Pleural mesothelioma from fluoro-edenite exposure: PACAP and PAC1 receptor. A preliminary report.

Pleural mesothelioma is a devastating malignancy primarily associated with asbestos exposure. However, emerging evidence suggests that exposure to fluoro-edenite fibers, a naturally occurring mineral fiber, can also lead to the development of pleural mesothelioma. In this study, based on the hypothesis that pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-preferring receptor (PAC1R) expressions could be dysregulated in pleural mesothelioma samples and that they could potentially act as diagnostic or prognostic biomarkers, we aimed to investigate the immunohistochemical expression of PACAP and PAC1R in pleural biopsies from patients with pleural mesothelioma exposed to fluoro-edenite fibers. A total of 12 patients were included in this study, and their biopsies were processed for immunohistochemical analysis to evaluate the expression of PACAP and its receptor. The study revealed a correlation between the overexpression of PACAP and PAC1R and shorter overall survival in patients with malignant mesothelioma. These findings suggest that PACAP and PAC1R expression levels could serve as potential prognostic biomarkers for malignant mesothelioma. Furthermore, the immunohistochemical analysis of PACAP and PAC1R may provide valuable information for clinicians to guide therapeutic decisions and identify patients with poorer prognosis.

Expression of stathmin in asbestos-like fibers-induced mesothelioma: A preliminary report.

BACKGROUND: Mesothelioma is strongly associated with exposure to asbestos fibers, however, recent studies have also linked exposure to "naturally occurring asbestos" fibers with this disease. Fluoro-edenite, a silicate mineral found in the southeast of Biancavilla (Sicily, Italy), has been identified as a potential risk factor for mesothelioma. Unfortunately, this cancer often has a poor prognosis, and current diagnostic and prognostic biomarkers are inadequate. Histological subtype, gender, and age at diagnosis are the most significant parameters for mesothelioma. Stathmin, a cytosolic protein that regulates cell growth and migration and is overexpressed in many human malignancies, has not yet been linked to mesothelioma survival or clinical-pathological variables. AIM: The aim of this study was to investigate the immunohistochemical expression of stathmin in ten mesothelioma tissue samples with available clinical and follow-up data. MATERIAL AND METHODS: Paraffin-embedded tissue samples from ten mesothelioma patients were processed for immunohistochemical analyses to evaluate stathmin expression. RESULTS: Our findings suggest that stathmin overexpression is associated with shorter overall survival in patients with mesothelioma. Furthermore, stathmin expression was significantly correlated with the survival time of mesothelioma patients. CONCLUSION: Our results suggest that stathmin expression may serve as a potential prognostic biomarker for mesothelioma. This biomarker could be used to promptly identify patients with poor prognosis and to guide clinicians in the selection of treatment options.

Immunohistochemical expression of cAMP in fluoroedenite­induced malignant pleural mesothelioma: Preliminary results.

Despite advances in understanding of the biology of malignant pleural mesothelioma (MPM), the prognosis of this malignancy remains poor. Although asbestos still remains the main pathogenic agent of MPM, other asbestos­like fibers such as fluoro­edenite (FE) fibers, induce MPM. Notable incidence and mortality rates of MPM have been found in Biancavilla, Italy, where FE fibers have been extracted from building materials for >50 years. Cyclic adenosine monophosphate (cAMP) is a secondary messenger that plays a key role in several physiological and pathological mechanisms regulating protein kinase A (PKA) and the CREB pathway. Hyperactivation of the cAMP/PKA/CREB pathway is involved in many neoplastic processes, including tumor cell proliferation, invasion and metastatic spread. The present study investigated immunohistochemical expression of cAMP in patients with FE­induced MPM, which included six males and four females with an age range of 50­93 years. There was high immunoexpression of cAMP in 5 out of 10 tumors while the remaining 5 cases showed low immunoexpression. In addition, there was a correlation between cAMP overexpression and decreased survival times (mean overall survival times, 7.5 months in high expression group vs. 18 months in low expression group).

Infrared thermography for the evaluation of adolescent and juvenile idiopathic scoliosis: A systematic review.

