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Undertaking a high volume of physical activity is associated with reduced risk of a broad range of clinically diagnosed cancers. These findings, which imply that physical activity induces physiological changes that avert or suppress neoplastic activity, are supported by preclinical intervention studies in rodents demonstrating that structured regular exercise commonly represses tumour growth. In Part 1 of this review, we summarise epidemiology and preclinical evidence linking physical activity or regular structured exercise with reduced cancer risk or tumour growth. Despite abundant evidence that physical activity commonly exerts anti-cancer effects, the mechanism(s)-of-action responsible for these beneficial outcomes is undefined and remains subject to ongoing speculation. In Part 2, we outline why altered immune regulation from physical activity - specifically to T cells - is likely an integral mechanism. We do this by first explaining how physical activity appears to modulate the cancer immunoediting process. In doing so, we highlight that augmented elimination of immunogenic cancer cells predominantly leads to the containment of cancers in a ‘precancerous’ or ‘covert’ equilibrium state, thus reducing the incidence of clinically diagnosed cancers among physically active individuals. In seeking to understand how physical activity might augment T cell function to avert cancer outgrowth, in Part 3 we appraise how physical activity affects the determinants of a successful T cell response against immunogenic cancer cells. Using the cancer immunogram as a basis for this evaluation, we assess the effects of physical activity on: (i) general T cell status in blood, (ii) T cell infiltration to tissues, (iii) presence of immune checkpoints associated with T cell exhaustion and anergy, (iv) presence of inflammatory inhibitors of T cells and (v) presence of metabolic inhibitors of T cells. The extent to which physical activity alters these determinants to reduce the risk of clinically diagnosed cancers – and whether physical activity changes these determinants in an interconnected or unrelated manner – is unresolved. Accordingly, we analyse how physical activity might alter each determinant, and we show how these changes may interconnect to explain how physical activity alters T cell regulation to prevent cancer outgrowth.

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Objectives: Myeloma is characterised by the presence of monoclonal immunoglobulin (M-protein) and the free light chain (FLC) in blood. We investigated whether these Mproteins and FLC are detectable in myeloma patients' saliva to evaluate its utility for non-invasive screening and monitoring of haematological malignancies.Methods: A total of 57 patients with monoclonal gammopathy and 26 age-matched healthy participants provided paired serum and saliva samples for immunoglobulin characterisation and quantification.Results: Myeloma patients had IgG or IgA M-protein levels ranging up to five times and FLC levels up to a thousand times normal levels of polyclonal immunoglobulins.Despite these highly elevated levels, only two IgG and no IgA M-proteins or FLC could be detected in paired saliva samples. Most patients had reduced levels of serum polyclonal immunoglobulins, but all had normal levels of salivary IgA. Conclusions:Immunoglobulin transfer from blood is not determined by levels in the systemic circulation and more likely dictated by periodontal inflammation and the integrity of the oral epithelium. Immunoglobulins secreted by bone marrow plasma cells do not substantially enter saliva, which represents a poor medium for myeloma diagnosis. These findings, along with normal salivary IgA levels despite systemic immunoparesis, support a strong partitioning of oral from systemic humoral immunity.

the V ̇E-V ̇CO2 slope in the obese population as defined by the body mass index (BMI > 29.9) can be expected to be lower due to limitations in ventilation imposed by excess abdominal adipose tissue. This subsequently leads to a false normal interpretation rather than blunted ventilatory response to exercise in the obese. Yet these findings are inconsistent as some obese subjects demonstrate normal ventilatory patterns. PURPOSE: To determine the performance of a predictive V ̇E-V ̇CO2 slope equation that was derived in a lean subject population in a group of obese subjects during exercise. METHODS: 20 obese (O, BMI 40.2 + 6.1 kg/m2) and 10 lean otherwise normal subjects (L, BMI 24.9 + 2.2) were tested. Subjects performed symptom-limited incremental tests on a cycle ergometer (CE) and treadmill (TM). Ventilation and pulmonary gas exchange were measured breath by breath (Vyaire, Yorba Linda, California). The derived V ̇E-V ̇CO2 slope from both mode of exercises was compared to Sun et al. (2002) predictive V ̇E-V ̇CO2 slope equation: 34.38 + 0.082 (age) -0.0723 (height). RESULTS:The average predicted V ̇E-V ̇CO2 slope value in the O subjects was 25.7 +/-1.1. There was no difference between the predicted and derived measurements during CE (26.6 +/-3.2) and TM (26.9 +/-3.0), p=0.21 and p=0.07, respectively. There were also no differences observed between the predicted V ̇E-V ̇CO2 slope (24.7 +/-1.3) in the L when compared to CE (25.8 +/-3.8) and TM (26.5 +/-2.8), p=0.32 and p=0.09, respectively. CONCLUSIONS: The predictive V ̇E-V ̇CO2 slope equation that was derived from a non-obese subject population performed just as well in our O subjects, and as expected in our L subjects. Of note, waist to hip ratio in the L and O subjects were 0.94 +/-0.09 and 0.92 +/-0.04 despite the large differences in BMI. Therefore, future research with larger subject pool is warranted to investigate the role of adipose tissue distribution on ventilatory response during exercise.