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.

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.

Interactions between ethanol and cigarette smoke in a mouse lung carcinogenesis model.

Both ethanol and cigarette smoke are classified as human carcinogens. They can synergize, especially in tissues of the upper aerodigestive tract that are targeted by both agents. The main objective of the present study was to evaluate the individual and combined effects of ethanol and smoke in the respiratory tract, either following transplacental exposure and/or postnatal exposure. We designed two consecutive studies in mouse models by exposing Swiss H mice to oral ethanol and/or inhaled mainstream cigarette smoke for up to 4 months, at various prenatal and postnatal life stages. Clastogenic effects and histopathological alterations were evaluated after 4 and 8 months, respectively. Ethanol was per se devoid of clastogenic effects in mouse peripheral blood erythrocytes. However, especially in mice exposed both transplacentally throughout pregnancy and in the postnatal life, ethanol administration was associated not only with liver damage but also with pro-angiogenetic effects in the lung by stimulating the proliferation of blood vessels. In addition, these mice developed pulmonary emphysema, alveolar epithelial hyperplasias, microadenomas, and benign tumors. On the other hand, ethanol interfered in the lung carcinogenesis process resulting from the concomitant exposure of mice to smoke. In fact, ethanol significantly attenuated some smoke-related preneoplastic and neoplastic lesions in the respiratory tract, such as alveolar epithelial hyperplasia, microadenomas, and even malignant tumors. In addition, ethanol attenuated cigarette smoke clastogenicity. In conclusion, preclinical studies provide evidence that, in spite of its pulmonary toxicity, ethanol may mitigate some noxious effects of cigarette smoke in the respiratory tract.

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.