INTRODUCTION: Adolescent and Juvenile Idiopathic Scoliosis are a three-dimensional spine deformity characterized by a muscle alteration of the convex and concave sides of the scoliosis, which can be evaluated with different non-invasive and radiation-free methods such as infrared thermography. The objective of the present review is to assess infrared thermography as a potential method to evaluate alterations of the scoliosis. MATERIALS AND METHODS: A systematic review was performed by collecting articles from PubMed, Web of Science, Scopus, and Google Scholar, published from 1990 to April 2022, on the use of infrared thermography to evaluate adolescent and juvenile idiopathic scoliosis. Relevant data were collected in tables, and the primary outcomes were discussed narratively. RESULTS: Of the 587 articles selected, only 5 were in line with the objective of this systematic review and were eligible for the inclusion criteria. The findings of the selected articles corroborate the applicability of infrared thermography as an objective method to assess the thermal differences of the muscles between the convex and concave sides of scoliosis. The overall quality of the research was uneven in the reference standard method and assessment of measures. CONCLUSION: Infrared thermography is providing promising results to discriminate thermal differences in scoliosis evaluation, albeit there are still some concerns about considering it as a diagnostic tool for scoliosis evaluation because specific recommendations for collecting data are not met. We propose additional recommendations to existing guidelines to perform thermal acquisition to reduce errors and provide the best results to the scientific community.

Small RNA-Seq Transcriptome Profiling of Mesothelial and Mesothelioma Cell Lines Revealed microRNA Dysregulation after Exposure to Asbestos-like Fibers.

Environmental exposure to fibers of respirable size has been identified as a risk for public health. Experimental evidence has revealed that a variety of fibers, including fluoro-edenite, can develop chronic respiratory diseases and elicit carcinogenic effects in humans. Fluoro-edenite (FE) is a silicate mineral first found in Biancavilla (Sicily, Italy) in 1997. Environmental exposure to its fibers has been correlated with a cluster of malignant pleural mesotheliomas. This neoplasm represents a public health problem due to its long latency and to its aggression not alerted by specific symptoms. Having several biomarkers providing us with data on the health state of those exposed to FE fibers or allowing an early diagnosis on malignant pleural mesothelioma, still asymptomatic patients, would be a remarkable goal. To these purposes, we reported the miRNA transcriptome in human normal mesothelial cell line (MeT-5A) and in the human malignant mesothelioma cell line (JU77) exposed and not exposed to FE fibers. The results showed a difference in the number of deregulated miRNAs between tumor and nontumor samples both exposed and not exposed to FE fibers. As a matter of fact, the effect of exposure to FE fibers is more evident in the expression of miRNA in the tumor samples than in the nontumor samples. In the present paper, several pathways involved in the pathogenesis of malignant pleural mesothelioma have been analyzed. We especially noticed the involvement of pathways that have important functions in inflammatory processes, angiogenesis, apoptosis, and necrosis. Besides this amount of data, further studies will be designed for the selection of the most significant miRNAs to test and validate their diagnostic potential, alone or in combination with other protein biomarkers, in high-risk individuals' liquid biopsy to have a noninvasive tool of diagnosis for this neoplasm.

Evaluation of Cardiovascular Activity and Emotional Experience in Healthcare Workers (HCWs) Operating in COVID-19 Wards.

The new 2019 coronavirus or SARS-CoV-2 has been the first biological agent to generate, in this millennium, such a global health emergency as to determine the adoption of public health measures. During this sanitary emergency, the emotional experience of healthcare workers (HCWs) has been hugely tested by several factors. In fact, HCWs have been exposed to greatly tiring physical, psychological and social conditions. The authors investigated the cardiocirculatory activity of a group of HCWs as well as how they perceived stress while working in COVID-19 wards. In particular, every HCW underwent a medical check, an electrocardiographic base exam, systolic and diastolic pressure measurement, and cardio frequency measurement. Furthermore, each HCW was provided with a cardiac Holter device (HoC) and a pressure Holter (Hop). Some psychological factors were considered in order to quantify the stress perceived by each HCW while at work through the administration of two questionnaires: the "Social Stigma towards Patients due to COVID Scale (SSPCS)" and the "Professional Quality of Life Scale (ProQOL)". The HoC and HoP analysis results for HCWs working in COVID-19 OU wards showed significant variations in cardiocirculatory activity. From the analysis of the SSPCS questionnaire answers, it is clear that all of them showed a sense of duty towards their patients. The analysis of the ProQOL questionnaire answers showed that the prevailing attitude is fear; however, HCWs did not absolutely discriminate against those who had COVID-19 nor did they refuse to help those in need. Continuous monitoring of these employees, also carried out through occupational medicine surveillance, allows for the detection of critical conditions and the implementation of actions aimed at preventing chronic processes.

