Skip to main content
Top
Published in: Clinical and Translational Medicine 1/2018

Open Access 01-12-2018 | Perspective

Cancer; an induced disease of twentieth century! Induction of tolerance, increased entropy and ‘Dark Energy’: loss of biorhythms (Anabolism v. Catabolism)

Author: Mahin Khatami

Published in: Clinical and Translational Medicine | Issue 1/2018

Login to get access

Abstract

Maintenance of health involves a synchronized network of catabolic and anabolic signals among organs/tissues/cells that requires differential bioenergetics from mitochondria and glycolysis (biological laws or biorhythms). We defined biological circadian rhythms as Yin (tumoricidal) and Yang (tumorigenic) arms of acute inflammation (effective immunity) involving immune and non-immune systems. Role of pathogens in altering immunity and inducing diseases and cancer has been documented for over a century. However, in 1955s decision makers in cancer/medical establishment allowed public (current baby boomers) to consume million doses of virus-contaminated polio vaccines. The risk of cancer incidence and mortality sharply rose from 5% (rate of hereditary/genetic or innate disease) in 1900s, to its current scary status of 33% or 50% among women and men, respectively. Despite better hygiene, modern detection technologies and discovery of antibiotics, baby boomers and subsequent 2–3 generations are sicker than previous generations at same age. American health status ranks last among other developed nations while America invests highest amount of resources for healthcare. In this perspective we present evidence that cancer is an induced disease of twentieth century, facilitated by a great deception of cancer/medical establishment for huge corporate profits. Unlike popularized opinions that cancer is 100, 200 or 1000 diseases, we demonstrate that cancer is only one disease; the severe disturbances in biorhythms (differential bioenergetics) or loss of balance in Yin and Yang of effective immunity. Cancer projects that are promoted and funded by decision makers are reductionist approaches, wrong and unethical and resulted in loss of millions of precious lives and financial toxicity to society. Public vaccination with pathogen-specific vaccines (e.g., flu, hepatitis, HPV, meningitis, measles) weakens, not promotes, immunity. Results of irresponsible projects on cancer sciences or vaccines are increased population of drug-dependent sick society. Outcome failure rates of claimed ‘targeted’ drugs, ‘precision’ or ‘personalized’ medicine are 90% (± 5) for solid tumors. We demonstrate that aging, frequent exposures to environmental hazards, infections and pathogen-specific vaccines and ingredients are ‘antigen overload’ for immune system, skewing the Yin and Yang response profiles and leading to induction of ‘mild’, ‘moderate’ or ‘severe’ immune disorders. Induction of decoy or pattern recognition receptors (e.g., PRRs), such as IRAK-M or IL-1dRs (‘designer’ molecules) and associated genomic instability and over-expression of growth promoting factors (e.g., pyruvate kinases, mTOR and PI3Ks, histamine, PGE2, VEGF) could lead to immune tolerance, facilitating cancer cells to hijack anabolic machinery of immunity (Yang) for their increased growth requirements. Expression of constituent embryonic factors would negatively regulate differentiation of tumor cells through epithelial–mesenchymal-transition and create “dual negative feedback loop” that influence tissue metabolism under hypoxic conditions. It is further hypothesized that induction of tolerance creates ‘dark energy’ and increased entropy and temperature in cancer microenvironment allowing disorderly cancer proliferation and mitosis along with increased glucose metabolism via Crabtree and Pasteur Effects, under mitophagy and ribophagy, conditions that are toxic to host survival. Effective translational medicine into treatment requires systematic and logical studies of complex interactions of tumor cells with host environment that dictate clinical outcomes. Promoting effective immunity (biological circadian rhythms) are fundamental steps in correcting host differential bioenergetics and controlling cancer growth, preventing or delaying onset of diseases and maintaining public health. The author urges independent professionals and policy makers to take a closer look at cancer dilemma and stop the ‘scientific/medical ponzi schemes’ of a powerful group that control a drug-dependent sick society before all hopes for promoting public health evaporate.
Footnotes
1
Cancer/Medical establishment is referred to the most powerful decision making group within the Government (NIH/NCI-FDA-CDC-DHHS), Big pharma, major organizations (AACR, ACS, ASCO, AMA), cancer research and treatment centers, major medical schools. Members of establishment (5–10 × 103) with carrier longevity of 35–65 years are decision makers in charge of research directions, publicity and funding. The temporary or permanent handlers of establishment (directors of institutes, divisions or departments, deputies and staff (30–100 × 103) and the world’s largest lobbying group (3–5 × 106) carry out the directions of members of establishment. War on cancer has been made as an imaginary problem that cannot be solved for over six decades [5, 7, 16].
 
2
Health Impact News December 10, 2017—reported from World Mercury Project Team—Anthrax Vaccine: Safety Concerns-‘Pilots Would Rather Leave the Military than be Forced to get Anthrax Vaccine’.
 
3
US Senator Grassley Investigates Vaccine Corruption in Unsanctioned Experimental Herpes Vaccine: Human Research. Health Impact News, January 12, 2018.
 
4
Wagstaff A, Culyer AJ. Four decades of health economics through a bibliometric lens. J Health Econ. 2012;31:406–39. https://​doi.​org/​10.​1016/​j.​jhealeco.​2012.​03.​002.
 
5
Khatami M (2016) Book review: Safety concerns for HPV vaccination of young generation, paid by Obamacare and V.P. Biden Moonshot initiative. Global Vaccines and Immunology, ISSN: 2397-575X, 2016 https://​oatext.​com/​pdf/​GVI-1-118.​pdf.
 
6
Tom Valentine: Polio vaccine spreads cancer. Dark Politricks. Part II, SHOAH, June 21, 2011.
 
7
Brian Shilhavy. The Truth About Vaccines: DocuSeries with 60 Top Health Experts Reveal What is Censored in Mainstream Media, Jan 13, 2018; U.S. Government continues to pay out millions to victims injured by the flu shot. Reflects report from Department of Justice (DOJ) on cases settled for vaccine injuries and death mandated by National Vaccine Injury Compensation Program (NVICP), March 8, 2018.
 
8
Daily Mail-UK Media Publication.”HPV vaccine destroying the lives of ‘Thousands’ of girls”, Accessed from Health Impact News, Sept. 28, 2017.
 
9
Gordon Duff. Is American medicine a war crime? Veterans Today, July 3, 2012. http://​www.​veteranstoday.​com/​2012/​07/​03/​is-american-medicine-a-war-crime/​.
 
10
Holtzman A: Dr. Leon Dmochowski and Dr. R. Lee Clark—Truth Tobacco Industry Documents.5-page Letter, to Paul D. Smith, VP and General Counsel, Philip Morris Inc., January 06, 1965. https://​industrydocument​s.​library.​ucsf.​edu/​tobacco/​docs/​[ID], Ness Motley Law Firm. https://​industrydocument​s.​library.​ucsf.​edu/​tobacco/​docs/​qymd0040—Bates Number: 10051001761005100180 [7].
 
11
The Cancer letter, “His six-month ‘listening tour’ almost over, Sharpless discusses his vision for NCI”, February 23, 2018.
 
12
Phillip Zelikow was one of the architects behind creation of war against powerless nations.
 
13
In February 2012, National Cancer Institute (NCI) Board meeting (NCAB) report on cancer therapy, it was admitted that success rate being 15%; in March 2012, during Metabolon conference in Bethesda, Maryland, company professionals reported that 95% of cancer drugs that are developed fail [7].
 
14
June 1, 2012, E Berger (CNBC program) in an interview with then president of MD Anderson, DePinho confirmed that 95% of cancer drugs for solid tumors fail—http://​blog.​chron.​com/​sciguy/​2012/​06/​m-d-anderson-president-goes-on-cnbc-extols-his-own-company.
 
15
Brill S. (2013) Special Report, Bitter pill: Why medical bills are killing us. Time (USA edition) March 4, 2013, 16-55.
 
16
Beil L. (2012) How much would you pay for 3 more months of life? Newsweek, 9/3/2012. Vol. 160, Issue 10, 40-44.
 
17
Milton Friedman, Nobel Laureate in Economic Sciences (1976), for his achievements in the field of consumption analyses, monetary history and theory and demonstration of the complexity of stabilization policy. Source: The Nobel Foundation.
 
