Chemically modified tetracyclines as inhibitors of matrix metalloproteinases

Drug Resistance Updates

Volumn 7, Issue 3, 2004, Pages 195-208

  Acharya, Milin R ^a,b   Venitz, Jürgen ^b   Figg, William D ^a   Sparreboom, Alex ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

Author keywords

Anticancer drugs; Chemically modified tetracyclines; Drug development; Matrix metalloproteinase

Indexed keywords

12ALPHA DEOXY 4 DEDIMETHYLAMINOTETRACYCLINE; 4 DEDIMETHYLAMINO 4 HYDROXYTETRACYCLINE; 4 DEDIMETHYLAMINOCHLOROTETRACYCLINE; 4 DEDIMETHYLAMINODOXYCYCLINE; 4 DEDIMETHYLAMINOSANCYCLINE; 4 DEDIMETHYLAMINOTETRACYCLINE; AE 941; BATIMASTAT; CGS 27023A; CHEMICALLY MODIFIED TETRACYCLINE; DOXYCYCLINE; MARIMASTAT; MATRIX METALLOPROTEINASE; MMI 270; PRINOMASTAT; REBIMASTAT; TANOMASTAT; TETRACYCLINE DERIVATIVE; TETRACYCLINE NITRILE; TETRACYCLINE PYRAZOLE; UNCLASSIFIED DRUG;

CANCER; CANCER GROWTH; CANCER INVASION; CANCER THERAPY; CLINICAL TRIAL; DRUG DESIGN; DRUG INDICATION; DRUG MECHANISM; DRUG POTENCY; DRUG TARGETING; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME KINETICS; ENZYME MECHANISM; ENZYME REGULATION; HUMAN; METASTASIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TARGETING; REVIEW;

EID: 3543090958     PISSN: 13687646     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.drup.2004.04.002     Document Type: Article

References (126)

1. Amin A.R., Patel R.N., Thakker G.D., Lowenstein C.J., Attur M.G., Abramson S.B. Post-transcriptional regulation of inducible nitric oxide synthase mRNA in murine macrophages by doxycycline and chemically modified tetracyclines. FEBS Lett. 410:1997;259-264
2. Basset P., Wolf C., Chambon P. Expression of the stomelysin gene in fibroblastic cells of invasive carcinoma of the breast and other human tissues: a review. Breast Cancer Res. Treat. 24:1993;185-193
3. Bergers G., Javaherian K., Lo K., Folkman J., Hanahan D. Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science. 284:1999;808-812
4. Bettany J.T., Peet N.M., Wolowacz R.G., Skerry T.M., Grabowski P.S. Tetracyclines induce apoptosis in osteoclasts. Bone. 27:2000;75-80
5. Bettany J.T., Wolowacz R.G. Tetracycline derivatives induce apoptosis selectively in cultured monocytes and macrophages but not in mesenchymal cells. Adv. Dent. Res. 12:1998;136-143
6. Blavier L., Patrick I., Declerck S., Yves A. Tissue inhibitors of matrix metalloproteinases in cancer. Ann. N.Y. Acad. Sci. 878:1999;108-119
7. Boolbol S.K., Dannenberg A.J., Chadburn A., et al. Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis. Cancer Res. 56:1996;2556-2560
8. Broxterman H.J., Lankelma J., Hoekman K. Resistance to cytotoxic and anti-angiogenic agents: similarities and differences. Drug Resist. Update. 6:2003;111-127
