KAI1 reverses the epithelial-mesenchymal transition in human pancreatic cancer cells.

BACKGROUND: Epithelial-mesenchymal transition (EMT) plays an important role in pancreatic cancer (PC). In the present study, we investigated the effects of KAI1 gene overexpression on the EMT of human PC cell lines, MIA PaCa-2 and PACN-1. METHODS: Plasmids overexpressing KAI1 and pCMV were transfected into MIA PaCa-2 and PACN-1 cells, respectively. After selection of differently transfected cells by G418, KAI1 protein levels were examined by Western blotting, and transfected cells were renamed as MIA PaCa-2-K, MIA PaCa-2-p, PACN-1-K and PACN-1-p. Wound healing and Transwell migration assays were then performed comparing the two groups of cells. EMT-related markers were analyzed by Western blotting. RESULTS: The percentage of wound closure significantly decreased in MIA PaCa-2-K cells compared with MIA PaCa-2-p and MIA PaCa-2 cells after 24, 48 and 72 h (P < 0.05). In PACN-1-K cells, the percentage of wound closure significantly decreased as well (P < 0.05). Numbers of invading MIA PaCa-2, MIA PaCa-2-p and MIA PaCa-2-K cells were determined as 48.0 ±â€¯15.4, 50.0 ±â€¯12.4, and 12.0 ±â€¯3.8, respectively. The corresponding numbers of invading PACN-1, PACN-1-p and PACN-1-K cells were 29.0 ±â€¯10.6, 31.0 ±â€¯11.4, and 8.0 ±â€¯4.2, respectively. KAI1 overexpression induced a significant upregulation of E-cadherin and also significant downregulation of Snail, vimentin, matrix metalloproteinase 2 (MMP2) and MMP9 (all P < 0.05) in PC cells. CONCLUSIONS: KAI1 reversed EMT-related marker expression and inhibited migration and invasion of PC cells. Thus, KAI1 might represent a novel potential therapeutic target for PC.

Pancreatic cancer: diagnosis and treatments.

Pancreatic cancer is one of the deadliest cancers, with exceptionally high mortality. Despite the relatively low incidence rate (10th), it is the fourth leading cause of cancer-related deaths in most developed countries. To improve the early diagnosis of pancreatic cancer and strengthen the standardized comprehensive treatment are still the main focus of pancreatic cancer research. Here, we summarized the rapid developments in the diagnosis and treatments of pancreatic cancer. Regarding diagnosis, we reviewed advances in medical imaging technology, tumor markers, molecular biology (e.g., gene mutation), and proteomics. Moreover, great progress has also been made in the treatments of this disease, including surgical resection, chemotherapy, targeted radiotherapy, targeted minimally invasive treatment, and molecular targeted therapy. Therefore, we also recapitulated the development, advantages, and disadvantages of each of the treatment methods in this review.

Prognostic significance of cyclooxygenase-2 protein in pancreatic cancer: a meta-analysis.

We conducted a meta-analysis of relevant cohort studies to investigate the relationships between cyclooxygenase-2 (COX-2) protein and the prognosis of pancreatic cancer. The following electronic databases were searched without language restrictions: MEDLINE (1966∼2013), the Library Database (Issue 12, 2013), EMBASE (1980∼2013), CINAHL (1982∼2013), Web of Science (1945∼2013), and the Chinese Biomedical Database (CBM) (1982∼2013). Meta-analysis was performed using the STATA statistical software. Six cohort studies with a total of 712 pancreatic cancer patients were involved in this meta-analysis. Our findings showed that COX-2-positive patients were significantly associated with a shorter overall survival (OS) than COX-2-negative patients (hazard ratio (HR) = 1.48, 95 % confidence interval (95%CI) = 1.12∼1.85, P < 0.001). A subgroup analysis by ethnicity also revealed that pancreatic cancer patients with an abnormal COX-2 expression exhibited a worse OS than COX-2-negative patients among both Asians and Caucasians (Asians: HR = 1.40, 95%CI = -0.09∼2.89, P = 0.066; Caucasians: HR = 1.49, 95%CI = 1.11∼1.87, P < 0.001, respectively). Our findings provide empirical evidence that abnormal COX-2 expression may be strongly correlated with poor prognosis for patients with pancreatic cancer. Thus, COX-2 protein may be a useful biomarker for pancreatic cancer.

