Epistemology of the origin of cancer: a new paradigm

BMC Cancer

Björn LDM Brücher¹  Ijaz S Jamall² 

[1] Bon Secours Cancer Institute, Richmond, VA, USA

[2] Risk-Based Decisions, Inc., Sacramento, CA, USA

关键词: Neoplasm;    Tumor;    Carcinogenesis;    Fibrosis;    Inflammation;    Paradigm;    Cancer;   

Others  :  858827
DOI  :  10.1186/1471-2407-14-331

 received in 2014-03-14, accepted in 2014-05-06,  发布年份 2014

【 摘 要 】

Background

Carcinogenesis is widely thought to originate from somatic mutations and an inhibition of growth suppressors, followed by cell proliferation, tissue invasion, and risk of metastasis. Fewer than 10% of all cancers are hereditary; the ratio in gastric (1%), colorectal (3-5%) and breast (8%) cancers is even less. Cancers caused by infection are thought to constitute some 15% of the non-hereditary cancers. Those remaining, 70 to 80%, are called “sporadic,” because they are essentially of unknown etiology. We propose a new paradigm for the origin of the majority of cancers.

Presentation of hypothesis

Our paradigm postulates that cancer originates following a sequence of events that include (1) a pathogenic stimulus (biological or chemical) followed by (2) chronic inflammation, from which develops (3) fibrosis with associated changes in the cellular microenvironment. From these changes a (4) pre-cancerous niche develops, which triggers the deployment of (5) a chronic stress escape strategy, and when this fails to resolve, (6) a transition of a normal cell to a cancer cell occurs. If we are correct, this paradigm would suggest that the majority of the findings in cancer genetics so far reported are either late events or are epiphenomena that occur after the appearance of the pre-cancerous niche.

Testing the hypothesis

If, based on experimental and clinical findings presented here, this hypothesis is plausible, then the majority of findings in the genetics of cancer so far reported in the literature are late events or epiphenomena that could have occurred after the development of a PCN. Our model would make clear the need to establish preventive measures long before a cancer becomes clinically apparent. Future research should focus on the intermediate steps of our proposed sequence of events, which will enhance our understanding of the nature of carcinogenesis. Findings on inflammation and fibrosis would be given their warranted importance, with research in anticancer therapies focusing on suppressing the PCN state with very early intervention to detect and quantify any subclinical inflammatory change and to treat all levels of chronic inflammation and prevent fibrotic changes, and so avoid the transition from a normal cell to a cancer cell.

Implication of the hypothesis

The paradigm proposed here, if proven, spells out a sequence of steps, one or more of which could be interdicted or modulated early in carcinogenesis to prevent or, at a minimum, slow down the progression of many cancers.

