In situ observation of structural changes in polycrystalline silver catalysts by environmental scanning electron microscopy

Morphology changes induced in polycrystalline silver catalysts as a result of heating in either oxygen, water or oxygen-methanol atmospheres have been investigated by environmental scanning electron microscopy (ESEM), FT-Raman spectroscopy and temperature programmed desorption (TPD). The silver catalyst of interest consisted of two distinct particle types, one of which contained a significant concentration of sub-surface hydroxy species (in addition to surface adsorbed atomic oxygen). Heating the sample to 663 K resulted in the production of 'pin-holes' in the silver structure as a consequence of near-surface explosions caused by sub-surface hydroxy recombination. Furthermore, 'pin-holes' were predominantly found in the vicinity of surface defects, such as platelets and edge structures. Reaction between methanol and oxygen also resulted in the formation of 'pin-holes' in the silver surface, which were inherently associated with the catalytic process. A reaction mechanism is suggested that involves the interaction of methanol with sub-surface oxygen species to form sub-surface hydroxy groups. The sub-surface hydroxy species subsequently erupt through the silver surface to again produce 'pin-holes'.

Fabrication and mechanical and thermal behaviour of graphene oxide/epoxy nanocomposites

Bulk amount of graphite oxide was prepared by oxidation of graphite using the modified Hummers method and its ultrasonication in organic solvents yielded graphene oxide (GO). X-ray diffraction (XRD) pattern, X-ray photoelectron (XPS), Raman and Fourier transform infrared (FTIR) spectroscopy indicated the successful preparation of GO. XPS survey spectrum of GO revealed the presence of 66.6 at% C and 30.4 at% O. Scanning electron microscopy (SEM) and Transmission electron microscopy (TEM) images of the graphene oxide showed that they consist of a large amount of graphene oxide platelets with a curled morphology containing of a thin wrinkled sheet like structure. AFM image of the exfoliated GO signified that the average thickness of GO sheets is ~1.0 nm which is very similar to GO monolayer. GO/epoxy nanocomposites were prepared by typical solution mixing technique and influence of GO on mechanical and thermal properties of nanocomposites were investigated. As for the mechanical behaviour of GO/epoxy nanocomposites, 0.5 wt% GO in the nanocomposite achieved the maximum increase in the elastic modulus (~35%) and tensile strength (~7%). The TEM analysis provided clear image of microstructure with homogeneous dispersion of GO in the polymer matrix. The improved strength properties of GO/epoxy nanocomposites can be attributed to inherent strength of GO, the good dispersion and the strong interfacial interactions between the GO sheets and the polymer matrix. However, incorporation of GO showed significant negative effect on composite glass transition temperature (Tg). This may arise due to the interference of GO on curing reaction of epoxy.

Excursion guidance criteria to guide control of peak emission and exposure to airborne engineered particles

The overall aim of our research was to characterize airborne particles from selected nanotechnology processes and to utilize the data to develop and test quantitative particle concentration-based criteria that can be used to trigger an assessment of particle emission controls. We investigated particle number concentration (PNC), particle mass (PM) concentration, count median diameter (CMD), alveolar deposited surface area, elemental composition, and morphology from sampling of aerosols arising from six nanotechnology processes. These included fibrous and non-fibrous particles, including carbon nanotubes (CNTs). We adopted standard occupational hygiene principles in relation to controlling peak emission and exposures, as outlined by both Safe Work Australia, (1) and the American Conference of Governmental Industrial Hygienists (ACGIH®). (2) The results from the study were used to analyses peak and 30-minute averaged particle number and mass concentration values measured during the operation of the nanotechnology processes. Analysis of peak (highest value recorded) and 30-minute averaged particle number and mass concentration values revealed: Peak PNC20–1000 nm emitted from the nanotechnology processes were up to three orders of magnitude greater than the local background particle concentration (LBPC). Peak PNC300–3000 nm was up to an order of magnitude greater, and PM2.5 concentrations up to four orders of magnitude greater. For three of these nanotechnology processes, the 30-minute average particle number and mass concentrations were also significantly different from the LBPC (p-value < 0.001). We propose emission or exposure controls may need to be implemented or modified, or further assessment of the controls be undertaken, if concentrations exceed three times the LBPC, which is also used as the local particle reference value, for more than a total of 30 minutes during a workday, and/or if a single short-term measurement exceeds five times the local particle reference value. The use of these quantitative criteria, which we are terming the universal excursion guidance criteria, will account for the typical variation in LBPC and inaccuracy of instruments, while precautionary enough to highlight peaks in particle concentration likely to be associated with particle emission from the nanotechnology process. Recommendations on when to utilize local excursion guidance criteria are also provided.

