@article{Ahuja2023-sp,

title = {Immune resilience despite inflammatory stress promotes longevity  and favorable health outcomes including resistance to infection},

author = {Sunil K Ähuja and Muthu Saravanan Manoharan and Grace C Lee and Lyle R McKinnon and Justin A Meunier and Maristella Steri and Nathan Harper and Edoardo Fiorillo and Alisha M Smith and Marcos I Restrepo and Anne P Branum and Matthew J Bottomley and Valeria Orr`u and Fabio Jimenez and Andrew Carrillo and Lavanya Pandranki and Caitlyn A Winter and Lauryn A Winter and Alvaro A Gaitan and Alvaro G Moreira and Elizabeth A Walter and Guido Silvestri and Christopher L King and Yong-Tang Zheng and Hong-Yi Zheng and Joshua Kimani and T Blake Ball and Francis A Plummer and Keith R Fowke and Paul N Harden and Kathryn J Wood and Martin T Ferris and Jennifer M Lund and Mark T Heise and Nigel Garrett and Kristen R Canady and Salim S Abdool Karim and Susan J Little and Sara Gianella and Davey M Smith and Scott Letendre and Douglas D Richman and Francesco Cucca and Hanh Trinh and Sandra Sanchez-Reilly and Joan M Hecht and Jose A Cadena Zuluaga and Antonio Anzueto and Jacqueline A Pugh and South Texas Veterans Health Care System COVID-19 team and Brian K Agan and Robert Root-Bernstein and Robert A Clark and Jason F Okulicz and Weijing" He},

doi = {10.1038/s41467-023-38238-6},

year  = {2023},

date = {2023-06-01},

urldate = {2023-06-01},

journal = {Nat. Commun.},

volume = {14},

number = {1},

pages = {3286},

abstract = {Some people remain healthier throughout life than others but the 

 underlying reasons are poorly understood. Here we hypothesize 

 this advantage is attributable in part to optimal immune 

 resilience (IR), defined as the capacity to preserve and/or 

 rapidly restore immune functions that promote disease resistance 

 (immunocompetence) and control inflammation in infectious 

 diseases as well as other causes of inflammatory stress. We gauge 

 IR levels with two distinct peripheral blood metrics that 

 quantify the balance between (i) CD8+ and CD4+ T-cell levels and 

 (ii) gene expression signatures tracking longevity-associated 

 immunocompetence and mortality-associated inflammation. Profiles 

 of IR metrics in ~48,500 individuals collectively indicate that 

 some persons resist degradation of IR both during aging and when 

 challenged with varied inflammatory stressors. With this 

 resistance, preservation of optimal IR tracked (i) a lower risk 

 of HIV acquisition, AIDS development, symptomatic influenza 

 infection, and recurrent skin cancer; (ii) survival during 

 COVID-19 and sepsis; and (iii) longevity. IR degradation is 

 potentially reversible by decreasing inflammatory stress. 

 Overall, we show that optimal IR is a trait observed across the 

 age spectrum, more common in females, and aligned with a specific 

 immunocompetence-inflammation balance linked to favorable 

 immunity-dependent health outcomes. IR metrics and mechanisms 

 have utility both as biomarkers for measuring immune health and 

 for improving health outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ahuja2023-yn,

title = {Immune resilience despite inflammatory stress promotes longevity 

 and favorable health outcomes including resistance to infection},

author = {Sunil K Ähuja and Muthu Saravanan Manoharan and Grace C Lee and Lyle R McKinnon and Justin A Meunier and Maristella Steri and Nathan Harper and Edoardo Fiorillo and Alisha M Smith and Marcos I Restrepo and Anne P Branum and Matthew J Bottomley and Valeria Orr`u and Fabio Jimenez and Andrew Carrillo and Lavanya Pandranki and Caitlyn A Winter and Lauryn A Winter and Alvaro A Gaitan and Alvaro G Moreira and Elizabeth A Walter and Guido Silvestri and Christopher L King and Yong-Tang Zheng and Hong-Yi Zheng and Joshua Kimani and T Blake Ball and Francis A Plummer and Keith R Fowke and Paul N Harden and Kathryn J Wood and Martin T Ferris and Jennifer M Lund and Mark T Heise and Nigel Garrett and Kristen R Canady and Salim S Abdool Karim and Susan J Little and Sara Gianella and Davey M Smith and Scott Letendre and Douglas D Richman and Francesco Cucca and Hanh Trinh and Sandra Sanchez-Reilly and Joan M Hecht and Jose A Cadena Zuluaga and Antonio Anzueto and Jacqueline A Pugh and South Texas Veterans Health Care System COVID-19 team and Brian K Agan and Robert Root-Bernstein and Robert A Clark and Jason F Okulicz and Weijing" He},

year  = {2023},

date = {2023-06-01},

journal = {Nat. Commun.},

volume = {14},

number = {1},

pages = {3286},

abstract = {Some people remain healthier throughout life than others but the 

 underlying reasons are poorly understood. Here we hypothesize 

 this advantage is attributable in part to optimal immune 

 resilience (IR), defined as the capacity to preserve and/or 

 rapidly restore immune functions that promote disease resistance 

 (immunocompetence) and control inflammation in infectious 

 diseases as well as other causes of inflammatory stress. We gauge 

 IR levels with two distinct peripheral blood metrics that 

 quantify the balance between (i) CD8+ and CD4+ T-cell levels and 

 (ii) gene expression signatures tracking longevity-associated 

 immunocompetence and mortality-associated inflammation. Profiles 

 of IR metrics in ~48,500 individuals collectively indicate that 

 some persons resist degradation of IR both during aging and when 

 challenged with varied inflammatory stressors. With this 

 resistance, preservation of optimal IR tracked (i) a lower risk 

 of HIV acquisition, AIDS development, symptomatic influenza 

 infection, and recurrent skin cancer; (ii) survival during 

 COVID-19 and sepsis; and (iii) longevity. IR degradation is 

 potentially reversible by decreasing inflammatory stress. 

 Overall, we show that optimal IR is a trait observed across the 

 age spectrum, more common in females, and aligned with a specific 

 immunocompetence-inflammation balance linked to favorable 

 immunity-dependent health outcomes. IR metrics and mechanisms 

 have utility both as biomarkers for measuring immune health and 

 for improving health outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37232846,

title = {PD-L1 Expression in Cutaneous Angiosarcomas: A Systematic Review with Meta-Analysis},

author = {Renato Lobrano and Panagiotis Paliogiannis and Angelo Zinellu and Giuseppe Palmieri and Ivana Persico and Arduino A Mangoni and Antonio Cossu},

doi = {10.3390/curroncol30050388},

issn = {1718-7729},

year  = {2023},

date = {2023-05-17},

urldate = {2023-05-17},

journal = {Curr Oncol},

volume = {30},

number = {5},

pages = {5135--5144},

abstract = {Cutaneous angiosarcoma (CAS) is the most common type of angiosarcoma that predominantly affects older Caucasians. The outcomes of immunotherapy in CAS are currently under investigation in relation to the expression of programmed death ligand 1 (PD-L1) and other biomarkers. We performed a systematic review and metanalysis of data from the current literature reporting on PD-L1 immunohistochemistry expression. A systematic search of publications in the electronic databases PubMed, Web of Science, and Scopus was conducted using the following terms: "PD-L1" and "angiosarcomas". A total of ten studies reporting on 279 cases were identified and included in the meta-analysis. The pooled prevalence of PD-L1 expression in CAS was 54% (95% CI 36-71%), with high heterogeneity (I = 84.81%,  < 0.001). In sub-group analysis, the proportion of PD-L1 expression in CAS was significantly ( = 0.049) lower in Asian studies (ES = 35%, 95% CI 28-42%, I = 0.0%,  = 0.46) than in European studies (ES = 71%, 95% CI 51-89%, I = 48.91%,  = 0.12).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Casula2023,

title = {Comparison between Three Different Techniques for the Detection of EGFR Mutations in Liquid Biopsies of Patients with Advanced Stage Lung Adenocarcinoma},

author = {Milena Casula and Marina Pisano and Panagiotis Paliogiannis and Maria Colombino and Maria Cristina Sini and Angelo Zinellu and Davide Santeufemia and Antonella Manca and Stefania Casula and Silvia Tore and Renato Lobrano and  and Antonio Cossu and Giuseppe Palmieri},

doi = {10.3390/ijms24076410},

issn = {1422-0067},

year  = {2023},

date = {2023-04-00},

journal = {IJMS},

volume = {24},

number = {7},

publisher = {MDPI AG},

abstract = {Oncogenic mutations in the EGFR gene are targets of tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma (LC) patients, and their search is mandatory to make decisions on treatment strategies. Liquid biopsy of circulating tumour DNA (ctDNA) is increasingly used to detect EGFR mutations, including main activating alterations (exon 19 deletions and exon 21 L858R mutation) and T790M mutation, which is the most common mechanism of acquired resistance to first- and second-generation TKIs. In this study, we prospectively compared three different techniques for EGFR mutation detection in liquid biopsies of such patients. Fifty-four ctDNA samples from 48 consecutive advanced LC patients treated with TKIs were tested for relevant EGFR mutations with Therascreen® EGFR Plasma RGQ-PCR Kit (Qiagen). Samples were subsequently tested with two different technologies, with the aim to compare the EGFR detection rates: real-time PCR based Idylla™ ctEGFR mutation assay (Biocartis) and next-generation sequencing (NGS) system with Ion AmpliSeq Cancer Hotspot panel (ThermoFisher). A high concordance rate for main druggable EGFR alterations was observed with the two real-time PCR-based assays, ranging from 100% for T790M mutation to 94% for L858R variant and 85% for exon 19 deletions. Conversely, lower concordance rates were found between real-time PCR approaches and the NGS method (L858R: 88%; exon19-dels: 74%; T790M: 37.5%). Our results evidenced an equivalent detection ability between PCR-based techniques for circulating EGFR mutations. The NGS assay allowed detection of a wider range of EGFR mutations but showed a poor ability to detect T790M.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Comparison between Three Different Techniques for the Detection of EGFR Mutations in Liquid Biopsies of Patients with Advanced Stage Lung Adenocarcinoma},

author = {Casula Milena and Pisano Marina and Paliogiannis Panagiotis and Colombino Maria and Sini Maria Cristina and Zinellu Angelo},

year  = {2023},

date = {2023-03-29},

urldate = {2023-03-29},

journal = {International Journal of Molecular Sciences},

volume = {24},

number = {6410},

abstract = {Oncogenic mutations in the EGFR gene are targets of tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma (LC) patients and their search is mandatory to make decisions on treatment strategies. Liquid biopsy of circulating tumour DNA (ctDNA) is increasingly used to detect EGFR mutations including main activating alterations (exon 19 deletions and exon 21 L858R mutation) and T790M mutation which is the most common mechanism of acquired resistance to first- and second-generation TKIs. In this study we prospectively compared three different techniques for EGFR mutation detection in liquid biopsies of such patients. Fifty-four ctDNA samples from 48 consecutive advanced LC patients treated with TKIs were tested for relevant EGFR mutations with Therascreen® EGFR Plasma RGQ-PCR Kit (Qiagen). Samples were subsequently tested with two different technologies with the aim to compare the EGFR detection rates: real-time PCR based Idylla™ ctEGFR mutation assay (Biocartis) and next-generation sequencing (NGS) system with Ion AmpliSeq Cancer Hotspot panel (ThermoFisher). A high concordance rate for main druggable EGFR alterations was observed with the two real-time PCR-based assays ranging from 100% for T790M mutation to 94% for L858R variant and 85% for exon 19 deletions. Conversely lower concordance rates were found between real-time PCR approaches and the NGS method (L858R: 88%; exon19-dels: 74%; T790M: 37.5%). Our results evidenced an equivalent detection ability between PCR-based techniques for circulating EGFR mutations. The NGS assay allowed detection of a wider range of EGFR mutations but showed a poor ability to detect T790M.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Serra2023-ve,

