References on the Administration of Metalloproteinase Inhibitors
Using ALZET® Osmotic Pumps

16341 Swapna Asuthkar,, Kiran Kumar Velpula,, Chandramu Chetty,, Bharathi Gorantla,, Jasti S. Rao  ONCOTARGET 2012; 3(-11-):1439-1454. >>> Plasmid, miR-211-overexpressing; Plasmid, MMP-9; CSF/CNS; Mice (Nude); 2004; animal info (nude mice); functionality of mp verified by tissue levels; cancer (glioblastoma multiforme); Xenograft study; Dose (3-6 mg/kg);.

15034 Marshall, D.C., Lyman, S.K., McCauley, S., Kovalenko, M., Spangler, R., Liu, C., Lee, M., O'Sullivan, C., Barry-Hamilton, V., Ghermazien, H., Mikels-Vigdal, A., Garcia, C.A., Jorgensen, B., Velayo, A.C., Wang, R., Adamkewicz, J.I., Smith, V., Smith, V. Selective Allosteric Inhibition of MMP9 Is Efficacious in Preclinical Models of Ulcerative Colitis and Colorectal Cancer. PLoS One 2015; 10(--):U2689-U2714. >>> Marimastat; DMSO; water; SC; Rat; 2ML4; Controls received mp w/ vehicle; animal info (male, Lewis); 50% DMSO used; behavioral testing (resting posture, gait);.

14971 Iyer, R.P., Patterson, N.L., Zouein, F.A., Ma, Y.G., Dive, V., Bras, L.E.D., Lindsey, M.L., Lindsey, M.L. Early matrix metalloproteinase-12 inhibition worsens post-myocardial infarction cardiac dysfunction by delaying inflammation resolution. INTERNATIONAL JOURNAL OF CARDIOLOGY 2015; 185(--):198-208. >>> RXP 470.1; Saline; SC; Mice; 1007D; Controls received mp w/ vehicle; animal info (male, C57BL6J, 3-6 months old, myocardial infarction); cardiovascular; immunology; enzyme inhibitor (matrix metalloproteinase-12);.

13687 Meides, A., Gutschalk, C.M., Devel, L., Beau, F., Czarny, B., Hensler, S., Neugebauer, J., Dive, V., Angel, P., Mueller, M.M., Mueller, M.M. Effects of selective MMP-13 inhibition in squamous cell carcinoma depend on estrogen. International Journal of Cancer 2014; 135(--):2749-2759. >>> MMP-13 inhibitor; PEG 200; DMSO; Mice (nude); 2004; Control animals received mp w/ vehicle; animal info (C57BL/6N, ovariectomized); MMP-13 inhibitor also known as compound 1, was synthesized from 2,4 pyridine dicarboxylic acid and 4-Fluoro3-Methylbenzylamine;"Delivery of the inhibitor was achieved by an osmotic minipump, as constant blood levels of inhibitor are more effective than bolus injections to fully block MMP-13 activity during long term treatments."pg 2759; dose-response; cancer; enzyme inhibitor (matrix metalloproteinases).

12516 Mazurek, S.G.N., Li, J., Nabozny, G.H., Reinhart, G.A., Muthukumarana, A.C., Harrison, P.C., Fryer, R.M. Functional biomarkers of musculoskeletal syndrome (MSS) for early in vivo screening of selective MMP-13 inhibitors. Journal of Pharmacological and Toxicological Methods 2011; 64(-1-):89-96. >>> Marimastat; DMSO; water; SC; Rat; 2ML2; Controls received mp w/ vehicle; animal info (Sprague Dawley, male, 180-370); wound clips used; enzyme inhibitor (matrix metalloproteinase, MMP-13).

12249 Smith, A.W., Nealey, K.A., Wright, J.W., Walker, B.M. Plasticity associated with escalated operant ethanol self-administration during acute withdrawal in ethanol-dependent rats requires intact matrix metalloproteinase systems. NEUROBIOLOGY OF LEARNING AND MEMORY 2011; 96(-2-):199-206. >>> FN-439; CSF/CNS; Rat; 2006; Controls received mp w/ artificial CSF; animal info (Wistar, adult, male); enzyme inhibitor (matrix metalloproteinase); cannula placement verified via histology with 0.6% cresyl violet, 2 ul over 60 s.

