Principles and Applications of Medical Oncology in Exotic Animals.

Diagnoses of neoplasia in exotic animals have historically been made at death or just before euthanasia. Routine physical examinations are enabling early diagnosis while accessibility and affordability of advanced diagnostics are improving. With increasing expectations for care, treatment options are more frequently explored. Numerous oncologic medications have been adopted from human and small animal medicine and successfully used in exotic animals. Although there is a need for extended research, this article evaluates which medications have been used thus far for treatment protocols in zoologic and exotic animal species.

Safety of administering the canine melanoma DNA vaccine (Oncept) to cats with malignant melanoma - a retrospective study.

Objectives A xenogeneic human tyrosinase DNA vaccine was developed for treatment of dogs with oral malignant melanoma (Oncept; Merial). No studies have evaluated the safety or efficacy of this vaccine in cats. The purpose of this study was to evaluate the safety of the canine melanoma vaccine in cats diagnosed with melanoma. Methods Medical records were reviewed from cats diagnosed with malignant melanoma and treated with the canine melanoma DNA vaccine (Oncept). Data regarding signalment, melanoma location, treatments received, vaccine adverse effects and cause of death were collected. Results A total of 114 melanoma vaccines were administered to 24 cats. Seven cats (11.4%) had clinical adverse effects from a total of 13 vaccines classified as grade 1 or 2 based on the Veterinary Cooperative Oncology Group's common terminology criteria for adverse events v1.1. These included pain on vaccine administration, brief muscle fasciculation, transient inappetence, depression, nausea and mild increase in pigmentation at the injection site. Nineteen cats were deceased at study close. The most common cause of death was melanoma (14 cats). Hematological and biochemical changes were observed in six cats, five of which had concurrent disease or treatments that likely caused or greatly contributed to the laboratory abnormalities found. Therefore, these adverse events were considered unlikely to be caused by the melanoma vaccine. One cat had transient grade 1 hypoalbuminemia, which was possibly caused by the vaccination but not thoroughly evaluated. Conclusions and relevance The canine melanoma DNA vaccine can be safely administered to cats, with minimal risk of adverse effects.

Exploration of paclitaxel (Taxol) as a treatment for malignant tumors in cats: a descriptive case series.

Paclitaxel, an effective chemotherapeutic agent in human oncology, has received little evaluation in feline patients. The diluent used to solubilize paclitaxel, polyoxyethylated castor oil (Cremophor EL), causes anaphylactoid reactions in human and dogs, which limits enthusiasm for use of this agent in veterinary oncology. Nine feline patients with measurable malignant tumors were treated with paclitaxel at a dosage of 80 mg/m(2) intravenously every 21 days for up to two doses. Adverse effects, including evidence of toxicity and anaphylactoid reactions, were assessed. Tumor response, progression and patient time to progression (TTP) were also recorded. Adverse effects included grade III and IV thrombocytopenia, grade III gastrointestinal signs (vomiting and constipation) and hypersensitivity reactions, seen in a total of five patients. Anaphylactoid reactions resolved with appropriate management. Stable disease and partial response were observed in 56% of feline patients. Median TTP was 28 days (range 15-45 days). Intravenous paclitaxel is a safe treatment option for feline malignant tumor patients. Future investigation is warranted to explore the effectiveness and appropriate application of this agent for specific tumor types.

Detection of retinoid receptors in non-neoplastic canine lymph nodes and in lymphoma.

This study evaluated the difference in retinoid receptor expression between non-neoplastic lymph nodes and nodal lymphoma in dogs. Retinoid receptor expression was evaluated by immunohistochemistry in 32 canine lymph nodes. The lymph nodes had been previously diagnosed as non-neoplastic (6 normal and 7 hyperplastic lymph nodes) and B- and T-cell lymphoma (19 cases). Immunohistochemistry for retinoic acid receptors and retinoid-X receptors (and their subtypes α, ß, and γ) was performed in all cases. In addition, immunohistochemistry for CD3 and CD79a was performed in all lymphoma cases. Non-neoplastic lymphocytes were negative for all retinoid receptors. Retinoic acid receptor-γ was detected in 100% of B-cell lymphoma and 78% of T-cell lymphoma, while retinoid X receptor-γ was positive in 78% of T-cell lymphoma cases. When normal lymph node architecture was still present, a contrast between retinoid-negative benign cells and retinoid-positive malignant cells was clear. Retinoid receptors were expressed in neoplastic, but not in benign lymphocytes, suggesting their value for both diagnosis and treatment of canine lymphoma.

