AIM： To compare gene expression profiles of pancreatic adenocarcinoma tissue specimens, human pancreatic and colon adenocarcinoma and leukemia cell lines and normal pancreas samples in order to distinguish differenti...AIM： To compare gene expression profiles of pancreatic adenocarcinoma tissue specimens, human pancreatic and colon adenocarcinoma and leukemia cell lines and normal pancreas samples in order to distinguish differentially expressed genes and to validate the differential expression of a subset of genes by quantitative real-time RT-PCR （RT-QPCR） in endoscopic ultrasound-guided fine needle aspiration （EUS-guided FNA） specimens.METHODS： Commercially dedicated cancer cDNA macroarrays （Atlas Human Cancer 1.2） containing 1176 genes were used. Different statistical approaches （hierarchical clustering, principal component analysis （PCA） and SAM） were used to analyze the expression data. RT-QPCR and immunohistochemical studies were used for validation of results.RESULTS： RT-QPCR validated the increased expression of LCN2 （lipocalin 2） and for the first time PLAT （tissue-type plasminogen activator or tPA） in malignant pancreas as compared with normal pancreas. Immunohistochemical analysis confirmed the increased expression of LCN2 protein localized in epithelial cells of ducts invaded by carcinoma. The analysis of PLAT and LCN2 transcripts in 12 samples obtained through EUS-guided FNA from patients with pancreatic adenocarcinoma showed significantly increased expression levels in comparison with those found in normal tissues, indicating that a sufficient amount of high quality RNA can be obtained with this technique.CONCLUSION： Expression profiling is a useful method to identify biomarkers and potential target genes. Molecular analysis of EUS-guided FNA samples in pancreatic cancer appears as a valuable strategy for the diagnosis of pancreatic adenocarcinomas.展开更多
Despite tremendous efforts from scientists and clinicians worldwide, pancreatic adenocarcinoma(PDAC) remains a deadly disease due to the lack of early diagnostic tools and reliable therapeutic approaches. Consequently...Despite tremendous efforts from scientists and clinicians worldwide, pancreatic adenocarcinoma(PDAC) remains a deadly disease due to the lack of early diagnostic tools and reliable therapeutic approaches. Consequently, a majority of patients(80%) display an advanced disease that results in a low resection rate leading to an overall median survival of less than 6 months. Accordingly, robust markers for the early diagnosis and prognosis of pancreatic cancer, or markers indicative of survival and/or metastatic disease are des-perately needed to help alleviate the dismal prognosis of this cancer. In addition, the discovery of new therapeutic targets is mandatory to design effective treatments. In this review, we will highlight the translational studies demonstrating that microRNAs may soon translate into clinical applications as long-awaited screening tools and therapeutic targets for PDAC.展开更多
Pancreatic ductal adenocarcinoma remains one of the most deadly types of tumor. Endoscopic ultrasoundguided fine-needle aspiration(EUS-FNA) is a safe, cost-effective, and accurate technique for evaluating and staging ...Pancreatic ductal adenocarcinoma remains one of the most deadly types of tumor. Endoscopic ultrasoundguided fine-needle aspiration(EUS-FNA) is a safe, cost-effective, and accurate technique for evaluating and staging pancreatic tumors. However, EUS-FNA may be inconclusive or doubtful in up to 20% of cases. This review underlines the clinical interest of the molecular analysis of samples obtained by EUS-FNA in assessing diagnosis or prognosis of pancreatic cancer, especially in locally advanced tumors. On EUS-FNA materials DNA, mRNA and miRNA can be extracted, amplified, quantified and subjected to methylation assay. Kras mutation assay, improves diagnosis of pancreatic cancer. When facing to clinical and radiological presentations of pseudo-tumorous chronic pancreatitis, wildtype Kras is evocative of benignity. Conversely, in front of a pancreatic mass suspected of malignancy, a mutated Kras is highly evocative of pancreatic adenocarci-noma. This strategy can reduce false-negative diagnoses, avoids the delay of making decisions and reduces loss of surgical resectability. Similar approaches are conducted using analysis of miRNA expression as well as Mucin or markers of invasion(S100P, S100A6, PLAT or PLAU). Beyond the diagnosis approach, the prediction of response to treatment can be also investigated form biomarkers expression within EUS-FNA materials.展开更多
