Objective To systematically review the diagnostic value of combined detection of K-ras gene mutation in peripheral blood and serum tumor markers for pancreatic cancer. Methods Databases including PubMed, The Cochrane Library (Issue 3, 2016), Elsevier, BMJ, CBM, CNKI and WanFang Data were searched from 2000 to March 2016 to collect diagnostic tests about the diagnostic value of combined detection of K-ras gene mutation in peripheral blood and serum tumor markers in pancreatic cancer. Two reviewers independently screened literature, extracted data and assessed the methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.3 software. Results A total of 23 studies involving 2?071 patients were included. The results of meta-analysis showed that the sensitivity (SE) and specificity (SP) of K-ras gene mutation in peripheral blood were 65% and 92% respectively in the diagnosis for pancreatic cancer. The results of the detection of tumor marker CA19-9 were 78% and 81% respectively. The SE and SP indexes in the parallel and serial combinations of CA19-9 together with CA242 were 85%, 72%, 70% and 83% respectively. And the SE, SP indexes in the parallel and serial combinations of K-ras gene mutation combined detection with CA19-9 were 90%, 63%, 47% and 96%. The positive likelihood ratio of the parallel combination of K-ras gene mutation in peripheral blood and CA19-9 (+LR=10.89) was higher than the other three detection methods, while the negative likelihood ratio of the serial combination of K-ras gene mutation in peripheral blood and CA19-9 (-LR=0.15) was lower than the other three detection methods, which indicated that the combined detection of K-ras gene mutation in peripheral blood and and CA19-9 had a better diagnostic performance than the single dectection of K-ras gene mutation or CA19-9 or the combined detection of CA19-9 and CA242 respectively. Comparing the area under curve (AUC) of SROC curve of the two combined diagnoses, the results showed that the diagnostic value of the parallel combination of K-ras gene mutation in peripheral blood and CA19-9 (AUC=0.87) was higher than that of the parallel combination of serum tumor markers CA19-9 and CA242. Conclusion Current evidence indicates that the combined detection of K-ras gene mutation and and tumor marker CA19-9 levels in peripheral blood can improve the diagnostic accuracy for pancreatic cancer. Due to the limited quantity and quality of included studies, above conclusions need to be verified by conducting more high quality studies.
【Abstract】 Objective To explore the features of Ki-ras mutations at codon 12 in Chinese patients of pancreatic cancer and to compare these features with those in Western countries. Methods Fifty-nine samples were collected during operations for pancreatic adenocarcinoma in our hospital from December 1989 to November 1997. The patients, age ranged from 30 to 73 years 〔(55.5±10.4) years〕,with 38 males and 21 female. TNM staging of the patients: stage Ⅰ(n=4); stage Ⅱ(n=8), stage Ⅲ(n=42),stage Ⅳ(n=5). PCR was used to amplify target gene and Dot blot hybridization for detecting Ki-ras mutations at codon 12 was performed in fifty-nine specimens of Chinese pancreatic cancer. The data of Ki-ras mutations at codon 12 from Western countries were gotten by Medline system. Results Ki-ras mutation at codon 12 was detected in 76.3% of the patients in this group. The frequency of double mutation of Ki-ras at codon 12 in this group (15.6%) was highest than that in western countries. Our results were compared with those reported in Western countries. The results suggested that there were the significant differences in the substitution of Ki-ras mutations at codon 12 and in the ratio of transition to transversion in pancreatic cancer among various countries. Conclusion Ki-ras mutations at codon 12 is frequent in Chinese pancreatic cancer, and a gene component to pancreatic cancer may be different among various countries. In addition, the effect of Ki-ras mutations at codon 12 on prognosis of patients with pancreatic cancer is different in various countries.
Objective To detect the activity of lactate dehydrogenase (LDH) and LDH isoenzyme, and to explore the relation between biological behavior ofpancreatic cancer and glycolysis. MethodsConsecutive 12 cases of pancreatic ductal adenocarcinoma and 12 benign lesions such as insulinoma from October 2006 to July 2008 were collected, as well as normal pancreatic tissues. The total activity of the LDH was detected by the LDH testing kits, and the iosenzyme pattern of LDH was inspected by the France Sebia hydrasys. ResultsCompared to the normal tissue, LDH activity ofpancreatic cancer and adjacent non-cancerous tissue was significantly higher (P＜0.05). LDH iosenzyme pattern in cancer tissue was also significantly different, the percentage of LDH4 and LDH5 increased obviously, and were greater than that innormal tissue (P＜0.05). ConclusionThe alteration of LDH activity and its isoenzyme pattern are possibly related to the pathogenesis of pancreatic cancer. Inhibit the LDH activity may be a new therapeutic strategy.
