Search Results (22)

Mast cell tumours (MCT) are the most common cutaneous neoplasms in dogs, with variable behaviours and patient survival time. Both indolent and aggressive forms have been described, but much remains to be explored regarding prognosis and therapy. Evidence has highlighted the influence of microbiota on multiple health and disease processes, including certain types of cancer in humans. However, knowledge remains scarce regarding microbiota biology and its interactions in both humans and canine cancer patients. This study aimed to characterise the faecal microbiota of dogs with MCT and compare it with that of healthy individuals. Twenty-eight dogs diagnosed with MCT and twenty-eight healthy dogs were enrolled in the study. Faecal samples were collected and analysed by Illumina sequencing of 16S rRNA genes. Alpha diversity was significantly lower in dogs with cancer, and the species diversity InvSimpson Indexwas reduced (p = 0.019). Principal coordinate analysis showed significant differences in the bacterial profile of the two groups: there was a significant lower abundance of the genera Alloprevotella, Holdemanella, Erysipelotrichaceae_UCG-003, and Anaerobiospirillum and, conversely, a significant increase in the genera Escherichia-Shigella and Clostridium sensu stricto 1 in diseased dogs. At the phylum level, Bacteroidota was significantly reduced in diseased dogs (25% in controls vs. 19% in MCT dogs). In conclusion, sequencing analysis provided an overview of the bacterial profile and showed statistical differences in the microbial communities of dogs with MCT compared with healthy dogs, suggesting a link between the gut microbiota and MCT in this species. Full article

Skin photoageing remains a topic of considerable concern. Retinol (RT) and retinyl palmitate (RP) have shown preliminary therapeutic efficacy; nevertheless, the high irritation associated with RT and the relatively modest efficacy of RP have constrained their broader application. Consequently, this study explored the effects and biosafety of RT and RP in repairing UV-induced skin ageing through a series of in vitro cell experiments, in vitro hemolysis assays, UV-irradiated mouse models, and molecular simulation techniques. The findings revealed that the interaction between RT and RP achieved complementary and enhanced therapeutic outcomes. Specifically, this combination improved the biosafety profile of retinoid formulations, accelerated cell migration rates, and facilitated the activation of the peroxisome proliferator-activated receptor α (PPARα) pathway. Moreover, the action of RT and RP further mitigated epidermal hyperplasia, mast cell infiltration, and the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α), while stimulating the synthesis of type I collagen. Metabolomics and transcriptomics analyses indicated that RT and RP exerted complementary effects through metabolic pathways, significantly elevating the overall therapeutic efficacy. Network pharmacology and molecular docking studies unveiled that the structural similarity between RT and RP was one of the contributors to their enhancement. In conclusion, this study demonstrated that the combined application of RT and RP exhibited marked effects. Through their mutual action, they not only potentiated each other’s therapeutic effects but also achieved complementary and optimised therapeutic outcomes, thereby substantially enhancing the overall efficacy. Full article

Chlorambucil is used in veterinary medicine for various cancers, while Toceranib, which was licenced for treating canine mast cell tumours, is now used against other solid tumours. Both drugs are generally safe, but their combined use has not been studied. This study aimed to investigate retrospectively the safety profile of the Chlorambucil–Toceranib combination against canine solid tumours. Thirty-eight dogs received this combination. Chlorambucil was administered at a median dose intensity of 15.1 mg/m² per week, while Toceranib was given at the median dosage of 2.5 mg/kg on a Monday–Wednesday–Friday schedule. Dosages were individually adjusted according to commercially available tablet formulation, co-morbidities, and adverse events (AEs). The resulting clinical benefit rate (CBR) and overall response rate (ORR) were 55.3% and 10.5%, respectively. The median progressive free survival (PFS) and median survival time (MST) were 45.5 (12–537) days and 259 (42–1178) days, respectively. Gastrointestinal AEs occurred in 39.5% of cases (n = 15), 15.8% (n = 6) experienced UPC elevation, while hematological and biochemistry AEs affected 13.2% (n = 5) each. Most of these AEs were grades 1–2 (G1–2). None of the dogs interrupted treatment due to AEs, and the combination appeared safe. Larger prospective clinical trials are required to confirm our findings and investigate its efficacy across various cancers. Full article

