Evaluation of long-term outcome and prognostic factors of feline squamous cell carcinomas treated with photodynamic therapy using liposomal phosphorylated meta-tetra(hydroxylphenyl)chlorine.

OBJECTIVES: The aim of this study was to evaluate the efficacy, long-term outcome and prognostic factors of feline squamous cell carcinoma (SCC) treated with photodynamic therapy (PDT). METHODS: Cats with histologically verified SCC of the head and neck received an intravenous injection of liposomal phosphorylated meta-tetra(hydroxylphenyl)chlorine (mTHPC) and 4 h later 652 nm light was delivered by a diode laser. One group received ⩽10 J/cm2, the other 20 J/cm2. Tumour response and duration were analysed with stage, tumour diameter, location and treatment intensity as prognostic factors. RESULTS: In total, 63 lesions in 38 cats underwent treatment with ⩽10 J/cm2 (n = 22) and 20 J/cm2 (n = 41). Overall response rate was 84% (complete remission 61%, partial remission 22%) with a mean progression-free interval of 35 months (median not reached) and a median overall survival time of 40 months (95% confidence interval 33-47). With regard to tumour stage, invasiveness yielded a highly significant worse outcome ( P <0.017). All patients with invasive tumours showed progression at less than 6 months. Larger lesions were associated with inferior control and treatment intensity, and tumour location did not influence response and duration. CONCLUSIONS AND RELEVANCE: PDT using a systemic photosensitiser leads to excellent long-term tumour control in the majority of cats. However, invasive and large tumours had a clearly inferior outcome, even if treated with the higher-dose intensity. This suggests that advanced lesions are not indications for PDT.

Bidirectional Regulation of COX-2 Expression Between Cancer Cells and Macrophages.

BACKGROUND/AIM: Our aim was to investigate the crosstalk between tumor and immune cells (M2 macrophages) and its effects on cyclo-oxygenase-2 (COX2) regulation in canine mammary tumors (CMT). MATERIALS AND METHODS: Sh1b CMT cells and human BT474 mammary or HT29 colon cancer cells were co-cultured with canine peripheral blood mononuclear cells (PBMCs) or with macrophage-like differentiated THP1 monocytes (dTHP1). Intracellular COX2 expression by PBMCs, dTHP1 and cancer cells was evaluated by flow cytometry. RESULTS: Co-culturing of Sh1b and canine PBMCs induced COX2 overexpression in CMT cells. In turn, COX2 expression by PBMCs, mostly CD68+ macrophages, was attenuated by co-culture with Sh1b (p=0.0001). In accordance, co-culture with dTHP1 prompted intracellular production of COX2 in both Sh1b CMT cells and HT29 human colon cancer cells and reduced production of COX2 in BT474 human mammary cancer cells. The intracellular COX2 expression from dTHP1 decreased when treated with conditioned medium from cultured Sh1b and HT29 cancer cells. CONCLUSION: Bidirectional COX2 regulation between cancer and monocytes/macrophages might shape a tolerogenic tumor microenvironment in CMT.

Does categorisation of lymphoma subtypes according to the World Health Organization classification predict clinical outcome in cats?

