@article{%a1:%Y_365,

title = {Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium.},

author = {Li Q and Wojciechowski R and Simpson CL and Hysi PG and Verhoeven VJ and Ikram MK and Hohn R and Vitart V and Hewitt AW and Oexle K and Mkela KM and MacGregor S and Pirastu M and Fan Q and Cheng CY and St Pourcain B and McMahon G and Kemp JP and Northstone K and Rahi JS and Cumberland PM and Martin NG and Sanfilippo PG and Lu Y and Wang YX and Hayward C and Polasek O and Campbell H and Bencic G and Wright AF and Wedenoja J and Zeller T and Schillert A and Mirshahi A and Lackner K and Yip SP and Yap MK and Ried JS and Gieger C and Murgia F and Wilson JF and Fleck B and Yazar S and Vingerling JR and Hofman A and Uitterlinden A and Rivadeneira F and Amin N and Karssen L and Oostra BA and Zhou X and Teo YY and Tai ES and Vithana E and Barathi V and Zheng Y and Siantar RG and Neelam K and Shin Y and Lam J and Yonova-Doing E and Venturini C and Hosseini SM and Wong HS and Lehtimaki T and Kahonen M and Raitakari O and Timpson NJ and Evans DM and Khor CC and Aung T and Young TL and Mitchell P and Klein B and van Duijn CM and Meitinger T and Jonas JB and Baird PN and Mackey DA and Wong TY and Saw SM and Parssinen O and Stambolian D and Hammond CJ and Klaver CC and Williams C and Paterson AD and Bailey-Wilson JE and Guggenheim JA and CREAM Consortium},

url = {https://link.springer.com/article/10.1007%2Fs00439-014-1500-y},

doi = {10.1007/s00439-014-1500-y},

year  = {2015},

date = {2015-02-25},

journal = {Human Genetics},

volume = {134},

number = {2},

pages = {131-146},

abstract = {To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E−8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E−07), TOX (rs7823467, P = 3.47E−07) and LINC00340 (rs12212674, P = 1.49E−06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = −0.59, P = 2.10E−04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_359,

title = {Environmental immune disruptors, inflammation and cancer risk.},

author = {Thompson PA and Khatami M and Baglole CJ and Sun J and Harris S and Moon EY and Al-Mulla F and Al-Temaimi R and Brown D and Colacci A and Mondello C and Raju J and Ryan E and Woodrick J and Scovassi AI and Singh N and Vaccari M and Roy R and Forte S and Memeo L and Salem HK and Amedei A and Hamid RA and Lowe L and Guarnieri T and Bisson WH},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S232/316570},

doi = {10.1093/carcin/bgv038},

year  = {2015},

date = {2015-02-21},

urldate = {2015-02-21},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S232-253},

abstract = {An emerging area in environmental toxicology is the role that chemicals and chemical mixtures have on the cells of the human immune system. This is an important area of research that has been most widely pursued in relation to autoimmune diseases and allergy/asthma as opposed to cancer causation. This is despite the well-recognized role that innate and adaptive immunity play as essential factors in tumorigenesis. Here, we review the role that the innate immune cells of inflammatory responses play in tumorigenesis. Focus is placed on the molecules and pathways that have been mechanistically linked with tumor-associated inflammation. Within the context of chemically induced disturbances in immune function as co-factors in carcinogenesis, the evidence linking environmental toxicant exposures with perturbation in the balance between pro- and anti-inflammatory responses is reviewed. Reported effects of bisphenol A, atrazine, phthalates and other common toxicants on molecular and cellular targets involved in tumor-associated inflammation (e.g. cyclooxygenase/prostaglandin E2, nuclear factor kappa B, nitric oxide synthesis, cytokines and chemokines) are presented as example chemically mediated target molecule perturbations relevant to cancer. Commentary on areas of additional research including the need for innovation and integration of systems biology approaches to the study of environmental exposures and cancer causation are presented. The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_363,

title = {Gallic acid exerts a protective or an anti-proliferative effect on glioma T98G cells via dose-dependent epigenetic regulation mediated by miRNAs.},

author = {Paolini A and Curti V and Pasi F and Mazzini G and Nano R and Capelli E},

url = {https://www.spandidos-publications.com/ijo/46/4/1491},

doi = {10.3892/ijo.2015.2864},

year  = {2015},

date = {2015-02-20},

journal = {International Journal of Oncology},

volume = {46},

number = {4},

pages = {1491-1497},

abstract = {Glioblastoma multiforme (GBM) is the most malignant primary brain tumor in adulthood, characterized by very high recurrence. Following the limited results for conventional therapies, novel therapeutic agents are under investigation. Among the putative new molecules, gallic acid (GA) represents a promising new anticancer drug. The anticancer effect of this drug has been based on its antioxidant effects. The aim of the present study was to investigate the toxic effects of GA on the T98G human glioblastoma cell line and its capacity to modulate the expression of microRNAs targeting the genes involved in tumor growth and invasion. Cytotoxicity, clonogenic ability and cell migration after GA treatment were tested. Moreover, the expression of miRNAs that target genes for antioxidant mitochondrial enzymes (mir-17-3p), p-21 protein (mir-21-5p) and ATM (mir-421-5p) was determined by qRT-PCR. The results confirmed in the T98G cells the anti-proliferative effect of GA reported for other glioma cell lines and showed that the miRNA expression changes depending on GA concentrations. Different GA concentrations can determine a protective or a toxic effect on tumor cells. Thus, the key for GA to induce a specific anticancer action is to use an optimal concentration that avoids these twin effects.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_385,

title = {New light in flavin autofluorescence.},

author = {Croce AC and Bottiroli G},

url = {https://www.ejh.it/index.php/ejh/article/view/2576},

doi = {10.4081/ejh.2015.2576},

year  = {2015},

date = {2015-02-20},

journal = {European Journal of Histochemistry },

volume = {59},

number = {4},

pages = {2576},

abstract = {Our attention was captured by the interesting debate on the identification of lipofuscins, lipofuscin-like lipopigments, or flavins as the responsible for intracellular autofluorescence (AF) detected in epithelial cancer stem cells when exciting at 480-490 nm. Evidence was provided leading to ascribe AF emission to flavins accumulating in cytoplasmic structures, bounded to membranes and bearing ATP-dependent ABCG2 transporters. Flavins were then proposed as an intrinsic AF biomarker of cancer stem cells, with advantageous implications on cell invasiveness and chemoresistance investigations. It is however worth recalling the huge amount of literature on flavins and NAD(P)H as AF biomarkers of cell energetic metabolism and redox state, an aspect that should not be overlooked in the renewed course to extend the potential of flavins as AF biomarkers, entailing also a recent proposal of Flavin-based fluorescent proteins as substitutes of Green fluorescent proteins.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_328,

title = {A dual role for beta1 integrin in an in vitro Streptococcus mitis/human gingival fibroblasts co-culture model in response to TEGDMA.},

author = {{Di Nisio C} and {De Colli M} and {di Giacomo V} and Rapino M and {Di Valerio V} and Marconi GD and Gallorini M and {Di Giulio} M and Cataldi A and Zara S},

doi = {10.1111/iej.12379},

year  = {2015},

date = {2015-02-19},

journal = {International Endodontic Journal},

volume = {48},

number = {9},

abstract = {AIM: To evaluate the effect of TEGDMA on human gingival fibroblasts (HGFs) in vitro co-cultured with Streptococcus mitis, focusing on the signalling pathways underlying cell tissue remodelling and inflammatory response processes. METHODOLOGY:β1 integrin expression was evaluated by means of imaging flow cytometry. The Western blot technique was used to investigate the expression of protein kinase C (PKC), extracellular signal-regulated kinase (ERK), matrix metalloproteinase 9 (MMP9) and 3 (MMP3). RT-PCR was performed to quantify nuclear factor-kb subunits (Nf-kb1, ReLa), IkB kinase β (IkBkB), cyclooxygenase II (COX-2) and tumour necrosis factor-α (TNF-α) mRNA levels. Statistical analysis was performed using the analysis of variance (anova). RESULTS:

When HGFs are co-cultured with S. mitis, β1 integrin intensity, phosphorylated PKC (p-PKC), activated ERK (p-ERK), IkBkB mRNA level and MMP9 expression increased (for all molecules P < 0.05 HGFs versus HGFs co-cultured with S. mitis). A higher level of MMP3 in HGFs treated with TEGDMA was recorded (P < 0.05 HGFs versus HGFs exposed to TEGDMA). COX-2 inflammatory factor mRNA level appeared higher in HGFs exposed to 1 mmol L(-1) TEGDMA (P < 0.01 HGFs versus HGFs exposed to TEGDMA), whereas TNF-α gene expression was higher in HGFs co-cultured with S. mitis (P < 0.05 HGFs versus HGFs co-cultured with S. mitis).CONCLUSIONS: beta1 integrin triggered the signalling pathway, transduced by p-PKCα and involving ERK 1 and 2 and MMPs. This pathway resulted in an unbalanced equilibrium in tissue remodelling process, along with inflammatory response when HGFs are exposed to bacteria or biomaterial alone. On the contrary, the TEGDMA/S. mitis combination restored the balance between extracellular matrix deposition and degradation and prevented an inflammatory response. 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_342,

title = {Causes of genome instability: the effect of low dose chemical exposures in modern society.},

author = {Langie SA and Koppen G and Desaulniers D and Al-Mulla F and Al-Temaimi R and Amedei A and Azqueta A and Bisson WH and Brown D and Brunborg G and Charles AK and Chen T and Colacci A and Darroudi F and Forte S and Gonzalez L and Hamid RA and Knudsen LE and Leyns L and {Lopez de Cerain Salsamendi A} and Memeo L and Mondello C and Mothersill C and Olsen AK and Pavanello S and Raju J and Rojas E and Roy R and Ryan E and Ostrosky-Wegman P and Salem HK and Scovassi AI and Singh N and Vaccari M and {Van Schooten FJ} and Valverde M and Woodrick J and Zhang L and van Larebeke N and Kirsch-Volders M and Collins AR},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S61/311923},

doi = {10.1093/carcin/bgv031},

year  = {2015},

date = {2015-02-19},

urldate = {2015-02-19},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S61-88},

abstract = {Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis.The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_372,

title = {Human nuclear ARGONAUTE 2 interacts in vivo only with small RNAs and not with DNA.},

author = {Gioia U and {d'Adda di Fagagna F}},

url = {https://www.tandfonline.com/doi/full/10.1080/15384101.2015.1044171},

doi = {10.1080/15384101.2015.1044171},

year  = {2015},

date = {2015-02-19},

journal = {Cell Cycle},

volume = {14},

number = {13},

pages = {2001-2002},

abstract = {Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology. The Author 2015. Published by Oxford University Press.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_327,

title = {A DDB2 mutant protein unable to interact with PCNA promotes cell cycle progression of human transformed embryonic kidney cells.},

author = {Perucca P and Sommatis S and Mocchi R and Prosperi E and Stivala LA and Cazzalini O},

url = {https://www.tandfonline.com/doi/full/10.1080/15384101.2015.1120921},

doi = {10.1080/15384101.2015.1120921},

year  = {2015},

date = {2015-02-18},

journal = {Cell Cycle},

volume = {14},

number = {24},

pages = {3920-3928},

abstract = {DNA damage binding protein 2 (DDB2) is a protein involved in the early step of DNA damage recognition of the nucleotide excision repair (NER) process. Recently, it has been suggested that DDB2 may play a role in DNA replication, based on its ability to promote cell proliferation. We have previously shown that DDB2 binds PCNA during NER, but also in the absence of DNA damage; however, whether and how this interaction influences cell proliferation is not known. In this study, we have addressed this question by using HEK293 cell clones stably expressing DDB2(Wt) protein, or a mutant form (DDB2(Mut)) unable to interact with PCNA. We report that overexpression of the DDB2(Mut) protein provides a proliferative advantage over the wild type form, by influencing cell cycle progression. In particular, an increase in the number of S-phase cells, together with a reduction in p21(CDKN1A) protein level, and a shorter cell cycle length, has been observed in the DDB2(Mut) cells. These results suggest that DDB2 influences cell cycle progression thanks to its interaction with PCNA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_339,

title = {Autophagy in acute leukemias: A double-edged sword with important therapeutic implications},

author = {Evangelisti C and Evangelisti C and Chiarini F and Lonetti A and Buontempo F and Neri LM and McCubrey JA and Martelli AM},

url = {https://www.sciencedirect.com/science/article/pii/S0167488914003486?via%3Dihub},

doi = {10.1016/j.bbamcr.2014.09.023},

year  = {2015},

date = {2015-02-18},

journal = {Biochimica et Biophysica Acta (BBA) - Molecular Cell Research},

volume = {1853},

number = {1},

pages = {14-26},

abstract = {Macroautophagy, usually referred to as autophagy, is a degradative pathway wherein cytoplasmatic components such as aggregated/misfolded proteins and organelles are engulfed within double-membrane vesicles (autophagosomes) and then delivered to lysosomes for degradation. Autophagy plays an important role in the regulation of numerous physiological functions, including hematopoiesis, through elimination of aggregated/misfolded proteins, and damaged/superfluous organelles. The catabolic products of autophagy (amino acids, fatty acids, nucleotides) are released into the cytosol from autophagolysosomes and recycled into bio-energetic pathways. Therefore, autophagy allows cells to survive starvation and other unfavorable conditions, including hypoxia, heat shock, and microbial pathogens. Nevertheless, depending upon the cell context and functional status, autophagy can also serve as a death mechanism. The cohort of proteins that constitute the autophagy machinery function in a complex, multistep biochemical pathway which has been partially identified over the past decade. Dysregulation of autophagy may contribute to the development of several disorders, including acute leukemias. In this kind of hematologic malignancies, autophagy can either act as a chemo-resistance mechanism or have tumor suppressive functions, depending on the context. Therefore, strategies exploiting autophagy, either for activating or inhibiting it, could find a broad application for innovative treatment of acute leukemias and could significantly contribute to improved clinical outcomes. These aspects are discussed here after a brief introduction to the autophagic molecular machinery and its roles in hematopoiesis.Copyright  2014 Elsevier B.V. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_404,

title = {RNA-processing proteins regulate Mec1/ATR activation by promoting generation of RPA-coated ssDNA.},

author = {Manfrini N and Trovesi C and Wery M and Martina M and Cesena D and Descrimes M and Morillon A and {d'Adda di Fagagna F} and Longhese MP},

url = {https://www.embopress.org/doi/full/10.15252/embr.201439458},

doi = {10.15252/embr.201439458},

year  = {2015},

date = {2015-02-18},

journal = {Embo Reports},

volume = {16},

number = {2},

pages = {221-231},

abstract = {Eukaryotic cells respond to DNA double-strand breaks (DSBs) by activating a checkpoint that depends on the protein kinases Tel1/ATM and Mec1/ATR. Mec1/ATR is activated by RPA-coated single-stranded DNA (ssDNA), which arises upon nucleolytic degradation (resection) of the DSB. Emerging evidences indicate that RNA-processing factors play critical, yet poorly understood, roles in genomic stability. Here, we provide evidence that the Saccharomyces cerevisiae RNA decay factors Xrn1, Rrp6 and Trf4 regulate Mec1/ATR activation by promoting generation of RPA-coated ssDNA. The lack of Xrn1 inhibits ssDNA generation at the DSB by preventing the loading of the MRX complex. By contrast, DSB resection is not affected in the absence of Rrp6 or Trf4, but their lack impairs the recruitment of RPA, and therefore of Mec1, to the DSB. Rrp6 and Trf4 inactivation affects neither Rad51/Rad52 association nor DSB repair by homologous recombination (HR), suggesting that full Mec1 activation requires higher amount of RPA-coated ssDNA than HR-mediated repair. Noteworthy, deep transcriptome analyses do not identify common misregulated gene expression that could explain the observed phenotypes. Our results provide a novel link between RNA processing and genome stability. 2014 The Authors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_329,

title = {A novel X-linked trichothiodystrophy associated with a nonsense mutation in RNF113A.},

author = {Corbett MA and Dudding-Byth T and Crock PA and Botta E and Christie LM and Nardo T and Caligiuri G and Hobson L and Boyle J and Mansour A and Friend KL and Crawford J and Jackson G and Vandeleur L and Hackett A and Tarpey P and Stratton MR and Turner G and Gécz J and Field M},