KAI1 inhibits lymphangiogenesis and lymphatic metastasis of pancreatic cancer in vivo.

BACKGROUND: Several studies have shown that KAI1 inhibits tumor metastasis, but its mechanism is not clear. The present study aimed to determine the role of KAI1 in lymphatic metastasis, specifically in pancreatic cancer. METHODS: The KAI1 gene was transfected into the pancreatic cancer cell line MIA PaCa-2 and PANC-1 by using liposomes and selected by G418, and the protein was measured by Western blotting. After successful infection, the cell growth curve was studied by MTT, vascular endothelial growth factor C (VEGF-C) secretion by pancreatic cancer cell were measured by ELISA. The KAI1 and pCMV transfected MIA PaCa-2 cells were renamed as MIA PaCa-2-K and MIA PaCa-2-p. These two kinds of cells were injected into the subcuticular layer of nude mice; both tumor growth and metastasis through the lymphatic nodes were assessed. Lymphangiogenesis in tumors was measured by immunohistochemistry. RESULTS: The VEGF-C secretion was significantly reduced in MIA PaCa-2 cells compared with PANC-1 cells after being transfected with the KAI1 gene. The growth rate of subcutaneous tumors was similar after the injection of MIA PaCa-2-K, MIA PaCa-2, and MIA PaCa-2-p. MIA PaCa-2-K tumors showed slower lymphangiogenesis and lymph node metastasis compared with MIA PaCa-2 and MIA PaCa-2-p tumors. CONCLUSION: The overexpression of KAI1 inhibits the lymphangiogenesis and lymph node metastasis of MIA PaCa-2 pancreatic tumors.

Effects of postoperative use of proton pump inhibitors on gastrointestinal bleeding after endoscopic variceal treatment during hospitalization.

BACKGROUND: Endoscopic variceal treatment (EVT) is recommended as the mainstay choice for the management of high-risk gastroesophageal varices and acute variceal bleeding in liver cirrhosis. Proton pump inhibitors (PPIs) are widely used for various gastric acid-related diseases. However, the effects of PPIs on the development of post-EVT complications, especially gastrointestinal bleeding (GIB), remain controversial. AIM: To evaluate the effects of postoperative use of PPIs on post-EVT complications in patients with liver cirrhosis during hospitalization. METHODS: Patients with a diagnosis of liver cirrhosis who were admitted to the Department of Gastroenterology of the General Hospital of Northern Theater Command, treated by an attending physician between January 2016 and June 2020 and underwent EVT during their hospitalization were included. Logistic regression analyses were performed to explore the effects of postoperative use of PPIs on the development of post-EVT complications during hospitalization. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 143 patients were included. The incidence of post-EVT GIB and other post-EVT complications was 4.90% and 46.85%, respectively. In the overall analyses, postoperative use of PPIs did not significantly reduce the risk of post-EVT GIB (OR = 0.525, 95%CI = 0.113-2.438, P = 0.411) or other post-EVT complications (OR = 0.804, 95%CI = 0.413-1.565, P = 0.522). In the subgroup analyses according to the enrollment period, type and route of PPIs after the index EVT, use of PPIs before the index EVT, use of vasoactive drugs after the index EVT, indication of EVT (prophylactic and therapeutic), and presence of portal venous system thrombosis, ascites, and hepatocellular carcinoma, the effects of postoperative use of PPIs on the risk of post-EVT GIB or other post-EVT complications remain not statistically significant. CONCLUSION: Routine use of PPIs after EVT should not be recommended in patients with liver cirrhosis for the prevention of post-EVT complications during hospitalization.

KAI1/CD82 gene and autotaxin-lysophosphatidic acid axis in gastrointestinal cancers.

