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Biomarker Research

Emily M Christman, Parthasarathy Chandrakesan, Nathaniel Weygant, John T Maple, William M Tierney, Kenneth J Vega, Courtney W Houchen
Background: Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) incidence has been increasing in the United States for greater than 30 years. For the majority of EAC patients, treatment is limited and prognosis poor. Doublecortin like kinase-1 (DCLK1) is a cancer stem cell marker with elevated expression in BE patients with high grade dysplasia and/or EAC. This prospective cohort study was designed to compare serum DCLK1 levels before and after EAC treatment with endoscopic mucosal resection (EMR) and/or radio-frequency ablation (RFA)...
2019: Biomarker Research
Shabnum Khawaja, Lena Jafri, Imran Siddiqui, Madiha Hashmi, Farooq Ghani
In current clinical practice, Serum Creatinine (SCr) is a commonly used marker for the diagnosis of acute kidney injury (AKI). Unfortunately, due to a delayed increase in SCr, it is unable to accurately estimate the timing of the injury. The purpose of this study was to assess the ability of plasma neutrophil gelatinase-associated lipocalin (pNGAL) to predict AKI in critically ill adult patients . The study was conducted at the Section of Chemical Pathology, Department of Pathology& Laboratory Medicine in collaboration with Department of Anesthesiology, at Aga Khan University Hospital in Karachi, Pakistan...
2019: Biomarker Research
Anthony Khoo, Joseph Frasca, David Schultz
Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterised by significant clinical heterogeneity and as such reliable biomarkers are required to measure disease activity and assess treatment response. Recent advances in our understanding of disease pathogenesis and the discovery of novel serum-based, electrophysiologic and imaging biomarkers allow clinicians to make more informed decisions regarding individualised treatment regimes. As a chronic immune-mediated process typified by relapse following withdrawal of immunomodulatory therapy, a substantial proportion of patients with CIDP require long term treatment with intravenous immunoglobulin (IVIg), a scarce and expensive donor-derived resource...
2019: Biomarker Research
Dipanjan Basu, Cláudia M Salgado, Janki R Patel, Joie Zabec, Ryan M Hoehl, Bruce Bauer, Miguel Reyes-Múgica
Factors regulating transcription of pluripotency genes in congenital nevo-melanocytes are not known. Nevo-melanocytes belong somewhere in-between the ends of a spectrum where the normal epidermal melanocyte represents one end and a melanoma cell with multiple genetic abnormalities represents the other. Cells from large/giant congenital nevi (L/GCMN), unlike normal melanocytes, grow colonies on soft agar and express pluripotency markers, similar to melanoma cells. In this study normal melanocytes, SKMEL28 melanoma cells and nevo-melanocytes isolated from three L/GCMN patients were exposed to niche factors bFGF and IGF1 in vitro at physiological doses, and expression of a panel of pluripotency markers was determined by RT-PCR...
2019: Biomarker Research
Sebastian Lundgren, Helena Fagerström-Vahman, Cheng Zhang, Liv Ben-Dror, Adil Mardinoglu, Mathias Uhlen, Björn Nodin, Karin Jirström
There is a great unmet clinical need to identify patients with thin primary cutaneous melanomas (T1, Breslow thickness ≤ 1 mm) who have a high risk for tumour recurrence and death from melanoma. Kin of IRRE-like protein 1 (KIRREL/NEPH1) is expressed in podocytes and involved in glomerular filtration. Screening in the Human Protein Atlas portal revealed a particularly high expression of KIRREL in melanoma, both at the mRNA and protein levels. In this study, we followed up on these findings and examined the prognostic value of KIRREL in a population-based cohort...
2019: Biomarker Research
M J Morris, L B Hesson, R C Poulos, R L Ward, J W H Wong, N A Youngson
Background: Altered mitochondrial function and large-scale changes to DNA methylation patterns in the nuclear genome are both hallmarks of colorectal cancer (CRC). Mitochondria have multiple copies of a 16 kb circular genome that contains genes that are vital for their function. While DNA methylation is known to alter the nuclear genome in CRC, it is not clear whether it could have a similar influence in mtDNA; indeed, currently, the issue of whether mitochondrial genome (mtDNA) methylation occurs is controversial...
2018: Biomarker Research
Christine V Ichim, Dzana D Dervovic, Lap Shu Alan Chan, Claire J Robertson, Alden Chesney, Marciano D Reis, Richard A Wells
Background: In patients with myelodysplastic syndrome (MDS), bone marrow cells have an increased predisposition to apoptosis, yet MDS cells outcompete normal bone marrow (BM)-- suggesting that factors regulating growth potential may be important in MDS. We previously identified v-Erb A related-2 (EAR-2, NR2F6) as a gene involved in control of growth ability. Methods: Bone marrow obtained from C57BL/6 mice was transfected with a retrovirus containing EAR-2-IRES-GFP...
2018: Biomarker Research
Natalia Castaño-Rodríguez, Georgia L Popple, Gloria Liliana Porras-Hurtado, José Luis Cardona-Deazza, Juan José Montoya-Martinez, Antonio Javier Cadavid-Velez, Héctor William Toro-Hidalgo, Alba Ruth Cobo-Alvarado, Ofelia Del Socorro Hincapié-Rincón, Stephen M Riordan, Nadeem O Kaakoush
OPCML hypermethylation is considered a promising cancer biomarker. We examined methylation levels in the first exon of OPCML in two patient cohorts within the esophageal adenocarcinoma and gastric adenocarcinoma cascades and in a range of cell-lines using a custom PyroMark CpG assay. Methylation levels were significantly higher in esophageal tissue with histologically confirmed glandular mucosa as compared to tissue from normal esophagi or gastro-esophageal reflux disease. Higher levels of OPCML methylation were absent in the adjacent normal esophageal tissue of patients with glandular mucosa...
2018: Biomarker Research
Rosemarie Tremblay-LeMay, Nasrin Rastgoo, Maryam Pourabdollah, Hong Chang
Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is of great interest in human cancer. It has been shown to have a dual nature, as it can act as a gene repressor or activator. Studies have highlighted the various roles of EZH2 in the pathophysiology of multiple myeloma (MM). It was also shown to have a role in the development of drug resistance in MM. There are several ongoing clinical trials of EZH2 inhibitors in haematological malignancies. Pre-clinical studies have provided a rationale for the therapeutic relevance of EZH2 inhibitors in MM...
2018: 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
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