New molecular and therapeutic insights into canine diffuse large B cell lymphoma elucidates the role of the dog as a model for human disease

open21siopenAresu, Luca; Ferraresso, Serena; Marconato, Laura; Cascione, Luciano; Napoli, Sara; Gaudio, Eugenio; Kwee, Ivo; Tarantelli, Chiara; Testa, Andrea; Maniaci, Chiara; Ciulli, Alessio; Hillmann, Petra; Bohnacker, Thomas; Wymann, Matthias P; Comazzi, Stefano; Milan, Massimo; Riondato, Fulvio; Dalla Rovere, Giulia; Giantin, Mery; Giannuzzi, Diana; Bertoni, FrancescoAresu, Luca; Ferraresso, Serena; Marconato, Laura; Cascione, Luciano; Napoli, Sara; Gaudio, Eugenio; Kwee, Ivo; Tarantelli, Chiara; Testa, Andrea; Maniaci, Chiara; Ciulli, Alessio; Hillmann, Petra; Bohnacker, Thomas; Wymann, Matthias P; Comazzi, Stefano; Milan, Massimo; Riondato, Fulvio; Dalla Rovere, Giulia; Giantin, Mery; Giannuzzi, Diana; Bertoni, Francesc

The role of serological biomarkers in the diagnosis and management of autoimmune pancreatitis

Introduction: Autoimmune pancreatitis (AIP) is a fibroinflammatory disease of the pancreas. Type 1 AIP is the pancreatic manifestation of a systemic IgG4-related disease and is associated with serum elevation of IgG4, tissue infiltration of IgG4-positive plasma cells, and multiorgan involvement. Although serum IgG4 elevation is considered a useful diagnostic tool, the concomitant presence of more diagnostic criteria is needed to achieve diagnosis. No other biomarkers have been approved in clinical practice in type 1 AIP. Type 2 AIP is a pancreatic-specific disease associated with inflammatory bowel disease. No specific biomarkers for type 2 AIP have been identified. Areas covered: The role of serum IgG4 in the diagnosis, management and follow-up of patients with type 1 AIP. Moreover, data on other emerging biomarkers for type 1 and 2 AIP have been reported. Expert opinion: The diagnosis of AIP is challenging in clinical practice, especially for focal forms without multiorgan involvement, where distinction from pancreatic cancer can be difficult. Despite the strong association with type 1 AIP, serum IgG4 should only be measured when the suspicion for the disease is high, considering its limited sensitivity. New biomarkers with high diagnostic yield for both type 1 and type 2 AIP are needed

IL-1R8 Downregulation and Concomitant TLR7 and TLR9 Upregulation Are Related to the Pathogenesis of Canine Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common hematological malignancy in humans and dogs. Several studies disclosed some similarities between the two species, including the constitutive activation of the NF-κB pathway as a fundamental underlying pathogenetic mechanism. In humans, the downregulation of IL-1R8 is implicated in DLBCL development, but its role in dogs has not been explored so far. To gain insight into the pathogenesis of this tumor in dogs, we evaluated the mRNA and protein expression of IL-1R8 in 12 control lymph nodes obtained from dogs not bearing tumors and from 50 dogs with DLBCL. Moreover, we analyzed through qRT-PCR the expression of TLR7, TLR9, MYC, and p52 genes that are known to be involved in the IL-1R8 regulatory network. IL-1R8 and p52 were downregulated in DLBCLs compared to control lymph nodes (p < 0.001), while a higher expression of TLR7, TLR9, and MYC was observed in DLBCLs (p < 0.01). Immunohistochemistry confirmed the gene expression results, revealing a significantly lower IL-1R8 staining score in DLBCLs compared to control lymph nodes (p < 0.0001). Taken together, these results suggest that IL-1R8 downregulation may represent one of the mechanisms driving DLBCL pathogenesis in dogs, mainly through the dysregulation of the Toll-like/interleukin receptors signaling cascade and the aberrant activation of the classical NF-κB pathway

Environmental risk factors for the development of oral squamous cell carcinoma in cats