The KAI1/CD82 gene inhibits the metastasis of most tumors and is remarkably correlated with tumor invasion and prognosis. Cell metabolism dysregulation is an important cause of tumor occurrence, development, and metastasis. As one of the important characteristics of tumors, cell metabolism dysregulation is attracting increasing research attention. Phospholipids are an indispensable substance in the metabolism in various tumor cells. Phospholipid metabolites have become important cell signaling molecules. The pathological role of lysophosphatidic acid (LPA) in tumors was identified in the early 1990s. Currently, LPA inhibitors have entered clinical trials but are not yet used in clinical treatment. Autotaxin (ATX) has lysophospholipase D (lysoPLD) activity and can regulate LPA levels in vivo. The LPA receptor family and ATX/lysoPLD are abnormally expressed in various gastrointestinal tumors. According to our recent pre-experimental results, KAI1/CD82 might inhibit the migration and metastasis of cancer cells by regulating the ATX-LPA axis. However, no relevant research has been reported. Clarifying the mechanism of ATX-LPA in the inhibition of cancer metastasis by KAI1/CD82 will provide an important theoretical basis for targeted cancer therapy. In this paper, the molecular compositions of the KAI1/CD82 gene and the ATX-LPA axis, their physiological functions in tumors, and their roles in gastrointestinal cancers and target therapy are reviewed.

Successful treatment of acute symptomatic extensive portal venous system thrombosis by 7-day systemic thrombolysis.

Acute portal venous system thrombosis (PVST) can cause acute mesenteric ischemia and even intestinal infarction, which are potentially fatal, and requires recanalization in a timely fashion. Herein, we report a 56-year-old man with acute non-cirrhotic symptomatic extensive PVST who achieved portal vein recanalization after systemic thrombolysis combined with anticoagulation. Initially, anticoagulation with enoxaparin sodium for 4 d was ineffective, and then systemic thrombolysis for 7 d was added. After that, his abdominal pain completely disappeared, and portal vein system vessels became gradually patent. Long-term anticoagulation therapy was maintained. In conclusion, 7-d systemic thrombolysis may be an effective and safe choice of treatment for acute symptomatic extensive PVST which does not respond to anticoagulation therapy.

Overexpression of KAI1 induces autophagy and increases MiaPaCa-2 cell survival through the phosphorylation of extracellular signal-regulated kinases.

KAI1, a metastasis-suppressor gene belonging to the tetraspanin family, is known to inhibit cancer metastasis without affecting the primary tumorigenicity by inhibiting the epidermal growth factor (EGF) signaling pathway. Recent studies have shown that hypoxic conditions of solid tumors induce high-level autophagy and KAI1 expression. However, the relationship between autophagy and KAI1 remains unclear. By using transmission electron microscopy, confocal microscopy, and Western blotting, we found that KAI1 can induce autophagy in a dose- and time-dependent manner in the human pancreatic cell line MiaPaCa-2. KAI1-induced autophagy was confirmed by the expression of autophagy-related proteins LC3 and Beclin 1. KAI1 induces autophagy through phosphorylation of extracellular signal-related kinases rather than that of AKT. KAI1-induced autophagy protects MiaPaCa-2 cells from apoptosis and proliferation inhibition partially through the downregulation of poly [adenosine diphosphate (ADP)-ribose] polymerase (PARP) cleavage and caspase-3 activation.

Human dendritic cells transfected with amplified MUC1 mRNA stimulate cytotoxic T lymphocyte responses against pancreatic cancer in vitro.

BACKGROUND AND AIM: Mucin (MUC) 1 is an epithelial cell glycoprotein that is aberrantly overexpressed in many adenocarcinomas, including pancreatic cancer (PC), providing an ideal tumor-associated antigen and target for immunotherapy. In this study, we investigated whether the cytotoxic T lymphocytes (CTLs) induced by dendritic cells (DCs) transfected with amplified MUC1 mRNA could respond against PC in vitro. METHODS: Amplified mRNA encoding MUC1 were transfected into DCs using electroporation with an optimized setting and the MUC1 expression were evaluated by quantitative real-time polymerase chain reaction and Western blot. The MUC1 specific CTL responses were measured using the standard chromium 51 (51Cr)-release assays and the interferon-γ release assay. RESULTS: Dendritic cells could be transfected with amplified MUC1 mRNA efficiently. The transfected DCs were remarkably effective in stimulating MUC1-specific CTL responses in vitro. The function of MUC1 specific CTLs, induced by MUC1 mRNA-transfected DCs, was restricted by major histocompatibility complex (MHC) class I antigen presentation. CONCLUSION: The CTL responses stimulated by DCs transfected with MUC1 mRNA could only recognize and lyse HLA-A2+/MUC1+ PC and other target cells under restriction by MHC class I-specific antigen presentation, providing a preclinical rationale for using MUC1 as a target structure for immunotherapeutic strategies against PC.

