research
Chiara Agnoletto, Linda Minotti, Laura Brulle-Soumare, Lorenzo Pasquali, Marco Galasso, Fabio Corrà, Federica Baldassari, Jean-Gabriel Judde, Stefano Cairo, Stefano Volinia
Background: We aim to characterize the heterogeneous circulating tumour cells (CTCs) in peripheral blood, independently of physical or immunological purification, by using patient-derived xenografts (PDXs) models. CTC studies from blood generally rely on enrichment or purification. Conversely, we devised a method for the inclusive study of human cells from blood of PDX models, without pre-selection or enrichment. Methods: A qRT-PCR assay was developed to detect human and cancer-related transcripts from CTCs in PDXs...
2018: Biomarker Research
Callinice D Capo-Chichi, Kathy Q Cai, Xiang-Xi Xu
Background: In most women with ovarian cancer, the diagnosis occurs after dissemination of tumor cells beyond ovaries. Several molecular perturbations occur ahead of tumor initiation including loss of lamin A/C. Our hypothesis was that the loss of nuclear structural proteins A type lamins (lamin A/C) transcribed from LMNA gene and substrate for active caspase-6 maybe one of the molecular perturbations. Our objective is to investigate the association between the loss of lamin A/C and the overexpression of caspase-6 in ovarian cancer cells...
2018: Biomarker Research
Amandeep Aujla, Katherine Linder, Chaitanya Iragavarapu, Michael Karass, Delong Liu
Recurrent gene mutations have been described with varying frequencies in myelodysplasia (MDS) /myeloproliferative neoplasm (MPN) overlap syndromes (MMOS). Recent work has placed significant focus on understanding the role of gene lesions involving the spliceosomal machinery in leukemogeneis. SRSF2 is a gene encoding critical spliceosomal proteins. SRSF2 mutations appear to play an important role in pathogenesis of MMOS, particularly in chronic myelomonocytic leukemia. Inhibition of splicing may be a new therapeutic approach...
2018: Biomarker Research
Vipulkumar Patel, Alok K Dwivedi, Sneha Deodhar, Ina Mishra, David P Cistola
Background: Metabolic syndrome is a cluster of abnormalities that increases the risk for type 2 diabetes and atherosclerosis. Plasma and serum water T2 from benchtop nuclear magnetic resonance relaxometry are early, global and practical biomarkers for metabolic syndrome and its underlying abnormalities. In a prior study, water T2 was analyzed against ~ 130 strategically selected proteins and metabolites to identify associations with insulin resistance, inflammation and dyslipidemia...
2018: Biomarker Research
Huining Kang, Nitesh D Sharma, Christian K Nickl, Meenakshi Devidas, Mignon L Loh, Stephen P Hunger, Kimberly P Dunsmore, Stuart S Winter, Ksenia Matlawska-Wasowska
For children and young adults with T-lineage acute lymphoblastic leukemia (T-ALL), event free survival following relapse is < 10%. We recently showed that rearrangements of the mixed lineage leukemia gene ( KMT2A -R) are associated with induction failure and an inferior survival in T-ALL. Because there are currently no molecular features that inform treatment strategies in T-ALL, we hypothesized that transcriptional alterations related to KMT2A-R and MLLT10-R T-ALL could identify biologically relevant genes and signaling pathways for the development of targeted therapies for these groups of patients...
2018: Biomarker Research
Austin B Henslee, Timothy A Steele
Background: Aggressive natural killer cell leukemia is a devastating disease, with an average patient survival time of less than 2 months following diagnosis. Due to P-glycoprotein-mediated resistance of the tumor cells most forms of chemotherapy are of limited efficacy, therefore new treatment strategies are needed. Statin drugs have recently been found to inhibit the growth of various tumor cell types. Methods: We investigated the effects of statin drug-mediated mevalonate pathway inhibition on cell proliferation, tumor-induced cytotoxicity, cell cycle progression and ERK MAP kinase signal transduction pathway activation...
