Immunological similarities between cancer and chronic fatigue syndrome: The common link to fatigue?

Anticancer Research

Volumn 29, Issue 11, 2009, Pages 4717-4726

  Meeus, Mira ^a,b   Mistiaen, Wilhelm ^a   Lambrecht, L U C ^c,d,e   Nijs, J O ^a,b  

^a Hogeschool Antwerpen   (Belgium)

^b VRIJE UNIVERSITEIT BRUSSEL   (Belgium)

^c Private Practice for Internal Medicine   (Belgium)

^d Private Practice for Internal Medicine   (Belgium)

^e NONE   (Belgium)

Author keywords

Exercise; Fatigue; Intracellular immune dysfunction; Natural killer cell; NF B; Nitric oxide; Nuclear factor kappa beta; Oxidative stress; Protein kinase R; Review; RNase L

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN;

CANCER PATIENT; CELL FUNCTION; CELLULAR IMMUNITY; CHRONIC FATIGUE SYNDROME; HUMAN; IMMUNOPATHOLOGY; NATURAL KILLER CELL; PRIORITY JOURNAL; REVIEW; TUMOR IMMUNITY;

FATIGUE; FATIGUE SYNDROME, CHRONIC; HUMANS; NEOPLASMS;

EID: 75149183179     PISSN: 02507005     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (102)

1. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG and Komaroff A: The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 121: 953-959, 1994.
2. Irvine DM, Vincent L, Bubela N, Thompson L and Graydon J: A critical appraisal of the research literature investigating fatigue in the individual with cancer. Cancer Nurs 14: 188-199, 1991.
3. Smets EM, Garssen B, Schuster-Uitterhoeve AL and de Haes JC: Fatigue in cancer patients. Br J Cancer 68: 220-224, 1993.
4. Prue G, Rankin J, Allen J, Gracey J and Cramp F: Cancer-related fatigue: A critical appraisal. Eur J Cancer 42: 846-863, 2006.
5. Stone PC and Minton O: Cancer-related fatigue. Eur J Cancer 44: 1097-1104, 2008.
6. Vogelzang NJ, Breitbart W, Cella D, Curt GA, Groopman JE, Horning SJ, Itri LM, Johnson DH, Scherr SL and Portenoy RK: Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results of a tripart assessment survey. The Fatigue Coalition. Semin Hematol 34: 4-12, 1997.
7. Cella D, Peterman A, Passik S, Jacobsen P and Breitbart W: Progress toward guidelines for the management of fatigue. Oncology (Williston Park) 12: 369-377, 1998.
8. Borneman T, Piper BF, Sun VC, Koczywas M, Uman G and Ferrell B: Implementing the Fatigue Guidelines at one NCCN member institution: process and outcomes. J Natl Compr Canc Netw 5: 1092-1101, 2007.
9. Holley S: Cancer-related fatigue. Suffering a different fatigue. Cancer Pract 8: 87-95, 2000.
10. Hann DM, Jacobsen PB, Martin SC, Kronish LE, Azzarello LM and Fields KK: Fatigue in women treated with bone marrow transplantation for breast cancer: a comparison with women with no history of cancer. Support Care Cancer 5: 44-52, 1997.
11. Nieboer P, Buijs C, Rodenhuis S, Seynaeve C, Beex LV, van der Wall E, Richel DJ, Nooij MA, Voest EE, Hupperets P, Mulder NH, van der Graaf WT, TenVergert EM, van Tinteren H and de Vries EG: Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or highdose chemotherapy: a longitudinal study. J Clin Oncol 23: 8296-8304, 2005.
12. Servaes P, Verhagen S and Bleijenberg G: Determinants of chronic fatigue in disease-free breast cancer patients: a cross-sectional study. Ann Oncol 13: 589-598, 2002.
13. Servaes P, van der Werf S, Prins J, Verhagen S and Bleijenberg G: Fatigue in disease-free cancer patients compared with fatigue in patients with chronic fatigue syndrome. Support Care Cancer 9: 11-17, 2001.
14. Servaes P, Gielissen MF, Verhagen S and Bleijenberg G: The course of severe fatigue in disease-free breast cancer patients: a longitudinal study. Psychooncology 16: 787-795, 2007.
15. Servaes P, Verhagen C and Bleijenberg G: Fatigue in cancer patients during and after treatment: prevalence, correlates and interventions. Eur J Cancer 38: 27-43, 2002.
16. Collado-Hidalgo A, Bower JE, Ganz PA, Cole SW and Jrwin MR: Inflammatory biomarkers for persistent fatigue in breast cancer survivors. Clin Cancer Res 12: 2759-2766, 2006.
17. Stone P, Richards M, A'Hern R and Hardy J: Fatigue in patients with cancers of the breast or prostate undergoing radical radiotherapy. J Pain Symptom Manage 22: 1007-1015, 2001.
18. Ahlberg K, Ekman T and Gaston-Johansson F: The experience of fatigue, other symptoms and global quality of life during radiotherapy for uterine cancer. Int J Nurs Stud 42: 377-386, 2005.
19. von Meyenfeldt M: Cancer-associated malnutrition: an introduction. Eur J Oncol Nurs 9(Suppl 2): S35-38, 2005.
20. Ahlberg K, Ekman T, Wallgren A and Gaston-Johansson F: Fatigue, psychological distress, coping and quality of life in patients with uterine cancer. J Adv Nurs 45: 205-213, 2004.
21. Servaes P, Verhagen S, Schreuder HW, Veth RP and Bleijenberg G: Fatigue after treatment for malignant and benign bone and soft tissue tumors. J Pain Symptom Manage 26: 1113-1122, 2003.
22. Romito F, Montanaro R, Corvasce C, Di Bisceglie M and Mattioli V: Is cancer-related fatigue more strongly correlated to haematological or to psychological factors in cancer patients? Support Care Cancer 16: 943-946, 2008.
