The effect of adenovirus expressing wild-type p53 on 5-fluorouracil chemosensitivity is related to p53 status in pancreatic cancer cell lines

Eisold, S.; Linnebacher, Michael; Ryschich, Eduard; Antolovic, Dalibor; Hinz, Ulf; Klar, E.; Schmidt, Jan

doi:10.3748/wjg.v10.i24.3583

Cited by 29 publications

(27 citation statements)

References 32 publications

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“…Sequencing analysis was also performed on exons 1 and 2 of the K-ras gene and exons 5, 6, 7 and 8 of p53 to verify data reported in the literature. 24,25 Flow cytometric analysis-cell cycle perturbation analysis. Exponentially growing cells were trypsinized and 2 x 10 5 cells/60-mm Petri dish were incubated for 18-24 h at 37˚C before drug exposure.…”

Section: Methodsmentioning

confidence: 99%

Modulation of drug cytotoxicity by iressa (ZD1839) in pancreatic cancer cell lines

Rosetti

Tesei

Ulivi

et al. 2005

Cancer Biology & Therapy

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High expression of the epidermal growth factor receptor (EGFR) family confers a growth advantage on malignant cells in various tumor types. Most pancreatic cancers express EGFR, which seems to play an important role in the acquisition of aggressive clinical behaviour and in tumor invasion. Iressa (ZD1839), a quinazoline tyrosine kinase inhibitor selective for the EGF receptor, has shown good anti-tumor activity in both preclinical and clinical studies. Using two pancreatic cancer cell lines that express different EGFR and ErbB-2 levels, we analyzed the activity of Iressa and evaluated its modulation effect on four conventional cytotoxic drugs: gemcitabine, oxaliplatin, docetaxel and SN38. Iressa was tested at scalar doses up to the plasma peak level concentration and showed a similar weak cytostatic effect in both cell lines. Conversely, an additive or weak synergistic effect was observed when the drug was administered simultaneously with or following cytotoxic drugs. Our data show that Iressa has only a weak activity at doses within the plasmatic peak concentration and that its effect is independent of EGFR and p42/p44 expression and phosphorylation levels. This is in agreement with recent literature data that attribute an essential role to a specific EGFR mutation in mediating response to Iressa. This mutation was absent in both pancreatic cell lines tested.

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Section: Methodsmentioning

confidence: 99%

Modulation of drug cytotoxicity by iressa (ZD1839) in pancreatic cancer cell lines

Rosetti

Tesei

Ulivi

et al. 2005

Cancer Biology & Therapy

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“…Chemotherapy with 5-FU was largely ineffective in hPANC-1 cells probably because of inactivation in this cell line of the p53 gene, which is implicated in cell cycle arrest (Eisold et al 2004). The p53 tumor suppressor gene is functionally inactivated in about 50% of all human malignancies, including up to 60% of pancreatic cancer .…”

Section: Tablementioning

confidence: 99%

“…The p53 tumor suppressor gene is functionally inactivated in about 50% of all human malignancies, including up to 60% of pancreatic cancer . Indeed several reports have suggested that the p53 status of the tumor cells may be an important response determinant to 5-FU-based chemotherapy (Ahnen et al 1998, Lenz et al 1998, Eisold et al 2004. Even though we already knew that expression of wt-p53 was required for 5-FU-induced apoptosis and to potentiate the 5-FU-cytotoxicity (Lowe et al 1993, Bunz et al 1999, Eisold et al 2004, we decided to verify if the combination 5-FU and T 3 could inhibit the tumor proliferation in a p53-independent manner (Dinda et al 2002).…”

