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Article: Combining sCD163 with CA 19-9 Increases the Predictiveness of Pancreatic Ductal Adenocarcinoma.

Stuhr, Liva K / Madsen, Kasper / Johansen, Astrid Z / Chen, Inna M / Hansen, Carsten P / Jensen, Lars H / Hansen, Torben F / Kløve-Mogensen, Kirstine / Nielsen, Kaspar R / Johansen, Julia S

Cancers

2023 Volume 15, Issue 3

Abstract: The objective of this study was to evaluate the diagnostic and prognostic potential of soluble CD163 (sCD163) in patients with pancreatic ductal adenocarcinoma (PDAC). Preoperative serum samples from 255 patients with PDAC were analyzed for sCD163 using ... ...

Abstract	The objective of this study was to evaluate the diagnostic and prognostic potential of soluble CD163 (sCD163) in patients with pancreatic ductal adenocarcinoma (PDAC). Preoperative serum samples from 255 patients with PDAC were analyzed for sCD163 using a commercially available enzyme-linked immunosorbent assay. The diagnostic value of sCD163 was evaluated using receiver operating characteristic (ROC) curves. The prognostic significance of sCD163 was evaluated by Cox regression analysis and Kaplan-Meier survival curves. sCD163 was significantly increased in patients with PDAC, across all stages, compared to healthy subjects (stage 1:
Language	English
Publishing date	2023-01-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15030897
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Article ; Online: Pre-existing TGF-β-specific T-cell immunity in patients with pancreatic cancer predicts survival after checkpoint inhibitors combined with radiotherapy.

Mortensen, Rasmus Erik Johansson / Holmström, Morten Orebo / Lisle, Thomas Landkildehus / Hasselby, Jane P / Willemoe, Gro L / Met, Özcan / Marie Svane, Inge / Johansen, Julia / Nielsen, Dorte L / Chen, Inna M / Andersen, Mads Hald

Journal for immunotherapy of cancer

2023 Volume 11, Issue 3

Abstract: Background: Circulating transforming growth factor-β (TGF-β)-specific T cells that recognize TGF-β-expressing immune regulatory cells have been described in patients with cancer. TGF-β-derived peptide vaccination modulates the tumor microenvironment and ...

Abstract	Background: Circulating transforming growth factor-β (TGF-β)-specific T cells that recognize TGF-β-expressing immune regulatory cells have been described in patients with cancer. TGF-β-derived peptide vaccination modulates the tumor microenvironment and has shown clinical effects in animal models of pancreatic cancer (PC). TGF-β-expressing regulatory cells are especially elevated in PC and may prevent the clinical response to immune checkpoint inhibitors (ICIs). Thus, in the present study we investigated the significance of TGF-β-specific T-cell immunity in patients with PC treated with ICI combined with radiotherapy in a randomized phase 2 study (CheckPAC). Methods: Immune responses to a TGF-β-derived epitope entitled TGF-β-15 as well as epitopes from Results: PBMCs from 32 patients were analyzed for immune responses to the TGF-β-derived epitope entitled TGF-β-15. Patients with a strong TGF-β-specific immune response at treatment initiation had longer progression-free and overall survival, compared with patients with a weak or no TGF-β-specific immune response. This remained significant in multivariate analysis. Patients with weak and strong TGF-β-specific responses displayed similar responses towards viral antigens. Furthermore, we show that TGF-β-specific T cells from a clinical responder specifically reacted to and lysed autologous, regulatory immune cells. Finally, mimicking a TGF-β-15 vaccination, we showed that repeated stimulations with the TGF-β-15 epitope Conclusion: A strong TGF-β-15 specific immune response was associated with clinical benefit and improved survival after ICI/radiotherapy for patients with PC. Importantly, the lack of TGF-β-specific T cells in some patients was not caused by a general immune dysfunction. TGF-β-specific T cells recognized regulatory immune cells and could be introduced
MeSH term(s)	Cancer Vaccines/therapeutic use ; Epitopes ; Immune Checkpoint Inhibitors/therapeutic use ; Immunity, Cellular ; Leukocytes, Mononuclear ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/radiotherapy ; T-Lymphocytes/immunology ; Transforming Growth Factor beta ; Tumor Microenvironment ; Vaccines, Subunit ; Humans ; Pancreatic Neoplasms
Chemical Substances	Cancer Vaccines ; Epitopes ; Immune Checkpoint Inhibitors ; Transforming Growth Factor beta ; Vaccines, Subunit
Language	English
Publishing date	2023-12-14
Publishing country	England
Document type	Clinical Trial, Phase II ; Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2022-006432
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Article ; Online: Pancreatic cancer symptom trajectories from Danish registry data and free text in electronic health records.

