@article{%a1:%Ybv,

title = {Asparagine sustains cellular proliferation and c‑Myc expression in glutamine‑starved cancer cells},

author = {Chiodi I and Perini C and Berardi D and Mondello C},

url = {https://www.spandidos-publications.com/or/45/6/96},

doi = {10.3892/or.2021.8047},

year  = {2021},

date = {2021-08-30},

journal = {Oncology reports},

volume = {45},

number = {6},

pages = {96},

abstract = {During tumorigenesis, oncogene activation and metabolism rewiring are interconnected. Activated c‑Myc upregulates several genes involved in glutamine metabolism, making cancer cells dependent on high levels of this amino acid to survive and proliferate. After studying the response to glutamine deprivation in cancer cells, it was found that glutamine starvation not only blocked cellular proliferation, but also altered c‑Myc protein expression, leading to a reduction in the levels of the canonical c‑Myc isoform and an increase in the expression of c‑Myc 1, a c‑Myc isoform translated from an in‑frame 5' CUG codon. In an attempt to identify nutrients able to counteract glutamine deprivation effects, it was shown that, in the absence of glutamine, asparagine permitted cell survival and proliferation, and maintained c‑Myc expression as in glutamine‑fed cells, with high levels of canonical c‑Myc and c‑Myc 1 almost undetectable. In asparagine‑fed cells, global protein translation was higher than in glutamine‑starved cells, and there was an increase in the levels of glutamine synthetase (GS), whose activity was essential for cellular viability and proliferation. In glutamine‑starved asparagine‑fed cells, the inhibition of c‑Myc activity led to a decrease in global protein translation and GS synthesis, suggesting an association between c‑Myc expression, GS levels and cellular proliferation, mediated by asparagine when exogenous glutamine is absent.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_438,

title = {Life Style Factors, Tumor Cell Plasticity and Cancer Stem Cells},

author = {Chiodi I and Mondello C},

url = {https://www.sciencedirect.com/science/article/pii/S1383574220300284?via%3Dihub},

doi = {10.1016/j.mrrev.2020.108308},

year  = {2020},

date = {2020-01-01},

journal = {Mutation Research - Reviews in Mutation Research},

volume = {784},

pages = {108308},

abstract = {Cancers are heterogeneous tissues and a layer of heterogeneity is determined by the presence of cells showing stemness traits, known as cancer stem cells (CSCs). Evidence indicates that CSCs are important players in tumor development, progression and relapse. Oncogenic transformation of normal stem cells can give rise to CSCs, but CSCs can also originate from de-differentiation of bulk tumor cells. Thus, factors promoting the increase of normal stem cell pools or stimulating the acquisition of stemness features by tumor cells can have serious consequences on cancer origin and progression. In this review, we will first give an overview of the CSC model of cancer development and we will then discuss the role of life style factors, such as high caloric diet, alcohol drinking and smoking, on the widening of stem cell pools and the induction of CSC features in tumors. Finally, we will discuss some healthy life style factors that can help to prevent cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%v,

title = {Cellular response to glutamine and/or glucose deprivation in in vitro transformed human fibroblasts.},

