Search Results (109)

Studies worldwide report cutaneous neoplasms in dogs; however, data in the arid regions of Mexico remain scarce. Here we report the main malignant cutaneous neoplasms diagnosed by fine needle aspiration cytology (FNAC), and describe the associations with age, sex and breed in Mexicali. Neoplastic lesions accounted for 25.52% (698/2735) of the cases, of which 56.59% (395/698) were malignant. The highest prevalence was observed in dogs aged 9–12 years (n = 193), intact males (n = 162), and mixed-breed dogs (n = 247). Round cell neoplasms (n = 309), including lymphoma, transmissible venereal tumors (TVT), and mast cell tumors (MCT), were the most common cell lineage. Using dogs aged 0–4 years as the reference group, dogs aged 9–12 years had 0.241 times the odds of developing malignant neoplasms (95% CI: 0.141–0.415, p = 0.0025). Using neutered males as the reference group, intact females showed 2.499 times the odds of developing malignant neoplasms (95% CI: 1.462–4.271, p = 0.0042). Compared to mixed-breed dogs, Schnauzers (OR = 0.161) showed significantly lower odds of malignancy (95% CI: 0.082–0.317, p = 0.0004), while Pitbull Terriers had 1.748 times more chance of present malignant neoplasia (95% CI: 1.014–3.013, p < 0.0001). This study provides significant epidemiological evidence on canine cutaneous neoplasms in an arid region of Mexico, identifying key risk factors and distribution patterns that can guide preventive, diagnostic, and therapeutic strategies tailored to regional characteristics. Full article

This study aims to investigate the prognostic impact of cellular components of the tumor microenvironment (TME), analyzed through immunohistochemistry, in oral squamous cell carcinoma (OSCC). This review was conducted following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Searches were performed in EMBASE, Medline/PubMed, Cochrane Collaboration Library, Web of Science, ScienceDirect, Scopus, and Google Scholar. After applying the study criteria, 59 articles were included, involving the analysis of cancer-associated fibroblasts (CAFs), immune cells, and endothelial cells. It was found that TME rich in α-SMA-positive CAFs, tumor-associated macrophages, and dendritic cells contribute to the invasion and progression of OSCC, resulting in a poorer prognosis. In contrast, the presence of high amounts of NK CD57⁺ cells, CD8⁺/CD45RO⁺ T cells, and PNAd⁺ endothelial cells are associated with anti-tumor immune responses in OSCC and improved survival rates. CD3⁺ and CD4⁺ T cells, Treg cells, B cells, and mast cells have shown little to no evidence of prognostic utility. Several stromal components of TME were found to have a strong impact on the aggressiveness of OSCC, reaffirming the potential use of these biomarkers as prognostic tools and therapeutic targets. Full article

The tumor microenvironment (TME) is crucial for the onset, development, and resistance to treatment of lung cancer. The tumor microenvironment consisting of a complex array of immune cells, fibroblasts, endothelial cells, extracellular matrix elements, and signaling molecules, facilitates tumor growth and spread while inhibiting the body’s antitumor immune response. In lung cancer, tumor-associated macrophages, cancer-associated fibroblasts, mast cells, and dendritic cells interact through cytokines, chemokines, growth factors, and matrix metalloproteinases to create an immunosuppressive and proangiogenic milieu. Hypoxic conditions within the TME further enhance cancer cell adaptability through hypoxia-inducible factors (HIFs), promoting epithelial–mesenchymal transition, immune evasion, and metastasis. Moreover, miRNAs have emerged as key regulators of gene expression within the TME, offering novel insights into tumor behavior and potential therapeutic targets. Targeting dynamic interactions within the TME, particularly through the modulation of immune responses, angiogenesis, and stromal remodeling, offers promising avenues for precision pharmacological approaches. This review covers the current understanding of the lung TME, highlighting its impact on cancer pathophysiology and treatment strategies. Understanding and therapeutically reprogramming the TME may pave the way for personalized and more effective interventions for lung cancer treatment. Full article

