Epidemiology of cancers of infectious origin and prevention strategies

Infectious and parasitic diseases represent the third cause of cancer worldwide. A number of infectious and parasitic agents have been suspected or recognized to be associated with human cancers, including DNA viruses, such as papillomaviruses (several HPV types), herpesviruses (EBV and KSHV), polyomaviruses (SV40, MCV, BK, and JCV), and hepadnaviruses (HBV); RNA viruses, such as flaviviruses (HCV), defective viruses (HDV), and retroviruses (HTLV-I, HTLV-II, HIV-1, HIV-2,HERV-K, and XMRV); bacteria, such as H. pylori, S. typhi, S. bovis, Bartonella, and C. pneumoniae; protozoa, such as P. falciparum; trematodes, such as S. haematobium, S. japonicum, S. mansoni, O. viverrini, O. felineus, and C. sinensis. Each one of the chronic infections with H. pylori, HPV, and HBV/HCV is responsible for approximately the 5% of all human cancers. The primary prevention of infection-related cancers is addressed both to avoidance and eradication of chronic infections and to protection of the host organism. Vaccines provide fundamental tools for the prevention of infectious diseases and related cancers. The large-scale application of the HBV vaccine has already shown to favorably affect the epidemiological burden of primary hepatocellular carcinoma, and HPV vaccines have specifically been designed in order to prevent cervical cancer and other HPV-related cancers. The secondary prevention of infection-associated cancers has already found broad applications in the control of cervical cancer. Detection of early gastric cancer by endoscopy has been applied in Asian countries. Avoidance of local relapses, invasion, and metastasis may be achieved by applying tertiary prevention, which targets specific mechanisms, such as angiogenesis

Cancerogenesi orale del cromo esavalente in relazione alla riduzione nell'ambiente gastrico

La determinazione della capacità riducente del succo gastrico umano in individui sani, in condizioni di digiuno e non, è un punto critico per la valutazione del pericolo cancerogeno da ingestione di cromo esavalente Cr(VI) e per lo sviluppo di modelli farmacocinetici quantitativi utilizzati nella valutazione del rischio. Nel presente studio, le reazioni di riduzione del Cr(VI) sono state valutate in 16 campioni di succo gastrico pre e postprandiali, prelevati da 8 volontari sani. Il succo gastrico umano era efficace sia nel ridurre il Cr(VI), come analizzato utilizzando il metodo colorimetrico s-difenilcarbazide, che nell'attenuare la sua mutagenicità nel test di Ames. La capacità media (± SE) di riduzione del Cr(VI) nei campioni post prandiali (20,4 ± 2,61 mg Cr(VI)/ml di fluido gastrico) era notevolmente superiore a quella dei campioni pre-prandiali (10,2 ± 2,39 mg Cr (VI ) / ml di fluido gastrico). Quando si utilizza il test di mutagenesi, la diminuzione della mutagenicità prodotta da campioni pre e post prandiali corrisponde rispettivamente, alla perdita di 13,3 ± 1,91 e 25,6 ± 2,89 mg Cr(VI) di succo gastrico/ml. La riduzione del Cr(VI) è stata rapida e soprattutto, completa in 30 min di reazione con il succo gastrico. La diminuita capacità di riduzione del Cr(VI) è stata correlata all'incremento dei valori di pH (4 a 8). L’attenuazione della risposta mutagenica è coerente con la mancanza di danno al DNA osservato nel tratto gastrointestinale di roditori dopo la somministrazione di Cr(VI) in acqua potabile. Questi risultati evidenziano la necessità di determinare la cinetica di riduzione del Cr(VI) nel tratto gastrointestinale umano in modo da valutarne i potenziali rischi per la salute dell'uomo derivanti dalla presenza del Cr(VI) nell’acqua potabile

Modulation of smoke-induced DNA and microRNA alterations in mouse lung by licofelone, a triple COX-1, COX-2 and 5-LOX inhibitor

