Veterinary and comparative oncology最新文献

Inflammatory mammary carcinoma (IMC) is the most aggressive variant of invasive mammary tumours in dogs and in women. Decorin is an extracellular matrix molecule whose expression can be reduced or absent in various human cancers, which is associated with a poor prognosis. E-cadherin is a cell adhesion protein whose expression is reduced in several neoplasms. However, it is overexpressed in inflammatory breast cancers of women. EGFR is also associated with cancer development and is commonly overexpressed in aggressive neoplasms. This study aimed to characterise the expressions of Decorin, E-cadherin, and EGFR in canine inflammatory and non-inflammatory mammary carcinomas (IMC and non-IMC) and to evaluate their expression levels as prognostic indicators for survival and occurrence of metastases. Thirty-three IMC and 43 non-IMC cases were analysed retrospectively and submitted to immunohistochemical analysis. The reactions were quantified in five high-power field images from areas of the highest intensity and frequency of immunostaining (hot spots). We found significantly lower expression of Decorin and higher of E-cadherin and EGFR in canine IMCs. Patients with tumours that exhibited Decorin expression in less than 26.35% of epithelial cells had shorter survival (p = 0.0410) and a higher occurrence of distant metastases (p = 0.0115). E-cadherin is overexpressed in canine IMCs (p < 0.0001), similar to what occurs in women, reinforcing that dogs can be used as a study model for human IMC. EGFR overexpression in canine IMCs (p = 0.0322) provides evidence for potential targeted therapy with tyrosine kinase inhibitors.

Early-delayed side effects (EDSEs) following treatment of canine intracranial meningiomas with 1-3-fraction stereotactic radiation therapy (SRT) can cause worsening neurologic signs, and one potential method of mitigating this toxicity is reducing the dose per fraction. Twenty dogs with imaging-diagnosed intracranial meningiomas and telephone follow-up of at least 6 months received a protocol of 6 Gy × 5, daily (30 Gy). A 'possible EDSE' was defined as mental dullness, neurologic exacerbation of existing neurologic signs or new neurologic signs occurring within 1-4 months of completing SRT, regardless of the response to steroids and even if an MRI was not performed. A 'probable EDSE' was defined as mental dullness, neurologic exacerbation of existing neurologic signs or new neurologic signs occurring within 1-4 months of completing SRT. These signs were either reversible with the initiation or increased doses of prednisolone, or follow-up MRI revealed no evidence of an alternate explanation. No dogs experienced acute radiotoxicity or clinical signs compatible with EDSEs. The protocol appears to result in limited acute radiotoxicity, and further evaluation of the frequency of long-term toxicities and relative efficacy should be undertaken.

The treatment of canine transmissible venereal tumour (CTVT) has evolved since its initial description in 1810. Initially considered untreatable in the early 20th century, extensive research over time has significantly advanced our understanding of its aetiopathogenesis. This led to successful chemotherapy treatments, which have shown superior outcomes compared to surgical interventions. Vincristine, in particular, has proven effective in treating CTVT. However, the development of chemoresistance underscores the need to explore alternative therapeutic options. This systematic review provides a comprehensive analysis of CTVT treatment practices from 1950 to 2023, aiming to establish a gold standard and enhance clinical decision-making. Initially, 3633 studies were identified, with 42 meeting the eligibility criteria. Our findings suggest that vincristine sulphate monotherapy is the recommended first-line treatment for CTVT. Administering vincristine intravenously at a dosage of 0.5-0.75 mg/m² weekly for 4-6 sessions resulted in a 93.1% (67.4%-100%) complete response rate in dogs. Extending the treatment to eight sessions increased the complete response rate to 98.9% (83.3%-100%). Radiation therapy, lomustine and doxorubicin are viable second-line treatment options; however, extensive cohort studies are required to confirm their efficacy in achieving remission in vincristine-resistant cases. Additionally, no clear criteria could be established for initiating treatment with drugs other than vincristine in previously untreated dogs. Surgery is considered a third-line option. Notably, complete remission is anticipated following recommended systemic and local therapies in nearly all cases. Despite concerns about chemoresistance, current guidelines indicate a favourable response to suggested treatments even in resistant cases.

