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Tetsuo Akimoto

Publications and source records attributed to Tetsuo Akimoto.

25 records · Page 2Linked to original sources
PubMed2002

[Prostate cancer].

The incidence of prostate cancer has been increasing gradually in Japan, and the optimal use of radiation therapy is important to improve therapeutic outcome and quality of life. The clinical trials conducted by RTOG and EORTC have made it clear that dose escalation results in improvement of the local control rate in early stage localized prostate cancer and androgen ablation in combination with radiation therapy improves biochemical control and the progression-free survival rate in locoregionally advanced prostate cancer. To select optimal patients for dose escalation study and to determine the optimal use of androgen ablation, it has become clear that the Gleason score and pretreatment PSA value provide valuable information in addition to clinical stage. In terms of prophylactic irradiation to pelvic lymph nodes, there has been no definitive evidence that prophylactic irradiation of clinically or pathologically uninvolved pelvic lymph nodes improves the overall survival rate. Brachytherapy including 125-I or 103-Pd permanent implants and high-dose-rate brachytherapy is now widely used in the treatment of prostate cancer, but clear indications have not yet been determined because of the lack of clinical trials. In this paper, we summarize evidence concerning the role of radiation therapy in the treatment of prostate cancer and also describe the biological basis of prostate cancer, which influences the optimal selection of treatment modalities.

Brachytherapy↗
PubMedDate not supplied

Signal transduction pathway to low-dose radiation-induced apoptosis in peripheral PNET cells.

We investigated the signal transduction pathway to low-dose radiation-induced apoptosis in vitro in the human peripheral primitive neuroectodermal tumor (pPNET) cell line with wild-type p53 established in our laboratory. Apoptosis was induced by 2Gy irradiation in an almost p53-dependent manner in this model except for a deficiency of the cleavage of caspase-9. It was detected 3 hours after irradiation by fragmentation assay. The expressions of p53, p21WAF-1 and Bax increased, in contrast to the gradually decreasing expression of Bcl-2, as observed by immunoblotting. Following this, cleavages of caspase-3 and PARP reached peak levels. There were no detectable increases in ERK expression and caspase-9 cleavage. In respect of the probability of other pathways to apoptosis, this cell line will provide a useful model both for investigating low-dose radiation-induced signal transduction pathway and for analyzing the biological characteristics of pPNET.

Adult↗
PubMedDate not supplied

Combined effect of hyperthermia at 42 degrees C and irradiation dose of 2 Gy on two rat yolk sac tumor cell lines with different radio-thermosensitivity in vitro.

BACKGROUND: Two rat yolk sac tumor cell lines, NMT-1 and NMT-1R, are of the same origin and of different sensitivity to irradiation and to heat. The aim of this study was to investigate the sensitivities of these two cell lines to combined treatments of low-dose irradiation at 2 Gy and hyperthermia at 42 degrees C. MATERIALS AND METHODS: The cell survival was assayed by soft agar clonogenic assay. After the survival curves of radiation alone and of heat alone at various temperatures were estimated, not only the effect of irradiation on heat, but the effect of heat on irradiation were evaluated with sequential treatments in both cell lines. These effects on survival curves were evaluated by the enhancement ratios at isosurvival levels of 37%, 10% and 1%, respectively. RESULTS: NMT-1 was more sensitive to radiation but more resistant to heat than NMT-1R. For 1% survival level, radiosensitivity in NMT-1 was 1.32 times that in NMT-1R, while thermal sensitivity at 42 degrees C in NMT-1R was 2.73 times that in NMT-1. For sequential treatment, thermosensitization by a radiation dose of 2 Gy in radiosensitive NMT-1 was greater than that in radioresistant NMT-1R. Following heat at 42 degrees C for 1 hour, increased radiosensitivity in NMT-1R was significant, whereas the same heat treatment produced an increase in the radiation sensitivity of NMT-1 with a reduction of the survival curve shoulder but with less slope modification. There was no difference in the surviving fraction in the time-course of a combination of heat and irradiation at various intervals within 6 hours for NMT-1 except for heating immediately after irradiation. However a significant increase in survival was observed when heat was applied more than 3 hours after 2 Gy irradiation for NMT1-R. CONCLUSION: These results from our cell lines with the same origin were useful for investigation into the interaction of irradiation with heat.

