scholarly journals Dysregulation of miRNAs Targeting the IGF-1R Pathway in Pancreatic Ductal Adenocarcinoma

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1856
Author(s):  
Maria Dobre ◽  
Vlad Herlea ◽  
Cătălina Vlăduţ ◽  
Mihai Ciocîrlan ◽  
Vasile Daniel Balaban ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Signaling Pathway ◽  
Treatment Options ◽  
Therapy Resistance ◽  
Pancreatic Disease ◽  
Pancreatic Tissue ◽  
Ductal Adenocarcinoma ◽  
Normal Tissues ◽  
Pdac Tissue

Background: Pancreatic ductal adenocarcinoma (PDAC), the most prevalent neoplastic lethal pancreatic disease, has a poor prognosis and an increasing incidence. The insulin-like growth factor-1 receptor (IGF-1R) signaling pathway is considered to be a contributing factor to the progression, metastasis, and therapy resistance of PDAC. Currently available treatment options for PDAC are limited, but microRNAs (miRNAs) may represent a new therapeutic strategy for targeting genes involved in the IGF-1R signaling pathway. Method: We investigated the expression levels of 21 miRNAs involved in the IGF-1R signaling pathway in pancreatic tissue from 38 patients with PDAC and 11 controls (five patients with chronic pancreatitis and six patients with normal pancreatic tissue). Results: We found 19 differentially expressed miRNAs between the PDAC cases and the controls. In particular, miR-100-5p, miR-145-5p, miR-29c-3p, miR-9-5p, and miR-195-5p were exclusively downregulated in PDAC tissue but not in chronic pancreatitis or normal pancreatic tissues; both control types presented similar levels. We also identified miR-29a-3p, miR-29b-3p, and miR-7-5p as downregulated miRNAs in PDAC tissues as compared with normal tissues but not with pancreatitis tissues. Conclusions: We identified a panel of miRNAs that could represent putative therapeutic targets for the development of new miRNA-based therapies for PDAC.

scholarly journals Pancreatic Ductal Adenocarcinoma: Preclinical in vitro and ex vivo Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Beate Gündel ◽  
Xinyuan Liu ◽  
Matthias Löhr ◽  
Rainer Heuchel
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Ex Vivo ◽  
Treatment Options ◽  
3D Cell Culture ◽  
Therapy Resistance ◽  
Ductal Adenocarcinoma ◽  
The Past ◽  
Slow Progress

Pancreatic ductal adenocarcinoma (PDAC) is one of the most overlooked cancers despite its dismal median survival time of 6 months. The biggest challenges in improving patient survival are late diagnosis due to lack of diagnostic markers, and limited treatment options due to almost complete therapy resistance. The past decades of research identified the dense stroma and the complex interplay/crosstalk between the cancer- and the different stromal cells as the main culprits for the slow progress in improving patient outcome. For better ex vivo simulation of this complex tumor microenvironment the models used in PDAC research likewise need to become more diverse. Depending on the focus of the investigation, several in vitro and in vivo models for PDAC have been established in the past years. Particularly, 3D cell culture such as spheroids and organoids have become more frequently used. This review aims to examine current PDAC in vitro models, their inherent limitations, and their successful implementations in research.

scholarly journals Altered DNA methylation in ion transport and immune signalling genes is associated with severity in Pancreatic Ductal Adenocarcinoma

2021 ◽  
Author(s):  
Ankita Chatterjee ◽  
Akash Bararia ◽  
Debopriyo Ganguly ◽  
Paromita Roy ◽  
Sudeep Banerjee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Pancreatic Tissue ◽  
Differential Methylation ◽  
Ductal Adenocarcinoma ◽  
P Value ◽  
Tissue Samples ◽  
Normal Tissues ◽  
Transcription Regulators

