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PDAC blood markers

Zixuan Yang, Norbert Senninger, Isabelle Flammang, Qifa Ye, Sameer A Dhayat
PURPOSE: LAPTM4B is upregulated in a wide range of cancers associated with poor prognosis. However, the clinical impact of LAPTM4B as diagnostic and prognostic marker in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Thus, the aim of the present study was to investigate the expression of LAPTM4B as circulating marker in PDAC. METHODS: Expression analysis of LAPTM4B-35 in pancreatic tissue and preoperative blood serum samples of 169 patients with PDAC UICC Stages I-IV (n = 98), chronic pancreatitis (n = 41), and healthy controls (n = 30) by immunohistochemistry, Western blot, and ELISA...
February 18, 2019: Journal of Cancer Research and Clinical Oncology
Indu Khatri, Koelina Ganguly, Sunandini Sharma, Joseph Carmicheal, Sukhwinder Kaur, Surinder K Batra, Manoj K Bhasin
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a 5-year survival rate of <8%. Its dismal prognosis stems from inefficient therapeutic modalities owing to the lack of understanding about pancreatic cancer pathogenesis. Considering the molecular complexity and heterogeneity of PDAC, identification of novel molecular contributors involved in PDAC onset and progression using global "omics" analysis will pave the way to improved strategies for disease prevention and therapeutic targeting...
January 15, 2019: Scientific Reports
Xiao-Hui Zhao, Zai-Rui Wang, Chang-Long Chen, Ling Di, Zhuo-Fei Bi, Zhi-Hua Li, Yi-Min Liu
AIM: To evaluate the clinical properties of three subpopulations of circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: We identified CTCs for expression of the epithelial cell marker cytokeratin or epithelial cell adhesion molecule (EpCAM) (E-CTC), the mesenchymal cell markers vimentin and twist (M-CTC), or both (E/M-CTC) using the CanPatrol system. Between July 2014 and July 2016, 107 patients with PDAC were enrolled for CTC evaluation...
January 7, 2019: World Journal of Gastroenterology: WJG
Yuanjie Pang, Michael V Holmes, Zhengming Chen, Christiana Kartsonaki
We aimed to review the epidemiologic literature examining lifestyle, metabolic risk factors, and blood-based biomarkers including multi-omics (genomics, proteomics, and metabolomics) and to discuss how these predictive markers can inform early diagnosis of pancreatic ductal adenocarcinoma (PDAC). A search of the PubMed database was conducted in June 2018 to review epidemiologic studies of (1) lifestyle and metabolic risk factors for PDAC, genome-wide association studies (GWAS), and risk prediction models incorporating these factors and (2) blood-based biomarkers for PDAC (conventional diagnostic markers, metabolomics, and proteomics)...
December 14, 2018: Journal of Gastroenterology and Hepatology
Susan Tsai, Laura McOlash, Shuang Jia, Jian Zhang, Pippa Simpson, Mary L Kaldunski, Mohammed Aldakkak, Jenny Grewal, Katie Palen, Michael B Dwinell, Bryon D Johnson, Alexander Mackinnon, Martin J Hessner, Jill A Gershan
BACKGROUND: Despite the accessibility of blood, identification of systemic biomarkers associated with cancer progression has been challenging. The aim of this study was to determine a difference in baseline serum immune signatures in patients that experienced early pancreatic ductal adenocarcinoma (PDAC) metastasis with patients that did not. We hypothesized that immune mediators would differ in the baseline serum of these patient cohorts. To test this hypothesis, novel approaches of systemic immune analysis were performed...
December 7, 2018: Cancer Epidemiology, Biomarkers & Prevention
S Timme-Bronsert, P Bronsert, M Werner, B Kulemann, J Höppner
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a disease with a poor prognosis. PDAC shows characteristic mutations within codon 12/13. Circulating tumor cells (CTC) detected in blood samples of patients with cancer are hypothesized as the means of systemic tumor spread. But less is known about morphological/molecular characteristics or the pathophysiological meaning of PDAC CTC. OBJECTIVES: The aim of the study was a cytomorphological and genetic analysis of CTC from patients with PDAC followed by the correlation of the results with those of the corresponding tumor in the pancreas...
November 27, 2018: Der Pathologe
V L Veenstra, H Damhofer, C Waasdorp, L B van Rijssen, M J van de Vijver, F Dijk, H W Wilmink, M G Besselink, O R Busch, D K Chang, P J Bailey, A V Biankin, H M Kocher, J P Medema, J S Li, R Jiang, D W Pierce, H W M van Laarhoven, M F Bijlsma
Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma that harbors tumor-promoting properties. No good biomarkers exist to monitor the effect of stromal targeting therapies or to predict response. We set out to identify such non-invasive markers for PDAC stroma and predict response to therapy. Gene expression datasets, co-culture experiments, xenografts, and patient samples were analyzed. Serum samples were measured from a cohort of 58 resected patients, and 87 metastatic or locally advanced PDAC patients...
