scholarly journals c-Met and PD-L1 on Circulating Exosomes as Diagnostic and Prognostic Markers for Pancreatic Cancer

2019 ◽  
Vol 20 (13) ◽  
pp. 3305 ◽  
Author(s):  
Alexander Lux ◽  
Christoph Kahlert ◽  
Robert Grützmann ◽  
Christian Pilarsky
Keyword(s):  
Pancreatic Cancer ◽  
Survival Time ◽  
Fluorescence Intensity ◽  
Culture Media ◽  
Diagnostic Odds Ratio ◽  
Postoperative Survival ◽  
Ductal Adenocarcinoma ◽  
Serum Samples ◽  
Pancreatic Cell ◽  
Significant Difference

Exosomes are membrane vesicles which offer potential as blood derived biomarkers for malign tumors in clinical practice. Pancreatic cancer is counted among cancer diseases with the highest mortality. The present work seeks to assess whether pancreatic carcinomas release exosomes which express c-Met (proto-oncogene mesenchymal-epithelial transition factor) and PD-L1 (programmed cell death 1 ligand 1), and whether the detection of such expression in serum has diagnostic or prognostic meaning for the affected patients. Exosome isolation was performed on culture media of one benign pancreatic cell line and ten pancreatic carcinoma cell lines as well as on serum samples from 55 patients with pancreatic ductal adenocarcinoma (PDAC), 26 patients with chronic pancreatitis and 10 patients with benign serous cyst adenoma of the pancreas. Exosomes were bound to latex beads and stained with antibodies against c-Met or PD-L1. Analysis of fluorescence intensity was performed by flow cytometry. In terms of c-Met, the mean fluorescence intensity of PDAC-patients was significantly higher than the fluorescence intensity of the comparative patients with benign disease (p < 0.001). A diagnostic test based on c-Met resulted in a sensitivity of 70%, a specificity of 85% and a diagnostic odds ratio of 13:2. The specificity of the test can be further improved by combining it with the established tumor marker carbohydrate antigen 19-9 (CA 19-9). In addition, c-Met-positive patients showed a significantly shorter postoperative survival time (9.5 vs. 21.7 months, p < 0.001). In terms of PD-L1, no significant difference between fluorescence intensity of PDAC-patients and comparative patients was detectable. However, PD-L1-positive PDAC-patients also showed a significantly shorter postoperative survival time (7.8 vs. 17.2 months, p = 0.043). Thus, both markers can be considered as negative prognostic factors.

scholarly journals Cohort study of the overall survival of patients with pancreatic cancer in a hospital of specialties of Quito-Ecuador in the period 2007–2017

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Andrés Moreno Roca ◽  
Luciana Armijos Acurio ◽  
Ruth Jimbo Sotomayor ◽  
Carlos Céspedes Rivadeneira ◽  
Carlos Rosero Reyes ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cohort Study ◽  
Survival Time ◽  
Univariate Analysis ◽  
Rank Test ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Icd 10 ◽  
The Difference ◽  
Clinical Records

Abstract Objectives Pancreatic cancers in most patients in Ecuador are diagnosed at an advanced stage of the disease, which is associated with lower survival. To determine the characteristics and global survival of pancreatic cancer patients in a social security hospital in Ecuador between 2007 and 2017. Methods A retrospective cohort study and a survival analysis were performed using all the available data in the electronic clinical records of patients with a diagnosis of pancreatic cancer in a Hospital of Specialties of Quito-Ecuador between 2007 and 2017. The included patients were those coded according to the ICD 10 between C25.0 and C25.9. Our univariate analysis calculated frequencies, measures of central tendency and dispersion. Through the Kaplan-Meier method we estimated the median time of survival and analyzed the difference in survival time among the different categories of our included variables. These differences were shown through the log rank test. Results A total of 357 patients diagnosed with pancreatic cancer between 2007 and 2017 were included in the study. More than two-thirds (69.9%) of the patients were diagnosed in late stages of the disease. The median survival time for all patients was of 4 months (P25: 2, P75: 8). Conclusions The statistically significant difference of survival time between types of treatment is the most relevant finding in this study, when comparing to all other types of treatments.

Can IL-2R Alpha be a Valuable Marker along with Ca 19–9 in the Diagnosis of Chronic Pancreatitis and Pancreatic Cancer?