9. Cancer Trials, 2001. National Cancer Institute (http://www.cancer.gov/ clinical.htm).
10. Catterall J.B., Cawston T.E. Assays of matrix metalloproteinases (MMPs) and MMP inhibitors: bioassays and immunoassays applicable to cell culture medium, serum, and synovial fluid. Methods Mol. Biol. 225:2003;353-364
11. Chambers A., Matrisian L. Changing views of the role of matrix metalloproteinases in metastasis. J. Natl. Cancer Inst. 89:1997;1260-1270
12. Chen J., Bookbinder M., Ryan M.E., Golub L.M., Ashley R., Ramamurthy N.S. Biodistribution of radiolabeled [(3)H] CMT-3 in rats. Curr. Med. Chem. 8:2001;253-256
13. Cianfrocca M., Cooley T.P., Lee J.Y., Rudek M.A., Scadden D.T., Ratner L., Pluda J.M., Figg W.D., Krown S.E., Dezube B.J. Matrix metalloproteinase inhibitor COL-3 in the treatment of AIDS-related Kaposi's sarcoma: a phase I AIDS malignancy consortium study. J. Clin. Oncol. 20:2002;153-159
14. Cillari E., Milano S., D'Agostino P., Di Bella G., La Rosa M., Barbera C., Ferlazzo V., Cammarata G., Grimaudo S., Tolomeo M., Feo S. Modulation of nitric oxide production by tetracyclines and chemically modified tetracyclines. Adv. Dent. Res. 12:1998;126-130
15. Coussens L.M., Fingelton B., Matrisian L.M. MMP inhibitors and cancer: trials and tribulations. Science. 295:2002;2387-2392
16. Curran S., Murray G.I. Matrix metalloproteinases in tumor invasion and metastasis. J. Pathol. 189:1999;300-308
17. D'Agostino P., Ferlazzo V., Milano S., La Rosa M., Di Bella G., Caruso R., Barbera C., Grimaudo S., Tolomeo M., Feo S., Cillari E. Anti-inflammatory effects of chemically modified tetracyclines by the inhibition of nitric oxide and interleukin-12 synthesis in J774 cell line. Int. Immunopharmacol. 1:2001;1765-1776
18. D'Agostino P., Ferlazzo V., Milano S., La Rosa M., Di Bella G., Caruso R., Barbera C., Grimaudo S., Tolomeo M., Feo S., Cillari E. Chemically modified tetracyclines induce cytotoxic effects against J774 tumour cell line by activating the apoptotic pathway. Int. Immunopharmacol. 3:2003;63-73
19. David L., Nesland J.M., Holm R., Sobrinho-Simoes M. Expression of laminin, collagen IV, fibronectin, and type IV collagenase in gastric carcinoma. An immunohistochemical study of 87 patients. Cancer. 73:1994;518-527
20. Duivenvoorden W., Hirte H., Singh G. Use of tetracycline as an inhibitor of matrix metalloproteinase activity secreted by human bone-metastasizing cancer cells. Invasion Metast. 17:1997;312-322
21. Egeblad M., Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat. Rev. Cancer. 2:2002;161-174
22. Eklund K.K., Sorsa T. Tetracycline derivative CMT-3 inhibits cytokine production, degranulation, and proliferation in cultured mouse and human mast cells. Ann. N.Y. Acad. Sci. 878:1999;689-691
23. Fife R., Sledge G. Effects of doxycycline on in vitro growth, migration, and gelatinase activity of breast carcinoma cells. J. Lab. Clin. Med. 125:1995;407-411
24. Fife R., Sledge G., Roth B., Proctor C. Effects of doxycycline on human prostate cancer cells in vitro. Cancer Lett. 127:1998;37-41
25. Fife R.S., Rougraff B., Proctor C., Sledge G. Induction of apoptosis by doxycycline in cultured human osteosarcoma cells. J. Lab. Clin. Med. 130:1997;530-534
