Cianchetti E

Nutrition and cancer prevention

Cancer cells invade surrounding tissues and metastasize to distant sites. Diet high in fat is a strong link to, and perhaps causes, a high incidence of tumours. Trans-fatty acid might impair the function and it could be involved in the development of cancer. Cholesterol is also strongly suspected to be involved in the development of tumours, therefore it is important for everyone to eat well, especially for people with cancer to prevent the body tissues from breaking down and helping to rebuild the normal tissue that may have been affected by the treatments. Factors secreted by adipocytes and macrophages such as TNF-alpha and other inflammatory proteins are involved in inflammation in cancer. In addition, MCSF which up-regulates adipocyte tissue is also important for the stimulation of fat cell proliferation and is expressed by human adipocytes. Many cytokines, such as IL-1, IL-6, IL-8, IL-32, IL-33 and MCP-1, are biomarkers for cancer and chronic diseases along with transcription factors NFkB and AP-1; these last two factors are important bioactive substances on the molecular mechanism of the control of genes which in turn affect cellular metabolism. In this paper we revisit the interrelationship between cancer and metabolism.

Vascular Endothelial Growth Factor (VEGF), Mast Cells and Inflammation

Vascular endothelial growth factor (VEGF) is one of the most important inducers of angiogenesis, therefore blocking angiogenesis has led to great promise in the treatment of various cancers and inflammatory diseases. VEGF, expressed in response to soluble mediators such as cytokines and growth factors, is important in the physiological development of blood vessels as well as development of vessels in tumors. In cancer patients VEGF levels are increased, and the expression of VEGF is associated with poor prognosis in diseases. VEGF is a mediator of angiogenesis and inflammation which are closely integrated processes in a number of physiological and pathological conditions including obesity, psoriasis, autoimmune diseases and tumor. Mast cells can be activated by anti-IgE to release potent mediators of inflammation and can also respond to bacterial or viral antigens, cytokines, growth factors and hormones, leading to differential release of distinct mediators without degranulation. Substance P strongly induces VEGF in mast cells, and IL-33 contributes to the stimulation and release of VEGF in human mast cells in a dose-dependent manner and acts synergistically in combination with Substance P. Here we report a strong link between VEGF and mast cells and we depict their role in inflammation and immunity.

IL-37 (IL-1F7) the newest anti-inflammatory cytokine which suppresses immune responses and inflammation.

Cytokines such as interleukins, chemokines and interferons are immunomodulating and inflammatory agents, characterized by considerable redundancy, in that many cytokines appear to share similar functions. Virtually all nucleated cells, but especially epithelial cells and macrophages, are potent producers of cytokines. The objective of this study is to review the detailed mechanism of action and the biological profiles of IL-37, the newest anti-inflammatory cytokine. This review focuses on IL-37, a key cytokine in regulating inflammatory responses, mainly by inhibiting the expression, production and function of proinflammatory cytokines: IL-1 family pro-inflammatory effects are markedly suppressed by IL-37.

Atherosclerosis: a classic inflammatory disease.

Atherosclerosis is an inflammatory disease due to a diet high in saturated fat, hypercholesterolemia, obesity, hypoglycemia, etc. mainly mediated by the infiltration of macrophage and T cells into the vascular wall. Once the endothelial is damaged monocytes penetrate the tissue and are transformed in scavenger cells. Upon stimulation of Th1 cells, a group of cytokines is released and contributes to the inflammatory response of atherosclerotic tissue. When macrophages proliferate they amplify inflammatory response through the secretion of growth factors and cytokines such as TNF and IL-1. In addition, chemokines such as RANTES and other C-C chemokines are generated, and matrix metalloprotinease 9 (MMP-9) are produced by activated monocytes. However, the immune system in atherosclerosis still remains unclear. Here, in this study we revisited the inter-relationship between atherosclerosis and inflammation.

Changes of Topoisomerase IIα Expression in Breast Tumors after Neoadjuvant Chemotherapy Predicts Relapse-Free Survival

Purpose: To assess the value of changes in the expression of topoisomerase IIα (TopoII) and the proto-oncogene erbB-2 (HER-2) as predictors of relapse-free survival in women with operable breast cancer treated with anthracycline-based neoadjuvant chemotherapy. Patients and Methods: Seventy-seven patients with primary breast cancer who had undergone neoadjuvant anthracycline-based chemotherapy were included in the present study. TopoII and HER-2 were measured by immunohistochemistry in prechemotherapy and postchemotherapy (at the time of surgery) tumor specimens, and the value of their changes as predictors of relapse-free survival were evaluated by Kaplan-Meier and Cox proportional hazard regression analyses. Results: Neoadjuvant chemotherapy resulted in a significant reduction in the percentage of cells expressing TopoII (P < 0.0001). No significant change was observed for HER-2. TopoII and HER-2 expression before chemotherapy predicted tumor response to treatment. Changes in TopoII expression after chemotherapy were strongly associated with a poor relapse-free survival (P < 0.0001) in a Cox multivariate analysis adjusted for other clinicopathologic prognostic factors. Conclusion: Changes in TopoII expression after anthracycline-based neoadjuvant chemotherapy is an independent predictor of a poor relapse-free survival in patients with breast cancer. Tumor cells displaying an increased TopoII expression after treatment may be responsible for relapses, and may, therefore, define a group of patients with anthracycline-resistant breast cancer.

