The Dog as a Model to Study the Tumor Microenvironment.

Cancer is a complex and dynamic disease with an outcome that depends on a strict crosstalk between tumor cells and other components in tumor microenvironment, namely, tumor-infiltrating immune cells, fibroblasts, cancer stem cells, adipocytes, and endothelial cells. Within the tumor microenvironment, macrophages and T-lymphocytes appear to be key effectors during the several steps of tumor initiation and progression. Tumor cells, through the release of a plethora of signaling molecules, can induce immune tolerance, by avoiding immune surveillance, and inhibit immune cells cytotoxic functions. Furthermore, as the tumor grows, tumor microenvironment reveals a series of dysfunctional conditions that potentiate a polarization of harmful humoral Th2 and Th17, an upregulation of Treg cells, and a differentiation of macrophages into the M2 subtype, which contribute to the activation of several signaling pathways involving important tissue biomarkers (COX-2, EGFR, VEGF) implicated in cancer aggressiveness and poor clinical outcomes. In order to maintain the tumor growth, cancer cells acquire several adaptations such as neovascularization and metabolic reprogramming. An extensive intracellular production of lactate and protons is observed in tumor cells as a result of their high glycolytic metabolism. This contributes not only for the microenvironment pH alteration but also to shape the immune response that ultimately impairs immune cells capabilities and effector functions.In this chapter, the complexity of tumor microenvironment, with special focus on macrophages, T-lymphocytes, and the impact of lactate efflux, was reviewed, always trying to demonstrate the strong similarities between data from studies of humans and dogs, a widely proposed model for comparative oncology studies.

The role of COX expression in the prognostication of overall survival of canine and feline cancer: A systematic review.

Cyclooxygenase (COX) isoforms-1 and -2 have been extensively investigated in cancer. Although COX-2 is the isoform most studied and has been described in several malignancies associated with histologic criteria of malignancy and worse prognosis, COX-1 has also been linked to some forms of cancer. With the present review our aim was to summarize the current state of knowledge and clarify if and in which type of tumours COX-1 and/or COX-2 expression have real prognostic implications. We searched PubMed database for prognostic studies using predefined inclusion criteria in order to ascertain the prognostic value of COX-1 and COX-2 in malignant neoplasia in dogs and cats. Eighteen studies were analysed. COX-2 was shown to be a negative prognostic factor in canine and feline mammary tumours, canine mast cell tumour, canine melanoma, canine osteosarcoma and canine renal cell carcinoma. COX-1 showed a negative prognostic value in feline oral squamous cell carcinoma (SCC). We found high heterogeneity among studies regarding COX immunohistochemical evaluation methodology even in the same type of neoplasia pointing out the need for its standardization at least by tumour type. The available data support the use of COX-2 as a prognostic factor in canine (mammary carcinoma, mast cell tumour, melanoma, osteosarcoma and renal carcinoma) and feline (mammary carcinoma) cancers. For COX-1, its use is advised in feline oral SCC.

Skeletal muscle dispersion (400-1000 nm) and kinetics at optical clearing.

Skeletal muscle dispersion and optical clearing (OC) kinetics were studied experimentally to prove the existence of the refractive index (RI) matching mechanism of OC. Sample thickness and collimated transmittance spectra were measured during treatments with glucose (40%) and ethylene glycol (EG; 99%) solutions and used to obtain the time dependence of the RI of tissue fluids based on the proposed theoretical model. Calculated results demonstrated an increase of RI of tissue fluids and consequently proved the occurrence of the RI matching mechanism. The RI increase was observed for the wavelength range between 400 and 1000 nm and for the 2 probing molecules explored. We found that for 30 min treatment with 40% glucose and 99% EG, RI of sarcoplasm plus interstitial fluid was increased at 800 nm from 1.328 to 1.348 and from 1.328 to 1.369, respectively.