Presence of a mouse mammary tumour virus-like in feline lymphomas: a preliminary study

Abstract: The mouse mammary tumour virus (MMTV) is implicated in the aetiology of murine mammary carcinomas and a variant of it, the type B leukemogenic virus, can cause murine thymic lymphomas. Interestingly, a MMTV-like virus is suspected to be involved in human breast cancer and feline mammary carcinomas. However, to date, no cases of MMTV-like sequence amplifications have been described in lymphoid neoplasms in veterinary literature. The aim of this study was to investigate the presence of env nucleotide sequences and protein 14 (p14) of a MMTV-like virus in fifty-three feline lymphoma samples. Our results show that MMTV-like sequences were detected in 5/53 tumours (9.4%): three gastrointestinal lymphomas (one B-type diffuse large, one B-type small non-cleaved, and one T-type diffuse mixed lymphoma); and two nasal lymphomas (one B-type diffuse small cleaved lymphoma and one B-type diffuse mixed lymphoma). P14 expression was detected in the cytoplasm, and rarely in nuclei, exclusively of neoplastic cells from PCR-positive tumours. The correlation between the presence of the MMTV-env like sequences (MMTVels) and p14 antigen was statistically significant in nasal lymphomas. All cats with MMTVels-positive lymphoma had a history of contact with the outdoor environment and/or catteries, and two deceased subjects shared their environment with cats that also died of lymphoma. In conclusion, this study succeeds in demonstrating the presence of MMTVels and p14 in feline lymphomas. The characterization of the immunophenotype of MMTVels-positive lymphomas could contribute to the understanding of a possible role of a MMTV-like virus in feline tumour aetiology. The significant association between the presence of the viral sequences in lymphoid tumours and their nasal localization, together with the data collected through supplementary anamnesis, should be further analysed in order to understand the epidemiology of the virus

Epigenetics: an Opportunity to Shape Innate and Adaptive Immune Responses

Epigenetics connects genetic and environmental factors: it includes DNA methylation, histone post-translational modifications and the regulation of chromatin accessibility by non-coding RNAs, all of which control constitutive or inducible gene transcription. This plays a key role in harnessing the transcriptional programs of both innate and adaptive immune cells due to its plasticity and environmental-driven nature, piloting myeloid and lymphoid cell fate decision with no change in their genomic sequence. In particular, epigenetic marks at the site of lineage specific transcription factors and maintenance of cell type-specific epigenetic modifications, referred to as "epigenetic memory", dictate cell differentiation, cytokine production and functional capacity following repeated antigenic exposure in memory T cells. Moreover, metabolic and epigenetic reprogramming occurring during a primary innate immune response leads to enhanced responses to secondary challenges, a phenomenon known as "trained immunity". Here we discuss how stable and dynamic epigenetic states control immune cell identity and plasticity in physiological and pathological conditions. Dissecting the regulatory circuits of cell fate determination and maintenance is of paramount importance for understanding the delicate balance between immune cell activation and tolerance, in healthy conditions and in autoimmune diseases. This article is protected by copyright. All rights reserved

Metabolic-imaging of human glioblastoma live tumors: A new precision-medicine approach to predict tumor treatment response early

Glioblastoma (GB) is the most severe form of brain cancer, with a 12-15 month median survival. Surgical resection, temozolomide (TMZ) treatment, and radiotherapy remain the primary therapeutic options for GB, and no new therapies have been introduced in recent years. This therapeutic standstill is primarily due to preclinical approaches that do not fully respect the complexity of GB cell biology and fail to test efficiently anti-cancer treatments. Therefore, better treatment screening approaches are needed. In this study, we have developed a novel functional precision medicine approach to test the response to anticancer treatments in organoids derived from the resected tumors of glioblastoma patients

Indagine sul ruolo di GPX6 nel carcinoma mammario metastatico.

