The proteomic analysis of cisplatin resistance in breast cancer cells.

Resistance to cisplatin represents a major obstacle in the effective management of many cancers, including metastatic breast cancer. We aimed to gain further understanding of the mechanisms underlying development of cisplatin resistance using an in vitro cell line model. The MCF-7 breast cancer cell line and a novel derivative displaying significant resistance to cisplatin were analyzed using two-dimensional gel electrophoresis.

Methylation of TIMP3 in esophageal squamous cell carcinoma.

Aim: To measure the frequency of DNA methylation of the tissue inhibitor of metalloproteinase 3 (TIMP3) promoter and relate this to any change of gene expression in esophageal squamous cell carcinoma in patients from a region of high incidence in China.

Methods: Cancer cell lines were treated with or without the demethylating reagent 5-aza-2'-deoxycytidine. Methylation of the TIMP3 promoter was assessed in three regions by melt curve analysis and its expression was assessed by real-time RT-PCR.

A point prevalence survey of wounds in north-east England.

Objective: To review current wound-care practice and the standard of wound care in Hull and East Yorkshire; obtain information on prevalence, treatment and outcomes; provide a basis for estimating the extent of the problem, treatment modalities used, service provision and future needs; highlight areas of care in need of improvement; highlight areas with excellent wound practices and gain information for future research projects within the population of the region.

Method: Point prevalence interface audit of community and acute trusts.

Results: The cumulative wound prevalence for the region was 12%.

The effects of a COX-2 inhibitor meloxicam on squamous cell carcinoma of the esophagus in vivo.

Our previous study showed that aspirin induced apoptosis of esophageal cancer cells in vitro by inhibiting the pathway of NF-kappaB downstream regulation of cyclooxygenase-2. The purpose of this study was to determine if similar changes occurred in vivo in the tumors of patients with SCC of the esophagus who were given a preferential COX-2 inhibitor, meloxicam. Fifty-three patients who had an esophagectomy for SCC were allocated randomly to either a Treatment group (n = 25) or a control group (n = 28).

The quality of trials in operative surgery.

Objective: This study aimed to assess the reported quality of trials in operative surgery.

Summary Background Data: Randomized controlled trials (RCTs) in operative surgery have previously been criticized for using weak methodology despite no evidence to suggest their quality is any different from nonsurgical trials.

Study Design: All surgical RCTs published in the British Medical Journal, the Journal of the American Medical Association, The Lancet, and the New England Journal of Medicine between 1998 and 2004 were identified.

The putative roles of the ubiquitin/proteasome pathway in resistance to anticancer therapy.

The ubiquitin/proteasome (UP) pathway plays a significant role in many important biological functions and alterations in this pathway have been shown to contribute to the pathology of many human diseases, including cancer. Proteasome inhibition has been well established as a rational strategy for the treatment of multiple myeloma and is currently under investigation for the treatment of other haematological malignancies and solid tumours. Recent evidence suggests that proteasome inhibition may also sensitise tumour cells to the actions of both conventional chemotherapy and radiotherapy, suggesting that this pathway may modify clinical response to anticancer therapy.

Peroxisome proliferator-activated receptor-alpha agonist fenofibrate regulates IL-12 family cytokine expression in the CNS: relevance to multiple sclerosis.

The interleukin-12 (IL-12) family of cytokines which includes IL-12, IL-23, and IL-27 play critical roles in T cell differentiation and are important modulators of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Previously, we demonstrated that peroxisome proliferator-activated receptor (PPAR) -alpha agonists suppress the development of EAE. The present studies demonstrated that the PPAR-alpha agonist fenofibrate inhibited the secretion of IL-12p40, IL-12p70 (p35/p40), IL-23 (p19/p40), and IL-27p28 by lipopolysaccharide-stimulated microglia.

The cost of wound care for a local population in England.

The objective of this study is to estimate the cost of wound care in a local population of approximately 590 000 using results from a wound care audit carried out in Hull and the East Riding of Yorkshire as a basis. Full results of the audit will be published separately. An audit in June 2005 provided information on patients with wounds and on their treatment.

Surgery is associated with lower morbidity and longer survival in elderly breast cancer patients over 80.

As breast cancer is the most frequent cancer in the elderly with a peak incidence of 1 in 10 by the age of 80, it is important to establish optimum therapy in this group. We conducted a case note-based retrospective study of all elderly primary breast cancer patients aged 80 and above between 1992 and 2002. The type of treatment, complications, disease progression, recurrence, and overall survival were recorded.

Representation of moving wavefronts of whisker deflection in rat somatosensory cortex.

Rats rhythmically sweep their whiskers over object features, generating sequential deflections of whisker arcs. Such moving wavefronts of whisker deflection are likely to be fundamental elements of natural somatosensory input. To determine how moving wavefronts are represented in somatosensory cortex (S1), we measured single- and multiunit neural responses in S1 of anesthetized rats to moving wavefronts applied through a piezoelectric whisker deflector array.

Expression microarray analysis reveals genes associated with in vitro resistance to cisplatin in a cell line model.

We aimed to investigate the mechanisms of cisplatin resistance using an in vitro cancer model. A derivative breast cancer cell line (MCF-7CR) was established which demonstrated significant resistance to cisplatin at clinically relevant low concentrations compared to the MCF-7 parental cell line. Expression microarray analysis was used to identify targets from a 3k cancer-related oligonucleotide platform which were differentially expressed between the derivative and parental cell lines.