Chronic inflammation plays a crucial role in the carcinogenesis process and in particular in smoking-related carcinogenesis. Therefore, anti-inflammatory agents provide an interesting perspective in the prevention of smoking-associated cancers. Among nonsteroidal anti-inflammatory drugs (NSAIDs), licofelone is a triple inhibitor of both cyclooxygenases (COX-1 and COX-2) and of 5-lipooxygenase (5-LOX) that has shown some encouraging results in cancer prevention models. We previously showed that the dietary administration of licofelone, starting after weanling, to Swiss H mice exposed for 4 months to mainstream cigarette smoke since birth attenuated preneoplastic lesions of inflammatory nature in both lung and urinary tract, and had some effects on the yield of lung tumors at 7.5 months of age. The present study aimed at evaluating the early modulation by licofelone of pulmonary DNA and RNA alterations either in smoke-free or smoke-exposed H mice after 10 weeks of exposure. Licofelone protected the mice from the smoke-induced loss of body weight and significantly attenuated smoke-induced nucleotide alterations by decreasing the levels of bulky DNA adducts and 8-hydroxy-2'-deoxyguanosine in mouse lung. Moreover, the drug counteracted dysregulation by smoke of several pulmonary microRNAs involved in stress response, inflammation, apoptosis, and oncogene suppression. However, even in smoke-free mice administration of the drug had significant effects on a broad panel of microRNAs and, as assessed in a subset of mice used in a parallel cancer chemoprevention study, licofelone even enhanced the smoke-induced systemic genotoxic damage after 4 months of exposure. Therefore, caution should be paid when administering licofelone to smokers for long periods

Estimates of the incidence of infection-related cancers in Italy and Italian regions in 2018

Introduction. Chronic infections and infestations represent one of the leading causes of cancer. Eleven agents have been categorized by the International Agency for Research on Cancer (IARC) in Group 1, 3 in Group 2A and 4 in Group 2B. We previously estimated that the incidence of cancers associated with infectious agents accounted for the 8.5% of new cancer cases diagnosed in Italy in 2014. Methods. In the present study we evaluated the incidence of cancer in Italy and in the 20 Italian regions in 2018, based on the data of Cancer Registries, and calculated the fraction attributable to infectious agents. Results. Cancers of infectious origin contributed to the overall burden of cancer in Italy with more than 27,000 yearly cases, the 92% of which was attributable to Helicobacter pylori, human papillomaviruses, and hepatitis B and C viruses. With the exception of papillomavirus-related cancers, the incidence of cancers of infectious origin was higher in males (16,000 cases) than in females (11,000 cases). There were regional and geographical variations of cancers depending on the type of cancer and on the gender. Nevertheless, the overall figures were rather similar, the infection-related cancers accounting for the 7.2, 7.6, and 7.1% of all cancers in Northern, Central, and Southern Italy, respectively. Conclusions. The estimate of the incidence of cancers attributable to infectious agents in Italy in 2018 (7.3% of all cancer cases) is approximately half of the worldwide burden, which has been estimated by IARC to be the 15.4% of all cancer cases in 2012

Modulation of genomic and epigenetic end-points by celecoxib

Celecoxib, a nonsteroidal anti-inflammatory drug that selectively targets cyclooxygenase-2, is a promising cancer chemopreventive agent. However, safety concerns have been raised in clinical trials evaluating its ability to prevent colorectal adenomas. The rationale for the herein reported studies was to analyze genomic and epigenetic end-points aimed at investigating both the chemopreventive properties of celecoxib towards cigarette smoke-associated molecular alterations and its possible adverse effects. We carried out three consecutive studies in mice treated with either smoke and/or celecoxib. Study 1 investigated early DNA alterations (DNA adducts, oxidative DNA damage, and systemic genotoxic damage) and epigenetic alterations (expression of 1,135 microRNAs) in lung and blood of Swiss H mice; Study 2 evaluated the formation of DNA adducts in lung, liver, and heart; and Study 3 evaluated the expression of microRNAs in 10 organs and 3 body fluids of ICR (CD-1) mice. Surprisingly, the oral administration of celecoxib to smoke-free mice resulted in the formation of DNA adducts in both lung and heart and in dysregulation of microRNAs in mouse organs and body fluids. On the other hand, celecoxib attenuated smoke-related DNA damage and dysregulation of microRNA expression. In conclusion, celecoxib showed pleiotropic properties and multiple mechanisms by counteracting the molecular damage produced by smoke in a variety of organs and body fluids. However, administration of celecoxib to non-smoking mice resulted in evident molecular alterations, also including DNA and RNA alterations in the heart, which may bear relevance in the pathogenesis of the cardiovascular adverse effects of this drug

