scholarly journals 4287 Extracellular vesicles as biomarkers for early detection of pancreatic cancer

2020 ◽  
Vol 4 (s1) ◽  
pp. 7-7
Author(s):  
Charles P Hinzman ◽  
Shivani Bansal ◽  
Yaoxiang Li ◽  
Partha Banerjee ◽  
Amrita Cheema
Keyword(s):  
Pancreatic Cancer ◽  
Early Detection ◽  
Cell Lines ◽  
Extracellular Vesicles ◽  
Late Stage ◽  
Normal Cell ◽  
Normal Pancreas ◽  
Pancreas Cell ◽  
Potential Biomarkers

OBJECTIVES/GOALS: Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related deaths by 2030. Though many other cancers have seen improvements in patient survival rates, patients diagnosed with PDAC have a 5-year survival rate of only ~9%. A major contributor to decreased survival is late-stage diagnosis of the disease. New methods of early detection are urgently needed. Extracellular vesicles (EVs) are secreted from cells of all tissue types into the circulation. EVs play important roles in a variety of diseases. They have shown to promote cancer progression and they are being studied as potential biomarkers for disease diagnosis. The purpose of this study was to perform qualitative and quantitative characterization of small-molecule profiles of EVs derived from various pancreatic cancer (PC) and normal pancreas cell lines, to provide proof-of-concept for evaluating the efficacy of leveraging EVs as potential biomarkers of PDAC. METHODS/STUDY POPULATION: EVs were isolated from the conditioned media of six PC and two normal pancreas cell lines using differential ultracentrifugation with filtration. EV enrichment was validated using quantitative ELISA, immunoblot and transmission electron microscopy. Targeted liquid chromatography coupled to mass spectrometry (LC-MS/MS) and untargeted (UPLC-QTOF-MS) metabolomics were used to analyze the biochemical composition of EVs. RESULTS/ANTICIPATED RESULTS: The biochemical profile of PC EVs was found to be significantly different from the profiles of normal cell EVs. Interestingly, amino acids were downregulated in PC EVs as compared to normal cell EVs. However, PC EVs were enriched in lactate and malate. PC EVs also had significant upregulation in other small molecules such as xanthosine, guanosine diphosphate and nicotinamide. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that the biochemical characterization of EVs using metabolomics has the potential to yield biomarkers which can delineate cancer cell-derived EVs from normal cell-derived EVs. Further work will test the clinical significance of these findings by similar analyses of plasma of PDAC patients. Furthermore, these profiles may be detectable before progression of the disease to late-stage PDAC, leading to the development of assays for earlier diagnosis in patients.

A Serum Marker for Early Pancreatic Cancer with a Possible Link to Diabetes

2021 ◽  
Author(s):  
Hoonsik Nam ◽  
Sunmi Kang ◽  
Min Seok Park ◽  
Suyeon Kang ◽  
Han Sun Kim ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Normal Cell ◽  
Diagnostic Performance ◽  
Early Stage ◽  
Serum Marker ◽  
Diabetic Patients ◽  
Diagnostic Biomarker ◽  
Diabetic Status ◽  
Validation Set

Abstract Background Pancreatic cancer (PC) has a grim prognosis, and an early diagnostic biomarker has been highly desired. The molecular link between diabetes and PC has not been well-established. Methods Bioinformatics screening was performed for a serum PC marker. Experiments in cell lines (5 PC and 1 normal cell lines), mouse models, and human tissue staining (37 PC and 10 normal cases) were performed to test asprosin production from PC. Asprosin’s diagnostic performance was tested with serums from multi-center cohorts (347 PC, 209 normal, and 55 additional diabetic subjects) and evaluated according to PC status, stages, and diabetic status, which was compared with that of CA19-9. Results Asprosin, a diabetes-related hormone, was found from the bioinformatics screening, and its production from PC was confirmed. Serum asprosin levels from multi-center cohorts yielded an age-adjusted diagnostic AUC of 0.987 (95% confidence interval [CI] = 0.961 to 0.997), superior to that of CA19-9 (AUC = 0.876, 95% CI = 0.847 to 0.905), and a cut-off of 7.18 ng/mL, at which the validation set exhibited a sensitivity of 0.957 and a specificity of 0.924. Importantly, the performance was maintained in early-stage and non-metastatic PC, consistent with the tissue staining. A slightly lower performance against additional diabetic patients (n = 55) was restored by combining asprosin and CA19-9 (AUC = 0.985, 95% CI = 0.975 to 0.995). Conclusion Asprosin is presented as an early-stage PC serum marker that may provide clues for PC-induced diabetes. Larger prospective clinical studies are warranted to solidify its utility.

Abstract 931: Enrichment and characterization of propagating circulating tumor cells from late stage prostate and pancreatic cancer patients

2015 ◽  
Author(s):  
James I. Lim ◽  
Charles J. Ryan ◽  
Thomas Krahn ◽  
Nikolas H. Stoecklein ◽  
Johannes Fischer ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Late Stage

scholarly journals MicroRNA-196a and -196b as Potential Biomarkers for the Early Detection of Familial Pancreatic Cancer

2014 ◽  
Vol 7 (4) ◽  
pp. 464-471 ◽  
Author(s):  
Emily P. Slater ◽  
Konstantin Strauch ◽  
Susanne Rospleszcz ◽  
Annette Ramaswamy ◽  
Irene Esposito ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Detection ◽  
Familial Pancreatic Cancer ◽  
Potential Biomarkers

scholarly journals Nanoparticle-Aided Detection of Colorectal Cancer-Associated Glycoconjugates of Extracellular Vesicles in Human Serum