2004 ◽  
Vol 19 (3) ◽  
pp. 196-202
Author(s):  
B. Kayhan ◽  
B. Kayhan ◽  
M. Akdoğ;an
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Interleukin 2 ◽  
Carbohydrate Antigen ◽  
Control Group ◽  
Serum Samples ◽  
Cancer Group ◽  
Abdominal Symptoms ◽  
Significant Difference ◽  
Inflammatory Processes

Background Pancreatic cancer is characterized initially by non-specific abdominal symptoms followed by rapid tumor progression. Although chronic pancreatitis is a benign disorder, it can be one of the causative factors of pancreatic cancer. The level of the tumor marker carbohydrate antigen 19–9 (CA 19–9) in pancreatic cancer does not correlate with the stage of the neoplasm. Soluble interleukin 2 receptor (sIL-2R) is a cytokine that shows increased levels during some inflammatory processes and malignant disorders. Aim Our aim in this study was to investigate whether sIL-2Rα levels can be used in association with CA 19–9 in the early diagnosis of pancreatic cancer and chronic pancreatitis. Patients Serum samples were obtained from the blood of 21 pancreatic cancer patients without distant metastasis who were deemed inoperable, 16 chronic pancreatitis patients and 20 normal volunteers. Results We did not find any significant differences in CA 19–9 levels between normal controls and patients with chronic pancreatitis. There was a significant difference in the levels between the control group and the pancreatic cancer group (p=0.003) and between patients with chronic pancreatitis and those with pancreatic cancer (p=0.004). Although there was no significant difference in sIL-2Rα levels between the control group and the patient groups, we found a slight correlation between sIL-2Rα and CA 19–9 levels in the pancreatic cancer group (p=0.003, r=0.623) and a more marked correlation in the chronic pancreatitis group (p<0.01, r=0.751). Conclusion According to our results, sIL-2Rα alone is not a good candidate marker in the diagnosis of pancreatic cancer; it can, however, be used in association with CA 19–9 for this purpose.

scholarly journals Upregulation of KLK8 Predicts Poor Prognosis in Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Qing Hua ◽  
Tianjiao Li ◽  
Yixuan Liu ◽  
Xuefang Shen ◽  
Xiaoyan Zhu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Culture Media ◽  
Disease Free Survival ◽  
Mtor Pathway ◽  
Gene Set Enrichment Analysis ◽  
Human Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC) is a growing cause of cancer-related mortality worldwide. Kallikrein-related peptidase 8 (KLK8) has potential clinical values in many cancers. However, the clinicopathological significances of KLK8 in PDAC remain unknown. We explored the relationship of KLK8 to clinicopathological features of PDAC based on public databases. KLK8 expression was examined in human PDAC tissues. Cell proliferation and apoptosis were evaluated in KLK8-overexpressed human pancreatic cancer cell lines Mia-paca-2 and Panc-1. The related signaling pathways of KLK8 involved in pancreatic cancer progression were analyzed by gene set enrichment analysis (GSEA) and further verified in in vitro studies. We found that KLK8 was up-regulated in tumor tissues in the TCGA-PAAD cohort, and was an independent prognostic factor for both overall survival and disease-free survival of PDAC. KLK8 mRNA and protein expressions were increased in PDAC tissues compared with para-cancerous pancreas. KLK8 overexpression exerted pro-proliferation and anti-apoptotic functions in Mia-paca-2 and Panc-1 cells. GSEA analysis showed that KLK8 was positively associated with PI3K-Akt-mTOR and Notch pathways. KLK8-induced pro-proliferation and anti-apoptotic effects in Mia-paca-2 and Panc-1 cells were attenuated by inhibitors for PI3K, Akt, and mTOR, but not by inhibitor for Notch. Furthermore, overexpression of KLK8 in Mia-paca-2 and Panc-1 cells significantly increased epidermal growth factor (EGF) levels in the culture media. EGF receptor (EGFR) inhibitor could block KLK8-induced activation of PI3K/Akt/mTOR pathway and attenuate pro-proliferation and anti-apoptotic of KLK8 in Mia-paca-2 and Panc-1 cells. In conclusion, KLK8 overexpression exerts pro-proliferation and anti-apoptotic functions in pancreatic cancer cells via EGF signaling-dependent activation of PI3K/Akt/mTOR pathway. Upregulated KLK8 in PDAC predicts poor prognosis and may be a potential therapeutic target for PDAC.

