scholarly journals The Clinical Significance of PIWIL3 and PIWIL4 Expression in Pancreatic Cancer

2020 ◽  
Vol 9 (5) ◽  
pp. 1252 ◽  
Author(s):  
Weiyao Li ◽  
Javier Martinez-Useros ◽  
Nuria Garcia-Carbonero ◽  
Maria J. Fernandez-Aceñero ◽  
Alberto Orta ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cell ◽  
Cell Lines ◽  
Tumor Cell Line ◽  
P Element ◽  
Human Pancreatic Cancer ◽  
Tumor Cell Lines ◽  
Pancreatic Cell ◽  
Elevated Expression ◽  
Healthy Control

P-element-induced wimpy testis (PIWI) proteins have been described in several cancers. PIWIL1 and PIWIL2 have been recently evaluated in pancreatic cancer, and elevated expression of PIWIL2 conferred longer survival to patients. However, PIWIL3’s and PIWIL4’s role in carcinogenesis is rather controversial, and their clinical implication in pancreatic cancer has not yet been investigated. In the present study, we evaluated PIWIL1, PIWIL2, PIWIL3 and PIWIL4 expression in pancreatic cancer-derived cell lines and in one non-tumor cell line as healthy control. Here, we show a differential expression in tumor and non-tumor cell lines of PIWIL3 and PIWIL4. Subsequently, functional experiments with PIWIL3 and/or PIWIL4 knockdown revealed a decrease in the motility ratio of tumor and non-tumor cell lines through downregulation of mesenchymal factors in pro of epithelial factors. We also observed that PIWIL3 and/or PIWIL4 silencing impaired undifferentiated phenotype and enhanced drug toxicity in both tumor- and non-tumor-derived cell lines. Finally, PIWIL3 and PIWIL4 evaluation in human pancreatic cancer samples showed that patients with low levels of PIWIL4 protein expression presented poor prognosis. Therefore, PIWIL3 and PIWIL4 proteins may play crucial roles to keep pancreatic cell homeostasis not only in tumors but also in healthy tissues.

scholarly journals Establishment and Characterization of Immortalized Miniature Pig Pancreatic Cell Lines Expressing Oncogenic K-RasG12D

2020 ◽  
Vol 21 (22) ◽  
pp. 8820
Author(s):  
Hae-Jun Yang ◽  
Bong-Seok Song ◽  
Bo-Woong Sim ◽  
Yena Jung ◽  
Unbin Chae ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tumor Biology ◽  
Human Pancreatic Cancer ◽  
Miniature Pig ◽  
Pancreatic Cell ◽  
Treatment And Prevention ◽  
Acinar To Ductal Metaplasia

In recent decades, many studies on the treatment and prevention of pancreatic cancer have been conducted. However, pancreatic cancer remains incurable, with a high mortality rate. Although mouse models have been widely used for preclinical pancreatic cancer research, these models have many differences from humans. Therefore, large animals may be more useful for the investigation of pancreatic cancer. Pigs have recently emerged as a new model of pancreatic cancer due to their similarities to humans, but no pig pancreatic cancer cell lines have been established for use in drug screening or analysis of tumor biology. Here, we established and characterized an immortalized miniature pig pancreatic cell line derived from primary pancreatic cells and pancreatic cancer-like cells expressing K-rasG12D regulated by the human PTF1A promoter. Using this immortalized cell line, we analyzed the gene expression and phenotypes associated with cancer cell characteristics. Notably, we found that acinar-to-ductal transition was caused by K-rasG12D in the cell line constructed from acinar cells. This may constitute a good research model for the analysis of acinar-to-ductal metaplasia in human pancreatic cancer.

scholarly journals Establishment of transplantable porcine tumor cell lines derived from MHC- inbred miniature swine

Blood ◽  
2007 ◽  
Vol 110 (12) ◽  
pp. 3996-4004 ◽  
Author(s):  
Patricia S. Cho ◽  
Diana P. Lo ◽  
Krzysztof J. Wikiel ◽  
Haley C. Rowland ◽  
Rebecca C. Coburn ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Tumor Cell Line ◽  
Blood Analysis ◽  
Large Animal ◽  
Tumor Cell Lines ◽  
Miniature Swine ◽  
Serial Transfer ◽  
Large Animal Models ◽  
Immunocompromised Mice

