Cigarette Smoking and Human Gut Microbiota in Healthy Adults: A Systematic Review

The intestinal microbiota is a crucial regulator of human health and disease because of its interactions with the immune system. Tobacco smoke also influences the human ecosystem with implications for disease development. This systematic review aims to analyze the available evidence, until June 2021, on the relationship between traditional and/or electronic cigarette smoking and intestinal microbiota in healthy human adults. Of the 2645 articles published in PubMed, Scopus, and Web of Science, 13 were included in the review. Despite differences in design, quality, and participants’ characteristics, most of the studies reported a reduction in bacterial species diversity, and decreased variability indices in smokers’ fecal samples. At the phylum or genus level, the results are very mixed on bacterial abundance both in smokers and non-smokers with two exceptions. Prevotella spp. appears significantly increased in smokers and former smokers but not in electronic cigarette users, while Proteobacteria showed a progressive increase in Desulfovibrio with the number of pack-years of cigarette (p = 0.001) and an increase in Alphaproteobacteria (p = 0.04) in current versus never smokers. This attempt to systematically characterize the effects of tobacco smoking on the composition of gut microbiota gives new perspectives on future research in smoking cessation and on a new possible use of probiotics to contrast smoke-related dysbiosis

Body mass index in HER2-negative metastatic breast cancer treated with first-line paclitaxel and bevacizumab

The evidence emerged from the TOURANDOT trial encourages evaluating the role of anthropometric determinants on treatment outcomes in HER2-negative metastatic breast cancer patients treated with bevacizumab-including regimens. We thus analyzed data from a subgroup of these patients from a larger cohort previously assessed for treatment outcomes. Patients were included in the present analysis if body mass index values had been recorded at baseline. Clinical benefit rates, progression free survival and overall survival were assessed for the overall study population and subgroups defined upon molecular subtype. One hundred ninety six patients were included (N:196). Body mass index showed no impact on clinical benefit rates in the overall study sample and in the luminal cancer subset (p = 0.12 and p = 0.79, respectively), but did so in the triple negative subgroup, with higher rates in patients with body mass index ≥25 (p = 0.03). In the overall study sample, body mass index did no impact progression free or overall survival (p = 0.33 and p = 0.67, respectively). Conversely, in triple negative patients, progression free survival was significantly longer with body mass index ≥25 (6 vs 14 months, p = 0.04). In this subset, overall survival was more favorable (25 vs 19 months, p = 0.02). The impact of the molecular subtype was confirmed in multivariate models including the length of progression free survival, and number of metastatic sites (p < 0.0001). Further studies are warranted to confirm our findings in more adequately sized, ad hoc, prospective studies

Role of key-regulator genes in melanoma susceptibility and pathogenesis among patients from South Italy

Background. Several genetic alterations have been demonstrated to contribute to the development and progression of melanoma. In this study, we further investigated the impact of key-regulator genes in susceptibility and pathogenesis of such a disease. Methods. A large series (N = 846) of sporadic and familial cases originating from South Italy was screened for germline mutations in p16CDKN2A, BRCA2, and MC1R genes by DHPLC analysis and automated DNA sequencing. Paired primary melanomas and lymph node metastases from same patients (N = 35) as well as melanoma cell lines (N = 18) were analyzed for somatic mutations in NRAS, BRAF, and p16CDKN2A genes. Results. For melanoma susceptibility, investigations at germline level indicated that p16CDKN2A was exclusively mutated in 16/545 (2.9%) non-Sardinian patients, whereas BRCA2 germline mutations were observed in 4/91 (4.4%) patients from North Sardinia only. Two MC1R germline variants, Arg151Cys and Asp294His, were significantly associated with melanoma in Sardinia. Regarding genetic events involved in melanoma pathogenesis at somatic level, mutually-exclusive mutations of NRAS and BRAF genes were observed at quite same rate (about two thirds) in cultured and in vivo melanomas (either primary or metastatic lesions). Conversely, p16CDKN2A gene alterations were observed at increased rates moving from primary to metastatic melanomas and melanoma cell lines. Activation of the ERK gene product was demonstrated to be consistently induced by a combination of molecular alterations (NRAS/BRAF mutations and p16CDKN2A silencing). Conclusion. Our findings further clarified that: a) mutation prevalence in melanoma susceptibility genes may vary within each specific geographical area; b) multiple molecular events are accumulating during melanomagenesis

Mutational concordance between primary and metastatic melanoma: A next-generation sequencing approach

Background: Cutaneous malignant melanoma (CMM) is one of the most common skin cancers worldwide. Limited information is available in the current scientific literature on the concordance of genetic alterations between primary and metastatic CMM. In the present study, we performed next-generation sequencing (NGS) analysis of the main genes participating in melanoma pathogenesis and progression, among paired primary and metastatic lesions of CMM patients, with the aim to evaluate levels of discrepancies in mutational patterns. Methods: Paraffin-embedded tumor tissues of the paired lesions were retrieved from the archives of the institutions participating in the study. NGS was performed using a specific multiple-gene panel constructed by the Italian Melanoma Intergroup (IMI) to explore the mutational status of selected regions (343 amplicons; amplicon range: 125-175 bp; coverage 100%) within the main 25 genes involved in CMM pathogenesis; sequencing was performed with the Ion Torrent PGM System. Results: A discovery cohort encompassing 30 cases, and a validation cohort including eleven Sardinian patients with tissue availability from both the primary and metachronous metastatic lesions were identified; the global number of analyzed tissue specimens was 90. A total of 829 genetic non-synonymous variants were detected: 101 (12.2%) were pathogenic/likely pathogenic, 131 (15.8%) were benign/likely benign, and the remaining 597 (72%) were uncertain/unknown significance variants. Considering the global cohort, the consistency in pathogenic/pathogenic like mutations was 76%. Consistency for BRAF and NRAS mutations was 95.2% and 85.7% respectively, without statistically significant differences between the discovery and validation cohort. Conclusions: Our study showed a high level of concordance in mutational patterns between primary and metastatic CMM, especially when pathogenic mutations in driver genes were considered

