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Article ; Online: miRNAs in the Box: Potential Diagnostic Role for Extracellular Vesicle-Packaged miRNA-27a and miRNA-128 in Breast Cancer.

Giordano, Cinzia / Accattatis, Felice Maria / Gelsomino, Luca / Del Console, Piercarlo / Győrffy, Balázs / Giuliano, Mario / Veneziani, Bianca Maria / Arpino, Grazia / De Angelis, Carmine / De Placido, Pietro / Pietroluongo, Erica / Zinno, Francesco / Bonofiglio, Daniela / Andò, Sebastiano / Barone, Ines / Catalano, Stefania

International journal of molecular sciences

2023 Volume 24, Issue 21

Abstract: Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer "theranostic" tools, with strong clinical relevance. Although their potential in breast cancer diagnosis has been widely reported, further ... ...

Abstract	Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer "theranostic" tools, with strong clinical relevance. Although their potential in breast cancer diagnosis has been widely reported, further studies are still required to address this challenging issue. The present study examined the expression profiles of EV-packaged miRNAs to identify novel miRNA signatures in breast cancer and verified their diagnostic accuracy. Circulating EVs were isolated from healthy controls and breast cancer patients and characterized following the MISEV 2018 guidelines. RNA-sequencing and real-time PCR showed that miRNA-27a and miRNA-128 were significantly down-regulated in patient-derived EVs compared to controls in screening and validation cohorts. Bioinformatics analyses of miRNA-target genes indicated several enriched biological processes/pathways related to breast cancer. Receiver operating characteristic (ROC) curves highlighted the ability of these EV-miRNAs to distinguish breast cancer patients from non-cancer controls. According to other reports, the levels of EV-miRNA-27a and EV-miRNA-128 are not associated with their circulating ones. Finally, evidence from the studies included in our systematic review underscores how the expression of these miRNAs in biofluids is still underinvestigated. Our findings unraveled the role of serum EV-derived miRNA-27a and miRNA-128 in breast cancer, encouraging further investigation of these two miRNAs within EVs towards improved breast cancer detection.
MeSH term(s)	Humans ; Female ; MicroRNAs/metabolism ; Breast Neoplasms/diagnosis ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Extracellular Vesicles/genetics ; Extracellular Vesicles/metabolism
Chemical Substances	MicroRNAs
Language	English
Publishing date	2023-10-28
Publishing country	Switzerland
Document type	Systematic Review ; Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242115695
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas.

Varadi, Melinda / Nagy, Nikolett / Reis, Henning / Hadaschik, Boris / Niedworok, Christian / Modos, Orsolya / Szendroi, Attila / Ablat, Jason / Black, Peter C / Keresztes, David / Csizmarik, Anita / Olah, Csilla / Gaisa, Nadine T / Kiss, Andras / Timar, Jozsef / Toth, Erika / Csernak, Erzsebet / Gerstner, Arpad / Mittal, Vinay /

Karkampouna, Sofia / Kruithof de Julio, Marianna / Gyorffy, Balazs / Bedics, Gabor / Rink, Michael / Fisch, Margit / Nyirady, Peter / Szarvas, Tibor

Cancer medicine

2023 Volume 12, Issue 7, Page(s) 9041–9054

Abstract: Objective: Administration of targeted therapies provides a promising treatment strategy for urachal adenocarcinoma (UrC) or primary bladder adenocarcinoma (PBAC); however, the selection of appropriate drugs remains difficult. Here, we aimed to establish ...