title = {Polygenic risk score and biochemical/environmental variables 

 predict a low-risk profile of age-related macular degeneration 

 in Sardinia},

author = {Rita Serra and Vincenzo Rallo and Antonio Pinna and Maristella Steri and Maria Grazia Piras and Michele Marongiu and Florence Coscas and Myriam Gorospe and David Schlessinger and Edoardo Fiorillo and Francesco Cucca and Andrea Angius},

year  = {2023},

date = {2023-03-01},

journal = {Ärbeitsphysiologie"},

volume = {261},

number = {3},

pages = {691--698},

publisher = {Springer Science and Business Media LLC},

abstract = {PURPOSE: To ascertain the prevalence and clinical and genetic 

 features of age-related macular degeneration (AMD) in subjects 

 living in the Lanusei valley, Central Sardinia, Italy, involved 

 in a study on ageing (SardiNIA project). METHODS: A total of 814 

 volunteers aged $geq$ 50 years, randomly selected from the 

 SardiNIA project dataset, were included. A color fundus (CF) 

 photograph of the 30° central retina of each eye was obtained 

 and graded according to the Age-Related Eye Disease Study 

 system. Life-style choices were investigated using standardized 

 questionnaires. The concentrations of several inflammatory 

 biomarkers (i.e., complement component, fibrinogen, and 

 C-reactive protein) were measured. Polygenic risk score (PRS) 

 was calculated and compared with results obtained from a 

 European cohort. RESULTS: A total of 756 subjects had gradable 

 CF photographs for AMD detection. In 91.3%, no signs of AMD 

 were observed. The prevalence rates of early and late AMDs were 

 6.9% and 0.6%, respectively. A total of 85% of subjects were 

 physically active; only 13.5% were current smokers. Low 

 concentrations of complement component, fibrinogen, and 

 C-reactive protein were found. We calculated the polygenic risk 

 scores (PRS) using 40 AMD markers distributed on several 

 candidate genes in Europeans and Sardinians. The mean PRS value 

 was significantly lower in Sardinians than in the Europeans (0.21 vs. 0.248, respectivel},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36425957,

title = {CFDP1 is a neuroblastoma susceptibility gene that regulates transcription factors of the noradrenergic cell identity},

author = {D. Formicola and V. A. Lasorsa and S. Cantalupo and A. Testori and A. Cardinale and M. Avitabile and S. Diskin and A. Iolascon and M. Capasso},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {HGG Adv},

volume = {4},

number = {1},

pages = {100158},

abstract = {acts as oncogene in NB. In addition, we provide evidence that genetic predisposition to NB can be mediated by the alteration of noradrenergic lineage-specific gene expression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Serra2022-xa,

title = {Quantifying the detrimental effects of multiple freeze/thaw  cycles on primary human lymphocyte survival and function},

author = {Valentina Serra and Edoardo Fiorillo and Francesco Cucca and Valeria Orr`u},

doi = {10.3390/ijms24010634.},

year  = {2022},

date = {2022-12-01},

urldate = {2022-12-01},

journal = {Int. J. Mol. Sci.},

volume = {24},

number = {1},

pages = {634},

publisher = {MDPI AG},

abstract = {The use of cryopreserved peripheral blood mononuclear cells is 

 common in biological research. It is widely accepted that 

 primary cells are rendered unusable by several freezing cycles, 

 although this practice might be very helpful when the biological 

 material is valuable and its re-collection is impractical. To 

 determine the extent to which primary cells undergoing repeated 

 freezing cycles are comparable to one another and to fresh 

 samples, we evaluated overall lymphocyte viability, their 

 proliferation and cytokine production capabilities, as well as 

 the levels of 27 cell subtypes in ten human peripheral blood 

 mononuclear cells frozen for five years and repeatedly thawed. 

 As expected, we observed a progressive increase in cell death 

 percentages on three rounds of thawing, but the frequency of the 

 main lymphocyte subsets was stable across the three thawings. 

 Nevertheless, we observed a significant reduction of B cell 

 frequency in frozen samples compared to fresh ones. On repeated 

 thawings and subsequent conventional stimulation, lymphocyte 

 proliferation significantly decreased, and IL-10, IL-6, GM-CSF, 

 IFN-gamma, and IL-8 showed a trend to lower values.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis},

author = {Gaia Rocchitta and Carla Rozzo and Marina Pisano and Davide Fabbri and Maria Antonietta Dettori and

Paolo Ruzza and Claudia Honisch and Roberto Dallocchio and Alessandro Dessì and Rossana Migheli and

PierAndrea Serra and Giovanna Delogu},

url = {https://doi.org/10.3390/molecules27227942

https://irgb.cnr.it/wp-content/uploads/2024/05/Rocchitta-et-al-2022-2.pdf},

doi = {https://doi.org/10.3390/molecules27227942},

year  = {2022},

date = {2022-11-16},

urldate = {2022-11-16},

journal = {Molecules},

volume = {27},

number = {7942},

pages = {1-24},

abstract = {Tyrosinase is a well-known copper-containing metalloenzyme typically involved in the synthesis of melanin. Recently, curcumin and several synthetic derivatives have been recognized as tyrosinase inhibitors with interesting anti-melanogenic therapeutic activity. In this study, three curcumin-inspired compounds 1, 6 and 7 were prepared in yields ranging from 60 to 88 % and spectrophotometric, electrochemical, in vitro and in silico analyses were carried out. The viability of PC12 cells, a rat pheochromocytoma derived-cell line, with compounds 1, 6 and 7, showed values around 80% at 5 uM concentration. In cell proliferation assays, compounds 1, 6 and 7 did not show significant toxicity on fibroblasts nor melanoma cells up to 10 uM with viability values over 90%. The inhibition of tyrosinase activity was evaluated both by a UV-Vis spectroscopic method at two different concentrations, 0.2 and 2.0 uM, and by amperometric assay with IC50 for compounds 1, 6 and 7 ranging from 11 to 24 nM. Melanin content assays on human melanoma cells were performed to test the capability of compounds to inhibit melanin biosynthesis. All compounds exerted a decrease in melanin content, with compound 7 being the most effective by showing a melanogenesis inhibition up to four times greater than arbutin at 100 uM. Moreover, the antioxidant activity of the selected inhibitors was evaluated against H2O2 in amperometric experiments, whereby compound 7 was about three times more effective compared to compounds 1 and 6. The tyrosinase X-ray structure of Bacterium megaterium crystal was used to carry out molecular docking studies in the presence of compounds 1, 6 and 7 in comparison with that of kojic acid and arbutin, two conventional tyrosinase inhibitors. Molecular docking of compounds 6 and 7 confirmed the high affinity of these compounds to tyrosinase protein.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chen2022-am,

title = {Influence of the microbiome, diet and genetics on 

 inter-individual variation in the human plasma metabolome},

author = {Lianmin Chen and Daria V Zhernakova and Alexander Kurilshikov and Sergio Andreu-Sánchez and Daoming Wang and Hannah E Augustijn and Arnau Vich Vila and Lifelines Cohort Study and Rinse K Weersma and Marnix H Medema and Mihai G Netea and Folkert Kuipers and Cisca Wijmenga and Alexandra Zhernakova and Jingyuan Fu},

year  = {2022},

date = {2022-11-01},

journal = {Nat. Med.},

volume = {28},

number = {11},

pages = {2333--2343},

publisher = {Springer Science and Business Media LLC},

abstract = {The levels of the thousands of metabolites in the human plasma 

 metabolome are strongly influenced by an individual's genetics 

 and the composition of their diet and gut microbiome. Here, by 

 assessing 1,183 plasma metabolites in 1,368 extensively 

 phenotyped individuals from the Lifelines DEEP and Genome of the 

 Netherlands cohorts, we quantified the proportion of 

 inter-individual variation in the plasma metabolome explained by 

 different factors, characterizing 610, 85 and 38 metabolites as 

 dominantly associated with diet, the gut microbiome and 

 genetics, respectively. Moreover, a diet quality score derived 

 from metabolite levels was significantly associated with diet 

 quality, as assessed by a detailed food frequency questionnaire. 

 Through Mendelian randomization and mediation analyses, we 

 revealed putative causal relationships between diet, the gut 

 microbiome and metabolites. For example, Mendelian randomization 

 analyses support a potential causal effect of Eubacterium 

 rectale in decreasing plasma levels of hydrogen sulfite-a toxin 

 that affects cardiovascular function. Lastly, based on analysis 

 of the plasma metabolome of 311 individuals at two time points 

 separated by 4 years, we observed a positive correlation between 

 the stability of metabolite levels and the amount of variance in 

 the levels of that metabolite that could be explained in our 

 analysis. Altogether, characterization of factors that explain 

 inter-individual variation in the plasma metabolome can help 

 design approaches for modulating diet or the gut microbiome to 

 shape a healthy metabolome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36543896,

title = {Analysis of the oral microbiome during hormonal cycle and its alterations in menopausal women: the },

author = {A Tramice and D Paris and A Manca and F A Guevara Agudelo and S Petrosino and L Siracusa and M Carbone and D Melck and F Raymond and F Piscitelli},

doi = {10.1038/s41598-022-26528-w},

issn = {2045-2322},

year  = {2022},

date = {2022-09-21},

journal = {Sci Rep},

volume = {12},

number = {1},

pages = {22086},

abstract = {The maintenance of human health is dependent on a symbiotic relationship between humans and associated bacteria. The diversity and abundance of each habitat's signature microbes vary widely among body areas and among them the oral microbiome plays a key role. Significant changes in the oral cavity, predominantly at salivary and periodontal level, have been associated with changes in estrogen levels. However, whether the oral microbiome is affected by hormonal level alterations is understudied. Hence the main objective pursued by AMICA project was to characterize the oral microbiome (saliva) in healthy women through: profiling studies using "omics" technologies (NMR-based metabolomics, targeted lipidomics by LC-MS, metagenomics by NGS); SinglePlex ELISA assays; glycosidase activity analyses and bioinformatic analysis. For this purpose, thirty-nine medically healthy women aged 26-77 years (19 with menstrual cycle and 20 in menopause) were recruited. Participants completed questionnaires assessing detailed medical and medication history and demographic characteristics. Plasmatic and salivary levels of sexual hormones were assessed (FSH, estradiol, LH and progesteron) at day 3 and 14 for women with menstrual cycle and only once for women in menopause. Salivary microbiome composition was assessed through meta-taxonomic 16S sequencing and overall, the salivary microbiome of most women remained relatively stable throughout the menstrual cycle and in menopause. Targeted lipidomics and untargeted metabolomics profiling were assessed through the use of LC-MS and NMR spectroscopy technologies, respectively and significant changes in terms of metabolites were identified in saliva of post-menopausal women in comparison to cycle. Moreover, glycosyl hydrolase activities were screened and showed that the β-D-hexosaminidase activity was the most present among those analyzed. Although this study has not identified significant alterations in the composition of the oral microbiome, multiomics analysis have revealed a strong correlation between 2-AG and α-mannosidase. In conclusion, the use of a multidisciplinary approach to investigate the oral microbiome of healthy women provided some indication about microbiome-derived predictive biomarkers that could be used in the future for developing new strategies to help to re-establish the correct hormonal balance in post-menopausal women.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35601448,

