An overview of new biomolecular pathways in pathogen-related cancers

Papers of special note have been highlighted as:• of interest; •• of considerable interest

References

• 1 Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J. Gen. Physiol. 8(6), 519–530 (1927).•• This is the first report on common metabolic alteration in cancer consisting in the nonoxidative breakdown of glucose and the glycolytic anaerobic-catabolism of sugars decoupled from the oxidative mitochondrial breakdown of pyruvate.
  Medline CASGoogle Scholar
• 2 Lindau Nobel Laureate Meetings org. Otto Warburg Lecture – On the Primary Causes and on the Secondary Causes of Cancer. www.mediatheque.lindau-nobel.org
  Google Scholar
• 3 Kim JW, Dang CV. Cancer's molecular sweet tooth and the Warburg effect. Cancer Res. 66(18), 8927–8930 (2006).
  Medline CASGoogle Scholar
• 4 Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 100(1), 57–70 (2000).•• The article describes the grouping of all cancer metabolic changes in six major pathways.
  Medline CASGoogle Scholar
• 5 Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 144(5), 646–674 (2011).•• The cancer hallmarks are revisited in light of new discoveries and more pathways, such as reprogramming of energy metabolism and evading immune destruction, are added to the list of cancer hallmarks.
  Medline CASGoogle Scholar
• 6 Tayer W. Appendix I. In: Celsus Cornelius A. De Medicina. Latin Transcription by F. Marx, Teubner edition1915; English translation by W. G. Spencer, Loeb edition 1938. Loeb Classical Library edition, 1935 (2002). http://penelope.uchicago.edu
  Google Scholar
• 7 Hippocrates of Cos. Book VI, 38. In: Aphorisms (Greek and Latin bilingual edition). Foes A (Eds.). Bibliothèque numérique Medic@: MS 595 – BIUM 2. bibliothèques interuniversitaires de médecine (BIUM), Paris, published apud Andreae Wecheli heredes, Claudium Marnium et Joannem Aubrium, Francofurti, (1595). www2.biusante.parisdescartes.fr
  Google Scholar
• 8 Hajdu SI. A note from history: landmarks in history of cancer, part 1. Cancer 117(5), 1097–1102 (2011).
  MedlineGoogle Scholar
• 9 Celsus Cornelius A. Book V 28, 2A-C. In: De Medicina. Latin Transcription by F. Marx, Teubner edition1915; English translation by W. G. Spencer, Loeb edition 1938. Loeb Classical Library edition, 1935, (2002). http://penelope.uchicago.edu
  Google Scholar
• 10 Galenus Claudius of Pergamon. De Methodo Medendi, Liber XIV. In: Claudii Galeni Opera Omnia (Vol. X). Kühn KG (Ed.). Car. Cnoblochii, Leipzig, 945–1026 (1825). www2.biusante.parisdescartes.fr.
  Google Scholar
• 11 Galenus Claudius of Pergamon. De Tumoribus praeter naturam, Cap. XII. In: Claudii Galeni Opera Omnia (Vol. VII). Kühn KG (Ed.). Car. Cnoblochii, Leipzig, 705–732 (1824). www2.biusante.parisdescartes.fr.
  Google Scholar
• 12 Adriani Ravesteini. Lexicon Medicum Graeco-Latinum a Batholomeo Castello Messanense inchoatum. Art. Med. Doct. ex Hippocr. Galen. Avicenn. atque aliorum celeberrimorum Medicorum Monumnetis. Arnoldum Leers, Roterodami (1665). https://books.google.it.
  Google Scholar
• 13 TCGA. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455(7216), 1061–1068 (2008).
  MedlineGoogle Scholar
• 14 TCGA. Integrated genomic analyses of ovarian carcinoma. Nature 474(7353), 609–615 (2011).
  MedlineGoogle Scholar
• 15 TCGA. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513(7517), 202–209 (2014).
  MedlineGoogle Scholar
• 16 TCGA. Comprehensive genomic characterization of squamous cell lung cancers. Nature 489(7417), 519–525 (2012).
  MedlineGoogle Scholar
• 17 TCGA. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507(7492), 315–322 (2014).
  MedlineGoogle Scholar
• 18 TCGA. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499(7456), 43–49 (2013).
  MedlineGoogle Scholar
• 19 TCGA. Comprehensive molecular characterization of human colon and rectal cancer. Nature 487(7407), 330–337 (2012).
