Syndecan-1 expression--a novel prognostic marker in pancreatic cancer

OBJECTIVE: Syndecan-1 is a transmembrane receptor that participates in cell-cell and cell-matrix interactions, cell proliferation and cell migration. Expression of syndecan-1 is downregulated in many cancers, but in pancreatic ductal adenocarcinoma it is upregulated. Method: We studied the immunohistochemical expression of syndecan-1 in 144 pancreatic adenocarcinomas and evaluated the prognostic value of syndecan-1 expression. Formalin-fixed, paraffin-embedded specimens were stained with mouse monoclonal antibody B-B4 against human syndecan-1. The epithelial and stromal staining was separately evaluated and compared with patient survival, clinical stage and histological grade. RESULT: Epithelial immunoreactivity was observed in most of the pancreatic carcinoma samples: in 70 (49%) of the samples the epithelial staining was weak, in 48 (33%) moderate, in 18 (12%) strong and in only 8 (6%) of the samples the epithelial staining was negative. Stromal staining was weak in 24 (17%), moderate in 31 (22%), strong in 11 (8%) and negative in 78 (54%) of the pancreatic carcinoma samples. Lack of stromal expression predicted a better prognosis (p = 0.002; HR 1.7) and it was independent of stage (p = 0.01; HR = 1.5) and grade (p = 0.0004; HR 2.1) in multivariate analysis. Epithelial expression predicted better prognosis for patients that underwent surgery for cure (n = 94, p = 0.03). CONCLUSION: Stromal syndecan-1 expression is an independent prognostic marker in pancreatic cancer, whereas epithelial syndecan-1 expression predicts better prognosis only in resectable disease.     

'Think before you buy under-18s drink': evaluation of a community alcohol intervention

Hazardous consumption of alcohol by teenagers is a significant public health problem in New Zealand. Concern about supply of alcohol to minors motivated 'Think before you buy under-18s drink', a campaign to reduce alcohol-related harm by discouraging inappropriate supply of alcohol by adults. Two intervention districts and a comparison district, in the South Island of New Zealand, were selected for the purpose of evaluating the campaign. Primary outcome measures were changes in the prevalence of parent supply to their teenager (13-17 years) for unsupervised drinking (SUD), and changes in the prevalence of binge drinking among teenagers. At baseline, 49% of teenagers reported a recent episode of binge drinking. SUD in the past month was reported by 36% of teenagers. Recent purchases of alcohol by under-18s were common (bottle shops: 16%; pubs/bars: 11%). In contrast to teenagers, only 2% of parents reported SUD in the past month. Levels of binge drinking decreased in all three districts. Analysis of data from 474 teenagers who completed questionnaires, at baseline and follow-up, showed decreased SUD in Ashburton and Waitaki relative to Clutha, although this was not significant (OR=0.73; 95% CI: 0.43, 1.25). Discrepancies between teenager and parent reports of SUD may be due to the latter providing a socially desirable survey response and to differences in the interpretation of what constitutes adult supervision. The lack of a significant association between changes in SUD and binge drinking may be a consequence of teenagers obtaining relatively small amounts of alcohol from their parents and larger quantities from other sources, e.g. peers (some of whom may be able to purchase alcohol legally) and from licensed premises.     

Functional endothelial cells derived from rhesus monkey embryonic stem cells

We have used rhesus monkey embryonic stem (ES) cells to study endothelial cell development. Rhesus ES cells (R366.4 cell line) exposed to medium containing vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF), and epidermal growth factor (EGF) assumed a relatively uniform endothelial cell morphology and could be propagated and expanded with a consistent phenotype and normal karyotype. When placed in Matrigel, these rhesus ES cell-derived endothelial cells (RESDECs) formed capillary-like structures characteristic of endothelial cells. Immunohistochemical and flow cytometric analysis of RESDECs showed that they take up acetylated low-density lipoprotein (LDL), express CD146, von Willebrand factor, and the integrin alpha v beta 3, and bind the lectin ulex europaeus agglutinin-1. These cells also express the VEGF receptor Flk-1 and secrete VEGF. When introduced in a Matrigel plug implanted subcutaneously in mice, RESDECs formed intact vessels and recruited new endothelial cell growth. In vivo function was demonstrated by coinjection of RESDECs with murine tumor cells subcutaneously into immunocompromised adult mice. RESDECs injected alone did not form measurable tumors. Tumor cells grew more rapidly and had increased vascularization when coinjected with the RESDECs. Immunohistochemical staining demonstrated that the RESDECs participated in forming the tumor neovasculature. RESDECs provide a novel means to examine the mechanisms of endothelial cell development, and may open up new therapeutic strategies.     

Lack of MMP-9 expression is a marker for poor prognosis in Dukes’ B colorectal cancer

Background

Matrix metalloproteinases (MMPs) play a role in cancer progression by degrading extracellular matrix and basement membranes, assisting in tumour neovascularization and in supporting immune response in cancer.