【 授权许可】

   
2014 Brücher and Jamall; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Anderson WAD: Pathology, Volume One. 6th edition. St. Louis: The CV Mosby Company; 1971.
• [2]Howard WT, Schultz OS: Studies in the Biology of Tumor Cells. New York: The Rockefeller Institute of Medical Research; 1911.
• [3]Vogelstein B, Kinzler KW: Cancer genes and the pathways they control. Nat Med 2004, 10(8):789-799.
• [4]Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell 2011, 144(5):646-674.
• [5]Bauer KH: Mutationstheorie der Geschwulst-Entstehung. Berlin: Julius Springer Verlag; 1928.
• [6]Knudson A: Mutation and cancer: statistical study in Retinoblastoma. Proc Natl Acad Sci U S A 1971, 68(4):820-823.
• [7]Watson JD, Crick FH: Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature 1953, 171(4356):737-738.
• [8]Friedman M, Friedland GW: Medicine’s 10 Greatest Discoveries. Yale University Press; 1998.
• [9]Cobb M: 1953: when genes become “information”. Cell 2013, 153(3):503-506.
• [10]Ashley DJB: The two “hit” and multiple “hit” theories of carcinogenesis. Br J Cancer 1969, 23(2):313-328.
• [11]Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 1990, 61(5):759-767.
• [12]Hanahan D, Weinberg RA: The hallmarks of cancer. Cell 2000, 100(1):57-70.
• [13]Cleaver JE: Photosensitivity brings light to a new transcription-coupled DNA repair cofactor. Nat Genet 2012, 44(5):447-478.
• [14]Rosenfeld S: Are the somatic mutation and tissue organization field theories of carcinogenesis incompatible? Cancer Inform 2013, 12:221-229.
• [15]Versteeg R: Cancer: tumours outside the mutation box. Nature 2014, 506(7489):438-439.
• [16]Mack SC, Witt H, Piro RM, Gu L, Zuyderduyn S, Stütz AM, Wang X, Gallo M, Garzia L, Zayne K, Zhang X, Ramaswamy V, Jäger N, Jones DT, Sill M, Pugh TJ, Ryzhova M, Wani KM, Shih DJ, Head R, Remke M, Bailey SD, Zichner T, Faria CC, Barszczyk M, Stark S, Seker-Cin H, Hutter S, Johann P, Bender S, et al.: Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature 2014, 506(7489):445-450.
• [17]Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, Lee R, Tatevossian RG, Phoenix TN, Thiruvenkatam R, White E, Tang B, Orisme W, Gupta K, Rusch M, Chen X, Li Y, Nagahawhatte P, Hedlund E, Finkelstein D, Wu G, Shurtleff S, Easton J, Boggs K, Yergeau D, Vadodaria B, Mulder HL, Becksford J, Gupta P, Huether R, et al.: C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. Nature 2014, 506(7489):451-455.
• [18]Roche B, Sprouffske K, Hbid H, Missé D, Thomas F: Peto’s paradox revisited: theoretical evolutionary dynamics of cancer in wild populations. Evol Appl 2013, 6(1):109-116.
• [19]Kim EB, Fang X, Fushan AA, Huang Z, Lobanov AV, Han L, Marino SM, Sun X, Turanov AA, Yang P, Yim SH, Zhao X, Kasaikina MV, Stoletzki N, Peng C, Polak P, Xiong Z, Kiezun A, Zhu Y, Chen Y, Kryukov GV, Zhang Q, Peshkin L, Yang L, Bronson RT, Buffenstein R, Wang B, Han C, Li Q, Chen L, et al.: Genome sequencing reveals insights into physiology and longevity of the naked mole rat. Nature 2011, 479(7372):223-227.
• [20]Grivennikov SI, Greten FR, Karin M: Immunity, Inflammation, and Cancer. Cell 2010, 140(6):883-899.
• [21]Tomlinson IP, Novelli MR, Bodmer WF: The mutation rate and cancer. Proc Natl Acad Sci U S A 1996, 93(25):14800-14803.
• [22]Blattner WA: Human retroviruses: their role in cancer. Proc Assoc Am Physicians 1999, 111(6):563-572.
• [23]Parkin DM: The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006, 118(12):3030-3044.
• [24]Pisani P, Parkin DM, Muñoz N, Ferlay J: Cancer and infection: estimates of the attributable fraction in 1990. Cancer Epidemiol Biomarkers Prev 1997, 6(6):387-400.
• [25]Liu B, Nicolaides NC, Markowitz S, Willson JK, Parsons RE, Jen J, Papadopolous N, Peltomaki P, de la Chapelle A, Hamilton SR, Kinzler KW, Vogelstein B: Mismatch repair gene defects in sporadic colorectal cancers with microsatellite instability. Nat Genet 1995, 9(1):48-55.
• [26]Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW: Cancer genome landscapes. Science 2013, 339(6127):1546-1558.
• [27]Tomasetti C, Vogelstein B, Parmigiani G: Half or more of the somatic mutations in cancers of self-renewing tissues originate prior to tumor initiation. Proc Natl Acad Sci U S A 2013, 110(6):1999-2004.
• [28]Da Cunha AB: Genetic analysis of the polymorphism of color pattern in Drosophila polymorphia. Evolution 1949, 3(3):239-251.
• [29]National Center for Biotechnology Information, United States National Library of Medicine: NCBI dbSNP build 138 for human. 2013. http://www.ncbi.nlm.nih.gov/mailman/pipermail/dbsnp-announce/2013q3/000133.html webcite
• [30]Human Genome Project 2013: The science behind the human genome project: understanding the basics. http://web.ornl.gov/sci/techresources/Human_Genome/project/info.shtml webcite
• [31]European Bioinformatics Institute (EBI) and Wellcome Trust Sanger: Ensemble database 2013. http://useast.ensembl.org/Homo_sapiens/Location/Chromosome?r=1 webcite
• [32]Watson JD, Baker TA, Bell SP, Gann A, Levine M, Losick R: Molecular Biology of the Gene. 5th edition. Pearson: CSHL Press; 2004:732. Benjamin Cummings Publishers, San Francisco, CA; ISBN: 0-8053-4635-X
• [33]Brouha B: Hot L1s account for the bulk of retrotransposition in the human population. Proc Natl Acad Sci U S A 2003, 100(9):5280-5285.
• [34]Bennett EA, Keller H, Mills RE, Schmidt S, Moran JV, Weichenrieder O, Devine SE: Active Alu retrotransposons in the human genome. Genome Res 2008, 18(12):1875-1883.
