The association of 5alpha-reductase II (SRD5A2) and 17 hydroxylase (CYP17) gene polymorphisms with prostate cancer patients in the Turkish population

To date, research has led to the invention of multiple genes and their single nucleotide polymorphisms (SNPs) and environmental factors that influence the prostate cancer (PCa) pathogenesis. Therefore, the genes involved in these pathways are candidates for PCa predisposition. It is thought that polymorphisms of 5alpha-reductase II (SRD5A2) and 17 hydroxylase (CYP17) genes are likely to increase susceptibility. The aim of this study was to investigate the risk association of SRD5A2 and CYP17 gene polymorphisms in the development and progression of PCa in the Turkish population. In this study, 100 PCa patients and 105 healthy controls were studied. SRD5A2 and CYP17 gene polymorphisms were determined by real-time PCR and polymerase chain reaction-restriction length polymorphisms (PCR-RFLP) techniques. First, the AT and TT genotypes of SRD5A2 gene at codon 49 were not observed. Second, there was no significant association between the polymorphisms at codon 89 and the risk of PCa. Third, in the CYP17 gene, the A1A1 genotype is more common (46%) in cases than controls (32.4%). The odds ratios (ORs) of the A1A1 genotype was found at 1.69 (95% confidence interval [CI], 0.77-3.74) compare with the A2A2 genotype. Genotyping results of the SRD5A2 and CYP17 genes were also analyzed in relation to prostate-specific antigen (PSA) levels, Gleason score (GS), and tumor stage, but no statistically significant difference was observed (P > 0.05). Finally, we conclude that there was no evidence of an association between CYP17 (P = 0.134) and SRD5A2 (P = 0.784) polymorphism and PCa risk in the Turkish population.     

A new approach to sepsis treatment by rasagiline: a molecular,biochemical and histopathological study

Molecular Biology Reports - We aimed to investigate the effects of rasagiline on acute lung injury that develops in the sepsis model induced with the cecal ligation and puncture in rats. The rats...     

A short synthesis of D-glycero-D-manno-heptose 7-phosphate

D-glycero-D-manno-Heptopyranose 7-phosphate-an intermediate in the biosynthesis of nucleotide-activated heptoses-has been prepared in good overall yield from benzyl 5,6-dideoxy-2,3-O-isopropylidene-alpha-D-lyxo-(Z)-hept-5-enofuranoside by a short-step synthesis. Phosphitylation using the phosphoramidite procedure followed by in situ oxidation afforded the corresponding 7-O-phosphotriester derivative in high yield. Subsequent osmylation proceeded in good diastereoselectivity (4:1) to furnish the D-glycero-D-manno-configured derivative, which was separated from the L-glycero-L-gulo-isomer by chromatography. Hydrogenolysis led to simultaneous removal of the benzyl and isopropylidene groups and afforded the target compound in high yield, which serves as a substrate of bacterial heptose 7-phosphate kinases.     

Systemic administration of anti-NGF increases A-type potassium currents and decreases pancreatic nociceptor excitability in a rat model of chronic pancreatitis

We have previously shown that pancreatic sensory neurons in rats with chronic pancreatitis (CP) display increased excitability associated with a decrease in transient inactivating potassium currents (I(A)), thus accounting in part for the hyperalgesia associated with this condition. Because of its well known role in somatic hyperalgesia, we hypothesized a role for the nerve growth factor (NGF) in driving these changes. CP was induced by intraductal injection of trinitrobenzene sulfonic acid (TNBS) in rats. After 3 wk, anti-NGF antibody or control serum was injected intra-peritoneally daily for 1 wk. This protocol was repeated in another set of experiments in control rats (receiving intraductal PBS instead of TNBS). Pancreatic nociceptors labeled with the dye Dil were identified, and patch-clamp recordings were made from acutely dissociated DRG neurons. Sensory neurons from anti-NGF-treated rats displayed a lower resting membrane potential, increased rheobase, decreased burst discharges in response to stimulatory current, and decreased input resistance compared with those treated with control serum. Under voltage-clamp condition, neuronal I(A) density was increased in anti-NGF-treated rats compared with rats treated with control serum. However, anti-NGF treatment had no effect on electrophysiological parameters in neurons from control rats. The expression of Kv-associated channel or ancillary genes Kv1.4, 4.1, 4.2, 4.3, and DPP6, DPP10, and KCHIPs 1-4 in pancreas-specific nociceptors was examined by laser-capture microdissection and real-time PCR quantification of mRNA levels. No significant differences were seen among those. These findings emphasize a key role for NGF in maintaining neuronal excitability in CP specifically via downregulation of I(A) by as yet unknown mechanisms.     

Insulin-like growth factor I (Igf-1) gene polymorphism in patients with non-metastatic breast cancer

We aimed to assess the association between IGF-I gene (CA repeats) polymorphism in breast cancer patients and their clinicopathological features, as well as disease recurrence and survival. Seventy-six non-metastatic breast cancer patients were enrolled in the present study. The IGF-I (CA) repeats were studied with polymerase chain reaction by using proper primers belonging to these gene areas from DNA samples. Results show that the non 19- non 19 homozygote were more common in patients without lymph node involvement (p=0.04), with low histological grade (p=0.04), with positive hormone receptor status (p=0.01), and in patients without recurrence (p=0.06). These results suggest that the non 19-non 19 carriers have some favorable prognostic factors, and IGF-I gene polymorphism (CA repeats) may affect disease recurrence and overall survival.     

