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Activation of pancreatic stellate cells (PSCs) to cancer-associated fibroblasts (CAFs) is responsible for the extensive desmoplastic reaction observed in PDAC stroma: a key driver of pancreatic ductal adenocarcinoma (PDAC) chemoresistance leading to poor prognosis. Specialized pro-resolving mediators (SPMs) are prime modulators of inflammation and its resolution, traditionally thought to be produced by immune cells. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipid mediator profiling PSCs as well as primary human CAFs express enzymes and receptors to produce and respond to SPMs. Human PSC/CAF SPM secretion profile can be modulated by rendering these cells activated [transforming growth factor beta (TGF-β)] or quiescent [all- trans retinoic acid (ATRA)]. ATRA-induced nuclear translocation of arachidonate-15-lipoxygenase (ALOX15) was linked to increased production of n-3 docosapentaenoic acid-derived Resolvin D5 (RvD5 n-3 DPA ), among other SPMs. Inhibition of RvD5 n-3 DPA formation increases cancer cell invasion, whereas addback of this molecule reduced activated PSC-mediated cancer cell invasion. We also observed that circulating concentrations of RvD5 n-3 DPA levels were decreased in peripheral blood of metastatic PDAC patients when compared with those measured in plasma of non-metastatic PDAC patients. Together, these findings indicate that RvD5 n-3 DPA may regulate cancer-stroma cross-talk and invasion., Competing Interests: Author JD is an inventor on patents related to the composition of matter and/or use of pro-resolving mediators, some of which are licensed by Brigham and Women’s Hospital or Queen Mary University of London for clinical development. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Aguirre, Goulart, Barts Pancreas Tissue Bank, Dalli and Kocher.)

Pancreatic cancer is a disease with high unmet clinical need. Pancreatic cancer is also characterised by an intense fibrotic stroma, which harbours many immune cells. Studies in both human and animal models have demonstrated that the immune system plays a crucial role in modulating tumour onset and progression. In human pancreatic ductal adenocarcinoma, high B-cell infiltration correlates with better patient survival. Hence, B cells have received recent interest in pancreatic cancer as potential therapeutic targets. However, the data on the role of B cells in murine models is unclear as it is dependent on the pancreatic cancer model used to study. Nevertheless, it appears that B cells do organise along with other immune cells such as a network of follicular dendritic cells (DCs), surrounded by T cells and DCs to form tertiary lymphoid structures (TLS). TLS are increasingly recognised as sites for antigen presentation, T-cell activation, B-cell maturation and differentiation in plasma cells. In this review we dissect the role of B cells and provide directions for future studies to harness the role of B cells in treatment of human pancreatic cancer., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to declare., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with a dismal 5-year survival rate. PDAC has a complex tumour microenvironment; characterised by a robust desmoplastic stroma, extensive infiltration of immunesuppressive cells such as immature myeloid cells, tumour-associated macrophages, neutrophils and regulatory T cells, and the presence of exhausted and senescent T cells. The cross-talk between cells in this fibrotic tumour establishes an immune-privileged microenvironment that supports tumour cell escape from immune-surveillance, disease progression and spread to distant organs. PDAC tumours, considered to be non-immunogenic or cold, express low mutation burden, low infiltration of CD8 + cytotoxic lymphocytes that are localised along the invasive margin of the tumour border in the surrounding fibrotic tissue, and often display an exhausted phenotype. Here, we review the role of T cells in pancreatic cancer, examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of T cells as therapy., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To estimate the burden of excess weight in Brazilian adolescents., Design: Systematic review with meta-analysis., Setting: We searched the literature in four databases (MEDLINE/PubMed, EMBASE, SciELO and LILACS). Studies were included if they had cross-sectional or cohort design and enrolled Brazilian adolescents. Studies based on self-reported measures were excluded. Random effect models were used to calculate prevalence estimates and their 95 % CI., Participants: Brazilian adolescents (10 to 19 years old)., Results: One hundred and fifty-one studies were included. Trend analyses showed a significant increase in the prevalence of excess weight in the last decades: 8·2 % (95 % CI 7·7, 8·7) until year 2000, 18·9 (95 % CI 14·7, 23·2) from 2000 to 2009, and 25·1 % (95 % CI 23·4, 26·8) in 2010 and after. A similar temporal pattern was observed in the prevalence of overweight and obesity separately. In sensitivity analyses, lower prevalence of excess weight was found in older adolescents and those defined using International Obesity Task Force cut-off points. The Southeast and South regions had the highest prevalence of excess weight, overweight and obesity. No significant difference in prevalence by sex was found, except for studies before the year 2000., Conclusions: The prevalence of overweight and obesity in Brazilian adolescents is high and continues to rise. Public policies on an individual level and targeting modifications in the obesogenic environment are necessary.

