Lipoxins and Resolvins in Patients With Pancreatic Cancer: A Preliminary Report

Eicosanoids are bioactive lipids derived from arachidonic acid, which have emerged as key regulators of a wide variety of pathophysiological processes in recent times and are implicated as mediators of gastrointestinal cancer. In this study, we investigated the systemic levels of lipoxygenase (LOX)-derived lipoxin A4 and B4, together with resolvin D1 and D2 in patients with pancreatic adenocarcinoma (n = 68), as well as in healthy individuals (n = 32). Systemic concentrations of the aforementioned immunoresolvents were measured using an enzyme-linked immunosorbent assay (ELISA). In this study, we observed that compared with concentrations in healthy individuals, the peripheral concentrations of the aforementioned eicosanoids were significantly elevated (2- to 10-fold) in patients with pancreatic cancer (in all cases p<0.00001). No significant association was observed between eicosanoid levels and the TNM clinical staging. Furthermore, we observed no significant differences in concentrations of the analyzed bioactive lipids between patients diagnosed with early-stage (TNM stage I-II) and more advanced disease (TNM stage III-IV). Receiver operating characteristic (ROC) curve analysis of each aforementioned immunoresolvent showed area under the curve values ranging between 0.79 and 1.00. Sensitivity, specificity, as well as positive and negative predictive values of the eicosanoids involved in the detection/differentiation of pancreatic adenocarcinoma ranged between 56.8% and 100%. In summary, our research is the first study that provides clinical evidence to support a systemic imbalance in LOX-derived lipoxins and resolvins as the mechanism underlying the pathogenesis of pancreatic adenocarcinoma. This phenomenon occurs regardless of the clinical TNM stage of the disease. Furthermore, our study is the first to preliminarily highlight the role of peripheral levels of immunoresolvents, particularly resolvin D1, as potential novel biomarkers of pancreatic cancer in humans.

Download Full-text

An assessment of the impact of geographic variation on resection rates and survival for early-stage pancreatic adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15052 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15052-e15052

Author(s):

Bradley D. McDowell ◽

Brian J. Smith ◽

Anna M Button ◽

James R. Howe ◽

Elizabeth A. Chrischilles ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Pancreatic Adenocarcinoma ◽

Early Stage ◽

Stage I ◽

Stage Ii ◽

Survival Times ◽

Resection Rate ◽

Selection Factors ◽

The Impact

e15052 Background: Pancreatic resection is the only known curative option for pancreatic adenocarcinoma. Resection has been previously reported to be underutilized in patients with early stage disease. To develop a better understanding of this issue and control for treatment selection factors, we examined the relationship between geographic area resection rates and survival in patients with stage I/II pancreatic cancer. Methods: We queried Surveillance, Epidemiology, and End Results (SEER) data for patients with stage I/II cancer of the pancreatic head diagnosed from 2004-2009. We excluded patients with less than 3mo survival. Resection rates were calculated within Health Service Areas (HSAs) across all 18 SEER regions. Resection rate was defined as the number of patients who had an operation divided by the total number diagnosed with early stage pancreatic cancer. Multivariate Cox regression was used to estimate the overall survival effect of HSA rates while controlling for age, gender, marital status, poverty level, education, and AJCC stage. Results: 8,323 patients with stage I (n=1,454) and stage II (n=6,869) disease were analyzed. Pancreatectomy was performed in 476 patients (32.7%) with stage I disease and 3,846 (56.0%) with stage II disease. HSA resection rates were arranged into five groups (quintiles) which ranged from 42.7 to 65.7% (Table). Across the quintiles, median overall survival increased from 11 to 14 months, suggesting a positive association with resection rate. Multivariate analysis revealed that for every 10.00% increase in resection rate, the risk of overall death decreased by 5.26% (p<0.001). Conclusions: Patients with early stage pancreatic cancer who live in areas with higher resection rates have longer average survival times. Because geography should not influence treatment response, we conclude that efforts to raise resection rates should increase survival times in patients for whom there is uncertainty about the risk/benefits of resection. [Table: see text]

Download Full-text

Serum REG4 protein in pancreatic cancer as a tumor marker: A prospective study

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15063 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15063-15063

Author(s):

A. Sawaki ◽

R. Takayama ◽

N. Mizuno ◽

M. Tajika ◽

N. Hoki ◽

...

