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

Comparison of the prognostic value of inflammation based pathological and biochemical criteria in patients undergoing potentially curative resection for colorectal cancer

<b>Objective</b>: To examine interrelationships between the local inflammatory response (Klintrup and Jass scores) and the systemic inflammatory response (Glasgow prognostic score [GPS]), and compare their prognostic value in patients undergoing curative resection for colorectal cancer. <b>Background</b>: Both localized peritumoral inflammatory cell infiltrate and the host systemic inflammatory response are known to have prognostic value in colorectal cancer. However, the interrelationships of biochemical and cellular components of the systemic inflammatory response and the local inflammatory response are poorly understood. <b>Methods</b>: Retrospective study of 287 patients who underwent surgery between 1997 and 2004. Data were collected from routine preoperative blood tests. Routine pathology specimens were scored according to Jass and Klintrup criteria for peritumoral infiltrate. <b>Results</b>: Increased Dukes stage was associated with less peritumoral infiltrate (Jass criteria: P < 0.001, Klintrup criteria: P < 0.01). Increased modified GPS (mGPS) was associated with increased circulating white cell (P < 0.01) and neutrophil (P < 0.01) counts and low lymphocyte counts (P < 0.01). Increased circulating white cell count was associated with increased neutrophil count (P < 0.001) and low-grade peritumoral infiltrate (P < 0.05, Klintrup criteria). Jass and Klintrup criteria for peritumoral infiltrate were directly associated (P < 0.001). On univariate survival analysis of patients with node-negative disease (Dukes A and B), age (P < 0.01), mGPS (P < 0.01), neutrophil count (P < 0.05), and Klintrup criteria (P < 0.05) were associated with cancer-specific survival. On multivariate survival analysis in node-negative disease, the mGPS (hazard ratio: 2.61, 95% CI: 1.27-5.35, P < 0.01) and Klintrup criteria (hazard ratio: 6.31, 95% CI: 1.40-28.44, P < 0.05) were independently associated with cancer-specific survival. <b>Conclusions</b>: The results of the present study suggest low peritumoral infiltrate (Klintrup criteria) and increased systemic inflammation (mGPS criteria) are linked through the cell-mediated immune system. Furthermore, both pathologic (Klintrup) and biochemical (mGPS) measures of the inflammatory response predict survival after colorectal cancer surgery

Neoadjuvant Therapy in Early Breast Cancer:Treatment Considerations and Common Debates in Practice

Neoadjuvant treatment offers a number of benefits for patients with early breast cancer, and is an important option for consideration by multidisciplinary teams. Despite literature showing its efficacy, the use of neoadjuvant therapy varies widely. Here we discuss the clinical evidence supporting the use of neoadjuvant therapy in early stage breast cancer, including patient selection, monitoring response, surgery and radiotherapy considerations, with the aim of assisting multidisciplinary teams to determine patient suitability for neoadjuvant treatment

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4

Monetary-unit sampling An investigation

In 2 volsAvailable from British Library Document Supply Centre- DSC:DX182943 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Economic and technical analysis of distributed utility benefits for hydrogen refueling stations. Final report

This report presents the potential economic benefits of operating hydrogen refueling stations to accomplish two objectives: supply pressurized hydrogen for vehicles, and supply distributed utility generation, transmission and distribution peaking energy and capacity to the utility. The study determined under what circumstances using a hydrogen-fueled generator as a distributed utility generation source, co-located with the hydrogen refueling station components (electrolyzer and storage), would result in cost savings to the station owner, and hence lower hydrogen production costs. The systems studied include a refueling station (including such components as an electrolyzer, storage, hydrogen dispensers, and compressors) plus on-site hydrogen fueled electricity generation units (e.g., fuel cells or combustion engines). The operational strategy is to use off-peak electricity in the electrolyzer to fill hydrogen storage, and to dispatch the electricity generation about one hour per day to meet the utility`s local and system peaks. The utility was assumed to be willing to pay for such service up to its avoided generation, fuel, transmission and distribution costs