Pancreatic ductal adenocarcinoma (PDAC), characterized by dense desmoplastic stroma laid down by pancreatic stellate cells (PSC), has no reliable diagnostic biomarkers for timely detection. A multi-center cohort of PDAC patients and controls (chronic pancreatitis, intra-ductal papillary neoplasms, gallstones and otherwise healthy) donated serum in an ethically approved manner. Serum PTX3 above 4.34 ng/mL has a higher sensitivity (86%, 95% confidence interval (CI): 65-97%) and specificity (86%, 95% CI: 79-91%), positive predictive value (97%) and likelihood ratio (6.05), and is superior when compared to serum CA19-9 and CEA for detection of PDAC. In vitro and ex vivo analyses of PTX3, in human PDAC samples, PSCs, cell lines and transgenic mouse model for PDAC, suggest that PTX3 originates from stromal cells, mainly PSC. In activated PSC, PTX3 secretion could be downregulated by rendering PSC quiescent using all-trans-retinoic acid (ATRA). PTX3 organizes hyaluronan in conjunction with tumor necrosis factor-stimulated gene 6 (TSG-6) and facilitates stellate and cancer cell invasion. In SCALOP clinical trial (ISRCTN96169987) testing chemo-radiotherapy without stromal targeting, PTX3 had no prognostic or predictive role. However, in STARPAC clinical trial (NCT03307148), stromal modulation by ATRA even at first dose is accompanied with serum PTX3 response in patients who later go on to demonstrate disease control but not those in whom the disease progresses. PTX3 is a putative stromally-derived biomarker for PDAC which warrants further testing in prospective, larger, multi-center cohorts and within clinical trials targeting stroma.

Pancreatic cancer remains one of medicine's largest areas of unmet need. With five-year survival rates of < 8%, little improvement has been made in the last 50 years. Typically presenting with advance stage disease, treatment options are limited. To date, surgery remains the only potentially curative option, however, with such late disease presentation, the majority of patients are unresectable. Thus, new therapeutic options and a greater understanding of the complex stromal interactions within the tumour microenvironment are sorely needed to revise the dismal outlook for pancreatic cancer patients. Natural killer (NK) cells are crucial effector units in cancer immunosurveillance. Often used as a prognostic biomarker in a range of malignancies, NK cells have received much attention as an attractive target for immunotherapies, both as cell therapy and as a pharmaceutical target. Despite this interest, the role of NK cells in pancreatic cancer remains poorly defined. Nevertheless, increasing evidence of the importance of NK cells in this dismal prognosis disease is beginning to come to light. Here, we review the role of NK cells in pancreatic cancer, examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of NK cells as therapy., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background & Aims: The association between markers of nutritional status (handgrip strength [HGS] and adductor pollicis muscle thickness [APMT]) and clinical markers of congestive heart failure (CHF) severity is currently unclear. The objective of this study was to evaluate the association between HGS, APMT, as markers of nutritional status and CHF severity., Methods: APMT and muscle strength was measured in 500 CHF patients bilaterally. Nutritional status was assessed by Subjective Global Assessment (SGA). Functional classification was performed according to guidelines provided by the New York Heart Association (NYHA) and ejection fraction (EF) was measured to classify CHF severity. Poisson regression, adjusted for sex and age, was performed to verify the association between nutritional factors and CHF severity markers., Results: The majority of patients (75.8%) were ≥60 years old and 53.6% were either overweight or obese. SGA identified 42.2% of the patients as malnourished, 12.6% with low APMT, and 29.0% with low HGS. Most of the patients were classified as NYHA III/IV (56.8%) and almost one third of patients (31.1%) had EF ≤ 40%. HGS and APMT were significantly lower in malnourished male patients and in male patients with a lower EF or worse NYHA classification. Even after controlling for the EF, malnourished patients showed a 2.5-fold increased risk of CHF severity by NYHA classification and for each kilogram of increase in the HGS, there was a significant decrease of 2% in the risk (RR: 0.98 p < 0.001). Malnourished patients presented a 52% higher risk (RR: 1.52 p = 0.016) of having a low EF, whereas for each APMT increase, there was a 5% decrease in the risk (RR: 0.95 p < 0.001), even after controlling for NYHA classification., Conclusions: Malnutrition is highly prevalent among patients with CHF and it is associated with the functional class and the severity of the disease. Objective markers of strength (HGS) and muscle (APMT) are independently associated with the CHF severity, assessed by NYHA classification and EF, respectively, even after adjustment for other confounding variables. Thus, the implementation of these nutritional assessment methods in hospital routines, either by SGA or by objective methods, such as HGS and APMT, can configure effective measurements for early detection of malnutrition in patients at higher risk, and possibly a way to avoid their further functional decline., Competing Interests: Conflict of interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Pre-clinical models have shown that targeting pancreatic stellate cells with all-trans-retinoic-acid (ATRA) reprograms pancreatic stroma to suppress pancreatic ductal adenocarcinoma (PDAC) growth. Here, in a phase Ib, dose escalation and expansion, trial for patients with advanced, unresectable PDAC (n = 27), ATRA is re-purposed as a stromal-targeting agent in combination with gemcitabine-nab-paclitaxel chemotherapy using a two-step adaptive continual re-assessment method trial design. The maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D, primary outcome) is the FDA/EMEA approved dose of gemcitabine-nab-paclitaxel along-with ATRA (45 mg/m 2 orally, days 1-15/cycle). Dose limiting toxicity (DLT) is grade 4 thrombocytopenia (n = 2). Secondary outcomes show no detriment to ATRA pharmacokinetics.. Median overall survival for RP2D treated evaluable population, is 11.7 months (95%CI 8.6-15.7 m, n = 15, locally advanced (2) and metastatic (13)). Exploratory pharmacodynamics studies including changes in diffusion-weighted (DW)-MRI measured apparent diffusion coefficient after one cycle, and, modulation of cycle-specific serum pentraxin 3 levels over various cycles indicate stromal modulation. Baseline stromal-specific retinoid transport protein (FABP5, CRABP2) expression may be predicitve of response. Re-purposing ATRA as a stromal-targeting agent with gemcitabine-nab-paclitaxel is safe and tolerable. This combination will be evaluated in a phase II randomized controlled trial for locally advanced PDAC. Clinical trial numbers: EudraCT: 2015-002662-23; NCT03307148. Trial acronym: STARPAC.