Literature
1.
go back to reference Ehrlich P (1909) Uber den jetzigen Stand der Karzinomforschung. Ned Tijdschr Geneeskd 5:273–290 Ehrlich P (1909) Uber den jetzigen Stand der Karzinomforschung. Ned Tijdschr Geneeskd 5:273–290
4.
go back to reference Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315:1650–1659PubMedCrossRef Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315:1650–1659PubMedCrossRef
6.
go back to reference Khatami M (2012) Unresolved inflammation and cancer: loss of natural immune surveillance as the correct ‘target’ for therapy! Seeing the ‘elephant’ in the light of logic. Cell Biochem Biophys 62:501–509PubMedCrossRef Khatami M (2012) Unresolved inflammation and cancer: loss of natural immune surveillance as the correct ‘target’ for therapy! Seeing the ‘elephant’ in the light of logic. Cell Biochem Biophys 62:501–509PubMedCrossRef
9.
go back to reference Day A (2009) ‘An American tragedy’, the cutter incident and its implications for the Salk polio vaccine in New Zealand 1955–1960. Health Hist. 11:42–61 Day A (2009) ‘An American tragedy’, the cutter incident and its implications for the Salk polio vaccine in New Zealand 1955–1960. Health Hist. 11:42–61
10.
go back to reference Stewart SE (1953) Leukemia in mice produced by a filterable agent present in AKR leukemic tissues with notes on a sarcoma produced by the same agent [abstract]. Anat Rec 117:532 Stewart SE (1953) Leukemia in mice produced by a filterable agent present in AKR leukemic tissues with notes on a sarcoma produced by the same agent [abstract]. Anat Rec 117:532
11.
go back to reference Cutrone R, Lednicky J, Dunn G, Rizzo P, Bocchetta M, Chumakov K et al (2005) Some oral poliovirus vaccines were contaminated with infectious SV40 after 1961. Cancer Res 65(22):10273–10279PubMedCrossRef Cutrone R, Lednicky J, Dunn G, Rizzo P, Bocchetta M, Chumakov K et al (2005) Some oral poliovirus vaccines were contaminated with infectious SV40 after 1961. Cancer Res 65(22):10273–10279PubMedCrossRef
13.
go back to reference Strickler HD, Goedert JJ (1998) Exposure to SV40-contaminated poliovirus vaccine and the risk of cancer—a review of the epidemiological evidence. Dev Biol Stand 94:235–244PubMed Strickler HD, Goedert JJ (1998) Exposure to SV40-contaminated poliovirus vaccine and the risk of cancer—a review of the epidemiological evidence. Dev Biol Stand 94:235–244PubMed
14.
go back to reference Eddy BE, Stewart SE, Stanton MF, Marcotte JM (1959) Induction of tumors in rats by tissue-culture preparations of SE polyoma virus. J Natl Cancer Inst 22:161–171PubMed Eddy BE, Stewart SE, Stanton MF, Marcotte JM (1959) Induction of tumors in rats by tissue-culture preparations of SE polyoma virus. J Natl Cancer Inst 22:161–171PubMed
16.
19.
go back to reference Grubeck-Loebenstein B, Della Bella S, Iorio AM, Michel JP, Pawelec G, Solana R (2009) Immunosenescence and vaccine failure in the elderly. Aging Clin Exp Res 21:201–229PubMedCrossRef Grubeck-Loebenstein B, Della Bella S, Iorio AM, Michel JP, Pawelec G, Solana R (2009) Immunosenescence and vaccine failure in the elderly. Aging Clin Exp Res 21:201–229PubMedCrossRef
20.
go back to reference Khatami M (2017) Cancer statistics and concerns for safety of drugs or vaccines: increased population of drug-dependent sick society! Inflammation aging and cancer. Springer, Cham, pp 213–260 Khatami M (2017) Cancer statistics and concerns for safety of drugs or vaccines: increased population of drug-dependent sick society! Inflammation aging and cancer. Springer, Cham, pp 213–260
21.
go back to reference Neustadt RE, Fineberg HV (eds) (1978) The swine flu affair: decision-making on a slippery disease. National Academies Press, Washington, DC Neustadt RE, Fineberg HV (eds) (1978) The swine flu affair: decision-making on a slippery disease. National Academies Press, Washington, DC
22.
go back to reference Barbanti-Brodano G, Sabbioni S, Martini F, Negrini M, Corallini A, Tognon M (2004) Simian virus 40 infection in humans and association with human diseases: results and hypotheses. Virology 318(1):1–9PubMedCrossRef Barbanti-Brodano G, Sabbioni S, Martini F, Negrini M, Corallini A, Tognon M (2004) Simian virus 40 infection in humans and association with human diseases: results and hypotheses. Virology 318(1):1–9PubMedCrossRef
23.
go back to reference Horvath BL, Fornosi F (1964) Excretion of SV-40 virus after oral administration of contaminated polio vaccine. Acta Microbiol Acad Sci Hung. 11:271–275PubMed Horvath BL, Fornosi F (1964) Excretion of SV-40 virus after oral administration of contaminated polio vaccine. Acta Microbiol Acad Sci Hung. 11:271–275PubMed
26.
go back to reference Khatami M, Donnelly JJ, John T, Rockey JH (1984) Vernal conjunctivitis. Model studies in guinea pigs immunized topically with fluoresceinyl ovalbumin. Arch Ophthalmol 102:1683–1688PubMedCrossRef Khatami M, Donnelly JJ, John T, Rockey JH (1984) Vernal conjunctivitis. Model studies in guinea pigs immunized topically with fluoresceinyl ovalbumin. Arch Ophthalmol 102:1683–1688PubMedCrossRef
27.
go back to reference Khatami M, Donnelly JJ, Rockey JH (1985) Induction and down-regulation of conjunctival type-1 hypersensitivity reactions in guinea pigs sensitized topically with fluoresceinyl ovalbumin. Ophthal Res 17:139–147CrossRef Khatami M, Donnelly JJ, Rockey JH (1985) Induction and down-regulation of conjunctival type-1 hypersensitivity reactions in guinea pigs sensitized topically with fluoresceinyl ovalbumin. Ophthal Res 17:139–147CrossRef
28.
go back to reference Haldar JP, Khatami M, Donnelly JJ, Rockey JH (1988) Experimental allergic conjunctivitis: production of different isotypes of antibody by conjunctival-associated lymphoid tissue in culture. Regional Immunol. 1:92–99 Haldar JP, Khatami M, Donnelly JJ, Rockey JH (1988) Experimental allergic conjunctivitis: production of different isotypes of antibody by conjunctival-associated lymphoid tissue in culture. Regional Immunol. 1:92–99
29.
go back to reference Khatami M, Donnelly JJ, Haldar JP, Rockey JH (1989) Massive follicular lymphoid hyperplasia in experimental chronic recurrent allergic conjunctivitis. Arch Ophthalmol 107:433–438PubMedCrossRef Khatami M, Donnelly JJ, Haldar JP, Rockey JH (1989) Massive follicular lymphoid hyperplasia in experimental chronic recurrent allergic conjunctivitis. Arch Ophthalmol 107:433–438PubMedCrossRef
30.
go back to reference Helleboid L, Khatami M, Wei Z-G, Rockey JH (1991) Histamine and prostacyclin: primary and secondary release in allergic conjunctivitis. Invest Ophthalmol Vis Sci 32:2281–2289PubMed Helleboid L, Khatami M, Wei Z-G, Rockey JH (1991) Histamine and prostacyclin: primary and secondary release in allergic conjunctivitis. Invest Ophthalmol Vis Sci 32:2281–2289PubMed
31.
go back to reference Khatami M (2005) Developmental phases of inflammation-induced massive lymphoid hyperplasia and extensive changes in epithelium in an experimental model of allergy: implications for a direct link between inflammation and carcinogenesis. Am J Ther 12:117–126PubMedCrossRef Khatami M (2005) Developmental phases of inflammation-induced massive lymphoid hyperplasia and extensive changes in epithelium in an experimental model of allergy: implications for a direct link between inflammation and carcinogenesis. Am J Ther 12:117–126PubMedCrossRef
32.
go back to reference Khatami M (2005) Cyclooxygenase inhibitor ketorolac or mast cell stabilizers: immunological challenges in cancer therapy. Clin Cancer Res 11:1349–1351PubMed Khatami M (2005) Cyclooxygenase inhibitor ketorolac or mast cell stabilizers: immunological challenges in cancer therapy. Clin Cancer Res 11:1349–1351PubMed
33.
