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  • Author or Editor: Carolyn J. Henry x
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Abstract

Objective—To evaluate use of a radiolabeled peptide nucleic acid–peptide conjugate (RaPP) targeting B-cell leukemia-lymphoma 2 (BCL2) mRNA for scintigraphic detection of neoplastic lymphocytes in dogs with B-cell lymphoma and to assess associations among RaPP uptake, time to tumor progression (TTP), and BCL2 mRNA expression.

Animals—11 dogs with B-cell lymphoma and 1 clinically normal dog.

Procedures—Scintigraphic images were acquired 1 hour after IV injection of the RaPP. Regions of interest (ROIs) were drawn around lymph nodes, liver, and spleen; ROI intensity (relative to that of an equally sized region of muscle in the same image) was measured. Each ROI was also subjectively categorized as positive or negative for increased RaPP uptake. Expression of BCL2 mRNA was determined via quantitative reverse transcriptase PCR assay of a lymph node sample from dogs with lymphoma. Associations among imaging results, TTP, and BCL2 mRNA expression were evaluated.

Results—Increased RaPP uptake was detected in affected tissues of dogs with lymphoma. Dogs with superficial cervical lymph node ROIs categorized as negative (n = 8) for increased RaPP uptake had a significantly longer TTP than did dogs for which this ROI was considered positive (2). Measured intensity of mandibular and superficial cervical lymph node ROIs was negatively associated with TTP. Associations among BCL2 mRNA and ROI intensity or TTP were not significant.

Conclusions and Clinical Relevance—Increased RaPP uptake at mandibular or superficial cervical lymph node ROIs may be a negative prognostic indicator in dogs with lymphoma. A larger investigation is needed to determine clinical value of the RaPP for disease detection and prognostication.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare distributions of survivin among tissues from urinary bladders of dogs with cystitis, transitional cell carcinoma (TCC), or histologically normal urinary bladders.

Sample Population—24 archived and 7 fresh-frozen specimens of urinary bladders from dogs with cystitis.

Procedures—Immunohistochemical analysis of archived tissue specimens was performed to identify survivin protein in the nucleus and cytoplasm of cells by use of polyclonal rabbit anti-survivin antibody. Tissues that contained ≥ 5% immunoreactive cells were considered positive for survivin protein. Reverse-transcription PCR analysis was performed on fresh-frozen tissues to identify survivin mRNA. Data on tissues from dogs with TCC or histologically normal urinary bladders that were obtained during another study were used for statistical comparisons.

Results—Twelve of 24 (50%) cystitic tissues were positive for nuclear survivin, compared with 28 of 41 (68%) TCC tissues and 0 of 46 (0%) normal tissues. Two of 24 (8%) cystitic tissues were positive for cytoplasmic survivin, compared with 7 of 41 (17%) TCC tissues and 17 of 46 (37%) normal tissues. Proportions of specimens that contained nuclear or cytoplasmic survivin were significantly different between cystitic and normal tissues but not between cystitic and TCC tissues. Four of 7 cystitic tissues were positive for survivin mRNA, which was comparable with results for TCC and normal tissues.

Conclusions and Clinical Relevance—Nuclear survivin was detected in TCC and cystitic tissues but not in normal urinary bladder tissues. Additional studies are needed to determine whether nuclear survivin contributes to the development or progression of TCC.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To conduct a phase I-II clinical trial of hyaluronan-cisplatin nanoconjugate (HA-Pt) in dogs with naturally occurring malignant tumors.

ANIMALS 18 healthy rats, 9 healthy mice, and 16 dogs with cancer.

PROCEDURES HA-Pt was prepared and tested by inductively coupled plasma mass spectrometry; DNA-platinum adduct formation and antiproliferation effects of cisplatin and HA-Pt were compared in vitro. Effects of cisplatin (IV) and HA-Pt (SC) in rodents were tested by clinicopathologic assays. In the clinical trial, dogs with cancer received 1 to 4 injections of HA-Pt (10 to 30 mg/m2, intratumoral or peritumoral, q 3 wk). Blood samples were collected for pharmacokinetic analysis; CBC, serum BUN and creatinine concentration measurement, and urinalysis were conducted before and 1 week after each treatment. Some dogs underwent hepatic enzyme testing. Tumors were measured before the first treatment and 3 weeks after each treatment to assess response.

RESULTS No adverse drug effects were detected in pretrial assessments in rodents. Seven of 16 dogs completed the study; 3 had complete tumor responses, 3 had stable disease, and 1 had progressive disease. Three of 7 dogs with oral and nasal squamous cell carcinoma (SCC) that completed the study had complete responses. Myelosuppression and cardiotoxicosis were identified in 6 and 2 dogs, respectively; none had nephrotoxicosis. Four of 5 dogs with hepatic enzymes assessed had increased ALT activities, attributed to diaquated cisplatin products in the HA-Pt. Pharmacokinetic data fit a 3-compartment model.

CONCLUSIONS AND CLINICAL RELEVANCE HA-Pt treatment resulted in positive tumor responses in some dogs, primarily those with SCC. The adverse effect rate was high.

IMPACT FOR HUMAN MEDICINE Oral SCC in dogs has characteristics similar to human head and neck SCC; these results could be useful in developing human treatments.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate safety and efficacy of LDI-100, a preparation containing human chorionic gonadotropin (hCG) and bacillus Calmette-Guerin (BCG), in the treatment of dogs with mast cell tumors and to compare results with those from a control group receiving single-agent vinblastine.

Animals—95 dogs with measurable grade II or III mast cell tumors.

Procedures—Dogs were randomized to receive either LDI-100 (1.35 ng of BCG and 2 units of hCG, SC, q 24 h) or vinblastine (2 mg/m2, IV, q 1 wk) for 6 weeks. Tumors were measured at baseline and day 42, and dogs were monitored for signs of toxicosis. Clinical performance scores were recorded at each visit. Differences in host factors (sex, weight, and age), clinical performance score, tumor response, and adverse events were analyzed.

Results—46 dogs received LDI-100, and 49 dogs received vinblastine. No significant differences were found between the 2 treatment groups with regard to host factors or clinical performance score. Tumor response (≥50% reduction) rates were similar between the LDI-100 and vinblastine group (28.6% and 11.7%, respectively). Dogs in the LDI-100 group had significantly less neutropenia than the vinblastine group.

Conclusions and Clinical Relevance—hCG and BCG have immunomodulatory and antitumor effects against a variety of malignancies in humans and dogs. In this study, LDI-100 provided clinical responses comparable to single-agent vinblastine chemotherapy but without myelosuppression. LDI-100 is a promising new agent that should be further investigated for multimodality therapy of mast cell tumors in dogs.

Full access
in American Journal of Veterinary Research