Modulating mesenchymal stromal cell function with cholesterol synthesis inhibitors

Current Medicinal Chemistry

Volumn 18, Issue 34, 2011, Pages 5196-5205

  Poggi, A ^a   Zocchi, M R ^b  

^a UNIVERSITY OF GENOA   (Italy)

^b SAN RAFFAELE HOSPITAL   (Italy)

Author keywords

Bone marrow; Cholesterol inhibitors; Mesenchymal stromal cells; Natural killer cells; Statins; Tumor microenvironment

Indexed keywords

ANACETRAPIB; ATORVASTATIN; AVASIMIBE; BEZAFIBRATE; CERIVASTATIN; CHOLESTEROL; CIPROFIBRATE; CLOFIBRATE; COLESEVELAM; COMPACTIN; DALCETRAPIB; EZETIMIBE; FENOFIBRATE; FLUINDOSTATIN; GEMFIBROZIL; IMPLITAPIDE; MEVINOLIN; PITAVASTATIN; PRAVASTATIN; ROSUVASTATIN; SIMVASTATIN; TORCETRAPIB;

ARTICLE; B LYMPHOCYTE; CANCER CELL CULTURE; CANCER INHIBITION; CATARACT; CELL FUNCTION; CELL POPULATION; CELL PROLIFERATION; CHOLESTEROL SYNTHESIS; CHRONIC LYMPHATIC LEUKEMIA; COLON CANCER; DEMENTIA; DENDRITIC CELL; ENDOTHELIUM CELL; FIBROBLAST; FOLLICULAR LYMPHOMA; HUMAN; HYPERCHOLESTEROLEMIA; HYPERLIPIDEMIA; HYPERTENSION; INFLAMMATION; LEUKEMIA CELL; LUNG CANCER; LYMPHOMA; MACROPHAGE; MESENCHYME CELL; MULTIPLE MYELOMA; MYELOID LEUKEMIA; NATURAL KILLER CELL; NON INSULIN DEPENDENT DIABETES MELLITUS; STROMA CELL; T LYMPHOCYTE; TUMOR GROWTH; TUMOR MICROENVIRONMENT; TUMOR PROMOTION;

ANIMALS; ANTICHOLESTEREMIC AGENTS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MESENCHYMAL STROMAL CELLS; TUMOR MICROENVIRONMENT;

EID: 82255195391     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/092986711798184244     Document Type: Article

References (155)

1. Pahan, K. Lipid-lowering drugs. Cell. Mol. Life Sci., 2006, 63, 1165-78. (Pubitemid 43939003)
2. Kwak, B. R.; Mulhaupt, F.; Mach, F.; Atherosclerosis: anti-inflammatory and immunomodulatory activities of statins. Autoimmun Rev., 2003, 2, 332-338. (Pubitemid 37211387)
3. Fildes, J. E.; Shaw. S. M.; Williams, S. G.; Yonan, N. Potential immunologic effects of statins in cancer following transplantation. Cancer Immunol. Immunother., 2009, 58, 461-467.
4. Jakóbisiak, M.; Golab, J. Potential antitumor effects of statins. Int. J. Oncol, 2003, 23, 1055-1069.
5. Chng, W. J.; Lau, L. G.; Yusof, N. Mow BM. Targeted therapy in multiple myeloma. Cancer Control, 2005, 12, 91-104. (Pubitemid 40647052)
6. Drucker, L.; Afensiev, F.; Radnay, J.; Shapira, H.; Lishner, M. Coadministration of simvastatin and cytotoxic drugs is advantageous in myeloma cell lines. Anticancer Drugs., 2004, 15, 79-84. (Pubitemid 39140176)
7. Osadchy, A.; Drucker, L.; Radnay, J.; Shapira, H.; Lishner, M. Microenvironment factors do not afford myeloma cell lines protection from simvastatin. Eur. J. Haematol, 2004, 73, 183-90. (Pubitemid 39062242)
8. Schmidmaier, R.; Simsek, M.; Baumann, P.; Emmerich, B.; Meinhardt, G. Synergistic antimyeloma effects of zoledronate and simvastatin. Anticancer Drugs, 2006, 17, 621-629 (Pubitemid 44265862)
9. Schmidmaier, R.; Baumann, P.; Bumeder, I.; Meinhardt, G.; Straka, C.; Emmerich, B. First clinical experience with simvastatin to overcome drug resistance in refractory multiple myeloma. Eur. J. Haematol, 2007, 79, 240-243. (Pubitemid 47231166)
10. van de Donk, N. W.; Bloem, A. C.; van der Spek, E., Lokhorst, H. M. New treatment strategies for multiple myeloma by targeting BCL-2 and the mevalonate pathway. Curr. Pharm. Des., 2006, 12, 327-340.
11. Fonseca, A. C.; Resende, R.; Oliveira, C. R.; Pereira, CM. Cholesterol and statins in Alzheimer's disease: current controversies. Exp. Neurol, 2009, Sep. 24
12. Sabbagh, M. N. Drug development for Alzheimer's disease: where are we now and where are we headed? Am. J. Geriatr. Pharmacother., 2009, 7, 167-85.
13. McGuinness, B., Craig, D.; Bullock, R.; Passmore, P. Statins for the prevention of dementia. Cochrane Database Syst. Rev, 2009, Apr. 15(2):CD003160.
