Gold nanoparticles enhance radiation sensitization and suppress colony formation in a feline injection site sarcoma cell line, in vitro.

Injection Site Sarcomas (ISS) are highly invasive feline malignant tumors that are frequently associated with routine vaccination. Current treatment modalities include chemotherapy, radiation, and radical surgery. ISS have been shown to be one of the most treatment resistant of feline cancers with high rates of recurrence. Previous studies have shown that gold and other high atomic number nanoparticles have the ability to increase the dose of radiation deposited into tissue by generating secondary electrons. The focus of the current study was to assess the effects of gold nanoparticles (AuNP) on ISS cytotoxicity and colony formation both as a standalone treatment and in combination with electron beam radiation. Cells from an established ISS cell line were co-cultured with 15nm AuNP at 0.0, 0.25, 0.5, 1.0, 2.0 and 4.0mM. AuNP cytotoxicity was evaluated by assessing changes in cellularity, cell proliferation, cell cycle and viability/apoptosis/necrosis. The radiosensitizing potential of AuNP on ISS replication was assessed by the clonogenic assay. AuNP were found to significantly decrease cellular proliferation. However, the acute viability and cell cycle of ISS was not significantly altered. Interestingly, AuNP alone were shown to significantly impair colony formation. In the presence of 9MeV electron radiation, AuNP numerically decreased colony formation in ISS cells compared to cells treated with radiation only. AuNP may have efficacy as a long term therapeutic agent for decreasing ISS growth.

Expression of Apoptosis-regulating Proteins Bcl-2 and Bax in Lymph Node Aspirates from Dogs with Lymphoma.

BACKGROUND: Dysregulated apoptosis is a hallmark of tumorigenesis, and is also involved in resistance to cytotoxic treatment, and might be relevant in lymphoma in dogs. HYPOTHESIS/OBJECTIVES: That Bcl-2/Bax expression patterns differ between lymphoma immunophenotypes, and that Bcl-2/Bax ratio is correlated with prognosis. ANIMALS: Fifty-five client-owned dogs with multicentric lymphoma and 5 healthy dogs. METHODS: Prospective, case-control study. We compared 3 methods (flow cytometry, qRT-PCR, Western blot) for Bcl-2 and Bax quantification in a subset of dogs. The effect of time on Bcl-2/Bax ratios measured by flow cytometry was assessed in lymphoma cell lines. Immunophenotype and Bcl-2/Bax expression by flow cytometry were determined in LN aspirates from all dogs with multicentric lymphoma compared to healthy dogs. Progression-free survival (PFS) was retrospectively evaluated in a group of dogs all receiving similar treatment. RESULTS: Bcl-2/Bax ratios remain consistent for at least 5 days after sample collection. Bcl-2/Bax ratio was higher in dogs with T-cell lymphoma (TCL; median 0.97, range 0.37-1.36) compared to B-cell lymphoma (BCL; median 0.36, range 0.07-1.45) (P < .0001) and normal dogs (median 0.36, range 0.21-0.48) (P = .0006), respectively. Dogs with Bcl-2/Bax ratios higher than the median of the group experienced a median PFS of 101 days and dogs with ratios equal and lower than the median had PFS of 130 days (P = .19). CONCLUSIONS AND CLINICAL IMPORTANCE: Higher intrinsic resistance to apoptosis following cytotoxic treatment might contribute to the less favorable prognosis associated with multicentric TCL in dogs. Whether Bcl-2/Bax will be helpful to identify canine BCL and TCL with more aggressive and more indolent behavior, respectively, should be evaluated in larger prospective clinical studies.

Patient characteristics, histopathological findings and outcome in 97 cats with extranodal subcutaneous lymphoma (2007-2011).

This study describes epidemiologic, clinical, macro- and microscopic tumour characteristics and outcome in 97 cats with subcutaneous lymphoma, an uncommon variant of feline extranodal lymphoma. Middle-aged (median 11 years), male (60.8%), Domestic Shorthair cats (89.7%) were commonly affected. Most tumours presented as a painless, firm, subcutaneous nodule or mass, with predilection to the lateral thoracic or abdominal wall, and the interscapular region. Deep subcutaneous invasion with extension into superficial or underlying tissues, extensive central areas of necrosis and peripheral inflammation were characteristic histopathological findings. Prevalence of retroviral infection was low. Local relapses after therapy were common (43.5%), and 32.2% had distant involvement later in course. Median overall survival was 148 days. Subcutaneous lymphoma should be considered a rare but important differential diagnosis for a subcutaneous mass in cats. Tumours show an aggressive biological behaviour. Treatment options including prognosis should be investigated in further studies.

Changes in prevalence of progressive feline leukaemia virus infection in cats with lymphoma in Germany.

Progressive infection with feline leukaemia virus (FeLV) is considered one of the major risk factors for development of feline lymphoma. The aim of this study was to compare cats with lymphoma between 1980 and 1994 (first period) and between 1995 and 2009 (second period) concerning FeLV antigenaemia and age distribution. In addition, differences between FeLV antigen-positive and antigen-negative cats with lymphoma regarding patients' characteristics, tumour location and outcome were evaluated. There was a significant decrease in the percentage of lymphoma cases associated with progressive FeLV infection from the first (59 per cent) to the second (13 per cent) observation period. FeLV antigen-positive cats were significantly younger (median 3.7 v 11.3 years), and had significantly shorter response duration (median 25 days v 472 days) with therapy. In the cats of the second period, gastrointestinal and extranodal lymphomas were the most common anatomical sites, and the majority of those cats were FeLV antigen-negative. Thus, other aetiologies than progressive FeLV infection must have a greater impact on cancerogenesis among affected cats with lymphoma to date.

Thirteen-week dose-intensifying simultaneous combination chemotherapy protocol for malignant lymphoma in dogs.

This prospective study aimed to record the toxicity profile of a dose-intensifying simultaneous chemotherapy (DISC) protocol for lymphoma in dogs. Remission rates and the duration of the protocol were also evaluated. Twenty-one dogs were studied. Diagnosis was based on cytological or histological assessments. The DISC protocol is a 13-week maintenance-free protocol. L-Asparaginase (400 iu/kg) was administered subcutaneously on day 1, followed by weekly simultaneous intravenous administration of vincristine (0.7 mg/m(2) = 100 per cent), cyclophosphamide (200 mg/m(2) = 100 per cent) and doxorubicin (30 mg/m(2) = 100 per cent) at a starting dose level of 33 per cent. Dose levels were given twice and then increased by 5 to 7 per cent if grade 0 or I toxicities were seen, to a maximum dose level of 60 per cent. Two dogs experienced a grade IV toxicity (asymptomatic neutropenia in one dog and sepsis in the other). Two episodes of asymptomatic grade III thrombocytopenia and one episode of neutropenia were recorded. Other toxic events were infrequent and mild. Only one dog required hospitalisation for less than 72 hours. Seventeen dogs (80.9 per cent) achieved complete remission, one (4.8 per cent) achieved partial remission, two (9.5 per cent) had stable disease and in one (4.8 per cent) disease progressed.