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Journal ArticleDOI

A Compendium of Potential Biomarkers of Pancreatic Cancer

TL;DR: A compendium of potential biomarkers that can be systematically validated by the pancreatic cancer community is described.
Abstract: Akhilesh Pandey and colleagues describe a compendium of potential biomarkers that can be systematically validated by the pancreatic cancer community.

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Journal ArticleDOI
TL;DR: In this paper, it is shown that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer, and it is clear that multi-disciplinary care is the best way to care for patients.
Abstract: Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in our understanding of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer.

770 citations


Cites background from "A Compendium of Potential Biomarker..."

  • ...The list of genes abnormally overexpressed in pancreatic cancer is large, and includes proteins such as mesothelin, trefoil factor 1, prostate stem cell antigen, claudin 4, and several of the S100-related proteins.(92) These overexpressed genes are potentially clinically important for 2 reasons....

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  • ...that are secreted, could form the basis for a clinical test for the detection of pancreatic cancer.(92) Of interest, Wang et al have suggested that one could integrate our understanding of the genes that are genetically altered with those that are expressed in pancreatic cancer to develop a test that detects mutant proteins shed by the cancers....

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Book ChapterDOI
01 Jan 2010
TL;DR: Local aggressiveness consists in the invasion of contiguous structures and organs (spleen, stomach, left adrenal gland, colon, and peritoneum), whereas distant metastases can occur in liver, lungs, adrenals, kidneys, bones, brain, and skin.
Abstract: PDAC is an aggressive disease and early infiltrates peripancreatic tissues and adjacent organs, and gives distant metastasis and peritoneal involvement, making often surgical resection impossible. About 80% of PDACs are inoperable at the time of diagnosis. However, even if radiologically resectable, some PDAC microscopically involves the resection margins (pancreatic, retroperitoneal, or biliary, the retroperitoneal being the most important because it cannot be evaluated intraoperatorially) resulting in a nonradical excision. Local aggressiveness consists in the invasion of contiguous structures and organs (spleen, stomach, left adrenal gland, colon, and peritoneum), whereas distant metastases can occur in liver, lungs, adrenals, kidneys, bones, brain, and skin.

663 citations

Journal ArticleDOI
TL;DR: Serum CA 19-9 serum levels can provide important information with regards to prognosis, overall survival, and response to chemotherapy as well as predict post-operative recurrence, but non-specific expression in several benign and malignant diseases, false negative results in Lewis negative genotype and an increased false positive results in the presence of obstructive jaundice severely limit the universal applicability of serum CA 19,9 levels in pancreatic cancer management.
Abstract: Background: Serum carbohydrate antigen (CA 19-9) is the most common tumor marker assessed in pancreatic cancer patients; nevertheless few articles have comprehensively evaluated the evidence for its utility in pancreatic cancer management. Methods: Literature search was performed using Medline with keywords “pancreatic cancer” “tumor markers” “CA 19-9” “diagnosis” “screening” “prognosis” “resectability” and “recurrence”. All English language articles pertaining to the role of CA 19-9 in pancreatic cancer were critically analyzed to determine its utility as a biomarker for pancreatic cancer. Results: Serum CA 19-9 is the most extensively validated pancreatic cancer biomarker with multiple clinical applications. CA 19-9 serum levels have a sensitivity and specificity of 79-81% and 82-90% respectively for the diagnosis of pancreatic cancer in symptomatic patients; but are not useful as a screening marker because of low positive predictive value (0.5-0.9%). Pre-operative CA 19-9 serum levels provide useful prognostic information as patients with normal levels ( 37 U/ml) (12-15 months). A CA 19-9 serum level of 100 U/ml suggest unresectablity or metastatic disease. Normalization or a decrease in post-operative CA 19-9 serum levels by ≥ 20-50% from baseline following surgical resection or chemotherapy is associated with prolonged survival compared to failure of CA 19-9 serum levels to normalize or an increase. Important limitations to CA 19-9 serum level evaluation in pancreatic cancer include poor sensitivity, false negative results in Lewis negative phenotype (5-10%) and increased false positivity in the presence of obstructive jaundice (10-60%). Conclusion: CA 19-9 is the most extensively studied and validated serum biomarker for the diagnosis of pancreatic cancer in symptomatic patients. CA 19-9 serum levels can provide important information with regards to prognosis, overall survival, and response to chemotherapy as well as predict post-operative recurrence. However, non-specific expression in several benign and malignant diseases, false negative results in Lewis negative genotype and an increased false positive results in the presence of obstructive jaundice severely limit the universal applicability of serum CA 19-9 levels in pancreatic cancer management.