author = {Chiodi I and Picco G and Martino C and Mondello C},

url = {https://www.spandidos-publications.com/or/41/6/3555},

doi = {10.3892/or.2019.7125},

year  = {2019},

date = {2019-02-22},

journal = {Oncology reports},

volume = {41},

number = {6},

pages = {3555-3564},

abstract = {Neoplastic transformation is characterized by metabolic rewiring to sustain the elevated biosynthetic demands of highly proliferative cancer cells. To obtain the precursors for macromolecule biosynthesis, cancer cells avidly uptake and metabolize glucose and glutamine. Thus, targeting the availability or metabolism of these nutrients is an attractive anticancer therapeutic strategy. To improve our knowledge concerning how cancer cells respond to nutrient withdrawal, the response to glutamine and/or glucose starvation was studied in human in vitro transformed fibroblasts, deeply characterized at the cellular and molecular level. Concomitant starvation of both nutrients led to rapid loss of cellular adhesion (~16 h after starvation), followed by cell death. Deprivation of glucose alone had the same effect, although at a later time (~48 h after starvation), suggesting that glucose plays a key role in enabling cell attachment to the extracellular matrix. Glutamine deprivation did not induce rapid cell death, but caused a prolonged arrest of cellular proliferation; the cells started dying only 96 h after starvation. Before massive cell death occurred, the effects of all the starvation conditions were reversible. Autophagy activation was observed in cells incubated in the absence of glucose for more than 48 h, while autophagy was not detected under the other starvation conditions. Markers of apoptotic cell death, such as caspase 3, caspase 9 and poly(ADP‑ribose) polymerase 1 (PARP‑1) proteolytic fragments, were not observed under any growth condition. Glucose and/or glutamine deprivation caused very rapid PARP‑1 activation, with marked PARP‑1 (poly‑ADP) ribosylation and protein (poly‑ADP) ribosylation. This activation was not due to starvation‑induced DNA double‑strand breaks, which appeared at the late stages of deprivation, when most cells died. Collectively, these results highlight a broad range of consequences of glucose and glutamine starvation, which may be taken into account when nutrient availability is used as a target for anticancer therapies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_355,

title = {Disruptive environmental chemicals and cellular mechanisms that confer resistance to cell death.},

author = {Narayanan KB and Ali M and Barclay BJ and Cheng Q and {D'Abronzo L} and Dornetshuber-Fleiss R and Ghosh PM and Gonzalez Guzman MJ and Lee TJ and Leung PS and Li L and Luanpitpong S and Ratovitski E and Rojanasakul Y and Romano MF and Romano S and Sinha RK and Yedjou C and Al-Mulla F and Al-Temaimi R and Amedei A and Brown DG and Ryan EP and Colacci A and Hamid RA and Mondello C and Raju J and Salem HK and Woodrick J and Scovassi AI and Singh N and Vaccari M and Roy R and Forte S and Memeo L and Kim SY and Bisson WH and Lowe L and Park HH},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S89/312579},

doi = {10.1093/carcin/bgv032},

year  = {2019},

date = {2019-02-15},

urldate = {2019-02-15},

journal = {Carcinogenesis},

volume = {36},

number = {1},

pages = {S89-110},

abstract = {Cell death is a process of dying within biological cells that are ceasing to function. This process is essential in regulating organism development, tissue homeostasis, and to eliminate cells in the body that are irreparably damaged. In general, dysfunction in normal cellular death is tightly linked to cancer progression. Specifically, the up-regulation of pro-survival factors, including oncogenic factors and antiapoptotic signaling pathways, and the down-regulation of pro-apoptotic factors, including tumor suppressive factors, confers resistance to cell death in tumor cells, which supports the emergence of a fully immortalized cellular phenotype. This review considers the potential relevance of ubiquitous environmental chemical exposures that have been shown to disrupt key pathways and mechanisms associated with this sort of dysfunction. Specifically, bisphenol A, chlorothalonil, dibutyl phthalate, dichlorvos, lindane, linuron, methoxychlor and oxyfluorfen are discussed as prototypical chemical disruptors; as their effects relate to resistance to cell death, as constituents within environmental mixtures and as potential contributors to environmental 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_323,

title = {Cells with stemness features are generated from in vitro transformed human fibroblasts.},

author = {Bono B and Ostano P and Peritore M and Gregnanin I and Belgiovine C and Liguori M and Allavena P and Chiorino G and Chiodi I and Mondello C},