Background/Objectives: AllergoOncology is a new field of study that investigates the relationship between allergic inflammation and cancer. Mast cells and eosinophils are two critical players in allergy reactions, where they can interact and release bioactive granules. The electron microscope is an indispensable tool for analyzing membrane contacts and degranulation patterns in mast cells and eosinophils. The aim of the present ultrastructural study is to analyze the interactions between tumor-associated eosinophils and mast cells (TATEM) in nine cases of gastric cancer. Methods: Seventy-two gastric cancer samples were analyzed using light microscopy, and nine cases exhibiting TATEM were selected for additional examination by transmission electron microscopy. Results: In seven cases, there was direct interaction between non-activated eosinophils and mast cells demonstrating piecemeal degranulation and/or exocytosis. In cases 8 and 9, both cell types showed more advanced stages of degranulation. Mast cells exhibited either massive degranulation (anaphylactic type) or signs of recovery, while eosinophils displayed cytolysis, with or without extracellular trap formation (ETosis). The concurrent activation of both cell types may indicate a collaborative immune response that could affect tumor behavior. There was a trend toward an association with low-stage (I-II) gastric cancer in patients with TATEM, but this difference was not statistically significant (p = 0.06). Conclusions: This work is the first investigation to present ultrastructural evidence of the intimate relationship between degranulating mast cells and cytolytic eosinophils, with or without ETosis, in gastric cancer. These findings support the emerging field of AllergoOncology, which examines the role of allergy-like immune responses in tumor immunity. Full article

Background and Aims: In this research, we sought to enhance our comprehension of liver cancer’s genetic architecture by employing Mendelian randomization (MR) techniques to establish causative relationships between particular genetic variations and liver cancer susceptibility. Methods: We integrated data from the public databases with MR analysis to identify differentially expressed genes (DEGs) associated with Hepatocellular Carcinoma (HCC). We conducted functional enrichment analyses to determine the biological processes and signaling cascades associated with the identified DEGs. We also used the CIBERSORT deconvolution method to evaluate immune cell composition in HCC tissues, followed by correlation studies examining relationships between our key genes of interest and various immune cell populations. Additionally, we validated our findings using a rat model of HCC and clinical HCC samples. Results: We obtained two key genes, EHD4 and PPARGC1A, which co-regulated M0 macrophages, suggesting their role in macrophage polarization and tumor progression. In addition, PPARGC1A is associated with resting and activated mast cells, suggesting its involvement in regulating the tumor microenvironment. Detection of rat and clinical samples further confirmed the upregulation of these genes in HCC, supporting their potential as therapeutic targets. Conclusions: Our findings emphasize the significant involvement of EHD4 and PPARGC1A in HCC, specifically regarding their influence on tumor-associated macrophage polarization and broader immune microenvironment modulation. These findings offer new insights into the molecular mechanisms driving HCC and suggest that targeting these genes may provide novel strategies for personalized treatment. Full article

CD300 family members are immunoglobulin superfamily receptors that regulate immune cell function through either activating or inhibitory signals. Among them, CD300a is a prototypical inhibitory receptor, highly expressed in both myeloid and lymphoid lineages, and plays a pivotal role in the pathogenesis of inflammation and tumor immunity. CD300a transduces inhibitory signals in several immune cells—including mast cells, eosinophils, monocytes, dendritic cells (DCs), neutrophils, and natural killer (NK) cells—by recruiting SHP-1 phosphatase to immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and suppressing activation pathways such as Toll-like receptor (TLR)-MyD88 and FcεRI signaling. Recent studies suggest that tumor cells may hijack CD300a-associated pathways to establish an immunosuppressive microenvironment that facilitates immune evasion, tumor survival, and potentially metastatic spread. Proposed mechanisms include reduced DC-mediated type I interferon (IFN) production, diminished NK cell cytotoxicity, and negative regulation of mast cell– and eosinophil-dependent anti-tumor responses. Although some of these findings are derived from in vivo models, the cumulative evidence positions CD300a as a critical immune checkpoint in tumor-associated immune regulation. In addition to its established roles in hematologic malignancies—including chronic lymphocytic leukemia, acute lymphoblastic leukemia, and acute myeloid leukemia—CD300a has also been implicated in modulating tumor-associated immune responses in other pathological contexts. While most studies emphasize its immune cell–mediated effects, emerging evidence suggests that CD300a may directly influence tumor progression by regulating immune homeostasis, intracellular signaling, and tumor microenvironment interactions. Collectively, these findings establish CD300a as a pleiotropic immunoregulatory molecule in both hematologic and non-hematologic malignancies, underscoring the need to further explore its broader relevance and therapeutic potential in cancer immunology. Full article

