The MYCN-HMGA2-CDKN2A pathway in non-small cell lung carcinoma--differences in histological subtypes.

Background: Extensive research has increased our understanding of the molecular alterations needed for non-small cell lung cancer (NSCLC) development. Deregulation of a pathway including MYCN, HMGA2 and CDKN2A, with the participation of DICER1, is of importance in several solid tumours, and may also be of significance in the pathogenesis of NSCLC.

Methods: Gene expression of MYCN, HMGA2, CDKN2A and DICER1 were investigated with RT-qPCR in surgically resected NSCLC tumour tissue from 175 patients.

Genome-wide DNA methylation analyses in lung adenocarcinomas: Association with EGFR, KRAS and TP53 mutation status, gene expression and prognosis.

Background: DNA methylation alterations are early events in tumorigenesis and important in the regulation of gene expression in cancer cells. Lung cancer patients have in general a poor prognosis, and a deeper insight into the epigenetic landscape in lung adenocarcinoma tumors and its prognostic implications is needed.

Results: We determined whole-genome DNA methylation profiles of 164 fresh frozen lung adenocarcinoma samples and 19 samples of matched normal lung tissue using the Illumina Infinium 450K array.

Construction of a plasmid coding for green fluorescent protein tagged cathepsin L and data on expression in colorectal carcinoma cells.

The endo-lysosomal cysteine cathepsin L has recently been shown to have moonlighting activities in that its unexpected nuclear localization in colorectal carcinoma cells is involved in cell cycle progression (Tamhane et al., 2015) [1]. Here, we show data on the construction and sequence of a plasmid coding for human cathepsin L tagged with an enhanced green fluorescent protein (phCL-EGFP) in which the fluorescent protein is covalently attached to the C-terminus of the protease.

Lung cancer treatment is influenced by income, education, age and place of residence in a country with universal health coverage.

Selection of lung cancer treatment should be based on tumour characteristics, physiological reserves and preferences of the patient. Our aims were to identify and quantify other factors associated with treatment received. Lung cancer patient data from 2002 to 2011 were obtained from the national population-based Cancer Registry of Norway, Statistics Norway and the Norwegian Patient Register.

Identification of prostate cancer biomarkers in urinary exosomes.

Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers since tumour-specific molecules can be found in exosomes isolated from biological fluids. We have here investigated the proteome of urinary exosomes by using mass spectrometry to identify proteins differentially expressed in prostate cancer patients compared to healthy male controls. In total, 15 control and 16 prostate cancer samples of urinary exosomes were analyzed.

Biological properties of extracellular vesicles and their physiological functions.

In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored.

Hypoxia as a cause of treatment failure in non-small cell carcinoma of the lung.

Hypoxia is an important factor in tumor biology and is both a predictive and a prognostic factor in non-small cell lung cancer. The negative effect of low oxygenation on radiation therapy effect has been known for decades, but more recent research has emphasized that hypoxia also has a profound effect on a tumor's aggression and metastatic propensity. In this review, current knowledge on both these aspects of treatment failure in NSCLC due to hypoxia has been discussed, along with a presentation of modern methods for hypoxia measurement and current therapeutical interventions to circumvent the negative effect of hypoxia on treatment results.

Four DNA methylation biomarkers in biliary brush samples accurately identify the presence of cholangiocarcinoma.

Unlabelled: Early detection of the highly aggressive malignancy cholangiocarcinoma (CCA) remains a challenge but has the potential to render the tumor curable by surgical removal. This study evaluates a biomarker panel for the diagnosis of CCA by DNA methylation analyses of biliary brush samples. The methylation status of 13 candidate genes (CDO1, CNRIP1, DCLK1, FBN1, INA, MAL, SEPT9, SFRP1, SNCA, SPG20, TMEFF2, VIM, and ZSCAN18) was investigated in 93 tissue samples (39 CCAs and 54 nonmalignant controls) using quantitative methylation-specific polymerase chain reaction.

