Alberto Izzotti
@unige.it
Department of Experimentla Medicine
University of Genoa
RESEARCH INTERESTS
cancer prevention
envrionmental monitoring
Scopus Publications
Scopus Publications
Giovanni Barco, Zumama Khalid, Alessandra Pulliero, Claudio Angelinetta, Ubaldo Prati, and Alberto Izzotti
MDPI AG
The possible future emergence of new SARS-CoV-2 virus variants pushes the development of new chemoprophylaxis protocols complementary to the unspecific and specific immune-prophylaxis measures currently used. The SARS-CoV-2 virus is particularly sensitive to oxidation, due to the relevant positive electrical charge of its spike protein used as a ligand for target cells. The present study evaluated the safety and efficacy of a new oxidant preparation, liquid hyperoxygen (IOL), to neutralize the SARS-CoV-2 virus. IOL was incubated with throat swabs containing a human-type virus. The samples were then incubated with cells expressing the ACE2 receptor and, therefore, very sensitive to SARS-CoV-2 infection. The ability to neutralize SARS-CoV-2 was determined by assessing the amount of viral nucleic acid inside cells by PCR. The results obtained indicate that IOL, even at considerable dilutions, is capable, after incubation times of less than 30 min and even equal to 5 min, of completely inhibiting SARS-CoV-2 infection. This inhibitory effect has been shown to be due to the oxidizing capacity of the IOL. This oxidizing capacity is exerted towards the virus but does not damage eukaryotic cells either in the in vitro or in vivo skin models. Obtained results indicate that the use of IOL, a hydrophilic liquid mixture saturated with highly reactive oxygen and nitrogen species, is a new powerful, safe, and effective tool for preventing possible future outbreaks of the COVID-19 disease.
Hailong Chen, Weiwei Yan, Dechang Xu, Qi Wang, Ying Yu, Jing Huang, Qian Zhou, Wei Xiao, David Lukanovic, Fabio Barra,et al.
AME Publishing Company
Background Endometrial cancer (EC) is an epithelial malignancy occurring in the endometrium, with a 5-year mortality rate of above 10%. However, there is currently a lack of studies exploring the potential of a predictive model of tumor-specific death after surgery in these patients. Methods From January 2015 to December 2017, data related to 482 patients with EC admitted to the Dushu Lake Hospital Affiliated to Soochow University were analyzed. Patients were divided into death (n=62) and survival (n=420) groups according to whether tumor-specific death occurred at 5 years postoperatively or not. The clinical characteristics of the two groups were compared, and the risk factors for tumor-specific death in patients with EC 5 years after surgery were investigated by logistics regression analysis. A nomogram prediction model was established according to the relevant risk factors. Results Tumor size, Ki-67 positive rate, Federation International of Gynecology and Obstetrics (FIGO) stage, and the rate of vascular tumor thrombus between the two groups (P<0.05) were found to be the statistically significant factors. Positive Ki-67, tumor size >3.35 cm, stage III, and vascular tumor thrombus were factors that influenced the tumor-specific death at 5 years after surgery (P<0.05). The predictive model obtained an area under the receiver operating characteristic (ROC) curves in the training and verification sets of 0.847 [95% confidence interval (CI): 0.779–0.916] and 0.886 (95% CI: 0.803–0.969), respectively. Conclusions The nomogram prediction model, which was established in this study, was proved to be valuable in predicting tumor-specific death 5 years after the surgery in patients with EC.
Clelia Norese, Elena Nicosia, Katia Cortese, Valentina Gentili, Roberta Rizzo, Sabrina Rizzo, Elena Grasselli, Giulia De Negri Atanasio, Maria Cristina Gagliani, Micaela Tiso,et al.
