Reliability of cyclin A assessment on tissue microarrays in breast cancer compared to conventional histological slides

Cyclin A has in some studies been associated with poor breast cancer survival, although all studies have not confirmed this. Its prognostic significance in breast cancer needs evaluation in larger studies. Tissue microarray (TMA) technique allows a simultaneous analysis of large amount of tumours on a single microscopic slide. This makes a rapid screening of molecular markers in large amount of tumours possible. Because only a small tissue sample of each tumour is punched on an array, the question has arisen about the representativeness of TMA when studying markers that are expressed in only a small proportion of cells. For this reason, we wanted to compare cyclin A expression on TMA and on traditional large sections. Two breast cancer TMAs were constructed of 200 breast tumours diagnosed between 1997–1998. TMA slides and traditional large section slides of these 200 tumours were stained with cyclin A antibody and analysed by two independent readers. The reproducibility of the two readers' results was good or even very good, with kappa values 0.71–0.87. The agreement of TMA and large section results was good with kappa value 0.62–0.75. Cyclin A overexpression was significantly (P<0.001) associated with oestrogen receptor and progesterone receptor negativity and high grade both on TMA and large sections. Cyclin A overexpression was significantly associated with poor metastasis-free survival both on TMA and large sections. The relative risks for metastasis were similar on TMA and large sections. This study suggests that TMA technique could be useful to study histological correlations and prognostic significance of cyclin A on breast cancer on a large scale

A high proliferation rate measured by cyclin A predicts a favourable chemotherapy response in soft tissue sarcoma patients

A small but not insignificant number of patients experience a prolonged survival after treatment of metastatic soft tissue sarcoma. This must be weighed against the majority of the patients who benefit little from the therapy, but nevertheless experience its side-effects. It would therefore be of utmost importance to be able to screen for those patients who respond to the treatment. Since proliferating cells are more sensitive to chemotherapy than non-proliferative cells, we measured the proliferation rate of the primary tumour of 55 soft tissue sarcoma patients with locally advanced or metastatic disease by determining the flow cytometric S phase fraction and immunohistochemical Ki-67 and cyclin A scores. S phase fraction or Ki-67 score did not predict chemotherapy response or progression-free survival. A high cyclin A score, however, correlated with a better chemotherapy response (P = 0.02) and longer progression-free survival time (P = 0.04). Our results suggest that a high cyclin A score predicts chemotherapy sensitivity. © 1999 Cancer Research Campaig

Comparison of the Ki-67 score and S-phase fraction as prognostic variables in soft-tissue sarcoma

Immunohistochemically determined Ki-67 scores and flow cytometrically determined S-phase fractions were successfully evaluated from the primary tumours of 123 patients with soft-tissue sarcoma. All patients had either limb or superficial trunk tumours. Ki-67 score correlated strongly with ploidy, S-phase fraction and grade. Ki-67 did not correlate with the size of the primary tumour. When analysed as a continuous variable, Ki-67 was a stronger predictor of both metastasis-free survival and disease-specific overall survival (P= 0.003 and 0.04 respectively) than was the S-phase fraction (P= 0.06 and 0.07 respectively). We tested the relevance of different cut-point values by dividing the whole material into two parts at every 10% (e.g. 10% of patients vs. the remaining 90%, 20% vs. 80%, etc.). We counted the relative risk and confidence interval at all these cut-off points. Ki-67 had good prognostic discriminating power irrespective of the cut-point value, but S-phase fraction lost its prognostic power at higher cut-point values. In conclusion, we found that Ki-67 is a useful prognostic tool in the treatment of soft-tissue sarcoma patients irrespective of the cut-point value. S-phase fraction can be used at lower cut-point values. © 1999 Cancer Research Campaig

Immunohistochemical estimation of cell cycle phase in laryngeal neoplasia

We previously developed an immunohistochemical method for estimating cell cycle state and phase in tissue samples, including biopsies that are too small for flow cytometry. We have used our technique to examine whether primary abnormalities of the cell cycle exist in laryngeal neoplasia. Antibodies against the markers of cell cycle entry, minichromosome maintenance protein-2 (Mcm-2) and Ki67, and putative markers of cell cycle phase, cyclin D1 (G1-phase), cyclin A (S-phase), cyclin B1 (G2-phase) and phosphohistone H3 (Mitosis) were applied to paraffin-embedded sections of normal larynx (n=8), laryngeal dysplasia (n=10) and laryngeal squamous cell carcinoma (n=10). Cells expressing each marker were determined as a percentage of total cells, termed the labelling index (LI), and as a percentage of Mcm-2-positive cells, termed the labelling fraction (LF). The frequency of coexpression of each putative phase marker was investigated by confocal microscopy. There was a correlation between Mcm-2 and Ki67 LIs (ρ=0.93) but Mcm-2 LIs were consistently higher. All cells expressing a phase marker coexpressed Mcm-2, whereas Ki67 was not expressed in a proportion of these cells. The putative phase markers showed little coexpression. Labelling index values increased on progression from normal larynx through laryngeal dysplasia to squamous cell carcinoma for Mcm-2 (P=0.001), Ki67 (P=0.0002), cyclin D1 (P=0.015), cyclin A (P=0.0001) and cyclin B1 (P=0.0004). There was no evidence of an increase in the LF for any phase marker. Immunohistochemistry can be used to estimate cell cycle state and phase in laryngeal biopsies. Our data argues against primary cell cycle phase abnormalities in laryngeal neoplasia

