"Doxycycline" TUMOR TIDBITS, AN EMAIL NEWSLETTER FROM GULF COAST VETERINARY ONCOLOGY Number 106; September 20, 2003. ======================================================================= THIS WEEK'S ANNOUNCEMENTS FROM GULF COAST VETERINARY ONCOLOGY *Call our Houston or San Antonio offices regarding our ongoing clinical trials. *Visit our web pages about our Foundation Golf Tournament November 11th. *Visit www.gcvs.com for more information. ======================================================================= THIS WEEK'S TUMOR TIDBIT: Doxycycline. ======================================================================= Complications arising from the onset and growth of metastatic disease is one of the major causes of death from cancer in veterinary patients. Several enzyme systems have been implicated in the metastatic process, but the matrix metalloproteinases (MMPs, a family of collagenases) appear to be the major group involved in most instances of neoplastic invasion. Increased MMP activity has been correlated with the metastatic potential of many cancers of dogs, including osteosarcoma, melanoma, hemangiosarcoma, and lymphoma. MMPs also play a role in tumor angiogenesis; necessary for tumor growth and proliferation. Tetracyclines are antimicrobial agents that can suppress MMP activity in a variety of tissues, including gingiva, bone, and cartilage. Several reports have indicated that tetracyclines can suppress tumor MMPs, reduce angiogenesis, and inhibit tumor invasion through basement membranes. Induction of apoptosis (programmed cell death) is another mechanism by which doxycycline inhibits tumor cell proliferation. Although there may be many indications for the role of Doxycycline in the inhibition of cancer proliferation, metastasis and angiogenesis, Doxycycline is also highly osteotropic and thus may have greater value in managing primary bone cancer patient or in the prevention of bone metastasis. Canine osteosarcoma cells express MMP-1, MMP-2 and MMP-9 as well as other endogenous collagenases that are responsible for the progression and metastasis of this tumor. When doxycycline was applied to canine osteosarcoma cells in vitro at 5 ug/ul (equivalent to a delivered dosage of 5 mg/kg orally in dogs), cell proliferation was suppressed by greater than 50%, collagenase activity was significantly reduced by 35%, and collagenase (MMP-1) activity was significantly decreased. Patient studies are ongoing, and for the brief reasons above (hence a Tidbit), we include Doxycycline at a dosage of 5 mg/kg orally once daily as one part of our multimodality approach in the management of cancer in dogs. Some light reading: Cakir Y, Hahn KA. Direct action by doxycycline against canine osteosarcoma cell proliferation and collagenase (MMP-1) activity in vitro. Int J In Vivo Res 1999; 13: 327-332. Fife RS, Sledge GW Jr. Effects of doxycycline on in vitro growth, migration, and gelatinase activity of breast carcinoma cells. J Lab Clin Med. 1995 Mar;125(3):407-11. 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. Iwasaki H, Inoue H, Mitsuke Y, Badran A, Ikegaya S, Ueda T. Doxycycline induces apoptosis by way of caspase-3 activation with inhibition of matrix metalloproteinase in human T-lymphoblastic leukemia CCRF-CEM cells. J Lab Clin Med. 2002 Dec;140(6):382-6. Yarbrough J, Merryman J, Hahn KA. Cell survival can be influenced by the inhibition of the Na+ dependent HCO3-/Cl- ion exchanger. Int J In Vivo Res 1999; 13:375-384. ======================================================================= As always, we hope this info helps and don't hesitate to call or email us Gulf Coast Veterinary Oncology! Kevin A. Hahn, DVM, PhD, Diplomate ACVIM (Oncology), drhahn@gcvs.com Janet K. Carreras, VMD, Diplomate ACVIM (Oncology), drcarreras@gcvs.com Glen K. King, DVM, MS, Diplomate ACVR (Radiology & Radiation Therapy), drking@gcvs.com Gulf Coast Veterinary Diagnostic Imaging & Oncology 1111 West Loop South, Suite 150, Houston, TX 77027 P: 713.693.1166 F: 713.693.1167 W: www.gcvs.com ======================================================================= Copyright © 2003, Gulf Coast Veterinary Oncology