Papers by Tiziana Guarnieri
American Journal of Rhinology, 1999
The cavernous sinuses are the most peculiar feature of the nasal angioarchitecture, due to their ... more The cavernous sinuses are the most peculiar feature of the nasal angioarchitecture, due to their ability to retain a large quantity of blood in reply to a variety of topical and systemic stimuli. Recently, nitric oxide (NO) has seemed to be crucially involved in the nasal vascular regulation. The distribution of NO-synthase (NOS), the enzyme that catalyzes the formation of NO, was studied in the endothelium of nasal blood vessels by the ultracytochemical detection of reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) enzymic activity. The endothelium of the cavernous sinuses appeared strongly positive, whereas the endothelium of arterioles was occasionally labeled. The endothelial cells of capillaries and venules were found to be NADPH-d negative. The strong enzymic activity observed in the cavernous sinuses suggests a major role of NO in the capacitance vessels compared to the resistance vessels. The hypothesis of a reciprocal inhibition between the NOS enzymic pathways present in the respiratory epithelium and in the endothelium of cavernous sinuses is put forward. The nasal disorders characterized by anomalous vasomotility and vascular permeability could be caused in part by the irregular control of these complex interactions.
Neuroscience Letters, 1989
Sensors
The development of predictive in vitro sensing tools able to provide rapid information on the dif... more The development of predictive in vitro sensing tools able to provide rapid information on the different bioactivities of a sample is of pivotal importance, not only to monitor environmental toxicants, but also to understand their mechanisms of action on diverse molecular pathways. This mechanistic understanding is highly important for the characterization of toxicological hazards, and for the risk assessment of chemicals and environmental samples such as surface waters and effluents. Prompted by this need, we developed and optimized a straightforward bioluminescent multiplexed assay which enables the measurement of four bioactivities, selected for their relevance from a toxicological perspective, in bioluminescent microtissues. The assay was developed to monitor inflammatory, antioxidant, and toxic activity, and the presence of heavy metals, and was successfully applied to the analysis of river water samples, showing potential applicability for environmental analyses. The assay, whi...
Journal of Translational Medicine, 2019
Background It has been established that children with Autism Spectrum Disorders (ASD) are affecte... more Background It has been established that children with Autism Spectrum Disorders (ASD) are affected by oxidative stress, the origin of which is still under investigation. In the present work, we evaluated inflammatory and pro-oxidant soluble signature in non-syndromic ASD and age-matched typically developing (TD) control children. Methods We analyzed leukocyte gene expression of inflammatory cytokines and inflammation/oxidative-stress related molecules in 21 ASD and 20 TD children. Moreover, in another—comparable—group of non-syndromic ASD (N = 22) and TD (N = 21) children, we analyzed for the first time the protein expression of the four members of the antioxidant enzyme family of peroxiredoxins (Prx) in both erythrocyte membranes and in plasma. Results The gene expression of IL6 and of HSP70i, a stress protein, was increased in ASD children. Moreover, gene expression of many inflammatory cytokines and inflammation/oxidative stress-related proteins correlated with clinical features,...
Cells
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the pathogenic agent of Coronavir... more Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the pathogenic agent of Coronavirus-Induced Disease-2019 (COVID-19), a multi-organ syndrome which primarily targets the respiratory system. In this review, considering the large amount of data pointing out the role of the Aryl hydrocarbon Receptor (AhR) in the inflammatory response and in the modulation of innate and adaptive immunity, we describe some mechanisms that strongly suggest its involvement in the management of COVID-19′s inflammatory framework. It regulates both the expression of Angiotensin Converting Enzyme-2 (ACE-2) and its stabilizing partner, the Broad neutral Amino acid Transporter 1 (B0AT1). It induces Indolamine 2,3 dioxygenase (IDO-1), the enzyme which, starting from Tryptophan (Trp), produces Kynurenine (Kyn, Beta-Anthraniloyl-L-Alanine). The accumulation of Kyn and the depletion of Trp arrest T cell growth and induce apoptosis, setting up an immune-tolerant condition, whereas AhR and interferon typ...
Aims: Cancer stem cell biology is tightly connected to the regulation of the pro-inflammatory cyt... more Aims: Cancer stem cell biology is tightly connected to the regulation of the pro-inflammatory cytokine network. The concept of cancer stem cells ‘‘inflammatory addiction’ ’ leads to envisage the potential role of anti-inflammatory molecules as new anti-cancer targets. Here we report on the relationship between nuclear receptors activity and the modulation of the pro-inflammatory phenotype in breast cancer stem cells. Methods: Breast cancer stem cells were expanded as mammospheres from normal and tumor human breast tissues and from tumorigenic (MCF7) and non tumorigenic (MCF10) human breast cell lines. Mammospheres were exposed to the supernatant of breast tumor and normal mammary gland tissue fibroblasts. Results: In mammospheres exposed to the breast tumor fibroblasts supernatant, autocrine tumor necrosis factor-a signalling engenders the functional interplay between peroxisome proliferator activated receptor-a and hypoxia inducible factor-1a (PPARa/HIF1a). The two proteins promote...
