High mobility group AT-hook 2 promotes tumorigenicity of pancreatic cancer cells via upregulating ANLN.

HMGA2 is associated with the regulation of cellular biological processes in various human disorders and cancer progression, yet little is known about how HMGA2 controls tumorigenesis. This study uncovered the mechanism of HMGA2-mediated regulation of tumorigenicity in pancreatic cancer. We showed that HMGA2 was highly expressed in pancreatic cancer cells and correlated with poor prognosis. HMGA2 expression knockdown inhibited the tumorigenicity of pancreatic cancer cells. Conversely, overexpression of HMGA2 promoted tumorigenicity. Combination of ChIP-Seq, RNA-Seq and dual-luciferase reporter assays revealed HMGA2 could directly regulate ANLN expression. Furthermore, we found ANLN could mediate the HMGA2-induced effects on pancreatic cancer cells. The identification of the regulatory mechanism of HMGA2 and ANLN will provide insights into the progression for human pancreatic cancer.

[Individualized surgical treatment and prognosis of intraductal papillary mucinous neoplasms of the pancreas].

OBJECTIVE: To investigate the clinical manifestation, individualized surgical treatment, and prognosis of intraductal papillary mucinous neoplasms (IPMN) of pancreas. METHODS: The clinical data of 56 IPMN cases treated between January 2007 and December 2011 was retrospectively analyzed. Among the 56 patients (38 male and 18 female, mean age (61 ± 7) years), 26 were main-duct type, 18 were branch-duct type, 12 were mixed type. Pancreatectomy was performed on 48 cases, including pancreaticoduodenectomy on 29 patients, distal pancreatectomy on 17 patients, and total pancreatectomy on 2 patients. RESULTS: The overall postoperative morbidity rate was 27.1% (13/48), there was no perioperative mortality. Pathology showed 31 cases of noninvasive IPMN, 17 cases of invasive IPMN, and 7 cases of lymph node metastasis. The rate of invasive tumors was 46.2% (12/26) in main duct type, 3/12 in mixed type, and 2/18 in branch duct type IPMN, the difference was statistically significant (χ(2) = 6.385, P = 0.041). The five-year survival rate for patients with noninvasive and invasive neoplasms was 100% and 24.6%, respectively. The prognosis of invasive cases with lymph node metastasis was significantly worse than those without lymph node metastasis (P = 0.017). A regular follow-up without surgical treatment was performed on 8 cases with asymptomatic side branch IPMN less than 3 cm in diameter, and no progression was found during the follow-up. CONCLUSIONS: IPMN has a relative good prognosis. Main duct type and mixed type IPMN have a higher malignant potential, and should receive a surgical treatment. Patients of branch duct type IPMN with a <3 cm diameter lesion and no clinical manifestations can be managed with close follow-up only.

[The diagnosis and management strategies for gastrointestinal hemorrhage following pancreaticoduodenectomy].

OBJECTIVE: To analyze the causes and clinical features of gastrointestinal hemorrhage following pancreaticoduodenectomy (PD), and to provide the management strategies for this complication. METHODS: The clinic data of 412 patients who underwent PD from January 2000 to April 2010 was retrospectively reviewed. There were 232 male and 180 female patients, average age was (60 ± 12) years. The mode of procedure was standard PD and the Child's reconstruction of digestive tract, whose anastomosic steps encluded gastroenterostomy following chlangioenterostomy and pancreaticoenterostomy, was employed. Etiology of gastrointestinal haemorrhage, diagnostic methods and treatment strategy was recorded and analyzed. RESULTS: The postoperative mobidity was 37.1% (153/412), the rate of haemorrhagic complications was 6.6% (27/412), and gastrointestinal hemorrhage was recorded in 11 patients (2.7%). The bleeding rate of pancreaticointestinal anastomosis and gastricointestinal anastomosis were 5/11 and 4/11, respectively. Among these 11 patients, early hemorrhage occurred in 6 patients, 7 patients were due to technical failure. In order to control this kind of complication, open abdominal operation alone was performed on 4 patients, endoscopic management was performed on 3 patients and succeeded in 2 patients, vascular interventional therapy was performed on 5 patients and succeeded in 2 patients, and Re-laparotomy following vascular interventional therapy was performed on 2 patients successfully. CONCLUSIONS: Gastrointestinal hemorrhage following PD always occurred in early stage and reliable hemostasis during operation is the key points for prevention. Angiography is minimally invasive and holds the diagnostic value. Timely and decisive reoperation is an important method to management of postoperative gastrointestinal hemorrhage.