  MedlineGoogle Scholar
• 20 TCGA. Comprehensive molecular portraits of human breast tumours. Nature 490(7418), 61–70 (2012).
  MedlineGoogle Scholar
• 21 Martinez E, Yoshihara K, Kim H, Mills GM, Trevino V, Verhaak RG. Comparison of gene expression patterns across 12 tumor types identifies a cancer supercluster characterized by TP53 mutations and cell cycle defects. Oncogene doi:10.1038/onc.2014.216 (2014) (Epub ahead of print).• Describes common transcriptional footprints across cancer types and highlights that tumor subtypes are commonly unified by a limited number of molecular themes.
  Google Scholar
• 22 Verhaak RG, Hoadley KA, Purdom E et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17(1), 98–110 (2010).
  Medline CASGoogle Scholar
• 23 Hu X, Stern HM, Ge L et al. Genetic alterations and oncogenic pathways associated with breast cancer subtypes. Mol. Cancer Res. 7(4), 511–522 (2009).
  Medline CASGoogle Scholar
• 24 Turner NC, Reis-Filho JS. Basal-like breast cancer and the BRCA1 phenotype. Oncogene 25(43), 5846–5853 (2006).
  Medline CASGoogle Scholar
• 25 Foulkes WD, Stefansson IM, Chappuis PO et al. Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J. Natl Cancer Inst. 95(19), 1482–1485 (2003).
  Medline CASGoogle Scholar
• 26 Hernando E, Nahle Z, Juan G et al. Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control. Nature 430(7001), 797–802 (2004).
  Medline CASGoogle Scholar
• 27 Puc J, Keniry M, Li HS et al. Lack of PTEN sequesters CHK1 and initiates genetic instability. Cancer Cell 7(2), 193–204 (2005).
  Medline CASGoogle Scholar
• 28 Shen WH, Balajee AS, Wang J et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell 128(1), 157–170 (2007).
  Medline CASGoogle Scholar
• 29 Rouzier R, Perou CM, Symmans WF et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin. Cancer Res. 11(16), 5678–5685 (2005).
  Medline CASGoogle Scholar
• 30 Bosco EE, Wang Y, Xu H et al. The retinoblastoma tumor suppressor modifies the therapeutic response of breast cancer. J. Clin. Invest. 117(1), 218–228 (2007).
  Medline CASGoogle Scholar
• 31 McCabe N, Turner NC, Lord CJ et al. Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Res. 66(16), 8109–8115 (2006).
  Medline CASGoogle Scholar
• 32 Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4), 663–676 (2006).
  Medline CASGoogle Scholar
• 33 Chiou SH, Wang ML, Chou YT et al. Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial–mesenchymal transdifferentiation. Cancer Res. 70(24), 10433–10444 (2010).
  Medline CASGoogle Scholar
• 34 Lopez-Bertoni H, Lal B, Li A et al. DNMT-dependent suppression of microRNA regulates the induction of GBM tumor-propagating phenotype by Oct4 and Sox2. Oncogene doi:10.1038/onc.2014.334 (2014) (Epub ahead of print).
  MedlineGoogle Scholar
• 35 Cao L, Zhou Y, Zhai B et al. Sphere-forming cell subpopulations with cancer stem cell properties in human hepatoma cell lines. BMC Gastroenterol. 11, 71 (2011).
  Medline CASGoogle Scholar
• 36 Bareiss PM, Paczulla A, Wang H et al. SOX2 expression associates with stem cell state in human ovarian carcinoma. Cancer Res. 73(17), 5544–5555 (2013).
  Medline CASGoogle Scholar
• 37 Ma L, Lai D, Liu T, Cheng W, Guo L. Cancer stem-like cells can be isolated with drug selection in human ovarian cancer cell line SKOV3. Acta Biochim. Biophys. Sin.(Shanghai) 42(9), 593–602 (2010).
  Medline CASGoogle Scholar
• 38 Goldie SJ, Mulder KW, Tan DW, Lyons SK, Sims AH, Watt FM. FRMD4A upregulation in human squamous cell carcinoma promotes tumor growth and metastasis and is associated with poor prognosis. Cancer Res. 72(13), 3424–3436 (2012).
  Medline CASGoogle Scholar
• 39 Passegue E, Jamieson CH, Ailles LE, Weissman IL. Normal and leukemic hematopoiesis: are leukemias a stem cell disorder or a reacquisition of stem cell characteristics? Proc. Natl Acad. Sci. USA 100(Suppl. 1), 11842–11849 (2003).
