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Showing 1 - 200 of 370 Journals sorted alphabetically
Acta Biochimica et Biophysica Sinica     Hybrid Journal   (Followers: 6, SJR: 0.881, h-index: 38)
Adaptation     Hybrid Journal   (Followers: 8, SJR: 0.111, h-index: 4)
Aesthetic Surgery J.     Hybrid Journal   (Followers: 6, SJR: 1.538, h-index: 35)
African Affairs     Hybrid Journal   (Followers: 59, SJR: 1.512, h-index: 46)
Age and Ageing     Hybrid Journal   (Followers: 85, SJR: 1.611, h-index: 107)
Alcohol and Alcoholism     Hybrid Journal   (Followers: 16, SJR: 0.935, h-index: 80)
American Entomologist     Full-text available via subscription   (Followers: 6)
American Historical Review     Hybrid Journal   (Followers: 139, SJR: 0.652, h-index: 43)
American J. of Agricultural Economics     Hybrid Journal   (Followers: 40, SJR: 1.441, h-index: 77)
American J. of Epidemiology     Hybrid Journal   (Followers: 171, SJR: 3.047, h-index: 201)
American J. of Hypertension     Hybrid Journal   (Followers: 23, SJR: 1.397, h-index: 111)
American J. of Jurisprudence     Hybrid Journal   (Followers: 17)
American J. of Legal History     Full-text available via subscription   (Followers: 6, SJR: 0.151, h-index: 7)
American Law and Economics Review     Hybrid Journal   (Followers: 25, SJR: 0.824, h-index: 23)
American Literary History     Hybrid Journal   (Followers: 12, SJR: 0.185, h-index: 22)
Analysis     Hybrid Journal   (Followers: 23)
Annals of Botany     Hybrid Journal   (Followers: 36, SJR: 1.912, h-index: 124)
Annals of Occupational Hygiene     Hybrid Journal   (Followers: 28, SJR: 0.837, h-index: 57)
Annals of Oncology     Hybrid Journal   (Followers: 49, SJR: 4.362, h-index: 173)
Annals of the Entomological Society of America     Full-text available via subscription   (Followers: 8, SJR: 0.642, h-index: 53)
Annals of Work Exposures and Health     Hybrid Journal  
AoB Plants     Open Access   (Followers: 4, SJR: 0.78, h-index: 10)
Applied Economic Perspectives and Policy     Hybrid Journal   (Followers: 19, SJR: 0.884, h-index: 31)
Applied Linguistics     Hybrid Journal   (Followers: 51, SJR: 1.749, h-index: 63)
Applied Mathematics Research eXpress     Hybrid Journal   (Followers: 1, SJR: 0.779, h-index: 11)
Arbitration Intl.     Full-text available via subscription   (Followers: 20)
Arbitration Law Reports and Review     Hybrid Journal   (Followers: 13)
Archives of Clinical Neuropsychology     Hybrid Journal   (Followers: 26, SJR: 0.96, h-index: 71)
Aristotelian Society Supplementary Volume     Hybrid Journal   (Followers: 2, SJR: 0.102, h-index: 20)
Arthropod Management Tests     Hybrid Journal   (Followers: 2)
Astronomy & Geophysics     Hybrid Journal   (Followers: 47, SJR: 0.144, h-index: 15)
Behavioral Ecology     Hybrid Journal   (Followers: 49, SJR: 1.698, h-index: 92)
Bioinformatics     Hybrid Journal   (Followers: 304, SJR: 4.643, h-index: 271)
Biology Methods and Protocols     Hybrid Journal  
Biology of Reproduction     Full-text available via subscription   (Followers: 9, SJR: 1.646, h-index: 149)
Biometrika     Hybrid Journal   (Followers: 19, SJR: 2.801, h-index: 90)
BioScience     Hybrid Journal   (Followers: 30, SJR: 2.374, h-index: 154)
Bioscience Horizons : The National Undergraduate Research J.     Open Access   (Followers: 1, SJR: 0.213, h-index: 9)
Biostatistics     Hybrid Journal   (Followers: 16, SJR: 1.955, h-index: 55)
BJA : British J. of Anaesthesia     Hybrid Journal   (Followers: 148, SJR: 2.314, h-index: 133)
BJA Education     Hybrid Journal   (Followers: 64, SJR: 0.272, h-index: 20)
Brain     Hybrid Journal   (Followers: 61, SJR: 6.097, h-index: 264)
Briefings in Bioinformatics     Hybrid Journal   (Followers: 44, SJR: 4.086, h-index: 73)
Briefings in Functional Genomics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 50)
British J. for the Philosophy of Science     Hybrid Journal   (Followers: 34, SJR: 1.267, h-index: 38)
British J. of Aesthetics     Hybrid Journal   (Followers: 26, SJR: 0.217, h-index: 18)
British J. of Criminology     Hybrid Journal   (Followers: 527, SJR: 1.373, h-index: 62)
British J. of Social Work     Hybrid Journal   (Followers: 83, SJR: 0.771, h-index: 53)
British Medical Bulletin     Hybrid Journal   (Followers: 7, SJR: 1.391, h-index: 84)
British Yearbook of Intl. Law     Hybrid Journal   (Followers: 27)
Bulletin of the London Mathematical Society     Hybrid Journal   (Followers: 3, SJR: 1.474, h-index: 31)
Cambridge J. of Economics     Hybrid Journal   (Followers: 58, SJR: 0.957, h-index: 59)