Seroprevalencija virusa hepatitisa E u krava s ruralnih područja južne Italije

Hepatitis E virus (HEV) is considered to be an emerging zoonotic disease, which causes numerous cases of hepatitis and deaths worldwide each year. Pigs are a host reservoir of HEV, but numerous other wild and domestic species can be infected. The aim of this study was to carry out serological screening of anti-HEV antibodies in cattle in the Sicily region (Southern Italy). Between April and December 2018, 231 serum samples were collected from cows and analysed with enzyme-linked immunosorbent assay (ELISA), for detection of HEV antibodies (IgG). The overall prevalence of anti-HEV antibodies was 36.36% (84/231; 95% CI 30-43). There were statistically significant differences in the HEV seroprevalence in animals of different ages (12 months: 39.30%; >24 months: 54.10%) (P0.05). This study shows that further investigation of HEV in cattle is required to understand better the epidemiology in farm animals and the potential zoonotic risks for humans. This is the first report of HEV seroprevalence for cows in Italy, which provides baseline data for further studies and for control of HEV infection in cattle.Virus hepatitisa E (HEV) smatra se emergentnom zoonozom koja uzrokuje brojne slučajeve hepatitisa i uginuća širom svijeta svake godine. Svinja je rezervoar HEV-a, no mogu se zaraziti i brojne druge divlje i domaće vrste. Cilj ovog istraživanja bio je provesti serološki probir anti-HEV protutijela u goveda na Siciliji (južna Italija). Od travnja do prosinca 2018. prikupljen je ukupno 231 uzorak seruma krava i analiziran testom ELISA za detekciju protutijela na HEV (IgG). Prevalencija anti-HEV protutijela bila je 36,36 % (84/231; 95 % CI 30 – 43). Pronađena je statistički znakovita razlika (P 12 mjeseci: 39,30 %; > 24 mjeseci: 54,10 %). Nije zabilježena statistički znakovita razlika (P> 0,05) s obzirom na spol (31,37 % u mužjaka i 37,38 % u ženki). Rezultati ukazuju na potrebu daljnjih istraživanja HEV-a u goveda kako bi se bolje razumjela epidemiologija u farmskih životinja i potencijalan zoonotski rizik za ljude. Ovo je prvo izvješće o seroprevalenciji HEV-a u krava u Italiji, kojim se pružaju referentni podaci za daljnja istraživanja i kontrolu infekcije HEV-om u goveda

Extracellular Vesicles in Biological Fluids. A Biomarker of Exposure to Cigarette Smoke and Treatment with Chemopreventive drugs

Extracellular vesicles (EVs) are released from cells and enter into body fluids thereby providing a toxicological mechanism of cell-cell communication. The present study aimed at assessing (a) the presence of EVs in mouse body fluids under physiological conditions, (b) the effect of exposure of mice to cigarette smoke for 8 weeks, and (c) modulation of smoke-related alterations by the nonsteroidal anti-inflammatory drug celecoxib, a selective cyclooxygenase-2 inhibitor. To this purpose, ICR (CD-1) mice were either unexposed or exposed to cigarette smoke, either treated or untreated with oral celecoxib. EVs, isolated from bronchoalveolar lavage fluid (BALF), blood serum, and urines, were analyzed by nanoparticle tracking analysis and flow cytometry. EVs baseline concentrations in BALF were remarkably high. Larger EVs were detected in urines. Smoking increased EVs concentrations but only in BALF. Celecoxib remarkably increased EVs concentrations in the blood serum of both male and female smoking mice. The concentration of EVs positive for EpCAM, a mediator of cell-cell adhesion in epithelia playing a role in tumorigenesis, was much higher in urines than in BALF, and celecoxib significantly decreased their concentration. Thus, the effects of smoke on EVs concentrations were well detectable in the extracellular environment of the respiratory tract, where they could behave as delivery carriers to target cells. Celecoxib exerted both protective mechanisms in the urinary tract and adverse systemic effects of likely hepatotoxic origin in smoke-exposed mice. Detection of EVs in body fluids may provide an early diagnostic tool and an end-point exploitable for preventive medicine strategies.

