Cutaneous mast cell tumor in a captive Bush dog (Speothos venaticus): pathological and immunophenotypical aspects - case report

ABSTRACT A senile male captive bush dog (Speothos venaticus) presented a small perianal cutaneous nodule. Histologically, there was an ulcerated round cell tumor composed of well differentiated mast cells with abundant intracytoplasmic purple Giemsa-positive granules, with a diffuse eosinophilic infiltrate. Immunohistochemistry revealed that 30% of the neoplastic cells were positive for Kit in the cytoplasm and cell membrane, and all neoplastic cells were negative for MAC and CD3. Less than 10% of the neoplastic cells were positive for Ki67. At necropsy other primary tumors were identified in this animal, including an intestinal adenoma, an adrenal cortex adenoma and a testicular interstitial cell tumor.

Transcriptomic and Proteomic Study on the High-Fat Diet Combined With AOM/DSS-Induced Adenomatous Polyps in Mice

ObjectiveTo screen and identify molecular targets and bacteria genus leading to adenomatous polyps in mouse induced by high-fat diet (HFD) +AOM/DSS using omics technology.MethodsThe molecular targets of colorectal adenoma disease were obtained from the GeneCards and OMIM database. The SPF C57BL mice were randomly divided into blank (Control) and AOM/DSS+HFD colorectal adenoma model (ADH) groups. The ADH model group was intraperitoneally injected with AOM reagent. Then, mice were given with 2.5% DSS (in free drinking water) and high-fat diet to establish the mouse model. During this period, the changes of physical signs of mice in each group were observed. After the end of modeling, HE staining was used to evaluate the histopathological change of mice. The differentially expressed genes and proteins in the Control group and ADH group were detected by RNA-seq transcriptome sequencing and Tandem Mass Tags (TMT) quantitative proteomics. The histological results were analyzed by intersection with the intestinal adenoma molecular targets obtained from the database. Moreover, the changes of intestinal flora in the two groups were examined. The correlation between targets and differential bacteria was analyzed and verified by Parallel Reaction Monitoring (PRM) to comprehensively evaluate the mouse model of adenomatous polyp induced by AOM/DSS+HFD.ResultsThe general condition and histopathological results of mice confirmed that the ADH mouse model was successfully established and tubular adenoma was formed. A total of 604 genes and 42 proteins related to intestinal adenoma were obtained by histological analysis and database intersection analysis. The intestinal microflora of ADH mice was different from that of normal mice, and the constituents and abundance of intestinal flora were similar to those of human intestinal adenoma. GATA4 and LHPP were selected as potential pathological markers of the model mice by correlation analysis of targets and intestinal flora. The results of PRM verification were highly consistent with the results of RNA-Seq transcriptome sequencing and TMT analysis.ConclusionThe pathological results, molecular pathological markers and the changes of intestinal flora suggest that the mouse ADH model is ideal for studying the transformation of inflammatory cancer. The ADH model will be helpful for understanding the occurrence and development of human colorectal cancer at the transcriptomic and proteomic level.

Blood bacterial DNA, intestinal adenoma and colorectal cancer

Objective We aimed to investigate the relation of blood bacterial DNA load and profiling with intestinal adenoma (IA) and colorectal cancer (CRC) patients. Design We performed 16S rRNA gene analysis of blood from 100 incident histologically confirmed CRC cases, 100 IA and 100 healthy subjects, matched to cases by centre, sex and age. Bacterial load was analysed using multiple conditional logistic regression. Differences in terms of abundance of bacteria between groups were estimated through analysis based on negative binomial distribution normalization. Random Forest was applied to predict the group assignment. Results We found an overrepresentation of blood 16S rRNA gene copies in colon cancer as compared to tumor-free controls (IA and healthy subjects). The odds ratio of colon cancer for the highest versus the lowest three quintiles of gene copies was 2.62. (95% confidence interval=1.22-5.65). No difference was found for rectal cancer and IA. For high 16S rRNA, community diversity was higher in colon cancers than controls. CRC cases had an enrichment of Peptostreptococcaceae and Acetobacteriaceae and a reduced abundance of Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae. Identified variables predicted CRC from control and IA patients with an accuracy of 0.70. Conclusion Colon cancer patients had a higher DNA bacterial load and a different bacterial profiling as compared to healthy subjects, IA and rectal cancers, indicating a higher passage of bacteria from gastrointestinal tract to bloodstream. Further studies are needed to confirm this result and exploit it to conceive new non-invasive techniques for an early diagnosis of CRC.

Consumption of Select Dietary Emulsifiers Exacerbates the Development of Spontaneous Intestinal Adenoma

Inflammation is a well-characterized critical driver of gastrointestinal cancers. Previous findings have shown that intestinal low-grade inflammation can be promoted by the consumption of select dietary emulsifiers, ubiquitous component of processed foods which alter the composition and function of the gut microbiota. Using a model of colitis-associated cancer, we previously reported that consumption of the dietary emulsifiers carboxymethylcellulose or polysorbate-80 exacerbated colonic tumor development. Here, we investigate the impact of dietary emulsifiers consumption on cancer initiation and progression in a genetical model of intestinal adenomas. In APCmin mice, we observed that dietary emulsifiers consumption enhanced small-intestine tumor development in a way that appeared to be independent of chronic intestinal inflammation but rather associated with emulsifiers’ impact on the proliferative status of the intestinal epithelium as well as on intestinal microbiota composition in both male and female mice. Overall, our findings further support the hypothesis that emulsifier consumption may be a new modifiable risk factor for colorectal cancer (CRC) and that alterations in host–microbiota interactions can favor gastrointestinal carcinogenesis in individuals with a genetical predisposition to such disorders.