url = {https://jmg.bmj.com/content/52/4/269.long},

doi = {10.1136/jmedgenet-2014-102418},

year  = {2015},

date = {2015-02-17},

journal = {Journal of Medical Genetics},

volume = {52},

number = {4},

pages = {269-274},

abstract = {Trichothiodystrophy (TTD) is a group of rare autosomal recessive disorders that variably affect a wide range of organs derived from the neuroectoderm. The key diagnostic feature is sparse, brittle, sulfur deficient hair that has a 'tiger-tail' banding pattern under polarising light microscopy. PATIENTS AND METHODS: We describe two male cousins affected by TTD associated with microcephaly, profound intellectual disability, sparse brittle hair, aged appearance, short stature, facial dysmorphism, seizures, an immunoglobulin deficiency, multiple endocrine abnormalities, cerebellar hypoplasia and partial absence of the corpus callosum, in the absence of cellular photosensitivity and ichthyosis. Obligate female carriers showed 100% skewed X-chromosome inactivation. Linkage analysis and Sanger sequencing of 737 X-chromosome exons and whole exome sequencing was used to find the responsible gene and mutation. RESULTS: Linkage analysis localised the disease allele to a 7.75 Mb interval from Xq23-q25. We identified a nonsense mutation in the highly conserved RNF113A gene (c.901 C>T, p.Q301*). The mutation segregated with the disease in the family and was not observed in over 100,000 control X chromosomes. The mutation markedly reduced RNF113A protein expression in extracts from lymphoblastoid cell lines derived from the affected individuals. CONCLUSIONS: The association of RNF113A mutation with non-photosensitive TTD identifies a new locus for these disorders on the X chromosome. The extended phenotype within this family includes panhypopituitarism, cutis marmorata and congenital short oesophagus. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_331,

title = {An Association Rule Mining Approach to Discover lncRNAs Expression Patterns in Cancer Datasets.},

author = {Cremaschi P and Carriero R and Astrologo S and Colì C and Lisa A and Parolo S and Bione S},

url = {10.1155/2015/146250},

doi = {10.1155/2015/146250},

year  = {2015},

date = {2015-02-14},

journal = {Biomed Research International},

volume = {2015},

pages = {146250},

abstract = {In the past few years, the role of long noncoding RNAs (lncRNAs) in tumor development and progression has been disclosed although their mechanisms of action remain to be elucidated. An important contribution to the comprehension of lncRNAs biology in cancer could be obtained through the integrated analysis of multiple expression datasets. However, the growing availability of public datasets requires new data mining techniques to integrate and describe relationship among data. In this perspective, we explored the powerness of the Association Rule Mining (ARM) approach in gene expression data analysis. By the ARM method, we performed a meta-analysis of cancer-related microarray data which allowed us to identify and characterize a set of ten lncRNAs simultaneously altered in different brain tumor datasets. The expression profiles of the ten lncRNAs appeared to be sufficient to distinguish between cancer and normal tissues. A further characterization of this lncRNAs signature through a comodulation expression analysis suggested that biological processes specific of the nervous system could be compromised.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_340,

title = {Biology of the cell cycle inhibitor p21CDKN1A: molecular mechanisms and relevance in chemical toxicology.},

author = {Dutto I and Tillhon M and Cazzalini O and Stivala LA and Prosperi E},

url = {https://link.springer.com/article/10.1007/s00204-014-1430-4},

doi = { 10.1007/s00204-014-1430-4},

year  = {2015},

date = {2015-02-14},

journal = {Archives of Toxicology},

volume = {89},

pages = {155–178},

abstract = {The cell cycle inhibitor p21(CDKN1A) is a protein playing multiple roles not only in the DNA damage response, but also in many cellular processes during unperturbed cell growth. The main, well-known function of p21 is to arrest cell cycle progression by inhibiting the activity of cyclin-dependent kinases. In addition, p21 is involved in the regulation of transcription, apoptosis, DNA repair, as well as cell motility. However, p21 appears to a have a dual-face behavior because, in addition to its tumor suppressor functions, it may act as an oncogene, depending on the cell type and on the cellular localization. As a biomarker of the cell response to different toxic stimuli, p21 expression and functions have been analyzed in an impressive number of studies investigating the activity of several types of chemicals, in order to determine their possible harmful effects on human cells. Here, we review these studies in order to highlight the different roles p21 may play in the cell response to chemical exposure and to better evaluate the information provided by this biomarker.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_325,

title = {A basal level of DNA damage and telomere deprotection increases the sensitivity of cancer cells to G-quadruplex interactive compounds.},

author = {Salvati E and Rizzo A and Iachettini S and Zizza P and Cingolani C and D'Angelo C and Porru M and Mondello C and Aiello A and Farsetti A and Gilson E and Leonetti C and Biroccio A},

url = {https://academic.oup.com/nar/article/43/3/1759/2411627},

doi = {10.1093/nar/gkv006},

year  = {2015},

date = {2015-02-13},

journal = {Nucleic Acids Research},

volume = {43},

number = {3},

pages = {1759-1769},

abstract = {Here, with the aim of obtaining insight into the intriguing selectivity of G-quadruplex (G4) ligands toward cancer compared to normal cells, a genetically controlled system of progressive transformation in human BJ fibroblasts was analyzed. Among the different comparative evaluations, we found a progressive increase of DNA damage response (DDR) markers throughout the genome from normal toward immortalized and transformed cells. More interestingly, sensitivity to G4 ligands strongly correlated with the presence of a basal level of DNA damage, including at the telomeres, where the chromosome ends were exposed to the DDR without concurrent induction of DNA repair activity, as revealed by the lack of 53BP1 recruitment and telomere aberrations. The link between telomere uncapping and the response to G4 stabilization was directly assessed by showing that a partial TRF2 depletion, causing a basal level of telomere localized DDR, rendered telomerized fibroblasts prone to G4-induced telomere damage and anti-proliferative defects. Taken together these data strongly indicate that the presence of a basal level of telomere-associated DDR is a determinant of susceptibility to G4 stabilization. The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_337,

title = {Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.},

author = {{Goodson WH 3d} and Lowe L and Carpenter DO and Gilbertson M and Manaf Ali A and {Lopez de Cerain Salsamendi A} and Lasfar A and Carnero A and Azqueta A and Amedei A and Charles AK and Collins AR and Ward A and Salzberg AC and Colacci A and Olsen AK and Berg A and Barclay BJ and Zhou BP and Blanco-Aparicio C and Baglole CJ and Dong C and Mondello C and Hsu CW and Naus CC and Yedjou C and Curran CS and Laird DW and Koch DC and Carlin DJ and Felsher DW and Roy D and Brown DG and Ratovitski E and Ryan EP and Corsini E and Rojas E and Moon EY and Laconi E and Marongiu F and Al-Mulla F and Chiaradonna F and Darroudi F and Martin FL and Van Schooten FJ and Goldberg GS and Wagemaker G and Nangami G and Calaf GM and Williams G and Wolf GT and Koppen G and Brunborg G and Kim Lyerly H and Krishnan H and Ab Hamid H and Yasaei H and Sone H and Kondoh H and Salem HK and Hsu HY and Park HH and Koturbash I and Miousse IR and Scovassi AI and Klaunig JE and Vondráček J and Raju J and Roman J and Wise JP Sr and Whitfield JR and Woodrick J and Christopher JA and Ochieng J and Martinez-Leal JF and Weisz J and Kravchenko J and Sun J and Prudhomme KR and Narayanan KB and Cohen-Solal KA and Moorwood K and Gonzalez L and Soucek L and Jian L and D'Abronzo LS and Lin LT and Li L and Gulliver L and McCawley LJ and Memeo L and Vermeulen L and Leyns L and Zhang L and Valverde M and Khatami M and Romano MF and Chapellier M and Williams MA and Wade M and Manjili MH and Lleonart M and Xia M and Gonzalez MJ and Karamouzis MV and Kirsch-Volders M and Vaccari M and Kuemmerle NB and Singh N and Cruickshanks N and Kleinstreuer N and van Larebeke N and Ahmed N and Ogunkua O and Krishnakumar PK and Vadgama P and Marignani PA and Ghosh PM and Ostrosky-Wegman P and Thompson P and Dent P and Heneberg P and Darbre P and Sing Leung P and Nangia-Makker P and Cheng QS and Robey RB and Al-Temaimi R and Roy R and Andrade-Vieira R and Sinha RK and Mehta R and Vento R and Di Fiore R and Ponce-Cusi R and Dornetshuber-Fleiss R and Nahta R and Castellino RC and Palorini R and Abd Hamid R and Langie SA and Eltom S and Brooks SA and Ryeom S and Wise SS and Bay SN and Harris SA and Papagerakis S and Romano S and Pavanello S and Eriksson S and Forte S and Casey SC and Luanpitpong S and Lee TJ and Otsuki T and Chen T and Massfelder T and Sanderson T and Guarnieri T and Hultman T and Dormoy V and Odero-Marah V and Sabbisetti V and Maguer-Satta V and Rathmell WK and Engström W and Decker WK and Bisson WH and Rojanasakul Y and Luqmani Y and Chen Z and Hu Z},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S254/316933},

