Molecular Link Mechanisms between Inflammation and Cancer

Abstract

Inflammation is part of the body's response to internal and external environmental stimuli that normally eliminate the aggressor agent and restore the tissue physiology. However, when it becomes chronic, it can cause several pathologies such as cardiovascular, diabetes, rheumatoid arthritis, Alzheimer's autoimmune diseases and cancer. Currently, epidemiological data indicate that over 25% of all cancers are related to chronic infections and other types of unresolved inflammation. Further evidence of this relationship is the fact that prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risk to developing many types of cancers. Some randomized trials have shown that NSAIDs have protective action against colon adenomas, breast, prostate, and lung cancers. The inflammation present on tumor microenvironment is characterized by leukocyte infiltration, ranging in size, distribution and composition, as: tumor-associated macrophages (TAM), mast cells, dendritic cells, natural killer (NK) cells, neutrophils, eosinophils and lymphocytes. These cells produce a variety of cytotoxic mediators such as reactive oxygen and nitrogen species (ROS and RNS respectively), serine and cysteine proteases, membrane perforating agents, matrix metalloproteinase (MMP), tumor necrosis factor α (TNFα), interleukins (IL-1, IL-6, IL-8), interferons (IFNs) and enzymes, as cyclooxygenase-2 (COX-2), lipooxygenase-5 (LOX-5) and phospholipase A2 (PLA2), which activate or are activated by transcription factors as nuclear factor κB (NF-κB) and signal transducers and activators of transcription-3 (STAT3). Initially this paper will briefly review the main mediators present on tumor microenvironment, addressing the cytokines, chemokines, transcription factors, eicosanoid, and kinins and later, will present an overview of the role of inflammation in the different steps of carcinogenesis.

Anti-inflammatory therapies in TRAMP mice: delay in PCa progression

“…Nowadays, different studies have shown the involvement of the inflammatory process in the development and progression of several cancer types, including PCa (De Marzo et al 1999, Hamid et al 2011, Vendramini-Costa & Carvalho 2012, Thapa & Ghosh 2015. It is known that the etiology of prostatic inflammation is multifactorial, involving infectious agents, factors related to aging, eating habits among others (De Marzo et al 2007).…”

Depression in cancer: The many biobehavioral pathways driving tumor progression

“…Chronic inflammation characterised by elevated levels of pro-inflammatory cytokines leads to activation of inducible nitric oxide synthase (iNOS) and increased activity of several transcription factors, such as NF-κB (nuclear factor κB), AP-1 (activator protein 1) and STAT3 (signal transducer and activator of transcription 3) leading in turn to upregulated activity of NADPH oxidase (NOX) and mitochondrial oxidoreductases 91 . The activation of these enzymes and transcription factors lead to the chronic activation of a wide range of inflammatory pathways subsequent to the up-regulation of COX-2 (cyclo-oxygenase-2), and the development of a state of chronic O&NS characterised by excessive production of reactive oxygen species (ROS), such as the superoxide anion, and reactive nitrogen species (RNS), such as nitric oxide (NO), which are known to play a major role in the pathogenesis and pathophysiology of major depression and inflammatory cancers 92 .…”

Intravenous Flurbiprofen Axetil Enhances Analgesic Effect of Opioids in Patients with Refractory Cancer Pain by Increasing Plasma β-Endorphin

“…Flurbiprofen axetil is a new type of non-selective COX inhibitors, which has been widely used for preemptive analgesia (Sánchez et al, 2012), the prevention of propofol injection pain (Mizushima et al, 1986;Park et al, 1999), and the reduction of postoperative pain (Xu et al, 2008;Vendramini-Costa et al, 2012) and cancer pain (Davies et al, 1995;Hao et al, 2013), including metastatic bone pain and multiple breakthrough pain. Wu et al reported that intravenous flurbiprofen axetil can provide better analgesic effect and few side effects for the patients with refractory cancer pain (Wu et al, 2009).…”