Hjaltelin, Jessica Xin / Novitski, Sif Ingibergsdóttir / Jørgensen, Isabella Friis / Siggaard, Troels / Vulpius, Siri Amalie / Westergaard, David / Johansen, Julia Sidenius / Chen, Inna M / Juhl Jensen, Lars / Brunak, Søren

eLife

2023 Volume 12

Abstract: Pancreatic cancer is one of the deadliest cancer types with poor treatment options. Better detection of early symptoms and relevant disease correlations could improve pancreatic cancer prognosis. In this retrospective study, we used symptom and disease ... ...

Abstract	Pancreatic cancer is one of the deadliest cancer types with poor treatment options. Better detection of early symptoms and relevant disease correlations could improve pancreatic cancer prognosis. In this retrospective study, we used symptom and disease codes (ICD-10) from the Danish National Patient Registry (NPR) encompassing 6.9 million patients from 1994 to 2018,, of whom 23,592 were diagnosed with pancreatic cancer. The Danish cancer registry included 18,523 of these patients. To complement and compare the registry diagnosis codes with deeper clinical data, we used a text mining approach to extract symptoms from free text clinical notes in electronic health records (3078 pancreatic cancer patients and 30,780 controls). We used both data sources to generate and compare symptom disease trajectories to uncover temporal patterns of symptoms prior to pancreatic cancer diagnosis for the same patients. We show that the text mining of the clinical notes was able to complement the registry-based symptoms by capturing more symptoms prior to pancreatic cancer diagnosis. For example, 'Blood pressure reading without diagnosis', 'Abnormalities of heartbeat', and 'Intestinal obstruction' were not found for the registry-based analysis. Chaining symptoms together in trajectories identified two groups of patients with lower median survival (<90 days) following the trajectories 'Cough→Jaundice→Intestinal obstruction' and 'Pain→Jaundice→Abnormal results of function studies'. These results provide a comprehensive comparison of the two types of pancreatic cancer symptom trajectories, which in combination can leverage the full potential of the health data and ultimately provide a fuller picture for detection of early risk factors for pancreatic cancer.
MeSH term(s)	Humans ; Electronic Health Records ; Retrospective Studies ; Routinely Collected Health Data ; Pancreatic Neoplasms/diagnosis ; Pancreatic Neoplasms/epidemiology ; Jaundice ; Denmark/epidemiology ; Pancreatic Neoplasms
Language	English
Publishing date	2023-11-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.84919
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Article ; Online: Plasma YKL-40 is associated with prognosis in patients with metastatic pancreatic cancer receiving immune checkpoint inhibitors in combination with radiotherapy.

Johansen, Astrid Z / Novitski, Sif I / Hjaltelin, Jessica X / Theile, Susann / Boisen, Mogens K / Brunak, Søren / Madsen, Daniel H / Nielsen, Dorte L / Chen, Inna M

Frontiers in immunology

2023 Volume 14, Page(s) 1228907

Abstract: Background: YKL-40, also known as chitinase-3-like protein 1 (CHI3L1), is a secreted glycoprotein produced by various cell types including stromal, immune, and cancer cells. It contributes to cancer progression through tumor-promoting inflammation and ... ...