Journal of Human Evolution
International Journal of Molecular Sciences
Aryl hydrocarbon receptor (AhR), an evolutionary conserved transcription factor, is a pleiotropic... more Aryl hydrocarbon receptor (AhR), an evolutionary conserved transcription factor, is a pleiotropic signal transductor. Thanks to its promiscuous ligand binding domain, during the evolution of eukaryotic cells its developmental functions were integrated with biosensor functions. Its activation by a multitude of endogenous and exogenous molecules stimulates its participation in several pathways, some of which are linked to inflammation and breast cancer (BC). Over time, the study of this malignancy has led to the identification of several therapeutic targets in cancer cells. An intense area of study is dedicated to BC phenotypes lacking adequate targets. In this context, due to its high constitutive activation in BC, AhR is currently gaining more and more attention. In this review, I have considered its interactions with: 1. the immune system, whose dysregulation is a renowned cancer hallmark; 2. interleukin 6 (IL6) which is a pivotal inflammatory marker and is closely correlated to br...
American Journal of Physiology-Cell Physiology
Aryl hydrocarbon receptor (AhR), a highly conserved intracellular transcription factor, is activa... more Aryl hydrocarbon receptor (AhR), a highly conserved intracellular transcription factor, is activated by a plethora of ligands of both exogenous and endogenous nature. Besides activating xenobiotic metabolizing enzymes, it is involved in the differentiation and development of hematopoietic, hepatic, nervous and immune systems. More and more data describe its role in the regulation of immune responses and in the onset and progression of inflammation. Particularly, established results view AhR as a downstream target of inflammatory molecules, since its transcription is regulated by the inflammatory cascade. Interleukin 6 (IL-6) has been described to sustain early stages of inflammation and to influence the expression of AhR either directly, following STAT3 activation, or in combination with other inflammatory mediators, e.g. Transforming Growth Factor β (TGF-β). In selected inflammatory milieus, once activated, AhR interacts with its targets including the IL-6 promoter, thus originatin...
Current Cancer Drug Targets, 2015
Epidemiological data suggest that Non Steroidal Anti Inflammatory Drugs (NSAIDs) and Cyclooxygena... more Epidemiological data suggest that Non Steroidal Anti Inflammatory Drugs (NSAIDs) and Cyclooxygenase 2 (COX2) inhibitors (COXibs) can exert chemopreventive and antitumour effects in many human neoplasia. This is particularly true in colon cancer (CC), where the regular assumption of these molecules has been shown to exert chemopreventive and chemotherapeutic effects. Since the late '90s there was a progressive increase of experimental evidence, indicating that in CC the antiproliferative effects of NSAIDs and COXibs could be both dependent and independent from COXs inhibition, and that these effects do not necessarily exclude each other. This review will examine some of these COX-independent cellular pathways, with a focus on those involved in the inhibition of CC cells proliferation through transcription factors crosstalk.
The present invention relates to the use of annellated pyrrole compounds and in particular ML3000... more The present invention relates to the use of annellated pyrrole compounds and in particular ML3000 (licofelone), salts or derivatives thereof, for cancer management, and in general to the use of a compound of Formula (I): wherein the variables have the meanings given in the present description, for the prevention and/or treatment of neoplasia, in particular neoplasia selected from the group consisting of papilloma, carcinoma, adenoma and adenocarcinoma, e. g. human airway or colorectal carcinoma, preferably fast-growing, multi drug resistant and/or COX-2 -< negative neoplasia. The invention further relates to pharmaceutical compositions for the aforesaid purposes, comprising annellated pyrrole compounds and in particular ML3000 (licofelone), optical isomers, salts or derivatives thereof, as well as to a method of = treating and/or preventing neoplasia and/or restoring the ability to undergo apoptosis in a cell having lost the same. This treatment ameliorates, diminishes, actively ...