12136 Spolidoro, M., Putignano, E., Munafo, C., Maffei, L., Pizzorusso, T. Inhibition of Matrix Metalloproteinases Prevents the Potentiation of Nondeprived-Eye Responses after Monocular Deprivation in Juvenile Rats. Cerebral Cortex 2012; 22(-3-):725-734. >>> GM6001; Saline; CSF/CNS (visual cortex); Rat; 1007D; 2002; Controls received mp w/ vehicle; animal info (Long-Evans hooded, P21-P45).

11938 Allard, S., Leon, W.C., Pakavathkumar, P., Bruno, M.A., Ribeiro-da-Silva, A., Cuello, A.C. Impact of the NGF Maturation and Degradation Pathway on the Cortical Cholinergic System Phenotype. Journal of Neuroscience 2012; 32(-6-):2002-2012. >>> Antiplasmin, alpha-2; MMP2-9I, type 1; Saline; sodium acetate; DMSO; CSF/CNS (medial prefrontal cortex); Rat; 2002; Controls received mp w/ vehicle; animal info (Wistar, male, 350 g); Plastics One bilateral cannula used; 1% DMSO used; enzyme inhibitor (matrix metalloproteinase); behavioral testing (water maze test); neurodegenerative (Alzheimer's disease); bilateral infusion;.

11818 Romero-Grimaldi, C., Murillo-Carretero, M., Lopez-Toledano, M.A., Carrasco, M., Castro, C., Estrada, C. ADAM-17/Tumor Necrosis Factor-alpha-Converting Enzyme Inhibits Neurogenesis and Promotes Gliogenesis from Neural Stem Cells. Stem Cells 2011; 29(-10-):1628-1639. >>> GM6001; PBS; DMSO; CSF/CNS; Mice; Controls received mp w/ vehicle; animal info (adult, 2-3 mo old, male, female, PN7, CD1); 0.4% DMSO used; enzyme inhibitor (metalloprotease); ALZET brain infusion kit III used.

11746 Frant, J., Veerendhar, A., Chernilovsky, T., Nedvetzki, S., Vaksman, O., Hoffman, A., Breuer, E., Reich, R. Orally Active, Antimetastatic, Nontoxic Diphenyl Ether-Derived Carbamoylphosphonate Matrix Metalloproteinase Inhibitors. ChemMedChem 2011; 6(-8-):1471-1477. >>> Marimastat; Propylene glycol; DMSO; SC; Rat; 2ML2; animal info (male, Lewis, 150-180 g); 50% DMSO used.

10931 Cirillo, G., Bianco, M.R., Colangelo, A.M., Cavaliere, C., Daniele, D., Zaccaro, L., Alberghina, L., Papa, M. Reactive astrocytosis-induced perturbation of synaptic homeostasis is restored by nerve growth factor. NEUROBIOLOGY OF DISEASE 2011; 41(-3-):630-639. >>> Nerve growth factor, beta, recomb.; GM6001; CSF, artificial; albumin, rat serum; CSF/CNS (intrathecal, subarachnoid space); Rat; 2001; Controls received mp w/ vehicle; animal info (Sprague-Dawley, male, 250-300 g); enzyme inhibitor (metalloproteinase); PE10 connected to PE60 tubing.

10925 Aagren, M.S., Andersen, T.L., Andersen, L., Schiodt, C.B., Surve, V., Andreassen, T.T., Risteli, J., Franzen, L.E., Delaisse, J.M., Heegaard, A.M., Jorgensen, L.N. Nonselective matrix metalloproteinase but not tumor necrosis factor-alpha inhibition effectively preserves the early critical colon anastomotic integrity. International Journal of Colorectal Disease 2011; 26(-3-):329-337. >>> GM6001; AG3340; DMSO; SC; Rat; 2ML1; Controls received mp w/ vehicle; animal info (male Sprague-Dawley, 205-360 g); enzyme inhibitor (matrix metalloproteinase, MMP); 50% DMSO used.

9918 Skipper, J.B., McNally, L.R., Rosenthal, E.L., Wang, W.Q., Buchsbaum, D.J. In vivo Efficacy of Marimastat and Chemoradiation in Head and Neck Cancer Xenografts. ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES 2009; 71(-1-):1-5. >>> Marimastat; DMSO; SC; Mice (nude); 2002; Controls received mp w/vehicle; cancer; animal info (3 mo old, female).