Oestrogen and progesterone receptor status of individual foci in multifocal invasive ductal breast cancer.

Widespread acceptance of breast conserving surgery for early breast cancer has led to renewed interest in multifocality, which is seen in 13-63% of breast cancers. According to current guidelines, oestrogen/progesterone receptor status is assessed on the sample obtained at initial core biopsy or the main tumour focus in multifocal breast cancer (more than one distinct tumour focus in a quadrant). We assessed receptor status of individual foci in multifocal breast cancer.

Immune activation in patients with irritable bowel syndrome.

Background And Aims: We set out to test the hypothesis that irritable bowel syndrome (IBS) is characterized by an augmented cellular immune response with enhanced production of proinflammatory cytokines. We further aimed to explore whether symptoms and psychiatric comorbidity in IBS are linked to the release of proinflammatory cytokines.

Methods: We characterized basal and Escherichia coli lipopolysaccharide (LPS)-induced cytokine production in peripheral blood mononuclear cells (PBMCs) from 55 IBS patients (18 mixed-, 17 constipation-, 20 diarrhea-predominant) and 36 healthy controls (HCs).

Optimum mesh and port sizes for laparoscopic incisional hernia repair.

Purpose: Since incisional hernia repair was introduced into laparoscopic surgical practice it has been recognized that larger meshes can be problematic to successfully insert through laparoscopic ports. This study aims to facilitate the choice of mesh and port by documenting the minimum port sizes realistically needed for insertion of different types and sizes of onlay mesh. It also aims to evaluate the optimal insertion techniques.

A pilot study on the effect of topical negative pressure on quality of life.

Objective: To discover the impact of topical negative pressure (TNP) on quality of life.

Method: An exploratory prospective cohort study was conducted on 26 patients undergoing TNP. The Cardiff Wound Impact Schedule (CWIS), a wound-specific tool, was used to investigate quality-of-life scores before therapy and four weeks after therapy or at wound closure.

Direct polymerase chain reaction amplification of formalin-fixed, paraffin-wax-embedded tissue after automated sequential laser microdissection and pressure catapulting.

A robust method to facilitate rapid laser microdissection and pressure catapulting (LMPC) coupled with direct polymerase chain reaction (dPCR) to eliminate the need for extraction of DNA before a PCR-based assay is described. This sequential LMPC-dPCR method is rapid and decreases the number of processing steps, reducing the chance of tissue loss and contamination.

Peroxisome proliferator-activated receptor-gamma agonists suppress the production of IL-12 family cytokines by activated glia.

The IL-12 family of cytokines, which include IL-12, IL-23, and IL-27, play critical roles in the differentiation of Th1 cells and are believed to contribute to the development of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Relatively little is known concerning the expression of IL-12 family cytokines by cells of the CNS, the affected tissue in MS. Previously, we and others demonstrated that peroxisome proliferator-activated receptor (PPAR)-gamma agonists suppress the development of EAE, alter T cell proliferation and phenotype, and suppress the activation of APCs.

Management of early breast cancer in the elderly.

Breast cancer is the most common malignancy in women with an age related increase in incidence ranging from 1 in 50 at age 50 to 1 in 10 at age 80. This is particularly significant in view of the changing demographics in the western population, characterised by an aging population and increased life expectancy. However in spite of favourable prognostic factors and less aggressive biological behaviour, elderly breast cancer patients receive less aggressive treatment when compared with their younger counterparts.

Liver X receptor and retinoid X receptor agonists inhibit inflammatory responses of microglia and astrocytes.

Liver X receptors (LXRs) are nuclear receptors previously identified to be important in lipid metabolism. Recent reports suggest that LXR agonists also exhibit anti-inflammatory properties in mouse models of atherosclerosis and contact dermatitis. In the present study, we investigated the effects of LXR agonists on mouse microglia and astrocytes.

Recurrence rates after DCE-MRI image guided planning for breast-conserving surgery following neoadjuvant chemotherapy for locally advanced breast cancer patients.

Background: Neoadjuvant therapy results in a significant increase in breast-conserving surgery. However, traditional imaging methods are unable to accurately predict the extent of viable residual disease leading to uncertainty in surgical planning and some previous studies have shown a disproportionately high incidence of locoregional recurrence. Dynamic contrast enhanced-MRI (DCE-MRI) has been shown to provide a potentially more accurate prediction of residual disease.

Breast reduction surgery in the UK and Ireland - current trends.

Introduction: This paper reviews the current status of bilateral breast reduction surgery in the UK and Ireland. It examines the pre-operative, operative and postoperative management of women.

Patients And Methods: A questionnaire established information about surgeons' experience, bilateral breast reduction work-load, pre-operative assessment, selection criteria, issues of operative technique and postoperative management.

Cyclooxygenase-2 expression in squamous cell carcinoma of the esophagus.

Increased cyclooxygenase-2 expression has been reported to be a poor prognostic indicator in a number of cancers. In this study we investigated the relationship between COX-2 expression in squamous cell carcinoma of the esophagus and tumor characteristics and patient survival. The study group consisted of 90 men and 48 women who underwent esophagectomy for squamous cell carcinoma of the esophagus between October 1984 and May 1985.