• [35]Wicker T, Sabot F, Hua-Van A, Bennetzen JL, Capy P, Chalhoub B, Flavell A, Leroy P, Morgante M, Panaud O, Paux E, SanMiguel P, Schulman AH: A unified classification system for eukaryotic transposable elements. Nat Rev Genet 2007, 8(12):973-982.
• [36]Slavkin HC, Greulich RC: Extracellular Matrix Influences on Gene Expression. New York: Academic Press Inc; 1975:833pp.
• [37]Mecham RP, Madaras JG, Senior RM: Extracellular matrix-specific induction of elastogenic differentiation and maintenance of phenotypic stability in bovine ligament fibroblasts. J Cell Biol 1984, 98(5):1804-1812.
• [38]Zhe X, Cher ML, Bonfil RD: Circulating tumor cells: finding the needle in the haystack. Am J Cancer Res 2011, 1(6):740-751.
• [39]Fidler JJ: Metastasis: guantitative analysis of distribution and fate of tumor embolilabeled with 125 I-5-iodo-2′-deoxyuridine. J Natl Cancer Inst 1970, 45(4):773-782.
• [40]Loeb LA: Endogenous carcinogenesis: molecular oncology into the twenty-first century–presidential address. Cancer Res 1989, 49(20):5489-5496.
• [41]Lindahl T: Instability and decay of the primary structure of DNA. Nature 1993, 362(6422):709-715.
• [42]Ames BN, Gold LS, Willett WC: The causes and prevention of cancer. Proc Natl Acad Sci U S A 1995, 92(12):5258-5265.
• [43]Wood RD, Mitchell M, Sgouros J, Lindahl T: Human DNA repair genes. Science 2001, 291(5507):1284-1289.
• [44]Cervantes RB, Stringer JR, Shao C, Tischfield JA, Stambrook PJ: Embryonic stem cells and somatic cells differ in mutation frequency and type. Proc Natl Acad Sci U S A 2002, 99(6):3586-3590.
• [45]Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA: Environmental and chemical carcinogenesis. Semin Cancer Biol 2004, 14(6):473-486.
• [46]Yamagiwa K, Ichikawa K: Experimentelle Studie über die Pathogenese der Epithelialgeschwülste [Experimental study of the pathogenesis of epithelial tumours]. Mitt Med Fak Tokyo 1915, 15:295-344.
• [47]Rambourg A, Leblond CP: Electron microscope observations on the carbohydrate-rich cell coat present at the surface of cells in the rat. J Cell Biol 1967, 32(1):27-53.
• [48]Choi Y, Chung H, Jung H, Couchman JR, Oh ES: Syndecans as cell surface receptors: unique structure equates with functional diversity. Matrix Biol 2011, 30(2):93-99.
• [49]Curry FE, Adamson RH: Endothelial glycocalyx: permeability barrier and mechanosensor. Ann Biomed Eng 2012, 40(4):828-839.
• [50]Sackmann E, Groennenwein : Cell adhesion as dynamic interplay of lock-and-key, generic and elastic forces. Prog Theor Phys Suppl 2006, 165:78-99.
• [51]Bakhti M, Snaidero N, Schneider D, Aggarwal S, Möbius W, Janshoff A, Eckhardt M, Nave KA, Simons M: Loss of electrostatic cell-surface repulsion mediates myelin membrane adhesion and compaction in the central nervous system. Proc Natl Acad Sci U S A 2013, 110(8):3143-3148.
• [52]Singh A, Ramnath RD, Foster RR, Wylie EC, Fridén V, Dasgupta I, Haraldsson B, Welsh GI, Mathieson PW, Satchell SC: Reactive oxygen species modulate the barrier function of the human glomerular endothelial glycocalyx. PLoS One 2013, 8(2):e55852.
• [53]Drake-Holland AJ, Noble MI: The important new drug target in cardiovascular medicine–the vascular glycocalyx. Cardiovasc Hematol Disord Drug Targets 2009, 9(2):118-123.
• [54]Pott P: Chirurgical observations Volume 3. London: L Hawes, W Clark, and R Collins; 1775:177-183.
• [55]Virchow R: Ueber bewegliche thierische Zellen. Arch Path Anat Physiol 1863, 28:237-240.
• [56]Da Costa JC, III: Carcinomatous changes in an area of chronic ulceration, or Marjolin’s ulcer. Ann Surg 1903, 37(4):496-502.
• [57]Gye WE: The cancer problem. Br Med J 1926, 2(3436):865-870.
• [58]Lee WJ, Miura M: Mechanisms of systemic wound response in Drosophila. Curr Top Dev Biol 2014, 108:153-183.
• [59]Beaudry VG, Ihrie RA, Jacobs SB, Nguyen B, Pathak N, Park E, Attardi LD: Loss of the desmosomal component perp impairs wound healing in vivo. Dermatol Res Pract 2010, 2010:759731.
• [60]Gingalewski C, Wang K, Clemens MG, De Maio A: Posttranscriptional regulation of connexin 32 expression in liver during acute inflammation. J Cell Physiol 1996, 166(2):461-467.
• [61]Ehrlich P: Beiträge zur Theorie und Praxis der histologischen Färbung. Dissertation at Leipzig University; 1878.
• [62]Dyduch G, Kaczmarczyk K, Okoń K: Mast cells and cancer: enemies or allies? Pol J Pathol 2012, 63(1):1-7.
• [63]Gilfillan AM, Tkaczyk C: Integrated signalling pathways for mast-cell activation. Nat Rev Immunol 2006, 6(3):218-230.
• [64]Trivedi NH, Guentzel MN, Rodriguez AR, Yu JJ, Forsthuber TG, Arulanandam BP: Mast cells: multitalented facilitators of protection against bacterial pathogens. Expert Rev Clin Immunol 2013, 9(2):129-138.
• [65]Suurmond J, van Heemst J, van Heiningen J, Dorjée AL, Schilham MW, van der Beek FB, Huizinga TW, Schuerwegh AJ, Toes RE: Communication between human mast cells and CD4(+) T cells through antigen-dependent interactions. Eur J Immunol 2013, 43(7):1758-1768.
• [66]Powrie F, Correa-Oliveira R, Mauze S, Coffman RL: Regulatory interactions between CD45RBhigh and CD45RBlow CD4+ T cells are important for the balance between protective and pathogenic cell-mediated immunity. J Exp Med 1994, 179(2):589-600.
• [67]Monaco C, Andreakos E, Young S, Feldmann M, Paleolog E: T cell-mediated signaling to vascular endothelium: induction of cytokines, chemokines, and tissue factor. J Leukoc Biol 2002, 71(4):659-668.
• [68]Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G: Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003, 348(3):203-213.
• [69]Marrogi AJ, Munshi A, Merogi AJ, Ohadike Y, El-Habashi A, Marrogi OL, Freeman SM: Study of tumor infiltrating lymphocytes and transforming growth factor-beta as prognostic factors in breast carcinoma. Int J Cancer 1997, 74(5):492-501.