Keyword(s):

Pancreatic Cancer ◽

Prospective Study ◽

Early Stage ◽

Diagnostic Sensitivity ◽

Enzyme Linked Immunosorbent Assay ◽

T Stage ◽

Stage 4 ◽

A Prospective Study ◽

Stage 1 ◽

And Control

15063 Background: Pancreatic cancer (PC) shows the worst mortality rate in common malignancies, with 5-year survival rate of 4%. The only way to cure the disease is surgical resection of early stage PC. Establishment of a screening strategy to detect early stage PC is eagerly expected. REG4, a member of the regenerating islet-derived (REG) family, are secreted proteins that play a role in tissue regeneration and inflammation in digestive organs. We reported overexpression of REG4 in PC cells and serum, and preliminary data of the serum REG4 level of pancreatic disease patients including PC patients. We conducted a prospective study to evaluate the role of serum REG4 in PC. Methods: The series included 57 patients diagnosed pathologically as PC between November 2004 and December 2005. Serum REG4 was quantified by standard sandwich ELISA (Enzyme Linked Immunosorbent Assay) using original kit (MBL116: provided by Medical and Biological Laboratories Co., LTD, Japan) before treatment. The upper limit of the test was set at 3.52ng/ml and was based on studies of serum from 48 healthy control subjects. Results: With a specificity of 100%, the diagnostic sensitivity and accuracy were 63.2% and 80.0%, respectively. The ROC (receiver operating characteristic) analysis showed that area under the curve was 0.91. REG4 levels were a significant differences between PC and control (p<0.001), between each T stage and control (T1,T2, T3 or T4 v control), and between each TMN stage and control (stage 1, stage 2, stage 3 or stage 4 v control), but were not a statistical significance with T stage (T1 v T2 v T3 v T4), M stage (M0 v M1) or TNM stage (stage 1 v stage 2 v stage 3 v stage 4) in PC patients. The diagnostic sensitivity of carcinoembryonic antigen (CEA>5.0ng/ml) and carbohydrate antigen19–9 (CA19–9>50U/ml) was 56.5% and 68.4%, respectively. No significant correlation was demonstrated between REG4 and CA19–9 (coefficient of correlation [rs]=0.45). Conclusions: This study shows the potential of serum REG4 as a screening test for PC, especially for early PC. REG4 is considered to be a more useful marker in combination with CA19- 9. No significant financial relationships to disclose.

Download Full-text

Significant upstaging of patients with stage I pancreatic cancer from clinical to pathologic staging.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.349 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 349-349

Author(s):

Heather Stuart ◽

Caroline Ripat ◽

Basem Azab ◽

Danny Yakoub ◽

Dido Franceschi ◽

...

Keyword(s):

Pancreatic Cancer ◽

Early Stage ◽

Clinical Stage ◽

Stage I ◽

Clinical Staging ◽

Early Stage Disease ◽

Risk Of Mortality ◽

Stage Disease ◽

Pathologic Staging ◽

Group 2

349 Background: Clinical staging of patients with pancreatic cancer is essential to determine if neo-adjuvant treatment, surgery or palliative treatment is required. Patients with early stage disease often receive upfront surgery, where as patients with more advanced disease often receive neo-adjuvant therapy. Therefore the accuracy of clinical staging significantly influences management decisions. This study investigates the correlation between clinical and pathologic staging for patients with stage I pancreatic cancer. Methods: A retrospective review of patients with pancreatic cancer in National Cancer Data Base from 1998-2006 was preformed. The clinical stage of patients with presumed stage I disease was compared to the postoperative pathologic stage. Cox proportional hazard ratio model and regression analysis were used to determine factors associated with mortality and upstaging, respectively. Results: 1697 patients with clinical stage I pancreatic cancer were divided into two groups. Group 1 was comprised of patients who were stage I postoperatively and Group 2 was comprised of patients that were upstaged to either stage II, III or IV postoperatively. There were 704 (41%) in group 1 and 993 (59%) in group 2. Within group 2, 595 (60%) were stage II, 321 (32%) were stage III and 77 (8%) were stage IV. Patients that were upstaged after surgery had an increased risk of mortality (HR 1.414, p < 0.001), whereas patients that received adjuvant chemotherapy had a decreased risk of mortality (HR 0.799, p < 0.001). Compared to Grade 1 tumors, Grade 2 and 3 tumors on biopsy were most likely to be upstaged on final pathology (p < 0.001). Conclusions: Patients with stage I pancreatic cancer are often candidates for upfront surgery, however this study demonstrates that a large number are upstaged on postoperative staging. Recognizing this may lead clinicians to administer neo-adjuvant treatment in a greater number of patients with early stage disease in order to optimize survival.