Détection des récepteurs aux rétinoïdes dans les ganglions lymphatiques canins non néoplasiques et dans les lymphomes. Cette étude a évalué la différence dans l'expression des récepteurs de l'acide rétinoïque entre les ganglions lymphatiques non néoplasiques et les lymphomes ganglionnaires chez les chiens. L'expression des récepteurs de l'acide rétinoïde a été évaluée par immunohistochimie dans 32 ganglions lymphatiques canins. Les ganglions lymphatiques avaient été antérieurement diagnostiqués comme étant non néoplasiques (6 ganglions lymphatiques normaux et 7 hyperplasiques) et les lymphomes B et T (19 cas). L'immunohistochimie pour les récepteurs de l'acide rétinoïque et les récepteurs X de rétinoïde (et leurs sous-types α, ß et γ) a été réalisée dans tous les cas. De plus, l'immunohistochimie pour CD3 et CD79a a été réalisée dans tous les cas de lymphomes. Les lymphocytes non néoplasiques étaient négatifs pour tous les récepteurs de rétinoïde. Le récepteur-γ d'acide rétinoïque a été détecté dans 100 % des lymphomes B et dans 78 % des lymphomes T, tandis que le récepteur-γ X de rétinoïde était positif dans 78 % des cas de lymphome T. Lorsqu'une architecture normale des ganglions lymphatiques était présente, le contraste entre les cellules bénignes négatives pour la rétinoïde et les cellules malignes positives pour la rétinoïde était clair. Les récepteurs de rétinoïde étaient exprimés dans les lymphocytes néoplasiques, mais non dans les lymphocytes bénins, suggérant leur valeur pour le diagnostic et le traitement des lymphomes canins.(Traduit par Isabelle Vallières).

Pharmacologic inhibition of MEK signaling prevents growth of canine hemangiosarcoma.

Angiosarcoma is a rare neoplasm of endothelial origin that has limited treatment options and poor five-year survival. As a model for human angiosarcoma, we studied primary cells and tumorgrafts derived from canine hemangiosarcoma (HSA), which is also an endothelial malignancy with similar presentation and histology. Primary cells isolated from HSA showed constitutive extracellular signal-regulated kinase (ERK) activation. The mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor CI-1040 reduced ERK activation and the viability of primary cells derived from visceral, cutaneous, and cardiac HSA in vitro. HSA-derived primary cells were also sensitive to sorafenib, an inhibitor of B-Raf and multireceptor tyrosine kinases. In vivo, CI-1040 or PD0325901 decreased the growth of cutaneous cell-derived xenografts and cardiac-derived tumorgrafts. Sorafenib decreased tumor size in both in vivo models, although cardiac tumorgrafts were more sensitive. In human angiosarcoma, we noted that 50% of tumors stained positively for phosphorylated ERK1/2 and that the expression of several MEK-responsive transcription factors was upregulated. Our data showed that MEK signaling is essential for the growth of HSA in vitro and in vivo and provided evidence that the same pathways are activated in human angiosarcoma. This indicates that MEK inhibitors may form part of an effective therapeutic strategy for the treatment of canine HSA or human angiosarcoma, and it highlights the use of spontaneous canine cancers as a model of human disease.

Development of a survey instrument to assess health-related quality of life in small animal cancer patients treated with chemotherapy.