Section: Tablementioning

confidence: 99%

“…Indeed several reports have suggested that the p53 status of the tumor cells may be an important response determinant to 5-FU-based chemotherapy (Ahnen et al 1998, Lenz et al 1998, Eisold et al 2004. Even though we already knew that expression of wt-p53 was required for 5-FU-induced apoptosis and to potentiate the 5-FU-cytotoxicity (Lowe et al 1993, Bunz et al 1999, Eisold et al 2004, we decided to verify if the combination 5-FU and T 3 could inhibit the tumor proliferation in a p53-independent manner (Dinda et al 2002). We have shown that T 3 was able to enhance the inhibitory effect of chemotherapy on cell growth at 24, 48 and 72 h, and the existence of synergism between T 3 and the selected drugs has been demonstrated by the traditional analysis of isobologram.…”

Section: Tablementioning

confidence: 99%

“…Intrinsic limitations of chemotherapy might be endogenous or due to resistance of pancreatic tumor cells to anti-cancer drugs. At the present time, gemcitabine (dFdCyd), cisplatin (DDP), and fluoropyrimidine 5-fluorouracil (5-FU) are considered the conventional drugs of choice in the treatment of pancreas cancer (Symon et al 2002, Eisold et al 2004, Halloran et al 2004. dFdCyd inhibits the ribonucleotide reductase and DNA synthesis causing a redistribution of cells into the early S-phase of cell cycle with a radiosensitizing and cytotoxic activity (Huang et al 1991, Ruiz van Haperen et al 1993, van Moorsel et al 2000, Pauwels et al 2005.…”

Section: Introductionmentioning

confidence: 99%

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3,3′,5-Triiodo-l-thyronine inhibits ductal pancreatic adenocarcinoma proliferation improving the cytotoxic effect of chemotherapy

Michienzi

Bucci

Falzacappa

et al. 2007

Journal of Endocrinology

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The pancreatic adenocarcinoma is an aggressive and devastating disease, which is characterized by invasiveness, rapid progression, and profound resistance to actual treatments, including chemotherapy and radiotherapy. At the moment, surgical resection provides the best possibility for long-term survival, but is feasible only in the minority of patients, when advanced disease chemotherapy is considered, although the effects are modest. Several studies have shown that thyroid hormone, 3,3 0 ,5-triiodo-L-thyronine (T 3 ) is able to promote or inhibit cell proliferation in a cell type-dependent manner. The aim of the present study is to investigate the ability of T 3 to reduce the cell growth of the human pancreatic duct cell lines chosen, and to increase the effect of chemotherapeutic drugs at conventional concentrations. Three human cell lines hPANC-1, Capan1, and HPAC have been used as experimental models to investigate the T 3 effects on pancreatic adenocarcinoma cell proliferation. The hPANC-1 and Capan1 cell proliferation was significantly reduced, while the hormone treatment was ineffective for HPAC cells. The T 3 -dependent cell growth inhibition was also confirmed by fluorescent activated cell sorting analysis and by cell cycle-related molecule analysis. A synergic effect of T 3 and chemotherapy was demonstrated by cell kinetic experiments performed at different times and by the traditional isobologram method. We have showed that thyroid hormone T 3 and its combination with low doses of gemcitabine (dFdCyd) and cisplatin (DDP) is able to potentiate the cytotoxic action of these chemotherapic drugs. Treatment with 5-fluorouracil was, instead, largely ineffective. In conclusion, our data support the hypothesis that T 3 and its combination with dFdCyd and DDP may act in a synergic way on adenopancreatic ductal cells.

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Antimetabolites

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Cancer Drug Discovery and Development

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The effect of adenovirus expressing wild-type p53 on 5-fluorouracil chemosensitivity is related to p53 status in pancreatic cancer cell lines

Cited by 29 publications

References 32 publications

Modulation of drug cytotoxicity by iressa (ZD1839) in pancreatic cancer cell lines

Modulation of drug cytotoxicity by iressa (ZD1839) in pancreatic cancer cell lines

3,3′,5-Triiodo-l-thyronine inhibits ductal pancreatic adenocarcinoma proliferation improving the cytotoxic effect of chemotherapy

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