128 research outputs found
Functional properties of ion channels and transporters in tumour vascularization
Vascularization is crucial for solid tumour growth and invasion, providing metabolic support and sustaining metastatic dissemination. It is now accepted that ion channels and transporters play a significant role in driving the cancer growth at all stages. They may represent novel therapeutic, diagnostic and prognostic targets for anti-cancer therapies. On the other hand, although the expression and role of ion channels and transporters in the vascular endothelium is well recognized and subject of recent reviews, only recently has their involvement in tumour vascularization been recognized. Here, we review the current literature on ion channels and transporters directly involved in the angiogenic process. Particular interest will be focused on tumour angiogenesis in vivo as well as in the different steps that drive this process in vitro, such as endothelial cell proliferation, migration, adhesion and tubulogenesis. Moreover, we compare the ‘transportome’ system of tumour vascular network with the physiological one
Pain, smell, and taste in adults: a narrative review of multisensory perception and interaction
Every day our sensory systems perceive and integrate a variety of stimuli containing information vital for our survival. Pain acts as a protective warning system, eliciting a response to remove harmful stimuli; it may also be a symptom of an illness or present as a disease itself. There is a growing need for additional pain-relieving therapies involving the multisensory integration of smell and taste in pain modulation, an approach that may provide new strategies for the treatment and management of pain. While pain, smell, and taste share common features and are strongly linked to emotion and cognition, their interaction has been poorly explored. In this review, we provide an overview of the literature on pain modulation by olfactory and gustatory substances. It includes adult human studies investigating measures of pain threshold, tolerance, intensity, and/or unpleasantness. Due to the limited number of studies currently available, we have structured this review as a narrative in which we comment on experimentally induced and clinical pain separately on pain-smell and pain-taste interaction. Inconsistent study findings notwithstanding, pain, smell, and taste seem to interact at both the behavioral and the neural levels. Pain intensity and unpleasantness seem to be affected more by olfactory substances, whereas pain threshold and tolerance are influenced by gustatory substances. Few pilot studies to date have investigated these effects in clinical populations. While the current results are promising for the future, more evidence is needed to elucidate the link between the chemical senses and pain. Doing so has the potential to improve and develop novel options for pain treatment
Performance validity tests in nonlitigant patients with functional motor disorder
Background: Performance Validity Tests (PVTs) are used in neuropsychological assessments to detect patterns of performance suggesting that the broader evaluation may be an invalid reflection of an individual's abilities. Data on Functional motor disorder (FMD) are currently poor and conflicting. Objectives: We aimed to examine the rate of failure at three different PVTs of non-litigant, non-compensation seeking FMD patients, and we compared their performance to that of healthy controls and controls asked to simulate malingering (healthy simulators). Methods: We enrolled 29 non-litigant, non-compensation seeking patients with a clinical diagnosis of FMD, 29 healthy controls and 29 healthy simulators. Three PVTs, the Coin in the Hand Test (CIH), the Rey 15-item Test (REY) and the Finger Tapping Test (FTT), were employed. Results: FMD Patients showed low rates of failure at the CIH and REY tests (7% and 10%, respectively) and slightly higher at the FTT (15%, n=26) test, which implies a motor task. Their performance was statistically comparable to that of healthy controls but statistically different from that of healthy simulators (p<0.001). 93% of FMD patients, 7% of healthy simulators, and 100% of healthy controls passed at least two of the three tests. Conclusions: PVT performance of non-litigant, non-compensation seeking patients with FMD ranged from 7 to 15%. Patient's performance was comparable to controls and significantly differed from that of simulators. This simple battery of three PVTs could be of practical utility and routinely used in clinical practice