Download Full-text

Two-Step Epstein-Barr Virus Immunoglobulin A Enzyme-Linked Immunosorbent Assay System for Serological Screening and Confirmation of Nasopharyngeal Carcinoma

Clinical and Vaccine Immunology ◽

10.1128/cvi.00425-08 ◽

2009 ◽

Vol 16 (5) ◽

pp. 706-711 ◽

Cited By ~ 21

Author(s):

Dewi K. Paramita ◽

Jajah Fachiroh ◽

Sofia M. Haryana ◽

Jaap M. Middeldorp

Keyword(s):

Early Stage ◽

Immunoglobulin A ◽

Enzyme Linked Immunosorbent Assay ◽

Serological Screening ◽

Predictive Values ◽

Elisa System ◽

Barr Virus ◽

Confirmation Test ◽

Ebv Dna ◽

Epstein Barr

ABSTRACT Undifferentiated nasopharyngeal carcinoma (NPC; WHO type III) is 100% associated with Epstein-Barr virus (EBV) infection and the fourth most prevalent cancer in Indonesian males. Therapy failure is high, since most patients come to the hospital at an advanced stage of disease. Screening for early-stage NPC is needed. Here, a simple and economical two-step enzyme-linked immunosorbent assay (ELISA) system is proposed for diagnosing NPC in high-risk populations, employing the peptide-based immunoglobulin A (IgA) EBNA1 plus viral capsid antigen p18 ELISA as an initial screening test and the IgA early antigen (EA) ELISA using a different set of EBV antigens as a confirmation test. A total of 151 NPC patients and 199 regional healthy EBV carriers were used to evaluate the two-step ELISA approach. Routinely, EBV IgG immunoblotting is used as a standard confirmation test. The sensitivity and specificity for diagnosing NPC by the two-step ELISA approach increased from 85.4% to 96.7% and 90.1% to 98%, respectively, with positive predictive values and negative predictive values increasing from 78.7 and 93.9% to 97.3 and 97.5%, respectively, relative to the immunoblotting confirmation system. On discrepant samples, additional testing was done by EBV DNA load quantification in blood. Results showed that 5/11 discrepant NPC samples with an elevated IgA EA ELISA also had elevated an EBV DNA load in the circulation (range, 3,200 to 25,820 copies/ml). Therefore, the IgA EA ELISA is proposed as a confirmation test in first-line NPC serological screening studies. This two-step EBV ELISA system provides a standardized approach for NPC screening and may be used in combination with dried blood sampling in future field studies for identification of early-stage NPC in high-risk regions.

Download Full-text

Plasma asprosin, CCDC80 and ANGPTL4 levels are associated with metabolic and cardiovascular risk in patients with inflammatory bowel disease

Physiological Research ◽

10.33549/physiolres.934547 ◽

2021 ◽

pp. 203-211

Author(s):

Hao-Hua Wang ◽

Wan-Ying Luo ◽

Min Lin ◽

Xiao-Jing Li ◽

Guang-Da Xiang ◽

...

Keyword(s):

Insulin Resistance ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Early Stage ◽