26. Fife R.S., Sledge G.W. Jr., Sissons S., Zerler B. Effects of tetracyclines on angiogenesis in vitro. Cancer Lett. 153:2000;75-78
27. Fingleton B., Heppner G., Crawford H., Matrisian L. Matrilysin in early stage intestinal tumorigenesis. APMIS. 107:1999;102-110
28. Fong K., Kida Y., Zimmermann P., Smith P. TIMP-1 and adverse prognosis in non-small cell lung cancer. Clin. Cancer Res. 2:1996;1364-1372
29. Gabler W.L., Smith J., Tsukuda N. Comparison of doxycycline and a chemically modified tetracycline inhibition of leukocyte functions. Res. Commun. Chem. Pathol. Pharmacol. 78:1992;151-160
30. Gelmon K., Eiserhauer E., Harris A., Ratain M., Workman P. Anticancer agents targeting signaling molecules and cancer cell environment: challenges for drug development? J. Natl. Cancer Inst. 91:1999;1281-1287
31. Gilbertson-Beadling S., Powers E.A., Stamp-Cole M., Scott P.S., Wallace T.L., Copeland J., Petzold G., Mitchell M., Ledbetter S., Poorman R. The tetracycline analogs minocycline and doxycycline inhibit angiogenesis in vitro by a non-metalloproteinase-dependent mechanism. Cancer Chemother. Pharmacol. 36:1995;418-424
32. Golub L.M. Reduction with tetracyclines of excessive collagen degradation in periodontal and other diseases. N.Y. State Dent. J. 56:1990;24-26
33. Golub L.M., Ramamurthy N., McNamara T.F., Gomes B., Wolff M., Casino A., Kapoor A., Zambon J., Ciancio S., Schneir M. Tetracyclines inhibit tissue collagenase activity. A new mechanism in the treatment of periodontal disease. J. Periodont. Res. 19:1984;651-655
34. Golub L.M., Goodson J.M., Lee H.M., Vidal A.M., McNamara T.F., Ramamurthy N.S. Tetracyclines inhibit tissue collagenases. Effects of ingested low-dose and local delivery systems. J. Periodontol. 56:1985a;93-97
35. Golub L.M., Wolff M., Lee H.M., McNamara T.F., Ramamurthy N.S., Zambon J., Ciancio S. Further evidence that tetracyclines inhibit collagenase activity in human crevicular fluid and from other mammalian sources. J. Periodont. Res. 20:1985b;12-23
36. Golub L.M., McNamara T.F., D'Angelo G., Greenwald R.A., Ramamurthy N.S. A non-antibacterial chemically-modified tetracycline inhibits mammalian collagenase activity. J. Dent. Res. 66:1987;1310-1314
37. Golub L.M., Ramamurthy N.S., McNamara T.F., Greenwald R.A., Rifkin B.R. Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old family of drugs. Crit. Rev. Oral. Biol. Med. 2:1991;297-321
38. Golub L., Greenwald R., Ramamurthy N., Zucker S., Ramsammy L., McNamara T. Tetracyclines (TCs) inhibit matrix metalloproteinases (MMPs): in vivo effects in arthritic and diabetic rats and new in vitro studies. Matrix. 1:1992a;315-316
39. Golub L.M., Suomalainen K., Sorsa T. Host modulation with tetracyclines and their chemically modified analogues. Curr. Opin. Dent. 2:1992b;80-90
40. Golub L.M., Lee H.M., Ryan M.E., Giannobile W.V., Payne J., Sorsa T. Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms. Adv. Dent. Res. 12:1998;12-26
41. Greenwald, R.A., Hillen, W., Nelson, M., 2001. Tetracyclines in Biology, Chemistry and Medicine. Basel, Boston, p. 336.