KAI1 inhibits HGF-induced invasion of pancreatic cancer by sphingosine kinase activity.

BACKGROUND: KAI1/CD82 has been reported to attenuate the process of metastases in a variety of tumors; however, its mechanism of action in invasion has not been fully elucidated. The present study aimed to investigate the importance of KAI1 in invasion and its correlation with activation of sphingosine kinase (SPK) in human pancreatic cancer PANC1 and Miapaca-2 cell lines. METHODS: The expression of KAI1 in PANC1 and Miapaca-2 cells, which was mediated by recombinant adenovirus (Ad-KAI1), was assessed by a flow cytometer and Western blotting. After successful infection was established, in vitro growth curve and invasive ability in Boyden Chamber assay were studied. The presence of KAI1 correlating with c-Met and SPK was detected by co-immunoprecipitation and [gamma-32P] ATP incorporation. RESULTS: KAI1 genes had no significant effects on the curve representing cell growth. After infection with the KAI1 gene, decreased invasive ability in the Boyden Chamber assay was observed in PANC1 and Miapaca-2 cells that were induced by hepatocyte growth factor. Over-expression of KAI1 in the cells led to the deactivation of SPK and a decreased level of intracellular sphingosine-1-phosphate. No correlation was observed between c-Met and KAI1 during co-immunoprecipitation. CONCLUSION: The results of this study for the first time demonstrated a regulatory role for KAI1 in SPK activation, which leads to decreased invasive ability in disease progression of human pancreatic cancer.

[Binding capability of lidamycin apoprotein to human breast cancer detected by tissue microarrays].

This study is to investigate the binding capability of lidamycin apoprotein (LDP), an enediyne-associated apoprotein of the chromoprotein antitumor antibiotic family, to human breast cancer and normal tissues, the correlation of LDP binding capability to human breast cancer tissues and the expression of tumor therapeutic targets such as VEGF and HER2. In this study, the binding capability of LDP to human breast cancer tissues was detected with tissue microarray. The correlation study of LDP binding capability to human breast tumor tissues and relevant therapeutic targets was performed on breast cancer tissue microarrays. Immunocytochemical examination was used to detect the binding capability of LDP to human breast carcinoma MCF-7 cells. As a result, tissue microarray showed that LDP staining of 73.2% (30/41) of breast cancer tissues was positive, whereas that of 48.3% (15/31) of the adjacent normal breast specimens was positive. The difference between the tumor and normal samples was significant (Chi2 = 4.63, P < 0.05). LDP immunoreactivity in breast cancer correlated significantly with the overexpression of VEGF and HER2 (P < 0.001 and < 0.01, r = 0.389 and 0.287, respectively). Determined with confocal immunofluorescent analysis, LDP showed the binding capability to mammary carcinoma MCF-7 cells. It is demonstrated that LDP can bind to human breast cancer tissues and there is significant difference between the breast cancer tissues and the corresponding normal tissues. Notably, the binding reactivity shows positive correlation with the expression of VEGF and HER2 in breast carcinoma tissues. The results imply that LDP may have a potential use as targeting drug carrier in the research and development of new anticancer therapeutics. This study may provide reference for drug combination of LDM and other therapeutic agents.

Portal hypertension in a patient with biliary hamartomas: A case report.