Cambridge J. of Regions, Economy and Society     Hybrid Journal   (Followers: 11, SJR: 1.067, h-index: 22)
Cambridge Quarterly     Hybrid Journal   (Followers: 11, SJR: 0.1, h-index: 7)
Capital Markets Law J.     Hybrid Journal   (Followers: 1)
Carcinogenesis     Hybrid Journal   (Followers: 2, SJR: 2.439, h-index: 167)
Cardiovascular Research     Hybrid Journal   (Followers: 12, SJR: 2.897, h-index: 175)
Cerebral Cortex     Hybrid Journal   (Followers: 41, SJR: 4.827, h-index: 192)
CESifo Economic Studies     Hybrid Journal   (Followers: 16, SJR: 0.501, h-index: 19)
Chemical Senses     Hybrid Journal   (Followers: 1, SJR: 1.436, h-index: 76)
Children and Schools     Hybrid Journal   (Followers: 6, SJR: 0.211, h-index: 18)
Chinese J. of Comparative Law     Hybrid Journal   (Followers: 3)
Chinese J. of Intl. Law     Hybrid Journal   (Followers: 21, SJR: 0.737, h-index: 11)
Chinese J. of Intl. Politics     Hybrid Journal   (Followers: 9, SJR: 1.238, h-index: 15)
Christian Bioethics: Non-Ecumenical Studies in Medical Morality     Hybrid Journal   (Followers: 11, SJR: 0.191, h-index: 8)
Classical Receptions J.     Hybrid Journal   (Followers: 24, SJR: 0.1, h-index: 3)
Clinical Infectious Diseases     Hybrid Journal   (Followers: 59, SJR: 4.742, h-index: 261)
Clinical Kidney J.     Open Access   (Followers: 4, SJR: 0.338, h-index: 19)
Community Development J.     Hybrid Journal   (Followers: 24, SJR: 0.47, h-index: 28)
Computer J.     Hybrid Journal   (Followers: 7, SJR: 0.371, h-index: 47)
Conservation Physiology     Open Access   (Followers: 2)
Contemporary Women's Writing     Hybrid Journal   (Followers: 11, SJR: 0.111, h-index: 3)
Contributions to Political Economy     Hybrid Journal   (Followers: 5, SJR: 0.313, h-index: 10)
Critical Values     Full-text available via subscription  
Current Legal Problems     Hybrid Journal   (Followers: 26)
Current Zoology     Full-text available via subscription   (SJR: 0.999, h-index: 20)
Database : The J. of Biological Databases and Curation     Open Access   (Followers: 11, SJR: 1.068, h-index: 24)
Digital Scholarship in the Humanities     Hybrid Journal   (Followers: 12)
Diplomatic History     Hybrid Journal   (Followers: 19, SJR: 0.296, h-index: 22)
DNA Research     Open Access   (Followers: 4, SJR: 2.42, h-index: 77)
Dynamics and Statistics of the Climate System     Open Access   (Followers: 3)
Early Music     Hybrid Journal   (Followers: 15, SJR: 0.124, h-index: 11)
Economic Policy     Hybrid Journal   (Followers: 63, SJR: 2.052, h-index: 52)
ELT J.     Hybrid Journal   (Followers: 25, SJR: 1.26, h-index: 23)
English Historical Review     Hybrid Journal   (Followers: 51, SJR: 0.311, h-index: 10)
English: J. of the English Association     Hybrid Journal   (Followers: 13, SJR: 0.144, h-index: 3)
Environmental Entomology     Full-text available via subscription   (Followers: 11, SJR: 0.791, h-index: 66)
Environmental Epigenetics     Open Access   (Followers: 1)
Environmental History     Hybrid Journal   (Followers: 26, SJR: 0.197, h-index: 25)
EP-Europace     Hybrid Journal   (Followers: 2, SJR: 2.201, h-index: 71)
Epidemiologic Reviews     Hybrid Journal   (Followers: 10, SJR: 3.917, h-index: 81)
ESHRE Monographs     Hybrid Journal  
Essays in Criticism     Hybrid Journal   (Followers: 16, SJR: 0.1, h-index: 6)
European Heart J.     Hybrid Journal   (Followers: 49, SJR: 6.997, h-index: 227)
European Heart J. - Cardiovascular Imaging     Hybrid Journal   (Followers: 8, SJR: 2.044, h-index: 58)
European Heart J. - Cardiovascular Pharmacotherapy     Full-text available via subscription   (Followers: 1)
European Heart J. - Quality of Care and Clinical Outcomes     Hybrid Journal  
European Heart J. Supplements     Hybrid Journal   (Followers: 7, SJR: 0.152, h-index: 31)
European J. of Cardio-Thoracic Surgery     Hybrid Journal   (Followers: 8, SJR: 1.568, h-index: 104)
European J. of Intl. Law     Hybrid Journal   (Followers: 160, SJR: 0.722, h-index: 38)
European J. of Orthodontics     Hybrid Journal   (Followers: 4, SJR: 1.09, h-index: 60)
European J. of Public Health     Hybrid Journal   (Followers: 22, SJR: 1.284, h-index: 64)
European Review of Agricultural Economics     Hybrid Journal   (Followers: 11, SJR: 1.549, h-index: 42)
European Review of Economic History     Hybrid Journal   (Followers: 28, SJR: 0.628, h-index: 24)
European Sociological Review     Hybrid Journal   (Followers: 41, SJR: 2.061, h-index: 53)
Evolution, Medicine, and Public Health     Open Access   (Followers: 11)
