scholarly journals Biophysical interactions between pancreatic cancer cells and pristine carbon nanotube substrates: Potential application for pancreatic cancer tissue engineering

2017 ◽  
Vol 106 (5) ◽  
pp. 1637-1644 ◽  
Author(s):  
Brigitta Matta-Domjan ◽  
Alice King ◽  
Stella Totti ◽  
Csaba Matta ◽  
George Dover ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tissue Engineering ◽  
Carbon Nanotube ◽  
Cancer Cells ◽  
Potential Application ◽  
Cancer Tissue ◽  
Pancreatic Cancer Tissue ◽  
Pancreatic Cancer Cells ◽  
Biophysical Interactions

scholarly journals LncRNA TP73-AS1 sponges miR-141-3p to promote the migration and invasion of pancreatic cancer cells through the up-regulation of BDH2

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Xian-Ping Cui ◽  
Chuan-Xi Wang ◽  
Zhi-Yi Wang ◽  
Jian Li ◽  
Ya-Wen Tan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Human Pancreatic Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Pancreatic Cancer Cells ◽  
Candidate Target ◽  
Direct Target

Abstract LncRNA TP73 antisense RNA 1T (TP73-AS1) plays an important role in human malignancies. However, the levels of TP73-AS1 and its functional mechanisms in pancreatic cancer metastasis remain unknown, and the clinical significance of TP73-AS1 in human pancreatic cancer is also unclear. In the present study, the levels of TP73-AS1 and its candidate target miR-141 in pancreatic cancer and adjacent normal tissue were detected using qRT-PCR. The association between TP73-AS1 levels and the clinicopathologic characteristics of pancreatic cancer patients were analyzed. The relationship between TP73-AS1 and miR-141, and miR-141 and its candidate target 3-hydroxybutyrate dehydrogenase type 2 (BDH2) was confirmed using dual-luciferase reporter assays. TP73-AS1 and/or miR-141 were knocked down using siRNA or an inhibitor in pancreatic cancer cells and cell migration and invasion then examined. The results showed that TP73-AS1 was up-regulated in pancreatic cancer tissue and cell lines. High levels of TP73-AS1 were correlated with poor clinicopathological characteristics and shorter overall survival. MiR-141 was a direct target for TP73-AS1, while BDH2 was a direct target for miR-141. The knockdown of TP73-AS1 significantly inhibited the migration and invasion of pancreatic cancer cells, while the miR-141 inhibitor significantly restored the migration and invasion. Therefore, TP73-AS1 positively regulated BDH2 expression by sponging miR-141. These findings suggest that TP73-AS1 serves as an oncogene and promotes the metastasis of pancreatic cancer. Moreover, TP73-AS1 could serve as a predictor and a potential drug biotarget for pancreatic cancer.

scholarly journals On the Evaluation of a Novel Hypoxic 3D Pancreatic Cancer Model as a Tool for Radiotherapy Treatment Screening

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6080
Author(s):  
Gabrielle Wishart ◽  
Priyanka Gupta ◽  
Andrew Nisbet ◽  
Giuseppe Schettino ◽  
Eirini Velliou
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Collagen I ◽  
Cancer Tissue ◽  
Pancreatic Cancer Cells ◽  
Post Radiation ◽  
The Impact ◽  
Radiotherapy Treatment

