Abonnement à la biblothèque: Guest
Portail numérique Bibliothèque numérique eBooks Revues Références et comptes rendus Collections
Critical Reviews™ in Eukaryotic Gene Expression
Facteur d'impact: 2.156 Facteur d'impact sur 5 ans: 2.255 SJR: 0.649 SNIP: 0.599 CiteScore™: 3

ISSN Imprimer: 1045-4403
ISSN En ligne: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukaryotGeneExpr.2020035187
pages 369-375

Laser Disrupts AKT Hydrogen Network in Cancer

Ziv Radisavljevic
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA


The cancer metastatic process is supported by the strong AKT hydrogen bond network. This network is formed by positive feedback loops generated in the cancer hypoxic microenvironment through the genomic AKT signaling locus. Laser paired photons disrupt the hydrogen network of the AKT active site by laser catalyzed fusion inducing the disappearance of the malignant phenotype. Paired photons increase photon density and energy at the target, inducing fusion of the AKT hydrogen network in cancer. Thus, targeting the network of the AKT active site by paired photons laser guided electrons catalyzes fusion and dismantles the hydrogen bond network, causing conversion of hydrogen into deuterium or helium. This results in the disappearance of cancer complexity, robustness, and malignant phenotype, leading to cancer cell apoptosis and effective clinical applications.


  1. Radisavljevic Z. Nitric oxide suppression triggers apoptosis through the FKHRL1 (FOXO3a)/ROCK kinase pathway in human breast carcinoma cells. Cancer. 2003;97:1358-63.

  2. Radisavljevic Z. Locus of fragility in robust breast cancer system. J Cell Biochem. 2004;92:1020-4.

  3. Radisavljevic Z. Inactivated tumor suppressor Rb by nitric oxide promotes mitosis in human breast cancer cells. J Cell Biochem. 2004;92:1-5.

  4. Radisavljevic Z. AKT as locus of fragility in robust cancer system. J Cell Biochem. 2008;104:2071-7.

  5. Radisavljevic Z. AKT as locus of cancer angiogenic robustness and fragility. J Cell Physiol. 2013;228:21-4.

  6. Radisavljevic Z. AKT as locus of cancer positive feedback loops and extreme robustness. J Cell Physiol. 2013;228:522-4.

  7. Radisavljevic Z. AKT as locus of cancer multidrug resistance and fragility. J Cell Physiol. 2013;228:671-4.

  8. Radisavljevic Z. AKT as locus of cancer phenotype. J Cell Biochem. 2015;116:1-5.

  9. Radisavljevic Z. AKT as locus of cancer positive loops conversion and chemotherapy. Crit Rev Eukaryot Gene Expr. 2015;25:199-202.

  10. Radisavljevic Z. AKT as locus of cancer unknown primary site. J Cell Biochem. 2016;117:1066-8.

  11. Radisavljevic Z. AKT as locus of hydrogen bond network in cancer. J Cell Biochem. 2018;119:130-3.

  12. Radisavljevic Z. Muon disrupts AKT hydrogen bond network in cancer. J Cell Physiol. 2019;234:7994-8. doi: 10.1002/jcp.27554.

  13. Radisavljevic Z. Lysosome activates AKT inducing cancer and metastasis. J Cell Biochem. 2019;120:12123-7. doi: 10.1002/jcb.28752.

  14. Radisavljevic ZM, Gonzalez-Flecha B. Signaling through Cdk2, importin-a and NuMA is required for H2O2-induced mitosis in primary type II pneumocytes. Biochim Biophys Acta Mol Cell Res. 2003;1640:163-70.

  15. Radisavljevic ZM, Gonzalez-Flecha B. TOR kinase and Ran are downstream from PI3K/Akt in H2O2-induced mitosis. J Cell Biochem. 2004;91:1293-300.

  16. Radisavljevic Z, Avraham H, Avraham S. Vascular endothelial growth factor up-regulates ICAM-1 expression via the phosphatidylinositol 3 OH-kinase/AKT/nitric oxide pathway and modulates migration of brain microvascular endothelial cells. J Biol Chem. 2000;275:20770-4.