Animals↗
PubMedDate not supplied

Interaction of radiation and etoposide on two cell lines with different radiosensitivities in vitro.

PURPOSE: To investigate the differences between two rat yolk sac tumor cell lines with different radiosensitivities in etoposide sensitivity and in the sensitizing effect of etoposide in combination with irradiation. MATERIALS AND METHODS: NMT-1 is a parent radiosensitive cell line and NMT-1R is a variant radioresistant cell line. The effects were assessed by clonogenic assay. Apoptosis was evaluated by DNA fragmentation to investigate the mechanism of cell death. RESULTS: Etoposide potentiation of radiation sensitivity was manifested by elimination of the initial shoulder of the cell survival curve in radioresistant NMT-1R cells. However, there was no enhancement effect in radiosensitive NMT-1 cells. The incidence of apoptosis was elevated in NMT-1R cells treated with etoposide and radiation. CONCLUSION: Etoposide had a supra-additive effect in combination with irradiation for radioresistant NMT-1R cells due to the induction of apoptosis. However, a suppra-additive effect was not seen in radiosensitive NMT-1 cells.

Animals↗
PubMedDate not supplied

Changes in the localization of heat shock protein 72 correlated with development of thermotolerance in human esophageal cancer cell line.

BACKGROUND: The aim of this study was to investigate the relationship between the changes in the localization of heat shock proteins (Hsps) and acquisition of thermotolerance. MATERIALS AND METHODS: A human esophageal cancer cell line was used. Fractionated heat treatment with different recovery times was performed to develop thermotolerance. Changes in the localization and the expression of Hsps were examined by the immunofluorescence and immunoblot analysis. In order to inhibit Hsps induction, Hsp inhibitor, KNK437, was used. In addition, changes in susceptibility of apoptosis induction were also evaluated in thermotolerant or non-thermotolerant cells. RESULTS: Thermotolerance reached its peak at the recovery time of 120 minutes after the first heat and maximum thermotolerance was observed in consistence with the timing of appearance of cytoplasmic Hsp72. Suppression of cytoplasmic Hsp72 positivity caused by KNK437 resulted in inhibition of acquisition of thermotolerance. Caspase-3 activation and PARP cleavage, that were suppressed in thermotolerant cells, re-appeared by using KNK437, in combination with heat. CONCLUSION: The cytoplasmic localization of Hsp72 might be correlated with the development of thermotolerance.

Acclimatization↗
PubMedDate not supplied

Selective inhibition of survival signal transduction pathways enhanced radiosensitivity in human esophageal cancer cell lines in vitro.

PURPOSE: The purpose of this study was to examine how selective inhibition of the survival signal transduction pathways affects radiosensitivity in human cancer cell lines. MATERIALS AND METHODS: Two human esophageal cancer cell lines, TE-1 (mutant p53) and TE2 (wild-type p53), were used. To inhibit the pathways selectively, 3 specific kinase inhibitors, AG1478 (an inhibitor of EGFR), PD98059 (an inhibitor of MEK) and LY294002 (an inhibitor of PI3K), were combined with radiation. RESULTS: Radiation in combination with these kinase inhibitors potentiated radiation-induced cell killing synergistically. Enhancement ratios were greater in TE-2 than those in TE-1. Radiation in combination with kinase inhibitors increased the expression of the active form of caspase-3 and the PARP cleavage only in TE-2 that has wild-type p53. CONCLUSION: Targeting the key molecules of the survival signal transduction pathway resulted in potentiation of radiation-induced cell killing. The results of this study suggest that the survival signal transduction pathways would be a molecular target in enhancing radiosensitivity.

Caspase 3↗