Veterinary and comparative oncology最新文献

The use of compounded formulations of chemotherapy in veterinary medicine is common. The purpose of this study was to evaluate the drug amount of two compounded chemotherapeutics (chlorambucil and cyclophosphamide) from multiple veterinary compounding pharmacies, to determine if there was a difference in drug amounts between those that came from 503A versus 503B pharmacies, and finally to determine heterogeneity in drug amounts within each individual pharmacy. Nine veterinary compounding pharmacies (eight 503A, one 503B) were sampled in total, with two different batches sampled from each pharmacy. Each capsule's actual concentration was compared to the intended (prescribed) concentration. Of the 68 total samples obtained, 20 (29%) tested outside the FDA-acceptable discrepancy of ±10%. Of these, 12 (60%) were chlorambucil and 8 (40%) were cyclophosphamide. 503A cyclophosphamide samples had an average discrepancy of 6.6% from the intended dose while samples from the 503B pharmacy had a discrepancy of 1.8%. 503A chlorambucil samples had an average discrepancy of 10.4% from the intended dose while samples from the 503B pharmacy had a discrepancy of 9.6%. Heterogeneity within the same pharmacy and batch ranged from 0.1% to 51% for the 503A pharmacies and 2.6% to 7.5% for the 503B pharmacy. Heterogeneity between different batches within the same pharmacy ranged from 0.4% to 58.3% for the 503A pharmacies and 5% to 14.8% for the 503B pharmacy. Although the drug amounts of compounded cyclophosphamide and chlorambucil manufactured by the 503B compounding pharmacy was more reliably maintained compared to that compounded by the 503A pharmacies, there was ultimately still potential for variability in drug amounts regardless of the pharmacy designation.

A comprehensive understanding of the tumour immune microenvironment (TIME) is essential for advancing precision medicine and identifying potential therapeutic targets. This study focused on canine urothelial carcinoma (cUC) recognised for its high sensitivity to cyclooxygenase (COX) inhibitors. Using immunohistochemical techniques, we quantified the infiltration of seven immune cell populations within cUC tumour tissue to identify clinicopathological features that characterise the TIME in cUC. Our results revealed several notable factors, including the significantly higher levels of CD3⁺ T cells and CD8⁺ T cells within tumour cell nests in cases treated with preoperative COX inhibitors compared to untreated cases. Based on the immunohistochemistry data, we further performed a comparative analysis using publicly available RNA-seq data from untreated cUC tissues (n = 29) and normal bladder tissues (n = 4) to explore the link between COX-prostanoid pathways and the immune response to tumours. We observed increased expression of COX-2, microsomal prostaglandin E2 synthase-1 (mPGES-1) and mPGES-2 in cUC tissues. However, only mPGES-2 showed a negative correlation with the cytotoxic T-cell (CTL)-related genes CD8A and granzyme B (GZMB). In addition, a broader analysis of solid tumours using The Cancer Genome Atlas (TCGA) database revealed similar patterns in several human tumours, suggesting a common mechanism in dogs and humans. Our results suggest that the COX-2/mPGES-2 pathway may act as a cross-species tumour-intrinsic factor that weakens anti-tumour immunity, and that COX inhibitors may convert TIME from a 'cold tumour' to a 'hot tumour' state by counteracting COX/mPGES-2-mediated immunosuppression.

Canine mammary gland tumour (CMT) is the most common spontaneous tumour in intact female dogs and often exhibits metastases. Auranofin (AF) is a gold complex used for treating rheumatism. The excellent anti-tumour ability of AF has been demonstrated in various types of human and canine tumours. In this study, five CMT cell lines (CIPp, CMT-7364, CHMp, CIPm and CTBp) and three CMT primary cells (G7894, L1883 and L6783) were used to explore the anti-tumour effect of AF on CMT. Two CMT cell lines (CIPp and CMT-7364) were used to search the underlying mechanism of the effect of AF on CMT. The results showed that AF inhibited the growth, migration, invasion, and colony formation abilities of CMT cells. Additionally, the growth of CMT in a 3D cell culture model was effectively suppressed by AF. Furthermore, AF induced cell apoptosis of CMT cells via the PI3K/AKT pathway. In conclusion, AF effectively induces CMT apoptosis by regulating the PI3K/AKT pathway, indicating that AF should be explored as a potential CMT treatment in future studies.