go back to reference Khatami M (2005) Standardizing criteria on cancer biomarkers as foundation of a database: Creating a common language (data elements) for cancer biomarkers tracking and utilization for professionalsin oncology research. Federal Register; HHS Reference No. E-147-2005/0—Research Tool. Government-Owned Inventions; Availability for Licensing. 70(140): 42350–42351 Khatami M (2005) Standardizing criteria on cancer biomarkers as foundation of a database: Creating a common language (data elements) for cancer biomarkers tracking and utilization for professionalsin oncology research. Federal Register; HHS Reference No. E-147-2005/0—Research Tool. Government-Owned Inventions; Availability for Licensing. 70(140): 42350–42351
34.
go back to reference Khatami M (2007) Standardizing cancer biomarkers criteria: data elements as foundation of a database. M-CSF (model marker) for early detection of cancer. Cell Biochem Biophys 47:187–198PubMedCrossRef Khatami M (2007) Standardizing cancer biomarkers criteria: data elements as foundation of a database. M-CSF (model marker) for early detection of cancer. Cell Biochem Biophys 47:187–198PubMedCrossRef
35.
go back to reference Khatami M (2008) “Yin and Yang” in inflammation: duality in innate immune cell function and tumorigenesis. Exp Opin Biol Ther. 8:1461–1472CrossRef Khatami M (2008) “Yin and Yang” in inflammation: duality in innate immune cell function and tumorigenesis. Exp Opin Biol Ther. 8:1461–1472CrossRef
36.
go back to reference Khatami M (2009) Inflammation, aging, and cancer: tumoricidal versus tumorigenesis of immunity: a common denominator mapping chronic diseases. Cell Biochem Biophys 55:55–79PubMedCrossRef Khatami M (2009) Inflammation, aging, and cancer: tumoricidal versus tumorigenesis of immunity: a common denominator mapping chronic diseases. Cell Biochem Biophys 55:55–79PubMedCrossRef
37.
go back to reference Khatami M (2011) Unresolved inflammation: ‘immune tsunami’ or erosion of integrity in immuneprivilegedand immune-responsive tissues and acute and chronic inflammatory diseases or cancer. Expert Opin Biol Ther. 11:1419–1432PubMedCrossRef Khatami M (2011) Unresolved inflammation: ‘immune tsunami’ or erosion of integrity in immuneprivilegedand immune-responsive tissues and acute and chronic inflammatory diseases or cancer. Expert Opin Biol Ther. 11:1419–1432PubMedCrossRef
38.
go back to reference Khatami M (2014) Chronic inflammation: synergistic interactions of recruiting macrophages (TAMs) eosinophils (Eos) with host mast cells (MCs) and tumorigenesis in CALTs. MCSF, suitable biomarker for cancer diagnosis! Cancers. 6:297–322PubMedPubMedCentralCrossRef Khatami M (2014) Chronic inflammation: synergistic interactions of recruiting macrophages (TAMs) eosinophils (Eos) with host mast cells (MCs) and tumorigenesis in CALTs. MCSF, suitable biomarker for cancer diagnosis! Cancers. 6:297–322PubMedPubMedCentralCrossRef
40.
go back to reference Khatami M (2012) Inflammation, aging and cancer: friend or Foe? In: Khatami M (ed) Inflammation, chronic diseases and cancer-cell and molecular biology, immunology and clinical bases. Rijeka, InTech, pp 3–30CrossRef Khatami M (2012) Inflammation, aging and cancer: friend or Foe? In: Khatami M (ed) Inflammation, chronic diseases and cancer-cell and molecular biology, immunology and clinical bases. Rijeka, InTech, pp 3–30CrossRef
46.
go back to reference Jabaut J, Ckless K (2012) Inflammation, immunity and redox signaling. In: Khatami M (ed) Inflammation, chronic diseases and cancer. Cell and molecular biology, immunology and clinical bases. Rijeka, InTech, pp 145–160 Jabaut J, Ckless K (2012) Inflammation, immunity and redox signaling. In: Khatami M (ed) Inflammation, chronic diseases and cancer. Cell and molecular biology, immunology and clinical bases. Rijeka, InTech, pp 145–160
47.
go back to reference Huck V, Niemeyer A, Goerge T, Schnaeker EM, Ossig R, Rogge P et al (2007) Delay of acute intracellular pH recovery after acidosis decreases endothelial cell activation. J Cell Physiol 211:399–409PubMedCrossRef Huck V, Niemeyer A, Goerge T, Schnaeker EM, Ossig R, Rogge P et al (2007) Delay of acute intracellular pH recovery after acidosis decreases endothelial cell activation. J Cell Physiol 211:399–409PubMedCrossRef
48.
go back to reference Liao D, Johnson RS (2007) Hypoxia: a key regulator of angiogenesis in cancer. Cancer Metastasis Rev 26:281–290PubMedCrossRef Liao D, Johnson RS (2007) Hypoxia: a key regulator of angiogenesis in cancer. Cancer Metastasis Rev 26:281–290PubMedCrossRef
50.
51.
go back to reference Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE, Newman AB et al (2011) Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc. 12:249–256PubMedCrossRef Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE, Newman AB et al (2011) Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc. 12:249–256PubMedCrossRef
52.
go back to reference Leeuwenburgh C (2008) Molecular inflammation: underpinning of aging and age-related diseases. Ageing Res Rev. 8:18–30PubMedPubMedCentral Leeuwenburgh C (2008) Molecular inflammation: underpinning of aging and age-related diseases. Ageing Res Rev. 8:18–30PubMedPubMedCentral
53.
go back to reference Hipkiss AR (2006) Does chronic glycolysis accelerate aging? Could this explain how dietary restriction works? Ann N Y Acad Sci 1067:361–368PubMedCrossRef Hipkiss AR (2006) Does chronic glycolysis accelerate aging? Could this explain how dietary restriction works? Ann N Y Acad Sci 1067:361–368PubMedCrossRef
54.
go back to reference Wilde L, Roche M, Domingo-Vidal M, Tanson K, Philip N, Curry J, Martinez-Outschoorn U (2017) Metabolic coupling and the reverse effect in cancer: implication for novel biomarker and anticancer agent development. Semin Oncol 44:198–203PubMedCrossRefPubMedCentral Wilde L, Roche M, Domingo-Vidal M, Tanson K, Philip N, Curry J, Martinez-Outschoorn U (2017) Metabolic coupling and the reverse effect in cancer: implication for novel biomarker and anticancer agent development. Semin Oncol 44:198–203PubMedCrossRefPubMedCentral
57.
go back to reference Ribot J, Romagnoli P, van Meerwijk JP (2006) Agonist ligands expressed by thymic epithelium enhance positive selection of regulatory T lymphocytes from precursors with a normally diverse TCR repertoire. J Immunol 177(2):1101PubMedCrossRef Ribot J, Romagnoli P, van Meerwijk JP (2006) Agonist ligands expressed by thymic epithelium enhance positive selection of regulatory T lymphocytes from precursors with a normally diverse TCR repertoire. J Immunol 177(2):1101PubMedCrossRef
59.
go back to reference Sehl ME, Eugene Yates F (2001) Kinetics of human aging: I. Rates of senescence between ages 30 and 70 years in healthy people. J Gerontol A Biol Sci Med Sci 56:198–208CrossRef Sehl ME, Eugene Yates F (2001) Kinetics of human aging: I. Rates of senescence between ages 30 and 70 years in healthy people. J Gerontol A Biol Sci Med Sci 56:198–208CrossRef
60.
go back to reference Arking R (1998) The biology of aging: observation and principles, 2nd edn. Sinauer Associates Inc, Sunderland, pp 153–250 Arking R (1998) The biology of aging: observation and principles, 2nd edn. Sinauer Associates Inc, Sunderland, pp 153–250
61.
62.
go back to reference Paludan C, Schmid D, Landhalter M, Vockerodt M, Kube D, Tuschl T, Munz C (2005) Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science 307:593–596PubMedCrossRef Paludan C, Schmid D, Landhalter M, Vockerodt M, Kube D, Tuschl T, Munz C (2005) Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science 307:593–596PubMedCrossRef
63.
go back to reference Klinker MW, Lizzio V, Reed TJ, Fox DA, Lundy SK (2014) Human B cell-derived lymphoblastoid cell lines constitutively produce Fas ligand and secrete MHCII (+)FasL(+) killer exosomes. Front Immunol. 5:144PubMedPubMedCentralCrossRef Klinker MW, Lizzio V, Reed TJ, Fox DA, Lundy SK (2014) Human B cell-derived lymphoblastoid cell lines constitutively produce Fas ligand and secrete MHCII (+)FasL(+) killer exosomes. Front Immunol. 5:144PubMedPubMedCentralCrossRef
64.
go back to reference Keibel A, Singh V, Sharma MC (2009) Inflammation, microenvironment, and the immune system in cancer progression. Curr Pharm Des 15:1949–1955PubMedCrossRef Keibel A, Singh V, Sharma MC (2009) Inflammation, microenvironment, and the immune system in cancer progression. Curr Pharm Des 15:1949–1955PubMedCrossRef
