Background and Aims Gastric stem cells are located in the isthmus of the gastric glands, and give rise to epithelial progenitors that undergo bipolar migration and differentiation into pit and oxyntic lineages. While gastric mucus neck cells, located below the isthmus, express trefoil factor family 2 (TFF2) protein, TFF2 mRNA transcripts are concentrated in cells above the neck region in normal corpus mucosa, suggesting that TFF2 transcription is a marker of gastric progenitor cells. Methods Using a BAC strategy, we generated a transgenic mouse with a tamoxifen-inducible Cre under the control of the TFF2 promoter (TFF2-BAC-CreERT2) and analyzed the lineage derivation from TFF2 mRNA transcript-expressing (TTE) cells. Results TTE cells were localized to the isthmus, above and distinct from TFF2 protein-expressing mucus neck cells. Lineage tracing revealed that these cells migrated towards the bottom of the gland within 20 days, giving rise to parietal, mucous neck and chief cells, but not to ECL cells. Surface mucus cells were not derived from TTE cells, and the progeny of the TTE lineage did not survive beyond 200 days. TTE cells were localized in the isthmus adjacent to Dclk1+ putative progenitor cells. Induction of spasmolytic polypeptide-expressing metaplasia (SPEM) with DMP-777-induced acute parietal cell loss revealed that this metaplastic phenotype might arise in part through transdiferentiation of chief cells as opposed to expansion of mucus neck or progenitor cells. Conclusion TFF2-transcript-expressing cells are progenitors for mucus neck, parietal and zymogenic, but not for pit or ECL cell lineages in the oxyntic gastric mucosa.

Background-Chronic pancreatitis is a significant cause of morbidity and a known risk factor for pancreatic adenocarcinoma. Interleukin-1β is a proinflammatory cytokine involved in pancreatic inflammation. We sought to determine whether targeted overexpression of interleukin-1β in the pancreas could elicit localized inflammatory responses and chronic pancreatitis.

Transcatheter arterial chemoembolisation (TACE) has been reported to be an efficient treatment of liver metastases of endocrine tumours in short series of patients. However, several factors seem to affect its results. The aim of this work is to identify predictors of response to TACE for liver metastases of endocrine tumours. A total of 163 TACE procedures were performed in 67 patients between 1994 and 2004. Forty-four patients were treated with streptozotocin and 23 with doxorubicin. Primary tumour was located in the pancreas for 19 patients, and had been removed in 43. Thirty-eight tumours were functioning. Response rate was 37% (confidence interval [CI] 95%: 28 -49%). Median time to progression (TTP) was 14.5 months (CI 95%: 9 -41). In multivariate analysis (n ¼ 43), predictors of tumour response were body mass index (BMI) (odds ratio [OR]: 1.3; CI 95%: 1.04 -1.63; P ¼ 0.022), functioning type of tumour (OR: 7.31; CI 95%: 1.26 -42.5; P ¼ 0.027), arterial phase enhancement on abdominal computed tomography (CT) (OR: 8.11; CI 95%:1.06 -62; P ¼ 0.044) and use of streptozotocin for cytotoxic agent (OR: 21.3; CI 95%: 1.48 -306; P ¼ 0.025). Analysis of TTP predictors showed that BMI (hazard ratio [HR]: 0.85; CI 95%: 0.76 -0.86; P ¼ 0.01) and arterial phase enhancement (HR: 0.3; CI 95%: 0.12 -0.73; P ¼ 0.008) were associated with delayed progression. This large study confirms the previously reported results of TACE regarding its efficacy for the treatment of liver metastases of endocrine tumours. Arterial phase enhancement on abdominal CT and BMI are predictors of treatment's efficacy. Streptozotocin should be the preferred cytotoxic agent in order to save anthracycline for systemic chemotherapy.