scholarly journals A Proteomic Study on the Personalized Protein Corona of Liposomes. Relevance for Early Diagnosis of Pancreatic DUCTAL Adenocarcinoma and Biomarker Detection

2021 ◽  
Vol 2 (2) ◽  
pp. 82-93
Author(s):  
Luca Digiacomo ◽  
Francesca Giulimondi ◽  
Daniela Pozzi ◽  
Alessandro Coppola ◽  
Vincenzo La Vaccara ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Diagnosis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Protein Corona ◽  
Detection Sensitivity ◽  
Ductal Adenocarcinoma ◽  
Protein Biomarkers ◽  
Ca 19.9 ◽  
Proteomic Study

Due to late diagnosis, high incidence of metastasis, and poor survival rate, pancreatic cancer is one of the most leading cause of cancer-related death. Although manifold recent efforts have been done to achieve an early diagnosis of pancreatic cancer, CA-19.9 is currently the unique biomarker that is adopted for the detection, despite its limits in terms of sensitivity and specificity. To identify potential protein biomarkers for pancreatic ductal adenocarcinoma (PDAC), we used three model liposomes as nanoplatforms that accumulate proteins from human plasma and studied the composition of this biomolecular layer, which is known as protein corona. Indeed, plasma proteins adsorb on nanoparticle surface according to their abundance and affinity to the employed nanomaterial, thus even small differences between healthy and PDAC protein expression levels can be, in principle, detected. By mass spectrometry experiments, we quantified such differences and identified possible biomarkers for PDAC. Some of them are already known to exhibit different expressions in PDAC proteomes, whereas the role of other relevant proteins is still not clear. Therefore, we predict that the employment of nanomaterials and their protein corona may represent a useful tool to amplify the detection sensitivity of cancer biomarkers, which may be used for the early diagnosis of PDAC, with clinical implication for the subsequent therapy in the context of personalized medicine.

scholarly journals KIF4A Regulates the Progression of Pancreatic Ductal Adenocarcinoma through Proliferation and Invasion

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jing Chen ◽  
Cui-Cui Zhao ◽  
Fei-Ran Chen ◽  
Guo-Wei Feng ◽  
Fei Luo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Disease Free Survival ◽  
High Expression ◽  
Ductal Adenocarcinoma ◽  
Migration And Invasion

Background. Pancreatic cancer is a malignant tumor of the digestive tract, which is difficult to diagnose and treat due to bad early diagnosis. We aimed to explore the role of kinesin superfamily 4A (KIF4A) in pancreatic ductal adenocarcinoma (PDAC). Methods. We first used the bioinformatic website to screen the data of pancreatic cancer in TCGA, and KIF4A protein was detected among the 86 specimens of patients in our hospital combined with clinic-pathological characteristics and survival analysis. KIF4A loss-expression cell lines were established by RNA interference (RNAi). In addition, we performed in vitro cell assays to detect the changes in cell proliferation, migration, and invasion. The proteins involved in the proliferation and metastasis of cancer cells were also detected by western blot. The above results could be proved in vivo. Further, the correlation between KIF4A and CDC5L was analyzed by TCGA and IHC data. Results. We first found a high expression of KIF4A in pancreatic cancer, suggesting a role of KIF4A in the development of pancreatic cancer. KIF4A was found to be differentially expressed ( P < 0.05 ) among the 86 specimens of patients in our hospital and was significantly associated with PDAC TNM stages and tumor size. High KIF4A expression also significantly worsened overall survival (OS) and disease-free survival rate (DFS) ( P < 0.05 , respectively). In addition, cell proliferation, migration, and invasion were inhibited by the KIF4A-shRNA group compared with the control ( P < 0.05 , respectively). In the end, knockdown of KIF4A could inhibit tumor development and metastasis in vivo. Further, the positive correlation between KIF4A and CDC5L existed, and KIF4A might promote pancreatic cancer proliferation by affecting CDC5L expression. Conclusion. In conclusion, the high expression level of KIF4A in PDAC was closely related to poor clinical and pathological status, lymphatic metastasis, and vascular invasion. KIF4A might be involved in promoting the development of PDAC in vitro and in vivo, which might be a new therapeutic target of PDAC.

scholarly journals CCAAT/Enhancer-Binding Protein Delta (C/EBPδ): A Previously Unrecognized Tumor Suppressor that Limits the Oncogenic Potential of Pancreatic Ductal Adenocarcinoma Cells

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2546
Author(s):  
Leonie Hartl ◽  
JanWillem Duitman ◽  
Hella L. Aberson ◽  
Kan Chen ◽  
Frederike Dijk ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Suppressor ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Binding Protein ◽  
Ductal Adenocarcinoma ◽  
Ductal Cells ◽  
Enhancer Binding Protein ◽  
Adenocarcinoma Cells ◽  
Ccaat Enhancer Binding Protein