  17. Khazanov A, Koganov G, Shuker R. Laser-noise suppression in the dressed-atom approach. II. Minimization principle for conventionally pumped lasers. Phys Rev A. 1993;48:1671-82.

  18. Driscoll JA, Bubin S, Varga K. Laser-induced electron emission from nanostructures: A first-principles study. Phys Rev B. 2011;83:233405.

  19. Yaakobi B, Pelah I, Hoose J. Preheat by fast electrons in laser-fusion experiments. Phys Rev Lett. 1976;37:836-9.

  20. Storm EK, Ahlstrom HG, Boyle MJ, Campbell DE, Coleman LW, Glaros SS, Kornblum HN, Lerche RA, MacQuigg DR, Phillion DW, Rainer F, Rienecker R, Rupert VC, Slivinsky VW, Speck DR, Swift CD, Tirsell KG. Laser fusion experiments at 4 TW. Phys Rev Lett. 1978;40:1570-3.

  21. Shen B, Zhang X, Yu MY. Laser-confined fusion. Phys Rev E. 2005;71:015401.

  22. Glenzer SH, MacGowan BJ, Michel P, Meezan NB, Suter LJ, Dixit SN, Kline JL, Kyrala GA, Bradley DK, Callahan DA, Dewald EL, Divol L, Dzenitis E, Edwards MJ, Hamza AV, Haynam CA, Hinkel DE, Kalantar DH, Kilkenny JD, Landen OL, Lindl JD, LePape S, Moody JD, Nikroo A, Parham T, Schneider MB, Town RPJ, Wegner P, Widmann K, Whitman P, Young BKF, Van Wonterghem B, Atherton LJ, Moses EI. Symmetric inertial confinement fusion implosions at ultra-high laser energies. Science. 2010;327:1228-31. doi: 10.1126/science.1185634.

  23. Karsch S, Dusterer S, Schwoerer H, Ewald F, Habs D, Hegelich M, Pretzler G, Pukhov A, Witte K, Sauerbrey R. High-intensity laser induced ion acceleration from heavy-water droplets. Phys Rev Lett. 2003;91:015001.

  24. Margarone D, Velyhan A, Dostal J, Ullschmied J, Perin JP, Chatain D, Garcia S, Bonnay P, Pisarczyk T, Dudzak R, Rosinski M, Krasa J, Giuffrida L, Prokupek J, Scuderi V, Psikal J, Kucharik M, De Marco M, Cikhardt J, Krousky E, Kalinowska Z, Chodukowski T, Cirrone GAP, Korn G. Proton acceleration driven by a nanosecond laser from a cryogenic thin solid-hydrogen ribbon. Phys Rev X. 2016;6:041030.

  25. Snavely RA, Key MH, Hatchet SP, Cowan TE, Roth M, Phillips TW, Stoyer MA, Henry EA, Sangster TC, Singh MS, Wilks SC, MacKinnon A, Offenberger A, Pennington DM, Yasuike K, Langdon AB, Lasinski BF, Johnson J, Perry MD, Campbell EM. Intense high-energy proton beams from petawatt-laser irradiation of solids. Phys Rev Lett. 2000:85:2945-8.

  26. Gaillard SA, Kluge T, Flippo KA, Bussmann M, Gall B, Lockard T, Geissel M, Offermann DT, Schollmeier M, Sentoku Y, Cowan TE. Increased laser-accelerated proton energies via direct laser-light-pressure acceleration of electrons in microcone targets. Phys Plasmas. 2011;18:056710. doi: 10.1063/1.3575624.

  27. Wagner F, Deppert O, Brabetz C, Fiala P, Kleinschmidt A, Poth P, Schanz VA, Tebartz A, Zielbauer B, Roth M, Stohlker T, Bagnoud V. Maximum proton energy above 85 MeV from the relativistic interaction of laser pulses with micrometer thick CH2 targets. Phys Rev Lett. 2016;116:205002.

  28. Maksimchuk A, Gu S, Flippo K, Umstadter D, Bychenkov VYu. Forward ion acceleration in thin films driven by a high-intensity laser. Phys Rev Lett. 2000;84:4108-11.

