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  • Author or Editor: Susan M. LaRue x
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SUMMARY

Vascular medial thickening is a prominent finding in people and animals with refractory neonatal pulmonary hypertension. Smooth muscle cells are capable of 2 distinct growth responses in vivo: hypertrophy or hyperplasia. Hypertrophic smooth muscle cells may undergo dna synthesis without cell division, leading to a polyploid state. To better understand the nature of smooth muscle cell growth in healthy and pulmonary hypertensive neonatal calves, we measured incorporation of the thymidine analog bromodeoxyuridine (BrdUrd) and total dna content in medial cells from control (pulmonary arterial pressure = 32 ± 2 mm of Hg) and hypobaric hypoxia-exposed (pulmonary arterial pressure = 120 ± 7 mm of Hg) calves. Labeling of medial cells with BrdUrd measured by flow cytometry was increased (P < 0.02) in pulmonary arteries of hypoxia-exposed calves (n = 5), compared with control calves (n = 5). Immunohistochemical localization of BrdUrd indicated that BrdUrd labeling of large elastic pulmonary arteries from hypoxia-exposed calves was increased almost exclusively in the outer half of the medial wall. Increased BrdUrd labeling of muscular pulmonary arteries from hypoxia exposed calves was observed in the arterial media and adventitia, and tended to exit in clusters. Analysis of dna content by flow cytometry indicated a decrease (P < 0.05) in percentage of tetraploid medial cells in pulmonary arteries from hypoxia-exposed calves, compared with control calves. Bivariate analysis for BrdUrd labeling and dna content of cells from the pulmonary arteries of hypoxia-exposed calves indicated a subpopulation of diploid cells with positive BrdUrd labeling, suggestive of dna synthesis and subsequent cell division. Results are suggestive of smooth muscle cell hyperplasia in the vascular media of hypoxia-exposed calves.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate outcomes of stereotactic body radiation therapy (SBRT) in cats with injection-site sarcomas (ISS) via assessment of local responses and recurrences, survival times, and complications.

Design—Retrospective case series.

Animals—11 cats with ISS.

Procedures—Medical records of cats that were treated with SBRT for ISS between June 2008 and July 2012 were reviewed; information on patient demographics (age, sex, and breed), oncological histories (including prior treatment and histologic grade), details of SBRT plans (tumor volume, treatment field sizes, and prescription), response to treatment (including toxicoses), progression-free intervals, and survival times were extracted.

Results—Acute radiation-associated toxicoses were infrequent and limited to mild, self-limiting dermatitis and colitis in 2 and 1 of the 11 cats, respectively. No late radiation-associated toxicoses were observed. The objective response rate was 8 of 11 cats; these patients either had a partial or complete response as determined on the basis of CT or physical examination findings. The median progression-free interval was 242 days, and the median overall survival time was 301 days; median follow-up time of censored subjects was 173 days.

Conclusions and Clinical Relevance—SBRT was completed in 3 to 5 days and was well tolerated when used to treat cats with ISS. Measurable tumor responses were achieved in most cats in this study. Stereotactic body radiation therapy provided a means for palliation of ISS; further investigation is required to determine whether SBRT is a valid treatment option for downstaging disease prior to definitive surgery.

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate the expression of Ki67 and epidermal growth factor receptor (EGFR), mitotic index (MI), and microvascular density (MVD) in feline oral squamous cell carcinoma (SCC) via immunohistochemical staining on archival tumor tissues and to seek a correlation between these markers and clinical variables.

Sample—22 archived tumor samples of feline oral SCC.

Procedures—Immunohistochemical staining for Ki67, MVD, and EGFR was performed and scored. Patient survival information was obtained from the medical records. These molecular markers as well as MI were correlated with tumor locations and patient survival time.

Results—The 22 tumors had wide variation in Ki67 expression, MI, MVD, and EGFR expression. Tongue SCC had higher MVD than did mandibular and maxillary SCC. Tumor expression of EGFR was inversely proportional to survival time.

Conclusions and Clinical Relevance—Results suggested that EGFR expression might be a valuable prognostic factor for treatment outcome in feline oral SCC. It also identified higher angiogenesis in tongue SCC, compared with mandibular and maxillary SCC, which may account for a different clinical outcome. Further prospective characterization of feline oral SCC may provide a better understanding of the underlying molecular factors that drive its behavior and offer the possibility for future patient-specific treatment plans.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To develop an orthotopic model of canine osteosarcoma in athymic rats as a model for evaluating the effects of stereotactic radiotherapy (SRT) on osteosarcoma cells.

Animals—26 athymic nude rats.

Procedures—3 experiments were performed. In the first 2 experiments, rats were injected with 1 × 106 Abrams canine osteosarcoma cells into the proximal aspect of the tibia (n = 12) or distal aspect of the femur (6). Tumor engraftment and progression were monitored weekly via radiography, luciferase imaging, and measurement of urine pyridinoline concentration for 5 weeks and histologic evaluation after euthanasia. In the third experiment, 8 rats underwent canine osteosarcoma cell injection into the distal aspect of the femur and SRT was administered to the affected area in three 12-Gy fractions delivered on consecutive days (total radiation dose, 36 Gy). Percentage tumor necrosis and urinary pyridinoline concentrations were used to assess local tumor control. The short-term effect of SRT on skin was also evaluated.