Suppression of the epidermal growth factor receptor inhibits epithelial-mesenchymal transition in human pancreatic cancer PANC-1 cells.

BACKGROUND: Aberrant expression of epidermal growth factor receptor (EGFR) has been detected in pancreatic cancer; however, the mechanisms of EGFR in inducing pancreatic cancer development have not been adequately elucidated. The objective of this study was to determine the role of EGFR in mediating epithelial-mesenchymal transition (EMT) in pancreatic cancer cells. METHODS: Pancreatic cancer cell line PANC-1 was transfected with small interfering RNA of EGFR by use of a lentiviral expression vector to establish an EGFR-knockdown cell line (si-PANC-1). PANC-1 cells transfected with lentiviral vector expressing negative control sequence were used as negative control (NC-PANC-1). Scratch assay and transwell study were used to analyze cell migration and invasion. Real-time PCR and Western blotting were used to detect the expression of EMT markers E-cadherin, N-cadherin, vimentin, and fibronectin and transcription factors snail, slug, twist1, and sip1 in PANC-1, NC-PANC-1, and si-PANC-1 cells. Immunofluorescent staining with these antibodies and confocal microscopy were used to observe their cellular location and morphologic changes. RESULTS: After RNA interference of EGFR, the migration and invasion ability of si-PANC-1 cells decreased significantly. The expression of epithelial phenotype marker E-cadherin increased and the expression of mesenchymal phenotype markers N-cadherin, vimentin, and fibronectin decreased, indicating reversion of EMT. We also observed intracellular translocation of E-cadherin. Expression of transcription factors snail and slug in si-PANC-1 cells decreased significantly. CONCLUSION: Suppression of EGFR expression can significantly inhibit EMT of pancreatic cancer PANC-1 cells. The mechanism may be related with the down-regulation of the expression of transcription factors snail and slug.

[Effects and mechanisms of combined suppression of epidermal growth factor receptor and hedgehog signaling on proliferation in pancreatic cancer cells].

OBJECTIVE: To explore the synergistic effects on proliferation and apoptosis by targeted suppression of epidermal growth factor receptor (EGFR) in combination with blockade of Hedgehog signaling pathways in pancreatic cancer cells and examine the synergistic mechanism of Hedgehog and EGFR signaling pathways. METHODS: The sequences of RNA interference targeting EGFR gene were designed, synthesized and cloned into the pFU-GW-RNAi vector. And a stable transfection cell line was obtained by transfecting the human Panc-1 cells with lentivirus. The expressions of Shh and Gli1 were tested by real-time polymerase chain reaction (PCR). The antiproliferative effect was examined by the assays of colony formation and methyl thiazolyl tetrazolium (MTT). Fluorescence activated cell sorter (FACS) was applied to assay the apoptotic rate in all experimental groups. Western blot was applied to detect the phosphorylation levels of ERK and AKT.In vivo nude mice tumorigenicity model was used to test the effect of growth inhibition. RESULTS: The RNAi technology with lentivirus could restrain the expression of EGFR gene. After the blocking of EGFR and Hedgehog signaling pathways by RNAi silencing, the chemosensitivity to cyclopamine significantly increased in human pancreatic cancer cells. The half-inhibitory concentration (IC 50) of cyclopamine declined from (2.978 ± 0.336) to (1.698 ± 0.057) µmol/L (P < 0.05). The prophase apoptotic rate of co-treated group was as high as 38.75% and it was significantly higher than the RNAi silencing EGFR (17.65%) and control groups (3.02%) (P < 0.05). The results of tumor xenografts assay showed that the tumor volume of co-treated group (394.8 ± 87.5 mm(3)) was significantly lower than that of simple EGFR RNAi (594.7 ± 86.1 mm(3)) and single cyclopamine treated group (771.3 ± 82.9 mm(3)); the combination treatment could also produce obviously synergistic antiproliferative effect in colony formation assays. After RNAi silencing EGFR, the phosphorylation levels of ERK and AKT decreased significantly versus the control group. Further reduction was obtained with the combined use of cyclopamine in the co-treated group. CONCLUSION: The blocking of EGFR and Hedgehog signaling pathways by RNAi silencing may further inhibit cell proliferation and increase apoptosis in vivo and in vitro in human pancreatic cancer cells. The synergism of Hh and EGFR signaling pathways may be correlated with the phosphorylation levels of ERK and AKT.

