Development of PancRISK, a urine biomarker-based risk score for stratified screening of pancreatic cancer patients

© The Author(s) 2019. Published by Springer Nature on behalf of Cancer Research UK.BACKGROUND: An accurate and simple risk prediction model that would facilitate earlier detection of pancreatic adenocarcinoma (PDAC) is not available at present. In this study, we compare different algorithms of risk prediction in order to select the best one for constructing a biomarker-based risk score, PancRISK. METHODS: Three hundred and seventy-nine patients with available measurements of three urine biomarkers, (LYVE1, REG1B and TFF1) using retrospectively collected samples, as well as creatinine and age, were randomly split into training and validation sets, following stratification into cases (PDAC) and controls (healthy patients). Several machine learning algorithms were used, and their performance characteristics were compared. The latter included AUC (area under ROC curve) and sensitivity at clinically relevant specificity. RESULTS: None of the algorithms significantly outperformed all others. A logistic regression model, the easiest to interpret, was incorporated into a PancRISK score and subsequently evaluated on the whole data set. The PancRISK performance could be even further improved when CA19-9, commonly used PDAC biomarker, is added to the model. CONCLUSION: PancRISK score enables easy interpretation of the biomarker panel data and is currently being tested to confirm that it can be used for stratification of patients at risk of developing pancreatic cancer completely non-invasively, using urine samples.Peer reviewe

Survey of five major grapevine viruses infecting Blatina and Žilavka cultivars in Bosnia and Herzegovina

The sanitary status of grapevines has not yet been considered sufficiently in vineyards throughout Bosnia and Herzegovina (BiH). An extensive survey of five major grapevine viruses in the country was carried out in 2019. A total of 630 samples from the two dominant autochthonous cultivars, namedZ? ilavka and Blatina, were tested by DAS-ELISA for the presence of grapevine leafroll-associated viruses (GLRaV-1 and 3), grapevine fleck virus (GFkV), grapevine fanleaf virus (GFLV) and Arabis mosaic virus (ArMV). Eighty-eight %of the samples were positive for at least one virus, and all five viruses were detected, thought with different incidence, i.e. GLRaV-3 (84%), GFLV (43%), GLRaV-1 (14%), GFkV (10%) and ArMV (0.2%). The majority of infected plants (about 75%) were asymptomatic. Specific virus symptoms were observed in the remaining infected plants, together with the reported GLRaV vectors, Planococcus ficus and Parthenolecanium corni, while nematodes of the Xiphinema genus were not found in the GFLV- or ArMV-infected vineyards. The GLRaV-3 CP phylogenetic analyses showed 75-100% nucleotide identity between the BiH and reference isolates, and the BiH isolates clustered into the major group. The dNS/dS ratio indicated a negative selection of the virus population, and the lack of geographical structuring within the population was observed. In addition, putative GLRaV-3 recombinants with breakpoints in the 5' of the CP gene were detected, while no recombinant strains were identified for the other four viruses. The obtained results indicate a deteriorated sanitary status of the cultivated grapevines, the prevalence and intraspecies genetic diversity of GLRaV-3 throughout the country. The establishment of certified grapevine material and adequate virus vector control is therefore of primary importance to prevent further spread of these viruses. This study presents the results of the first molecular characterisation of grapevine viruses in Bosnia and Herzegovina

Molecular Analysis of Precursor Lesions in Familial Pancreatic Cancer

PMCID: PMC3553106This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Regularized gene selection in cancer microarray meta-analysis