Abstract	Objective: Administration of targeted therapies provides a promising treatment strategy for urachal adenocarcinoma (UrC) or primary bladder adenocarcinoma (PBAC); however, the selection of appropriate drugs remains difficult. Here, we aimed to establish a routine compatible methodological pipeline for the identification of the most important therapeutic targets and potentially effective drugs for UrC and PBAC. Methods: Next-generation sequencing, using a 161 cancer driver gene panel, was performed on 41 UrC and 13 PBAC samples. Clinically relevant alterations were filtered, and therapeutic interpretation was performed by in silico evaluation of drug-gene interactions. Results: After data processing, 45/54 samples passed the quality control. Sequencing analysis revealed 191 pathogenic mutations in 68 genes. The most frequent gain-of-function mutations in UrC were found in KRAS (33%), and MYC (15%), while in PBAC KRAS (25%), MYC (25%), FLT3 (17%) and TERT (17%) were recurrently affected. The most frequently affected pathways were the cell cycle regulation, and the DNA damage control pathway. Actionable mutations with at least one available approved drug were identified in 31/33 (94%) UrC and 8/12 (67%) PBAC patients. Conclusions: In this study, we developed a data-processing pipeline for the detection and therapeutic interpretation of genetic alterations in two rare cancers. Our analyses revealed actionable mutations in a high rate of cases, suggesting that this approach is a potentially feasible strategy for both UrC and PBAC treatments.
MeSH term(s)	Humans ; Urinary Bladder/pathology ; Proto-Oncogene Proteins p21(ras)/genetics ; Adenocarcinoma/genetics ; Adenocarcinoma/pathology ; Mutation ; Urinary Bladder Neoplasms/pathology ; High-Throughput Nucleotide Sequencing
Chemical Substances	Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
Language	English
Publishing date	2023-01-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.5639
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Article ; Online: Smoking-related O4-ethylthymidine formation in human lung tissue and comparisons with bulky DNA adducts.

Anna, Lívia / Kovács, Katalin / Gyorffy, Erika / Schoket, Bernadette / Nair, Jagadeesan

Mutagenesis

2011 Volume 26, Issue 4, Page(s) 523–527

Abstract: Tobacco smoke contains many alkylating agents that can react with DNA to produce O(4)-ethylthymidine (O(4)-etT) and several other types of promutagenic base modifications. Our aims were (i) to confirm results of a pilot study (Godschalk, R., Nair, J., ... ...

Abstract	Tobacco smoke contains many alkylating agents that can react with DNA to produce O(4)-ethylthymidine (O(4)-etT) and several other types of promutagenic base modifications. Our aims were (i) to confirm results of a pilot study (Godschalk, R., Nair, J., Schooten, F. J., Risch, A., Drings, P., Kayser, K., Dienemann, H. and Bartsch, H. (2002) Comparison of multiple DNA adduct types in tumor adjacent human lung tissue: effect of cigarette smoking. Carcinogenesis, 23, 2081-2086) on the formation of O(4)-etT in smokers' lung; (ii) to explore associations between levels of O(4)-etT and smoking status and (iii) to investigate whether a correlation exists between levels of O(4)-etT and bulky (polycyclic aromatic hydrocarbons-derived) DNA adducts. Archived DNA samples originated from histologically normal peripheral lung tissues of 64 Hungarian lung cancer patients, who underwent lung resection. O(4)-etT was determined by an immunoenriched (32)P-postlabelling-high-performance liquid chromatography method. Levels of bulky DNA adducts were determined by the nuclease P1 adduct-enriched (32)P-postlabelling. O(4)-etT levels ranged from 0.01 to 3.91 adducts/10(8) thymidines. In the combined group of subjects who smoked until surgery or gave up smoking at most 1 year before it, the mean level of O(4)-etT was 1.7-fold (P = 0.015) and of bulky DNA adducts 2.2-fold (P < 0.0001) higher than in long-term ex-smokers (LES) and never-smokers (NS) combined. We found no significant correlation between the individual levels of the two DNA adduct types. No dose-response was detected between O(4)-etT formation and smoking dose. In one-third of LES, O(4)-etT levels were above the 2.0-fold mean level of adducts found in NS, indicating its high persistence. Our results confirm the smoking-related formation of O(4)-etT in human lung DNA that should be explored as biomarker. Its long persistence in target tissue implicates a role of this potentially miscoding lesion in tobacco smoking-associated cancers.
MeSH term(s)	Adult ; Aged ; DNA Adducts/metabolism ; Female ; Humans ; Lung/metabolism ; Male ; Middle Aged ; Smoking/metabolism ; Thymidine/analogs & derivatives ; Thymidine/chemistry ; Thymidine/metabolism
Chemical Substances	DNA Adducts ; O(4)-ethylthymidine (59495-22-6) ; Thymidine (VC2W18DGKR)
Language	English
Publishing date	2011-07
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632903-2
ISSN	1464-3804 ; 0267-8357
ISSN (online)	1464-3804
ISSN	0267-8357
DOI	10.1093/mutage/ger011
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Article ; Online: miRNAs in the Box