9844 Wright, J.W., Meighan, P.C., Brown, T.E., Wiediger, R.V., Sorg, B.A., Harding, J.W. Habituation-induced neural plasticity in the hippocampus and prefrontal cortex mediated by MMP-3. Behavioural Brain Research 2009; 203(-1-):27-34. >>> MMP-3i; CSF/CNS; Rat; 2001; Controls received mp aCSF; functionality of mp verified by residual volume; animal info (male, Sprague Dawley, 300-350g); behavioral testing (head-shake response habituation); cannula placement verified w/icv injection of fast green dye; enzyme inhibitor (metalloproteinase-3).

9462 Chow, J.P.H., Fujikawa, A., Shimizu, H., Suzuki, R., Noda, M. Metalloproteinase- and gamma-Secretase-mediated Cleavage of Protein-tyrosine Phosphatase Receptor Type Z. Journal of Biological Chemistry 2008; 283(-45-):30879-30889. >>> GM6001; DMSO; CSF/CNS; Mice; 1007D; Controls received mp w/ vehicle; enzyme inhibitor (metalloproteinase); ALZET brain infusion kit 3 used; dental cement and stay screws used; animal info (male, C57BL/6, wt, Ptprz -/-, adult); 50% DMSO used.

9352 Kasaoka, T., Nishiyama, H., Okada, M., Nakajima, M. Matrix metalloproteinase inhibitor, MMI270 (CGS27023A) inhibited hematogenic metastasis of B16 melanoma cells in both experimental and spontaneous metastasis models. CLINICAL&EXPERIMENTAL METASTASIS 2008; 25(-7-):827-834. >>> MMI270; DMSO; PEG 300; SC; Mice; 2004; 2004; Comparison of SC injections vs. mp; enzyme inhibitor (matrix metalloproteinase); cancer (melanoma); animal info (7 wks old, BDF1, male, lymphadrectomy; 50% DMSO used; 50% PEG 300 used.

8196 Bruno, M.A., Cuello, A.C. Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degradation by a protease cascade. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2006; 103(-17-):6735-6740. >>> Neuroserpin; GM6001; CSF, artificial, PBS; CSF/CNS (parietal cortex); Rat; 2001; Controls received mp w/ vehicle into contralateral side; enzyme inhibitor (tpa, metalloproteinase); multiple pumps per animal (2); animal info (Fischer 344, 6 month old); Lynch coil with air-oil spacer at mp end of tubing; bilateral infusion cannulae; tissue perfusion (parietal cortex).

8294 Fridman, J.S., Caulder, E., Hansbury, M., Liu, X.D., Yang, G.J., Wang, Q., Lo, Y., Zhou, B.B., Pan, M., Thomas, S.M., Grandis, J.R., Zhuo, J.C., Yao, W.Q., Newton, R.C., Friedman, S.M., Scherle, P.A., Vaddi, K. Selective inhibition of ADAM metalloproteases as a novel approach for modulating ErbB pathways in cancer. Clinical Cancer Research 2007; 13(-6-):1892-1902. >>> Marimastat; INCB3619; SC; Mice; mice (nude); Controls received mp w/ vehicle; enzyme inhibitor (metalloprotease); cancer (squamous cell carcinoma, breast, lung carcinoma); toxicology; animal info (BALB/c, CD-1 nu/nu); ErbB ligand shedding inhibitor; half-life (pg 1894)"<2h in the mouse"6.1h in larger animals.

7458 Lakka, S.S., Gondi, C.S., Dinh, D.H., Olivero, W.C., Gujrati, M., Rao, V.H., Sioka, C., Rao, J.S. Specific interference of urokinase-type plasminogen activator receptor and matrix metalloproteinase-9 gene expression induced by double-stranded RNA results in decreased invasion, tumor growth, and angiogenesis in gliomas. Journal of Biological Chemistry 2005; 280(-23-):21882-21892. >>> RNA, small interfering; RNA, small interfering, uPAR; RNA, small interfering, MMP-9; CSF/CNS; Mice (nude); 1002; Controls received mp w/ PBS or empty vector; cancer (glioblastoma); siRNA is within a plasmid vector (pUM vector); antiangiogenesis; gene therapy.