2021 ◽  
Vol 22 (19) ◽  
pp. 10329
Author(s):  
Rufus Vinod ◽  
Randa Mahran ◽  
Erica Routila ◽  
Janne Leivo ◽  
Kim Pettersson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Human Serum ◽  
Cell Lines ◽  
Extracellular Vesicles ◽  
Late Stage ◽  
Early Stage ◽  
Biological Fluids ◽  
Serum Samples ◽  
Benign Condition ◽  
Hek 293

Extracellular vesicles (EVs) are found in all biological fluids, providing potential for the identification of disease biomarkers such as colorectal cancer (CRC). EVs are heavily glycosylated with specific glycoconjugates such as tetraspanins, integrins, and mucins, reflecting the characteristics of the original cell offering valuable targets for detection of CRC. We report here on europium-nanoparticle (EuNP)-based assay to detect and characterize different surface glycoconjugates of EVs without extensive purification steps from five different CRC and the HEK 293 cell lines. The promising EVs candidates from cell culture were clinically evaluated on small panel of serum samples including early-stage (n = 11) and late-stage (n = 11) CRC patients, benign condition (n = 11), and healthy control (n = 10). The majority of CRC cell lines expressed tetraspanin sub-population and glycovariants of integrins and conventional tumor markers. The subpopulation of CD151 having CD63 expression (CD151CD63) was significantly (p = 0.001) elevated in early-stage CRC (8 out of 11) without detecting any benign and late-stage samples, while conventional CEA detected mostly late-stage CRC (p = 0.045) and with only four early-stage cases. The other glycovariant assays such as CEACon-A, CA125WGA, CA 19.9Ma696, and CA 19.9Con-A further provided some complementation to the CD151CD63 assay. These results indicate the potential application of CD151CD63 assay for early detection of CRC patients in human serum.

scholarly journals A multi-omics approach identifies pancreatic cancer cell extracellular vesicles as mediators of the unfolded protein response in normal pancreatic epithelial cells.

2021 ◽  
Author(s):  
Charles P Hinzman ◽  
Shivani Bansal ◽  
Yaoxiang Li ◽  
Anton Iliuk ◽  
Michael Girgis ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Epithelial Cells ◽  
Palmitic Acid ◽  
Er Stress ◽  
Extracellular Vesicles ◽  
Normal Pancreas ◽  
Normal Cells ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Although cancer-derived extracellular vesicles (cEVs) are thought to play a pivotal role in promoting cancer progression events, their precise effect on neighboring normal cells is unknown. In this study, we investigated the impact of pancreatic cancer ductal adenocarcinoma (PDAC) derived EVs on recipient non-tumorigenic pancreatic normal epithelial cells upon internalization. We show that PDAC cEVs increase the proliferation and invasive capability of treated normal cells. We further demonstrate that cEVs induce endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in treated normal pancreatic epithelial cells within 24 hours. Subsequently, these cells release several inflammatory cytokines. Leveraging a layered multi-omics approach, we analyzed EV cargo from a panel of 6 PDAC and 2 normal pancreas cell lines, using multiple EV isolation methods. We found that cEVs were enriched for an array of biomolecules which can induce or regulate ER stress and the UPR, including palmitic acid, sphingomyelins, metabolic regulators of tRNA charging and proteins which regulate trafficking and degradation. We further show that palmitic acid, at doses relevant to those found in cEVs, is sufficient to induce ER stress in normal pancreas cells. These results suggest that cEV cargo packaging may be designed to disseminate proliferative and invasive characteristics upon internalization by distant recipient normal cells, hitherto unreported. This study is among the first to highlight a major role for PDAC cEVs to induce stress in treated normal pancreas cells that may modulate a systemic response leading to altered phenotypes. For the first time, our study implicates cEV transported palmitic acid as a potential driver in this process. These findings highlight the importance of EVs in mediating disease etiology and open potential areas of investigation toward understanding the role of cEV lipids in promoting cell transformation in the surrounding microenvironment.

Characterization of Ovarian Cancer-Derived Extracellular Vesicles by Surface-Enhanced Raman Spectroscopy

The Analyst ◽  
2021 ◽  
Author(s):  
Nina Culum ◽  
Tyler T. Cooper ◽  
Gilles Lajoie ◽  
Thamara Dayarathna ◽  
Stephen H. Pasternak ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Raman Spectroscopy ◽  
Extracellular Vesicles ◽  
Late Stage ◽  
Surface Enhanced Raman Spectroscopy ◽  
Gynecological Malignancy ◽  
Surface Enhanced ◽  
Surface Enhanced Raman

Ovarian cancer is the most lethal gynecological malignancy, owing to the fact that most cases are diagnosed at a late stage. To improve prognosis and reduce mortality, we must develop...

scholarly journals Characterization of novel carcinoma cell lines for the analysis of therapeutical strategies fighting pancreatic cancer

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Dietmar Zechner ◽  
Florian Bürtin ◽  
Jonas Amme ◽  
Tobias Lindner ◽  
Tobias Radecke ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Carcinoma Cell Lines

scholarly journals A novel bioinformatics pipeline for identification and characterization of fusion transcripts in breast cancer and normal cell lines

2011 ◽  
Vol 39 (15) ◽  
pp. e100-e100 ◽  
Author(s):  
Yan W. Asmann ◽  
Asif Hossain ◽  
Brian M. Necela ◽  
Sumit Middha ◽  
Krishna R. Kalari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Normal Cell ◽  
Bioinformatics Pipeline ◽  
Fusion Transcripts ◽  
Identification And Characterization
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