doi = {10.1093/carcin/bgv039},

year  = {2015},

date = {2015-02-13},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S254-96},

abstract = {Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology. The Author 2015. Published by Oxford University Press.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_354,

title = {Disruptive chemicals, senescence and immortality.},

author = {Carnero A and Blanco-Aparicio C and Kondoh H and Lleonart ME and Martinez-Leal JF and Mondello C and Scovassi AI and Bisson WH and Amedei A and Roy R and Woodrick J and Colacci A and Vaccari M and Raju J and Al-Mulla F and Al-Temaimi R and Salem HK and Memeo L and Forte S and Singh N and Hamid RA and Ryan EP and Brown DG and Wise JP Sr and Wise SS and Yasaei H},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S19/311053},

doi = {10.1093/carcin/bgv029},

year  = {2015},

date = {2015-02-13},

urldate = {2015-02-13},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S19-37},

abstract = {Carcinogenesis is thought to be a multistep process, with clonal evolution playing a central role in the process. Clonal evolution involves the repeated 'selection and succession' of rare variant cells that acquire a growth advantage over the remaining cell population through the acquisition of 'driver mutations' enabling a selective advantage in a particular micro-environment. Clonal selection is the driving force behind tumorigenesis and possesses three basic requirements: (i) effective competitive proliferation of the variant clone when compared with its neighboring cells, (ii) acquisition of an indefinite capacity for self-renewal, and (iii) establishment of sufficiently high levels of genetic and epigenetic variability to permit the emergence of rare variants. However, several questions regarding the process of clonal evolution remain. Which cellular processes initiate carcinogenesis in the first place? To what extent are environmental carcinogens responsible for the initiation of clonal evolution? What are the roles of genotoxic and non-genotoxic carcinogens in carcinogenesis? What are the underlying mechanisms responsible for chemical carcinogen-induced cellular immortality? Here, we explore the possible mechanisms of cellular immortalization, the contribution of immortalization to tumorigenesis and the mechanisms by which chemical carcinogens may contribute to these processes. The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_358,

title = {Effect of new berberine derivatives on colon cancer cells.},

author = {Guamán Ortiz LM and Croce AL and Aredia F and Sapienza S and Fiorillo G and Syeda TM and Buzzetti F and Lombardi P and Scovassi AI},

url = {https://academic.oup.com/abbs/article/47/10/824/1754528},

doi = {10.1093/abbs/gmv077},

year  = {2015},

date = {2015-02-13},

journal = {Acta Biochimica et Biophysica Sinica},

volume = {47},

number = {10},

pages = {824-33},

abstract = {The natural alkaloid berberine has been recently described as a promising anticancer drug. In order to improve its efficacy and bioavailability, several derivatives have been designed and synthesized and found to be even more potent than the lead compound. Among the series of berberine derivatives we have produced, five compounds were identified to be able to heavily affect the proliferation of human HCT116 and SW613-B3 colon carcinoma cell lines. Remarkably, these active compounds exhibit high fluorescence emission property and ability to induce autophagy. The Author 2015. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_373,

title = {Improving clinical trial design for Duchenne muscular dystrophy.},

author = {Merlini L and Sabatelli P},

url = {https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-015-0408-z},

doi = {10.1186/s12883-015-0408-z},

year  = {2015},

date = {2015-02-13},

journal = {BMC Neurology},

volume = {15},

pages = {153},

abstract = {BACKGROUND: Currently, the most promising therapies for Duchenne muscular dystrophy (DMD) are exon skipping and stop codon read-through, two strategies aimed at restoring the expression of dystrophin. A phase 3 clinical trial with drisapersen, a drug designed to induce exon 51-skipping, has failed to show significant improvement of the primary outcome measure, the six-minute walk test. DISCUSSION: Here, we review some key points that should be considered when designing clinical trials for these new therapies. First, younger patients have more functional abilities and more muscle fibers to preserve than older patients and therefore are better subjects for trials designed to demonstrate the success of new treatments. Second, the inclusion of patients on corticosteroids both in the treatment and placebo groups is of concern because the positive effect of corticosteroids might mask the effect of the treatment being tested. Additionally, the reasonable expectation from these therapies is the slowing of disease progression rather than improvement. Therefore, the appropriate clinical endpoints are the prolongation of the ability to stand from the floor, climb stairs, and walk, not an increase in muscle strength or function. Hence, the time frames for the detection of new dystrophin, which occurs within months, and the ability to demonstrate a slowing of disease progression, which requires years, are strikingly different. Finally, placebo-controlled trials are difficult to manage if years of blindness are required to demonstrate a slowing of disease progression. Thus, accelerated/conditional approval for new therapies should be based on surrogate biochemical outcomes: the demonstration of de novo dystrophin production and of its beneficial effect on the functional recovery of muscle fiber. These data suggest that clinical trials for DMD patients must be adapted to the particular characteristics of the disease in order to demonstrate the expected positive effect of new treatments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_324,

title = {3D silicon microstructures: a new tool for evaluating biological aggressiveness of tumour cells.},

author = {Mazzini G and Carpignano F and Surdo S and Aredia F and Torchio M and Erba E and Danova M and Scovassi AI and Barillaro G and Merlo S},

url = {https://ieeexplore.ieee.org/document/7239627},

doi = {10.1109/TNB.2015.2476351},

year  = {2015},

date = {2015-02-12},

urldate = {2015-02-12},

journal = {IEEE Trans Nanobioscience },

volume = {14},

number = {7},

pages = {797-805},

abstract = {In this work, silicon micromachined structures (SMS), consisting of arrays of 3-μm-thick silicon walls separated by 50-μm-deep, 5-μm-wide gaps, were applied to investigate the behavior of eight tumor cell lines, with different origins and biological aggressiveness, in a three-dimensional (3D) microenvironment. Several cell culture experiments were performed on 3D-SMS and cells grown on silicon were stained for fluorescence microscopy analyses. Most of the tumor cells lines recognized in the literature as highly aggressive (OVCAR-5, A375, MDA-MB-231, and RPMI-7951) exhibited a great ability to enter and colonize the narrow deep gaps of the SMS, whereas less aggressive cell lines (OVCAR-3, Capan-1, MCF7, and NCI-H2126) demonstrated less penetration capability and tended to remain on top of the SMS. Quantitative image analyses of several fluorescence microscopy fields of silicon samples were performed for automatic cell recognition and count, in order to quantify the fraction of cells inside the gaps, with respect to the total number of cells in the examined field. Our results show that higher fractions of cells in the gaps are obtained with more aggressive cell lines, thus supporting in a quantitative way the observation that the behavior of tumor cells on the 3D-SMS depends on their aggressiveness level.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_332,

title = {An integrated optofluidic device for single-cell sorting driven by mechanical properties.},

author = {Yang T and Paiè P and Nava G and Bragheri F and {Martinez Vazquez R} and Minzioni P and Veglione M and Di Tano M and Mondello C and Osellame R and Cristiani I},

url = {https://pubs.rsc.org/en/content/articlelanding/2015/LC/C4LC01496K#!divAbstract},