  29. Clark EL, Krushelnick K, Davies JR, Zepf M, Tatarakis M, Beg FN, Machacek A, Norreys PA, Santala MIK, Watts I, Dangor AE. Measurements of energetic proton transport through magnetized plasma from intense laser interactions with solids. Phys Rev Lett. 2000;84:670-3.

  30. Izumi N, Sentoku Y, Habara H, Takahashi K, Ohtani F, Sonomoto T, Kodama R, Norimatsu T, Fujita H, Kitagawa Y, Mima K, Tanaka KA, Yamanaka T. Observation of neutron spectrum produced by fast deuterons via ultraintense laser plasma interactions. Phys Rev E. 2002;65:036413.

  31. Hatchett SP, Brown CG, Cowan TE, Henry EA, Johnson JS, Key MH, Koch JA, Langdon AB, Lasinski BF, Lee RW, Mackinnon AJ, Pennington DM, Perry MD, Phillips TW, Roth M, Sangster TC, Singh MS, Snavely RA, Stoyer MA, Wilks SC, Yasuike K. Electron, photon, and ion beams from the relativistic interaction of petawatt laser pulses with solid targets. Phys Plasmas. 2000;7:2076-82.

  32. Mackinnon AJ, Borghesi M, Hatchett S, Key MH, Patel PK, Campbell H, Schiavi A, Snavely R, Wilks SC, Willi O. Effect of plasma scale length on multi-MeV proton production by intense laser pulses. Phys Rev Lett. 2001;86:1769-72.

  33. Wilks SC, Langdon AB, Cowan TE, Roth M, Singh M, Hatchett S, Key MH, Pennington D, MacKinnon A, Snavely RA. Energetic proton generation in ultra-intense laser-solid interactions. Phys Plasmas. 2001;8:542-9. doi: 10.1063/1.1333697.

  34. Hegelich M, Karsch S, Pretzler G, Habs D, Witte K, Guenther W, Allen M, Blazevic A, Fuchs J, Gauthier JC, Geissel M, Audebert P, Cowan T, Roth M. MeV ion jets from short-pulse-laser interaction with thin foils. Phys Rev Lett. 2002;89(8):085002.

  35. Pukhov A. Three-dimensional simulations of ion acceleration from a foil irradiated by a short-pulse laser. Phys Rev Lett. 2001;86:3562-5.

  36. Brueckner KA, Jorna S. Laser-driven fusion. Rev Mod Phys. 1974;46:325-67.

  37. Loomis WA, Gordon BA, Pipkin FM, Pordes SH, Shambroom WD, Verhey LJ, Wilson R, Anderson HL, Fine RM, Heisterberg RH, Matis HS, Mo L, Myrianthopoulos LC, Wright SC, Francis WR, Hicks RG, Kirk TBW, Bharadwaj VK, Booth NE, Kirkbride GI, Quirk TW, Skuja A, Staton MA, Williams WSC. Hadron production in muon-proton and muon-deuteron collisions. Phys Rev D. 1979;19:2543-71.

  38. Pati S, Jat RA, Mukerjee SK, Parida SC. Hydrogen isotope effect on thermodynamic and kinetics of hydrogen/deuterium absorption-desorption in Pd0 77Ag010Cu013 alloy. J Phys Chem C. 2015;119:10314-20.

  39. Zylstra AB, Frenje JA, Gatu Johnson M, Hale GM, Brune CR, Bacher A, Casey DT, Li CK, McNabb D, Paris M, Petrasso RD, Sangster TC, Sayre DB, Seguin FH. Proton spectra from He3+T and He3+He3 fusion at low center-of-mass energy, with potential implications for solar fusion cross sections. Phys Rev Lett. 2017; 119:222701.

  40. Last I, Jortner J. Nucleosynthesis driven by Coulomb explosion within a single nanodroplet. Phys Rev A. 2008;77:033201.

  41. Zigler A, Palchan T, Bruner N, Schleifer E, Eisenmann S, Botton M, Henis Z, Pikuz SA, Faenov AY Jr, Gordon D, Sprangle P. 5.5-7.5 MeV proton generation by a moderate-intensity ultrashort-pulse laser interaction with H2O nanowire targets. Phys Rev Lett. 2011; 106:134801.