23. Donovan KA, Small BJ, Andrykowski MA, Munster P and Jacobsen PB: Utility of a cognitive-behavioral model to predict fatigue following breast cancer treatment. Health Psychol 26: 464-472, 2007.
24. van der Werf SP, Prins JB, Vercoulen JH, van der Meer JW and Bleijenberg G: Identifying physical activity patterns in chronic fatigue syndrome using actigraphic assessment. J Psychosom Res 49: 373-379, 2000.
25. Vercoulen JH, Bazelmans E, Swanink CM, Fennis JF, Galama JM, Jongen PJ, Hommes O, Van der Meer JW and Bleijenberg G: Physical activity in chronic fatigue syndrome: assessment and its role in fatigue. J Psychiatr Res 31: 661-673, 1997.
26. Jason LA, Torres-Harding SR, Carrico AW and Taylor RR: Symptom occurrence in persons with chronic fatigue syndrome. Biol Psychol 59: 15-27, 2002.
27. Nishikai M, Tomomatsu S, Hankins RW, Takagi S, Miyachi K, Kosaka S and Akiya K: Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary FM: a possible marker for hypersomnia and cognitive disorders. Rheumatology 40: 806-810, 2001.
28. Bisbal C and Silverman RH: Diverse functions of RNase L and implications in pathology. Biochimie 89: 789-798, 2007.
29. Malathi K, Dong B, Gale M Jr and Silverman RH: Small self-RNA generated by RNase L amplifies antiviral innate immunity. Nature 448: 816-819, 2007.
30. Suhadolnik RJ, Peterson DL, O'Brien K, Cheney PR, Herst CV, Reichenbach NL, Kon N, Horvath SE, Iacono KT, Adelson ME, De Meirleir K, De Becker P, Charubala R and Pfleiderer W: Biochemical evidence for a novel low molecular weight 2-5A-dependent RNase L in chronic fatigue syndrome. J Interferon Cytokine Res 17: 377-385, 1997.
31. Suhadolnik RJ, Reichenbach NL, Hitzges P, Sobol RW, Peterson DL, Henry B, Ablashi DV, Muller WE, Schroder HC, Carter WA et al: Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome. Clin Infect Dis 18(Suppl 1): S96-104, 1994.
32. Suhadolnik RJ, Peterson DL, Cheney PR, Horvath SE, Reichenbach NL, O'Brien K, Lombardi V, Welsch S, Furr EG, Charabala R and Pfleiderer W: Biochemical dysregulation of the 2-5A synthetase/RNase L antiviral defense pathway in chronic fatigue syndrome. J Chronic Fatigue Syndr 5: 223-242, 1999.
33. Shetzline SE, Martinand-Mari C, Reichenbach NL, Buletic Z, Lebleu B, Pfleiderer W, Charabala R, De Meirleir K, De Becker P, Peterson DL, Herst CV, Englebienne P and Suhadolnik RJ: Structural and functional features of the 37-kDa 2-5A-dependent RNase L in chronic fatigue syndrome. J Interferon Cytokine Res 22: 443-456, 2002.
34. Nijs J and De Meirleir K: Impairments of the 2-5A synthetase/RNase L pathway in chronic fatigue syndrome. In Vivo 19: 1013-1021, 2005.
35. Demettre E, Bastide L, D'Haese A, De Smet K, De Meirleir K, Tiev KP, Englebienne P and Lebleu B: Ribonuclease L proteolysis in peripheral blood mononuclear cells of chronic fatigue syndrome patients. J Biol Chem 277: 35746-35751, 2002.
36. Shetzline SE and Suhadolnik RJ: Characterization of a 2′,5′-oligoadenylate (2-5A)-dependent 37-kDa RNase L: azido photoaffinity labeling and 2-5A-dependent activation. J Biol Chem 276: 23707-23711, 2001.
37. Englebienne P: RNase L in health and disease - What did we learn recently? J Chron Fatig Syndr 11: 97-107, 2003.
38. Englebienne P, Herst CV, De Smet K, D'Haese A and De Meirleir K: Interactions between RNase L ankyrin-like domain and ABC transporters as a possible origin for pain, ion transport, CNS and immune disorders of chronic fatigue immune dysfunction syndrome. J Chron Fatig Syndr 8: 83-102, 2001.
39. De Meirleir K, Bisbal C, Campine I, De Becker P, Salehzada T, Demettre E and Lebleu B: A 37 kDa 2-5A binding protein as a potential biochemical marker for chronic fatigue syndrome. Am J Med 108: 99-105, 2000.
40. Silverman RH: Implications for RNase L in prostate cancer biology. Biochemistry 42: 1805-1812, 2003.
41. Liu W, Liang SL, Liu H, Silverman R and Zhou A: Tumour suppressor function of RNase L in a mouse model. Eur J Cancer 43: 202-209, 2007.