Classic Hodgkin lymphoma (cHL) is a B-cell lymphoma in which tumour cells, the so-called Hodgkin Reed–Sternberg (HRS) cells, are admixed with non-malignant cell types that are a functional part of the disease. Immune cells, fibroblasts, specialised mesenchymal cells, and microvasculature together make up the tumour microenvironment and have functional interactions with tumour cells. HRS cells are surrounded by T and B cells admixed with plasma cells, macrophages, eosinophils, and mast cells. A cross-talk occurs between HRS cells and immune cells of the TME. This cross-talk is mediated either by a large network of cytokines and chemokines expressed by HRS cells or molecules produced by different cell types of the TME, i.e., CD30/CD30L, CD40/CD40L, OX40L/OX40, Il- 3/Il-3R, CCR5/CCL5, CD74 macrophage migration inhibitory factor/macrophages, and PD-L1/PD-1. The over-expression of CD30 and CD40, members of the TNF receptor family, is a hallmark of HRS cells. This review highlights the current development of newer therapeutic strategies as a means of immune checkpoint blockade and suggests that further research should explore innovative molecules aimed at targeting components of HL that are involved in cancer cell growth and/or immune escape. Hopefully, this will influence sensitivity or resistance to checkpoint inhibitor therapy in an individual patient. Full article

Electrochemotherapy (ECT) in combination with the gene electrotransfer of interleukin 12 (IL-12 GET) has been successfully used in veterinary medicine for the treatment of mast cell tumours (MCT), but the biomarkers that could predict response to this treatment have not yet been investigated. The aim of this study was to determine the plasma nucleosome and serum ferritin concentrations, as well as the lactate dehydrogenase (LDH) activity, in the serum of treated patients before and one and six months after treatment to evaluate their utility as potential biomarkers that could predict response to the combined treatment. The study was conducted in 48 patients with a total of 86 MCTs that we treated with the combined treatment. The blood samples used for analysing the potential predictive biomarkers were taken before treatment and one and six months after treatment, when the response to treatment was also assessed. The Nu. Q^® Vet Cancer Test, the Canine Ferritin ELISA Kit, and the RX Daytona+ automated biochemical analyser were used to analyse the blood samples. The results showed that the plasma nucleosome concentration (before treatment (BT): 32.84 ng/mL (median); one month after treatment (1 M AT): 58.89 ng/mL (median); p = 0.010) and serum LDH activity (BT: 59.75 U/L (median); 1 M AT: 107.5 U/L (median); p = 0.012) increased significantly one month after treatment and that the increase correlated significantly with the presence of a more pronounced local reaction (necrosis, swelling, etc.) at that time point for both markers (nucleosome: BT (necrosis): 21.61 ng/mL (median); 1 M AT (necrosis): 69.92 ng/mL (median), p = 0.030; LDH: BT (necrosis): 54.75 U/L (median); 1 M AT (necrosis): 100.3 U/L (median), p = 0.048). Therefore, both the plasma nucleosome concentration and serum LDH activity could serve as early indicators of the effect of the treatment. In this context, the serum ferritin concentration showed no significant predictive potential for treatment response (p > 0.999 for all comparisons). In conclusion, this study provides some new and important observations on the use of predictive biomarkers in veterinary oncology. Furthermore, it emphasises the need for the continued identification and validation of potential predictive biomarkers in dogs with MCT and other malignancies undergoing ECT treatment in combination with IL-12 GET to ultimately improve treatment outcomes. Full article