doi = {10.1039/c4lc01496k},

year  = {2015},

date = {2015-02-12},

journal = {Lab on a Chip},

volume = {15},

number = {5},

pages = {1262-1266},

abstract = {We present a novel optofluidic device for real-time sorting on the basis of cell mechanical properties, measured by optical stretching. The whole mechanism, based on optical forces, does not hamper the viability of the tested cells, which can be used for further analysis. The device effectiveness is demonstrated by extracting a sample population enriched with highly metastatic cells from a heterogeneous cell mixture.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_334,

title = {An overview of new translational, clinical and therapeutic perspectives in laminopathies and other nuclear envelope-related diseases.},

author = {{De Sandre-Giovannoli A} and Levy N Ben Yaou R and Leturcq F Lattanzi G and Bonne G},

url = {https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-10-S2-I1#citeas},

doi = {10.1186/1750-1172-10-S2-I1},

year  = {2015},

date = {2015-02-12},

journal = {Orphanet Journal of Rare Diseases},

volume = {10},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_341,

title = {Carvacrol codrugs: a new approach in the antimicrobial plan.},

author = {Cacciatore I and Di Giulio M and Fornasari E and Di Stefano A and Cerasa LS and Marinelli L and Turkez H and Di Campli E and Di Bartolomeo S and Robuffo I and Cellini L},

url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120937},

doi = {10.1371/journal.pone.0120937},

year  = {2015},

date = {2015-02-12},

journal = {Plos One},

volume = {10},

number = {4},

pages = {e0120937},

abstract = {OBJECTIVE: The increasing prevalence of antibiotic-resistant bacterial infections led to identify alternative strategies for a novel therapeutic approach. In this study, we synthesized ten carvacrol codrugs - obtained linking the carvacrol hydroxyl group to the carboxyl moiety of sulphur-containing amino acids via an ester bond - to develop novel compounds with improved antimicrobial and antibiofilm activities and reduced toxicity respect to carvacrol alone. METHOD: All carvacrol codrugs were screened against a representative panel of Gram positive (S. aureus and S. epidermidis), Gram negative (E. coli and P. aeruginosa) bacterial strains and C. albicans, using broth microdilution assays. FINDINGS: Results showed that carvacrol codrug 4 possesses the most notable enhancement in the anti-bacterial activity displaying MIC and MBC values equal to 2.5 mg/mL for all bacterial strains, except for P. aeruginosa ATCC 9027 (MIC and MBC values equal to 5 mg/mL and 10 mg/mL, respectively). All carvacrol codrugs 1-10 revealed good antifungal activity against C. albicans ATCC 10231. The cytotoxicity assay showed that the novel carvacrol codrugs did not produce human blood hemolysis at their MIC values except for codrugs 8 and 9. In particular, deepened experiments performed on carvacrol codrug 4 showed an interesting antimicrobial effect on the mature biofilm produced by E. coli ATCC 8739, respect to the carvacrol alone. The antimicrobial effects of carvacrol codrug 4 were also analyzed by TEM evidencing morphological modifications in S. aureus, E. coli, and C. albican CONCLUSION: The current study presents an insight into the use of codrug strategy for developing carvacrol derivatives with antibacterial and antibiofilm potentials, and reduced cytotoxicity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_344,

title = {Chemical compounds from anthropogenic environment and immune evasion mechanisms: potential interactions.},

author = {Kravchenko J and Corsini E and Williams MA and Decker W and Manjili MH and Otsuki T and Singh N and Al-Mulla F and Al-Temaimi R and Amedei A and Colacci AM and Vaccari M and Mondello C and Scovassi AI and Raju J and Hamid RA and Memeo L and Forte S and Roy R and Woodrick J and Salem HK and Ryan EP and Brown DG and Bisson WH and Lowe L and Lyerly HK},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S111/313145},

doi = {10.1093/carcin/bgv033},

year  = {2015},

date = {2015-02-12},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S111-27},

abstract = {An increasing number of studies suggest an important role of host immunity as a barrier to tumor formation and progression. Complex mechanisms and multiple pathways are involved in evading innate and adaptive immune responses, with a broad spectrum of chemicals displaying the potential to adversely influence immunosurveillance. The evaluation of the cumulative effects of low-dose exposures from the occupational and natural environment, especially if multiple chemicals target the same gene(s) or pathway(s), is a challenge. We reviewed common environmental chemicals and discussed their potential effects on immunosurveillance. Our overarching objective was to review related signaling pathways influencing immune surveillance such as the pathways involving PI3K/Akt, chemokines, TGF-beta, FAK, IGF-1, HIF-1alpha, IL-6, IL-1alpha, CTLA-4 and PD-1/PDL-1 could individually or collectively impact immunosurveillance. A number of chemicals that are common in the anthropogenic environment such as fungicides (maneb, fluoxastrobin and pyroclostrobin), herbicides (atrazine), insecticides (pyridaben and azamethiphos), the components of personal care products (triclosan and bisphenol A) and diethylhexylphthalate with pathways critical to tumor immunosurveillance. At this time, these chemicals are not recognized as human carcinogens; however, it is known that they these chemicalscan simultaneously persist in the environment and appear to have some potential interfere with the host immune response, therefore potentially contributing to promotion interacting with of immune evasion mechanisms, and promoting subsequent tumor growth and progression. The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_347,

title = {Circulating endothelial cells and their subpopulations: role as predictive biomarkers in antiangiogenic therapy for colorectal cancer.},

author = {Manzoni M and Comolli G and Torchio M and Mazzini G and Danova M},

url = {https://www.sciencedirect.com/science/article/pii/S1533002814001339?via%3Dihub},

doi = {10.1016/j.clcc.2014.12.002},

year  = {2015},

date = {2015-02-12},

journal = {Clinical Colorectal Cancer},

volume = {14},

number = {1},

pages = {11-17},

abstract = {Several anticancer therapies have been developed to block angiogenesis, a key mechanism in tumor growth and metastasis. The predominantly cytostatic action of these compounds makes an assessment of their clinical activities inadequate if based only on the reduction of the tumor dimensions, as this may not reflect their true biologic efficacy. Thus, it is crucial to identify biomarkers that permit the recognition of potentially responsive subjects and to spare toxicity in those who are unlikely to benefit from treatment. Circulating endothelial cells (CECs) have been recently indicated as potential surrogate biomarkers of angiogenesis in several types of cancer. The possibility of rapidly quantifying these cells represents a promising tool for monitoring the clinical outcome of tumors with the potential to assess response to various treatments. However, the identification and quantification of CECs is technically difficult and not well standardized. A variety of methods to detect CECs in patients with solid tumors have been used; these are based on different technical approaches, combinations of surface markers, sample handling, and staining protocols. With an expanding interest in the field of potential clinical applications for CECs in oncology, the development of standardized protocols for analysis is mandatory. The aim of this review was to critically summarize the available data concerning the clinical value of CECs and their subpopulations as biomarkers of antiangiogenic therapy in patients with metastatic colorectal cancer. Copyright 2015 Elsevier Inc. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_348,

title = {Combining X-ray Crystallography and Molecular Modeling toward the Optimization of Pyrazolo[3,4-d]pyrimidines as Potent c-Src Inhibitors Active in Vivo against Neuroblastoma.},

author = {Tintori C and Fallacara AL and Radi M and Zamperini C and Dreassi E and Crespan E and Maga G and Schenone S and Musumeci F and Brullo C and Richters A and Gasparrini F and Angelucci A and Festuccia C and {Delle Monache S} and Rauh D and Botta M},

url = {https://pubs.acs.org/doi/10.1021/jm5013159},

doi = {10.1021/jm5013159},

year  = {2015},

date = {2015-02-12},

journal = {Journal of Medicinal Chemistry},

volume = {58},

number = {1},

pages = {347-361},

abstract = {c-Src is a tyrosine kinase belonging to the Src-family kinases. It is overexpressed and/or hyperactivated in a variety of cancer cells, thus its inhibition has been predicted to have therapeutic effects in solid tumors. Recently, the pyrazolo[3,4-d]pyrimidine 3 was reported as a dual c-Src/Abl inhibitor. Herein we describe a multidisciplinary drug discovery approach for the optimization of the lead 3 against c-Src. Starting from the X-ray crystal structure of c-Src in complex with 3, Monte Carlo free energy perturbation calculations were applied to guide the design of c-Src inhibitors with improved activities. As a result, the introduction of a meta hydroxyl group on the C4 anilino ring was computed to be particularly favorable. The potency of the synthesized inhibitors was increased with respect to the starting lead 3. The best identified compounds were also found active in the inhibition of neuroblastoma cell proliferation. Furthermore, compound 29 also showed in vivo activity in xenograft model using SH-SY5Y cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_352,