Frontiers Media SA
IntroductionCoastal seawater pollution poses a public health risk due to the potential ingestion of contaminated water during recreational activities. Wastewater-based epidemiology has revealed the abundant presence of SARS-CoV-2 in seawater emitted from wastewater outlets. The objective of this research was to investigate the impact of seawater on SARS-CoV-2 infectivity to assess the safety of recreational activities in seawater.MethodsWild SARS-CoV-2 was collected from oral swabs of COVID-19 affected patients and incubated for up to 90 min using the following solutions: (a) standard physiological solution (control), (b) reconstructed seawater (3.5% NaCl), and (c) authentic seawater (3.8%). Samples were then exposed to two different host systems: (a) Vero E6 cells expressing the ACE2 SARS-CoV-2 receptor and (b) 3D multi-tissue organoids reconstructing the human intestine. The presence of intracellular virus inside the host systems was determined using plaque assay, quantitative real-time PCR (qPCR), and transmission electron microscopy.ResultsUltrastructural examination of Vero E6 cells revealed the presence of virus particles at the cell surface and in replicative compartments inside cells treated with seawater and/or reconstituted water only for samples incubated up to 2 min. After a 90-min incubation, the presence of the virus and its infectivity in Vero E6 cells was reduced by 90%. Ultrastructural analysis performed in 3D epi-intestinal tissue did not reveal intact viral particles or infection signs, despite the presence of viral nucleic acid detected by qPCR. Indeed, viral genes (Orf1ab and N) were found in the intestinal luminal epithelium but not in the enteric capillaries. These findings suggest that the intestinal tissue is not a preferential entry site for SARS-CoV-2 in the human body. Additionally, the presence of hypertonic saline solution did not increase the susceptibility of the intestinal epithelium to virus penetration; rather, it neutralized its infectivity.ConclusionOur results indicate that engaging in recreational activities in a seawater environment does not pose a significant risk for COVID-19 infection, despite the possible presence of viral nucleic acid deriving from degraded and fragmented viruses.
Fabio Barra, Alberto Izzotti, and Stefano Bogliolo
Wiley
Assiya Kussainova, Olga Bulgakova, Akmaral Aripova, Milana Ibragimova, Alessandra Pulliero, Dinara Begimbetova, Rakhmetkazhi Bersimbaev, and Alberto Izzotti
MDPI AG
Asbestos is a known carcinogen; however, the influence of chrysotile asbestos on the development of tumor-related diseases remains a subject of intense debate within the scientific community. To analyze the effect of asbestos, we conducted a study using the MRC5 cell line. We were able to demonstrate that chrysotile asbestos stimulated the production of reactive oxygen species (ROS), leading to cell death and DNA damage in the MRC5 cell line, using various techniques such as ROS measurement, comet assay, MTT assay, and qPCR. In addition, we found that chrysotile asbestos treatment significantly increased extracellular mitochondrial DNA levels in the culture medium and induced significant changes in the expression profile of several miRNAs, which was the first of its kind. Thus, our research highlights the importance of studying the effects of chrysotile asbestos on human health and reveals multiple adverse effects of chrysotile asbestos.
Gabriela Coronel Vargas, Alberto Izzotti, Camillo Rosano, and Sebastiano La Maestra
MDPI AG
In the past four decades, the Amazon rainforest has emerged as a crucial zone for crude oil extraction in the South American region. In the Ecuadorian Amazon rainforest, hydrocarbon blocks (called “bloques”) cover vast zones, including agricultural and livestock farms, protected natural regions and the territories of uncontacted indigenous tribes. This study proposes a micronuclei assay on Vicia faba following a 24 h exposure to various soil samples collected from Bloque 57 in Ecuador. Sampling was conducted between the Dayuma and Aguarico zones, approximately 30 km from Nueva Loja city. The research aimed to assess the impact of different soil samples, particularly those from areas affected by crude oil spills, to induce micronuclei and mitotic index changes in V. faba roots. Results: The soil pollution caused by crude oil is not the sole factor contributing to cytotoxicity and genotoxicity in V. faba. Most samples from areas polluted by crude oil outside the small-scale farm showed no significant difference in micronuclei rate compared to negative control and Amazon unpolluted soil. Conversely, samples from the small-scale farm displayed a statistically significant genotoxic effect. Furthermore, samples collected from open-air wastewater pools demonstrated higher levels of cytotoxicity compared to the controls and those from small-scale farms. The mitotic index was lower in seedlings exposed to wastewater in open-air pools, especially for the 20 cm deep samples. This phenomenon could be linked to bitumen-like substances and oils floating on the surface, attaching to the small roots and causing suffocation.