Reactive Hyperemia ◽

Enzyme Linked Immunosorbent Assay ◽

Model Assessment ◽

Healthy Individuals ◽

Brachial Artery Diameter ◽

Inflammatory Bowel

Asprosin, coiled-coil domain-containing 80(CCDC80) and angiopoietin-like 4(ANGPTL4) are newly discovered adipocytokine that affects glucose tolerance, insulin resistance and cardiovascular diseases. The goal of this study was to investigate if a relationship exists among asprosin, CCDC80 and ANGPTL4 and inflammatory bowel disease (IBD). Fifty subjects with newly diagnosed IBD and fifty healthy individuals were enrolled. Patients were treated with standard therapies for 3 months. Plasma asprosin, CCDC80 and ANGPTL4 levels were measured with enzyme-linked immunosorbent assay. High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia (flow-mediated dilation, FMD) and after sublingual glyceryltrinitrate. Compare with healthy individuals, plasma CCDC80, erythrocyte sedi¬mentation rate (ESR), C-reactive protein (CRP) levels and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly higher (p < 0.05, respectively), whereas plasma asprosin, ANGPTL4 levels and FMD were significantly lower in both UC and CD patients (p < 0.05). Plasma CCDC80 levels were significantly higher in patients with CD (p < 0.05), while plasma asprosin and ANGPTL4 levels were lower (pP < 0.05) as compared with those in patients with UC. Standard therapies increased plasma asprosin, ANGPTL4 levels and FMD in both UC and CD (p < 0.05), UC and CD patientswhile decreased plasma CCDC80, ESR, CRP levels and HOMA-IR (p < 0.05). The changes in HOMA-IR and FMD were correlated with the changes in plasma asprosin, CCDC80 and ANGPTL4 levels over the study period (p < 0.05). Plasma asprosin, CCDC80 and ANGPTL4 levels may be applied as a significant marker for early stage of insulin resistance and atherosclerosis in IBD, especially of CD.

Download Full-text

Endosialin (TEM1) as a Diagnostic, Progression, and Prognostic Serum Marker for Patients With Colorectal Cancer—A Preliminary Study

Cancer Control ◽

10.1177/1073274820903351 ◽

2020 ◽

Vol 27 (1) ◽

pp. 107327482090335

Author(s):

Łukasz Pietrzyk ◽

Paulina Wdowiak

Keyword(s):

Colorectal Cancer ◽

Serum Concentration ◽

Early Stage ◽

Serum Marker ◽

Carbohydrate Antigen ◽

Stage I ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Individuals ◽

Serum Samples ◽

The Mean

Colorectal cancer (CRC) is one of the most common cancers worldwide usually diagnosed in the advanced stage. In this study, the serum concentration of tumor endothelial marker 1 (TEM1) was measured and correlated with clinicopathological features to evaluate whether TEM1 might serve as a biomarker for early CRC diagnosis, progression, and prognosis. The concentration of TEM1 was measured in the serum samples of 45 patients with CRC and 35 healthy individuals using enzyme-linked immunosorbent assay test. The mean serum concentration of TEM1 was significantly higher in the patients with CRC compared to the healthy individuals (1.31 ± 0.16 vs 0.92 ± 0.90 ng/mL; P < .001). The mean concentration of TEM1 significantly increased in the patients having CRC with early stage (stage I + II) compared to noncancer control individuals (stage I + II vs control 1.21 ± 0.13 ng/mL: 0.92 ± 0.90 ng/mL; P < .001). The TEM1 concentration in blood serum also showed a significant association with the development of T stages ( P < .001), N stages ( P < .001), and M stages ( P = .006). The TEM1 sensitivity and specificity in CRC detection are higher than routinely used blood markers (carcinoembryonic antigen [CEA] and carbohydrate antigen [Ca 19-9]). Patients with high TEM1 concentration (≥1.055 ng/mL) had a worse overall survival rate compared to the patients having CRC with low TEM1 concentration (<1.055 ng/mL). In conclusion, TEM1 can act as a potential diagnostic, progression, and prognostic serum biomarker for patients with CRC; TEM1 might be a good supplement for commonly used markers CEA and Ca 19-9.

Download Full-text

The Relationship of Plasma miR-29a and Oxidized Low Density Lipoprotein with Atherosclerosis

Cellular Physiology and Biochemistry ◽

10.1159/000453202 ◽

2016 ◽

Vol 40 (6) ◽

pp. 1521-1528 ◽

Cited By ~ 16

Author(s):

Yu-Qing Huang ◽

An-Ping Cai ◽

Ji-Yan Chen ◽

Cheng Huang ◽

Jie Li ◽

...