title = {Aquivion perfluorosulfonic superacid as an effective catalyst for selective epoxidation of vegetable oils},

author = {Riccardo Polese and Elisa Pintus and Luca Nuvoli and Monica Tiana and Salvatore Pintus and Giuseppe Satta and Andrea Beccu and Silvia Gaspa and Massimo Carraro and Lidia De Luca and Ugo Azzena and Luisa Pisano},

doi = {10.1098/rsos.211554},

issn = {2054-5703},

year  = {2022},

date = {2022-09-06},

journal = {R Soc Open Sci},

volume = {9},

number = {4},

pages = {211554},

abstract = {The acid-promoted epoxidation of vegetable oils was studied using a variety of acidic ion exchange resins as heterogeneous acid catalysts. Quantitative and selective epoxidation of a series of vegetable oils with different composition of saturated, mono-, di- and tri-unsaturated fatty acids was obtained upon identification of the more efficient catalyst and experimental conditions. Furthermore, optimized reaction conditions were successfully applied to the epoxidation of a waste cooking oil, thus extending our procedure to the valorization of a biowaste, an area of increasing importance within a more sustainable society. The use of quantitative HNMR besides making accurate evaluation of the amounts of reagents to be employed and of the selectivity, allowed facile and rapid quantification of mono-, di- and tri-epoxides, thus providing an indirect indication on the fatty acid composition of the vegetable oils, even in the presence of very low quantities of linolenic acid.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zhernakova2022-av,

title = {Age-dependent sex differences in cardiometabolic risk factors},

author = {Daria V Zhernakova and Trishla Sinha and Sergio Andreu-Sánchez and Jelmer R Prins and Alexander Kurilshikov and Jan-Willem Balder and Serena Sanna and Lifelines Cohort Study and Lude Franke and Jan A Kuivenhoven and Alexandra Zhernakova and Jingyuan Fu},

year  = {2022},

date = {2022-09-01},

urldate = {2022-09-01},

journal = {Nat. Cardiovasc. Res.},

volume = {1},

number = {9},

pages = {844--854},

publisher = {Springer Science and Business Media LLC},

abstract = {Cardiometabolic diseases (CMDs) are a major cause of mortality 

 worldwide, yet men and women present remarkable differences in 

 disease prognosis, onset and manifestation. Here we characterize 

 how sex differences in cardiometabolic risk factors vary with 

 age by examining 45 phenotypes and 6 lifestyle factors in 

 146,021 participants of the Dutch population cohort Lifelines. 

 We show that sex differences are present in 71% of the studied 

 phenotypes. For 31% of these phenotypes, the phenotypic 

 difference between sexes is dependent on age. CMD risk factors 

 show various patterns of age-related sex differences, ranging 

 from no difference for phenotypes such as body mass index (BMI) 

 to strong age-modified sex differences for lipid levels. We also 

 identify lifestyle factors that influence phenotypes in a sex- 

 and age-dependent manner. These results highlight the importance 

 of taking age into account when studying sex differences in 

 CMDs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36030436b,

title = {Deciphering clinical significance of BCL11A isoforms and protein expression roles in triple-negative breast cancer subtype},

author = {A. Angius and G. Pira and P. Cossu-Rocca and G. Sotgiu and L. Saderi and M. R. Muroni and P. Virdis and D. Piras and R. Vincenzo and C. Carru and D. Coradduzza and M. G. Uras and P. Cottu and A. Fancellu and S. Orrù and P. Uva and M. R. " De Miglio},

url = {https://link.springer.com/article/10.1007/s00432-022-04301-w},

doi = {10.1007/s00432-022-04301-w},

year  = {2022},

date = {2022-08-28},

journal = {J Cancer Res Clin Oncol},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35896539,

title = {Maternal and perinatal obesity induce bronchial obstruction and pulmonary hypertension via IL-6-FoxO1-axis in later life},

author = {J. Selle and K. Dinger and V. Jentgen and D. Zanetti and J. Will and T. Georgomanolis and C. Vohlen and R. Wilke and B. Kojonazarov and O. Klymenko and J. Mohr and S. V Koningsbruggen-Rietschel and C. J. Rhodes and A. Ulrich and D. Hirani and T. Nestler and M. Odenthal and E. Mahabir and S. Nayakanti and S. Dabral and T. Wunderlich and J. Priest and W. Seeger and J. tsch and S. S. Pullamsetti and M. A. Alejandre Alcazar},

year  = {2022},

date = {2022-07-01},

journal = {Nat Commun},

volume = {13},

number = {1},

pages = {4352},

abstract = {s/forced vital capacity ratio Z-score (used as proxy for lung function) and asthma. We conclude that the interleukin-6-FoxO1 pathway in SMC is a molecular mechanism by which perinatal obesity programs the bronchial and vascular structure and function, thereby driving CLD development. Thus, FoxO1 reconstitution provides a potential therapeutic option for preventing this metabolic programming of CLD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fabre2022-znd,

title = {The longitudinal dynamics and natural history of clonal 

 haematopoiesis},

author = {Margarete A Fabre and José Guilherme Almeida and Edoardo Fiorillo and Emily Mitchell and Aristi Damaskou and Justyna Rak and Valeria Orr`u and Michele Marongiu and Michael Spencer Chapman and M S Vijayabaskar and Joanna Baxter and Claire Hardy and Federico Abascal and Nicholas Williams and Jyoti Nangalia and I nigo Martincorena and Peter J Campbell and Eoin F McKinney and Francesco Cucca and Moritz Gerstung and George S Vassiliou},

year  = {2022},

date = {2022-06-01},

journal = {Nature},

volume = {606},

number = {7913},

pages = {335--342},

publisher = {Springer Science and Business Media LLC},

abstract = {Clonal expansions driven by somatic mutations become pervasive 

 across human tissues with age, including in the haematopoietic 

 system, where the phenomenon is termed clonal haematopoiesis1-4. 

 The understanding of how and when clonal haematopoiesis 

 develops, the factors that govern its behaviour, how it 

 interacts with ageing and how these variables relate to 

 malignant progression remains limited5,6. Here we track 697 

 clonal haematopoiesis clones from 385 individuals 55 years of 

 age or older over a median of 13 years. We find that 92.4% of 

 clones expanded at a stable exponential rate over the study 

 period, with different mutations driving substantially different 

 growth rates, ranging from 5% (DNMT3A and TP53) to more than 

 50% per year (SRSF2P95H). Growth rates of clones with the same 

 mutation differed by approximately $pm$5% per year, 

 proportionately affecting slow drivers more substantially. By 

 combining our time-series data with phylogenetic analysis of 

 1,731 whole-genome sequences of haematopoietic colonies from 7 

 individuals from an older age group, we reveal distinct patterns 

 of lifelong clonal behaviour. DNMT3A-mutant clones 

 preferentially expanded early in life and displayed slower 

 growth in old age, in the context of an increasingly competitive 

 oligoclonal landscape. By contrast, splicing gene mutations 

 drove expansion only later in life, whereas TET2-mutant clones 

 emerged across all ages. Finally, we show that mutations driving 

 faster clonal growth carry a higher risk of malignant 

 progression. Our findings characterize the lifelong natural 

 history of clonal haematopoiesis and give fundamental insights 

 into the interactions between somatic mutation, ageing and 

 clonal selection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fabre2022-znc,

title = {The longitudinal dynamics and natural history of clonal 

 haematopoiesis},

author = {Margarete A Fabre and José Guilherme Almeida and Edoardo Fiorillo and Emily Mitchell and Aristi Damaskou and Justyna Rak and Valeria Orr`u and Michele Marongiu and Michael Spencer Chapman and M S Vijayabaskar and Joanna Baxter and Claire Hardy and Federico Abascal and Nicholas Williams and Jyoti Nangalia and I nigo Martincorena and Peter J Campbell and Eoin F McKinney and Francesco Cucca and Moritz Gerstung and George S Vassiliou},

year  = {2022},

date = {2022-06-01},

journal = {Nature},

volume = {606},

number = {7913},

pages = {335--342},

publisher = {Springer Science and Business Media LLC},

abstract = {Clonal expansions driven by somatic mutations become pervasive 

 across human tissues with age, including in the haematopoietic 

 system, where the phenomenon is termed clonal haematopoiesis1-4. 

 The understanding of how and when clonal haematopoiesis 

 develops, the factors that govern its behaviour, how it 

 interacts with ageing and how these variables relate to 

 malignant progression remains limited5,6. Here we track 697 

 clonal haematopoiesis clones from 385 individuals 55 years of 

 age or older over a median of 13 years. We find that 92.4% of 

 clones expanded at a stable exponential rate over the study 

 period, with different mutations driving substantially different 

 growth rates, ranging from 5% (DNMT3A and TP53) to more than 

 50% per year (SRSF2P95H). Growth rates of clones with the same 

 mutation differed by approximately $pm$5% per year, 

 proportionately affecting slow drivers more substantially. By 

 combining our time-series data with phylogenetic analysis of 

 1,731 whole-genome sequences of haematopoietic colonies from 7 

 individuals from an older age group, we reveal distinct patterns 

 of lifelong clonal behaviour. DNMT3A-mutant clones 

 preferentially expanded early in life and displayed slower 

 growth in old age, in the context of an increasingly competitive 

 oligoclonal landscape. By contrast, splicing gene mutations 

 drove expansion only later in life, whereas TET2-mutant clones 

 emerged across all ages. Finally, we show that mutations driving 

 faster clonal growth carry a higher risk of malignant 

 progression. Our findings characterize the lifelong natural 

 history of clonal haematopoiesis and give fundamental insights 

 into the interactions between somatic mutation, ageing and 

 clonal selection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fabre2022-znb,

title = {The longitudinal dynamics and natural history of clonal  haematopoiesis},

author = {Margarete A Fabre and José Guilherme Almeida and Edoardo Fiorillo and Emily Mitchell and Aristi Damaskou and Justyna Rak and Valeria Orr`u and Michele Marongiu and Michael Spencer Chapman and M S Vijayabaskar and Joanna Baxter and Claire Hardy and Federico Abascal and Nicholas Williams and Jyoti Nangalia and I nigo Martincorena and Peter J Campbell and Eoin F McKinney and Francesco Cucca and Moritz Gerstung and George S Vassiliou},

doi = {10.1038/s41586-022-04785-z},

year  = {2022},

date = {2022-06-01},

urldate = {2022-06-01},

journal = {Nature},

volume = {606},

number = {7913},

pages = {335--342},

publisher = {Springer Science and Business Media LLC},

abstract = {Clonal expansions driven by somatic mutations become pervasive 

 across human tissues with age, including in the haematopoietic 

 system, where the phenomenon is termed clonal haematopoiesis1-4. 