Emerging Role of Exosomal-Derived Long Noncoding RNAs in Human PDAC.

Background: The incidence and mortality of pancreatic ductal adenocarcinoma (PDAC) are increasing recently. Most patients with PDAC are diagnosed at advanced stage because of the high invasiveness of cancer cells and the lack of typical early symptoms. Therefore, early diagnosis of PDAC is very important to improve the prognosis. Exosomes play crucial role in intercellular communication and deliver the contents to recipient cells to regulate their biological behaviors. Recent evidence suggests emerging role of exosomes in the carcinogenesis of a variety of cancers including PDAC. Long noncoding RNAs (LncRNAs) have been reported to be involved in the development of PDAC. It has been proved that LncRNAs have the potential to be biomarkers and therapeutic targets for PDAC. Moreover, increasing number of studies focus on the role of exosomal LncRNAs in PDAC. Summary: In this review, we summarize the current status on our understanding of the role of exosomal-derived LncRNAs in the progression and metastasis of PDAC. Key Messages: We focus on challenges in the potential of exosomal-derived LncRNAs as novel diagnostic and prognostic markers and therapeutic targets of PDAC. In addition, we provide an overview about the demonstrated important role of exosomal LncRNAs in the progression of PDAC.

Preoperative Anemia Is a Predictor of Worse Postoperative Outcomes Following Open Pancreatoduodenectomy: A Propensity Score-Based Analysis.

Background: Preoperative anemia is a common clinical situation proved to be associated with severe outcomes in major surgeries, but not in pancreatic surgery. We aim to study the impact of preoperative anemia on morbidity and mortality in patients undergoing open pancreatoduodenectomy and use propensity score matching (PSM) to balance the basal data and reduce bias. Methods: We analyzed the data of consecutive patients undergoing open pancreatoduodenectomy with a complete record of preoperative hemoglobin, at two pancreatic centers in China between 2015 and 2019. Anemia is defined as hemoglobin less than 12 g/dl for male and 11 g/dl for female, following Chinese criteria. We compared clinical and economic outcomes before and after PSM and used logistic regression analysis to assess the correlation between variables and anemia. Results: The unmatched initial cohort consisted of 517 patients. A total of 148 cases (28.6%) were diagnosed with anemia at admission, and no case received a preoperative blood transfusion or anti-anemia therapy. After PSM, there were 126 cases in each group. The rate of severe postoperative complications was significantly higher in the anemia group than in the normal group (43.7% vs. 27.0%, p = 0.006), among which the differences in prevalence of clinically relevant postoperative pancreatic fistula (CR-POPF) (31.0% vs. 15.9%, p = 0.005) and cardiac and cerebrovascular events (4.0% vs. 0.0%, p = 0.024) were the most significant. The costs involved were more in the anemia group (26958.2 ± 21671.9 vs. 20987.7 ± 10237.9 USD, p = 0.013). Among anemic patients, receiver operating characteristic (ROC) curve analysis shows the cut-off value of hemoglobin, below which, patients are prone to suffer from major complications (104.5 g/l in male and 90.5 g/l in female). Among all patients, multivariate analysis showed that preoperative obstructive jaundice [odds ratio (OR) = 1.813, 95% confidence interval (CI) (1.206-2.725), p = 0.004] and pancreatic ductal adenocarcinoma [OR = 1.861, 95% CI (1.178-2.939), p = 0.008] were predictors of anemia. Among paired patients, preoperative anemia [OR = 2.593, 95% CI (1.481-5.541), p = 0.001] and malignant pathology [OR = 4.266, 95% CI (1.597-11.395), p = 0.004] were predictors of postoperative severe complications. Conclusion: Preoperative anemia is a predictor of worse postoperative outcomes following open pancreatoduodenectomy and needs to be identified and treated.

Fate of Surgical Patients with Small Nonfunctioning Pancreatic Neuroendocrine Tumors: An International Study Using Multi-Institutional Registries.