OBJECTIVE: To develop a quality of life (QOL) survey for use in a canine cancer chemotherapy setting, validate the instrument's utility, identify key questions that facilitate client and clinician communication regarding decisions in patient care, and use human and veterinary QOL literature to develop a comprehensive yet simple proxy survey instrument. DESIGN: Survey. ANIMALS: 29 canine chemotherapy patients. PROCEDURES: Patients were evaluated by both owners and veterinarians at the time of initial visit to the clinic and at 3 and 6 weeks after the initiation of chemotherapy. This survey consisted of a longitudinal evaluation of QOL with 6 components addressing the animal's QOL retrospectively, before onset of cancer; changes in the animal's QOL since manifestation of disease; changes in the animal's QOL with regard to treatment response; owner's QOL and its impact on priorities in decision making; clinician's impression of the owner's priorities and QOL; and clinician's impression of the dog's QOL. RESULTS: Multiple regression analysis indicated 3 significant predictors of canine cancer patient QOL to be play behaviors, signs of illness, and canine happiness as perceived by owners. CONCLUSIONS AND CLINICAL RELEVANCE: The QOL instrument was easy to use and enhanced client perception of patient care and clinician concern. Owners enjoyed the opportunity to complete the survey. Since questions regarding play behaviors, clinical signs of disease, and canine happiness were significant indicators of changes in QOL, these should be included in future studies. Quality of life assessment may facilitate treatment decisions and assessment of canine patients undergoing chemotherapy.

Clinicopathologic significance of histologic grade, pgp, and p53 expression in canine lymphoma.

To characterize the expression of P-glycoprotein (Pgp) and p53 in different histologic grades of canine multicentric lymphosarcoma (LSA), 31 cases of LSA without prior treatment were studied. The expression levels of the Pgp and p53 proteins were evaluated for their clinicopathologic significance among standard histologic evaluation. Immunohistochemistry (IHC) was performed on formalin-fixed, paraffin-embedded archival samples of 31 previously untreated LSA cases to detect the expression of Pgp and p53. All dogs were subsequently treated with a combination chemotherapy protocol. Remission and survival durations were evaluated for correlation with histologic grade and presence of drug resistance markers. Of the 31 cases, 24 (80%) and 7 (22%) were positive for Pgp and p53, respectively. Overall, the median survival and duration of remission in the study was 246 days and 137 days, respectively. The National Cancer Institute working formulation histologic grade was not associated with either survival or duration of first remission (DOR). The Pgp protein expression and DOR and survival was not statistically significant. Expression of p53 was statistically correlated with survival.

Expression of the Bcl-2 apoptotic marker in cats diagnosed with inflammatory bowel disease and gastrointestinal lymphoma.

Immunolabeling for the critical lymphocyte survival factor, Bcl-2, of intestinal biopsies from cats with histologic evidence of inflammatory bowel disease (IBD) or gastrointestinal (GI) lymphoma was evaluated to determine if expression differed significantly between these two disease processes. Immunolabeling for Bcl-2 was performed on small intestinal endoscopic or full thickness biopsy sections from 55 cats. Diagnosis of IBD, T-cell lymphoma or B-cell lymphoma was established previously. The percentage of infiltrating lymphocytes that were positively labeled for Bcl-2 was subjectively determined for each case. Eight cats were diagnosed with IBD and 47 cats with lymphoma. A significantly higher percentage of cells were positively immunolabeled for Bcl-2 in cats with GI lymphoma [median (range); 90 (5-95)%] compared with cats with IBD [60 (15-95)%] (P = 0.029). However, the overall degree of positive immunolabeling in both groups tended to be high. This over-expression of Bcl-2 may prove useful as a therapeutic target for IBD and GI lymphoma in cats.

Treatment-related toxicities in tumor-bearing cats treated with temozolomide alone or in combination with doxorubicin: a pilot assessment.

A retrospective study assessing treatment-related toxicities in tumor-bearing cats treated with temozolomide (TMZ) alone or in combination with doxorubicin was conducted. TMZ was administered orally once a day for 5 days every 3 weeks at a dose of 20 mg/cat. Tumor response was evaluated with standard World Health Organization criteria and toxicity was monitored using veterinary co-operative oncology group-common terminology criteria for adverse events (VCOG--CTCAE) criteria. Ten tumor-bearing cats with various types of malignancies were treated with TMZ-based chemotherapy. Eight cats were evaluable for response. Two cats achieved a complete response, one achieved stable disease and five achieved a partial response. Four grade III and one grade IV hematological toxicities, and one grade IV gastrointestinal toxicity were observed. Four cats were euthanased as a result of apparent toxicity. One cat was euthanased as a result of severe and prolonged myelosuppression with fever. Three were euthanased for grade III pleural and pericardial effusions. Effusion was seen in cats treated with higher cumulative dose of TMZ (P = 0.0046). Planned additional case accrual was discontinued because of unacceptable levels of toxicity despite evidence of efficacy in some of the cats. Additional investigation is needed to elucidate this unexpected apparent cumulative toxicity.