Tissue engineering is evolving to mimic intricate ecosystems of tumour microenvironments (TME) to more readily map realistic in vivo niches of cancerous tissues. Such advanced cancer tissue models enable more accurate preclinical assessment of treatment strategies. Pancreatic cancer is a dangerous disease with high treatment resistance that is directly associated with a highly complex TME. More specifically, the pancreatic cancer TME includes (i) complex structure and complex extracellular matrix (ECM) protein composition; (ii) diverse cell populations (e.g., stellate cells), cancer associated fibroblasts, endothelial cells, which interact with the cancer cells and promote resistance to treatment and metastasis; (iii) accumulation of high amounts of (ECM), which leads to the creation of a fibrotic/desmoplastic reaction around the tumour; and (iv) heterogeneous environmental gradients such as hypoxia, which result from vessel collapse and stiffness increase in the fibrotic/desmoplastic area of the TME. These unique hallmarks are not effectively recapitulated in traditional preclinical research despite radiotherapeutic resistance being largely connected to them. Herein, we investigate, for the first time, the impact of in vitro hypoxia (5% O2) on the radiotherapy treatment response of pancreatic cancer cells (PANC-1) in a novel polymer (polyurethane) based highly macroporous scaffold that was surface modified with proteins (fibronectin) for ECM mimicry. More specifically, PANC-1 cells were seeded in fibronectin coated macroporous scaffolds and were cultured for four weeks in in vitro normoxia (21% O2), followed by a two day exposure to either in vitro hypoxia (5% O2) or maintenance in in vitro normoxia. Thereafter, in situ post-radiation monitoring (one day, three days, seven days post-irradiation) of the 3D cell cultures took place via quantification of (i) live/dead and apoptotic profiles and (ii) ECM (collagen-I) and HIF-1a secretion by the cancer cells. Our results showed increased post-radiation viability, reduced apoptosis, and increased collagen-I and HIF-1a secretion in in vitro hypoxia compared to normoxic cultures, revealing hypoxia-induced radioprotection. Overall, this study employed a low cost, animal free model enabling (i) the possibility of long-term in vitro hypoxic 3D cell culture for pancreatic cancer, and (ii) in vitro hypoxia associated PDAC radio-protection development. Our novel platform for radiation treatment screening can be used for long-term in vitro post-treatment observations as well as for fractionated radiotherapy treatment.

scholarly journals bax, but notbcl-2, influences the prognosis of human pancreatic cancer

Gut ◽  
1998 ◽  
Vol 43 (3) ◽  
pp. 414-421 ◽  
Author(s):  
H Friess ◽  
Z Lu ◽  
H U Graber ◽  
A Zimmermann ◽  
G Adler ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Northern Blot ◽  
In Situ Hybridisation ◽  
Biological Significance ◽  
Human Pancreatic Cancer ◽  
Cancer Tissue ◽  
Mrna Levels ◽  
Pancreatic Cancer Cells

Background—bcl-2and bax belong to thebcl-2-related gene family, which marks a new class of genes that influence apoptosis. Thebcl-2 oncogene acts as a broad antiapoptotic factor and extends both normal and tumour cell survival. In contrast, the bax gene is a promoter of apoptosis.Aims—To analyse the expression of bcl-2 andbax in pancreatic cancer and correlate the results with clinical parameters.Patients—Pancreatic cancer tissue samples were obtained from 28 female and 32 male patients (median age 63, range 43–79 years) having surgery for pancreatic cancer. Normal pancreatic tissues obtained from 18 previously healthy organ donors served as controls.Methods—The levels ofbcl-2 and baxmRNA expression were analysed by northern blot and the exact site of mRNA transcription was determined by in situ hybridisation. The presence of the corresponding proteins was determined by immunohistochemistry.Results—Northern blot analysis indicated that, in comparison with the normal pancreas,bcl-2 mRNA was overexpressed in 30% andbax mRNA in 61% of the pancreatic cancer samples. Concomitant overexpression ofbcl-2 and bax was present in 26% of the cancer samples. Pancreatic adenocarcinomas exhibited 3.7-fold and 5.4-fold increases (p<0.001) inbcl-2 and baxmRNA levels respectively. In situ hybridisation showed that bothbcl-2 and baxmRNA were expressed in the cancer cells. Immunohistochemical analysis showed positive Bcl-2 and Bax immunostaining in 28 and 83% of the cancer samples respectively. In multivariate analysis (Cox regression model), bax expression was found to be a strong indicator of survival (p<0.001). Patients whose tumours exhibited Bax immunostaining lived significantly longer (12 months) than those whose tumours were Bax negative (five months) (p<0.039). In contrast, no relation was found between Bcl-2 and survival time.Conclusions—The data indicate that genes that are involved in the regulation of apoptosis are upregulated in human pancreatic cancer cells. Prolonged survival times in patients in whom apoptosis promoting factors are upregulated indicate that apoptotic pathways are of biological significance in pancreatic cancer.