583 citations

Journal ArticleDOI
TL;DR: The GeneMANIA Cytoscape plugin brings fast gene function prediction capabilities to the desktop using over 800 networks from six organisms and each related gene is traceable to the source network used to make the prediction.
Abstract: Summary: The GeneMANIA Cytoscape plugin brings fast gene function prediction capabilities to the desktop. GeneMANIA identifies the most related genes to a query gene set using a guilt-by-association approach. The plugin uses over 800 networks from six organisms and each related gene is traceable to the source network used to make the prediction. Users may add their own interaction networks and expression profile data to complement or override the default data. Availability and Implementation: The GeneMANIA Cytoscape plugin is implemented in Java and is freely available at http://www.genemania.org/plugin/. Contact:gary.bader@utoronto.ca; quaid.morris@utoronto.ca

535 citations

Journal ArticleDOI
TL;DR: This Perspective compares areas of proteomics broadly usable today with those that require significant technical and conceptual development and hopes to provide nonexperts with a guide for calibrating expectations of what can realistically be learned from a proteomics experiment and for gauging the planning and execution effort.
Abstract: The evolution of mass spectrometry-based proteomic technologies has advanced our understanding of the complex and dynamic nature of proteomes while concurrently revealing that no 'one-size-fits-all' proteomic strategy can be used to address all biological questions. Whereas some techniques, such as those for analyzing protein complexes, have matured and are broadly applied with great success, others, such as global quantitative protein expression profiling for biomarker discovery, are still confined to a few expert laboratories. In this Perspective, we attempt to distill the wide array of conceivable proteomic approaches into a compact canon of techniques suited to asking and answering specific types of biological questions. By discussing the relationship between the complexity of a biological sample and the difficulty of implementing the appropriate analysis approach, we contrast areas of proteomics broadly usable today with those that require significant technical and conceptual development. We hope to provide nonexperts with a guide for calibrating expectations of what can realistically be learned from a proteomics experiment and for gauging the planning and execution effort. We further provide a detailed supplement explaining the most common techniques in proteomics.

430 citations


Additional excerpts

  • ...A commonly successful technique has been initial discovery in pooled samples to identify dominant effects and then verification and exploration of biodiversity in follow-up studies on individual sample...

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References
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Journal ArticleDOI
TL;DR: ONCOMINE is presented, a cancer microarray database and web-based data-mining platform aimed at facilitating discovery from genome-wide expression analyses and novel biomarkers and therapeutic targets are discovered.

3,244 citations

Journal ArticleDOI
TL;DR: A summary of the GEO database structure and user facilities is provided, and recent enhancements to database design, performance, submission format options, data query and retrieval utilities are described.
Abstract: The Gene Expression Omnibus (GEO) repository at the National Center for Biotechnology Information (NCBI) archives and freely disseminates microarray and other forms of high-throughput data generated by the scientific community. The database has a minimum information about a microarray experiment (MIAME)-compliant infrastructure that captures fully annotated raw and processed data. Several data deposit options and formats are supported, including web forms, spreadsheets, XML and Simple Omnibus Format in Text (SOFT). In addition to data storage, a collection of user-friendly web-based interfaces and applications are available to help users effectively explore, visualize and download the thousands of experiments and tens of millions of gene expression patterns stored in GEO. This paper provides a summary of the GEO database structure and user facilities, and describes recent enhancements to database design, performance, submission format options, data query and retrieval utilities. GEO is accessible at http://www.ncbi.nlm.nih.gov/geo/