14. Harris, M. L.; Bron, A. J.; Brown, N. A.; Keech, A. C.; Wallendszus, K. R.; Armitage, J. M.; MacMahon, S.; Snibson, G.; Collins, R. Absence of effect of simvastatin on the progression of lens opacities in a randomised placebo controlled study. Br. J. Ophthalmol, 1995, 79, 996-1002.
15. Chylack, L. T. Jr.; Mantell, G.; Wolfe, J. K.; Friend, J.; Rosner, B. Lovastatin and the human lens; results of a two year study. Optom. Vis. Sci, 1993, 70, 937-943. (Pubitemid 23342722)
16. Anton, K.; Glod, J. Targeting the tumor stroma in cancer therapy. Curr Pharm Biotechnol, 2009, 2, 185-191.
17. Korc, M.; Friesel, R. E. The role of fibroblast growth factors in tumor growth. Curr Cancer Drug Targets., 2009, 5, 639-651.
18. Chen, W.; Frank, M. E.; Jin, W.; Wahl, S. M. TGF-beta released by apoptotic T cells contributes to an immunosuppressive milieu. Immunity., 2001, 14, 715-725. (Pubitemid 32592419)
19. Frey, A. B.; Monu, N. Signaling defects in anti-tumor T cells. Immunol Rev., 2008, 222, 192-205. (Pubitemid 351430368)
20. Li, M. O.; Wan, Y. Y.; Sanjabi, S.; Robertson, A. K.; Flavell, R. A. Transforming growth factor-P regulation of immune responses. Annu. Rev. Immunol., 2006, 24, 99-146.
21. Biswas, S.; Criswell, T. L.; Wang, S. E.; Arteaga, C. L. Inhibition of transforming growth factor-P signaling in human cancer: targeting a tumor suppressor network as a therapeutic strategy. Clin. Cancer Res., 2006, 12, 4142-4146.
22. Dorhoi, A.; Kaufmann, S. H. Fine-tuning of T cell responses during infection. Curr Opin Immunol, 2009, 21, 367-77.
23. Trinchieri, G. Biology of natural killer cells. Adv. Immunol, 1989, 47, 187-376. (Pubitemid 20010960)
24. Moretta, A.; Bottino, C.; Vitale, M.; Pende, D.; Biassoni, R.; Mingari, MC.; Moretta, L. Receptors for HLA class-I molecules in human natural killer cells. Annu. Rev. Immunol, 1996, 14, 619-648. (Pubitemid 26130196)
25. Lanier, L. L. NK cell receptors. Annu. Rev. Immunol, 1998, 16, 359-393. (Pubitemid 28183369)
26. Long, E. O. Regulation of immune responses through inhibitory receptors. Annu. Rev. Immunol, 1999, 17, 875-904. (Pubitemid 29241142)
27. Vivier, E.; Tomasello, E.; Baratin, M.; Walzer, T.; Ugolini, S. Functions of natural killer cells. Nature Immunol, 2008, 9, 503-510. (Pubitemid 351560519)
28. Bryceson, Y. T.; March, M. E.; Ljunggren, H. G.; Long, E. O. Activation, coactivation, and costimulation of resting human natural killer cells. Immunol. Rev, 2006, 214, 73-91. (Pubitemid 44707903)
29. Smits, E. L.; Anguille, S.; Cools, N.; Berneman, Z. N.; Van Tendeloo, V. F. Dendritic Cell-Based Cancer Gene Therapy. Hum Gene Ther., 2009, 20:1106-1118.
30. Pittet, M. J. Behavior of immune players in the tumor microenvironment. Curr Opin Oncol, 2009, 21, 53-59.
31. Raulet, D. H. Roles of the NKG2D immunoreceptor and its ligands. Nature Rev Immunol, 2003, 3, 781-90. (Pubitemid 37328656)
32. Hayday, A. C. Gammadelta T cells and the lymphoid stress-surveillance response. Immunity, 2009, 31, 184-96.
33. Nausch, N.; Cerwenka, A. NKG2D ligands in tumor immunity. Oncogene., 2008, 27, 5944-58.
34. González, S.; López-Soto, A.; Suarez-Alvarez, B.; López-Vázquez, A.; López-Larrea, C. NKG2D ligands: key targets of the immune response. Trends Immunol, 2008, 29, 397-403.
35. Champsaur, M.; Lanier, L. L. Effect of NKG2D ligand expression on host immune responses. Immunol Rev, 2010, 235, 267-285.
36. Ferrarini, M.; Ferrero, E.; Dagna, L.; Poggi, A.; Zocchi, M. R. Human γδ T cells: a nonredundant system in the immune-surveillance against cancer. Trends Immunol, 2002, 23, 14-17.