Background/Objectives: Mast cell tumors (MCTs) are the second most common malignant neoplasms in dogs. Histopathological grading and clinical staging are the main tools for estimating biological behavior and disease extent; thus, both are essential for therapeutic decision-making and prognostication. However, the biological behavior of MCTs in dogs is variable, and it sometimes deviates from expectations. In a previous study, we identified 12 transcripts whose expression profile allowed a clear distinction between Kiupel low-grade and high-grade cutaneous MCTs (cMCTs) and was associated with prognosis. Building on these findings, this study evaluated the predictive potential of these transcripts’ expression profiles in classifying cMCTs into low-grade and high-grade. Methods: A logistic regression classifier based on the expression profiles of the identified transcripts and able to classify cMCTs as low- or high-grade was developed and subsequently tested on a novel dataset of 50 cMCTs whose expression profiles have been determined in this study through qPCR. Results: The developed logistic regression classifier reaches an accuracy of 67% and an area under the receiver operating characteristic curve (AUC) of 0.76. Interestingly, the molecular classification clearly identifies stage-IV disease (90% true positive rate). Conclusions: qPCR analysis of these biomarkers combined with the machine learning-based classifier might serve as a tool to support cMCT clinical management at diagnosis. Full article

The purpose of the present study was to evaluate mast cell density in squamous cell carcinoma tissues of dogs and cats to assess species differences. Skin squamous cell carcinoma tissues from dogs (n = 15: n = 10 from body sites and n = 5 nail bed specimens) and cats (n = 15, n = 10 from ears and n = 5 nasal planum specimens) were examined. Intratumoral mast cell density (IMCD), peritumoral mast cell density (PMCD) and total mast cells density (TMCD) as a sum of IMCD and PMCD were calculated from Giemsa-stained slides at high magnification in 1 mm² using an Olympus microscope (Olympus BX41, Tokyo, Japan) equipped with a digital Olympus DP72 image camera and CellSensDimension software V1.16). Both intratumoral and peritumoral tissues of the squa.mous cell carcinoma were divided into two categories: (1) loose, well-vascularized, rich in lymphocytes and plasmocytes, macrophages and neutrophils; and (2) fibrous, with few or no lymphocytes, plasmocytes, macrophages and neutrophils (the presence of neutrophils can be associated with actinic keratosis, mechanical irritation of the tumor in some anatomical areas during scratching with teeth, but, in general, neutrophils are associated with more invasive squamous cell carcinoma). In cats, a markedly higher total number of mast cells was found, and the number was also higher in intratumoral and peritumoral tissues. A similar tendency was found in both dogs and cats—a markedly higher number of mastocytes was found in both peritumoral and intratumoral loose, well-vascularized connective tissue. Conversely, lower numbers of mast cells were found in both intratumoral and peritumoral compact fibrous tissue in both animal species. Full article

Integrating network pharmacological analysis and bioinformatic techniques, this study systematically investigated the molecular mechanisms of six medicinal food homologous plants (Astragalus membranaceus, Ganoderma lucidum, Dioscorea opposite, Curcuma longa, Glycyrrhiza uralensis, and Pueraria lobata) against colorectal cancer. Through screening the TCMSP database, 303 active compounds and 453 drug targets were identified. By integrating differential expression gene analysis with WGCNA on the GSE41258 dataset from the GEO database, 49 potential therapeutic targets were identified. GO and KEGG enrichment analyses demonstrated that these targets are primarily involved in drug response, fatty acid metabolism, and key cancer-related pathways. Cross-validation using three machine learning algorithms—LASSO regression, SVM-RFE, and Random Forest—pinpointed four critical target genes: CA1, CCND1, CXCL2, and EIF6. Further, CIBERSORT immune infiltration analysis revealed strong associations between these core genes and the tumor immune microenvironment in colorectal cancer patients, notably in modulating M0 macrophage infiltration and mast cell activity. Molecular docking analyses confirmed robust binding interactions between active compounds and core target proteins. This study systematically elucidated the molecular mechanisms of six medicinal food homologous plants against colorectal cancer, providing scientific evidence for their rational clinical application. Full article

Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous tumor, and distinguishing its subtypes holds significant value for diagnosis, treatment, and the prognosis. Methods: Unsupervised clustering analysis was conducted to classify HCC subtypes. Subtype signature genes were identified using LASSO, SVM, and logistic regression. Survival-related genes were identified using Cox regression, and their expression and function were validated via qPCR and gene interference. GO, KEGG, GSVA, and GSEA were used to determine enriched signaling pathways. ESTIMATE and CIBERSORT were used to calculate the stromal score, tumor purity, and immune cell infiltration. TIDE was employed to predict the patient response to immunotherapy. Finally, drug sensitivity was analyzed using the oncoPredict algorithm. Results: Two HCC subtypes with different gene expression profiles were identified, where subtype S1 exhibited a significantly shorter survival time. A subtype scoring formula and a nomogram were constructed, both of which showed an excellent predictive performance. COL11A1 and ACTL8 were identified as survival-related genes among the signature genes, and the downregulation of COL11A1 could suppress the invasion and migration of HepG2 cells. Subtype S1 was characterized by the upregulation of pathways related to collagen and the extracellular matrix, as well as downregulation associated with the xenobiotic metabolic process and fatty acid degradation. Subtype S1 showed higher stromal scores, immune scores, and ESTIMATE scores and infiltration of macrophages M0 and plasma cells, as well as lower tumor purity and infiltration of NK cells (resting/activated) and resting mast cells. Subtype S2 was more likely to benefit from immunotherapy. Subtype S1 appeared to be more sensitive to BMS-754807, JQ1, and Axitinib, while subtype S2 was more sensitive to SB505124, Pevonedistat, and Tamoxifen. Conclusions: HCC patients can be classified into two subtypes based on their gene expression profiles, which exhibit distinctions in terms of signaling pathways, the immune microenvironment, and drug sensitivity. Full article

Canine mast cell tumors (MCTs) are common skin neoplasms with varying biological behaviors. The KIT proto-oncogene plays a key role in the development of these tumors, and internal tandem duplications on exon 11 are usually associated with more aggressive behavior, increased local recurrence, and decreased survival time. However, apart from exons 8–11 and 17, there is limited understanding of the overall KIT mutational landscape in canine MCTs. This work aims to analyze the entire KIT coding sequence (21 exons) in a cohort of 62 MCTs, which included 38 cutaneous and 24 subcutaneous tumors, and potentially identify new variants. In addition to confirming previously reported activating KIT mutations in exons 8, 9, and 11, we identified new variants in exons 2, 3, 5, 16, and the 3′ untranslated region (UTR). Notably, these last variants include an amino acid change (Asp/His) in exon 16. Additionally, we confirmed a differential prevalence of KIT variants in cutaneous and subcutaneous MCTs. These findings enhance our understanding of the KIT proto-oncogene coding sequence and provide valuable information for future confirmatory studies. Full article

Bruton’s tyrosine kinase (BTK), a cytoplasmic tyrosine kinase, plays a pivotal role in B cell biology and function. As an essential component of the B cell receptor (BCR) signaling pathway, BTK is expressed not only in B cells but also in myeloid cells, including monocytes/macrophages, dendritic cells, neutrophils, and mast cells. BTK inhibitors (BTKis) have revolutionized the treatment of chronic lymphocytic leukemia (CLL) and other B cell malignancies. Besides their well-characterized role in inhibiting BCR signaling, BTKis also exert significant immunological influences outside the tumor cell that extend their therapeutic potential and impact on the immune system in different ways. This work elucidates the immunomodulatory mechanisms associated with BTK inhibition, focusing on CLL and other clinical contexts. We discuss how BTK inhibition affects various immune cells, including B cells, T cells, and macrophages. The effects of BTKis on the profiles of cytokines, also fundamental parts of the tumor microenvironment (TME), are summarized here as well. This review also appraises the implications of these immunomodulatory actions in the management of autoimmune diseases and infections. Summarizing the dual role of BTK inhibition in modulating malignant lymphocyte and immune cell functions, this paper highlights the broader potential clinical use of compounds targeting BTK. Full article