Objectives The purpose of this study was to specify lymphoma subtypes according to the World Health Organization (WHO) classification in a group of cats and to investigate their potential prognostic value. Methods Records of cats from the University of Veterinary Medicine Vienna suffering from lymphoma were reviewed in this retrospective study. To diagnose various subtypes specified in the WHO classification, histopathological and immunohistochemical examinations, as well as clonality assays in some cases, were performed. Results Of the 30 cats included in this study and classified according to the WHO guidelines, peripheral T-cell lymphoma was the most prevalent lymphoma subtype (37% of cases; n = 11), followed by diffuse large B-cell (23%; n = 7), intestinal T-cell (10%; n = 3), T-cell-rich B-cell (10%; n = 3), large granular lymphocytic (7%; n = 2), anaplastic large T-cell (7%; n = 2), B-cell small lymphocytic (3%; n = 1) and T-cell angiotropic lymphoma (3%; n = 1). The median survival time (MST) was 5.4 months (range 6 days to 2.2 years), with two cats still alive after 1.7 and 2.0 years, respectively. Treating cats prior to chemotherapy with glucocorticoids did not worsen their prognosis. Adding to chemotherapy, radiotherapy or surgery did not improve the clinical outcome. We observed that patients with intestinal T-cell lymphoma lived significantly longer (MST 1.7 years) than those with a diffuse large B-cell (MST 4.5 months) or peripheral T-cell lymphoma (MST 6.1 months). Cats with T-cell-rich B-cell lymphoma survived significantly longer (MST 1.2 years) than those with a diffuse large B-cell lymphoma. Conclusions and relevance A detailed diagnosis of feline lymphoma can be obtained by allocating different subtypes according to the WHO classification. From the eight detected lymphoma subtypes, two, intestinal T-cell lymphoma and T-cell-rich B-cell lymphoma, showed promising survival times in cats.

Cutaneous T-cell lymphoma - Sézary syndrome in a Boxer.

A 7-year-old male Boxer with a 3.5-year history of atopy and food hypersensitivity was presented with multiple poorly circumscribed nodules and maculae of the skin and tongue, and jaundiced mucosal membranes. Cytologic and histopathologic examination of the skin lesions revealed cutaneous epitheliotropic lymphoma. Cells were CD3(+) and CD8(+) in flow cytometry. The CBC showed a moderate leukocytosis with 16% atypical lymphocytes with irregularly cleaved nuclei. Flow cytometric phenotyping of peripheral blood showed an elevated proportion of the CD8(+) T-lymphocyte subpopulation, indicating a malignant population of T-cell origin, and the electropherogram of the PCR antigen receptor rearrangement produced a monoclonal peak for TCRγ. Liver enzyme activities were markedly increased and abdominal ultrasound examination showed increased echogenicity of the liver and enlarged abdominal lymph nodes. Fine-needle aspirates of the liver confirmed infiltration with lymphocytes exhibiting the same morphology as the cells detected in skin and peripheral blood. Treatment was induced with L-asparaginase, lomustine, and prednisone. Partial clinical remission of the skin and tongue lesions was achieved within 10 days, and hematologic abnormalities resolved. Despite further treatment with L-asparaginase and lomustine, the dog relapsed within one month and was euthanized. Presence of malignant lymphocytes in skin, peripheral blood, and liver indicate a rare variant of leukemic cutaneous T-cell lymphoma, equivalent of Sézary syndrome in a dog. This case report describes the use of flow cytometry as a complementary tool for lymphocyte characterization of skin lesions for the first time.

Radiation up-regulates the expression of VEGF in a canine oral melanoma cell line.

To evaluate radiosensitivity and the effects of radiation on the expression of vascular endothelial growth factor (VEGF) and VEGF receptors in the canine oral melanoma cell line, TLM 1, cells were irradiated with doses of 0, 2, 4, 6, 8 and 10 Gray (Gy). Survival rates were then determined by a MTT assay, while vascular endothelial growth factor receptor (VEGFR)-1 and -2 expression was measured by flow cytometry and apoptotic cell death rates were investigated using an Annexin assay. Additionally, a commercially available canine VEGF ELISA kit was used to measure VEGF. Radiosensitivity was detected in TLM 1 cells, and mitotic and apoptotic cell death was found to occur in a radiation dose dependent manner. VEGF was secreted constitutively and significant up-regulation was observed in the 8 and 10 Gy irradiated cells. In addition, a minor portion of TLM 1 cells expressed vascular endothelial growth factor receptor (VEGFR)-1 intracellularly. VEGFR-2 was detected in the cytoplasm and was down-regulated following radiation with increasing dosages. In TLM 1 cells, apoptosis plays an important role in radiation induced cell death. It has also been suggested that the significantly higher VEGF production in the 8 and 10 Gy group could lead to tumour resistance.