42. Gu Y., Lee H.M., Roemer E.J., Musacchia L., Golub L.M., Simon S.R. Inhibition of tumor cell invasiveness by chemically modified tetracyclines. Curr. Med. Chem. 8:2001;261-270
43. Guay G.G., Rothstein D.M. Expression of the tetK gene from Staphylococcus aureus in Escherischia coli: comparison of substrate specifities of TetA(B), TetA(C), and TetK efflux proteins. Antimicrob. Agents Chemother. 37:1993;191-198
44. Gupta M.K., Mishra P., Prathipati P., Saxena A.K. 2D-QSAR in hydroxamic acid derivatives as peptide deformylase inhibitors and antibacterial agents. Bioorg. Med. Chem. 10:2002;3713-3716
45. Hanemaaijer R., Visser H., Koolwijk P., Sorsa T., Salo T., Golub L.M., van Hinsbergh V.W. Inhibition of MMP synthesis by doxycycline and chemically modified tetracyclines (CMTs) in human endothelial cells. Adv. Dent. Res. 12:1998;114-118
46. Heath E.I., Grochow L.B. Clinical potential of matrix metalloprotease inhibitors in cancer therapy. Drugs. 59:2000;1043-1055
47. Hendrix M.J., Seftor E.A., Kirschmann D.A., Quaranta V., Seftor R.E. Remodeling of the microenvironment by aggressive melanoma tumor cells. Ann. N.Y. Acad. Sci. 995:2003;151-161
48. Henriet P., Blavier L., DeClerck Y. Tissue inhibitors of metalloproteinases (TIMP) in invasion and proliferation. APMIS. 107:1999;111-119
49. Hess A.R., Seftor E.A., Seftor R.E., Hendrix M.J. Phosphoinositide 3-kinase regulates membrane Type 1-matrix metalloproteinase (MMP) and MMP-2 activity during melanoma cell vasculogenic mimicry. Cancer Res. 63:2003;4757-4762
50. Hewitt R.E., Leach I.H., Powe D.G., Clark I.M., Cawston T.E., Turner D.R. Distribution of collagenase and tissue inhibitor of metalloproteinases (TIMP) in colorectal tumours. Int. J. Cancer. 49:1991;666-672
51. Hidalgo M., Eckhardt G.S. Development of matrix metalloproteinase inhibitors in cancer therapy. J. Natl. Cancer Inst. 93:2001;178-193
52. Imren S., Kohn D.B., Shimada H., Blavier L., DeClerck Y.A. Overexpression of tissue inhibitor of metalloproteinases-2 retroviral-mediated gene transfer in vivo inhibits tumor growth and invasion. Cancer Res. 56:1996;2891-2895
53. Johansson N., Ahonen M., Kahari V.M. Matrix metalloproteinases in tumor invasion. Cell. Mol. Life Sci. 57:2000;5-15
54. Kahari V.M., Saarilho-Kere U. Matrix metalloproteinases in skin. Exp. Dermatol. 6:1997;199-213
55. Kahari V.M., Saarialho-Kere U. Matrix metalloproteinases and their inhibitors in tumor growth and invasion. Ann. Med. 31:1999;34-45
56. Karameris A., Panagou P., Tsilalis T., Bouros D. Association of expression of metalloproteinases and their inhibitors with the metastatic potential of squamous lung carcinomas. Am. J. Respir. Crit. Care Med. 156:1997;1930-1936
57. Karimbux N.Y., Ramamurthy N.S., Golub L.M., Nishimura I. Tissue healing with doxycycline and chemically modified tetracycline treatments in rats with Porphyromonas gingivalis-induced periodontitis. Ann. N.Y. Acad. Sci. 732:1994;433-435
58. Kirkwood K.L., Golub L.M., Bradford P.G. Non-antimicrobial and antimicrobial tetracyclines inhibit IL-6 expression in murine osteoblasts. Ann. N.Y. Acad. Sci. 878:1999;667-670
59. Kleiner D.E., Stetler-Stevenson W.G. Matrix metalloproteinases and metastasis. Cancer Chemother. Pharmacol. 43:1999;S42-S51
60. Lauhio A., Konttinen Y.T., Salo T., Tschesche H., Nordstrom D., Lahdevirta J., Golub L.M., Sorsa T. The in vivo effect of doxycycline treatment on matrix metalloproteinases in reactive arthritis. Ann. N.Y. Acad. Sci. 732:1994;431-432
61. Lauhio A., Salo T., Tjaderhane L., Lahdevirta J., Golub L.M., Sorsa T. Tetracyclines in treatment of rheumatoid arthritis. Lancet. 346:1995;645-646
