1. Mirabello L, Rebecca JT , Savage SA. Osteosarcoma incidence and survival improvement. Cancer. 2009;115(7):1531–43.
2. Lindsey BA, Markel JE, Kleinerman ES. Osteosarcoma Overview. Rheumatol Ther. 2017;4(1):25–43.
3. Durfee RA, Mohammed M, Luu HH. Review of Osteosarcoma and Current Management. Rheumatol Ther. 2016;3(2):221–43.
4. Bruland ØS, Høifødt H, Hall KS, Smeland S, Fodstad Ø. Bone marrow micrometastases studied by an immunomagnetic isolation procedure in extremity localized non-metastatic osteosarcoma patients. In: Jaffe N., Bruland O. BS, editor. Pediatric and Adolescent Osteosarcoma Cancer Treatment and Research [Internet]. Springer, Boston, MA; 2009. p. 509–15. Available from: https://pubmed.ncbi.nlm.nih.gov/20213412/
5. Huang X, Zhao J, Bai J, Shen H, Zhang B, Deng L, et al. Risk and clinicopathological features of osteosarcoma metastasis to the lung: A population-based study. J Bone Oncol. 2019;16(November 2018).
6. Nataraj V, Rastogi S, Khan SA, Sharma MC, Agarwala S, Vishnubhatla S, et al. Prognosticating metastatic osteosarcoma treated with uniform chemotherapy protocol without high dose methotrexate and delayed metastasectomy: a single center experience of 102 patients. Clin Transl Oncol. 2016;18(9):937–44.
7. Zhang Y, Yang J, Zhao N, Wang C, Kamar S, Zhou Y, et al. Progress in the chemotherapeutic treatment of osteosarcoma. Oncol Lett. 2018;16(5):6228–37.
8. Sleire L, Førde-Tislevoll HE, Netland IA, Leiss L, Skeie BS, Enger PØ. Drug repurposing in cancer. Pharmacol Res [Internet]. 2017;124:74–91. Available from: http://dx.doi.org/10.1016/j.phrs.2017.07.013
9. Galván-Salazar HR, Soriano-Hernández AD, Montes-Galindo DA, Espíritu GC, Guzman-Esquivel J, Rodríguez-Sánchez IP, et al. Preclinical trial on the use of doxycycline for the treatment of adenocarcinoma of the duodenum. Mol Clin Oncol. 2016;5(5):657–9.
10. Lin CC, Lo MC, Moody RR, Stevers NO, Tinsley SL, Sun D. Doxycycline targets aldehyde dehydrogenase‑positive breast cancer stem cells. Oncol Rep. 2018 Jun;39(6):3041-3047.
11. Matsumoto T, Uchiumi T, Monji K, Yagi M, Setoyama D, Amamoto R, Matsushima Y, Shiota M, Eto M, Kang D. Doxycycline induces apoptosis via ER stress selectively to cells with a cancer stem cell-like properties: importance of stem cell plasticity. Oncogenesis. 2017 Nov 29;6(11):397.
12. Scatena C, Roncella M, Di Paolo A, Aretini P, Menicagli M, Fanelli G, Marini C, Mazzanti CM, Ghilli M, Sotgia F, Lisanti MP, Naccarato AG. Doxycycline, an Inhibitor of Mitochondrial Biogenesis, Effectively Reduces Cancer Stem Cells (CSCs) in Early Breast Cancer Patients: A Clinical Pilot Study. Front Oncol. 2018 Oct 12;8:452.
13. Cakir Y HK. Direct action by doxycycline against canine osteosarcoma cell proliferation and collagenase (MMP-1) activity in vitro. In Vivo (Brooklyn) [Internet]. 1999;13(4):327–31. Available from: https://pubmed.ncbi.nlm.nih.gov/10586373/.
14. Fife RS, Rougraff BT, Proctor C, Sledge GW Jr. Inhibition of proliferation and induction of apoptosis by doxycycline in cultured human osteosarcoma cells. J Lab Clin Med. 1997 Nov;130(5):530-4.
15. Roomi MW, Kalinovsky T, Rath M, Niedzwiecki A. In vitro modulation of MMP-2 and MMP-9 in pediatric human sarcoma cell lines by cytokines, inducers and inhibitors. Int J Oncol. 2014;44(1):27–34.
16. Lipowsky HH, Sah R, Lescanic A. Relative roles of doxycycline and cation chelation in endothelial glycan shedding and adhesion of leukocytes. Am J Physiol - Hear Circ Physiol. 2011;300(2):415–23.