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading cancers worldwide and has a poor survival, with a relative five-year survival rate of only 8.5%. In this study we investigated epigenetic marks associated with PDAC severity and prognosis, through studying alterations in DNA methylation patterns. Methods: DNA methylome for tumor and adjacent normal tissue samples from PDAC patients (n=7) were generated using Illumina 450K bead chips. Differentially methylated positions (DMPs) were identified with |delta beta| > 0.2 and p-value<0.01 by comparing tumors with the adjacent normal tissues. Validation of differential methylation and associated gene expression at selected genes was carried out in an independent cohort PDAC patient. Results: We identified 76 DMPs in PDAC patients that mapped to 43 genes. Among them, 44.7% (n=34) were hypo-methylated and 55.3% (n=42) were hyper-methylated DMPs in cancer samples. The trends of change in methylation at these 76 DMPs from well to moderate were like that from moderate to poorly differentiated cancer samples. The gradual trend in differential methylation was observed both in our cohort and the TCGA-PAAD cohort, suggesting methylation marks can serve as early indicators of disease pathology. Altered promoter methylation, which may affect gene expression, was observed for transcription regulators (BHLHE23, GSC2, FOXE1 and TWIST1), gated ion channels (KCNA6, and CACNB2), tumor suppressors (RASSF1, SPRED2, and NPY) and genes functioning in interferon signalling (SIGIRR, MX2, and OAS2). We also have compared the TCGA-PAAD dataset with normal pancreatic tissue data from GTEx V8 dataset leading to a confluent observation. Conclusions: We reported the first study on methylome in PDAC tumors from patients in India. We identified altered DNA methylation associated with increasing severity in PDAC among some genes like SIGIRR, MX2 along with other previously reported loci. We also concluded a confluence in our observation when comparing the TCGA-PAAD dataset with GTEx V8 dataset.

Sa1469 Differential Expression of Hedgehog Signaling Pathway in Pancreatic Ductal Adenocarcinoma (PDAC) and Chronic Pancreatitis (CP)

2016 ◽  
Vol 150 (4) ◽  
pp. S324
Author(s):  
Katarzyna Winter ◽  
Janusz Strzelczyk ◽  
Monika Dzieniecka ◽  
Malgorzata Wagrowska-Danilewicz ◽  
Marian Danilewicz ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Differential Expression ◽  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Ductal Adenocarcinoma ◽  
Hedgehog Signaling Pathway

Expression of Hedgehog signaling pathway in pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP)

Pancreatology ◽  
2015 ◽  
Vol 15 (3) ◽  
pp. S88
Author(s):  
Katarzyna Winter ◽  
Janusz Strzelczyk ◽  
Monika Dzieniecka ◽  
Malgorzata Wagrowska-Danilewicz ◽  
Marian Danilewicz ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Ductal Adenocarcinoma ◽  
Hedgehog Signaling Pathway

scholarly journals The WNT5A/ROR2 signaling pathway in pancreatic ductal adenocarcinoma (PDAC)

2020 ◽  
Author(s):  
Lydia Remtisch ◽  
Georg Wiltberger ◽  
Katrin Schierle ◽  
Moulla Yousef ◽  
René Thieme ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Signaling Pathway ◽  
Prognostic Value ◽  
Expression Patterns ◽  
Tumor Stroma ◽  
Pancreatic Tissue ◽  
Ductal Adenocarcinoma ◽  
Normal Pancreatic Tissue ◽  
Variable Expression ◽  
Wnt5a Expression