• [70]Vesalainen S, Lipponen P, Talja M, Syrjanen K: Histological grade, perineural infiltration, tumour-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma. Eur J Cancer 1994, 30A(12):1797-1803.
• [71]Nakano O, Sato M, Naito Y, Suzuki K, Orikasa S, Aizawa M, Suzuki Y, Shintaku I, Nagura H, Ohtani H: Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res 2001, 61(13):5132-5136.
• [72]Schumacher K, Haensch W, Roefzaad C, Schlag PM: Prognostic significance of activated CD8(+) T cell infiltrations within esophageal carcinomas. Cancer Res 2001, 61(10):3932-3936.
• [73]Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H, Ohtani H: CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 1998, 58(16):3491-3494.
• [74]Halpern AC, Schuchter LM: Prognostic models in melanoma. Semin Oncol 1997, 24(1 Suppl 4):S2-S7.
• [75]Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, Kagnoff MF, Karin M: IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 2004, 118(3):285-296.
• [76]Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E, Ben-Neriah Y: NF-ƙB functions as a tumour promoter in inflammation-associated cancer. Nature 2004, 431(7007):461-466.
• [77]Grivennikov SI, Karin M: Immunity and oncogenesis: a vicious connection. Curr Opin Genet Dev 2010, 20(1):65-71.
• [78]Silver R, Curley JP: Mast cells on the mind: new insights and opportunities. Trends Neurosci 2013, 36(9):513-521.
• [79]Yang J, Weinberg RA: Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 2008, 14(6):818-829.
• [80]Nathan C, Ding A: Nonresolving inflammation. Cell 2010, 140(6):871-882.
• [81]Dvorak HF: Tumors: wounds that do not heal. Similarities bewtween tumor stroma generation and wound healing. N Engl J Med 1986, 315(26):1650-1659.
• [82]Chaffer CL, Weinberg RA: A perspective on cancer cell metastasis. Science 2011, 331(6024):1559-1564.
• [83]Hirshberg A, Leibovich P, Horowitz I, Buchner A: Metastatic tumors to postextraction sites. J Oral Maxillofac Surg 1993, 51(12):1334-1337.
• [84]Scott A, Khan KM, Cook JL, Duronio V: What is inflammation? Are we ready to move beyond Celsus? Inflammation 2004, 38(3):248-249.
• [85]Porth C: Essentials of pathophysiology: concepts of altered health states. Hagerstown, MD: Lippincott Williams & Wilkins; 2007:270.
• [86]Karin M, Lawrence T, Nizet V: Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer. Cell 2006, 124(4):823-835.
• [87]Mantovani A: Molecular Pathways liking inflammation and cancer. Curr Mol Med 2010, 10(4):369-373.
• [88]Kozak W, Kluger MJ, Tesfaigzi J, Kozak A, Mayfield KP, Wachulec M, Dokladny K: Molecular Mechanisms of fever and endogenous antipyresis. Ann N Y Acad Sci 2000, 917:121-134.
• [89]Prehn RT, Lappe MA: An immuno stimulation theory of tumor development. Transplant Rev 1971, 7:26-54.
• [90]Medzhitov R: Inflammation 2010: new adventures of an old flame. Cell 2010, 140(6):771-776.
• [91]Olsson MG, Nilsson EJ, Rutardóttir S, Paczesny J, Pallon J, Akerström B: Bystander cell death and stress response is inhibited by the radical scavenger α(1)-microglobulin in irradiated cell cultures. Radiat Res 2010, 174(5):590-600.
• [92]Szasz T, Thakali K, Fink GD, Watts SW: A comparison of arteries and veins in oxidative stress: producers, destroyers, function, and disease. Exp Biol Med 2007, 232(1):27-37.
• [93]Madsen CD, Sahai E: Cancer dissemination – lessens from Leukocytes. Cell 2010, 19(1):13-26.
• [94]Vliagoftis H, Hutson AM, Mahmudi-Azer S, Kim H, Rumsaeng V, Oh CK, Moqbel R, Metcalfe DD: Mast cells express connexins on their cytoplasmic membrane. J Allergy Clin Immunol 1999, 103(4):656-662.
• [95]Eugenin EA, Branes MC, Berman JW, Saez JC: TNF-alpha plus IFN-gamma induce connexin43 expression and formation of gap junctions between human monocytes/macrophages that enhance physiological responses. J Immunol 2003, 170(3):1320-1328.
• [96]Jara PI, Boric MP, Saez JC: Leukocytes express connexin 43 after activation with lipopolysaccharide and appear to form gap junctions with endothelial cells after ischemia-reperfusion. Proc Natl Acad Sci U S A 1995, 92(15):7011-7015.
• [97]Gonzalez HE, Eugenin EA, Garces G, Solis N, Pizarro M, Accatino L, Saez JC: Regulation of hepatic connexins in cholestasis: possible involvement of Kupffer cells and inflammatory mediators. Am J Physiol Gastrointest Liver Physiol 2002, 282(6):G991-G1001.
• [98]Aronica E, Gorter J, Jansen G, Leenstra S, Yankaya B, Troost D: Expression of connexin 43 and connexin 32 gap-junction proteins in epilepsy-associated brain tumors and in the perilesional epileptic cortex. Acta Neuropathol 2001, 101(5):449-459.
• [99]Eugenin EA: Role of Connexin/Pannexin containing channels in infectious diseases. FEBS Lett 2014, 588(8):1389-1395.
• [100]Henle W, Henle G: Epidemiologic aspects of Epstein-Barr-Virus (EBV)-associated diseases. Ann N Y Acad Sci 1980, 354:326-331.
• [101]Waldboomers JMM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N: Human Papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999, 189(1):12-19.
• [102]Marshall BJ: The pathogenesis of non-ulcer dyspepsia. Med J Aust 1985, 143(7):319.
• [103]Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH, Stemmermann GN, Nomura A: Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res 1995, 55(10):2111-2115.
• [104]Heczko U, Smith VC, Meloche RM, Buchan AM, Finlay BB: Characteristics of Helicobacter pylori attachment to human primary antral epithelial cells. Microbes Infect 2000, 2(14):1669-1676.
