Biomechanical Properties of Common Carotid Arteries Assessed by Circumferential 2D Strain and β Stiffness Index in Patients With Ankylosing Spondylitis.

Objective: Ankylosing spondylitis (AS) is associated with an elevated risk of cardiovascular disease (CVD) related to atherosclerosis, preceded by arterial stiffness. We aimed to examine common carotid artery (CCA) biomechanical properties using ultrasound to calculate β stiffness index (indicating arterial stiffness) and, a more recently developed technique, 2-dimensional (2D) speckle tracking strain (indicating arterial motion and deformation, strain) to (1) compare with age- and sex-matched controls, and (2) analyze relationships between strain and stiffness with disease characteristics and traditional risk factors for CVD in patients with AS.

Methods: In this cross-sectional study, a cohort of 149 patients with AS, mean age 55.

Patterns of comorbidity and disease characteristics among patients with ankylosing spondylitis-a cross-sectional study.

The knowledge of the development of comorbidities in patients with ankylosing spondylitis (AS) is limited. The aim of this study was to analyse associations between AS disease characteristics and comorbidity and to evaluate patterns of comorbidities in patients with AS. Patients with AS, fulfilling the modified New York Criteria, were identified (n = 346, mean age 56 ± 15 years, 75% men, 99% HLA B27 positive).

Effect of surface treatments and aging in water on bond strength to zirconia.

The current study evaluated the effects of various pretreatments and aging in water on the bond strength to hot isostatic pressed yttrium-oxide partially stabilized zirconia. Sixty zirconia ceramic specimens (Denzir) were randomly divided into three groups of 20. One group of specimens (n=10) was then bonded to each other using a resin composite cement (RelyX Unicem), the second group (n=10) was bonded with RelyX Unicem and a metal primer (Metal Primer II), while the third group (n=10) was bonded with RelyX Unicem and a ceramic primer (Ceramic Primer).

Inhibitory effects of estrogen receptor beta on specific hormone-responsive gene expression and association with disease outcome in primary breast cancer.

Introduction: The impact of interactions between the two estrogen receptor (ER) subtypes, ERalpha and ERbeta, on gene expression in breast cancer biology is not clear. The goal of this study was to examine transcriptomic alterations in cancer cells co-expressing both receptors and the association of gene expression signatures with disease outcome.

Methods: Transcriptional effects of ERbeta overexpression were determined in a stably transfected cell line derived from ERalpha-positive T-47D cells.

Quantitative real-time PCR analysis and microarray-based RNA expression of HER2 in relation to outcome.

Background: Our aim was to use quantitative real-time PCR (Q-PCR) and RNA expression profiles (RNA-EPs) to investigate HER2 status in relation to outcome.

Patients And Methods: Cut-off levels for Q-PCR and RNA-EP were established in relation to immunohistochemistry (IHC) validated by FISH in a test set of frozen tissue samples from 40 primary breast cancers. The HER2 status was subsequently studied in another validation set of 306 tumors, where Q-PCR and RNA-EP results were compared with previously carried out IHC that we had validated by chromogenic in situ hybridization (CISH).

Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer.

Histologic grading of breast cancer defines morphologic subtypes informative of metastatic potential, although not without considerable interobserver disagreement and clinical heterogeneity particularly among the moderately differentiated grade 2 (G2) tumors. We posited that a gene expression signature capable of discerning tumors of grade 1 (G1) and grade 3 (G3) histology might provide a more objective measure of grade with prognostic benefit for patients with G2 disease. To this end, we studied the expression profiles of 347 primary invasive breast tumors analyzed on Affymetrix microarrays.

Gene expression in 16q is associated with survival and differs between Sørlie breast cancer subtypes.

We have investigated the relationship between gene expression and chromosomal positions in 402 breast cancer patients. Using an overrepresentation approach based on Fisher's exact test, we identified disproportionate contributions of specific chromosomal positions to genes associated with survival. Our major finding is that the gene expression in the long arm of chromosome 16 stands out in its relationship to survival.

Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome.

The beneficial effect of the selective estrogen receptor (ER) modulator tamoxifen in the treatment and prevention of breast cancer is assumed to be through its ability to antagonize the stimulatory actions of estrogen, although tamoxifen can also have some estrogen-like agonist effects. Here, we report that, in addition to these mixed agonist/antagonist actions, tamoxifen can also selectively regulate a unique set of >60 genes, which are minimally regulated by estradiol (E2) or raloxifene in ERalpha-positive MCF-7 human breast cancer cells. This gene regulation by tamoxifen is mediated by ERalpha and reversed by E2 or ICI 182,780.

Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients.

Background: Molecular markers and the rich biological information they contain have great potential for cancer diagnosis, prognostication and therapy prediction. So far, however, they have not superseded routine histopathology and staging criteria, partly because the few studies performed on molecular subtyping have had little validation and limited clinical characterization.

Methods: We obtained gene expression and clinical data for 412 breast cancers obtained from population-based cohorts of patients from Stockholm and Uppsala, Sweden.

Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study.

Background: Postmenopausal hormone-replacement therapy (HRT) increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood.

Methods: We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays.

Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis.

Background: Histologic grade in breast cancer provides clinically important prognostic information. However, 30%-60% of tumors are classified as histologic grade 2. This grade is associated with an intermediate risk of recurrence and is thus not informative for clinical decision making.

Gene expression profiling spares early breast cancer patients from adjuvant therapy: derived and validated in two population-based cohorts.

Introduction: Adjuvant breast cancer therapy significantly improves survival, but overtreatment and undertreatment are major problems. Breast cancer expression profiling has so far mainly been used to identify women with a poor prognosis as candidates for adjuvant therapy but without demonstrated value for therapy prediction.