37. Nauta, A. J.; Fibbe, W. E. Immunomodulatory properties of mesenchymal stromal cells. Blood, 2007, 110, 3499-3506. (Pubitemid 350159613)
38. Pittenger, M. F.; Mackay, A. M.; Beck, S. C.; Jaiswal, R. K.; Douglas, R.; Mosca, J. D.; Moorman, M. A.; Simonetti, D. W.; Craig, S.; Marshak, D. R. Multilineage potential of adult human mesenchymal stem cells. Science, 1999, 284, 143-147. (Pubitemid 29282067)
39. Tse, W. T.; Pendleton, J. D.; Beyer, W. M.; Egalka, M. C.; Guinan, E. C. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation, 2003, 75, 389-397. (Pubitemid 36222968)
40. Di Nicola, M.; Carlo-Stella, C.; Magni, M.; Milanesi, M.; Stucchi, C.; Cleris, L. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood, 2002, 99, 3838-3843. (Pubitemid 34534559)
41. Le Blanc, K. Immunomodulatory effects of fetal and adult mesenchymal stem cells. Cytotherapy, 2003, 5, 485-489. (Pubitemid 38028708)
42. Le Blanc, K.; Tammik, L.; Sundberg, B.; Haynesworth, S. E.; Ringden, O. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand. J. Immunol, 2003, 57, 11-20. (Pubitemid 38019084)
43. Potian, J. A.; Aviv, H.; Ponzio, N. M.; Harrison, J. S.; Rameshwar, P. Vetolike activity of mesenchymal stem cells: functional discrimination between cellular responses to alloantigens and recall antigens. J. Immunol, 2003, 171, 3426-3434. (Pubitemid 37254543)
44. Beyth, S.; Borovsky, Z.; Mevorach, D.; Liebergall, M.; Gazit, Z.; Aslan, H.; Galun, E.; Rachmilewitz, J. Human mesenchymal stem cells alter antigenpresenting cell maturation and induce T cell unresponsiveness. Blood, 2005, 105, 2214-2219. (Pubitemid 40731815)
45. Meisel, R.; Zibert, A.; Laryea, M.; Gobel, U.; Daubener, U.; Dilloo, D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2, 3-dioxygenase-mediated tryptophan degradation. Blood, 2004, 103, 4619-4621. (Pubitemid 38745993)
46. Aggarwal, S., Pittenger, M. F. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood, 2005, 105, 1815-1822. (Pubitemid 40223708)
47. Augello, A.; Tasso, R.; Negrini, S. M.; Amateis, A.; Indiveri, F.; Cancedda, R.; Pennesi, G. Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed cell death 1 pathway. Eur. J. Immunol, 2005, 35, 1482-1490. (Pubitemid 40691430)
48. Le Blanc, K.; Rasmusson, I.; Sundberg, B., Götherström, C.; Hassan, M.; Uzunel, M.; Ringdén, O. Treatment of severe acute graft-versus host disease with third party haploidentical mesenchymal stem cells. Lancet, 2004, 363, 1439-1441. (Pubitemid 38586721)
49. Poggi, A.; Zocchi, M. R. Role of bone marrow stromal cells in the generation of human CD8 (+) regulatory T cells. Hum. Immunol, 2008, 69, 755-759.
50. Prevosto, C.; Zancolli, M.; Canevali, P.; Zocchi, M. R.; Poggi, A. Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem celllymphocyte interaction. Haematologica, 2007, 92, 881-888. (Pubitemid 350144234)
51. Otsuki, T.; Sakaguchi, H.; Eto, M.; Fujii, T.; Hatayama, T.; Takata, A.; Tsujioka, T.; Sugihara, T.; Hyodoh, F. IL-6 is a key factor in growth inhibition of human myeloma cells induced by pravastatin, an HMG-CoA reductase inhibitor. Int. J. Oncol, 2003, 23, 763-768.
52. Djouad, F.; Plence, P.; Bony, C.; Tropel, P.; Apparailly, F.; Sany, J.; Noël, D.; Jorgensen, C. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood, 2003, 102, 3837-3844. (Pubitemid 37409409)
53. Meads, M. B.; Hazlehurst, L. A.; Dalton, W. S. The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance. Clin Cancer Res., 2008, 14, 2519-2526.
54. Mishra, P. J.; Mishra, P. J.; Glod, J. W.; Banerjee, D. Mesenchymal stem cells: flip side of the coin. Cancer Res. 2009, 4, 1255-1258.
55. Erratum in: Cancer Res. 2009, 7, 3240.
56. Sottero, B.; Gamba, P.; Gargiulo, S.; Leonarduzzi, G.; Poli, G. Cholesterol oxidation products and disease: an emerging topic of interest in medicinal chemistry. Curr Med Chem., 2009, 16, 685-705.
57. Tomkin, G. H. Ezetimibe-new anti-atherogenic properties? British Journal of Pharmacology, 2009, 156, 1216-1217.
58. Nissen, S. E. Analyses of cancer data from three ezetimibe trials. N Engl. J. Med, 2009, 360, 86-87.
59. Peto, R.; Emberson, J.; Landray, M.; Baigent, C.; Collins, R.; Clare, R.; Califf, R. Analyses of cancer data from three ezetimibe trials. N. Engl. J. Med., 2008, 359, 1357-1366.
60. Sonnett, T. E.; Levien, T. L.; Neumiller, J. J.; Gates, B. J.; Setter, S. M. Colesevelam hydrochloride for the treatment of type 2 diabetes mellitus. Clin. Ther., 2009, 31, 245-259.
61. Masson, D. Anacetrapib, a cholesterol ester transfer protein (CETP) inhibitor for the treatment of atherosclerosis. Curr. Opin. Investig. Drugs., 2009, 10, 980-987.
62. Joy, T.; Hegele, R. A. The end of the road for CETP inhibitors after torcetrapib? Curr. Opin. Cardiol., 2009, 24, 364-371.