Circulating exosomal microRNAs as novel detection biomarkers in pancreatic cancer

2020 ◽  
Author(s):  
Lun Wu(Former Corresponding Author) ◽  
Wen-Bo Zhou ◽  
Jiao Zhou ◽  
Ying Wei ◽  
Hong-Mei Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Rna Isolation ◽  
Serum Levels ◽  
Tumor Stage ◽  
Serum Samples ◽  
Expression Levels ◽  
Transmission Electron ◽  
Significant Difference ◽  
Novel Biomarkers ◽  
Exosomal Mirna

Abstract Background Circulating exosomal microRNAs are reflective of the characteristics of the tumor, are valuable biomarkers in different types of tumors, and play important roles in tumor progression and metastasis. The purpose of this study was to investigate the circulating exosomal microRNAs miRNA-21 and miRNA-210 as novel biomarkers for patients with pancreatic cancer (PC).Methods Serum exosomal microRNAs were extracted from the serum of PC and chronic pancreatitis (CP) patients using an RNA Isolation kit. To identify the exosomes in the serum, we used transmission electron micrographs for the crystalline structure, western blotting, and NanoSight for exosomal markers and nanoparticle characterization. The relative expression levels of exosomal microRNAs were quantified using quantitative PCR and compared between PC and CP patients.Results A total of 40 serum samples (30 PC and 10 CP) were collected. The expression levels of both exosomal miRNA-21 and miRNA-210 were obviously higher in PC patients compared with those in CP patients (both P<0.001). However, no significant difference in the relative serum levels of free miR-21 and miR-210 was observed between these two groups (both P>0.05). Exosomal miRNA-21 and miRNA-210 were related to tumor stage, as well as other factors. The diagnostic of exosomal miRNA-21 and miRNA-210 levels was 83% and 85%, respectively. Furthermore, when combining the expression of exosomal miRNA with serum CA19-9, the accuracy increased to 90%.Conclusions We herein identified that the serum exosomal miRNAs miRNA-21 and miRNA-210 may be of value as potential biomarkers and therapeutic targets for the diagnosis and treatment of PC.

scholarly journals Optimizing the Profile of [99mTc]Tc–NT(7–13) Tracers in Pancreatic Cancer Models by Means of Protease Inhibitors

2020 ◽  
Vol 21 (21) ◽  
pp. 7926
Author(s):  
Panagiotis Kanellopoulos ◽  
Berthold A. Nock ◽  
Eric P. Krenning ◽  
Theodosia Maina
Keyword(s):  
Pancreatic Cancer ◽  
Ace Inhibitors ◽  
Severe Combined Immunodeficiency ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Cell ◽  
Cancer Models ◽  
The Impact ◽  
Human Colon Adenocarcinoma

Background: The overexpression of neurotensin subtype 1 receptors (NTS1Rs) in human tumors may be elegantly exploited for directing neurotensin (NT)-based radionuclide carriers specifically to cancer sites for theranostic purposes. We have recently shown that [99mTc]Tc–DT1 ([99mTc]Tc–[N4–Gly7]NT(7–13)) and [99mTc]Tc–DT5 ([99mTc]Tc–[N4–βAla7,Dab9]NT(7–13)) show notably improved uptake in human colon adenocarcinoma WiDr xenografts in mice treated with neprilysin (NEP) inhibitors and/or angiotensin-converting enzyme (ACE) inhibitors compared with untreated controls. Aiming toward translation of this promising approach in NTS1R-positive pancreatic ductal adenocarcinoma (PDAC) patients, we now report on the impact of registered NEP/ACE inhibitors on the performance of [99mTc]Tc–DT1 and [99mTc]Tc–DT5 in pancreatic cancer models. Methods: The cellular uptake of [99mTc]Tc–DT1 and [99mTc]Tc–DT5 was tested in a panel of pancreatic cell lines, and their stability was assessed in mice treated or not treated with Entresto, lisinopril, or their combinations. Biodistribution was conducted in severe combined immunodeficiency (SCID) mice bearing pancreatic AsPC-1 xenografts. Results: The Entresto + lisinopril combination maximized the metabolic stability of the fast-internalizing [99mTc]Tc–DT1 in mice, resulting in notably enhanced tumor uptake (7.05 ± 0.80% injected activity (IA)/g vs. 1.25 ± 0.80% IA/g in non-treated controls at 4 h post-injection; p < 0.0001). Conclusions: This study has shown the feasibility of optimizing the uptake of [99mTc]Tc–DT1 in pancreatic cancer models with the aid of clinically established NEP/ACE inhibitors, in favor of clinical translation prospects.