Impact of Capsaicin on Mast Cell Inflammation

Mast cells are inflammatory cells, and they are prominent in inflammatory diseases such as allergy and asthma. Mast cells possess high-affinity receptors for IgE (FCεRI) and the cross-linking of these receptors is essential to trigger the secretion of granules containing arachidonic acid metabolism [such as prostaglandin (PG) D2, leukotriene (LT) B4, and LTC4], histamine, cytokines, chemokines, and proteases, including mast cell-specific chymases and tryptases. Activation of mast cells provokes the secretion of cytokines and mediators that are responsible for the pathologic reaction of immediate hypersensitivity. Sensory nerve stimulation by irritants and other inflammatory mediators provokes the release of neuropeptides, causing an increase in vascular permeability, plasma extravasation and edema. Trigeminal nerve stimulation actives dura mast cells and increases vascular permeability, effects inhibited by capsaicin. Capsaicin causes release of sensory neuropeptide, catecholamines and vasodilation. Several studies have reported that capsaicin is effective in relief and prevention of migraine headaches, improves digestion, helps to prevent heart disease, and lowers blood cholesterol and blood pressure levels. The findings reported in these studies may have implications for the pathophysiology and possible therapy of neuroinflammatory disorders.

Endothelial cells, cholesterol, cytokines, and aging.

It has been reported that high levels of cholesterol and triglycerides are associated with increased risk of developing atherosclerosis and shorter life. In fact, vascular endothelial dysfunction occurs during the human aging process. Accumulation of lipids in vascular endothelium activates leukocytes to produce cytokines and chemokines which recruit macrophages. On the other hand, macrophages augment inflammatory response and secrete vascular endothelial growth factor, a key cytokine that mediates angiogenesis and inflammatory response. In addition, hyperlipidaemia is one of the main risk factors for aging, hypertension and diabetes. Here, we review the interrelationship between endothelial cells, high level of cholesterol, and aging.

IL-36 Receptor Antagonist with Special Emphasis on IL-38:

IL-36 is another family member of IL-1 and induces the production of proinflammatory cytokines and activates MAPK and NFκB pathways. IL-36 is a common mediator of innate and adaptive immune response and is inhibited by IL-36 receptor antagonist (RA). IL-36RA acts on IL-36 receptor ligand which exerts proinflammatory effect in vivo and in vitro. IL-38 binds to IL-36 receptor as does IL-36RA and has similar biological effects on immune cells. IL-38 is also a member of IL-1 cytokine and shares some characteristics of IL-1RA, binding the same IL-1 receptor type I. IL-38 plays a role in the pathogenesis of inflammatory diseases, exerting protective effect in some autoimmune diseases. Both IL-38 and IL-36RA have an anti-inflammatory biological effect, however in some cases have contrary effects.

Physical exercises for breast cancer survivors: effects of 10 weeks of training on upper limb circumferences

[Purpose] The aims of this study were to verify the effects on upper limb circumferences and total body extracellular water of 10 weeks of Nordic Walking (NW) and Walking (W), both alone and combined with a series of exercises created for breast cancer survivors, the ISA method. [Subjects and Methods] Twenty breast cancer survivors were randomly assigned to 4 different training groups and evaluated for upper limb circumferences, total body and extracellular water. [Results] The breast cancer survivors who performed NW, alone and combined with the ISA method, and Walking combined with the ISA method (but not alone) showed significantly reduced arm and forearm circumferences homolateral to the surgical intervention. [Conclusion] For breast cancer survivors, NW, alone and combined with the ISA method, and Walking combined with the ISA method should be prescribed to prevent the onset and to treat light forms of upper limb lymphedema because Walking training practiced alone had no significant effect on upper limb circumference reduction.

Inhibitor Effect of Antioxidant Flavonoids Quercitin, and Capsaicin in Mast Cell Inflammation

Mast cells are essential not only for allergies but also for innate and acquired immunity, autoimmunity and inflammation, and they are recognized as a new type of immunoregulatory cells capable of producing different cytokines. Natural compounds have long been recognized to possess anti-inflammatory, antioxidant and anticancergenic activity. Quercitin is an inhibitor for mast cells and is a potent antioxidant, cytoprotective and anti-inflammatory compound and has a negative effect on intracellular regulator signal events initiated by FceRI receptor cross-linking and other activating receptors on mast cells. These observations candidate quercitin as a therapeutic compound in association with other therapeutic molecules. Capsaicin is a compound derived from peppers, especially capsicum, and is involved in stimulating circulation aiding digestion and relieving pain. Capsaicin receptor sub type I (VRI) is expressing in neurons and is present in a number of brain nuclei and in non-neuronal tissues, mediating inflammatory response. Capsaicin is involved in migraine, allergic symptoms, arthritis pain and gastric secretion. In this paper we review the biological effects of quercitin and capsaicin.