scholarly journals Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach

2020 ◽  
Vol 21 (7) ◽  
pp. 2403
Author(s):  
Sahar Ghassem-Zadeh ◽  
Katrin Hufnagel ◽  
Andrea Bauer ◽  
Jean-Louis Frossard ◽  
Masaru Yoshida ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Autoimmune Pancreatitis ◽  
Large Scale ◽  
Gastrointestinal Disease ◽  
Protein Microarray ◽  
Cost Effective ◽  
Protein Microarrays ◽  
Large Scale Analysis ◽  
Diagnostic Modalities

Identification of disease-associated autoantibodies is of high importance. Their assessment could complement current diagnostic modalities and assist the clinical management of patients. We aimed at developing and validating high-throughput protein microarrays able to screen patients’ sera to determine disease-specific autoantibody-signatures for pancreatic cancer (PDAC), chronic pancreatitis (CP), autoimmune pancreatitis and their subtypes (AIP-1 and AIP-2). In-house manufactured microarrays were used for autoantibody-profiling of IgG-enriched preoperative sera from PDAC-, CP-, AIP-1-, AIP-2-, other gastrointestinal disease (GID) patients and healthy controls. As a top-down strategy, three different fluorescence detection-based protein-microarrays were used: large with 6400, intermediate with 345, and small with 36 full-length human recombinant proteins. Large-scale analysis revealed 89 PDAC, 98 CP and 104 AIP immunogenic antigens. Narrowing the selection to 29 autoantigens using pooled sera first and individual sera afterwards allowed a discrimination of CP and AIP from PDAC. For validation, predictive models based on the identified antigens were generated which enabled discrimination between PDAC and AIP-1 or AIP-2 yielded high AUC values of 0.940 and 0.925, respectively. A new repertoire of autoantigens was identified and their assembly as a multiplex test will provide a fast and cost-effective tool for differential diagnosis of pancreatic diseases with high clinical relevance.

Crizotinib and Testing for ALK

2011 ◽  
Vol 9 (12) ◽  
pp. 1335-1341 ◽  
Author(s):  
Alice T. Shaw ◽  
Benjamin Solomon ◽  
Mari Mino Kenudson
Keyword(s):  
Large Scale ◽  
Cost Effective ◽  
Screening Strategy ◽  
Current Standard ◽  
Multicenter Studies ◽  
Kinase Gene ◽  
Anaplastic Lymphoma ◽  
Anaplastic Lymphoma Kinase Gene ◽  
Diagnostic Modalities ◽  
Us Fda

Crizotinib was recently approved by the US FDA for the treatment of advanced non–small cell lung cancer (NSCLC) harboring the ALK (anaplastic lymphoma kinase) gene rearrangement. To ensure identification of patients most likely to benefit, the FDA approved crizotinib concurrently with a companion diagnostic test—the Vysis ALK Break Apart FISH Probe Kit. This kit was used in 1 of the 2 pivotal trials leading to the FDA approval of crizotinib and has become the gold standard for detecting ALK rearrangement in NSCLC. Although ALK FISH is clinically validated, the assay can be technically challenging and costly. Therefore, other diagnostic modalities are being explored, including immunohistochemistry (IHC) and reverse transcriptase–polymerase chain reaction. This article provides an overview of the diagnostic assays available for detecting ALK rearrangement. Each assay, including ALK FISH, has its strengths and weaknesses. Recent work with commercially available ALK antibodies suggests that IHC-based tests may represent a reliable and cost-effective screening strategy; however, large multicenter studies comparing IHC with FISH are needed to validate ALK IHC. While ALK FISH remains the current standard for diagnosing ALK positivity, large-scale screening of patients with newly diagnosed advanced NSCLC, as recommended by NCCN, may require development and validation of alternative screening strategies, such as combination IHC and FISH.

scholarly journals PET-PANC: multicentre prospective diagnostic accuracy and health economic analysis study of the impact of combined modality 18fluorine-2-fluoro-2-deoxy-d-glucose positron emission tomography with computed tomography scanning in the diagnosis and management of pancreatic cancer

2018 ◽  
Vol 22 (7) ◽  
pp. 1-114 ◽  
Author(s):  
Paula Ghaneh ◽  
Robert Hanson ◽  
Andrew Titman ◽  
Gill Lancaster ◽  
Catrin Plumpton ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Diagnostic Accuracy ◽  
Cost Effective ◽  
Diagnostic Value ◽  
Pet Ct ◽  
Diagnostic Work ◽  
Work Up ◽  
Diagnostic Work Up