  Medline CASGoogle Scholar
• 40 Mani SA, Guo W, Liao MJ et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4), 704–715 (2008).
  Medline CASGoogle Scholar
• 41 Biddle A, Liang X, Gammon L et al. Cancer stem cells in squamous cell carcinoma switch between two distinct phenotypes that are preferentially migratory or proliferative. Cancer Res. 71(15), 5317–5326 (2011).
  Medline CASGoogle Scholar
• 42 Levine AJ. The common mechanisms of transformation by the small DNA tumor viruses: The inactivation of tumor suppressor gene products: p53. Virology 384(2), 285–293 (2009).• Describes a common transforming mechanism of small DNA viruses consisting in the alteration of p53-related pathways.
  Medline CASGoogle Scholar
• 43 Yim EK, Park JS. The role of HPV E6 and E7 oncoproteins in HPV-associated cervical carcinogenesis. Cancer Res. Treat. 37(6), 319–324 (2005).
  MedlineGoogle Scholar
• 44 Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319(5866), 1096–1100 (2008).
  Medline CASGoogle Scholar
• 45 Peng R, Gordadze AV, Fuentes Panana EM et al. Sequence and functional analysis of EBNA-LP and EBNA2 proteins from nonhuman primate lymphocryptoviruses. J. Virol. 74(1), 379–389 (2000).
  Medline CASGoogle Scholar
• 46 Waltzer L, Perricaudet M, Sergeant A, Manet E. Epstein–Barr virus EBNA3A and EBNA3C proteins both repress RBP-J kappa-EBNA2-activated transcription by inhibiting the binding of RBP-J kappa to DNA. J. Virol. 70(9), 5909–5915 (1996).
  Medline CASGoogle Scholar
• 47 Subramanian C, Hasan S, Rowe M, Hottiger M, Orre R, Robertson ES. Epstein–Barr virus nuclear antigen 3C and prothymosin alpha interact with the p300 transcriptional coactivator at the CH1 and CH3/HAT domains and cooperate in regulation of transcription and histone acetylation. J. Virol. 76(10), 4699–4708 (2002).
  Medline CASGoogle Scholar
• 48 Kaye KM, Izumi KM, Kieff E. Epstein–Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation. Proc. Natl Acad. Sci USA 90(19), 9150–9154 (1993).
  Medline CASGoogle Scholar
• 49 Ikeda O, Sekine Y, Mizushima A et al. BS69 negatively regulates the canonical NF-kappaB activation induced by Epstein–Barr virus-derived LMP1. FEBS Lett. 583(10), 1567–1574 (2009).
  Medline CASGoogle Scholar
• 50 Caldwell RG, Wilson JB, Anderson SJ, Longnecker R. Epstein–Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals. Immunity 9(3), 405–411 (1998).
  Medline CASGoogle Scholar
• 51 Swanson-Mungerson M, Bultema R, Longnecker R. Epstein–Barr virus LMP2A imposes sensitivity to apoptosis. J. Gen. Virol. 91(Pt 9), 2197–2202 (2010).
  Medline CASGoogle Scholar
• 52 Friborg J Jr., Kong W, Hottiger MO, Nabel GJ. p53 inhibition by the LANA protein of KSHV protects against cell death. Nature 402(6764), 889–894 (1999).
  Medline CASGoogle Scholar
• 53 Cai QL, Knight JS, Verma SC, Zald P, Robertson ES. EC5S ubiquitin complex is recruited by KSHV latent antigen LANA for degradation of the VHL and p53 tumor suppressors. PLoS Pathog. 2(10), e116 (2006).
  MedlineGoogle Scholar
• 54 An J, Sun Y, Sun R, Rettig MB. Kaposi's sarcoma-associated herpesvirus encoded vFLIP induces cellular IL-6 expression: the role of the NF-kappaB and JNK/AP1 pathways. Oncogene 22(22), 3371–3385 (2003).
  Medline CASGoogle Scholar
• 55 Guasparri I, Wu H, Cesarman E. The KSHV oncoprotein vFLIP contains a TRAF-interacting motif and requires TRAF2 and TRAF3 for signalling. EMBO Rep. 7(1), 114–119 (2006).