Effect of aerobic interval training and caffeine on blood platelet function

Purpose: Hyperactive platelets contribute to the thrombotic response in humans, and exercise transiently increases platelet function. Caffeine is routinely used by athletes as an ergogenic aid, but the combined effect of exercise and caffeine on platelet function has not been investigated. Methods: Twelve healthy males were randomly assigned to one of four groups and undertook four experimental trials of a high-intensity aerobic interval training (AIT) bout or rest with ingestion of caffeine (3 mg·kg-1) or placebo. AIT was 8 × 5 min at approximately 75% peak power output (approximately 80% V?O2peak) and 1-min recovery (approximately 40% peak power output, approximately 50% V?O2peak) intervals. Blood/urine was collected before, 60, and 90 min after capsule ingestion and analyzed for platelet aggregation/activation. Results: AIT increased platelet reactivity to adenosine diphosphate (placebo 30.3%, caffeine 13.4%, P < 0.05) and collagen (placebo 10.8%, caffeine 5.1%, P < 0.05) compared with rest. Exercise placebo increased adenosine diphosphate-induced aggregation 90 min postingestion compared with baseline (40.5%, P < 0.05), but the increase when exercise was combined with caffeine was small (6.6%). During the resting caffeine protocol, collagen-induced aggregation was reduced (-4.3%, P < 0.05). AIT increased expression of platelet activation marker PAC-1 with exercise placebo (P < 0.05) but not when combined with caffeine. Conclusion: A single bout of AIT increases platelet function, but caffeine ingestion (3 mg·kg) does not exacerbate platelet function at rest or in response to AIT. Our results provide new information showing caffeine at a dose that can elicit ergogenic effects on performance has no detrimental effect on platelet function and may have the potential to attenuate increases in platelet activation and aggregation when undertaking strenuous exercise.

Exosomes in prostate cancer: Putting together the pieces of a puzzle

Exosomes have been shown to act as mediators for cell to cell communication and as a potential source of biomarkers for many diseases, including prostate cancer. Exosomes are nanosized vesicles secreted by cells and consist of proteins normally found in multivesicular bodies, RNA, DNA and lipids. As a potential source of biomarkers, exosomes have attracted considerable attention, as their protein content resembles that of their cells of origin, even though it is noted that the proteins, miRNAs and lipids found in the exosomes are not a reflective stoichiometric sampling of the contents from the parent cells. While the biogenesis of exosomes in dendritic cells and platelets has been extensively characterized, much less is known about the biogenesis of exosomes in cancer cells. An understanding of the processes involved in prostate cancer will help to further elucidate the role of exosomes and other extracellular vesicles in prostate cancer progression and metastasis. There are few methodologies available for general isolation of exosomes, however validation of those methodologies is necessary to study the role of exosomal-derived biomarkers in various diseases. In this review, we discuss “exosomes” as a member of the family of extracellular vesicles and their potential to provide candidate biomarkers for prostate cancer.

Superior piezoelectric composite films : taking advantage of carbon nanomaterials

Piezoelectric composites comprising an active phase of ferroelectric ceramic and a polymer matrix have recently attracted numerous sensory applications. However, it remains a major challenge to further improve their electromechanical response for advanced applications such as precision control and monitoring systems. We hereby investigated the incorporation of graphene platelets (GnPs) and multi-walled carbon nanotubes (MWNTs), each with various weight fractions, into PZT (lead zirconate titanate)/epoxy composites to produce three-phase nanocomposites. The nanocomposite films show markedly improved piezoelectric coefficients and electromechanical responses (50%) besides an enhancement of ~200% in stiffness. Carbon nanomaterials strengthened the impact of electric field on the PZT particles by appropriately raising the electrical conductivity of epoxy. GnPs have been proved far more promising in improving the poling behavior and dynamic response than MWNTs. The superior dynamic sensitivity of GnP-reinforced composite may be caused by GnPs’ high load transfer efficiency arising from their two-dimensional geometry and good compatibility with the matrix. Reduced acoustic impedance mismatch resulted from the improved thermal conductance may also contribute to the higher sensitivity of GnP-reinforced composite. This research pointed out the potential of employing GnPs to develop highly sensitive piezoelectric composites for sensing applications.