• [105]Ramesh S, Nash J, McCulloch PG: Reduction in membranous expression of beta-catenin and increased cytoplasmic E-cadherin expression predict poor survival in gastric cancer. Br J Cancer 1999, 81(8):1392-1397.
• [106]Jawhari AU, Noda M, Farthing MJ, Pignatelli M: Abnormal expression and function of the E-cadherin-catenin complex in gastric carcinoma cell lines. Br J Cancer 2000, 80(3–4):322-330.
• [107]Conlin VS, Curtis SB, Zhao Y, Moore ED, Smith VC, Meloche RM, Finlay BB, Buchan AM: Helicobacter pylori infection targets adherens junction regulatory proteins and results in increased rates of migration in human gastric epithelial cells. Infect Immun 2004, 72(9):5181-5192.
• [108]Parker H, Chitcholtan K, Hampton MB, Heenan JI: Uptake of Helicobacter pylori outer membrane vesicles by gastric epithelial cells. Infect Immun 2010, 78(12):5054-5061.
• [109]Kuehn MJ, Kesty NC: Bacterial outer membrane vesicles and the host-pathogen interaction. Genes Dev 2005, 19(22):2645-2655.
• [110]Dorward DW, Garon CF: DNA-binding proteins in cells and membrane blebs of Neisseria gonorrhoeae. J Bacteriol 1989, 171(8):4196-4201.
• [111]Kolling GL, Matthews KR: Export of virulence genes and Shiga toxin by membrane vesicles of Escherichia coli O157:H7. Appl Environ Microbiol 1999, 65(5):1843-1848.
• [112]Yaron S, Kolling GL, Simon L, Matthews KR: Vesicle-mediated transfer of virulence genes from Escherichia coli O157:H7 to other enteric bacteria. Appl Environ Microbiol 2000, 66(10):4414-4420.
• [113]Mellemkkjaer L, Linet MS, Gridley G, Frisch M, Møller H, Olsen JH: Rheumatoid arthritis and cancer risk. Eur J Cancer 1996, 32A(10):1753-1757.
• [114]Lotti M, Bergamo L, Murer B: Occupational toxicology of asbestos-related malignancies. Clin Toxicol (Phila) 2010, 48(6):485-496.
• [115]Uehara T, Ainslie GR, Kutanzi K, Pogribny IP, Muskhelishvili L, Izawa T, Yamate J, Kosyk O, Shymonyak S, Bradford BU, Boorman GA, Bataller R, Rusyn I: Molecular mechanisms of fibrosis-associated promotion of liver carcinogenesis. Toxicol Sci 2013, 132(1):53-63.
• [116]Bald T, Quast T 2, Landsberg J, Rogava M, Glodde N, Lopez-Ramos D, Kohlmeyer J, Riesenberg S, van den Boorn-Konijnenberg D, Hömig-Hölzel C, Reuten R, Schadow B, Weighardt H, Wenzel D, Helfrich I, Schadendorf D, Bloch W, Bianchi ME, Lugassy C, Barnhill RL, Koch M, Fleischmann BK, Förster I, Kastenmüller W, Kolanus W, Hölzel M, Gaffal E, Tüting T: Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma. Nature 2014, 507(7490):109-113.
• [117]Coffelt SB, de Visser KE: Cancer: Inflammation lights the way to metastasis. Nature 2014, 507(7490):48-49.
• [118]Lian IB, Tseng YT, Su CC, Tsai KY: Progression of precancerous lesions to oral cancer: results based on the Taiwan National health Insurance Database. Oral Oncol 2013, 49(5):427-430.
• [119]Smith RW: Observation upon the “Warty ulcer of Marjolin”. Dublin Q J Med Sci 1850, 9:257-274.
• [120]Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP: The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. Hepatol 2006, 45(4):529-538.
• [121]Ehrlich HP: A snapshot of direct cell-cell communications in wound healing and scarring. Adv Wound Care (New Rochelle) 2013, 2(4):113-121.
• [122]Mutsaers SE, Bishop JE, McGrouther G, Laurent GJ: Mechanisms of tissue repair: from wound healing to fibrosis. Int J Biochem Cell Biol 1997, 29(1):5-17.
• [123]Pinnell SR, Martin GR: The cross-linking of collagen and elastin: enzymatic conversion of lysin in peptide linkage to alpha-aminoadipic-delta-semialdehyde (allysine) by an extract from bone. Proc Natl Acad Sci U S A 1968, 61(2):708-716.
• [124]Paszek M, Zahir N, Johnson KR, Lakins JN, Rozenberg GI, Gefen A, Reinhart-King CA, Margulies SS, Dembo M, Boettiger D, Hammer DA, Weaver VM: Tensional homeostasis and the malignant phenotype. Cancer Cell 2005, 8(3):241-254.
• [125]Egeblad M, Rasch MG, Weaver VM: Dynamic interplasy between the collagen scaffold and tumor evolution. Curr Opin Cell Biol 2010, 22(5):697-706.
• [126]Jensen BV, Johansen JS, Skovsgaard T, Brandt J, Teisner B: Extracellular matrix building marked by the N-terminal propeptide of procollagen type I reflect aggressiveness of recurrent breast cancer. Int J Cancer 2002, 98(4):582-589.
• [127]Barkan D, El Touny LH, Michalowski AM, Smith JA, Chu I, Davis AS, Webster JD, Hoover S, Simpson RM, Gauldie J, Green JE: Metastatic growth from dormant cells induced by a col-1-enriched fibrotic environment. Cancer Res 2010, 70(14):5706-5716.
• [128]Chen LC, Tu SH, Huang CS, Chen CS, Ho CT, Lin HW, Lee CH, Chang HW, Chang CH, Wu CH, Lee WS, Ho YS: Human breast cancer cell metastasis is attenuated by lysyl oxidase inhibitors through down-regulation of focal adhesion kinase and the paxillin-signaling pathway. Breast Cancer Res Treat 2012, 134(3):989-1004.
• [129]Peyrol S, Raccurt M, Gerard F, Gleyzal C, Grimaud JA, Sommer P: Lysyl oxidase gene expression in the stromal reaction to in situ and invasive ductal breast carcinoma. Am J Pathol 1997, 150(2):497-507.
• [130]Erler JT, Bennewith KL, Nicolau M, Dornhöfer N, Kong C, Le QT, Chi JT, Jeffrey SS, Giaccia AJ: Lysyl oxidase is essential for hypoxia-induced metastasis. Nature 2006, 440(7088):1222-1226.
• [131]Cox TT, Bird D, Baker AM, Barker HE, Ho MW, Lang G, Erler JT: LOX-mediated collagen crosslinking is responsible for fibrosis-enhanced metastasis. Cancer Res 2013, 73(6):1721-1732.
• [132]Mammoto T, Jiang E, Jiang A, Mammoto A: ECM structure and tissue stiffness control postnatal lung development through the LRP5-Tie2 signaling system. Am J Respir Mol Biol 2013, 49(6):1009-1018.