62. Lee H.M., Golub L.M., Cao J., Teronen O., Laitinen M., Salo T., Zucker S., Sorsa T. CMT-3, a non-antimicrobial tetracycline (TC), inhibits MT1-MMP activity: relevance to cancer. Curr. Med. Chem. 8:2001;257-260
63. Li J., Huynh H., Chan E. Evidence for dissolution rate-limited absorption in COL-3, a MMPI, leading to the irregular absorption profile in rats after oral administration. Pharm. Res. 19:2002;1655-1662
64. Liotta L.A., Stetler-Stevenson W. Metalloproteinases and cancer invasion. Semin. Cancer Biol. 1:1990;99-106
65. Liotta L.A., Tryggvason K., Garbisa S., Hart I., Foltz C.M., Shafie S. Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature. 284:1980;67-68
66. Liu Y., Ramamurthy N., Marecek J., Lee H.M., Chen J.L., Ryan M.E., Rifkin B.R., Golub L.M. The lipophilicity, pharmacokinetics, and cellular uptake of different chemically-modified tetracyclines (CMTs). Curr. Med. Chem. 8:2001;243-252
67. Llavaneras A., Ramamurthy N.S., Heikkila P., Teronen O., Salo T., Rifkin B.R., Ryan M.E., Golub L.M., Sorsa T. A combination of a chemically modified doxycycline and a bisphosphonate synergistically inhibits endotoxin-induced periodontal breakdown in rats. J. Periodontol. 72:2001;1069-1077
68. Lokeshwar B.L. MMP inhibition in prostate cancer. Ann. N.Y. Acad. Sci. 878:1999;271-289
69. Lokeshwar B.L., Houston-Clark H.L., Selzer M.G., Block N.L., Golub L.M. Potential application of a chemically modified non-antimicrobial tetracycline (CMT-3) against metastatic prostate cancer. Adv. Dent. Res. 12:1998;97-102
70. Lokeshwar B.L., Escatel E., Zhu B. Cytotoxic activity and inhibition of tumor cell invasion by derivatives of a chemically modified tetracycline CMT-3 (COL-3). Curr. Med. Chem. 8:2001;271-279
71. Lokeshwar B.L., Selzer M.G., Zhu B.Q., Block N.L., Golub L.M. Inhibition of cell proliferation, invasion, tumor growth and metastasis by an oral non-antimicrobial tetracycline analog (COL-3) in a metastatic prostate cancer model. Int. J. Cancer. 98:2002;297-309
72. Lopez-Otin C., Overall C. Protease degradomics, a new challenge for proteomics. Nat. Rev. Mol. Cell. Biol. 3:2002;509-519
73. Lukkonen A., Sorsa T., Salo T., Tervahartiala T., Koivunen E., Golub L., Simon S., Stenman U.H. Down-regulation of trypsinogen-2 expression by chemically modified tetracyclines: association with reduced cancer cell migration. Int. J. Cancer. 86:2000;577-581
74. Makela M., Sorsa T., Uitto V.J., Salo T., Teronen O., Larjava H. The effects of chemically modified tetracyclines (CMTs) on human keratinocyte proliferation and migration. Adv. Dent. Res. 12:1998;131-135
75. Mealey K.L., Barhoumi R., Burghardt R.C., Safe S., Kochevar D.T. Doxycycline induces expression of P glycoprotein in MCF-7 breast carcinoma cells. Antimicrob. Agents Chemother. 46:2002;755-761
76. Meng Q., Xu J., Goldberg I.D., Rosen E.M., Greenwald R.A., Fan S. Influence of chemically modified tetracyclines on proliferation, invasion and migration properties of MDA-MB-468 human breast cancer cells. Clin. Exp. Metastasis. 18:2000;139-146
77. Mitsiades N., Poulaki V., Mitsiades C.S., Anderson K.C. Induction of tumour cell apoptosis by matrix metalloproteinase inhibitors: new tricks from a (not so) old drug. Exp. Opin. Investig. Drugs. 10:2001;1075-1084
78. Morin P.J. Drug resistance and the microenvironment: nature and nurture. Drug Resist. Update. 6:2003;169-172
79. Munoz-Mateu, M., de'Grafenried, L., Eckhardt, S., Malik, S., Rizzo, J., Kuhn, J., Rowinsky, E., Hidalgo, M., 2001. Pharmacodynamic studies of Col-3, a novel matrix metalloproteinase inhibitor in patients with advanced cancer. Proc. Am. Soc. Clin. Oncol. 20 302 (abstract).