Mast cell disorders range from benign proliferations to systemic diseases that cause anaphylaxis and other diverse symptoms to mast cell neoplasms with varied clinical outcomes. Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by KIT mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. The WHO 5th edition classification divides systemic mastocytosis into bone marrow mastocytosis, indolent systemic mastocytosis, smoldering systemic mastocytosis, aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia. The new ICC classifies SM slightly differently. The diagnosis of SM requires the integration of bone marrow morphologic, immunophenotypic, and molecular findings, as well as clinical signs and symptoms. Moreover, understanding the wide range of clinical presentations for patients with mast cell disorders is necessary for accurate and timely diagnosis. This review provides an updated overview of mast cell disorders, with a special emphasis on SM, including the latest approaches to diagnosis, prognostic stratification, and management of this rare disease. Full article

A study was conducted on BALB/c mice infected with Leishmania (Leishmania) amazonensis to analyse the effects of 0.5% miltefosine (MTF) hydrogel treatment on cutaneous leishmaniasis (CL) lesions. The mice were treated for 25 days topically, and lesion sizes, parasite loads, histopathology, ultrastructure, cytokines including interleukin 4 (IL-4), tumour necrosis factor alfa (TNFα), interferon gamma (IFNγ), IL-10, and vascular endothelial growth factor (VEGF) profiles were evaluated on days 0, 12, 25, and 85. After 12 days of treatment, the lesion sizes and parasite numbers decreased. By day 60 post treatment, there were no lesions and only a few parasites. At day 25, there was a temporary papillomatosis reaction, an increase in mast cells, a few giant cells, and granulomas, and a decrease in diffuse inflammatory infiltrate and parasites. Transmission electron microscopy (TEM) examination showed early ultrastructural changes, including macrophages without parasites and vacuoles containing electrodense material. At the different evaluated times, the cytokine regulation indexes (ICRs) decreased for IL-4, TNFα, and VEGF. According to the study, the 0.5% MTF hydrogel was effective and showed positive results from the early stages of usage. The MTF directly targeted parasites, downregulated the release of IL-4, TNFα, and VEGF, increased mast cell production, and induced granuloma reaction during evaluation periods. Full article

Grading, immunohistochemistry and c-kit mutation status are criteria for assessing the prognosis and therapeutic options of canine cutaneous mast cell tumours (MCTs). As a subset, canine digital MCTs have rarely been explored in this context. Therefore, in this retrospective study, 68 paraffin-embedded canine digital MCTs were analysed, and histological grading was assessed according to Patnaik and Kiupel. The immunohistochemical markers KIT and Ki67 were used, as well as polymerase chain reaction (PCR) for mutational screening in c-kit exons 8, 9, 11 and 14. Patnaik grading resulted in 22.1% grade I, 67.6% grade II and 10.3% grade III tumours. Some 86.8% of the digital MCTs were Kiupel low-grade. Aberrant KIT staining patterns II and III were found in 58.8%, and a count of more than 23 Ki67-positive cells in 52.3% of the cases. Both parameters were significantly associated with an internal tandem duplication (ITD) in c-kit exon 11 (12.7%). French Bulldogs, which tend to form well-differentiated cutaneous MCTs, had a higher proportion of digital high-grade MCTs and ITD in c-kit exon 11 compared with mongrels. Due to its retrospective nature, this study did not allow for an analysis of survival data. Nevertheless, it may contribute to the targeted characterisation of digital MCTs. Full article

Extracellular vesicles (EVs) produced by various immune cells, including B and T cells, macrophages, dendritic cells (DCs), natural killer (NK) cells, and mast cells, mediate intercellular communication and have attracted much attention owing to the novel delivery system of molecules in vivo. DCs are among the most active exosome-secreting cells of the immune system. EVs produced by cancer cells contain cancer antigens; therefore, the development of vaccine therapy that does not require the identification of cancer antigens using cancer-cell-derived EVs may have significant clinical implications. In this review, we summarise the molecular mechanisms underlying EV-based immune responses and their therapeutic effects on tumour vaccination. Full article

