【 Abstract 】 Objective Overexpressions of epidermal growth factor (EGF) and EGF receptor have been associated with progression and invasive phenotype of pancreatic cancer. However, the underlying molecular mechanism by which EGF worked in pancreatic cancer cells has not been completely understood. In this study, effect of EGF on the invasion and metastasis of pancreatic cancer cells and its regulatory mechanism were investigated. Methods The effects of EGF on the proliferation, adhesion and invasion of pancreatic cancer cells were detected by WST-1 proliferation assay, adhesion assay and invasive assay, respectively. The activity and expression of MMP-2 and MMP-9 were examined by zymography, Western blot and RT-PCR, respectively. The activity of NF- κ B was examined by EMSA. Results EGF could significantly promote the invasiveness of pancreatic cancer cells but did not affect cell proliferation or adhesion. The expressions of NF- κ B and MMP-9 were significantly increased by EGF, but EGF did not affect the activity and expression of MMP-2. Furthermore, EGF stimulated the NF- κ B binding activity. Pretreatment with NF- κ B inhibitors, pyrrolidine dithiocarbamate (PDTC), could significantly inhibit the activity of NF- κ B induced by EGF. Meanwhile, the EGF-induced expression and activity of MMP-9, as well as cell invasiveness were also inhibited by NF- κ B inhibitor. Conclusion EGF could increase the expression and promote the invasiveness of MMP-9 via the activation of NF- κ B in pancreatic cancer cells, which implies that NF- κ B inhibitant, such as PDTC, may diminish the invasiveness of pancreatic cancer cells.
ObjectiveTo investigate the relationship between insulin-like growth factor binding protein (IGFBP) gene with pancreatic cancer.
MethodsThe relevant literatures at home and abroad in recent years were reviewed. From the pancreatic cancer related genes, IGFBP related tumors and the correlation between IGFBP and pancreatic cancer research and other aspects of the previous research results were summaried.
ResultsMost of the studies suggested that IGFBP could inhibit the function of tumor cells through the IGF dependent pathway, but the deletion or mutation of IGFBP gene and its regulation mechanism are still unclear.
ConclusionIGFBP is closely related to the tumor, but its specific effects and mechanism of pancreatic cancer has not been settled. In order to affect the degree of cell differentiation, regulation of tumor growth and metastasis probability through the change of endogenous IGFBP gene level, the further studie is needed.
Objective To summary the principle of magnetic resonance spectroscopy imaging and its application progress in diagnosis and differential diagnosis of pancreatic cancer. Methods The newest related literatures of home and abroad were collected and reviewed. Results Magnetic resonance spectroscopy imaging was a technology using the magnetic resonance phenomena and chemical shift phenomena to measure molecular organization. The spectroscopy most commonly used in clinical and scientific research includes 1H， 31P， and 23Na. Conclusion Magnetic resonance spectroscopy as the only approach to noninvasive quantitative provding biochemical information in vivo， has an important significance to the diagnosis and differential diagnosis of pancreatic cancer.
Objective
To explore the risk factors of postoperative anxiety in patients with pancreatic cancer undergoing total pancreatectomy.
Methods
A total of 31 patients who underwent total pancreatectomy for pancreatic cancer between July 2011 and December 2016 were collected and analyzed in this retrospective study. The patients’ postoperative Self-Rating Anxiety Scale scores were collected, and the exposure factors were analyzed to identify the risk factors of postoperative anxiety through univariate analysis and multiple logistic regression analysis by SPSS 21.0 statistical software.
Results
In the 31 patients, there were 17 males and 14 females, with an average age of (66.16±9.09) years, an average body mass index of (21.11±3.10) kg/m2, and an average postoperative hospital stay of (14.58±7.47) days. There were 23 patients (74.2%) with postoperative anxiety, and 30 patients (96.8%) with hyperglycosemia required insulin therapy. The total perioperative mortality was 3.2%. In the univariate analysis, age (P=0.012), smoking history (P=0.043), preoperative diabetes mellitus (P=0.012), postoperative bile leakage (P=0.043), and postoperative abdominal infection (P=0.026) were related factors of the postoperative anxiety. In the multiple logistic regression analysis, patients without preoperative diabetes was an independent risk factor of postoperative anxiety (P=0.013).
Conclusions
For patients undergoing total pancreatectomy, it is needed to pay attention to the patients’ postoperative psychological conditions and assess the postoperative anxiety, especially for those without preoperative diabetes. To improve the life quality and long-term survival of these patients, health education and psychological intervention are needed.
ObjectiveTo summarize the therapeutic targets of pancreatic cancer (PC).
MethodsThe related literatures about the therapeutic targets of PC were reviewed.
ResultsPC was one of the most challenging tumor in worldwide, and was characterized as a highly aggressive disease with poor overall prognosis and a high mortality rate. The hallmark of PC was its poor response to radio-and chemo-therapy. Current chemotherapeutic regimens could not provide substantial survival benefit with a clear increase in overall survival. Recently, several new approaches which could significantly improve the clinical outcome of PC had been described, involving signal-transduction pathways, immune response, stroma reaction, and epigenetic changes.
ConclusionsMany therapeutic targets are involved in the treatment of PC. As current therapies failed to significantly improve the progression and the survival of PC, new therapeutic approaches and clinical studies are strongly required.
ObjectiveTo systematically review the influence of postoperative adjuvant chemotherapy for pancreatic cancer on survival.
MethodsWe comprehensively searched databases including The Cochrane Library (Issue 11, 2013), PubMed, EMbase, CBM, CNKI, VIP and WanFang Data from inception to December 2013 to collect randomized controlled trials (RCTs) about the influencing on survival of postoperative adjuvant chemotherapy for pancreatic cancer patients after operation. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies. Then meta-analysis was conducted using RevMan 5.2 software.