Melanoma is one of the most common canine oral malignant tumours and is highly aggressive and metastatic, even at the early stages of development. Surgery relies on wide excision of the primary tumour and regional lymphadenectomy, with or without adjuvant therapy. Tumour location and size are important when considering staging, which ultimately affects the curative intent of surgery. Nevertheless, absolute tumour volume (TV) is not related to the vast phenotypic variability within canine breeds. This study aimed to determine the cutoff values of two ratios-tumour-to-head volume (THR) and tumour-to-body volume (TBR)-and assess whether they could be associated with the odds of finding metastasis at presentation and/or the likelihood of achieving tumour-free excision margins. A retrospective case series involving 51 dogs was used to evaluate the preoperative head/neck and chest computed tomography and histopathology of the primary mass and excised lymph nodes. Higher TV, THR% and TBR% values were associated with bone lysis and mitotic count (MC). The Ki67 index was significantly associated with local and distant metastases at presentation, whereas MC was associated with local metastasis alone. Tumour-infiltrated surgical margins were associated with caudally located tumours, regardless of the tumour size. Dogs with lymph node metastasis at presentation were seven times more prone to have local relapse. TV, THR% and TBR% values were positively associated with local lymph node metastasis at presentation. Cutoff values for both TV and TBR% were proposed to predict lymph node metastasis at presentation (TV = 6.423 cm³ and TBR% = 0.043), being supported by post-surgical survival analysis.

Phosphorylated signal transducer and activator of transcription 3 (pSTAT3), which is related to anti-apoptosis, cellular proliferation, invasion and migration of tumours, has prognostic significance in malignant tumours in humans as well as in canine melanoma. However, the significance of pSTAT3 in canine liver tissues has not yet been evaluated. This study's objective was to compare its expression in canine normal, non-neoplastic hepatic disease and hepatocellular carcinoma (HCC) tissues by immunohistochemical analysis. Furthermore, the association between pSTAT3 immunostaining and clinicopathological factors was investigated. Overall, 68 canine liver tissues, including 10 normal liver tissues, 30 non-neoplastic hepatic disease tissues and 28 HCC tissues were examined, revealing distinct differences in pSTAT3 immunostaining among the groups. (p < 0.001). Additionally, high pSTAT3 immunostaining was significantly associated with increased tumour size (5 > cm) (p = 0.041), and metastasis (p = 0.046). Furthermore, Kaplan-Meier survival curve analysis revealed a correlation between high pSTAT3 immunostaining and poor disease-free survival (p = 0.013) and overall survival (p = 0.011). These findings suggest that overactivation of STAT3 is associated with poor prognosis in canine HCC. Therefore, pSTAT3 is considered a potential prognostic marker and therapeutic target for canine HCC.

Canine osteosarcoma (OSA) is a malignancy that has been shown to modulate the host immune system. Macrophage colony-stimulating factor (M-CSF; CSF1) and interleukin-34 (IL-34; IL34) are both ligands of colony stimulating factor 1 receptor (CSF-1R), and may play a role in the pathogenesis of a variety of human cancers, including OSA. This study aimed to, (1) assess M-CSF and IL-34 expression in canine OSA cell lines and tissue samples, and (2) determine any correlations between M-CSF and IL-34 expression and immune cell infiltrates within canine OSA tissues. Four canine OSA cell lines and canine osteoblasts were treated with control media, TNFα (10 ng/mL) or IL-1β (10 ng/mL) and analysed with RT-qPCR and ELISA. IL-34 and M-CSF mRNA and protein were detectable in all cell lines, however upregulation following TNFα or IL-1β exposure was only consistently observed for transcript expression. Baseline expression of CSF1 and IL34 mRNA in OSA cell lines was equal to or higher than that of canine osteoblasts. All 10 OSA tissue samples expressed IL34 and CSF1 transcripts to varying degrees. Furthermore, CSF1 and IL34 expression both showed a moderate to high degree of correlation with M1 macrophage lineage-associated transcripts (CD80 and IL15RA). There was a moderate degree of correlation between CSF1 and CD163, but no correlation between IL34 and either M2 macrophage-associated transcripts (CD163 and CCL24). In summary, IL-34 and M-CSF are expressed in canine OSA cell lines and tissues, and expression positively correlates with a wide range of immune-related transcripts.

Vincristine sulphate, a microtubule inhibitor, is used extensively in veterinary oncology for treating lymphoma. Neutropenia during multiagent protocols is a common reason for treatment delay and reduced dose intensity. This study evaluated toxicities associated with treating systemically well neutropenic lymphoma patients with vincristine. Lymphoma patients undergoing CHOP were evaluated retrospectively for instances of vincristine administration when absolute neutrophil counts (ANC) were 1.5 × 10⁹/L or below. Instances of vincristine administration when ANC was equal to or less than 1.5 × 10⁹/L were compared to vincristine administration where ANC was greater than 1.5 × 10⁹/L in the same patient. Univariate and multivariate modelling compared VCOG-CTCAE v1.1 grading of vomiting, diarrhoea, anorexia and 7-day neutrophil nadir between groups. The median dose of vincristine administered was 0.7 mg/m² for both study groups. A total of 112 doses of vincristine were administered to neutropenic patients (grade 2 n: 76, grade 3 n: 26, and grade 4 n: 10). These were compared to 223 doses of vincristine administered to the same patients when ANC was above 1.5 × 10⁹/L. Neutropenic administration was most prevalent 7 days following cyclophosphamide administration. Day 7 post-administration neutropenia was more prevalent in patients with ANC greater than 1.5 × 10⁹/L at the time of vincristine administration (neutropenic 9%; non-neutropenic 18%). Relative risk of 7-day neutropenia, vomiting, diarrhoea, and anorexia was similar between groups on multivariate analysis. Patients with lymphoma who receive vincristine when ANC is 1.5 × 10⁹/L or below are at no greater risk of adverse effects than the same patient who receives vincristine when neutrophil counts are greater than 1.5 × 10⁹/L.