BACKGROUND: Biliary hamartomas (BH) are a rare benign disease caused by malformation of the intrahepatic bile ducts. BH are occasionally diagnosed, but often lack obvious clinical symptoms. They are usually diagnosed by biopsy and imaging tests in clinical practice. Few studies have reported the association of BH with portal hypertension. CASE SUMMARY: A 40-year-old man was repeatedly admitted to our hospital due to hematochezia. The source of bleeding was considered to be gastroesophageal varices and portal hypertensive gastropathy by endoscopy. He had no history of hepatitis virus infection, alcohol abuse, drug-induced liver injury, or autoimmune liver disease. He underwent magnetic resonance imaging, which showed rounded, irregular, low-signal-T1 and high-signal-T2 lesions diffusely distributed on the liver, that were not communicated with the biliary system on magnetic resonance cholangiopancreatography. According to the imaging examination, the patient was considered to have a diagnosis of BH with portal hypertension. CONCLUSION: Based on the present case report, BH may be a potential etiology of portal hypertension.

Esophageal collateral veins in predicting esophageal variceal recurrence and rebleeding after endoscopic treatment: a systematic review and meta-analysis.

BACKGROUND: Endoscopic treatment is recommended for the management of esophageal varices. However, variceal recurrence or rebleeding is common after endoscopic variceal eradication. Our study aimed to systematically evaluate the prevalence of esophageal collateral veins (ECVs) and the association of ECVs with recurrence of esophageal varices or rebleeding from esophageal varices after endoscopic treatment. METHODS: We searched the relevant literature through the PubMed, EMBASE, and Cochrane Library databases. Prevalence of paraesophageal veins (para-EVs), periesophageal veins (peri-EVs), and perforating veins (PVs) were pooled. Risk ratio (RR) and odds ratio (OR) with 95% confidence intervals (CIs) were calculated for cohort studies and case-control studies, respectively. A random-effects model was employed. Heterogeneity among studies was calculated. RESULTS: Among the 532 retrieved papers, 28 were included. The pooled prevalence of para-EVs, peri-EVs, and PVs in patients with esophageal varices was 73%, 88%, and 54%, respectively. The pooled prevalence of para-EVs and PVs in patients with recurrence of esophageal varices was 87% and 62%, respectively. The risk for recurrence of esophageal varices was significantly increased in patients with PVs (OR = 9.79, 95% CI: 1.95-49.22, P = 0.006 for eight case-control studies), but not in those with para-EVs (OR = 4.26, 95% CI: 0.38-38.35, P = 0.24 for four case-control studies; RR = 1.81, 95% CI: 0.83-3.97, P = 0.14 for three cohort studies). Patients with para-EVs had a significantly higher incidence of rebleeding from esophageal varices (RR = 13.00, 95% CI: 2.43-69.56, P = 0.003 for two cohort studies). Statistically significant heterogeneity was notable across the meta-analyses. CONCLUSIONS: ECVs are common in patients with esophageal varices. Identification of ECVs could be helpful for predicting the recurrence of esophageal varices or rebleeding from esophageal varices after endoscopic treatment.

Endocrine glands-derived vascular endothelial growth factor protects pancreatic cancer cells from apoptosis via upregulation of the myeloid cell leukemia-1 protein.

Endocrine glands-derived vascular endothelial growth factor (EG-VEGF, also termed as Prok1)--a novel cytokine that selectively acts on the endothelial cells of endocrine glands--was recently reported to be involved in the regulation of tumor cell growth and survival. However, its roles in the regulation of pancreatic cancer progression remain unclear. In this report, we investigated the suppressive effects of EG-VEGF on pancreatic cancer cell apoptosis and the relevant mechanisms. By using reverse-transcriptase polymerase chain reaction (RT-PCR) we found that the Mia PaCa II cells of the pancreatic cancer cell line express the mRNAs of both EG-VEGF (Prok1) and its receptors. EG-VEGF protects pancreatic cancer cells from apoptosis through upregulation of myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic protein of the bcl-2 family. Treatment of pancreatic cancer cells with EG-VEGF results in the rapid phosphorylation of mitogen-activated protein kinase (MAPK), STAT3, and AKT, which are involved in the upregulation of Mcl-1 expression. EG-VEGF (Prok1) protects Mia PaCa II cells from apoptosis through G protein-coupled receptor (GPR)-induced activation of multiple signal pathways, and hence can be a novel target for pancreatic cancer therapy.

