scholarly journals Primary pancreatic ductal adenocarcinoma cell cultures represent the features of native tumours

Biologija ◽  
2019 ◽  
Vol 65 (1) ◽  
Author(s):  
Marija Ger ◽  
Eglė Žalytė ◽  
Algirdas Kaupinis ◽  
Benediktas Kurlinkus ◽  
Marius Petrulionis ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Cultures ◽  
Early Stage ◽  
Focal Adhesions ◽  
Chemotherapeutic Agents ◽  
Ductal Adenocarcinoma ◽  
Diagnostic Tools ◽  
Pdgf Receptor ◽  
Tissue Samples ◽  
Low Efficiency

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer due to the lack of diagnostic tools at the early stage and low efficiency of current chemotherapeutic approaches. The anticancer compounds with proven efficiency in established cell cultures often fail validation in further research. In this study, we employed PDAC patient-derived primary cell cultures to evaluate the efficiency of chemotherapeutic agents. Alongside, patients’ tissue samples were analysed by high-throughput differential proteomic analysis. We have shown that main firstline chemotherapeutic agents gemcitabine and FOLFIRINOX have little to no effect on the viability of patient-derived primary PDAC cells. The comparative proteomic and bioinformatic analysis of PDAC tumours shows an increase in the components of the extracellular matrix and focal adhesions and also overexpression of the downstream signaling from a variety of receptors, most notably PDGF receptor β and ErbB1 receptor. Consistently, all tumour-derived cell cultures assayed express a high level of PDGF receptor β. The enhancement of multiple signaling pathways leads to the increase in cell survival, proliferation, and resistance to apoptosis. Here we demonstrated the promising value of patient-derived primary PDAC cultures as a model for anticancer drug research and evaluation for individualized therapy.

scholarly journals Panel of serum miRNAs as potential non-invasive biomarkers for pancreatic ductal adenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Imteyaz Ahmad Khan ◽  
Safoora Rashid ◽  
Nidhi Singh ◽  
Sumaira Rashid ◽  
Vishwajeet Singh ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Early Stage ◽  
Ductal Adenocarcinoma ◽  
Next Generation ◽  
Serum Samples ◽  
Tissue Samples ◽  
Non Invasive ◽  
Specific Symptoms ◽  
Generation Sequencing

AbstractEarly-stage diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to non-specific symptoms. Circulating miRNAs in body fluids have been emerging as potential non-invasive biomarkers for diagnosis of many cancers. Thus, this study aimed to assess a panel of miRNAs for their ability to differentiate PDAC from chronic pancreatitis (CP), a benign inflammatory condition of the pancreas. Next-generation sequencing was performed to identify miRNAs present in 60 FFPE tissue samples (27 PDAC, 23 CP and 10 normal pancreatic tissues). Four up-regulated miRNAs (miR-215-5p, miR-122-5p, miR-192-5p, and miR-181a-2-3p) and four down-regulated miRNAs (miR-30b-5p, miR-216b-5p, miR-320b, and miR-214-5p) in PDAC compared to CP were selected based on next-generation sequencing results. The levels of these 8 differentially expressed miRNAs were measured by qRT-PCR in 125 serum samples (50 PDAC, 50 CP, and 25 healthy controls (HC)). The results showed significant upregulation of miR-215-5p, miR-122-5p, and miR-192-5p in PDAC serum samples. In contrast, levels of miR-30b-5p and miR-320b were significantly lower in PDAC as compared to CP and HC. ROC analysis showed that these 5 miRNAs can distinguish PDAC from both CP and HC. Hence, this panel can serve as a non-invasive biomarker for the early detection of PDAC.

scholarly journals MicroRNA-21 Is Induced Early in Pancreatic Ductal Adenocarcinoma Precursor Lesions