Evaluation and comparison of outcomes in dogs with periarticular and nonperiarticular histiocytic sarcoma.

OBJECTIVE: To evaluate and compare the outcomes of dogs with periarticular histiocytic sarcoma (PAHS) and histiocytic sarcoma of other anatomic locations (non-PAHS) and identify factors associated with outcome for dogs with PAHS. DESIGN: Retrospective cohort study. ANIMALS: 19 dogs with PAHS and 31 dogs with non-PAHS. PROCEDURES: Medical records of dogs with histiocytic sarcoma that underwent definitive local treatment (surgery or radiation), chemotherapy, or a combination of these were reviewed. Patient signalment, clinical signs, staging test results, clinicopathologic data, type of treatment, response, and outcome were collected, and potential risk factors in dogs with PAHS were identified and analyzed for an association with outcome. RESULTS: Dogs with PAHS lived significantly longer than did dogs with non-PAHS, with an overall median survival times of 391 (range, 48 to 980) and 128 (range, 14 to 918) days, respectively, despite the presence of suspected metastasis at diagnosis in 13 of 19 dogs with PAHS. Dogs with PAHS without evidence of metastasis at diagnosis lived significantly longer than did dogs with PAHS with evidence of metastasis, with median survival times of 980 (range, 83 to 980) and 253 (range, 48 to 441) days, respectively. Administration of prednisone in dogs with PAHS was associated with a significantly shorter time to tumor progression (TTP) and increased risk of tumor progression and death. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that dogs with PAHS may have a favorable outcome independent of metastatic status when treated with chemotherapy or aggressive multimodal treatment. The concurrent administration of prednisone may be a negative predictive factor for survival time and TTP in dogs with PAHS.

Treatment with DAV for advanced-stage hemangiosarcoma in dogs.

Hemangiosarcoma (HSA) is an aggressive disease that is fairly common in the dog. The authors evaluated a doxorubicin, dacarbazine, and vincristine (DAV) combination protocol in dogs with nonresectable stage II and stage III HSA. Twenty-four dogs were enrolled in this prospective, phase 2 study. Doxorubicin and dacarbazine were administered on day 1 while vincristine was administered on days 8 and 15. The protocol was repeated every 21 days for a maximum of six cycles or until disease progression. Toxicity and efficacy were assessed by clinical and laboratory evaluation and by questionnaires completed by the owners. Of the 24 included dogs, 19 were evaluable for response. The response rate (including five complete responses and four partial responses) was 47.4%. Median time to tumor progression was 101 days and median overall survival was 125 days. Significant toxicities were noted, including 41 high-grade hematologic and 12 high-grade gastrointestinal toxic events. Five dogs discontinued treatment due to chemotherapy-related toxicities, but no treatment-related deaths occurred. Multivariate analysis identified patient age (relative risk [RR], 2.3, P=0.049) to be negatively associated with time to progression whereas dacarbazine dose reductions (RR, 0.06, P=0.031) were positively associated with time to progression. Dacarbazine dose reduction was the sole factor positively associated with overall survival (RR, 0.28, P=0.015). In conclusion, the DAV combination appears to offer clinical responses and may prolong survival in dogs with advanced-stage HSA.

Evaluation of the use of chemotherapy and other prognostic variables for surgically excised canine thyroid carcinoma with and without metastasis.