Family Practice     Hybrid Journal   (Followers: 11, SJR: 1.048, h-index: 77)
Fems Microbiology Ecology     Hybrid Journal   (Followers: 9, SJR: 1.687, h-index: 115)
Fems Microbiology Letters     Hybrid Journal   (Followers: 20, SJR: 1.126, h-index: 118)
Fems Microbiology Reviews     Hybrid Journal   (Followers: 25, SJR: 7.587, h-index: 150)
Fems Yeast Research     Hybrid Journal   (Followers: 13, SJR: 1.213, h-index: 66)
Foreign Policy Analysis     Hybrid Journal   (Followers: 22, SJR: 0.859, h-index: 10)
Forestry: An Intl. J. of Forest Research     Hybrid Journal   (Followers: 16, SJR: 0.903, h-index: 44)
Forum for Modern Language Studies     Hybrid Journal   (Followers: 6, SJR: 0.108, h-index: 6)
French History     Hybrid Journal   (Followers: 32, SJR: 0.123, h-index: 10)
French Studies     Hybrid Journal   (Followers: 20, SJR: 0.119, h-index: 7)
French Studies Bulletin     Hybrid Journal   (Followers: 10, SJR: 0.102, h-index: 3)
Gastroenterology Report     Open Access   (Followers: 2)
Genome Biology and Evolution     Open Access   (Followers: 10, SJR: 3.22, h-index: 39)
Geophysical J. Intl.     Hybrid Journal   (Followers: 34, SJR: 1.839, h-index: 119)
German History     Hybrid Journal   (Followers: 25, SJR: 0.437, h-index: 13)
GigaScience     Open Access   (Followers: 3)
Global Summitry     Hybrid Journal  
Glycobiology     Hybrid Journal   (Followers: 14, SJR: 1.692, h-index: 101)
Health and Social Work     Hybrid Journal   (Followers: 49, SJR: 0.505, h-index: 40)
Health Education Research     Hybrid Journal   (Followers: 12, SJR: 0.814, h-index: 80)
Health Policy and Planning     Hybrid Journal   (Followers: 20, SJR: 1.628, h-index: 66)
Health Promotion Intl.     Hybrid Journal   (Followers: 21, SJR: 0.664, h-index: 60)
History Workshop J.     Hybrid Journal   (Followers: 27, SJR: 0.313, h-index: 20)
Holocaust and Genocide Studies     Hybrid Journal   (Followers: 24, SJR: 0.115, h-index: 13)
Human Molecular Genetics     Hybrid Journal   (Followers: 9, SJR: 4.288, h-index: 233)
Human Reproduction     Hybrid Journal   (Followers: 78, SJR: 2.271, h-index: 179)
Human Reproduction Update     Hybrid Journal   (Followers: 17, SJR: 4.678, h-index: 128)
Human Rights Law Review     Hybrid Journal   (Followers: 60, SJR: 0.7, h-index: 21)
ICES J. of Marine Science: J. du Conseil     Hybrid Journal   (Followers: 54, SJR: 1.233, h-index: 88)
ICSID Review     Hybrid Journal   (Followers: 10)
ILAR J.     Hybrid Journal   (Followers: 1, SJR: 1.099, h-index: 51)
IMA J. of Applied Mathematics     Hybrid Journal   (SJR: 0.329, h-index: 26)
IMA J. of Management Mathematics     Hybrid Journal   (Followers: 2, SJR: 0.351, h-index: 20)
IMA J. of Mathematical Control and Information     Hybrid Journal   (Followers: 2, SJR: 0.661, h-index: 28)
IMA J. of Numerical Analysis - advance access     Hybrid Journal   (SJR: 2.032, h-index: 44)
Industrial and Corporate Change     Hybrid Journal   (Followers: 8, SJR: 1.37, h-index: 81)
Industrial Law J.     Hybrid Journal   (Followers: 30, SJR: 0.184, h-index: 15)
Information and Inference     Free  
Integrative and Comparative Biology     Hybrid Journal   (Followers: 8, SJR: 1.911, h-index: 90)
Interacting with Computers     Hybrid Journal   (Followers: 10, SJR: 0.529, h-index: 59)
Interactive CardioVascular and Thoracic Surgery     Hybrid Journal   (Followers: 5, SJR: 0.743, h-index: 35)
Intl. Affairs     Hybrid Journal   (Followers: 52, SJR: 1.264, h-index: 53)
Intl. Data Privacy Law     Hybrid Journal   (Followers: 28)
Intl. Health     Hybrid Journal   (Followers: 5, SJR: 0.835, h-index: 15)
Intl. Immunology     Hybrid Journal   (Followers: 3, SJR: 1.613, h-index: 111)
Intl. J. for Quality in Health Care     Hybrid Journal   (Followers: 33, SJR: 1.593, h-index: 69)
Intl. J. of Constitutional Law     Hybrid Journal   (Followers: 60, SJR: 0.613, h-index: 19)
Intl. J. of Epidemiology     Hybrid Journal   (Followers: 148, SJR: 4.381, h-index: 145)
Intl. J. of Law and Information Technology     Hybrid Journal   (Followers: 4, SJR: 0.247, h-index: 8)
Intl. J. of Law, Policy and the Family     Hybrid Journal   (Followers: 29, SJR: 0.307, h-index: 15)
Intl. J. of Lexicography     Hybrid Journal   (Followers: 8, SJR: 0.404, h-index: 18)
Intl. J. of Low-Carbon Technologies     Open Access   (Followers: 1, SJR: 0.457, h-index: 12)
Intl. J. of Neuropsychopharmacology     Open Access   (Followers: 3, SJR: 1.69, h-index: 79)
Intl. J. of Public Opinion Research     Hybrid Journal   (Followers: 9, SJR: 0.906, h-index: 33)
