Hideo Niibe

The effects of p53 status and human papillomavirus infection on the clinical outcome of patients with Stage IIIB cervical carcinoma treated with radiation therapy alone

It has been suggested that the p53 tumor suppressor gene regulates the radiosensitivity in human malignancies after irradiation; however, in cervical carcinoma, the role of the p53 gene is still unclear because of inactivation of functional p53 by infection with human papillomavirus (HPV). The objective of this study was to clarify the effects of p53 status and HPV infection on the clinical outcome of patients with cervical carcinoma after undergoing radiation therapy.

Caffeine enhanced radiosensitivity of rat tumor cells with a mutant-type p53 by inducing apoptosis in a p53-independent manner

The radiosensitizing effects of caffeine on two rat yolk sac tumor cell lines with a different p53 status were investigated. A reduction of radiation-induced G(2) arrest was caused by caffeine at a concentration of 2 mM in both cell lines. The reduction of survival was observed in a combination of radiation and 2 mM caffeine only in a lower radiation dose range, but not in a higher dose range in NMT-1 with a wild type p53. Radiosensitization of caffeine was recognized even in a higher dose range for cells with a mutant-type p53. Apoptosis, which was not prominent after irradiation alone or caffeine treatment alone, was induced by irradiation in combination with caffeine in cells with a mutant-type p53 through a p53-independent pathway.

Stereotactic radiotherapy for locally recurrent nasopharyngeal carcinoma.

Objective: To determine the efficacy of stereotactic radiotherapy (SRT) in the treatment of recurrent nasopharyngeal carcinoma. Study Design: A retrospective review of the outcome of SRT for patients with recurrent nasopharyngeal carcinomas following definitive conventional radiation therapy. Methods: Five patients were treated with daily static multiportal irradiation. Two Gy was administered with eight isocentric portals in a single plane 5 days a week, and the plane was changed for every 20 to 30 Gy. Of these patients, three had poorly differentiated squamous cell carcinoma. Tumor sizes ranged from 1 to 15 cm 3 , with a median size 3.2 cm 3 . Median follow‐up time from SRT was 34 months (range, 4–61 mo). Results: Four of five recurrent tumors responded well and achieved complete regression. Three patients have survived without evidence of local recurrence with a median follow‐up time of 34 months. Marginal recurrence was observed at the posterosuperior wall in a patient with adenoid cystic carcinoma at 30 months after SRT. One patient who received SRT after the two complete courses of radiation therapy died 6 months after SRT as a result of rupture of a branch of the left carotid artery, but autopsy revealed no local residual tumor. Conclusions: Stereotactic radiotherapy with isocentric multiportals in one plane, which is changed at every 20 to 30 Gy, can provide local control with acceptable toxicity in patients with recurrent nasopharyngeal carcinoma, but increased clinical experience and longer follow‐up will be necessary to evaluate the overall role of this technique in nasopharyngeal carcinoma.

Interaction between low dose-rate irradiation, mild hyperthermia and low-dose caffeine in a human lung cancer cell line

PURPOSEnTo investigate cell killing by means of low dose-rate irradiation (LDRI) combined with concurrent mild hyperthermia and to determine the effect of low-dose caffeine on this combination treatment.nnnMATERIALS AND METHODSnHuman lung adenocarcinoma cells, LK87, were treated with LDRI (50 cGy/h) in combination with mild hyperthermia at 41 degrees C and low-dose caffeine (1 mM). Cell survival was estimated by clonogenic assay. Flow-cytometry was performed with PI staining using FACScan. Heat-shock protein (HSP72/73) was measured by the Western blotting method. All treatments were simultaneously performed for up to 48 h (24 Gy).nnnRESULTSnLDRI cytotoxicities were enhanced by hyperthermia at 41 degrees C. D0 calculated from the dose-response curve for LDRI combined with 41 degrees C was 3.46 Gy whereas it was 6.55 Gy for LDRI alone. The survival curve for LDRI +41 degrees C demonstrated no chronic thermotolerance up to 48 h. For LDRI + simultaneous low-dose caffeine, cell killing was also enhanced, where D0 was 3.38 Gy at 37 degrees C. Radiosensitization caused by caffeine was enhanced by combination with simultaneous mild hyperthermia at 41 degrees C, where D0=1.78 Gy. Cell cycle analysis demonstrated remarkable G2 and mild G1 arrest for LDRI alone, but only G1 arrest was observed for LDRI combined with 41 degrees C and for LDRI combined with caffeine. Strong and early G1 arrest was observed in the treatment with LDRI + caffeine at 41 degrees C. The amount of HSP72/73 in the combination of LDRI with caffeine at 41 degrees C was less than that at 41 degrees C alone.nnnCONCLUSIONnLDRI cytotoxicity was enhanced by non-lethal hyperthermia. Low dose caffeine produced further cell killing in the combination of LDRI with mild hyperthermia.

Biological Cell Survival Mapping for Radiofrequency Intracavitary Hyperthermia Combined with Simultaneous High Dose-rate Intracavitary Irradiation

We examined the best way to combine recently developed radiofrequency intracavitary hyperthermia with simultaneous high dose‐rate intracavitary brachytherapy in an original experimental model. Temperature distribution was measured with an experimental phantom which was immersed in a water bath with the temperature controlled at 37°C. Radiation dose distribution was calculated with a treatment‐planning computer. Cell survival was measured by colony assay with HeLa‐TG cells in vitro. Radiation dose response at 1‐7 Gy and time response with hyperthermia in the range of 40‐46°C were estimated. Radiation dose‐response curves in simultaneous treatment with hyperthermia for 30 min at 37 to 46°C were estimated and the surviving fractions in combined treatment were plotted against temperature. For intracavitary radiation alone, cell survival rates increased with increasing distance from the source. For intracavitary hyperthermia alone, the maximum temperature was observed at a depth of 13 mm from the surface of the applicator under suitable treatment conditions. Homogeneous cell killing from the surface of the applicator to a tumor depth of 13 mm was observed under a specific treatment condition. Our experimental model is useful for evaluating the best simultaneous combined treatment.