Prognostic Value of Ki67 and Other Clinical and Histopathological Factors in Canine Apocrine Gland Anal Sac Adenocarcinoma

Apocrine gland anal sac adenocarcinoma (AGASACA) is locally aggressive and highly metastatic to regional lymph nodes. The aim of this study was to evaluate the prognostic significance of Ki67 in surgically excised AGASACA. Prognostic impact of size, regional lymph nodes metastasis, hypercalcemia, histologic pattern, mitotic count, necrosis, inflammatory and lympho-vascular invasion, anisokaryosis and anisocytosis was also evaluated. Thirty-five dogs were included, twenty-four of which also had metastatic lymph nodes. When the entire population was evaluated, only metastatic disease spread to regional lymph nodes, and necrosis and inflammatory infiltration were correlated to prognosis. When only dogs with metastatic disease were evaluated, size, solid histologic pattern, presence of lymphatic and vascular invasion showed influence on prognosis. Ki67 index was not associated with survival time and disease free interval in any case. The results of this study showed that lymph nodes metastasis at diagnosis reduced disease free interval. Moreover, tumor size greater than 5.25 cm, presence of lymphatic and vascular invasion and a solid histologic pattern were associated with a shorter survival time in dogs with metastasis to regional lymph nodes. Ki67 expression was not significantly associated with prognosis, therefore it could not be considered as a prognostic factor in this tumor type, while the role of hypercalcemia remained unclear

Enhanced Expression of Interferon-γ-Induced Antigen-Processing Machinery Components in a Spontaneously Occurring Cancer

AbstractIn human tumors, changes in the surface expression and/or function of major histocompatibility complex (MHC) class I antigens are frequently found and may provide malignant cells with a mechanism to escape control of the immune system. This altered human lymphocyte antigen (HLA) class I phenotype can be caused by either structural alterations or dysregulation of genes encoding subunits of HLA class I antigens and/or components of the MHC class I antigen-processing machinery (APM). Herein we analyze the expression of several proteins involved in the generation of MHC class I epitopes in feline injection site sarcoma, a spontaneously occurring tumor in cats that is an informative model for the study of tumor biology in other species, including humans. Eighteen surgically removed primary fibrosarcoma lesions were analyzed, and an enhanced expression of two catalytic subunits of immunoproteasomes, PA28 and leucine aminopeptidase, was found in tumors compared to matched normal tissues. As a functional counterpart of these changes in protein levels, proteasomal activities were increased in tissue extracts from fibrosarcomas. Taken together, these results suggest that alterations in the APM system may account for reduced processing of selected tumor antigens and may potentially provide neoplastic fibroblasts with a mechanism for escape from T-cell recognition and destruction

Setting the Social Monitoring Framework for Nature-Based Solutions Impact: Methodological Approach and Pre-Greening Measurements in the Case Study from CLEVER Cities Milan

: Nature-based solutions (NBS) are currently being deployed in many European Commission Horizon 2020 projects in reaction to the increasing number of environmental threats, such as climate change, unsustainable urbanization, degradation and loss of natural capital and ecosystem services. In this research, we consider the application of NBS as a catalyst for social inclusivity in urban regeneration strategies, enabled through civic participation in the co-creation of green interventions with respect to social cohesion and wellbeing. This article is focused on a social monitoring framework elaborated within the H2020 CLEVER Cities project, with the city of Milan as a case study. Firstly, we overviewed the major regeneration challenges and expected co-benefits of the project, which are mainly human health and wellbeing, social cohesion and environmental justice, as well as citizen perception about safety and security related to the NBS implementation process. Secondly, we examined the relevance of using NBS in addressing social co-benefits by analyzing data from questionnaires against a set of five major indicators, submitted to citizens and participants of activities during pre-greening interventions: (1) Place, use of space and relationship with nature, (2) Perceived ownership and sense of belonging, (3) Psychosocial issues, social interactions and social cohesion, (4) Citizen perception about safety and security, and lastly, we analyzed (5) knowledge about CLEVER interventions and NBS benefits in relation to socio-demographics of the questionnaires’ respondents. Thirdly, we cross-referenced a wind-rose multi-model of co-benefits analysis for NBS across the regeneration challenges of the project. Because of the COVID-19 emergency, in this research we mainly focused on site observations and online questionnaires, as well as on monitoring pre-greening scenarios in three Urban Living Labs (ULLs) in Milan, namely CLEVER Action Labs. Lastly, this study emphasizes the expected social added values of NBS impact over long-term urban regeneration projects. Insights from the pre-greening surveys results accentuate the importance of the NBS interventions in citizens’ perceptions about their wellbeing, general health and strong sense of neighborhood belonging. A wider interest towards civic participation in co-management and getting informed about NBS interventions in the Milanese context is also noted.This document has been prepared in the framework of the European project CLEVER Cities. This project has received funding from the European Union’s Horizon 2020 innovation action program under grant agreement no. 776604. The sole responsibility for the content of this publication lies with the authors. It does not necessarily represent the opinion of the European Union. Neither the EASME nor the European Commission are responsible for any use that may be made of the information contained herein

