Veterinary and comparative oncology最新文献

Mammary tumours are the most common type of neoplasm in female dogs, with nearly half being malignant. Oncolytic Newcastle disease virus (NDV) therapy has emerged as a novel cancer treatment option; however, its precise oncolytic mechanism in canine mammary tumours (CMT) remain unclear. Ultrastructural analysis of NDV-infected CMT-U27 cells with locally damaged cell membranes and swollen and ruptured mitochondria revealed the occurrence of pyroptosis. Transcriptome sequencing further identified a significant upregulation of pyroptosis-related genes, including NLRP1, NOD2, caspase-1, and GSDMD. Subsequent examination of RNA and protein expression levels of pyroptosis-related molecules in vitro indicated that NDV induces pyroptosis in CMT-U27 cells via the caspase-1/GSDMD pathway. Additionally, inhibition of the TNFα/NF-κB pathway and knockdown of NOD-like receptor pyrin domain-containing protein 3 (NLRP3) using small interfering RNA demonstrated that the TNFα/NF-κB pathway can regulate NDV-induced pyroptosis through the NLRP3 inflammasome. In a xenograft model, intravenous administration of NDV significantly inhibited tumour growth, and prolonged the survival time in nude mice bearing CMT-U27 cells. NDV treatment enhances intratumoural pyrotosis in tumour bearing mice. In conclusion, these findings suggest that NDV induces pyroptosis in CMT-U27 cells through the TNFα/NF-κB/NLRP3 pathway, providing a foundation for future research into NDV's therapeutic potential in canine mammary cancer.

Carotid body paragangliomas represent an uncommon neoplasm in dogs. The objective of this study was to report outcomes and complications associated with surgical excision of carotid body paragangliomas in 21 dogs. Cases were recruited retrospectively via medical record review from 9 veterinary speciality centres. The perioperative complication rate was 52% (11/21). Complications encountered in this cohort related to removal of carotid body tumour included airway obstruction, aspiration pneumonia, megaesophagus, unilateral laryngeal paralysis, coughing and Horner's syndrome. The overall perioperative mortality rate was 4.7% (1/21 dogs) and median survival time was 554 days for the six patients with known dates of death. One- and two-year survival rates were 61% and 42%, respectively. This is the largest collection of carotid body paraganglioma cases reported in veterinary literature. Based on these results, surgical resection of carotid body paragangliomas was associated with low perioperative mortality and long survival times.

Nodal metastasis is a negative prognostic factor in dogs with mast cell tumours (MCTs), thus early detection enables more informed decision-making and provides valuable prognostic information. The aim of this study is to assess the concordance between histopathologic findings of LNs and cytology and flow cytometry (FC), respectively, and to evaluate the ability of FC to differentiate between metastatic (HN2-HN3) and non-metastatic (HN0-HN1) LNs. Overall, 117 LNs from 64 dogs with first occurring MCTs were submitted for cytology, histology and FC. LNs were cytologically and histologically classified according to Krick and Weishaar systems, respectively. Using FC, mast cells (MCs) were identified as IgE+ CD117+ CD5- CD21- cells and quantified as a percentage. When compared with histologic classification, cytology showed an accuracy of 88.2% in distinguishing between metastatic and non-metastatic LNs but did not detect 25.3% of metastatic cases. FC revealed an increase in the median percentages of MCs across histologic classes, progressing from HN0 to HN3. ROC curves pinpointed 0.3% as the optimal cut-off for distinguishing between metastatic and non-metastatic LNs, with an accuracy of 84.3%. A 1.1% cut-off proved valuable in identifying HN3 LNs. The combined interpretation of cytology and FC increased accuracy to 92.2%. An algorithm for guiding the combined interpretation of cytology and FC is suggested based on these findings. In conclusion, FC proves beneficial in enhancing the early detection of metastatic LNs, particularly when utilised alongside cytology. Histopathology remains essential for confirmation, enabling the discrimination of HN classes or, in doubtful cases, for the detection or exclusion of nodal metastases.