Abstract	Background: YKL-40, also known as chitinase-3-like protein 1 (CHI3L1), is a secreted glycoprotein produced by various cell types including stromal, immune, and cancer cells. It contributes to cancer progression through tumor-promoting inflammation and has been shown to inhibit the cytotoxicity of T and NK lymphocytes. Methods: Blood samples were collected from 84 patients with mPC who participated in the randomized phase II CheckPAC study, in which patients received nivolumab with or without ipilimumab combined with a single fraction of SBRT. Plasma YKL-40 was measured using a commercial ELISA kit. Results: Elevated baseline plasma YKL-40 was an independent predictor of shorter overall survival (OS) (HR 2.19, 95% CI 1.21-3.95). A ≥ 40% decrease in plasma YKL-40 during treatment was associated with longer progression-free survival ( Conclusion: This study contributes new knowledge regarding YKL-40 as a predictor of clinical benefit from ICIs and radiotherapy. These exploratory results warrant further investigation of YKL-40 as a biomarker for patients treated with immunotherapies. Clinical trial registration: Clinicaltrials.gov, identifier NCT02866383.
Language	English
Publishing date	2023-09-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1228907
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Article: High serum levels of the C-propetide of type V collagen (PRO-C5) are prognostic for short overall survival in patients with pancreatic ductal adenocarcinoma.

Nissen, Neel I / Johansen, Astrid Z / Chen, Inna M / Jensen, Christina / Madsen, Emilie A / Hansen, Carsten P / Thorlacius-Ussing, Jeppe / Karsdal, Morten / Johansen, Julia S / Diab, Hadi M H / Jørgensen, Lars N / Willumsen, Nicholas

Frontiers in molecular biosciences

2023 Volume 10, Page(s) 1158058

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2023-03-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2023.1158058
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Article: Protein Signatures and Individual Circulating Proteins, including IL-6 and IL-15, Associated with Prognosis in Patients with Biliary Tract Cancer.

Christensen, Troels D / Madsen, Kasper / Maag, Emil / Larsen, Ole / Jensen, Lars Henrik / Hansen, Carsten P / Markussen, Alice / Høgdall, Dan T S / Chen, Inna M / Nielsen, Dorte / Johansen, Julia S

Cancers

2023 Volume 15, Issue 4

Abstract: Biliary tract cancer (BTC) is a rare gastrointestinal cancer with a dismal prognosis. Biomarkers with clinical utility are needed. In this study, we investigated the association between survival and 89 immuno-oncology-related proteins, with the aim of ... ...

Abstract	Biliary tract cancer (BTC) is a rare gastrointestinal cancer with a dismal prognosis. Biomarkers with clinical utility are needed. In this study, we investigated the association between survival and 89 immuno-oncology-related proteins, with the aim of identifying prognostic biomarkers for BTC. The study included patients with BTC (
Language	English
Publishing date	2023-02-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15041062
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Article ; Online: A randomized phase II study of full dose gemcitabine versus reduced dose gemcitabine and nab-paclitaxel in vulnerable patients with non-resectable pancreatic cancer (DPCG-01).

Rasmussen, Louise Skau / Winther, Stine B / Chen, Inna M / Weber, Britta / Ventzel, Lise / Liposits, Gabor / Johansen, Julia Sidenius / Detlefsen, Sönke / Egendal, Ida / Shim, Susy / Christensen, Signe / Pfeiffer, Per / Ladekarl, Morten

BMC cancer

2023 Volume 23, Issue 1, Page(s) 552

Abstract: Background: According to current evidence, the best treatment for fit patients with non-resectable pancreatic cancer (PC) is combination chemotherapy, whereas frail patients are recommended gemcitabine (Gem) monotherapy. Randomized controlled trials in ... ...