  Medline CASGoogle Scholar
• 56 Wang XW, Forrester K, Yeh H, Feitelson MA, Gu JR, Harris CC. Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3. Proc. Natl Acad. Sci. USA 91(6), 2230–2234 (1994).
  Medline CASGoogle Scholar
• 57 Jung JK, Arora P, Pagano JS, Jang KL. Expression of DNA methyltransferase 1 is activated by hepatitis B virus X protein via a regulatory circuit involving the p16INK4a-cyclin D1-CDK 4/6-pRb-E2F1 pathway. Cancer Res. 67(12), 5771–5778 (2007).
  Medline CASGoogle Scholar
• 58 Kuo TC, Chao CC. Hepatitis B virus X protein prevents apoptosis of hepatocellular carcinoma cells by upregulating SATB1 and HURP expression. Biochem. Pharmacol. 80(7), 1093–1102 (2010).
  Medline CASGoogle Scholar
• 59 Khosravi R, Maya R, Gottlieb T, Oren M, Shiloh Y, Shkedy D. Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage. Proc. Natl Acad. Sci. USA 96(26), 14973–14977 (1999).
  Medline CASGoogle Scholar
• 60 Tellinghuisen TL, Rice CM. Interaction between hepatitis C virus proteins and host cell factors. Curr. Opin. Microbiol. 5(4), 419–427 (2002).
  Medline CASGoogle Scholar
• 61 Lu L, Wei L, Peng G et al. NS3 protein of hepatitis C virus regulates cyclooxygenase-2 expression through multiple signaling pathways. Virology 371(1), 61–70 (2008).
  Medline CASGoogle Scholar
• 62 Gong GZ, Jiang YF, He Y, Lai LY, Zhu YH, Su XS. HCV NS5A abrogates p53 protein function by interfering with p53-DNA binding. World J. Gastroenterol. 10(15), 2223–2227 (2004).
  Medline CASGoogle Scholar
• 63 Schmitz U, Tan SL. NS5A – from obscurity to new target for HCV therapy. Recent Pat Antiinfect. Drug Discov. 3(2), 77–92 (2008).
  Medline CASGoogle Scholar
• 64 Kim YM, Geiger TR, Egan DI, Sharma N, Nyborg JK. The HTLV-1 tax protein cooperates with phosphorylated CREB, TORC2 and p300 to activate CRE-dependent cyclin D1 transcription. Oncogene 29(14), 2142–2152 (2010).
  Medline CASGoogle Scholar
• 65 Gallo RC. History of the discoveries of the first human retroviruses: HTLV-1 and HTLV-2. Oncogene 24(39), 5926–5930 (2005).
  Medline CASGoogle Scholar
• 66 Buti L, Spooner E, Van d V, Rappuoli R, Covacci A, Ploegh HL. Helicobacter pylori cytotoxin-associated gene A (CagA) subverts the apoptosis-stimulating protein of p53 (ASPP2) tumor suppressor pathway of the host. Proc. Natl Acad. Sci. USA 108(22), 9238–9243 (2011).
  Medline CASGoogle Scholar
• 67 Nesic D, Buti L, Lu X, Stebbins CE. Structure of the Helicobacter pylori CagA oncoprotein bound to the human tumor suppressor ASPP2. Proc. Natl Acad. Sci. USA 111(4), 1562–1567 (2014).
  Medline CASGoogle Scholar
• 68 Saha A, Kaul R, Murakami M, Robertson ES. Tumor viruses and cancer biology: modulating signaling pathways for therapeutic intervention. Cancer Biol. Ther. 10(10), 961–978 (2010).
  Medline CASGoogle Scholar
• 69 Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63(6), 1129–1136 (1990).
  Medline CASGoogle Scholar
• 70 Dyson N, Howley PM, Munger K, Harlow E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 243(4893), 934–937 (1989).
  Medline CASGoogle Scholar
• 71 Hwang SG, Lee D, Kim J, Seo T, Choe J. Human papillomavirus type 16 E7 binds to E2F1 and activates E2F1-driven transcription in a retinoblastoma protein-independent manner. J. Biol. Chem. 277(4), 2923–2930 (2002).
  Medline CASGoogle Scholar
• 72 Allen JE, Maizels RM. Diversity and dialogue in immunity to helminths. Nat. Rev. Immunol. 11(6), 375–388 (2011).