80. Myers S.A., Wolowacz R.G. Tetracycline-based MMP inhibitors can prevent fibroblast-mediated collagen gel contraction in vitro. Adv. Dent. Res. 12:1998;86-93
81. Nagase H., Frederick-Woessner J. Jr. Matrix metalloproteinases. J. Biol. Chem. 270:1999;21491-21494
82. Nelson A.R., Fingleton B., Rothenberg M.L., Matrisian L.M. Matrix metalloproteinases: biologic activity and clinical implications. J. Clin. Oncol. 18:2000;1135-1149
83. Overall C., Lopez-Otin C. Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat. Rev. Cancer. 2:2002;657-672
84. Patel R.N., Attur M.G., Dave M.N., Patel I.V., Stuchin S.A., Abramson S.B., Amin A.R. A novel mechanism of action of chemically modified tetracyclines: inhibition of COX-2-mediated prostaglandin E2 production. J. Immunol. 163:1999;3459-3467
85. Pinsuwan S., Alvarez-Nunez F.A., Tabibi E.S., Yalkowsky S.H. Degradation kinetics of 4-dedimethylamino sancycline, a new anti-tumor agent, in aqueous solutions. Int. J. Pharm. 181:1999a;31-40
86. Pinsuwan S., Alvarez-Nunez F.A., Tabibi S.E., Yalkowsky S.H. Spectrophotometric determination of acidity constants of 4-dedimethylamino sancycline (Col-3), a new antitumor drug. J. Pharm. Sci. 88:1999b;535-537
87. Pirila E., Ramamurthy N., Maisi P., McClain S., Kucine A., Wahlgren J., Golub L., Salo T., Sorsa T. Wound healing in ovariectomized rats: effects of chemically modified tetracycline (CMT-8) and estrogen on matrix metalloproteinases-8, -13 and type I collagen expression. Curr. Med. Chem. 8:2001;281-294
88. Pirila E., Parikka M., Ramamurthy N.S., Maisi P., McClain S., Kucine A., Tervahartiala T., Prikk K., Golub L.M., Salo T., Sorsa T. Chemically modified tetracycline (CMT-8) and estrogen promote wound healing in ovariectomized rats: effects on matrix metalloproteinase-2, membrane type 1 matrix metalloproteinase, and laminin-5 gamma2-chain. Wound Repair Regen. 10:2002;38-51
89. Poulaki V., Mitsiades C.S., Mitsiades N. The role of Fas and FasL as mediators of anticancer chemotherapy. Drug Resist. Update. 4:2001;233-242
90. Powe D., Brough J., Carter G., Ravery V., Angulo J., Shamsa F. TIMP-3 mRNA expression is regionally increased in moderately and poorly differentiated colorectal adenocarcinoma. Br. J. Cancer. 75:1997;1678-1683
91. Pruzanski W., Stefanski E., Vadas P., McNamara T.F., Ramamurthy N., Golub L.M. Chemically modified non-antimicrobial tetracyclines inhibit activity of phospholipases A2. J. Rheumatol. 25:1998;1807-1812
92. Purcell W., Rudek M., Hidalgo M. Development of matrix metalloproteinase inhibitors in cancer therapy. Hematol. Oncol. Clin. North Am. 16:2002;1189
93. Ratnikov B.I., Deryugina E.I., Strongin A.Y. Gelatin zymography and substrate cleavage assays of matrix metalloproteinase-2 in breast carcinoma cells overexpressing membrane type-1 matrix metalloproteinase. Lab. Invest. 82:2002;1583-1590
94. Rawal S.Y., Rawal Y.B. Non-antimicrobial properties of tetracyclines - dental and medical implications. West Indian Med. J. 50:2001;105-108
95. Ray J.M., Stetler-Stevenson W. The role of matrix metalloproteinases and their inhibitors in tumor invasion, metastasis and angiogenesis. Eur. Respir. J. 7:1994;2060-2072