Cinzia Giordano / Felice Maria Accattatis / Luca Gelsomino / Piercarlo Del Console / Balázs Győrffy / Mario Giuliano / Bianca Maria Veneziani / Grazia Arpino / Carmine De Angelis / Pietro De Placido / Erica Pietroluongo / Francesco Zinno / Daniela Bonofiglio / Sebastiano Andò / Ines Barone / Stefania Catalano

International Journal of Molecular Sciences, Vol 24, Iss 21, p

Potential Diagnostic Role for Extracellular Vesicle-Packaged miRNA-27a and miRNA-128 in Breast Cancer

2023 Volume 15695

Abstract: Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer “theranostic” tools, with strong clinical relevance. Although their potential in breast cancer diagnosis has been widely reported, further ... ...

Abstract	Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer “theranostic” tools, with strong clinical relevance. Although their potential in breast cancer diagnosis has been widely reported, further studies are still required to address this challenging issue. The present study examined the expression profiles of EV-packaged miRNAs to identify novel miRNA signatures in breast cancer and verified their diagnostic accuracy. Circulating EVs were isolated from healthy controls and breast cancer patients and characterized following the MISEV 2018 guidelines. RNA-sequencing and real-time PCR showed that miRNA-27a and miRNA-128 were significantly down-regulated in patient-derived EVs compared to controls in screening and validation cohorts. Bioinformatics analyses of miRNA-target genes indicated several enriched biological processes/pathways related to breast cancer. Receiver operating characteristic (ROC) curves highlighted the ability of these EV-miRNAs to distinguish breast cancer patients from non-cancer controls. According to other reports, the levels of EV-miRNA-27a and EV-miRNA-128 are not associated with their circulating ones. Finally, evidence from the studies included in our systematic review underscores how the expression of these miRNAs in biofluids is still underinvestigated. Our findings unraveled the role of serum EV-derived miRNA-27a and miRNA-128 in breast cancer, encouraging further investigation of these two miRNAs within EVs towards improved breast cancer detection.
Keywords	breast cancer ; extracellular vesicles ; miRNAs ; miRNA-27a ; miRNA-128 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610 ; 616
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Correlation between biomarkers of human exposure to genotoxins with focus on carcinogen-DNA adducts.

Gyorffy, Erika / Anna, Lívia / Kovács, Katalin / Rudnai, Péter / Schoket, Bernadette

Mutagenesis

2008 Volume 23, Issue 1, Page(s) 1–18

Abstract: Correlations among biomarkers, an important issue in biomarker research, provide enhanced insight and understanding of the complexity of molecular mechanisms initiated by environmental genotoxic agents in the human organism. Occupational and ... ...

Abstract	Correlations among biomarkers, an important issue in biomarker research, provide enhanced insight and understanding of the complexity of molecular mechanisms initiated by environmental genotoxic agents in the human organism. Occupational and environmental exposures mostly represent mixtures of genotoxic agents, whereas the specificity of biomarker measurements varies widely. Here, we give an overview of the correlation studies with particular emphasis on DNA adduct biomarker analysis of exposure to polycyclic aromatic hydrocarbons (PAHs) and/or tobacco smoke. We have collected data on correlations between different DNA adduct detection methods, DNA adduct structures and DNA adduct levels in human tissues. Data are also presented on the correlation between DNA adducts and other biomarkers of exposure and of early biological effects, including protein adducts, urinary metabolites and cytogenetic end points. In numerous studies, 32P-postlabelling and immunoassay measurements of DNA adducts recognized the difference between exposure groups similarly; however, at the individual level, there was, in general, not a statistically significant correlation between the two determinations. Inconsistency was found regarding the correlation between the levels of total bulky adducts and specific single DNA adduct structures. A number of studies found a positive correlation between DNA adduct levels in target and surrogate tissues, although stratification for exposure level may have influenced the results. Characteristically, there was a positive correlation between DNA adduct levels in tumour and normal tissue pairs. In general, there was a lack of correlation between DNA adducts and urinary PAH metabolites, but after stratification for particular genetic polymorphisms correlation may have emerged between the two biomarkers of exposure. The correlations with cytogenetic biomarkers were very complex, with examples of both positive correlation and lack of correlation. Exploration of correlations among biomarkers contributes to the further progress of molecular cancer epidemiology and to the selection of the optimal biomarkers for the investigation of human exposure to carcinogens.
MeSH term(s)	Biomarkers/analysis ; Biomarkers/metabolism ; Carcinogens/metabolism ; DNA Adducts/metabolism ; Environmental Exposure ; Humans ; Mutagens/toxicity
Chemical Substances	Biomarkers ; Carcinogens ; DNA Adducts ; Mutagens
Language	English
Publishing date	2008-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	632903-2
ISSN	1464-3804 ; 0267-8357
ISSN (online)	1464-3804
ISSN	0267-8357
DOI	10.1093/mutage/gem043
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Article ; Online: Microenvironmental ammonia enhances T cell exhaustion in colorectal cancer.