scholarly journals The High PMNs Phagocytosis Resistance of Enterococcal Isolates from RTx Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Tomasz Jarzembowski ◽  
Agnieszka Daca ◽  
Jacek M. Witkowski ◽  
Ewa Bryl ◽  
Bolesław Rutkowski
Keyword(s):  
Flow Cytometry ◽  
High Risk ◽  
Fluorescence Intensity ◽  
Mean Fluorescence Intensity ◽  
Culture Media ◽  
Immunocompromised Patients ◽  
Bacterial Cells ◽  
Opportunistic Pathogens ◽  
Fluorescent Reporter ◽  
Significant Difference

Infections caused by opportunistic pathogens such as enterococci remain difficult to manage, especially in immunocompromised patients. Because of infections’ limited symptoms in such patients the additional problems are to find proper diagnostic criteria and the management of infection. Here we aimed to compare the resistance of commensal enterococcal strains and RTx patients’ isolates, to PMNs phagocytosis. Thirty-six enterococcal urine and faecal isolates from RTx patients and 17 faecal isolates from healthy volunteers were cultured in planktonic and biofilm forms in 37°C or 42°C. Another tested variable was the addition of immunosuppressant to the culture media. Bacterial cells were stained with fluorescent reporter (CFDA, PI) and incubated with PMNs. Results of phagocytosis were estimated as a mean fluorescence intensity (MFI) of PMNs using flow cytometry. Commensal enterococci cultured in all abovementioned (37°C and 42°C/the addition of immunosuppressant) conditions were less resistant to phagocytosis compared to RTx isolates. Observed significant difference in phagocytosis resistance suggests that patients in immunosuppression are colonized with high risk strains which may lead to the development of infection.

scholarly journals Evaluation of Influenza-Specific Humoral Response by Microbead Array Analysis

2011 ◽  
Vol 22 (1) ◽  
pp. 25-29 ◽  
Author(s):  
Yoav Keynan ◽  
Tavis Bodnarchuk ◽  
Stephen Wayne ◽  
Yan Li ◽  
Keith R. Fowke
Keyword(s):  
Influenza Vaccination ◽  
Fluorescence Intensity ◽  
Mean Fluorescence Intensity ◽  
New Caledonia ◽  
Small Sample ◽  
Antigen Specificity ◽  
Serum Samples ◽  
P Values ◽  
Significant Difference ◽  
Microbead Array

RATIONALE: Quantitation and determination of antigen specificity of systemic and mucosal immune responses to influenza vaccination is beneficial for future vaccine development. Previous methods to acquire this information were costly, time consuming and sample exhaustive. The benefits of suspension microbead array (MBA) analysis are numerous. The multiplex capabilities of the system conserve time, money and sample, while generating statistically powerful data.OBJECTIVE: To demonstrate the use of the assay by comparing the humoral influenza-specific responses of two cohorts from two countries that differed in circulating influenza strains and rates of influenza vaccination.METHODS: Influenza hemagglutinin (HA) from different strains were coated on microbeads and incubated with serum samples to capture immunoglobulin (Ig) A1and IgG1host antibodies.RESULTS: Statistically significant differences in IgA1and IgG1exist between the serum samples from Winnipeg (Manitoba) donors and those from Kenyan (Africa) donors. Data were compared using Mann-Whitney nonparametric tests. The Winnipeg donors had higher mean fluorescence intensity values, with significant P values for anti-HA IgA1to A/Wyoming/3/2003 (P=0.044), A/Vietnam/1203/2004 (P=0.0179), A/New Caledonia/20/99 (P<0.0001) and B/Tokyo/53/99 (P=0.0002). No differences were seen between the groups in their response to B/Jilin/20/2003. The Winnipeg donors had higher mean fluorescence intensity values, with significant P values for anti-HA IgG1to A/Wyoming/3/2003 (P=0.0135), B/Tokyo/53/99 (P=0.006) and B/Jilin20/2003 (P=0.026).CONCLUSION: Influenza-specific IgA1and IgG1antibodies were successfully detected using MBA technology. A significant difference in antibody response was observed between Winnipeg and Kenyan donor serums. MBA analysis is a relatively quick and cost-effective method for serum antibody analysis. The potential to simultaneously assay small sample volumes for a multitude of antigens makes this method invaluable for future vaccine response monitoring.

