A rare complication of prophylactical clip closure after colonic endoscopic submucosal dissection.

Prophylactic defect closure has been considered to prevent delayed bleeding after polypectomy. However, recent evidence has demonstrated its beneficial effect is limited to those ≥20 mm proximal nonpedunculated lesions. Despite this, prophylactic defect closure is widely performed in clinical practice after colonic endoscopic submucosal dissection (ESD). We present a rare complication of prophylactical clip closure after colonic ESD.

Endoscopic or Follow-up Treatment for Gastric Indeterminate Tumors Is the Preferred Method of Management.

Background: Endoscopic forceps biopsy (EFB) lacks precision in diagnosing indeterminate tumors. When the presence of early gastric cancer (EGC) is macroscopically suspected, but biopsy pathology fails to give a diagnosis of neoplasia, it causes problems in clinical management. The purpose of this study was to discuss the outcome of gastric indeterminate tumors and the clinical factors associated with predicting EGC. Methods: The medical records of 209 patients diagnosed with gastric indeterminate neoplasia by biopsy forceps were retrospectively studied. Initial endoscopic findings were analyzed and predictors of EGC were evaluated. Results: The final pathological diagnosis in 209 patients included adenocarcinoma (n = 7), high-grade intraepithelial neoplasia (n = 11), low-grade intraepithelial neoplasia (n = 21), and non-neoplastic lesion (n = 170). Multivariate analysis showed that older age (OR = 1.78; 95% CI = 1.17-2.71; p = 0.008), patients undergoing narrow band imaging (NBI) (OR = 3.40; 95% CI = 1.37-8.43; p = 0.008), and surface erosion (OR = 3.53; 95% CI = 1.41-8.84; p = 0.007) were associated with the upgraded group, and were significantly associated with risk. Univariate logistic regression analysis showed that among patients with NBI, the presence of demarcation line (DL) (OR = 24.00; 95% CI = 4.99-115.36; p < 0.0001), microvascular (MV) pattern irregularity (OR = 9.129; 95% CI = 2.36-35.34; p = 0.001), and the presence of white opaque substance (WOS) (OR = 10.77; 95% CI = 1.14-101.72; p = 0.038) were significant risk factors. Conclusions: For gastric indeterminate tumors, older patient age, lesion surface with erosion, clear DL visible under NBI observation, presence of WOS, and irregular MV pattern are suggestive of the high possibility of neoplasia and need to be focused on and may benefit more from endoscopic resection treatment as opposed to simple endoscopic follow-up.

The CCL21/CCR7 pathway plays a key role in human colon cancer metastasis through regulation of matrix metalloproteinase-9.

PURPOSE: CC chemokine receptor 7 (CCR7) and matrix metalloproteinase-9 (MMP-9) have been associated with lymph node metastasis in human colon cancer. Studies have suggested a potential link between CCR7 and MMP-9 in cancer; however, the molecular mechanism by which C-C ligand 21/CCR7 promotes tumour dissemination in human colon cancer is not well understood. Thus, we aimed to determine whether MMP-9 is regulated by the C-C ligand 21/CCR7 in human colon cancer. METHOD: RNA interference technology was employed to detect effect of CCR7 deficiency on the expression of MMP-9 in SW480 human colon cancer cells. We also evaluated the ability of CCR7 short hairpin RNA to inhibit MMP-9 production and tumour invasion in a xenografted mouse model by using whole-body fluorescence imaging and gelatin zymography. RESULT: We found that CCR7 short hairpin RNA significantly inhibited C-C ligand 21/CCR7-induced up-regulation of MMP-9 in SW480 cells. Furthermore, knockdown of CCR7 significantly limited the production of MMP-9 and colon cancer metastasis in a xenografted mouse model. Mice that received SW480/control cells had progressively enlarging tumours and more lymphatic metastases, and these animals did not survive as long as mice that received SW480/CCR7⁻ cells. CONCLUSION: MMP-9 and CCR7 may be useful targets for the treatment of lymphatic metastasis in colon cancer.

Antiproliferative effect of resveratrol in pancreatic cancer cells.

To investigate resveratrol, one of the food derived polyphenols that might be partially responsible for the beneficial effect on cancer, the in vitro antitumor activity of resveratrol against pancreatic cancer cell lines (PANC-1, BxPC-3 and AsPC-1) was examined, together with the mechanisms involved. The effects of resveratrol on the growth inhibition, apoptosis and cell cycle were assayed. The activity of caspases and the expression of Bcl-2, Bcl-xL, XIAP and Bax protein were detected. The results showed that resveratrol inhibited the proliferation of pancreatic cancer cells in a dose- and time-dependent manner. Resveratrol inhibited the cell growth of PANC-1, BxPC-3 and AsPC-1 cells with IC(50) values of 78.3 ± 9.6 µmol/L, 76.1 ± 7.8 µmol/L and 123.1 ± 6.5 µmol/L at 48 h, respectively. Incubation of pancreatic cancer cells with resveratrol resulted in cell apoptosis and cell cycle arrests. Resveratrol induced activation of caspases. Simultaneously, resveratrol regulated the expression of the antiapoptotic proteins Bcl-2, Bcl-xL and XIAP and the proapoptotic protein Bax. PANC-1 and BxPC-3 cells were more chemosensitive to resveratrol than AsPC-1 cells. In conclusion, resveratrol inhibited the proliferation of pancreatic cancer cells by inducing apoptotic cell death. There was different sensitivity to resveratrol in different pancreatic cancer cell lines.

