High-throughput omics approaches have long been used to uncover potential vulnerabilities in human personalized oncology but are often limited by the lack of functional validation. Therefore, we placed our emphasis on functional drug testing using patient-derived organoids (PDOs). However, PDOs generated from tumors mostly lack comparison with matching normal tissue, and the number of testable drugs is limited. Here, we demonstrate how matching the neoplastic and non-neoplastic mammary PDOs derived from the same dog can utilize targeted CRISPR/Cas9 screens to unveil cancer cell specific vulnerabilities. We performed two independent CRISPR/Cas9 dropout screens using sub-libraries targeting the epigenome (n = 1269) or druggable genes (n = 834) in paired PDOs derived from both carcinoma and normal mammary tissues from the same dog. A comparison of essential genes for tumor cells survival identified CDK2 as a functional vulnerability in canine mammary tumors (CMTs) that can be targeted with the PF3600 inhibitor. Additional potential targets were also uncovered, providing insights for personalized cancer treatments in dogs.

The intergranular corrosion behavior of friction-stir-welded 7N01-T5 aluminum alloy joints was investigated by using sliced samples extract from the top, middle and bottom layers of the joint, with the sliced direction parallel to the welding direction. The relationship between microstructure and local corrosion property of the welded joints was analyzed. The results show that the heat-affected zone (HAZ) of the weld exhibit the highest susceptibility to intergranular corrosion, and the corrosion degree of the top and bottom surface layers were more serious than the central layer in the HAZ, continuously dispersed precipitates on grain boundaries and the grains size may be the main factor which caused the different corrosion severity of HAZ. The thermo-mechanically affected zone (TMAZ) is characterized by a highly deformed structure, and the temperature reached in this local zone during welding is high enough for the strengthening precipitates, especially the precipitates on the grain boundary to be partially re-dissolved. The temperature gradient caused resistance to intergranular corrosion of TMAZ reduced from top to bottom surface. The stirred zone (SZ) experienced heavily plastic deformation and temperature cycling, the sensibility of intergranular corrosion was low, which is attributed to the sufficient re-dissolve of the strengthening precipitates during welding.

In vitro culture systems have advanced cancer biology, particularly through 2D and 3D tumor cultures. These have answered numerous scientific inquiries and propelled human oncologic research, with growing recognition of their potential to improve cancer treatment in companion animals, specifically cats and dogs. These species develop cancer spontaneously, closely resembling specific human cancer subtypes. For example, canine and feline mammary tumors are especially valuable for studying tumor biology. In vitro models from these tumors therefore offer a unique opportunity for veterinary cancer research. Recent 3D cell culture advancements provide promising platforms for predicting therapeutic responses in human cancer and may be applied to mammary tumors in animals. However, while limitations in fully recapitulating in vivo conditions and predicting chemotherapy response have been observed in colorectal tumoroids, similar challenges are emerging in mammary and breast tumors. In particular, canine mammary tumors and human breast cancers share critical heterogeneity and microenvironmental factors usually inadequately modeled in vitro. This review critically examines the predictivity of 3D mammary tumoroids from humans and companion animals, highlighting challenges related to stromal and immune cell preservation, reproducibility, and the translational gap between in vitro findings and clinical outcomes. We propose future directions to optimize these models for both comparative oncology and veterinary-specific applications.

Histological classification of mammary proliferative lesions in dogs and cats is essential for prognostic and predictive studies, as well as for comparative oncology; however, standardization of diagnoses is highly affected by substantial interobserver variability. In this study, a structured diagnostic algorithm based on the Davis–Thompson Foundation classification was assessed for the ability to improve interobserver agreement in the morphological diagnoses of mammary gland lesions in dogs and cats. Consensus diagnoses of 114 selected mammary lesions (91 canine, 23 feline) made by 16 veterinary pathologists with mammary tumor expertise were used as the gold standard, and 79 veterinary pathologists from 21 countries evaluated digitized whole slides in 2 rounds: a first reading without the algorithm and a second reading with the algorithm. Interobserver concordance was measured using unweighted kappa statistics for lesion category (hyperplastic/dysplastic, benign, malignant) and histological subtype. Across all lesions, agreement was higher for lesion category than for histological subtype. A slight improvement in concordance was observed when applying the algorithm, both for category (k = 0.72, before, and k = 0.73, after) and histotype classifications (k = 0.40, before to k = 0.42, after). Also, by using the algorithm, 73/79 raters (92%) modified at least 1 diagnosis and, among these, approximately two-thirds reached agreement with the gold standard in at least 1 case. Considering histotypes, malignant tumors with mixed epithelial and myoepithelial components showed persistently low agreement. Overall, the algorithm provided a reproducible diagnostic framework that may support training and improve standardization of canine and feline mammary tumor classification.

Oral melanomas are the most common oral malignancies in dogs and are characterized by an aggressive nature, invasiveness, and poor prognosis. With biological and genetic similarities to human oral melanomas, they serve as a valuable spontaneous comparative model. Primary cell cultures are widely used in human medicine and, more recently, in veterinary medicine to study tumorigenesis, cancer progression, and innovative therapeutic approaches. This study aims to establish two- and three-dimensional primary cell lines from oral canine melanomas using fine-needle aspiration as a minimally invasive sampling method. For this study, samples were collected from six dogs, represented by four primary oral melanomas and five lymph nodal metastases. The cells were digested to obtain single-cell suspensions, seeded in flasks, or processed with Matrigel^® to form organoids. The cell cultures were characterized through flow cytometry using antibodies against Melan-A, PNL2, and Sox-10. This technique offers a minimally invasive means to obtain cell samples, particularly beneficial for patients that are ineligible for surgical procedures, and enables the establishment of in vitro models crucial for comparative studies in mucosal melanoma oncology. To the best of our knowledge, this is the first work establishing neoplastic primary cell cultures via fine-needle aspiration in dogs.