In vitro canine distemper virus infection of canine lymphoid cells: a prelude to oncolytic therapy for lymphoma.

PURPOSE: Measles virus (MV) causes the regression of human lymphoma xenografts. The purpose of this study was to determine if canine lymphoid cells could be infected in vitro with MV or canine distemper virus (CDV, the canine Morbillivirus equivalent of MV) and determine if in vitro viral infection leads to apoptotic cell death. EXPERIMENTAL DESIGN: Reverse transcriptase-PCR was used to examine the expression of both signal lymphocyte activation molecule (CD150) and membrane cofactor molecule (CD46) mRNA. An attenuated CDV expressing enhanced green fluorescent protein was used to infect canine cells in vitro. Both flow cytometry and reverse transcriptase-PCR was used to document CDV infection. Cell death was examined using a propidium iodide staining assay and Annexin V binding. RESULTS: Canine lymphoid cell lines and neoplastic B and T lymphocytes collected from dogs with spontaneous lymphoma expressed the Morbillivirus receptor CD150 mRNA. In contrast, only neoplastic lymphocytes expressed detectable levels of CD46 mRNA. Although MV did not infect canine cells, CDV efficiently infected between 40% and 70% of all three canine lymphoid lines tested. More importantly, CDV infected 50% to 90% of neoplastic lymphocytes isolated from dogs with both B and T cell lymphoma. Apoptosis of CDV-infected cell lines was documented. CONCLUSIONS: Attenuated CDV may be a useful treatment for canine lymphoma. As such, dogs with lymphoma may represent a biologically relevant large animal model to investigate the feasibility, safety, and efficacy of Morbillivirus therapy in a clinical setting with findings that may have direct applicability in the treatment of human non-Hodgkin's lymphoma.

Serum thymidine kinase activity: an alternative to histologic markers of cellular proliferation in canine lymphoma.

Thymidine kinase (TK) is a cellular enzyme which is involved in a 'salvage pathway' of DNA synthesis. It is activated in the G1/S phase of the cell cycle, and its activity has been shown to correlate with the proliferative activity of tumor cells.... Clinical studies have reported high serum TK concentrations in a variety of neoplasias. The majority of these studies concerned hematological malignancies. TK seems to be a useful marker in non-Hodgkin's lymphoma, where it correlates with clinical staging and provides marked prognostic information on (progression-free) survival.

Concurrence between clinical and pathologic diagnoses in a veterinary medical teaching hospital: 623 cases (1989 and 1999).

OBJECTIVE: To determine whether there was a decline in the percentage of dogs undergoing necropsies and whether there was substantial agreement or disagreement between clinical and pathologic diagnoses. DESIGN: Retrospective study. ANIMALS: 623 dogs. PROCEDURE: Medical records of hospitalized dogs that died or were euthanatized and necropsied at a veterinary teaching hospital in 1989 and 1999 were reviewed. Clinical and pathologic diagnoses were recorded and compared. RESULTS: There was a significant decline in the necropsy rate of hospitalized dogs that died or were euthanatized in 1999, compared with 1989. In both 1989 and 1999, there was disagreement between the clinical and pathologic diagnoses in approximately a third of the cases. CONCLUSIONS AND CLINICAL RELEVANCE: Despite improved diagnostic methods, the accuracy of diagnosis did not improve significantly in 1999, compared with 1989. Necropsy is the best method to assess overall diagnostic accuracy. Increased availability of teaching funds may promote efforts to have necropsies performed in veterinary teaching hospitals.

Canine prostatic intraepithelial neoplasia: is the comparative model relevant?

BACKGROUND: Histologic sections from an archival collection of a veterinary teaching hospital were examined to determine the likelihood of detection of canine high-grade prostatic intraepithelial neoplasms (HGPIN), as a prelude to use of the canine model of prostatic carcinogenesis for chemopreventive strategies. METHODS: Tissue specimens representing clinically healthy (normal) prostate glands, benign prostatic hyperplasia, and prostatic carcinoma were examined in one tissue plane for histological evidence of HGPIN. RESULTS: No histological evidence of HGPIN was detected in 20 normal prostate glands or 95 prostate glands with benign prostatic hyperplasia. Seven of 20 prostatic carcinomas had synchronous HGPIN. CONCLUSIONS: Histological evidence of HGPIN is unlikely to be detected in the healthy or hyperplastic canine prostate gland with the clinically-procured biopsy. This might diminish the usefulness of canine HGPIN in temporal studies of chemoprevention of prostate cancer. HGPIN was found simultaneously with prostatic carcinoma in more than one-third of the carcinomas examined.

Vaccine site-associated sarcoma and malignant lymphoma in cats: a report of six cases (1997-2002).