url = {https://www.nature.com/articles/s41598-018-32197-5},

doi = {10.1038/s41598-018-32197-5},

year  = {2018},

date = {2018-02-15},

journal = {Scientific Reports},

volume = {8},

number = {1},

pages = {13838},

abstract = {Cancer stem cells (CSCs) have been involved in the maintenance, progression and relapse of several tumors, but their origin is still elusive. Here, in vitro transformed human fibroblasts (cen3tel cells) and the tumorsphere assay were used to search for and possibly characterize CSCs in transformed somatic cells. Cen3tel cells formed spheres showing self-renewal capacity and Sox2 overexpression, suggesting that they contained a subset of cells with CSC-like features. Sphere cells displayed deregulation of a c-MYC/miR-34a circuitry, likely associated with cell protection from apoptosis. Gene expression profiles of sphere cells revealed an extensive transcriptional reprogramming. Genes up-regulated in tumorspheres identified processes related to tumorigenesis and stemness, as cholesterol biosynthesis, apoptosis suppression, interferon and cytokine mediated signalling pathways. Sphere cells engrafted into NSG mice more rapidly than adherent cells, but both cell populations were tumorigenic. These results indicate that, during transformation, human somatic cells can acquire CSC properties, confirming the high plasticity of tumor cells. However, CSC-like cells are not the only tumorigenic population in transformed cells, indicating that the CSC phenotype and tumorigenicity can be uncoupled.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_319,

title = {A comprehensive strategy for the analysis of acoustic compressibility and optical deformability on single cells.},

author = {Yang T and Bragheri F and Nava G and Chiodi I and Mondello C and Osellame R and Berg-Sørensen K and Cristiani I and Minzioni P},

url = {http://www.nature.com/articles/srep23946},

doi = {10.1038/srep23946},

year  = {2016},

date = {2016-04-20},

journal = {Scientific Reports},

volume = {6},

pages = {23946},

abstract = {We realized an integrated microfluidic chip that allows measuring both optical deformability and acoustic compressibility on single cells, by optical stretching and acoustophoresis experiments respectively. Additionally, we propose a measurement protocol that allows evaluating the experimental apparatus parameters before performing the cell-characterization experiments, including a non-destructive method to characterize the optical force distribution inside the microchannel. The chip was used to study important cell-mechanics parameters in two human breast cancer cell lines, MCF7 and MDA-MB231. Results indicate that MDA-MB231 has both higher acoustic compressibility and higher optical deformability than MCF7, but statistical analysis shows that optical deformability and acoustic compressibility are not correlated parameters. This result suggests the possibility to use them to analyze the response of different cellular structures. We also demonstrate that it is possible to perform both measurements on a single cell, and that the order of the two experiments does not affect the retrieved values.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_292,

title = {Discovery of the First Potent and Selective Inhibitors of Human dCTP Pyrophosphatase 1.},

author = {{Goodson WH 3rd} 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 {Llona-Minguez S} and Hoglund A and Jacques SA and Johansson L and Calderon-Montano JM and Claesson M and Loseva O and Valerie NC and Lundbäck T and Piedrafita J and Maga G and Crespan E and Meijer L and Burgos Morón E and Baranczewski P and Hagbjork AL and Svensson R and Wiita E and Almlof I and Visnes T and Jeppsson F and Sigmundsson K and Jensen AJ and Artursson P and Jemth AS and Stenmark P and Warpman Berglund U and Scobie M and Helleday T},

url = {http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.5b01741},

doi = {10.1021/acs.jmedchem.5b01741},

year  = {2016},

date = {2016-02-18},

journal = {Journal of medicinal chemistry},

volume = {59},

number = {3},

pages = {1140-1148},

abstract = {The dCTPase pyrophosphatase 1 (dCTPase) regulates the intracellular nucleotide pool through hydrolytic degradation of canonical and noncanonical nucleotide triphosphates (dNTPs). dCTPase is highly expressed in multiple carcinomas and is associated with cancer cell stemness. Here we report on the development of the first potent and selective dCTPase inhibitors that enhance the cytotoxic effect of cytidine analogues in leukemia cells. Boronate 30 displays a promising in vitro ADME profile, including plasma and mouse microsomal half-lives, aqueous solubility, cell permeability and CYP inhibition, deeming it a suitable compound for in vivo studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_252,

title = {Snail levels control the migration mechanism of mesenchymal tumor cells.},

