Preparation of nitrogen doped hyper-crosslinked polymer-based hard carbon for high performance Li+/Na+ battery anode.

Hyper cross-linked polymers (HCPs), as a key precursor of hard carbon (HC) anode materials, stand out because of their capacity for molecular-scale structural design and comparatively straightforward preparation techniques, which are not seen in other porous materials synthesized procedure. A novel synthesis method of HCPs is developed in this paper, which is through the incorporation of functional macromolecules, the structural control and heteroatom doping of the product has been achieved, thus augmenting its electrochemical performance in batteries. In this work, carbonized tetraphenylporphyrin zinc (TPP-Zn) doped HCP-based hard carbon (CTHCP) with stable structure was prepared by Friedel-Crafts reaction and carbonization by using naphthalene and trace TPP-Zn as monomers, dimethoxybenzene (DMB) as crosslinking agent and FeCl3 as catalyst. The introduction of TPP-Zn, a functional macromolecule with unique two-dimensional structure, realized the pore structure regulation and N doping of the raw carbonized HCP-based hard carbon (CHCP). The results showed that CTHCP had higher mesoporous volume, N content and wider layer spacing than CHCP. In addition, CTHCP anode exhibited excellent Li+/Na+ storage performance, initial reversible capacity, rate performance and long cycle life. More amount of N-containing (N-5) active sites and mesoporous content in CTHCP anode was the main reason for the improvement of Na+ storage effect. While the increased interlayer spacing had a greater effect on the lithium storage capacity. This study uncovered the design rules of HC anode materials suitable for Li+/Na+ batteries and provided a new idea for the preparation of high-performance HC anode materials.

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.

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 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.

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.

Identification of nine microRNAs as potential biomarkers for lung adenocarcinoma.

Lung cancer is a leading global cause of cancer-related death, and lung adenocarcinoma (LUAD) accounts for ~ 50% of lung cancer. Here, we screened for novel and specific biomarkers of LUAD by searching for differentially expressed mRNAs (DEmRNAs) and microRNAs (DEmiRNAs) in LUAD patient expression data within The Cancer Genome Atlas (TCGA). The identified optimal diagnostic miRNA biomarkers were used to establish classification models (including support vector machine, decision tree, and random forest) to distinguish between LUAD and adjacent tissues. We then predicted the targets of identified optimal diagnostic miRNA biomarkers, functionally annotated these target genes, and performed receiver operating characteristic curve analysis of the respective DEmiRNA biomarkers, their target DEmRNAs, and combinations of DEmiRNA biomarkers. We validated the expression of selected DEmiRNA biomarkers by quantitative real-time PCR (qRT-PCR). In all, we identified a total of 13 DEmiRNAs, 2301 DEmRNAs and 232 DEmiRNA-target DEmRNA pairs between LUAD and adjacent tissues and selected nine DEmiRNAs (hsa-mir-486-1, hsa-mir-486-2, hsa-mir-153, hsa-mir-210, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-577, and hsa-mir-4732) as optimal LUAD-specific biomarkers with great diagnostic value. The predicted targets of these nine DEmiRNAs were significantly enriched in transcriptional misregulation in cancer and central carbon metabolism. Our qRT-PCR results were generally consistent with our integrated analysis. In summary, our study identified nine DEmiRNAs that may serve as potential diagnostic biomarkers of LUAD. Functional annotation of their target DEmRNAs may provide information on their roles in LUAD.

A C1-symmetric N-heterocyclic carbene catalysed oxidative spiroannulation of isatin-derived enals: highly enantioselective synthesis of spirooxindole δ-lactones.

A C1-symmetric N-heterocyclic carbene (NHC)-catalysed activation of isatin-derived enals under oxidative conditions was achieved. The in situ generated α,ß-unsaturated acyl azolium species was efficiently trapped by 1,3-dicarbonyl compounds via a Michael addition/spiroannualtion cascade, delivering a series of synthetically important spirooxindole δ-lactones with up to 96% enantioselectivity.

Inhibition of human lung cancer proliferation through targeting stromal fibroblasts by dihydromyricetin.

In the present study, the effects of dihydromyricetin on the proliferative potential of fibroblasts and lung carcinoma cells were investigated. Markedly higher expression levels of smooth muscle actin and platelet derived growth factors (PDGFs) were observed in the fibroblasts using reverse transcription-polymerase chain reaction analysis. The expression levels of PDGF-A and PDGF-B were also higher in the lung cancer cells. Western blot analysis revealed higher expression levels of the receptor for platelet-derived growth factor (PDGFRß) in the lysates from fibroblasts obtained from normal tissues and carcinoma tissues. Treatment of the fibroblasts with dihydromyricetin inhibited the expression of PDGFRß when treated with a 10 µM concentration for 48 h. Treatment of the fibroblasts with a 10 µM concentration of dihydromyricetin for 48 h led to complete inhibition of the activation of extracellular signal-regulated kinase (Erk)1/2 and Akt. The results of an MTT assay showed that treatment of the fibroblasts with dihydromyricetin significantly reduced the PDGF-mediated increase in the rate of proliferation. The rate of proliferation of the A549 lung cancer cells cultured with fibroblasts was markedly increased, compared with that of the A549 cells cultured alone. However, dihydromyricetin significantly (P<0.05) inhibited the proliferation rate of the A549 cells cultured with fibroblasts, compared with the untreated cultures. The proliferation rates of the A549 cancer cells, A549 cells cultured with fibroblasts, and A549 cells cultured with fibroblasts and treated with dihydromyricetin were found to be were 78.45, 98.45 and 21.37%, respectively. Dihydromyricetin inhibited the proliferative potential of fibroblasts in the lung cancer cells through targeting the activation of Erk1/2 and Akt. Therefore, there is scope for dihydromyricetin to be evaluated further for the treatment of lung cancer.

