Quantitative analysis of estrogen receptor heterogeneity in breast cancer

Immunohistochemical analyses (IHC) of biomarkers are extensively used for tumor characterization and as prognostic and predictive measures. The current standard of single slide analysis assumes that one 5 microM section is representative of the entire tumor. We used our automated image analysis technology (AQUA) using a modified IHC technique with fluorophores to compare estrogen receptor (ER) expression in multiple blocks/slides from cases of primary breast cancer with the objective of quantifying tumor heterogeneity within sections and between blocks. To normalize our ER scores and allow slide-to-slide comparisons, 0.6 microm histospots of representative breast cancer cases with known ER scores were assembled into a 'gold standard array' (GSA) and placed adjacently to each whole section. Overall, there was excellent correlation between AQUA scores and the pathologist's scores and reproducibility of GSA scores (mean linear regression R value 0.8903). Twenty-nine slides from 11 surgical cases were then analyzed totaling over 2000 AQUA images. Using standard binary assignments of AQUA (>10) and pathologist's (>10%) scores as being positive, there was fair concordancy between AQUA and pathologist scores (73%) and between slides from different blocks from the same cases (75%). However using continuous AQUA scores, agreement between AQUA and pathologist was far lower and between slides from different blocks from the same cases only 19%. Within individual slides there was also significant heterogeneity in a scattered pattern, most notably for slides with the highest AQUA scores. In sum, using a quantitative measure of ER expression, significant block-to-block heterogeneity was found in 81% of cases. These results most likely reflect both laboratory-based variability due to lack of standardization of immunohistochemistry and true biological heterogeneity. It is also likely to be dependent on the biomarker analyzed and suggests further studies should be carried out to determine how these findings may affect clinical decision-making processes.     

A representative of arylcyanomethylenequinone oximes effectively inhibits growth and formation of hyphae in Candida albicans and influences the activity of protein kinases in vitro

In this study, we applied various assays to reveal new activities of phenylcyanomethylenequinone oxime-4-(hydroxyimino) cyclohexa-2,5-dien-1-ylidene](phenyl)ethanenitrile (4-AN) for potential anti-microbial applications. These assays demonstrated (a) the antimicrobial effect on bacterial and fungal cultures, (b) the effect on the in vitro activity of the kinase CK2, (c) toxicity towards human erythrocytes, the Caco-2 cancer cell line, and embryonic development of Zebrafish. We demonstrated the activity of 4-AN against selected bacteria and Candida spp. The MIC ranging from 4?µg/ml to 125?µg/ml proved effective in inhibition of formation of hyphae and cell aggregation in Candida, which was demonstrated at the cytological level. Noteworthy, 4-AN was found to inhibit the CK2 kinase with moderate potency. Moreover, at low concentrations, it did not exert any evident toxic effects on human erythrocytes, Caco-2 cells, or Zebrafish embryos. 4-AN can be a potential candidate as a novel drug against Candida infections.     

Activation of phosphoinositide 3-kinase delta by antipsychotic drugs: Preliminary results

Background

Catalytic subunit delta of phosphoinositide 3-kinase, p110δ, encoded by the PIK3CD gene, was recently proposed as a target for pharmacological treatment of schizophrenia. Current antipsychotic drugs were found to decrease the mRNA expression of PIK3CD, but the mechanism of this process is not known. The aim of the study was to elucidate the mechanism by which antipsychotic drugs affect the mRNA expression of PIK3CD.

Brachial plexus injury after shoulder dislocation: a literature review

Neurosurgical Review - Brachial plexus injuries are among the rarest but at the same time the most severe complications of shoulder dislocation. The symptoms range from transient weakening or...     

Renal anaemia treatment in haemodialysis patients in the Central and Eastern European countries in everyday clinical practice follow-up

Background

Chronic kidney disease is almost always accompanied by anaemia. Erythropoietin-stimulating agents (ESA) can increase haemoglobin concentration and thus reduce the frequency of anaemia-related complications including the cardiovascular events.

Aim

The aim of the study was to collect prospective data on 12-month standard ESA therapy used in haemodialyzed patients in selected CEE countries as well as on cardiovascular complications, iron status and anaemia treatment.

