[An Improved Acute Pancreatitis Apoptosis/Necrosis In vitro Model of Acinar Cells].

OBJECTIVE: To improve the apoptosis/necrosis In vitromodel of ascites-induced acute pancreatitic (AP) acinar cells by using the co-culture system and mixed ascites technology for the first time. Furthermore, we compared this improved model with cerulein and cerulein+LPS models, and observed the effects of three models on acinar apoptotic/necrotic-related indicators. METHODS: The In vitrocultured rat acinar cells AR42J were divided in four groups: control group (medium+PBS), cerulein group (medium+10 nmol/L cerulein), cerulein+LPS group (medium+10 nmol/L cerulein+10 mg/L LPS) and improved ascites group. In the improved ascites group, the ascites of sodium taurocholate-induced rat model was mixed and added into the co-culture system to stimulated In vitrocultured homogenous acinar cells. The co-culture system was set as follows: the chambers with the pore size of 1 µm were placed in the cultue plate, and the culture medium and mixed ascites were respectively added to the culture plate and the chamber at a ratio of 1:1. The acinar cells in each group were collected after 24 h stimulation. The apoptotic/necrotic rates, the expressions of apoptosis/necrosis related proteins [B-cell lymphoma protein 2 (Bcl-2), Bcl-2-associated X protein (Bax) and receptor interacting protein 1 (RIP1)], and the ultra-structure of acinar cells were detected by flow cytometry, Western blot and transmission electron microscopy (TEM). RESULTS: The acinar cells in the improved ascites model were mainly characterized by necrosis; compared with the other 3 groups, the apoptosis rate and necrosis rate were both up-regulated, RIP1 and BAX protein expression levels were up-regulated, and Bcl-2 protein was down-regulated. TEM results showed the organelle structure of acinar cells was destroyed, and the cell membrane was degraded in the improved ascites model. Compared with the control group, apoptosis rate of acinar cells in the cerulein and cerulein+LPS models were increased and necrosis rate were not changed. The expression of pro-apoptotic protein Bax was increased, while the expression level of RIP1 was not significantly increased. TEM results showed that in cerulein group and cerulein+LPS group, the chromatin of the cells was condensed into a mass, the cytoplasm was degraded and the cell membrane was intact, showing typical apoptosis characteristics. CONCLUSION: Compared with cerulein and cerulein +LPS models, which mainly focus on apoptosis of acinar cells and applied to mild acute pancreatitis study, the improved ascites model mainly focuses on the necrosis of acinar cells and is a good model for studying acinar cell necrosis and severe acute pancreatitis.

Laparoscopic Versus Open Resection for Gastric Gastrointestinal Stromal Tumors (GISTs): A Size-Location-Matched Case-Control Study.

BACKGROUND: Laparoscopic resection for gastric gastrointestinal stromal tumors (GISTs) is technically feasible, but the long-term effect remains uncertain. This study aims to compare the long-term oncologic outcomes of laparoscopic versus open resection of GISTs by larger cases based on tumor size-location-matched study. METHODS: Between 2006 and 2015, 63 consecutive patients with a primary gastric GIST undergoing laparoscopic resection were enrolled in and matched (1:1) to patients undergoing open resection by tumor size and location. Clinical and pathologic parameters and surgical outcomes associated with each surgical type were collected and compared. RESULTS: The operation time, intraoperative blood loss, return of bowel function and oral intake, nasogastric tube retention time and postoperative stay were all shorter/faster in laparoscopic group than those in open group (P < 0.001). Postoperative complications were comparable except for the higher incidence of abdominal/incision pain in open group (9.52 vs 27%, P = 0.01). There was no statistical difference in recurrence rate (9.52 vs 15.87%, P = 0.29) and long-term recurrence-free survival between the two groups (P = 0.39). CONCLUSIONS: The long-term oncologic outcome of laparoscopic resection of primary gastric GISTs is comparable to that of open procedure, but laparoscopic procedure has the advantage of minimal invasion and is superior in postoperative recovery.

Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-κB activity.

Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of l-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor-κB (NF-κB) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-κB activation and less release of TNF-α and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis.

Prognostic role of the lymph node ratio in node positive colorectal cancer: a meta-analysis.