Delphinidin protects ß2m-/Thy1+ bone marrow-derived hepatocyte stem cells against TGF-ß1-induced oxidative stress and apoptosis through the PI3K/Akt pathway in vitro.

ß2m-/Thy1+ bone marrow-derived hepatocyte stem cells (BDHSCs) have a potential to be applied for cellular treatment in liver cirrhosis. However, the resultant tissue regeneration is restricted by transplanted cells' death. The accumulation of transforming growth factor beta 1 (TGF-ß1) in liver fibrosis local microenvironment may play an essential role in the rapid cell death of implanted ß2m-/Thy1+ BDHSCs. The main mechanism of poor survival of the target stem cells is still unknown. Delphinidin, an anthocyanidin, has potent antioxidant and anti-inflammatory activities. However, whether this bio-active ingredient can substantially contribute to ß2m-/Thy1+ BDHSCs' protection from TGF-ß1 induced apoptosis in vitro remains to be elucidated. In the present research, we determined whether delphinidin pretreatment can improve the survival of ß2m-/Thy1+ BDHSCs during exposure to TGF-ß1 and elucidated its underlying mechanisms. By using TGF-ß1, we induced the apoptosis of ß2m-/Thy1+ BDHSCs and assessed the apoptotic rates up to 24 h by flow cytometry. ß2m-/Thy1+ BDHSC proliferation was gauged using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl- 2H-tetrazolium bromide (MTT) assay. The expression grades of Bcl-2, Akt, caspase-3, and Bax were observed through Western blot analysis. We found that delphinidin can significantly impede TGF-ß1-induced apoptosis dose-dependently, scavenge reactive oxygen species (ROS), and inhibit the discharge of caspase-3 in ß2m-/Thy1+ BDHSCs. We also demonstrated that delphinidin can activate the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. The suppression of ROS and succeeding apoptosis was achieved by pretreatment with LY294002, a PI3K/Akt pathway inhibitor. In summary, our findings revealed that delphinidin can protect ß2m-/Thy1+ BDHSCs from apoptosis and ROS-dependent oxidative stress induced by the TGF-ß1 via PI3K/Akt signaling pathway. On the basis of these data, delphinidin can be regarded as a promising anti-apoptotic agent for enhancing ß2m-/Thy1+ BDHSC survival during cell transplantation in liver cirrhosis patients.

KAI1 is a potential target for anti-metastasis in pancreatic cancer cells.

AIM: To investigate whether KAI1, as a metastasis suppressor gene, is associated with invasive and metastatic ability of pancreatic cancer cells. METHODS: KAI1 gene was transfected into pancreatic cancer cell line MiaPaCa II by liposomes selected with G418. Expression of transfected cells was measured by Western blotting, immunofluorescence and immunocytochemistry. Tumor cell invasion and metastatic ability were detected through gelatinase activity and reconstituted basement membrane (Matrigel) assay. pCMV-KAI1 was directly injected into the heterotopic human pancreatic adenocarcinoma successfully established in the groin of BALB/C nude mice, by subcutaneous injection of MiaPaCa II pancreatic cancer cells. The statistical analysis between groups was determined by Student's two tailed t test. RESULTS: By Western blotting, MiaPaCa II cells transfected by KAI1 gene indicated KAI1 expression at approximately 29.1 kDa. Cytoplasm staining was positive and uniformly spread in transfected cancer cells, using immunohistochemistry and immunofluorescence. The most obvious difference was present after 30 h (MiaPaca II 43.6 +/- 9.42, pCMV-MiaPaca II 44.8 +/- 8.56, pCMV-KAI1-MiaPaca II 22.0 +/- 4.69, P < 0.05). Gelatinolysis revealed a wider and clearer band of gelatinolytic activity in non-transfected than in transfected cells (MiaPaCa II cells 30.8 +/- 0.57, transfected cells 28.1 +/- 0.65, P < 0.05). In vivo tumor growth rates of KAI1 transfectants with KAI1-Lipofectamine 1.22 +/- 0.31 in A group were lower than control 4.61 +/- 1.98 and pCMV-KAI 11.67 +/- 0.81. Analyses of metastases with and without KAI1 transfection in mice were different in liver and lung between controls 1.62 +/- 0.39, 0.45 +/- 0.09, pCMV-KAI 1.01 +/- 0.27, 0.33 +/- 0.09 and KAI1-Lipofectamine 0.99 +/- 0.21, 0.30 +/- 0.09 respectively (P < 0.05). CONCLUSION: High expression of KAI1 gene was found in transfected MiaPaCa II human pancreatic cancer cells with lower metastatic ability. KAI1 gene plays an important role in inhibiting metastasis of pancreatic cancer after direct injection into pancreatic adenocarcinoma. These results show that the suppressed invasion and motor function of pancreatic cancer cells may be a key reason why the KAI1 gene controls pancreatic cancer cell metastasis.