63. Davidson, M. H. Novel nonstatin strategies to lower low-density lipoprotein cholesterol. Curr Atheroscler Rep., 2009, 11, 67-70.
64. Ueshima, K.; Akihisa-Umeno, H.; Nagayoshi, A.; Takakura, S.; Matsuo, M.; Mutoh, S. Implitapide, a microsomal triglyceride transfer protein inhibitor, reduces progression of atherosclerosis in apolipoprotein E knockout mice fed a Western-type diet: involvement of the inhibition of postprandial triglyceride elevation. Biol Pharm Bull., 2005, 28, 247-252. (Pubitemid 40880003)
65. Abourbih S, Filion K. B.; Joseph, L.; Schiffrin, E. L.; Rinfret, S.; Poirier, P.; Pilote, L.; Genest, J.; Eisenberg, M. J. Effect of fibrates on lipid profiles and cardiovascular outcomes: a systematic review. Am J Med., 2009, 122, 962.e1-8.
66. Mor, A.; Dustin, M. L.; Philips, M. R. Small GTPases and LFA-1 reciprocally modulate adhesion and signaling. Immunol. Rev., 2007, 218, 114-125. (Pubitemid 47052308)
67. Billadeau, D. D.; Brumbaugh, K. M.; Dick, C. J.; Schoon, R. A.; Bustelo, X. R.; Leibson, P. J. The Vav-Rac1 pathway in cytotoxic lymphocytes regulates the generation of cell-mediated killing. J. Exp. Med., 1998, 188, 549-559. (Pubitemid 28369144)
68. Nonaka, M.; Uota, S.; Saitoh, Y.; Takahashi, M.; Sugimoto, H.; Amet, T.; Arai, A.; Miura, O.; Yamamoto, N.; Yamaoka, S. Role for protein geranylgeranylation in adult T-cell leukemia cell survival. Exp. Cell. Res., 2009, 315, 141-150.
69. Caligaris Cappio, F. Inflammation, the microenvironment and chronic lymphocytic leukemia. Haematologica, 2011, 96, 353-355.
70. Chiorazzi, N.; Rai, K. R.; Ferrarini, M. Chronic lymphocitic leucemia. N. Engl. J. Med., 2005, 352, 804-815.
71. Bruno, B.; Rotta, M.; Giaccone, L., Massaia, M.; Bertola, A.; Palombo, A.; Boccadoro, M. New drugs for treatment of multiple myeloma. Lancet Oncol., 2004, 5, 430-442. (Pubitemid 38878047)
72. Steidl, C.; Connors, J. M.; Gascoyne R. D. Molecular pathogenesis of Hodgkin's lymphoma: increasing evodence of the importance of the microenvironment. J. Clin. Oncol., 2011, 29, 1812-1826.
73. Yang, L.; Pang, Y.; Moses, H. L. TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression. Trends Immunol., 2010, 31, 220-227.
74. Baek, K. H.; Lee, W. Y.; Oh, K. W.; Tae, H. J.; Lee, J. M.; Lee, E. J.; Han, J. H.; Kang, M. I.; Cha, B. Y.; Lee, K. W.; Son, H. Y.; Kang, S. K. The effect of simvastatin on the proliferation and differentiation of human bone marrow stromal cells. J Korean Med Sci., 2005, 20, 438-44.
75. Ogata, A.; Chauhan, D.; Teoh, G.; Treon, S. P.; Urashima, M.; Schlossman, R. L. Anderson KC. IL-6 triggers cell growth via the Ras-dependent mitogenactivated protein kinase cascade. J Immunol., 1997, 159, 2212-2221. (Pubitemid 127681011)
76. Hideshima, T.; Nakamura, N.; Chauhan, D.; Anderson, K. Biologic sequelae of interleukin-6 induced PI3-K/Akt signaling in multiple myeloma. Oncogene, 2001, 20, 5991-6000. (Pubitemid 32955041)
77. Musso, A.; Zancolli, M.; Zocchi, M. R.; Poggi, A. Immunosuppression mediated by bone marrow stromal cells is downregulated by 3-hydroxy-3- methylglutaryl-coenzime A reductase inhibitors. Bone Marrow Transpl., 2008, 41, s324-s325.
78. Musso, A.; Zocchi, M. R.; Poggi, A. Relevance of the mevalonate biosynthetic pathway in the regulation of bone marrow mesenchymal stromal cell-mediated effects on T-cell proliferation and B-cell survival. Haematologica., 2011, 96, 16-23.
79. Erridge, C. The roles of pathogen-associated molecular patterns in atherosclerosis. Trends Cardiovasc Med., 2008, 18, 52-56. (Pubitemid 351282493)
80. Poggi, A., Prevosto, C.; Zancolli, M.; Canevali, P.; Musso, A., Zocchi, M. R. NKG2D and natural cytotoxicity receptors are involved in natural killer cell interaction with self-antigen presenting cells and stromal cells. Ann. N. Y. Acad. Sci., 2007, 1109, 47-57. (Pubitemid 47511344)
81. Poggi, A.; Zocchi, M. R. Antigen presenting cells and stromal cells trigger human natural killer lymphocytes to autoreactivity: evidence for the involvement of natural cytotoxicity receptors (NCR) and NKG2D. Clin. Dev. l Immunol., 2006, 13, 325-336. (Pubitemid 44950048)
82. Poggi, A.; Zocchi, M. R. Human natural killer lymphocytes through the engagement of natural cytotoxicity receptors and NKG2D can trigger self aggression. Autoimmun. Rev., 2007, 6, 295-299. (Pubitemid 46507988)
83. Zocchi, M. R.; Poggi, A. Editorial: Innate immunity and cytokines: how to regulate host response against pathogens avoiding autoreactivity. Curr. Med. Chem., 2005, 4, 113-114. (Pubitemid 40352656)
84. Zocchi, M. R.; Poggi, A. Triggering of apoptosis and pro-inflammatory cytokines in NK cells: regulation by cyclosporin A. Curr. Med. Chem., 2005, 4, 115-120. (Pubitemid 40352657)
85. Strasser, A.; Jost, P. J.; Nagata, S. The many roles of FAS receptor signaling in the immune system. Immunity., 2009, 30, 180-192.