96. Rifkin B.R., Vernillo A.T., Golub L.M., Ramamurthy N.S. Modulation of bone resorption by tetracyclines. Ann. N.Y. Acad. Sci. 732:1994;165-180
97. Rowinsky E., Eckhardt S., Rizzo J., Hammond L., Campbell E., Felton S., Denis L., Rha S., Schwartz G., Tolcher A., Izbecka E., Hidalgo M. Protracted daily treatment of COL-3, an oral tetracycline analog, MMP inhibitor is feasible a phase I, pharmacokinetic, and biological study. Proc. Am. Soc. Clin. Oncol. 19:2000a;700. (abstract)
98. Rowinsky E., Eckhardt S., Rizzo J., Hammond L., Campbell E., Felton S., Denis L., Rha S., Schwartz G., Tolcher A., Izbecka E., Hidalgo M. A phase I and pharmacokinetic PK study of COL-3 an oral tetracycline analog and selective MMP inhibitor. Clin. Cancer Res. 6:2000b;292a. (abstract)
99. Rudek M.A., March C.L., Bauer K.S. Jr., Pluda J.M., Figg W.D. High-performance liquid chromatography with mass spectrometry detection for quantitating COL-3, a chemically modified tetracycline, in human plasma. J. Pharm. Biomed. Anal. 22:2000;1003-1014
100. Rudek M.A., Figg W.D., Dyer V., Dahut W., Turner M.L., Steinberg S.M., Liewehr D.J., Kohler D.R., Pluda J.M., Reed E. Phase I clinical trial of oral COL-3, a matrix metalloproteinase inhibitor, in patients with refractory metastatic cancer. J. Clin. Oncol. 19:2001;584-592
101. Rudek M.A., Venitz J., Figg W.D. Matrix metalloproteinase inhibitors: do they have a place in anticancer therapy? Pharmacotherapy. 22:2002;705-720
102. Ryan M.E., Ramamurthy N.S., Golub L.M. Tetracyclines inhibit protein glycation in experimental diabetes. Adv. Dent. Res. 12:1998;152-158
103. Saikali Z., Singh G. Doxycycline and other tetracyclines in the treatment of bone metastasis. Anticancer Drugs. 14:2003;773-778
104. Schatzkin A., Gail M. The promise and peril of surrogate end-points in cancer research. Nat. Rev. Cancer. 2:2002;19-27
105. Seftor E.A., Seftor R.E., Nieva D.R., Hendrix M.J. Application of chemically modified tetracyclines (CMTs) in experimental models of cancer and arthritis. Adv. Dent. Res. 12:1998a;103-110
106. Seftor R.E., Seftor E.A., De Larco J.E., Kleiner D.E., Leferson J., Stetler-Stevenson W.G., McNamara T.F., Golub L.M., Hendrix M.J. Chemically modified tetracyclines inhibit human melanoma cell invasion and metastasis. Clin. Exp. Metastasis. 16:1998b;217-225
107. Seftor R.E., Seftor E.A., Koshikawa N., Meltzer P.S., Gardner L.M., Bilban M., Stetler-Stevenson W.G., Quaranta V., Hendrix M.J. Cooperative interactions of laminin 5 gamma2 chain, matrix metalloproteinase-2, and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma. Cancer Res. 61:2001;6322-6327
108. Seftor R.E., Seftor E.A., Kirschmann D.A., Hendrix M.J. Targeting the tumor microenvironment with chemically modified tetracyclines: inhibition of laminin 5 gamma2 chain promigratory fragments and vasculogenic mimicry. Mol. Cancer Ther. 1:2002;1173-1179
109. Selzer M.G., Zhu B., Block N.L., Lokeshwar B.L. CMT-3, a chemically modified tetracycline, inhibits bony metastases and delays the development of paraplegia in a rat model of prostate cancer. Ann. N.Y. Acad. Sci. 878:1999;678-682
110. Smith G., Mickler E., Hasty K., Brandt K. Specificity of inhibition of matrix metalloproteinase activity by doxycycline. Arthritis Rheum. 42:1999;1140-1146