42. Zhou A, Paranjape JM, Hassel BA, Nie H, Shah S, Galinski B and Silverman RH: Impact of RNase L overexpression on viral and cellular growth and death. J Interferon Cytokine Res 18: 953-961, 1998.
43. Xiang Y, Wang Z, Murakami J, Plummer S, Klein EA, Carpten JD, Trent JM, Isaacs WB, Casey G and Silverman RH: Effects of RNASEL mutations associated with prostate cancer on apoptosis induced by 2′,5′- oligoadenylates. Cancer Res 63: 6795-6801, 2003.
44. Wang L, McDonnell SK, Elkins DA, Slager SL, Christensen E, Marks AF, Cunningham JM, Peterson BJ, Jacobsen SJ, Cerhan JR, Blute ML, Schaid DJ and Thibodeau SN: Analysis of the RNASEL gene in familial and sporadic prostate cancer. Am J Hum Genet 71: 116-123, 2002.
45. Casey G, Neville PJ, Plummer SJ, Xiang Y, Kramroy LM, Klein EA, Catalona WJ, Nupponen N, Carpten JD, Trent JM, Silverman RH and Witte JS: RNASEL Arg462Gln variant is implicated in up to 13% of prostate cancer cases. Nat Genet 32: 581-583, 2002.
46. Bartsch DK, Fendrich V, Slater EP, Sina-Frey M, Rieder H, Greenhalf W, Chaloupka B, Hahn SA, Neoptolemos JP and Kress R: RNASEL germline variants are associated with pancreatic cancer. Int J Cancer 117: 718-722, 2005.
47. Wang L, Zhou A, Vasavada S, Dong B, Nie H, Church JM, Williams BR, Banerjee S and Silverman RH: Elevated levels of 2′,5′-linked oligoadenylate-dependent ribonuclease L occur as an early event in colorectal tumorigenesis. Clin Cancer Res 1: 1421-1428, 1995.
48. Uetani K, Der SD, Zamanian-Daryoush M, de La Motte C, Lieberman BY, Williams BR and Erzuram SC: Central role of double-stranded RNA-activated protein kinase in microbial induction of nitric oxide synthase. J Immunol 165: 988-996, 2000.
49. Paludan SR, Ellermann-Eriksen S and Mogensen SC: NF-kappaB activation is responsible for the synergistic effect of herpes simplex virus type 2 infection on interferon-gamma-induced nitric oxide production in macrophages. J Gen Virol 79(Pt 11): 2785-2793, 1998.
50. Maes M, Mihaylova I and Bosmans E: Not in the mind of neurasthenic lazybones but in the cell nucleus: patients with chronic fatigue syndrome have increased production of nuclear factor kappa beta. Neuro Endocrinol Lett 28: 456-462, 2007.
51. Maes M, Mihaylova I, Kubera M and Bosmans E: Not in the mind but in the cell: increased production of cyclo-oxygenase-2 and inducible NO synthase in chronic fatigue syndrome. Neuro Endocrinol Lett 28: 463-469, 2007.
52. Kurup RK and Kurap PA: Hypothalamic digoxin, cerebral chemical dominance and myalgic encephalomyelitis. Int J Neurosci 113: 683-701, 2003.
53. Cifone MG, Ulisse S and Santoni A: Natural killer cells and nitric oxide. Int Immunopharmacol 1: 1513-1524, 2001.
54. Nijs J and Fremont M: Intracellular immune dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome: state of the art and therapeutic implications. Expert Opin Ther Targets 12: 281-289, 2008.
55. Meeus M, Nijs J, McGregor N, Meeusen R, De Schutter G, Truijen S, Fremont M, Van Hoof E and De Meirleir K: Unravelling intracellular immune dysfunctions in chronic fatigue syndrome: interactions between protein kinase R activity, RNase L cleavage and elastase activity, and their clinical relevance. In Vivo 22: 115-121, 2008.
56. Conti A, Ageunnouz M, La Torre D, Cardali S, Angileri FF, Buemi C, Tomasello C, Iacopino DG, D'Avella D, Vita G and Tomasello F: Expression of the tumor necrosis factor receptor-associated factors 1 and 2 and regulation of the nuclear factor-kappaB antiapoptotic activity in human gliomas. J Neurosurg 103: 873-881, 2005.
57. Naugler WE and Karin M: NF-kappaB and cancer-identifying targets and mechanisms. Curr Opin Genet Dev 18: 19-26, 2008.
58. Angileri FF, Aguennouz M, Conti A, La Torre D, Cardali S, Crapi R, Tomasello C, Germano A, Vita G and Tomasello F: Nuclear factor-kappaB activation and differential expression of survivin and Bcl-2 in human grade 2-4 astrocytomas. Cancer 112: 2258-2266, 2008.
59. Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E and Ben-Neriah Y: NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431: 461-466, 2004.