scholarly journals Serum mesothelin and megakaryocyte potentiating factor in pancreatic and biliary cancers

2012 ◽  
Vol 50 (4) ◽  
Author(s):  
Elad Sharon ◽  
Jingli Zhang ◽  
Kevin Hollevoet ◽  
Seth M. Steinberg ◽  
Ira Pastan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Stage ◽  
Pancreatic Disease ◽  
Ductal Adenocarcinoma ◽  
Biliary Carcinoma ◽  
Healthy Donors ◽  
Significant Difference ◽  
Individual Participant ◽  
Pair Wise Comparison

AbstractTumor mesothelin overexpression is present in different malignancies, including the majority of patients with pancreatic or biliary cancers. The objective of this study was to evaluate the use of shed serum mesothelin and megakaryocyte potentiating factor (MPF) concentrations as biomarkers for these cancers.A total of 151 individuals, divided into five groups, were retrospectively analyzed: healthy donors (n=15), patients with benign non-pancreatic conditions (n=52), benign pancreatic conditions (n=33), biliary carcinoma (n=9), and pancreatic ductal adenocarcinoma (n=42). Mesothelin and MPF concentrations were measured in serum with the Mesomark™ and Human MPF ELISA, respectively.Mesothelin and MPF concentrations did not significantly differ among the five individual participant groups (p=0.34, p=0.33, respectively), nor did any other combination and pair-wise comparison of the participant groups demonstrated a significant difference in biomarker concentrations. In patients with pancreatic cancer, mesothelin or MPF concentrations were not associated with tumor stage (p=0.87, p=0.48, respectively) or differentiation grade (p=0.73, p=0.52, respectively).Serum mesothelin and MPF concentrations, measured with standard available ELISAs, were not specific for benign or pancreatic disease. Both biomarkers were not elevated in patients with pancreatic or biliary cancers, and consequently do not appear to be useful biomarkers for these malignancies.

scholarly journals Efficacy And Safety Of EUS-Guided Multimode Ablation Compared With Conventional Chemotherapy In Unresectable Pancreatic Cancer Patients

2021 ◽  
Author(s):  
Xixian Ruan ◽  
Zinan Zhang ◽  
Xiuyan Long ◽  
Ning Fang ◽  
Xiaoyu Yu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Size ◽  
Ductal Adenocarcinoma ◽  
Unresectable Pancreatic Cancer ◽  
Efficacy And Safety ◽  
Conventional Chemotherapy ◽  
Significant Difference ◽  
Group A ◽  
Mean Size ◽  
Group B

Abstract Background & Aims: To compare the feasibility and safety between multimode endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) and conventional chemotherapy in unresectable pancreatic ductal adenocarcinoma (PDAC).Methods: All the pathologically confirmed unresectable PDAC located in the head of the pancreas patients who underwent multimode EUS-RFA or conventional chemotherapy were retrospectively enrolled from June 2018 and April 2019. Patients who underwent multimode EUS-RFA (Group A) was performed through HybridTherm probe(HTP). Patients in Group B accepted nab-Paclitaxel plus Gemcitabine or S-1 plus Gemcitabine. The comparison between efficacy and safety of multimode EUS-RFA and conventional chemotherapy were analyzed by T test and MannWhitney test. A multivariate analysis was performed for each prognostic factor using the Cox proportional hazards model.Results: A total of 10 unresectable PDAC patients were retrospectively enrolled in Group A (mean size 9.46±5.94 cm3, range 2.00-21.09 cm3) and 9 patients in Group B (mean size 14.02±5.81cm3, range 4.60–24.62 cm3). The tumor size was significantly reduced before and after undergoing multimode EUS-RFA (P = 0.005), with an average tumor volume reduction of 38.1%.The tumor size was not significantly changed in Group B (P = 0.452). Statistically significant difference was observed in tumor size between Group A and Group B after treatment (P = 0.033). All patients died because of the progress of the tumor. The median lifetime from Group A&B was 9 months ranged 3-18 months VS 7 months ranged 1-7 months (P = 0.001). Overall no severe adverse events occurred in both groups.Conclusion: EUS-guided multimode ablation has the more feasibility in the treatment of unresectable pancreatic cancer than conventional chemotherapy. In this article, the limited data seems to show the trend of tumor shrinkage, pain relief, lifetime prolongation. Further studies are needed, such as expanding the sample size of patients and comparing the feasibility and safety among all the treatment.

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