AIM:To compare characteristics and outcomes of resected and nonresected main-duct and mixed intraductal papillary mucinous neoplasms of the pancreas(IPMN).METHODS:Over a 14-year period,50 patients who did not undergo ...AIM:To compare characteristics and outcomes of resected and nonresected main-duct and mixed intraductal papillary mucinous neoplasms of the pancreas(IPMN).METHODS:Over a 14-year period,50 patients who did not undergo surgery for resectable main-duct or mixed IPMN,for reasons of precluding comorbidities,age and/or refusal,were compared with 74 patients who underwent resection to assess differences in rates of survival,recurrence/occurrence of malignancy,and prognostic factors.All study participants had dilatation of the main pancreatic duct by ≥ 5 mm,with or without dilatation of the branch ducts.Some of the nonsurgical patients showed evidence of mucus upon perendoscopic retrograde cholangiopancreatography or endoscopic ultrasound and/or after fine needle aspiration.For the surgical patients,pathologic analysis of resected specimens confirmed a diagnosis of IPMN with involvement of the main pancreatic duct or of both branch ducts as well as the main pancreatic duct.Clinical and biologic follow-ups were conducted for all patients at least annually,through hospitalization or consultation every six months during the first year of follow-up,together with abdominal imaging analysis(magnetic resonance cholangiopancreatography or computed tomography) and,if necessary,endoscopic ultrasound with or without fine needle aspiration.RESULTS:The overall five-year survival rate of patients who underwent resection was significantly greater than that for the nonsurgical patients(74% vs 58%; P =0.019).The parameters of age(< 70 years) and absence of a nodule were associated with better survival(P < 0.05); however,the parameters of main pancreatic duct diameter > 10 mm,branch ductdiameter > 30 mm,or presence of extra pancreatic cancers did not significantly influence the prognosis.In the nonsurgical patients,pancreatic malignancy occurred in 36% of cases within a mean time of 33 mo(median:29 mo; range:8-141 mo).Comparison of the nonsurgical patients who experienced disease progression with those who did not progress showed no significant differences in age,sex,symptoms,subtype of IPMN,or follow-up period; only the size of the main pancreatic duct was significantly different between these two sub-groups,with the nonsurgical patients who experienced progression showing a greater diameter at the time of diagnosis(> 10 mm).CONCLUSION:Patients unfit for surgery have a 36% greater risk of developing pancreatic malignancy of the main-duct or mixed IPMN within a median of 2.5 years.展开更多
基金Supported by Contrat Universite Paul Sabatier,Toulouse,France,ASUPS 2000(N.Vaysse)AOL DRC Hopitaux de Toulouse 2001,(L.Buscail)Region Midi-Pyrenees(L.Buscail)H.Laurell was supported by a grant from European Community Plan 99 ECC QLG3-CT-1999-0908(C.Susini)The Agilent 2100 Bioanalyzer and the phosphoimager(Molecular Dynamics,Sunnyvale,CA,USA)were at the Transcriptome Platform,Toulouse Genopole,and at the molecular biology platform at the Institute Louis Bugnard,IFR31,Toulouse,France,respectively
文摘AIM： To compare gene expression profiles of pancreatic adenocarcinoma tissue specimens, human pancreatic and colon adenocarcinoma and leukemia cell lines and normal pancreas samples in order to distinguish differentially expressed genes and to validate the differential expression of a subset of genes by quantitative real-time RT-PCR （RT-QPCR） in endoscopic ultrasound-guided fine needle aspiration （EUS-guided FNA） specimens.METHODS： Commercially dedicated cancer cDNA macroarrays （Atlas Human Cancer 1.2） containing 1176 genes were used. Different statistical approaches （hierarchical clustering, principal component analysis （PCA） and SAM） were used to analyze the expression data. RT-QPCR and immunohistochemical studies were used for validation of results.RESULTS： RT-QPCR validated the increased expression of LCN2 （lipocalin 2） and for the first time PLAT （tissue-type plasminogen activator or tPA） in malignant pancreas as compared with normal pancreas. Immunohistochemical analysis confirmed the increased expression of LCN2 protein localized in epithelial cells of ducts invaded by carcinoma. The analysis of PLAT and LCN2 transcripts in 12 samples obtained through EUS-guided FNA from patients with pancreatic adenocarcinoma showed significantly increased expression levels in comparison with those found in normal tissues, indicating that a sufficient amount of high quality RNA can be obtained with this technique.CONCLUSION： Expression profiling is a useful method to identify biomarkers and potential target genes. Molecular analysis of EUS-guided FNA samples in pancreatic cancer appears as a valuable strategy for the diagnosis of pancreatic adenocarcinomas.