Esophageal cancer and bacterial part of gut microbiota - A multidisciplinary point of view.

There is an urgent need to search for new screening methods that allow early detection of esophageal cancer and thus achieve better clinical outcomes. Nowadays, it is known that the esophagus is not a sterile part of the gastrointestinal tract. It is colonized with various microorganisms therefore a "healthy" esophageal microbiome exists. The dysbiotic changes of esophageal microbiome can lead to the development of esophageal diseases including esophageal cancer. There is a strong consensus in the literature that the intestinal microbiome may be involved in esophageal carcinogenesis. Recently, emphasis has also been placed on the relationship between the oral microbiome and the occurrence of esophageal cancer. According to recent studies, some of the bacteria present in the oral cavity, such as Tannerella forsythia, Streptococcus anginosus, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Fusobacterium nucleatum may contribute to the development of this cancer. Moreover, the oral microbiome of patients with esophageal cancer differs significantly from that of healthy individuals. This opens new insights into the search for a microbiome-associated marker for early identification of patients at high risk for developing this cancer.

Ergonomic Evaluation of Young Agricultural Operators Using Handle Equipment Through Electromyography and Vibrations Analysis Between the Fingers.

Background: Agricultural handle equipment is present on all production areas' farms. They are handy and portable; however, excessive use can lead to acute traumas or accidental injuries. Repetitive movements, awkward postures, and hand-arm vibrations predispose them to pain and work-related musculoskeletal disorders. The purpose of this study was to observe the interaction of handle equipment in terms of electromyographic activity and analyze the postural work-related alterations. Materials and methods: Twenty male agricultural operators, mean age 24 ± 1.54 years, underwent the electromyographic analysis testing their muscular activities with a brushcutter, electric saw, and hedge trimmer in four different test conditions. Results: The brushcutter proved to be the agricultural handle equipment with the higher mean frequency (3.37 ± 0.38 Hz) and root mean square (5.25 ± 1.24 ms-2). Furthermore, the digital postural analysis showed a general asymmetry of the main arm and the respective side of the trunk. The head resulted right inclined in the anterior frontal plane by 5.7° ± 1.2°; the right scapula lower than the left in the posterior frontal plane (8.5° ± 1.8°), and a working trunk inclination of 34.15° ± 5.7°. Conclusions: Vibrations of handle equipment and awkward working postures represent a risk for agricultural operators. Preventive measures are required to avoid young operators from experiencing musculoskeletal disorders all lifelong.

SARS-CoV-2 Transmission Prevention Model Application in a Large Retail Company Before the Vaccine Introduction.

On 11 March 2020, following the spread of SARS-CoV-2, WHO declared a pandemic status. The impact on national health and economic systems has been huge. Therefore, many countries took measures to restrict the spread of the virus. Many work activities have been subjected to lockdown measures. However, some production activities, continued to remain open, i.e., large-scale food distribution, food industry, pharmacies, hospitals, etc. In order to contain the spread of the pandemic, public health measures have been implemented by the States to reduce the contagion of the virus in the workplace. Therefore, it was important to implement measures to contrast and contain the spread of SARS-CoV-2/COVID-19 in workplaces. The aim of this study was to adopt and implement a safety protocol useful to restrict the spread of SARS-CoV-2 in a large-scale retail trade company located in the south of Italy, before vaccination, during the first and second pandemic phases also exploiting telemedicine services. Antibody serological test cards were also used during the first pandemic wave and rapid antigenic swabs during the second to detect workers positive for SARS-CoV-2. A population of subjects who worked for another company similar for production activity and distribution on the territory was selected as the control group. During work activities, this group followed the minimum activity protocol provided by the Italian legislation (24 April 2020, Ministry Protocol), which provided the daily monitoring of the body temperature and in the case of SARS- CoV-2 positive subjects the extraordinary sanitation of the workplace. The measures implemented identified the positive subject for SARS-CoV-2 at an early stage. The protocol made it possible to significantly reduce the spread of the virus within large-scale retail distribution, and therefore, to avoid the temporary closure of the stores with a consequent reduction of economic losses compared with the control group.

