Isolation and Cryopreservation of Mononuclear Cells from Peripheral Blood and Bone Marrow of Blood Cancer Patients.

Peripheral blood and bone marrow aspirates are routinely obtained from blood cancer patients for diagnostic investigations and provide an accessible source of patient-specific cancer cells, as well as non-malignant cells, for research proposes. The simple and reproducible method presented here allows isolation of viable mononuclear cells, including malignant cells, from fresh peripheral blood or bone marrow aspirates using density gradient centrifugation. The cells obtained using the protocol described can be further purified for a variety of cellular, immunological, molecular, and functional assays.

False positivity in break apart fluorescence in-situ hybridization due to polyploidy.

Background: In-situ hybridization (ISH) is a diagnostic tool in the detection of chromosomal anomalies, which has important implications for diagnosis, classification and prediction of cancer therapy in various diseases. Certain thresholds of number of cells showing an aberrant pattern are commonly used to declare a sample as positive for genomic rearrangements. The phenomenon of polyploidy can be misleading in the interpretation of break apart fluorescence in-situ hybridization (FISH).

What works best in hiatus hernia repair, sutures alone, absorbable mesh or non-absorbable mesh? A systematic review and network meta-analysis of randomized clinical trials.

Laparoscopic hiatal hernia repair (HHR) and fundoplication is a common low risk procedure providing excellent control of gastro-oesophageal reflux disease and restoring of normal anatomy at the hiatus. HHR may fail, however, resulting in hiatus hernia (HH) recurrence, and the use of tension-free mesh-augmented hernioplasty has been proposed to reduce recurrence. Previous research on this topic has been heterogeneous, including study methods, mesh type used and technique performed.

A novel aryl-guanidinium derivative, VP79s, targets the signal transducer and activator of transcription 3 signaling pathway, downregulates myeloid cell leukaemia-1 and exhibits preclinical activity against multiple myeloma.

Aims: We have recently described a novel guanidinium-based compound, VP79s, which induces cytotoxicity in various cancer cell lines. Here, we aim to investigate the activity of VP79s and associated mechanisms of action in multiple myeloma (MM) cells in vitro and ex vivo.

Main Methods: The effects of VP79s on cell viability and induction of apoptosis was examined in a panel of drug-sensitive and drug-resistant MM cell lines, as well as ex vivo patient samples and normal donor lymphocytes and platelets.

Exploring the Anti-Cancer Mechanism of Novel 3,4'-Substituted Diaryl Guanidinium Derivatives.

We previously identified a guanidinium-based lead compound that inhibited BRAF through a hypothetic type-III allosteric mechanism. Considering the pharmacophore identified in this lead compound (i.e.

Quantifying postoperative mobilisation following oesophagectomy.

Objective: Early mobilisation is in integral component of postoperative recovery following complex surgical procedures such as oesophageal cancer resections, however evidence to guide early mobilisation protocols in critical care settings is limited. Furthermore, little is known about actual mobilisation levels postoperatively. This study quantified postoperative mobilisation post- oesophagectomy and investigated barriers to mobility.

Prevalence and clinical association of MET gene overexpression and amplification in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape project.

Introduction: In a well-defined NSCLC cohort of the ETOP Lungscape program, we explored the epidemiology of IHC MET overexpression and amplification, their inter-correlation, and their association to outcome.

Methods: Resected NSCLC were assessed for MET gene copy number (GCN) and expression using silver in-situ hybridization (SISH) and immunohistochemistry (IHC) on TMAs in a multicenter setting. MET amplification was defined as MET/centromere ratio≥2 (with average MET GCN≥4), high MET GCN as CGN≥5 and MET IHC+ as ≥2+ intensity in ≥50% of tumor cells.

Pro-inflammatory and tumour proliferative properties of excess visceral adipose tissue.

Obesity has been associated with increased incidence and mortality of oesophageal and colorectal adenocarcinoma. Excess central adiposity may drive this association through an altered inflammatory milieu. Utilising a unique adipose tissue bioresource we aimed to determine the pro-tumour properties of visceral adipose tissue.

Left ventricular structural and functional changes in the metabolic syndrome.

To test the hypothesis that the cardiac structural and functional abnormalities of the metabolic syndrome (MS) are independent of body mass index (BMI), 160 untreated patients (aged 47+/-1 years [mean +/- SEM], 53% male) underwent 2-dimensional echocardiography and tissue Doppler imaging and evaluation for MS. Participants with MS and controls were similar in age, BMI, and ejection fraction, but those with MS had greater left ventricular relative wall thickness (RWT) (0.43+/-0.

Wilms' tumor gene 1 (WT1) expression in childhood acute lymphoblastic leukemia: a wide range of WT1 expression levels, its impact on prognosis and minimal residual disease monitoring.

Wilms' tumor gene 1 (WT1) is overexpressed in the majority (70-90%) of acute leukemias and has been identified as an independent adverse prognostic factor, a convenient minimal residual disease (MRD) marker and potential therapeutic target in acute leukemia. We examined WT1 expression patterns in childhood acute lymphoblastic leukemia (ALL), where its clinical implication remains unclear. Using a real-time quantitative PCR designed according to Europe Against Cancer Program recommendations, we evaluated WT1 expression in 125 consecutively enrolled patients with childhood ALL (106 BCP-ALL, 19 T-ALL) and compared it with physiologic WT1 expression in normal and regenerating bone marrow (BM).

