History, Implementation and Current Use of the IFCC-IUPAC's Nomenclature for Properties and Units (NPU) Terminology in Denmark, Norway and Sweden.

Electronic exchange of health care data demands code/terminology systems. In the Scandinavian countries, the IFCC-IUPAC's Nomenclature for Properties and Units (NPU) terminology is used for results in biochemistry, pharmacology, and immunology. Implementation, use and administration of NPU has differed between the countries despite similar health care and lab sectors.

Properties and units in the clinical laboratory sciences part XXIV. Properties and units in clinical molecular genetics (technical report 2017).

This document describes the application of the syntax, semantic rules, and format of the Nomenclature for Properties and Units (NPU) terminology for coded dedicated kinds-of-property in the subject field of clinical molecular genetics. A vocabulary for NPU definitions in this field, based on international terminology and nomenclature, is introduced; examples of actual NPU definitions for different types of investigations are given and explained.

A transcriptomics data-driven gene space accurately predicts liver cytopathology and drug-induced liver injury.

Predicting unanticipated harmful effects of chemicals and drug molecules is a difficult and costly task. Here we utilize a 'big data compacting and data fusion'-concept to capture diverse adverse outcomes on cellular and organismal levels. The approach generates from transcriptomics data set a 'predictive toxicogenomics space' (PTGS) tool composed of 1,331 genes distributed over 14 overlapping cytotoxicity-related gene space components.

Arsenic alters global histone modifications in lymphocytes in vitro and in vivo.

Arsenic, an established carcinogen and toxicant, occurs in drinking water and food and affects millions of people worldwide. Arsenic appears to interfere with gene expression through epigenetic processes, such as DNA methylation and post-translational histone modifications. We investigated the effects of arsenic on histone residues in vivo as well as in vitro.

Toward the Replacement of Animal Experiments through the Bioinformatics-driven Analysis of 'Omics' Data from Human Cell Cultures.

This paper outlines the work for which Roland Grafström and Pekka Kohonen were awarded the 2014 Lush Science Prize. The research activities of the Grafström laboratory have, for many years, covered cancer biology studies, as well as the development and application of toxicity-predictive in vitro models to determine chemical safety. Through the integration of in silico analyses of diverse types of genomics data (transcriptomic and proteomic), their efforts have proved to fit well into the recently-developed Adverse Outcome Pathway paradigm.

YAP1 is a potential biomarker for cetuximab resistance in head and neck cancer.

Objectives: Targeted therapy against the epidermal growth factor receptor (EGFR) only variably represents a therapeutic advance in head and neck squamous cell carcinoma (HNSCC). This study addresses the need of biomarkers of treatment response to the EGFR-targeting antibody cetuximab (Erbitux®).

Materials And Methods: The intrinsic cetuximab sensitivity of HNSCC cell lines was assessed by a crystal violet assay.

Cancer biology, toxicology and alternative methods development go hand-in-hand.

Toxicological research faces the challenge of integrating knowledge from diverse fields and novel technological developments generally in the biological and medical sciences. We discuss herein the fact that the multiple facets of cancer research, including discovery related to mechanisms, treatment and diagnosis, overlap many up and coming interest areas in toxicology, including the need for improved methods and analysis tools. Common to both disciplines, in vitro and in silico methods serve as alternative investigation routes to animal studies.

The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing.

The aim of the SEURAT-1 (Safety Evaluation Ultimately Replacing Animal Testing-1) research cluster, comprised of seven EU FP7 Health projects co-financed by Cosmetics Europe, is to generate a proof-of-concept to show how the latest technologies, systems toxicology and toxicogenomics can be combined to deliver a test replacement for repeated dose systemic toxicity testing on animals. The SEURAT-1 strategy is to adopt a mode-of-action framework to describe repeated dose toxicity, combining in vitro and in silico methods to derive predictions of in vivo toxicity responses. ToxBank is the cross-cluster infrastructure project whose activities include the development of a data warehouse to provide a web-accessible shared repository of research data and protocols, a physical compounds repository, reference or "gold compounds" for use across the cluster (available via wiki.

Requirement of apoptotic protease-activating factor-1 for bortezomib-induced apoptosis but not for Fas-mediated apoptosis in human leukemic cells.

Bortezomib is a highly selective inhibitor of the 26S proteasome and has been approved for clinical use in the treatment of relapsing and refractory multiple myeloma and mantle cell lymphoma. Clinical trials are also underway to assess the role of bortezomib in several other human malignancies, including leukemia. However, the mechanism(s) by which bortezomib acts remain to be fully understood.

MAML1 acts cooperatively with EGR1 to activate EGR1-regulated promoters: implications for nephrogenesis and the development of renal cancer.

Mastermind-like 1 (MAML1) is a transcriptional coregulator of activators in various signaling pathways, such as Notch, p53, myocyte enhancer factor 2C (MEF2C) and beta-catenin. In earlier studies, we demonstrated that MAML1 enhanced p300 acetyltransferase activity, which increased the acetylation of Notch by p300. In this study, we show that MAML1 strongly induced acetylation of the transcription factor early growth response-1 (EGR1) by p300, and increased EGR1 protein expression in embryonic kidney cells.