This retrospective study compared the efficacy of surgery alone versus surgery in combination with chemotherapy in the treatment of canine thyroid carcinoma; potential prognostic factors were evaluated. Forty-four dogs with biopsy-confirmed thyroid carcinoma met the inclusion criteria. Twenty-eight dogs were treated with surgery alone and 16 with surgery and chemotherapy. The median survival of dogs treated with surgery and chemotherapy was 518 d, which was not statistically different from that of the dogs treated with surgery alone. The number of thyroid lobes removed at surgery was prognostic with respect to survival. Despite an overall metastatic rate of 48%, the addition of chemotherapy to surgical excision did not improve survival; however, this finding may be due to inadequate power to demonstrate a difference.

Treatment of an amelanotic melanoma using radiation therapy in a lesser Madagascar hedgehog tenrec (Echinops telfairi).

A 15-yr-old, male lesser Madagascar hedgehog tenrec (Echinops telfairi) presented with a mass caudal to the right ear. Cytology suggested a sarcoma. Surgical removal was attempted. Histology was consistent with a soft tissue sarcoma. The mass recurred within 331 days post operation. Radiation therapy was initiated. Computed tomography was used for staging in conjunction with three-dimensional computerized treatment planning software to permit accurate lesion localization and to optimize normal tissue sparing. A total dose of 6,480 cGy was administered in 24 fractions over 46 days. Transient hind limb paresis developed during the course of the radiation therapy, but resolved after 7 days with prednisone treatment. Minimal acute radiation toxicity was observed. The mass responded with at least a 90% reduction in volume following radiation treatment. The animal survived 266 days from the initiation of treatment. On necropsy, a small mass and granulation tissue were found at the site of the initial neoplasm, indicating good regional control of the tumor; however, extensive metastases to the spleen and liver were present. Immunohistochemically, the original, recurrent, and metastatic populations were strongly positive for HMB 45 and weakly positive for S-100, and the final diagnosis was metastatic amelanotic melanoma.

Use of a balloon-expandable metallic stent to relieve malignant urethral obstruction in a cat.

CASE DESCRIPTION: A 19-year-old neutered male domestic shorthair cat was evaluated because of signs of urinary tract obstruction. CLINICAL FINDINGS: Physical examination findings were consistent with urethral obstruction, and a mass could be palpated in the region of the bladder neck. Abdominal ultrasonography and thoracic radiography revealed a mass in the trigone of the urinary bladder and a solitary mass in the left caudal lung lobe. Cytologic examination of the urine sediment, samples obtained by means of traumatic urethral catheterization, and fine-needle aspirates of the bladder mass did not result in a diagnosis. TREATMENT AND OUTCOME: A balloon-expandable metallic stent was placed in the proximal portion of the urethra to relieve the malignant obstruction. After stent placement, the cat had signs of urinary incontinence and detrusor atony, both of which resolved with medical treatment. The cat was euthanized 1 month after stent placement because of progressive azotemia. Histologic examination of necropsy samples revealed grade III urothelial carcinoma and papillary pulmonary adenocarcinoma. CLINICAL RELEVANCE: Findings suggested that stent placement may be a viable palliative treatment in cats with malignant urinary obstruction.

Measurement of serum carboxyterminal cross-linked telopeptide of type I collagen concentration in dogs with osteosarcoma.

OBJECTIVE: To evaluate the usefulness of carboxyterminal cross-linked telopeptide of type I collagen (ICTP) concentrations for screening dogs for the presence of osteosarcoma. SAMPLE POPULATION: 32 client-owned dogs with osteosarcoma (27 dogs with osteosarcoma of the appendicular skeleton and 5 dogs with osteosarcoma of the axial skeleton) and 44 non-tumor-bearing control dogs. PROCEDURES: Serum was obtained from blood samples collected from dogs with osteosarcoma and from clinically normal dogs. The serum ICTP concentration was determined by use of a commercially available radioimmunoassay for ICTP. RESULTS: Mean +/- SD serum ICTP concentration in the tumor-bearing dogs was 7.32 +/- 2.88 ng/mL, and in clinically normal dogs, it was 6.77 +/- 2.31 ng/mL; values did not differ significantly. Mean serum ICTP concentration in dogs with appendicular osteosarcoma, compared with that of clinically normal dogs, was not significantly different. Mean serum ICTP concentration in dogs with axial skeletal tumor location was 10.82 +/- 2.31 ng/mL, compared with a value of 6.73 +/- 2.28 ng/mL in dogs with appendicular osteosarcoma. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of the results of this study, serum ICTP concentrations are not a clinically useful screening tool for the detection of appendicular osteosarcoma in dogs. Despite the observation that serum ICTP concentration was higher in dogs with axial osteosarcoma than in clinically normal dogs, serum ICTP concentration determination is not a suitable screening test for osteosarcoma.