Andrea Etrusco, Fabio Barra, Vito Chiantera, Simone Ferrero, Stefano Bogliolo, Giulio Evangelisti, Engin Oral, Mariana Pastore, Alberto Izzotti, Renato Venezia,et al.
Springer Science and Business Media LLC
Zumama Khalid, Simona Coco, Nadir Ullah, Alessandra Pulliero, Katia Cortese, Serena Varesano, Andrea Orsi, and Alberto Izzotti
MDPI AG
Background: Oncolytic viruses (OVs) have been utilized since 1990s for targeted cancer treatment. Our study examined the Measles–Mumps–Rubella (MMR) vaccine’s cancer-killing potency against Glioblastoma (GBM), a therapy-resistant, aggressive cancer type. Methodology: We used GBM cell lines, primary GBM cells, and normal mice microglial cells, to assess the MMR vaccine’s efficacy through cell viability, cell cycle analysis, intracellular viral load via RT-PCR, and Transmission Electron Microscopy (TEM). Results: After 72 h of MMR treatment, GBM cell lines and primary GBM cells exhibited significant viability reduction compared to untreated cells. Conversely, normal microglial cells showed only minor changes in viability and morphology. Intracellular viral load tests indicated GBM cells’ increased sensitivity to MMR viruses compared to normal cells. The cell cycle study also revealed measles and mumps viruses’ crucial role in cytopathic effects, with the rubella virus causing cell cycle arrest. Conclusion: Herein the reported results demonstrate the anti-cancer activity of the MMR vaccine against GBM cells. Accordingly, the MMR vaccine warrants further study as a potential new tool for GBM therapy and relapse prevention. Therapeutic potential of the MMR vaccine has been found to be promising in earlier studies as well.
Fabio Barra, Umberto Perrone, Simone Ferrero, Claudio Gustavino, Stefano Bogliolo, and Alberto Izzotti
Elsevier BV
Alessandra Pulliero, Luca Mastracci, Letizia Tarantini, Zumama Khalid, Valentina Bollati, and Alberto Izzotti
MDPI AG
Background: Let-7 is a tumor suppressor microRNA targeting the KRAS lung oncogene. Let-7a downregulation is reversible during the early stages of lung carcinogenesis but is irreversible in cancer cells. The aim of this study is to shed light on the relationship between oncogene (KRAS) mutation and let-7a downregulation in cigarette smoke (CS)-induced lung carcinogenesis. Methods: A total of 184 strain H Swiss albino mice were either unexposed (control) or exposed to CS for 2 weeks (short CS) or 8 months (long CS). After 8 months, the lungs were individually collected. The following end points have been evaluated: (a) DNA methylation of the let-7a gene promoter by bisulphite-PCR and pyrosequencing; (b) let-7a expression by qPCR; (c) KRAS mutation by DNA pyrosequencing; (d) cancer incidence by histopathological examination. Results: let-7a expression decreased by 8.3% in the mice exposed to CS for two weeks (CS short) and by 33.4% (p ≤ 0.01) in the mice exposed to CS for 8 months (CS long). No significant difference was detected in the rate of let-7a-promoter methylation between the Sham-exposed mice (55.1%) and the CS short-(53%) or CS long (51%)-exposed mice. The percentage of G/T transversions in KRAS codons 12 and 13 increased from 2.3% (Sham) to 6.4% in CS short– and to 11.5% in CS long–exposed mice. Cancer incidence increased significantly in the CS long–exposed mice (11%) as compared to both the Sham (4%) and the CS short–exposed (2%) mice. In the CS long–exposed mice, the correlation between let-7a expression and the number of KRAS mutations was positive (R = +0.5506) in the cancer-free mice and negative (R = −0.5568) in the cancer-bearing mice. Conclusions: The effects of CS-induced mutations in KRAS are neutralized by the high expression of let-7a in cancer-free mice (positive correlation) but not in cancer-bearing mice where an irreversible let-7a downregulation occurs (negative correlation). This result provides evidence that both genetic (high load of KRAS mutation) and epigenetic alterations (let-7a irreversible downregulation) are required to produce lung cancer in CS-exposed organisms.