7263 Matthey, B., Borchmann, P., Schnell, R., Tawadros, S., Lange, H., Huhn, M., Klimka, A., Tur, M.K., Barth, S., Engert, A., Hansen, H.P. Metalloproteinase inhibition augments antitumor efficacy of the anti-CD30 immunotoxin Ki-3(scFv)-ETA'against human lymphomas in vivo. International Journal of Cancer 2004; 111(-4-):568-574. >>> BB-3644; PBS; SC; Mice (SCID); 2001; Controls received mp w/ vehicle; comparison of IV injections vs. mp; enzyme inhibitor (metalloproteinases); cancer (lymphoma);"when BB-3644 was continuously applied via a small osmotic pump, the antitumor activity of a single dose of Ki-3(scFv)-ETA'was further enchanced with a tumor-free survival of all animals treated for more than 200 days."(p. 572).

7245 Levesque, J.P., Liu, F., Simmons, P.J., Betsuyaku, T., Senior, R.M., Pham, C., Link, D.C. Characterization of hematopoietic progenitor mobilization in protease-deficient mice. Blood 2004; 104(-1-):65-72. >>> MMI270; DMSO; PEG 300; SC; Mice; Controls received mp w/ vehicle; functionality of mp verified by serum MMI270 levels; enzyme inhibitor (metalloproteinase).

6819 Cox, M.J., Hawkins, U.A., Hoit, B.D., Tyagi, S.C. Attenuation of oxidative stress and remodeling by cardiac inhibitor of metalloproteinase protein transfer. Circulation 2004; 109(-17-):2123-2128. >>> CIMP; IP; Mice; 1002; Controls received no treatment/sham AVF surgery; enzyme inhibitor (metalloproteinase); cardiovascular; peptides; agent also known as (metalloproteinase, cardiac inhibitor).

6707 Nakamura, E.S., Koizumi, K., Kobayashi, M., Saiki, I. Inhibition of lymphangiogenesis-related properties of murine lymphatic endothelial cells and lymph node metastasis of lung cancer by the matrix metalloproteinase inhibitor MMI270. CANCER SCIENCE 2004; 95(-1-):25-31. >>> MMI270; DMSO; PEG 300; IP; Mice; 2004; Controls received mp w/ vehicle; no stress (see pg.27); enzyme inhibitor (matrix metalloproteinase); cancer (lung); MMI270 was formerly termed CGS27023A; 50% DMSO used; 50% PEG 300 used;"The continuous administration of MMI270 for 15 days using an osmotic pump led to a significant decrease in the weight of tumor-metastasized lymph nodes"(p. 29).

6536 Kawai, N., Kawanishi, M., Okada, M., Matsumoto, Y., Nagao, S. Treatment of cold injury-induced brain edema with a nonspecific matrix metalloproteinase inhibitor MMI270 in rats. Journal of Neurotrauma 2003; 20(-7-):649-657. >>> MMI270; DMSO; PEG 300; IP; Rat; 2001D; 2ML1; Controls received mp/ vehicle; no stress (see pg. 652); enzyme inhibitor (matrix metalloproteinase); MMI270 is: N-hydroxy-2(R)-[(4-methoxysulfony)(3-picolyl)-amino]-3-metyl butaneamide hydrochloride monohydrate.

6103 Wada, N., Otani, Y., Kubota, T., Kimata, M., Minagawa, A., Yoshimizu, N., Kameyama, K., Saikawa, Y., Yoshida, M., Furukawa, T., Fujii, M., Kumai, K., Okada, Y., Kitajima, M. Reduced angiogenesis in peritoneal dissemination of gastric cancer through gelatinase inhibition. CLINICAL&EXPERIMENTAL METASTASIS 2003; 20(-5-):431-435. >>> Marimastat; DMSO; water; SC; Mice (SCID); 2002; controls received mp w/ vehicle; enzyme inhibitor (matrix metalloprotease); marimastat, the broad-spectrum matrix metalloproteinase inhibitor was dissolved in 50% DMSO; angiogenesis inhibitor.

5585 Charoenrat, P., Rhys-Evans, P., Eccles, S. A synthetic matrix metalloproteinase inhibitor prevents squamous carcinoma cell proliferation by interfering with epidermal growth factor receptor autocrine loops. International Journal of Cancer 2002; 100(-5-):527-533. >>> Marimastat; DMSO; Water, sterile; SC; Mice; 2002; Controls received mp w/ vehicle; cancer; enzyme inhibitor (matrix metalloproteinase).