2018: Biomarker Research
Michelle X Yang, Ryan F Coates, Abiy Ambaye, Juli-Anne Gardner, Richard Zubarick, Yuan Gao, Joan Skelly, James G Liu, Mari Mino-Kenudson
Background: Diagnosing pancreatic ductal adenocarcinoma (PDAC) in the setting of metastasis with an unknown primary remains very challenging due to the lack of specific biomarkers. HNF-1B has been characterized as an important transcription factor for pancreatic development and was reported as a biomarker for clear cell subtype of PDAC. Methods: To investigate the diagnostic role of HNF-1B for PDAC, we used tissue microarray (TMA) and immunohistochemistry (IHC) to characterize HNF-1B expression in a large cohort of carcinomas, including 127 primary PDACs, 47 biliary adenocarcinomas, 17 metastatic PDACs, and 231 non-pancreaticobiliary carcinomas...
2018: Biomarker Research
Hiroo Katsuya, Lucy B M Cook, Aileen G Rowan, Yorifumi Satou, Graham P Taylor, Charles R M Bangham
The prognosis of adult T-cell leukemia-lymphoma (ATL) remains very poor, and there is an urgent clinical need to investigate novel therapies for ATL. The expression of phosphatidylinositol 3-kinase-δ (PI3k-δ) is normally restricted to hematopoietic cells and is known as a key determinant of cell survival in certain cancers. The inhibitor of PI3k-δ, idelalisib, has been shown to be effective in the treatment of chronic lymphocytic leukemia. Here, we report the expression of PI3k-δ and the ability of idelalisib to promote apoptosis in ex vivo ATL samples...
2018: Biomarker Research
Sandeep Kondisetty, Krishnakumar N Menon, Ginil Kumar Pooleri
Background: Carcinogenesis is a multistep process which involves interplay between the tumour cells and the matrix proteins. This occurs by adherence between the tumour cells and proteins in the extracellular matrix. VHL mutation affects through the hypoxia inducible factor (HIF) and causes changes in various tissue proteins like VEGF, PDGF, TGF, Fibronectin and others. As not much literature is available, we aim to quantify the changes of fibronectin protein in renal cell carcinoma (RCC) tissue...
2018: Biomarker Research
Kiera Walker, Nathaniel H Boyd, Joshua C Anderson, Christopher D Willey, Anita B Hjelmeland
Background: For glioblastoma (GBM) treatments to be effective in vivo, understanding the effects of the tumor microenvironment is imperative. In traditional cell culture conditions, glucose concentrations do not model physiologic levels, nor the diminished concentrations found in tumor niches. We therefore sought to profile the differences in kinase activity in GBM cells cultured in restricted glucose to identify pathways that could be targeted with small molecule inhibitors. Methods: Using the PamStation12 platform, we examined the ability of GBM lysates from cells cultured in standard or low glucose conditions to phosphorylate 144 tyrosine and 144 serine/threonine peptides that correspond to known protein phosphorylation sites...
2018: Biomarker Research
Marita Westhrin, Siv Helen Moen, Ida Bruun Kristensen, Glenn Buene, Anne Kærsgaard Mylin, Ingemar Turesson, Niels Abildgaard, Anders Waage, Therese Standal
Chemerin is a recently discovered adipokine shown to be involved in both inflammatory and metabolic processes. Here, we demonstrate that chemerin serum levels are elevated in patients with multiple myeloma and that it increases with disease progression. We found that chemerin is expressed by stromal cells and preadipocytes, whereas its receptor CCRL2 is expressed by primary myeloma cells, suggesting a paracrine signaling loop between bone marrow stromal cells/adipocytes and myeloma cells. This is the first study exploring chemerin and its receptors in multiple myeloma...
2018: Biomarker Research
Roberto J Arai, Vanessa Petry, Paulo M Hoff, Max S Mano
Metronomic therapy has been gaining importance in the neoadjuvant setting of breast cancer treatment. Its clinical benefits may involve antiangiogenic machinery. Cancer cells induce angiogenesis to support tumor growth by secreting factors, such as vascular endothelial growth factor (VEGF). In breast cancer, Trastuzumab (TZM) based treatment is of key importance and is believed to reduce diameter and volume of blood vessels as well as vascular permeability. Here in we investigated serum levels of angiogenic factors VEGF and MCSF in patients receiving metronomic neoadjuvant therapy with or without TZM...