G. La Rosa, D. Brandtner, G. Bonanno Ferraro, C. Veneri, P. Mancini, M. Iaconelli, L. Lucentini, C. Del Giudice, L. Orlandi, E. Suffredini,et al.
Elsevier BV
Irena Velkova, Martina Pasino, Zumama Khalid, Paola Menichini, Emanuele Martorana, Alberto Izzotti, and Alessandra Pulliero
MDPI AG
Ferroptosis is a cell death pathway triggered by an imbalance between the production of oxidants and antioxidants, which plays an emerging role in tumorigenesis. It is mainly regulated at three different levels including iron metabolism, the antioxidant response, and lipid metabolism. Epigenetic dysregulation is a “hallmark” of human cancer, with nearly half of all human cancers harboring mutations in epigenetic regulators such as microRNA. While being the crucial player in controlling gene expression at the mRNA level, microRNAs have recently been shown to modulate cancer growth and development via the ferroptosis pathway. In this scenario, some miRNAs have a function in upregulating, while others play a role in inhibiting ferroptosis activity. The investigation of validated targets using the miRBase, miRTarBase, and miRecords platforms identified 13 genes that appeared enriched for iron metabolism, lipid peroxidation, and antioxidant defense; all are recognized contributors of tumoral suppression or progression phenotypes. This review summarizes and discuss the mechanism by which ferroptosis is initiated through an imbalance in the three pathways, the potential function of microRNAs in the control of this process, and a description of the treatments that have been shown to have an impact on the ferroptosis in cancer along with potential novel effects.
Serena Varesano, Alessandra Pulliero, Emanuele Martorana, Gabriele Pizzino, Gabriele Raciti, Simona Coco, Valerio Gaetano Vellone, and Alberto Izzotti
MDPI AG
Human papillomavirus (HPV) is causatively associated with cervical cancer, the fourth most common malignant disease of women worldwide: (1) The aim of the proposed study is to implement routine diagnostics of HPV precancerous cervical lesions by introducing new molecular diagnostic tools. (2) Methods: This is a retrospective cohort study with a total of twenty-two formalin-fixed paraffin-embedded (FFPE) cervical samples of various sample type (nine biopsy and thirteen conization) each patient had a previous abnormal results of pap test or HPV DNA test. Genotyping, viral load and co-infections were determined. For each patient, the individual expression of 2549 microRNAs were evaluated by microarray and qPCR. (3) Results: Our data demonstrates that the microRNAs were commonly expressed in tissues biopsies. miR 4485-5p, miR4485-3p and miR-4497 were highly down-regulated in tissue biopsies with HPV precancerous cervical lesions. (4) Conclusions: the introduction of a microRNA analysis panel can improve early diagnosis, understand the nature of the lesion and, consequently, improve the clinical management of patients with HPV precancerous cervical lesions.
Iméne Ben Toumia, Tiziana Bachetti, Leila Chekir-Ghedira, Aldo Profumo, Marco Ponassi, Alessandro Di Domizio, Alberto Izzotti, Salvatore Sciacca, Caterina Puglisi, Stefano Forte,et al.