Bell, Hannah N / Huber, Amanda K / Singhal, Rashi / Korimerla, Navyateja / Rebernick, Ryan J / Kumar, Roshan / El-Derany, Marwa O / Sajjakulnukit, Peter / Das, Nupur K / Kerk, Samuel A / Solanki, Sumeet / James, Jadyn G / Kim, Donghwan / Zhang, Li / Chen, Brandon / Mehra, Rohit / Frankel, Timothy L / Győrffy, Balázs / Fearon, Eric R /

Pasca di Magliano, Marina / Gonzalez, Frank J / Banerjee, Ruma / Wahl, Daniel R / Lyssiotis, Costas A / Green, Michael / Shah, Yatrik M

Cell metabolism

2022 Volume 35, Issue 1, Page(s) 134–149.e6

Abstract: Effective therapies are lacking for patients with advanced colorectal cancer (CRC). The CRC tumor microenvironment has elevated metabolic waste products due to altered metabolism and proximity to the microbiota. The role of metabolite waste in tumor ... ...

Abstract	Effective therapies are lacking for patients with advanced colorectal cancer (CRC). The CRC tumor microenvironment has elevated metabolic waste products due to altered metabolism and proximity to the microbiota. The role of metabolite waste in tumor development, progression, and treatment resistance is unclear. We generated an autochthonous metastatic mouse model of CRC and used unbiased multi-omic analyses to reveal a robust accumulation of tumoral ammonia. The high ammonia levels induce T cell metabolic reprogramming, increase exhaustion, and decrease proliferation. CRC patients have increased serum ammonia, and the ammonia-related gene signature correlates with altered T cell response, adverse patient outcomes, and lack of response to immune checkpoint blockade. We demonstrate that enhancing ammonia clearance reactivates T cells, decreases tumor growth, and extends survival. Moreover, decreasing tumor-associated ammonia enhances anti-PD-L1 efficacy. These findings indicate that enhancing ammonia detoxification can reactivate T cells, highlighting a new approach to enhance the efficacy of immunotherapies.
MeSH term(s)	Animals ; Mice ; Ammonia ; T-Cell Exhaustion ; T-Lymphocytes ; Colorectal Neoplasms/pathology ; Immunotherapy ; Tumor Microenvironment
Chemical Substances	Ammonia (7664-41-7)
Language	English
Publishing date	2022-12-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2176834-1
ISSN	1932-7420 ; 1550-4131
ISSN (online)	1932-7420
ISSN	1550-4131
DOI	10.1016/j.cmet.2022.11.013
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Article ; Online: Cancer cells induce immune escape via glycocalyx changes controlled by the telomeric protein TRF2.

Cherfils-Vicini, Julien / Iltis, Charlene / Cervera, Ludovic / Pisano, Sabrina / Croce, Olivier / Sadouni, Nori / Győrffy, Balázs / Collet, Romy / Renault, Valérie M / Rey-Millet, Martin / Leonetti, Carlo / Zizza, Pasquale / Allain, Fabrice / Ghiringhelli, Francois / Soubeiran, Nicolas / Shkreli, Marina / Vivier, Eric / Biroccio, Annamaria / Gilson, Eric

The EMBO journal

2019 Volume 38, Issue 11

Abstract: Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with strong immunosuppressive activity that promote tumor growth. In this study, we describe a mechanism by which cancer cells control MDSCs in human cancers by upregulating TRF2, a ... ...

