Abstract:
:Prostate cancer (CaP), the most common malignancy in American men, presents its greatest challenge to clinicians when the cancer progresses to the hormone-refractory state. In the present investigation, we studied the combined effects of interferon (IFN) and onconase, each of which has reported antitumor activity, on growth and specific protein expression in JCA-1 cells. Cells were treated for up to 3 days with 1 and 5 microg/ml onconase, with and without concurrent addition of IFN-beta(ser) (10(3) IU/ml). Cell count and viability, and de novo RNA and protein synthesis were determined. Expression and subcellular distribution of STAT-1 were also assessed by immunoblot analysis. JCA-1 cells treated for 3 days with IFN or onconase showed a 15-30% reduction in cell proliferation, which was increased to 42-51% with both agents. Analysis of [35S]methionine incorporation into cells confirmed a more pronounced inhibitory effect elicited by IFN-beta and onconase; IFN-beta and 1 microg/ml onconase each decreased de novo protein synthesis by 23-25%, while the combination resulted in 59% suppression. Similar studies using incorporation of [3H]uridine into RNA yielded less significant effects. Further investigation using pre-labeled cellular RNA and proteins showed that either agent or their combination did not affect the turnover of macromolecules. To test whether the antiproliferative effects of IFN-beta and onconase were correlated with one or more specific gene changes, expression of an IFN-modulated protein, STAT-1, was determined. Both phosphorylated and unphosphorylated forms of STAT-1 and its subcellular distribution in the nucleus and cytoplasm, were increased 3-fold by IFN-beta. The IFN-elicited elevation of STAT-1 was not additionally augmented by onconase but was reduced 20-25% when onconase was simultaneously present as IFN-beta. These data show that the overall changes in STAT-1 did not correlate with the reduction in cell growth and the suppression of de novo protein/RNA synthesis elicited by these two agents, and imply that other target proteins are likely to be involved in the combined effects of IFN-beta and onconase in JCA-1 cells.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Tsai SY,Hsieh TC,Ardelt B,Darzynkiewicz Z,Wu JMkeywords:
subject
Has Abstractpub_date
2002-05-01 00:00:00pages
891-6issue
5eissn
1019-6439issn
1791-2423journal_volume
20pub_type
杂志文章abstract::The effects of a thymic peptide preparation (TP) on the immunocytotoxicity and cytokine secretion of peripheral blood lymphocytes and monocytes from patients with colorectal tumors, breast tumors and melanoma were studied in vitro. On average, breast tumor and melanoma patients showed significantly lower natural kille...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.10.3.481
更新日期:1997-03-01 00:00:00
abstract::Squamous cell carcinoma antigen (SCCA) is overexpressed in many squamous cell cancers and SCCA‑derived peptide-specific CD8(+) cytotoxic T lymphocytes can display cytotoxicity against tumor cells. In the present study, we screened the SCCA amino acid sequence for potential HLA-A*0201-binding CD8(+) T‑cell epitopes usi...
journal_title:International journal of oncology
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abstract::The mitogen-activated protein kinase (MAPK) cascade, which includes MAPK, MAP kinase kinase (MAPKK) and Raf-l, is involved in the signal transduction of growth factor receptors. We found that the MAPK and Raf-l proteins are increased in human breast cancer. Activated MAPKK was also observed. We then investigated wheth...
journal_title:International journal of oncology
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journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:10.3892/ijo.2015.3197
更新日期:2015-12-01 00:00:00
abstract::Astrocytomas are intracranial malignancies for which invasive growth and high motility of tumour cells preclude total resection; the tumours usually recur in a more aggressive and, eventually, lethal form. Clinical outcome is highly variable and the accuracy of morphology-based prognostic statements is limited. In ord...
journal_title:International journal of oncology
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journal_title:International journal of oncology
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journal_title:International journal of oncology
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doi:10.3892/ijo.5.6.1211
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更新日期:2009-06-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
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更新日期:2000-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2020-01-01 00:00:00
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journal_title:International journal of oncology
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doi:
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pub_type: 临床试验,杂志文章
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journal_title:International journal of oncology
pub_type: 杂志文章
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更新日期:1995-01-01 00:00:00
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journal_title:International journal of oncology
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更新日期:2005-08-01 00:00:00
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pub_type: 杂志文章
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journal_title:International journal of oncology
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journal_title:International journal of oncology
pub_type: 杂志文章
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