Frontiers Media SA
Background and purpose: Lung cancer is the leading cause of death in both men and women, constituting a major public health problem worldwide. Non-small-cell lung cancer accounts for 85%–90% of all lung cancers. We propose a compound that successfully fights tumor growth in vivo by targeting the enzyme GARS1.Experimental approach: We present an in-depth investigation of the mechanism through which Fraisinib [meso-(p-acetamidophenyl)-calix(4)pyrrole] affects the human lung adenocarcinoma A549 cell line. In a xenografted model of non-small-cell lung cancer, Fraisinib was found to reduce tumor mass volume without affecting the vital parameters or body weight of mice. Through a computational approach, we uncovered that glycyl-tRNA synthetase is its molecular target. Differential proteomics analysis further confirmed that pathways regulated by Fraisinib are consistent with glycyl-tRNA synthetase inhibition.Key results: Fraisinib displays a strong anti-tumoral potential coupled with limited toxicity in mice. Glycyl-tRNA synthetase has been identified and validated as a protein target of this compound. By inhibiting GARS1, Fraisinib modulates different key biological processes involved in tumoral growth, aggressiveness, and invasiveness.Conclusion and implications: The overall results indicate that Fraisinib is a powerful inhibitor of non-small-cell lung cancer growth by exerting its action on the enzyme GARS1 while displaying marginal toxicity in animal models. Together with the proven ability of this compound to cross the blood–brain barrier, we can assess that Fraisinib can kill two birds with one stone: targeting the primary tumor and its metastases “in one shot.” Taken together, we suggest that inhibiting GARS1 expression and/or GARS1 enzymatic activity may be innovative molecular targets for cancer treatment.
Umberto Perrone, Giulio Evangelisti, Antonio Simone Laganà, Stefano Bogliolo, Marcello Ceccaroni, Alberto Izzotti, Claudio Gustavino, Simone Ferrero, and Fabio Barra
Informa UK Limited
ABSTRACT Introduction Endometriosis is an estrogen-dependent disease that gives rise to pelvic pain and infertility. Although estroprogestins and progestins currently stand as the first-line treatments for this condition, demonstrating efficacy in two-thirds of patients, a significant portion of individuals experience only partial relief or symptom recurrence following the cessation of these therapies. The coexistence of superficial, deep endometriosis, and ovarian endometriomas, as three distinct phenotypes with unique pathogenetic and molecular characteristics, may elucidate the current heterogeneous biological response to available therapy. Areas Covered The objective of this review is to furnish the reader with a comprehensive summary pertaining to phase II-III hormonal treatments for endometriosis. Expert Opinion Ongoing research endeavors are directed toward the development of novel hormonal options for this benign yet debilitating disease. Among them, oral GnRH antagonists emerge as a noteworthy option, furnishing rapid therapeutic onset without an initial flare-up; these drugs facilitate partial or complete estrogen suppression, and promote prompt ovarian function recovery upon discontinuation, effectively surmounting the limitations associated with previously employed GnRH agonists. Limited evidence supports the use of selective estrogen and progesterone receptor modulators. Consequently, further extensive clinical research is imperative to garner a more profound understanding of innovative targets for novel hormonal options.
Alberto Izzotti
MDPI AG
Despite the impressive progress of therapies in recent years, cancer still remains the second leading cause of death in developed countries [...]
Imene Ben Toumia, Marco Ponassi, Paola Barboro, Erika Iervasi, Gabriela Coronel Vargas, Barbara Banelli, Stefano Fiordoro, Leila Chekir Ghedira, Franz Heinrich Kohnke, Alberto Izzotti,et al.
Springer Science and Business Media LLC
Alberto Izzotti, Paola Spatera, Zumama Khalid, and Alessandra Pulliero
MDPI AG
Particulate matter (PM) pollution is one of the major public health problems worldwide, given the high mortality attributable to exposure to PM pollution and the high pathogenicity that is found above all in the respiratory, cardiovascular, and neurological systems. The main sources of PM pollution are the daily use of fuels (wood, coal, organic residues) in appliances without emissions abatement systems, industrial emissions, and vehicular traffic. This review aims to investigate the causes of PM pollution and classify the different types of dust based on their size. The health effects of exposure to PM will also be discussed. Particular attention is paid to the measurement method, which is unsuitable in the risk assessment process, as the evaluation of the average PM compared to the evaluation of PM with punctual monitoring significantly underestimates the health risk induced by the achievement of high PM values, even for limited periods of time.
G. La Rosa, M. Iaconelli, C. Veneri, P. Mancini, G. Bonanno Ferraro, D. Brandtner, L. Lucentini, L. Bonadonna, M. Rossi, M. Grigioni,et al.
Elsevier BV
R. De Angelis, A. Piciocchi, M. Bugani, S. Rossi, M. Lastilla, R. Vento, A. Autore, N. Sebastiani, S. Palomba, V. Manno,et al.
