ppENKGene Methylation Status in the Development of Pancreatic Carcinoma

Objective. To explore the association of hypermethylation of the proenkephalin gene (ppENK) with pancreatic carcinoma and to identify the effects of a demethylating agent on pancreatic cell lines.Method. Human pancreatic cancer tissues and five pancreatic carcinoma cell lines, as well as normal pancreatic tissue, were used.ppENKmethylation status was detected by MS-PCR (methylation-specific PCR).Results. Methylation ofppENKwas detected in 90.3% (28/31) of the human pancreatic carcinoma tissues but was not seen in normal pancreatic tissue. There was no correlation between the extent of methylation ofppENKand the clinicopathological features of the pancreatic carcinomas. MethylatedppENKwas detected in all the pancreatic cancer cell lines and was associated with loss of mRNA expression in the pancreatic carcinoma cell lines and normal pancreatic tissue. After treatment with 5-aza-dC, methylatedppENKwas not detected and the inhibition ofppENKmRNA expression was reversed.Conclusions. Inhibition ofppENKexpression by a change in its methylation status plays an important role in pancreatic carcinogenesis.ppENKmethylation is thus an important molecular event that distinguishes pancreatic carcinoma tissue from normal pancreatic tissue. Effects on cell growth, apoptosis, and the cell cycle may contribute to changes ofppENKmethylation status.

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Stromelysin 3 is overexpressed in human pancreatic carcinoma and regulated by retinoic acid in pancreatic carcinoma cell lines

Gut ◽

10.1136/gut.43.5.692 ◽

1998 ◽

Vol 43 (5) ◽

pp. 692-698 ◽

Cited By ~ 20

Author(s):

Z von Marschall ◽

E O Riecken ◽

S Rosewicz

Keyword(s):

Pancreatic Cancer ◽

Pancreatic Carcinoma ◽

Cell Lines ◽

Carcinoma Cell ◽

Northern Blotting ◽

Human Pancreatic Cancer ◽

Carcinoma Cell Lines ◽

Dependent Inhibition ◽

Human Pancreatic Carcinoma Cell ◽

Stromelysin 3

Background—Matrix metalloproteinases play an important role in the control of local tumour growth and metastasis of human pancreatic cancer.Aims—To examine expression of recently discovered stromelysin 3 (STR-3) in human pancreatic cancer and pancreatic carcinoma cell lines and to investigate their regulation by retinoids.Methods—STR-3 expression was examined by immunohistochemistry in 21 human pancreatic carcinomas. Expression of STR-3 and regulation by retinoids was assessed in five human pancreatic carcinoma cell lines using western and northern blotting as well as nuclear run on assays.Results—There was pronounced overexpression of STR-3 in 17 of 21 (80.9%) pancreatic carcinoma specimens. STR-3 expression was predominantly located in peritumourous stromal cells. Six of 21 (28.5%) carcinomas also revealed STR-3 expression in epithelial tumour cells whereas no STR-3 expression was observed in non-transformed pancreas. All five pancreatic carcinoma cell lines expressed STR-3 mRNA and protein. Furthermore, retinoid treatment results in a time and dose dependent inhibition of STR-3 protein expression. This inhibition seems to be post-transcriptional as neither STR-3 gene transcription nor mRNA steady state concentrations were affected by retinoids.Conclusions—STR-3 overexpression in stromal as well as epithelial elements during pancreatic carcinogenesis might contribute to the aggressive local growth and metastasis of pancreatic cancer and can be therapeutically targeted by retinoids.

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Attempt to Tumor Dormancy Therapy for Pancreatic Cancer. Purification of the Novel Angiogenesis Inhibitor from Pancreatic Carcinoma Cell Lines.

The Japanese Journal of Gastroenterological Surgery ◽

10.5833/jjgs.34.420 ◽

2001 ◽

Vol 34 (4) ◽

pp. 420-424

Author(s):

Shinya Onizuka ◽

Oliver Kisker ◽

Steven Pirie-Shepherd ◽

Judah Folkman ◽

Takashi Kanematsu

Keyword(s):

Pancreatic Cancer ◽

Pancreatic Carcinoma ◽

Cell Lines ◽

Carcinoma Cell ◽

Angiogenesis Inhibitor ◽

Tumor Dormancy ◽

The Novel ◽

Carcinoma Cell Lines ◽

Tumor Dormancy Therapy

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Presence of survivin-specific cytotoxic T-lymphocytes (CTLs) in pancreatic cancer patients, and specific killing of human pancreatic carcinoma cells in vitro by survivin-specific CTLs

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.3070 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 3070-3070

Author(s):

D. Z. Chang ◽

K. Zhu ◽

S. Kopetz ◽

K. Voo ◽

Y. Li ◽

...