Adjuvant chemotherapy is a well-established treatment for large-breed dogs with appendicular osteosarcoma; however, it is unclear if it improves outcomes in small-breed dogs due to limited focused studies. This retrospective study aimed to investigate the oncologic outcomes of dogs weighting less than 15 kg with appendicular osteosarcoma that underwent curative resection with or without postoperative adjuvant chemotherapy. Endpoints were time to distant progression (TTDP) and overall survival (OS). Medical records from multiple institutions were reviewed, and 43 dogs were included in the analysis: 17 underwent surgery alone and 26 also received adjuvant chemotherapy. The median TTDP for all dogs was 265 days, with no significant difference between treatment groups. The median OS for all dogs was 270 days, and it was significantly different between amputated dogs (150 days) and those also receiving adjuvant chemotherapy (353 days, p = 0.002). In our cohort, osteosarcoma in small breeds behaved as aggressive as in large breeds. Adjuvant chemotherapy may prolong survival. Future randomised studies are needed to provide definitive evidence on the necessity of adjuvant chemotherapy to address metastatic spread in small-breed dogs with appendicular osteosarcoma.

Canine oral melanoma (OM) exhibits poor prognosis and limited treatment options. The success of immune checkpoint inhibitors (ICIs) in human melanoma has driven interest in similar therapeutic approaches in the dog, although the immunosuppressive mechanisms adopted by canine OM remain unclear. This study aimed to evaluate the expression of the immune checkpoints PD-1/PD-L1 and CTLA-4 by RNAscope in situ hybridization (ISH) in canine OM, to investigate their expression pattern and explore their potential role in melanoma progression. Twenty-four formalin-fixed, paraffin-embedded canine OM were included in the study. PD-L1 expression by tumour cells was detected in 100% melanomas (score 1-3), especially at the host-tumour interface. PD-1 and CTLA-4 expression by tumour cells was detected in 13/24 (54%, score 1-2) and 18/24 (75%, score 1) melanomas, respectively. Dual ISH-immunohistochemistry with Melanoma Triple Cocktail, CD3, CD20 and Iba1 demonstrated the expression of tested immune checkpoints in neoplastic and immune cells. Notably, PD-1 and CTLA-4 were predominantly expressed by tumour-infiltrating T lymphocytes, while PD-L1 was primarily expressed by tumour-associated macrophages. PD-1 expression in neoplastic cells was significantly correlated with mitotic count (p < 0.05), while no associations were found between immune checkpoint expression and disease-free interval or overall survival. Whole tumour PD-L1 and PD-1 expression, assessed by image analysis, correlated to PD-L1 scores in neoplastic cells and the grade of tumour-infiltrating lymphocytes, respectively. Collectively, PD-L1, PD-1 and CTLA-4 likely contribute to immunosuppression in canine OM. Further studies are warranted to investigate whether ISH can serve as a biomarker for selecting patients suitable for ICI treatment.

Body composition measurements (BCM), obtained via computed tomography (CT), have been used as predictors of survival, tumour recurrence, and post-surgical infections in human oncology. There are no reports on using BCM to predict outcomes of dogs with cancer. Elevated BCM is hypothesised to place extra stress on bones weakened by cancer. Pathologic fracture following stereotactic body radiation therapy for canine appendicular osteosarcoma (OSA) frequently results in limb amputation or euthanasia. Additional tools are needed to better predict the risk of fracture development. Our objectives were to determine if any relationships could be identified between BCM and the occurrence of a pathologic fracture and/or survival time in dogs with naturally occurring OSA. Forty-seven dogs with a confirmed OSA and whole-body CT pre-SBRT were included. Several BCM were evaluated, including abdominal volume, visceral adipose tissue volume, whole-body volume, whole-body adipose tissue volume, normalised cross-sectional area of the epaxial muscles at the mid-body of the 13th thoracic vertebra, and attenuations of adipose tissue and epaxial muscles. No BCMs were correlated with survival time. The volume of the entire body (cm³) was significantly positively associated with development of a fracture. No other BCM were correlated with the development of a fracture. The volume of the abdomen (cm³) among our patient subset was positively correlated with the volume of the entire body, and the volume of visceral adipose tissue (cm³) was positively correlated with the total body volume of adipose tissue (cm³). Additional research is needed to verify whether these findings are replicable in larger sample sizes and in prospective settings.

Integrating Artificial Intelligence (AI) through Natural Language Processing (NLP) can improve veterinary medical oncology clinical record analytics. Named Entity Recognition (NER), a critical component of NLP, can facilitate efficient data extraction and automated labelling for research and clinical decision-making. This study assesses the efficacy of the Bio-Epidemiology-NER (BioEN), an open-source NER developed using human epidemiological and medical data, on veterinary medical oncology records. The NER's performance was compared with manual annotations by a veterinary medical oncologist and a veterinary intern. Evaluation metrics included Jaccard similarity, intra-rater reliability, ROUGE scores, and standard NER performance metrics (precision, recall, F1-score). Results indicate poor direct translatability to veterinary medical oncology record text and room for improvement in the NER's performance, with precision, recall, and F1-score suggesting a marginally better alignment with the oncologist than the intern. While challenges remain, these insights contribute to the ongoing development of AI tools tailored for veterinary healthcare and highlight the need for veterinary-specific models.