Feline cancer is increasingly recognized as a major cause of mortality, yet data on tumor prevalence and behavior in cats, particularly in non-Western regions, remain limited. This study analyzed a decade of feline tumor data in Korea from 2012 to 2022, focusing on age, breed, and anatomical location as predictors of malignancy. Data were collected from 683 cats, with regression analysis applied to determine significant associations. Older cats exhibited a markedly higher risk of malignancy, particularly in mast cell and mammary tumors. Tumors in the mammary gland and alimentary tract had malignancy rates exceeding 90%, underscoring the need for early detection in these regions. Interestingly, squamous cell carcinoma was rare in the skin, in stark contrast to Western studies, likely reflecting differences in environmental exposure. While breed was not a statistically significant predictor, certain breeds, including Persians and Russian Blues, showed a higher frequency of malignancy. These findings highlight the importance of regional tumor research in cats and the need for larger, multicenter datasets that incorporate environmental, genetic, and lifestyle factors. Understanding these influences will help refine veterinary care and improve cancer treatment outcomes in feline populations. Full article

Virus-like particles (VLPs) have been studied and used as vaccines to control foot-and-mouth disease (FMD). Mast cells (MCs) express various pattern recognition receptors that recognize pathogens and secrete numerous cytokines to initiate and modulate immune responses. Our previous study showed that bone marrow-derived mast cells (BMMCs) can recognize foot-and-mouth disease virus-like particles (FMDV-VLPs) to differentially express various cytokines and that histone acetylation can regulate the cytokines secreted during BMMC recognition of FMDV-VLPs. To demonstrate the role of DNA methylation in this response process, BMMCs that recognize FMDV-VLPs were treated with azacytidine (5-AZA), an inhibitor of DNA methylation transferase. We prepared FMDV-VLPs as described previously and cultured the BMMCs. The transcription and expression of key cytokines and transcription factors were determined using real-time quantitative PCR (RT-qPCR) and Western blotting. Results showed that pre-treatment with AZA resulted in the increased transcription and expression of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-13, and IL-10, while the changes in IL-13 transcription and IL-6 expression were irrelevant to mannose receptors (MRs). Furthermore, analysis of the transcription factors indicated that both the transcription and expression of nuclear factor-kappa B (NF-κB) increased significantly in the AZA pre-treated group, indicating that DNA methylation may also regulate NF-κB expression to modulate TNF-α, IL-13, and IL-6. However, pre-treatment with AZA did not alter the expression of microphthalmia-associated transcription factor (MITF) or GATA-2. All the data demonstrate that DNA methylation negatively regulates the transcription and expression of TNF-α, IL-13, IL-10, and IL-6 secreted by recognizing FMDV-VLPs. These results provide new ideas for the mast cell-based design of more effective vaccine adjuvants and targeted therapies in the future. Full article

Liver cancer represents a substantial global health challenge, contributing significantly to worldwide morbidity and mortality. It has long been understood that tumors are not composed solely of cancerous cells, but also include a variety of normal cells within their structure. These tumor-associated normal cells encompass vascular endothelial cells, fibroblasts, and various inflammatory cells, including neutrophils, monocytes, macrophages, mast cells, eosinophils, and lymphocytes. Additionally, tumor cells engage in complex interactions with stromal cells and elements of the extracellular matrix (ECM). Initially, the components of what is now known as the tumor microenvironment (TME) were thought to be passive bystanders in the processes of tumor proliferation and local invasion. However, recent research has significantly advanced our understanding of the TME’s active role in tumor growth and metastasis. Tumor progression is now known to be driven by an intricate imbalance of positive and negative regulatory signals, primarily influenced by specific growth factors produced by both inflammatory and neoplastic cells. This review article explores the latest developments and future directions in understanding how the TME modulates liver cancer, with the aim of informing the design of novel therapies that target critical components of the TME. Full article