Keyword(s):

Early Stage ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Intima Media Thickness ◽

Enzyme Linked Immunosorbent Assay ◽

Low Density ◽

Oxidized Low Density Lipoprotein ◽

Predictive Values ◽

Chronic Inflammatory Condition ◽

The Relationship

Background/Aims: Atherosclerosis is a chronic inflammatory condition associated with a variety of vascular diseases. Previous studies showed that both miR-29a and oxidized low density lipoprotein (ox-LDL) were vital in the development of atherosclerosis. However, the relationship between miR-29a and ox-LDL remains unknown. This study was designed to investigate the association of miR-29a and ox-LDL and to test whether circulating miR-29a and ox-LDL levels could predict atherosclerosis. Methods: In 170 participants, plasma levels of miR-29a were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) while plasma ox-LDL levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. The relationship between miR-29a level and ox-LDL and carotid intima-media thickness (cIMT) was assessed using the Spearman correlation coefficient and multiple liner regression. Results: Compared with the normal cIMT group, the increased cIMT group had higher levels of ox-LDL (0.47 ± 0.08 vs 0.29 ± 0.06 ng/ml, p = 0.003) and miR-29a (32.93 ± 4.26 vs 26.37 ± 1.04, p < 0.001). A positive correlation was found between ox-LDL and miR-29a (r = 0.695, p < 0.001), and both the ox-LDL (r = 0.857, p < 0.001) and the miR-29a (r = 0.753, p < 0.001) were positively related to cIMT. Furthermore, multiple liner regression indicated that a significant correlation between ox-LDL and cIMT (β = 0.768, p < 0.001), as well as between miR-29a and cIMT (β = 0.686, p <0.001). The combination of miR-29a and ox-LDL (AUC = 0.926, p < 0.001) offered a better predictive value for atherosclerosis than either miR-29a (AUC = 0.759, p < 0.001) or ox-LDL (AUC = 0.762, p < 0.001) alone. Conclusion: Increased miR-29a and ox-LDL levels were associated with an early stage of atherosclerosis, and the combination of miR-29a and ox-LDL offered better predictive values for atherosclerosis than either alone.

Download Full-text

Scintigraphic Imaging of Neovascularization With 99mTc-3PRGD2 for Evaluating Early Response to Endostar Involved Therapies on Pancreatic Cancer Xenografts In Vivo

Frontiers in Oncology ◽

10.3389/fonc.2021.792431 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiaona Jin ◽

Chengyan Dong ◽

Kun Zheng ◽

Ximin Shi ◽

Yu Liu ◽

...

Keyword(s):

Pancreatic Cancer ◽

Early Stage ◽

Antiangiogenic Therapy ◽

Combined Treatment ◽

Repeated Measure ◽

Control Group ◽

Therapeutic Effects ◽

Scintigraphic Imaging ◽

Predictive Values ◽

Treatment Groups

BackgroundMolecular imaging targeting angiogenesis can specifically monitor the early therapeutic effect of antiangiogenesis therapy. We explore the predictive values of an integrin αvβ3-targeted tracer, 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2), for monitoring the efficacy of Endostar antiangiogenic therapy and chemotherapy in animal models.MethodsThe pancreatic cancer xenograft mice were randomly divided into four groups, with seven animals in each group and treated in different groups with 10 mg/kg/day of Endostar, 10 mg/kg/day of gemcitabine, 10 mg/kg/day of Endostar +10 mg/kg/day of gemcitabine at the same time, and the control group with 0.9% saline (0.1 ml/day). 99mTc-3PRGD2 scintigraphic imaging was carried out to monitor therapeutic effects. Microvessel density (MVD) was measured using immunohistochemical staining of the tumor tissues. The region of interest (ROI) of tumor (T) and contralateral corresponding site (NT) was delineated, and the ratio of radioactivity (T/NT) was calculated. Two-way repeated-measure analysis of variance (ANOVA) was used to assess differences between treatment groups.ResultsTumor growth was significantly lower in treatment groups than that in the control group (p < 0.05), and the differences were noted on day 28 posttreatment. The differences of 99mTc-3PRGD2 uptakes were observed between the control group and Endostar group (p = 0.033) and the combined treatment group (p < 0.01) on day 7 posttreatment and on day 14 posttreatment between the control group and gemcitabine group (p < 0.01). The accumulation of 99mTc-3PRGD2 was significantly correlated with MVD (r = 0.998, p = 0.002).ConclusionWith 99mTc-3PRGD2 scintigraphic imaging, the tumor response to antiangiogenic therapy, chemotherapy, and the combined treatment can be observed at an early stage of the treatments, much earlier than the tumor volume change. It provides new opportunities for developing individualized therapies and dose optimization.

Download Full-text