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COX-2 overexpression is associated with several hallmarks of carcinogenesis such as proliferation, angiogenesis, invasion and metastasis. Fifty cases of canine mast cell tumours ( MCT) were retrospectively evaluated and submitted to immunohistochemistry for COX-2, CD31, Ki-67, MAC-387 and CD3. Furthermore its relationship with clinicopathological variables and overall survival ( OS) was analysed. COX-2 intensity ( P = 0.016), but not COX-2 extension nor score was associated with decreased OS and higher grades of malignancy according to Patnaik ( P = 0.002) and Kiupel ( P < 0.001) grading systems. Cox-2 intensity was also associated with higher Ki-67 scores ( P = 0.009), higher mitotic index ( P = 0.022) and higher microvascularization density ( P = 0.045). No association was observed for COX-2 intensity and CD3-T lymphocyte ( P = 0.377) and macrophage infiltration ( P = 0.261) by MAC-387 immunollabelling, suggesting an active role of COX-2 in MCT oncogenesis mainly through proliferation and angiogenesis stimulation making it a potentially clinical relevant prognosis marker and therapeutic target. [ABSTRACT FROM AUTHOR]

Tumour-associated macrophages ( TAMs) have already been associated in human breast cancer to a poor prognosis. As a part of a tumoural microenvironment, TAMs have an important contribution influencing neoplastic progression. Hitherto, in canine mammary tumours ( CMT) the prognostic value of TAMs has not been reported. In this study, MAC387 immunohistochemical expression was evaluated in 59 CMTs (20 benign and 39 malignant). The TAM value was significantly higher in malignant than benign CMT ( P = 0.011). In malignant CMT, TAMs were associated with skin ulceration ( P = 0.022), histological type ( P = 0.044), nuclear grade ( P = 0.031) and tubular differentiation ( P = 0.042). The survival analysis revealed a significant association between tumours with higher levels of TAMs and the decrease in overall survival ( P = 0.030). TAMs have proven to have a prognostic value. These findings suggest the future possibility of using TAMs as a novel therapeutic target in CMT. [ABSTRACT FROM AUTHOR]

[Display omitted] • Unscrambling complex interference effects in blood spectroscopy. • Covariance mode search: finding the optimal covariance eigenvector equivalent to the Beer-Lambert law. • Validation using the interpretation of blood constituent absorbance and interference bands at the Covariance mode level. • Enabling analytical-grade reagent-less spectroscopy point-of-care technology for blood analysis. Current chemometrics and artificial intelligence methods are unable to deal with complex multi-scale interference of blood constituents in visible shortwave near-infrared spectroscopy point-of-care technologies. The major difficulty is to access the rich information in the spectroscopy signal, unscrambling and interpreting spectral interference to provide analytical quality quantifications. We present a new self-learning artificial intelligence method for spectral processing based on the search of covariance modes with direct correspondence to the Beer-Lambert law. Dog and cat hemograms were analyzed by impedance flow cytometry and standard laboratory methods (erythrocytes counts, hemoglobin, and hematocrit). Spectral records were performed for the same samples. The methodology was benchmarked against state-of-the-art chemometrics: a multivariate linear model of hemoglobin bands, similarity, partial least squares, local partial least squares, and artificial neural networks. The new method outperforms the state-of-the-art, providing analytical quality quantifications according to desired veterinary pathology guidelines (total errors of 1.69% to 7.14%), whereas chemometric methods cannot. The method finds relevant samples and spectral information that hold the quantitative information for a particular interference mode, in contrast to the current methods that do not hold a relationship with the Beer-Lambert law. It allows the interpretation of interference bands used in quantification, providing the capacity to determine if the composition of an unknown sample is predictable. This research is especially relevant for improving current optical point-of-care technologies that are affected by spectral interference and moving towards micro-sampling and reagent-less technologies in healthcare and veterinary medicine diagnosis. [ABSTRACT FROM AUTHOR]

COX-2 expression affects mammary tumourigenesis by promoting angiogenesis and cell proliferation, encouraging metastatic spread and tumour-associated inflammation. Samples of canine mammary tumours ( n = 109) were submitted to immunohistochemistry to detect COX-2, CD31, VEGF, Ki-67, CD3 and MAC387 expression. Concurrent high expression of COX-2/ CD31, COX-2/ VEGF, COX-2/Ki-67, COX-2/ CD3 and COX-2/ MAC was associated with elevated grade of malignancy, presence of intravascular emboli and presence of lymph node metastasis. Tumours with high COX-2 ( P < 0.001) and tumours with concurrent expression of high COX-2 and high CD31 ( P = 0.008); high VEGF ( P < 0.001); high Ki-67 ( P < 0.001); high CD3+ T-lymphocytes ( P = 0.002) and elevated MAC387 macrophages ( P = 0.024) were associated with shorter overall survival ( OS) time. Interestingly the groups with high COX-2/ CD31 and high COX-2/ VEGF retained their significance after multivariate analysis arising as independent predictors of OS. Present data highlight the importance of COX-2 in canine mammary tumourigenesis. [ABSTRACT FROM AUTHOR]