  Medline CASGoogle Scholar
• 73 Tornesello M, Annunziata C, Buonaguro L, Losito S, Greggi S, Buonaguro FM. TP53 and PIK3CA gene mutations in adenocarcinoma, squamous cell carcinoma and high-grade intraepithelial neoplasia of the cervix. J. Transl. Med. 12(1), 255 (2014).
  MedlineGoogle Scholar
• 74 Klingelhutz AJ, Foster SA, McDougall JK. Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature 380(6569), 79–82 (1996).
  Medline CASGoogle Scholar
• 75 Veldman T, Horikawa I, Barrett JC, Schlegel R. Transcriptional activation of the telomerase hTERT gene by human papillomavirus type 16 E6 oncoprotein. J. Virol. 75(9), 4467–4472 (2001).
  Medline CASGoogle Scholar
• 76 Oh ST, Kyo S, Laimins LA. Telomerase activation by human papillomavirus type 16 E6 protein: induction of human telomerase reverse transcriptase expression through Myc and GC-rich Sp1 binding sites. J. Virol. 75(12), 5559–5566 (2001).
  Medline CASGoogle Scholar
• 77 Veldman T, Liu X, Yuan H, Schlegel R. Human papillomavirus E6 and Myc proteins associate in vivo and bind to and cooperatively activate the telomerase reverse transcriptase promoter. Proc. Natl Acad. Sci. USA 100(14), 8211–8216 (2003).
  Medline CASGoogle Scholar
• 78 Kim WY, Sharpless NE. The regulation of INK4/ARF in cancer and aging. Cell 127(2), 265–275 (2006).
  Medline CASGoogle Scholar
• 79 Jarrard DF, Sarkar S, Shi Y et al. p16/pRb pathway alterations are required for bypassing senescence in human prostate epithelial cells. Cancer Res. 59(12), 2957–2964 (1999).
  Medline CASGoogle Scholar
• 80 Darbro BW. Mechanisms of human epithelial cell immortalization and p16NK4a induced telomere-independent sencescence [PhD thesis]. University of Iowa, Iowa City, IA, USA (2007). http://ir.uiowa.edu/etd/183.
  Google Scholar
• 81 Liggett WH Jr, Sidransky D. Role of the p16 tumor suppressor gene in cancer. J. Clin. Oncol. 16(3), 1197–1206 (1998).
  Medline CASGoogle Scholar
• 82 Sharpless NE. INK4a/ARF: a multifunctional tumor suppressor locus. Mutat. Res. 576(1–2), 22–38 (2005).
  Medline CASGoogle Scholar
• 83 Perez-Sayans M, Suarez-Penaranda JM, Padin-Iruegas ME et al. The loss of p16 expression worsens the prognosis of OSCC. Appl. Immunohistochem. Mol. Morphol. (2015).
  MedlineGoogle Scholar
• 84 Weinberger PM, Yu Z, Haffty BG et al. Molecular classification identifies a subset of human papillomavirus – associated oropharyngeal cancers with favorable prognosis. J. Clin. Oncol. 24(5), 736–747 (2006).
  Medline CASGoogle Scholar
• 85 Tornesello ML, Perri F, Buonaguro L, Ionna F, Buonaguro FM, Caponigro F. HPV-related oropharyngeal cancers: from pathogenesis to new therapeutic approaches. Cancer Lett. 351(2), 198–205 (2014).
  Medline CASGoogle Scholar
• 86 Kotake Y, Cao R, Viatour P, Sage J, Zhang Y, Xiong Y. pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene. Genes Dev. 21(1), 49–54 (2007).
  Medline CASGoogle Scholar
• 87 Tornesello ML, Buonaguro L, Giorgi-Rossi P, Buonaguro FM. Viral and cellular biomarkers in the diagnosis of cervical intraepithelial neoplasia and cancer. Biomed. Res. Int. 2013, 519619 (2013).
  MedlineGoogle Scholar
• 88 Li J, Muscarella P, Joo SH et al. Dissection of CDK4-binding and transactivation activities of p34(SEI-1) and comparison between functions of p34(SEI-1) and p16(INK4A). Biochemistry 44(40), 13246–13256 (2005).
  Medline CASGoogle Scholar
• 89 Li J, Poi MJ, Tsai MD. Regulatory mechanisms of tumor suppressor P16(INK4A) and their relevance to cancer. Biochemistry 50(25), 5566–5582 (2011).
  Medline CASGoogle Scholar
• 90 de Martel C, Ferlay J, Franceschi S et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol. 13(6), 607–615 (2012).