Carcinogenesis, 2015
An emerging area in environmental toxicology is the role that chemicals and chemical mixtures hav... more An emerging area in environmental toxicology is the role that chemicals and chemical mixtures have on the cells of the human immune system. This is an important area of research that has been most widely pursued in relation to autoimmune diseases and allergy/asthma as opposed to cancer causation. This is despite the well-recognized role that innate and adaptive immunity play as essential factors in tumorigenesis. Here, we review the role that the innate immune cells of inflammatory responses play in tumorigenesis. Focus is placed on the molecules and pathways that have been mechanistically linked with tumor-associated inflammation. Within the context of chemically induced disturbances in immune function as co-factors in carcinogenesis, the evidence linking environmental toxicant exposures with perturbation in the balance between pro- and anti-inflammatory responses is reviewed. Reported effects of bisphenol A, atrazine, phthalates and other common toxicants on molecular and cellular...
Carcinogenesis, 2015
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but c... more Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effe...
European journal of histochemistry : EJH, 1998
We report alterations in the pattern of NADPH-diaphorase staining, a marker of nitric oxide, in t... more We report alterations in the pattern of NADPH-diaphorase staining, a marker of nitric oxide, in the goldfish retina after kainic acid administration. The heavily stained ellipsoids of the photoreceptors, the heavily stained neurons of the inner plexiform layer and the labeled neurons of the ganglion cell layer are spared by excitotoxic insult, while the faintly medium sized neurons of the inner plexiform layer disappear after kainic acid administration. Furthermore, in the bipolar and in the horizontal retinal neurons we observe an induction of NADPH-diaphorase expression. The kainic acid-induced neurotoxicity evaluated by morphological observations and by measuring the levels of choline acetyltranferase in retinal homogenates, is not prevented by the administration of a nitric oxide synthase inhibitor.
Journal für Hirnforschung, 1997
Apoptosis is an important mechanism of cell death that occurs physiologically during development.... more Apoptosis is an important mechanism of cell death that occurs physiologically during development. Recently, it has been shown that the selective pattern of neuronal degeneration in some brain disorders or in excitotoxic animal models, can reveal signs of apoptosis. This work produces evidence that kainic acid, a non-NMDA receptor agonist, induces apoptotic cell death in the goldfish retina. DNA breaks are in situ detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL). This reaction shows a large number of positive cells in the inner nuclear layer 48 hours after intravitreal kainic acid administration. TUNEL staining of apoptotic death was prevented by the non-NMDA glutamate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) but not by the NMDA receptor antagonist MK-801 administration. Ultrastructural changes that occur in kainic acid affected retinal neurons (hypercondensation and clumping of the chromatin and shrinkage of the cyto...
Journal für Hirnforschung, 1989
The immunostaining proposed in this study identifies cells containing endogenous estrogens in the... more The immunostaining proposed in this study identifies cells containing endogenous estrogens in the Central Nervous System, in the presence of both very high and very low serum estrogen levels. Ten adult rats, seven normal and three ovariectomized females, were used for this study. Paraffin sections of hypothalamus and ovary of each female were stained using Avidin-Biotin Complex method and antiestradiol antiserum. Two different antiestradiol antisera were tested in this work: tests for method and antisera specificity are described. The immunostaining used here shows to be specific and sensitive revealing a higher number of labeled hypothalamic areas than those revealed by other techniques.
Pancreas, 2014
Resistance to gemcitabine is one of the main causes of treatment failure in pancreatic cancer. Co... more Resistance to gemcitabine is one of the main causes of treatment failure in pancreatic cancer. Compelling evidences have shown the involvement of nuclear factor κB (NF-κB) activation in such phenomenon. The protease inhibitor gabexate mesilate has been shown to inhibit NF-κB. We here investigated if combined treatment with this drug could improve gemcitabine antitumoral efficacy in pancreatic cancer cells. The effect of gabexate mesilate and gemcitabine, both used at concentrations achievable in human plasma, was assessed on in vitro pancreatic cancer cell growth, invasion, and tumor angiogenesis. The molecular mechanism at the basis of these effects was also investigated. Gabexate mesilate significantly increased gemcitabine anti-invasive and antiangiogenic efficacy. This effect was related to inhibition of gemcitabine-induced NF-κB activation by gabexate mesilate, which prevented RelA/p65 nuclear translocation and resulted in metalloproteinase 2, metalloproteinase 9, vascular endothelial growth factor, and interleukin 8 down-regulation. Combined treatment with gabexate mesilate also inhibited gemcitabine-induced extracellular-regulated kinase 1/2 and AKT activation by increased expression of Raf kinase inhibitor protein and phosphatase and tensin homolog. Combined treatment with gabexate mesilate sensitizes pancreatic cancer cells to gemcitabine by inhibition of the NF-κB pathway. The efficacy of this therapeutic strategy in pancreatic cancer patients remains to be established and deserves future clinical investigation.
Neurochemistry International, 1992
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Papers by Tiziana Guarnieri