title = {Defective DNA repair and increased chromatin binding of DNA repair factors in Down syndrome fibroblasts.},

author = {Necchi D and Pinto A and Tillhon M and Dutto I and Serafini MM and Lanni C and Govoni S and Racchi M and Prosperi E},

url = {https://www.sciencedirect.com/science/article/pii/S0027510715300282?via%3Dihub},

doi = {10.1016/j.mrfmmm.2015.07.009},

year  = {2015},

date = {2015-02-12},

journal = {Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis},

volume = {780},

pages = {15-23},

abstract = {Down syndrome (DS) is characterized by genetic instability, neurodegeneration, and premature aging. However, the molecular mechanisms leading to this phenotype are not yet well understood. Here, we report that DS fibroblasts from both fetal and adult donors show the presence of oxidative DNA base damage, such as dihydro-8-oxoguanine (8-oxodG), and activation of a DNA damage response (DDR), already during unperturbed growth conditions. DDR with checkpoint activation was indicated by histone H2AX and Chk2 protein phosphorylation, and by increased p53 protein levels. In addition, both fetal and adult DS fibroblasts were more sensitive to oxidative DNA damage induced by potassium bromate, and were defective in the removal of 8-oxodG, as compared with age-matched cells from control healthy donors. The analysis of core proteins participating in base excision repair (BER), such as XRCC1 and DNA polymerase beta, showed that higher amounts of these factors were bound to chromatin in DS than in control cells, even in the absence of DNA damage. These findings occurred in concomitance with increased levels of phosphorylated XRCC1 detected in DS cells. These results indicate that DS cells exhibit a BER deficiency, which is associated with prolonged chromatin association of core BER factors. Copyright 2015 Elsevier B.V. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_353,

title = {Discovery of Multitarget Antivirals Acting on Both the Dengue Virus NS5-NS3 Interaction and the Host Src/Fyn Kinases.},

author = {Vincetti P and Caporuscio F and Kaptein S and Gioiello A and Mancino V and Suzuki Y and Yamamoto N and Crespan E and Lossani A and Maga G and Rastelli G and Castagnolo D and Neyts J and Leyssen P and Costantino G and Radi M},

url = {https://pubs.acs.org/doi/10.1021/acs.jmedchem.5b00108},

doi = {10.1021/acs.jmedchem.5b00108},

year  = {2015},

date = {2015-02-12},

journal = {Journal of Medicinal Chemistry},

volume = {58},

number = {12},

abstract = {This study describes the discovery of novel dengue virus inhibitors targeting both a crucial viral protein-protein interaction and an essential host cell factor as a strategy to reduce the emergence of drug resistance. Starting from known c-Src inhibitors, a virtual screening was performed to identify molecules able to interact with a recently discovered allosteric pocket on the dengue virus NS5 polymerase. The selection of cheap-to-produce scaffolds and the exploration of the biologically relevant chemical space around them suggested promising candidates for chemical synthesis. A series of purines emerged as the most interesting candidates able to inhibit virus replication at low micromolar concentrations with no significant toxicity to the host cell. Among the identified antivirals, compound 16i proved to be 10 times more potent than ribavirin, showed a better selectivity index and represents the first-in-class DENV-NS5 allosteric inhibitor able to target both the virus NS5-NS3 interaction and the host kinases c-Src/Fyn.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_356,

title = {Dissecting metabolic syndrome components: data from an epidemiologic survey in a genetic isolate.},

author = {Biino G and Concas MP and Cena H and Parracciani D and Vaccargiu S and Cosso M and Marras F and D'Esposito V and Beguinot F and Pirastu M},

url = {https://springerplus.springeropen.com/articles/10.1186/s40064-015-1049-9},

doi = {10.1186/s40064-015-1049-9.},

year  = {2015},

date = {2015-02-12},

journal = {Springerplus},

volume = {4},

pages = {324},

abstract = {The metabolic syndrome (MetS) is a large-scale and expanding public-health and clinical threat worldwide. We investigated the determinants of MetS, assessed its prevalence and components and, estimated their genetic contribution, taking advantage of the special characteristics of Sardinian isolated populations. Inhabitants of 10 villages in Ogliastra region participated in a cross-sectional survey in 2002-2008 (n = 9,647). Blood samples, blood pressure (BP), anthropometry and, data from a standardized interview were collected. Prevalence of MetS was estimated by the direct method of standardization. Variables associated with the MetS were identified using multilevel logistic regression. Heritability was determined using variance component models. MetS Prevalence was 19.6% (95% CI 18.9-20.4%) according to NCEP-ATPIII, 24.8% (95% CI 24.0-25.6%) according to IDF and, 29% (95% CI 28.1-29.8%) according to AHA/NHLBI harmonized criteria, ranging from 9 to 26% among villages. The most prevalent combination was BP + HDL-cholesterol (HDL) + triglycerides (TRIG) (19%), followed by BP + HDL + waist circumference (WAIST) (17%) and, BP + HDL + TRIG + WAIST (13.6%). Heritability of MetS was 48% (p = 1.62 × 10(-25)), as the two most common combinations (BP + HDL + TRIG and BP + HDL + WAIST) showed heritability of 53 and 52%, respectively. The larger genetic components of the two most frequent combinations determining MetS deserve greater investigation in order to understand the underlying mechanisms. Besides, further studies are warranted to confirm these findings both in isolated and outbred populations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_419,

title = {Whole-genome sequence-based analysis of thyroid function.},

author = {Taylor PN and Porcu E and Chew S and {et al}},

url = {https://www.nature.com/articles/ncomms6681},

doi = {10.1038/ncomms6681},

year  = {2015},

date = {2015-02-12},

journal = {Nature Communications},

volume = {6},

pages = {5681},

abstract = {Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project (N=2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF≥1%) associated with TSH and FT4 (N=16,335). For TSH, we identify a novel variant in SYN2 (MAF=23.5%, P=6.15 × 10(-9)) and a new independent variant in PDE8B (MAF=10.4%, P=5.94 × 10(-14)). For FT4, we report a low-frequency variant near B4GALT6/SLC25A52 (MAF=3.2%, P=1.27 × 10(-9)) tagging a rare TTR variant (MAF=0.4%, P=2.14 × 10(-11)). All common variants explain ≥20% of the variance in TSH and FT4. Analysis of rare variants (MAF<1%) using sequence kernel association testing reveals a novel association with FT4 in NRG1. Our results demonstrate that increased coverage in whole-genome sequence association studies identifies novel variants associated with thyroid function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_326,

title = {A Common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults.},

author = {Bouzigon E and Nadif R and Thompson EE and Concas MP and Kuldanek S and Du G and {et al} and Biino G and Dizier MH and Pin I and Matran R and Lathrop M and Pirastu M and Demenais F and Ober C},

url = {https://onlinelibrary.wiley.com/doi/full/10.1111/cea.12461},

doi = {10.1111/cea.12461},

year  = {2015},

date = {2015-02-11},

journal = {Clinical and Experimental Allergy },

volume = {45},

number = {4},

pages = {797-806},

abstract = {"BACKGROUND: Exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation in the airways and for responsiveness to corticosteroids in asthmatics. OBJECTIVE: We sought to identify in adults the genetic determinants of fractional exhaled nitric oxide (FeNO) levels and to assess whether environmental and disease-related factors influence these associations. METHODS: We performed a genome-wide association study of FeNO through meta-analysis of two independent discovery samples of European ancestry: the outbred EGEA study (French Epidemiological study on the Genetics and Environment of Asthma, N = 610 adults) and the Hutterites (N = 601 adults), a founder population living on communal farms. Replication of main findings was assessed in adults from an isolated village in Sardinia (Talana study, N = 450). We then investigated the influence of asthma, atopy and tobacco smoke exposure on these genetic associations, and whether they were also associated with FeNO values in children of the EAGLE (EArly Genetics & Lifecourse Epidemiology, N = 8858) consortium. RESULTS: We detected a common variant in RAB27A (rs2444043) associated with FeNO that reached the genome-wide significant level (P = 1.6 × 10(-7) ) in the combined discovery and replication adult data sets. This SNP belongs to member of RAS oncogene family (RAB27A) and was associated with an expression quantitative trait locus for RAB27A in lymphoblastoid cell lines from asthmatics. A second suggestive locus (rs2194437, P = 8.9 × 10(-7) ) located nearby the sodium/calcium exchanger 1 (SLC8A1) was mainly detected in atopic subjects and influenced by inhaled corticosteroid use. These two loci were not associated with childhood FeNO values. CONCLUSIONS AND CLINICAL RELEVANCE:

This study identified a common variant located in RAB27A gene influencing FeNO levels specifically in adults and with a biological relevance to the regulation of FeNO levels. This study provides new insight into the biological mechanisms underlying FeNO levels in adults.