The Wikiplantbase project: the role of amateur botanists in building up large online floristic databases

The Wikiplantbase project, started in 2013, provides a framework where the full set of georeferenced floristic records of Tuscany and Sardinia can be entered, stored, updated and freely accessed through the Internet. Mainly thanks to the collaboration of amateur botanists, data have accumulated quickly. All records entered by collaborators are submitted to the project coordinators, who are enabled to accept, modify, or reject them. As of 22 November 2016, Wikiplantbase #Toscana holds 116,402 verified floristic records (90% based on published literature, 5% on unpublished herbarium specimens, 5% on field observations), and Wikiplantbase #Sardegna 40,043 (77% published literature, 18% unpublished herbarium specimens, 5% on field observations ). The records include over 90% of the specific and subspecific taxa known for Tuscany and about 70% – but rapidly growing – of those known for Sardinia. The most recorded species are Quercus ilex L. (Fagaceae) for Tuscany and Pistacia lentiscus L. (Anacardiaceae) for Sardinia. With minor software tweaking, the online platform Wikiplantbase might be adopted in other contexts, resulting in a well connected network of regional floristic databases suited to exploit the involvement – still largely untapped – of nonacademic collaborators, as advocated by citizen science

The Wikiplantbase project: the role of amateur botanists in building up large online floristic databases

The Wikiplantbase project, started in 2013, provides a framework where the full set of georeferenced floristic records of Tuscany and Sardinia can be entered, stored, updated and freely accessed through the Internet. Mainly thanks to the collaboration of amateur botanists, data have accumulated quickly. All records entered by collaborators are submitted to the project coordinators, who are enabled to accept, modify, or reject them. As of 22 November 2016, Wikiplantbase #Toscana holds 116,402 verified floristic records (90% based on published literature, 5% on unpublished herbarium specimens, 5% on field observations), and Wikiplantbase #Sardegna 40,043 (77% published literature, 18% unpublished herbarium specimens, 5% on field observations ). The records include over 90% of the specific and subspecific taxa known for Tuscany and about 70% – but rapidly growing – of those known for Sardinia. The most recorded species are Quercus ilex L. (Fagaceae) for Tuscany and Pistacia lentiscus L. (Anacardiaceae) for Sardinia. With minor software tweaking, the online platform Wikiplantbase might be adopted in other contexts, resulting in a well connected network of regional floristic databases suited to exploit the involvement – still largely untapped – of nonacademic collaborators, as advocated by citizen science

Serum proteomic test in advanced non-squamous non-small cell lung cancer treated in first line with standard chemotherapy

Background:VeriStrat is a blood-based proteomic test with predictive and prognostic significance in second-line treatments for non-small cell lung cancer (NSCLC). This trial was designed to investigate the role of VeriStrat in first-line treatment of advanced NSCLC with standard chemotherapy. Here we present the results for 76 non-squamous patients treated with a combination of carboplatin or cisplatin with pemetrexed.Methods:The test-assigned classifications of VeriStrat Good or VeriStrat Poor to samples collected at baseline. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and objective response. Exploratory analyses of end points separately in carboplatin/pemetrexed and cisplatin/pemetrexed subgroups were also conducted.Results:Patients classified as VeriStrat Good had longer PFS and OS than VeriStrat Poor: 6.5 vs 1.6 months and 10.8 vs 3.4 months, respectively; the corresponding hazard ratios (HRs) were 0.36 (P<0.0001) and 0.26 (P<0.0001); they were also more likely to achieve objective response. Prognostic significance of VeriStrat was confirmed in multivariate analysis. Significant differences in OS and PFS between Veristrat classifications were also found when treatment subgroups were analysed separately.Conclusions:The trial demonstrated clinical utility of VeriStrat as a prognostic test for standard first-line chemotherapy of non-squamous advanced NSCLC

Circulating cell-free DNA and circulating tumor cells as prognostic and predictive biomarkers in advanced non-small cell lung cancer patients treated with first-line chemotherapy

Cell-free DNA (cfDNA) and circulating tumor cells (CTCs) are promising prognostic and predictive biomarkers in non-small cell lung cancer (NSCLC). In this study, we examined the prognostic role of cfDNA and CTCs, in separate and joint analyses, in NSCLC patients receiving first line chemotherapy. Seventy-three patients with advanced NSCLC were enrolled in this study. CfDNA and CTC were analyzed at baseline and after two cycles of chemotherapy. Plasma cfDNA quantification was performed by quantitative PCR (qPCR) whereas CTCs were isolated by the ScreenCell Cyto (ScreenCell, Paris, France) device and enumerated according to malignant features. Patients with baseline cfDNA higher than the median value (96.3 hTERT copy number) had a significantly worse overall survival (OS) and double the risk of death (hazard ratio (HR): 2.14; 95% confidence limits (CL) = 1.24\u20133.68; p-value = 0.006). Conversely, an inverse relationship between CTC median baseline number (6 CTC/3 mL of blood) and OS was observed. In addition, we found that in patients reporting stable disease (SD), the baseline cfDNA and CTCs were able to discriminate patients at high risk of poor survival. cfDNA demonstrated a more reliable biomarker than CTCs in the overall population. In the subgroup of SD patients, both biomarkers identified patients at high risk of poor prognosis who might deserve additional/alternative therapeutic interventions

lung cancer predisposition in women with previous breast cancer identified by whole exome sequencing

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