Gene expression profiling has revealed molecular heterogeneity of diffuse large B cell lymphoma (DLBCL) in both humans and dogs. Two DLBCL subtypes based on cell of origin are generally recognized, germinal center B (GCB)-like and activated B cell (ABC)-like. A pilot study to characterize the transcriptomic phenotype of 11 dogs with multicentric BCL yielded two molecular subtypes distinguished on the basis of genes important in oxidative phosphorylation. We propose a metabolic classification of canine BCL that transcends cell of origin and shows parallels to a similar molecular phenotype in human DLBCL. We thus confirm the validity of this classification scheme across widely divergent mammalian taxa and add to the growing body of literature suggesting cellular and molecular similarities between human and canine non-Hodgkin lymphoma. Our data support a One Health approach to the study of DLBCL, including the advancement of novel therapies of relevance to both canine and human health., (Copyright © 2020 Wu, Chang, Polton, Stell, Szladovits, Macfarlane, Peters, Priestnall, Bacon, Kow, Stewart, Sharma, Goulart, Gribben, Xia and Garden.)

Regulatory T cells (Tregs) are a double-edged regulator of the immune system. Aberrations of Tregs correlate with pathogenesis of inflammatory, autoimmune and neoplastic disorders. Phenotypically and functionally distinct subsets of Tregs have been identified in humans and mice on the basis of their extensive portfolios of monoclonal antibodies (mAb) against Treg surface antigens. As an important veterinary species, dogs are increasingly recognised as an excellent model for many human diseases. However, insightful study of canine Tregs has been restrained by the limited availability of mAb. We therefore set out to characterise CD4 + CD25 high T cells isolated ex vivo from healthy dogs and showed that they possess a regulatory phenotype, function, and transcriptomic signature that resembles those of human and murine Tregs. By launching a cross-species comparison, we unveiled a conserved transcriptomic signature of Tregs and identified that transcript hip1 may have implications in Treg function.