65.
go back to reference Croce K, Libby P (2007) Intertwining of thrombosis and inflammation in atherosclerosis. Curr Opin Hematol 14:55–61PubMedCrossRef Croce K, Libby P (2007) Intertwining of thrombosis and inflammation in atherosclerosis. Curr Opin Hematol 14:55–61PubMedCrossRef
67.
go back to reference Rafi A, Castle SC, Uyemura K, Makinodan T (2003) Immune dysfunction in the elderly and its reversal by antihistamines. Biomed Pharmacol. 57:246–250CrossRef Rafi A, Castle SC, Uyemura K, Makinodan T (2003) Immune dysfunction in the elderly and its reversal by antihistamines. Biomed Pharmacol. 57:246–250CrossRef
72.
go back to reference Khatami M (2017) Theories of aging and chronic diseases: Chronic inflammation an interdependent ‘roadmap’ to age-associated illnesses. In: Inflammation aging cancer. Springer, Cham, pp 91–174CrossRef Khatami M (2017) Theories of aging and chronic diseases: Chronic inflammation an interdependent ‘roadmap’ to age-associated illnesses. In: Inflammation aging cancer. Springer, Cham, pp 91–174CrossRef
73.
74.
go back to reference Zimmermann E, Berentzen TL, Gamborg M, Sørensen TI, Baker JL (2016) Sex-specific associations between birth weight and adult primary liver cancer in a large cohort of Danish children. Int J Cancer 138:1410–1415PubMedCrossRef Zimmermann E, Berentzen TL, Gamborg M, Sørensen TI, Baker JL (2016) Sex-specific associations between birth weight and adult primary liver cancer in a large cohort of Danish children. Int J Cancer 138:1410–1415PubMedCrossRef
75.
go back to reference Mansur MB, van Delft FW, Colman SM, Furness CL, Gibson J, Emerenciano M et al (2015) Distinctive genotypes in infants with T-cell acute lymphoblastic leukaemia. Br J Haematol 171:574–584PubMedPubMedCentralCrossRef Mansur MB, van Delft FW, Colman SM, Furness CL, Gibson J, Emerenciano M et al (2015) Distinctive genotypes in infants with T-cell acute lymphoblastic leukaemia. Br J Haematol 171:574–584PubMedPubMedCentralCrossRef
79.
go back to reference Khatami M (2017) Cancer biology: severe cumulative hypersensitivity reactions. In: Inflammation, aging and cancer. Springer, Cham, pp 261–375CrossRef Khatami M (2017) Cancer biology: severe cumulative hypersensitivity reactions. In: Inflammation, aging and cancer. Springer, Cham, pp 261–375CrossRef
80.
go back to reference Greenhough A, Smartt HJ, Moore AE et al (2009) The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis 30:377–386PubMedCrossRef Greenhough A, Smartt HJ, Moore AE et al (2009) The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis 30:377–386PubMedCrossRef
81.
go back to reference Legan M (2010) Cyclooxygenase-2, p53 and glucose transporter-1 as predictors of malignancy in the development of gallbladder carcinomas. Bosn J Basic Med Sci. 10:192–196PubMedPubMedCentralCrossRef Legan M (2010) Cyclooxygenase-2, p53 and glucose transporter-1 as predictors of malignancy in the development of gallbladder carcinomas. Bosn J Basic Med Sci. 10:192–196PubMedPubMedCentralCrossRef
83.
go back to reference Bianchi G, Borgonovo G, Pistoia V, Raffaghello L (2011) Immunosuppressive cells and tumour microenvironment: focus on mesenchymal stem cells and myeloid derived suppressor cells. Histol Histopathol 26(7):941–951PubMed Bianchi G, Borgonovo G, Pistoia V, Raffaghello L (2011) Immunosuppressive cells and tumour microenvironment: focus on mesenchymal stem cells and myeloid derived suppressor cells. Histol Histopathol 26(7):941–951PubMed
84.
go back to reference Butler JM, Nolan DJ, Vertes EL, Varnum-Finney B, Kobayashi H, Hooper AT, Seandel M, Shido K, White IA, Kobayashi M et al (1999) Endothelial cells are essential for the self-renewal and repopulation of notch-dependent hematopoietic stem cells. Cell Stem Cell 6:251–264CrossRef Butler JM, Nolan DJ, Vertes EL, Varnum-Finney B, Kobayashi H, Hooper AT, Seandel M, Shido K, White IA, Kobayashi M et al (1999) Endothelial cells are essential for the self-renewal and repopulation of notch-dependent hematopoietic stem cells. Cell Stem Cell 6:251–264CrossRef
89.
go back to reference Khatami M (2017) Immune surveillance in health and diseases of aging: definitions of acute and chronic inflammation. In: Inflammation, aging and cancer. Springer, Cham, pp 37-89CrossRef Khatami M (2017) Immune surveillance in health and diseases of aging: definitions of acute and chronic inflammation. In: Inflammation, aging and cancer. Springer, Cham, pp 37-89CrossRef
90.
go back to reference Guha M, Srinivasan S, Raman P, Jiang Y, Kaufman BA, Taylor D, Dong D, Chakrabarti R, Picard M, Carstens RP, Kijima Y, Feldman M, Avadhani NG (2018) Aggressive triple negative breast cancers have unique molecular signature on the basis of mitochondrial genetic and functional defects. Biochim Biophys Acta. https://doi.org/10.1016/j.bbadis.2018.01.002 CrossRef Guha M, Srinivasan S, Raman P, Jiang Y, Kaufman BA, Taylor D, Dong D, Chakrabarti R, Picard M, Carstens RP, Kijima Y, Feldman M, Avadhani NG (2018) Aggressive triple negative breast cancers have unique molecular signature on the basis of mitochondrial genetic and functional defects. Biochim Biophys Acta. https://​doi.​org/​10.​1016/​j.​bbadis.​2018.​01.​002 CrossRef
93.
go back to reference Begley CG, Ellis LM (2012) Drug development: raise standards for preclinical cancer research. Nature 483:531–533PubMedCrossRef Begley CG, Ellis LM (2012) Drug development: raise standards for preclinical cancer research. Nature 483:531–533PubMedCrossRef
104.
go back to reference Jiang L, Zhang J, Monticone RE, Telljohann R, Wu J, Wang M, Lakatta EG (2012) Calpain-1 regulation of matrix metalloproteinase 2 activity in vascular smooth muscle cells facilitates age associated aortic wall calcification and fibrosis. Hypertension 60:1192–1199PubMedCrossRef Jiang L, Zhang J, Monticone RE, Telljohann R, Wu J, Wang M, Lakatta EG (2012) Calpain-1 regulation of matrix metalloproteinase 2 activity in vascular smooth muscle cells facilitates age associated aortic wall calcification and fibrosis. Hypertension 60:1192–1199PubMedCrossRef
106.
go back to reference Kaplan HJ, Niederkorn JY (2007) Regional immunity and immune privilege. Chem Immunol Allergy 92:11–26PubMedCrossRef Kaplan HJ, Niederkorn JY (2007) Regional immunity and immune privilege. Chem Immunol Allergy 92:11–26PubMedCrossRef
107.
go back to reference Emerit J, Edeas M, Bricaire F (2004) Neurodegenerative diseases and oxidative stress. Biomed Pharmacother 58:39–46PubMedCrossRef Emerit J, Edeas M, Bricaire F (2004) Neurodegenerative diseases and oxidative stress. Biomed Pharmacother 58:39–46PubMedCrossRef
108.
go back to reference Campisi J, Andersen JK, Kapahi P, Melov S (2011) Cellular senescence: a link between cancer and age-related degenerative disease? Sem Cancer Biol. 21:354–359 Campisi J, Andersen JK, Kapahi P, Melov S (2011) Cellular senescence: a link between cancer and age-related degenerative disease? Sem Cancer Biol. 21:354–359
109.
go back to reference Prattichizzo F, Bonafe M, Ceka A, Giuliani A, Rippo MR, Re M, Antonicelli R, Procopio AD, Olivieri F (2016) Endothelial cell senescence and inflammaging: microRNAs as biomarkers and innovative therapeutic tools. Curr Drug Targets 17:388–397PubMedCrossRef Prattichizzo F, Bonafe M, Ceka A, Giuliani A, Rippo MR, Re M, Antonicelli R, Procopio AD, Olivieri F (2016) Endothelial cell senescence and inflammaging: microRNAs as biomarkers and innovative therapeutic tools. Curr Drug Targets 17:388–397PubMedCrossRef
114.
go back to reference Bianchi ME (2007) DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 81:1–5PubMedCrossRef Bianchi ME (2007) DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 81:1–5PubMedCrossRef
115.
go back to reference Blackburn EH, Greider CW, Szostak JW (2006) Telomeres and telomerase: the path from maize, tetrahymena and yeast to human cancer and aging. Nat Med 12:1133–1138PubMedCrossRef Blackburn EH, Greider CW, Szostak JW (2006) Telomeres and telomerase: the path from maize, tetrahymena and yeast to human cancer and aging. Nat Med 12:1133–1138PubMedCrossRef