 2014 John Wiley & Sons Ltd."},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_333,

title = {An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells.},

author = {{Martinez Vazquez R} and Nava G and Veglione M and Yang T and Bragheri F and Minzioni P and Bianchi E and Di Tano M and Chiodi I and Osellame R and Mondello C and Cristiani I},

url = {https://academic.oup.com/ib/article-abstract/7/4/477/5199149?redirectedFrom=fulltext},

doi = {10.1039/c5ib00023h},

year  = {2015},

date = {2015-02-11},

journal = {Integrative Biology},

volume = {7},

number = {4},

pages = {477-484},

abstract = {Cellular mechanical properties constitute good markers to characterize tumor cells, to study cell population heterogeneity and to highlight the effect of drug treatments. In this work, we describe the fabrication and validation of an integrated optofluidic chip capable of analyzing cellular deformability on the basis of the pressure gradient needed to push a cell through a narrow constriction. We demonstrate the ability of the chip to discriminate between tumorigenic and metastatic breast cancer cells (MCF7 and MDA-MB231) and between human melanoma cells with different metastatic potential (A375P and A375MC2). Moreover, we show that this chip allows highlighting the effect of drugs interfering with microtubule organization (paclitaxel, combretastatin A-4 and nocodazole) on cancer cells, which leads to changes in the pressure-gradient required to push cells through the constriction. Our single-cell microfluidic device for mechanical evaluation is compact and easy to use, allowing for an extensive use in different laboratory environments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_338,

title = {Assessment of an efficient xeno-free culture system for human periodontal ligament stem cells.},

author = {Trubiani O and Piattelli A and Gatta V and Marchisio M and Diomede F and D'Aurora M and Merciaro I and Pierdomenico L and Maraldi NM and Zini N},

url = {https://www.liebertpub.com/doi/full/10.1089/ten.TEC.2014.0024?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&},

doi = {10.1089/ten.TEC.2014.0024},

year  = {2015},

date = {2015-02-11},

journal = {Tissue Engineering. Part C, Methods},

volume = {21},

number = {1},

pages = {52-64},

abstract = {The possibility of transplanting adult stem cells into damaged organs has opened new prospects for the treatment of several human pathologies. The purpose of this study was to develop a culture system for the expansion and production of human Periodontal Ligament Stem Cells (hPDLSCs) using a new xeno-free media formulation and ensuring the maintenance of the stem cells features comprising the multiple passage expansion, mesengenic lineage differentiation, cellular phenotype, and genomic stability, essential elements for conforming to translation to cell therapy. Somatic stem cells were isolated from the human periodontium using a minimally invasive periodontal access flap surgery in healthy donors. Expanded hPDLSCs in a xeno-free culture showed the morphological features of stem cells, expressed the markers associated with pluripotency, and a normal karyotype. Under appropriate culture conditions, hPDLSCs presented adipogenic and osteogenic potential; indeed, a very high accumulation of lipid droplets was evident in the cytoplasm of adipogenic-induced cells, and indisputable evidence of osteogenic differentiation, investigated by transmission electron microscopy, and analyzed for gene expression analysis has been shown. Based on these data, the novel xeno-free culture method might provide the basis for Good Manufacturing Procedure culture of autologous stem cells, readily accessible from human periodontium, and can be a resource to facilitate their use in human clinical studies for potential therapeutic regeneration.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_345,

title = {Chromatin dynamics and in vitro biomarkers in laminopathies: an overview},

author = {Lattanzi G},

url = {https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-10-S2-O12},

doi = {10.1186/1750-1172-10-S2-O12},

year  = {2015},

date = {2015-02-11},

journal = {Orphanet journal of rare diseases},

volume = {10},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_351,

title = {Current treatment strategies for inhibiting mTOR in cancer},

author = {Chiarini F and Evangelisti C and McCubrey JA and Martelli AM},

url = {https://www.sciencedirect.com/science/article/pii/S0165614714001953?via%3Dihub},

doi = {10.1016/j.tips.2014.11.004},

year  = {2015},

date = {2015-02-11},

journal = {Trends in Pharmacological Sciences},

volume = {36},

number = {2},

abstract = {Mammalian target of rapamycin (mTOR) is a Ser/Thr kinase that regulates a wide range of functions, including cell growth, proliferation, survival, autophagy, metabolism, and cytoskeletal organization. mTOR activity is dysregulated in several human disorders, including cancer. The crucial role of mTOR in cancer cell biology has stimulated interest in mTOR inhibitors, placing mTOR on the radar of the pharmaceutical industry. Several mTOR inhibitors have already undergone clinical trials for treating tumors, without great success, although mTOR inhibitors are approved for the treatment of some types of cancer, including advanced renal cell carcinoma. However, the role of mTOR inhibitors in cancer treatment continues to evolve as new compounds are continuously being disclosed. Here we review the three classes of mTOR inhibitors currently available for treating cancer patients. Moreover, we highlight efforts to identify markers of resistance and sensitivity to mTOR inhibition that could prove useful in the emerging field of personalized medicine.Copyright 2014 Elsevier Ltd. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_335,

title = {APLP2 Regulates Refractive Error and Myopia Development in Mice and Humans},

author = {Tkatchenko AV and Tkatchenko TV and Guggenheim JA and {et al} and Biino G and {et al} and Williams C},

url = {https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005432},

doi = {10.1371/journal.pgen.1005432},

year  = {2015},

date = {2015-02-05},

journal = {Plos Genetics},

volume = {11},

number = {8},

pages = {e1005432},

abstract = {Myopia is the most common vision disorder and the leading cause of visual impairment worldwide. However, gene variants identified to date explain less than 10% of the variance in refractive error, leaving the majority of heritability unexplained (""missing heritability""). Previously, we reported that expression of APLP2 was strongly associated with myopia in a primate model. Here, we found that low-frequency variants near the 5'-end of APLP2 were associated with refractive error in a prospective UK birth cohort (n = 3,819 children; top SNP rs188663068, p = 5.0 × 10-4) and a CREAM consortium panel (n = 45,756 adults; top SNP rs7127037, p = 6.6 × 10-3). These variants showed evidence of differential effect on childhood longitudinal refractive error trajectories depending on time spent reading (gene x time spent reading x age interaction, p = 4.0 × 10-3). Furthermore, Aplp2 knockout mice developed high degrees of hyperopia (+11.5 +/- 2.2 D, p < 1.0 × 10-4) compared to both heterozygous (-0.8 ± 2.0 D, p < 1.0 × 10-4) and wild-type (+0.3 ± 2.2 D, p < 1.0 × 10-4) littermates and exhibited a dose-dependent reduction in susceptibility to environmentally induced myopia (F(2, 33) = 191.0, p < 1.0 × 10-4). This phenotype was associated with reduced contrast sensitivity (F(12, 120) = 3.6, p = 1.5 × 10-4) and changes in the electrophysiological properties of retinal amacrine cells, which expressed Aplp2. This work identifies APLP2 as one of the ""missing"" myopia genes, demonstrating the importance of a low-frequency gene variant in the development of human myopia. It also demonstrates an important role for APLP2 in refractive development in mice and humans, suggesting a high level of evolutionary conservation of the signaling pathways underlying refractive eye development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_357,