Myeloid-derived suppressor cells (MDSCs) are key players in immune evasion, tumor progression and metastasis. MDSCs accumulate under various pathological states and fall into two functionally and phenotypically distinct subsets that have been identified in humans and mice: polymorphonuclear (PMN)-MDSCs and monocytic (M)-MDSCs. As dogs are an excellent model for human tumor development and progression, we set out to identify PMN-MDSCs and M-MDSCs in clinical canine oncology patients. Canine hypodense MHC class II - CD5 - CD21 - CD11b + cells can be subdivided into polymorphonuclear (CADO48A + CD14 - ) and monocytic (CADO48A - CD14 + ) MDSC subsets. The transcriptomic signatures of PMN-MDSCs and M-MDSCs are distinct, and moreover reveal a statistically significant similarity between canine and previously published human PMN-MDSC gene expression patterns. As in humans, peripheral blood frequencies of canine PMN-MDSCs and M-MDSCs are significantly higher in dogs with cancer compared to healthy control dogs (PMN-MDSCs: p < 0.001; M-MDSCs: p < 0.01). By leveraging the power of evolution, we also identified additional conserved genes in PMN-MDSCs of multiple species that may play a role in MDSC function. Our findings therefore validate the dog as a model for studying MDSCs in the context of cancer.

Objectives: Research on resilience has been gaining momentum, and it has already been shown that increased resilience creates positive changes at the individual and collective levels. Understanding of the factors associated with resilience may guide specific actions directed towards different populations. The objective of this study was to investigate these associated factors within a population of medical students., Design: Cross-sectional census., Setting: A public medical school in the state of Rio de Janeiro, Brazil., Participants: Out of a total of 551 medical students, five students were excluded due to inactive registrations, and four transferred students were also excluded, resulting in a total of 542 remaining participants., Measures: Adopting an anonymous questionnaire that included the Resilience Scale, in addition to questions related to sociodemographic, behavioural health-related and academic variables, the association between these variables and resilience was investigated., Results: The high rate of answers to each item constitutes a indication of students' interest in participating, whereas the lowest percentile was 97.1%. The mean resilience score obtained was considered moderate. Factors such as gender, race, previous schools attended, financial independence, living situation, parents' education level, religion, quota-based admission, smoking, alcohol abuse and use of illegal drugs were not associated with resilience. In a multivariate analysis using ordinal logistic regression, associations were maintained only between the highest resilience score and the non-use of habit-forming prescription drugs (OR: 0.58; 95% CI 0.41 to 0.80), having a better perception of one's own health (OR: 0.57; 95% CI 0.41 to 0.81) and being older (OR: 1.37; 95% CI 1.12 to 1.67)., Conclusion: The census performed with the medical students showed, with the multivariate analysis, that besides age, the variables most closely tied with resilience were health and medicalisation, and the variables connected with income and religion showed no association., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To verify the knowledge about food and nutrition and its association with the nutritional status of obese patients with noncommunicable diseases (NCDs), and to identify the relationship between information sources and level of knowledge., Method: Cross-sectional study that included 263 outpatients of a cardiology referral hospital in Porto Alegre, Rio Grande do Sul, Brazil. The participants filled out a questionnaire on socioeconomic data and knowledge about food and nutrition and had their nutritional status evaluated by body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR)., Results: BMI showed a significant inverse association with the percentage of correct answers (p=0.002), as well as WC (p=0.000) and WHR (p<0.001). This was also true for education (p<0.001) and female gender (p=0.005) compared to males. More than 60% of patients reported using television and 23% reported using newspaper as sources of nutritional information., Conclusion: Our study revealed a significant association between BMI and the level of knowledge about foods, showing that there is need for more information on obesity-related NCDs for greater understanding by patients.