Background Pancreatic cancer diagnosis and staging can be difficult in 10–20% of patients. Positron emission tomography (PET)/computed tomography (CT) adds precise anatomical localisation to functional data. The use of PET/CT may add further value to the diagnosis and staging of pancreatic cancer. Objective To determine the incremental diagnostic accuracy and impact of PET/CT in addition to standard diagnostic work-up in patients with suspected pancreatic cancer. Design A multicentre prospective diagnostic accuracy and clinical value study of PET/CT in suspected pancreatic malignancy. Participants Patients with suspected pancreatic malignancy. Interventions All patients to undergo PET/CT following standard diagnostic work-up. Main outcome measures The primary outcome was the incremental diagnostic value of PET/CT in addition to standard diagnostic work-up with multidetector computed tomography (MDCT). Secondary outcomes were (1) changes in patients’ diagnosis, staging and management as a result of PET/CT; (2) changes in the costs and effectiveness of patient management as a result of PET/CT; (3) the incremental diagnostic value of PET/CT in chronic pancreatitis; (4) the identification of groups of patients who would benefit most from PET/CT; and (5) the incremental diagnostic value of PET/CT in other pancreatic tumours. Results Between 2011 and 2013, 589 patients with suspected pancreatic cancer underwent MDCT and PET/CT, with 550 patients having complete data and in-range PET/CT. Sensitivity and specificity for the diagnosis of pancreatic cancer were 88.5% and 70.6%, respectively, for MDCT and 92.7% and 75.8%, respectively, for PET/CT. The maximum standardised uptake value (SUVmax.) for a pancreatic cancer diagnosis was 7.5. PET/CT demonstrated a significant improvement in relative sensitivity (p = 0.01) and specificity (p = 0.023) compared with MDCT. Incremental likelihood ratios demonstrated that PET/CT significantly improved diagnostic accuracy in all scenarios (p < 0.0002). PET/CT correctly changed the staging of pancreatic cancer in 56 patients (p = 0.001). PET/CT influenced management in 250 (45%) patients. PET/CT stopped resection in 58 (20%) patients who were due to have surgery. The benefit of PET/CT was limited in patients with chronic pancreatitis or other pancreatic tumours. PET/CT was associated with a gain in quality-adjusted life-years of 0.0157 (95% confidence interval –0.0101 to 0.0430). In the base-case model PET/CT was seen to dominate MDCT alone and is thus highly likely to be cost-effective for the UK NHS. PET/CT was seen to be most cost-effective for the subgroup of patients with suspected pancreatic cancer who were thought to be resectable. Conclusion PET/CT provided a significant incremental diagnostic benefit in the diagnosis of pancreatic cancer and significantly influenced the staging and management of patients. PET/CT had limited utility in chronic pancreatitis and other pancreatic tumours. PET/CT is likely to be cost-effective at current reimbursement rates for PET/CT to the UK NHS. This was not a randomised controlled trial and therefore we do not have any information from patients who would have undergone MDCT only for comparison. In addition, there were issues in estimating costs for PET/CT. Future work should evaluate the role of PET/CT in intraductal papillary mucinous neoplasm and prognosis and response to therapy in patients with pancreatic cancer. Study registration Current Controlled Trials ISRCTN73852054 and UKCRN 8166. Funding The National Institute for Health Research Health Technology Assessment programme.

scholarly journals Rapid Screening of the Epidermal Growth Factor Receptor Phosphosignaling Pathway via Microplate-Based Dot Blot Assays

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Amedeo Cappione ◽  
Janet Smith ◽  
Masaharu Mabuchi ◽  
Timothy Nadler
Keyword(s):  
Large Scale ◽  
Solid Phase ◽  
Growth Factor Receptor ◽  
Cost Effective ◽  
Protein Microarrays ◽  
Rapid Screening ◽  
Dot Blot ◽  
A431 Cells ◽  
Dot Blot Assay ◽  
Multiple Samples

Expression profiling on a large scale, as is the case in drug discovery, is often accomplished through use of sophisticated solid-phase protein microarrays or multiplex bead technologies. While offering both high-throughput and high-content analysis, these platforms are often too cost prohibitive or technically challenging for many research settings. Capitalizing on the favorable attributes of the standard ELISA and slot blotting techniques, we developed a modified dot blot assay that provides a simple cost-effective alternative for semiquantitative expression analysis of multiple proteins across multiple samples. Similar in protocol to an ELISA, but based in a membrane bound 96-well microplate, the assay takes advantage of vacuum filtration to expedite the tedious process of washing in between binding steps. We report on the optimization of the assay and demonstrate its use in profiling temporal changes in phosphorylation events in the well-characterized EGF-induced signaling cascade of A431 cells.