Abstract Background WNT5A/ROR2 signaling pathway has been shown to be involved in many human cancers. Its role in pancreatic ductal adenocarcinoma (PDAC) has not been clarified yet. The aim of this study was to determine the prognostic value of WNT5A-expression in conjunction with the ROR2-expression in the same tumor tissues of PDAC patients. Methods We retrospectively analyzed the expression of WNT5A and ROR2 in 117 paraffin-embedded PDAC specimens following surgical pancreatic resection by immunohistochemistry. The prognostic value of WNT5A and ROR2 was assessed using Kaplan-Meier survival curves and multivariate COX regression-models. Results High ROR2-expression was detected in 65.8% (77/117) of PDAC-tumors, in 28.2% (33/117) in tumor-stroma, and in 71.1% (65/90) of normal pancreatic tissue. High WNT5A-expression was found in 76.9% (90/117) of tumors, in 59.0% (69/117) of tumor-stroma, and in 83.0% (73/88) of normal pancreatic tissue. Spearman's correlation co-efficiency demonstrated weak association between ROR2- and WNT5A-expression in tumor (r = 0.184; p = 0.047), and no association in stroma (r = 0.036; p = 0.699). Multivariate analysis showed that regional lymph node invasion and differentiation were independent prognostic factors of survival, while ROR2- and WNT5A-expression not. Conclusions Variable expression patterns for ROR2 and WNT5A were demonstrated in PDAC and normal pancreatic tissues suggesting a role for WNT5A/ROR2 signalling pathway, not only in PDAC but also in the normal pancreatic tissue during inflammation. The lack of prognostic significance for ROR2- and WNT5A-expression in our cohort, either alone or in subgroup analysis, signifies the complexity of their role in PDAC, which is highly dependent on the different molecular receptor-ligand tissue contexts.

Comparison of Endoscopic Retrograde Pancreatography with Functional and Histologic Changes in Chronic Pancreatitis

1987 ◽  
Vol 28 (3) ◽  
pp. 289-293 ◽  
Author(s):  
H. A. Heij ◽  
H. Obertop ◽  
M. van Blankenstein ◽  
G. A. J. J. Nix ◽  
D. L. Westbroek
Keyword(s):  
Chronic Pancreatitis ◽  
Discriminant Analysis ◽  
Test Data ◽  
Pancreatic Surgery ◽  
Pancreatic Disease ◽  
Pancreatic Tissue ◽  
Endoscopic Retrograde Pancreatography ◽  
Endoscopic Retrograde ◽  
The Relationship ◽  
Histologic Changes

The findings from endoscopic retrograde pancreatography (ERP) and secretin-CCK test data were compared in 69 patients: 36 with chronic pancreatitis, 9 with possible chronic pancreatitis, and 24 without chronic pancreatic disease. The ERP findings were also compared with the histologic changes in pancreatic tissue in 18 patients who underwent pancreatic surgery for chronic pancreatitis. ERP films were reviewed according to the criteria proposed by Kasugai et coll. (8) with special attention paid to the side branches. Secretin-CCK test data were interpreted using the discriminant analysis. A good correlation between bicarbonate and chymotrypsin output and ductular changes at ERP was found. The results of ERP and the secretin-CCK test were compatible in 86 per cent of the patients. The relationship between ERP findings and histologic changes was not straightforward. It was concluded that ERP and the secretin-CCK test are complementary in the diagnosis of chronic pancreatitis. ERP does not necessarily represent the histology in chronic pancreatitis.

scholarly journals Chronic pancreatitis changes in high-risk individuals for pancreatic ductal adenocarcinoma

2019 ◽  
Vol 89 (4) ◽  
pp. 842-851.e1 ◽  
Author(s):  
Sushrut S. Thiruvengadam ◽  
Judith Chuang ◽  
Robert Huang ◽  
Mohit Girotra ◽  
Walter G. Park
Keyword(s):  
Chronic Pancreatitis ◽  
High Risk ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma

MicroRNA Signaling Pathway Network in Pancreatic Ductal Adenocarcinoma

2015 ◽  
Vol 42 (10) ◽  
pp. 563-577 ◽  
Author(s):  
Longhao Sun ◽  
Corrine Ying Xuan Chua ◽  
Weijun Tian ◽  
Zhixiang Zhang ◽  
Paul J. Chiao ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Signaling Pathway ◽  
Ductal Adenocarcinoma ◽  
Pathway Network
Sign in / Sign up

Export Citation Format

Share Document