CCAAT/enhancer-binding protein δ (C/EBPδ) is a transcription factor involved in growth arrest and differentiation, which has consequently been suggested to harbor tumor suppressive activities. However, C/EBPδ over-expression correlates with poor prognosis in glioblastoma and promotes genomic instability in cervical cancer, hinting at an oncogenic role of C/EBPδ in these contexts. Here, we explore the role of C/EBPδ in pancreatic cancer. We determined C/EBPδ expression in biopsies from pancreatic cancer patients using public gene-expression datasets and in-house tissue microarrays. We found that C/EBPδ is highly expressed in healthy pancreatic ductal cells but lost in pancreatic ductal adenocarcinoma. Furthermore, loss of C/EBPδ correlated with increased lymph node involvement and shorter overall survival in pancreatic ductal adenocarcinoma patients. In accordance with this, in vitro experiments showed reduced clonogenic capacity and proliferation of pancreatic ductal adenocarcinoma cells following C/EBPδ re-expression, concurrent with decreased sphere formation capacity in soft agar assays. We thus report a previously unrecognized but important tumor suppressor role of C/EBPδ in pancreatic ductal adenocarcinoma. This is of particular interest since only few tumor suppressors have been identified in the context of pancreatic cancer. Moreover, our findings suggest that restoration of C/EBPδ activity could hold therapeutic value in pancreatic ductal adenocarcinoma, although the latter claim needs to be substantiated in future studies.

scholarly journals How pancreatic adenocarcinoma might cause diabetes? The role of TGF- β

2021 ◽  
pp. 05-10
Author(s):  
Hanan F. Aly
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Pancreatic Adenocarcinoma ◽  
De Novo ◽  
Ductal Adenocarcinoma ◽  
Preneoplastic Lesions ◽  
Β Cells ◽  
Selective Depletion ◽  
New Onset

Pancreatic ductal adenocarcinoma (PDAC) is a deadly sickness that stays incurable due to past due diagnosis, which renders any healing intervention challenging. Most PDAC sufferers expand de novo diabetes, which exacerbates their morbidity and mortality. How PDAC triggers diabetes continues to be unfolding. Using a mouse version of KrasG12D-pushed PDAC, which faithfully recapitulates the development of the human sickness, we determined a large and selective depletion of β-cells, taking place very early on the degrees of preneoplastic lesions. Mechanistically, it turned into observed that accelerated TGF beta (TGF-β) signaling throughout PDAC development induced erosion of β-mobileular mass thru apoptosis. Suppressing TGF-β signaling, both pharmacologically thru TGF-β immunoneutralization or genetically thru deletion of Smad4 or TGF-β kind II receptor (TβRII), afforded size able safety in opposition to PDAC-pushed β-mobileular depletion. From a translational perspective, each activation of TGF-β signaling and depletion of β-cells often arise in human PDAC, imparting a mechanistic cause of the pathogenesis of diabetes in PDAC sufferers, and similarly implicating new- onset diabetes as a capability early prognostic marker for PDAC. In this mini review we try to analyze the principle relationships between pancreatic cancer and diabetes and vice versa in addition to the implication of TGF-β signaling as a likely goal for attenuating diabetes in pancreatic most cancers patients.

scholarly journals The Role of Stellate Cells in Pancreatic Ductal Adenocarcinoma: Targeting Perspectives

2021 ◽  
Vol 10 ◽  
Author(s):  
Yang Wu ◽  
Chun Zhang ◽  
Kuirong Jiang ◽  
Jens Werner ◽  
Alexandr V. Bazhin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Ductal Adenocarcinoma ◽  
Gastrointestinal Malignancy ◽  
Desmoplastic Reaction ◽  
Pancreatic Cancer Cells ◽  
Promising Strategy

Pancreatic ductal adenocarcinoma (PDAC) is a gastrointestinal malignancy with a dismal clinical outcome. Accumulating evidence suggests that activated pancreatic stellate cells (PSCs), the major producers of extracellular matrix (ECM), drive the severe stromal/desmoplastic reaction in PDAC. Furthermore, the crosstalk among PSCs, pancreatic cancer cells (PCCs) as well as other stroma cells can establish a growth-supportive tumor microenvironment (TME) of PDAC, thereby enhancing tumor growth, metastasis, and chemoresistance via various pathways. Recently, targeting stroma has emerged as a promising strategy for PDAC therapy, and several novel strategies have been proposed. The aim of our study is to give a profound review of the role of PSCs in PDAC progression and recent advances in stroma-targeting strategies.

scholarly journals CD248(TEM1/CD164L1/Endosialin): A new molecular target for anti-angiogenic therapy in Pancreatic ductal adenocarcinoma

2021 ◽  
Author(s):  
Huan Zhang ◽  
Zhujiang Dai ◽  
Yiqun Liao ◽  
Cheng Yan ◽  
Bin Zhao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Diagnosis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Poor Prognosis ◽  
Gene Network ◽  
Mirna Gene ◽  
Molecular Targets ◽  
Diagnosis And Treatment ◽  
Ductal Adenocarcinoma ◽  
Angiogenic Therapy