Unpleasant olfactory and gustatory stimuli increase pain unpleasantness in patients with chronic oral burning pain: an exploratory study
Background: Despite mounting evidence for the powerful influence of smell and taste substances in experimental pain, our knowledge of their effects in the clinical context is scarce, especially for patients with chronic oral burning pain. To fill this gap, we investigated the effect of olfactory and gustatory stimuli on pain perception in patients with chronic oral burning pain, a disabling condition that is difficult to manage and treat. Methods: Twenty-two patients with chronic oral burning pain underwent testing with a variety of olfactory and gustatory substances (pleasant, neutral, unpleasant) in multisensory interaction. The order of testing was randomized. Perception of pain intensity and unpleasantness was evaluated on a numerical rating scale at baseline and immediately after each test trial. Results: Pain unpleasantness but not pain intensity was found to be modulated by chemosensory stimuli. Unpleasant olfactory and gustatory stimuli increased the perception of pain unpleasantness compared to pleasant and neutral stimuli. Pain unpleasantness after unpleasant olfactory and gustatory stimuli correlated with psychological questionnaire subscale scores for distress (CORE-OM) and emotional awareness (TAS-20). Conclusions: Our findings suggest a role of unpleasant chemosensory stimuli in increasing the perception of pain unpleasantness in patients with chronic oral burning. The lack of an effect on pain intensity indicates a dissociation between sensory and affective pain components. Future research is needed to further study the association between chemosensory stimuli and emotional and subjective aspects in modulating chronic oral burning pain
Hedonicity in functional motor disorders: a chemosensory study assessing taste
The aim of this study was to explore hedonicity to basic tastes in patients with functional motor disorders (FMDs) that are often associated with impairment in emotional processing. We recruited 20 FMD patients and 24 healthy subjects, matched for age and sex. Subjects were asked to rate the hedonic sensation (i.e., pleasant, neutral, and unpleasant) on a\u2009-\u200910 to +10 scale to the four basic tastes (sweet, sour, salty, and bitter) at different concentrations, and neutral stimuli (i.e., no taste stimulation) by means of the Taste Strips Test. Anxiety, depression, and alexithymia were assessed. FMD patients rated the highest concentration of sweet taste (6.7\u2009\ub1\u20092.6) as significantly more pleasant than controls (4.7\u2009\ub1\u20092.5, p\u2009=\u20090.03), and the neutral stimuli significantly more unpleasant (patients:\u2009-\u20090.7\u2009\ub1\u20090.4, controls: 0.1\u2009\ub1\u20090.4, p\u2009=\u20090.013). Hedonic ratings were not correlated to anxiety, depression, or alexithymia scores. Hedonic response to taste is altered in FMD patients. This preliminary finding might result from abnormal interaction between sensory processing and emotional valence
Activation of P2X7 and P2Y11 purinergic receptors inhibits migration and normalizes tumor-derived endothelial cells via cAMP signaling
Purinergic signaling is involved in inflammation and cancer. Extracellular ATP accumulates in tumor interstitium, reaching hundreds micromolar concentrations, but its functional role on tumor vasculature and endothelium is unknown. Here we show that high ATP doses (>20 μM) strongly inhibit migration of endothelial cells from human breast carcinoma (BTEC), but not of normal human microvascular EC. Lower doses (1–10 mm result ineffective. The anti-migratory activity is associated with cytoskeleton remodeling and is significantly prevented by hypoxia. Pharmacological and molecular evidences suggest a major role for P2X7R and P2Y11R in ATP-mediated inhibition of TEC migration: selective activation of these purinergic receptors by BzATP mimics the anti-migratory effect of ATP, which is in turn impaired by their pharmacological or molecular silencing. Downstream pathway includes calcium-dependent Adenilyl Cyclase 10 (AC10) recruitment, cAMP release and EPAC-1 activation. Notably, high ATP enhances TEC-mediated attraction of human pericytes, leading to a decrease of endothelial permeability, a hallmark of vessel normalization. Finally, we provide the first evidence of in vivo P2X7R expression in blood vessels of murine and human breast carcinoma. In conclusion, we have identified a purinergic pathway selectively acting as an antiangiogenic and normalizing signal for human tumor-derived vascular endothelium
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