The current role and therapeutic targets of vitamin D in gastrointestinal inflammation and cancer.

Vitamin D, beyond its classical roles in the regulation of calcium and phosphorus homeostasis and bone metabolism, has been implicated in multiple pathological processes, including progression from inflammation to cancer development and also involvement in autoimmune diseases as well as cardiovascular disorders. In this review, we shall discuss the different roles of vitamin D and its therapeutic targets in different gastrointestinal diseases, focusing on colorectal cancer (CRC) and inflammatory bowel disease (IBD). To this end, vitamin D deficiency has been identified as a risk factor of CRC. On the other hand the active metabolite of vitamin D, 1, 25- dihydroxyvitamin D3 (1, 25(OH)2D3) has multiple anti-cancerous benefits including inhibition of proliferation, induction of apoptosis, promotion of differentiation and suppression of angiogenesis in tumors. In IBD, vitamin D is involved in the pathogenic process through the normalization of immune responses in the colon. With these experimental findings, well-designed and large-scale clinical trials are warranted to further define the therapeutic action of vitamin D in the prevention and/or treatment of IBD and further on CRC in humans.

Etiology and morphology of carditis: experiences from a single center in China.

OBJECTIVE: To investigate the type of cardiac mucosa and its relationship with age and gender of the participants and to determine the coincidence of endoscopic and pathological diagnosis of carditis as well as its etiology. METHODS: The data of 70 patients with carditis (the carditis group) and 30 individuals with endoscopically normal-appearing cardiac mucosa (the control group), including their baseline characteristics and histopathological findings, were reviewed. Their Helicobacter pylori (H. pylori) status was also reviewed. RESULTS: Three main types of cardiac mucosa: mucous, oxyntic and mixed types, were found in 45.0%, 40.0% and 15.0% of all the participants, respectively. The distribution of these types was related to the age of the participants but not to their gender. Moderate to severe mucosal inflammation was detected in 60.0% (18/30) of the control group. The etiologies of cardiac inflammation were H. pylori infection and gastroesophageal reflux disease (GERD). For antral H. pylori-negative participants, cardiac mucosal inflammation was correlated with esophageal mucosal inflammation (P < 0.05), while for those with antral H. pylori infection it was associated with antral mucosal inflammation (P < 0.01). CONCLUSIONS: The distribution of different cardiac mucosal types was related to the participants' age. Normal-appearing cardiac mucosa under endoscopy might present with histopathologically moderate to severe cardiac inflammation. The etiologies of cardiac inflammation were H. pylori infection and GERD. Different causes of carditis may result in the different histological performance of the cardia.

Comparison of intestinal metaplasia in gastric cardia and Barrett's esophagus.

OBJECTIVE: To evaluate and compare the pathological features and immunostaining pattern (cytokeratin 7 (CK-7), mucin core peptide 1 (Muc-1)) in Barrett's esophagus (BE) and cardiac intestinal metaplasia (CIM). METHODS: According to endoscopic diagnosis, patients with gastric cardiac inflammation and BE were selected from March 2008 to February 2009 in Renji Hospital, Shanghai Jiaotong University School of Medicine. Those patients who had histological findings of intestinal metaplasia (82 cases of CIM and 64 special type BE) were enrolled in our study. Hematoxylin-eosin, periodic acid-Schiff and Alcian blue staining and an immunohistochemical examination (CK-7, Muc-1) were undertaken in all of them. RESULTS: Squamous mucosa overlying the columnar crypts with intestinal metaplasia, also called buried metaplasia, was often found in the BE group (56.2%), mainly as an incomplete type (85.9%). Inflammation in the gastric antrum was more severe in the CIM group (45.1% vs 26.6%), in contrast, esophagitis was more severe in the BE group (53.1% vs 35.4%). CK-7 was highly expressed in the BE group (84.4%) in contrast to the CIM group (37.8%). There was no difference in the expression of Muc-1 in these two kinds of intestinal metaplasia (14.1% vs 19.5%). CONCLUSIONS: Buried intestinal metaplasia, mainly as an incomplete type, is the major predominant type of BE. The degree of inflammation in the gastric antrum and esophagus can differentiate BE from CIM to some extent. CK-7 immunohistochemical staining can help identify BE and CIM but Muc-1 cannot.

[Reduced expression of miR-218 and its significance in gastric cancer].

OBJECTIVE: To investigate the expression and function of miR-218 in gastric cancer. METHODS: miR-218 levels were evaluated in 20 non-cardia gastric cancer tissues using TaqMan stem-loop real-time PCR analysis. Pre-miR-218 and anti-miR-218 inhibitor were used to change the miR-218 expression level and examine its effects on cell proliferation, apoptosis, cell cycle and cell invasion. RESULTS: Comparing with the corresponding normal tissues, miR-218 expression was significantly reduced in the gastric cancer tissue (P < 0.01). Forced expression of miR-218 increased apoptosis in AGS cells. The proportion of apoptosis cells induced by transfection of pre-miR-218 was greater than that induced by control (21.6% vs. 10.4%, P = 0.032). Pre-miR-218 resulted in a significantly decreased cell growth activity (P < 0.01) and cell invasion (P < 0.05) of AGS cells compared with that of the control. CONCLUSION: miR-218 expression is reduced in gastric cancer. miR-218 may function as a tumor suppressor in gastric carcinoma.

Expression of polycomb protein EZH2 in multi-stage tissues of gastric carcinogenesis.

OBJECTIVE: To study the role and significance of the polycomb group (PcG) protein EZH2 (enhancer of zeste homolog 2) in the multi-step process of intestinal-type gastric carcinogenesis. METHODS: Gastric specimens were obtained from 142 patients with gastric disease, including 34 with chronic non-atrophic gastritis (NCAG), 33 chronic atrophic gastritis (CAG) with intestinal metaplasia (IM), 40 CAG with dysplasia (DYS) and 35 with intestinal-type gastric carcinomas (GC), and 32 Helicobacter pylori-negative controls. The EZH2 protein was stained by the immunohistochemical method and was expressed as the intensity and percentage of the total number of epithelial cells. The chronic gastritis and the grading of dysplasia were classified according to Chinese National Consensus on chronic gastritis and the Padova international classification. RESULTS: The EZH2 protein levels in the specimens of normal gastric tissue, NCAG, CAG with IM, DYS and intestinal-type GC were gradually increased (P < 0.05), but statistical significance was not found between the groups of DYS and GC. CONCLUSION: PcG protein EZH2 plays an important role in the multi-step process of intestinal-type gastric carcinogenesis.