86. Spaggiari, G. M.; Contini, P.; Dondero, A.; Carosio, R.; Puppo, F.; Indiveri, F.; Zocchi, M. R.; Poggi, A. Soluble HLA class I induces NK cell apoptosis upon the engagement of killer-activating HLA class I receptors through FasL-Fas interaction. Blood., 2002, 100, 4098-4107 (Pubitemid 35396878)
87. Spaggiari, G. M.; Contini, P.; Carosio, R.; Arvigo, M.; Ghio, M.; Oddone, D.; Dondero, A.; Zocchi, M. R.; Puppo, F.; Indiveri, F.; Poggi, A. Soluble HLA class I molecules induce natural killer cell apoptosis through the engagement of CD8: evidence for a negative regulation exerted by members of the inhibitory receptor superfamily. Blood., 2002, 99, 1706-1714 (Pubitemid 34533045)
88. Hillyard, D. Z.; Nutt, C. D.; Thomson, J.; McDonald, K. J.; Wan, R. K.; Cameron, A. J.; Mark, P. B.; Jardine, A. G. Statins inhibit NK cell cytotoxicity by membrane raft depletion rather than inhibition of isoprenylation. A th ero sc lero s is, 2007, 191, 319-325. (Pubitemid 46400716)
89. Tanaka, T.; Porter, C. M.; Horvath-Arcidiacono, J. A.; Bloom, E. T. Lipophilic statins suppress cytotoxicity by freshly isolated natural killer cells through modulation of granule exocytosis. Int. Immunol., 2007, 19, 163-173. (Pubitemid 46179011)
90. Raemer, P. C.; Kohl, K.; Watzl, C. Statins inhibit NK-cell cytotoxicity by interfering with LFA-1-mediated conjugate formation. Eur. J. Immunol., 2009, 39, 1456-1465.
91. Chichili, G. R.; Rodgers, W. Cytoskeleton-membrane interactions in membrane raft structure. Cell Mol Life Sci., 2009, 66, 2319-2328.
92. Kabouridis, P. S.; Jury, E. C. Lipid rafts and T-lymphocyte function: implications for autoimmunity. FEBS Lett., 2008, 582, 3711-3718.
93. Pani, B.; Singh, B. B. Lipid rafts/caveolae as microdomains of calcium signaling. Cell Calcium, 2009, 45, 625-633.
94. Kusama, T.; Mukai, M.; Endo, H.; Ishikawa, O.; Tatsuta, M.; Nakamura, H.; Inoue, M. Inactivation of Rho GTPases by p190 RhoGAP reduces human pancreatic cancer cell invasion and metastasis. Cancer Sci., 2006, 97, 848-853. (Pubitemid 44151264)
95. Glynn, S. A.; O'Sullivan, D.; Eustace, A. J.; Clynes, M.; O'Donovan, N. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, simvastatin, lovastatin and mevastatin inhibit proliferation and invasion of melanoma cells. BMC Cancer., 2008, 16, 8-9.
96. Cho, S. J.; Kim, J. S.; Kim, J. M.; Lee, J. Y.; Jung, H. C.; Song, I. S. Simvastatin induces apoptosis in human colon cancer cells and in tumor xenografts, and attenuates colitis-associated colon cancer in mice. Int. J. Cancer., 2008, 123, 951-957.
97. Riganti, C.; Doublier, S.; Costamagna, C.; Aldieri, E., Pescarmona, G.; Ghigo, D.; Bosia, A. Activation of nuclear factor-kappa B pathway by simvastatin and RhoA silencing increases doxorubicin cytotoxicity in human colon cancer HT29 cells. Mol. Pharmacol., 2008, 74, 476-484.
98. Wong, W. W.; Tan, M. M.; Xia, Z.; Dimitroulakos, J.; Minden, M. D.; Penn, L. Z. Cerivastatin triggers tumor-specific apoptosis with higher efficacy than lovastatin. Clin. Cancer. Res., 2001, 7, 2067-2075. (Pubitemid 32994846)
99. Lu, G.; Xiao, H.; You, H.; Lin, Y.; Jin, H.; Snagaski, B., Yang, C. S. Synergistic inhibition of lung tumorigenesis by a combination of green tea polyphenols and atorvastatin. Clin. Cancer Res., 2008, 14, 4981-4988.