117.
go back to reference Minouchi K, Kaneko S, Kobayashi K (2002) Mutation of p53 gene in regenerative nodules in cirrhotic liver. J Hepatol 37:231–239PubMedCrossRef Minouchi K, Kaneko S, Kobayashi K (2002) Mutation of p53 gene in regenerative nodules in cirrhotic liver. J Hepatol 37:231–239PubMedCrossRef
118.
120.
go back to reference Ramakrishna G, Anwar T, Angara RK, Chatterjee N, Kiran S, Singh S (2012) Role of cellular senescence in hepatic wound healing and carcinogenesis. Eur J Cell Biol 91:739–747PubMedCrossRef Ramakrishna G, Anwar T, Angara RK, Chatterjee N, Kiran S, Singh S (2012) Role of cellular senescence in hepatic wound healing and carcinogenesis. Eur J Cell Biol 91:739–747PubMedCrossRef
124.
go back to reference Calado RT, Brudno J, Mehta P, Kovacs JJ, Wu C, Zago MA et al (2011) Constitutional telomerase mutations are genetic risk factors for cirrhosis. Hepatology 53:1600–1607PubMedCrossRef Calado RT, Brudno J, Mehta P, Kovacs JJ, Wu C, Zago MA et al (2011) Constitutional telomerase mutations are genetic risk factors for cirrhosis. Hepatology 53:1600–1607PubMedCrossRef
125.
go back to reference Fiorini E, Merck E, Wilson A, Ferrero I, Jiang W, Koch U, Auderset F, Laurenti E, Tacchini- Cottier F, Pierres M et al (2009) Dynamic regulation of notch 1 and notch 2 surface expression during T cell development and activation revealed by novel monoclonal antibodies. J Immunol. 183:7212–7222PubMedCrossRef Fiorini E, Merck E, Wilson A, Ferrero I, Jiang W, Koch U, Auderset F, Laurenti E, Tacchini- Cottier F, Pierres M et al (2009) Dynamic regulation of notch 1 and notch 2 surface expression during T cell development and activation revealed by novel monoclonal antibodies. J Immunol. 183:7212–7222PubMedCrossRef
126.
go back to reference Wang Z, Lin H, Hua F, Hu ZW (2013) Repairing DNA damage by XRCC6/KU70 reverses TLR4-deficiency-worsened HCC development via restoring senescence and autophagic flux. Autophagy. 9:925–927PubMedPubMedCentralCrossRef Wang Z, Lin H, Hua F, Hu ZW (2013) Repairing DNA damage by XRCC6/KU70 reverses TLR4-deficiency-worsened HCC development via restoring senescence and autophagic flux. Autophagy. 9:925–927PubMedPubMedCentralCrossRef
127.
go back to reference Nagini S, Sophia J, Mishra R (2018) Glycogen synthase kinases: moonlighting proteins with theranostic potential in cancer. Semin Cancer Biol. S1044 Nagini S, Sophia J, Mishra R (2018) Glycogen synthase kinases: moonlighting proteins with theranostic potential in cancer. Semin Cancer Biol. S1044
133.
go back to reference Kensler TW, Spira A, Garber JE, Szabo E, Lee J, Dong Z, Dannenberg AJ, Hait WN, Blackburn E, Davidson NE, Foti M, Lippman SM (2016) Transforming cancer prevention through precision medicine and immune-oncology. Cancer Prev Res 9(1):2–10CrossRef Kensler TW, Spira A, Garber JE, Szabo E, Lee J, Dong Z, Dannenberg AJ, Hait WN, Blackburn E, Davidson NE, Foti M, Lippman SM (2016) Transforming cancer prevention through precision medicine and immune-oncology. Cancer Prev Res 9(1):2–10CrossRef
135.
go back to reference Haslett C (1992) Resolution of acute inflammation and the role of apoptosis in the tissue fate of granulocytes. Clin Sci 83(6):639–648CrossRef Haslett C (1992) Resolution of acute inflammation and the role of apoptosis in the tissue fate of granulocytes. Clin Sci 83(6):639–648CrossRef
141.
go back to reference Boström M, Ninham BW (2005) Energy of an ion crossing a low dielectric membrane: the role of dispersion self-free energy. Biophys Chem 114:95–101PubMedCrossRef Boström M, Ninham BW (2005) Energy of an ion crossing a low dielectric membrane: the role of dispersion self-free energy. Biophys Chem 114:95–101PubMedCrossRef
145.
go back to reference Sutendra G, Dromparis P, Kinnaird A, Stenson TH, Haromy A et al (2013) Mitochondrial activation by inhibition of PDKII suppresses HIF1a signaling and angiogenesis in cancer. Oncogene 32:1638–1650PubMedCrossRef Sutendra G, Dromparis P, Kinnaird A, Stenson TH, Haromy A et al (2013) Mitochondrial activation by inhibition of PDKII suppresses HIF1a signaling and angiogenesis in cancer. Oncogene 32:1638–1650PubMedCrossRef
147.
go back to reference Ubah OC, Wallace HM (2014) Cancer therapy: targeting mitochondria and other sub-cellular organelles. Curr Pharm Des 20(2):201–222PubMedCrossRef Ubah OC, Wallace HM (2014) Cancer therapy: targeting mitochondria and other sub-cellular organelles. Curr Pharm Des 20(2):201–222PubMedCrossRef
148.
go back to reference Berge K, Tronstad KJ, Bohov P, Madsen L, Berge RK (2003) Impact of mitochondrial beta-oxidation in fatty acid-mediated inhibition of glioma cell proliferation. J Lipid Res 44:118–127PubMedCrossRef Berge K, Tronstad KJ, Bohov P, Madsen L, Berge RK (2003) Impact of mitochondrial beta-oxidation in fatty acid-mediated inhibition of glioma cell proliferation. J Lipid Res 44:118–127PubMedCrossRef
149.
go back to reference Cairns RA, Harris IS, Mak TW (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 11:85–95PubMedCrossRef Cairns RA, Harris IS, Mak TW (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 11:85–95PubMedCrossRef
151.
go back to reference Tyagi S, Gupta P, Saini AS, Kaushal C, Sharma S (2011) The peroxisome proliferator-activated receptor: a family of nuclear receptors role in various diseases. J Adv Pharm Technol Res. 2:236–240PubMedPubMedCentralCrossRef Tyagi S, Gupta P, Saini AS, Kaushal C, Sharma S (2011) The peroxisome proliferator-activated receptor: a family of nuclear receptors role in various diseases. J Adv Pharm Technol Res. 2:236–240PubMedPubMedCentralCrossRef
154.
155.
go back to reference Dulek DE, Peebles RS Jr (2011) Viruses and asthma. Biochim Biophys Acta 1810(1080e):90 Dulek DE, Peebles RS Jr (2011) Viruses and asthma. Biochim Biophys Acta 1810(1080e):90
156.
go back to reference Cundell DR, Mickle KE (2016) Developing the perfect antihistamine for use in allergic conditions: a voyage in H1 selectivity. eBook, Front Clin Drug Res Anti Allergy Agents Cundell DR, Mickle KE (2016) Developing the perfect antihistamine for use in allergic conditions: a voyage in H1 selectivity. eBook, Front Clin Drug Res Anti Allergy Agents
157.
go back to reference Massari NA, Medina VA, Martinel Lamas DJ, Cricco GP, Croci M, Sambuco L, Bergoc RM, Rivera ES (2011) Role of H4 receptor in histamine-mediated responses in human melanoma. Melanoma Res 21:395–404PubMedCrossRef Massari NA, Medina VA, Martinel Lamas DJ, Cricco GP, Croci M, Sambuco L, Bergoc RM, Rivera ES (2011) Role of H4 receptor in histamine-mediated responses in human melanoma. Melanoma Res 21:395–404PubMedCrossRef
158.
go back to reference Bakker RA, Schoonus SB, Smit MJ, Timmerman H, Leurs R (2011) Histamine H(1)-receptor activation of nuclear factor-kappa B: roles for G beta gamma- and G alpha(q/11)-subunits in constitutive and agonist-mediated signaling. Mol Pharmacol 60:1133–1142CrossRef Bakker RA, Schoonus SB, Smit MJ, Timmerman H, Leurs R (2011) Histamine H(1)-receptor activation of nuclear factor-kappa B: roles for G beta gamma- and G alpha(q/11)-subunits in constitutive and agonist-mediated signaling. Mol Pharmacol 60:1133–1142CrossRef
159.
go back to reference Palada V, Terzić J, Mazzulli J et al (2012) Histamine N-methyltransferase Thr105Ile polymorphism is associated with Parkinson’s disease. Neurobiol Aging 33(836):e1–e3 Palada V, Terzić J, Mazzulli J et al (2012) Histamine N-methyltransferase Thr105Ile polymorphism is associated with Parkinson’s disease. Neurobiol Aging 33(836):e1–e3
160.
go back to reference Petersen J, Raithel M, Schwelberger HG (2002) Histamine N-methyltransferase and diamine oxidase gene polymorphisms in patients with inflammatory and neoplastic intestinal diseases. Inflamm Res 51(suppl):S91–S92PubMed Petersen J, Raithel M, Schwelberger HG (2002) Histamine N-methyltransferase and diamine oxidase gene polymorphisms in patients with inflammatory and neoplastic intestinal diseases. Inflamm Res 51(suppl):S91–S92PubMed