I tumori di grado 1 dell’istotipo non speciale (BC-NST/G1) presentano la prognosi migliore. Esistono rari casi in cui questi tumori metastatizzano ai linfonodi ascellari, quindi con un comportamento più aggressivo. È stata eseguita precedentemente una analisi di sequenziamento di tutto l’esoma (WES) di tumori BC-NST G1 da campioni di FFPE. Sono stati analizzati campioni G1 Luminal A con presenza e assenza di metastasi. Dai risultati del WES, è stata identificata la presenza di uno SNP (rs406113) (A>C) nel gene GPX6, presente esclusivamente nel gruppo metastatico. Lo scopo di questo studio è stato quello di indagare il ruolo di GPX6 nello sviluppo delle metastasi nel carcinoma mammario. Abbiamo confermato che la presenza dello SNP rs406113 è associata ad una minore trascrizione di mRNA e ad una minore espressione proteica di GPX6. Abbiamo studiato la presenza dello SNP in ulteriori gruppi di casi di carcinoma mammario riscontrando che la presenza di metastasi è piu frequente nei soggetti con l’allele variante. Dallo studio su linee cellulari commerciali di carcinoma mammario Luminali A, ZR751 (C/C) e MFC7 (A/A) per lo SNP, abbiamo confermato quanto riscontrato nei pazienti. Sono stati condotti studi enzimatici per indagare l’attività di GPX6 nel comportamento delle cellule tumorali. I risultati ottenuti suggeriscono che la presenza dello SNP rs406113 è associata ad un comportamento cellulare più aggressivo, probabilmente implicato nella capacità di migrazione

Proposing the program of health surveillance for workers in large organized distribution [Proposta di programma di sorveglianza sanitaria nei lavoratori della grande distribuzione organizzata]

The whole of trading enterprises with many average/big saling-centres forms what is today commonly known as Large Organized Distribution (LOD). The main risks regarding the people working in the LOD are: MM, repetitive motion of upper limbs, fixed postures, unfavourable microclimatic conditions and, moreover, the probability of labour accidents. In order to analyse the risks due to MM and false postures, we have used the ergonomic software "Classic Jack" distributed by EAI-UGS, which has beeen very helpful to find out the most dangerous labour operations (e.g. charging and discharging of goods, fragmentation and reassembling of manufactures, goods-shelving, branding and labelling). We have, then, suggested a programme of health surveillance that includes a medical examination, eventual x-Ray exams, specialized examination and a posturologic visit. This posturologic visit has got an olistic diagnostics approach, whose research after the causes that could be responsible for the checked diseases concerns not only the damaged area, but also other parts of the body (ocular system, auditive system, podalic system, masticatory apparatus)

Is food protein induced enterocolitis syndrome only a non IgE-mediated food allergy?

Food protein induced enterocolitis syndrome (FPIES) is classified as non-IgE-mediated or cell-mediated food allergy, although there is an atypical phenotype so defined for the presence of specific IgEs. All diagnostic criteria for FPIES include the absence of skin or respiratory symptoms of IgE-mediated type. We present four cases that suggest that specific IgEs may have a pathogenic role, resulting in the existence of different FPIES phenotypes. This could be important from a diagnostic and therapeutic point of view

Is food protein induced enterocolitis syndrome only a non IgE-mediated food allergy?

Food protein induced enterocolitis syndrome (FPIES) is classified as non-IgE-mediated or cell-mediated food allergy, although there is an atypical phenotype so defined for the presence of specific IgEs. All diagnostic criteria for FPIES include the absence of skin or respiratory symptoms of IgE-mediated type. We present four cases that suggest that specific IgEs may have a pathogenic role, resulting in the existence of different FPIES phenotypes. This could be important from a diagnostic and therapeutic point of view

Yogurt is tolerated by the majority of children with IgE-mediated cow's milk allergy

Background: Children with IgE-mediated cow's milk allergy (IgE-CMA) with gastrointestinal symptoms tolerate yogurt at 100%. Yogurt tolerance in children with IgE-CMA with urticaria and anaphylaxis was 7%. Methods: We enrolled children with IgE-CMA with cutaneous, respiratory, gastrointestinal and anaphylactic symptoms. All performed prick by prick (PbP) and oral food challenge (OFC) with yogurt. Some children performed also an OFC with CM mixed with wheat flour and baked, baked liquid CM, parmesan. Results: 34 children were enrolled, 31/34 (91%) with systemic adverse reaction after ingestion of CM (systemic CMA), 3/34 (9%) with isolated contact urticaria (ICU CMA). PbP with yogurt was negative only in one patient. OFC with yogurt was passed (that is, the OFC was negative) by 20/31 (64%) of the children with systemic CMA. 10/11 (91%) of the patients who failed OFC (that is, the OFC was positive) with yogurt were positive to SPT with casein vs. 8/20 (40%) of the patients who passed it (p = 0.018). None of the 19 children who passed OFC with yogurt failed all OFC with processed CM forms other than yogurt that tested vs. 4/8 among those who failed OFC with yogurt (p = 0.006). The rub test with yogurt was negative in 1/3 (33%) of the patients with ICU CMA. Conclusions: The results of our study are placed alongside others already present in the literature and concerning other methods of processing CM proteins and help to reduce the dietary restrictions of the majority of children with systemic IgE-CMA