100. Ahn, K. S.; Sethi, G.; Aggarwal, B. B. Simvastatin potentiates TNF-alphainduced apoptosis through the down-regulation of NF-kappaB-dependent antiapoptotic gene products: role of IkappaBalpha kinase and TGF-betaactivated kinase-1. J Immunol., 2007, 178, 2507-2516. (Pubitemid 46233452)
101. Kotamraju, S.; Williams, C. L.; Kalyanaraman, B. Statin-induced breast cancer cell death: role of inducible nitrix oxide and arginase-dependent pathways. Cancer Res., 2007, 67, 7386-7394. (Pubitemid 47206569)
102. Di Paolo, A.; Danesi, R.; Cardini, D.; Bocci, G.; Innocenti, F.; Fogli, S.; Baracchini, S.; Marchetti, A.; Bevilacqua, G.; Del Tacca, M. Manumycin inhibits ras signal transduction pathway and induces apoptosis in COLO320-DM human colon tumour cells. Br J Cancer., 2000, 82, 905-912. (Pubitemid 30085245)
103. Winiarska, M.; Bil, J.; Wilczek, E.; Wilczynski, G. M.; Lekka, M.; Engelberts, P. J.; Mackus, W. J.; Gorska, E.; Bojarski, L.; Stoklosa, T.; Nowis, D.; Kurzaj, Z.; Makowski, M.; Glodkowska, E.; Issat, T.; Mrowka, P.; Lasek, W.; Dabrowska-Iwanicka, A.; Basak, G. W.; Wasik, M.; Warzocha, K.; Sinski, M., Gaciong, Z.; Jakobisiak, M.; Parren, P. W.; Golab, J. Statins impair antitumor effects of rituximab by inducing conformational changes of CD20. PLoS Med., 2008, 5, e64.
104. von Tresckow, B.; von Strandmann, E. P.; Sasse, S.; Tawadros, S.; Engert, A.; Hansen, H. P. Simvastatin-dependent apoptosis in Hodgkin's lymphoma cells and growth impairment of human Hodgkin's tumors in vivo. Haematologica., 2007, 92, 682-685. (Pubitemid 350144272)
105. van der Spek, E.; Bloem, A. C.; van de Donk, N. W.; Bogers, L. H.; van der Griend, R.; Kramer, M. H.; de Weerdt, O.; Wittebol, S.; Lokhorst, H. M. Dosefinding study of high-dose simvastatin combined with standard chemotherapy in patients with relapsed or refractory myeloma or lymphoma. Haematologica., 2006, 91, 542-545.
106. Issat, T.; Nowis, D.; Jakóbisiak, M.; Golab, J. Lovastatin potentiates antitumor effects of saquinavir against human lymphoma cells. Oncol. Rep., 2004, 12, 1371-1375.
107. Cohen, J. I. HMG CoA reductase inhibitors (statins) to treat Epstein-Barr virus-driven lymphoma. Br. J. Cancer., 2005, 92, 1593-1598. (Pubitemid 40756467)
108. Sassano, A.; Lo Iacono, M.; Antico, G.; Jordan, A.; Uddin, S.; Calogero, R. A.; Platanias, L. C. Regulation of leukemic cell differentiation and retinoidinduced gene expression by statins. Mol. Cancer Ther., 2009, 8, 15-25.
109. Calabro, A.; Tai, J.; Allen, S. L.; Budman, D. R. In-vitro synergism of m-TOR inhibitors, statins, and classical chemotherapy: potential implications in acute leukemia. Anticancer Drugs, 2008, 19, 705-712.
110. Sassano, A.; Katsoulidis, E.; Antico, G.; Altman, J. K.; Redig, A. J.; Minucci, S.; Tallman, M. S.; Platanias, L. C. Suppressive effects of statins on acute promyelocytic leukemia cells. Cancer Res., 2007, 67, 4524-4532. (Pubitemid 46815104)
111. Wu, J.; Wong, W. W.; Khosravi, F.; Minden, M. D.; Penn, L. Z. Blocking the Raf/MEK/ERK pathway sensitizes acute myelogenous leukemia cells to lovastatin-induced apoptosis. Cancer Res., 2004, 64, 6461-6468. (Pubitemid 39297901)
112. Chapman-Shimshoni, D.; Yuklea, M.; Radnay, J.; Shapiro, H.; Lishner, M. Simvastatin induces apoptosis of B-CLL cells by activation of mitochondrial caspase 9. Exp. Hematol., 2003, 31, 779-783. (Pubitemid 37075970)
113. Müller-Tidow, C.; Kiehl, M.; Sindermann, J. R.; Probst, M.; Banger, N.; Zühlsdorf, M.; Chou, T. C.; Berdel, W. E.; Serve, H.; Koch, O. M. Synergistic growth inhibitory effects of interferon-alpha and lovastatin on bcr-abl positive leukemic cells. Int. J. Oncol., 2003, 23, 151-158.