Abstract Background Risk factors for oral squamous cell carcinoma (OSCC) in cats are derived from a single study dated almost 20 years ago. The relationship between inflammation of oral tissues and OSCC is still unclear. Objectives To investigate previously proposed and novel potential risk factors for OSCC development, including oral inflammatory diseases. Animals Hundred cats with OSCC, 70 cats with chronic gingivostomatitis (CGS), 63 cats with periodontal disease (PD), and 500 controls. Methods Prospective, observational case‐control study. Cats with OSCC were compared with an age‐matched control sample of client‐owned cats and cats with CGS or PD. Owners of cats completed an anonymous questionnaire including demographic, environmental and lifestyle information. Results On multivariable logistic regression, covariates significantly associated with an increased risk of OSCC were rural environment (OR: 1.77; 95% CI: 1.03‐3.04; P = .04), outdoor access (OR: 1.68; 95% CI: 1.07‐2.63; P = .02), environmental tobacco smoke (OR: 1.77; 95% CI: 1.05‐3; P = .03), and petfood containing chemical additives (OR: 1.98; 95% CI: 1.04‐3.76; P = .04). Risk factors shared with CGS and PD were outdoor access and petfood containing chemical additives, respectively. A history of oral inflammation was reported in 35% of cats with OSCC but did not emerge as a risk factor. Conclusions and Clinical Importance The study proposes novel potential risk factors for OSCC in cats. Although a history of inflammatory oral disease was not significantly more frequent compared with random age‐matched controls, OSCC shared several risk factors with CGS and PD

The features and clinical outcomes of inflammatory bowel disease associated with autoimmune pancreatitis: A greater awareness is needed

: The prevalence of inflammatory bowel disease (IBD) has been described in 5% to 40% of autoimmune pancreatitis (AIP) patients. The aim of our study was to evaluate the prevalence, endoscopic features, and outcome of IBD in association with AIP.A retrospective analysis including all consecutive patients with AIP and a histological diagnosis of IBD from 2010 to 2020 was performed. Demographical data, AIP, and IBD features, as well as clinical course, were recorded.Among 267 AIP patients, 45 were diagnosed with ulcerative colitis (UC) (27 men, mean age 31.6), all with a diagnosis of type 2 AIP. The most frequent presentation of AIP was acute pancreatitis (55.5%). Both diffuse (51.1%) and focal (48.9%) pancreatic involvement were observed. The AIP relapse rate was 11.1% over a mean follow-up of 55 months. In 69% of patients, the interval time between the diagnosis of AIP and UC was <1 year. When UC was present at AIP onset, UC was in clinical remission in 50% of patients. Fecal calprotectin levels, when available, were elevated in 86.6% of these patients. Mostly, mild-moderate pancolitis was initially diagnosed (55.5%). During follow-up, escalation therapy for UC was required in 40% of patients after a mean time of 45 months. Two patients (4.4%) underwent colectomy.The prevalence of UC in AIP patients was 17%. Mild pancolitis with a low rate of colectomy was found. Greater awareness is needed to avoid a delayed diagnosis of UC, and the dosage of fecal calprotectin levels could have a role in this setting

A Target Animal Effectiveness Study on Adjuvant Peptide-Based Vaccination in Dogs with Non-Metastatic Appendicular Osteosarcoma Undergoing Amputation and Chemotherapy

Despite efforts to develop novel treatment strategies, human and canine osteosarcomas continue to have poor prognosis and limited overall survival. The aim of this clinical trial was to test the antitumor effect and safety of multiple dermal administrations of a peptide-based anticancer vaccine in dogs with non-metastatic appendicular osteosarcoma undergoing standard of care (SOC), consisting of limb amputation and adjuvant chemotherapy. Salmonella-infected canine osteosarcoma cells were induced to release immunogenic peptides in the extracellular space via Cx43 hemichannels opening; the secretome was collected and constituted the vaccine. Dogs with non-metastatic appendicular osteosarcoma were eligible for recruitment. Following limb amputation and adjuvant carboplatin, dogs were vaccinated on a monthly basis for six times and followed up with serial thoracic radiographs. A population of dogs undergoing SOC treatment (amputation and adjuvant carboplatin) before the vaccine was available served as controls. Primary endpoints were time to metastasis (TTM) and tumor-specific survival (TSS). Secondary endpoints were feasibility, toxicity, T-cell and humoral immune responses. A total of 20 dogs were vaccinated along with SOC and 34 received SOC only. Vaccine-specific humoral and T-cell responses were observed; their amplitude correlated with TSS. Vaccine-associated toxicity was not recorded. TTM and TSS were significantly longer in vaccinated versus unvaccinated dogs (TTM: 308 vs. 240 days, respectively; p = 0.010; TSS: 621 vs. 278 days, respectively; p = 0.002). In dogs with non-metastatic osteosarcoma undergoing SOC, the addition of a bacteria-based vaccination strategy increased TTM, thereby prolonging survival, while maintaining a safe profile. Additionally, vaccinated dogs developed a long-term tumor-specific response, as documented by the immunomonitoring of these patients over time. These results hold promise for future management of canine osteosarcoma