Dimethylfumarate (DMF) inhibits signals transmitted by Rel proteins and is used for the treatment of inflammatory skin diseases such as psoriasis, but potential effects DMF on tumor progression have yet not been analyzed. We show that reduced melanoma growth metastasis in severe combined immunodeficient mouse models. To identify targets action, we analyzed mRNA expression DMF-treated melanomas gene chip arrays. Using BiblioSphere software data analysis, significantly regulated genes were...

Functional intestinal disorders constitute major, potentially lethal health problems in humans. Consequently, research focuses on elucidating the underlying pathobiological mechanisms and establishing therapeutic strategies. In this context, organoids have emerged as a potent vitro model they faithfully recapitulate structure function of segment represent. Interestingly, human-like diseases also affect dogs, making canine promising tool for comparative research. Therefore, we generated from...

Bovine papillomavirus types 1 and 2 (BPV-1 BPV-2) are known to induce common equine skin tumours, termed sarcoids. Recently, it was demonstrated that vaccination with BPV-1 virus-like particles (VLPs) is safe highly immunogenic in horses. To establish a challenge model for evaluation of the protective potential VLPs, four foals were injected intradermally infectious virions viral genome-based control inocula, monitored daily tumour development. Blood taken before inoculation at weekly...

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that affects humans and several domestic animal species, including cats dogs. In this study, we have analyzed duodenal organoids derived from canine IBD patients using quantitative proteomics. Our objective was to investigate whether these show phenotypic traits of the compared with control obtained healthy donors. To aim, were subjected proteomics analysis via liquid chromatography–mass spectrometry. The data revealed...

Abstract Epithelial damage due to gastrointestinal disorders frequently causes severe disease in horses. To study the underlying pathophysiological processes, we aimed establish equine jejunum and colon enteroids (eqJE, eqCE) mimicking vivo epithelium. Therefore, were cultivated four different media for differentiation subsequently characterized histomorphologically, on mRNA protein level comparison native epithelium of same donor horses identify ideal culture conditions an vitro model...

Cell-free circulating tumor DNA in the plasma of cancer patients has become a common point interest as indicator therapy options and treatment response clinical research. Especially patient- tumor-specific single nucleotide variants that accurately distinguish from wild type are promising targets. The reliable detection quantification these single-base is technically challenging. Currently, variety techniques applied, with no apparent "gold standard". Here we present novel qPCR protocol...

Equine malignant melanoma (EMM) is a frequently occurring dermoepidermal tumor in grey horses. Currently available therapies are either challenging or inefficient. Betulinic acid (BA), naturally triterpenoid, promising compound for cancer treatment. To evaluate the potential of BA as topical therapy EMM, its anticancer effects on primary equine cells and dermal fibroblasts percutaneous permeation through isolated skin were assessed vitro.BA showed antiproliferative cytotoxic both time-...

<i>Background:</i> This study set out to investigate the antitumor effects of a treatment strategy combining mTOR inhibitor CCI-779 with cisplatin in vitro and human melanoma SCID mouse model. <i>Methods:</i> In 518A2, Mel-JUSO or 607B cell lines were incubated CCI-779, plus cisplatin. Based on these results, 4-group, parallel, controlled experimental design was initiated vivo. mice injected cells, after development tumors received daily injections solvent. On days 2...

Background Inhibition of mTOR complex 1 (mTORC1) with rapamycin leads to phosphorylation AKT in some cancer cells, unknown biological consequences. The role this melanoma is unknown, although preliminary clinical data indicate poor activity rapalogues melanoma. Objectives We aimed at elucidating the after mTORC1 inhibition cells. Methods Western blotting, apoptosis assays, cell cycle analyses and viability assays were performed analyse effects LY294002 treatment on For suppression 2 (mTORC2)...

We have previously shown that immunization of horses with bovine papillomavirus type 1 (BPV1) L1 virus-like particles (VLPs) is safe and highly immunogenic BPV1 2 (BPV2) are closely related serotypes. Here we evaluated the protective potential a VLP vaccine against experimental BPV2 challenge studied safety immunogenicity bivalent equine (EcPV2)/BPV1 vaccine. Fourteen healthy were immunized VLPs (100 µg per injection) plus adjuvant on days 0 28, while seven remained unvaccinated. On day 42,...