The lymph node ratio (LNR) (i.e. the number of metastatic lymph nodes divided by the number of totally resected lymph nodes) has recently emerged as an important prognostic factor in colorectal cancer (CRC). However, the tumor node metastasis (TNM) staging system for colorectal cancer does not consider it as a prognostic parameter. Therefore, we conducted a meta-analysis to evaluate the prognostic role of the LNR in node positive CRC. A systematic search was performed in PubMed, Embase and the Cochrane Library for relevant studies up to November 2015. As a result, a total of 75,838 node positive patients in 33 studies were included in this meta-analysis. Higher LNR was significantly associated with shorter overall survival (OS) (HR = 1.91; 95% CI 1.71-2.14; P = 0.0000) and disease free survival (DFS) (HR = 2.75; 95% CI: 2.14-3.53; P = 0.0000). Subgroup analysis showed similar results. Based on these results, LNR was an independent predictor of survival in colorectal cancer patients and should be considered as a parameter in future oncologic staging systems.

Effect of (131)I gelatin microspheres on hepatocellular carcinoma in nude mice and its distribution after intratumoral injection.

In this study, we investigated the effect of (131)I gelatin microspheres ((131)I-GMSs) on human hepatocellular carcinoma cells (HepG2) in nude mice (Balb/c) and the biodistribution of (131)I-GMSs after intratumoral injection. The treatment group and control group animals received intratumoral injections of 1 mCi (131)I-GMSs and GMSs unlabeled (131)I, respectively. The size of the implanted tumor was measured once a week for 8 weeks, and the survival time was calculated from the day of injection to 64 days post-injection. Another 35 animals received intratumoral injections of 0.2 mCi (131)I-GMSs and were subject to single-photon emission computed tomography (SPECT) on days 1, 8, 16, 24 and 32 post-injection. Samples of various organs were collected and used to calculate tissue concentrations on days 1, 4, 8, 16 and 24. Free thyroxine (FT4) in fetal bovine serum was tested to evaluate thyroid function. The tumors were collected for histological examination. (131)I-GMSs produced a pronounced reduction in HepG2 tumor volume, and the overall survival was 73.3% in the treatment group and only 13.3% in the control group (P < 0.001). Tissue radioactivity concentration measurements and SPECT demonstrated that the injected (131)I-GMSs mainly accumulated within the tumors. The concentration of FT4 was stable during the observation period. The microspheres could be observed by histological methods on day 32. (131)I-GMSs suppressed the growth of HepG2 in the nude mice and were retained in the tumor for a long period of time after injection. Direct intratumoral injection of (131)I-GMSs offers a promising modality for the treatment of hepatocellular carcinoma.

Interventional therapy for human breast cancer in nude mice with 131I gelatin microspheres (¹³¹I-GMSs) following intratumoral injection.

INTRODUCTION: The aim of this study was to investigate the effects of 131I gelatin microspheres (131I-GMS) on human breast cancer cells (MCF-7) in nude mice and the biodistribution of 131I-GMSs following intratumoral injections. METHODS: A total of 20 tumor-bearing mice were divided into a treatment group and control group and received intratumoral injections of 2.5 mci 131I-GMSs and nonradioactive GMSs, respectively. Tumor size was measured once per week. Another 16 mice received intratumoral injections of 0.4 mci 131I-GMSs and were subjected to single photon emission computed tomography (SPECT) scans and tissue radioactivity concentration measurements on day 1, 4, 8 and 16 postinjection. The 20 tumor-bearing mice received intratumoral injections of 0.4 mci [131I] sodium iodide solution and were subjected to SPECT scans and intratumoral radioactivity measurements at 1, 6, 24, 48 and 72 h postinjection. The tumors were collected for histological examination. RESULTS: The average tumor volume in the 131I-GMSs group on post-treatment day 21 decreased to 86.82 ± 63.6%, while it increased to 893.37 ± 158.12% in the control group (P < 0.01 vs. the 131I-GMSs group). 131I-GMSs provided much higher intratumoral retention of radioactivity, resulting in 19.93 ± 5.24% of the injected radioactivity after 16 days, whereas the control group retained only 1.83 ± 0.46% of the injected radioactivity within the tumors at 1 h postinjection. CONCLUSIONS: 131I-GMSs suppressed the growth of MCF-7 in nude mice and provided sustained intratumoral radioactivity retention. The results suggest the potential of 131I-GMSs for clinical applications in radiotherapy for breast cancer.