1,400 citations

Journal ArticleDOI
TL;DR: Data indicate that stellate cells have an important role in supporting and promoting pancreatic cancer, and the presence of HPSCs in tumors increases the growth and metastasis of these cells.
Abstract: Pancreatic adenocarcinoma is characterized by a dense background of tumor associated stroma originating from abundant pancreatic stellate cells. The aim of this study was to determine the effect of human pancreatic stellate cells (HPSC) on pancreatic tumor progression. HPSCs were isolated from resected pancreatic adenocarcinoma samples and immortalized with telomerase and SV40 large T antigen. Effects of HPSC conditioned medium (HPSC-CM) on in vitro proliferation, migration, invasion, soft-agar colony formation, and survival in the presence of gemcitabine or radiation therapy were measured in two pancreatic cancer cell lines. The effects of HPSCs on tumors were examined in an orthotopic murine model of pancreatic cancer by co-injecting them with cancer cells and analyzing growth and metastasis. HPSC-CM dose-dependently increased BxPC3 and Panc1 tumor cell proliferation, migration, invasion, and colony formation. Furthermore, gemcitabine and radiation therapy were less effective in tumor cells treated with HPSC-CM. HPSC-CM activated the mitogen-activated protein kinase and Akt pathways in tumor cells. Co-injection of tumor cells with HPSCs in an orthotopic model resulted in increased primary tumor incidence, size, and metastasis, which corresponded with the proportion of HPSCs. HPSCs produce soluble factors that stimulate signaling pathways related to proliferation and survival of pancreatic cancer cells, and the presence of HPSCs in tumors increases the growth and metastasis of these cells. These data indicate that stellate cells have an important role in supporting and promoting pancreatic cancer. Identification of HPSC-derived factors may lead to novel stroma-targeted therapies for pancreatic cancer.

1,010 citations


"A Compendium of Potential Biomarker..." refers background in this paper

  • ...The role of the stromal component in pancreatic cancer progression is also being investigated, and recent reports provide experimental evidence to show the effect of the tumor microenvironment in promoting pancreatic cancers [14]....

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Journal ArticleDOI
TL;DR: The purpose of this meeting was to define an international acceptable set of diagnostic criteria for PanINs and IPMNs and to address a number of ambiguities that exist in the previously reported classification systems for these neoplasms.
Abstract: Invasive pancreatic ductal adenocarcinoma is an almost uniformly fatal disease. Several distinct noninvasive precursor lesions can give rise to invasive adenocarcinoma of the pancreas, and the prevention, detection, and treatment of these noninvasive lesions offers the potential to cure early pancreatic cancers. Noninvasive precursors of invasive ductal adenocarcinoma of the pancreas include pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms. Diagnostic criteria, including a distinct ovarian-type stroma, and a consistent nomenclature are well established for mucinous cystic neoplasms. By contrast, consistent nomenclatures and diagnostic criteria have been more difficult to establish for PanINs and IPMNs. Because both PanINs and IPMNs consist of intraductal neoplastic proliferations of columnar, mucin-containing cells with a variable degree of papilla formation, the distinction between these two classes of precursor lesions remains problematic. Thus, considerable ambiguities still exist in the classification of noninvasive neoplasms in the pancreatic ducts. A meeting of international experts on precursor lesions of pancreatic cancer was held at The Johns Hopkins Hospital from August 18 to 19, 2003. The purpose of this meeting was to define an international acceptable set of diagnostic criteria for PanINs and IPMNs and to address a number of ambiguities that exist in the previously reported classification systems for these neoplasms. We present a consensus classification of the precursor lesions in the pancreatic ducts, PanINs and IPMNs.

991 citations


"A Compendium of Potential Biomarker..." refers background in this paper

  • ...Pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms are well-defined precursor lesions of invasive pancreatic cancer [6]....

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Journal ArticleDOI
TL;DR: The ArrayExpress Repository and Data Warehouse is a database of gene expression profiles selected from the repository and consistently re-annotated, which contains data from >50 000 hybridizations and >1 500‬000 individual expression profiles.
Abstract: UNLABELLED ArrayExpress is a public database for high throughput functional genomics data. ArrayExpress consists of two parts--the ArrayExpress Repository, which is a MIAME supportive public archive of microarray data, and the ArrayExpress Data Warehouse, which is a database of gene expression profiles selected from the repository and consistently re-annotated. Archived experiments can be queried by experiment attributes, such as keywords, species, array platform, authors, journals or accession numbers. Gene expression profiles can be queried by gene names and properties, such as Gene Ontology terms and gene expression profiles can be visualized. ArrayExpress is a rapidly growing database, currently it contains data from >50,000 hybridizations and >1,500,000 individual expression profiles. ArrayExpress supports community standards, including MIAME, MAGE-ML and more recently the proposal for a spreadsheet based data exchange format: MAGE-TAB. AVAILABILITY www.ebi.ac.uk/arrayexpress.

644 citations

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