Tumor location determines midkine level and its association with the disease progression in colorectal cancer patients: a pilot study

Purpose

The purpose of this study was to evaluate midkine, multipotential cytokine, and growth factor in colorectal cancer (CRC) stratified by tumor location.

Methods

Midkine was assessed immunoenzymatically in paired cancerous and noncancerous tissues from 53 CRCs and referred to CRC stage, tumor location, and size, and circulating cytokine levels.

Results

Midkine was higher in cancerous versus noncancerous tissue in 98?% cases (424.2 vs. 31.1?pg/mg, p?p?=?0.005) due to higher midkine level in noncancerous rectal than colonic tissue (45.5 vs. 26.2?pg/mg, p?=?0.074). Tumor location affected midkine association with CRC stage. Midkine fold change was higher in advanced stages of rectal cancers (16.8 vs. 5.3, respectively in III/IV vs. I/II, p?=?0.013), while it tended to be lower in colonic ones (25.3 vs. 47.8, p?=?0.134). In addition, fold change in midkine level was higher in rectal N1 than N0 cancers (17.3 vs. 16.5, p?=?0.032), while it tended to be lower in colonic cancers (23.6 vs. 50.1, p?=?0.085). Midkine negatively correlated with tumor size (r?=?0.40, p?=?0.017), while it tended to positively correlate with its serum levels (r?=?0.45, p?=?0.081).

Conclusions

Midkine is differently expressed in tumors arising from colonic and rectal mucosa, where it may play diverse roles in carcinogenesis. High midkine expression in noncancerous rectal mucosa might contribute to, a characteristic for rectal cancers, higher incidence of local recurrence. Divergent expression of midkine and its association pattern ought to be taken into account while designing midkine-directed therapies for CRC.     

FGF23 contributes to insulin sensitivity in obese adolescents - preliminary results

Fibroblast growth factor‐23 (FGF23) is a hormonal regulator of circulating phosphate and vitamin D levels. Recent investigations revealed that besides a key role in the pathogenesis of calcium–phosphorus disorders, in some patients FGF23 may be an indicator of cardiovascular complications. As a ‘hormone‐like’ factor, it may also be involved in some metabolic processes, especially in the metabolism of glucose and fat. Its potential contribution to metabolic syndrome (MS) development has not been confirmed yet. Objective The study was to examine the possible correlations between FGF23 serum levels and body composition, blood pressure and selected parameters of glucose, insulin and fat metabolism in adolescents with simple obesity. Patients and design In 68 (35 female) adolescents (mean age 13·9 years) with simple obesity [mean BMI SDS 4·9 (95% CI 4·4–5·4)], the levels of FGF23, total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol and triglycerides were measured. Standard oral glucose tolerance tests were performed with the assessment of fasting and after 120′ postload glucose and insulin levels; the insulin resistance index HOMA‐IR was calculated. Results Regardless of gender, there was a significant inverse correlation between FGF23 and fasting insulin level (r = ?0·3), as well as HOMA‐IR (r = ?0·29). Multiple regression model showed the independent association between FGF23 and HOMA‐IR. Conclusion FGF23 seems to be a novel factor contributing to insulin sensitivity. Further investigations are needed to define its role in the development of MS.     

Soluble ST2 protein in chronic heart failure is independent of traditional factors

Introduction

ST2 protein is the interleukin 33 (IL-33) receptor, whose serum level depends on the biomechanical strain of cardiac myocytes. The aim of this study was to analyse the relationship between soluble ST2 (sST2) level and traditional factors in patients with chronic heart failure.

Material and methods

Sixty-six patients (mean age 62 years, 75% males) in stable NYHA class I-III with left ventricular ejection fraction < 45% were included in the study. Clinical, biochemical, electrocardiographic, echocardiographic and angiographic data were analysed. Patients were divided into groups depending on sST2 median: > 0.28 ng/ml (n = 31) vs. ≤ 0.28 ng/ml (n = 35). sST2 was measured using a quantitative ELISA kit. In order to define factors associated with sST2 levels uni- and multivariate regression analysis was performed.

Results

There was no relationship between sST2 levels and age (p = 0.67), body mass index (p = 0.19), hsTnT (p = 0.7) or other analysed parameters (all p > 0.05), except for N-terminal prohormone B-type natriuretic peptide (NT-proBNP). A significant positive correlation between sST2 and NT-proBNP was found (p = 0.013, R = 0.395). Multivariate analysis revealed that the stage of coronary artery disease and NT-proBNP were independent factors associated with sST2 concentration (p = 0.04). Intriguing is the fact that the fewer the sclerotic changes present in arteries, the higher was the sST2 level (β = –0.381, p = 0.04).

Conclusions

sST2 protein is independent of traditional factors which usually affect levels of NT-proBNP. In chronic heart failure, sST2 protein may be of greater importance in idiopathic dilated cardiomyopathy than in ischaemic aetiology, which seems to be associated with the molecular mechanism (biomechanical strain) related to sST2.     

Mechanisms underlying the developmental origins of disease

It is well established that there is a relationship between patterns of early growth and subsequent risk of development of metabolic diseases such as type 2 diabetes and cardiovascular disease. Studies in both humans and in animal models have provided strong evidence that the early environment plays an important role in mediating these relationships. The concept of the developmental origins of health and disease is therefore widely accepted. The mechanisms by which an event in very early life can have a permanent effect on the long-term health of an individual are still relatively poorly understood. However a growing body of evidence has implicated a number of candidate mechanisms. These include permanent changes in an organ structure, programmed changes in gene expression through epigenetic modifications and persistent effects on regulation of cellular ageing. Understanding the extent and nature of these processes may enable the identification of individuals at risk of metabolic disease as well as providing insight into potential preventative and intervention strategies.