Work Ability after Breast Cancer: Study of Healthcare Personnel Operating in a Hospital of South Italy.

Breast cancer (BrC) treatment can produce disabilities that often impact the quality of daily life and impact the social and working relationships of the patient. This paper looked into the remaining work ability in a group of female healthcare personnel (HCPs) with BrC in Southern Italy. Each HCP was subjected to a medical check, routine blood tests, and a questionnaire on the work ability index (WAI). Of 980 (100%) HCWs undergoing health control, 6% (n = 54) had experienced BRC, and only 66.6% (n = 36) agreed to take part in the study. A total of 28 (78%) were on night shifts. The WAI score was quite low in 5 (13.8%) cases, moderate in 10 (27.7%) cases, good in 14 (38.8%) cases, and excellent in 7 (19.5%) HCWs. Among all health figures, in nurses as well as technical staff, lower WAI scores were observed. HCWs reported various comorbidities, which affected WAI score, such as limited mobility in the upper limbs, arm/shoulder pain, numbness, and lymphoedema. The main complication that negatively affects any work activity is the morbidity in the upper limbs. This seems to affect the ability to perform tasks, and the re-entry to work is highlighted on sick leave days.

Expression of Matrix Metalloproteinases 7 and 9, Desmin, Alpha-Smooth Muscle Actin and Caldesmon, in Odontogenic Keratocyst Associated with NBCCS, Recurrent and Sporadic Keratocysts.

Nevoid basal cell carcinoma syndrome (NBCCS) associated odontogenic keratocysts (OKCs) show more aggressive behavior and it has a higher frequency of relapse than non-syndromic OKCs. Stromal myofibroblasts (MFs), characterized by α-smooth muscle actin (αSMA), desmin and caldesmon expression, and metalloproteinases (MMPs) have an essential role in the remodeling of the extracellular matrix (ECM). The aim of the study is to analyze the immunohistochemical expression of MMP-7, MMP-9, αSMA and other new markers in the study of OKCs MFs such as desmin and caldesmon in NBCCS-associated OKCs compared to recurrent and sporadic keratocysts. Fourty 40 patients (23 M and 17 F) underwent surgery to remove the OKCs. The histological sections in paraffin were incubated with markers antibodies and a semi-quantitative score was used to evaluate the immunoreactivity. Densitometric analysis showed a very significantly increased expression of αSMA, caldesmon, MMP-7 and MMP-9 in NBCCS-OKCs compared to non-syndromic OKCs (p < 0.001). However, desmin showed a not significant increased expression in non-syndromic OKC compared to NBCCS-OKCs specimens in which desmin was slightly or not at all expressed. NBCSS-OKCs showed a greater distribution of MFs compared to the other OKCs subtypes. Further studies will be needed to evaluate whether the different expressions of these markers can be correlated to a different clinical behavior.

Dysregulation of microRNAs and tRNA-derived ncRNAs in mesothelial and mesothelioma cell lines after asbestiform fiber exposure.