Patients and methods

Fifty centres in 3 countries participated in the study. A group of 398 haemodialysed stable patients (M-231, F-167) aged 19–90 years (57.5 ± 14.7) on standard ESA therapy for chronic renal anaemia were recruited. Twelve-month prospective data on iron parameters, ESA therapy and cardiovascular events were collected. The use of iron, folic acid and blood transfusions were also assessed. Patient were divided into three groups according to ESA therapy start: group A—patients who received ESA after start of haemodialysis, group B—patients who received ESA within 3 months from the day of first haemodialysis and group C—patients who had received ESA more than 3 months before haemodialysis. Chi² test for qualitative data and Kruskall–Wallis test for quantitative data with p < 0.05 were used in statistical analysis.

Results

At prestudy period, the mean weekly dose of ESA in group C was statistically lower than in the remaining two groups (3,823 ± 3,169 vs. 5,276 ± 2,915 and 6,427 ± 3,441 units/week, p < 0.001), but during prospective phase of the study the doses did not differ among groups A, B and C. No major fluctuation of ESA administration schedule was observed during the study in the groups; however, at majority of visits, the mean frequency of ESA administration in group C was statistically higher than in groups A and B. At baseline visit, the haemoglobin concentration in group A patients (10.86 ± 1.34 g/dL) was slightly lower than in group B (11.26 ± 1.43 g/dL) and group C (10.98 ± 1.35 g/dL) (p = 0.025), but at subsequent visits these differences disappeared and mean haemoglobin concentration was stable around 11 g/dL. Ferritin concentration increased from 280 ± 241 at baseline to 506 ± 405 at month 12, and no important differences in the groups were observed. The other haematological parameters (haematocrit, iron concentration) remained stable during the entire study. The frequency of blood transfusion and total volume of blood in group C were lower than in groups A and B. During the prospective 12-month follow-up, 23 (5.8 %) of the patients died and 35 (8.8 %) were transplanted. No differences in death or transplantation rate were observed among groups A, B and C. The number of patients with adverse events, serious adverse events or drug-related adverse events in all groups was similar. In conclusion, ESA therapy increased haemoglobin concentration and no major differences in haematological parameters among the groups were observed during the entire study irrespective of early versus late start. Mortality, cardiovascular events or other adverse events were similar among the groups during the observation period; however, the limitation of the study is the sample size.     

Mechanical,Chemical, and Processing Properties of Specimens Manufactured from Poly-Ether-Ether-Ketone (PEEK) Using 3D Printing

As part of the experiments herein, the mechanical properties of specimens made of poly-ether-ether-ketone (PEEK) material using 3D printing technology were determined. Two populations of specimens were investigated, the first of which contained an amorphous structure, while the other held a crystal structure. The studies also investigated the influence of the print directionality on the mechanical properties obtained. Static tensile, three-point bending, and impact tests were carried out. The results for the effect of the structure type on the tensile properties showed that the modulus of elasticity was approximately 20% higher for the crystal than for the amorphous PEEK form. The Poisson’s ratios were similar, but the ratio was slightly higher for the amorphous samples than the crystalline ones. Furthermore, the studies included a chemical PEEK modification to increase the hydrophilicity. For this purpose, nitrite and hydroxyl groups were introduced into the chain by chemical reactions. The results demonstrate that the modified PEEK specimens had worse thermoplastic properties than the unmodified specimens.     

Mechanical and Combustion Properties of Agglomerates of Wood of Popular Eastern European Species

The objective of the reported project was to produce wood agglomerates from popular East European species to determine their strength and combustion properties. Closed-die pellets were produced from sawdust of six types of wood common on the East European market: pine, willow, oak, poplar, birch, and beech. The properties of pellets, determined by the type of wood, were influenced by the compaction pressure and the moisture content of the sawdust. The highest average pellet density was obtained for oak sawdust, while the lowest density was obtained for poplar pellets. Expansion of pellets after removing from the die was found to be dependent on the wood species, and as expected, on compaction pressure. The pellet expansion increased after 2 h of conditioning in the laboratory and with an increase in moisture content. The highest and the smallest strength were obtained for oak pellets and for birch sawdust, respectively. The strength of the pellets increased by more than 100% with an increase in the compaction pressure from 60 MPa to 120 MPa. The average strength decreased by 65% with increasing moisture content. For all tested materials, drop resistance remained at a high level, acceptable in industrial practice. The highest calorific value of 18.97 MJ/kg was obtained for pine pellets. The highest ash value of 1.52% was obtained for willow pellets and the lowest value of 0.32% for pine pellets.