  MedlineGoogle Scholar
• 91 Tornesello ML, Buonaguro L, Tatangelo F, Botti G, Izzo F, Buonaguro FM. Mutations in TP53, CTNNB1 and PIK3CA genes in hepatocellular carcinoma associated with hepatitis B and hepatitis C virus infections. Genomics 102(2), 74–83 (2013).
  Medline CASGoogle Scholar
• 92 Mesri EA, Feitelson MA, Munger K. Human viral oncogenesis: a cancer hallmarks analysis. Cell Host. Microbe 15(3), 266–282 (2014).•• The article describes the pathogenesis of human oncogenic viruses and their effect on different cancer hallmarks.
  Medline CASGoogle Scholar
• 93 Bolukbas C, Bolukbas FF, Horoz M, Aslan M, Celik H, Erel O. Increased oxidative stress associated with the severity of the liver disease in various forms of hepatitis B virus infection. BMC Infect. Dis. 5, 95 (2005).
  MedlineGoogle Scholar
• 94 Fujita N, Sugimoto R, Ma N et al. Comparison of hepatic oxidative DNA damage in patients with chronic hepatitis B and C. J. Viral Hepat. 15(7), 498–507 (2008).
  Medline CASGoogle Scholar
• 95 Jaeschke H. Reactive oxygen and mechanisms of inflammatory liver injury: present concepts. J. Gastroenterol. Hepatol. 26(Suppl.1), 173–179 (2011).
  Medline CASGoogle Scholar
• 96 Lee YI, Hwang JM, Im JH et al. Human hepatitis B virus-X protein alters mitochondrial function and physiology in human liver cells. J. Biol. Chem. 279(15), 15460–15471 (2004).
  Medline CASGoogle Scholar
• 97 Zemel R, Issachar A, Tur-Kaspa R. The role of oncogenic viruses in the pathogenesis of hepatocellular carcinoma. Clin. Liver Dis. 15(2), 261–26x (2011).
  MedlineGoogle Scholar
• 98 Hu L, Chen L, Yang G et al. HBx sensitizes cells to oxidative stress-induced apoptosis by accelerating the loss of Mcl-1 protein via caspase-3 cascade. Mol. Cancer 10, 43 (2011).
  Medline CASGoogle Scholar
• 99 Sieghart W, Losert D, Strommer S et al. Mcl-1 overexpression in hepatocellular carcinoma: a potential target for antisense therapy. J. Hepatol. 44(1), 151–157 (2006).
  Medline CASGoogle Scholar
• 100 Wang WL, London WT, Lega L, Feitelson MA. HBxAg in the liver from carrier patients with chronic hepatitis and cirrhosis. Hepatology 14(1), 29–37 (1991).
  Medline CASGoogle Scholar
• 101 Martin-Vilchez S, Lara-Pezzi E, Trapero-Marugan M, Moreno-Otero R, Sanz-Cameno P. The molecular and pathophysiological implications of hepatitis B X antigen in chronic hepatitis B virus infection. Rev. Med. Virol. 21(5), 315–329 (2011).
  Medline CASGoogle Scholar
• 102 Jin YM, Yun C, Park C, Wang HJ, Cho H. Expression of hepatitis B virus X protein is closely correlated with the high periportal inflammatory activity of liver diseases. J. Viral Hepat. 8(5), 322–330 (2001).
  Medline CASGoogle Scholar
• 103 Gong G, Waris G, Tanveer R, Siddiqui A. Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-kappa B. Proc. Natl Acad. Sci. USA 98(17), 9599–9604 (2001).
  Medline CASGoogle Scholar
• 104 Okuda M, Li K, Beard MR et al. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology 122(2), 366–375 (2002).
  Medline CASGoogle Scholar
• 105 Boudreau HE, Emerson SU, Korzeniowska A, Jendrysik MA, Leto TL. Hepatitis C virus (HCV) proteins induce NADPH oxidase 4 expression in a transforming growth factor beta-dependent manner: a new contributor to HCV-induced oxidative stress. J. Virol. 83(24), 12934–12946 (2009).
  Medline CASGoogle Scholar
• 106 de Mochel NS, Seronello S, Wang SH et al. Hepatocyte NAD(P)H oxidases as an endogenous source of reactive oxygen species during hepatitis C virus infection. Hepatology 52(1), 47–59 (2010).
