title: Constructal approach to cell membranes transport: Amending the 'Norton-Simon' hypothesis for cancer treatment.
abstract: To investigate biosystems, we propose a new thermodynamic concept that analyses ion, mass and energy flows across the cell membrane. This paradigm-shifting approach has a wide applicability to medically relevant topics including advancing cancer treatment. To support this claim, we revisit 'Norton-Simon' and evolving it from an already important anti-cancer hypothesis to a thermodynamic theorem in medicine. We confirm that an increase in proliferation and a reduction in apoptosis trigger a maximum of ATP consumption by the tumor cell. Moreover, we find that positive, membrane-crossing ions lead to a decrease in the energy used by the tumor, supporting the notion of their growth inhibitory effect while negative ions apparently increase the cancer's consumption of energy hence reflecting a growth promoting impact. Our results not only represent a thermodynamic proof of the original Norton-Simon hypothesis but, more concretely, they also advance the clinically intriguing and experimentally testable, diagnostic hypothesis that observing an increase in negative ions inside a cell in vitro, and inside a diseased tissue in vivo, may indicate growth or recurrence of a tumor. We conclude with providing theoretical evidence that applying electromagnetic field therapy early on in the treatment cycle may maximize its anti-cancer efficacy.
authors.affiliation: Dipartimento Energia, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Lucia
authors.affiliation: Department of Medical Sciences, University of Torino, Corso A.M. Dogliotti 14, 10126 Torino, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ponzetto
authors.affiliation: Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.|ThinkMotu LLC, Wellesley, MA 02481, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Deisboeck
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001692:Biological Transport; D016923:Cell Death; D002462:Cell Membrane / Q000378:metabolism*; D008938:Mitosis; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy*; D013816:Thermodynamics
chemical_list: D000255:Adenosine Triphosphate
references.citation: Oncologist. 2005 Jun-Jul;10(6):370-81
references.pmid: 15967831
references.citation: Math Biosci. 2003 Feb;181(2):177-207
references.pmid: 12445761
references.citation: Nat Rev Cancer. 2014 May;14(5):296
references.pmid: 24705651
references.citation: Am J Pathol. 1997 Feb;150(2):409-15
references.pmid: 9033256
references.citation: Br J Pharmacol. 2012 Jun;166(4):1247-60
references.pmid: 22233416
references.citation: Mol Biol Cell. 2014 Dec 1;25(24):3835-50
references.pmid: 25425556
references.citation: Cancer Res. 1996 Mar 1;56(5):941-3
references.pmid: 8640781
references.citation: Phys Life Rev. 2011 Oct;8(3):209-40
references.pmid: 21683663
references.citation: Pflugers Arch. 2014 Apr;466(4):801-10
references.pmid: 24449277
references.citation: Nat Rev Mol Cell Biol. 2008 Apr;9(4):323-32
references.pmid: 18354422
references.citation: Prog Histochem Cytochem. 2009;43(4):177-264
references.pmid: 19167986
references.citation: Nat Clin Pract Oncol. 2006 Aug;3(8):406-7
references.pmid: 16894366
references.citation: Cell Mol Bioeng. 2014 Sep 1;7(3):432-445
references.pmid: 25295125
references.citation: Biol Open. 2013 Mar 15;2(3):306-13
references.pmid: 23519324
references.citation: J Theor Biol. 2005 Aug 21;235(4):476-84
references.pmid: 15935166
references.citation: Theor Biol Med Model. 2015;12:29
references.pmid: 26620568
references.citation: Protein Cell. 2014 Jul;5(7):518-31
references.pmid: 24756566
references.citation: Tissue Eng Part A. 2008 Sep;14(9):1461-8
references.pmid: 18601591
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):11765-72
references.pmid: 11050207
references.citation: Cell Biol Int. 2010 Apr;34(4):379-84
references.pmid: 20055760
references.citation: Nat Med. 2014 Apr;20(4):360-7
references.pmid: 24633304
references.citation: Clin Cancer Res. 2002 Apr;8(4):1284-91
references.pmid: 11948144
references.citation: J Gen Physiol. 1943 Sep 20;27(1):37-60
references.pmid: 19873371
references.citation: IMA J Math Appl Med Biol. 1997 Mar;14(1):39-69
references.pmid: 9080687
references.citation: Stem Cells Dev. 2011 May;20(5):843-50
references.pmid: 21126173
references.citation: J R Soc Interface. 2015 Jun 6;12(107). pii: 20150245. doi: 10.1098/rsif.2015.0245
references.pmid: 25972435
references.citation: Sci Rep. 2014;4:6763
references.pmid: 25342534
references.citation: Acta Pharmacol Sin. 2013 Jan;34(1):129-36
references.pmid: 23222271
references.citation: Neuron. 2008 Sep 25;59(6):846-60
references.pmid: 18817726
references.citation: Math Biosci. 2000 Mar;164(1):17-38
references.pmid: 10704636
references.citation: Bull Math Biol. 2003 Sep;65(5):903-31
references.pmid: 12909255
references.citation: BMC Cell Biol. 2011;12:4
references.pmid: 21255452
references.citation: J Biol Chem. 2012 Sep 14;287(38):31666-73
references.pmid: 22822055
references.citation: Science. 1988 Apr 8;240(4849):177-84
references.pmid: 2451290
references.citation: Cancer Res. 2009 Nov 1;69(21):8507-15
references.pmid: 19861540
references.citation: J Cell Physiol. 2010 Jul;224(1):165-77
references.pmid: 20333647
references.citation: Biochemistry. 2011 Oct 4;50(39):8264-9
references.pmid: 21888353
references.citation: Dis Model Mech. 2013 May;6(3):595-607
references.pmid: 23471912
references.citation: Philos Trans A Math Phys Eng Sci. 2006 Dec 15;364(1849):3319-34
references.pmid: 17090462
references.citation: Pflugers Arch. 2013 Feb;465(2):221-32
references.pmid: 23179380
references.citation: Cell Biol Int. 1999;23(3):157-61
references.pmid: 10562436
references.citation: Br J Pharmacol. 2014 Feb;171(4):945-60
references.pmid: 24460676
references.citation: Annu Rev Biochem. 2004;73:705-48
references.pmid: 15189157
references.citation: J Theor Biol. 2006 Sep 21;242(2):440-53
references.pmid: 16650438
references.citation: Front Physiol. 2013 Jul 17;4:185
references.pmid: 23882223
references.citation: J Pathol. 1997 May;182(1):1-8
references.pmid: 9227334
references.citation: Phys Biol. 2012 Dec;9(6):065002
references.pmid: 23196890
references.citation: Cancer Res. 2000 Jul 15;60(14):3683-8
references.pmid: 10919633
references.citation: Cancer Res. 2000 Feb 15;60(4):916-21
references.pmid: 10706105
references.citation: Science. 2004 Aug 20;305(5687):1147-50
references.pmid: 15326353
references.citation: Med Hypotheses. 2002 Feb;58(2):144-7
references.pmid: 11812192
references.citation: Int J Radiat Oncol Biol Phys. 2001 Oct 1;51(2):349-53
references.pmid: 11567808
references.citation: J Physiol. 1949 Mar 1;108(1):37-77
references.pmid: 18128147