114. Li, H. Y.; Appelbaum, F. R.; Willman, C. L.; Zager, R. A.; Banker, D. E. Cholesterol-modulating agents kill acute myeloid leukemia cells and sensitize them to therapeutics by blocking adaptive cholesterol responses. Blood, 2003, 101, 3628-3634. (Pubitemid 36857952)
115. Wong, W. W.; Dimitroulakos, J.; Minden, M. D.; Penn, L. Z. HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia., 2002, 16, 508-519. (Pubitemid 34460459)
116. Dimitroulakos, J.; Thai, S.; Wasfy, G. H.; Hedley, D. W.; Minden, M. D.; Penn, L. Z. Lovastatin induces a pronounced differentiation response in acute myeloid leukemias. Leuk. Lymphoma, 2000, 40, 167-178. (Pubitemid 32124359)
117. Cafforio, P.; Dammacco, F.; Gernone, A.; Silvestris, F. Statins activate the mitochondrial pathway of apoptosis in human lymphoblasts and myeloma cells. Carcinogenesis, 2005, 26, 883-891. (Pubitemid 41214316)
118. Moreau AS, Jia X, Patterson CJ, Roccaro AM, Xu L, Sacco A, O'Connor K, Soumerai J, Ngo HT, Hatjiharissi E, Hunter ZR, Ciccarelli B, Manning R, Ghobrial IM, Leleu X, Treon SP. The HMG-CoA inhibitor, simvastatin, triggers in vitro anti-tumour effect and decreases IgM secretion in Waldenstrom macroglobulinaemia. Br J Haematol., 2008, 142, 775-85.
119. Shipman, C. M.; Croucher, P. I.; Russell, R. G.; Helfrich, M. H.; Rogers, M. J. The bisphosphonate incadronate (YM175) causes apoptosis of human myeloma cells in vitro by inhibiting the mevalonate pathway. Cancer Res., 1998, 58, 5294-5297. (Pubitemid 28551102)
120. Karp, I.; Behlouli, H.; Lelorier, J.; Pilote, L. Statins and Cancer Risk. Am. J. Med., 2008, 12, 302-309. (Pubitemid 351417853)
121. Pedersen, T. R. Lipid-lowering drugs and risk for cancer. Curr. Atheroscler. Rep., 2009, 11, 350-357.
122. Thompson, J. S.; Sood, A.; Arora, R. Statins and Cancer: A Potential Link? Am. J. Ther., 2009, May 15.
123. Coogan, P. F.; Rosenberg, L.; Strom, B. L. Statin use and the risk of 10 cancers. Epidemiology., 2007, 18, 213-219.
124. Kuoppala, J.; Lamminpää, A.; Pukkala, E. Statins and cancer: a systematic review and meta-analysis. Eur. J. Cancer., 2008, 44, 2122-2132.
125. Taylor, M. L.; Wells, B. J.; Smolak, M. J. Statins and cancer: a meta-analysis of case-control studies. Eur. J. Cancer. Prev., 2008, 17, 259-268. (Pubitemid 351549667)
126. Iwata, H.; Matsuo, K.; Hara, S.; Takeuchi, K.; Aoyama, T.; Murashige, N.; Kanda, Y.; Mori, S.; Suzuki, R.; Tachibana, S.; Yamane, M.; Odawara, M.; Mutou, Y.; Kami, M. Use of hydroxy-methyl-glutaryl coenzyme A reductase inhibitors is associated with risk of lymphoid malignancies. Cancer Sci., 2006, 97, 133-138. (Pubitemid 43379481)
127. Taras, D.; Blanc, J. F.; Rullier, A.; Dugot-Senant, N.; Laurendeau, I.; Vidaud, M.; Rosenbaum, J. Pravastatin reduces lung metastasis of rat hepatocellular carcinoma via a coordinated decrease of MMP expression and activity. J Hepatol. 2007, 46, 69-76. (Pubitemid 44834427)
128. Ikeda, M.; Kato, N. Life style-related diseases of the digestive system: cell culture system for the screening of anti-hepatitis C virus (HCV) reagents: suppression of HCV replication by statins and synergistic action with interferon. J Pharmacol Sci. 2007, 105, 145-150. (Pubitemid 350106803)
129. Argo, C. K.; Loria, P.; Caldwell, S. H.; Lonardo, A. Statins in liver disease: a molehill, an iceberg, or neither? Hepatology, 2008, 48, 662-669.
130. Farwell, W. R.; Scranton, R. E.; Lawler, E. V.; Lew, R. A.; Brophy, M. T.; Fiore, L. D.; Gaziano, J. M. The association between statins and cancer incidence in a veterans population. J. Natl Cancer Inst., 2008, 100, 134-139. (Pubitemid 351480564)
131. Platz, E. A. Re: The association between statins and cancer incidence in a veterans population. J Natl Cancer Inst., 2008, 100, 972. (Pubitemid 351957510)
132. Ravnskov, U. Re: The association between statins and cancer incidence in a veterans population. J Natl Cancer Inst., 2008, 100, 972-973. (Pubitemid 351957511)
133. Goldstein, M. R.; Mascitelli, L.; Pezzetta, F. Do statins prevent or promote cancer? Curr Oncol., 2008, 15, 76-77.
134. Trompet, S.; Jukema, J. W.; Katan, M. B.; Blauw, G. J.; Sattar, N.; Buckley, B.; Caslake, M.; Ford, I.; Shepherd, J.; Westendorp, R. G.; de Craen, A. J. Apolipoprotein e genotype, plasma cholesterol, and cancer: a mendelian randomization study Am. J. Epidemiol., 2009, 170, 1415-1421. Epub 2009 Nov. 4.