scholarly journals Screening of Pancreatic Cancer for Early Diagnosis

2021 ◽  
Vol 96 (2) ◽  
pp. 110-115
Author(s):  
Jae Hyuck Chang
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
General Population ◽  
Early Detection ◽  
Early Diagnosis ◽  
Average Risk ◽  
Cystic Lesions ◽  
Diagnostic Modalities ◽  
Low Prevalence ◽  
New Onset

Over 80% of patients with pancreatic ductal adenocarcinomas (PDAs) present with symptomatic, surgically unresectable disease. If a “stage shift” from the current 20% proportion of resectability to early detection could be achieved, this would greatly improve the survival of patients with this generally dismal disease. Although the goal of early detection is laudable, the relatively low prevalence of PDA renders general population screening unfeasible. To avoid the perils of overdiagnosis and to focus early detection efforts on individuals deemed to be at higher-than-average risk, we need to define such subsets of individuals, such as kindred of existing patients and those with precursor cystic lesions, chronic pancreatitis, and new-onset diabetes. The next step is to determine when and how often to monitor at-risk individuals and the diagnostic modalities that will be employed in the surveillance. Enormous challenges remain in terms of validated blood-based biomarkers, imaging modalities, and when and how often surveillance.

scholarly journals Methylation content sensitive enzyme ddRAD (MCSeEd): a reference-free, whole genome profiling system to address cytosine/ adenine methylation changes

2019 ◽  
Author(s):  
Gianpiero Marconi ◽  
Stefano Capomaccio ◽  
Cinzia Comino ◽  
Alberto Acquadro ◽  
Ezio Portis ◽  
...  
Keyword(s):  
Large Scale ◽  
Reference Genome ◽  
Cost Effective ◽  
Whole Genome ◽  
High Coverage ◽  
Reduced Representation ◽  
Large Scale Analysis ◽  
Genome Methylation ◽  
Cost Effective Approach ◽  
Single Nucleotide Polymorphism Calling

AbstractMethods for investigating DNA methylation nowadays either require a reference genome and high coverage, or investigate only CG methylation. Moreover, no large-scale analysis can be performed for N6-methyladenosine (6mA). Here we describe the methylation content sensitive enzyme double-digest restriction-site-associated DNA (ddRAD) technique (MCSeEd), a reduced-representation, reference-free, cost-effective approach for characterizing whole genome methylation patterns across different methylation contexts (e.g., CG, CHG, CHH, 6mA). MCSeEd can also detect genetic variations among hundreds of samples. MCSeEd is based on parallel restrictions carried out by combinations of methylation insensitive and sensitive endonucleases, followed by next-generation sequencing. Moreover, we present a robust bioinformatic pipeline (available at https://bitbucket.org/capemaster/mcseed/src/master/) for differential methylation analysis combined with single nucleotide polymorphism calling without or with a reference genome.

scholarly journals Tumor-Forming Autoimmune Pancreatitis Confused with Pancreatic Cancer That Developed during the Course of Chronic Pancreatitis

2017 ◽  
Vol 50 (11) ◽  
pp. 888-896
Author(s):  
Nobutake Tanaka ◽  
Tsutomu Fujii ◽  
Suguru Yamada ◽  
Hideki Takami ◽  
Masamichi Hayashi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Autoimmune Pancreatitis

scholarly journals Optimization of Rolling-Circle Amplified Protein Microarrays for Multiplexed Protein Profiling

2003 ◽  
Vol 2003 (5) ◽  
pp. 299-307 ◽  
Author(s):  
Weiping Shao ◽  
Zhimin Zhou ◽  
Isabelle Laroche ◽  
Hong Lu ◽  
Qiuling Zong ◽  
...  
Keyword(s):  
High Throughput ◽  
Signal Amplification ◽  
Protein Microarray ◽  
Cost Effective ◽  
Protein Microarrays ◽  
Clinical Applications ◽  
Protein Profiling ◽  
Antibody Microarray ◽  
High Throughput Analysis ◽  
Rolling Circle

Protein microarray-based approaches are increasingly being used in research and clinical applications to either profile the expression of proteins or screen molecular interactions. The development of high-throughput, sensitive, convenient, and cost-effective formats for detecting proteins is a necessity for the effective advancement of understanding disease processes. In this paper, we describe the generation of highly multiplexed, antibody-based, specific, and sensitive protein microarrays coupled with rolling-circle signal amplification (RCA) technology. A total of 150 cytokines were simultaneously detected in an RCA sandwich immunoassay format. Greater than half of these proteins have detection sensitivities in the pg/ml range. The validation of antibody microarray with human serum indicated that RCA-based protein microarrays are a powerful tool for high-throughput analysis of protein expression and molecular diagnostics.