60. Inoue J, Gohda J, Akiyama T and Semba K: NF-kappaB activation in development and progression of cancer. Cancer Sci 98: 268-274, 2007.
61. Shen HM and Tergaonkar V: NFkappaB signaling in carcinogenesis and as a potential molecular target for cancer therapy. Apoptosis 14: 348-363, 2009.
62. Whiteside TL and Friberg D: Natural killer cells and natural killer cell activity in chronic fatigue syndrome. Am J Med 105: 27S-34S, 1998.
63. Siegel SD, Antoni MH, Fletcher MA, Maher K, Segota MC and Klimas N: Impaired natural immunity, cognitive dysfunction, and physical symptoms in patients with chronic fatigue syndrome: preliminary evidence for a subgroup? J Psychosom Res 60: 559-566, 2006.
64. Tirelli U, Marotta G, Improta S and Pinto A: Immunological abnormalities in patients with chronic fatigue syndrome. Scand J Immunol 40: 601-608, 1994.
65. Levine PH, Whiteside TL, Friberg D, Bryant J, Colclough G and Herberman RB: Dysfunction of natural killer activity in a family with chronic fatigue syndrome. Clin Immunol Immunopathol 88: 96-104, 1998.
66. Aoki T, Miyakoshi H, Usuda Y and Herberman RB: Low NK syndrome and its relationship to chronic fatigue syndrome. Clin Immunol Immunopathol 69: 253-265, 1993.
67. Arnon TI, Markel G and Mandelboim O: Tumor and viral recognition by natural killer cells receptors. Semin Cancer Biol 16: 348-358, 2006.
68. Terunuma H, Deng X, Dewan Z, Fujimoto S and Yamamoto N: Potential role of NK cells in the induction of immune responses: implications for NK cell-based immunotherapy for cancers and viral infections. Int Rev Immunol 27: 93-110, 2008.
69. Strayer DR, Carter WA, Mayberry SD, Pequignot E and Brodsky I: Low natural cytotoxicity of peripheral blood mononuclear cells in individuals with high familial incidences of cancer. Cancer Res 44: 370-374, 1984.
70. Strayer DR, Carter WA and Brodsky I: Familial occurrence of breast cancer is associated with reduced natural killer cytotoxicity. Breast Cancer Res Treat 7: 187-192, 1986.
71. Hersey P, Edwards A, Honeyman M and McCarthy WH: Low natural killer cell activity in familial melanoma patients and their relatives. Br J Cancer 40: 113-122, 1979.
72. Whiteside TL and Herberman RB: The role of natural killer cells in immune surveillance of cancer. Curr Opin Immunol 7: 704-710, 1995.
73. Pollack S: Chronic fatigue syndrome and immune dysfunction: cause or effect? Isr Med Assoc J 4: 883-885, 2002.
74. Jenkins DC, Charles IG, Thomsen LL, Moss DW, Holmes LS, Baylis SA, Rhodes P, Westmore K, Emson PC and Moncada S: Roles of nitric oxide in tumor growth. Proc Natl Acad Sei USA 92: 4392-4396, 1995.
75. Wink DA, Vodovotz Y, Laval J, Laval F, Dewhirst MW and Mitchell JB: The multifaceted roles of nitric oxide in cancer. Carcinogenesis 19: 711-721, 1998.
76. Colakogullari M, Ulukaya E, Yilmaztepe A, Ocakoglu G, Yilmaz M, Karadag M and Tokullugil A: Higher serum nitrate levels are associated with poor survival in lung cancer patients. Clin Biochem 39: 898-903, 2006.
77. Kaya E, Keskin L, Aydogdu I, Kuku I, Bayraktar N and Erkut MA: Oxidant/antioxidant parameters and their relationship with chemotherapy in Hodgkin's lymphoma. J Int Med Res 33: 687-692, 2005.
78. Shephard RJ and Shek PN: Effects of exercise and training on natural killer cell counts and cytolytic activity: a meta-analysis. Sports Med 28: 177-195, 1999.
79. Woods JA, Davis JM, Smith JA and Nieman DC: Exercise and cellular innate immune function. Med Sci Sports Exerc 31: 57-66, 1999.
80. Mackinnon LT: Advances in Exercise Immunology. Leeds Mackinnon LT, Human Kinestics, pp. 94-96, 1999.
81. Fulle S, Pietrangelo T, Mancinelli R, Saggini R and Fano G: Specific correlations between muscle oxidative stress and chronic fatigue syndrome: a working hypothesis. J Muscle Res Cell Motil 28: 355-362, 2007.
82. Nicolson GL and Conklin KA: Reversing mitochondrial dysfunction, fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy. Clin Exp Metastasis 25: 161-169, 2008.