CD44 expression in oro-pharyngeal carcinoma tissues and cell lines.

Expression of CD44, a transmembrane hyaluronan-binding glycoprotein, is variably considered to have prognostic significance for different cancers, including oral squamous cell carcinoma. Although unclear at present, tissue-specific expression of particular isoforms of CD44 might underlie the different outcomes in currently available studies. We mined public transcriptomics databases for gene expression data on CD44, and analyzed normal, immortalized and tumour-derived human cell lines for splice variants of CD44 at both the transcript and protein levels.

Differentiation-promoting culture of competent and noncompetent keratinocytes identifies biomarkers for head and neck cancer.

Aberrant contact-inhibited proliferation and differentiation induction couple with tumor severity, albeit with an imprecise association with prognosis. Assessment of contact inhibition and differentiation-promoting culture in this study of normal and immortalized oral keratinocytes (NOK and SVpgC2a, respectively) demonstrated elevated cloning ability and saturation density in the immortalized versus normal state, including consistent absence of differentiated morphological features. Transcriptomic analysis implicated 48 gene ontology categories, 8 molecular networks, and 10 key regulator genes in confluency-induced differentiation of NOK, all of which remained nonregulated in SVpgC2a.

Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines.

Background: Radiotherapy is the main therapy for head and neck squamous cell carcinoma (HNSCC); however, treatment resistance and local recurrence are significant problems, highlighting the need for predictive markers. In this study, we evaluated selected proteins, mutations, and single nucleotide polymorphisms (SNPs) involved in apoptosis, cell proliferation, and DNA repair alone or combined as predictive markers for radioresponse in 42 HNSCC cell lines.

Methods: The expression of epidermal growth factor receptor, survivin, Bax, Bcl-2, Bcl-X(L) , cyclooxygenase-2 (COX-2), and heat shock protein 70 was analyzed by ELISA.

Fibronectin 1 is a potential biomarker for radioresistance in head and neck squamous cell carcinoma.

Radiotherapy remains the backbone of head and neck cancer therapy but response is sometimes impeded by tumor radioresistance. Identifying predictive biomarkers of radiotherapy response is a crucial step towards personalized therapy. The aim of this study was to explore gene expression data in search of biomarkers predictive of the response to radiotherapy in head and neck squamous cell carcinoma (HNSCC).

Formaldehyde dehydrogenase: beyond phase I metabolism.

Formaldehyde dehydrogenase, formally Class III alcohol dehydrogenase (ADH3), has recently been discovered to partially regulate nitrosothiol homeostasis by catalyzing the reduction of the endogenous nitrosylating agent S-nitrosoglutathione (GSNO). Several studies have implicated this enzyme, and in particular GSNO reduction, as playing an important role in conditions such as asthma, cardiovascular disease, and immune function. While ADH3 has received considerable attention in the biomedical literature where it is often referred to as GSNO reductase (GSNOR), ADH3-mediated GSNO reduction has received comparatively less attention in the environmental toxicology community.

Matrix metalloproteinase-7 and -13 expression associate to cisplatin resistance in head and neck cancer cell lines.

Concomitant chemoradiotherapy is a common treatment for advanced head and neck squamous cell carcinomas (HNSCC). Cisplatin is the backbone of chemotherapy regimens used to treat HNSCC. Therefore, the aim of this study was to identify predictive markers for cisplatin treatment outcome in HNSCC.

Multiple genotypic aberrances associate to terminal differentiation-deficiency of an oral squamous cell carcinoma in serum-free culture.

Oral squamous cell carcinoma (OSCC) lines proliferative in the serum-free conditions devised for normal oral keratinocytes (NOK) are virtually absent, complicating studies of carcinogenesis. A tongue squamous cell carcinoma generated under conditions for normal cell culture an apparently immortal line (termed LK0412) that has undergone >or=200 population doublings from over a year in culture. LK0412 exhibited epithelial morphology, intermediate filaments, desmosomes, and cytokeratin.

The application of normal, SV40 T-antigen-immortalised and tumour-derived oral keratinocytes, under serum-free conditions, to the study of the probability of cancer progression as a result of environmental exposure to chemicals.

In vitro models are currently not considered to be suitable replacements for animals in experiments to assess the multiple factors that underlie the development of cancer as a result of environmental exposure to chemicals. An evaluation was conducted on the potential use of normal keratinocytes, the SV40 T-antigen-immortalised keratinocyte cell line, SVpgC2a, and the carcinoma cell line, SqCC/Y1, alone and in combination, and under standardised serum-free culture conditions, to study oral cancer progression. In addition, features considered to be central to cancer development as a result of environmental exposure to chemicals, were analysed.

Bioinformatics processing of protein and transcript profiles of normal and transformed cell lines indicates functional impairment of transcriptional regulators in buccal carcinoma.

Normal and two transformed buccal keratinocyte lines were cultured under a standardized condition to explore mechanisms of carcinogenesis and tumor marker expression at transcript and protein levels. An approach combining three bioinformatic programs allowed coupling of abundant proteins and large-scale transcript data to low-abundance transcriptional regulators. The analysis identified previously proposed and suggested novel protein biomarkers, gene ontology categories, molecular networks, and functionally impaired key regulator genes for buccal/oral carcinoma.