ResultsA total of 7 RCTs involving 1 079 patients were included (544 cases and 535 controls). The results of meta-analysis showed that, compared with single radical correction, the patients with adjuvant chemotherapy were better in prolonging total survival time (WMD=5.45, 95%CI 2.52 to 8.39, P=0.000 3), and increasing 2-year (RR=1.17, 95%CI 1.01 to 1.35, P=0.03) as well as 5-year survival rates (RR=1.80, 95%CI 1.24 to 2.62, P=0.002) with significant differences. But for 1-year survival rates, no significant difference was found between the two groups (RR=1.02, 95%CI 0.94 to 1.11, P=0.65).
ConclusionCurrent evidence shows that postoperative adjuvant chemotherapy should be applied after resection of pancreatic cancer.
Objective To investigate the expressions of CXCR4 and β-catenin in pancreatic cancer, explore the relationship between them, and explore the possible biomarkers about invasion and metastasis of pancreatic cancer. Methods Forty-eight samples of pancreatic cancer and 20 samples of normal pancreas tissues were selected. The expressions of CXCR4 and β-catenin were examined by the immunohistological technique. Spearman, Chi-square， and rank test were used to analyze the relation between the protein expressions and clinical characteristics. Survival analysis was evaluated by Kaplan-Meier product limit method and Log-rank test. Variables were evaluated by Cox proportional hazards analysis. The size of test was 0.05. Results The positive expression rates of CXCR4 and β-catenin in pancreatic cancer tissues were 85.4% (41/48) and 75.0% (36/48), respectively. Co-expression rate of CXCR4 and β-catenin was 70.8% (34/48). There were significant differences between various CXCR4 staining and lymph node metastasis and TNM stage (P=0.012, 0.005, respectively). β-catenin positive expression was associated with lymph node metastasis (P=0.047). However, abnormal β-catenin positive expression could not determine the clinical survival. Kaplan-Meier estimated curves suggested that clinical prognosis was poor for patients with CXCR4 expression. Multivariate analysis showed that CXCR4, late TNM stage, and lymph node metastasis were independent prognostic factors for pancreatic cancer. Conclusions Both CXCR4 and β-catenin abnormally express in pancreatic cancer. CXCR4 may be an important marker for pancreatic cancer progression.
ObjectiveTo summary the detection methods of circulating tumor cells (CTCs) in pancreatic cancer patients and its clinical application.
MethodsRelated domestic and foreign literatures were reviewed.
ResultsPancreatic cancer is one of the common malignant tumors in the world. The early diagnosis rate is low, the incidence of local invasion and metastasis is high, and the prognosis is very poor. The CTCs is one of the important causes of postoperative recurrence and metastasis, its detection methods based on immunocytochemistry (ICC) and reverse transcription polymerase chain reaction (RT-PCR).
ConclusionsDetection of CTCs, regarding as a "real-time liquid biopsy", it has a high application value in the early diagnosis, treatment, prognosis and effect evaluation of pancreatic cancer, and it has become research frontier and focus.
Objective To observe the effect of epidermal growth factor (EGF) on the proliferation, adhesion, invasiveness and the activation of nuclear factor-κB (NF-κB), matrix metalloproteinases (MMPs) expression and explore related mechanisms in pancreatic cancer cells. Methods Cell invasion assay, proliferation assay and adhesion assay were used to examine the proliferation, adhesion and invasiveness of pancreatic cancer cells, respectively. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA), and MMPs protein and mRNA expressions were investigated by gelatin zymography, Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Results EGF increased the invasiveness of pancreatic cancer cell in a dose-dependent manner (P＜0.05), but did not affect cell proliferation or adhesion. The expressions of MMP-9 mRNA and protein significantly increased after induction by EGF and were highest when EGF concentration was 50 ng/ml, while there was no effect on the expressions of MMP-2 mRNA and protein. Furthermore, NF-κB activity increased with increased concentration of EGF in a concentration-dependent manner (P＜0.05). In addition, NF-κB activity and the expressions of MMP-9 mRNA and protein by pretreatment with both pyrrolidine dithiocarbamate (PDTC) and EGF decreased when compared that by pretreatment with EGF alone. The invasiveness of pancreatic cancer cell by pretreatment with both PDTC and EGF decreased when compared that by pretreatment with EGF alone and nothing (P＜0.05).Conclusion The findings indicate that the NF-κB-mediated MMP-9 induction is essential for EGF-induced invasiveness in pancreatic cancer cells, which can be inhibited by PDTC.
ObjectiveTo study the expression of lipid associated with neutrophil gelatinase associated lipocalin (NGAL) in nude mice orthotopic pancreatic cancer tissues and the relationship between the occurred and development of pancreatic cancer.
MethodsThe expressions of NGAL mRNA and protein of pancreatic cancer tissues and their adjacent tissues, and normal pancreatic tissues in nude mice were detected by using RT-PCR and immunohistochemical methods.
ResultsThe expressions of NGAL mRNA in pancreatic cancer tissues and adjacent tissues were significantly higher than that in normal pancreatic tissues (P < 0.05), and the expression of NGAL mRNA in pancreatic carcinoma tissues was significantly higher than that in para carcinoma tissues (P < 0.05). The strong positive expression rate of NGAL protein in pancreatic carcinoma tissues was significantly higher than thoes in para carcinoma tissues and normal pancreatic tissues (P < 0.05).
ConclusionsNGAL is highly expressed in pancreatic cancer tissues, and NGAL may be an important regulatory factor in the development of pancreatic cancer.