Results—Tumors developed in 10 of 12 tibial sites and all 14 femoral sites. Administration of SRT to rats with femoral osteosarcoma was feasible and successful. Mean tumor necrosis of 95% was achieved histologically, and minimal adverse skin effects were observed.

Conclusions and Clinical Relevance—The orthotopic model of canine osteosarcoma in rats developed in this study was suitable for evaluating the effects of local tumor control and can be used in future studies to evaluate optimization of SRT duration, dose, and fractionation schemes. The model could also allow evaluation of other treatments in combination with SRT, such as chemotherapy or bisphosphonate, radioprotectant, or parathyroid hormone treatment.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare use of doxorubicin, surgery, and radiation versus surgery and radiation alone for treatment of cats with vaccine-associated sarcoma.

Design—Retrospective study.

Animals—25 cats with vaccine-associated sarcomas.

Procedure—Time to first recurrence and survival time were compared between the 2 treatment groups. The number of surgeries (1 or > 1) were compared with respect to time to first recurrence and survival time.

Results—Median time to first recurrence was 661 days for the group that received doxorubicin, surgery, and radiation. Median time to first recurrence has not yet been attained for the group treated with surgery and radiation alone. Median survival time was 674 days for the group treated with doxorubicin, surgery, and radiation and 842 days for the group treated with surgery and radiation alone. For time to first recurrence and survival time, significant differences were not detected between cats that had 1 surgery and those that had > 1 surgery.

Conclusions and Clinical Relevance—Significant differences between the 2 treatment groups were not detected. The efficacy of doxorubicin in the treatment of vaccine-associated sarcomas is uncertain. (J Am Vet Med Assoc 2001;218:547–550)

Full access
in Journal of the American Veterinary Medical Association

Summary:

Eighty-seven cats with histologically confirmed malignant tumors were used in a prospective study to determine the toxicity of mitoxantrone, a dihydroxyquinone derivative of anthracene, which was administered at 21-day intervals at dosages ranging from 2.5 to 6.5 mg/m2 of body surface, iv. Eleven of these cats were treated concurrently with radiation but were evaluated separately. Each cat was evaluated for signs of toxicosis for 3 weeks after each dose was administered or until the cat developed progressive disease, or until the cat's quality of life diminished to an unacceptable level as determined by the owner or attending veterinarian. Although the primary purpose of this study was to determine a clinically useful dosage and to characterize the toxicoses associated with mitoxantrone administration, each cat was monitored for response to treatment. Forty-nine cats had been refractory to 1 or more treatment modalities prior to inclusion in this study.

The most common signs of toxicosis after treatment with mitoxantrone were vomiting, anorexia, diarrhea, lethargy, sepsis secondary to myelosuppression, and seizures. Two cats died of complications that may have been attributed to mitoxantrone: 1 of cardiomyopathy and the other of pulmonary edema of an undetermined cause. Older cats were more likely to develop signs of toxicosis after the third or fourth mitoxantrone treatment than younger cats (P ≤ 0.05). Cats with signs of toxicosis during the 21-day interval after administration of the first dose of mitoxantrone were significantly (P ≤ 0.05) more likely to develop signs of toxicosis during the 21-day interval between the second and third doses of mitoxantrone. Similarly, cats that became toxic during the 21-day interval between the second and third doses were significantly (P ≤ 0.05) more likely to become toxic during the 21-day interval between the third and fourth doses. Controlling for age, breed, and dose of mitoxantrone, cats that became toxic after the first treatment were 2.4 times more likely to have poor performance status than the non toxic cats. Tumor-bearing cats had some degree of myelosuppression 7 days after they were given mitoxantrone at 6.5 mg/m2, iv (median neutrophil count, 2,440 cells/μl; range, 1,595 to 6,300 cells/μl).

Complete or partial remission (> 50% reduction volume reduction) was obtained in 18.4% (14/76) of cats given mitoxantrone alone. Remission was recorded in 17.6% (9/51) of cats with carcinoma, 11.8% (2/17) of the cats with lymphoma, and 37.5% (3/8) of the cats with sarcoma.

Because the cats with squamous cell carcinoma had a poor response to mitoxantrone, an additional 11 cats with squamous cell carcinoma were treated concurrently with radiation (44 to 65 Gy, 10 to 15 fractions) over a 3-week period beginning at the time the first dose of mitoxantrone (2.5 to 6 mg/m2) was given. None of these 11 cats had any signs of toxicosis attributable to mitoxantrone chemotherapy. Eight cats had a complete remission (median, 170 days; range, 28 to 485 days), and 1 had a partial remission that lasted 60 days.

Free access
in Journal of the American Veterinary Medical Association