Demethylating Agent 5-Aza-2′-Deoxycytidine Enhances Susceptibility of Bladder Transitional Cell Carcinoma to Cisplatin

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作者：Donghao Shang ; Yuting Liu ; Yoshiyuki Matsui ; Noriyuki Ito ; Hiroyuki Nishiyama ; Toshiyuki Kamoto ; Osamu Ogawa
关键词：Late Pleistocene ; Darhad Basin ; Mongolia ; Glacial chronology ; Paleolakes
刊名：Urology
出版年：2008
期刊代码：267_00904295
类别：med
出版时间：June 2008
卷：71
期：6
页码：1220-1225
文件大小：933 K

摘要

Initial screening for enhancement of the inhibitory effects of MMC, cisplatin and gemcitabine on viability by treatment with the 2 hTERT AS-ODNs ASt2206 and ASt2331 was performed in 4 TCC cell lines prior to CT. Apoptosis was assessed by annexin V staining and detection of activated caspase-3 using Western blot analysis. Nonsense (NS)-ODN served as a control in all experiments.

ass="h4">Results:

All cell lines responded to the anticancer agents tested. Treatment with AS plus CT resulted in a significantly stronger inhibition of viability than the NS plus CT control in the majority of combinations, indicating an AS specific enhancement effect. For example, ASt2331 plus MMC decreased viability to 17%in contrast to NS plus MMC (58%) in EJ28 cells. All ASt2331 plus CT combinations specifically increased the rate of apoptosis 1.3 to 3.0-fold compared with NS plus CT. Apoptosis induction was associated with caspase 3 activation.

ass="h4">Conclusions:

Enhancement of cytotoxic drug effects on the growth of TCC cells by hTERT AS-ODNs presented herein allows a dose decrease in chemotherapy and confirms the suitability of hTERT as a target in a specific therapy approach.

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Immunology Lettersa>

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Immunology Letters, Volume 40, Issue 2, May 1994, Pages 117-124
Anton B. Alexandroff, Andrew M. Jackson, Kesavan Esuvaranathan, Stephen Prescott, Keith James

Abstract

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We have studied the autocrine regulation of essential expression of the intercellular adhesion molecule-1 (ICAM-1) on 8 transitional cell carcinoma (TCC) cell lines (histopathological grades 1–3). The constitutive expression of ICAM-1 was regulated by soluble factors in an autocrine fashion. These factors were produced by all cell lines, with the exception of the MGH-U1 cell line. The effects observed could be largely attributed to IL-1α. However, the residual ICAM-1 inducing activity (up to 30%of ICAM-1 induction) could not be associated with any known ICAM-1 inducers (IFNγ, TNFα, TNFβ, IL-1α, IL-1β, IL-4, retinoic acid, LPS). In contrast to recombinant derived cytokines, the IL-1α present in tissue culture supernatant was only able to induce ICAM-1 on high-grade tumours and not low-grade cells. This discriminative effect is similar to that noted following in vitro culture of tumour cells with an style='font-style: italic'>bacillus Calmette-Guerinan> organisms. Whether the production of soluble factors (e.g., IL-1α) by TCC cell lines plays an essential autocrine role for bladder tumours and/or affects the interaction with cells of the immune system needs to be investigated further.

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Urologya>

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Urology, Volume 61, Issue 2, February 2003, Pages 468-473
G. Fechner, F. G. E. Perabo, D. H. Schmidt, L. Haase, E. Ludwig, H. Schueller, J. Blatter, S. C. Mller, P. Albers

Abstract

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ass="h3">Objectives

Despite clinical use, the radiosensitizing effect of gemcitabine (2′2′-difluorodeoxycytidine) in human transitional cell carcinoma (TCC) has not been shown to date. We investigated gemcitabine as a radiosensitizer for human TCC cells.

ass="h3">Methods

Monolayer cultures of RT112 (G1, p53 wild type), RT4 (G1-G2, p53 wild type), T24 (G3, p53, mutant type), and SUP (G4, p53 mutant type) cells were incubated in medium with gemcitabine. Electron beam radiation was applied alone, simultaneous, or 3, 6, 12, and 24 hours after gemcitabine. Jurkat leukemia cells were used as controls for radiation toxicity. Cell survival was determined 6, 12, 24, 48, and 72 hours after radiation by microculture tetrazolium assay. DNA damage was evaluated by flow cytometric assessment of poly(ADP-ribose) polymerase, and apoptosis was determined by terminal-deoxynucleotidyltransferase-mediated dUTP nick-end labeling and flow cytometric assessment after annexin-V and propidium iodide labeling.

ass="h3">Results

In all TCC cell lines, radiation alone caused only little and insignificant growth inhibitory effects at 10 Gy. Gemcitabine alone had a dose-dependent cytotoxic and apoptosis inducing effect on all TCC cell lines independent of p53 status. Assays combining radiation with gemcitabine in different dose and time schedules demonstrated no radiosensitizing effect in TCC cells.

ass="h3">Conclusions

Gemcitabine is effective in TCC cell lines independent of p53 status. A radiosensitizing effect could not be demonstrated. Again, p53 status was not predictive of the radioresponse in the bladder cancer cell lines. Clinical studies with gemcitabine and radiotherapy might nevertheless yield different results but should be performed with utmost caution.

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ass="h4">Basic and Translational Science

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Demethylating Agent 5-Aza-2′-Deoxycytidine Enhances Susceptibility of Bladder Transitional Cell Carcinoma to Cisplatin