 The understanding of how and when clonal haematopoiesis 

 develops, the factors that govern its behaviour, how it 

 interacts with ageing and how these variables relate to 

 malignant progression remains limited5,6. Here we track 697 

 clonal haematopoiesis clones from 385 individuals 55 years of 

 age or older over a median of 13 years. We find that 92.4% of 

 clones expanded at a stable exponential rate over the study 

 period, with different mutations driving substantially different 

 growth rates, ranging from 5% (DNMT3A and TP53) to more than 

 50% per year (SRSF2P95H). Growth rates of clones with the same 

 mutation differed by approximately $pm$5% per year, 

 proportionately affecting slow drivers more substantially. By 

 combining our time-series data with phylogenetic analysis of 

 1,731 whole-genome sequences of haematopoietic colonies from 7 

 individuals from an older age group, we reveal distinct patterns 

 of lifelong clonal behaviour. DNMT3A-mutant clones 

 preferentially expanded early in life and displayed slower 

 growth in old age, in the context of an increasingly competitive 

 oligoclonal landscape. By contrast, splicing gene mutations 

 drove expansion only later in life, whereas TET2-mutant clones 

 emerged across all ages. Finally, we show that mutations driving 

 faster clonal growth carry a higher risk of malignant 

 progression. Our findings characterize the lifelong natural 

 history of clonal haematopoiesis and give fundamental insights 

 into the interactions between somatic mutation, ageing and 

 clonal selection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fabre2022-zn,

title = {The longitudinal dynamics and natural history of clonal 

 haematopoiesis},

author = {Margarete A Fabre and José Guilherme Almeida and Edoardo Fiorillo and Emily Mitchell and Aristi Damaskou and Justyna Rak and Valeria Orr`u and Michele Marongiu and Michael Spencer Chapman and M S Vijayabaskar and Joanna Baxter and Claire Hardy and Federico Abascal and Nicholas Williams and Jyoti Nangalia and I nigo Martincorena and Peter J Campbell and Eoin F McKinney and Francesco Cucca and Moritz Gerstung and George S Vassiliou},

year  = {2022},

date = {2022-06-01},

journal = {Nature},

volume = {606},

number = {7913},

pages = {335--342},

publisher = {Springer Science and Business Media LLC},

abstract = {Clonal expansions driven by somatic mutations become pervasive 

 across human tissues with age, including in the haematopoietic 

 system, where the phenomenon is termed clonal haematopoiesis1-4. 

 The understanding of how and when clonal haematopoiesis 

 develops, the factors that govern its behaviour, how it 

 interacts with ageing and how these variables relate to 

 malignant progression remains limited5,6. Here we track 697 

 clonal haematopoiesis clones from 385 individuals 55 years of 

 age or older over a median of 13 years. We find that 92.4% of 

 clones expanded at a stable exponential rate over the study 

 period, with different mutations driving substantially different 

 growth rates, ranging from 5% (DNMT3A and TP53) to more than 

 50% per year (SRSF2P95H). Growth rates of clones with the same 

 mutation differed by approximately $pm$5% per year, 

 proportionately affecting slow drivers more substantially. By 

 combining our time-series data with phylogenetic analysis of 

 1,731 whole-genome sequences of haematopoietic colonies from 7 

 individuals from an older age group, we reveal distinct patterns 

 of lifelong clonal behaviour. DNMT3A-mutant clones 

 preferentially expanded early in life and displayed slower 

 growth in old age, in the context of an increasingly competitive 

 oligoclonal landscape. By contrast, splicing gene mutations 

 drove expansion only later in life, whereas TET2-mutant clones 

 emerged across all ages. Finally, we show that mutations driving 

 faster clonal growth carry a higher risk of malignant 

 progression. Our findings characterize the lifelong natural 

 history of clonal haematopoiesis and give fundamental insights 

 into the interactions between somatic mutation, ageing and 

 clonal selection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fabre2022-bk,

title = {The longitudinal dynamics and natural history of clonal 

 haematopoiesis},

author = {Margarete A Fabre and José Guilherme Almeida and Edoardo Fiorillo and Emily Mitchell and Aristi Damaskou and Justyna Rak and Valeria Orr`u and Michele Marongiu and Michael Spencer Chapman and M S Vijayabaskar and Joanna Baxter and Claire Hardy and Federico Abascal and Nicholas Williams and Jyoti Nangalia and I nigo Martincorena and Peter J Campbell and Eoin F McKinney and Francesco Cucca and Moritz Gerstung and George S Vassiliou},

year  = {2022},

date = {2022-06-01},

journal = {Nature},

volume = {606},

number = {7913},

pages = {335--342},

publisher = {Springer Science and Business Media LLC},

abstract = {Clonal expansions driven by somatic mutations become pervasive 

 across human tissues with age, including in the haematopoietic 

 system, where the phenomenon is termed clonal haematopoiesis1-4. 

 The understanding of how and when clonal haematopoiesis 

 develops, the factors that govern its behaviour, how it 

 interacts with ageing and how these variables relate to 

 malignant progression remains limited5,6. Here we track 697 

 clonal haematopoiesis clones from 385 individuals 55 years of 

 age or older over a median of 13 years. We find that 92.4% of 

 clones expanded at a stable exponential rate over the study 

 period, with different mutations driving substantially different 

 growth rates, ranging from 5% (DNMT3A and TP53) to more than 

 50% per year (SRSF2P95H). Growth rates of clones with the same 

 mutation differed by approximately $pm$5% per year, 

 proportionately affecting slow drivers more substantially. By 

 combining our time-series data with phylogenetic analysis of 

 1,731 whole-genome sequences of haematopoietic colonies from 7 

 individuals from an older age group, we reveal distinct patterns 

 of lifelong clonal behaviour. DNMT3A-mutant clones 

 preferentially expanded early in life and displayed slower 

 growth in old age, in the context of an increasingly competitive 

 oligoclonal landscape. By contrast, splicing gene mutations 

 drove expansion only later in life, whereas TET2-mutant clones 

 emerged across all ages. Finally, we show that mutations driving 

 faster clonal growth carry a higher risk of malignant 

 progression. Our findings characterize the lifelong natural 

 history of clonal haematopoiesis and give fundamental insights 

 into the interactions between somatic mutation, ageing and 

 clonal selection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Liquid Biopsy in the Oncological Management of a Histologically Undiagnosed Lung Carcinoma: A Case Report},

author = {Giovanni M. Fadda and Renato Lobrano and Milena Casula and Marina Pisano and Antonio Pazzola and Antonio Cossu and Giuseppe Palmieri and Panagiotis Paliogiannis},

year  = {2022},

date = {2022-05-10},

urldate = {2022-05-10},

journal = {Journal of Personalized Medicine },

volume = {12},

number = {1874 },

abstract = {Lung cancer is one of the most common and lethal cancers worldwide. Numerous medications targeting specific molecular alterations in non-small cell lung cancer have been introduced in the last decade and have revolutionized the clinical management of the disease. Their use has brought to a parallel evolution of molecular testing techniques to identify alterations in druggable molecular targets within the genetic material of the tumors. To perform molecular testing biopsy or surgery tissue specimens are needed which in addition allow the histological characterization of the tumors. Unfortunately in real-life practice not all the patients are suitable for biopsy or surgery procedures. The use of liquid biopsy for blood extracted tumoral DNA analysis is a promising approach in unbiopsied cases but it is also weighted by several methodological and technical limitations. We report here a case of histologically undiagnosed lung cancer managed with a liquid biopsy and subsequently with anti-EGFR treatment. Our report highlights that the use of liquid biopsy molecular testing in specific clinical situations can offer treatment opportunities for fragile patients affected by lung cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Landscape of immune-related signatures induced by targeting of different epigenetic regulators in melanoma: implications for immunotherapy},

author = {Anichini Andrea and Molla Alessandra and Nicolini Gabriella and Perotti Valentina Eleonora and Sgambelluri Francesco and Covre Alessia and Fazio Carolina and Lofiego Maria Fortunata and Di Giacomo Anna Maria and Coral Sandra and Manca Antonella and Sini Maria Cristina and Pisano Marina and Noviello Teresa and Caruso Francesca and Brich Silvia and Pruneri Giancarlo and Maurichi Andrea and Santinami Mario and Ceccarelli Michele and Palmieri Giuseppe and Maio Michele and Mortarini Roberta},

url = {https://jeccr.biomedcentral.com/articles/10.1186/s13046-022-02529-5},

year  = {2022},

date = {2022-05-10},

urldate = {2022-05-10},

journal = {JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH},

volume = {41},

number = {325},

abstract = {Background: Improvement of efficacy of immune checkpoint blockade (ICB) remains a major clinical goal. Association of ICB with immunomodulatory epigenetic drugs is an option. However epigenetic inhibitors show a heterogeneous landscape of activities. Analysis of transcriptional programs induced in neoplastic cells by distinct classes of epigenetic drugs may foster identification of the most promising agents.Methods: Melanoma cell lines characterized for mutational and differentiation profile were treated with inhibitors of DNA methyltransferases (guadecitabine) histone deacetylases (givinostat) BET proteins (JQ1 and OTX-015) and enhancer of zeste homolog 2 (GSK126). Modulatory effects of epigenetic drugs were evaluated at the gene and protein levels. Master molecules explaining changes in gene expression were identified by Upstream Regulator (UR) analysis. Gene set enrichment and IPA were used respectively to test modulation of guadecitabine-specific gene and UR signatures in baseline and on-treatment tumor biopsies from melanoma patients in the Phase Ib NIBIT-M4 Guadecitabine + Ipilimumab Trial. Prognostic significance of drug-specific immune-related genes was tested with Timer 2.0 in TCGA tumor datasets.Results: Epigenetic drugs induced different profiles of gene expression in melanoma cell lines. Immune-related genes were frequently upregulated by guadecitabine irrespective of the mutational and differentiation profiles of the melanoma cell lines to a lesser extent by givinostat but mostly downregulated by JQ1 and OTX-015. GSK126 was the least active drug. Quantitative western blot analysis confirmed drug-specific modulatory profiles. Most of the guadecitabine-specific signature genes were upregulated in on-treatment NIBIT-M4 tumor biopsies but not in on-treatment lesions of patients treated only with ipilimumab. A guadecitabine-specific UR signature containing activated molecules of the TLR NF-kB and IFN innate immunity pathways was induced in drug-treated melanoma mesothelioma and hepatocarcinoma cell lines and in a human melanoma xenograft model. Activation of guadecitabine-specific UR signature molecules in on-treatment tumor biopsies discriminated responding from non-responding NIBIT-M4 patients. Sixty-five % of the immune-related genes upregulated by guadecitabine were prognostically significant and conferred a reduced risk in the TCGA cutaneous melanoma dataset.Conclusions: The DNMT inhibitor guadecitabine emerged as the most promising immunomodulatory agent among those tested supporting the rationale for usage of this class of epigenetic drugs in combinatorial immunotherapy approaches.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Serra2022-nw,

title = {Comparison of whole blood cryopreservation methods for extensive  flow cytometry immunophenotyping},

author = {Valentina Serra and Valeria Orr`u and Sandra Lai and Monia Lobina and Maristella Steri and Francesco Cucca and Edoardo Fiorillo},

doi = {10.3390/cells11091527},

year  = {2022},

date = {2022-05-01},

urldate = {2022-05-01},

journal = {Cells},

volume = {11},

number = {9},

pages = {1527},

publisher = {MDPI AG},

abstract = {Fresh blood immunophenotyping by flow cytometry, based on the 

 reliable simultaneous detection of several markers in a cell, is 

 the method of choice to study the circulating human immune 

 system. Especially in large and multicenter studies, high sample 

 quality is difficult to achieve, and adequate collection and 

 storage of samples with fine-tuned whole blood cryopreservation 

 is mandatory. Here, we compared the quality of immunophenotypic 

 data obtained from fresh blood with those obtained after five 

 cryopreservation methods by quantifying the levels of 41 immune 

 cell populations. They comprised B and T lymphocyte subsets and 

 their maturation stages, as well as monocytes and granulocytes. 