A Small Jejunal Angioleiomyoma Detected by Double-Balloon Enteroscopy: A Case Report.

BACKGROUND Angioleiomyoma in the small intestine is a rare cause of gastrointestinal bleeding. Only 7 cases of angioleiomyoma in the small intestine were reported in the English literature, with 4 of them causing gastrointestinal bleeding. The diagnosis of angioleiomyomas in the small intestine before surgery is difficult. CASE REPORT We report the case of a 42-year-old man with recurrent melena who underwent repeated esophagogastroduodenoscopy and colonoscopy, without positive finding. During a double-balloon enteroscopy, an elevated lesion with a diameter of 6 mm was found in the jejunum. The lesion was resected laparoscopically assisted with double-balloon enteroscpy. A microscopic examination showed fibric membrane of the mass and numerous vascular channels surrounded by proliferated smooth muscle. There were exudative fibrin and many thrombi formed by red blood cells. Immunohistochemistry was positive for SMA and CD34. A pathological diagnosis of jejunal angioleiomyoma with thrombus was established. During a 5-year follow-up, there was no further gastrointestinal bleeding. CONCLUSIONS The gastroenterologists should consider angioleiomyoma in the small intestine when assessing obscure gastrointestinal bleeding.

[Comparison of the acetabular orientation after minimally-invasive total hip arthroplasty with and without computer-navigation: a clinical report of 106 hip in 87 patients].

OBJECTIVE: To evaluate the acetabular angle after minimally-invasive total hip arthroplasty (MIS-THA) with or without computer-navigation. METHODS: 87 consecutive orthopedic patients (106 hips) underwent MIS-THA with computer-navigation (40 cases with 53 hips) or without computer-navigation (47 cases with 53 hips). The full leg length and pelvis were measured with radiography preoperatively and post-operatively. RESULTS: The average length of incision of the navigation group was 8.9 cm (7.8 - 10.5 cm), and the average length of incision of the non-navigation group was 9.1 cm (7.5 - 11 cm) The average cup inclination on the plain post-operative radiography of the navigation group was 40.58 degrees +/- 5.09 degrees (30 degrees - 54 degrees ), only the cup abduction being 54 degrees , significantly less steep than that of the control group [44.17 degrees +/- 8.71 degrees (28 degrees - 70 degrees , t' = 2.56. P = 0.012). Among the 47 control cases 40 cases showed the cup abduction of 30 degrees - 50 degrees , 3 showed the cup abduction of < 30 degrees , and 10 showed the cup abduction of > 50 degrees . The computer-navigation MIS-THA was significantly more accurate than the conventional MIS-THA. Pearson chi-square test showed that there was not significant difference in the percentage of cases with acetabular abduction < 30 degrees , between these two groups (chi(2) = 1.37, P = 0.24), and there was a significant difference in the percentage of cases with acetabular abduction > 50 degrees , between these two groups (chi(2) = 8.22, P = 0.0042). There was a significant difference in the percentage of cases with the acetabular abduction < 30 degrees and > 50 degrees calculated together between these 2 groups (chi(2) = 11.85, P = 0.0006), CONCLUSION: MIS-THA with computer-navigation allows accurate orientation of the cup implant components without direct visualization of the bony landmarks.

Endoscopic retrograde cholangiopancreatography with double balloon enteroscope in patients with altered gastrointestinal anatomy: A meta-analysis.