2010 ◽  
Vol 56 (4) ◽  
pp. 603-612 ◽  
Author(s):  
Maël Chalret du Rieu ◽  
Jérôme Torrisani ◽  
Janick Selves ◽  
Talal Al Saati ◽  
Anny Souque ◽  
...  
Keyword(s):  
Early Detection ◽  
Mouse Model ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Early Stage ◽  
Survival Rates ◽  
Ductal Adenocarcinoma ◽  
Early Event ◽  
Precursor Lesions ◽  
Tissue Samples ◽  
Ductal Cells

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) has the poorest overall prognosis among gastrointestinal cancers; however, curative resection in early-stage PDAC greatly improves survival rates, indicating the importance of early detection. Because abnormal microRNA production is commonly detected in cancer, we investigated noninvasive precursor pancreatic intraepithelial neoplasia (PanIN) lesions for microRNA production as a potential early biomarker of PDAC. Methods: Pathologists identified and classified ductal lesions. We extracted total RNA from laser-capture microdissected PanIN tissue samples from a conditional KRAS(G12D) mouse model (n = 29) or of human origin (n = 38) (KRAS is v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog). MicroRNA production was quantified by quantitative real-time PCR. Internal controls included 5S and U6 RNAs. Results: Production of microRNAs miR-21, miR-205, and miR-200 paralleled PanIN progression in the KRAS(G12D) mouse model, compared with microRNA production in samples of nonpathologic ducts. miR-21 demonstrated the highest relative concentrations in the precursor lesions. Interestingly, miR-205 and miR-21 up-regulation preceded phenotypic changes in the ducts. The production of microRNAs miR-21, miR-221, miR-222, and let-7a increased with human PanIN grade, with peak production occurring in hyperplastic PanIN-2/3 lesions. In situ hybridization analysis indicated miR-21 production to be concentrated in pathologic ductal cells. miR-21 production was regulated by KRAS(G12D) and epidermal growth factor receptor in PDAC-derived cell lines. Conclusions: Aberrant microRNA production is an early event in the development of PanIN. Our findings indicate that miR-21 warrants further investigation as a marker for early detection of PDAC.

scholarly journals The Emerging Role of Microbiota and Microbiome in Pancreatic Ductal Adenocarcinoma

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 565
Author(s):  
Sona Ciernikova ◽  
Maria Novisedlakova ◽  
Danka Cholujova ◽  
Viola Stevurkova ◽  
Michal Mego
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Malignant Tumors ◽  
Current Knowledge ◽  
Early Stage ◽  
Poor Response ◽  
Response To Therapy ◽  
Oral Microbiome ◽  
Ductal Adenocarcinoma ◽  
The Impact

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant tumors due to the absence of biomarkers for early-stage detection and poor response to therapy. Since mounting evidence supports the role of microbiota composition in tumorigenesis and cancer treatment, the link between microbiome and PDAC has been described. In this review, we summarize the current knowledge regarding the impact of the gut and oral microbiome on the risk of PDAC development. Microenvironment-driven therapy and immune system interactions are also discussed. More importantly, we provide an overview of the clinical trials evaluating the microbiota role in the risk, prognosis, and treatment of patients suffering from PDAC and solid tumors. According to the research findings, immune tolerance might result from the microbiota-derived remodeling of pancreatic tumor microenvironment. Thus, microbiome profiling and targeting represent the potential trend to enhance antitumor immunity and improve the efficacy of PDAC treatment.

scholarly journals Prognostic Fifteen-Gene Signature for Early Stage Pancreatic Ductal Adenocarcinoma

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0133562 ◽  
Author(s):  
Dung-Tsa Chen ◽  
Ashley H. Davis-Yadley ◽  
Po-Yu Huang ◽  
Kazim Husain ◽  
Barbara A. Centeno ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Early Stage ◽  
Gene Signature ◽  
Ductal Adenocarcinoma