162.
go back to reference García Martín E, Martínez C, Serrador M et al (2015) Diamine oxidase rs10156191 and rs2052129 variants are associated with the risk for migraine. Headache 55:276–286PubMedCrossRef García Martín E, Martínez C, Serrador M et al (2015) Diamine oxidase rs10156191 and rs2052129 variants are associated with the risk for migraine. Headache 55:276–286PubMedCrossRef
163.
164.
go back to reference Sharpless NS, Muenter MD, Tyce GM (1975) Effect of L-DOPA on endogenous histamine metabolism. Med Biol. 53:85–92PubMed Sharpless NS, Muenter MD, Tyce GM (1975) Effect of L-DOPA on endogenous histamine metabolism. Med Biol. 53:85–92PubMed
165.
go back to reference Sharpless NS, Thal LJ, Perlow MJ, Tabaddor K, Waltz JM, Shapiro KN, Amin IM, Engel J Jr, Crandall PH (1984) Vasoactive intestinal peptide in cerebrospinal fluid. Peptides 5(2):429–433PubMedCrossRef Sharpless NS, Thal LJ, Perlow MJ, Tabaddor K, Waltz JM, Shapiro KN, Amin IM, Engel J Jr, Crandall PH (1984) Vasoactive intestinal peptide in cerebrospinal fluid. Peptides 5(2):429–433PubMedCrossRef
166.
go back to reference Vizuete ML, Merino M, Venero JL et al (2000) Histamine infusion induces a selective dopaminergic neuronal death along with an inflammatory reaction in rat substantia nigra. J Neurochem 75:540–552PubMedCrossRef Vizuete ML, Merino M, Venero JL et al (2000) Histamine infusion induces a selective dopaminergic neuronal death along with an inflammatory reaction in rat substantia nigra. J Neurochem 75:540–552PubMedCrossRef
171.
go back to reference Tkaczyk C, Okayama Y, Woolhiser MR, Hagaman DD, Gilfillan AM, Metcalfe DD (2001) Activation of human mast cells through the high affinity IgG receptor. Mol Immunol 38:1289–1293CrossRef Tkaczyk C, Okayama Y, Woolhiser MR, Hagaman DD, Gilfillan AM, Metcalfe DD (2001) Activation of human mast cells through the high affinity IgG receptor. Mol Immunol 38:1289–1293CrossRef
172.
go back to reference Hansson GK, Libby P (2006) The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol 6:508–519PubMedCrossRef Hansson GK, Libby P (2006) The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol 6:508–519PubMedCrossRef
173.
go back to reference Shan L, Bossers K, Luchetti S et al (2012) Alterations in the histaminergic system in the substantia nigra and striatum of Parkinson’s patients: a postmortem study. Neurobiol Aging 33:1488.e1–1488.e13CrossRef Shan L, Bossers K, Luchetti S et al (2012) Alterations in the histaminergic system in the substantia nigra and striatum of Parkinson’s patients: a postmortem study. Neurobiol Aging 33:1488.e1–1488.e13CrossRef
176.
go back to reference Gøtzsche PC (2013) Deadly medicines and organised crime. How big pharma has corrupted health care. Radcliffe Publishing, London Gøtzsche PC (2013) Deadly medicines and organised crime. How big pharma has corrupted health care. Radcliffe Publishing, London
177.
go back to reference Faguet GB (2005) In the war on cancer: an anatomy of failure-a blueprint for the future. Springer, Cham, p 227 Faguet GB (2005) In the war on cancer: an anatomy of failure-a blueprint for the future. Springer, Cham, p 227
181.
183.
go back to reference Simmons JD, Lee YL, Mulekar S, Kuck JL, Brevard SB, Gonzalez RP et al (2013) Elevated levels of plasma mitochondrial DNA DAMPs are linked to clinical outcome in severely injured human subjects. Ann Surg 258:591–596PubMed Simmons JD, Lee YL, Mulekar S, Kuck JL, Brevard SB, Gonzalez RP et al (2013) Elevated levels of plasma mitochondrial DNA DAMPs are linked to clinical outcome in severely injured human subjects. Ann Surg 258:591–596PubMed
185.
go back to reference Kumar A, Dandekar JU, Bhat PJ (2017) Fermentative metabolism impedes p53-dependent apoptosis in a Crabtree-positive but not in Crabtree-negative yeast. J Biosci 42(4):585–601PubMedCrossRef Kumar A, Dandekar JU, Bhat PJ (2017) Fermentative metabolism impedes p53-dependent apoptosis in a Crabtree-positive but not in Crabtree-negative yeast. J Biosci 42(4):585–601PubMedCrossRef
191.
go back to reference Fukata M, Vamadevan AS, Abreu MT (2009) Toll-like receptors(TLRs) and nod-like receptors (NLRs) in inflammatory disorders. Semin Immunol 21:242–253PubMedCrossRef Fukata M, Vamadevan AS, Abreu MT (2009) Toll-like receptors(TLRs) and nod-like receptors (NLRs) in inflammatory disorders. Semin Immunol 21:242–253PubMedCrossRef
193.
go back to reference Seki M, Kohno S, Newstead MW et al (2010) Critical role of IL-1 receptor-associated kinase-M in regulating chemokine dependent deleterious inflammation in murine influenza pneumonia. J Immunol. 184:1410–1418PubMedCrossRef Seki M, Kohno S, Newstead MW et al (2010) Critical role of IL-1 receptor-associated kinase-M in regulating chemokine dependent deleterious inflammation in murine influenza pneumonia. J Immunol. 184:1410–1418PubMedCrossRef
194.
go back to reference del Fresno C, Otero K, Gomez-Garcia L et al (2005) Tumor cells deactivate human monocytes by up-regulating IL-1 receptor associated kinase-M expression via CD44 and TLR4. J Immunol. 174:3032–3040PubMedCrossRef del Fresno C, Otero K, Gomez-Garcia L et al (2005) Tumor cells deactivate human monocytes by up-regulating IL-1 receptor associated kinase-M expression via CD44 and TLR4. J Immunol. 174:3032–3040PubMedCrossRef
195.
go back to reference Kobayashi K, Hernandez LD, Galan JE et al (2002) IRAK-M is a negative regulator of Toll like receptor signaling. Cell 110:191–202PubMedCrossRef Kobayashi K, Hernandez LD, Galan JE et al (2002) IRAK-M is a negative regulator of Toll like receptor signaling. Cell 110:191–202PubMedCrossRef
196.
go back to reference Tazi KA, Quioc JJ, Saada V et al (2006) Upregulation of TNF-alpha production signaling pathways in monocytes from patients with advanced cirrhosis: possible role of Akt and IRAK-M. J Hepatol 45:280–289PubMedCrossRef Tazi KA, Quioc JJ, Saada V et al (2006) Upregulation of TNF-alpha production signaling pathways in monocytes from patients with advanced cirrhosis: possible role of Akt and IRAK-M. J Hepatol 45:280–289PubMedCrossRef
197.
go back to reference Weersma RK, Oostenbrug LE, Nolte IM et al (2007) Association of interleukin-1 receptor associated kinase M (IRAK-M) and inflammatory bowel diseases. Scand J Gastroenterol 42:827–833PubMedCrossRef Weersma RK, Oostenbrug LE, Nolte IM et al (2007) Association of interleukin-1 receptor associated kinase M (IRAK-M) and inflammatory bowel diseases. Scand J Gastroenterol 42:827–833PubMedCrossRef
198.
go back to reference Lagler H, Sharif O, Haslinger I et al (2009) TREM-1 activation alters the dynamics of pulmonary IRAK-M expression in vivo and improves host defense during pneumococcal pneumonia. J Immunol. 183:2027–2036PubMedCrossRef Lagler H, Sharif O, Haslinger I et al (2009) TREM-1 activation alters the dynamics of pulmonary IRAK-M expression in vivo and improves host defense during pneumococcal pneumonia. J Immunol. 183:2027–2036PubMedCrossRef
199.
go back to reference Wesche H, Gao X, Li X et al (1999) IRAK-M is a novel member of the Pelle/interleukin-1 receptorassociated kinase (IRAK) family. J Biol Chem 274:19403–19410PubMedCrossRef Wesche H, Gao X, Li X et al (1999) IRAK-M is a novel member of the Pelle/interleukin-1 receptorassociated kinase (IRAK) family. J Biol Chem 274:19403–19410PubMedCrossRef
201.
202.
go back to reference Dunlop K, Cedrone M, Staples JF, Regnault TR (2015) Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity. Forum Nutr. 7:1202–1216 Dunlop K, Cedrone M, Staples JF, Regnault TR (2015) Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity. Forum Nutr. 7:1202–1216
203.
go back to reference Marshall S (2006) Role of insulin, adipocyte hormones, and nutrient-sensing pathways in regulating fuel metabolism and energy homeostasis: a nutritional perspective of diabetes, obesity, and cancer. Sci STKE. 2006(346):re7PubMedCrossRef Marshall S (2006) Role of insulin, adipocyte hormones, and nutrient-sensing pathways in regulating fuel metabolism and energy homeostasis: a nutritional perspective of diabetes, obesity, and cancer. Sci STKE. 2006(346):re7PubMedCrossRef
