Isoprenaline Induces Periostin Expression in Gastric Cancer

PURPOSE: Periostin mediates critical steps in gastric cancer and is involved in various signaling pathways. However, the roles of periostin in promoting gastric cancer metastasis are not clear. The aim of this study was to investigate the relevance between periostin expression and gastric cancer progression and the role of stress-related hormones in the regulation of cancer development and progression. MATERIALS AND METHODS: Normal, cancerous and metastatic gastric tissues were collected from patients diagnosed with advanced gastric cancer. The in vivo expression of periostin was evaluated by in situ hybridization and immunofluorescent staining. Meanwhile, human gastric adenocarcinoma cell lines MKN-45 and BGC-803 were used to detect the in vitro expression of periostin by using quantitative real-time polymerase chain reaction (PCR) and western blotting. RESULTS: Periostin is expressed in the stroma of the primary gastric tumors and metastases, but not in normal gastric tissue. In addition, we observed that periostin is located mainly in pericryptal fibroblasts, but not in the tumor cells, and strongly correlated to the expression of α-smooth muscle actin (SMA). Furthermore, the distribution patterns of periostin were broader as the clinical staging of tumors progressed. We also identified a role of stress-related signaling in promoting cancer development and progression, and found that isoprenaline upregulated expression levels of periostin in gastric cancer cells. CONCLUSION: These findings suggest that the distribution pattern of periostin was broader as the clinical staging of the tumor progressed and found that isoprenaline upregulated expression levels of periostin in gastric cancer cells.

Pentoxifylline decreases serum level of adhesion molecules in atherosclerosis patients

Inflammation is involved in development, progression, and complications of atherosclerotic disease. Clinical studies have indicated that the level of monocyte chemoattractant protein 1 [MCP-1], IL-18, and adhesion molecules correlates with the severity of atherosclerosis and can predict future cardiovascular events. Experimental studies have shown pentoxifylline [PTX] reduces these factors in animal models. The purpose of the present pilot study was to evaluate effect of PTX on a group of inflammatory biomarkers in patients with coronary artery disease [CAD]. Forty patients with angiographically documented CAD, who fulfilled inclusion and exclusion criteria, were entered in the double-blind, randomized, pilot clinical study. The patients were randomly given PTX [400 mg three times daily] or placebo [3 tab/day] for 2 months. Serum concentrations of MCP-1, IL-18, intercellular adhesion Molecule 1 [ICAM-1], and vascular cell adhesion molecule 1 [VCAM-1] were measured before and at the end of intervention by enzyme-linked immunosorbant assay. Our study showed that the serum levels of ICAM-1 and VCAM-1 was decreased in the study population after two-month treatment [P<0.05]. Based on the results of our pilot study, administration of PTX in CAD patients significantly decreases adhesion molecules levels

Effect of photodynamic therapy on the extracellular matrix and associated components

In many countries, photodynamic therapy (PDT) has been recognized as a standard treatment for malignant conditions (for example, esophageal and lung cancers) and non-malignant ones such as age-related macular degeneration and actinic keratoses. The administration of a non-toxic photosensitizer, its selective retention in highly proliferating cells and the later activation of this molecule by light to form reactive oxygen species that cause cell death is the principle of PDT. Three important mechanisms are responsible for the PDT effectiveness: a) direct tumor cell kill; b) damage of the tumor vasculature; c) post-treatment immunological response associated with the leukocyte stimulation and release of many inflammatory mediators like cytokines, growth factors, components of the complement system, acute phase proteins, and other immunoregulators. Due to the potential applications of this therapy, many studies have been reported regarding the effect of the treatment on cell survival/death, cell proliferation, matrix assembly, proteases and inhibitors, among others. Studies have demonstrated that PDT alters the extracellular matrix profoundly. For example, PDT induces collagen matrix changes, including cross-linking. The extracellular matrix is vital for tissue organization in multicellular organisms. In cooperation with growth factors and cytokines, it provides cells with key signals in a variety of physiological and pathological processes, for example, adhesion/migration and cell proliferation/differentiation/death. Thus, the focus of the present paper is related to the effects of PDT observed on the extracellular matrix and on the molecules associated with it, such as, adhesion molecules, matrix metalloproteinases, growth factors, and immunological mediators.