17. Siddhartha R, Garg M. Molecular and clinical insights of matrix metalloproteinases into cancer spread and potential therapeutic interventions. Toxicol Appl Pharmacol. 2021 Sep 1;426:115593.
18. Quintero-Fabián S, Arreola R, Becerril-Villanueva E, Torres-Romero JC, Arana-Argáez V, Lara-Riegos J, et al. Role of Matrix Metalloproteinases in Angiogenesis and Cancer. Front Oncol. 2019;9(December):1–21.
19. Tang H, Tang Z, Jiang Y, Wei W, Lu J. Pathological and therapeutic aspects of matrix metalloproteinases: Implications in osteosarcoma. Asia Pac J Clin Oncol. 2019;15(4):218–24.
20. Ebrahem Q, Chaurasia SS, Vasanji A, Qi JH, Klenotic PA, Cutler A, et al. Cross-talk between vascular endothelial growth factor and matrix metalloproteinases in the induction of neovascularization in vivo. Am J Pathol [Internet]. 2010;176(1):496–503. Available from: http://dx.doi.org/10.2353/ajpath.2010.080642
21. Hurst RE, Bastian A, Bailey-Downs L, Ihnat MA. Targeting dormant micrometastases: Rationale, evidence to date and clinical implications. Ther Adv Med Oncol. 2016;8(2):126–37.
22. Armakolas A, Kaparelou M, Dimakakos A, Papageorgiou E, Armakolas N, Antonopoulos A, et al. Oncogenic role of the Ec peptide of the IGF-1Ec isoform in prostate cancer. Mol Med. 2015;21:167–79.
23. Liang CC, Park AY, Guan JL. In vitro scratch assay: A convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007;2(2):329–33.
24. Rieger AM, Nelson KL, Konowalchuk JD, Barreda DR. Modified annexin V/propidium iodide apoptosis assay for accurate assessment of cell death. J Vis Exp. 2011;(50):3–6.
25. Hong ES, Burkett SS, Morrow J, Lizardo MM, Osborne T, Li SQ, et al. Characterization of the metastatic phenotype of a panel of established osteosarcoma cells. Oncotarget. 2015;6(30):29469–81.
26. Lauvrak SU, Munthe E, Kresse SH, Stratford EW, Namløs HM, Meza-Zepeda LA, Myklebost O. Functional characterisation of osteosarcoma cell lines and identification of mRNAs and miRNAs associated with aggressive cancer phenotypes. Br J Cancer. 2013 Oct 15;109(8):2228-36. doi: 10.1038/bjc.2013.549.
27. Jacques C, Renema N, Ory B, Walkley CR, Grigoriadis AE, Heymann D. Murine Models of Bone Sarcomas. Methods Mol Biol. 2019;1914:331-342.
28. Price JE. Spontaneous and experimental metastasis models: nude mice. Methods Mol Biol. 2014;1070:223-33.
29. Yuan J, Ossendorf C, Szatkowski JP, Bronk JT, Maran A, Yaszemski M, Bolander ME, Sarkar G, Fuchs B. Osteoblastic and osteolytic human osteosarcomas can be studied with a new xenograft mouse model producing spontaneous metastases. Cancer Invest. 2009 May;27(4):435-42.
30. Luu HH, Kang Q, Park JK, Si W, Luo Q, Jiang W, Yin H, Montag AG, Simon MA, Peabody TD, Haydon RC, Rinker-Schaeffer CW, He TC. An orthotopic model of human osteosarcoma growth and spontaneous pulmonary metastasis. Clin Exp Metastasis. 2005;22(4):319-29.
31. Scott MC, Tomiyasu H, Garbe JR, Cornax I, Amaya C, O’Sullivan MG, et al. Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity and biological behavior. DMM Dis Model Mech. 2016;9(12):1435–44.
32. Uluçkan Ö, Segaliny A, Botter S, Santiago JM, Mutsaers AJ. Preclinical mouse models of osteosarcoma. Bonekey Rep. 2015 May 6;4:670.
33. Tang X, Wang X, Zhao YY, Curtis JM, Brindley DN. Doxycycline attenuates breast cancer related inflammation by decreasing plasma lysophosphatidate concentrations and inhibiting NF-ΚB activation. Mol Cancer. 2017;16(1):1–13.
34. Fourman MS, Mahjoub A, Mandell JB, Yu S, Tebbets JC, Crasto JA, et al. Quantitative primary tumor indocyanine green measurements predict osteosarcoma metastatic lung burden in a mouse model. Clin Orthop Relat Res. 2018;476(3):479–87.