• [133]Manov I, Hirsh M, Iancu TC, Malik A, Sotnichenko N, Band M, Avivi A, Shams I: Pronounced cancer resistance in a subterranean rodent, the blind mole-rat, Spalax: in vivo and in vitro evidence. BMC Biol 2013, 11:91. BioMed Central Full Text
• [134]Tian X, Azpurua J, Hine C, Vaidya A, Myakishev-Rempel M, Ablaeva J, Mao Z, Nevo E, Gorbunova V, Seluanov A: High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature 2013, 499(7458):346-349.
• [135]Nishioka T, Eustace A, West C: Lysyl oxidase: from basic science to future cancer treatment. Cell Struct Funct 2012, 37(1):75-80.
• [136]Payne SL, Fogelgren B, Hess AR, Seftor EA, Wiley EL, Fong SF, Csiszar K, Hendrix MJ, Kirschmann DA: Lysyl oxidase regulates breast cancer cell migration and adhesion through a hydrogen peroxide-mediated mechanism. Cancer Res 2005, 65(24):11429-11436.
• [137]Ruiz LA, Dutil J, Ruiz A, Fourquet J, Abac S, Laboy J, Flores I: Single-nucleotide polymorphisms in the lysyl oxidase-like protein 4 and complement component 3 genes are associated with increased risk for endometriosis and endometriosis-associated infertility. Fertil Steril 2011, 96(2):512-515.
• [138]Bouez C, Reynaud C, Noblesse E, Thépot A, Gleyzal C, Kanitakis J, Perrier E, Damour O, Sommer P: The lysyl oxidase LOX is absent in basal and squamous cell carcinomas and its knockdown induces an invading phenotype in a skin equivalent model. Clin Cancer Res 2006, 12(5):1463-1469.
• [139]Rost T, Pyritz V, Rathcke IO, Görögh T, Dünne AA, Werner JA: Reduction of LOX- and LOXL2-mRNA expression in head and neck squamous cell carcinomas. Anticancer Res 2003, 23(2B):1565-1573.
• [140]Kaneda A, Kaminishi M, Yanagihara K, Sugimura T, Ushijima T: Identification of silencing of nine genes in human gastric cancers. Cancer Res 2002, 62(22):6645-6650.
• [141]He J, Tang HJ, Wang YY, Xiong MH, Zhou F, Shao K, Li TP: Expression of lysyl oxidase gene in upper digestive tract carcinomas and its clinical significance. Ai Zheng 2002, 21(6):671-674.
• [142]Kaneda A, Wakazono K, Tsukamoto T, Watanabe N, Yagi Y, Tatematsu M, Kaminishi M, Sugimura T, Ushijima T: Lysyl oxidase is a tumor suppressor gene inactivated by methylation and loss of heterozygosity in human gastric cancers. Cancer Res 2004, 64(18):6410-6415.
• [143]Tsuchiya MI, Okuda H, Takaki Y, Baba M, Hirai S, Ohno S, Shuin T: Renal cell carcinoma-and pheochromocytoma-specific altered gene expression profiles in VHL mutant clones. Oncol Rep 2005, 13(6):1033-1041.
• [144]Kirschmann DA, Seftor EA, Fong SF, Nieva DR, Sullivan CM, Edwards EM, Sommer P, Csiszar K, Hendrix MJ: A molecular role for lysyl oxidase in breast cancer invasion. Cancer Res 2002, 62(15):4478-4483.
• [145]Sethi A, Mao W, Wordinger RJ, Clark AF: Transforming growth factor-beta induces extracellular matrix protein cross-linking lysyl oxidase (LOX) genes in human trabecular meshwork cells. Invest Ophthalmol Vis Sci 2011, 52(8):5240-5250.
• [146]Chen H, Li D, Saldeen T, Mehta JL: Transforming growth factor-beta(1) modulates oxidatively modified LDL-induced expression of adhesion molecules: role of LOX-1. Circ Res 2001, 89(12):1155-1160.
• [147]Toubas J, Beck S, Pageaud AL, Huby AC, Mael-Ainin M, Dussaule JC, Chatziantoniou C, Chadjichristos CE: Alteration of connexin expression is an early signal for chronic kidney disease. Am J Physiol Renal Physiol 2011, 301(1):F24-F32.
• [148]Kopitz C, Gerg M, Ister D, Pennington CJ, Hauser S, Krell HW, Brew K, Nagase H, Stangl M, von Weyhern CWH, Brücher BLDM, Coussens LM, Edwards DR, Krüger A: Elevated host TIMP-1 establishes an invasion-promoting gene expression signature in experimental and clinical liver metastasis. Cancer Res 2007, 67(18):8615-8623.
• [149]Hunter RL, Markert CL: Histochemical demonstration of enzymes separated by zone electrophoresis in starch gels. Science 1957, 125(3261):1294-1295.
• [150]Kim Y, Boyd CD, Csiszar K: A new gene with sequence and structural similarity to the gene encoding human lysyl oxidase. J Biol Chem 1995, 270(13):7176-7182.
• [151]Hornstra IK, Birge S, Starcher B, Bailey AJ, Mecham RP, Shapiro SD: Lysyl oxidase is required for vascular and diaphragmatic development in mice. J Biol Chem 2003, 278(16):14387-14393.
• [152]Szabó Z, Light E, Boyd CD, Csiszár K: The human lysyl oxidase-like gene maps between STS markers D15S215 and GHLC.GCT7C09 on chromosome 15. Hum Genet 1997, 101(2):198-200.
• [153]Maisonneuve P, Marshall BC, Knapp EA, Lowenfels AB: Cancer risk in cystic fibrosis: a 20-year nationwide study from the United States. J Natl Cancer Inst 2013, 105(2):122-129.
• [154]Abraham SC, Krasinskas AM, Correa AM, Hofstetter WL, Ajani JA, Swisher SG, Wu TT: Duplication of the muscularis mucosae in Barrett esophagus: underrecognized feature and it implication for staging of adenocarcinoma. Am J Surg Pathol 2007, 31(11):1719-1725.
• [155]Bailey JR, Bland PW, Tarlton JF, Peters I, Moorghen M, Sylvester PA, Probert CS, Whiting CV: IL-13 promotes collagen accumulation in Crohn’s disease fibrosis by down-regulation of fibroblast MMP synthesis: a role for innate lymphoid cells? PLoS One 2012, 7(12):e52332.
• [156]Takahara M, Chen S, Kido M, Takeuchi S, Uchi H, Tu Y, Moroi Y, Furue M: Stromal CD10 expression, as well as increased dermal macrophages and decreased Langerhans cells, are associated with malignant transformation of keratinocytes. J Cutan Pathol 2009, 36(6):668-674.
• [157]Detlefsen S, Sipos B, Feyerabend B, Loppel G: Pancreatic fibrosis with age and ductal papillary hyperplasia. Virchows Arch 2005, 447(5):800-805.