 Three methods used fixative solutions and two other methods used 

 dimethyl sulfoxide solutions to preserve cell viability. The 

 fixative methods prevented detection of markers critical for 

 identification of B and T cell subsets, including CD27, CXCR3, 

 and CCR6. The other two methods permitted reliable 

 discrimination of most immune-cell populations in thawed 

 samples, though some cell frequencies varied compared to the 

 corresponding fresh sample. Of those two methods, the one 

 preserving blood in media containing dimethyl sulfoxide produced 

 results that were most similar to those with fresh samples.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Liquid Biopsy-Driven Cetuximab Rechallenge Strategy in Molecularly Selected Metastatic Colorectal Cancer Patients},

author = {Stefano Mariani and Marco Puzzoni and Riccardo Giampieri and Pina Ziranu and Valeria Pusceddu and Clelia Donisi and Mara Persano and Giovanna Pinna and Erika Cimbro and Alissa Parrino and Dario Spanu and Andrea Pretta and Eleonora Lai and Nicole Liscia and Alessio Lupi and Enrica Giglio and Grazia Palomba and Milena Casula and Marina Pisano and Giuseppe Palmieri and Mario Scartozzi},

year  = {2022},

date = {2022-04-21},

urldate = {2022-04-21},

journal = {Frontiers in Oncology},

volume = {12},

number = {852583},

abstract = {Background: Rechallenge with EGFR inhibitors represents a promising strategy for patients with RAS wild type (WT) colorectal cancer (CRC) but definitive selection criteria are lacking. Recently the RAS WT status on circulating tumor DNA (ct-DNA) emerged as a potential watershed for this strategy. Our study explored the liquid biopsy-driven cetuximab rechallenge in a RAS and BRAF WT selected population. Methods: CRC patients with RAS and BRAF WT both on tumor tissue and on ct-DNA at baseline receiving rechallenge with cetuximab were eligible for our analysis. Ct-DNA was analyzed for RAS-BRAF mutations with pyro-sequencing and nucleotide sequencing assays. Real-time PCR and droplet digital PCR were performed to confirm the RAS-BRAF mutational status. Results: A total of 26 patients were included in our analysis. In the global population RR was 25.0% median overall survival (mOS) was 5.0 months and median progression-free survival (mPFS) was 3.5 months. Previous response to anti-EGFR was associated with improved mPFS (5.0 vs. 2.0 months HR: 0.26 p = 0.048) and anti-EGFR free interval > 14 months and anti-EGFR free interval > 16 months were associated with improved mPFS (respectively 7.0 vs. 3.0 months HR: 0.27 p = 0.013 and not reached vs. 3.0 months HR: 0.20 p = 0.002) and with improved mOS (respectively 13.0 vs. 5.0 months HR: 0.27 p = 0.013 and 13.0 vs. 5.0 months HR: 0.20 p = 0.002). Previous lines >2 were correlated with improved mPFS (4.0 vs. 1.0 month HR: 0.05 p = 0.041) and with improved mOS (7.0 vs. 1.0 month HR: 0.045 p = 0.034). In a multiple logistic regression model only the anti-EGFR free interval was confirmed to be a significant predictor for mOS and mPFS. Conclusions: Liquid biopsy-driven cetuximab rechallenge was confirmed to be effective. The clinical outcome was consistent with available results from phase II studies. In addition to the molecular selection through the analysis of ct-DNA for RAS the long anti-EGFR free interval is confirmed as a prospective selection criterion for this therapeutic option.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35131881,

title = {Genetic Analysis in African American Children Supports Ancestry-Specific Neuroblastoma Susceptibility},

author = {A. Testori and Z. Vaksman and S. J. Diskin and H. Hakonarson and M. Capasso and A. Iolascon and J. M. Maris and M. Devoto},

year  = {2022},

date = {2022-04-01},

journal = {Cancer Epidemiol Biomarkers Prev},

volume = {31},

number = {4},

pages = {870--875},

abstract = {Neuroblastoma is rarer in African American (AA) children compared with American children of European descent. AA children affected with neuroblastoma, however, more frequently develop the high-risk form of the disease. We have genotyped an AA cohort of 629 neuroblastoma cases (254 high-risk) and 2,990 controls to investigate genetic susceptibility to neuroblastoma in AAs. 10-6 in the EA GWAS, and explained 2% of neuroblastoma risk variance. The significance of the polygenic score dropped rapidly with inclusion of additional SNPs. These findings suggest that several common variants contribute to risk of neuroblastoma in an ancestry-specific fashion. This work supports the need for GWAS to be performed in populations of all races and ethnicities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34605909,

title = {Functional annotation and investigation of the 10q24.33 melanoma risk locus identifies a common variant that influences transcriptional regulation of OBFC1},

author = {A. Cardinale and S. Cantalupo and V. A. Lasorsa and A. Montella and F. Cimmino and M. Succoio and M. Vermeulen and M. P. Baltissen and M. Esposito and M. Avitabile and D. Formicola and A. Testori and F. Bonfiglio and P. Ghiorzo and M. Scalvenzi and F. Ayala and N. Zambrano and M. M. Iles and M. Xu and M. H. Law and K. M. Brown and A. Iolascon and M. Capasso},

year  = {2022},

date = {2022-03-01},

journal = {Hum Mol Genet},

volume = {31},

number = {6},

pages = {863--874},

abstract = {The 10q24.33 locus is known to be associated with susceptibility to cutaneous malignant melanoma (CMM), but the mechanisms underlying this association have been not extensively investigated. We carried out an integrative genomic analysis of 10q24.33 using epigenomic annotations and in vitro reporter gene assays to identify regulatory variants. We found two putative functional single nucleotide polymorphisms (SNPs) in an enhancer and in the promoter of OBFC1, respectively, in neural crest and CMM cells, one, rs2995264, altering enhancer activity. The minor allele G of rs2995264 correlated with lower OBFC1 expression in 470 CMM tumors and was confirmed to increase the CMM risk in a cohort of 484 CMM cases and 1801 controls of Italian origin. Hi-C and chromosome conformation capture (3C) experiments showed the interaction between the enhancer-SNP region and the promoter of OBFC1 and an isogenic model characterized by CRISPR-Cas9 deletion of the enhancer-SNP region confirmed the potential regulatory effect of rs2995264 on OBFC1 transcription. Moreover, the presence of G-rs2995264 risk allele reduced the binding affinity of the transcription factor MEOX2. Biologic investigations showed significant cell viability upon depletion of OBFC1, specifically in CMM cells that were homozygous for the protective allele. Clinically, high levels of OBFC1 expression associated with histologically favorable CMM tumors. Finally, preliminary results suggested the potential effect of decreased OBFC1 expression on telomerase activity in tumorigenic conditions. Our results support the hypothesis that reduced expression of OBFC1 gene through functional heritable DNA variation can contribute to malignant transformation of normal melanocytes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Serra2022-br,

title = {Genetic variant within CDK6 regulates immune response to  palbociclib treatment},

author = {Valentina Serra and Valeria Orr`u and Maristella Steri and Edoardo Fiorillo and Francesco Cucca and Magdalena Zoledziewska},

doi = {10.1016/j.clim.2021.108777},

year  = {2022},

date = {2022-02-01},

urldate = {2022-02-01},

journal = {Clin. Immunol.},

volume = {235},

number = {108777},

pages = {108777},

publisher = {Elsevier BV},

abstract = {Everyone carries a set of genetic variants that contribute to 

 regulation of the levels of blood cells, with unknown clinical 

 impact. One of them, rs445 within the cell-cycle checkpoint gene 

 CDK6, reduces the levels of myeloid cell types including 

 granulocytes. We treated CD3+ T cells and whole blood with 

 palbociclib in 41 individuals, who were stratified by genotype 

 for analyses. In T cells we assessed cell cycle and apoptosis, 

 whereas in whole blood, apoptosis in activated (CD11b+), 

 unactivated (CD11b-) granulocytes, cytotoxic (CD8 + CD4-), and 

 helper (CD8-CD4+) T cells. We find that rs445 modulates the 

 immune response of CD8+ T cells. It also increases the level of 

 apoptotic CD11b + activated granulocytes after palbociclib 

 treatment, which, in synergy with neutropenia, may affect drug 

 related adverse events. These results suggest that the effect of 

 palbociclib treatment may depend on underlying genetically 

 encoded individual immune response as well as the direct 

 response to the drug.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35012520,

title = {Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study},

author = {Panagiotis Paliogiannis and Maria Colombino and Maria Cristina Sini and Antonella Manca and Milena Casula and Grazia Palomba and Marina Pisano and Valentina Doneddu and Angelo Zinellu and Davide Santeufemia and and Giovanni Sotgiu and Antonio Cossu and Giuseppe Palmieri},

doi = {10.1186/s12890-021-01803-0},

issn = {1471-2466},

year  = {2022},

date = {2022-01-10},

journal = {BMC Pulm Med},

volume = {22},

number = {1},

pages = {32},

abstract = {BACKGROUND: Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. The aim of this study was to evaluate the global survival in a real-life cohort of patients with LAC harboring driver genetic alterations.



METHODS: A series of 1282 consecutive Sardinian LAC patients who underwent genetic testing from January 2011 through July 2016 was collected. Molecular tests were based on the clinical needs of each single case (EGFR-exon18/19/21, ALK, and, more recently, BRAF-exon15), and the availability of tissue (KRAS, MET, and presence of low-frequency EGFR-T790M mutated alleles at baseline).



RESULTS: The mean follow-up time of the patients was 46 months. EGFR, KRAS, and BRAF mutations were detected in 13.7%, 21.3%, and 3% of tested cases, respectively; ALK rearrangements and MET amplifications were found respectively in 4.7% and 2% of tested cases. As expected, cases with mutations in exons 18-21 of EGFR, sensitizing to anti-EGFR tyrosine kinase inhibitors (TKIs) agents, had a significantly longer survival in comparison to those without (p < 0.0001); conversely, KRAS mutations were associated with a significantly lower survival (p = 0.0058). Among LAC patients with additional tissue section available for next-generation sequencing (NGS)-based analysis, 26/193 (13.5%) patients found positive for even low-rate EGFR-T790M mutated alleles at baseline were associated with a highly significant lower survival in comparison to those without (8.7 vs. 47.4 months, p < 0.0001).