35. Frohlich JR, Alarcón CN, Toarmino CR, Sunseri AK, Hockman TM. Comparison of Serial Blood Collection by Facial Vein and Retrobulbar Methods in C57BL/6 Mice. J Am Assoc Lab Anim Sci. 2018 Jul 1;57(4):382-391.
36. Parasuraman S, Raveendran R, Kesavan R. Blood sample collection in small laboratory animals. J Pharmacol Pharmacother. 2010;1(2):87–93.
37. Jirkof P, Tourvieille A, Cinelli P, Arras M. Buprenorphine for pain relief in mice: repeated injections vs sustained-release depot formulation. Lab Anim. 2015 Jul;49(3):177-87.
38. Yu Y, Lee P, Ke Y, Zhang Y, Yu Q, Lee J, Li M, Song J, Chen J, Dai J, Do Couto FJ, An Z, Zhu W, Yu GL. A humanized anti-VEGF rabbit monoclonal antibody inhibits angiogenesis and blocks tumor growth in xenograft models. PLoS One. 2010 Feb 5;5(2):e9072.
39. Kim SW, Roh J, Park CS. Immunohistochemistry for Pathologists: Protocols, Pitfalls, and Tips. J Pathol Transl Med. 2016 Nov;50(6):411-418. doi: 10.4132/jptm.2016.08.08.
40. Raimondi L, De Luca A, Costa V, Amodio N, Carina V, Bellavia D, Tassone P, Pagani S, Fini M, Alessandro R, Giavaresi G. Circulating biomarkers in osteosarcoma: new translational tools for diagnosis and treatment. Oncotarget. 2017 Aug 3;8(59):100831-100851.
41. Zhu QS, Rosenblatt K, Huang KL, Lahat G, Brobey R, Bolshakov S, Nguyen T, Ding Z, Belousov R, Bill K, Luo X, Lazar A, Dicker A, Mills GB, Hung MC, Lev D. Vimentin is a novel AKT1 target mediating motility and invasion. Oncogene. 2011 Jan 27;30(4):457-70.
42. Jolly MK, Ware KE, Xu S, Gilja S, Shetler S, Yang Y, Wang X, Austin RG, Runyambo D, Hish AJ, Bartholf DeWitt S, George JT, Kreulen RT, Boss MK, Lazarides AL, Kerr DL, Gerber DG, Sivaraj D, Armstrong AJ, Dewhirst MW, Eward WC, Levine H, Somarelli JA. E-Cadherin Represses Anchorage-Independent Growth in Sarcomas through Both Signaling and Mechanical Mechanisms. Mol Cancer Res. 2019 Jun;17(6):1391-1402.
43. Cates JM, Dupont WD. Cytologic anaplasia is a prognostic factor in osteosarcoma biopsies, but mitotic rate or extent of spontaneous tumor necrosis are not: a critique of the College of American Pathologists Bone Biopsy template. Mod Pathol. 2017 Jan;30(1):52-59.
44. Jong R, Davis AM, Mendes MG, Wunder JS, Bell RS, Kandel R. Proliferative activity (ki-67 expression) and outcome in high grade osteosarcoma: a study of 27 cases. Sarcoma. 2000;4(1-2):47-55.
45. Ren L, Khanna C. Role of ezrin in osteosarcoma metastasis. Adv Exp Med Biol. 2014;804:181-201.
46. Rastogi S, Kumar R, Sankineani SR, Marimuthu K, Rijal L, Prakash S, Jalan D, Khan SA, Sharma MC. Role of vascular endothelial growth factor as a tumour marker in osteosarcoma: a prospective study. Int Orthop. 2012 Nov;36(11):2315-21.
47. Huang H. Matrix Metalloproteinase-9 (MMP-9) as a Cancer Biomarker and MMP-9 Biosensors: Recent Advances. Sensors (Basel). 2018 Sep 27;18(10):3249.
48. Lucchetti J, Fracasso C, Balducci C, Passoni A, Forloni G, Salmona M, Gobbi M. Plasma and Brain Concentrations of Doxycycline after Single and Repeated Doses in Wild-Type and APP23 Mice. J Pharmacol Exp Ther. 2019 Jan;368(1):32-40.
49. Dickens DS, Cripe TP. Effect of combined cyclooxygenase-2 and matrix metalloproteinase inhibition on human sarcoma xenografts. J Pediatr Hematol Oncol. 2003 Sep;25(9):709-14.
