The relationship between angiogenesis and cyclooxygenase-2 expression in prostate cancer

<b>OBJECTIVE</b>: To test the hypothesis that angiogenesis in prostate cancer is associated with tumour invasion and metastasis, and that this is mediated through increased cyclooxygenase-2 (COX-2) expression. <b>PATIENTS AND METHODS</b>: Angiogenesis was assessed in 105 patients with either prostate cancer (79) or benign prostatic hyperplasia (BPH, 26) and these data correlated with levels of COX-2 expression in the same dataset. The mean microvessel density (MVD) was analysed as a marker of angiogenesis, using the endothelial antigen CD34 stained by immunohistochemistry. <b>RESULTS</b>: There was no difference in MVD in progressive tumour stages compared with BPH. There was a negative correlation between MVD and COX-2 expression, but the effect of increased COX-2 expression on MVD was not marked. <b>CONCLUSION</b>: These data suggest that COX-2 drives tumour spread in prostate cancer by means other than the promotion of angiogenesis

Amplification of the androgen receptor may not explain the development of androgen-independent prostate cancer

Objective To examine the role of androgen receptor (AR) gene amplification and aneusomy of the X chromosome in the development of antiandrogen-resistant prostate cancer. Patients and methods Twenty patients with prostate cancer resistant to androgen-deprivation therapy were selected for study. The records of patients with tumours before and after antiandrogen therapy, and with a full clinical follow-up, were retrieved. AR gene amplification and X chromosome copy number were assessed by fluorescence in situ hybridization using a labelled probe at locus Xq11-13 for the AR gene and a labelled a-satellite probe for the X chromosome. At least 20 nuclei were scored over three tumour areas by two independent observers. Results Aneusomy of the X chromosome was reported respectively in seven (35%) and 11 (55%) tumours before and after hormone relapse, the AR gene copy number was increased in seven (35%) and 13 (65%), respectively, and AR gene amplification was detected in one (5%) and three (15%), respectively. Neither increased AR copy number nor AR amplification in primary tumours precluded a biological response to androgen-deprivation therapy. Conclusion The rate of AR gene amplification is too low to be solely responsible for the development of antiandrogen-resistant prostate cancer. Also, the presence of amplified AR and cells aneusomic for the X chromosome in primary tumours that respond to androgen-deprivation therapy suggests that an increase in AR gene copy number does not prevent a tumour from responding to this therapy. Therefore other mechanisms which could cause hormone-refractory prostate cancer must be investigated before it is understood why so many patients relapse with this disease

The CAG trinucleotide repeat length in the androgen receptor does not predict the early onset of prostate cancer

Objective To relate the repeat length of the androgen-receptor CAG trinucleotide to the age of onset of prostate cancer, stage and grade of disease. Patients and methods After obtaining ethical approval, 265 patients with locally confined or locally advanced/metastatic prostate cancer were identified and evaluated for age at diagnosis (less than 65 years and greater than 75 years). DNA was extracted from peripheral blood lymphocytes and 1 mug aliquots subjected to polymerase chain reaction using fluorescently labelled primers. Samples were then run on an ABI 377 gene scan analysis gel with an internal molecular weight marker. The length of the CAG repeat was determined by comparing the gene scan product size to samples where the CAG repeat length had been quantified using direct sequencing. The Kruskal-Wallis, Mann-Whitney and Wilcoxon two sample tests were used to analyse the data. Results The mean (range) length of the CAG repeat in the androgen receptor was 22.2 (10-31) in the younger and 22.5 (16-32) in the older group, and was not statistically different. There was no significant association between the CAG repeat length and the age of onset of prostate cancer (P = 0.568) or with stage (P = 0.577) and grade (P = 0.891) of prostate cancer. Conclusion These results suggest that there is no correlation between the androgen receptor CAG repeat length and the age of onset, stage and grade of prostate cancer, confirming recent doubts from other similar studies of a suggested correlation between shorter androgen receptor CAG repeat and early onset and aggressiveness of prostate cancer

Russian wheat aphid biotype RWASA2 causes more vascular disruption than RWASA1 on resistant barley lines

AbstractWe investigated the comparative effects of the feeding damage caused by two Russian wheat aphid (RWA, Diuraphis noxia Kurdjumov) biotypes, RWASA1 and RWASA2, on leaves of three RWA-resistant barley (Hordeum vulgare L.) lines from the USDA-ARS, and used a South African non-resistant cultivar as control. The relationship between aphid breeding capacity and the structural damage inflicted by the aphids was studied, using wide-field fluorescence and transmission electron microscopy (TEM). Colonies of the two biotypes grew rapidly on all four barley lines during a 10day feeding exposure but as expected, population size and density were generally lower on the resistant lines than on the non-resistant cultivar. The new South African biotype, RWASA2, bred significantly faster than the original RWASA1 biotype. The feeding and water uptake-related damage sustained by phloem and xylem tissues of the resistant lines suggest that RWASA2 was a more aggressive feeder and caused substantially more cell damage than RWASA1. Examination of wound callose distribution after aphid feeding revealed that high levels of wound callose occurred in non-resistant and in resistant lines. Reduction in aphid population size, as well as ultrastructural damage during feeding by RWA biotypes on resistant lines, signals potential antibiotic and tolerant responses of the barley lines to aphid feeding. We infer from callose distribution and ultrastructural studies, that phloem transport would be substantially reduced in the non-resistant PUMA and to a lesser extent in the resistant STARS lines, which suggests that the STARS lines may be a potential source of RWASA1 and RWASA2-resistance

Forged in the Fires of COVID-19: The Evolution of Systemic Therapy for Online Practice and Beyond

