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Metastasis is one of the defining features of pancreatic ductal adenocarcinoma (PDAC) that contributes to poor prognosis. In this study, the palmitoyl transferase ZDHHC20 was identified in an in vivo shRNA screen as critical for metastatic outgrowth, with no effect on proliferation and migration in vitro, or primary PDAC growth in mice. This phenotype is abrogated in immunocompromised animals, and in animals with depleted natural killer (NK) cells, indicating that ZDHHC20 affects the interaction of tumour cells and the innate immune system. Using a chemical genetics platform for ZDHHC20-specific substrate profiling, a number of novel substrates of this enzyme were identified. These results describe a role for palmitoylation in enabling distant metastasis that could not have been detected using in vitro screening approaches and identify potential effectors through which ZDHHC20 promotes metastasis of PDAC.

Background Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. We investigated the efficacy of high-fibre diets combined with irradiation in C57BL/6 mice bearing bladder cancer flank allografts. Result Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance. Although local immunity was suppressed, psyllium plus resistant starch increased caecal isoferulic acid levels, associated with a favourable response. Both diets mitigated the acute radiation injury caused by 14 Gy. All high fibre diets increased caecal short-chain fatty acid levels. Similar gut microbiota profiles in cancer patients and low-fibre diet mice indicates scope for testing dietary fibre supplements in human intervention studies. Conclusion These supplements may be useful in combinations with radiotherapy in patients with pelvic malignancy.

Environmental carcinogenic exposures are major contributors to global disease burden yet how they promote cancer is unclear. Over 70 years ago, the concept of tumour promoting agents driving latent clones to expand was first proposed. In support of this model, recent evidence suggests that human tissue contains a patchwork of mutant clones, some of which harbour oncogenic mutations, and many environmental carcinogens lack a clear mutational signature. We hypothesised that the environmental carcinogen

To report the diagnosis and treatment of a radial artery pseudoaneurysm in a cat.Clinical report.Maine Coon cat (8-year-old neutered male).Ultrasonographic and angiographic examination of a fluctuant, nonpainful, 3 cm × 1.5 cm subcutaneous swelling on the craniomedial distal aspect of the right radius that occurred 40 days after suspected cat bite trauma was consistent with a radial artery pseudoaneurysm. After ligation of the radial artery proximal to the lesion, the pseudoaneurysm was surgically excised.The excised tissue had hemorrhage and fibrin surrounded by a thick fibrous granulating capsule of variably mature fibroblasts and focal areas of inflammatory cells (lymphocytes, plasma cells, and macrophages) consistent with a pseudoaneurysm. Surgical excision resulted in resolution of clinical signs.Ultrasonography enabled prompt, noninvasive diagnosis of pseudoaneurysm. Angiography or computed tomography may be useful to aid diagnosis and assess the collateral blood supply to the manus before surgical treatment.

The present study sought to quantitatively examine mucosal inflammatory and immune responses in dogs with gastritis and the relationship of these responses to infection with Helicobacter. Gastric biopsies from 30 dogs were evaluated for B- and T-lymphocytes, neutrophils, eosinophils, macrophages, and mast cells. Mucosal atrophy, fibrosis, cellularity, and severity of gastritis were graded qualitatively. Messenger-RNA (mRNA) for actin, interleukin-1beta (IL-1beta), IL-4, IL-8, and IL-10, transforming growth factor beta (TGF-beta), and interferon gamma (IFN-gamma) was quantified by polymerase chain reaction (PCR). The presence of Helicobacter spp. was determined by urease activity, histology, PCR, and enzyme-linked immunosorbent assay. mRNA for IL-1beta, IL-8, IL-10, TGF-beta, and IFN-gamma was detected in most dogs. IL-4 mRNA was detected in only 1 dog. Correlations were observed for IL-1beta versus IL-8 and IL-10; IL-8 versus IL-10, IFN-gamma, and TGF-beta; and IL-10 versus IFN-y. Mucosal pathology was related to cytokine mRNA expression (neutrophils to IL-8 and IFN-gamma, macrophages and lymphocytes to IFN-gamma, and fibrosis to IL-1beta). Gastritis was categorized as lymphoplasmacytic in all dogs, and its histologic severity correlated with atrophy, infiltration with lymphocytes and macrophages, and expression of IL-10 and IFN-gamma. Of the dogs examined, 76.7% were infected with Helicobacter spp. Infection was associated with increased expression of TGF-beta and fibrosis. Circulating anti-Helicobacter immunoglobulin G titers were higher in uninfected than infected dogs. We conclude that lymphoplasmacytic gastritis in dogs is characterized by concurrent activation of proinflammatory and immunomodulatory cytokines, with increased mRNA expression related to mucosal pathology. No significant associations between Helicobacter infection and proinflammatory cytokine expression, severity of gastritis, or differences in the pathogenicity of different Helicobacter spp. were found.