205.
go back to reference Vigneri R, Goldfine ID, Frittitta L (2016) Insulin, insulin receptors, and cancer. J Endocrinol Investig. 39(12):1365–1376CrossRef Vigneri R, Goldfine ID, Frittitta L (2016) Insulin, insulin receptors, and cancer. J Endocrinol Investig. 39(12):1365–1376CrossRef
209.
go back to reference Gonzalez-Leon MC, Soares-Schanoski A, del Fresno C et al (2006) Nitric oxide induces SOCS-1 expression in human monocytes in a TNF-alpha-dependent manner. J Endotoxin Res 12:296–306PubMedCrossRef Gonzalez-Leon MC, Soares-Schanoski A, del Fresno C et al (2006) Nitric oxide induces SOCS-1 expression in human monocytes in a TNF-alpha-dependent manner. J Endotoxin Res 12:296–306PubMedCrossRef
211.
go back to reference Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M (2005) Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 120:649–661PubMedCrossRef Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M (2005) Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 120:649–661PubMedCrossRef
212.
go back to reference Marcucci G, Baldus CD, Ruppert AS et al (2005) Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a cancer and leukemia group B study. J Clin Oncol 23:9234–9242PubMedCrossRef Marcucci G, Baldus CD, Ruppert AS et al (2005) Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a cancer and leukemia group B study. J Clin Oncol 23:9234–9242PubMedCrossRef
213.
go back to reference Nigou J, Zelle-Rieser C, Gilleron M et al (2001) Mannosylated lipoarabinomannans inhibit IL-12 production by human dendritic cells: evidence for a negative signal delivered through the mannose receptor. J Immunol. 166:7477–7485PubMedCrossRef Nigou J, Zelle-Rieser C, Gilleron M et al (2001) Mannosylated lipoarabinomannans inhibit IL-12 production by human dendritic cells: evidence for a negative signal delivered through the mannose receptor. J Immunol. 166:7477–7485PubMedCrossRef
214.
go back to reference Mages J, Dietrich H, Lang R (2007) A genomewide analysis of LPS tolerance in macrophages. Immunobiology 212:723–737PubMedCrossRef Mages J, Dietrich H, Lang R (2007) A genomewide analysis of LPS tolerance in macrophages. Immunobiology 212:723–737PubMedCrossRef
215.
go back to reference Grigor EJM, Fergusson DA, Haggar F, Kekre N, Atkins H, Shorr R, Holt RA, Hutton B, Ramsay T, Seftel M, Jonker D, Daugaard M, Thavorn K, Presseau J, Lalu MM (2017) Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in patients with haematological and solid malignancies: protocol for a systematic review and meta-analysis. BMJ Open 7(12):e019321. https://doi.org/10.1136/bmjopen-2017-019321 PubMedPubMedCentralCrossRef Grigor EJM, Fergusson DA, Haggar F, Kekre N, Atkins H, Shorr R, Holt RA, Hutton B, Ramsay T, Seftel M, Jonker D, Daugaard M, Thavorn K, Presseau J, Lalu MM (2017) Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in patients with haematological and solid malignancies: protocol for a systematic review and meta-analysis. BMJ Open 7(12):e019321. https://​doi.​org/​10.​1136/​bmjopen-2017-019321 PubMedPubMedCentralCrossRef
216.
go back to reference Ben-David Y, Giddens EB, Letwin K et al (1991) Erythroleukemia induction by friend murine leukemia virus: insertional activation of a new member of the ets gene family, Fli-1, closely linked to c-ets-1. Genes Dev 5:908–918PubMedCrossRef Ben-David Y, Giddens EB, Letwin K et al (1991) Erythroleukemia induction by friend murine leukemia virus: insertional activation of a new member of the ets gene family, Fli-1, closely linked to c-ets-1. Genes Dev 5:908–918PubMedCrossRef
218.
go back to reference Barrett AJ, Savani BN (2009) Does chemotherapy modify the immune surveillance of hematological malignancies? Leukemia 23(1):53–58PubMedCrossRef Barrett AJ, Savani BN (2009) Does chemotherapy modify the immune surveillance of hematological malignancies? Leukemia 23(1):53–58PubMedCrossRef
219.
go back to reference King DA, Matheson E, Chirina S, Shankar A, Broman-Fulks J (2013) The status of baby boomers’ health in the United States: the healthier generation? JAMA Intern Med. 173(5):385–386PubMedCrossRef King DA, Matheson E, Chirina S, Shankar A, Broman-Fulks J (2013) The status of baby boomers’ health in the United States: the healthier generation? JAMA Intern Med. 173(5):385–386PubMedCrossRef
221.
go back to reference Khatami M, Roel LE, Li W, Rockey JH (1986) Ascorbate regeneration in bovine ocular tissues by NADH-dependent semidehydroascorbate reductase. Exp Eye Res 43:167–175PubMedCrossRef Khatami M, Roel LE, Li W, Rockey JH (1986) Ascorbate regeneration in bovine ocular tissues by NADH-dependent semidehydroascorbate reductase. Exp Eye Res 43:167–175PubMedCrossRef
222.
go back to reference Ricketts TC (2011) The health care workforce: will it be ready as the boomers age? A review of how we can know (or not know) the answer. Annu Rev Public Health 32:417–430PubMedCrossRef Ricketts TC (2011) The health care workforce: will it be ready as the boomers age? A review of how we can know (or not know) the answer. Annu Rev Public Health 32:417–430PubMedCrossRef
225.
go back to reference Wang H (2018) A protocol for investigating the association of vaccination and anti-NMDA receptor encephalitis. Front Biosci 1(10):229–237CrossRef Wang H (2018) A protocol for investigating the association of vaccination and anti-NMDA receptor encephalitis. Front Biosci 1(10):229–237CrossRef
226.
go back to reference Kammula US, Marincola FM (1999) Cancer immunotherapy: is there real progress at last? BioDrugs. 11(4):249–260PubMedCrossRef Kammula US, Marincola FM (1999) Cancer immunotherapy: is there real progress at last? BioDrugs. 11(4):249–260PubMedCrossRef
227.
go back to reference Amiri-Kordestani L, Fojo T (2012) Why do phase III clinical trials in oncology fail so often? J Natl Cancer Inst 104:568–569PubMedCrossRef Amiri-Kordestani L, Fojo T (2012) Why do phase III clinical trials in oncology fail so often? J Natl Cancer Inst 104:568–569PubMedCrossRef
228.
go back to reference Amiri-Kordestani L, Basseville A, Kurziel K, Fojo AT, Bates SE (2012) Targeting MDR in breast and lung cancer: discriminating its potential importance from the failure of drug resistance reversal studies. Drug Resist Update 15:50–61CrossRef Amiri-Kordestani L, Basseville A, Kurziel K, Fojo AT, Bates SE (2012) Targeting MDR in breast and lung cancer: discriminating its potential importance from the failure of drug resistance reversal studies. Drug Resist Update 15:50–61CrossRef
229.
go back to reference Stanely M (2010) Prophylactic human papillomavirus vaccines: will they do their job? J Intern Med 267:251–258CrossRef Stanely M (2010) Prophylactic human papillomavirus vaccines: will they do their job? J Intern Med 267:251–258CrossRef
231.
go back to reference Mayer RJ (2009) Targeted therapy for advanced colorectal cancer—more is not always better. N Engl J Med 360:623–625PubMedCrossRef Mayer RJ (2009) Targeted therapy for advanced colorectal cancer—more is not always better. N Engl J Med 360:623–625PubMedCrossRef
232.
233.
go back to reference Rodgers GM III, Becker PS, Blinder M, Cella D, Chanan-Khan A, Cleeland C, Coccia PF, Djulbegovic B, Gilreath JA, Kraut EH, Matulonis UA, Millenson MM et al (2012) Cancer- and chemotherapy-induced anemia. J Natl Compr Cancer Netw. 10:628–653CrossRef Rodgers GM III, Becker PS, Blinder M, Cella D, Chanan-Khan A, Cleeland C, Coccia PF, Djulbegovic B, Gilreath JA, Kraut EH, Matulonis UA, Millenson MM et al (2012) Cancer- and chemotherapy-induced anemia. J Natl Compr Cancer Netw. 10:628–653CrossRef
234.
go back to reference Sinha G (2008) Expensive cancer drugs with modest benefit ignite debate over solutions. J Natl Cancer Inst 100:1347–1349PubMedCrossRef Sinha G (2008) Expensive cancer drugs with modest benefit ignite debate over solutions. J Natl Cancer Inst 100:1347–1349PubMedCrossRef
239.
