Interleukin (IL)-10 is expressed in many solid tumours and plays an ambiguous role in controlling cancer growth and metastasis. In order to determine whether IL-10 is involved in tumour progression ...and prognosis in nonsmall cell lung cancer (NSCLC), IL-10 expression in tumour cells and tumour-associated macrophages (TAMs) and its associations, if any, with clinicopathological features were investigated. Paraffin-embedded sections of surgical specimens obtained from 50 patients who had undergone surgery for NSCLC were immunostained with an antibody directed against IL-10. TAMs and tumour cells positive for IL-10 were subsequently quantified. IL-10-positive TAM percentage was higher in patients with stage II, III and IV NSCLC, and in those with lymph node metastases compared with patients with stage I NSCLC. High IL-10 expression by TAMs was a significant independent predictor of advanced tumour stage, and thus was associated with worse overall survival. Conversely, IL-10 expression by tumour cells did not differ between stages II, III and IV and stage I NSCLC. In conclusion, interleukin-10 expression by tumour-associated macrophages, but not by tumour cells, may play a role in the progression and prognosis of nonsmall cell lung cancer. These results may be useful in the development of novel approaches for anticancer treatments.
A stress reaction involving increased cortisol release, which has not been documented thus far, might affect the assessment of selectivity of catheterization during adrenal venous sampling (AVS).
To ...investigate whether an ACTH-driven cortisol release occurs during AVS and whether it influences the assessment of selectivity by the step-up of cortisol (plasma cortisol concentrations, PCC) between the adrenal vein blood (PCC(SIDE)) and the inferior vena cava (PCC(IVC)), e.g. the selectivity index (SI).
We determined the SI in samples obtained simultaneously at starting AVS (t-15) and again after 15 min (t0) in 34 consecutive patients with proven aldosterone-producing adenoma. We then calculated the SI with PCC(SIDE) obtained at t-15 and at t0, and the PCC(IVC) values obtained at the different time point, thus simulating sequential AVS.
The PCC(SIDE) and the SI fell significantly from t-15 to t0 on both the sides. When PCC(SIDE) obtained at t-15 was combined with PCC(IVC) at t0, the SI values were higher than those obtained with simultaneously drawn samples. This led to label as selective more AVS studies than with bilaterally simultaneous data, especially when using higher cutoffs for the SI.
A transient increase in cortisol release from both adrenal glands occurs in the majority of the patients who undergo AVS. This stress reaction can influence the assessment of both the selectivity of the catheterization during the sequential AVS technique and the lateralization of aldosterone excess.
Synthetic biomaterials combined with cells and osteogenic factors represent a promising approach for the treatment of a number of orthopedic diseases, such as bone trauma and congenital ...malformations. To guarantee optimal biological properties, bone substitutes are prepared with a 3D structure and porosity grade functional to drive cell migration and proliferation, diffusion of factors, vascularization and cell waste expulsion. In this study, synthetic hydroxyapatite (HA) or rat bone extracellular matrix (BP) were examined in an effort to optimize the mechanical properties and osteogenic activity of poly-ε-caprolactone scaffolds prepared with alginate threads (PCL-AT). Using rabbit bone marrow-derived mesenchymal stem cells (rMSCs), the effects of PCL composite substrates on cell adhesion, growth and osteogenic differentiation were evaluated. Micro-CT analysis and scanning electron microscopy evidenced that porous PCL scaffolds containing HA or BP acquire a trabecular bone-like structure with interconnected pores homogenously distributed and are characterized by a pore diameter of approximately 10 µm (PCL-AT-BP) or ranging from 10 to 100 µm. Although the porosity grade of both PCL-AT-HA and PCL-AT-BP promoted optimal conditions for the cell growth of rMSCs at the early phase, the presence of BP was crucial to prolong the cell viability at the late phase. Moreover, a precocious expression of Runx2 (at 7 days) was observed in PCL-AT-BP in combination with osteogenic soluble factors suggesting that BP controls better than HA the osteogenic maturation process in bone substitutes.
Background: Chemokines are involved in the influx of leukocytes into the airways in inflammatory lung diseases. The differential cell recruitment characteristic of TH1 versus TH2 immune responses may ...be associated with differential chemokine expression. Objective: We investigated the expression of chemokines; monocyte chemotactic proteins (MCPs) 1, 3, and 4; eotaxin; and IFN-γ–inducible protein 10 (IP-10) in both TH1- and TH2-mediated lung diseases. Methods: By using immunocytochemistry and in situ hybridization, we examined the protein and mRNA expression, respectively, in bronchoalveolar lavage and biopsy samples in subjects with asthma, tuberculosis, sarcoidosis, and chronic bronchitis. Results: Increased immunoreactivity and mRNA expression of IP-10 and of the MCPs was found in the bronchoalveolar lavage fluid and biopsy specimens of subjects with asthma and tuberculosis compared with that of control subjects (P < .005). IP-10, however, was particularly increased in subjects with sarcoidosis (P < .001). Eotaxin, on the other hand, was increased only in patients with asthma when compared with control subjects (P < .005). Conclusion: This study demonstrates that MCP-1, MCP-3, and MCP-4 expression is not specifically associated with lung diseases characterized by a particular cytokine profile. In contrast, IP-10 is mostly expressed in TH1-mediated diseases, and eotaxin expression seems to be specifically associated with lung diseases of a TH2 cytokine profile. (J Allergy Clin Immunol 2001;107:664-70.)