<p>Abstract</p> <p>Background</p> <p>In cancer studies, it is common that multiple microarray experiments are conducted to measure the same clinical outcome and expressions of the same set of genes. An important goal of such experiments is to identify a subset of genes that can potentially serve as predictive markers for cancer development and progression. Analyses of individual experiments may lead to unreliable gene selection results because of the small sample sizes. Meta analysis can be used to pool multiple experiments, increase statistical power, and achieve more reliable gene selection. The meta analysis of cancer microarray data is challenging because of the high dimensionality of gene expressions and the differences in experimental settings amongst different experiments.</p> <p>Results</p> <p>We propose a Meta Threshold Gradient Descent Regularization (MTGDR) approach for gene selection in the meta analysis of cancer microarray data. The MTGDR has many advantages over existing approaches. It allows different experiments to have different experimental settings. It can account for the joint effects of multiple genes on cancer, and it can select the same set of cancer-associated genes across multiple experiments. Simulation studies and analyses of multiple pancreatic and liver cancer experiments demonstrate the superior performance of the MTGDR.</p> <p>Conclusion</p> <p>The MTGDR provides an effective way of analyzing multiple cancer microarray studies and selecting reliable cancer-associated genes.</p

Tumor microenvironment defines the invasive phenotype of AIP-mutation-positive pituitary tumors

The molecular mechanisms leading to aryl hydrocarbon receptor interacting protein (AIP) mutation-induced aggressive, young-onset growth hormone-secreting pituitary tumors are not fully understood. In this study, we have identified that AIP-mutation-positive tumors are infiltrated by a large number of macrophages compared to sporadic tumors. Tissue from pituitary-specific Aip-knockout (AipFlox/Flox;Hesx1Cre/+) mice recapitulated this phenotype. Our human pituitary tumor transcriptome data revealed the "epithelial-to-mesenchymal transition (EMT) pathway" as one of the most significantly altered pathways in AIPpos tumors. Our in vitro data suggest that bone marrow-derived macrophage-conditioned media induces more prominent EMT-like phenotype and enhanced migratory and invasive properties in Aip-knockdown somatomammotroph cells compared to non-targeting controls. We identified that tumor-derived cytokine CCL5 is upregulated in AIP-mutation-positive human adenomas. Aip-knockdown GH3 cell-conditioned media increases macrophage migration, which is inhibited by the CCL5/CCR5 antagonist maraviroc. Our results suggest that a crosstalk between the tumor and its microenvironment plays a key role in the invasive nature of AIP-mutation-positive tumors and the CCL5/CCR5 pathway is a novel potential therapeutic target

Supplementary data for article: Pantelić, N.; Zmejkovski, B. B.; Kolundžija, B.; Crnogorac, M. Đ.; Vujić, J. M.; Dojčinović, B.; Trifunović, S. R.; Stanojković, T. P.; Sabo, T. J.; Kaluđerović, G. N. In Vitro Antitumor Activity, Metal Uptake and Reactivity with Ascorbic Acid and BSA of Some Gold(III) Complexes with N,N′-Ethylenediamine Bidentate Ester Ligands. Journal of Inorganic Biochemistry 2017, 172, 55–66. https://doi.org/10.1016/j.jinorgbio.2017.04.001

Supplementary material for: [https://doi.org/10.1016/j.jinorgbio.2017.04.001]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2478]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3070

A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.

© 2014 Haider et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Improved usage of the repertoires of pancreatic ductal adenocarcinoma (PDAC) profiles is crucially needed to guide the development of predictive and prognostic tools that could inform the selection of treatment options

Rituximab in adult minimal change disease and focal segmental glomerulosclerosis - What is known and what is still unknown?

Primary forms of minimal change disease and focal segmental glomerulosclerosis are rare podocytopathies and clinically characterized by nephrotic syndrome. Glucocorticoids are the cornerstone of the initial immunosuppressive treatment in these two entities. Especially among adults with minimal change disease or focal segmental glomerulosclerosis, relapses, steroid dependence or resistance are common and necessitate re-initiation of steroids and other immunosuppressants. Effective steroid-sparing therapies and introduction of less toxic immunosuppressive agents are urgently needed to reduce undesirable side effects, in particular for patients whose disease course is complex. Rituximab, a B cell depleting monoclonal antibody, is increasingly used off-label in these circumstances, despite a low level of evidence for adult patients. Hence, critical questions concerning drug-safety, long-term efficacy and the optimal regimen for rituximab-treatment remain unanswered. Evidence in the form of large, multicenter studies and randomized controlled trials are urgently needed to overcome these limitations