Several treatment guidelines for sporadic, nonmetastatic nonfunctioning neuroendocrine tumors of the pancreas (NF-pNETs) have recommended resection, however, tumors ≤ 2 cm do not necessarily need surgery. This study aims to establish a surgical treatment plan for NF-pNETs ≤ 2 cm. From 2000 to 2017, 483 patients who underwent resection for NF-pNETs ≤ 2 cm in 18 institutions from Korea and China were enrolled and their medical records were reviewed. The median age was 56 (range 16-80) years. The 10-year overall survival rate (10Y-OS) and recurrence-free survival rate (10Y-RFS) were 89.8 and 93.1%, respectively. In multivariable analysis, tumor size (>1.5 cm; HR 4.28, 95% CI 1.80-10.18, p = 0.001) and nodal metastasis (HR 3.32, 95% CI 1.29-8.50, p = 0.013) were independent adverse prognostic factors for OS. Perineural invasion (HR 4.36, 95% CI 1.48-12.87, p = 0.008) and high Ki-67 index (≥3%; HR 9.06, 95% CI 3.01-27.30, p < 0.001) were independent prognostic factors for poor RFS. NF-pNETs ≤ 2 cm showed unfavorable prognosis after resection when the tumor was larger than 1.5 cm, Ki-67 index ≥ 3%, or nodal metastasis was present. NF-pNET patients with tumors ≤ 1.5 cm can be observed if the preoperative Ki-67 index is under 3%, and if nodal metastasis is not suspected in preoperative radiologic studies. These findings support the clinical use to make decisions about small NF-pNETs.

[Regulatory mechanisms of Hedgehog signaling pathway for epithelial-mesenchymal transition in pancreatic cancer cells].

OBJECTIVE: To explore the blocking effects of hedgehog signaling pathway on the processes of cell migration, invasion and epithelial-mesenchymal transition (EMT) in human pancreatic cancer cells and elucidate its possible mechanisms. METHODS: The lentiviral expression vector for RNA interference of human Smoothened (SMO) gene was constructed to silence the expression of SMO. And RNAi against SMO was used to suppress the hedgehog signaling pathway in human pancreatic cancer Panc-1 cells. The in vitro invasion capacity in Panc-1 cells was assessed by Matrigel/Transwell chamber assay. Real-time PCR (polymerase chain reaction) and Western blot were used to detect the expressions of such EMT markers as E-cadherin, N-cadherin, ß-catenin, vimentin and fibronectin and such transcription factors as Snail, Slug, Twist1 and Sip1. RESULTS: The stable interference of SMO could suppress the hedgehog signaling activity in Panc-1 cells. The inhibition of hedgehog signaling reduced the in vitro invasion capacity significantly in Panc-1 cells. The expression of E-cadherin significantly increased while N-cadherin, vimentin and fibronectin were significantly down-regulated in the RNAi group. Compared to the control group, the expressions of Snail and Slug were significantly reduced in the SMO knock-down group. CONCLUSION: The inhibition of hedgehog signaling pathway reduces the in vitro invasion capacity in human pancreatic cancer cells. And the EMT process is significantly suppressed. The mechanism is partially correlated with the down-regulations of Snail and Slug.

Preoperative Nutrition Support May Reduce the Prevalence of Postoperative Pancreatic Fistula after Open Pancreaticoduodenectomy in Patients with High Nutritional Risk Determined by NRS2002.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a severe complication which may be caused by a perioperative nutrition problem. We aimed to study whether patients with high nutritional risk (NRS2002 score ≥ 5) might benefit from preoperative nutrition support regarding the risk of CR-POPF after open pancreaticoduodenectomy. METHODS: Consecutive patients undergoing open pancreaticoduodenectomy with complete record of NRS2002 at two Chinese institutions between 2013 and 2018 were analysed. CR-POPF was diagnosed following the 2016 ISGPS criteria. Nutrition support included oral nutrition supplement and enteral and parenteral nutrition. Clinical and economic outcomes were analysed. RESULTS: 522 cases were included. 135 cases (25.9%) were at high nutritional risk (NRS2002 score ≥ 5), among which 41 cases (30.4%) received preoperative nutrition support. The CR-POPF rate was significantly lower in the preoperative nutrition support group compared with the no nutrition support group (12.2% versus 28.7%, P = 0.038). Multivariate analysis showed that preoperative nutrition support was a protective factor for CR-POPF in patients at high risk [OR 0.339, 95% CI (0.115-0.965), P = 0.039]. Higher albumin and a larger diameter of the main pancreatic duct were found to be other protectors for CR-POPF. CONCLUSIONS: Patients with high nutritional risk (NRS2002 score ≥ 5) may profit from preoperative nutritional support manifested in the reduction of CR-POPF.