go back to reference Hubbard LL, Ballinger MN, Thomas PE et al (2010) A role for IL-1 receptor-associated kinase-M in prostaglandin E(2)-induced immunosuppression post-bone marrow transplantation. J Immunol. 184:6299–6308PubMedCrossRef Hubbard LL, Ballinger MN, Thomas PE et al (2010) A role for IL-1 receptor-associated kinase-M in prostaglandin E(2)-induced immunosuppression post-bone marrow transplantation. J Immunol. 184:6299–6308PubMedCrossRef
243.
go back to reference Sapey E, Greenwood H, Walton G, Mann E, Love A, Aaronson N, Insall RH, Stockley RA, Lord JM (2014) Phosphoinositide 3-kinase inhibition restores neutrophil accuracy in the elderly: toward targeted treatments for immunosenescence. Blood 123:239–248PubMedPubMedCentralCrossRef Sapey E, Greenwood H, Walton G, Mann E, Love A, Aaronson N, Insall RH, Stockley RA, Lord JM (2014) Phosphoinositide 3-kinase inhibition restores neutrophil accuracy in the elderly: toward targeted treatments for immunosenescence. Blood 123:239–248PubMedPubMedCentralCrossRef
244.
go back to reference Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A et al (2014) PI3 Kdelta inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med 370:1008–1018PubMedPubMedCentralCrossRef Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A et al (2014) PI3 Kdelta inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med 370:1008–1018PubMedPubMedCentralCrossRef
246.
go back to reference Einstein MH, Baron M, Levin MJ, Chatterjee A, Edwards RP, Zepp F (2009) HPV-010 study group et al.: comparison of the immunogenicity and safety of cervarix and gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18–45 years. Hum Vaccines 5:705–719CrossRef Einstein MH, Baron M, Levin MJ, Chatterjee A, Edwards RP, Zepp F (2009) HPV-010 study group et al.: comparison of the immunogenicity and safety of cervarix and gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18–45 years. Hum Vaccines 5:705–719CrossRef
248.
go back to reference Maya-Monteiro CM, Bozza PT (2008) Leptin and mTOR: partners in metabolism and inflammation. Cell Cycle 7(12):1713–1717PubMedCrossRef Maya-Monteiro CM, Bozza PT (2008) Leptin and mTOR: partners in metabolism and inflammation. Cell Cycle 7(12):1713–1717PubMedCrossRef
249.
go back to reference Peng Y, Li L, Huang M, Duan C, Zhang L, Chen J (2014) Angiogenin interacts with ribonuclease inhibitor regulating PI3K/AKT/mTOR signaling pathway in bladder cancer cells. Cell Signal 26(12):2782–2792PubMedCrossRef Peng Y, Li L, Huang M, Duan C, Zhang L, Chen J (2014) Angiogenin interacts with ribonuclease inhibitor regulating PI3K/AKT/mTOR signaling pathway in bladder cancer cells. Cell Signal 26(12):2782–2792PubMedCrossRef
251.
go back to reference de la Haba G, Khatami M, Cooper GW, Backlund P, Flaks JG (1999) Alanine or pyruvate is required for the development of myotubes from myoblasts and cortisol satisfies this requirement. Mol Cell Biochem 198(1–2):163–170PubMedCrossRef de la Haba G, Khatami M, Cooper GW, Backlund P, Flaks JG (1999) Alanine or pyruvate is required for the development of myotubes from myoblasts and cortisol satisfies this requirement. Mol Cell Biochem 198(1–2):163–170PubMedCrossRef
252.
go back to reference Li W, Shen S, Khatami M, Rockey JH (1984) Stimulation of retinal capillary pericyte protein and collagen synthesis in culture by high glucose concentration. Diabetes 33:785–789PubMedCrossRef Li W, Shen S, Khatami M, Rockey JH (1984) Stimulation of retinal capillary pericyte protein and collagen synthesis in culture by high glucose concentration. Diabetes 33:785–789PubMedCrossRef
254.
go back to reference Khatami M, Li W, Rockey JH (1986) Kinetics of ascorbate transport by cultured retinal capillary pericytes. Invest Ophthalmol Vis Sci 27:1665–1671PubMed Khatami M, Li W, Rockey JH (1986) Kinetics of ascorbate transport by cultured retinal capillary pericytes. Invest Ophthalmol Vis Sci 27:1665–1671PubMed
255.
go back to reference Khatami M, Stramm E, Rockey JH (1986) Ascorbate transport in cultured cat retinal pigment epithelial cells. Exp Eye Res 43:607–615PubMedCrossRef Khatami M, Stramm E, Rockey JH (1986) Ascorbate transport in cultured cat retinal pigment epithelial cells. Exp Eye Res 43:607–615PubMedCrossRef
256.
go back to reference Khatami M (1988) Na+-linked active transport of ascorbate into cultured bovine retinal pigment epithelial cells: heterologous inhibition by glucose. Membr Biochem. 7:115–130CrossRef Khatami M (1988) Na+-linked active transport of ascorbate into cultured bovine retinal pigment epithelial cells: heterologous inhibition by glucose. Membr Biochem. 7:115–130CrossRef
257.
go back to reference Khatami M, Suldan Z, David I, Li W, Rockey JH (1988) Inhibitory effects of pyridoxal phosphate, ascorbate and aminoguanidine on nonenzymatic glycosylation. Life Sci 43:1725–1731PubMedCrossRef Khatami M, Suldan Z, David I, Li W, Rockey JH (1988) Inhibitory effects of pyridoxal phosphate, ascorbate and aminoguanidine on nonenzymatic glycosylation. Life Sci 43:1725–1731PubMedCrossRef
258.
go back to reference Li W, Shen S, Robertson G, Khatami M, Rockey JH (1984) Increased solubility of newly synthesized collagen in retinal capillary pericyte cultures by nonenzymatic glycosylation. Ophthal Res. 16:315–321CrossRef Li W, Shen S, Robertson G, Khatami M, Rockey JH (1984) Increased solubility of newly synthesized collagen in retinal capillary pericyte cultures by nonenzymatic glycosylation. Ophthal Res. 16:315–321CrossRef
259.
go back to reference Khatami M, Rockey JH (1988) Regulation of inositol uptake by glucose in cultured retinal pigment epithelial cells. Biochem Cell Biol 66:951–957PubMedCrossRef Khatami M, Rockey JH (1988) Regulation of inositol uptake by glucose in cultured retinal pigment epithelial cells. Biochem Cell Biol 66:951–957PubMedCrossRef
260.
go back to reference Khatami M (1990) Regulation of MI transport in retinal pigment epithelium by sugars, amiloride and pH gradients: potential impairment of pump-leak balance in diabetic maculopathy. Membr Biochem. 9:279–292PubMedCrossRef Khatami M (1990) Regulation of MI transport in retinal pigment epithelium by sugars, amiloride and pH gradients: potential impairment of pump-leak balance in diabetic maculopathy. Membr Biochem. 9:279–292PubMedCrossRef
265.
go back to reference Tissot van Patot MC, Murray AJ, Beckey V, Cindrova-Davies T, Johns J et al (2010) Human placental metabolic adaptation to chronic hypoxia, high altitude: hypoxic preconditioning. Am J Physiol Regul Integr Comp Physiol 298(1):R16672CrossRef Tissot van Patot MC, Murray AJ, Beckey V, Cindrova-Davies T, Johns J et al (2010) Human placental metabolic adaptation to chronic hypoxia, high altitude: hypoxic preconditioning. Am J Physiol Regul Integr Comp Physiol 298(1):R16672CrossRef
266.
go back to reference Nakada T (2010) Conversion of brain cytosol profile from fetal to adult type during the perinatal period: taurine-NAA exchange. Proc Jpn Acad Ser B Phys Biol Sci. 86:630–642PubMedPubMedCentralCrossRef Nakada T (2010) Conversion of brain cytosol profile from fetal to adult type during the perinatal period: taurine-NAA exchange. Proc Jpn Acad Ser B Phys Biol Sci. 86:630–642PubMedPubMedCentralCrossRef
267.
go back to reference Sevigny CP, Li L, Awad AS, Huang L, McDuffie M, Linden J et al (2007) Activation of adenosine 2A receptors attenuates allograft rejection and alloantigen recognition. J Immunol. 178(7):4240–4249PubMedCrossRef Sevigny CP, Li L, Awad AS, Huang L, McDuffie M, Linden J et al (2007) Activation of adenosine 2A receptors attenuates allograft rejection and alloantigen recognition. J Immunol. 178(7):4240–4249PubMedCrossRef
Metadata
Title
Cancer; an induced disease of twentieth century! Induction of tolerance, increased entropy and ‘Dark Energy’: loss of biorhythms (Anabolism v. Catabolism)
Author
Mahin Khatami
Publication date
01-12-2018
Publisher
Springer Berlin Heidelberg
Published in
Clinical and Translational Medicine / Issue 1/2018
Electronic ISSN: 2001-1326
DOI
https://doi.org/10.1186/s40169-018-0193-6

Other articles of this Issue 1/2018

Clinical and Translational Medicine 1/2018 Go to the issue