Intl. J. of Refugee Law     Hybrid Journal   (Followers: 33, SJR: 0.231, h-index: 21)
Intl. J. of Transitional Justice     Hybrid Journal   (Followers: 13, SJR: 0.833, h-index: 12)
Intl. Mathematics Research Notices     Hybrid Journal   (Followers: 1, SJR: 2.052, h-index: 42)
Intl. Political Sociology     Hybrid Journal   (Followers: 31, SJR: 1.339, h-index: 19)
Intl. Relations of the Asia-Pacific     Hybrid Journal   (Followers: 18, SJR: 0.539, h-index: 17)
Intl. Studies Perspectives     Hybrid Journal   (Followers: 7, SJR: 0.998, h-index: 28)
Intl. Studies Quarterly     Hybrid Journal   (Followers: 39, SJR: 2.184, h-index: 68)
Intl. Studies Review     Hybrid Journal   (Followers: 18, SJR: 0.783, h-index: 38)
ISLE: Interdisciplinary Studies in Literature and Environment     Hybrid Journal   (Followers: 1, SJR: 0.155, h-index: 4)
ITNOW     Hybrid Journal   (Followers: 2, SJR: 0.102, h-index: 4)
J. of African Economies     Hybrid Journal   (Followers: 15, SJR: 0.647, h-index: 30)
J. of American History     Hybrid Journal   (Followers: 43, SJR: 0.286, h-index: 34)
J. of Analytical Toxicology     Hybrid Journal   (Followers: 13, SJR: 1.038, h-index: 60)
J. of Antimicrobial Chemotherapy     Hybrid Journal   (Followers: 13, SJR: 2.157, h-index: 149)
J. of Antitrust Enforcement     Hybrid Journal   (Followers: 1)
J. of Applied Poultry Research     Hybrid Journal   (Followers: 3, SJR: 0.563, h-index: 43)
J. of Biochemistry     Hybrid Journal   (Followers: 43, SJR: 1.341, h-index: 96)
J. of Chromatographic Science     Hybrid Journal   (Followers: 16, SJR: 0.448, h-index: 42)
J. of Church and State     Hybrid Journal   (Followers: 11, SJR: 0.167, h-index: 11)
J. of Competition Law and Economics     Hybrid Journal   (Followers: 35, SJR: 0.442, h-index: 16)
J. of Complex Networks     Hybrid Journal   (Followers: 1, SJR: 1.165, h-index: 5)
J. of Conflict and Security Law     Hybrid Journal   (Followers: 13, SJR: 0.196, h-index: 15)
J. of Consumer Research     Full-text available via subscription   (Followers: 43, SJR: 4.896, h-index: 121)
J. of Crohn's and Colitis     Hybrid Journal   (Followers: 10, SJR: 1.543, h-index: 37)
J. of Cybersecurity     Hybrid Journal   (Followers: 3)
J. of Deaf Studies and Deaf Education     Hybrid Journal   (Followers: 9, SJR: 0.69, h-index: 36)
J. of Design History     Hybrid Journal   (Followers: 16, SJR: 0.166, h-index: 14)
J. of Economic Entomology     Full-text available via subscription   (Followers: 6, SJR: 0.894, h-index: 76)
J. of Economic Geography     Hybrid Journal   (Followers: 39, SJR: 2.909, h-index: 69)
J. of Environmental Law     Hybrid Journal   (Followers: 23, SJR: 0.457, h-index: 20)
J. of European Competition Law & Practice     Hybrid Journal   (Followers: 19)
J. of Experimental Botany     Hybrid Journal   (Followers: 14, SJR: 2.798, h-index: 163)
J. of Financial Econometrics     Hybrid Journal   (Followers: 23, SJR: 1.314, h-index: 27)
J. of Global Security Studies     Hybrid Journal   (Followers: 3)
J. of Heredity     Hybrid Journal   (Followers: 4, SJR: 1.024, h-index: 76)
J. of Hindu Studies     Hybrid Journal   (Followers: 7, SJR: 0.186, h-index: 3)
J. of Hip Preservation Surgery     Open Access  
J. of Human Rights Practice     Hybrid Journal   (Followers: 20, SJR: 0.399, h-index: 10)
J. of Infectious Diseases     Hybrid Journal   (Followers: 39, SJR: 4, h-index: 209)
J. of Insect Science     Open Access   (Followers: 8, SJR: 0.388, h-index: 31)

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Journal Cover Carcinogenesis
  [SJR: 2.439]   [H-I: 167]   [2 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0143-3334 - ISSN (Online) 1460-2180
   Published by Oxford University Press Homepage  [370 journals]
  • Back_Cover
    • PubDate: 2017-10-13
      DOI: 10.1093/carcin/bgw130
      Issue No: Vol. 38, No. 10 (2017)
  • Editorial_Board
    • PubDate: 2017-10-13
      DOI: 10.1093/carcin/bgw131
      Issue No: Vol. 38, No. 10 (2017)
  • Front_Cover
    • PubDate: 2017-10-13
      DOI: 10.1093/carcin/bgw132
      Issue No: Vol. 38, No. 10 (2017)
  • Instructions_to_Authors
    • PubDate: 2017-10-13
      DOI: 10.1093/carcin/bgw133
      Issue No: Vol. 38, No. 10 (2017)
  • Subscriptions
    • PubDate: 2017-10-13
      DOI: 10.1093/carcin/bgw134
      Issue No: Vol. 38, No. 10 (2017)
  • Table_of_Contents
    • PubDate: 2017-10-13
      DOI: 10.1093/carcin/bgw135
      Issue No: Vol. 38, No. 10 (2017)
  • Melatonin as a promising agent to treat ovarian cancer: molecular
    • Authors: Chuffa L; Reiter R, Lupi L.
