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.

scholarly journals Acinar transformed ductal cells exhibit differential mucin expression in a tamoxifen-induced pancreatic ductal adenocarcinoma mouse model

Biology Open ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. bio052878
Author(s):  
Kavita Mallya ◽  
Dhanya Haridas ◽  
Parthasarathy Seshacharyulu ◽  
Ramesh Pothuraju ◽  
Wade M. Junker ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mouse Model ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Intraepithelial Neoplasia ◽  
Ductal Adenocarcinoma ◽  
Chemotherapy Response ◽  
Pancreatic Intraepithelial Neoplasia ◽  
Ductal Cells ◽  
Mucin Expression ◽  
Acinar To Ductal Metaplasia

ABSTRACTPancreatic cancer (PC) is acquired postnatally; to mimic this scenario, we developed an inducible KrasG12D; Ptf1a-CreER™ (iKC) mouse model, in which Kras is activated postnatally at week 16 upon tamoxifen (TAM) administration. Upon TAM treatment, iKC mice develop pancreatic intraepithelial neoplasia (PanIN) lesions and PC with metastasis at the fourth and fortieth weeks, respectively, and exhibited acinar-to-ductal metaplasia (ADM) and transdifferentiation. Kras activation upregulated the transcription factors Ncoa3, p-cJun and FoxM1, which in turn upregulated expression of transmembrane mucins (Muc1, Muc4 and Muc16) and secretory mucin (Muc5Ac). Interestingly, knockdown of KrasG12D in multiple PC cell lines resulted in downregulation of MUC1, MUC4, MUC5AC and MUC16. In addition, iKC mice exhibited ADM and transdifferentiation. Our results show that the iKC mouse more closely mimics human PC development and can be used to investigate pancreatic ductal adenocarcinoma (PDAC) biomarkers, early onset of PDAC, and ADM. The iKC model can also be used for preclinical strategies such as targeting mucin axis alone or in combination with neo-adjuvant, immunotherapeutic approaches and to monitor chemotherapy response.

scholarly journals Developmental Pathways Direct Pancreatic Cancer Initiation from Its Cellular Origin

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Maximilian Reichert ◽  
Karin Blume ◽  
Alexander Kleger ◽  
Daniel Hartmann ◽  
Guido von Figura
Keyword(s):  
Pancreatic Cancer ◽  
Poor Prognosis ◽  
Intraepithelial Neoplasia ◽  
Developmental Pathways ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Intraepithelial Neoplasia ◽  
Cellular Origin ◽  
Mucinous Neoplasm ◽  
Cancer Initiation ◽  
Advanced Stages

Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis, since it is usually diagnosed at advanced stages. In order to employ tools for early detection, a better understanding of the early stages of PDA development from its main precursors, pancreatic intraepithelial neoplasia (PanIN), and intraductal papillary mucinous neoplasm (IPMN) is needed. Recent studies on murine PDA models have identified a different exocrine origin for PanINs and IPMNs. In both processes, developmental pathways direct the initiation of PDA precursors from their cellular ancestors. In this review, the current understanding of early PDA development is summarized.

scholarly journals Differentiation of Pancreatic Ductal Adenocarcinoma From Chronic Pancreatitis by PAM4 Immunohistochemistry

2014 ◽  
Vol 138 (2) ◽  
pp. 220-228 ◽  
Author(s):  
Chanjuan Shi ◽  
Nipun Merchant ◽  
Guy Newsome ◽  
David M. Goldenberg ◽  
David V. Gold
Keyword(s):  
Monoclonal Antibody ◽  
Chronic Pancreatitis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Early Stage ◽  
High Specificity ◽  
Intraepithelial Neoplasia ◽  
Tissue Microarrays ◽  
Ductal Adenocarcinoma ◽  
Precursor Lesions ◽  
Pancreatic Intraepithelial Neoplasia

Context.—PAM4 is a monoclonal antibody that shows high specificity for pancreatic ductal adenocarcinoma (PDAC) and its neoplastic precursor lesions. A PAM4-based serum immunoassay is able to detect 71% of early-stage patients and 91% with advanced disease. However, approximately 20% of patients diagnosed with chronic pancreatitis (CP) are also positive for circulating PAM4 antigen. The specificity of the PAM4 antibody is critical to the interpretation of the serum-based and immunohistochemical assays for detection of PDAC. Objective.—To determine whether PAM4 can differentiate PDAC from nonneoplastic lesions of the pancreas. Design.—Tissue microarrays of PDAC (N = 43) and surgical specimens from CP (N = 32) and benign cystic lesions (N = 19) were evaluated for expression of the PAM4 biomarker, MUC1, MUC4, CEACAM5/6, and CA19-9. Results.—PAM4 and monoclonal antibodies (MAbs) to MUC1, MUC4, CEACAM5/6, and CA19-9 were each reactive with the majority of PDAC cases; however, PAM4 was the only monoclonal antibody not to react with adjacent, nonneoplastic parenchyma. Although PAM4 labeled 19% (6 of 32) of CP specimens, reactivity was restricted to pancreatic intraepithelial neoplasia associated with CP; inflamed tissues were negative in all cases. In contrast, MUC1, MUC4, CEACAM5/6, and CA19-9 were detected in 90%, 78%, 97%, and 100% of CP, respectively, with reactivity also present in nonneoplastic inflamed tissue. Conclusions.—PAM4 was the only monoclonal antibody able to differentiate PDAC (and pancreatic intraepithelial neoplasia precursor lesions) from benign, nonneoplastic tissues of the pancreas. These results suggest the use of PAM4 for evaluation of tissue specimens, and support its role as an immunoassay for detection of PDAC.

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.

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.

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 Aberrant MicroRNAs in Pancreatic Cancer: Researches and Clinical Implications

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Tao Sun ◽  
Xiangyu Kong ◽  
Yiqi Du ◽  
Zhaoshen Li
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Poor Prognosis ◽  
Vital Role ◽  
High Rate ◽  
Ductal Adenocarcinoma ◽  
Clinical Implications ◽  
Circulating Mirnas ◽  
Current Review ◽  
Wide Range

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a high rate of mortality and poor prognosis. Numerous studies have proved that microRNA (miRNA) may play a vital role in a wide range of malignancies, including PDAC, and dysregulated miRNAs, including circulating miRNAs, are associated with PDAC proliferation, invasion, chemosensitivity, and radiosensitivity, as well as prognosis. Greater understanding of the roles of miRNAs in PDAC could provide insights into this disease and identify potential diagnostic markers and therapeutic targets. The current review focuses on recent advances with respect to the roles of miRNAs in PDAC and their practical value.

scholarly journals c-Fos/ERK promotes the progression from pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma

2016 ◽  
Vol 36 (6) ◽  
pp. 3413-3420 ◽  
Author(s):  
Lei You ◽  
Xiaoxia Ren ◽  
Yongxing Du ◽  
Wenjing Zhao ◽  
Ming Cui ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Intraepithelial Neoplasia ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Intraepithelial Neoplasia
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