PDGFRs expression in dogs affected by malignant oral melanomas: correlation with prognosis

Canine malignant melanoma (CMM) is the most common canine oral tumour, and up to 70-75% of dogs in stage II-III die within 1 year after surgery. The purpose of this study was to evaluate the expression of platelet-derived growth factors receptors (PDGFR)-α and -β in stage II and III CMMs and to correlate it with prognosis. PDGFRs expression was evaluated by immunohistochemistry on 48 cases of formalin-fixed CMM samples and correlated with clinical-pathological findings and outcome after surgery. PDGFRs co-expression was observed in 37.5% of cases. Positivity for PDGFR-α and -β receptor was present in 54.2 and 47.9% of cases, respectively. Ki67 values >19.5% were ascertained in 66.7% of cases. Statistical analysis showed that PDGFRs co-expression and Ki67 values > 19.5% were both associated with worse prognosis. PDGFRs expression suggests a role in the pathogenesis and progression of CMM, and α and β co-expression appears to be associated to worse prognosi

Effects of forced swimming stress on ERK and histone H3 phosphorylation in limbic areas of Roman high-and low-avoidance rats

Stressful events evoke molecular adaptations of neural circuits through chromatin remodeling and regulation of gene expression. However, the identity of the molecular pathways activated by stress in experimental models of depression is not fully understood. We investigated the effect of acute forced swimming (FS) on the phosphorylation of the extracellular signal-regulated kinase (ERK)1/2 (pERK) and histone H3 (pH3) in limbic brain areas of genetic models of vulnerability (RLA, Roman low-avoidance rats) and resistance (RHA, Roman high-avoidance rats) to stress-induced depression-like behavior. We demonstrate that FS markedly increased the density of pERK-positive neurons in the infralimbic (ILCx) and the prelimbic area (PrLCx) of the prefrontal cortex (PFCx), the nucleus accumbens, and the dorsal blade of the hippocampal dentate gyrus to the same extent in RLA and RHA rats. In addition, FS induced a significant increase in the intensity of pERK immunoreactivity (IR) in neurons of the PFCx in both rat lines. However, RHA rats showed stronger pERK-IR than RLA rats in the ILCx both under basal and stressed conditions. Moreover, the density of pH3-positive neurons was equally increased by FS in the PFCx of both rat lines. Interestingly, pH3-IR was higher in RHA than RLA rats in PrLCx and ILCx, either under basal conditions or upon FS. Finally, colocalization analysis showed that in the PFCx of both rat lines, almost all pERK-positive cells express pH3, whereas only 50% of the pH3-positive neurons is also pERK-positive. Moreover, FS increased the percentage of neurons that express exclusively pH3, but reduced the percentage of cells expressing exclusively pERK. These results suggest that (i) the distinctive patterns of FS-induced ERK and H3 phosphorylation in the PFCx of RHA and RLA rats may represent molecular signatures of the behavioural traits that distinguish the two lines and (ii) FS-induced H3 phosphorylation is, at least in part, ERK-independent