Search Results

You are looking at 1 - 3 of 3 items for

  • Author or Editor: May B. Chien x
  • Refine by Access: All Content x
Clear All Modify Search

Abstract

Objective—To evaluate splenic mast cell tumors (MCT) of cats for activating mutations in the protooncogene c-kit.

Sample Population—10 formalin-fixed, paraffinembedded splenic MCT from cats in the pathology database of the Veterinary Medical Teaching Hospital at the University of California, Davis.

Procedure—Genomic DNA was isolated from tumor specimens, and the polymerase chain reaction (PCR) procedure was performed for exons 11, 12, and 17. The PCR products were analyzed by use of agarose gel electrophoresis and then directly sequenced.

Results—We did not identify mutations in the juxtamembrane domain (encoded by exons 11 and 12) or catalytic domain (encoded by exon 17) of c-kit in any of the splenic MCT specimens.

Conclusions and Clinical Relevance—Although mutations in the proto-oncogene c-kitoccur frequently in naturally developing MCT in dogs and aggressive mastocytosis in humans, the data reported here documented that dysregulation of Kit function through activating mutations is unlikely in splenic MCT of cats. Therapeutic strategies aimed at inhibiting Kit signaling (ie, kinase inhibitors such as imatinib [STI571]) may not be of benefit for the treatment of this disease in cats. (Am J Vet Res 2002;63:1129–1133).

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the prevalence of activating internal tandem duplications (ITDs) in exons 11 and 12 of c-kit in mast cell tumors (MCTs) of dogs and to correlate these mutations with prognosis.

Sample Population—157 formalin-fixed, paraffinembedded MCTs from dogs in the pathology database of the Veterinary Medical Teaching Hospital at the University of California, Davis.

Procedure—Genomic DNA was isolated from tumor specimens and a polymerase chain reaction procedure was performed to determine whether there were ITDs in exons 11 and 12.

Results—We identified ITDs in 1 of 12 (8%) grade-I, 42 of 119 (35%) grade-II, and 9 of 26 (35%) grade-III tumors (overall prevalence, 52 of 157 [33%]). Logistic regression analysis revealed that the odds of grade-II and -III tumors possessing an ITD were approximately 5 times greater than that for grade-I tumors, although these odds did not differ significantly. Although MCTs possessing an ITD were twice as likely to recur after excision and twice as likely to result in metastasis as those without an ITD, these values also did not differ significantly.

Conclusions and Clinical Relevance—These results provide evidence that ITDs in c-kit occur frequently in MCTs of dogs. The high prevalence of c-kit activating mutations in MCTs of dogs combined with the relative abundance of mast cell disease in dogs provide an ideal naturally developing tumor in which to test the safety and efficacy of novel small-molecule kinase inhibitors such as imatinib mesylate. (Am J Vet Res 2002;63:1718–1723)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate canine histiocytic sarcoma cell lines and tumor samples for dysregulation of the Kit/stem-cell factor (SCF), Flt3/Flt3 ligand (Flt3L), and Met/hepatocyte growth factor (HGF) receptor tyrosine kinase signaling pathways, as these are known to contribute to the differentiation and survival of normal dendritic cells as well as malignant transformation of dendritic cells in mouse models.

Sample Population—4 histiocytic sarcoma tumor cell lines and 35 formalin-fixed histiocytic sarcoma specimens obtained from dogs.

Procedure—Histiocytic sarcoma cell lines were evaluated for expression of Kit/SCF, Flt3/Flt3L, and Met/HGF by use of reverse transcriptase-PCR procedures. Histiocytic sarcoma cell lines and tumor samples were evaluated for mutations in Kit, Flt3, and Met by use of PCR analysis of genomic DNA, followed by both sequencing and fluorescent PAGE for deletions or internal tandem duplications. The ability of the multitargeted split-kinase inhibitor SU11654 to block proliferation and induce apoptosis of histiocytic sarcoma cell lines was also evaluated.

Results—No mutations in Kit, Flt3, and Met were identified in any of the cell lines or tumor samples evaluated. Furthermore, SU11654 did not induce cellcycle arrest or apoptosis of histiocytic sarcoma lines, even at supratherapeutic doses.

Conclusions and Clinical Relevance—These data suggest that dysregulation of Kit/SCF, Flt3/Flt3L, and Met/HGF signaling pathways is unlikely to occur in histiocytic sarcomas of dogs and that inhibitors of the Kit, Flt3, and Met pathways are unlikely to provide clinical benefit to dogs with histiocytic sarcomas.

Full access
in American Journal of Veterinary Research