[Surgical complications after pancreatoduodenectomy: risk factors and treatments].

OBJECTIVE: To explore the impact factors and treatment of post pancreatoduodenectomy complications. METHODS: The clinical data of 412 cases between January 1995 and April 2010 underwent pancreatoduodenectomy were analyzed retrospectively. There were 232 male, 180 female. Univariate and multivariate logistic regression model were used to identify the risk factors related to occurrence of postoperative complications. RESULTS: The overall postoperative morbidity rate was 37.1% (153/412), and mortality rate was 4.6% (19/412). Total uncinate process resection, type of pancreatic-enteric anastomosis, duct diameter and pancreatic texture had effects on postoperative pancreatic fistula statistically. Total uncinate process resection, the amount of intra-operative blood loss ≥ 600 ml and pancreatic fistula were identified as significant risk factors for post pancreatoduodenectomy hemorrhage by means of univariate analysis. Delayed gastric empting occurrence in the patients with pylorus-preserving pancreaticoduodenectomy was higher than those with standard pancreaticoduodenectomy significantly. The multivariate Logistic regression analysis revealed that duct diameter and pancreatic texture were the independent risk factors of pancreatic fistula. Total uncinate process resection, the amount of intra-operative blood loss ≥ 600 ml and pancreatic fistula were independent risk factors of bleeding. There were no statistically significant differences between the radical group and the standard group when postoperative complication rates were analyzed (P < 0.05). CONCLUSIONS: Pancreaticojejunal anastomoses by means of duct-to-mucosa is fit for the patients with dilated pancreatic duct and end-to-end invaginated pancreaticojejunostomy is fit for the patients with undilated pancreatic duct. The prevention of postoperative bleeding depends on total uncinate process resection and meticulous hemostatic technique during operation. The pancreatic fistula is one of the most important factors which can result in postoperative bleeding. Pancreaticoduodenectomy combines with SMV/PV resection and extended lymphadenectomy do not significantly increase the morbidity rates.

Retrospective analysis of 45 cases of localized retroperitoneal Castleman disease from a single center.

BACKGROUND: Castleman disease (CD) is a rare lymphoproliferative disease characterized by high heterogeneity in clinical manifestation and prognosis. This study aimed to summarize clinical features of localized retroperitoneal CD and our experiences to improve the diagnosis and treatment of this disease. METHODS: Clinical data of 45 patients with localized retroperitoneal CD were retrospectively analyzed. The differences in clinical features between groups with and without paraneoplastic pemphigus (PNP) were compared. Survival was analyzed between groups depending on whether complicating with PNP, bronchiolitis obliterans (BO), gender, age and uni-centric CD (UCD)/multi-centric CD (MCD), respectively. RESULTS: Significant differences were observed between patient groups in the prevalence of retroperitoneal CD with PNP complicated with BO (P=0.010), the constituent ratios of initial symptoms (P<0.001) and the duration from appearance of the initial symptoms to being diagnosed (P=0.009). Among 45 cases, 43 tumors had clear margins and intact envelops and were completely resected, 40 patients were cured or significantly relieved, 3 patients were not significantly relieved, 2 patients received palliative surgical therapy and eventually relapsed and died after surgery. There were significant differences in the survival rate between groups depending on complication with BO, gender and age (≤40 and >40 years) (all P<0.05). CONCLUSIONS: Prompt and complete removal of the retroperitoneal CD tumor is critical to the management of this disease, as palliative resection tends to cause relapse and lead to a poor prognosis. Retroperitoneal CD patients with PNP may develop complications from BO leading to death. Complication with PNP, complication with BO, male gender and age ≥40 years were identified as prognostic risk factors for patients with localized retroperitoneal CD.

[Surgical treatment and prognosis analysis of localized retroperitoneal Castleman disease: a study of 20 cases].