Abstract Apical‐out intestinal organoids are a relatively simple method of gaining access to the apical cell surface and have faced increasing scientific interest over last few years. can thus be used for disease modelling compare differing effects on basolateral versus surface. However, these ‘inside‐out’ die quickly cannot propagated as long their basal‐out counterparts. Here, we show that apical‐out drastically reduced proliferative potential, evidenced by immunohistochemical staining...

The antiapoptotic protein Bcl-2 contributes to a more chemoresistant phenotype of nonsmall cell lung cancer and therefore serves as an important target for novel anticancer strategies. Interestingly, docetaxel standard care treatment has been shown inactivate the function by phosphorylation. We investigated expression status cells in response cisplatin or its effect on sensitizing downregulation employing small interfering RNA approach. was assessed Western blotting RT-PCR. Cell...

Canine oral malignant melanoma (COMM) is a potentially lethal cancer disease. We established primary cell lines from mostly amelanotic COMM and metastases assessed lesions derived cells for Melan A, PNL2 CD146 expression. Then, migration invasion of CD146-enriched vs -depleted were analysed. Epithelial-to-mesenchymal transition (EMT) was addressed by Vimentin-staining MMP2/MMP9 zymography. Phagocytic behaviour analysed histopathological examination phagocytosis assay. While A- PNL2-staining...

Malignant melanomas (MMs) are the abnormal proliferation of melanocytes and one lethal skin cancers in humans, equines, canines. Accordingly, MMs companion animals can serve as naturally occurring animal models, completing conventional cancer models. The common constitutive activation MAPK PI3K pathways has been described all three species. Targeting related is considered a potential option comparative oncologic approaches. Herein, we present cross-species analysis exposing set ten melanoma...

Given the high prevalence of intestinal disease in humans and animals, there is a strong need for clinically relevant models recapitulating gastrointestinal systems, ideally replacing vivo accordance with principles 3R. We established canine organoid system analysed neutralising effects recombinant versus natural antibodies on Clostridioides difficile toxins A B this vitro system. Sulforhodamine cytotoxicity assays 2D FITC-dextran barrier integrity basal-out apical-out organoids revealed...

Anti-VEGF agents were found to have clinical implications for the successful treatment of vascular-driven diseases in humans. In this study, a detailed biological characterization bevacizumab variety vitro assays was carried out determine effect on equine umbilical vein endothelial cells (EqUVEC). EqUVECs harvested from cords clinically healthy horses and exposed different concentrations (1, 2, 4, 6, 8 mg/mL) (Avastin®). Assays concerning drug's safety (cell viability proliferation assay)...

The pro-apoptotic prostate apoptosis response-4 gene product Par-4 sensitizes cells to the induction of programmed cell death. In this study we examined expression in human melanoma lines and metastases. heterogeneous detected prompted us investigate biological relevance a xenotransplantation model. Overexpression by transfection decreased tumour development xenotransplanted A375-C6 SCID mice correlated an increase apoptosis. These data suggest that high protein could qualify as prognostic...

Summary Two novel interleukin‐24 (IL‐24) splice variants were identified in normal human melanocytes by sequencing cloned polymerase chain reaction (PCR) products that are not expressed metastatic melanoma. These gene have been generated differential skipping of exons 3 (IL‐24 delE3) and 5 delE5). IL‐24 delE3 has limited sequence identity to the IL‐24‐interacting protein mda‐7s, delE5 is homologous IL‐24.

There is a large body of evidence supporting bovine papillomavirus types 1 and 2 (BPV1; BPV2) as aetiological agents equine sarcoids. However, there conflicting data regarding BPV1/2 infection in sarcoid-free equids.Data obtained between 2007 2017 by screening sarcoids nonsarcoid tumours vs. samples from healthy equids are presented to help clarify this issue.Cross-sectional study.Tumour material horses, donkeys mules with confirmed (n = 130), suspected 120), or lesions 70), skin biopsies...