Cancer is a significant cause of morbidity and mortality in domestic cats. In humans, an understanding of the oncogenome of different cancer types has proven critical and is deeply interwoven into all aspects of patient care, including diagnostics, prognostics and treatments through the application of targeted therapies. Investigations into understanding the genetics of feline cancers started with cytogenetics and was then expanded to studies at a gene-specific level, looking for mutations and expression level changes of genes that are commonly mutated in human cancers. Methylation studies have also been performed and together with a recently generated high-quality reference genome for cats, next-generation sequencing studies are starting to deliver results. This review summarises what is currently known of the genetics of both common and rare cancer types in cats, including lymphomas, mammary tumours, squamous cell carcinomas, soft tissue tumours, mast cell tumours, haemangiosarcomas, pulmonary carcinomas, pancreatic carcinomas and osteosarcomas. Shining a spotlight on our current understanding of the feline oncogenome will hopefully serve as a springboard for more much-needed research into the genetics of cancer in domestic cats. Full article

Mast cell tumour (MCT) is a common cutaneous and subcutaneous neoplasia in dogs. It can metastasise to lymph nodes (LNs), and this adversely affects the prognosis and treatment. The study aims to evaluate the SLN mapping of MCTs with radiographic indirect lymphography. Dogs that underwent clinical staging were prospectively enrolled. Lipiodol was injected around the MCT or the surgical scar. After 24 h, LNs that picked up contrast were radiographically assessed. Twenty-six dogs with 29 MCTs were included. MCTs were confirmed histologically, while SLNs were evaluated either by cytology and/or histology. SLNs were detectable in 23 dogs with 26 MCTs. Lymphatic vessels were visible in 19 MCTs. In nine MCTs, at least two SLNs picked up contrast. In particular, seven MCTs involved two SLNs, and two MCTs involved three different SLNs. In nine MCTs, at least a SLN was metastatic. This study indicates that the lymph drainage pattern of the MCTs may be different for each MCT, and more than one SLN can be involved. Indirect lymphangiography with Lipiodol allowed the detection of the SLN in 90% of MCTs. This provided clinically relevant information to remove the LN and stage the patient. Full article

Necroptosis is a newly defined form of programmed cell death that plays an important role in cancers. However, necroptosis-related lncRNAs (NRLs) involved in colorectal cancer (CRC) have not yet been thoroughly studied. Methods: In this study, a 4-NRL model was developed based on the least absolute shrinkage and selection operator (LASSO) algorithm. A series of informatic, in vitro and in vivo analyses were applied to validate the prognostic value of the model and the potential function of the hub lncRNA MYOSLID. Results: The model exhibited an excellent capacity for the prediction of overall survival and other clinicopathological features of CRC patients using Kaplan–Meier (K–M) survival curves and receiver operating characteristic (ROC) curves. Furthermore, a significant difference in the levels of immune cells, such as CD4 memory T cells and activated mast cells, between two risk groups was observed. The low-risk patients had a higher expression of immune checkpoints, such as PDCD1 (PD-1) and CD274 (PD-L1). The levels of MYOSLID, a hub lncRNA in our model, were higher in CRC tissues than in normal tissues. Knockdown of MYOSLID induced necroptosis and inhibited the proliferation of CRC cells in vitro and in vivo. Interestingly, knockdown of MYOSLID also increased the percentage of CD4⁺ and CD8⁺ T cells in subcutaneously transplanted tumours. Conclusion: Our model is a promising biomarker that can be used to predict clinical outcomes in CRC patients, and MYOSLID plays an important role in regulating necroptosis and immune cell infiltration in CRC. Full article