Objective To summarize the domestic and abroad articles related to the research on the relation between microRNA （miRNA） and pancreatic cancer，and explore the important effects of miRNA expression patterns in diagnosis of pancreatic cancer. Methods “microRNA and pancreatic cancer” were searched as key words by PubMed and CNKI series full-text database retrieval systems from 2000 to 2012. Totally 60 English papers and 15 Chinese papers were obtained. Choice criteria：the basic research of miRNA and pancreatic cancer，the clinical research of miRNA and pancreatic cancer， and the prospect of miRNA in pancreatic cancer diagnosis and treatment. According to the choice criteria，31 papers were finally analyzed. Results The miRNA expression spectrum and specific miRNA expression such as miR-21，miR-34，miR-217，miR-196a，miR-10a，miR-155，miR-221，miR-222，miR-181a，miR-181b，miR-181d， and the family members of miR-200 and let-7 might be used as tumor markers to differentiate pancreatic cancer from normal pancreas，chronic pancreatitis or pancreatic endocrine tumors，and might be used as prognostic factor to predict the outcome. Conclusions miRNA expression spectrum are not only related to diagnosis of pancreatic cancer， but also have provided a new research direction and method for gene therapy of pancreatic cancer．
【 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 systematically review the expression of E-cadherin protein and the risk of pancreatic cancer. MethodsWe searched PubMed, EMbase, The Cochrane Library, CNKI, VIP, CBM and WanFang Data from inception to October 2016 to collect case-control studies about the correlation between E-cadherin protein expression and the risk of pancreatic cancer. Two reviewers independently screened the literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed using RevMan 5.2 software and Stata 12.0 software. ResultsSeventeen studies (986 cases in pancreatic cancer group and 433 cases in normal pancreatic tissue group) were finally included. The results of meta-analysis showed that: the expression of E-cadherin protein in the pancreatic cancer group was lower than normal tissue group (OR=0.04, 95%CI 0.01 to 0.23, P=0.000 2), poor differentiation group was lower than high or middle differentiation group (OR=0.44, 95%CI 0.26 to 0.76, P=0.003), lymph node metastasis group was lower than without lymph node metastasis group (OR=0.50, 95% CI 0.31 to 0.81, P=0.005), and the difference was statistically significant. However, there was no significant difference between the clinical stageⅠ-Ⅱ group and Ⅲ-Ⅳ group (OR=0.63, 95%CI 0.25 to 1.59, P=0.33), pancreatic head cancer group and pancreatic body and tail cancer group (OR=1.22, 95%CI 0.72 to 2.07, P=0.46), pancreatic cancer with nerve invasion group and without nerve invasion group (OR=1.45, 95%CI 0.81 to 2.62, P=0.21), pancreatic cancer with vascular invasion group and without vascular invasion group (OR=0.55, 95%CI 0.13 to 2.22, P=0.40). ConclusionLower expression of E-cadherin protein is significantly associated with the risk of pancreatic cancer. Due to the limited quality and quanity of includied studies, the above conclusion should be approved by more studies.
Objective To investigate the inhibitory effect of survivin antisense oligonucleotides (ASODN) on proliferation of pancreatic cancer cells PANC-1. Methods The ASODN and sense oligodeoxynucleotides (SODN) were complementary to survivin sequences. FAM-marked ASODN was transfected into PANC-1 cells mediated by positive ion liposome as ASODN group. Blank control group (normal cells), negative control group (normal medium)， and SODN group were established for comparison. The transfection efficiency was detected by flow cytometry (FCM) after transfection; MTT assay was used to detect cytotoxicity; Cell morphological changes were examined by transmission electron microscopy; The cell cycle and apoptotic rate were analyzed by FCM; Immunohistochemical staining techniques were used, and the expressions of survivin were observed under light microscopy, examined and analysed by computer image. Results ①The transfection efficiency was 31.9%, 37.4%, 41.4%, 52.6%, 24.2%, 11.4%, 16.1%, and 15.5% when the transfecting concentration of ASODN was 50, 100, 150, 200, 250, 400, 600, and 800 nmol/L, respectively; The transfection efficiency was 12.0%, 50.8%, and 11.2% when the inoculated cells was 2×104/well, 2×105/well, and 2×106/well, respectively; The transfection efficiency was 58.8%, 34.0%, and 23.6% when 2 μl, 3 μl, and 4 μl liposome was used during transfection, respectively. ②Cell gap was oversize, morphous was round, adherent cells were less after transfection under fluorescence microscope. ③The inhibition rate in the ASODN group was higher than that in each control group (Plt;0.05) on 24, 36, 48 h after treating by survivin ASODN, which increased as time prolonged (Plt;0.05). ④The apoptosis showed a ladder-shaped line in the ASODN group. ⑤Apoptotic morphology was demonstrated in the ASODN group, such as apoptotic cells with nuclear chromatin highly concentrated, crescent nuclear staining aggregated by the side nuclear membrane, nucleolus disappeared by AO and EB stains. ⑥The apoptotic rate 〔（38.1±3.4）%〕 in the ASODN group was higher than that in the SODN group 〔（4.16±1.7）%〕, Plt;0.05. ⑦G2/M cell cycle arrested in the ASODN group. ⑧After transfection, the expression of survivin protein in the ASODN group was significantly lower than that of each control group (Plt;0.05). Conclusions The optimal transfection conditions are as following: the cell count of 2×105/well, concentration of ASODN 200 nmol/L, and cationic liposome oligofectamine 2 μl, respectively. Survivin ASODN can inhibit the proliferation of pancreatic cancer cells and induce their apoptosis.
ObjectiveTo review the recent advances in the pancreatic cancer stem cells field and identify the research trend in future. MethodsCurrent literatures on pancreatic cancer stem cells were collected and reviewed. ResultsPancreatic cancer was a highly lethal disease and was usually diagnosed at a late stage, for which there were few effective therapies. Emerging evidence had suggested that pancreatic cancer cells proposed a heterogeneous organization. A subpopulation of stem celllike cells sustains tumor growth, propagation, metastasis, and resistance to standard chemotherapy. Cancer stem cells were identified based on their expression of different sets of cell surface markers and functional characteristics. Some important signaling pathways which maintain self-renewal and metastasis were upregulated in pancreatic cancer stem cells. ConclusionsCurrent findings clearly suggest that specific elimination of cancer stem cells is possible and therapeutically relevant. An improved understanding of the biological behavior of such cells may lead to the development of novel diagnosis and treatment regimens for pancreatic cancer.
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.
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.