CONCLUSIONS: In addition to its predictive value for addressing targeted therapy approaches, the assessment of as more inclusive mutation analysis at baseline may provide clues about factors significantly impacting on global survival in advanced LAC patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Exploring interaction modes between polysaccharide-based selectors and biologically active 4,4 ′ -bipyridines by experimental and computational analysis. },

author = {Roberto Dallocchio and Alessandro Dessì and Barbara Sechi and Bezhan Chankvetadze and Sergio Cossu and Victor Mamane and Emmanuel Aubert and Carla Rozzo and Giuseppe Palmieri and Ylenia Spissu and Paola Peluso. },

url = {https://irgb.cnr.it/wp-content/uploads/2024/05/Dallocchio-et-al-2022.pdf},

doi = {10.1016/j.jcoa.2022.100030},

issn = {2772-3917},

year  = {2022},

date = {2022-01-06},

urldate = {2022-01-06},

journal = {Journal of Chromatography Open},

volume = {2},

number = {100030},

pages = {1-10},

abstract = {In the last few years, chiral 4,4 ′ -bipyridine derivatives have been developed for different applications in catalysis, enantioseparation science, supramolecular and theoretical chemistry by modulating the activity of the molecu- lar system through the introduction of specific substituents in the heteroaromatic scaffold. More recently, the biological activity of 2 ′ -substituted-3,3 ′ ,5,5 ′ -tetrachloro-2-iodo-4,4 ′ -bipyridines has been explored in the field of transthyretin (TTR) fibrillogenesis inhibition, and the anticancer cytotoxicity of some derivatives is currently under systematic investigation. In this frame, the high-performance liquid chromatography (HPLC) enantiosepa- ration of four atropisomeric 2,2 ′ -disubstituted-4,4 ′ -bipyridines (R, R’ = Ar, I), which contain multiple interaction sites, such as hydrogen bonding (HB) donors and acceptors, halogen bond (XB) donors, and ?-extended electronic clouds, was explored by using n -hexane (Hex)/2-propanol (2-PrOH) 90:10 v/v as a mobile phase (MP), and eight chiral columns with coated and immobilized amylose- and cellulose-based selectors. The impact of subtle struc- tural variations of analytes and selectors on their mutual intermolecular interactivity was evaluated in terms of retention ( k ) and selectivity ( ?) factors. On this basis, chromatographic analysis based on systematic screening of analytes and selectors was integrated with electrostatic potential ( V ) analysis and molecular dynamics (MD) sim- ulations as computational techniques. The effect of temperature on retention, selectivity, and enantiomer elution order (EEO) of the analytes with coated and immobilized amylose tris (3,5-dimethylphenylcarbamate) was also considered by comparing the variation of the thermodynamic profile associated with each enantioseparation. Chromatographic responses proved to be strictly dependent on specific regions within the analyte, and functions of different interactions sites of the analytes as the structure of the chiral selector changes were significantly disclosed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Boulad2022-ka,

title = {Lentiviral globin gene therapy with reduced-intensity  conditioning in adults with $beta$-thalassemia: a phase 1 trial},

author = {Farid Boulad and Aurelio Maggio and Xiuyan Wang and Paolo Moi and Santina Acuto and Friederike Kogel and Chayamon Takpradit and Susan Prockop and Jorge Mansilla-Soto and Annalisa Cabriolu and Ashlesha Odak and Jinrong Qu and Keyur Thummar and Fang Du and Lingbo Shen and Simona Raso and Rita Barone and Rosario Di Maggio and Lorella Pitrolo and Antonino Giambona and Maura Mingoia and John K Everett and Pascha Hokama and Aoife M Roche and Vito Adrian Cantu and Hriju Adhikari and Shantan Reddy and Eric Bouhassira and Narla Mohandas and Frederic D Bushman and Isabelle Rivi`ere and Michel Sadelain},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nat. Med.},

volume = {28},

number = {1},

pages = {63--70},

publisher = {Springer Science and Business Media LLC},

abstract = {$beta$-Thalassemias are inherited anemias that are caused by 

 the absent or insufficient production of the $beta$ chain of 

 hemoglobin. Here we report 6-8-year follow-up of four adult 

 patients with transfusion-dependent $beta$-thalassemia who were 

 infused with autologous CD34+ cells transduced with the 

 TNS9.3.55 lentiviral globin vector after reduced-intensity 

 conditioning (RIC) in a phase 1 clinical trial ( NCT01639690) . 

 Patients were monitored for insertional mutagenesis and the 

 generation of a replication-competent lentivirus (safety and 

 tolerability of the infusion product after RIC-primary endpoint) 

 and engraftment of genetically modified autologous CD34+ cells, 

 expression of the transduced $beta$-globin gene and 

 post-transplant transfusion requirements (efficacy-secondary 

 endpoint). No unexpected safety issues occurred during 

 conditioning and cell product infusion. Hematopoietic gene 

 marking was very stable but low, reducing transfusion 

 requirements in two patients, albeit not achieving transfusion 

 independence. Our findings suggest that non-myeloablative 

 conditioning can achieve durable stem cell engraftment but 

 underscore a minimum CD34+ cell transduction requirement for 

 effective therapy. Moderate clonal expansions were associated 

 with integrations near cancer-related genes, suggestive of 

 non-erythroid activity of globin vectors in stem/progenitor 

 cells. These correlative findings highlight the necessity of 

 cautiously monitoring patients harboring globin vectors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35115688b,

title = {Challenges and future directions for studying effects of host genetics on the gut microbiome},

author = {S. Sanna and A. Kurilshikov and A. Graaf and J. Fu and A. Zhernakova},

url = {https://www.nature.com/articles/s41588-021-00983-z},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nat Genet},

volume = {54},

number = {2},

pages = {100--106},

abstract = {1,000 participants have been published, yet only a few genetic loci have been consistently confirmed across multiple studies. Here we discuss the state of the art for mbGWAS, focusing on current challenges such as the heterogeneity of microbiome measurements and power issues, and we elaborate on potential future directions for genetic analysis of the microbiome.},

note = {[DOI:hrefhttps://dx.doi.org/10.1038/s41588-021-00983-z10.1038/s41588-021-00983-z] [PubMed:hrefhttps://www.ncbi.nlm.nih.gov/pubmed/3278393532783935]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35115690,

title = {Effect of host genetics on the gut microbiome in 7,738 participants of the Đutch Microbiome Project},

author = {E. A. Lopera-Maya and A. Kurilshikov and A. Graaf and S. Hu and S. Andreu-Sánchez and L. Chen and A. V. Vila and R. Gacesa and T. Sinha and V. Collij and M. A. Y. Klaassen and L. A. Bolte and M. F. B. Gois and P. B. T. Neerincx and M. A. Swertz and H. J. M. Harmsen and C. Wijmenga and J. Fu and R. K. Weersma and A. Zhernakova and S. Sanna and R. Aguirre-Gamboa and P. Deelen and L. Franke and J. A. Kuivenhoven and E. A. Lopera-Maya and I. M. Nolte and S. Sanna and H. Snieder and M. A. Swertz and J. M. Vonk and C. Wijmenga},

url = {https://www.nature.com/articles/s41588-021-00992-y},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nat Genet},

volume = {54},

number = {2},

pages = {143--151},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34959343,

title = {Combining Human Genetics of Multiple Sclerosis with Oxidative Stress Phenotype for Đrug Repositioning},

author = {S. Olla and M. Steri and A. Formato and M. B. Whalen and S. Corbisiero and C. Agresti},

year  = {2021},

date = {2021-12-01},

urldate = {2021-12-01},

journal = {Pharmaceutics},

volume = {13},

number = {12},

abstract = {In multiple sclerosis (MS), oxidative stress (OS) is implicated in the neurodegenerative processes that occur from the beginning of the disease. Unchecked OS initiates a vicious circle caused by its crosstalk with inflammation, leading to demyelination, axonal damage and neuronal loss. The failure of MS antioxidant therapies relying on the use of endogenous and natural compounds drives the application of novel approaches to assess target relevance to the disease prior to preclinical testing of new drug candidates. To identify drugs that can act as regulators of intracellular oxidative homeostasis, we applied an in silico approach that links genome-wide MS associations and molecular quantitative trait loci (QTLs) to proteins of the OS pathway. We found 10 drugs with both central nervous system and oral bioavailability, targeting five out of the 21 top-scoring hits, including arginine methyltransferase (CARM1), which was first linked to MS. In particular, the direction of brain expression QTLs for CARM1 and protein kinase MAPK1 enabled us to select BIIB021 and PEITC drugs with the required target modulation. Our study highlights OS-related molecules regulated by functional MS variants that could be targeted by existing drugs as a supplement to the approved disease-modifying treatments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34845919,

title = {Large-Scale Plasma Protein Profiling of Incident Myocardial Infarction, Ischemic Stroke, and Ħeart Failure},

author = {L. Lind and D. Zanetti and M. Ingelsson and S. Gustafsson and J. v and T. L. Assimes},

year  = {2021},

date = {2021-12-01},

journal = {J Am Heart Assoc},

volume = {10},

number = {23},

pages = {e023330},

abstract = {=0.0038). Conclusions Large-scale proteomics seem useful for the discovery of new risk markers for CVD and to improve risk prediction in an elderly population of men. Further studies are needed to replicate the findings in independent samples of both men and women of different ages.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Calabrò2021,

title = {Tremelimumab plus durvalumab retreatment and 4-year outcomes in patients with mesothelioma: a follow-up of the open label, non-randomised, phase 2 NIBIT-MESO-1 study},

author = {Luana Calabrò and Giulia Rossi and Aldo Morra and Claudio Rosati and Ornella Cutaia and Maria Grazia Daffinà and Maresa Altomonte and Anna Maria Di Giacomo and Milena Casula and Carolina Fazio and Giuseppe Palmieri and Diana Giannarelli and Alessia Covre and Michele Maio},

doi = {10.1016/s2213-2600(21)00043-6},

issn = {2213-2600},

year  = {2021},

date = {2021-09-00},

journal = {The Lancet Respiratory Medicine},

volume = {9},

number = {9},

pages = {969--976},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34502367,

title = {The  CagY Protein Drives Gastric Th1 and Th17 Inflammation and B Cell Proliferation in Gastric MALT Lymphoma},

author = {Chiara Della Bella and Maria Felicia Soluri and Simone Puccio and Marisa Benagiano and Alessia Grassi and Jacopo Bitetti and Fabio Cianchi and Daniele Sblattero and Clelia Peano and Mario Milco D'Elios},