[Significance of IL-1beta-induced ectopic expression of CDX2 in the intestinal metaplasia of gastric epithelium].

OBJECTIVE: To evaluate the effect of IL-1beta on the expression of CDX2 in human gastric epithelial cell line GES-1 and its role in the intestinal metaplasia. METHODS: GES-1 cells were treated with IL-1beta in different concentrations and the expressions of CDX2 mRNA and protein were detected by real-time PCR, immunocytochemistry and Western blot at different time points. GES-1 cells were then pre-treated with NF-KappaB pathway inhibitor PDTC, and the expression of CDX2 mRNA and protein induced by IL-1beta were detected. The cell ultra-structure of GES-1 cells was observed by electronic microscope after GES-1 being treated with IL-1beta for 25 days. RESULTS: Levels of CDX2 mRNA and protein were 0.0749 + or - 0.0021 and 0.56 + or - 0.04 in the cells treated with 1 microg/L IL-1beta(P<0.05). After pre-treatment with PDTC, levels of CDX2 mRNA and protein were 0.0006 + or - 0.0002 and 0.40 + or - 0.06(P<0.05). Some changes in the cell ultra-structure of GES-1 were found by electronic microscope when GES-1 was treated with IL-1beta for 25 days. CONCLUSION: IL-1beta can stimulate CDX2 mRNA and protein expression in GES-1 cells through the NF-KappaB signal pathway, indicating that IL-1beta plays an important role in the intestinal metaplasia.

[Role of CCL21/CCR7 in invasion of colorectal carcinoma cell line SW480].

BACKGROUND AND OBJECTIVE: Chemokine receptor CCR7 is up-regulated in gastrointestinal carcinomas and is significantly associated with lymphatic invasion and lymph node metastasis. This study was to investigate the role and mechanism of CCL21/CCR7 in invasion of colorectal carcinoma cell line SW480. METHODS: The invasive capacity of SW480 cells was examined using Wound healing assay and Transwell assay. Expression of matrix metalloproteinase-9 (MMP-9) was measured by Western blot. SW480 cells were pre-incubated with CCL21 for 2 h before exposure to VP-16 (20 ng/mL). Cell proliferation was measured using MTT assay. Cell apoptosis was analyzed by flow cytometry and Hoechst33258 staining. RESULTS: Compared to the control group, more cells in the CCL21 treatment group migrated into the gap at same time points; the count of SW480 cells penetrating through the membrane after the treatment of 100ng/mL CCL21 increased significantly [(113+/-7) vs. (48+/-4)] (P<0.05); and the relative expression of MMP-9 in the CCL21 treatment group was enhanced evidently [(0.83+/-0.02) vs. (0.38+/-0.01)] (P<0.05). Although CCL21 alone did not promote proliferation of SW480 cells, pre-incubation of cells with 100ng/mL CCL21 attenuated the inhibitory effect of VP-16 on proliferation of SW480 from 68.3% to 47.4%, and reduced the apoptotic rate from (65.2+/-5.2)% to (48.7+/-3.1)%. CONCLUSION: CCL21 enhances the invasive ability of SW480 cells, induces MMP-9 expression, and promotes the survival of SW480 cells under the suboptimal circumstance in vitro.

Can an allograft become harmonious with its recipient by analogous mechanisms to the long-term survival of a parasite in its host? Transplantation is similar to parasitism and chronic parasite infection can prolong allograft survival.

Organ transplantation is very similar to the parasitism, the immune responses to the allograft and parasite share some general characters in acute stage. But host-parasite interplay seems harmonious and clinically asymptomatic carriers act as long-term reservoirs for transmission even several decades. It is proposed that the allograft also can survive long-term like the parasite harmonious with the host if we exploit the mechanism of the parasitism. How can the parasite escape the immunologic cleaning? Recent research found that: (1) Almost all the parasites infection can break the balance of Th1/Th2 and induce the Th2 bias. The level of cytokine excreted by Th2 is increased. (2) Parasite infection can interfere in antigen presentation processing through cystatins and "dendritic cell paralysis". (3) Regulatory T cells were found surrounding the local site of parasite worms. (4) Parasite infections can switch of eicosanoid metabolism, and the anti-inflammatory mediator of the plasma is increasingly manifest in the chronic infection stage. And in animal model, chronic infection can prolong the allograft survival. If the hypotheses are correct, it will give another novel therapeutic option for patients with organ transplantation.