• [158]Arimura K, Aoshiba K, Tsuji T, Tamaoki J: Chronic low-grade systemic inflammation causes DNA damage in the lungs of mice. Lung 2012, 190(6):613-620.
• [159]Bag S, Conjeti S, Das RK, Pal M, Anura A, Paul RR, Ray AK, Sengupta S, Chatterjee J: Computational analysis of p63(+) nuclei distribution pattern by graph theoretic approach in an oral pre-cancer (sub-mucous fibrosis). J Pathol Inform 2013, 4:35.
• [160]Pearse AM, Swift K: Allograft theory: transmission of devil facial-tumour disease. Nature 2006, 439(7076):549.
• [161]Siddle HV, Kreiss A, Eldridge MD, Noonan E, Clarke CJ, Pyecroft S, Woods GM, Belov K: Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial. Proc Natl Acad Sci U S A 2007, 104(41):16221-16226.
• [162]Siddle HV, Kreiss A, Tovar C, Yuen CK, Cheng Y, Belov K, Swift K, Pearse AM, Hamede R, Jones ME, Skjødt K, Woods GM, Kaufman J: Reversible epigenetic down-regulation of MHC molecules by devil facial tumour disease illustrates immune escape by a contagious cancer. Proc Natl Acad Sci U S A 2013, 110(13):5103-5108.
• [163]Siddle HV, Kaufman J: A tale of two tumours: comparison of the immune escape strategies of contagious cancers. Mol Immunol 2013, 55(2):190-193.
• [164]Oohara T, Tohma H, Aono G, Ukawa S, Kondo Y: Intestinal metaplasia of the regenerative epithelia in 549 gastric ulcers. Hum Pathol 1983, 14(12):1066-1071.
• [165]Hurst V IV, Goldberg PL, Minnear FL, Heimark RL, Vincent PA: Rearrangement of adherens junctions by transforming growth factor-beta1: role of contraction. Am J Physiol 1999, 276(4Pt1):L582-L595.
• [166]Shinto O, Yashiro M, Kawajiri H, Shimizu K, Shimizu T, Miwa A, Hirakawa K: Inhibitory effect of a TGFbeta receptor type-I inhibitor, Ki26894, on invasiveness of scirrhous gastric cancer cells. Br J Cancer 2010, 102(5):844-851.
• [167]Wang T, Zhang L, Shi C, Sun H, Wang J, Li R, Zou Z, Ran X, Su Y: TGF-β-induced miR-21 negatively regulates the antiproliferative activity but has no effect on EMT of TGF-β in HaCaT cells. Int J Biochem Cell Biol 2012, 44(2):366-376.
• [168]Xie L, Wu M, Lin H, Liu C, Yang H, Zhan J, Sun S: An increased ratio of serum miR-21 to miR-181a levels is associated with the early pathogenic process of chronic obstructive pulmonary disease in asymptomatic heavy smokers. Mol Biosyst 2014. Epub ahead of print
• [169]Viñals F, Pouysségur J: Transforming growth factor beta1 (TGF-beta1) promotes endothelial cell survival during in vitro angiogenesis via an autocrine mechanism implicating TGF-alpha signaling. Mol Cell Biol 2001, 21(21):7218-7230.
• [170]Zeng Z, dos Sarbassov D, Samudio IJ, Yee KW, Munsell MF, Ellen Jackson C, Giles FJ, Sabatini DM, Andreeff M, Konopleva M: Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML. Blood 2007, 109(8):3509-3512.
• [171]Thiem S, Pierce TP, Palmieri M, Putoczki TL, Buchert M, Preaudet A, Farid RO, Love C, Catimel B, Lei Z, Rozen S, Gopalakrishnan V, Schaper F, Hallek M, Boussioutas A, Tan P, Jarnicki A, Ernst M: mTORC1 inhibition restricts inflammation-associated gastrointestinal tumorigenesis in mice. J Clin Invest 2013, 123(2):767-781.
• [172]Xie J, Wang C, Huang DY, Zhang Y, Xu J, Kolesnikov SS, Sung KL, Zhao H: TGF-beta1 induces the different expressions of lysyl oxidases and matrix metalloproteinases in anterior cruciate ligament and medial collateral ligament fibroblasts after mechanical injury. J Biomech 2013, 46(5):890-898.
• [173]Pez F, Dayan F, Durivault J, Kaniewski B, Aimond G, Le Provost GS, Deux B, Clézardin P, Sommer P, Pouysségur J, Reynaud C: The HIF-1-inducible lysyl oxidase activates HIF-1 via the Akt pathway in a positive regulation loop and synergizes with HIF-1 in promoting tumor cell growth. Cancer Res 2011, 71(5):1647-1657.
• [174]Schlessinger K, Hall A: GSK-3beta sets Snail’s pace. Nat Cell Biol 2004, 6(10):913-915.
• [175]Peinado H, Quintanilla M, Cano A: Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions. J Biol Chem 2003, 278(23):21113-21123.
• [176]Peinado H, Olmeda D, Cano A: Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 2007, 7(6):415-428.
• [177]Noren NK, Liu BP, Burridge K, Kreft B: p120 catenin regulates the actin cytoskeleton via Rho family GTPases. J Cell Biol 2000, 150(3):567-580.
• [178]Yilmaz M, Christofori G: Mechanisms of motility in metastasizing cells. Mol Cancer Res 2010, 8(5):629-642.
• [179]Hsu CL, Muerdter CP, Knickerbocker AD, Walsh RM, Zepeda-Rivera MA, Depner KH, Sangesland M, Cisneros TB, Kim JY, Sanchez-Vazquez P, Cherezova L, Regan RD, Bahrami NM, Gray EA, Chan AY, Chen T, Rao MY, Hille MB: Cdc42 GTPase and Rac1 GTPase act downstream of p120 catenin and require GTP exchange during gastrulation of zebrafish mesoderm. Dev Dyn 2012, 241(10):1545-1561.
• [180]Yanagisawa M, Anastasiadis PZ: p120 catenin is essential for mesenchymal cadherin-mediated regulation of cell motility and invasiveness. J Cell Biol 2006, 174(7):1087-1096.
• [181]Semina EV, Rubina KA, Rutkevich PN, Voyno-Yasenetskaya TA, Parfyonova YV, Tkachuk VA: T-cadherin activates Rac1 and Cdc42 and changes endothelial permeability. Biochemistry (Mosc) 2009, 74(4):362-370.
• [182]Bialkowska K, Kulkarni S, Du X, Goll DE, Saido TC, Fox JE: Evidence that beta3 integrin-induced Rac activation involves the calpain-dependent formation of integrin clusters that are distinct from the focal complexes and focal adhesions that form as Rac and RhoA become active. J Cell Biol 2000, 151(3):685-696.
• [183]Migeotte I, Omelchenko T, Hall A, Anderson KV: Rac1-dependent collective cell migration is required for specification of the anterior-posterior body axis of the mouse. PLoS Biol 2010, 8(8):e1000442.