Mast cell tumours (MCTs) are the most frequent cutaneous neoplasia of the dog, and they have very variable biological behaviour and survival times. Surgery is still the best treatment, and despite the several adjuvant therapies described, many cases are very aggressive and resistant to these treatments making it urgent to find new therapeutic targets. Nowadays, immunotherapy targeting immune checkpoints has been described as a complementary treatment for several human cancers, but it is still very scarcely studied in veterinary medicine. Therefore, this study aimed to investigate the expression of the checkpoint proteins programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) to evaluate their potential as therapeutic targets for MCT. Through immunohistochemical study, it was analysed the expression of PD-L1 and CTLA-4 in 74 MCT cases from the archive of the Veterinary Pathology Laboratory of the University of Porto (LabPatVet). Tumour size, histological grade, ki-67 proliferation index, mitotic count and presence of metastatic disease were also assessed. Most of the cases expressed both immune checkpoints in neoplastic cells. There was a statistically significant inverse association between the expression of CTLA-4 and MCT grade (p < 0,001) and mitotic count (p < 0.001). PD-L1 was significantly and negatively related to HG (p = 0.004), and tumour size (р = 0.014). Tumour size, histological grade and mitotic count were positively associated with metastatic disease. Additionally, it was observed that the expression of PD-L1 and CTLA-4 was interrelated (p < 0.001). This study demonstrated that MCT cells express both PD-L1 and CTLA-4 and that their expression was associated with MCT prognostic factors.

Canine lymphoma represents a biologically and metabolically heterogeneous group of neoplasms that arise from malignant transformation of lymphoid cells. An accurate diagnosis is crucial because of its impact on survival. Current diagnostic methods include clinical laboratory tests and imaging, most of which are invasive and lack sensitivity and specificity. Interestingly, recent work in cancer patients focuses on the search for biomarkers for diagnosis, investigation of treatment response mechanisms, treatment efficacy and prognosis and the discovery of tumour metabolic pathways using metabolomic analysis. In this study, we compare the metabolite profiles in serum from 37 dogs with multicentric lymphoma (22 B-cell lymphomas/LB, 9 CD45+ T-cell lymphomas/LTCD45+, 6 CD45- T-cell lymphomas/LTCD45-) and 25 healthy dogs using ¹H nuclear magnetic resonance spectroscopy (NMR). ¹H NMR-based metabolite profiling analysis recognised lipids and 22 metabolites, with 16 of them altered, and was shown to be an effective approach for differentiating samples from dogs with lymphoma and healthy controls based on principal component analysis of the NMR data. We also investigated variations in the serum metabolome between immunophenotypes and the control group through pairwise comparisons of the healthy against the LB, LTCD45+ and LTCD45- groups, respectively which showed similar metabolomic profiles. In addition, there were significant differences in the levels of five individual metabolites based on the univariate statistical analysis. Our results showed alterations in energy, protein and lipid metabolism, suggesting glucose, lactate, N-acetyl glycoproteins (NAGs), scyllo-inositol and choline as possible new candidate biomarkers in canine multicentric lymphoma.

The standard of care treatment for localised feline nasal lymphoma (FeNL) is radiation therapy (RT). Early local or systemic failure occurs in 17%-45% of cats treated with RT with or without chemotherapy. The aim of this study was to determine if pre-treatment biopsy characteristics could predict early tumour progression in FeNL. Inclusion criteria consisted of histologically confirmed FeNL, available paraffin blocks of diagnostic quality, localised to the sinonasal cavity on staging pre-RT, treated with IMRT/IGRT (10 × 4.2 Gy) without chemotherapy and at least 1 year follow-up. All pre-RT biopsies were reviewed and evaluated with CD3, CD20, CD79a, pan-CK and Ki-67 immunohistochemistry and the mitotic activity index was determined. The primary endpoint was progression-free survival (PFS) at 1 year and hazard-ratios (HR) with confidence interval (CI) were calculated. Twenty-eight cats fit the inclusion criteria, and all had diffuse large B-cell lymphoma. Seventeen cats (61%) were progression free at 1 year. Of the 11 cats that progressed in the first year, two had local progression, two had both local and systemic progression and seven had systemic progression. The mitotic index (HR: 1.03, CI 0.9-1.19, p = 0.645), Ki-67 (HR: 1.00, CI 0.98-1.02, p = 0.845) and > 30% of tumour-infiltrating T cells (HR: 0.38, CI 0.09-1.56, p = 0.175) were not significantly associated with PFS. In this uniformly RT treated population of FeNL, none of the evaluated pre-RT histologic parameters could predict early treatment failure.