Increasing numbers of dogs and cats with cancer are treated with stereotactic radiosurgery, stereotactic radiation therapy or stereotactic body radiotherapy (SRS, SRT or SBRT). We provide a systematic review of the current data landscape with a focus on technical and dosimetric data of stereotactic radiotherapy in veterinary oncology. Original peer-reviewed articles on dogs and cats with cancer treated with SRT were included. The systematic search included Medline via PubMed and EMBASE. The study was performed according to the Preferred Reporting Items for Systematic Reviews (PRISMA) statement. We assessed the manuscripts regarding outcome reporting, treatment planning, dose prescription, -delivery and -reporting as well as quality assurance. As of February 2024, there are 80 peer-reviewed publications on various disease entities on SRS, SRT and SBRT in veterinary medicine. Overall, we found often insufficient or highly variable technical data, with incomplete information to reproduce these treatments. While in some instances, technical factors may not impact clinical outcome, the variability found in protocols, outcome and toxicity assessments precludes accurate and reliable conclusions for a benefit of stereotactic radiotherapy for many of the treated diseases. In line with the extensive recommendations from human stereotactic radiotherapy practise, we propose a draft of reporting items for future stereotactic radiation treatments in veterinary medicine. SRS, SRT and SBRT have specific clinical and technological requirements that differ from those of standard radiation therapy. Therefore, a deep understanding of the methodologies, as well as the quality and precision of dose delivery, is essential for effective clinical knowledge transfer.

Canine lymphoma, the most prevalent haematopoietic tumour in dogs, presents significant challenges in veterinary oncology. This study investigates the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in small-sized dogs (≤10 kg) with multicentric lymphoma. In this retrospective study, we examined medical records and haematological data from 35 dogs to assess the association between NLR and two key outcomes: time-to-progression (TTP) and lymphoma-specific survival (LSS) using Cox proportional hazards models. Our findings revealed a significant correlation between elevated NLR and a worse prognosis, as evidenced by TTP (p = 0.005) and LSS (p = 0.001). NLR is linked to increased hazard ratios (HRs) for the time-to-progression rate (TTPR) at 180, 360 and 540 days (p = 0.001, p = 0.003 and p = 0.005, respectively) and the lymphoma-specific survival rate (LSSR) at the same intervals (p = 0.016, p = 0.001 and p = 0.001, respectively). Cutoff value of 3.764 for NLR was established, above which there is a significantly increased risk of early disease progression and decreased survival. Additionally, our analysis indicates that dogs with substage b exhibited earlier progression than those with substage a, evident in overall (p = 0.026) and TTPR at 180 days (p = 0.004), 360 days (p = 0.018), 540 days (p = 0.026) and LSSR at 180 days (p = 0.033). The results underscore the potential of NLR as a prognostic marker in cases of dogs ≤10 kg with multicentric lymphoma, suggesting that higher NLR is associated with a poorer prognosis.

Only a limited number of tumour biomarkers are currently available in veterinary medicine, particularly in cats. Cell-free DNA (cfDNA) is an extracellular DNA fragment released upon cell death and is considered a minimally invasive biomarker for the diagnosis and monitoring of various human malignancies. This study aimed to clarify the utility of circulating cfDNA as a liquid biopsy for various feline tumours. Plasma samples were collected from 44 cats with various tumours, 24 cats with other diseases and 10 healthy controls. A follow-up study was conducted in three tumour-bearing patients. All cfDNA concentrations were quantified via real-time polymerase chain reaction (PCR), which provided short and long fragments of a newly identified feline LINE-1 gene. We found that cfDNA levels were significantly higher in cats with various tumours than in those with other diseases or healthy controls. The cfDNA concentration was not correlated with serum amyloid A (SAA) levels. Cats with tumours exhibited elevated cfDNA levels that predicted tumour-bearing with a sensitivity and specificity of 50.5% and 91.2%, respectively (AUC 0.736; p < 0.001). In lymphoma cases, cats with high cfDNA levels had significantly shorter survival times than those with low cfDNA levels (median: 33 days vs. 178 days; p = 0.003). In addition, the cfDNA levels of the three patients correlated with clinical status during follow-up. Collectively, these findings indicate the potential of cfDNA as a useful biomarker for the diagnosis, therapeutic monitoring and prognostic assessment of tumours in cats.