• [184]Perlaky L, Smetana K, Busch RK, Saijo Y, Busch H: Nucleolar and nuclear aberrations in human lox tumor cells following treatment with p120 antisense oligonucleotide ISIS-3466. Cancer Lett 1993, 74(1–2):125-135.
• [185]Roura S, Domínguez D: Inducible expression of p120Cas1B isoform corroborates the role for p120-catenin as a positive regulator of E-cadherin function in intestinal cancer cells. Biochem Biophys Res Commun 2004, 320(2):435-441.
• [186]Bezdekova M, Brychtova S, Sedlakova E, Langova K, Brychta T, Belej K: Analysis of snail-1, e-cadherin and claudin-1 expression in colorectal adenomas and carcinomas. Int J Mol Sci 2012, 13(2):1632-1643.
• [187]Ohkubo T, Ozawa M: The transcription factor Snail downregulates the tight junction components independently of E-cadherin downregulation. J Cell Sci 2004, 117(Pt 9):1675-1685.
• [188]Cano A, Pérez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, Portillo F, Nieto MA: The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol 2000, 2(2):76-83.
• [189]Miyoshi A, Kitajima Y, Sumi K, Sato K, Hagiwara A, Koga Y, Miyazaki K: Snail and SIP1 increase cancer invasion by upregulating MMP family in hepatocellular carcinoma cells. Br J Cancer 2004, 90(6):1265-1273.
• [190]Guaita S, Puig I, Franci C, Garrido M, Dominguez D, Batlle E, Sancho E, Dedhar S, De Herreros AG, Baulida J: Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression. J Biol Chem 2002, 277(42):39209-39216.
• [191]Wells JM, Melton DA: Vertebrate endoderm development. Annu Rev Cell Dev Biol 1999, 15:393-410.
• [192]Swift GH, Liu Y, Rose SD, Bischof LJ, Steelman S, Buchberg AM, Wrigth CVE, MacDonald RJ: An endocrine-exocrine switch in the activity of the pancreatic homeodomain protein PDX1 through formation of a trimeric complex with PBX1b and MRG1 (MEIS2). Mol Cell Biol 1998, 18(9):5109-5120.
• [193]Thiery JP, Acloque H, Huang RY, Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell 2009, 139(5):871-890.
• [194]Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA: The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008, 133(4):704-715.
• [195]Morel AP: Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 2008, 3(8):e2888.
• [196]Braun AC: Thermal studies on the factors responsible for tumor initiation in crown gall. Am J Biol 1947, 34(4):234-240.
• [197]Braun AC: Cellular Autonomy in crown gall. Phytopathology 1951, 41:963-966.
• [198]Braun AC: A physiological basis for autonomous growth of the crown-gall tumor cell. Proc Natl Acad Sci U S A 1958, 44(4):344-349.
• [199]Zaenen I, Van Larebeke N, Teuchy H, Van Montagu M, Schell J: Supercoiled circular DNA in crown-gall inducing Agrobacterium strains. J Mol Biol 1974, 86(1):109-127.
• [200]Chilton MD, Drummond MH, Merio DJ, Sciaky D, Montoya AL, Gordon MP, Nester EW: Stable incorporation of plasmid DNA into higher plant cells: the molecular basis of crown gall tumorigenesis. Cell 1977, 11(2):263-271.
• [201]Chilton MD, Currier TC, Farrand SK, Bendich AJ, Gordon MP, Nester EW: Agrobacterium tumefaciens DNA and PS8 bacteriophage DNA not detected in crown gall tumors. Proc Natl Acad Sci U S A 1974, 71(9):3672-3676.
• [202]Chilton MD, Saiki RK, Yadav N, Gordon MP, Quetier F: T-DNA from Agrobacterium Ti plasmid is in the nuclear DNA fraction of crown gall tumor cells. Proc Natl Acad Sci U S A 1980, 77(7):4060-4064.
• [203]Eskeland G, Kjaerheim A: Regeneration of parietal peritoneum in rats. 2. An electron microscopical study. Acta Pathol Microbiol Scand 1966, 68(3):379-395.
• [204]Eskeland G: Regeneration of parietal peritoneum in rats. 1. A light microscopical study. Acta Pathol Microbiol Scand 1966, 68(3):353-378.
• [205]Eskeland G: Growth of autologous peritoneal fluid cells in intraperitoneal diffusion chambers in rats. 1. A light microscopical study. Acta Pathol Microbiol Scand 1966, 68(4):481-500.
• [206]Eskeland G, Kjaerheim A: Growth of autologous peritoneal fluid cells in intraperitoneal diffusion chambers in rats. 2. An electron microscopical study. Acta Pathol Microbiol Scand 1966, 68(4):501-516.
• [207]Ryan GB, Grobetry J, Main OG: Mesothelial injury and recovery. Am J Path 1973, 71(1):93-112.
• [208]Watters WB, Buck RC: Scanning electron microscopy of mesothelial regeneration in the rat. Lab Invest 1972, 26(5):604-609.
• [209]Xin L: Cells of origin for cancer: an updated view from prostate cancer. Oncogene 2013, 32(32):3655-3663.
• [210]Nakano Y, Oyamada M, Dai P, Nakagami T, Kinoshita S, Takamatsu T: Connexin43 knockdown accelerates wound healing but inhibits mesenchymal transition after corneal endothelial injury in vivo. Invest Ophthalmol Vis Sci 2008, 49(1):93-104.
• [211]González-Mariscal L, Lechuga S, Garay E: Role of tight junctions in cell proliferation and cancer. Prog Histochem Cytochem 2007, 42(1):1-57.
• [212]Arthur JC, Perez-Chanona E, Mühlbauer M, Tomkovich S, Uronis JM, Fan TJ, Campbell BJ, Abujamel T, Dogan B, Rogers AB, Rhodes JM, Stintzi A, Simpson KW, Hansen JJ, Keku TO, Fodor AA, Jobin C: Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 2012, 338(6103):120-123.
• [213]Henle W, Diehl V, Kohn G, zur Hausen H, Henle G: Herpes-type virus and chromosome marker in normal leukocytes after growth irradiated Burkitt cells. Science 1967, 157(3792):1064-1065.
• [214]Dürst M, Gissmann L, Ikenberg H, zur Hausen H: A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci U S A 1983, 80(12):3812-3815.
• [215]Boshart M, Gissmann L, Ikenberg H, Kleinheinz A, Scheurlen W, Zur Hausen H: A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer. EMBO J 1984, 3(5):1151-1157.