author = {Belgiovine C and Chiesa G and Chiodi I and Frapolli R and Bonezzi K and Taraboletti G and D'Incalci M and Mondello C},

url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907273/},

doi = {10.3892/ol.2016.4642},

year  = {2016},

date = {2016-03-16},

journal = {Oncology Letters},

volume = {12},

number = {1},

pages = {767-771},

abstract = {Cancer cells use two major types of movement: Mesenchymal, which is typical of cells of mesenchymal origin and depends on matrix metalloproteinase (MMP) activity, and amoeboid, which is characteristic of cells with a rounded shape and relies on the activity of Rho-associated kinase (ROCK). The present authors previously demonstrated that, during neoplastic transformation, telomerase-immortalized human fibroblasts (cen3tel cells) acquired a ROCK-dependent/MMP independent mechanism of invasion, mediated by the downregulation of the ROCK cellular inhibitor Round (Rnd)3/RhoE. In the present study, cen3tel transformation was also demonstrated to be paralleled by downregulation of Snail, a major determinant of the mesenchymal movement. To test whether Snail levels could determine the type of movement adopted by mesenchymal tumor cells, Snail was ectopically expressed in tumorigenic cells. It was observed that ectopic Snail did not increase the levels of typical mesenchymal markers, but induced cells to adopt an MMP-dependent mechanism of invasion. In cells expressing ectopic Snail, invasion became sensitive to the MMP inhibitor Ro 28-2653 and insensitive to the ROCK inhibitor Y27632, suggesting that, once induced by Snail, the mesenchymal movement prevails over the amoeboid one. Snail-expressing cells had a more aggressive behavior in vivo, and exhibited increased tumor growth rate and metastatic ability. These results confirm the high plasticity of cancer cells, which can adopt different types of movement in response to changes in the expression of specific genes. Furthermore, the present findings indicate that Rnd3 and Snail are possible regulators of the type of invasion mechanism adopted by mesenchymal tumor cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_261,

title = {Telomere and telomerase stability in human diseases and cancer.},

author = {Chiodi I and Mondello C},

year  = {2016},

date = {2016-03-11},

journal = {Frontiers In  Bioscience},

volume = {21},

pages = {203-224},

abstract = {Telomeres are the nucleoprotein structures at the end of linear eukaryotic chromosomes required for genome stability. Telomerase is the specialized enzyme deputed to their elongation. Maintenance of a proper telomere structure, an accurate regulation of telomerase biogenesis and activity, as well as a correct telomere-telomerase interaction and a faithful telomeric DNA replication are all processes that a cell has to precisely control to safeguard its functionality. Here, we review key factors that play a role in the development of these processes and their relationship with human health.},

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_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_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_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_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_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_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_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_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_378,

title = {Mechanisms of environmental chemicals that enable the cancer hallmark of evasion of growth suppression.},

author = {Nahta R and Al-Mulla F and Al-Temaimi R and Amedei A and Andrade-Vieira R and Bay S and G Brown D and Calaf GM and Castellino RC and Cohen-Solal KA and Colacci A and Cruickshanks N and Dent P and Di Fiore R and Forte S and Goldberg GS and Hamid RA and Krishnan H and Laird DW and Lasfar A and Marignani PA and Memeo L and Mondello C and Naus CC and Ponce-Cusi R and Raju J and Roy D and Roy R and P Ryan E and Salem HK and Scovassi AI and Singh N and Vaccari M and Vento R and Vondracek J and Wade M and Woodrick J and Bisson WH},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S2/310663},

doi = {10.1093/carcin/bgv028},

year  = {2015},

date = {2015-06-30},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S2-18},

abstract = {As part of the Halifax Project, this review brings attention to the potential effects of environmental chemicals on important molecular and cellular regulators of the cancer hallmark of evading growth suppression. Specifically, we review the mechanisms by which cancer cells escape the growth-inhibitory signals of p53, retinoblastoma protein, transforming growth factor-beta, gap junctions and contact inhibition. We discuss the effects of selected environmental chemicals on these mechanisms of growth inhibition and cross-reference the effects of these chemicals in other classical cancer hallmarks. 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_379,