111. Sorsa T., Suomalainen K., Ingman T., Lindy O., Lauhio A., Saari H., Halinen S., Konttinen Y.T., Golub L.M. Collagenase inhibition by tetracyclines. Duodecim. 107:1991;1966-1969
112. Stetler-Stevenson W.G., Hewitt R., Corcoran M. MMP and tumor invasion: from correlation and casualty to the clinic. Semin. Cancer Biol. 7:1996;147-154
113. Talhouk R., Bissel M., Werb Z. Coordinated expression of extracellular matrix degrading proteinases and their inhibitors regulates mammary epithelial function during involution. J. Cell. Biol. 118:1992;1271-1282
114. Taniguchi S., Ilamura T., Kasuki T. Correlation between spontaneous metastatic potential and type I collagenolytic activity in a human pancreatic cell line (SUIT-2) and sublines. Clin. Exp. Metast. 10:1992;259-266
115. Teicher B.A., Herman T.S., Holden S.A., Wang Y.Y., Pfeffer M.R., Crawford J.W., Frei E. III Tumor resistance to alkylating agents conferred by mechanisms operative only in vivo. Science. 247:1990;1457-1461
116. Tolomeo M., Grimaudo S., Milano S., La Rosa M., Ferlazzo V., Di Bella G., Barbera C., Simoni D., D'Agostino P., Cillari E. Effects of chemically modified tetracyclines (CMTs) in sensitive, multidrug resistant and apoptosis resistant leukaemia cell lines. Br. J. Pharmacol. 133:2001;306-314
117. Trachtman H., Futterweit S., Greenwald R., Moak S., Singhal P., Franki N., Amin A.R. Chemically modified tetracyclines inhibit inducible nitric oxide synthase expression and nitric oxide production in cultured rat mesangial cells. Biochem. Biophys. Res. Commun. 229:1996;243-248
118. Tsuiji M., Kawano S., Dubois R.N. Cyclooxygenase-2 expression in human colon cancer cells increase metastatic potential. Proc. Natl. Acad. Sci. U.S.A. 94:1997;3336-3340
119. Vernillo, A.T., Ramamurthy, N.S., Golub, L.M., Rifkin, B.R., 1994. The nonantimicrobial properties of tetracycline for the treatment of periodontal disease. Curr. Opin. Periodontol., 111-118.
120. Weissleder R. Scaling down imaging: molecular mapping of cancer in mice. Nat. Rev. Cancer. 2:2002;11-18
121. West K.A., Castillo S.S., Dennis P.A. Activation of the PI3K/Akt pathway and chemotherapeutic resistance. Drug Resist. Update. 5:2002;234-248
122. Wilson C., Heppner K., Labosky P., Hogan B., Matrisian L. Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc. Natl. Acad. Sci. U.S.A. 94:1997;1402-1407
123. Wysocki A.B., Staiano-Coico L., Grinnell F. Wound fluid from chronic leg ulcers contains elevated levels of MMP-2 and MMP-9. J. Invest. Dermatol. 101:1993;64-68
124. Yoshiji H., Gomez D., Horgeirsson U. Enhanced RNA expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in human breast cancer. Br. J. Cancer. 69:1996;131-134
125. Yu Z., Leung M.K., Ramamurthy N.S., McNamara T.F., Golub L.M. HPLC determination of a chemically modified nonantimicrobial tetracycline: biological implications. Biochem. Med. Metab. Biol. 47:1992;10-20
126. Zeng Z., Cohen A., Zhang Z., Stetler-Stevenson W., Guillem J. Elevated tissue inhibitor of metalloproteinase 1 RNA in colorectal cancer stroma correlates with lymph nodes and distinct metastasis. Clin. Cancer Res. 1:1995;899-906