      Pages: 945 - 952
      Abstract: AbstractOvarian cancer (OC) has the highest mortality rate of all gynecological cancers, and most patients develop chemoresistance after first-line treatments. Despite recent advances, the 5-year relative survival is ~45% for all OC subtypes, and invasive epithelial OC has only a 17% survival rate when diagnosed at a late stage. Identification of new efficacious molecules or biomarkers represents important opportunities in the treatment of OC. The pharmacological and physiological properties of melatonin indicate this agent could be useful against OC progression and metastasis. In normal cells, melatonin has potent antioxidant and anti-apoptotic actions. Conversely, melatonin has pro-oxidant as well as anti-proliferative, anti-angiogenic and immunomodulatory properties in many cancer types including hormone-dependent cancers. Although melatonin receptors have been identified in OC cells, the exact mechanism by which melatonin induces anticancer activities remains incompletely understood. Clinical studies have reported negative correlation between aggressiveness of OC and serum levels of melatonin, reinforcing the idea that melatonin may be a critical factor determining OC development. In vitro and in vivo studies suggest melatonin differentially regulates multiple signaling pathways in OC cells. This focused review explores the potential mechanisms of action of melatonin on cultured OC cells and in experimental models of OC in an attempt to clarify how melatonin modulates the signaling pathways involved in cancer cell apoptosis, survival, inflammation, proliferation and metabolic processes. Based on the evidence presented, we feel that melatonin, as an agent that controls cellular signals associated with malignancy, may be beneficial in combination with other therapeutics for OC treatment.
      PubDate: 2017-06-02
      DOI: 10.1093/carcin/bgx054
      Issue No: Vol. 38, No. 10 (2017)
  • Defining key concepts of intestinal and epithelial cancer biology through
           the use of mouse models
    • Authors: Phesse T; Durban V, Sansom O.
      Pages: 953 - 965
      Abstract: AbstractOver the past 20 years, huge advances have been made in modelling human diseases such as cancer using genetically modified mice. Accurate in vivo models are essential to examine the complex interaction between cancer cells, surrounding stromal cells, tumour-associated inflammatory cells, fibroblast and blood vessels, and to recapitulate all the steps involved in metastasis. Elucidating these interactions in vitro has inherent limitations, and thus animal models are a powerful tool to enable researchers to gain insight into the complex interactions between signalling pathways and different cells types. This review will focus on how advances in in vivo models have shed light on many aspects of cancer biology including the identification of oncogenes, tumour suppressors and stem cells, epigenetics, cell death and context dependent cell signalling.
      PubDate: 2017-08-23
      DOI: 10.1093/carcin/bgx080
      Issue No: Vol. 38, No. 10 (2017)
  • PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the
           transcription of cell cycle genes
    • Authors: Singh D; Gholamalamdari O, Jadaliha M, et al.
      Pages: 966 - 975
      Abstract: AbstractBreast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatin-associated proteins play crucial roles in BC initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in BC progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma. Survival data analyses revealed that the levels of PSIP1 showed a negative association with TNBC patient survival. Depletion of PSIP1/p75 significantly reduced the tumorigenicity and metastatic properties of TNBC cell lines while its over-expression promoted tumorigenicity. Further, gene expression studies revealed that PSIP1 regulates the expression of genes controlling cell-cycle progression, cell migration and invasion. Finally, by interacting with RNA polymerase II, PSIP1/p75 facilitates the association of RNA pol II to the promoter of cell cycle genes and thereby regulates their transcription. Our findings demonstrate an important role of PSIP1/p75 in TNBC tumorigenicity by promoting the expression of genes that control the cell cycle and tumor metastasis.
      PubDate: 2017-06-17
      DOI: 10.1093/carcin/bgx062
      Issue No: Vol. 38, No. 10 (2017)
  • UV radiation-induced SUMOylation of DDB2 regulates nucleotide excision
    • Authors: Han C; Zhao R, Kroger J, et al.
      Pages: 976 - 985
      Abstract: AbstractSubunit 2 of DNA damage-binding protein complex (DDB2) is an early sensor of nucleotide excision repair (NER) pathway for eliminating DNA damage induced by UV radiation (UVR) and cisplatin treatments of mammalian cells. DDB2 is modified by ubiquitin and poly(ADP-ribose) (PAR) in response to UVR, and these modifications play a crucial role in regulating NER. Here, using immuno-analysis of irradiated cell extracts, we have identified multiple post-irradiation modifications of DDB2 protein. Interestingly, although the DNA lesions induced by both UVR and cisplatin are corrected by NER, only the UV irradiation, but not the cisplatin treatment, induces any discernable DDB2 modifications. We, for the first time, show that the appearance of UVR-induced DDB2 modifications depend on the binding of DDB2 to the damaged chromatin and the participation of functionally active 26S proteasome. The in vitro and in vivo analysis revealed that SUMO-1 conjugations comprise a significant portion of these UVR-induced DDB2 modifications. Mapping of SUMO-modified sites demonstrated that UVR-induced SUMOylation occurs on Lys-309 residue of DDB2 protein. Mutation of Lys-309 to Arg-309 diminished the DDB2 SUMOylation observable both in vitro and in vivo. Moreover, K309R mutated DDB2 lost its function of recruiting XPC to the DNA damage sites, as well as the ability to repair cyclobutane pyrimidine dimers following cellular UV irradiation. Taken together, our results indicate that DDB2 is modified by SUMOylation upon UV irradiation, and this post-translational modification plays an important role in the initial recognition and processing of UVR-induced DNA damage occurring within the context of chromatin.