A phase II study of mitomycin C and oral etoposide for advanced adenocarcinoma of the upper gastrointestinal tract

Background: Mitomycin C and etoposide have both demonstrated activity against gastric carcinoma. Etoposide is a topoisomerase II inhibitor with evidence for phase-specific and schedule-dependent activity. Patients and method. Twenty-eight consecutive patients with advanced upper gastrointestinal adenocarcinoma were treated with intravenous (i.v.) bolus mitomycin C 6 mg/m2 on day 1 every 21 days to a maximum of four courses. Oral etoposide capsules 50 mg b.i.d. (or 35 mg b.i.d. liquid) were administered days 1 to 10 extending to 14 days in subsequent courses if absolute neutrophil count >1.5 x 109/l on day 14 of first course, for up to six courses. Results: Twenty-six patients were assessed for response of whom 12 had measurable disease and 14 evaluable disease. Four patients had a documented response (one complete remission, three partial remissions) with an objective response rate of 15% (95% confidence interval (95% CI) 4%-35%). Eight patients had stable disease and 14 progressive disease. The median survival was six months. The schedule was well tolerated with no treatment-related deaths. Nine patients experienced leucopenia (seven grade II and two grade III). Nausea and vomiting (eight grade II, one grade III), fatigue (eight grade II, two grade III) and anaemia (seven grade II, two grade III) were the predominant toxicities. Conclusion: This out-patient schedule is well tolerated and shows modest activity in the treatment of advanced upper gastrointestinal adenocarcinoma. Further studies using protracted schedules of etoposide both orally and as infusional treatment should be developed.

Prognostic factors for malignant mesothelioma in 142 patients : validation of CALGB and EORTC prognostic scoring systems

Background The incidence of malignant mesothelioma is increasing. There is the perception that survival is worse in the UK than in other countries. However, it is important to compare survival in different series based on accurate prognostic data. The European Organisation for Research and Treatment of Cancer (EORTC) and the Cancer and Leukaemia Group B (CALGB) have recently published prognostic scoring systems. We have assessed the prognostic variables, validated the EORTC and CALGB prognostic groups, and evaluated survival in a series of 142 patients. Methods Case notes of 142 consecutive patients presenting in Leicester since 1988 were reviewed. Univariate analysis of prognostic variables was performed using a Cox proportional hazards regression model. Statistically significant variables were analysed further in a forward, stepwise multivariate model. EORTC and CALGB prognostic groups were derived, Kaplan-Meier survival curves plotted, and survival rates were calculated from life tables. Results Significant poor prognostic factors in univariate analysis included male sex, older age, weight loss, chest pain, poor performance status, low haemoglobin, leukocytosis, thrombocytosis, and non-epithelial cell type (p<0.05). The prognostic significance of cell type, haemoglobin, white cell count, performance status, and sex were retained in the multivariate model. Overall median survival was 5.9 (range 0-34.3) months. One and two year survival rates were 21.3% (95% CI 13.9 to 28.7) and 3.5% (0 to 8.5), respectively. Median, one, and two year survival data within prognostic groups in Leicester were equivalent to the EORTC and CALGB series. Survival curves were successfully stratified by the prognostic groups. Conclusions This study validates the EORTC and CALGB prognostic scoring systems which should be used both in the assessment of survival data of series in different countries and in the stratification of patients into randomised clinical studies.

Tumor necrosis correlates with angiogenesis and is a predictor of poor prognosis in malignant mesothelioma

Objectives: Malignant mesothelioma (MM) is a fatal tumor of increasing incidence related to asbestos exposure. Microscopic tumor necrosis (TN) is a poor prognostic factor in solid tumors, but it has not been characterized in MM. We wished to evaluate the incidence of TN in MM and its correlations with clinicopathologic factors, angiogenesis, and survival. Methods: TN was graded in 171 routine formalin-fixed, paraffin-embedded hematoxylin-eosinstained tumor sections by two independent observers. Angiogenesis was assessed by the microvessel count (MVC) of CD34 immunostained sections. TN was correlated with survival by Kaplan-Meier and log-rank analysis, and stepwise, multivariate Cox models were used to compare TN with angiogenesis and established prognostic factors and prognostic scoring systems. Results: TN was identified in 39 cases (22.8%) and correlated with low hemoglobin (p = 0.01), thrombocytosis (p = 0.04), and high MVC (p = 0.02). TN was a poor prognostic factor in univariate analysis (p = 0.008). Patients with TN had a median survival of 5.3 months vs 8.3 months in negative cases. Independent indicators of poor prognosis in multivariate analysis were nonepithelioid cell type (p = 0.0001), performance status > 0 (p = 0.007), and increasing MVC (p = 0.004) but not TN. TN contributed independently to the European Organisation for Research and Treatment of Cancer (EORTC) [p = 0.03] and to the Cancer and Leukemia Group B (CALGB) [p = 0.03] prognostic groups in respective multivariate Cox analyses. Conclusions: TN correlates with angiogenesis and is a poor prognostic factor in MM. TN contributes to the EORTC and CALGB prognostic scoring systems.

