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- Author or Editor: Nilanjana Banerji x
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Objective—To determine somatic alterations in p53 in vaccine-associated feline sarcoma (VAFS).
Animals—27 domestic shorthair cats undergoing first surgical treatment for primary VAFS with no history of chemotherapy or γ radiation.
Procedures—Sequence analysis was performed on the genomic sequence of p53 (between exons 5 through 9) from tumor and blood samples obtained from the cats. Cats were monitored for 3 years and disease-free intervals and survival times calculated.
Results—Eight single nucleotide polymorphisms were detected within the genomic sequence of p53, with 20 of 27 cats (74%) having heterozygosity at ≥ 1 polymorphic site. Somatic loss of heterozygosity at p53 was detected in the primary tumors of 12 of these 20 (60%) cats. Such allelic deletion was significantly associated with rapid tumor recurrence and reduced overall survival. Point mutations were rare, occurring in 3 of 27 primary tumors. The finding of malignant cells in the surgical margins was significantly associated with disease recurrence, but clear margins (with no detectable malignant cells) were not predictive of positive outcome.
Conclusions and Clinical Relevance—p53 status is an indicator of postsurgical recurrence and overall survival in cats with VAFS. Careful follow-up is important in treating vaccine-site tumors containing allelic deletion of p53, whereas aggressive surgical treatment may be sufficient to control primary vaccination site tumors without the allelic loss.
Objective—To establish 2 vaccine-associated feline sarcoma (VAFS) cell lines and to determine their in vitro sensitivity to the chemotherapeutic agents doxorubicin and mitoxantrone.
Sample Population—Tumor specimens collected from 2 cats undergoing surgery for removal of vaccine- associated sarcomas.
Procedures—Tumor specimens were minced and treated with trypsin under aseptic conditions to obtain single-cell suspensions, which were then cultured in vitro in medium supplemented with 5% heat-inactivated fetal bovine serum. Growth rates and sensitivity after 24 hours of exposure to various concentrations (0.1 to 100 μg/ml) of doxorubicin and mitoxantrone were assessed for each cell line. Survival of cells was estimated 3 days after exposure to the 2 agents, and the concentration of each drug that resulted in a 50% reduction in the number of viable cells (IC50) was calculated.
Results—Two tumor-derived cell lines (FSA and FSB) were successfully established and determined to be sensitive to doxorubicin and mitoxantrone. Under the conditions tested, the IC50 of doxorubicin were 0.6 and 1.5 μg/ml for cell lines FSB and FSA, respectively. The IC50 of mitoxantrone was 0.4 μg/ml for both cell lines.
Conclusions and Clinical Relevance—The establishment of VAFS cell lines provides a tool for the in vitro screening of antitumor drugs. Doxorubicin and mitoxantrone were effective in decreasing the number of viable cells in the 2 cell lines tested. Both of these anthracycline antibiotics have been used to treat various neoplasias in cats, and their efficacy for adjuvant treatment of vaccine-associated sarcomas should be further evaluated. (Am J Vet Res 2001;62:1354–1357).
Objective—To determine the in vitro sensitivity of 4 vaccine-associated feline sarcoma (VAFS) cell lines to the chemotherapeutic agents vincristine and paclitaxel.
Sample Population—Cell lines derived from 4 VAFS specimens.
Procedure—Cell lines were cultured in vitro and individually exposed to various concentrations of vincristine and paclitaxel. Survival was estimated after 24 and 72 hours of exposure to each drug, and the drug concentrations that resulted in 50 and 90% reduction in number of viable cells (IC50 and IC90, respectively) were calculated.
Results—Both vincristine and paclitaxel had significant dose-dependent effects on the viability of the VAFS cell lines. After 72 hours of drug exposure, the IC50 and IC90 of vincristine for the 4 cell lines were between 0.005 to 0.039 µg/ml and 0.045 to 1.027 µg/ml, respectively. The IC50 and IC90 values for paclitaxel were between 0.037 to 0.092 µg/ml and 2.450 to 15.413 µg/ml, respectively.
Conclusions—Results of pharmacokinetic studies on vincristine and paclitaxel in other species suggest that concentrations greater than the IC50 values may be possible for both drugs in feline patients as well. The drug concentrations at which viable cell numbers were reduced by 90% may also be attained in vivo for some cases, but detailed information is needed regarding the distribution, concentration, duration of availability, and toxicity of various drugs in cats. Carefully chosen combinations of antineoplastic agents need to be screened to identify treatment protocols that may be further evaluated clinically for the treatment of VAFS. (Am J Vet Res 2002;63:728–732)