BACKGROUND/AIMS: The aim of this study was to evaluate the effectiveness and safety of endoscopic retrograde cholangiopancreatography with double balloon enteroscope (DBE-ERCP) in patients with altered gastrointestinal anatomy in a meta-analysis. MATERIALS AND METHODS: A comprehensive literature search was conducted on PubMed, EMBASE, and Cochrane library covering the period from January 2001 to December 2015. Data were selected and abstracted from eligible studies and were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. RESULTS: Ten studies involving a total of 301 patients were included in the analysis. The pooled enteroscopy, diagnostic, and therapeutic success rates were 89.75% [95% confidence interval (CI): 79.65-94.30%], 79.92% (95% CI: 68.06-89.59%), and 63.55% (95% CI: 53.70-72.86%), respectively. DBE-ERCP-related complications occurred in 18 patients including perforation (5), pancreatitis (3), cholangitis (9), and bleeding (1). The incidence of DBE-ERCP-related complication was 6.27% (95% CI: 2.61-11.38%). CONCLUSION: Diagnostic and therapeutic DBE-ERCPs are feasible in patients with altered gastrointestinal anatomy. DBE-ERCP may be considered when pancreaticobiliary diseases occur in patients undergoing Roux-en-Y reconstruction or pancreaticoduodenectomy.

Dendritic cells engineered to secrete anti-DcR3 antibody augment cytotoxic T lymphocyte response against pancreatic cancer in vitro.

AIM: To investigate the enhanced cytotoxic T lymphocyte responses against pancreatic cancer (PC) in vitro induced by dendritic cells (DCs) engineered to secrete anti-DcR3 monoclonal antibody (mAb). METHODS: DCs, T lymphocytes and primary PC cells were obtained from PC patients. DCs were transfected with a designed humanized anti-DcR3 monoclonal antibody heavy and light chain mRNA and/or total tumor RNA (DC-tumor-anti-DcR3 RNA or DC-total tumor RNA) by using electroporation technology. The identification, concentration and function of anti-DcR3 mAb secreted by DC-tumor-anti-DcR3 RNA were determined by western blotting and enzyme-linked immunosorbent assay. After co-culturing of autologous isolated PC cells with target DCs, the effects of secreting anti-DcR3 mAb on RNA-DCs' viability and apoptosis were assessed by MTT assay and flow cytometry. Analysis of enhanced antigen-specific immune response against PC induced by anti-DcR3 mAb secreting DCs was performed using a 51Cr releasing test. T cell responses induced by RNA-loaded DCs were analyzed by measuring cytokine levels, including IFN-γ, IL-10, IL4, TNF-α and IL-12. RESULTS: The anti-DcR3 mAb secreted by DCs reacted with recombinant human DcR3 protein and generated a band with 35 kDa molecular weight. The secreting mAb was transient, peaking at 24 h and becoming undetectable after 72 h. After co-incubation with DC-tumor-anti-DcR3 RNA for designated times, the DcR3 level in the supernatant of autologous PC cells was significantly down-regulated (P < 0.05). DCs secreting anti-DcR3 mAb could improve cell viability and slow down the apoptosis of RNA-loaded DCs, compared with DC-total tumor RNA (P < 0.01). The anti-DcR3 mAb secreted by DC-tumor-anti-DcR3 RNA could enhance the induction of cytotoxic T lymphocytes (CTLs) activity toward RNA-transfected DCs, primary tumor cells, and PC cell lines, compared with CTLs stimulated by DC-total tumor RNA or control group (P < 0.05). Meanwhile, the antigen-specific CTL responses were MHC class I-restricted. The CD4+ T cells and CD8+ T cells incubated with anti-DcR3 mAb secreting DCs could produce extremely higher level IFN-γ and lower level IL4 than those incubated with DC-total tumor RNA or controls (P < 0.01). CONCLUSION: DCs engineered to secrete anti-DcR3 antibody can augment CTL responses against PC in vitro, and the immune-enhancing effects may be partly due to their capability of down-regulating DC apoptosis and adjusting the Th1/Th2 cytokine network.