Methods

We studied the prognostic value of immunohistochemical expression of MMP-2, MMP-8, and MMP-9 in a series of 619 colorectal cancer patients using tissue microarray specimens.

Results

Of the samples, 56% were positive for MMP-2, 78% for MMP-8, and 60% for MMP-9. MMP-9 associated with low WHO grade (p?<?0.001). In univariate analysis of Dukes’ B tumours, MMP-9 negativity associated with poor survival (p?=?0.018), and MMP-9 positivity was an independent prognostic marker in multivariate analysis of these tumours (p?=?0.034).

Conclusion

Negative MMP-9 expression can predict poor prognosis in Dukes’ B colorectal tumours and may prove useful for identifying patients, who should be offered adjuvant treatment.

     

Does consumption of two portions of salmon per week enhance the antioxidant defense system in pregnant women?

Salmon is a rich source of marine n-3 fatty acids, which may increase oxidative stress and, in turn, could affect the antioxidant defense system in blood plasma and erythrocytes of pregnant women. The Salmon in Pregnancy Study provided two meals of salmon per week to pregnant women from week 20 of gestation; the control group maintained their habitual diet low in oily fish. Higher selenium and retinol plasma concentrations were observed after dietary salmon supplementation. Besides, a concomitant increase in selenium and glutathione concentration as well as glutathione peroxidase and reductase activities were detected as pregnancy progressed. However, tocopherols, retinol, β-carotene, and coenzyme Q(10) decreased in late pregnancy. Collectively, our findings lead to the hypothesis that increased farmed salmon intake may increase antioxidant defenses during pregnancy. Clinical trials identifier NCT00801502.     

Long-term outcome of right ventricular outflow tract reconstruction with bicuspidalized homografts

Objective: Given the shortage of small-sized cryopreserved homografts for right ventricle (RV) to pulmonary artery (PA) reconstructions, more readily available larger-sized homografts can be used after size reduction by bicuspidalization. The aim of our study was to determine and compare function over time of standard and bicuspidalized homografts in infants younger than 12 months, including patients with a Ross or extended Ross procedure. Methods: All consecutives infants under the age of 1 year, who underwent a surgical procedure in which a homograft was placed in the RV-PA position between January 1994 and April 2009, were included. Prospectively collected data from serial, standardized echocardiography from all patients were extracted from the database, and hospital records were retrospectively reviewed. Results: A total of 40 infants had a valved homograft conduit placed in the RV-PA position. In 20 of those patients, a bicuspidalized homograft was used. Twelve patients underwent a Ross procedure, of whom seven had an additional Konno-type aortic annulus enlargement. Median follow-up was 146 months (interquartile range (IQR), 117–170; total patient years: 178) in the group with standard use of the homograft and 95 months (IQR, 11–104; total patient years: 78) in the group with bicuspidalized conduits. Freedom from re-intervention (re-operation or percutaneous) was not different in the standard and bicuspidalized groups for all and Ross or Konno–Ross procedures (Tarone-Ware, p = 0.65 and p = 0.47, respectively). Consecutive echocardiographic maximum velocities in the right ventricular outflow tract were similar in the standard and bicuspidalized groups. Conclusion: When proper sized cryopreserved homografts for placement in the RV-PA position in Ross, Konno–Ross, and other procedures in infants under the age of 1 year are not readily available, bicuspidalized homografts provide an acceptable alternative.     

Effects of intracoronary injection of autologous bone marrow-derived stem cells on natriuretic peptides and inflammatory markers in patients with acute ST-elevation myocardial infarction

Background

Intracoronary administration of autologous bone marrow stem cells (BMC) has been shown to result in a subtle improvement of global left ventricular ejection fraction after ST-elevation myocardial infarction (STEMI), but the overall benefits of BMC therapy are still unclear. We studied the influence of intracoronary injections of BMC on levels of natriuretic peptides and inflammatory mediators, which are well established prognostic biomarkers, in patients with STEMI.

Methods

In this randomized, double-blind study, consecutive patients with an acute STEMI treated with thrombolysis followed by PCI 2?C6?days after STEMI, were randomly assigned to receive either intracoronary BMC or placebo medium into the infarct-related artery. Blood samples were drawn for biochemical determinations.

Results

From baseline to 6?months, there was a significant decrease in the levels of N-terminal probrain natriuretic peptide (NT-proBNP), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) in the whole patient population (P?<?0.001 for all). However, no difference was observed between the BMC group (n?=?39) and the placebo group (n?=?39) in the change of the levels of NT-proANP (median ?54 vs. +112?pmol/L), NT-proBNP (?88 vs. ?115?pmol/L) or inflammatory markers IL-6 (?3.86 vs. ?5.61?pg/mL), hsCRP (?20.29 vs. ?22.36?mg/L) and tumor necrosis factor ?? (?0.12 vs. ?0.80?pg/mL) between baseline and 6?months.

Conclusion

Intracoronary BMC therapy does not appear to exert any significant effects on the secretion of natriuretic peptides or inflammatory biomarkers in STEMI patients.