Development of Pancreatic Cancer: Targets for Early Detection and Treatment

2016 ◽  
Vol 34 (5) ◽  
pp. 525-531 ◽  
Author(s):  
Markus M. Lerch ◽  
Julia Mayerle ◽  
Ujjwal Mahajan ◽  
Matthias Sendler ◽  
F. Ulrich Weiss ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Early Detection ◽  
Tyrosine Kinases ◽  
Histone Deacetylases ◽  
Hedgehog Signaling ◽  
Pharmaceutical Preparations ◽  
Chemotherapeutic Agents ◽  
Ductal Adenocarcinoma ◽  
Diagnostic Tools

Background: Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer death worldwide and compared to other malignancies its share in cancer mortality is expected to rise further. This is due to a lack of sensitive diagnostic tools that would permit earlier detection in a potentially curable stage and the very slow progress in finding effective drug treatments for pancreatic cancer. Key Messages: Aside from genetic predispositions and environmental agents, chronic pancreatitis is by far the greatest risk factor for PDAC. It also shares several etiological factors with pancreatic cancer and represents its most challenging differential diagnosis. Biomarkers that can distinguish between chronic pancreatitis and PDAC may therefore be suitable for the latter's early detection. Moreover, targeting the natural history of chronic pancreatitis would be one approach to prevent PDAC. Targeting tumor-cell signaling directly by interfering with receptor tyrosine kinases has shown some efficacy, although the results in clinical trials were less encouraging than for other cancers. Other compounds developed have targeted the formation of extracellular matrix around the tumor, the proteolytic activity in the tumor environment, histone deacetylases, hedgehog signaling and heat shock proteins, but none has yet found its way into routine patient care. Attempts to individualize treatment according to the tumor's somatic mutation profile are novel but so far impractical. Conclusions: Progress in the treatment of pancreatic cancer has been exceedingly slow and mostly dependent on improved pharmaceutical preparations or combinations of established chemotherapeutic agents. The promise of major breakthroughs implied in targeting tumor signal transduction events has so far not materialized.

scholarly journals New Hope for Pancreatic Ductal Adenocarcinoma Treatment Targeting Endoplasmic Reticulum Stress Response: A Systematic Review

2018 ◽  
Vol 19 (9) ◽  
pp. 2468 ◽  
Author(s):  
Nuria Garcia-Carbonero ◽  
Weiyao Li ◽  
Marticela Cabeza-Morales ◽  
Javier Martinez-Useros ◽  
Jesus Garcia-Foncillas
Keyword(s):  
Systematic Review ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Early Stage ◽  
Stress Factors ◽  
Endoplasmic Reticulum Stress Response ◽  
Ductal Adenocarcinoma ◽  
Mutational Status ◽  
Chemotherapeutic Treatment

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumours, and its incidence is rising worldwide. Although survival can be improved by surgical resection when these tumours are detected at an early stage, this cancer is usually asymptomatic, and disease only becomes apparent after metastasis. Several risk factors are associated with this disease, the most relevant being chronic pancreatitis, diabetes, tobacco and alcohol intake, cadmium, arsenic and lead exposure, certain infectious diseases, and the mutational status of some genes associated to a familial component. PDAC incidence has increased in recent decades, and there are few alternatives for chemotherapeutic treatment. Endoplasmic reticulum (ER) stress factors such as GRP78/BiP (78 kDa glucose-regulated protein), ATF6α (activating transcription factor 6 isoform α), IRE1α (inositol-requiring enzyme 1 isoform α), and PERK (protein kinase RNA-like endoplasmic reticulum kinase) activate the transcription of several genes involved in both survival and apoptosis. Some of these factors aid in inducing a non-proliferative state in cancer called dormancy. Modulation of endoplasmic reticulum stress could induce dormancy of tumour cells, thus prolonging patient survival. In this systematic review, we have compiled relevant results concerning those endoplasmic reticulum stress factors involved in PDAC, and we have analysed the mechanism of dormancy associated to endoplasmic reticulum stress and its potential use as a chemotherapeutic target against PDAC.

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