The role and importance of neutrophils in cancer has become increasingly apparent over the past decade. Neutrophils accumulate in the peripheral blood of patients with cancer, especially in those with advanced-stage disease, and a high circulating neutrophil-to-lymphocyte ratio is a robust biomarker of poor clinical outcome in various cancers. To date, most studies investigating the role of neutrophils in cancer have involved animal models or investigated the function of circulating human neutrophils. Thus, only limited information is available on the roles of intratumoural neutrophils (also known as tumour-associated neutrophils (TANs)) in patients with cancer. In this Review, we initially describe the evidence correlating the neutrophil-to-lymphocyte ratio with prognosis, followed by a discussion on the predictive value of TANs, which remains debatable, with conflicting data from different cancer types, including variations based on neutrophil location within and/or around the tumour. We then explore available data on the implications of TAN phenotypes and functions for cancer development and progression, highlighting the reported effects of various treatments on TANs and how neutrophils might affect therapeutic efficacy. Finally, we examine the various compounds capable of modulating neutrophils and suggest future research directions that might ultimately enable the manipulation of TANs in patients with cancer.

Tumour-associated neutrophils in patients with cancer

The major hindrance in the development and sustainability of aquaculture industry is the occurrence of various diseases in the farming systems. Today, preventive and management measures are central concern to overcome such outbreak of diseases. Immunostimulants are considered as an effective tool for enhancing immune status of cultured organisms. Among different immunostimulants used in aquaculture practices, β-glucan is one of the promising immunostimulant, which is a homopolysaccharide of glucose molecule linked by the glycoside bond. It forms the major constituents of cell wall of some plants, fungi, bacteria, mushroom, yeast, and seaweeds. Major attention on β-glucan was captivated with the gain in knowledge on its receptors and the mechanism of action. The receptor present inside the animal body recognizes and binds to β-glucan, which in turn renders the animal with high resistance and enhanced immune response. This review highlights β-glucan as an immunostimulant, its effective dosages, and route of administration and furthermore provides an outline on role of β-glucan in enhancing growth, survival, and protection against infectious pathogens pertaining to fishes and shellfishes. Study also summarizes the effect of β-glucan on its receptors, recognition of proteins, immune-related enzymes, immune-related gene expression and their mechanisms of action.

Beta-glucan: an ideal immunostimulant in aquaculture (a review).

Antitumor polysaccharides from mushrooms: a review on the structural characteristics, antitumor mechanisms and immunomodulating activities.

Background
A large body of literature suggests that certain polysaccharides affect immune system function. Much of this literature, however, consists of in vitro studies or studies in which polysaccharides were injected. Their immunologic effects following oral administration is less clear. The purpose of this systematic review was to consolidate and evaluate the available data regarding the specific immunologic effects of dietary polysaccharides.

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Immunomodulatory dietary polysaccharides: a systematic review of the literature.

Research has proved a relationship between functional components of food, health and well-being. Thus, functional components of food can be effectively applied in the treatment and prevention of diseases. They act simultaneously at different or identical target sites with the potential to impart physiological benefits and promotion of wellbeing including reducing the risk of cancer, cardiovascular disease, osteoporosis, inflammation, type II diabetes, and other chronic degenerative diseases, lowering of blood cholesterol, neutralization of reactive oxygen species and charged radicals, anticarcinogenic effect, low-glycaemic response, etc. Previously, it was thought that functional ingredients such as non-starchy carbohydrates including soluble and insoluble dietary fibres, fucoidan; antioxidants including polyphenols, carotenoids, tocopherols, tocotrienols, phytosterols, isoflavones, organosulphur compounds; plant sterols and soy phytoestrogens occur only in plant foods (whole grains, fruits, and vegetables) as phytochemicals. However, probiotics, prebiotics, conjugated linolenic acid, long-chain omega-3, −6 and −9-polyunsaturated fatty acids, and bioactive peptides have proved that functional components are equally available in animal products such as milk, fermented milk products and cold-water fish. The way a food is processed affects its functional components. Many processing techniques have been found to lower the concentration of functional components in food. Conversely, other techniques were found to increase them. Hence, in a time when the role of a healthy diet in preventing non-communicable diseases is well accepted, the borderline between food and medicine is becoming very thin.