Monocytes are key cells of the innate immune system. Their phenotypic and functional roles have been investigated in humans, mice and other animals, such as the rat, pig and cow. To date, detailed phenotypic analysis of monocytes has not been undertaken in dogs. Two important surface markers in human monocytes are CD14 and MHC class II (MHC II). By flow cytometry, we demonstrated that canine monocytes can be subdivided into three separate populations: CD14 pos MHC II neg , CD14 pos MHC II pos and CD14 neg MHC II pos . Both light and transmission electron microscopy confirmed the monocytic identity of all three populations. The CD14 pos MHC II neg population could be distinguished on an ultrastructural level by their smaller size, the presence of more numerous, larger granules, and more pseudopodia than both of the other populations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The prevalence of overweight in children with CHD is about 26.9%. Increase in adipose tissue is related to the secretion of proinflammatory markers such as C-reactive protein. Assuming that children with CHD are exposed to other inherent risk factors for heart disease, our objective was to evaluate the correlation between levels of C-reactive protein and body mass index in children and adolescents with CHD., Methods: A cross-sectional study with 377 children and adolescents with CHD in a clinical setting of a reference hospital was carried out. C-reactive protein data were collected after 12 hours of fasting. Nutritional status was classified according to body mass index. The patients were divided into three groups: cyanotic, acyanotic, and minimal heart defects (controls)., Results: The mean age was 9.9±4.2 years, and 53.6% of the sample included males. The cyanotic group represented 22.3%, acyanotic 42.2%, and minimal defects 35.5% of the sample. The average body mass index percentile was 57.23±32.06. The median values of C-reactive protein were as follows: cyanotic 0.340, acyanotic with clinical repercussion 0.203, and minimal defects 0.128. There was a significant difference between the minimal defects and the cyanotic groups (p=0.023). There was a significant correlation between C-reactive protein and body mass index percentile (r=0.293, p<0.01). C-reactive protein levels were higher in girls (p=0.034). There were no significant correlations between C-reactive protein and age or birth weight., Conclusion: The correlation between body mass index percentile and C-reactive protein was confirmed in this population. The prevention of overweight is paramount to avoid overlapping modifiable risk factors to those already inherent to the CHD.

Background:: Schools have become a key figure for the promotion of health and obesity interventions, bringing the development of critical awareness to the construction and promotion of a healthy diet, physical activity, and the monitoring of the nutritional status in childhood and adolescence., Objectives:: To describe a study protocol to evaluate the effectiveness of an intervention designed to improve knowledge of food choices in the school environment., Methods:: This is a cluster-randomized, parallel, two-arm study conducted in public elementary and middle schools in Brazil. Participants will be children and adolescents between the ages of 5 and 15 years, from both genders. The interventions will be focusing on changes in lifestyle, physical activities and nutritional education. Intervention activities will occur monthly in the school's multimedia room or sports court. The control group arm will receive usual recommendations by the school. The primary outcome variable will be anthropometric measures, such as body mass index percentiles and levels of physical activity by the International Physical Activity Questionnaire., Results:: We expect that after the study children will increase the ingestion of fresh food, reduce excessive consumption of sugary and processed foods, and reduce the hours of sedentary activities., Conclusion:: The purpose of starting the dietary intervention at this stage of life is to develop a knowledge that will enable for healthy choices, providing opportunities for a better future for this population., Fundamento:: As escolas tornaram-se essenciais para a promoção de saúde e de intervenções para obesidade, propiciando o desenvolvimento de consciência crítica para a construção e promoção de dieta saudável, atividade física e monitoramento do status nutricional na infância e adolescência., Objetivos:: Descrever um protocolo de estudo para avaliar a eficiência de uma intervenção projetada para aprimorar o conhecimento sobre escolhas alimentares no ambiente escolar., Métodos:: Estudo clínico randomizado em cluster, paralelo, de dois braços, conduzido em escolas públicas de ensino fundamental e médio no Brasil. Os participantes serão crianças e adolescentes entre 5 e 15 anos de idade, dos dois sexos. As intervenções se concentrarão em mudanças de estilo de vida, atividade física e educação nutricional. As atividades de intervenção ocorrerão mensalmente na sala de multimídia ou quadra de esportes das escolas. O grupo controle receberá as recomendações usuais através da escola. O desfecho primário será a mudança nas medidas antropométricas, como índice de massa corporal e os níveis de atividade física conforme o Questionário Internacional de Atividade Física., Resultados:: Esperamos que, após o estudo, as crianças aumentem o consumo de alimentos frescos, reduzam o consumo excessivo de alimentos açucarados e processados, e reduzam as horas gastas em atividades sedentárias., Conclusão:: O propósito de iniciar a intervenção dietética nessa fase da vida é desenvolver o conhecimento que permitirá escolhas saudáveis, propiciando oportunidades para um melhor futuro para essa população.