Six cats developed malignant lymphoma 3 to 45 months after treatment for vaccine site-associated sarcoma. During the same time period, 184 cats were evaluated in the teaching hospital for vaccine site-associated sarcomas. Feline vaccine site-associated sarcoma is not believed to be associated with feline leukemia virus (FeLV) infection. Five of six cats were negative by enzyme-linked immunosorbent assay for FeLV antigens at the times of diagnosis of both sarcoma and lymphoma, and no cats were infected with feline immunodeficiency virus.

Clinical evaluation of mitoxantrone and piroxicam in a canine model of human invasive urinary bladder carcinoma.

PURPOSE: Cyclooxygenase inhibitors show promise in chemoprevention and therapy of certain carcinomas, an effect that may be additive to that of standard chemotherapy. The purpose of this study was to evaluate the efficacy of combined therapy using the cyclooxygenase inhibitor, piroxicam, and mitoxantrone against a relevant canine model of human invasive bladder cancer. EXPERIMENTAL DESIGN: Fifty-five dogs with transitional cell carcinoma of the urinary bladder were enrolled in this nonrandomized one-armed prospective multi-institutional clinical trial. Mitoxantrone was administered i.v. (5 mg/m(2)) every 21 days for four treatments, and piroxicam was administered p.o. (0.3 mg/kg/day) for the study duration. Tumor staging was performed at baseline, day 42 and every 3 months after protocol completion. Endpoints included time-to-treatment failure and survival time (ST). RESULTS: Response data were available for 48 dogs and included one complete response, 16 partial responses, 22 with disease stabilization, and 9 with progressive disease for an overall 35.4% measurable response rate. Subjective improvement occurred in 75% of treated dogs. Median time-to-treatment failure and ST were 194 and 350 days, respectively. Using censoring and end point definitions similar to those of previous reports of dogs treated with piroxicam alone, the median ST in this study was 291 days, compared with 181 days with piroxicam alone. Diarrhea and azotemia were the most common treatment complications. CONCLUSIONS: Mitoxantrone/piroxicam induced remission more frequently than previously reported for either drug as a single agent in this canine model of invasive human transitional cell carcinoma. Additional evaluation of these drugs in combination protocols should be explored.

bcl-2 and MIB-1 labeling indexes in cats with lymphoma.

Immunohistochemistry was used to examine feline lymphoid tumors for bcl-2 and MIB-1 expression. Tumor tissues from 29 cats were selected to represent 2 groups--cats that did not respond to chemotherapy and cats that responded to therapy. Median bcl-2 immunoreactivity was 60%, and median MIB-1 reactivity was 47%. There was no significant difference in median survival time between cats with tumors with high levels of bcl-2 expression and those with low levels of expression. There was no significant difference in median survival time between cats with tumors with high levels of MIB-1 expression and those with low levels of expression. Mean bcl-2 immunoreactivity was significantly (P = .0004) higher in low-grade (73.2%) than in high-grade (16.9%) lymphomas, whereas the mean MIB-1 immunoreactivity was significantly (P = .0201) higher in high-grade (61.2%) lymphomas than in low-grade (35.0%) lymphomas. The mean bcl-2 immunoreactivity was significantly (P = .0042) greater in T-cell lymphomas (66.8%) than in B-cell lymphomas (22.8%), whereas the mean MIB-1 immunoreactivity was significantly (P = .0052) lower in T-cell lymphomas (36.4%) than in B-cell lymphomas (65.2%). Although expression of bcl-2 and MIB-1 did not appear to be linked to responses to chemotherapy in cats with lymphoma, the data suggest a possible role for these regulatory proteins in the biology of feline lymphomas.

Computer-assisted image analysis of neovascularization in thyroid neoplasms from dogs.

OBJECTIVE: To develop a computer-assisted image analysis procedure for quantitation of neovascularization in formalin-fixed paraffin-embedded specimens of thyroid gland tissue from dogs with and without thyroid gland neoplasia. SAMPLE POPULATION: 47 thyroid gland carcinomas, 8 thyroid gland adenomas, and 8 specimens of thyroid tissue from dogs without thyroid gland abnormalities (normal). PROCEDURE: Serial tissue sections were prepared and stained with antibodies against human CD31 or factor VIII-related antigen (factor VIII-rag). The areas of highest vascularity were identified in CD31-stained sections, and corresponding areas were then identified in factor VIII-rag-stained sections. Image analysis was used to calculate the total vascular density in each section, and neovascularization, expressed as a percentage, was determined as the absolute value of the total vascular density derived from factor VIII-rag-stained sections minus the vascular density derived from CD31-stained sections. RESULTS: Mean vascular density of thyroid gland carcinomas derived from CD31-stained sections was significantly greater than density derived from factor VII I-rag-stained sections. This incremental difference was presumed to represent degree of neovascularization. However, significant differences were not detected between vascular densities derived from CD31 and factor VIII-rag-stained sections for either normal thyroid gland tissue or thyroid gland adenomas. No significant correlations were found between vascular density in thyroid gland carcinomas and survival time following surgery. CONCLUSION AND CLINICAL RELEVANCE: A computer-assisted image analysis method was developed for quantifying neovascularization in thyroid gland tumors of dogs. This method may allow identification of dogs with tumors that are most likely to respond to treatment with novel antiangiogenesis agents.