Abstract	Background: According to current evidence, the best treatment for fit patients with non-resectable pancreatic cancer (PC) is combination chemotherapy, whereas frail patients are recommended gemcitabine (Gem) monotherapy. Randomized controlled trials in colorectal cancer and a post-hoc analysis of gemcitabine and nab-paclitaxel (GemNab) in PC suggest, however, that reduced dose of combination chemotherapy may be feasible and more efficient compared to monotherapy in frail patients. The aim of this study is to investigate whether reduced dose GemNab is superior to full dose Gem in patients with resectable PC, who are not candidates for full dose combination chemotherapy in first line. Methods: The Danish Pancreas Cancer Group (DPCG)-01 trial is a national multicenter prospective randomized phase II trial. A total of 100 patients in ECOG performance status 0-2 with non-resectable PC, not candidate for full dose combination chemotherapy in first line, but eligible for full dose Gem, will be included. Patients are randomized 1:1 to either full dose Gem or GemNab in 80% of recommended dose. The primary endpoint is progression-free survival. Secondary endpoints are overall survival, overall response rate, quality of life, toxicity and rate of hospitalizations during treatment. The correlation between blood inflammatory markers, including YKL-40 and IL-6, circulating tumor DNA, and tissue biomarkers of resistance to chemotherapy and outcome will be explored. Finally, the study will include measures of frailty (G8, modified G8, and chair-stand-test) to assess whether scoring would enable a personalized allocation to different treatments or indicates a possibility for interventions. Discussion: Single-drug treatment with Gem has for frail patients with non-resectable PC been the main treatment option for more than thirty years, but the impact on outcome is modest. If improved results and sustained tolerability with reduced dose combination chemotherapy can be shown, this could change the future practice for this increasing group of patients. Trial registration: ClinicalTrials.gov Identifier: NCT05841420. Secondary Identifying No: N-20210068. EudraCT No: 2021-005067-52. Protocol version: 1.5, 16-MAY-2023.
MeSH term(s)	Humans ; Gemcitabine ; Deoxycytidine ; Quality of Life ; Prospective Studies ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Pancreatic Neoplasms/pathology ; Paclitaxel ; Albumins ; Randomized Controlled Trials as Topic ; Pancreatic Neoplasms
Chemical Substances	Gemcitabine ; 130-nm albumin-bound paclitaxel ; Deoxycytidine (0W860991D6) ; Paclitaxel (P88XT4IS4D) ; Albumins
Language	English
Publishing date	2023-06-16
Publishing country	England
Document type	Multicenter Study ; Clinical Trial, Phase II ; Journal Article
ZDB-ID	2041352-X
ISSN	1471-2407 ; 1471-2407
ISSN (online)	1471-2407
ISSN	1471-2407
DOI	10.1186/s12885-023-11035-6
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Article: Inflammatory Biomarker Score Identifies Patients with Six-Fold Increased Risk of One-Year Mortality after Pancreatic Cancer.

Kjaergaard, Alisa D / Chen, Inna M / Johansen, Astrid Z / Nordestgaard, Børge G / Bojesen, Stig E / Johansen, Julia S

Cancers

2021 Volume 13, Issue 18

Abstract: We examined whether elevated plasma C-reactive protein (CRP), carbohydrate antigen (CA) 19-9, interleukin-6 (IL-6) and YKL-40, individually or combined, can identify poor survivors among patients with pancreatic ductal adenocarcinoma (PDAC). We measured ... ...

Abstract	We examined whether elevated plasma C-reactive protein (CRP), carbohydrate antigen (CA) 19-9, interleukin-6 (IL-6) and YKL-40, individually or combined, can identify poor survivors among patients with pancreatic ductal adenocarcinoma (PDAC). We measured CRP, CA 19-9, IL-6 and YKL-40 in 993 patients at the time of PDAC diagnosis. The biomarker score was the sum of biomarker categories, coded 0, 1 and 2 for low, intermediate and high plasma concentrations, respectively. High vs. low levels of CRP, CA 19-9 and IL-6 were each independently associated with a two-fold increased risk of one-year mortality. CRP performed best in patients with advanced and CA 19-9 in patients with low cancer stages. YKL-40 was not associated with mortality and, therefore, was not included in the biomarker score. Compared to the biomarker score = 0, the multifactorially adjusted hazard ratios for one-year mortality were 1.56 (95% confidence interval: 0.99-2.44) for score = 1, 2.22 (1.41-3.49) for score = 2, 3.44 (2.20-5.38) for score = 3, 5.13 (3.21-8.17) for score = 4 and 6.32 (3.84-10.41) for score = 5-6 (
Language	English
Publishing date	2021-09-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13184599
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Article ; Online: Type XXII Collagen Complements Fibrillar Collagens in the Serological Assessment of Tumor Fibrosis and the Outcome in Pancreatic Cancer.

Madsen, Emilie A / Thorlacius-Ussing, Jeppe / Nissen, Neel I / Jensen, Christina / Chen, Inna M / Johansen, Julia S / Diab, Hadi M H / Jørgensen, Lars N / Hansen, Carsten P / Karsdal, Morten A / Willumsen, Nicholas

Cells

2022 Volume 11, Issue 23

Abstract: Circulating fragments of type III collagen, measured by PRO-C3, has shown promising results as a tumor fibrosis biomarker. However, the fibrotic tumor microenvironment consists of many other collagens with diverse functions and unexplored biomarker ... ...