The relationship between the local and systemic inflammatory responses and survival in patients undergoing curative surgery for colon and rectal cancers

<p><b>Introduction</b></p> <p>Both local (Klintrup criteria) and systemic (Glasgow Prognostic Score, mGPS) inflammatory responses have been reported to be independent predictors of cancer-specific survival in colorectal cancer. However, high-grade local inflammatory response appears more common in rectal and high mGPS more common in colonic tumors. Whether relationships with survival are similar in colon and rectal tumors is unclear. The present study assesses the prognostic value of local and systemic inflammation in colon and rectal cancers and defines 3-year survival according to inflammation-based criteria for stage II/III disease.</p> <p><b>Methods</b></p> <p>Two hundred forty colon and 140 rectal cancer patients underwent potentially curative surgery between 1997 and 2007. C-reactive protein and albumin (mGPS) were measured preoperatively. Routine pathology specimens were scored according to Klintrup criteria for peritumoral infiltrate.</p> <p><b>Results</b></p> <p>Patients with colon cancers were older (P <0.05) and had higher T stage (P < 0.001) and mGPS (P ≤  0.001) compared with rectal cancers. The proportions of patients with a high-grade tumor inflammatory cell infiltrate were similar in colon and rectal cancers. mGPS and Klintrup criteria were independent predictors of cancer survival. The mGPS hazard ratios were 1.56 and 1.76 for the mGPS, and the Klintrup hazard ratios were 2.12 and 5.74 for colon and rectum, respectively. For stages II and III colorectal cancer, 3-year survival was 91% and 73%, respectively. Three-year survival varied between 100% and 68% depending on Klintrup score/ mGPS in stage II disease and between 97% and 60% in stage III disease.</p> <p><b>Conclusion</b></p> <p>Local and systemic inflammatory responses are important independent predictors of survival in colon and rectal cancers. These scores combined with tumor–node–metastases stage improve the prediction of survival in these patients.</p&gt

Constraining fault growth rates and fault evolution in New Zealand

Understanding how faults propagate, grow and interact in fault systems is important because they are primarily responsible for the distribution of strain in the upper crust. They localise deformation and stress release, often producing surface displacements that control sedimentation and fluid flow either by acting as conduits or barriers. Identifying fault spatial distribution, quantifying activity, evaluating linkage mechanism, and estimating fault growth rates are key components in seismic risk evaluation. Scientists from the National Institute of Water and Atmospheric Research (NIWA), New Zealand, and the Southampton Oceanography Centre (UK) are working on a collaborative project which aims to improve understanding of the processes of faulting in the Earth’s crust. The program comprises two research cruises to survey the Whakatane Graben, New Zealand, which is a zone of intense seismicity, active extensional faulting, and rapid subsidence within the back-arc region of the Pacific-Australia plate boundary zone (Fig. 1). Few places in the world offer the same potential to study the mechanisms by which major crustal faults have grown from small to large scale structures capable of generating moderate to large magnitude earthquakes. The aim of the project it to provide new insights into fundamental questions such as: (i) how do faults interact and link together to form fault systems, and (ii) how do fault propagation and linkage change with time? One of the most exciting results from the work in the Whakatane Graben is the potential for improving understanding of how and at what rates faults grow. The first survey was funded by the New Zealand Foundation for Research Science and Technology (FRST), and took place in November 1999 during which conventional marine geophysical data were collected. The second cruise is funded by the British Natural Environment Research Council (NERC), and is scheduled for January 2001. It will focus on the acquisition of high frequency shallow seismic and sidescan sonar data . This study of the Whakatane Graben will represent the most detailed regional investigation of active marine faults undertaken anywhere in the New Zealand region. Arguably, it could also become a case study of extensional fault growth and continental rift development of global significance.<br/