      PubDate: 2017-07-22
      DOI: 10.1093/carcin/bgx076
      Issue No: Vol. 38, No. 10 (2017)
  • Genome-scale identification of microRNA-related SNPs associated with risk
           of head and neck squamous cell carcinoma
    • Authors: Wilkins O; Titus A, Gui J, et al.
      Pages: 986 - 993
      Abstract: AbstractPolymorphisms in microRNAs and their target sites can disrupt microRNA-dependent gene regulation, and have been associated with cancer susceptibility. However, genome-scale analyses of microRNA-related genetic variation in cancer are lacking. We tested the associations of ~40 000 common [minor allele frequency (MAF) ≥5%], microRNA-related single nucleotide polymorphisms (miR-SNPs), with risk of head and neck squamous cell carcinoma (HNSCC) in a discovery population, and validated selected loci in an independent population among a total of 2198 cases and 2180 controls. Joint analyses across the discovery and validation populations revealed six novel miR–SNP associations with risk of HNSCC. An upstream variant of MIR548H4 (rs7834169), replicated its association with overall HNSCC risk as well as risk of oral cavity cancer. Four other variants were specifically associated with oral cavity cancer risk (rs16914640, rs1134367, rs7306991 and rs1373756). 3ʹUTR variant of HADH, rs221347 and rs4975616, located within known cancer risk locus 5p15.33, were specific to risk of laryngeal cancer. High confidence predicted microRNA binding sites were identified for CLEC2D, LOC37443, KDM8 and HADH overlapping rs16914640, rs7306991, rs1134367 and rs221347, respectively. Furthermore, we identified several microRNA interactions with KDM8 and HADH predicted to be disrupted by genetic variation at rs1134367 and rs221347. These results suggest microRNA-related genetic variation may contribute to the genetic susceptibility of HNSCC, and that more powerful evaluation of this class of genetic variation and their relationship with cancer risk is warranted.
      PubDate: 2017-06-05
      DOI: 10.1093/carcin/bgx056
      Issue No: Vol. 38, No. 10 (2017)
  • Telomere length, ATM mutation status and cancer risk in
           Ataxia-Telangiectasia families
    • Authors: Renault A; Mebirouk N, Cavaciuti E, et al.
      Pages: 994 - 1003
      Abstract: AbstractRecent studies have linked constitutive telomere length (TL) to aging-related diseases including cancer at different sites. ATM participates in the signaling of telomere erosion, and inherited mutations in ATM have been associated with increased risk of cancer, particularly breast cancer. The goal of this study was to investigate whether carriage of an ATM mutation and TL interplay to modify cancer risk in ataxia-telangiectasia (A-T) families.The study population consisted of 284 heterozygous ATM mutation carriers (HetAT) and 174 non-carriers (non-HetAT) from 103 A-T families. Forty-eight HetAT and 14 non-HetAT individuals had cancer, among them 25 HetAT and 6 non-HetAT were diagnosed after blood sample collection. We measured mean TL using a quantitative PCR assay and genotyped seven single-nucleotide polymorphisms (SNPs) recurrently associated with TL in large population-based studies.HetAT individuals were at increased risk of cancer (OR = 2.3, 95%CI = 1.2–4.4, P = 0.01), and particularly of breast cancer for women (OR = 2.9, 95%CI = 1.2–7.1, P = 0.02), in comparison to their non-HetAT relatives. HetAT individuals had longer telomeres than non-HetAT individuals (P = 0.0008) but TL was not associated with cancer risk, and no significant interaction was observed between ATM mutation status and TL. Furthermore, rs9257445 (ZNF311) was associated with TL in HetAT subjects and rs6060627 (BCL2L1) modified cancer risk in HetAT and non-HetAT women.Our findings suggest that carriage of an ATM mutation impacts on the age-related TL shortening and that TL per se is not related to cancer risk in ATM carriers. TL measurement alone is not a good marker for predicting cancer risk in A-T families.
      PubDate: 2017-07-21
      DOI: 10.1093/carcin/bgx074
      Issue No: Vol. 38, No. 10 (2017)
  • A prospective study of immune and inflammation markers and risk of lung
           cancer among female never smokers in Shanghai
    • Authors: Shiels M; Shu X, Chaturvedi A, et al.
      Pages: 1004 - 1010
      Abstract: AbstractThere is a paucity of data on risk factors for lung cancer among never smokers. Here, we have carried out the first large study of circulating inflammation markers and lung cancer risk among female never smokers in Shanghai. A study of 248 lung cancer cases in female never smokers and 263 controls was nested within the Shanghai Women’s Health Study (n = 75221), matched by dates of birth and blood collection (mean follow-up time = 7.5 years). Prediagnostic plasma levels of 65 inflammation markers were measured using a Luminex bead-based assay. Odds ratios (ORs) were estimated with multivariable logistic regression. Nine of 61 evaluable markers were statistically significantly associated with lung cancer risk among never smoking Chinese women (P-trend across categories <0.05). Soluble interleukin-6 receptor [sIL-6R; highest versus lowest category OR = 2.37; 95% confidence interval (CI) 1.40–4.02) and chemokine (C–C motif) ligand 2/monocyte chemotactic protein 1; (OR = 1.62; 95% CI 0.94–2.80) were associated with an increased risk of lung cancer, whereas interleukin (IL)-21 (OR = 0.53; 95%CI 0.31–0.93), chemokine (C–X3–C motif) ligand 1/fractalkine (OR = 0.54; 95% CI 0.30–0.96), soluble vascular endothelial growth factor receptor 2 (sVEGFR2, OR = 0.45; 95% CI 0.26–0.76), sVEGFR3 (OR = 0.53; 95% CI 0.32–0.90), soluble tumor necrosis factor receptor I (OR = 0.49; 95% CI 0.29–0.83), IL-10 (OR = 0.60; 95% CI 0.34–1.05) and C-reactive protein (OR = 0.63; 95% CI 0.37–1.06) were associated with a decreased risk. sIL-6R remained significantly associated with lung cancer risk >7.5 years prior to diagnosis. Markers involved in various aspects of the immune response were associated with subsequent lung cancer risk, implicating inflammation in the etiology of lung cancer among female never smokers.