November 16, 2018: Oncogenesis
Max Michael Traeger, Jan Rehkaemper, Hansjoerg Ullerich, Konrad Steinestel, Eva Wardelmann, Norbert Senninger, Sameer Abdallah Dhayat
PURPOSE: Early treatment of pancreatic ductal adenocarcinoma (PDAC) is significantly delayed due to the lack of liquid biopsy markers for early diagnosis at surgically resectable tumor stages. Recent studies suggest that microRNA-205 (miR-205) is involved in PDAC progression by post-transcriptional regulation of epithelial-to-mesenchymal transition (EMT). However, the clinical potential of miR-205 as diagnostic and prognostic marker remains undefined and its exact role in PDAC is still ambiguous...
December 2018: Journal of Cancer Research and Clinical Oncology
Sisi Ye, Li Bai
Purpose: We aimed to compare and validate the prognostic value of inflammation-based prognostic scores for patients with resectable pancreatic ductal adenocarcinoma (PDAC) and to establish a novel, effective nomogram incorporating inflammation-based prognostic scores to predict disease-free survival (DFS) in these patients. Patients and methods: Clinicopathological characteristics and follow-up data were retrieved from our prospective database. A total of 420 patients with PDAC who underwent radical resection were evaluated between January 2007 and December 2016...
2018: Cancer Management and Research
Shin-Heng Chiou, Madeleine Dorsch, Eva Kusch, Santiago Naranjo, Margaret M Kozak, Albert C Koong, Monte M Winslow, Barbara M Grüner
Expression of the chromatin-associated protein HMGA2 correlates with progression, metastasis and therapy resistance in pancreatic ductal adenocarcinoma (PDAC). Hmga2 has also been identified as a marker of a transient subpopulation of PDAC cells that has increased metastatic ability. Here, we characterize the requirement for Hmga2 during growth, dissemination, and metastasis of PDAC in vivo using conditional inactivation of Hmga2 in well-established autochthonous mouse models of PDAC. Overall survival, primary tumour burden, presence of disseminated tumour cells in the peritoneal cavity or circulating tumour cells in the blood, and presence and number of metastases were not significantly different between mice with Hmga2-wildtype or Hmga2-deficient tumours...
September 18, 2018: Scientific Reports
Anda J Stroese, Hansjoerg Ullerich, Gabriele Koehler, Verena Raetzel, Norbert Senninger, Sameer A Dhayat
PURPOSE: Recently, we identified the microRNA-99 family as unfavorable prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to evaluate its value as circulating biomarker for PDAC. METHODS: Tissue and corresponding preoperative blood samples of 181 patients with PDAC UICC Stages I-IV (n = 90), intraductal papillary mucinous neoplasm (IPMN, n = 11), chronic pancreatitis (n = 40), pancreatic cystadenoma (n = 20), and age-matched healthy blood serum controls (n = 20) were collected between 2014 and 2017 prospectively...
December 2018: Journal of Cancer Research and Clinical Oncology
Miguel Ángel Morcillo, Ángel García de Lucas, Marta Oteo, Eduardo Romero, Natalia Magro, Marta Ibáñez, Alfonso Martínez, Guillermo Garaulet, Alicia G Arroyo, Pedro Pablo López-Casas, Manuel Hidalgo, Francisca Mulero, Jorge Martínez-Torrecuadrada
Pancreatic ductal adenocarcinoma (PDAC) continues to be one of the deadliest cancers for which optimal diagnostic tools are still greatly needed. Identification of PDAC-specific molecular markers would be extremely useful to improve disease diagnosis and follow-up. MT1-MMP has long been involved in pancreatic cancer, especially in tumour invasion and metastasis. In this study, we aim to ascertain the suitability of MT1-MMP as a biomarker for positron emission tomography (PET) imaging. Two probes were assessed and compared for this purpose, an MT1-MMP-specific binding peptide (MT1-AF7p) and a specific antibody (LEM2/15), labelled, respectively, with 68 Ga and with 89 Zr...
2018: Contrast Media & Molecular Imaging
Sameer Abdallah Dhayat, Max Michael Traeger, Jan Rehkaemper, Anda Jana Stroese, Konrad Steinestel, Eva Wardelmann, Iyad Kabar, Norbert Senninger
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive carcinoma entities worldwide with early and rapid dissemination. Recently, we discussed the role of microRNAs as epigenetic regulators of Epithelial-to-Mesenchymal Transition (EMT) in PDAC. In this study, we investigated their value as diagnostic and prognostic markers in tissue and blood samples of 185 patients including PDAC, non-malignant pancreatic disorders, and age-matched healthy controls. Expression of the microRNA-200-family (microRNAs -141, -200a, -200b, -200c, -429) and microRNA-148a was significantly downregulated in tissue of PDAC Union internationale contre le cancer (UICC) Stage II...
September 13, 2018: Cancers
Alexandros Giakoustidis, Kyriakos Neofytou, Mafalda Costa Neves, Dimitrios Giakoustidis, Eleni Louri, David Cunningham, Satvinder Mudan
Backgrounds/Aims: It is important to point out that the identification of inflammation is an essential component of the pathogenesis and the progression of cancer. In this study, we analysed the neutrophil-to-lymphocyte ratio (NLR) and the platelets-to-lymphocyte ratio (PLR), with an overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC), who were treated with a resection following or not following a procedure of neoadjuvant chemotherapy/chemoradiation. We intended to identify the significance of the role of NLR and PLR, as prognostic markers in patients undergoing surgery for PDAC...