Abstract	Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with strong immunosuppressive activity that promote tumor growth. In this study, we describe a mechanism by which cancer cells control MDSCs in human cancers by upregulating TRF2, a protein required for telomere stability. Specifically, we showed that the TRF2 upregulation in cancer cells has extratelomeric roles in activating the expression of a network of genes involved in the biosynthesis of heparan sulfate proteoglycan, leading to profound changes in glycocalyx length and stiffness, as revealed by atomic force microscopy. This TRF2-dependent regulation facilitated the recruitment of MDSCs, their activation via the TLR2/MyD88/IL-6/STAT3 pathway leading to the inhibition of natural killer recruitment and cytotoxicity, and ultimately tumor progression and metastasis. The clinical relevance of these findings is supported by our analysis of cancer cohorts, which showed a correlation between high TRF2 expression and MDSC infiltration, which was inversely correlated with overall patient survival.
MeSH term(s)	Animals ; Cells, Cultured ; Female ; Gene Expression Regulation, Neoplastic ; Glycocalyx/genetics ; Glycocalyx/metabolism ; HEK293 Cells ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Nude ; Myeloid-Derived Suppressor Cells/metabolism ; Myeloid-Derived Suppressor Cells/physiology ; NIH 3T3 Cells ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/mortality ; Neoplasms/pathology ; Telomere/metabolism ; Telomeric Repeat Binding Protein 2/genetics ; Telomeric Repeat Binding Protein 2/physiology ; Tumor Escape/genetics ; Tumor Escape/physiology
Chemical Substances	TERF2 protein, human ; Telomeric Repeat Binding Protein 2
Language	English
Publishing date	2019-04-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	586044-1
ISSN	1460-2075 ; 0261-4189
ISSN (online)	1460-2075
ISSN	0261-4189
DOI	10.15252/embj.2018100012
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Zs.A 1808: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Ribosomal protein S11 influences glioma response to TOP2 poisons.

Oncogene

2020 Volume 39, Issue 27, Page(s) 5068–5081

Abstract: Topoisomerase II poisons are one of the most common class of chemotherapeutics used in cancer. We and others had shown that a subset of glioblastomas, the most malignant of all primary brain tumors in adults, is responsive to TOP2 poisons. To identify ... ...

Abstract	Topoisomerase II poisons are one of the most common class of chemotherapeutics used in cancer. We and others had shown that a subset of glioblastomas, the most malignant of all primary brain tumors in adults, is responsive to TOP2 poisons. To identify genes that confer susceptibility to this drug in gliomas, we performed a genome-scale CRISPR knockout screen with etoposide. Genes involved in protein synthesis and DNA damage were implicated in etoposide susceptibility. To define potential biomarkers for TOP2 poisons, CRISPR hits were overlapped with genes whose expression correlates with susceptibility to this drug across glioma cell lines, revealing ribosomal protein subunit RPS11, 16, and 18 as putative biomarkers for response to TOP2 poisons. Loss of RPS11 led to resistance to etoposide and doxorubicin and impaired the induction of proapoptotic gene APAF1 following treatment. The expression of these ribosomal subunits was also associated with susceptibility to TOP2 poisons across cell lines from gliomas and multiple other cancers.
MeSH term(s)	Apoptotic Protease-Activating Factor 1/metabolism ; Brain Neoplasms/drug therapy ; Brain Neoplasms/genetics ; CRISPR-Cas Systems ; Cell Line, Tumor ; DNA Breaks, Double-Stranded/drug effects ; DNA Repair/drug effects ; DNA Topoisomerases, Type II/metabolism ; Doxorubicin/pharmacology ; Etoposide/pharmacology ; Gene Knockout Techniques ; Glioblastoma/drug therapy ; Glioblastoma/genetics ; Humans ; Ribosomal Proteins/metabolism ; Topoisomerase II Inhibitors/pharmacology
Chemical Substances	APAF1 protein, human ; Apoptotic Protease-Activating Factor 1 ; RPS11 protein, human ; Ribosomal Proteins ; Topoisomerase II Inhibitors ; Etoposide (6PLQ3CP4P3) ; Doxorubicin (80168379AG) ; DNA Topoisomerases, Type II (EC 5.99.1.3)
Language	English
Publishing date	2020-06-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-020-1342-0
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Article: Use of reversed-phase liquid chromatography for determining the lipophilicity of alpha-aryl-N-cyclopropylnitrones.

Balogh, György T / Szántó, Zoltán / Forrai, Erika / Gyorffy, Werner / Lopata, Antal

Journal of pharmaceutical and biomedical analysis

2005 Volume 39, Issue 5, Page(s) 1057–1062

Abstract: The relationship between a reversed-phase high-performance liquid chromatography (RP-HPLC) retention parameter and various calculated log P-values of our previously synthesized alpha-aryl-N-cyclopropyl-nitrone derivatives was investigated. The RP-HPLC ... ...