      PubDate: 2017-07-22
      DOI: 10.1093/carcin/bgx075
      Issue No: Vol. 38, No. 10 (2017)
  • Kinome expression profiling of human neuroblastoma tumors identifies
           potential drug targets for ultra high-risk patients
    • Authors: Russo R; Cimmino F, Pezone L, et al.
      Pages: 1011 - 1020
      Abstract: AbstractNeuroblastoma (NBL) accounts for >7% of malignancies in patients younger than 15 years. Low- and intermediate-risk patients exhibit excellent or good prognosis after treatment, whereas for high-risk (HR) patients, the estimated 5-year survival rates is still <40%. The ability to stratify HR patients that will not respond to standard treatment strategies is critical for informed treatment decisions. In this study, we have generated a specific kinome gene signature, named Kinome-27, which is able to identify a subset of HR-NBL tumors, named ultra-HR NBL, with highly aggressive clinical behavior that not adequately respond to standard treatments. We have demonstrated that NBL cell lines expressing the same kinome signature of ultra-HR tumors (ultra-HR-like cell lines) may be selectively targeted by the use of two drugs [suberoylanilide hydroxamic acid (SAHA) and Radicicol], and that the synergic combination of these drugs is able to block the ultra-HR-like cells in G2/M phase of cell cycle. The use of our signature in clinical practice will allow identifying patients with negative outcome, which would benefit from new and more personalized treatments. Preclinical in vivo studies are needed to consolidate the SAHA and Radicicol treatment in ultra-HR NBL patients.
      PubDate: 2017-08-29
      DOI: 10.1093/carcin/bgx077
      Issue No: Vol. 38, No. 10 (2017)
  • Plasma DNA methylation marker and hepatocellular carcinoma risk prediction
           model for the general population
    • Authors: Wu H; Yang H, Wang Q, et al.
      Pages: 1021 - 1028
      Abstract: AbstractMetastases in the later stages of hepatocellular carcinoma (HCC) cause the majority of deaths associated with the disease, making early detection crucial to patient survival. Risk models assessing HCC risk in the general population can be used for risk stratification for further HCC surveillance, however, none have been validated externally. Methylation of circulating DNA shows potential for non-invasive diagnosis of HCC. We conducted a prospective case–control study nested within a community-based cohort. We measured methylation levels in six genes (CDKN2A, RASSF1A, STEAP4, TBX2, VIM and ZNF154) which were identified in our previous work, using pre-diagnostic plasma DNA from 237 HCC cases and 257 matched controls. We found TBX2 hypermethylation was associated with increased HCC risk, with ORs (95% CI) of 3.2 (1.8–6.0). The associations were mainly among high-risk subjects; among subjects infected with HBV/HCV, the OR (95% CI) of TBX2 methylation was 5.3 (2.2–12.7). Among subjects with high risk scores, the ORs (95% CIs) were 7.8 (1.5–38.6) for Wen-HCC model ≥16, 5.8 (2.2–15.5) for Hung-HCC ≥15 and 7.5 (2.2–26.0) for Michikawa-HCC ≥8. Adding TBX2 methylation improved the accuracy of risk models for a high-risk population, with the area under the curve (AUC) of 76% for Wen-HCC score with TBX2 methylation compared with 69% with Wen-HCC alone. The AUCs were 63% for Hung-HCC score plus TBX2 methylation, and 53% for Hung-HCC alone, 65% for Michikawa-HCC score plus TBX2 methylation and 58% for Michikawa-HCC alone. Our findings suggest the potential increase in risk assessment discrimination and accuracy from incorporation of DNA methylation.
      PubDate: 2017-08-03
      DOI: 10.1093/carcin/bgx078
      Issue No: Vol. 38, No. 10 (2017)
  • Polymorphisms in genes related to epithelial–mesenchymal transition and
           risk of non-small cell lung cancer
    • Authors: Xie K; Ye Y, Zeng Y, et al.