Withaferin A induces mitochondrial-dependent apoptosis in non-small cell lung cancer cells via generation of reactive oxygen species.

PURPOSE: Withaferin A (WA) is a bioactive lactone, isolated from natural sources, mainly found in Withania somnifera, and was known to be highly effective against a variety of tumor cells both in vitro and in vivo. Accumulating experimental evidence suggests the involvement of reactive oxygen species (ROS) in WA-mediated cytotoxicity against cancer cells. Hence, the purpose of this study was to investigate the effect of WA in non-small cell lung cancer (NSCLC) cells and also the role of ROC in WA-mediated cytotoxicity. METHODS: In the present study we investigated the cytotoxic potential of WA against NSCLC cell line A549 and also highlighted the mechanism of cytotoxicity of this compound. Non-carcinoma WI-38 and PBMC cell lines were used as controls. RESULTS: WA treatment resulted in a dose-dependent cytotoxicity in A549 cells, while the non-carcinoma cells WI-38 and PBMC were unaffected. Further experimental approaches revealed that ROS plays a major role in WAinduced apoptosis in NSCLC cells. CONCLUSION: WA induces oxidative damage to NSCLC cells with minimum toxicity to normal cells.

A meta-analysis of interlaminar minimally invasive discectomy compared to conventional microdiscectomy for lumbar disk herniation.

A meta-analysis was conducted to evaluate the evidence that compared the safety and efficacy of interlaminar minimally invasive discectomy (ILMI) and conventional microdiscectomy (MD) for treating lumbar disk herniation (LDH) patients and to develop GRADE based recommendations for using the procedures to treat LDH. Eleven studies, encompassing 1012 patients, met the inclusion criteria. Overall, the results of the meta-analysis indicated that there were significant differences between the two groups in blood loss (SMD=-0.93, 95% CI -1.84, -0.02; p=0.05), and the number of days stays in hospital (SMD=-0.79, 95% CI -1.55, -0.04; p=0.04). However, there were no significant differences in the short-term back visual analog scale (VAS) scores (SMD=-0.34, 95% CI -0.81, 0.14; p=0.16), the long-term back VAS scores (SMD=0.13, 95% CI -0.04, 0.30; p=0.14), the short-term leg VAS scores (SMD=0.14, 95% CI -0.01, 0.29; p=0.07), the long-term leg VAS scores (SMD=0.12, 95% CI -0.05, 0.30; p=0.17), the short-term Oswestry disability index (ODI) scores (SMD=0.01, 95% CI -0.14, 0.15; p=0.92), the long-term ODI scores (SMD=0.11, 95% CI -0.03, 0.25; p=0.14), and the incidence of complications (RR=1.22, 95% CI 0.88, 1.69; p=0.24). The results of this meta-analysis demonstrate that ILMI and MD are both safe and effective surgical procedures for treating LDH. Compared with MD, ILMI can shorten days in hospital, decrease the mounts of blood loss during surgery. However, the overall GRADE evidence quality was very low. Therefore, further validation is required, and medical institutions should conduct high-quality studies.

[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.

[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.

Hedgehog signaling pathway regulates human pancreatic cancer cell proliferation and metastasis.

Pancreatic cancer is one of the most aggressive and devastating malignancies. The Hedgehog (Hh) pathway has been reported to play an important role in pancreatic cancer development and progression. The aim of this study was to examine the activation of the Hh pathway in human pancreatic cancer tissue samples and pancreatic cancer cell lines, and the molecular mechanisms involved in the Hh pathway mediated effects on pancreatic cancer cell proliferation and invasion. The expression levels of Hh molecules in human pancreatic cancer tissue samples and pancreatic cancer cell lines were evaluated using RT-PCR. The role of the Hh pathway in cell proliferation and invasion was evaluated using flow cytometry, MTT, colony formation assays and transwell invasion assays, and the expression of cancer stem cell markers and epithelial-mesenchymal transition (EMT) were evaluated using flow cytometry and RT-PCR. Tumorigenicity assays were used to further investigate the role of the Hh pathway in vivo. Hh molecules were highly expressed in human pancreatic cancer tissue samples and pancreatic cancer cell lines. Inhibition of the Hh pathway notably decreased cell proliferation and induced apoptosis through inhibition of the PI3K/AKT pathway and cancer stem cells. Furthermore, inhibition of the Hh signaling pathway significantly inhibited EMT by suppressing the activation of transcription factors Snail and Slug, which are correlated with significantly reduced pancreatic cancer cell invasion, suggesting that the Hh signaling pathway is involved in early metastasis. These results indicate that activation of the Hh pathway is a common event. Inhibition of the Hh pathway may be a potential molecular target of new therapeutic strategies for pancreatic cancer.