Abstract The lack of transplantable tumors has limited assessment of graft-versus-tumor effects following hematopoietic cell transplantation in clinically relevant large-animal models. We describe the derivation and characterization of porcine tumor cell lines with initial efforts of tumor transplantation using immunocompromised mice and highly inbred sublines of Massachusetts General Hospital major histocompatibility complex (MHC)–inbred miniature swine. Autopsies were performed routinely on swine that died unexpectedly or had suspicion of malignancy based on clinical symptoms or peripheral blood analysis. Tissue samples were obtained for pathology, phenotyped by flow cytometry, and placed in culture. Based on growth, lines were selected for passage into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice and miniature swine. Porcine tumor recipients were preconditioned with total body irradiation from 0 to 500 cGy or with a 30-day course of oral cyclosporine. We identified 19 cases of hematologic tumors. Nine distinct tumor cell lines were established from 8 of these cases, including 3 derived from highly inbred sublines. In vivo tumor growth and serial transfer were observed in immunocompromised mice for one tumor cell line and in miniature swine for 1 of 2 tumor cell lines expanded for this purpose. These results suggest the possibility of developing a transplantable tumor model in this large-animal system.

scholarly journals Isolation, Structure Elucidation, and Antiproliferative Activity of Butanolides and Lignan Glycosides from the Fruit of Hernandia nymphaeifolia

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 4005
Author(s):  
Simayijiang Aimaiti ◽  
Yohei Saito ◽  
Shuichi Fukuyoshi ◽  
Masuo Goto ◽  
Katsunori Miyake ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Antiproliferative Activity ◽  
Optical Rotation ◽  
Human Tumor ◽  
Tumor Cell Line ◽  
2D Nmr ◽  
Significant Activity ◽  
Tumor Cell Lines

Seven new butanolides, peltanolides A–G (1–7), and two lignan glucosides, peltasides A (8) and B (9), along with eleven known compounds, 10–20, were isolated from a crude CH3OH/CH2Cl2 (1:1) extract of the fruit of Hernandia nymphaeifolia (Hernandiaceae). The structures of 1–9 were characterized by extensive 1D and 2D NMR spectroscopic and HRMS analysis. The absolute configurations of newly isolated compounds 1–9 were determined from data obtained by optical rotation and electronic circular dichroism (ECD) exciton chirality methods. Butanolides and lignan glucosides have not been isolated previously from this genus. Several isolated compounds were evaluated for antiproliferative activity against human tumor cell lines. Lignans 15 and 16 were slightly active against chemosensitive tumor cell lines A549 and MCF-7, respectively. Furthermore, both compounds displayed significant activity (IC50 = 5 µM) against a P-glycoprotein overexpressing multidrug-resistant tumor cell line (KB-VIN) but were less active against its parent chemosensitive cell line (KB).

ING3 as a novel regulator of pancreatic cancer growth and aggressiveness.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 304-304
Author(s):  
Marina Koutsioumpa ◽  
Maria Hatziapostolou ◽  
Christos Polytarchou ◽  
Swapna Joshi ◽  
Dimitrios Iliopoulos
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Cell Lines ◽  
Colony Formation ◽  
Genetic Alterations ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cell ◽  
Qrt Pcr ◽  
Chromatin Regulators

304 Background: Recent studies demonstrate that chromatin regulation by posttranslational means, such as histone methylation or acetylation, is an essential control mechanism in tumorigenesis and tumor progression. Accumulative findings support the notion that pancreatic cancer tumorigenesis is not only governed by genetic alterations but also aberrant epigenetic regulation. The aim of the present study was to identify and assess the role of chromatin regulators in pancreatic cancer. Methods: The gene expression profile of chromatin regulators was assessed using gene expression microarray analysis in pancreatic cancer and uninvolved human tissues. Validation of microarray findings was performed by qRT-PCR in two extended cohorts of patients and by immunohistochemistry in pancreas tumor tissue microarrays. PANC-1, MIA Paca-2, Capan-2, HPAF-II and AsPC-1 cell lines were used for in vitro assays. Efficiency of knockdown experiments, performed by RNAi interference assays and shRNA-expressing lentiviral vectors, was evidenced by qRT-PCR and Western Blot Analysis. Cell proliferation, invasion and colony formation assays were conducted in genetically modified cells. The significance of variability between the results from each group and corresponding control was determined by unpaired t-test. Results: Differential expression analysis of chromatin regulators in pancreatic cancer versus uninvolved tissues demonstrates that 27 epigenetic molecules are significantly de-regulated (>1.5 fold, P<0.05). By hierarchical clustering, the samples are classified into two major groups that reflect the normal and cancer state. The decreased expression of inhibitor of growth family member 3 (ING3), a component of the NuA4 histone acetyl-transferase complex, was further validated by qRT-PCR and immunohistochemistry analysis in tumor tissues. Transient or stable silencing of ING3 caused significant increase of viability, proliferation, colony formation and invasion in several pancreatic cell lines. Conclusions: Our data show that human pancreatic cancer is characterized by loss of ING3 expression and we defined a potential role of the latter in pancreatic cancer cell growth and invasion.

scholarly journals Cell-Type-Dependent Thyroid Hormone Effects on Glioma Tumor Cell Lines

