Background: Imatinib mesylate is a small molecule targeted at dysregulated protein-tyrosine kinase. Mutation of c-kit exon 11, which induces constitutive phosphorylation of KIT, is one of the mechanisms for the development or progression of mast cell tumor (MCT) in dogs. The purpose of this study was to examine the therapeutic potential of imatinib mesylate in canine MCT.Hypothesis: Imatinib mesylate has activity against MCT in dogs, and response to treatment can be correlated to presence of mutation within exon 11 of c-kit.Animals: Twenty-one dogs with MCT with gross tumor burden and median tumor size of 7.2 cm (range, 1.0-25.3 cm) before treatment.Methods: Tumors were analyzed for mutation of c-kit exon 11. Imatinib mesylate was administered PO to the dogs at a dose of 10 mg/kg daily for 1-9 weeks.Results: Ten of 21 dogs (48%) had some beneficial response to imatinib mesylate treatment within 14 days of treatment initiation. All 5 dogs with a demonstrable c-kit mutation in exon 11 responded to the drug (1 complete remission, 4 partial remission).Conclusions and Clinical Importance: Imatinib mesylate has clinical activity against MCT in dogs. Response could not be predicted based on presence of absence of a mutation in exon 11 of c-kit.

Anionic polymerizations of the three acetal-protected styrene derivatives 2-(2-vinylphenyl)-(3a), 2-(3-vinylphenyl)-(3b), and 2-(4-vinylphenyl)-1,3-dioxolanes (3c) were carried out in THE at -78 °C with a variety of initiators. The meta isomeric monomer, 3b, underwent anionic living polymerization to produce polymers of controlled molecular weights and narrow molecular weight distributions. New welldefined block copolymers of both the ABA and the BAB types were readily synthesized by the sequential polymerizations of 3b and styrene and vice versa. On the contrary, complications were observed in the polymerizations of the ortho and para isomers, 3a and 3c. Soluble polymers with very broad molecular weight distributions from 3a and insoluble polymers from 3c were obtained in low yields by these polymerizations. Thus, the anionic polymerization behavior was significantly influenced by the difference in placement of the acetal group on the aromatic ring of the monomer. To explain these results, we propose a reaction mechanism based on the base-induced l,6(or l,4)-elimination of the acetal to generate the very reactive p(or o)-xylene intermediate. This is the first clear example that shows the positional effect of this substituent in the anionic polymerization of styrene derivatives. The anionic polymerizations of some related styrene derivatives containing acetal functionalities are also described.

Abstract.A 59-year-old woman with papillary thyroid carcinoma inside of an autonomously functioning thyroid nodule is described in this report. The patient was referred to our clinic because of rapid weight loss and swelling on the left side of the neck. Ultrasonography of the thyroid demonstrated a nonhomogeneous nodule in the lower part of an enlarged left lobe. Both 99m Tc and 123 I thyroid scintigraphic imaging showed a hot area corresponding to the nodule with lower uptake in the remaining thyroid tissue. Histopathological examination of the nodule revealed papillary adenocarcinoma, and the immunohistochemistry proved weak but positive staining for triiodothyronine and thyroxine. Based on these findings, the nodule was diagnosed as a functioning papillary adenocarcinoma. Although thyroid carcinoma manifesting as a hot nodule on the radionuclide isotope scan is an extremely rare occurrence, the current case is clinically important because it suggests that the diagnosis of a hot nodule cannot always rule out thyroid carcinoma in the nodule, and that even a hot nodule requires careful management so that the malignancy is not overlooked.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is associated with joint destruction. Imatinib mesylate (imatinib) is an inhibitor that specifically targets a set of protein tyrosine kinase, such as abl, c-kit, and platelet-derived growth factor receptor (PDGFR) and it is widely used to treat chronic myeloid leukemia (CML). The purpose of the present study is to determine whether imatinib can provide benefit in the arthritis induced by anti-collagen type II antibody (CAIA) in mice, a model that provides an opportunity to study the effector inflammatory phase of arthritis without involving the priming phase of the immune responses. Mice treated with intraperitoneal administration of imatinib (1 or 10 mg/kg) prior to the development of CAIA displayed significant reductions in the severity of CAIA as assessed by arthritis score, histology, and synovial PDGF and vascular endothelial growth factor expression. In addition, treatment of the mice that had developed CAIA with intraperitoneal administration of imatinib (1 or 10 mg/kg) inhibited the progression of arthritis as assessed by those parameters. These results suggest that imatinib prevents and treats CAIA. Imatinib may thus have both a preventive and therapeutic potential for the joint inflammation at the effector stage of RA.

This study was undertaken to investigate the age-related differences of monocyte chemotactic protein-1 (MCP-1) and matrix metalloproteinase-3 (MMP-3) expression in mouse intervertebral disc (IVD) and to determine whether MMP-3 plays a role in disc degeneration. Expression of MCP-1 and MMP-3 mRNA in mouse IVD was assessed by quantitative PCR. The ability of MCP-1 and MMP-3 expression in IVD to respond to TNF-a or TWEAK stimulation was examined by quantitative PCR, WB, ELISA, and immunohistochemistry. IVD derived from MMP-3-deficient and wild-type mice were compared using Safranin-O staining and immunohistochemistry. mRNA levels of MCP-1 and MMP-3 in IVD significantly diminished and the ability of MCP-1 or MMP-3 expression to respond to TNF-a or TWEAK stimulation was significantly reduced as age increased. IVD derived from 64-week-old wild-type mice showed clearly diffuse proteoglycan loss by Safranin-O staining and immunohistochemistry compared with younger mice. However, no loss of proteoglycan and typeII collagen were observed in IVD derived from 64-week-old MMP-3-deficient mice. MCP-1 and MMP-3 expression in mouse IVD showed age-related decreases. The response to inflammation in IVD also displayed age-related changes. Therefore, disc degeneration may vary with the patients' age and targeting MMP-3 may be a possible future therapeutic strategy for disc degeneration. ß