Methods: We obtained the gene expression profiles of 159 population-derived breast cancer patients, and used hierarchical clustering to identify the signature associated with prognosis and impact of adjuvant therapies, defined as distant metastasis or death within 5 years.

An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival.

Perturbations of the p53 pathway are associated with more aggressive and therapeutically refractory tumors. However, molecular assessment of p53 status, by using sequence analysis and immunohistochemistry, are incomplete assessors of p53 functional effects. We posited that the transcriptional fingerprint is a more definitive downstream indicator of p53 function.

Ductal carcinoma in situ of the breast with different histopathological grades and corresponding new breast tumour events: analysis of loss of heterozygosity.

To compare chromosomal alterations in ductal carcinoma in situ (DCIS) of different histopathological grades and to study aberrations between primary DCIS and corresponding ipsi- or contralateral new in situ or invasive tumours, a study was undertaken of the pattern of loss of heterozygosity (LOH) at chromosomal regions in which LOH has previously been described in invasive breast cancer. LOH was analysed using 19 microsatellite markers located on chromosomes 3p, 6q, 8p, 8q, 9p, 11p, 11q, 16q, 17p, and 17q in 30 women with a primary DCIS. Eleven women with DCIS of grade 1 and 19 with grade 3 according to the EORTC classification system were included.

Low frequency of BRAF and CDKN2A mutations in endometrial cancer.

Several pathways have been implicated in the pathogenesis of endometrial carcinoma. Based on recent reports, BRAF mutations provide an alternative route for activation of the RAS signalling pathway. The CDKN2A (p16) tumour suppressor gene is also altered in several tumour types.

Significant impact of promoter hypermethylation and the 540 C>T polymorphism of CDKN2A in cutaneous melanoma of the vertical growth phase.

Promoter hypermethylation, mutations, and loss of heterozygosity in the CDKN2A gene as well as polymorphisms at the 3'-untranslated region were determined in vertical growth phase melanomas. Methylation-specific polymerase chain reaction in soluti and in situ showed that 19% of the cases were hypermethylated at the CDKN2A promoter region, and some of these cases were heterogeneous with both methylated and unmethylated tumor cells. Methylation was associated with increased tumor cell proliferation by Ki-67 expression (P = 0.

Genetic status of cell cycle regulators in squamous cell carcinoma of the oesophagus: the CDKN2A (p16(INK4a) and p14(ARF) ) and p53 genes are major targets for inactivation.

We determined inactivation of the CDKN2A (p16(INK4a) and p14(ARF)) gene in 21 cases of oesophageal squamous cell carcinoma (OSCC). The tumours were also analysed for mutations in exons 5-8 and allelic losses in the p53 gene. In addition, we screened the CDKN2B (p15 INK4b), CDKN2C (p18 INK4c), CDK4 and p53R2 genes for mutations in the tumour tissues.

Polymorphic insertion of additional repeat within an area of direct 8 bp tandem repeats in the 5'-untranslated region of the p53R2 gene and cancer risk.

p53R2 is a recently cloned gene that functions in p53-induced DNA repair. In the 5'-untranslated region of the p53R2 gene two direct tandem 8 bp repeats are located. Within the region of these 8 bp direct repeats we have detected the insertion of an additional repeat.

A single nucleotide polymorphism in the 3'untranslated region of the CDKN2A gene is common in sporadic primary melanomas but mutations in the CDKN2B, CDKN2C, CDK4 and p53 genes are rare.

In this report we present the results of mutational analysis of the CDKN2B, CDKN2C, CDK4, p53 genes and 5'UTR of the CDKN2A gene in a set of 44 sporadic primary melanomas, which had been earlier analysed for mutations in the CDKN2A (p16/p14(ARF)) gene. No tumour-associated mutations were detected except in 1 melanoma where we found a CC>T* deletion-mutation in the codon 151-152 (exon 5) of the p53 gene. On the basis of our preliminary results, we did extended genotyping of the 500 C>G and 540 C>T polymorphisms in the 3'UTR of the CDKN2A gene in 229 melanoma cases and 235 controls.

Analysis of G(1)/S checkpoint regulators in metastatic melanoma.

We have analyzed the expression of the CDKN1A (p21(CIP1)), CDKN1B (p27(Kip1)), TP53, RB1 and MDM2 proteins and tumor cell proliferation by immunohistochemical staining in 59 cases of metastatic melanoma. The genomic status of the CDKN2A (INK4-ARF, p16/p14(ARF)), CDKN2B (p15) and CDKN2C (p18) genes was determined by PCR-SSCP (single-strand conformation polymorphism) in 46 of these cases. These results were correlated with various clinico-pathological parameters, including the outcome of combined chemoimmunotherapy.

Increased frequency of LOH on chromosome 9 in sporadic primary melanomas is associated with increased patient age at diagnosis.

We carried out statistical analysis of the frequency of loss of heterozygosity (LOH) at 10 microsatellite markers on chromosome 9. In 44 microdissected sporadic primary melanomas a comparison of LOH frequency data with other patient data, like age at diagnosis and tumour thickness, showed an interesting correlation between patient age at diagnosis and frequency of LOH on chromosome 9. The patient group with age >72 years at diagnosis (n = 22, mean age 82.

Loss of heterozygosity at chromosome 9p21 (INK4-p14ARF locus): homozygous deletions and mutations in the p16 and p14ARF genes in sporadic primary melanomas.

Loss of heterozygosity (LOH) was determined in 45 sporadic primary melanomas at six polymorphic microsatellite markers that flank the INK4a (p16-p14ARF) locus on chromosome 9p21. We also determined allelic loss at two markers on chromosome 9q and two markers at the Rb locus on chromosome 13. Homozygous deletion of the p16 and p14ARF genes was determined by a fluorescent-based quantitative multiplex polymerase chain reaction method.