Ursodeoxycholic acid inhibits translocation of protein kinase C in human colonic cancer cell lines.

Deoxycholic acid (DCA) has been implicated in colonic carcinogenesis through effects mediated by protein kinase C (PKC) activation. By contrast, ursodeoxycholic acid (UDCA) is reported to reduce colon cancer incidence in ulcerative colitis. The aim of this study was to investigate whether UDCA modulated DCA-induced PKC isoenzyme translocation to its site of activity.

Ret/PTC chimeric transcripts in an Irish cohort of sporadic papillary thyroid carcinoma.

Ret rearrangements are common in papillary thyroid carcinoma (PTC), with ret/PTC-3 commonly seen in children exposed to ionizing radiation. In this context ret/PTC-3 has been correlated with solid variant morphology, poorer prognosis, and aggressive tumor behavior. We aimed to assess the prevalence of the common ret chimeric transcripts (ret/PTC-1 and ret/PTC-3) in a group of sporadic PTC and correlate them with tumor morphology.

Evaluation of renal function following treatment with 5-aminosalicylic acid derivatives in patients with ulcerative colitis.

Background: A number of cases of nephrotoxicity have been reported in patients with inflammatory bowel disease taking oral 5-aminosalicylic acid (5-ASA).

Aim: To evaluate the effects of 9 months of therapy with mesalazine or olsalazine on renal function in patients with ulcerative colitis in remission.

Methods: Forty patients with ulcerative colitis in complete remission for 6 months were randomized to either olsalazine (n=20) or mesalazine (n=20 for nine months).

Soluble adhesion molecules in inflammatory bowel disease.

Background: Soluble adhesion molecules are elevated in a number of inflammatory conditions.

Aims: To investigate the correlation of soluble intercellular adhesion molecule-1 (sICAM-1) and sE-selectin with the activity of inflammatory bowel disease (IBD).

Methods: sICAM-1 and sE-selectin were measured by an enzyme-linked immunosorbent assay (ELISA) in 53 patients with ulcerative colitis (UC) and 38 patients with Crohn's disease (CD).

The urban diet and Crohn's disease: is there a relationship?

The aetiology and pathogenesis of Crohn's disease (CD) remain to be elucidated. In addition to genetic influences and immune mediated cytokine gene activation, various specific and non-specific environmental factors are considered to be associated with the induction and/or exacerbation of inflammatory bowel disease (IBD). The incidence of CD is higher in urban areas than in the rural, environment.

Diagnosis of gluten-sensitive enteropathy: is exclusive reliance on histology appropriate?

Objective: Coeliac disease is a prevalent disorder but frequently remains undiagnosed because of varied modes of clinical presentation. In this study, methods for the detection of coeliac disease were evaluated in a clinical practice setting.

Methods: Small intestinal histology, IgA anti-endomysial and IgG anti-gliadin antibody tests were performed on 441 unselected, consecutive patients under investigation for small intestinal disease.

Epithelial cell folate depletion occurs in neoplastic but not adjacent normal colon mucosa.

Background & Aims: Restricted folate supply is associated with the development of carcinoma, and folate supplements have a protective effect in colorectal carcinoma. This effect may be mediated through correction of local folate deficiency. The aim of this study was to define the folate content of neoplastic colonic epithelial cells and its relation to that of adjacent normal tissue and circulating levels.

Effects of anabolic steroids on acute phase responses in intra-abdominal sepsis.

The acute phase response is an important adaptive response to sepsis and injury. As anabolic steroids increase protein synthesis we postulated that these agents might also increase hepatic acute phase protein synthesis. Male Wistar rats were pretreated with testosterone or danazol for 48 h prior to caecal ligation and puncture (CLP).

Tumour marker detection in oesophageal carcinoma.

Levels of the tumour markers CEA, CA 19-9, CA 125 and SCC were measured in 58 patients presenting with oesophageal carcinoma and compared with levels in patients with benign oesophageal disease and levels in normal volunteers. CEA and CA 19-9 were significantly increased in the patients with oesophageal cancer, however, individual sensitivity for CEA, CA 19-9, CA 125 and SCC was only 28, 34, 10, and 32%, respectively. The combined sensitivity of all markers was 64% and specificity was 80%.

Folate status of gastrointestinal epithelial cells is not predicted by serum and red cell folate values in replete subjects.

Localised folate deficiency has been implicated in colonic carcinogenesis and supplementation has been proposed for certain populations at risk. However, identifying those groups that may benefit is difficult as the relation between blood folate and gut epithelial cell values is unknown. The aim of this study was to define this relation.

Prostaglandin E2 and leukotriene B4 synthesis by peripheral leucocytes in alcoholics.

Alcohol inhibits phospholipase (PL) activity in a number of animal models. We have therefore measured prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), liberated by stimulated peripheral blood mononuclear cells (PBMC) and neutrophils respectively in chronic alcoholics and in control subjects. Peripheral blood mononuclear cells from alcoholics produced less PGE2 (p less than 0.