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1.
Vet Immunol Immunopathol ; 271: 110741, 2024 May.
Article in English | MEDLINE | ID: mdl-38520894

ABSTRACT

Tumor-infiltrating lymphocyte (TIL) density plays an important role in anti-tumor immunity and is associated with patient outcome in various human and canine malignancies. As a first assessment of the immune landscape of the tumor microenvironment in canine renal cell carcinoma (RCC), we retrospectively analyzed clinical data and quantified CD3, FoxP3, and granzyme B immunostaining in formalin-fixed paraffin-embedded tumor samples from 16 dogs diagnosed with renal cell carcinoma treated with ureteronephrectomy. Cell density was low for all markers evaluated. Increased numbers of intratumoral FoxP3 labelled (+) cells, as well as decreased granzyme B+: FoxP3+ TIL ratio, were associated with poor patient outcomes. Our initial study of canine RCC reveals that these tumors are immunologically cold and Tregs may play an important role in immune evasion.


Subject(s)
CD3 Complex , Carcinoma, Renal Cell , Dog Diseases , Forkhead Transcription Factors , Granzymes , Kidney Neoplasms , Lymphocytes, Tumor-Infiltrating , Animals , Dogs , Carcinoma, Renal Cell/veterinary , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/enzymology , CD3 Complex/analysis , CD3 Complex/metabolism , Dog Diseases/immunology , Dog Diseases/enzymology , Forkhead Transcription Factors/analysis , Forkhead Transcription Factors/metabolism , Granzymes/metabolism , Granzymes/analysis , Immunohistochemistry/veterinary , Kidney Neoplasms/veterinary , Kidney Neoplasms/immunology , Kidney Neoplasms/enzymology , Lymphocytes, Tumor-Infiltrating/immunology , Retrospective Studies
2.
Vet Comp Oncol ; 20(3): 688-696, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35442554

ABSTRACT

Canine splenic hemangiosarcoma (HSA) is an aggressive tumour of vascular endothelium that carries a grave prognosis following standard of care treatment with surgery and doxorubicin. A previous pilot study revealed potential anti-tumour activity of I'm-Yunity polysaccharopeptide (PSP) for canine HSA. The aim of this prospective study was to assess patient outcome when treated with PSP alone or in combination with doxorubicin post-splenectomy compared to patients treated with surgery and doxorubicin that received a placebo in place of PSP. Dogs undergoing splenectomy for splenic HSA were eligible. Following splenectomy, owners were offered treatment with PSP alone or adjuvant doxorubicin chemotherapy (unblinded). Patients with owners that selected to proceed with doxorubicin chemotherapy were blindly randomized to receive placebo or PSP. Dogs were evaluated weekly for 15 weeks, then scheduled for monthly visits until death. One hundred and one dogs were included in the final analysis: 51 PSP alone, 25 doxorubicin/placebo, and 25 combination PSP/doxorubicin. On multivariate analysis, dogs treated with single agent PSP, female dogs, decreased haematocrit at diagnosis, and stage III disease were negatively significantly associated with outcome; however, an interaction between treatment group and sex was documented. Gender-specific outcomes revealed no significant difference in survival between treatment groups for male dogs, but female dogs treated with PSP alone had significantly reduced survival compared to females receiving doxorubicin/placebo (HR 0.21; p = .004). Anaemia (HR 5.28; p < .001) and stage III disease (HR 2.9; p = .014) remained negatively associated with survival when controlling for sex and treatment group. The addition of PSP to doxorubicin post-splenectomy did not improve survival in dogs with splenic HSA.