Effect of miR-210 on Proliferation and Migration of Pancreatic Cancer Cells Through Regulating Runx3 Level

2020 ◽  
Vol 10 (12) ◽  
pp. 1827-1831
Author(s):  
Wanggang Xu ◽  
Yingmin Kuang ◽  
Dan Wang ◽  
Zhen Li ◽  
Renpin Xia
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cancer Cells ◽  
Suppressor Gene ◽  
Cancer Tissue ◽  
Pancreatic Cancer Cells ◽  
And Migration ◽  
Pcr Targeting ◽  
Proliferation And Migration

miR-210 is closely related to the occurrence of pancreatic cancer. In addition, Runx3 is a tumor suppressor gene and inhibits tumorigenesis. However, miR-210?s effect on Runx3 level is unclear. Therefore, Our study explored miR-210?s effect on the proliferation and migration of pancreatic cancer cells. PANC-1 cell line was transfected with miR-210 Mimics or miR-210 Mimic+pFBD-Runx3 plasmids followed by analysis of miR-210 and Runx3 level by qRT-PCR, targeting relationship by the dual fluorescein reporter assay, Runx3 and Tubulin protein expression by Western blot, cell proliferation by MTT assay and cell migration by Transwell assay. Compared with normal tissue, miR-210 was significantly upregulated in pancreatic cancer tissue (P < 0.01), while Runx3 mRNA was significantly downregulated (P < 0.01). Runx3 was a target protein of miR-210. miR-210 Mimics transfection significantly reduced Runx3 level and increased cell proliferation, which was significantly reduced in the miR-210 Mimic+pFBD-Runx3 group. miR-210 Mimics significantly promote cell migration and the addition of Runx3 prevented miR-210 Mimics-induced cell migration. miR-210 binds to the 3′-UTR region of Runx3 mRNA, reduces Runx3 expression, and promotes cell proliferation and migration. Increased Runx3 can inhibit miR-210?s effect on pancreatic cancer cells.

scholarly journals Role of Peroxisome Proliferator-Activated Receptorβ/δand B-Cell Lymphoma-6 in Regulation of Genes Involved in Metastasis and Migration in Pancreatic Cancer Cells

PPAR Research ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Jeffrey D. Coleman ◽  
Jerry T. Thompson ◽  
Russell W. Smith ◽  
Bogdan Prokopczyk ◽  
John P. Vanden Heuvel
Keyword(s):  
Pancreatic Cancer ◽  
Basement Membrane ◽  
Cancer Cells ◽  
Target Genes ◽  
B Cell Lymphoma ◽  
Human Pancreatic Cancer ◽  
Cancer Tissue ◽  
Peroxisome Proliferator ◽  
Matrix Remodeling ◽  
Pancreatic Cancer Cells

PPARβ/δis a ligand-activated transcription factor that regulates various cellular functions via induction of target genes directly or in concert with its associated transcriptional repressor,BCL-6. Matrix remodeling proteinases are frequently over-expressed in pancreatic cancer and are involved with metastasis. The present study tested the hypothesis thatPPARβ/δis expressed in human pancreatic cancer cells and that its activation could regulateMMP-9, decreasing cancer cells ability to transverse the basement membrane. In human pancreatic cancer tissue there was significantly higher expression ofMMP-9andPPARβ/δ, and lower levels ofBCL-6mRNA.PPARβ/δactivation reduced the TNFα-induced expression of various genes implicated in metastasis and reduced the invasion through a basement membrane in cell culture models. Through the use of short hairpin RNA inhibitors ofPPARβ/δ,BCL-6, andMMP-9, it was evident thatPPARβ/δwas responsible for the ligand-dependent effects whereasBCL-6dissociation upon GW501516 treatment was ultimately responsible for decreasingMMP-9expression and hence invasion activity. These results suggest thatPPARβ/δplays a role in regulating pancreatic cancer cell invasion through regulation of genes via ligand-dependent release ofBCL-6and that activation of the receptor may provide an alternative therapeutic method for controlling migration and metastasis.

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