The value of CDX2 and cytokeratins 7 and 20 expression in differentiating colorectal adenocarcinomas from extraintestinal gastrointestinal adenocarcinomas: cytokeratin 7-/20+ phenotype is more specific than CDX2 antibody

Background

Breast carcinomas can be classified into five subtypes based on gene expression profiling or immunohistochemical characteristics. Among these subtypes, basal-like breast carcinomas (BLBCs) are one of the most studied group, due to their poor prognosis. The aim of this study was to investigate the prevalance, morphological and immunohistochemical features of BLBCs, in Turkish population.

Methods

Five hundred invasive breast carcinomas were reviewed for several morphological features and immunostained for oestrogen and progesterone receptors, c-ERB-B2, cytokeratin5/6, cytokeratin14, vimentin and epidermal growth factor receptor (EGFR). Basal-like breast carcinoma was defined as a triple negative tumor with cytokeratin5/6 and/or EGFR positive.

Results

The prevalance of BLBC was 9.6%. All medullary carcinomas and 55.6% of metaplastic carcinomas showed basal-like immunophenotype. Patients with BLBC were younger (p=0.04) and had higher-grade tumors (p<0.0001). Morphologic features associated with BLBC included increased mitosis, nuclear pleomorphism, presence of geographic and/or central necrosis, pushing margin of invasion and stromal lymphocytic response (p<0.0001). Presence of prominent nucleoli and vesicular nuclear chromatin were the cytological features correlated with basal-like phenotype (p<0.0001). On multivariate analyses, BLBCs were associated with high mitotic number (p<0.0001), the presence of vesicular chromatin (p=0.004), high tubular grade (p=0.011), lymphocytic response (p=0.031) and the absence of carcinoma insitu (p=0.039). Vimentin was positive in 53.2% of BLBCs, while cytokeratin14 was less frequently expressed (27.7%).

Conclusions

BLBCs have some distinctive, but not pathognomonical, morphological features. Paying attention to these features and adding cytokeratin14 and vimentin to the immunohistochemical panel can help the definitive diagnosis of BLBCs.

Virtual slide

http://www.diagnosticpathology.diagnomx.eu/vs/5962175467857400     

An isogenetic myoblast expression screen identifies DUX4-mediated FSHD-associated molecular pathologies

Facioscapulohumeral muscular dystrophy (FSHD) is caused by an unusual deletion with neomorphic activity. This deletion derepresses genes in cis; however which candidate gene causes the FSHD phenotype, and through what mechanism, is unknown. We describe a novel genetic tool, inducible cassette exchange, enabling rapid generation of isogenetically modified cells with conditional and variable transgene expression. We compare the effects of expressing variable levels of each FSHD candidate gene on myoblasts. This screen identified only one gene with overt toxicity: DUX4 (double homeobox, chromosome 4), a protein with two homeodomains, each similar in sequence to Pax3 and Pax7. DUX4 expression recapitulates key features of the FSHD molecular phenotype, including repression of MyoD and its target genes, diminished myogenic differentiation, repression of glutathione redox pathway components, and sensitivity to oxidative stress. We further demonstrate competition between DUX4 and Pax3/Pax7: when either Pax3 or Pax7 is expressed at high levels, DUX4 is no longer toxic. We propose a hypothesis for FSHD in which DUX4 expression interferes with Pax7 in satellite cells, and inappropriately regulates Pax targets, including myogenic regulatory factors, during regeneration.     

Conventional and Molecular Identification of Bacteria with Magnesite Enrichment Potential from Local Quarries in Erzurum

In this study, the bacteria having ore enrichment potential were isolated from three different magnesite quarries located in Erzurum-Askale borderlines. The obtained isolates were identified and characterized according to the conventional (morphological, physiological and biochemical tests) and molecular techniques (fatty acid methyl ester profiles (FAME), BOX PCR and 16S rDNA). According to sequence analysis, they were determined as Exiguobacterium aurantiacum (4), Exiguobacterium sibiricum (2), Bacillus sp. (2), Staphylococcus epidermidis (2), Staphylococcus haemolyticus (1), Shewanella baltica (1) and Klebsiella oxytoca (1), respectively.     

Reproductive biology of Raja clavata (Elasmobranchii: Rajidae) from Southern Black Sea coast around Turkey

Specimens of Raja clavata were monthly collected at the coast of Havaalan? (Trabzon/Turkey) from January 2009 to December 2009 at depths between 20 and 40?m. A total of 230 individuals of thornback ray (131 females and 99 males) were collected by bottom trawls during research cruises. Using logistic regression, it was determined that TL at 50% maturity of males was 718?mm TL and of females 746?mm TL. The ovarian fecundity ranged from 27 to 60 yellow follicles in both ovaries. Females carrying egg cases were found in July and October. Variations in the gonadosomatic and hepatosomatic indices indicated a continuous reproductive cycle during the year.