135. Wenger, N. K.; Lewis, S. J.; Welty, F. K.; Herrington, D. M.; Bittner, V. TNT Steering Committee and Investigators. Beneficial effects of aggressive lowdensity lipoprotein cholesterol lowering in women with stable coronary heart disease in the Treating to New Targets (TNT) study. Heart., 2008, 94, 434-439. (Pubitemid 351444674)
136. Goldstein, M. R.; Mascitelli, L.; Pezzetta, F. The double-edged sword of statin immunomodulation. Int. J. Cardiol., 2009, 135, 128-130
137. Yakirevich, E.; Resnick, M. B. Regulatory T lymphocytes: pivotal components of the host antitumor response. J. Clin. Oncol., 2007, 25, 2506-2508. (Pubitemid 47041221)
138. Mascitelli, L.; Pezzetta, F.; Goldstein, M. R. Statin induced angiogenesis and tumour growth. Eur. J. Intern. Med., 2009, 20, e159.
139. Goldstein, M. R.; Mascitelli, L.; Pezzetta, F. Might the widespread use of statin drugs explain the increase in prevalence of breast carcinoma in situ? Med, Hypotheses., 2010, 74, 613-614.
140. Wang, C. Y.; Shui, H. A.; Chang, T. C. In vivo evidence of duality effects for lovastatin in a nude mouse cancer model. Int. J. Cancer., 2009, 126, 578-582.
141. Goldstein, M. R.; Mascitelli, L.; Pezzetta, F. Statins and colorectal cancer: the jury is still out. A m. J. Gastroenterol., 2009, 104, 2858-2859.
142. Trompet, S.; van Vliet, P.; de Craen, A. J.; Jolles, J.; Buckley, B. M.; Murphy, M. B.; Ford, I.; Macfarlane, P. W.; Sattar, N.; Packard, C. J.; Stott, D. J.; Shepherd, J.; Bollen, E. L.; Blauw, G. J.; Jukema, J. W.; Westendorp, R. G. Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J. Neurol., 2010, 257, 85-90.
143. El-Serag, H. B.; Johnson, M. L.; Hachem, C.; Morgana, R. O. Statins are associated with a reduced risk of hepatocellular carcinoma in a large cohort of patients with diabetes. Gastroente rolog y, 2009, 136, 1601-1608.
144. Kim, W.; Yoon, J. H.; Kim, J. R.; Jang, I. J.; Bang, Y. J.; Kim, Y. J.; Lee, H. S. Synergistic anti-tumor efficacy of lovastatin and protein kinase C-beta inhibitor in hepatocellular carcinoma. Cancer Chemother. Pharmacol., 2009, 64, 497-507.
145. Mausner-Fainberg, K.; Luboshits, G.; Mor, A.; Maysel-Auslender, S:, Rubinstein, A:, Keren, G.; George, J. The effect of HMG-CoA reductase inhibitors on naturally occurring CD4+CD25+ T cells. Athe roscle rosis, 2008, 197, 829-839. (Pubitemid 351417882)
146. Prieto, G. A.; Rosenstein, Y. Oestradiol potentiates the suppressive function of human CD4+CD25+ regulatory T cells by promoting their proliferation. Immunology, 2006, 118, 58-65.
147. Wang, H.; Zhao, L.; Sun, Z.; Sun, L.; Zhang, B.; Zhao, Y. A potential side effect of cyclosporin A: inhibition of CD4 (+) CD25 (+) regulatory T cells in mice. Transplantation, 2006, 11, 1484-1492. (Pubitemid 44967632)
148. Rotta M, Storer BE, Storb RF, Martin PJ, Heimfeld S, Peffer A, Maloney DG, Deeg HJ, Sandmaier BM, Appelbaum FR, Mielcarek M. Doonor statin treatment protects against severe acute graft-versus-host disease after related allogeneic hematopoietic cell transplantation. Blood, 2010, 115, 1288-95.
149. Issat T, Nowis D, Bil J, Winiarska M, Jakobisiak M, Golab J. Antitumor effects of the combination of cholesterol reducing drugs. Oncol Rep., 2011, Apr. 13. doi: 10.3892/or.2011.1261. [Epub ahead of print]
150. Cravedi, P. A.; Ruggenenti, P. A. Remuzzi, G. Sirolimus to replace calcineurin inhibitors? Too early yet. Lancet, 2009, 9671, 1235-1236.
151. Palmer, J. M.; Chen, B. J. Deoliveira, D.; Le, N. D.; Chao, N. J. Novel mechanism of Rapamycin in GVHD: increase in interstitial regulatory T cells. Bone Marrow Transplant., 2010, 45, 379-84.
152. Strauss, L.; Czystowska, M. Szajnik, M.; Mandapathil, M.; Whiteside, T. L.; Differential responses of human regulatory T cells (Treg) and effector T cells to rapamycin. PLoS One, 2009, 6, e5994
153. Thomson, A. W.; Turnquist, H. R.; Raimondi, G. Immunoregulatory functions of mTOR inhibition. Nat Rev Immunol., 2009, 5, 324-337.
154. Lee KJ, Moon JY, Choi HK, Kim HO, Hur G Y, Jung KH, Lee S Y, Kim JH, Shin C, Shim JJ, In KH, Yoo SH, Kang KH, Lee S Y. Immune regulatory effects of simvastatin on regulatory T cell-mediated tumour immune tolerance. Clin Exp Immunol., 2010, 161, 298-305.
155. Kim YC, Kim KK, Shevach EM. Simvastatin induces Foxp3+ T regulatory cells by modulation of transforming growth factor-beta signal transduction. Immunology, 2010, 130, 484-93.