50. Fields GB. The Rebirth of Matrix Metalloproteinase Inhibitors: Moving Beyond the Dogma. Cells. 2019 Aug 27;8(9):984.
51. Sparano JA, Bernardo P, Stephenson P, Gradishar WJ, Ingle JN, Zucker S, Davidson NE. Randomized phase III trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eastern Cooperative Oncology Group trial E2196. J Clin Oncol. 2004 Dec 1;22(23):4683-90.
52. Evans JD, Stark A, Johnson CD, Daniel F, Carmichael J, Buckels J, Imrie CW, Brown P, Neoptolemos JP. A phase II trial of marimastat in advanced pancreatic cancer. Br J Cancer. 2001 Dec 14;85(12):1865-70.
53. Bramhall SR, Hallissey MT, Whiting J, Scholefield J, Tierney G, Stuart RC, Hawkins RE, McCulloch P, Maughan T, Brown PD, Baillet M, Fielding JW. Marimastat as maintenance therapy for patients with advanced gastric cancer: a randomised trial. Br J Cancer. 2002 Jun 17;86(12):1864-70.
54. Rudek MA, Figg WD, Dyer V, Dahut W, Turner ML, Steinberg SM, Liewehr DJ, Kohler DR, Pluda JM, Reed E. Phase I clinical trial of oral COL-3, a matrix metalloproteinase inhibitor, in patients with refractory metastatic cancer. J Clin Oncol. 2001 Jan 15;19(2):584-92.
55. Hanafy E, Al Jabri A, Gadelkarim G, Dasaq A, Nazim F, Al Pakrah M. Tumor histopathological response to neoadjuvant chemotherapy in childhood solid malignancies: is it still impressive? J Investig Med. 2018 Feb;66(2):289-297.
56. Basile P, Greengard E, Weigel B, Spector L. Prognostic Factors for Development of Subsequent Metastases in Localized Osteosarcoma: A Systematic Review and Identification of Literature Gaps. Sarcoma. 2020 Mar 18;2020:7431549.
57. Sannino G, Marchetto A, Kirchner T, Grünewald TGP. Epithelial-to-Mesenchymal and Mesenchymal-to-Epithelial Transition in Mesenchymal Tumors: A Paradox in Sarcomas? Cancer Res. 2017 Sep 1;77(17):4556-4561.
58. Qin Y, Zhang Q, Lee S, Zhong WL, Liu YR, Liu HJ, Zhao D, Chen S, Xiao T, Meng J, Jing XS, Wang J, Sun B, Dai TT, Yang C, Sun T, Zhou HG. Doxycycline reverses epithelial-to-mesenchymal transition and suppresses the proliferation and metastasis of lung cancer cells. Oncotarget. 2015 Dec 1;6(38):40667-79.
59. Deryugina EI, Quigley JP. Tumor angiogenesis: MMP-mediated induction of intravasation- and metastasis-sustaining neovasculature. Matrix Biol. 2015 May-Jul;44-46:94-112.
60. Li LT, Jiang G, Chen Q, Zheng JN. Ki67 is a promising molecular target in the diagnosis of cancer (review). Mol Med Rep. 2015 Mar;11(3):1566-72.
61. Khan K, Long B, Deshpande GM, Fox PL. Bidirectional Tumor-Promoting Activities of Macrophage Ezrin. Int J Mol Sci. 2020 Oct 19;21(20):7716.
62. Zhang Y, Zhang L, Zhang G, Li S, Duan J, Cheng J, Ding G, Zhou C, Zhang J, Luo P, Cai D, Kuang L, Zhou Y, Tong L, Yu X, Zhang L, Xu L, Yu L, Shi X, Ke A. Osteosarcoma metastasis: prospective role of ezrin. Tumour Biol. 2014 Jun;35(6):5055-9.
63. PosthumaDeBoer J, Witlox MA, Kaspers GJ, van Royen BJ. Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature. Clin Exp Metastasis. 2011 Jun;28(5):493-503.
64. Stefanovic S, Wirtz R, Deutsch TM, Hartkopf A, Sinn P, Varga Z, Sobottka B, Sotiris L, Taran FA, Domschke C, Hennigs A, Brucker SY, Sohn C, Schuetz F, Schneeweiss A, Wallwiener M. Tumor biomarker conversion between primary and metastatic breast cancer: mRNA assessment and its concordance with immunohistochemistry. Oncotarget. 2017 May 19;8(31):51416-51428.
65. Cekanova M, Rathore K. Animal models and therapeutic molecular targets of cancer: utility and limitations. Drug Des Devel Ther. 2014 Oct 14;8:1911-21.