A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data.

Background: A polygenic hazard score (PHS), the weighted sum of 54 SNP genotypes, was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening.

Methods: United Kingdom population incidence data (Cancer Research United Kingdom) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason score ≥7, stage T3-T4, PSA ≥10, or nodal/distant metastases).

Genome-wide association study of prostate cancer-specific survival.

Background: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical.

Methods: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia.

Spectrum and frequencies of BRCA1/2 mutations in Bulgarian high risk breast cancer patients.

Background: About 3885 women are diagnosed with breast cancer and 1285 die from the disease each year in Bulgaria. However no genetic testing to identify the mutations in high-risk families has been provided so far.

Methods: We evaluated 200 Bulgarian women with primary invasive breast cancer and with personal/ family history of breast cancer for the presence of unequivocally damaging germline mutations in BRCA1/2 using Sanger sequencing.

Mutational Status of CDKN2A and TP53 Genes in Laryngeal Squamous Cell Carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is the second most common tumour of the head and neck. It is characterized by frequent aberrations in two cell-cycle regulators--CDKN2A and TP53. However, LSCC has been often studied as a part of the group of head and neck cancers and not as an individual entity.

Auditory outcome after cochlear implantation in patients with congenital nonsyndromic hearing loss: influence of the GJB2 status.

Objective: To compare the audiologic outcome after cochlear implantation between 2 groups of patients with congenital nonsyndromic sensorineural hearing loss.

Study Design: Retrospective cohort study.

Setting: Department of Otorhinolaryngology, University hospital (tertiary referral center).

Promoter hypermethylation of CDKN2A, MGMT, MLH1, and DAPK genes in laryngeal squamous cell carcinoma and their associations with clinical profiles of the patients.

Background: Laryngeal squamous cell carcinoma (laryngeal SCC) is a frequently occurring cancer of the head and neck area. Epigenetic changes of tumor-related genes contribute to its genesis and progression.

Methods: We assessed promoter methylation status of the selected genes (CDKN2A, MGMT, MLH1, and DAPK) using methylation-sensitive high resolution melting (MS-HRM) in 100 patients with laryngeal SCC and studied the correlations with clinical characteristics.

Resistin - the link between adipose tissue dysfunction and insulin resistance in patients with obstructive sleep apnea.

Background: Resistin is an adipocytokine, associated with obesity and inflammation. Its exact role in insulin resistance and diabetes in the general population is still controversial. The relation between resistin plasma levels, insulin resistance and risk of impaired glucose metabolism in OSA patients has not been investigated.

CK2 is acting upstream of MEK3/6 as a part of the signal control of ERK1/2 and p38 MAPK during keratinocytes autocrine differentiation.

Protein kinase CK2 (formerly termed "casein kinase II") is a ubiquitously in mammalian cells distributed Ser/Thr kinase, with global role in cell regulation. Although, the involvement of CK2 in cell signalling is vast-investigated, virtually nothing is known about its contribution to signal control of keratinocytes differentiation. Here we show that, in autocrine differentiating keratinocytes, inhibition of the CK2 activity induced by 4,5,6,7-tetrabromobenzotriazole (TBB) causes reciprocal changes in the activities of major signal transduction regulators of keratinocytes differentiation, i.

No evidence of association between 118A>G OPRM1 polymorphism and heroin dependence in a large Bulgarian case-control sample.

The μ-opioid receptor is the primary site of action of most opioids. The 118A>G (rs1799971) polymorphism in exon 1 of the μ-opioid receptor gene (OPRM1) leads to an Asn40Asp amino acid change that affects a putative N-glycosylation site. It has been widely investigated for association with alcohol and drug dependence and pain sensitivity, with mixed results.

CHEK2 I157T and endometrial cancer.

Endometrial cancer (EC) is the most common malignancy of the female reproductive system in the industrialized world. Similar to other common diseases, gene variations are believed to be able to alter an individual's predisposition to developing the disease. The CHEK2 gene encodes a tumor suppressor that takes part in various cell processes, including cell cycle regulation, DNA repair, and apoptosis.

Frequency and application of the hot spot BRAF gene mutation (p.V600E) in the diagnostic strategy for Hereditary Nonpolyposis Colorectal Cancer.

Background: BRAF somatic mutations were reported with high frequency in sporadic colorectal cancers (CRCs) with microsatellite instability (MSI). The hot spot c. 1799 T>A, p.

Vanadate-induced inhibition of BCR-triggered apoptosis is coupled with tyrosine phosphorylation and induction of G2M growth arrest in Ramos-BL B cells.

The regulation of the tyrosine phosphorylation of key signaling molecules by tyrosine kinases and phosphatases is essential for BCR-triggered signaling cascades during B cell selection process. We used the non-selective tyrosine phosphatase inhibitor vanadate to study the importance of the late regulation of the tyrosine phosphorylation for BCR-triggered G1 growth arrest and apoptosis in Ramos-BL B cells. Vanadate induces G2M growth arrest in a dose-dependent manner and prevents BCR-triggered apoptosis.

Regulation of tyrosine phosphorylation during the CD40-mediated rescue of Ramos-BL B cells from BCR-triggered apoptosis.

The regulation of tyrosine phosphorylation is essential for BCR-triggered cellular responses during the selection process in the germinal centres. We were interested in examining the temporal regulation of tyrosine phosphorylation following CD40 cross-linking of anti-IgM-triggered Ramos-BL B cells. CD40 co-stimulation of anti-IgM-treated Ramos-BL B cells rescued them from growth inhibition and apoptosis, even when anti-CD40 Abs were added up to 12 h after the cross-linking of the BCR.

delta-Opioid agonist induced regulation of E2F1 DNA binding activity in NG108-15 cells.

Activation of opioid receptors have been implicated in the modulation of cell proliferation and the E2F family of transcription factors may play a role in opioid inhibition of DNA synthesis. Gel shift assays and Western blotting of nuclear extracts from NG108-15 cells revealed increased E2F1 DNA binding activity and higher levels of E2F1 following activation of delta-opioid receptors. It is suggested that DADLE-induced regulation of E2F DNA binding activity involves ERKs.