  42. Petrov GM, Davis J, Velikovich AL, Kepple PC, Dasgupta A, Clark RW, Borisov AB, Boyer K, Rhodes CK. Modeling of clusters in a strong 248-nm laser field by a three-dimensional relativistic molecular dynamic model. Phys Rev E. 2005;71(3 Pt 2B):036411.

  43. Goers AJ, Hine GA, Feder L, Miao B, Salehi F, Wahlstrand JK, Milchberg HM. Multi-MeV electron acceleration by subterawatt laser pulses. Phys Rev Lett. 2015;115: 194802.

  44. Paradkar BS, Krishnagopal S. Electron heating in radiation-pressure-driven proton acceleration with a circularly polarized laser. Phys Rev E. 2016;93:023203.

  45. Siminos E, Grech M, Skupin S, Schlegel T, Tikhonchuk VT. Effect of electron heating on self-induced transparency in relativistic intensity laser-plasma interaction. Phys Rev E. 2012;86:056404.

  46. Paradkar BS, Krasheninnikov SI, Beg FN. Mechanism of heating of pre-formed plasma electrons in relativistic laser-matter interaction. Phys Plasmas. 2012;19:060703.

  47. Krasheninnikov SI. On stochastic heating of electrons by intense laser radiation in the presence of electrostatic po-tential well. Phys Plasmas. 2014;21:104510.

  48. Radisavljevic Z. Lysosome AKT targeting in metastatic cancer. Crit Rev Eukaryot Gene Expr. 2020;30:121-3. doi: 10.1615/CritRevEukaryotGeneExpr.2020032762.

  49. Wang Y, Zhao H, Wang D, Hao M, Kong C, Zhao X, Gao Y, Li J, Liu B, Yang B, Zhang H, Jiang J. Inhibition of autophagy promoted apoptosis and suppressed growth of hepatocellular carcinoma upon photothermal exposure. J Biomed Nanotechnol. 2019;15:813-21. doi: 10.1166/ jbn.2019.2714.

  50. Li Y, Li X, Doughty A, West C, Wang L, Zhou F, Nordquist RE, Chen WR. Phototherapy using immunologically modified carbon nanotubes to potentiate checkpoint blockade for metastatic breast cancer. Nanomedicine. 2019;18:44-53. doi: 10.1016/j.nano.2019.02.009.

  51. Bae JM, Eun SH, Oh SH, Shin JH, Kang HY, Kim KH, Lee SC, Choi CW. The 308-nm excimer laser treatment does not increase the risk of skin cancer in patients with vitiligo: A population-based retrospective cohort study. Pigment Cell Melanoma Res. 2019;32:714-8. doi: 10.1111/ pcmr.12781.

  52. Tanabashi M, Hagiwara K, Hikasa K, Nakamura K, Sumino Y, Takahashi F, Tanaka J, Agashe K, Aielli G, Amsler C, Antonelli M. (Particle Data Group) Review of particle physics. Phys Rev D. 2018;98:030001.

Articles with similar content:

AKT as Locus of Cancer Positive Loops Conversion and Chemotherapy
Critical Reviews™ in Eukaryotic Gene Expression, Vol.25, 2015, issue 3
Ziv Radisavljevic
Lysosome AKT Targeting in Metastatic Cancer
Critical Reviews™ in Eukaryotic Gene Expression, Vol.30, 2020, issue 2
Ziv Radisavljevic
Human Prostate Carcinogenesis
Critical Reviews™ in Oncogenesis, Vol.8, 1997, issue 4
Hsiang-fu Kung, Johng S. Rhim
Radiation-Induced Cell Death: Signaling and Pharmacological Modulation
Critical Reviews™ in Oncogenesis, Vol.23, 2018, issue 1-2
Alex Philchenkov
Avelumab: A Novel Anti-PD-L1 Agent in the Treatment of Merkel Cell Carcinoma and Urothelial Cell Carcinoma
Critical Reviews™ in Immunology, Vol.38, 2018, issue 3
Amanda Teets, Linda Pham, Rahul Deshmukh, Lana Hochmuth, Emma Lan Tran