Invading edge vs. inner (edvin) patterns of vascularization : an interplay between angiogenic and vascular survival factors defines the clinical behaviour of non-small cell lung cancer

Neo-angiogenesis during neoplastic growth involves endothelial mitogenic and migration stimuli produced by cancer or tumour stromal cells. Although this active angiogenesis takes place in the tumour periphery, the process of vessel growth and survival in inner areas and its clinical role remain largely unexplored. The present study compared the microvessel score (MS) as well as the single endothelial cell score (ECS) in the invading edge and in inner areas of non-small cell lung carcinomas (NSCLCs). Three different patterns of vascular growth were distinguished: the edvin (edge vs. inner) type 1, where a low MS was observed in both peripheral and inner tumour areas; the edvin type 2, where a high MS was noted in the invading front but a low MS in inner areas; and the edvin type 3, where both peripheral and inner tumour areas had a high MS. The ECS was high in the invading edge in edvin type 2 and 3 cases and was sharply decreased in both types in inner areas, suggesting that endothelial cell migration is unlikely to contribute to the angiogenic process in areas away from the tumour front. Expression of the vascular endothelial growth factor (VEGF) and of thymidine phosphorylase (TP) was associated with a high MS in the invading edge. VEGF was associated with a high MS in inner areas (edvin 3), while TP expression was associated with edvin type 2, showing that VEGF (and not TP) contributes to the preservation of the inner vasculature. Both edvin type 2 and 3 cases showed an increased incidence of node metastasis, but edvin type 3 cases had a poorer prognosis, even in the N1-stage group. The present study suggests that tumour factors regulating angiogenesis and vascular survival are not identical. A possible method is reported to quantify these two parameters by comparing the MS in the invading edge and inner areas (edvin types). This observation may contribute to the evaluation of the effectiveness of different therapeutic approaches, namely vascular targeting vs. anti-angiogenesis. Copyright (C) 2000 John Wiley and Sons, Ltd.

Phase II study of liarozole in advanced non-small cell lung cancer

The aim of this phase II study was to investigate the efficacy and tolerability of liarozole, a novel benzimidazole derivative, in non-small cell lung cancer (NSCLC). Liarozole 300 mg twice daily orally was evaluated in 14 patients with stage IIIB and IV NSCLC. 8 patients had received prior treatment with chemotherapy and/or radiotheraphy. WHO toxocity grading and response criteria were used. Liarozole was well tolerated. Grade 2 toxicities included alopecia (1 patient), dermatological toxicity (5 patients), dry mouth (2 patients) and nausea and vomiting (2 patients). Leukocytosis was seen in 5 patients, including 2 cases with an elevated white cell count pretreatment. Liarozole was discontinued in 1 patient who developed intolerable progressive pruritis associated with an erythematous rash. No objective tumour response was seen, all 14 patients developing progressive disease with 4 months of commencing treatment. Liarozole was well tolerated but was ineffective as single as single agent therapy in the management of NSCLC. The side-effect profile was compatible with inhibition of retinoic acid degradation.

Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

Carbonic anhydrase IX expression, a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer

Purpose To evaluate carbonic anhydrase (CA) IX as a surrogate marker of hypoxia and investigate the prognostic significance of different patterns of expression in non-small-cell lung cancer (NSCLC). Methods Standard immunohistochemical techniques were used to study CA IX expression in 175 resected NSCLC tumors. CA IX expression was determined by Western blotting in A549 cell lines grown under normoxic and hypoxic conditions. Measurements from microvessels to CA IX positivity were obtained. Results CA IX immunostaining was detected in 81.8% of patients. Membranous (m) (P = .005), cytoplasmic (c) (P = .018), and stromal (P < .001) CA IX expression correlated with the extent of tumor necrosis (TN). The mean distance from vascular endothelium to the start of tumor cell positivity was 90 μm, which equates to an oxygen pressure of 5.77 mmHg. The distance to blood vessels from individual tumor cells or tumor cell clusters was greater if they expressed mCA IX than if they did not (P < .001). Hypoxic exposure of A549 cells for 16 hours enhanced CAIX expression in the nuclear and cytosolic extracts. Perinuclear (p) CA IX (P = .035) was associated with a poor prognosis. In multivariate analysis, pCA IX (P = .004), stage (P = .001), platelet count (P = .011), sex (P = .027), and TN (P = .035) were independent poor prognostic factors. Conclusion These results add weight to the contention that mCA IX is a marker of tumor cell hypoxia. The absence of CA IX staining close to microvessels suggests that these vessels are functionally active. pCA IX expression is representative of an aggressive phenotype. © 2003 by American Society of Clinical Oncology.