Abstract The dual role of tumour-infiltrating macrophages and lymphocytes on nonsmall cell lung cancer (NSCLC) progression and prognosis may be due to the differential activity of their phenotypes. ...To investigate the impact of inflammatory cells on NSCLC, we first quantified the number of macrophages (CD68+) and lymphocytes (CD8+ and CD4+) and the percentage of CD8+ cells expressing IL-10 (CD8+/IL-10+) in tumour stroma and epithelium. Then, we evaluated the possible relationships between the numbers of these cells and the clinicopathological features and the overall survival of patients. Paraffin-embedded sections of surgical specimens from 64 patients who had undergone surgery for NSCLC were immunostained with antibodies directed against CD68, CD4, CD8 and IL-10. The percentage of CD8+/IL-10+ cells was higher in cancer stroma of patients with stage I NSCLC than in those with stages II, III, and IV. High percentages of stromal CD8+/IL-10+ cells were associated with longer overall patient survival. In contrast, the number of CD68+, CD8+ and CD4+ cells did not differ between stage I NSCLC and stages II, III, and IV. In conclusion, the survival advantage of patients with stage I NSCLC may be related to the anti-tumour activity of the CD8+/IL-10+ cell phenotype.
Purpose
Contrast-enhanced ultrasonography (CEUS) is an appealing alternative to computed tomography angiography (CTA) for the follow-up of patients who underwent endovascular abdominal aortic ...aneurysm repair (EVAR). We sought to evaluate the accuracy of CEUS compared with a particularly tailored protocol of CTA performed with a 64-row multidetector CT.
Materials and methods
The study prospectively enrolled 88 consecutive patients for CEUS and CTA imaging during follow-up after EVAR, yielding 142 paired examinations. The outcome is represented by three main goals: identification and characterisation of endoleaks, evaluation of graft patency and measurement of aneurysm diameter. Triple-phase CTA was the gold standard.
Results
Sensitivity and specificity of CEUS compared with CTA in endoleak and graft patency evaluation were 91.89% and 100% and 72% and 100%, respectively. A very high correlation between CTA and CEUS diameter measurements was established. CEUS did not appear superior to CTA in endoleak detection, probably because a tailored CTA protocol with a delayed phase (180 s) allows detection of low-flow endoleaks.
Conclusions
Patient management was not different
sta
following CEUS and CTA results. CTA cannot yet be completely replaced, but several limitations (radiation exposure, contrast agent) encourage redefining the routine follow-up imaging modality. We suggest an algorithm of surveillance alternating CTA and CEUS.
The aim of this study was to determine whether the T-helper 2-type cytokines interleukin (IL)-13 and -4 are involved in mucus hypersecretion, the hallmark of chronic bronchitis (CB). Surgical ...specimens were examined from 33 subjects undergoing lung resection for localised peripheral malignant pulmonary lesions: 21 smokers with symptoms of CB, 10 asymptomatic smokers (AS) and two nonsmokers with normal lung function. The number of IL-4 and -13 positive (+) cells in the central airways was quantified. To better assess the cytokine profile, a count was also made of IL-5+ and interferon (IFN)-gamma+ cells. Compared to AS, the CB group had an increased number of IL-13+ and -4+ cells in the bronchial submucosa, while the number of IL-5+ and IFN-gamma+ cells were similar in all the groups. No significant associations were found between the number of cells expressing IL-13 or -4 and the number of inflammatory cells. Double labelling showed that 13.2 and 12.9% of IL-13+ cells were also CD8+ and CD4+, whereas 7.5 and 5% of IL-4+ cells were CD8+ and CD4+, respectively. In conclusion, T-helper-2 and -1 protein expression is present in the central airways of smokers and interleukin-4 and -13 could contribute to mucus hypersecretion in chronic bronchitis.
Summary
Background
We previously reported that in moderate‐to‐severe asthma there is a deficit of IL‐10 secretion that could prevent the production of soluble HLA‐G (sHLA‐G), a non‐classical human ...leucocyte antigen class I molecule with tissue‐protective properties in inflammatory responses.
Objective
Our objective was to investigate the production of sHLA‐G and the secretion of IL‐10 by peripheral blood mononuclear cells (PBMCs) in asthma induced by isocyanates and to compare the results with those obtained in non‐occupational allergic asthma.
Method
sHLA‐G and IL‐10 were measured by ELISA in the culture supernatants of unstimulated or lipopolysaccharide (LPS)‐stimulated PBMCs obtained from 20 subjects with isocyanate asthma, 16 asymptomatic subjects exposed to isocyanates, 18 subjects with non‐occupational allergic asthma, and 26 healthy control subjects.
Results
Occupational exposure to isocyanates was associated with high baseline levels of secretion of IL‐10 by PBMCs, whether or not the exposed subjects had asthmatic symptoms. However, spontaneous production of sHLA‐G by PBMC was significantly higher in subjects with isocyanate asthma compared with asymptomatic‐exposed controls. In contrast, PBMCs from subjects with non‐occupational allergic asthma produced sHLA‐G only after LPS stimulation.
Conclusions
sHLA‐G production and IL‐10 secretion are influenced by workplace exposure to isocyanates and by development of asthma. The different behaviour of both sHLA‐G and IL‐10 in asthma induced by isocyanates compared with non‐occupational allergic asthma suggests a heterogeneous biological role for HLA‐G molecules and for IL‐10, a key cytokine of immune and inflammatory responses.
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