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Efficacy of cytotoxic agents used in the treatment of testicular germ cell tumours under normoxic and hypoxic conditions in vitro.

Koch S, Mayer F, Honecker F, Schittenhelm M, Bokemeyer C - Br. J. Cancer (2003)

Bottom Line: Inhibitory concentrations IC(50) of the tested agents under both conditions were compared.Selected results were confirmed by flow-cytometric assessment of the apoptotic index.All drugs were less effective under hypoxic conditions, including mitomycin C (eg, 1.6-fold increase of IC(50) in hypoxia compared to normoxia for NT2) and cisplatin (eg, NT2: two-fold increase).

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Hematology, Immunology, and Rheumatology, Medizinische Klinik, University of Tübingen Medical Center, Otfried-Müller-Str. 10, Tuebingen 72076, Germany.

ABSTRACT
Platinum-based chemotherapy is the main treatment element to achieve cure for patients with metastatic germ cell tumours. Drug resistance in testicular germ cell tumours (TGCTs) is rare and the reasons are not fully understood. While recent investigations have indicated decreased efficacy of chemotherapy in several tumour types under hypoxic conditions, this aspect has not been investigated in TGCTs so far. Furthermore, for cisplatin - the most active drug in this disease - controversial effects of hypoxia on cytotoxic efficacy have been reported. The relative efficacy of cytotoxic agents for the treatment of TGCT patients was studied in three different cell lines derived from human embryonal carcinomas (EC) in an in vitro hypoxia model. NT2, 2102 EP, and NCCIT were tested for their sensitivity towards cisplatin, etoposide, bleomycin, 4-OOH-ifosfamide, carboplatin, paclitaxel, gemcitabine, oxaliplatin, irinotecan, and mitomycin C under normoxic and hypoxic conditions using the MTT assay. Inhibitory concentrations IC(50) of the tested agents under both conditions were compared. Selected results were confirmed by flow-cytometric assessment of the apoptotic index. In all cells, doubling times were prolonged in hypoxia (NT2

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Cell viability, expressed as percent of the control (%means±s.d., which is indicated by the bars of the line plots) of EC cells in culture after 72 h. (A) NT2 cells treated with mitomycin C. (B) 2102 EP cells treated with cisplatin. Note that both drugs, mitomycin C and cisplatin, are less effective in hypoxia.
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fig1: Cell viability, expressed as percent of the control (%means±s.d., which is indicated by the bars of the line plots) of EC cells in culture after 72 h. (A) NT2 cells treated with mitomycin C. (B) 2102 EP cells treated with cisplatin. Note that both drugs, mitomycin C and cisplatin, are less effective in hypoxia.

Mentions: Under hypoxic conditions, all drugs tested were less effective (Table 1), including mitomycin C (eg, increase of IC50 in normoxia compared to hypoxia for NT2: 1.7-fold increase, Figure 1AFigure 1


Efficacy of cytotoxic agents used in the treatment of testicular germ cell tumours under normoxic and hypoxic conditions in vitro.

Koch S, Mayer F, Honecker F, Schittenhelm M, Bokemeyer C - Br. J. Cancer (2003)

Cell viability, expressed as percent of the control (%means±s.d., which is indicated by the bars of the line plots) of EC cells in culture after 72 h. (A) NT2 cells treated with mitomycin C. (B) 2102 EP cells treated with cisplatin. Note that both drugs, mitomycin C and cisplatin, are less effective in hypoxia.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376846&req=5

fig1: Cell viability, expressed as percent of the control (%means±s.d., which is indicated by the bars of the line plots) of EC cells in culture after 72 h. (A) NT2 cells treated with mitomycin C. (B) 2102 EP cells treated with cisplatin. Note that both drugs, mitomycin C and cisplatin, are less effective in hypoxia.
Mentions: Under hypoxic conditions, all drugs tested were less effective (Table 1), including mitomycin C (eg, increase of IC50 in normoxia compared to hypoxia for NT2: 1.7-fold increase, Figure 1AFigure 1

Bottom Line: Inhibitory concentrations IC(50) of the tested agents under both conditions were compared.Selected results were confirmed by flow-cytometric assessment of the apoptotic index.All drugs were less effective under hypoxic conditions, including mitomycin C (eg, 1.6-fold increase of IC(50) in hypoxia compared to normoxia for NT2) and cisplatin (eg, NT2: two-fold increase).

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Hematology, Immunology, and Rheumatology, Medizinische Klinik, University of Tübingen Medical Center, Otfried-Müller-Str. 10, Tuebingen 72076, Germany.

ABSTRACT
Platinum-based chemotherapy is the main treatment element to achieve cure for patients with metastatic germ cell tumours. Drug resistance in testicular germ cell tumours (TGCTs) is rare and the reasons are not fully understood. While recent investigations have indicated decreased efficacy of chemotherapy in several tumour types under hypoxic conditions, this aspect has not been investigated in TGCTs so far. Furthermore, for cisplatin - the most active drug in this disease - controversial effects of hypoxia on cytotoxic efficacy have been reported. The relative efficacy of cytotoxic agents for the treatment of TGCT patients was studied in three different cell lines derived from human embryonal carcinomas (EC) in an in vitro hypoxia model. NT2, 2102 EP, and NCCIT were tested for their sensitivity towards cisplatin, etoposide, bleomycin, 4-OOH-ifosfamide, carboplatin, paclitaxel, gemcitabine, oxaliplatin, irinotecan, and mitomycin C under normoxic and hypoxic conditions using the MTT assay. Inhibitory concentrations IC(50) of the tested agents under both conditions were compared. Selected results were confirmed by flow-cytometric assessment of the apoptotic index. In all cells, doubling times were prolonged in hypoxia (NT2

Show MeSH
Related in: MedlinePlus