Elsevier BV
E. Fulcheri, F. Buffelli, C. Fiore, A. Izzotti, M. T. Piccardo, Maria Beatrice Chiozza, Paolo Petralia, R. Ciliberti and A. Bonsignore
This is an open access journal distributed in accordance with the CC-BY-NC-ND (Creative Commons AttributionNonCommercial-NoDerivatives 4.0 International) license: the work can be used by mentioning the author and the license, but only for non-commercial purposes and only in the original version. For further information: https://creativecommons. org/licenses/by-nc-nd/4.0/deed.en PATHOLOGICA 2022;114:238-240; DOI: 10.32074/1591-951X-773
A. Pulliero, A. Izzotti, L. Pastorino, and S. Gandolfi
Elsevier BV
A. Izzotti, E. Grasselli, M. Barbaresi, M. Bixio, M. Colombo, U. Pfeffer, A. Pulliero, D. Sossai, A. Borneto, A. Boccaccio,et al.
Elsevier BV
Alessandra Pulliero, Simona Iodice, Angela Cecilia Pesatori, Luisella Vigna, Zumama Khalid, Valentina Bollati, and Alberto Izzotti
MDPI AG
Bulky DNA adducts are a combined sign of aromatic chemical exposure, as well as an individual’s ability to metabolically activate carcinogens and repair DNA damage. The present study aims to investigate the association between PM exposure and DNA adducts in blood cells, in a population of 196 adults with an unhealthy BMI (≥25). For each subject, a DNA sample was obtained for quantification of DNA adducts by sensitive32P post-labelling methods. Individual PM10 exposure was derived from daily mean concentrations measured by single monitors in the study area and then assigned to each subject by calculating the mean of the 30 days (short-term exposure), and of the 365 (long-term exposure) preceding enrolment. Multivariable linear regression models were used to study the association between PM10 and DNA adducts. The majority of analysed samples had bulky DNA adducts, with an average value of 3.7 ± 1.6 (mean ± SD). Overall, the findings of the linear univariate and multiple linear regression showed an inverse association between long-term PM10 exposure and adduct levels; this unexpected result might be since the population consists of subjects with an unhealthy BMI, which might show an atypical reaction to airborne urban pollutants; a hermetic response which happens when small amounts of pollutants are present. Pollutants can linger for a long time in the adipose tissue of obese persons, contributing to an increase in oxidative DNA damage, inflammation, and thrombosis when exposure is sustained.
Olga Bulgakova, Assiya Kussainova, Anuarbek Kakabayev, Akmaral Aripova, Gulim Baikenova, Alberto Izzotti, and Rakhmetkazhi Bersimbaev
Elsevier BV
OBJECTIVE
According to the World Health Organization, radon is the second leading cause of lung cancer after smoking. Cell free circulating mitochondrial DNA (cf mtDNA) have been used not only as a biomarker of carcinogenesis but also as a biomarker of exposure to radiation, but nothing is known about changes in the level of cf mtDNA following radon exposure. Therefore, the purpose of this study was to estimate the cf mtDNA copy number as a biomarker of the response to radon exposure in lung cancer pathogenesis.
METHODS
207 subjects were examined including 41 radon-exposed lung cancer patients, 40 lung cancer patients without radon exposure and 126 healthy controls exposed/not exposed to high level of radon. Total cell free circulating DNA from blood samples was extracted and used to detect cell free circulating mitochondrial DNA copy number by quantitative real-time polymerase chain reaction (qRT-PCR).
RESULTS
Our data indicate that the level of cf mtDNA in the radon-induced lung cancer patients was significantly higher than that of the other study participants. There was a significant difference in the level of cf mtDNA in the blood plasma of healthy volunteers exposed and not exposed to high doses of radon. Moreover, in healthy volunteers living in areas with high radon levels, the mtDNA copy number was higher than that in patients with lung cancer who were not exposed to high doses of radon.
CONCLUSION
Our study provides evidence for a possible role of cf mtDNA as a promising biomarker of lung cancer induced by exposure to high dose of radon.