Methylated RASSF1A in malignant peripheral nerve sheath tumors identifies neurofibromatosis type 1 patients with inferior prognosis.

Background: Malignant peripheral nerve sheath tumor (MPNST) is a rare and highly aggressive disease with no evidence of effect from adjuvant therapy. It is further associated with the hereditary syndrome neurofibromatosis type 1 (NF1). Silencing of the tumor suppressor gene RASSF1A through DNA promoter hypermethylation is known to be involved in cancer development, but its impact in MPNSTs remains unsettled.

Years of life lost as a measure of cancer burden on a national level.

Background: The severity of cancers is often measured in number of deaths. However, number of years of life lost (YLL) may be a more appropriate indicator of impact on society. Here we have calculated the YLL of adult cancers in Norway for the year 2012, as well as for the previous 15-year period.

Genomic characterization of ependymomas reveals 6q loss as the most common aberration.

Ependymomas are rare tumors of the central nervous system (CNS). They are classified based on tumor histology and grade, but the prognostic value of the WHO grading system remains controversial. Treatment is mainly surgical and by radiation.

The chaperone domain BRICHOS prevents CNS toxicity of amyloid-β peptide in Drosophila melanogaster.

Aggregation of the amyloid-β peptide (Aβ) into toxic oligomers and amyloid fibrils is linked to the development of Alzheimer's disease (AD). Mutations of the BRICHOS chaperone domain are associated with amyloid disease and recent in vitro data show that BRICHOS efficiently delays Aβ42 oligomerization and fibril formation. We have generated transgenic Drosophila melanogaster flies that express the Aβ42 peptide and the BRICHOS domain in the central nervous system (CNS).

Differential DNA methylation analysis of breast cancer reveals the impact of immune signaling in radiation therapy.

Radiotherapy (RT) is a central treatment modality for breast cancer patients. The purpose of our study was to investigate the DNA methylation changes in tumors following RT, and to identify epigenetic markers predicting treatment outcome. Paired biopsies from patients with inoperable breast cancer were collected both before irradiation (n = 20) and after receiving 10-24 Gray (Gy) (n = 19).

Mutation screening of the TP53 gene by temporal temperature gel electrophoresis (TTGE).

A protocol for detection of mutations in the TP53 gene using temporal temperature gradient electrophoresis (TTGE) is described. TTGE is a mutation detection technique that separates DNA fragments differing by single base pairs according to their melting properties in a denaturing gel. It is based on constant denaturing conditions in the gel combined with a temperature gradient during the electrophoretic run.

Regulation of exosome release by glycosphingolipids and flotillins.

Exosomes are released by cells after fusion of multivesicular bodies with the plasma membrane. The molecular mechanism of this process is still unclear. We investigated the role of sphingolipids and flotillins, which constitute a raft-associated family of proteins, in the release of exosomes.

Unique microRNA-profiles in EGFR-mutated lung adenocarcinomas.

The findings of mutations and the development of targeted therapies have improved lung cancer management. Still, the prognosis remains poor, and we need to know more about the genetic and epigenetic alterations in lung cancer. MicroRNAs are involved in crucial biological processes like carcinogenesis by regulating gene expression at the post-transcriptional level.

Modifications in dynamic contrast-enhanced magnetic resonance imaging parameters after α-particle-emitting ²²⁷Th-trastuzumab therapy of HER2-expressing ovarian cancer xenografts.

Purpose: The purpose of this study was to investigate the effect of α-particle-emitting (227)Th-trastuzumab radioimmunotherapy on tumor vasculature to increase the knowledge about the mechanisms of action of (227)Th-trastuzumab.

Methods And Materials: Human HER2-expressing SKOV-3 ovarian cancer xenografts were grown bilaterally in athymic nude mice. Mice with tumor volumes 253 ± 36 mm(3) (mean ± SEM) were treated with a single injection of either (227)Th-trastuzumab at a dose of 1000 kBq/kg body weight (treated group, n=14 tumors) or 0.