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Functional components and medicinal properties of food: a review

Summary. β -Glucans are naturally occurring polysaccharides. These glucose polymers are constituents of the cell wall of certain pathogenic bacteria and fungi. The healing and immunostimulating properties of mushrooms have been known for thousands of years in the Eastern countries. These mushrooms contain biologically active polysaccharides that mostly belong to group of β -glucans. These substances increase host immune defense by activating complement system, enhancing macrophages and natural killer cell function. The induction of cellular responses by mushroom and other β -glucans is likely to involve their specific interaction with several cell surface receptors, as complement receptor 3 (CR3; CD11b/CD18), lactosylceramide, selected scavenger receptors, and dectin-1 ( β GR). β -Glucans also show anticarcinogenic activity. They can prevent oncogenesis due to the protective effect against potent genotoxic carcinogens. As immunostimulating agent, which acts through the activation of macrophages and NK cell cytotoxicity, β -glucan can inhibit tumor growth in promotion stage too. Antiangiogenesis can be one of the pathways through which β -glucans can reduce tumor proliferation, prevent tumor metastasis. β -Glucan as adjuvant to cancer chemotherapy and radiotherapy demonstrated the positive role in the restoration of hematopiesis following by bone marrow injury. Immunotherapy using monoclonal antibodies is a novel strategy of cancer treatment. These antibodies activate complement system and opsonize tumor cells with iC3b fragment. In contrast to microorganisms, tumor cells, as well as other host cells, lack β -glucan as a surface component and cannot trigger complement receptor 3-dependent cellular cytotoxicity and initiate tumor-killing activity. This mechanism could be induced in the presence of β -glucans.

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Effects of beta-glucans on the immune system.

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Azoto oksido ir kitų endotelio išskiriamų medžiagų svarba

Objective. During the photodynamic treatment, complement system is activated and tumor cells are opsonized with iC3b fragment. β-glucans can enhance cytotoxicity of iC3bopsonized cells due to their specific interaction with complement receptor 3 (CR3; CD11b/CD18) on the surface of the effector cells. In contrast to microorganisms, tumor cells lack β-glucan as a surface component and cannot trigger complement receptor 3-dependent cellular cytotoxicity and initiate tumor-killing activity. This mechanism could be induced in the presence of β-glucans. This study aimed at determining the influence of coadministration of β-glucan from barley on the efficacy of photodynamic tumor therapy (PDT). Material and methods. C57 Bl/6 female mice bearing Lewis lung carcinoma were used throughout the study. Mice were randomized into groups (15 in each group) and exposed to the treatment with intravenous Photofrin injection (dose, 10 mg/kg) and after 24 h following laser illumination, or with oral administration of β-glucan from barley at a dose of 400 μg/mouse per day up to 5 days, or with their combination. Tumor growth dynamics and survival of the treated and untreated mice were monitored. Results. Tumor volume in all treated groups was significantly lower (P<0.001) than that in the control group. The most effective tumor growth suppression (P=0.033) was achieved in mice treated with combination of PDT and β-glucan from barley as compared with PDT alone. The best survival was achieved in the same group, but difference was not significant as compared to the control group (P=0.143) and to PDT alone group (P=0.319). Conclusions. The present study demonstrates that coadministration of β-glucan from barley can enhance efficacy of photodynamic therapy.

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Treatment of Lewis lung carcinoma by photodynamic therapy and glucan from barley.

/pdf/azoto-oksido-sinteze-ir-veikimo-mechanizmai-lastelese-58mlibq2za.pdf

Azoto oksido sintezė ir veikimo mechanizmai ląstelėse

This study investigated possible implication of nitric oxide and prostanoids in anaphylactic reaction in small mesenteric and coronary arteries. Material and methods. Isolated arteries from guinea pigs, sensitized with 0.5 mL of horse serum or sham-sensitized, were challenged with 1% of horse serum in vitro. Contractile responses of arteries (normalized diameter, 350–450 μm) were recorded by a small blood vessel wire myograph. For inhibition of the release of NO or prostanoids, vessels were pretreated with N(G)-nitro-L-arginine methyl ester (30 μM) or indomethacin (10 μM), respectively. Results. Antigen challenge was followed by contraction of both coronary and mesenteric vessels. Two patterns of contraction were observed: 1) peak contraction – an immediate transient contraction of relatively high amplitude; this was the most common pattern; 2) biphasic: the initial peak contraction was followed by a slow growing contraction with low amplitude. Biphasic pattern was observed in 60% of the mesenteric vessels and 40% of the coronary vessels. Inhibition of NO synthase significantly increased the peak contraction in the coronary vessels and the second-phase contraction in the mesenteric vessels. Inhibition of cyclooxygenase caused a decrease in the peak and second-phase contraction of both the coronary and mesenteric vessels. Conclusions. Despite anaphylactic contraction, nitric oxide seems to be released from the endothelium following antigen challenge in the small coronary and mesenteric arteries. This may contribute to the development of hypotension during anaphylaxis. Prostanoids are playing a different role – the contracting products of cyclooxygenase pathway are important for the development of anaphylactic contraction of the small isolated arteries.

/pdf/anaphylaxis-of-small-arteries-putative-role-of-nitric-oxide-4pga37gieh.pdf

Egidijus Kėvelaitis

Papers

Effects of beta-glucans on the immune system.

Azoto oksido ir kitų endotelio išskiriamų medžiagų svarba

Treatment of Lewis lung carcinoma by photodynamic therapy and glucan from barley.

Azoto oksido sintezė ir veikimo mechanizmai ląstelėse

Anaphylaxis of small arteries: putative role of nitric oxide and prostanoids