Telomere length in normal and neoplastic canine tissues.

OBJECTIVE: To determine the mean telomere restriction fragment (TRF) length in normal and neoplastic canine tissues. SAMPLE POPULATION: 57 solid-tissue tumor specimens collected from client-owned dogs, 40 samples of normal tissue collected from 12 clinically normal dogs, and blood samples collected from 4 healthy blood donor dogs. PROCEDURES: Tumor specimens were collected from client-owned dogs during diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital, whereas 40 normal tissue samples were collected from 12 control dogs. Telomere restriction fragment length was determined by use of an assay kit. A histologic diagnosis was provided for each tumor by personnel at the Veterinary Diagnostic Laboratory at the University of Illinois. RESULTS: Mean of the mean TRF length for 44 normal samples was 19.0 kilobases (kb; range, 15.4 to 21.4 kb), and the mean of the mean TRF length for 57 malignant tumors was 19.0 kb (range, 12.9 to 23.5 kb). Although the mean of the mean TRF length for tumors and normal tissues was identical, tumor samples had more variability in TRF length. CONCLUSIONS AND CLINICAL RELEVANCE: Telomerase, which represents the main mechanism by which cancer cells achieve immortality, is an attractive therapeutic target. The ability to measure telomere length is crucial to monitoring the efficacy of telomerase inhibition. In contrast to many other mammalian species, the length of canine telomeres and the rate of telomeric DNA loss are similar to those reported in humans, making dogs a compelling choice for use in the study of human anti-telomerase strategies.

Efficacy of temozolomide or dacarbazine in combination with an anthracycline for rescue chemotherapy in dogs with lymphoma.

OBJECTIVE: To compare results of treatment with temozolomide or dacarbazine, in combination with an anthracycline, in dogs with relapsed or refractory lymphoma. DESIGN: Nonrandomized, controlled clinical trial. ANIMALS: 63 dogs with relapsed or refractory lymphoma. PROCEDURES: Chemotherapy was administered in 21-day cycles. A combination of temozolomide and an anthracycline (doxorubicin or dactinomycin) was administered to 21 dogs and a combination of dacarbazine and an anthracycline was administered to 42 dogs. Efficacy and toxicoses were assessed. Results-Thirteen of the 18 (72%) dogs treated with the temozolomide-anthracycline combination and 25 of the 35 (71%) dogs treated with the dacarbazine-anthracycline combination had a complete or partial response. Median duration of response to rescue chemotherapy was 40 days (range, 0 to 217 days) for dogs in the temozolomide group and 50 days (range, 0 to 587 days) for dogs in the dacarbazine group. The incidence of high-grade hematologic toxicoses was significantly higher among dogs in the dacarbazine group than among dogs in the temozolomide group, but the incidence of gastrointestinal tract toxicoses was not significantly different between groups. There were no significant differences between groups in regard to proportion of dogs with a complete or partial response, duration of response to rescue chemotherapy, survival time following rescue chemotherapy, or overall survival time. CONCLUSIONS AND CLINICAL RELEVANCE: Both combinations had promise in the treatment of dogs with relapsed or refractory lymphoma, although administration of temozolomide was more convenient than administration of dacarbazine and caused fewer hematologic toxicoses.

Isolation, characterization, and expression of stromelysin-1 in primary tumors of dogs.