83. Malmberg KJ: Effective immunotherapy against cancer: a question of overcoming immune suppression and immune escape? Cancer Immunol Immunother 53: 879-892, 2004.
84. Nijs J, Meeus M, McGregor NR, Meeusen R, de Schutter G, van Hoof E and de Meirleir K: Chronic fatigue syndrome: exercise performance related to immune dysfunction. Med Sci Sports Exerc 37: 1647-1654, 2005.
85. Snell CR, Vanness JM, Strayer DR and Stevens SR: Exercise capacity and immune function in male and female patients with chronic fatigue syndrome (CFS). In Vivo 19: 387-390, 2005.
86. Snell CR, Vanness JM, Strayer DR and Stevens SR: Physical performance and prediction of 2-5A synthetase/RNase L antiviral pathway activity in patients with chronic fatigue syndrome. In Vivo 16: 107-109, 2002.
87. Tiev KP, Briant M, Ziani M, Cabane J, Demettre E and Lebleu B: Variability of the RNase L isoform ratio (37 kiloDaltons/83 kiloDaltons) in diagnosis of chronic fatigue syndrome. Clin Diagn Lab Immunol 12: p366, 2005.
88. Qian ZM, Xiao DS, Ke Y and Liao QK: Increased nitric oxide is one of the causes of changes of iron metabolism in strenuously exercised rats. Am J Physiol Regul Integr Comp Physiol 280: R739-743, 2001.
89. Tatsumi T, Matoba S, Kawahara A, Keira N, Shiraishi J, Akashi K, Kobara M, Tanaka T, Katamura M, Nakagawa C, Ohta B, Shirayama T, Takeda K, Asayama J, Fliss H and Nakagawa M: Cytokine-induced ǹitric oxide production inhibits mitochondrial energy production and impairs contractile function in rat cardiac myocytes. J Am Coll Cardiol 35: 1338-1346, 2000.
90. Lee BN, Dantzer R, Langley KE, Bennett GJ, Dougherty PM, Dunn AJ, Meyers CA, Miller AH, Payne R, Reuben JM, Wang XS and Cleeland CS: A cytokine-based neuroimmunologic mechanism of cancer-related symptoms. Neuroimmuno-modulation 11: 279-292, 2004.
91. Na YM, Kim MY, Kim YK, Ha YR and Yoon DS: Exercise therapy effect on natural killer cell cytotoxic activity in stomach cancer patients after curative surgery. Arch Phys Med Rehabil 81: 777-779, 2000.
92. Fulcher KY and White PD: Strength and physiological response to exercise in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry 69: 302-307, 2000.
93. Irwin ML, Crumley D, McTiernan A, Bernstein L, Baumgartner R, Gilliland FD, Kriska A and Ballard-Barbash R: Physical activity levels before and after a diagnosis of breast carcinoma: the Health, Eating, Activity, and Lifestyle (HEAL) study. Cancer 97: 1746-1757, 2003.
94. Courneya KS and Friedenreich CM: Relationship between exercise pattern across the cancer experience and current quality of life in colorectal cancer survivors. J Altern Complement Med 3: 215-226, 1997.
95. Courneya KS and Friedenreich CM: Determinants of exercise during colorectal cancer treatment: an application of the theory of planned behavior. Oncol Nurs Forum 24: 1715-1723, 1997.
96. Thorsen L, Courneya KS, Stevinson C and Fossa SD: A systematic review of physical activity in prostate cancer survivors: outcomes, prevalence, and determinants. Support Care Cancer 16: 987-997, 2008.
97. Irwin ML: Physical activity interventions for cancer survivors. Br J Sports Med 43: 32-38, 2009.
98. Irwin ML and Mayne ST: Impact of nutrition and exercise on cancer survival. Cancer J 14: 435-441, 2008.
99. Sorensen B, Streib JE, Strand M, Make B, Giclas PC, Fleshner M and Jones JF: Complement activation in a model of chronic fatigue syndrome. J Allergy Clin Immunol 112: 397-403, 2003.
100. Jammes Y, Steinberg JG, Mambrini O, Bregeon F and Delliaux S: Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise. J Intern Med 257: 299-310, 2005.
101. Schmitz KH, Holtzman J, Courneya KS, Masse LC, Duval S and Kane R: Controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 14: 1588-1595, 2005.
102. Cohen LA, Choi KW and Wang CX: Influence of dietary fat, caloric restriction, and voluntary exercise on TV-nitrosomethylurea-induced mammary tumorigenesis in rats. Cancer Res 48: 4276-4283, 1988.