OBJECTIVE: To investigate the clinical characteristics, surgical treatment and prognosis analysis of localized retroperitoneal Castleman disease (CD), and to improve the level of diagnosis and treatment of retroperitoneal Castleman disease with paraneoplastic pemphigus (PNP). METHODS: The clinical data of retroperitoneal CD with PNP from January 1993 to May 2009 were compared with CD without PNP retrospectively, including clinical features, tumor site, lab examination, surgical treatment, pathologic subtype and results of surgery. RESULTS: (1) Retroperitoneal Castleman disease more likely originated in para-kidney and iliac fossa with middle age of 36 years old, especially in left retroperitoneum. Of the 20 cases, 18 tumors (90%) were hyaline vascular variants and 2 were mixed variants. There was no statistical difference in gender, age, tumor site and pathological subtype between two groups. (2) Retroperitoneal CD with PNP more likely complicated with bronchiolitis obliterans (BO) and high level of serum CEA/CA242. (3) Retroperitoneal Castleman tumors had clear margin, intact envelop and were easily resectable, however the biological behavior of CD with PNP might tend malignant changing, invade adjacent blood vessel or seed locally, and eventually relapse after operation. (4) The 5-year survival rate of retroperitoneal CD with PNP was 42.8%, significantly lower than those without PNP. The average survival time was 30 months. Bronchiolitis obliterans and radical resection were the key effect in prognosis of retroperitoneal CD. CONCLUSIONS: Retroperitoneal CD with PNP has distinctive clinical features. Early diagnosis, prompt removal of tumor and termination secretion of causative antibody are critical to the management of this disease.

[The diagnosis and surgical management for patients with variants of hepatic arteries in the procedure of pancreaticoduodenectomy].

OBJECTIVE: To study the principle and surgical managements for the patients with anatomic variants of hepatic artery in the procedure of pancreaticoduodenectomy (PD). METHODS: One hundred and seventy-six patients who underwent PD between January 2000 and July 2007 were investigated retrospectively. Hepatic arterial variants were analyzed according to the intraoperative finding and CT imaging were reviewed postoperatively. RESULTS: Hepatic arterial variants were found intraoperatively in 20 cases of all 176 patients. Accessory right heptic artery, replaced right heptic artery and common heptic artery arising from the superior mesenteric artery (SMA) were present in 9 (5.1%), 5 (2.8%), 4 (2.3%) cases respectively,and replaced right heptic artery coming from the gastroduodenal artery was present in 2 cases (2.9%). All the variants of hepatic arteries arising from the superior mesenteric artery could be observed in spiral CT imaging. Most of the variant arteries were dissected intact intraoperatively except 2 cases with accessory right heptic artery arising from SMA. CONCLUSIONS: Performing CT scan preoperatively, especially CTA,is effective to diagnose these disorders. Skillful surgical techniques can manage the anatomic variants safely.

[Clinical analysis of post pancreatoduodenectomy hemorrhage].

OBJECTIVE: To explore the factors of post pancreatoduodenectomy hemorrhage. METHODS: The clinical data of 263 cases between January 1998 and April 2008 underwent pancreatoduodenectomy were analyzed prospectively. RESULTS: The overall mortality rate was 4.94% (13/263). Postoperative bleeding occurred in 23 patients (8.75%), with 8 episodes ending fatally (34.8%). The tumor size, Child classification, caput total resection and pancreatic leakage were identified as significant risk factors for post pancreatoduodenectomy hemorrhage by means of univariate analysis. The multivariate Logistic regression analysis revealed that all of the five factors turned out to be the independent risk factors. CONCLUSIONS: The prevention of these bleeding complications depends in the first place on meticulous hemostatic technique. The pancreatic leakage is also one of the most important factors due to postoperative bleeding. The prophylactic use of somatostatin is not necessary.

The effect of celecoxib on tissue factor expression in pancreatic cancer cells.