Abstract	The relationship between a reversed-phase high-performance liquid chromatography (RP-HPLC) retention parameter and various calculated log P-values of our previously synthesized alpha-aryl-N-cyclopropyl-nitrone derivatives was investigated. The RP-HPLC experiments were carried out with acetonitrile-water and methanol-water mixtures as mobile phases and with two kinds of stationary phases of different polarity. The retention parameter, log k(w) was obtained by linear extrapolation of the log k retention to pure water as the mobile phase. The calculated log P-values were C log P, ACD/log P, R log P, A log P, LogKow, X log P and M log P. Statistically, highly significant correlations were found between log k(w) and the calculated log P-values with squared correlation coefficients ranging from 0.771 (with A log P) to 0.956 (with C log P). In addition, the comparative molecular similarity indices analysis (CoMSIA) method was also applied to correlate the log k(w) retention parameter of the compounds with their molecular fields. Statistically significant CoMSIA models were obtained between log k(w) and the hydrophobic and steric molecular fields of our compounds. The CoMSIA models describe how the structure of the nitrone derivatives influences (through hydrophobic and steric interactions with the stationary phase) the chromatographic retention of the compounds.
MeSH term(s)	Chemical Phenomena ; Chemistry, Physical ; Chromatography, High Pressure Liquid ; Lipids/chemistry ; Methanol ; Nitrogen Oxides/chemistry ; Solvents ; Water
Chemical Substances	Lipids ; Nitrogen Oxides ; Solvents ; Water (059QF0KO0R) ; Methanol (Y4S76JWI15)
Language	English
Publishing date	2005-10-04
Publishing country	England
Document type	Journal Article
ZDB-ID	604917-5
ISSN	1873-264X ; 0731-7085
ISSN (online)	1873-264X
ISSN	0731-7085
DOI	10.1016/j.jpba.2005.05.019
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Article: Validation of biomarkers for the study of environmental carcinogens: a review.

Gallo, Valentina / Khan, Aneire / Gonzales, Carlos / Phillips, David H / Schoket, Bernadette / Györffy, Erika / Anna, Livia / Kovács, Katalin / Møller, Peter / Loft, Steffen / Kyrtopoulos, Soterios / Matullo, Giuseppe / Vineis, Paolo

Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals

2008 Volume 13, Issue 5, Page(s) 505–534

Abstract: There is a need for validation of biomarkers. Our aim is to review published work on the validation of selected biomarkers: bulky DNA adducts, N-nitroso compounds, 1-hydroxypyrene, and oxidative damage to DNA. A systematic literature search in PubMed was ...

Abstract	There is a need for validation of biomarkers. Our aim is to review published work on the validation of selected biomarkers: bulky DNA adducts, N-nitroso compounds, 1-hydroxypyrene, and oxidative damage to DNA. A systematic literature search in PubMed was performed. Information on the variability and reliability of the laboratory tests used for biomarkers measurements was collected. For the evaluation of the evidence on validation we referred to the ACCE criteria. Little is known about intraindividual variation of DNA adduct measurements, but measurements have a good repeatability irrespective of the technique used for their identification; reproducibility improved after the correction for a laboratory factor. A high-sensitivity method is available for the measurement of 1-hydroxypyrene in urine. There is consensus on validation of biomarkers of oxidative damage DNA based on the comet assay and chromatographic measurement in blood while urinary measurements by chromatographic assays are well validated, and ELISA-based assays appear to lack specificity. Immunoassays for the quantification of adducts of N-nitroso compounds are useful for large epidemiological studies, given their sensitivity, the small amount of DNA required and their potential for rapid and high-throughput analysis.
MeSH term(s)	Biomarkers/analysis ; Carcinogens, Environmental/analysis ; DNA Adducts ; DNA Damage ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay ; Humans ; Oxidative Stress
Chemical Substances	Biomarkers ; Carcinogens, Environmental ; DNA Adducts
Language	English
Publishing date	2008-10-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review ; Validation Studies
ZDB-ID	1324372-x
ISSN	1354-750X
ISSN	1354-750X
DOI	10.1080/13547500802054611
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