Experimental evidence demonstrated that fluoro-edenite (FE) can develop chronic respiratory diseases and elicit carcinogenic effects. Environmental exposure to FE fibers is correlated with malignant pleural mesothelioma (MPM). An early diagnosis of MPM, and a comprehensive health monitoring of the patients exposed to FE fibers are two clinical issues that may be solved by the identification of specific biomarkers. We reported the microRNA (miRNA) and transfer RNA-derived non coding RNA (tRNA-derived ncRNA) transcriptome in human normal mesothelial and malignant mesothelioma cell lines exposed or not exposed to several concentration FE fibers. Furthermore, an interactive mesothelioma-based network was derived by using NetME tool. In untreated condition, the expression of miRNAs and tRNA-derived ncRNAs in tumor cells was significantly different with respect to non-tumor samples. Moreover, interesting and significant changes were found after the exposure of both cells lines to FE fibers. The network-based pathway analysis showed several signaling and metabolic pathways potentially involved in the pathogenesis of MPM. From papers analyzed by NetME, it is clear that many miRNAs can positively or negatively influence various pathways involved in MPM. For the first time, the analysis of tRNA-derived ncRNAs molecules in the context of mesothelioma has been made by using in vitro systems. Further studies will be designed to test and validate their diagnostic potential in high-risk individuals' liquid biopsies.

Diagnostic and Prognostic Value of Three microRNAs in Environmental Asbestiform Fibers-Associated Malignant Mesothelioma.

Fluoro-edenite (FE) is an asbestiform fiber identified in Biancavilla (Sicily, Italy). Environmental exposure to FE has been associated with a higher incidence of malignant mesothelioma (MM). The present study aimed to validate the predicted diagnostic significance of hsa-miR-323a-3p, hsa-miR-101-3p, and hsa-miR-20b-5p on a subset of MM patients exposed to FE and matched with healthy controls. For this purpose, MM tissues vs. nonmalignant pleura tissues were analyzed through droplet digital PCR (ddPCR) to evaluate differences in the expression levels of the selected miRNAs and their MM diagnostic potential. In addition, further computational analysis has been performed to establish the correlation of these miRNAs with the available online asbestos exposure data and clinic-pathological parameters to verify the potential role of these miRNAs as prognostic tools. ddPCR results showed that the three analyzed miRNAs were significantly down-regulated in MM cases vs. controls. Receiver operating characteristic (ROC) analysis revealed high specificity and sensitivity rates for both hsa-miR-323a-3p and hsa-miR-20b-5p, which thus acquire a diagnostic value for MM. In silico results showed a potential prognostic role of hsa-miR-101-3p due to a significant association of its higher expression and increased overall survival (OS) of MM patients.

ATG7 immunohistochemical expression in malignant pleural mesothelioma. A preliminary report.

Literature evidence has demonstrated a high incidence of asbestos-related malignant pleural mesothelioma (MPM) in a Sicilian town (Biancavilla, Italy), where fluoro-edenite (FE) fibers were discovered some decades ago. As ATG7 immunohistochemical analysis has been ascribed as a prognostic tool of improved survival, we decided to investigate, in MPM patients, exposed and not exposed to FE fibers, the immunohistochemical expression of this autophagy-related protein named ATG7. We analyzed the correlation between ATG7 immunohistochemical level and clinicopathological parameters. Twenty MPM tissue samples, from patients with available clinical and follow-up data, were included in paraffin and processed for immunohistochemistry. The immunohistochemical results confirmed activation of the autophagic process in MPM. Densitometric and morphometric expressions of ATG7 were significantly increased in MPMs when compared to the control tissues. A significant association of a high level of ATG7 with increased survival was demonstrated, with a mean overall survival (OS) of 12.5 months for patients with high expression vs. a mean OS of 4.5 months for patients with low ATG7 expression. In addition, a significant correlation between ATG7 expression and the survival time of MPM patients was observed. This study represents a starting point to hypothesize the prognostic role of ATG7 which could be a reliable prognostic indicator in MPM.

Immunohistochemical Expression of Serine and Arginine-Rich Splicing Factor 1 (SRSF1) in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Study.