Multiple skin tumours in a Doberman Pinscher with colour dilution alopecia.

Abstract An 11-year-old Doberman Pinscher with clinical and histological skin features consistent with colour dilution alopecia had a long history of skin disease. The animal had hundreds of papules affecting the 'blue' haired áreas of the hair coat. The predominant skin lésions included keratinizing infundibular cysts, keratin horns, perifollicular dermatitis, and sebaceous hyperplasia; these lésions were often accompanied by fürunculosis and suppurative panniculitis. Over a 9-month period, 32 lésions were examined histologically, which included two lipomas, one infiltrative lipoma, one squamous papilloma, two mast cell tumours, four cavernous haemangiomas, one haemangiosarcoma, and three melanomas. It is unknown at present whether the colour dilution phenotype confers increased risk for tumours of the skin and or subcutaneous tissues. Résumé- Un doberman de 11 ans avec des manifestations cutanées cliniques et histologiques compatibles avec le díagnostic d'alopécie des couleurs diluées avait une longue histoire de problèmes cutanés. L'animal présentait des centaines de papules affectant les zones de couleur bleue. Les lésions cutanées prédominantes consistaient en kystes infundibulaires kératinisants, cornes cutanées, dermatite périfolliculaire et hyperplasie sébacée; ces lésions s'accompagnaient souvent de füronculose et de panniculite suppurative. Sur une période de 9 mois, 32 lésions ont fait l'objet d'un examen histologique, dont deux lipomes, un lipome infiltrant, un papillome, deux mastocytomes, quatre hémangiomes caverneux, un hémangiosarcome, et trois mélanomes. On ne sait actuellement pas si le phénotype couleur diluée constitue un facteur de risque accru pour les tumeurs de la peau et des tissus sous cutanés. [Madewell, B. R., Ihrke, P. J., Griffey, S. M. Multiple skin tumours in a Doberman Pinscher with colour dilution alopecia. (Tumeurs cutanées multiples chez un doberman présentant une alopécie des couleurs diluées.) Veterinary Dermatology 1997; 8: 59-62.] Resumen Un doberman pinscher de 11 años con caracteristicas clinicas e histológicas compatibles con alopecia de color diluido tenia una larga historia de enfermedad cutanea. El animal presentaba centenares de pápulas afectando las áreas de pelo "azul". Las lesiones prédominantes incluian quistes infundibulares queratinizados, cuernos de queratina, dermatitis perifolicular e hiperplasia sebácea; estas lesiones se acompañaban de fürunculosis y paniculitis supurativa. Durante un periodo de 9 meses, 32 lesiones fueron examinadas histológicamente, incluyendo 2 lipomas, un lipoma infiltrativo, un papiloma escamoso, dos mastocitomas, cuatro hemangiomas cavernosos, un hemangiosarcoma y tres melanomas. Se desconoce aún si el fenotipo de color diluido aumenta el riesgo para la aparición de tumores en tejidos cutáneos y subcutáneos. [Madewell, B. R., Ihrke, P. J., Griffey, S. M. Multiple skin tumours in a Doberman Pinscher with colour dilution alopecia. (Multiples tumores cutáneos en un Doberman Pinscher con alopecia de color diluido.) Veterinary Dermatology 1997; 8: 59-62.] Zusammenfassung- Ein elfjähriger Dobermann mit klinischen und histologischen Befunden, die bei Farbmutantenalopezie auftreten, wies eine lange Vorgeschichte mit Hautkrankheiten auf. Das Tier zeigte Hunderte von Papeln, die die "blau" behaarten Bezirke des Felles betrafen. Die vorherrschenden Hautveränderungen bestanden in keratinisierenden infundibulären Zysten, Keratinhörnern, perifollikulärer Dermatitis und Talgdrüsenhyperplasie; diese Veränderungen wurden oft von Furunkulose und eitriger Pannikulitis begleitet. Über eine Zeitspanne von 9 Monaten wurden 32 Veränderungen histologisch untersucht, wovon zwei in Lipomen bestanden, eine in einem infiltrativen Lipom, eine in einem squamösen Papillom, zwei in Mastzelltumoren, vier in kavernösen Hämangiomen, eine in einem Hämangiosarkom und drei in Melanomen. Es ist zur Zeit nicht bekannt, ob der Phänotyp mit der Farbverdünnung mit einem erhöhten Risiko für Tumoren der Haut und/oder des subkutanen Gewebes einhergeht. [Madewell, B. R., Ihrke, P. J., Griffey, S. M. Multiple skin tumours in a Doberman Pinscher with colour dilution alopecia. (Multiple Hauttumoren bei einem Dobermann mit Farbmutantenalopezie.) Veterinary Dermatology 1997; 8: 59-62.].