Background: Gastrointestinal masses in cats are of clinical relevance, but pathological studies with larger case numbers are lacking. Biomarkers such as miRNA have not yet been investigated in feline intestinal neoplasms. Methods: A retrospective analysis of pathology reports included 860 feline gastrointestinal masses. Immunohistochemistry was performed on 91 lymphomas, 10 sarcomas and 7 mast cell tumours (MCT). Analyses of miRNA-20b and miRNA-192 were performed on 11 lymphomas, 5 carcinomas and 5 control tissues by ddPCR. Results: The pathological diagnosis identified 679 lymphomas, 122 carcinomas, 28 sarcomas, 23 polyps, 7 MCT and 1 leiomyoma. Carcinomas and polyps were most commonly found in the large intestine, lymphomas were most commonly found in the stomach and small intestine and MCT only occurred in the small intestine. Besides the well-described small-cell, mitotic count <2 T-cell lymphomas and the large-cell B-cell lymphomas with a high mitotic count, several variants of lymphomas were identified. The values of miRNA-20b were found to be up-regulated in samples of all types of cancer, whereas miRNA-192 was only up-regulated in carcinomas and B-cell lymphomas. Conclusions: The histopathological and immunohistochemical (sub-)classification of feline intestinal masses confirmed the occurrence of different tumour types, with lymphoma being the most frequent neoplasm. Novel biomarkers such as miRNA-20b and miRNA-192 might have diagnostic potential in feline intestinal neoplasms and should be further investigated. Full article

Since small mammals are gaining popularity as pets in Poland, the number of tumour samples submitted for histopathological examination is quite high. This study was a retrospective analysis of cutaneous and subcutaneous tumours in small pet mammals submitted for histopathology in 2014–2021. The analysis included 256 tumours sampled from 103 guinea pigs, 53 rats, 43 pet rabbits, 21 ferrets, 17 hamsters, 8 degus, 5 African pygmy hedgehogs, 3 Mongolian gerbils and 3 chinchillas. Tumours were diagnosed based on routine histopathology, with additional immunohistochemistry when necessary. The results of this study revealed that the vast majority of cutaneous tumours in guinea pigs were benign, with a predominance of lipoma. Adnexal tumours constituted a significant percentage of cutaneous tumours in guinea pigs (24.3%, with the most common being trichofolliculoma), pet rabbits (46.5%, with the most common being trichoblastoma), ferrets (33.3%, mostly derived from sebaceous glands), hamsters (52.9%, with the most common being trichoepithelioma) and gerbils (66.7%, scent gland epithelioma). Soft tissue sarcomas were a predominant group of tumours in rats (52.8%, with the most common being fibrosarcoma), African pygmy hedgehogs (100%), degus (87.5%) and chinchillas (66.7%). Melanocytic tumours were only sporadically seen in small mammal pets. Mast cell tumours were diagnosed only in ferrets, while epitheliotropic T-cell lymphoma was diagnosed only in a hamster and a degu. In summary, malignant tumours constitute a significant percentage of cutaneous tumours in many species of small mammal pets. Therefore, each cutaneous tumour should be sampled for further cytologic or histopathologic diagnosis. Full article

A new combination of Toceranib (Toc; 5-[(5Z)-(5-Fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[2-(pyrrolidin-1-yl)ethyl]-1H-pyrrole-3-carboxamide) with nanohydroxyapatite (nHAp) was proposed as an antineoplastic drug delivery system. Its physicochemical properties were determined as crystallinity, grain size, morphology, zeta potential and hydrodynamic diameter as well as Toceranib release. The crystalline nanorods of nHAp were synthesised by the co-precipitation method, while the amorphous Toceranib was obtained by its conversion from the crystalline form during nHAp–Toc preparation. The surface interaction between both compounds was confirmed using Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV–Vis) and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS). The nHAp–Toc showed a slower and prolonged release of Toceranib. The release behaviour was affected by hydrodynamic size, surface interaction and the medium used (pH). The effectiveness of the proposed platform was tested by comparing the cytotoxicity of the drug combined with nHAp against the drug itself. The compounds were tested on NI-1 mastocytoma cells using the Alamar blue colorimetric technique. The obtained results suggest that the proposed platform shows high efficiency (the calculated IC50 is 4.29 nM), while maintaining the specificity of the drug alone. Performed analyses confirmed that nanohydroxyapatite is a prospective drug carrier and, when Toceranib-loaded, may be an idea worth developing with further research into therapeutic application in the treatment of canine mast cell tumour. Full article