CNT-based catalysts for H-2 production by ethanol reforming

Hydrogen production by steam reforming of ethanol (SRE) was studied using steam to ethanol ratio of 3 1 between the temperature range of 150-450 degrees C over metal and metal oxide nanoparticle catalysts (Ni, Co, Pt and Rh) supported on carbon nanotubes (CNTs) and compared to a commercial catalyst (Ni/Al2O3) The aim was to find out the suitability of CNTs supports with metal nanoparticles for the SRE reactions at low temperatures The idea to develop CNT based catalysts that have high selectivity for H-2 is one of the driving forces for this study The catalytic performance was evaluated in terms of ethanol conversion product gas composition hydrogen yield and selectivity to hydrogen The Co/CNT and Ni/CNT catalysts were found to have the highest activity and selectivity towards hydrogen formation among the catalysts studied Almost complete ethanol conversion is achieved over the Ni/CNT catalyst at 400 degrees C The highest hydrogen yield of 2 5 is however obtained over the Co/CNT catalyst at 450 degrees C The formation of CO and CH4 was very low over the Co/CNT catalyst compared to all the other tested catalysts The Pt and Rh CNT based catalysts were found to have low activity and selectivity in the SRE reaction Hydrogen production via steam reforming of ethanol at low temperatures using especially Co/CNT catalyst has thus potential in the future in e g the fuel cell applications (C) 2010 Professor T Nejat Veziroglu Published by Elsevier Ltd All rights reserve

Vanadia–zirconia and vanadia–hafnia catalysts for utilization of volatile organic compound emissions

Abstract Utilization is a sustainable and interesting alternative for the destructive treatment of volatile organic compounds due to avoided CO₂ emission. This work concentrates on the development of active and sulfur-tolerant catalysts for the utilization of contaminated methanol. Impregnated and sol–gel prepared vanadia–zirconia and vanadia–hafnia catalysts were thoroughly characterized by N₂ sorption, analytical (S)TEM, elemental analysis, XRD and Raman spectroscopy, and their performances were evaluated in formaldehyde production from methanol and methanethiol mixture. The results showed higher activity of the sol–gel prepared catalysts due to formation of mono- and polymeric vanadia species. Unfortunately, the most active vanadia sites were deactivated more easily than the metal-mixed oxide HfV₂O₇ and ZrV₂O₇ phases, as well as crystalline V₂O₅ observed in the impregnated catalysts. Metal-mixed oxide phases were formed in impregnated catalysts through formation of defects in HfO₂ and ZrO₂ structure during calcination at 600 °C, which was evidenced by Raman spectroscopy. The sol–gel prepared vanadia–zirconia and vanadia–hafnia catalysts were able to produce formaldehyde from contaminated methanol with high selectivity at temperature around 400 °C, while impregnated catalysts required 50–100 °C higher temperatures

Regeneration of sulfur-poisoned Pd-based catalyst for natural gas oxidation

Abstract Sulfur deactivation and regeneration behavior of the Pd/Al₂O₃ catalyst has been investigated via experimental characterization and density functional theory (DFT) simulations. During the sulfur exposure, PdO crystallites grow slightly while bulk Al₂(SO₄)₃ forms on the support. DFT calculations indicate that SOₓ species interact strongly with the catalyst surface making it chemically inactive in agreement with the experimental results. During the regeneration treatment (CH₄ conditions), PdO particles reduce, Al₂(SO₄)₃ is partially removed, and the activity for CH₄ conversion is increased. No full recovery can be observed due to remaining Al₂(SO₄)₃, the formation of encapsulating sulfur species, and the partial reduction of PdO particles. To reoxidize Pd, the catalyst is further regenerated (O₂ conditions). The resulting CH₄ conversion is at the same level than with the regenerated catalyst. Thus, a small amount of Al₂(SO₄)₃ appears to have a stronger effect on the performance than the state of Pd

Random networks of core-shell-like Cu-Cu₂O/CuO nanowires as surface plasmon resonance-enhanced sensors

Abstract The rapid oxide formation on pristine unprotected copper surfaces limits the direct application of Cu nanomaterials in electronics and sensor assemblies with physical contacts. However, it is not clear whether the growing cuprous (Cu₂O) and cupric oxides (CuO) and the formation of core-shell-like Cu-Cu₂O/CuO nanowires would cause any compromise for non-contact optical measurements, where light absorption and subsequent charge oscillation and separation take place such as those in surface plasmon-assisted and photocatalytic processes, respectively. Therefore, we analyze how the surface potential of hydrothermally synthetized copper nanowires changes as a function of time in ambient conditions using Kelvin probe force microscopy in dark and under light illumination to reveal charge accumulation on the nanowires and on the supporting gold substrate. Further, we perform finite element modeling of the optical absorption to predict plasmonic behavior of the nanostructures. The results suggest that the core-shell-like Cu-Cu₂O/CuO nanowires may be useful both in photocatalytic and in surface plasmon-enhanced processes. Here, by exploiting the latter, we show that regardless of the native surface oxide formation, random networks of the nanowires on gold substrates work as excellent amplification media for surface-enhanced Raman spectroscopy as demonstrated in sensing of Rhodamine 6G dye molecules