title = {DNA-protein interaction dynamics at the Lamin B2 replication origin.},

author = {Puzzi L and Marchetti L and Peverali FA and Biamonti G and Giacca M},

url = {https://www.tandfonline.com/doi/full/10.4161/15384101.2014.973337},

doi = {10.4161/15384101.2014.973337},

year  = {2015},

date = {2015-02-05},

journal = {Cell cycle},

volume = {14},

number = {1},

pages = {64-73},

abstract = {To date, a complete understanding of the molecular events leading to DNA replication origin activation in mammalian cells still remains elusive. In this work, we report the results of a high resolution chromatin immunoprecipitation study to detect proteins interacting with the human Lamin B2 replication origin. In addition to the pre-RC component ORC4 and to the transcription factors USF and HOXC13, we found that 2 components of the AP-1 transcription factor, c-Fos and c-Jun, are also associated with the origin DNA during the late G1 phase of the cell cycle and that these factors interact with ORC4. Both DNA replication and AP-1 factor binding to the origin region were perturbed by cell treatment with merbarone, a topoisomerase II inhibitor, suggesting that DNA topology is essential for determining origin function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_336,

title = {Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis.},

author = {Hu Z and Brooks SA and Dormoy V and Hsu CW and Hsu HY and Lin LT and Massfelder T and Rathmell WK and Xia M and Al-Mulla F and Al-Temaimi R and Amedei A and Brown DG and Prudhomme KR and Colacci A and Hamid RA and Mondello C and Raju J and Ryan EP and Woodrick J and Scovassi AI and Singh N and Vaccari M and Roy R and Forte S and Memeo L and Salem HK and Lowe L and Jensen L and Bisson WH and Kleinstreuer N},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S184/315846},

doi = {10.1093/carcin/bgv036},

year  = {2015},

date = {2015-02-04},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S184-202},

abstract = {One of the important 'hallmarks' of cancer is angiogenesis, which is the process of formation of new blood vessels that are necessary for tumor expansion, invasion and metastasis. Under normal physiological conditions, angiogenesis is well balanced and controlled by endogenous proangiogenic factors and antiangiogenic factors. However, factors produced by cancer cells, cancer stem cells and other cell types in the tumor stroma can disrupt the balance so that the tumor microenvironment favors tumor angiogenesis. These factors include vascular endothelial growth factor, endothelial tissue factor and other membrane bound receptors that mediate multiple intracellular signaling pathways that contribute to tumor angiogenesis. Though environmental exposures to certain chemicals have been found to initiate and promote tumor development, the role of these exposures (particularly to low doses of multiple substances), is largely unknown in relation to tumor angiogenesis. This review summarizes the evidence of the role of environmental chemical bioactivity and exposure in tumor angiogenesis and carcinogenesis. We identify a number of ubiquitous (prototypical) chemicals with disruptive potential that may warrant further investigation given their selectivity for high-throughput screening assay targets associated with proangiogenic pathways. We also consider the cross-hallmark relationships of a number of important angiogenic pathway targets with other cancer hallmarks and we make recommendations for future research. Understanding of the role of low-dose exposure of chemicals with disruptive potential could help us refine our approach to cancer risk assessment, and may ultimately aid in preventing cancer by reducing or eliminating exposures to synergistic mixtures of chemicals with carcinogenic potential.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_343,

title = {Characterization of the biological processes shaping the genetic structure of the Italian population.},

author = {Parolo S and Lisa A and Gentilini D and Di Blasio AM and Barlera S and Nicolis EB and Boncoraglio GB and Parati EA and Bione S},

url = {https://bmcgenet.biomedcentral.com/articles/10.1186/s12863-015-0293-x},

doi = {10.1186/s12863-015-0293-x.},

year  = {2015},

date = {2015-02-04},

journal = {BMC Genetics},

volume = {16},

pages = {132},

abstract = {BACKGROUND: The genetic structure of human populations is the outcome of the combined action of different processes such as demographic dynamics and natural selection. Several efforts toward the characterization of population genetic architectures and the identification of adaptation signatures were recently made. In this study, we provide a genome-wide depiction of the Italian population structure and the analysis of the major determinants of the current existing genetic variation. RESULTS: We defined and characterized 210 genomic loci associated with the first Principal Component calculated on the Italian genotypic data and correlated to the North-south genetic gradient. Using a gene-enrichment approach we identified the immune function as primarily involved in the Italian population differentiation and we described a locus on chromosome 13 showing combined evidence of North-south diversification in allele frequencies and signs of recent positive selection. In this region our bioinformatics analysis pinpointed an uncharacterized long intergenic non-coding (lincRNA), whose expression appeared specific for immune-related tissues suggesting its relevance for the immune function. CONCLUSIONS:

Our study, combining population genetic analyses with biological insights provides a description of the Italian genetic structure that in future could contribute to the evaluation of complex diseases risk in the population context.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_346,

title = {Chronic Replication Problems Impact Cell Morphology and Adhesion of DNA Ligase I Defective Cells.},

author = {Cremaschi P and Oliverio M and Leva V and Bione S and Carriero R and Mazzucco G and Palamidessi A and Scita G and Biamonti G and Montecucco A},

url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130561},

doi = {10.1371/journal.pone.0130561},

year  = {2015},

date = {2015-02-04},

journal = {Plos One},

volume = {10},

number = {7},

pages = {e0130561},

abstract = {Moderate DNA damage resulting from metabolic activities or sub-lethal doses of exogenous insults may eventually lead to cancer onset. Human 46BR.1G1 cells bear a mutation in replicative DNA ligase I (LigI) which results in low levels of replication-dependent DNA damage. This replication stress elicits a constitutive phosphorylation of the ataxia telangiectasia mutated (ATM) checkpoint kinase that fails to arrest cell cycle progression or to activate apoptosis or cell senescence. Stable transfection of wild type LigI, as in 7A3 cells, prevents DNA damage and ATM activation. Here we show that parental 46BR.1G1 and 7A3 cells differ in important features such as cell morphology, adhesion and migration. Comparison of gene expression profiles in the two cell lines detects Bio-Functional categories consistent with the morphological and migration properties of LigI deficient cells. Interestingly, ATM inhibition makes 46BR.1G1 more similar to 7A3 cells for what concerns morphology, adhesion and expression of cell-cell adhesion receptors. These observations extend the influence of the DNA damage response checkpoint pathways and unveil a role for ATM kinase activity in modulating cell biology parameters relevant to cancer progression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_409,

title = {TFIIH-dependent MMP-1 overexpression in trichothiodystrophy leads to extracellular matrix alterations in patient skin.},

author = {Arseni L and Lanzafame M and Compe E and Fortugno P and Afonso-Barroso A and Peverali FA and Lehmann AR and Zambruno G and Egly JM and Stefanini M and Orioli D},

url = {https://www.pnas.org/content/112/5/1499.long},

doi = {10.1073/pnas.1416181112},

year  = {2015},

date = {2015-02-03},

journal = {Proceedings of the National Academy of Sciences of the United States of America},

volume = {112},

number = {5},

pages = {1499-1504},

abstract = {Mutations in the XPD subunit of the DNA repair/transcription factor TFIIH result in distinct clinical entities, including the cancer-prone xeroderma pigmentosum (XP) and the multisystem disorder trichothiodystrophy (TTD), which share only cutaneous photosensitivity. Gene-expression profiles of primary dermal fibroblasts revealed overexpression of matrix metalloproteinase 1 (MMP-1), the gene encoding the metalloproteinase that degrades the interstitial collagens of the extracellular matrix (ECM), in TTD patients mutated in XPD compared with their healthy parents. The defect is observed in TTD and not in XP and is specific for fibroblasts, which are the main producers of dermal ECM. MMP-1 transcriptional up-regulation in TTD is caused by an erroneous signaling mediated by retinoic acid receptors on the MMP-1 promoter and leads to hypersecretion of active MMP-1 enzyme and degradation of collagen type I in the ECM of cell/tissue systems and TTD patient skin. In agreement with the well-known role of ECM in eliciting signaling events controlling cell behavior and tissue homeostasis, ECM alterations in TTD were shown to impact on the migration and wound-healing properties of patient dermal fibroblasts. The presence of a specific inhibitor of MMP activity was sufficient to restore normal cell migration, thus providing a potential approach for therapeutic strategies. This study highlights the relevance of ECM anomalies in TTD pathogenesis and in the phenotypic differences between TTD and XP.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}