BACKGROUND: Tissue factor (TF) is overexpressed in many malignant tumours and is linked to the pathogenesis and prognosis of such malignancies. In vitro studies have proved that reduced expression of TF has inhibitory effect on the angiogenesis and cell proliferation of the malignant tumour. Therefore, TF suppression has been raised as a possible treatment for malignant tumours. Here we investigated the effect of celecoxib on TF expression induced by tumour necrosis factor alpha (TNFalpha) in PANC-1 cells and a possible molecular mechanism underlying the celecoxib effect. METHODS: Various doses of celecoxib solution were added to standard cell numbers of PANC-1 cells mixed with equal dose of TNFalpha for 6 hours. The expression of tissue factor was detected quantitatively by Western blot, whilst the activation of nuclear factor kappaB was tested by electromobility shift assay. RESULTS: As the doses of celecoxib increased, the tissue factor expression was decreased in PANC-1 cells and so was the activation of nuclear factor kappaB. CONCLUSIONS: Celecoxib can downregulate the expression of tissue factor induced by TNFalpha in PANC-1 cells. This antitumour effect of celecoxib can be explained indirectly via its suppressive role in activation of nuclear factor kappaB.

[Influencing factor analysis of delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy].

OBJECTIVE: To investigate the influencing factors of delayed gastric emptying (DGE) after pylorus-preserving pancreaticoduodenectomy (PPPD) and its preventing managements. METHODS: Forty-two patients who underwent PPPD and 104 patients underwent standard Whipple procedure (SPD) between January 2000 and July 2006 were investigated retrospectively. The factors influencing the development of DGE following PPPD were analyzed statistically. RESULTS: There was no significant difference in mortality between PPPD and SPD (0/42 vs. 7/104, P = 0.193). Pancreatic fistula occurred much more frequently in SPD than in PPPD (29/104 vs. 1/42, P < 0.05). The occurrence of DGE after PPPD was higher significantly than that after SPD (35.7% vs. 18.3%, P = 0.024). More DGE occurred in patients with a operation time more than 6 hours than in patients whose operation lasted less than 6 hours (76.9% vs. 17.2%, P = 0.008). Meanwhile, DGE occurred in 20% of patients with the antero-colonic route for duodenojejunostomy and in 50% with retro-colonic route (P = 0.043). Multivariate analysis by logistic regression model showed postoperative intra-abdominal complications were not risk factors for DGE. Prophylactic use of somatostatin couldn't prevent DGE effectively. CONCLUSIONS: DGE is the most frequent postoperative complication after PPPD, it can be markedly reduced by shortening operative time and using antero-colonic duodenojejunostomy procedure. There is no medicine which could prevent DGE effectively.

[The role of human fibroblast growth factor receptor 1-IIIb isoform in proliferation of pancreatic ductal cells and its effects to mitogen-activated protein kinase].

OBJECTIVE: To study the role of IIIb isoform of human fibroblast growth factor receptor 1 (FGFR1-IIIb) in proliferation of pancreatic ductal cells and its effects on mitogen-activated protein kinase (MAPK). METHODS: Human pancreatic ductal cells of the line TAKA-1 were cultured. The plasmid of human full-length FGFR1-IIIb isoform, pSVK4/FGFR1-IIIb, was stable transfected into the cultured TAKA-1 pancreatic ductal cells facilitated by lipofectamine. Un-transfected TAKA-1 cells and TAKA-1 ductal cells transfected with blank plasmid were used as controls. The expression, distribution and character of protein of FGFR1-IIIb in the TAKA-1 cells were estimated by Western blotting, Northern blotting, immunofluorescence assay, and glycosylation assay. The function and mechanism of FGFR1-IIIb in the transfected pancreatic ductal cells stimulated by FGF were examined by MTT assay and MAPK assay. Tunicamycin, an inhibitor of N-terminal glycoprotein synthesis, was added into the culture fluid of the FGFR1-IIIb transfected TAKA-1 cells to observe the changes of the FGFR1 bands. RESULTS: FGFR1-IIIb, a glycosylated receptor at various levels at 120 kDa and between 130 - 150 kDa, was localized at moderate levels at the cell membrane and cytoplasm and at higher level in the perinuclear region of the cytoplasm of the pSVK4/FGFR1-IIIb-transfected cells. FGF-1, -2, and -4 significantly increased the growth of FGFR1-IIIb-transfected TAKA-1 cells, and at the same time induced the p44/p42 MAPK phosphorylation. CONCLUSION: Human FGFR1-IIIb receptor is a functional receptor in pancreatic ductal cells. FGF-1, -2, and -4 can increase the growth of FGFR1-IIIb-transfected pancreatic ductal cells, and the mechanism is that they can induce the p44/p42 MAPK phosphorylation.