Keyword(s):

Pancreatic Cancer ◽

T Lymphocytes ◽

Pancreatic Carcinoma ◽

Cell Lines ◽

Cytotoxic T Lymphocytes ◽

Carcinoma Cell ◽

Specific Ctls ◽

Carcinoma Cell Lines ◽

Ifn Γ

3070 Background: The apoptosis inhibitor protein Survivin is an attractive target for a cancer vaccine because of its differential overexpression by most human tumors, its importance for tumor survival, and its demonstrated immunogenicity. To examine Survivin’s potential as a vaccine target for pancreatic cancer (PC), we evaluated the presence of Survivin-specific cytotoxic T-lymphocytes (CTLs) in PC patients and assessed the specific killing of HLA-A*0201+ human pancreatic carcinoma cell lines in vitro by Survivin-specific CTL. Methods: Mononuclear cells from the peripheral blood (PBMC) of PC patients and normal donors and Survivin peptides were used to generate Survivin-specific CTLs in vitro. The presence of Survivin-specific CTLs was evaluated by IFN-γ ELISPOT analysis. Recognition of human PC cell lines (e.g., Panc-1 and CF-Pac-1) was analyzed by 51Cr release assays. Results: Multiple CTL lines were generated from different donors against a number of Survivin 9-mer and 10-mer peptides, including Sur5–14, Sur95–104, and Sur96–104 and altered forms of these peptides with enhanced HLA-A*0201 binding. Sur5–14 (TLPPAWQPFL) and new modified mSur95–104 (ELMLGEFLKL) peptides could generate specific CTL from the PBMC of most donors, and the resulting CTL showed cytotoxicity against Survivin peptide-pulsed Panc-1 and CF-Pac-1 in an HLA-A2-dependent manner. We found for the first time that mSur95–104 could elicit CTL activity that cross-reacted with wild-type peptide and 9-mer Sur96–104 in IFN-γ ELISPOT assays. In our preliminary analysis, we detected Survivin peptide-specific CTLs in four of five PC patients for Sur5–14 and three of five for mSur95–104. All five PC patients had a positive response to a pool of A2 peptides as positive controls, indicating their immune competence. Conclusions: CTLs specific for human Survivin peptide Sur5–14 and the modified peptides mSur95–104 were detected in majority of the PC patients tested. Further, Survivin-specific CTLs killed pancreatic carcinoma cell lines in vitro. Our results suggest that these two peptides are potential vaccines for the treatment of PC. No significant financial relationships to disclose.

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Zerumbone, a Southeast Asian Ginger Sesquiterpene, Induced Apoptosis of Pancreatic Carcinoma Cells through p53 Signaling Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/936030 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 25

Author(s):

Songyan Zhang ◽

Qiaojing Liu ◽

Yanju Liu ◽

Hong Qiao ◽

Yu Liu

Keyword(s):

Pancreatic Cancer ◽

Pancreatic Carcinoma ◽

Cell Lines ◽

Carcinoma Cell ◽

P53 Protein ◽

Tunel Staining ◽

P53 Signaling ◽

Carcinoma Cell Lines ◽

Anticancer Effects ◽

Induced Apoptosis

Pancreatic carcinoma is one common cancer with gradually increasing incidence during the past several decades. However, currently the candidate drugs to suppress pancreatic cancer remain lacking. This research was carried out to investigate if zerumbone, a natural cyclic sesquiterpene isolated from Zingiber zerumbet Smith, will produce the anticancer effects on pancreatic carcinoma cell lines. The results showed that zerumbone concentration, and time, dependently produced inhibitory actions on cell viability of PANC-1 cells. In addition, Hoechst 33342, AO/EB, TUNEL staining, and caspase-3 activity assay further showed that zerumbone induced apoptosis of PANC-1 cells. The expression of p53 protein was markedly upregulated, and the p21 level was also obviously elevated in zerumbone-treated PANC-1 cells. Moreover, ROS production was increased by about 149% in PANC-1 cells treated by zerumbone 30 μM. Zerumbone also produced the same antitumor activity in pancreatic carcinoma cell lines SW1990 and AsPC-1. In summary, we found that zerumbone was able to induce apoptosis of pancreatic carcinoma cell lines, indicating to be a promising treatment for pancreatic cancer.

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