  MedlineGoogle Scholar
• 107 Santos CX, Tanaka LY, Wosniak J, Laurindo FR. Mechanisms and implications of reactive oxygen species generation during the unfolded protein response: roles of endoplasmic reticulum oxidoreductases, mitochondrial electron transport, and NADPH oxidase. Antioxid. Redox. Signal. 11(10), 2409–2427 (2009).
  Medline CASGoogle Scholar
• 108 Kumthip K, Chusri P, Jilg N et al. Hepatitis C virus NS5A disrupts STAT1 phosphorylation and suppresses type I interferon signaling. J. Virol. 86(16), 8581–8591 (2012).
  Medline CASGoogle Scholar
• 109 Rehermann B. Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence. J. Clin. Invest. 119(7), 1745–1754 (2009).
  Medline CASGoogle Scholar
• 110 Brechot C. Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: old and new paradigms. Gastroenterology 127(5 Suppl. 1), S56-S61 (2004).
  Google Scholar
• 111 Jeong SW, Jang JY, Chung RT. Hepatitis C virus and hepatocarcinogenesis. Clin. Mol. Hepatol. 18(4), 347–356 (2012).
  MedlineGoogle Scholar
• 112 Ray RB, Meyer K, Ray R. Hepatitis C virus core protein promotes immortalization of primary human hepatocytes. Virology 271(1), 197–204 (2000).
  Medline CASGoogle Scholar
• 113 Peek RM Jr, Crabtree JE. Helicobacter infection and gastric neoplasia. J. Pathol. 208(2), 233–248 (2006).
  Medline CASGoogle Scholar
• 114 Ernst PB, Peura DA, Crowe SE. The translation of Helicobacter pylori basic research to patient care. Gastroenterology 130(1), 188–206 (2006).
  Medline CASGoogle Scholar
• 115 Segal ED, Cha J, Lo J, Falkow S, Tompkins LS. Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. Proc. Natl Acad. Sci. USA 96(25), 14559–14564 (1999).
  Medline CASGoogle Scholar
• 116 Viala J, Chaput C, Boneca IG et al. Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat. Immunol. 5(11), 1166–1174 (2004).
  Medline CASGoogle Scholar
• 117 Ding SZ, Zheng PY. Helicobacter pylori infection induced gastric cancer; advance in gastric stem cell research and the remaining challenges. Gut Pathog. 4(1), 18 (2012).
  Medline CASGoogle Scholar
• 118 Ding SZ, Fischer W, Kaparakis-Liaskos M et al. Helicobacter pylori-induced histone modification, associated gene expression in gastric epithelial cells, and its implication in pathogenesis. PLoS ONE 5(4), e9875 (2010).
  MedlineGoogle Scholar
• 119 Backert S, Naumann M. What a disorder: proinflammatory signaling pathways induced by Helicobacter pylori. Trends Microbiol. 18(11), 479–486 (2010).
  Medline CASGoogle Scholar
• 120 Lee IO, Kim JH, Choi YJ et al. Helicobacter pylori CagA phosphorylation status determines the gp130-activated SHP2/ERK and JAK/STAT signal transduction pathways in gastric epithelial cells. J. Biol. Chem. 285(21), 16042–16050 (2010).
  Medline CASGoogle Scholar
• 121 Jang BG, Kim WH. Molecular pathology of gastric carcinoma. Pathobiology 78(6), 302–310 (2011).
  Medline CASGoogle Scholar
• 122 O'Gorman A, Colleran A, Ryan A, Mann J, Egan LJ. Regulation of NF-kappaB responses by epigenetic suppression of IkappaBalpha expression in HCT116 intestinal epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 299(1), G96–G105 (2010).
  MedlineGoogle Scholar
• 123 Ohnishi N, Yuasa H, Tanaka S et al. Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc. Natl Acad. Sci. USA 105(3), 1003–1008 (2008).
  Medline CASGoogle Scholar
• 124 Hayashi D, Tamura A, Tanaka H et al. Deficiency of claudin-18 causes paracellular H+ leakage, up-regulation of interleukin-1beta, and atrophic gastritis in mice. Gastroenterology 142(2), 292–304 (2012).
  Medline CASGoogle Scholar
• 125 Marusawa H, Chiba T. Helicobacter pylori-induced activation-induced cytidine deaminase expression and carcinogenesis. Curr. Opin. Immunol. 22(4), 442–447 (2010).