Abstract	Circulating fragments of type III collagen, measured by PRO-C3, has shown promising results as a tumor fibrosis biomarker. However, the fibrotic tumor microenvironment consists of many other collagens with diverse functions and unexplored biomarker potential. One example hereof is type XXII collagen (COL22). In this study, we investigated the biomarker potential of COL22 by measuring this in serum. An ELISA, named PRO-C22, was developed and measured in two serum cohorts consisting of patients with various solid tumors (n = 220) and healthy subjects (n = 33) (Cohort 1), and patients with pancreatic ductal adenocarcinoma (PDAC) (n = 34), and healthy subjects (n = 20) (Cohort 2). In Cohort 1, PRO-C22 was elevated in the serum from patients with solid tumors, compared to healthy subjects (p < 0.01 to p < 0.0001), and the diagnostic accuracy (AUROC) ranged from 0.87 to 0.98, p < 0.0001. In Cohort 2, the high levels of PRO-C22, in patients with PDAC, were predictive of a worse overall survival (HR = 4.52, 95% CI 1.90−10.7, p = 0.0006) and this remained significant after adjusting for PRO-C3 (HR = 4.27, 95% CI 1.24−10.4, p = 0.0013). In conclusion, PRO-C22 has diagnostic biomarker potential in various solid tumor types and prognostic biomarker potential in PDAC. Furthermore, PRO-C22 complemented PRO-C3 in predicting mortality, suggesting an additive prognostic value when quantifying different collagens.
MeSH term(s)	Humans ; Biomarkers, Tumor ; Carcinoma, Pancreatic Ductal/diagnosis ; Collagen ; Fibrillar Collagens ; Fibrosis ; Pancreatic Neoplasms ; Tumor Microenvironment ; Pancreatic Neoplasms
Chemical Substances	Biomarkers, Tumor ; Collagen (9007-34-5) ; Fibrillar Collagens
Language	English
Publishing date	2022-11-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11233763
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Article ; Online: Prognostic value of circulating proteins in patients undergoing surgery for pancreatic cancer.

Lindgaard, Sidsel C / Sztupinszki, Zsófia / Maag, Emil / Hansen, Carsten P / Chen, Inna M / Johansen, Astrid Z / Hasselby, Jane P / Bojesen, Stig E / Nielsen, Dorte / Johansen, Julia S

Cancer medicine

2022 Volume 12, Issue 4, Page(s) 3972–3986

Abstract: Background: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death. Less than 20% of patients are diagnosed with resectable disease. Identifying truly resectable disease is challenging because 20%-40% of the patients ... ...

Abstract	Background: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death. Less than 20% of patients are diagnosed with resectable disease. Identifying truly resectable disease is challenging because 20%-40% of the patients subjected to resection are found to have advanced disease during surgery. The aim of our study was to identify panels of circulating proteins that could be used to distinguish patients with unresectable PDAC from patients with resectable PDAC and to identify prognostic signatures for both groups. Methods: We measured 92 circulating immuno-oncology-related proteins using the proximity extension assay from Olink Proteomics in 273 patients eligible for surgery for PDAC. Two bioinformaticians worked independently of one another on the same data. LASSO and Ridge regression were used in the statistical analyses. Results: One protein index for determining resectability had an AUC value of 0.66. Several indices for prognosis had AUC values between 0.50 and 0.75 and were therefore not better than existing prognostic markers. Discussion: Our study did not reveal any new high-performing protein panels that could be used to identify patients with inoperable PDAC before surgery. The panel of 92 proteins investigated has previously been found to be applicable for diagnostic use in patients with PDAC, but it does not seem to warrant further investigation regarding resectability in the subgroup of patients with PDAC referred to surgery.
MeSH term(s)	Humans ; Prognosis ; Pancreatic Neoplasms/diagnosis ; Pancreatic Neoplasms/surgery ; Pancreatic Neoplasms/pathology ; Carcinoma, Pancreatic Ductal/diagnosis ; Carcinoma, Pancreatic Ductal/surgery ; Carcinoma, Pancreatic Ductal/pathology ; Pancreatic Neoplasms
Language	English
Publishing date	2022-10-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.5240
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