The Serine and Arginine-Rich Splicing Factor 1 (SRSF1) has a proto-oncogenic function, being associated with angiogenesis and frequently overexpressed in many human malignant neoplasms. Its immunohistochemical expression has never been investigated in malignant pleural mesothelioma (MPM). We evaluated SRSF1 immunoexpression and its possible relation to angiogenesis in a selected cohort of 10 fluoro-edenite(FE)-induced MPM cases. METHODS: Immunohistochemical analyses with an anti-SRSF1 antibody were performed. We interpreted the cases as positive if tumor cell nuclei were stained; a semi-quantitative analysis of the cases was performed by evaluating the intensity of staining and the percentage of tumor positive cells. A microvessel density (MVD) count was also performed. RESULTS: High and low immunoexpressions of SRSF1 were seen in six and four MPMs, respectively. A trend of shorter overall survival was found in FE-induced MPM patients with SRSF1 overexpression. In addition, a significant association between high-MVD and high SRSF1 immunoexpression (p = 0.0476) was found. CONCLUSIONS: SRSF1 appears to be involved in MPM pathogenesis and its immunoexpression may represent a prognostic biomarker capable of identifying subgroups of patients with different prognosis. However, given the preliminary nature of the present study, further investigations on larger series, and additional in vitro studies, are required to validate our findings.

Anaphylactic Death: A New Forensic Workflow for Diagnosis.

Anaphylaxis is a life-threatening or fatal clinical emergency characterized by rapid onset, and death may be sudden. The margin of certainty about the diagnosis of anaphylactic death is not well established. The application of immunohistochemical techniques combined with the evaluation of blood tryptase concentrations opened up a new field of investigation into anaphylactic death. The present study investigated eleven autopsy cases of anaphylactic death, carried out between 2005 and 2017, by the Departments of Forensic Pathology of the Universities of Foggia and Catania (Italy). An analysis of the medical records was carried out in all autopsies. Seven autopsies were carried out on males and four on females. Of the eleven cases, one showed a history of asthma, one of food ingestion, two of oral administration of medications, six did not refer any allergy history, and one subject was unknown. All cases (100%) showed pulmonary congestion and edema; 7/11 (64%) of the cases had pharyngeal/laryngeal edema and mucus plugging in the airway; only one case (9%) had a skin reaction that was found during external examination. Serum tryptase concentration was measured in ten cases, and the mean value was 133.5 µg/L ± 177.9. The immunohistochemical examination using an anti-tryptase antibody on samples from the lungs, pharynx/larynx, and skin site of medication injection showed that all cases (100%) were strongly immunopositive for anti-tryptase antibody staining on lung samples; three cases (30%) were strongly immunopositive for anti-tryptase antibody staining on pharyngeal/laryngeal samples; and eight cases (80%) were strongly immunopositive for anti-tryptase antibody staining on skin samples. We conclude that a typical clinical history, blood tryptase level >40 µg/L, and strongly positive anti-tryptase antibody staining in the immunohistochemical investigation may represent reliable parameters in the determination of anaphylactic death with the accuracy needed for forensic purposes.

Update of in vitro, in vivo and ex vivo fluoro-edenite effects on malignant mesothelioma: A systematic review (Review).

Fluoro-edenite (FE), asbestiform fiber found in Biancavilla (Sicily, Italy), presents various characteristics similar to the asbestos group, in particular two fibrous phases tremolite and actinolite. Indeed, epidemiological studies have shown that FE fibers have similar effects to those of asbestos fibers. Such studies have reported a high incidence of malignant mesothelioma (MM), an aggressive neoplasm of the serosal membranes lining the pleural cavity, in individuals residing there due to FE exposure in Biancavilla related to environmental contamination. Evidence has led to the classification of FE as a Group 1 human carcinogen by the International Agency for Research on Cancer (IARC). The aim of this systematic review is to compare the results achieved in in vitro, in vivo and ex vivo experimental studies involving FE in order to update the current knowledge on the pathogenesis and molecular mechanisms responsible for FE-mediated MM development as well as the availability of effective biomarkers for MM prevention and diagnosis. This review is focused on the pathophysiological mechanisms mediated by inflammation induced by FE fiber exposure and which are responsible for MM development. This review also discusses the discovery of new diagnostic and prognostic biomarkers for the management of this pathology. It is known that the risk of cancer development increases with chronic inflammation, arising from enhanced reactive oxygen species (ROS) and NO• production stimulated by the body to remove exogenous agents, causing DNA damage and enhanced signal transduction that may lead to activation of oncogenes. Studies concerning MM biomarker discovery indicate that several biomarkers have been proposed for MM, but mesothelin is the only Food and Drug Administration (FDA)-approved biomarker for MM, with limitations. In recent studies, in silico analysis to identify selected miRNAs highly deregulated in cancer samples when compared with normal control have been developed. This in silico approach could represent an effort in the field of biomarker discovery for MM.