Canine cutaneous/subcutaneous soft-tissue sarcomas (STS) are diversely derived mesenchymal neoplasms with a risk of recurrence and/or metastasis depending on the extent of surgical excision and histologic grade. Lymphoid aggregates (LAs) are often described in these tumours but not characterised. In humans, LA characterised as tertiary lymphoid structures (TLSs) improve the prognosis of many tumours, including sarcomas. We sought to determine if LA meeting a size criterion (> 700 cells) in canine sarcomas met the criteria of TLS and the overall prevalence of LA of any size. RNA expression in large LAs versus aggregate-adjacent sarcoma tissue (AAS) was measured in laser capture microdissected tissue and compared to curl-derived RNA from aggregate-free sarcomas and lymph nodes. CD3, CD20, MUM-1 and PNAd expressions were measured using immunohistochemistry. CD20 and CD3 mRNA were more highly expressed in LA versus AAS (13.8 fold, p = 0.0003 and 2.3 fold, p = 0.043). This was supported by the IHC findings. The large LAs were also enriched in chemokine RNA expression characteristic of TLS (CXCR5 5.8 fold, p < 00001, CCL19 3.68 fold, p = 0.0209, CCL21 6.87 fold, p = 0.0209 and CXCL13 2.68 fold, p = 0.0924). Plasma cells and high endothelial venules were identified in LA containing tumours but not in control tissue. Large LAs were present in 12% of tumours, and LA of any size in 30%. We conclude that large LAs in canine STS are consistent with TLS.

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.

Data regarding the outcome of canine rib chondrosarcoma is sparse and varied. While grade of tumour is associated with outcome for canine appendicular chondrosarcoma, the association of grade with outcome for canine rib chondrosarcoma is unclear. This study aimed to correlate the grade of canine rib chondrosarcoma with median survival time. Retrospectively, cases of primary rib chondrosarcoma were identified, and tumours were graded based on a 3-tier adapted human grading scheme. Twenty-two patients were included in the survival analysis. The median survival time was 1427 days (range: 27-3354 days). This was not significantly different for patients with grade I versus II versus III (p = 0.82), grade I-II versus III (p = 0.34), or grade I versus II-III (p = 0.49). No variables assessed including age, weight, tumour location (cranial vs. caudal thorax; left vs. right hemithorax), tumour location on rib (proximal, middle, and distal), radiographic appearance (lytic, proliferative, or mixed), elevated serum alkaline phosphatase activity, grade, grade specific histologic features (matrix production, architecture, pleomorphism, cellularity, necrosis, and total score), adjunct therapy post-surgical excision, development of metastatic disease post-surgery, or local recurrence post-surgery were found to impact the risk of death due to chondrosarcoma. In this limited group of patients, the grading scheme reported here, and the other variables assessed did not appear to offer additional prognostic information. However, this data must be interpreted considering the small sample size and thus low statistical power. Additional studies are needed to determine the true impact of grade on outcome for canine rib chondrosarcomas.

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.

This multicenter retrospective study evaluated the effects of a time delay and steroids on the volume of peritumoral edema (VPTE) in dogs with extra-axial brain tumours. The hypothesis is that VPTE will decrease between the diagnostic (MRI-1) and RT planning (MRI-2) MRIs following the administration of steroids. Inclusion required paired MRI acquisitions within 3 months, with VPTE contouring for each MRI registered to the RT planning CT. No edema was defined as < 0.2 cm³, increased edema was > 30% VPTE increase and decreased edema was > 30% VPTE decrease. Forty-four dogs of which 34 (77%) received steroids between MRIs were included. The median time between the MRIs was 22 days (range: 8-74 days). Nine (20%) had no edema on both MRIs. The median MRI-1/VPTE: 0.83 cm³ (IQR: 0.15-2.06 cm³) and median MRI-2/VPTE: 0.40 cm³ (IQR: 0.06-1.12 cm³) were significantly different (p = 0.048). Compared to MRI-1/VPTE: 17 (39%) VPTE decreased, eight were stable and 10 increased. The median VPTE difference was -21%, range: -100 to +6287. With steroids, VPTE decreased in 15/34 (44%) and increasedin 6/34 (18%) (median VPTE diff: -60%) compared to no steroids (median VPTE diff: +25%). Steroids use was associated with change in VPTE (p = 0.009). Two dogs had clinical deterioration and were on steroids with documented VPTE increase (+86% and +1880%) without tumour progression. The change in VPTE is highly variable but reduction is associated with steroids. Notably, subjective improvement of clinical signs can be seen without significant decrease to the VPTE on imaging.

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.