title = {Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?},

author = {Robey RB and Weisz J and Kuemmerle NB and Salzberg AC and Berg A and Brown DG and Kubik L and Palorini R and Al-Mulla F and Al-Temaimi R and Colacci A and Mondello C and Raju J 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 Williams GP and Lowe L and Meyer J and Martin FL and Bisson WH and Chiaradonna F and Ryan EP},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S203/316346},

doi = {10.1093/carcin/bgv037},

year  = {2015},

date = {2015-03-13},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S203-231},

abstract = {Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic contributions of environmentally relevant low-dose chemical mixtures and the fact that exposures can influence multiple cancer-associated endpoints over varying timescales. Of these endpoints, dysregulated metabolism is one of the most common and recognizable features of cancer, but its specific roles in exposure-associated cancer development remain poorly understood. Most studies have focused on discrete aspects of cancer metabolism and have incompletely considered both its dynamic integrated nature and the complex controlling influences of substrate availability, external trophic signals and environmental conditions. Emerging high throughput approaches to environmental risk assessment also do not directly address the metabolic causes or consequences of changes in gene expression. As such, there is a compelling need to establish common or complementary frameworks for further exploration that experimentally and conceptually consider the gestalt of cancer metabolism and its causal relationships to both carcinogenesis and the development of other cancer hallmarks. A literature review to identify environmentally relevant exposures unambiguously linked to both cancer development and dysregulated metabolism suggests major gaps in our understanding of exposure-associated carcinogenesis and metabolic reprogramming. Although limited evidence exists to support primary causal roles for metabolism in carcinogenesis, the universality of altered cancer metabolism underscores its fundamental biological importance, and multiple pleiomorphic, even dichotomous, roles for metabolism in promoting, antagonizing or otherwise enabling the development and selection of cancer are suggested. Published by Oxford University Press 2015.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_412,

title = {The effect of environmental chemicals on the tumor microenvironment.},

author = {Casey SC and Vaccari M and Al-Mulla F and Al-Temaimi R and Amedei A and Barcellos-Hoff MH and Brown DG and Chapellier M and Christopher J and Curran C and Forte S and Hamid RA and Heneberg P and Koch DC and Krishnakumar PK and Laconi E and Maguer-Satta V and Marongiu F and Memeo L and Mondello C and Raju J and Roman J and Roy R and Ryan EP and Ryeom S and Salem HK and Scovassi AI and Singh N and Soucek L and Vermeulen L and Whitfield JR and Woodrick J and Colacci A and Bisson WH and Felsher DW},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S160/315417},

doi = {10.1093/carcin/bgv035},

year  = {2015},

date = {2015-03-06},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S160-183},

abstract = {Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis. 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_413,

title = {The impact of low-dose carcinogens and environmental disruptors on tissue invasion and metastasis.},

author = {Ochieng J and Nangami GN and Ogunkua O and Miousse IR and Koturbash I and Odero-Marah V and McCawley L and Nangia-Makker P and Ahmed N and Luqmani Y and Chen Z and Papagerakis S and Wolf GT and Dong C and Zhou BP and Brown DG 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 Amedei A and Al-Temaimi R and Al-Mulla F and Bisson WH and Eltom SE},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S128/313982},

doi = {10.1093/carcin/bgv034},

year  = {2015},

date = {2015-06-19},

urldate = {2015-06-19},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S128-159},

abstract = {The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial-mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis. 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_415,

title = {The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling.},

author = {Engstrom W and Darbre P and Eriksson S and Gulliver L and Hultman T and Karamouzis MV and Klaunig JE and Mehta R and Moorwood K and Sanderson T and Sone H and Vadgama P and Wagemaker G and Ward A 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 E and Brown DG and Bisson WH},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S38/311505},

doi = {10.1093/carcin/bgv030},

year  = {2015},

date = {2015-06-12},

urldate = {2015-06-12},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S38-60},

abstract = {The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}