Effect of vitamin D supplementation and ultraviolet B exposure on serum 25-hydroxyvitamin D concentrations in healthy volunteers: a randomized, crossover clinical trial.

Background: Solar ultraviolet (UV) radiation during the summer and vitamin D supplementation are two major sources of vitamin D for humans at northern latitudes. However, little is known about the relative efficiency of these two vitamin D sources.

Objectives: The main goal was to compare the efficiency of high-dose oral vitamin D3 supplementation (2000 IU per day for 30 days) with a simulated summer UV exposure [10 sunbed sessions to a total dose of 23·8 standard erythema doses (SED)] to improve vitamin D status.

Targeted alpha therapy with 227Th-trastuzumab of intraperitoneal ovarian cancer in nude mice.

Unlabelled: The aim of the current study was to investigate the therapeutic effect of 227Th-radioimmunotherapy on intraperitoneally growing human bioluminescent HER2 positive ovarian cancer cells.

Methods: In vitro toxicity of 227Th-trastuzumab in bioluminescent SKOV3-luc-D3 ovarian cancer cells was assessed in a growth assay. The biodistribution of intraperitoneally administrated 227Th-trastuzumab in athymic nude mice without tumor cells was determined.

Exosomal miRNAs as Biomarkers for Prostate Cancer.

miRNAs are small non-coding RNAs that finely regulate gene expression in cells. Alterations in miRNA expression have been associated with development of cancer, and miRNAs are now being investigated as biomarkers for cancer as well as other diseases. Recently, miRNAs have been found outside cells in body fluids.

Nuclear legumain activity in colorectal cancer.

The cysteine protease legumain is involved in several biological and pathological processes, and the protease has been found over-expressed and associated with an invasive and metastatic phenotype in a number of solid tumors. Consequently, legumain has been proposed as a prognostic marker for certain cancers, and a potential therapeutic target. Nevertheless, details on how legumain advances malignant progression along with regulation of its proteolytic activity are unclear.

Incidence and survival of malignant pleural mesothelioma in norway: a population-based study of 1686 cases.

Background: Asbestos-related malignant pleural mesothelioma is one of the most lethal tumor types. The advent of antimetabolite treatment as pemetrexed, introduced in the early 2000s, may have increased survival on a population basis. In this study, we have analyzed population-based incidence and survival data over the last 40 years.

Effect of the MDM2 promoter polymorphisms SNP309T>G and SNP285G>C on the risk of ovarian cancer in BRCA1 mutation carriers.

Background: While BRCA mutation carriers possess a 20-40% lifetime risk of developing ovarian cancer, knowledge about genetic modifying factors influencing the phenotypic expression remains obscure. We explored the distribution of the MDM2 polymorphisms SNP309T>G and the recently discovered SNP285G>C in Norwegian patients with BRCA related ovarian cancer.

Methods: 221 BRCA related ovarian cancer cases (BRCA1; n = 161 and BRCA2; n = 60) were tested for the MDM2 polymorphisms.

Proteomic analysis of microvesicles released by the human prostate cancer cell line PC-3.

Cancer biomarkers are invaluable tools for cancer detection, prognosis, and treatment. Recently, microvesicles have appeared as a novel source for cancer biomarkers. We present here the results from a proteomic analysis of microvesicles released to the extracellular environment by the metastatic prostate cancer cell line PC-3.

MGMT promoter methylation in gliomas-assessment by pyrosequencing and quantitative methylation-specific PCR.

Background: Methylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter is a favorable prognostic factor in glioblastoma patients. However, reported methylation frequencies vary significantly partly due to lack of consensus in the choice of analytical method.

Method: We examined 35 low- and 99 high-grade gliomas using quantitative methylation specific PCR (qMSP) and pyrosequencing.