Promjene intraokularnog tlaka i sistemskog krvnog tlaka u pasa za vrijeme vježbe umjerenog intenziteta na pokretnoj traci - kratki prikaz

Physical exercise in humans induces changes in intraocular pressure, relating to the type and intensity of the workload. The purpose of the present study was to evaluate the variations in intraocular pressure and arterial blood pressure in dogs that underwent physical exercise on a treadmill. Thirty dogs were submitted to physical exercise consisting of walking (15 minutes), trotting (20 minutes), and walking (10 minutes). The intraocular pressure, blood pressure and pulse rate were recorded for each dog before starting the treadmill exercise, immediately after it ended, and after 20 minutes of passive recovery. Two-way repeated analysis of variance measurement showed the significant effect of treadmill exercise (P≤0.01) on intraocular pressure, pulse rate and diastolic blood pressure. No significant changes were observed to systolic blood pressure. Intraocular pressure and diastolic blood pressure decreased significantly during the passive recovery, and were strongly related. The pulse rate was significantly lower during the passive recovery. Although the mechanism determining the reduction in intraocular pressure during exercise remains not fully understood, our results suggest that it is strongly related to variations in arterial blood pressure.physical exercise; eye; ocular variable; arterial blood pressure; dogTjelesna vježba u ljudi uzrokuje promjene u intraokularnom tlaku, ovisno o vrsti i intenzitetu opterećenja. cilj ovog istraživanja bio je procijeniti varijacije intraokularnog tlaka i arterijski krvni tlak u pasa podvrgnutih tjelesnoj aktivnosti na pokretnoj traci. Trideset pasa izloženo je tjelesnoj aktivnosti koja se sastojala od hodanja (15 minuta), trčanja u formi kasa (20 minuta) i hodanja (10 minuta). Za svakog su psa zabilježeni intraokularni tlak, krvni tlak i srčani puls prije početka aktivnosti, odmah nakon završetka aktivnosti i 20 minuta nakon oporavka. Dvosmjerna analiza varijance za ponovljena mjerenja pokazala je znakovit učinak vježbe na pokretnoj traci (P ≤ 0,01) na intraokularni tlak, srčani puls i dijastolički krvni tlak. Nije bilo znakovitih promjena u sistoličkom krvnom tlaku. Intraokularni tlak i dijastolički krvni tlak znakovito su se smanjili za vrijeme oporavka i bili u znatnoj korelaciji. Srčani puls bio je znakovito niži za vrijeme oporavka. Iako mehanizam koji utječe na smanjenje intraokularnog tlaka nije sasvim jasan, rezultati pokazuju da je on u čvrstoj vezi s promjenama arterijskog krvnog tlaka

Reduction of hexavalent chromium by fasted and fed human gastric fluid. I. Chemical reduction and mitigation of mutagenicity

Abstract Evaluation of the reducing capacity of human gastric fluid from healthy individuals, under fasted and fed conditions, is critical for assessing the cancer hazard posed by ingested hexavalent chromium [Cr(VI)] and for developing quantitative physiologically-based pharmacokinetic models used in risk assessment. In the present study, the patterns of Cr(VI) reduction were evaluated in 16 paired pre- and post-meal gastric fluid samples collected from 8 healthy volunteers. Human gastric fluid was effective both in reducing Cr(VI), as measured by using the s-diphenylcarbazide colorimetric method, and in attenuating mutagenicity in the Ames test. The mean (± SE) Cr(VI)-reducing ability of post-meal samples (20.4 ± 2.6 μg Cr(VI)/mL gastric fluid) was significantly higher than that of pre-meal samples (10.2 ± 2.3 μg Cr(VI)/mL gastric fluid). When using the mutagenicity assay, the decrease of mutagenicity produced by pre-meal and post-meal samples corresponded to reduction of 13.3 ± 1.9 and 25.6 ± 2.8 μg Cr(VI)/mL gastric fluid, respectively. These data are comparable to parallel results conducted by using speciated isotope dilution mass spectrometry. Cr(VI) reduction was rapid, with > 70% of total reduction occurring within 1 min and 98% of reduction is achieved within 30 min with post-meal gastric fluid at pH 2.0. pH dependence was observed with decreasing Cr(VI) reducing capacity at higher pH. Attenuation of the mutagenic response is consistent with the lack of DNA damage observed in the gastrointestinal tract of rodents following administration of ≤ 180 ppm Cr(VI) for up to 90 days in drinking water. Quantifying Cr(VI) reduction kinetics in the human gastrointestinal tract is necessary for assessing the potential hazards posed by Cr(VI) in drinking water