      Pages: 1029 - 1035
      Abstract: AbstractThe epithelial–mesenchymal transition (EMT) process is a crucial step for tumor invasion and metastasis. Previous research investigating EMT has mostly focused on its role in cancer progression. Recent studies showed that EMT and EMT-driving transcription factor (EMT-TF) expression are early events in lung cancer pathogenesis, implying a potential association between EMT and lung cancer risk. In this study, we examined whether genetic variants in EMT-related genes are associated with risk of non-small cell lung cancer (NSCLC). We used data from a genome-wide association study of 1482 NSCLC cases and 1544 healthy controls as the discovery phase, in which we analyzed 1602 single-nucleotide polymorphisms (SNPs) within 159 EMT-related genes. We then validated the significant SNPs in another 5699 cases and 5815 controls from the National Cancer Institute lung cancer genome-wide association study. Cumulative effects were evaluated for validated SNPs, and a gene-based test was performed to explore gene-level association with disease risk. In the discovery phase, 174 SNPs demonstrated significant associations with NSCLC risk. In the validation phase, seven SNPs mapped to EGFR, NOTCH3, ADGRF1 and SMAD3 were confirmed. Cumulative effect analysis of the significant SNPs demonstrated increasing risk with the number of unfavorable genotypes in the discovery and validation datasets. Gene-based analysis implicated ADGRF1, NOTCH3 and CDH1 as significant for NSCLC risk. Functional prediction revealed several potential mechanisms underlying these associations. Our results suggest that EMT-related gene variants may be involved in susceptibility to NSCLC; if confirmed, they might help identify higher-risk individuals.
      PubDate: 2017-08-04
      DOI: 10.1093/carcin/bgx079
      Issue No: Vol. 38, No. 10 (2017)
  • Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating
           PRC2 subunit EZH2, and the lncRNA PVT1 expression
    • Authors: Yoshida K; Toden S, Ravindranathan P, et al.
      Pages: 1036 - 1046
      Abstract: AbstractDevelopment of resistance to chemotherapeutic drugs is a major challenge in the care of patients with pancreatic ductal adenocarcinoma (PDAC). Acquired resistance to chemotherapeutic agents in PDAC has been linked to a subset of cancer cells termed ‘cancer stem cells’ (CSCs). Therefore, an improved understanding of the molecular events underlying the development of pancreatic CSCs is required to identify new therapeutic targets to overcome chemoresistance. Accumulating evidence indicates that curcumin, a phenolic compound extracted from turmeric, can overcome de novo chemoresistance and re-sensitize tumors to various chemotherapeutic agents. However, the underlying mechanisms for curcumin-mediated chemosensitization remain unclear. The Enhancer of Zeste Homolog-2 (EZH2) subunit of Polycomb Repressive Complex 2 (PRC2) was recently identified as a key player regulating drug resistance. EZH2 mediates interaction with several long non-coding RNAs (lncRNAs) to modulate epithelial–mesenchymal transition and cancer stemness, phenomena commonly associated with drug resistance. Here, we report the re-sensitization of chemoresistant PDAC cells by curcumin through the inhibition of the PRC2-PVT1-c-Myc axis. Using gemcitabine-resistant PDAC cell lines, we found that curcumin sensitized chemoresistant cancer cells by inhibiting the expression of the PRC2 subunit EZH2 and its related lncRNA PVT1. Curcumin was also found to prevent the formation of spheroids, a hallmark of CSCs, and to down-regulate several self-renewal driving genes. In addition, we confirmed our in vitro findings in a xenograft mouse model where curcumin inhibited gemcitabine-resistant tumor growth. Overall, this study indicates clinical relevance for combining curcumin with chemotherapy to overcome chemoresistance in PDAC.
      PubDate: 2017-07-17
      DOI: 10.1093/carcin/bgx065
      Issue No: Vol. 38, No. 10 (2017)
  • Sanguinarine inhibits pancreatic cancer stem cell characteristics by
           inducing oxidative stress and suppressing sonic hedgehog-Gli-Nanog pathway
    • Authors: Ma Y; Yu W, Shrivastava A, et al.
      Pages: 1047 - 1056
      Abstract: AbstractSonic hedgehog pathway is highly activated in pancreatic cancer stem cells (CSC) which play crucial roles in cancer initiation, progression and metastasis. However, the molecular mechanisms by which sanguinarine regulates pancreatic CSC characteristics is not well understood. The objectives of this study were to examine the molecular mechanisms by which sanguinarine regulates pancreatic CSC characteristics. Sanguinarine inhibited cell proliferation and colony formation and induced apoptosis through oxidative damage. Sanguinarine inhibited self-renewal capacity of pancreatic CSCs isolated from human and KrasG12D mice. Furthermore, sanguinarine suppressed epithelial-mesenchymal transition (EMT) by up-regulating E-cadherin and inhibiting N-cadherin. Significant decrease in expression level of Snail, Slug and Zeb1 corroborated the suppression of EMT in sanguinarine treated pancreatic CSCS. The ability of sanguinarine to inhibit pluripotency maintaining factors and CSC markers suggest that sanguinarine can be an effective agent for inhibiting pancreatic cancer growth and development by targeting CSCs. Furthermore, sanguinarine inhibited Shh-Gli pathway leading to modulation of Gli target genes in pancreatic CSCs. Chromatin immunoprecipitation assay demonstrated that Nanog directly binds to promoters of Cdk2, Cdk6, FGF4, c-Myc and Oct4, and sanguinarine inhibits the binding of Nanog with these genes, suggesting the direct involvement of Nanog in cell cycle, pluripotency and self-renewal. To further investigate the role of Shh-Gli-Nanog pathway, we regulated Shh signaling either by Shh protein or Nanog overexpression. Enforced activation of Shh or overexpression of Nanog counteracted the inhibitory effects of sanguinarine on pancreatic CSC proliferation, suggesting the actions of sanguinarine are mediated, at least in part, through Shh-Gli-Nanog pathway. Our studies suggest that sanguinarine can be used for the treatment and/or prevention of pancreatic cancer by targeting CSCs.
      PubDate: 2017-09-05
      DOI: 10.1093/carcin/bgx070
      Issue No: Vol. 38, No. 10 (2017)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
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