5478 Kimata, M., Otani, Y., Kubota, T., Igarashi, N., Yokoyama, T., Wada, N., Yoshimizu, N., Fujii, M., Kameyama, K., Okada, Y., Kumai, K., Kitajima, M. Matrix metalloproteinase inhibitor, marimastat, decreases peritoneal spread of gastric carcinoma in nude mice. Japanese Journal of Cancer Research 2002; 93(-7-):834-841. >>> Marimastat; DMSO; SC; Mice (nude); Controls received mp w/ vehicle; pumps replaced after 14 days; gastric cancer; enzyme inhibitor; matrix metalloproteinase inhibitor; 50% DMSO vehicle.

4921 Kiyama, T., Onda, M., Tokunaga, A., Efron, D.T., Barbul, A. Effect of matrix metalloproteinase inhibition on colonic anastomotic healing in rats.. JOURNAL OF GASTROINTESTINAL SURGERY 2001; 5(--):303-311. >>> BE16627B; DMSO; ethylene glycol; SC; Rat; 1003D; Controls received mp w/ vehicle; enzyme inhibitor; vehicle mix was 50:50 ratio; BE16627B is a matrix metalloproteinase inhibitor;.

4385 Prescott, M.F., Sawyer, W.K., Von Linden-Reed, J., Jeune, M., Chou, M., Caplan, S.L., Jeng, A.Y. Effect of matrix metalloproteinase inhibition on progression of atherosclerosis and aneurysm in LDL receptor-deficient mice overexpressing MMP-3, MMP-12, and MMP-13 and on restenosis in rats after balloon injury. Annals of the New York Academy of Sciences 1999; 878(--):179-190. >>> CGS 27023A; DMSO; SC; Rat; 2ML2; 2ML4; cardiovascular; enzyme Inhibitor; CGS 27023A is an orally active hydroxamic acid matrix metalloproteinase inhibitor.

4122 Karran, E.H., Young, T.J., Markwell, R.E., Harper, G.P. In vivo model of cartilage degradation - effects of a matrix metalloproteinase inhibitor. Annals of the Rheumatic Diseases 1995; 54(--):662-669. >>> MI-1; MI-2; Propylene glycol; cartilage, femoral head; rat; 2ML2; tissue perfusion (femoral head cartilage); good methods (p. 663); MI-1 and MI-2 are matrix metalloproteinase inhibitors; enzyme inhibitors.

3486 Conway, J.G., Wakefield, J.A., Brown, R.H., Marron, B.E., Sekut, L., Stimpson, S.A., McElroy, A., Menius, J.A., Jeffreys, J.J., Clark, R.L., McGeehan, G.M., Connolly, K.M. Inhibition of cartilage and bone destruction in adjuvant arthritis in the rat by a matrix metalloproteinase inhibitor. J. Exp. Med 1995; 182(--):449-457. >>> GI168; DMSO; Sodium citrate buffer; SC; rat; 2ML2; controls received mp w/vehicle; dose-response (see p. 451); immunology; multiple pumps per animal (2);"GI168 had poor oral bioavailability and a short plasma t 1/2 after subcutaneous injection... so minipump delivery was evaluated."p. 451; enzyme inhibitor (matrix metalloproteinase).

2887 Naito, K., Kanbayashi, N., Nakajima, S., Murai, T., Arakawa, K., Nishimura, S., Okuyama, A. Inhibition of growth of human tumor cells in nude mice by a metalloproteinase inhibitor. Int. J. Cancer 1994; 58(--):730-735. >>> BE16627B; Doxorubicin HCl; DMSO; Ethylene glycol; SC; Mice (nude); 2001; 2002; controls received vehicle or no treatment; pumps replaced; stress/ adverse reaction: skin inflammation and necrosis around delivery site in mice treated with Adriamycin (pg. 733); BE166278B animals were fine; stability verified for 18 days by assay; cancer; enzyme inhibitor; BE16627B is a metalloproteinase inhibitor; 2002 replaced w/ 2001 after 20 days; adriamycin is doxorubicin HCl.


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“Nicotine was chronically administered subcutaneously to rats via osmotic mini-pumps. This model was proved to be a convenient and efficacious alternative to multiple injections to mimic the chronic intake of smokers.” Cormier et al., Neuropharmacology 2003;44:642-652.