Effects of sulfated polysaccharides on tumour biology / Efectos de los polisacáridos sulfatados en la biología tumoral

Sulfated polysaccharides can act not only as anticoagulants but also as tumour inhibitors. Recent studies suggest that sulfated polysaccharides could affect tumour cells directly. Sulfated polysaccharides could inhibit the metastasis and proliferation of tumour cells by binding to growth factors and cell adhesion molecules. Moreover, sulfated polysaccharides could inhibit heparanase, which cleaves heparan sulfate chains of heparan sulfate proteoglycans and cause release of growth factors sequestered by heparan sulfate chains. Some sulfated polysaccharides can induce apoptosis and differentiation of tumour cells, but the mechanism is uncertain. In addition, sulfated polysaccharides can enhance the innate and adaptive immune response for tumour cells. Thus, the anti-tumour mechanism of sulfated polysaccharides can be explained, at least partly, through the effects on tumour biology directly.

Los polisacáridos sulfatados podrían actuar no solamente como anticoagulantes, sino también como inhibidores del tumor. Estudios recientes sugieren que los polisacáridos sulfatados podrían afectar directamente las células tumorales. Los polisacáridos tumorales podrían inhibir la metástasis y la proliferación de las células tumorales por medio de la unión con los factores de crecimiento y las moléculas de adhesión celular. Además, los polisacáridos sulfatados podrían inhibir la heparanasa, que rompe las cadenas de heparán-sulfato del proteoglicano de heparán-sulfato, dando lugar a la liberación de los factores de crecimiento secuestrados por las cadenas de heparán-sulfato. Algunos polisacáridos sulfatados podrían inducir la apoptosis y diferenciación de las células tumorales, pero el mecanismo es incierto. Además, los polisacáridos sulfatados podrían mejorar la respuesta inmunológica innata y adaptativa frente a las células tumorales. De este modo, el mecanismo antitumoral de los polisacáridos sulfatados pudiera explicarse – al menos parcialmente – a partir de los efectos sobre la biología tumoral directamente.

The action of red wine and purple grape juice on vascular reactivity is independent of plasma lipids in hypercholesterolemic patients

Although red wine (RW) reduces cardiovascular risk, the mechanisms underlying the effect have not been identified. Correction of endothelial dysfunction by RW flavonoids could be one mechanism. We measured brachial artery reactivity by high-resolution ultrasonography, plasma lipids, glucose, adhesion molecules (ICAM-1 and VCAM), and platelet function in 16 hypercholesterolemic individuals (8 men and 8 women; mean age 51.6 ± 8.1 years) without other risk factors. Twenty-four normal subjects were used as controls for vascular reactivity. Subjects randomly received RW, 250 ml/day, or purple grape juice (GJ), 500 ml/day, for 14 days with an equal wash-out period. At baseline, all 16 subjects were hypercholesterolemic (mean LDL = 181.0 ± 28.7 mg/dl) but HDL, triglycerides, glucose, adhesion molecules, and platelet function were within normal limits. Brachial artery flow-mediated dilation was significantly decreased compared to controls (9.0 ± 7.1 vs 12.1 ± 4.5 percent; P < 0.05) and increased with both GJ (10.1 ± 7.1 before vs 16.9 ± 6.7 percent after: P < 0.05) and RW (10.1 ± 6.4 before vs 15.6 ± 4.6 percent after; P < 0.05). RW, but not GJ, also significantly increased endothelium-independent vasodilation (17.0 ± 8.6 before vs 23.0 ± 12.0 percent after; P < 0.01). GJ reduced ICAM-1 but not VCAM and RW had no effect on either molecule. No significant alterations were observed in plasma lipids, glucose or platelet aggregability with RW or GJ. Both RW and GJ similarly improved flow-mediated dilation, but RW also enhanced endothelium-independent vasodilation in hypercholesterolemic patients despite the increased plasma cholesterol. Thus, we conclude that GJ may protect against coronary artery disease without the additional negative effects of alcohol despite the gender.