MacroH2A1 Immunoexpression in Breast Cancer.

MacroH2A1 has two splice isoforms, macroH2A1.1 and macroH2A1.2, that have been studied in several form of cancer. In the literature there are not many scientific papers dealing with the role of macroH2A1 in breast cancer. Breast cancer is the most frequent form of malignancy in females. It tend to metastasize to the bone in ~70% of patients. Despite treatment, new bone metastases will still occur in 30-50% of cases with advanced disease. Overall 5-year survival after the diagnosis of bone metastasis is ~20%. Osteoclasts and osteoblasts of the bone microenvironment are engaged by soluble factors released by neoplastic cells, resulting in bone matrix breakdown. This malfunction enhances the proliferation of the cancer cells, creating a vicious cycle. We investigated immunohistochemical expression of macroH2A1 in primitive breast cancer, focusing on the comparison of metastatic and non-metastatic cases. Furthermore, the immunohistochemical expression of macroH2A1 has been evaluated both in all cases of nodal metastases and in distant metastases. Our data demonstrated that macroH2A1 expression was higher expressed in metastatic breast cancer (77%) vs. non-metastatic breast cancer (32%). Also in analyzed metastases cases, a high macroH2A1 expression was detected: 85 and 80% in nodal and distant metastases cases, respectively. These results supported the fact that macroH2A1 is more highly expressed in breast cancer with worst prognosis.

Modulation of microRNA expression levels after naturally occurring asbestiform fibers exposure as a diagnostic biomarker of mesothelial neoplastic transformation.

Fluoro-edenite (FE) is a silicate mineral identified in the lava products of Monte Calvario from stone quarries located in the southeast of Biancavilla, a small city of the Etnean volcanic complex (Sicily, Italy). Inhalation of FE fibers has been associated with a higher incidence of Malignant Mesothelioma (MM), a highly aggressive neoplasm of the serosal membranes lining the pleural cavity. Only 5% of MM patients are diagnosed at an early stage and the median survival is approximate 6-12 months. Many diagnostic biomarkers have been proposed for MM. Several studies demonstrated that microRNAs (miRNAs) may be used as good non-invasive diagnostics, as well as prognostic biomarkers for various human diseases, including cancer. On these bases, the aim of the present study was to identify a set of miRNAs involved in the development and progression of MM and potentially used as diagnostic biomarkers. For these purposes, in silico analyses were performed on healthy/exposed to asbestos fibers subjects vs. patients with MM. These analyses revealed a set of miRNAs strictly involved in MM by merging the lists of miRNAs found differentially expressed in the three miRNA expression datasets analyzed. The result of these computational evaluations allowed the execution of functional in vitro experiments performed on normal pleural mesothelial cell line (MeT-5A) and MM cell line (JU77) in order to test the carcinogenetic effects and epigenetic modulation induced by FE exposure. The in vitro results showed that the expression levels of hsa-miR-323a-3p vary significantly in both supernatant- and cell-derived miRNAs derived from treated and untreated cells. Secreted and cellular hsa-miR-101-3p in MeT-5A treated with FE fibers and JU77 cells showed different trends of expression. As regard hsa-miR-20b-5p, there was no differential expression between secreted and cellular hsa-miR-20b-5p. This miRNA has been shown a significant up-regulation in JU77 cells vs. control and treated MeT-5A. As a future plan, translational analyses will be performed on a subset of patients chronically exposed to FE fibers to further verify the clinical role of such miRNAs in high-risk individuals and their possible use as biomarkers of FE exposure or MM early onset.