  Medline CASGoogle Scholar
• 126 Huang FY, Chan AO, Rashid A, Wong DK, Cho CH, Yuen MF. Helicobacter pylori induces promoter methylation of E-cadherin via interleukin-1beta activation of nitric oxide production in gastric cancer cells. Cancer 118(20), 4969–4980 (2012).
  Medline CASGoogle Scholar
• 127 Leung SY, Yuen ST, Chung LP, Chu KM, Chan AS, Ho JC. hMLH1 promoter methylation and lack of hMLH1 expression in sporadic gastric carcinomas with high-frequency microsatellite instability. Cancer Res. 59(1), 159–164 (1999).
  Medline CASGoogle Scholar
• 128 Deng N, Goh LK, Wang H et al. A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut 61(5), 673–684 (2012).
  Medline CASGoogle Scholar
• 129 Olivier M, Hollstein M, Hainaut P. TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb. Perspect. Biol. 2(1), a001008 (2010).
  MedlineGoogle Scholar
• 130 Murakami K, Fujioka T, Okimoto T et al. Analysis of p53 gene mutations in Helicobacter pylori-associated gastritis mucosa in endoscopic biopsy specimens. Scand. J. Gastroenterol. 34(5), 474–477 (1999).
  Medline CASGoogle Scholar
• 131 Piazzi G, Fini L, Selgrad M et al. Epigenetic regulation of Delta-Like1 controls Notch1 activation in gastric cancer. Oncotarget. 2(12), 1291–1301 (2011).
  MedlineGoogle Scholar
• 132 Tomita H, Takaishi S, Menheniott TR et al. Inhibition of gastric carcinogenesis by the hormone gastrin is mediated by suppression of TFF1 epigenetic silencing. Gastroenterology 140(3), 879–891 (2011).
  Medline CASGoogle Scholar
• 133 Amieva MR, Vogelmann R, Covacci A, Tompkins LS, Nelson WJ, Falkow S. Disruption of the epithelial apical–junctional complex by Helicobacter pylori CagA. Science 300(5624), 1430–1434 (2003).
  Medline CASGoogle Scholar
• 134 Saito Y, Murata-Kamiya N, Hirayama T, Ohba Y, Hatakeyama M. Conversion of Helicobacter pylori CagA from senescence inducer to oncogenic driver through polarity-dependent regulation of p21. J. Exp. Med. 207(10), 2157–2174 (2010).
  Medline CASGoogle Scholar
• 135 Bagnoli F, Buti L, Tompkins L, Covacci A, Amieva MR. Helicobacter pylori CagA induces a transition from polarized to invasive phenotypes in MDCK cells. Proc. Natl Acad. Sci. USA 102(45), 16339–16344 (2005).
  Medline CASGoogle Scholar
• 136 Bessede E, Staedel C, cuna Amador LA et al. Helicobacter pylori generates cells with cancer stem cell properties via epithelial–mesenchymal transition-like changes. Oncogene 33(32), 4123–4131 (2014).
  Medline CASGoogle Scholar
• 137 Serrano B, Alemany L, Tous S et al. Potential impact of a nine-valent vaccine in human papillomavirus related cervical disease. Infect. Agent Cancer 7(1), 38 (2012).
  MedlineGoogle Scholar
• 138 Buonaguro F, Tornesello M, Buonaguro L. The XIX century smallpox prevention in Naples and the risk of transmission of human blood-related pathogens. J. Transl. Med. 13(1), 33 (2015).
  MedlineGoogle Scholar
• 139 Kowdley KV, Gordon SC, Reddy KR et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N. Engl. J. Med. 370(20), 1879–1888 (2014).
  Medline CASGoogle Scholar
• 140 Malfertheiner P, Megraud F, O'Morain CA et al. Management of Helicobacter pylori infection – the Maastricht IV/Florence Consensus Report. Gut 61(5), 646–664 (2012).
  Medline CASGoogle Scholar
• 141 Campistol JM, Schena FP. Kaposi's sarcoma in renal transplant recipients – the impact of proliferation signal inhibitors. Nephrol. Dial. Transplant. 22 Suppl 1, i17–i22 (2007).
  Medline CASGoogle Scholar
• 142 Calistri E, Tiribelli M, Battista M et al. Epstein–Barr virus reactivation in a patient treated with anti-thymocyte globulin for severe aplastic anemia. Am. J. Hematol. 81(5), 355–357 (2006).
  Medline CASGoogle Scholar