Abstract Background: Pancreatic ductal adenocarcinoma (PDCA) is one of the malignant tumors with the worst prognosis with a 5-year survival rate of <1%, which is known as the "king of cancers". At present, there is a lack of effective early diagnosis and treatment plan for pancreatic cancer. Therefore, there is an urgent need to understand the molecular mechanisms of pancreatic cancer to generate innovative approaches for the development of effective early diagnosis and treatment strategies.Methods: In this study, we performed single gene pan-cancer analysis, gene co-expression analysis and gene regulatory correlation analysis to understand the molecular mechanism of CD248 in pancreatic cancer using bioinformatics tools. Additionally, we provided potential molecular targets for pancreatic cancer treatment by constructing the lncRNA-miRNA-gene network axis.Results: The results showed that CD248 is differentially expressed in normal and tumor tissues, and abnormally high expression predicts poor prognosis, is a proto-oncogene in pancreatic cancer. Besides, CD248 is associated with angiogenesis of tumors. We obtained three new lncRNA-miRNA-gene network axes, namely AC008040.1-hsa-miR-200c-3p-CD248 axis, AC055822.1-hsa-miR-200c-3p-CD248 axis, RRN3P2-hsa-miR-200c-3p-CD248 axis that provide promising molecular targets for anti-angiogenic therapy and diagnostic biomarkers for pancreatic cancer.Conclusion: In conclusion, this study shows that over-expression of CD248 (TEM1/CD164L1/Endosialin) is always present in breast cancer and predicts a poor prognosis, associated with tumor angiogenesis, suggesting it as an attractive therapeutic target for pancreatic cancer.

The Anti-Tumor Activity of Afatinib in Pancreatic Ductal Adenocarcinoma Cells

2020 ◽  
Vol 20 (12) ◽  
pp. 1447-1458
Author(s):  
Zhenyu Ye ◽  
Yecheng Li ◽  
Jiaming Xie ◽  
Zhenyu Feng ◽  
Xiaodong Yang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Underlying Mechanism ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Ductal Adenocarcinoma ◽  
Adenocarcinoma Cells ◽  
The Social ◽  
New Perspective

Background: Pancreatic Ductal Adenocarcinoma (PDAC) is the most common form of pancreatic cancer and leading causes of pancreatic cancer death because of most PDAC patients with advanced unresectable disease at that time, which is remarkably resistant to all forms of chemotherapy and radiotherapy. Objective: PDAC increases the social and patient's family burden. However, the PDAC pathogenesis is not identified. We are trying to uncover the underlying mechanism in the future. Methods: In our research, the drug-resistant cell line was successfully induced in the vitro by progressive concentrations of Afatinib, which we named it as BxPC3-AR. Results: It has been observed that the effect of autophagy was on the resistance of BxPC3-AR to Afatinib. Conclusion: It has been confirmed that autophagy plays a certain role in BxPC3-AR resistance to Afatinib. Our findings provide a new perspective on the role of autophagy in pancreatic ductal adenocarcinoma.

scholarly journals Advances in Early Detection of Pancreatic Cancer

Diagnostics ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 18 ◽  
Author(s):  
Atsushi Kanno ◽  
Atsushi Masamune ◽  
Keiji Hanada ◽  
Masataka Kikuyama ◽  
Masayuki Kitano
Keyword(s):  
Pancreatic Cancer ◽  
Early Detection ◽  
Early Diagnosis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Early Stage ◽  
Epidemiological Data ◽  
The United States ◽  
Ductal Adenocarcinoma ◽  
Intraductal Papillary Mucinous Neoplasms ◽  
Mucinous Neoplasms

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. PDAC is the fourth leading cause of death in the United States and Japan based on epidemiological data. Early detection of PDAC is very important to improve the prognosis of PDAC. Early detection of pancreatic ductal adenocarcinoma (PDAC) requires further examination after selecting cases with risk factors for the condition, such as family history, hereditary pancreatic carcinoma syndrome, intraductal papillary mucinous neoplasms, or chronic pancreatitis. The Japan Study Group on the Early Detection of Pancreatic Cancer has investigated and clarified the clinicopathological features for the early diagnosis of PDAC. In Japan, an algorithm for the early diagnosis of PDAC, which utilized the cooperation of local clinics and regional general hospitals, has been a breakthrough in the detection of early-stage PDAC. Further approaches for the early diagnosis of PDAC are warranted.

Metabonomic alterations from pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma facilitate the identification of biomarkers in serum for early diagnosis of pancreatic cancer

2016 ◽  
Vol 12 (9) ◽  
pp. 2883-2892 ◽  
Author(s):  
Xianchao Lin ◽  
Bohan Zhan ◽  
Shi Wen ◽  
Zhishui Li ◽  
Heguang Huang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Diagnosis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Poor Prognosis ◽  
Malignant Disease ◽  
Early Stage ◽  
Intraepithelial Neoplasia ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Intraepithelial Neoplasia

Pancreatic cancer is a highly malignant disease with a poor prognosis and it is essential to diagnose and treat the disease at an early stage.

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