Presumed Solitary Dissemination of Colon Cancer Mimicking Primary Cancer of the Small Intestine

A 69-year-old man with abdominal distention was referred to our hospital. The patient had undergone laparoscopic surgery for his Borrmann type 2 rectal cancer 2 years before. In addition to the re-elevation of serum CEA and CA19-9 levels, computed tomography (CT) showed intestinal dilatation, and positron emission CT showed a presumed tumor with abnormal fluorodeoxyglucose accumulation in the small intestine. We judged the small intestinal dilatation was highly due to the solitary recurrent peritoneal dissemination of rectal cancer and performed laparoscopic evaluation of the abdominal cavity followed by laparoscopic resection of the affected small intestine. The small intestinal tumor resembled the rectal cancer both on macroscopical and microscopical findings, that is, Borrmann type 2 phenotype and adenocarcinoma that was well differentiated in the part that protruded into the small intestinal lumen and whose degree of differentiation gradually decreased toward the serosa. In addition, abrupt disruption of the normal small intestinal epithelium and the lymphocytic aggregation, presumed tumor-infiltrating lymphocytes, just between the tumor and the small intestinal epithelium highly suggested the tumor originating from the colon cancer. The patient recovered uneventfully with marked decrease in tumor marker levels 1 month after the operation but did not receive colon cancer-oriented chemotherapy as adjuvant therapy for his financial reasons. Oncologists should note this type of recurrence to properly treat the patients with recurrent colorectal cancer.

MicroRNA-195 regulates Tuft cell function in the intestinal epithelium by altering translation of double cortin-like kinase 1

Intestinal Tuft cells sense luminal contents to influence the mucosal immune response against eukaryotic infection. Paneth cells secrete antimicrobial proteins as part of the mucosal protective barrier. Defects in Tuft and Paneth cells occur commonly in various gut mucosal disorders. MicroRNA-195 (miR-195) regulates the stability and translation of target mRNAs and is involved in many aspects of cell processes and pathologies. Here, we reported the posttranscriptional mechanisms by which miR-195 regulates Tuft and Paneth cell function in the small intestinal epithelium. Mucosal tissues from intestinal epithelial tissue-specific miR-195 transgenic (miR195-Tg) mice had reduced numbers of double cortin-like kinase 1 (DCLK1)-positive (Tuft) and lysozyme-positive (Paneth) cells, compared with tissues from control mice, but there were no effects on Goblet cells and enterocytes. Intestinal organoids expressing higher miR-195 levels from miR195-Tg mice also exhibited fewer Tuft and Paneth cells. Transgenic expression of miR-195 in mice failed to alter growth of the small intestinal mucosa but increased vulnerability of the gut barrier in response to lipopolysaccharide (LPS). Studies aimed at investigating the mechanism underlying regulation of Tuft cells revealed that miR-195 directly interacted with the Dclk1 mRNA via its 3'-untranslated region and inhibited DCLK1 translation. Interestingly, the RNA-binding protein HuR competed with miR-195 for binding Dclk1 mRNA and increased DCLK1 expression. These results indicate that miR-195 suppresses the function of Tuft and Paneth cells in the small intestinal epithelium and further demonstrate that increased miR-195 disrupts Tuft cell function by inhibiting DCLK1 translation via interaction with HuR.

A55 INVESTIGATING THE ROLE OF ENDOGENOUS INTERLEUKIN-10 IN INTESTINAL EPITHELIAL CELLS AND HOMEOSTASIS

Background IL-10 is appreciated for its potent anti-inflammatory effects on leukocytes in mucosal immunity. However, far less attention has been paid to the impact of IL-10 on epithelial cells, which make up the crucial barrier interface between the host mucosa and the external environment. Furthermore, most studies examine the effects of exogenous IL-10, disregarding the possible presence and function of autocrine or paracrine IL-10 in the epithelium. Aims Using ex vivo organoids we aimed to examine the small intestinal epithelium for IL-10 and dissect any role for endogenously produced cytokine. Methods We growed small intestinal organoids (enteroids) from crypts isolated from C57BL/6 mice (WT) and IL-10-gene knockout mice (IL-10KO). Cellular markers were characterized through qpCR, while IL-10 and IL-10 receptor localization was characterized though immunofluorescence. Results We discovered that cells in WT enteroids expressed IL-10 and IL-10R1 constitutively throughout development. Immunofluorescent staining revealed that IL-10 localizes to Paneth cells and appears to be secreted apically. Having established that IL-10 is secreted in enteroids, we compared enteroids from IL-10KO versus WT mice. IL-10KO enteroids developed to morphologically resemble WT enteroids; however, we detected an imbalance with lower secretory cell markers over absorptive cell types in the IL-10KO enteroids, measured as less mRNA for lysozyme, cryptdins and mucin-2. Addition of IL-10 to IL-10KO enteroids did not correct these defects, but did ameliorate the lineage balance by reducing absorptive cell lineage markers (sucrose isomaltase). IL-10R1 was localized on both apical and basolateral side of cell in enteroids. We suspect that epithelial-derived IL-10 likely acts on apical IL-10R, which may conduct a different response from basolateral receptor stimulation. Conclusions In conclusion, IL-10 is present in the small intestinal epithelium; more remains to be determined regarding the role this cytokine plays in gut development and homeostasis. Funding Agencies NSERC

Effects of ingested nanocellulose and nanochitosan materials on carbohydrate digestion and absorption in an in vitro small intestinal epithelium model

Nanoscale materials derived from natural biopolymers like cellulose and chitosan have many potentially useful agri-food and oral drug delivery applications. Because of their large and potentially bioactive surface areas and...