There has been a swift uptake in the use of teletherapy since the start of the COVID-19 pandemic, which has corresponded with an increase in clinical scholarship focused on conducting systemic therapy in an online format. A majority of this scholarship offers ideas for adapting therapeutic tasks developed around in-person contact for a remote format. The current article moves beyond adapting and offers ideas for remote systemic therapy that are born from our experiences of evolving through teletherapy. We begin by noting some of the significant differences between in-person therapy and teletherapy before describing how these differences can influence client presence and professionalism in session. Following this discussion, we offer ideas for how systemic therapists can enhance client presence, communicate the importance of the work, and inspire client initiative for change while working remotely

Androgen receptor phosphorylation status at serine 578 predicts poor outcome in prostate cancer patients

Purpose: Prostate cancer growth is dependent upon androgen receptor (AR) activation, regulated via phosphorylation. Protein kinase C (PKC) is one kinase that can mediate AR phosphorylation. This study aimed to establish if AR phosphorylation by PKC is of prognostic significance. Methods: Immunohistochemistry for AR, AR phosphorylated at Ser-81 (pARS81), AR phosphorylated at Ser-578 (pARS578), PKC and phosphorylated PKC (pPKC) was performed on 90 hormone-naïve prostate cancer specimens. Protein expression was quantified using the weighted histoscore method and examined with regard to clinico-pathological factors and outcome measures; time to biochemical relapse, survival from biochemical relapse and disease-specific survival. Results: Nuclear PKC expression strongly correlated with nuclear pARS578 (c.c. 0.469, p=0.001) and cytoplasmic pARS578 (c.c. 0.426 p=0.002). High cytoplasmic and nuclear pARS578 were associated with disease-specific survival (p<0.001 and p=0.036 respectively). High nuclear PKC was associated with lower disease-specific survival when combined with high pARS578 in the cytoplasm (p=0.001) and nucleus (p=0.038). Combined high total pARS81 and total pARS578 was associated with decreased disease-specific survival (p=0.005) Conclusions: pARS578 expression is associated with poor outcome and is a potential independent prognostic marker in hormone-naïve prostate cancer. Furthermore, PKC driven AR phosphorylation may promote prostate cancer progression and provide a novel therapeutic target

Design optimisation of air-fed full pressurised suits

This article is a post-print version of the published article which may be accessed at the link below.The JET machine and associated facilities require significant maintenance and enhancement installation activities in support of the experimental exploitation programme. A proportion of these activities are within radiological and respiratory hazardous environments. As such, breathing air-fed one-piece pressurised suits provide workers with protection from the inhalation of both airborne tritium and beryllium dust. The design of these suits has essentially developed empirically. There is a practical necessity to improve the design to optimise worker performance, protection and thermal comfort. This paper details the complexity of modeling the three-dimensional thermofluid domain between the inner surface of the suit and under garments that includes mass as well as heat transfer, suiting geometry, human metabolism and respiration and effects of limb movements. The methods used include computational fluid dynamics (CFD), theoretical adaptations of mixed-phase turbulent flow, profile scanning of a suit and actuating life size mannequin and data processing of the images and experimental validation trials. The achievements of the current programme and collaborations are presented in the paper and future endeavors are discussed.The author gratefully acknowledges the loan of the articulated mannequin from the Defence Science and Technology Laboratories. This work was funded jointly by EPSRC and by the European Communities under the contract of Association between EURATOM and UKAEA. The views and opinions expressed herein do not necessarily reflect those of the European Commission. This work was carried out within the framework of EFDA

In vitro growth characteristics of Fusarium langsethiae isolates recovered from oats and wheat grain in the UK

Fusarium langsethiae is a fungus that has recently been implicated in the contamination of small-grain cereal crops such as oats, wheat and barley with high levels of HT-2 and T-2 toxins in many European countries. The epidemiology of this fungus is not well known and may therefore be a bigger problem than currently thought to be. A study was carried out investigating the in vitro growth characteristics of F. langsethiae isolates from contaminated oats and wheat at various temperatures; 15, 20, 25 and 30 °C. Results indicated similar growth trends of oats and wheat isolates of F. langsethiae. Wheat isolates grew significantly (p<0.001) faster than oat isolates although this difference may have been confounded by the age of cultures, with oat isolates collected one year earlier. The estimated optimum growth temperature for all isolates was 24 °C. Isolates were macro-morphologically categorized as having lobed or entire colony margins, and either possessing one of the following colony colours: white, orange or purple. Since the estimated optimum growth temperature of F. langsethiae is typical in temperate summers when small-grain cereals are flowering, it is possible that this species can infect, colonise and possibly contaminate the developing grains with HT-2 and T-2 toxins which are of food safety concern

Solving Lattice QCD systems of equations using mixed precision solvers on GPUs

Modern graphics hardware is designed for highly parallel numerical tasks and promises significant cost and performance benefits for many scientific applications. One such application is lattice quantum chromodyamics (lattice QCD), where the main computational challenge is to efficiently solve the discretized Dirac equation in the presence of an SU(3) gauge field. Using NVIDIA's CUDA platform we have implemented a Wilson-Dirac sparse matrix-vector product that performs at up to 40 Gflops, 135 Gflops and 212 Gflops for double, single and half precision respectively on NVIDIA's GeForce GTX 280 GPU. We have developed a new mixed precision approach for Krylov solvers using reliable updates which allows for full double precision accuracy while using only single or half precision arithmetic for the bulk of the computation. The resulting BiCGstab and CG solvers run in excess of 100 Gflops and, in terms of iterations until convergence, perform better than the usual defect-correction approach for mixed precision.Comment: 30 pages, 7 figure