文摘Despite tremendous efforts from scientists and clinicians worldwide, pancreatic adenocarcinoma(PDAC) remains a deadly disease due to the lack of early diagnostic tools and reliable therapeutic approaches. Consequently, a majority of patients(80%) display an advanced disease that results in a low resection rate leading to an overall median survival of less than 6 months. Accordingly, robust markers for the early diagnosis and prognosis of pancreatic cancer, or markers indicative of survival and/or metastatic disease are des-perately needed to help alleviate the dismal prognosis of this cancer. In addition, the discovery of new therapeutic targets is mandatory to design effective treatments. In this review, we will highlight the translational studies demonstrating that microRNAs may soon translate into clinical applications as long-awaited screening tools and therapeutic targets for PDAC.
文摘Pancreatic ductal adenocarcinoma remains one of the most deadly types of tumor. Endoscopic ultrasoundguided fine-needle aspiration(EUS-FNA) is a safe, cost-effective, and accurate technique for evaluating and staging pancreatic tumors. However, EUS-FNA may be inconclusive or doubtful in up to 20% of cases. This review underlines the clinical interest of the molecular analysis of samples obtained by EUS-FNA in assessing diagnosis or prognosis of pancreatic cancer, especially in locally advanced tumors. On EUS-FNA materials DNA, mRNA and miRNA can be extracted, amplified, quantified and subjected to methylation assay. Kras mutation assay, improves diagnosis of pancreatic cancer. When facing to clinical and radiological presentations of pseudo-tumorous chronic pancreatitis, wildtype Kras is evocative of benignity. Conversely, in front of a pancreatic mass suspected of malignancy, a mutated Kras is highly evocative of pancreatic adenocarci-noma. This strategy can reduce false-negative diagnoses, avoids the delay of making decisions and reduces loss of surgical resectability. Similar approaches are conducted using analysis of miRNA expression as well as Mucin or markers of invasion(S100P, S100A6, PLAT or PLAU). Beyond the diagnosis approach, the prediction of response to treatment can be also investigated form biomarkers expression within EUS-FNA materials.
文摘AIM:To compare characteristics and outcomes of resected and nonresected main-duct and mixed intraductal papillary mucinous neoplasms of the pancreas(IPMN).METHODS:Over a 14-year period,50 patients who did not undergo surgery for resectable main-duct or mixed IPMN,for reasons of precluding comorbidities,age and/or refusal,were compared with 74 patients who underwent resection to assess differences in rates of survival,recurrence/occurrence of malignancy,and prognostic factors.All study participants had dilatation of the main pancreatic duct by ≥ 5 mm,with or without dilatation of the branch ducts.Some of the nonsurgical patients showed evidence of mucus upon perendoscopic retrograde cholangiopancreatography or endoscopic ultrasound and/or after fine needle aspiration.For the surgical patients,pathologic analysis of resected specimens confirmed a diagnosis of IPMN with involvement of the main pancreatic duct or of both branch ducts as well as the main pancreatic duct.Clinical and biologic follow-ups were conducted for all patients at least annually,through hospitalization or consultation every six months during the first year of follow-up,together with abdominal imaging analysis(magnetic resonance cholangiopancreatography or computed tomography) and,if necessary,endoscopic ultrasound with or without fine needle aspiration.RESULTS:The overall five-year survival rate of patients who underwent resection was significantly greater than that for the nonsurgical patients(74% vs 58%; P =0.019).The parameters of age(< 70 years) and absence of a nodule were associated with better survival(P < 0.05); however,the parameters of main pancreatic duct diameter > 10 mm,branch ductdiameter > 30 mm,or presence of extra pancreatic cancers did not significantly influence the prognosis.In the nonsurgical patients,pancreatic malignancy occurred in 36% of cases within a mean time of 33 mo(median:29 mo; range:8-141 mo).Comparison of the nonsurgical patients who experienced disease progression with those who did not progress showed no significant differences in age,sex,symptoms,subtype of IPMN,or follow-up period; only the size of the main pancreatic duct was significantly different between these two sub-groups,with the nonsurgical patients who experienced progression showing a greater diameter at the time of diagnosis(> 10 mm).CONCLUSION:Patients unfit for surgery have a 36% greater risk of developing pancreatic malignancy of the main-duct or mixed IPMN within a median of 2.5 years.