August 2018: Annals of Hepato-Biliary-Pancreatic Surgery
Mouad Edderkaoui, Chintan Chheda, Badr Soufi, Fouzia Zayou, Robert Hu, V Krishnan Ramanujan, Xinlei Pan, Laszlo G Boros, Jian Tajbakhsh, Anisha Madhav, Neil Bhowmick, Qiang Wang, Michael Lewis, Richard Tuli, Aida Habtezion, Ramachandran Murali, Stephen J Pandol
BACKGROUND & AIMS: Growth, progression, and drug resistance of pancreatic ductal adenocarcinomas (PDACs) have been associated with increased levels and activity of glycogen synthase kinase 3 beta (GSK3B) and histone deacetylases (HDACs). We designed and synthesized molecules that simultaneously inhibit the activities of both enzymes. We tested the effects of one of these molecules, metavert, in pancreatic cancer cells and mice with pancreatic tumors. METHODS: We tested the ability of metavert to bind GSK3B and HDACs using surface plasmon resonance...
August 23, 2018: Gastroenterology
Georgios Gemenetzis, Vincent P Groot, Jun Yu, Ding Ding, Jonathan A Teinor, Ammar A Javed, Laura D Wood, Richard A Burkhart, John L Cameron, Martin A Makary, Matthew J Weiss, Jin He, Christopher L Wolfgang
OBJECTIVES: Previous retrospective studies demonstrated that circulating tumor cells (CTCs) subtypes correlate with overall survival in patients with pancreatic ductal adenocarcinoma (PDAC). Herein, we report results of a prospective observational study on CTCs dynamics to assess their clinical significance. METHODS: The CLUSTER study is a prospective longitudinal study on PDAC CTCs dynamics (NCT02974764). Multiple peripheral blood samples were collected from 200 consecutively enrolled patients with presumed PDAC diagnosis...
September 2018: Annals of Surgery
Dong Dong, Li Jia, Lufang Zhang, Na Ma, Aimin Zhang, Yunli Zhou, Li Ren
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with few biomarkers to guide treatment options. Carbohydrate antigen 19.9 (CA19.9), the most frequently used biomarker for PDAC, is not sensitive and specific enough for the detection of the disease. This study aimed to evaluate serum periostin (POSTN) and CA242 as potential diagnostic biomarkers complementing CA19.9 in detecting pancreatic cancer. Blood samples were from 362 participants, including 213 patients with different stages of PDAC, 75 patients with benign pancreatic disease, and 74 healthy individuals...
September 2018: Cancer Science
Zhonghu Li, Wu Yanfang, Jie Li, Peng Jiang, Tao Peng, Kai Chen, Xin Zhao, Yujun Zhang, Ping Zhen, Jin Zhu, Xiaowu Li
Circular RNA (circ-RNA) and exosomes have recently been shown to play important roles in different tumors. However, the functions and regulatory mechanisms of exosomal circ-RNA in pancreatic ductal adenocarcinoma (PDAC) tumor progression remain unclear. Here, we identified a circular RNA (circ-PDE8A) from liver-metastatic PDAC cells by microarray analysis, detected its expression levels in clinical tissues and found that high circ-PDE8A expression was correlated with lymphatic invasion, TNM stage and a poor survival rate of PDAC patients...
September 28, 2018: Cancer Letters
Michael J Levy, Benjamin R Kipp, Dragana Milosevic, Amber R Schneider, Jesse S Voss, Rajeswari Avula, Sarah E Kerr, Michael R Henry, Edward Highsmith, Minetta C Liu, Ferga C Gleeson
BACKGROUND & AIMS: Cellular and nuclear material from tumors disseminates into the bloodstream (tumoremia), but it is not clear whether medical procedures cause release of this material or contribute to formation of metastases. We performed a prospective study of blood samples from patients with pancreatic adenocarcinoma (PDAC) to determine whether endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) associates with markers of tumoremia. METHODS: We obtained peripheral blood from 104 patients (35 with PDAC) before and after EUS-FNA of primary tumors; blood samples from 69 healthy individuals were used as controls...
October 2018: Clinical Gastroenterology and Hepatology
Xinxin Song, Shan Zhu, Yangchun Xie, Jiao Liu, Lingyi Sun, Dexing Zeng, Pengcheng Wang, Xiaochao Ma, Guido Kroemer, David L Bartlett, Timothy R Billiar, Michael T Lotze, Herbert J Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Maintenance of acid-base homeostasis is required for normal physiology, metabolism, and development. It is not clear how cell death is activated in response to changes in pH. We performed a screen to identify agents that induce cell death in a pH-dependent manner (we call this alkaliptosis) in pancreatic ductal adenocarcinoma cancer (PDAC) cells and tested their effects in mice. METHODS: We screened a library of 254 compounds that interact with G-protein-coupled receptors (GPCRs) to identify those with cytotoxic activity against a human PDAC cell line (PANC1)...
April 2018: Gastroenterology
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