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Liappas Alexandros ◽  
Mourouzis Iordanis ◽  
Zisakis Athanasios ◽  
Economou Konstantinos ◽  
Lea Robert-William ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Hormone ◽  
Tumor Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Tumor Cell Line ◽  
Fold Increase ◽  
Distinct Pattern ◽  
Tumor Cell Lines ◽  
Glioma Tumor

Purpose. The present study investigated the potential effects of long-term T3 treatment on glioma tumor cell lines. Thyroid hormone action on cell growth, differentiation and survival during development may be of therapeutic relevanceMethods and Results1321N1 cell line, an astrocytoma grade II, and U87MG, a glioblastoma grade IV, were exposed for 2 and 4 days in medium deprived of T3 and in medium containing 1 nM T3. T3 promoted re-differentiation in both cell lines. However, T3 increased cell proliferation in 1321N1 (2 days) which declined thereafter (4 days) while in U87MG resulted in suppression of cell proliferation. At the molecular level, a 2.9 fold increase in the expression of TRα1 receptor was observed in U87MG versus 1321N1,P< 0.05. TRβ1 receptor was undetectable. These changes corresponded to a distinct pattern of T3-induced kinase signaling activation; T3 had no effect on ERK activation in both cell lines but significantly increased phospho-Akt levels in 1321N1.Conclusion. In conclusion, T3 can re-differentiate glioma tumor cells, whereas its effect on cell proliferation appears to be dependent on the type of tumor cell line with aggressive tumors being more sensitive to T3. TRα1 receptor may, at least in part, be implicated in this response.

scholarly journals The Evaluation of Gene Oct4 Expression as a New Tumor Marker in Pancreatic Tumor and Non-Tumor Cell Lines

2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Shahri SSZ ◽  
Sayyedalhosseini S
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cell ◽  
Molecular Marker ◽  
Tumor Cell ◽  
Cell Lines ◽  
Cancer Detection ◽  
Pancreatic Tumor ◽  
Tumor Cell Lines ◽  
Self Renewal ◽  
Oct4 Expression

Introduction: Oct4 gene is one of the important genes involved in stem cell self-renewal control. Recently, this gene has been proposed as a novel molecular marker for cancer detection. Therefore, in this study we examined the expression of Oct4 gene in MIA Paca-2, PA-TU-8902 and AsPC-1 cell lines as well as pancreatic cancer.

Metabolism-based GP-2250 in combination with gemcitabine as a novel approach to pancreatic cancer: A mouse xenograft study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16750-e16750
Author(s):  
Chris Braumann ◽  
Marie Buchholz ◽  
Britta Majchrzak - Stiller ◽  
Stephan Hahn ◽  
Waldemar Uhl ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Combination Treatment ◽  
Cancer Metabolism ◽  
Pancreatic Tumor ◽  
Tumor Cell Lines

e16750 Background: GP-2250, a novel oxathiazine derivative, displayed apoptotic cytotoxicity against various tumor cell lines but not normal cells. It was therefore tested whether its antineoplastic potential - alone or in combination – could be leveraged specifically against pancreatic cancer. Methods: GP-2250 is a cancer metabolism-based therapeutic. It depleted metabolic energy through inhibition of the enzyme GAPDH (glyceraldehyde-3-phosphate dehydrogenase) which is rate limiting for aerobic glycolysis. ATP was decreased in a time- and dose-dependent manner in pancreatic tumor cell lines and ROS was increased. Mitochondrial dysfunction was triggered by an increased expression of Bax and decreased expression of Bcl2, leading to apoptosis. Cytotoxicity of GP-2250 was ROS-dependent. It was blocked by N-acetylcysteine. Results: GP-2250 substantially increased the sensitivity of pancreatic tumor cells to various chemotherapeutics in particular to gemcitabine (Gem). At doses which were inactive or barely active per se, the combination of GP-2250 and Gem caused striking cytotoxicity in patient-derived primary tumor cells in vitro, pointing to a strong synergy between the two agents. This finding was substantiated in vivo by patient-derived xenograft (PDX) studies in nude mice. While GP-2250 and Gem, given as monotherapy (500 mg/kg and 50 mg/kg respectively, 2x/week), showed only a limited antineoplastic response, the combination treatment resulted in a significantly higher anti-tumor activity as shown in further PDX. Tumor regression was found in 5 out of 9 PDX based on RECIST criteria. Stable disease was reached in 3 of the remaining grafts. In 1 xenograft, which was unresponsive to Gem, the combination treatment nevertheless achieved a reduction in tumor growth which significantly exceeded that of GP-2250 monotherapy. Conclusions: GP-2250 is a novel cancer metabolism-based therapeutic. GP-2250, in combination with Gem, strongly reduces tumor growth in patient-derived xenografts exceeding by far the response to monotherapy. GP-2250 is being evaluated in a Phase I clinical trial in patients diagnosed with advanced pancreatic cancer (Clinical Trial NCT03854110).

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