Objective—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.
Procedure—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. ( Am J Vet Res 2004;
Objective—To detect, isolate, and characterize feline
stromelysin-1 (ie, matrix metalloproteinase [MMP]-3)
in naturally developing tumors in cats.
Sample Population—31 tissue samples obtained
from primary tumors and 6 samples of normal tissues
Procedure—Biopsy specimens were obtained from
primary tumors. Primers were designed on the basis
of known sequences. The sequence of stromelysin-
1 was cloned and analyzed. An additional primer set
was used as a screening tool. Samples were
assayed in duplicate or triplicate, when possible.
Data obtained were analyzed for differences in
expression of stromelysin-1 with regard to overall
survival among cats of various sex, age, and disease
Results—A 1,181-bp cDNA nucleotide sequence was
amplified. The open reading frame encoded 393 amino
acids. This amino acid sequence shared 70% to 85%
sequence homology with sequences of other species.
In addition, samples were screened for stromelysin-1.
Of the 31 tumor samples tested, 16 (51.6%) had positive
results for expression of stromelysin-1. Total RNA
expression was detected in a diverse group of tumor
types. Prognostic factors associated with a shorter
duration of survival included evidence of metastasis and
metastasis associated with expression of stromelysin-1.
Conclusions and Clinical Relevance—Feline
stromelysin-1 contains all the conserved regions typically
found in members of the MMP family. Activity of
stromelysin-1 has been implicated in a wide number
of physiologic and pathologic processes. Identification
of this gene may lead to the development of useful
reagents to assist with diagnosis and management of
neoplastic diseases in cats. (Am J Vet Res 2004;
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.
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.
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.
Objective—To establish the diagnostic significance
of the telomeric repeat amplification protocol (TRAP)
assay in detecting feline malignancies.
Sample Population—Solid tissue specimens collected
from 33 client-owned cats undergoing diagnostic
or therapeutic procedures at the University of Illinois
Veterinary Medical Teaching Hospital between July
1997 and September 1999 and an additional 20 tissue
samples were collected from 3 clinically normal control
cats euthanatized at the conclusion of an unrelated
Procedure—The TRAP assay was used for detection
of telomerase activity. Each result was compared to
its respective histopathologic diagnosis.
Results—Twenty-nine of 31 malignant and 1 of 22
benign or normal tissue samples had telomerase
activity, indicating 94% sensitivity and 95% specificity
of the TRAP assay in our laboratory.
Conclusion and Clinical Relevance—The diagnostic
significance of telomerase activity has been
demonstrated in humans and recently in dogs by our
laboratory. We tested feline samples to determine
whether similar patterns of telomerase activity exist.
On the basis of our results, the TRAP assay may be
clinically useful in providing a rapid diagnosis of malignancy
in cats. The telomerase enzyme may also serve
as a therapeutic target in feline tumors. (Am J Vet Res
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 antitelomerase strategies.
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.
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.
Objective—To isolate and characterize the cDNA
sequence of canine stromelysin-1 (matrix metalloproteinase
[MMP]-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.
(Am J Vet Res 2005;66:1526–1535)