Background: In Brazil, the prevalence of systemic arterial hypertension (SAH) is approximately 30% of the total population. In 2010, SAH was the cause of death of about 9.4 million people worldwide. A healthy dietary pattern is important to maintain proper blood pressure levels and, consequently, disease control., Objectives: To describe the knowledge and practices of hypertensive patients cared for at a public hypertension outpatient clinic, and its relationship with high-sodium food., Methods: We applied a questionnaire to patients with questions related to sociodemographics, dietary pattern, frequency of ingestion of certain foods, and knowledge about their own disease., Results: We studied 221 patients, 56.1% of whom were women, and 53.8% had only elementary education. Their mean age was 57.7 ±13.5 years, and 75.6% of them reported having high blood pressure, and 11.3%, diabetes mellitus. Regarding dietary pattern, 62% used ready-to-use seasonings, but 94.1% reported not adding extra salt to their ready meals. Regarding patients' knowledge about high-sodium foods and SAH, only 8 patients had 100% of right answers, 37 patients had 73.8%, and 42 patients, 57% of right answers., Conclusion: Knowledge about SAH prevention and high-sodium foods was insufficient. Based on this study's findings, more effective educational strategies targeted at this population can be developed.

Malignant and atypical meningiomas are resistant to standard therapies and associated with poor prognosis. Despite progress in the treatment of other tumors with therapeutic vaccines, this approach has not been tested preclinically or clinically in these tumors. Spontaneous canine meningioma is a clinically meaningful but underutilized model for preclinical testing of novel strategies for aggressive human meningioma. We treated 11 meningioma-bearing dogs with surgery and vaccine immunotherapy consisting of autologous tumor cell lysate combined with toll-like receptor ligands. Therapy was well tolerated, and only one dog had tumor growth that required intervention, with a mean follow up of 585 days. IFN-γ-elaborating T cells were detected in the peripheral blood of 2 cases, but vaccine-induced tumor-reactive antibody responses developed in all dogs. Antibody responses were polyclonal, recognizing both intracellular and cell surface antigens, and HSP60 was identified as one common antigen. Tumor-reactive antibodies bound allogeneic canine and human meningiomas, showing common antigens across breed and species. Histologic analysis revealed robust infiltration of antibody-secreting plasma cells into the brain around the tumor in posttreatment compared with pretreatment samples. Tumor-reactive antibodies were capable of inducing antibody-dependent cell-mediated cytotoxicity to autologous and allogeneic tumor cells. These data show the feasibility and immunologic efficacy of vaccine immunotherapy for a large animal model of human meningioma and warrant further development toward human trials., (©2013 AACR.)

Dogs with naturally occurring cancer represent an important large animal model for drug development and testing novel immunotherapies. However, poorly defined immunophenotypes of canine leukocytes have limited the study of tumor immunology in dogs. The accumulation of myeloid derived suppressor cells (MDSCs) is known to be a key mechanism of immune suppression in tumor-bearing mice and in human patients. We sought to identify MDSCs in the blood of dogs with cancer. Peripheral blood mononuclear cells (PBMCs) from dogs with advanced or early stage cancer and from age-matched healthy controls were analyzed by flow cytometry and microscopy. Suppressive function was tested in T cell proliferation and cytokine elaboration assays. Semi-quantitative RT-PCR was used to identify potential mechanisms responsible for immunosuppression. PBMCs from dogs with advanced or metastatic cancer exhibited a significantly higher percentage of CD11b(+)CD14(-)MHCII(-) cells compared to dogs diagnosed with early stage non-metastatic tumors and healthy dogs. These CD11b(+) CD14(-)MHCII(-) cells constitute a subpopulation of activated granulocytes that co-purify with PBMCs, display polymorphonuclear granulocyte morphology, and demonstrate a potent ability to suppress proliferation and IFN-γ production in T cells from normal and tumor-bearing donors. Furthermore, these cells expressed hallmark suppressive factors of human MDSC including ARG1, iNOS2, TGF-β and IL-10. In summary our data demonstrate that MDSCs accumulate in the blood of dogs with advanced cancer and can be measured using this three-marker immunophenotype, thereby enabling prospective studies that can monitor MDSC burden.

The aim of this study was to evaluate the cicatricial repair of perforating cornea in rabbits, by using the N-butyl cyanoacrylate adhesive compared to the 910-polyglactine thread suture through macroscopic and histological assays. Corneas from 18 adult rabbits were perforated and subsequently occluded with N-butyl cyanoacrylate synthetic adhesive (right cornea) or by separated single points using the 910-polyglactine thread (left cornea). The rabbits were divided into groups containing three animals per group. Examination after 7, 15, and 30 days post-operative showed that both the synthetic adhesive and the suture were efficient in the occlusion of the surgical wounds, thus stabilizing the intra-ocular content. The N-butyl cyanoacrylate adhesive was shown to be superior to the 910-polyglactine suture thread with regards to the evolution and the organization of the healing process.