OBJECTIVE: To isolate and characterize the cDNA sequence of canine stromelysin-1 (matrix metalloproteinase [MMPI-3), screen various naturally developing primary tumors of dogs, and assess the effect of stromelysin-1 on survival of dogs with cancer. SAMPLE POPULATION: 3 canine cell lines and biopsy specimens of primary tumors collected from 54 dogs. PROCEDURE: 3 canine cell lines and biopsy specimens of primary tumors collected from 54 dogs at the University of Illinois Veterinary Teaching Hospital were used in the study. Primer sets based on human stromelysin-1 and consensus sequences were designed for expression, screening, and isolation. Two additional primer sets were designed for screening. Samples were assayed at least in duplicate. Data were analyzed for differences in expression of stromelysin-1 on the basis of sex, age, metastasis, malignant versus nonmalignant tissue origin, and duration of patient survival. RESULTS: A 1,479-bp cDNA nucleotide sequence was amplified from established canine cell lines. The open reading frame encoded a protein consisting of 478 amino acids. This sequence was 70% to 88% homologous with stromelysin-1 of other species at the amino acid level. Fifty-four samples were screened for stromelysin-1. Of these, 34 (63%) had positive results and 20 (37%) had negative results for expression. Stromelysin-1 and metastasis were associated with a poor prognosis for survival. CONCLUSIONS AND CLINICAL RELEVANCE: Stromelysin-1 is a potential activator of other members of the MMP family. Additional studies are needed to investigate the relationship between stromelysin-1 production and aggressive biological behavior of tumors in dogs.

Cobalt radiation with or without low-dose cisplatin for treatment of canine naso-sinus carcinomas.

The objective of this study was to determine if low-dose cisplatin could be added safely to radiation therapy for the treatment of naso-sinus carcinomas in dogs. Thirty-one dogs were evaluated; 18 of these dogs received cobalt radiation in combination with low-dose cisplatin while 13 dogs received radiation alone. No difference was observed for acute or late radiation effects. Cisplatin was administered at a dosage of 7.5 mg/m2 20 min prior to every other radiation treatment. An initial dose of 10 mg/m2 was intended but toxicity (primarily azotemia) was unacceptable. Cisplatin was administered as prescribed in 12 of 18 dogs. Cisplatin was discontinued in 2 dogs because of azotemia. In the other 4 dogs cisplatin was not administered as prescribed because the dogs were withdrawn from treatment due to disease progression or radiation effects. There was no long-term renal disease in patients who developed azotemia. The overall median survival was 433 days with 4 (12.9%) dogs still alive at the completion of the study.

Expression of matrix metalloproteinases in feline vaccine site-associated sarcomas.

OBJECTIVES: To screen for expression of 9 predominant members of the matrix metalloproteinase (MMP) family, including membrane-type matrix metalloproteinases (MT-MMPs) and tissue inhibitors of metalloproteinases (TIMPs), in primary tumor tissue biopsy specimens of vaccine site-associated sarcomas (VSS) in cats and compare expression profiles of VSS with expression profiles of non-VSS and carcinomas. SAMPLE POPULATION: 31 primary tumor tissue biopsy specimens and 6 nontumor (normal) tissue biopsy specimens. PROCEDURES: Tissue specimens were obtained from primary tumor biopsy specimens of cats. Primers for reverse transcriptase-polymerase chain reaction assay were designed on the basis of known sequences. Data were analyzed for patterns of expression of MMPs, MT-MMPs, and TIMPs. Differences in expression patterns were evaluated among cats of differing genders, ages, metastasis status, and overall survival durations, and between cats with VSS and cats with non-VSS tumor types. RESULTS: A total of 31 primary tumor tissue biopsy specimens and 6 nontumor (normal) tissue biopsy specimens were screened for the presence of 6 MMPs and 3 TIMPs. Matrix metalloproteinase and TIMP expression was found in non-VSS, carcinomas, and VSS. No significant differences were found in patterns of expression among tumor types. Metastasis was found to be the only predictive factor for overall survival duration. A significant correlation was found between MMP2 and MT-MMP16 expression and overall duration of survival. CONCLUSIONS AND CLINICAL RELEVANCE: The identification of MMPs in feline VSS supports an underlying inflammatory pathogenesis for this tumor. Expression of MMP2 and MT-MMP16 were correlated with survival time in our study.