doi = {10.3390/ijms22179459},

issn = {1422-0067},

year  = {2021},

date = {2021-08-01},

journal = {Int J Mol Sci},

volume = {22},

number = {17},

abstract = {BACKGROUND: the neoplastic B cells of the -related low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma proliferate in response to , however, the nature of the  antigen responsible for proliferation is still unknown. The purpose of the study was to dissect whether CagY might be the  antigen able to drive B cell proliferation.nnMETHODS: the B cells and the clonal progeny of T cells from the gastric mucosa of five patients with MALT lymphoma were compared with those of T cell clones obtained from five -infected patients with chronic gastritis. The T cell clones were assessed for their specificity to  CagY, cytokine profile and helper function for B cell proliferation.nnRESULTS: 22 of 158 CD4 (13.9%) gastric clones from MALT lymphoma and three of 179 CD4 (1.7%) clones from chronic gastritis recognized CagY. CagY predominantly drives Interferon-gamma (IFN-γ) and Interleukin-17 (IL-17) secretion by gastric CD4 T cells from -infected patients with low-grade gastric MALT lymphoma. All MALT lymphoma-derived clones dose dependently increased their B cell help, whereas clones from chronic gastritis lost helper activity at T-to-B-cell ratios greater than 1.nnCONCLUSION: the results obtained indicate that CagY drives both B cell proliferation and T cell activation in gastric MALT lymphomas.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Are Molecular Alterations Linked to Genetic Instability Worth to Be Included as Biomarkers for Directing or Excluding Melanoma Patients to Immunotherapy? },

author = {Giuseppe Palmieri and Carla Maria Rozzo and Maria Colombino and Milena Casula and Maria Cristina Sini and Antonella Manca and Marina Pisano and Valentina Doneddu and Panagiotis Paliogiannis and Antonio Cossu. },

url = {https://irgb.cnr.it/wp-content/uploads/2024/05/Palmieri-et-al-2021-1.pdf},

doi = {doi: 10.3389/fonc.2021.666624},

issn = {2234-943X},

year  = {2021},

date = {2021-05-05},

urldate = {2021-05-05},

journal = {Frontiers in Oncology},

volume = {11},

number = {666624},

pages = {1-11},

abstract = {The improvement of the immunotherapeutic potential in most human cancers, including melanoma, requires the identification of increasingly detailed molecular features underlying the tumor immune responsiveness and acting as disease-associated biomarkers. In recent past years, the complexity of the immune landscape in cancer tissues is being steadily unveiled with a progressive better understanding of the plethora of actors playing in such a scenario, resulting in histopathology diversification, distinct molecular subtypes, and biological heterogeneity. Actually, it is widely recognized that the intracellular patterns of alterations in driver genes and loci may also concur to interfere with the homeostasis of the tumor microenvironment components, deeply affecting the immune response against the tumor. Among others, the different events linked to genetic instability—aneuploidy/somatic copy number alteration (SCNA) or microsatellite instability (MSI)—may exhibit opposite behaviors in terms of immune exclusion or responsiveness.

In this review, we focused on both prevalence and impact of such different types of genetic instability in melanoma in order to evaluate whether their use as biomarkers in an integrated analysis of the molecular profile of such a malignancy may allow defining any potential predictive value for response/resistance to immunotherapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34205480,

title = {NGS-Based Analysis of Atypical Deep Penetrating Nevi},

author = {Antonella Manca and Maria Cristina Sini and Anna Maria Cesinaro and Francesca Portelli and Carmelo Urso and Maria Lentini and Roberta Cardia and Llucia Alos and Martin Cook and Sara Simi and Panagiotis Paliogiannis and Vincenzo De Giorgi and Antonio Cossu and Giuseppe Palmieri and Daniela Massi},

doi = {10.3390/cancers13123066},

issn = {2072-6694},

year  = {2021},

date = {2021-05-04},

journal = {Cancers (Basel)},

volume = {13},

number = {12},

abstract = {Deep penetrating nevi (DPNs) are rare melanocytic neoplasms consisting of pigmented spindled or epithelioid melanocytes with a distinctive wedge-shaped configuration showing activation of the WNT pathway, with unusual cyto-architectural features. It is unclear whether they show a distinct genomic profile associated with a diverse metastatic potential. We describe herein a cohort of 21 atypical DPNs analyzed by next-generation sequencing using the Ion AmpliSeq™ Comprehensive Cancer Panel. We found that β-catenin exon 3 was mutated in 95% and MAP kinase pathway genes in 71% of the cases. Less frequent mutations were observed in HRAS (19%) and MAP2K1 (24%). Isocitrate dehydrogenases 1 (IDH1) mutations, including R132C, V178I, and S278L, were identified in 38% of cases and co-existed with BRAF/HRAS mutations. The only case with progressive nodal disease carried alterations in the β-catenin pathway and mutations in IDH1 and NRAS (codon 61). By a comprehensive mutation analysis, we found low genetic heterogeneity and a lack of significant associations between specific gene mutations and histopathological features, despite atypical features. Whether the acquisition of an NRAS or IDH1 mutation in an atypical DPN may represent a molecular evolution implying a pathway to melanoma progression should be confirmed in a larger series.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Anticancer activity of two novel hydroxylated biphenyl compounds toward malignant melanoma cells.},

author = {Marina Pisano and Maria Antonietta Dettori and Davide Fabbri and Giovanna Delogu and Giuseppe Palmieri and Carla Rozzo. },

url = {https://irgb.cnr.it/wp-content/uploads/2024/05/Pisano-et-al-2021-reprint.pdf},

doi = {10.3390/ijms22115636},

issn = {1422-0067},

year  = {2021},

date = {2021-03-26},

urldate = {2021-03-26},

journal = {International Journal of Molecular Sciences},

volume = {22},

number = {5636},

pages = {1-18},

abstract = {Melanoma, the deadliest form of skin cancer, is still one of the most difficult cancers to treat despite recent advances in targeted and immune therapies. About 50% of advanced melanoma do not benefit of such therapies, and novel treatments are requested. Curcumin and its analogs have shown good anticancer properties and are being considered for use in combination with or sequence to recent therapies to improve patient outcomes. Our group previously published the synthesis and anticancer activity characterization of a novel curcumin-related compound against melanoma and neuroblastoma cells (D6). Here, two hydroxylated biphenyl compounds—namely, compounds 11 and 12—were selected among a small collection of previously screened C2-symmetric hydroxylated biphenyls structurally related to D6 and curcumin, showing the best antitumor potentiality against melanoma cells (IC50 values of 1.7 uM 0.5 uM for 11 and 2.0 uM 0.7 uM for 12) and no toxicity of normal fibroblasts up to 32 uM. Their antiproliferative activity was deeply characterized on five melanoma cell lines by performing dose-response and clonal growth inhibition assays, which revealed longlasting and irreversible effects for both compounds. Apoptosis induction was ascertained by the annexin V and TUNEL assays, whereas Western blotting showed caspase activation and PARP cleavage. A cell cycle analysis, following cell treatments with either compound 11 or 12, highlighted an arrest in the G2/M transition. Taking all this evidence together, 11 and 12 were shown to be good candidates as lead compounds to develop new anticancer drugs against malignant melanoma.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33475257,

title = {Modeling, optimization, and comparable efficacy of Ŧ cell and hematopoietic stem cell gene editing for treating hyper-IgM syndrome},

author = {V Vavassori and E Mercuri and G E Marcovecchio and M C Castiello and G Schiroli and L Albano and C Margulies and F Buquicchio and E Fontana and S Beretta and I Merelli and A Cappelleri and P M Rancoita and V Lougaris and A Plebani and M Kanariou and A Lankester and F Ferrua and E Scanziani and C Cotta-Ramusino and A Villa and L Naldini and P Genovese},

year  = {2021},

date = {2021-03-01},

journal = {EMBO Mol Med},

volume = {13},

number = {3},

pages = {e13545},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33125761,

title = {Pathobiologic Mechanisms of Neurodegeneration in Osteopetrosis Đerived From Structural and Functional Analysis of 14 ClC-7 Mutants},

author = {E Di Zanni and E Palagano and L Lagostena and D Strina and A Rehman and M Abinun and L De Somer and B Martire and J Brown and A Kariminejad and S Balasubramaniam and G Baynam and F Gurrieri and M A Pisanti and I De Maggio and M R Abboud and R Chiesa and C P Burren and A Villa and C Sobacchi and A Picollo},

year  = {2021},

date = {2021-03-01},

journal = {J Bone Miner Res},

volume = {36},

number = {3},

pages = {531--545},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kurilshikov2021-sr,

title = {Large-scale association analyses identify host factors 

 influencing human gut microbiome composition},

author = {Alexander Kurilshikov and Carolina Medina-Gomez and Rodrigo Bacigalupe and Djawad Radjabzadeh and Jun Wang and Ayse Demirkan and Caroline I Le Roy and Juan Antonio Raygoza Garay and Casey T Finnicum and Xingrong Liu and Daria V Zhernakova and Marc Jan Bonder and Tue H Hansen and Fabian Frost and Malte C Rühlemann and Williams Turpin and Jee-Young Moon and Han-Na Kim and Kreete Lüll and Elad Barkan and Shiraz A Shah and Myriam Fornage and Joanna Szopinska-Tokov and Zachary D Wallen and Dmitrii Borisevich and Lars Agreus and Anna Andreasson and Corinna Bang and Larbi Bedrani and Jordana T Bell and Hans Bisgaard and Michael Boehnke and Dorret I Boomsma and Robert D Burk and Annique Claringbould and Kenneth Croitoru and Gareth E Davies and Cornelia M Duijn and Liesbeth Duijts and Gwen Falony and Jingyuan Fu and Adriaan Graaf and Torben Hansen and Georg Homuth and David A Hughes and Richard G Ijzerman and Matthew A Jackson and Vincent W V Jaddoe and Marie Joossens and Torben Jørgensen and Daniel Keszthelyi and Rob Knight and Markku Laakso and Matthias Laudes and Lenore J Launer and Wolfgang Lieb and Aldons J Lusis and Ad A M Masclee and Henriette A Moll and Zlatan Mujagic and Qi Qibin and Daphna Rothschild and Hocheol Shin and Søren J Sørensen and Claire J Steves and Jonathan Thorsen and Nicholas J Timpson and Raul Y Tito and Sara Vieira-Silva and Uwe Völker and Henry Völzke and Urmo V osa and Kaitlin H Wade and Susanna Walter and Kyoko Watanabe and Stefan Weiss and Frank U Weiss and Omer Weissbrod and Harm-Jan Westra and Gonneke Willemsen and Haydeh Payami and Daisy M A E Jonkers and Alejandro Arias Vasquez and Eco J C Geus and Katie A Meyer and Jakob Stokholm and Eran Segal and Elin Org and Cisca Wijmenga and Hyung-Lae Kim and Robert C Kaplan and Tim D Spector and Andre G Uitterlinden and Fernando Rivadeneira and Andre Franke and Markus M Lerch and Lude Franke and Serena Sanna and Mauro DÁmato and Oluf Pedersen and Andrew D Paterson and Robert Kraaij and Jeroen Raes and Alexandra Zhernakova},

year  = {2021},

date = {2021-02-01},

journal = {Nat. Genet.},

volume = {53},

number = {2},

pages = {156--165},

publisher = {Springer Science and Business Media LLC},

abstract = {To study the effect of host genetics on gut microbiome 

 composition, the MiBioGen consortium curated and analyzed 

 genome-wide genotypes and 16S fecal microbiome data from 18,340 

 individuals (24 cohorts). Microbial composition showed high 

 variability across cohorts: only 9 of 410 genera were detected 

 in more than 95% of samples. A genome-wide association study of 

 host genetic variation regarding microbial taxa identified 31 

 loci affecting the microbiome at a genome-wide significant (P < 

 5 $times$ 10-8) threshold. One locus, the lactase (LCT) gene 

 locus, reached study-wide significance (genome-wide association study signal: P = 1.28 $times$ 10-20), and it showed an 