2018: Biomarker Research
Shixiang Guo, Andrew Fesler, Huaizhi Wang, Jingfang Ju
Despite tremendous research efforts focused on diagnosis and treatment, pancreatic ductal adenocarcinoma remains the third leading cause of cancer-related death in the United States, with a 5-year overall survival rate of less than 5%. Although resistance is rather complex, emerging evidence has demonstrated that epigenetic alterations (e.g. miRNA) have important roles in PDAC progression as well as resistance to therapy. Certain miRNAs have been identified as potential prognostic biomarkers in PDAC. In this review, we summarize the recent developments in miRNA research related to PDAC therapeutic resistance mechanisms and the potential of miRNAs as prognostic biomarkers for future clinical management of PDAC...
2018: Biomarker Research
Michelle E Penney, Patrick S Parfrey, Sevtap Savas, Yildiz E Yilmaz
Background: Colorectal cancer has significant impact on individuals and healthcare systems. Many genes have been identified to influence its pathogenesis. However, the genetic basis of mucinous tumor histology, an aggressive subtype of colorectal cancer, is currently not well-known. This study aimed to identify common and rare genetic variations that are associated with the mucinous tumor phenotype. Methods: Genome-wide single nucleotide polymorphism (SNP) data was investigated in a colorectal cancer patient cohort ( n  = 505)...
2018: Biomarker Research
Walter Blum, Thomas Henzi, Hugues-Etienne Châtel-Soulet, Laszlo Pecze, Janine Wörthmüller Rodriguez, Bart Vrugt, Beat Schwaller
Background: Calretinin is the most widespread positive marker for the immunohistochemical identification of malignant mesothelioma (MM) and was proposed to serve as a blood-based biomarker. Functionally, evidence has accumulated that calretinin might be implicated in MM tumorigenesis. We aimed to identify calretinin (CR; Calb2 ) in murine MM and reactive mesothelial cells in granuloma from asbestos-exposed NF2+/- mice, a line heterozygous for the tumor suppressor merlin (NF2), used as a mouse MM model...
2018: Biomarker Research
Isaac Ks Ng, Joanne Lee, Christopher Ng, Bustamin Kosmo, Lily Chiu, Elaine Seah, Michelle Meng Huang Mok, Karen Tan, Motomi Osato, Wee-Joo Chng, Benedict Yan, Lip Kun Tan
Background: Germline mutations in the RUNX1 transcription factor give rise to a rare autosomal dominant genetic condition classified under the entity: Familial Platelet Disorders with predisposition to Acute Myeloid Leukaemia (FPD/AML). While several studies have identified a myriad of germline RUNX1 mutations implicated in this disorder, second-hit mutational events are necessary for patients with hereditary thrombocytopenia to develop full-blown AML. The molecular picture behind this process remains unclear...
2018: Biomarker Research
Michelle X Yang, Ryan F Coates, Abiy Ambaye, Valerie Cortright, Jeannette M Mitchell, Alexa M Buskey, Richard Zubarik, James G Liu, Steven Ades, Maura M Barry
Background: Well-differentiated neuroendocrine tumors (NET) most frequently arise from the gastrointestinal tract (GI), pancreas, and lung. Patients often present as metastasis with an unknown primary, and the clinical management and outcome depend on multiple factors, including the accurate diagnosis with the tumor primary site. Determining the site of the NET with unknown primary remains challenging. Many biomarkers have been investigated in primary NETs and metastatic NETs, with heterogeneous sensitivity and specificity observed...
2018: Biomarker Research
Thomas Southworth, Sarah Mason, Alan Bell, Isabel Ramis, Marta Calbet, Anna Domenech, Neus Prats, Montserrat Miralpeix, Dave Singh
Background: Inhaled allergen challenges are often used to evaluate novel asthma treatments in early phase clinical trials. Current novel therapeutic targets in asthma include phosphoinositide 3-kinases (PI3K) delta and gamma, p38 mitogen-activated protein kinase (p38) and Janus kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signalling pathways. The activation of these pathways following allergen exposure in atopic asthma patients it is not known. Methods: We collected bronchial biopsies from 11 atopic asthma patients at baseline and after allergen challenge to investigate biomarkers of PI3K, p38 MAPK and JAK/STAT activation by immunohistochemistry...
2018: Biomarker Research
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