[Photostimulated luminescence and color centers research in BaCl(x)Br(2-x):Eu2+ phosphors].

Eu2+ doped BaCl(x)Br(2-x), phosphors were prepared by solid state method in the present paper. The crystal structure and luminescent properties were studied by XRD, excitation, emission, and photostimulation. The XRD patterns indicate thatthe samples are single phase of BaCl(x)Br(2-x). The X-ray diffraction peak shifts to larger angle as the value of X increases. The emission spectra is a narrow band with a peak locating at 405 nm, which is attributed to the transition of 4f(6)5d-->4f(7). The excitation spectrum excited by 405 nm is a broad band ranging from 250-380 nm with a peak locating at 303 nm. The photostimulation spectrum is a broad band ranging from 480-800 nm with a peak locating at 575 nm. Through fitting the spectrum curve, the photostimulation spectrum is composed of three bands with peaks locating at about 550, 610 and 685 nm. The three fitting bands correspond to the three color-centers belonging to F(Cl-), F(C1-Br) and F(Br-) centers, respectively. The photostimulation peaks show a blue shift with increasing the ratio of Cl/Br.

[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.

Combined effects of EGFR and Hedgehog signaling pathway inhibition on the proliferation and apoptosis of pancreatic cancer cells.

In the present study, we established a new experimental model to investigate the effects of EGFR targeting by RNAi, and the synergistic actions between the hedgehog (Hh) and EGFR signaling pathways on the proliferation and apoptosis in pancreatic cancer cells. Three human pancreatic cancer cell lines expressing EGFR shRNA were established, and gene expression inhibition was assessed in these lines using RT-PCR and western blot analysis. The effects of EGFR RNAi and Hh inhibition on cell proliferation and apoptosis were explored in vitro and in vivo. We observed that EGFR RNAi notably inhibited cell proliferation and colony formation, induced apoptosis and markedly decreased xenograft tumor growth. Furthermore, EGFR RNAi significantly enhanced cyclopamine sensitivity both in vitro and in vivo, and a synergistic decrease of both AKT and ERK phosphorylation was observed. The present study demonstrates that combined inhibition of both EGFR and Hh signaling pathways could establish a more promising antitumor approach than inhibiting each singly, and that there is a possible synergistic effect for Hh and EGFR signaling pathways on ERK and AKT phosphorylation.

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.

Utility of squamous cell carcinoma antigen, carcinoembryonic antigen, Cyfra 21-1 and neuron specific enolase in lung cancer diagnosis: a prospective study from China.

BACKGROUND: Early detection and diagnosis is urgent for the sake of effective treatment strategy for lung cancer. However, a convenient, economical and relatively precise method is not available. We here report a prospective study to find the possible value of the combined use of four popular tumor markers in the early diagnosis of lung cancer among patients with suspicious nodules in the lung. METHODS: Six hundred and sixty inpatients with suspicious nodules in the lung were divided into a lung cancer group and a benign pulmonary tumor group according to post-operative histological examinations. Serum levels of four tumor markers including squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), Cyfra 21-1 and neuron specific enolase (NSE) were assayed for each patient. Receiver operating characteristic (ROC) curves were constructed for each tumor marker. The power of lung cancer diagnosis of each tumor marker, as well as a combination of them were analyzed and compared. RESULTS: The serum levels (median, range) of SCC, CEA, Cyfra 21-1 and NSE were 0.44 (0.01 - 35.70) ng/ml, 2.49 (0.30 - 26.78) ng/ml, 2.30 (0.82 - 73.33) ng/ml and 10.54 (0.10 - 56.41) ng/ml respectively in lung cancer group, and were 0.32 (0.01 - 0.90) ng/ml, 1.60 (0.20 - 8.93) ng/ml, 1.41 (0.72 - 4.82) ng/ml and 9.36 (6.56 - 24.24) ng/ml respectively in the benign pulmonary tumor group. The difference in each tumor marker between the two groups was significant (P < 0.05). The ROCs of SCC, CEA, Cyfra 21-1 and NSE were 0.702 (95%CI, 0.654 - 0.751), 0.611 (95%CI, 0.563 - 0.659), 0.650 (95%CI, 0.601 - 0.700) and 0.598 (95%CI, 0.542 - 0.654) respectively, indicating very low power of these four tumor markers. When a combination of SCC, CEA, Cyfra 21-1 and NSE were employed, the diagnosis power was strengthened. CONCLUSION: SCC, CEA, Cyfra 21-1 and NSE are valuable in the early diagnosis of lung cancer among suspicious nodules in the lung, especially when they were assayed together for one patient.