 age-dependent association with Bifidobacterium abundance. Other 

 associations were suggestive (1.95 $times$ 10-10 < P < 5 

 $times$ 10-8) but enriched for taxa showing high heritability 

 and for genes expressed in the intestine and brain. A 

 phenome-wide association study and Mendelian randomization 

 identified enrichment of microbiome trait loci in the metabolic, 

 nutrition and environment domains and suggested the microbiome 

 might have causal effects in ulcerative colitis and rheumatoid 

 arthritis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Angius2021-bx,

title = {Portrait of cancer stem cells on colorectal cancer: Molecular 

 biomarkers, signaling pathways and miRNAome},

author = {Andrea Ängius and Antonio Mario Scanu and Caterina Arru and Maria Rosaria Muroni and Vincenzo Rallo and Giulia Deiana and Maria Chiara Ninniri and Ciriaco Carru and Alberto Porcu and Giovanna Pira and Paolo Uva and Paolo Cossu-Rocca and Maria Rosaria" De Miglio},

year  = {2021},

date = {2021-02-01},

journal = {Int. J. Mol. Sci.},

volume = {22},

number = {4},

pages = {1603},

publisher = {MDPI AG},

abstract = {Colorectal cancer (CRC) is a leading cause of cancer death 

 worldwide, and about 20% is metastatic at diagnosis and 

 untreatable. Increasing evidence suggests that the heterogeneous 

 nature of CRC is related to colorectal cancer stem cells 

 (CCSCs), a small cells population with stemness behaviors and 

 responsible for tumor progression, recurrence, and therapy 

 resistance. Growing knowledge of stem cells (SCs) biology has 

 rapidly improved uncovering the molecular mechanisms and 

 possible crosstalk/feedback loops between signaling pathways 

 that directly influence intestinal homeostasis and 

 tumorigenesis. The generation of CCSCs is probably connected to 

 genetic changes in members of signaling pathways, which control 

 self-renewal and pluripotency in SCs and then establish function 

 and phenotype of CCSCs. Particularly, various deregulated 

 CCSC-related miRNAs have been reported to modulate stemness 

 features, controlling CCSCs functions such as regulation of cell 

 cycle genes expression, epithelial-mesenchymal transition, 

 metastasization, and drug-resistance mechanisms. Primarily, 

 CCSC-related miRNAs work by regulating mainly signal pathways 

 known to be involved in CCSCs biology. This review intends to 

 summarize the epigenetic findings linked to miRNAome in the 

 maintenance and regulation of CCSCs, including their 

 relationships with different signaling pathways, which should 

 help to identify specific diagnostic, prognostic, and predictive 

 biomarkers for CRC, but also develop innovative CCSCs-targeted 

 therapies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ferrando2021-ga,

title = {Active human and porcine serum induce competence for genetic  transformation in the emerging zoonotic pathogen Streptococcus  suis},

author = {Maria Laura Ferrando and Alex Gussak and Saskia Mentink and Marcela Fernandez Gutierrez and Peter Baarlen and Jerry Mark Wells},

year  = {2021},

date = {2021-02-01},

urldate = {2021-02-01},

journal = {Pathogens},

volume = {10},

number = {2},

pages = {156},

publisher = {MDPI AG},

abstract = {The acquisition of novel genetic traits through natural 

 competence is a strategy used by bacteria in microbe-rich 

 environments where microbial competition, antibiotics, and host 

 immune defenses threaten their survival. Here, we show that 

 virulent strains of Streptococcus suis, an important zoonotic 

 agent and porcine pathogen, become competent for genetic 

 transformation with plasmid or linear DNA when cultured in 

 active porcine and human serum. Competence was not induced in 

 active fetal bovine serum, which contains less complement 

 factors and immunoglobulins than adult serum and was strongly 

 reduced in heat-treated or low-molecular weight fractions of 

 active porcine serum. Late competence genes, encoding the uptake 

 machinery for environmental DNA, were upregulated in the active 

 serum. Competence development was independent of the early 

 competence regulatory switch involving XIP and ComR, as well as 

 sigma factor ComX, suggesting the presence of an alternative 

 stress-induced pathway for regulation of the late competence 

 genes required for DNA uptake.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33670365,

title = {Integrated Genomics Identifies miR-181/ŦFAM Pathway as a Critical Đriver of Đrug Resistance in Melanoma},

author = {A Barbato and A Iuliano and M Volpe and R DÁlterio and S Brillante and F Massa and R De Cegli and S Carrella and M Salati and A Russo and G Russo and S Riccardo and D Cacchiarelli and M Capone and G Madonna and P A Ascierto and B Franco and A Indrieri and P Carotenuto},

year  = {2021},

date = {2021-02-01},

journal = {Int J Mol Sci},

volume = {22},

number = {4},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32091431,

title = {KIT and PDGFRa mutational patterns in Sardinian patients with gastrointestinal stromal tumors},

author = {Grazia Palomba and Panagiotis Paliogiannis and Maria C Sini and Maria Colombino and Milena Casula and Antonella Manca and Marina Pisano and Giovanni Sotgiu and Valentina Doneddu and Giuseppe Palmieri and Antonio Cossu},

doi = {10.1097/CEJ.0000000000000581},

issn = {1473-5709},

year  = {2021},

date = {2021-01-30},

journal = {Eur J Cancer Prev},

volume = {30},

number = {1},

pages = {53--58},

abstract = {Gastrointestinal stromal tumor (GIST) is the most common mesenchymal malignancy of the gastrointestinal tract. We provide in the present article the molecular characterization of a series of primary GISTs in a cohort of Sardinian patients (Italy), with the aim to describe the patterns of KIT and PDGFRa mutations and the corresponding clinical features. Ninety-nine Sardinian patients with histologically-proven diagnosis of GIST were included in the study. Medical records and pathology reports were used to assess the demographic and clinical features of the patients and the disease at the time of the diagnosis. Formalin-fixed, paraffin-embedded tissue samples were retrieved for each case, and mutation analysis of the KIT and PDGFRa genes was performed. KIT and PDGFRa mutations were detected in 81.8% and 5% of the cases, respectively. The most common KIT mutation was W557_K558del in exon 11, while D842V in exon 18 was the most common PDGFRa genetic alteration; V561D was the only PDGFRa mutation found in exon 12. The global "wild-type" cases, with no mutations in either the KIT or PDGFRa genes, were 13 (13.1%). The mean survival of those patients was approximately 46.9 (±43.9) months. Globally, 86.9% of Sardinian patients with GIST had a KIT or PDGFRa mutation; the former were more frequent in comparison with other Italian cohorts, while PDGFRa mutations were rare. No statistical differences in survival between mutated and wild-type cases, and between KIT and PDGFRa mutated cases were detected in our study.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33274847,

title = {Synthesis of Hydroxylated Biphenyls Derivatives Bearing an α,β-Unsaturated Ketone as Lead Structure for the Development of New Drug Candidates Against Malignant Melanoma},

author = {Maria Antonietta Dettori and Davide Fabbri and Marina Pisano and Carla Rozzo and Giovanna Delogu },

url = {https://irgb.cnr.it/wp-content/uploads/2024/05/reprint-1.pdf},

doi = {doi.org/10.1002/cmdc.202000709},

year  = {2021},

date = {2021-01-21},

urldate = {2021-01-21},

journal = {ChemMedChem},

volume = {16},

pages = {1022-1033},

abstract = {A small collection of C 2 -symmetry hydroxylated biphenyls derivatives featured with a α,β-unsaturated ketone as lead structure was prepared and the capability of such compounds to act as antiproliferative agents against four human malignant melanoma cell lines was assayed. The prodrug approach was applied in order to improve delivery of compounds into the cell by modulation of the phenolic-OH protective group. The hydroxylated biphenyl structure bearing an α,β-unsaturated ketone and a phenolic- O -prenylated chain would facilitated the delivery of the molecule and interactions with the biological targets. Four compounds showed antiproliferative activity resulting in IC 50 value in the range 1.2 - 2.8 µM..},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mingoia2021-hv,

title = {Induction of therapeutic levels of HbF in genome-edited 

 primary $beta$0 39-thalassaemia haematopoietic stem and 

 progenitor cells},

author = {Maura Mingoia and Cristian A Caria and Lin Ye and Isadora Asunis and M Franca Marongiu and Laura Manunza and M Carla Sollaino and Jiaming Wang and Annalisa Cabriolu and Ryo Kurita and Yukio Nakamura and Francesco Cucca and Yuet W Kan and M Giuseppina Marini and Paolo Moi},

year  = {2021},

date = {2021-01-01},

journal = {Br. J. Haematol.},

volume = {192},

number = {2},

pages = {395--404},

publisher = {Wiley},

abstract = {Hereditary persistence of fetal haemoglobin (HPFH) is the major 

 modifier of the clinical severity of $beta$-thalassaemia. The 

 homozygous mutation c.-196 C>T in the A$gamma$-globin (HBG1) 

 promoter, which causes Sardinian $delta$$beta$0 -thalassaemia, 

 is able to completely rescue the $beta$-major thalassaemia 

 phenotype caused by the $beta$0 39-thalassaemia mutation, 

 ensuring high levels of fetal haemoglobin synthesis during 

 adulthood. Here, we describe a CRISPR/Cas9 genome-editing 

 approach, combined with the non-homologous end joining (NHEJ) 

 pathway repair, aimed at reproducing the effects of this 

 naturally occurring HPFH mutation in both HBG promoters. After 

 selecting the most efficient guide RNA in K562 cells, we edited 

 the HBG promoters in human umbilical cord blood-derived 

 erythroid progenitor 2 cells (HUDEP-2) and in haematopoietic 

 stem and progenitor cells (HSPCs) from $beta$0 -thalassaemia 

 patients to assess the therapeutic potential of HbF induction. 

 Our results indicate that small deletions targeting the 

 -196-promoter region restore high levels of fetal haemoglobin 

 (HbF) synthesis in all cell types tested. In pools of HSPCs 

 derived from homozygous $beta$0 39-thalassaemia patients, a 

 20% editing determined a parallel 20% increase of HbF compared 

 to unedited pools. These results suggest that editing the region 

 of HBG promoters around the -196 position has the potential to 

 induce therapeutic levels of HbF in patients with most types of 

 $beta$-thalassaemia irrespective of the $beta$-globin gene 

 (HBB) mutations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31949009,

title = {Expanded circulating hematopoietic stem/progenitor cells as novel cell source for the treatment of ŦCIRG1 osteopetrosis},

author = {V Capo and S Penna and I Merelli and M Barcella and S Scala and L Basso-Ricci and E Draghici and E Palagano and E Zonari and G Desantis and P Uva and R Cusano and L Sergi Sergi and L Crisafulli and D Moshous and P Stepensky and K Drabko and Z Kaya and E Unal and A Gezdirici and G Menna and M Serafini and A Aiuti and S L Locatelli and C Carlo-Stella and A S Schulz and F Ficara and C Sobacchi and B Gentner and A Villa},

year  = {2021},

date = {2021-01-01},

journal = {Haematologica},

volume = {106},

number = {1},

pages = {74--86},

keywords = {},

pubstate = {published},

tppubtype = {article}

}