Subject(s)
Dog Diseases , Hemangiosarcoma , Splenic Neoplasms , Animals , Dog Diseases/drug therapy , Dogs , Doxorubicin/therapeutic use , Drugs, Chinese Herbal , Female , Hemangiosarcoma/drug therapy , Hemangiosarcoma/veterinary , Male , Pilot Projects , Polyporaceae , Prospective Studies , Proteoglycans , Splenic Neoplasms/drug therapy , Splenic Neoplasms/veterinary
3.
J Vet Intern Med ; 34(6): 2660-2670, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33140892

ABSTRACT

BACKGROUND: Epidemiologic studies suggest residential radon exposure might increase the risk of primary lung cancer in people, but these studies are limited by subject mobility. This limitation might be overcome by evaluating the association in pets. HYPOTHESIS: Primary pulmonary neoplasia (PPN) rate is higher in dogs and cats residing in counties with a high radon exposure risk (Environmental Protection Agency [EPA] zone 1) compared to zones 2 (moderate radon exposure risk) and 3 (low radon exposure risk). ANIMALS: Six hundred ninety client-owned dogs and 205 client-owned cats with PPN. METHODS: Retrospective review of medical records at 10 veterinary colleges identified dogs and cats diagnosed with PPN between 2010 and 2015. Each patient's radon exposure was determined by matching the patient's zip code with published county radon exposure risk. County level PPN rates were calculated using the average annual county cat and dog populations. The PPN counts per 100 000 dog/cat years at risk (PPN rates) were compared across radon zones for each species. RESULTS: The PPN rate ratio in counties in high radon zone (1) was approximately 2-fold higher than in counties in lower radon zones for dogs (rate ratio zone 1 to 2, 2.49; 95% confidence interval [CI], 1.56-4.00; rate ratio zone 1 to 3, 2.29; 95% CI, 1.46-3.59) and cats (rate ratio zone 1 to 2, 2.13; 95% CI, 0.95-4.79; zone 1 to 3, 1.81; 95% CI, 0.9-3.61). CONCLUSIONS AND CLINICAL IMPORTANCE: Exposure to household radon might play a role in development of PPN in dogs and cats.


Subject(s)
Cat Diseases , Dog Diseases , Lung Neoplasms , Radon , Animals , Cat Diseases/epidemiology , Cat Diseases/etiology , Cats , Dog Diseases/epidemiology , Dog Diseases/etiology , Dogs , Environmental Exposure/adverse effects , Lung Neoplasms/epidemiology , Lung Neoplasms/etiology , Lung Neoplasms/veterinary , Radon/analysis , Radon/toxicity , Retrospective Studies
4.
J Vet Intern Med ; 34(1): 274-282, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31721288

ABSTRACT

BACKGROUND: Lower urinary tract transitional cell carcinoma (TCC) is an important but rarely described disease of cats. OBJECTIVES: To report the clinical characteristics, treatments, and outcomes in a cohort of cats with lower urinary tract TCC and to test identified variables for prognostic relevance. ANIMALS: One-hundred eighteen client-owned cats with lower urinary tract carcinoma. METHODS: Medical records were retrospectively reviewed to obtain information regarding clinical characteristics, treatments, and outcomes. Recorded variables were analyzed statistically. RESULTS: Median age of affected cats was 15 years (range, 5.0-20.8 years) and median duration of clinical signs was 30 days (range, 0-730 days). The trigone was the most common tumor location (32/118; 27.1%) as assessed by ultrasound examination, cystoscopy, or both. Treatment was carried out in 73 of 118 (61.9%) cats. Metastatic disease was documented in 25 of 118 (21.2%) cats. Median progression-free survival and survival time for all cats were 113 days (95% confidence interval [CI], 69-153) and 155 days (95% CI, 110-222), respectively. Survival increased significantly (P < .001) when comparing cats across the ordered treatment groups: no treatment, treatment without partial cystectomy, and treatment with partial cystectomy. Partial cystectomy (hazard ratio [HR], 0.31; 95% CI, 0.17-0.87) and treatment with nonsteroidal anti-inflammatory drugs (HR, 0.55; 95% CI, 0.33-0.93) were significantly associated with longer survival times. CONCLUSIONS AND CLINICAL IMPORTANCE: The results support treatment using partial cystectomy and NSAIDs in cats with TCC.


Subject(s)
Carcinoma, Transitional Cell/veterinary , Cat Diseases/pathology , Cystectomy/veterinary , Urinary Bladder Neoplasms/veterinary , Animals , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Carcinoma, Transitional Cell/therapy , Cat Diseases/therapy , Cats , Cohort Studies , Retrospective Studies , Treatment Outcome , Urinary Bladder Neoplasms/therapy
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