scholarly journals Autoimmune pancreatitis with associated ulcerative colitis in a teenager

2018 ◽  
Vol 11 (1) ◽  
pp. e227888
Author(s):  
Carolina Isabel Gouveia ◽  
Laura Oliveira ◽  
António P Campos ◽  
José Cabral
Keyword(s):  
Ulcerative Colitis ◽  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Obstructive Jaundice ◽  
Autoimmune Pancreatitis ◽  
Pancreatic Mass ◽  
Rare Entity ◽  
Clinical Challenge ◽  
Head Of The Pancreas

Autoimmune pancreatitis (AIP) is a rare entity that is extremely uncommon in children. Its diagnosis is also a clinical challenge. This form of chronic pancreatitis often presents itself with obstructive jaundice and/or a pancreatic mass and it is sometimes misdiagnosed as pancreatic cancer. We describe the case of a 13-year-old boy with obstructive jaundice and a 4 cm mass in the head of the pancreas that was diagnosed as AIP with associated ulcerative colitis.

scholarly journals Methylation content sensitive enzyme ddRAD (MCSeEd): a reference-free, whole genome profiling system to address cytosine/adenine methylation changes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gianpiero Marconi ◽  
Stefano Capomaccio ◽  
Cinzia Comino ◽  
Alberto Acquadro ◽  
Ezio Portis ◽  
...  
Keyword(s):  
Large Scale ◽  
Reference Genome ◽  
Cost Effective ◽  
Whole Genome ◽  
High Coverage ◽  
Reduced Representation ◽  
Large Scale Analysis ◽  
Genome Methylation ◽  
Cost Effective Approach ◽  
Single Nucleotide Polymorphism Calling

Abstract Methods for investigating DNA methylation nowadays either require a reference genome and high coverage, or investigate only CG methylation. Moreover, no large-scale analysis can be performed for N6-methyladenosine (6 mA) at an affordable price. Here we describe the methylation content sensitive enzyme double-digest restriction-site-associated DNA (ddRAD) technique (MCSeEd), a reduced-representation, reference-free, cost-effective approach for characterizing whole genome methylation patterns across different methylation contexts (e.g., CG, CHG, CHH, 6 mA). MCSeEd can also detect genetic variations among hundreds of samples. MCSeEd is based on parallel restrictions carried out by combinations of methylation insensitive and sensitive endonucleases, followed by next-generation sequencing. Moreover, we present a robust bioinformatic pipeline (available at https://bitbucket.org/capemaster/mcseed/src/master/) for differential methylation analysis combined with single nucleotide polymorphism calling without or with a reference genome.

Pancreatic cancer or autoimmune pancreatitis: endosonography as a diagnostic reviser

2013 ◽  
Vol 154 (2) ◽  
pp. 62-68 ◽  
Author(s):  
Zoltán Szepes ◽  
Mariann Dobra ◽  
Csaba Góg ◽  
Edit Zábrák ◽  
Éva Makula ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Health Care Providers ◽  
Computer Tomography ◽  
Autoimmune Pancreatitis ◽  
Imaging Techniques ◽  
Tumor Staging ◽  
Cost Effective ◽  
Abdominal Ultrasound ◽  
Care Providers ◽  
Increased Risk

Conventional radiologic imaging (abdominal ultrasound, computer tomography) used in the differential diagnosis of post-hepatic jaundice can frequently provide inaccurate diagnosis. Inflammatory lesions may mimic neoplastic processes and malignancy may be accompanied by perifocal inflammation resulting in histological misdiagnosis. Furthermore, chronic and autoimmune pancreatitis are associated with an increased risk for pancreatic cancer. Radial endosonography has become a markedly important method in the imaging of the pancreas. It has a crucial role in the diagnosis and staging of pancreatic cancer. The authors present three cases where the diagnosis of pancreatic cancer determined by conventional imaging techniques (abdominal ultrasound, computer tomography, endoscopic retrograde cholangiopancreatography) was excluded or confirmed by the radial endosonography. The authors conclude that radial endosonography is an essential complementary method among imaging techniques of the pancreas and in tumor staging. Application of that may prevent unnecessary surgeries, which is obviously useful for patients and cost effective for health care providers. Orv. Hetil., 2013, 154, 62–68.

Sign in / Sign up

Export Citation Format

Share Document