Masato Ito

Nagoya City University, Nagoya, Aichi, Japan

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Publications (19)51.84 Total impact

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    ABSTRACT: We report a 64-year-old man with incidentally found uncorrected total anomalous pulmonary venous connection (TAPVC). There have been only a few case reports of untreated TAPVC diagnosed after 60 years of age. Also, this is a first case report of TAPVC in which ECG-gated CT and phase-contrast cine magnetic resonance imaging (PC-MRI) was performed. He was referred to our hospital for the surgery of rectal cancer. He had been diagnosed to have an arterial septal defect (ASD) and persistent left superior vena cava (PLSVC), and Eisenmenger's syndrome was thought to be the cause of cyanosis at first. The vertical vein in TAPVC was initially misdiagnosed as PLSVC on enhanced axial CT images reconstructed with 5-mm slice thickness with gapless. ECG-gated CT and PC-MRI were useful to confirm the diagnosis. The vertical vein in TAPVC is morphologically similar to PLSVC. This kind of abnormality would be somewhat difficult to diagnose on non-ECG-gated CT, and might be misdiagnosed as a large ASD and PLSVC.
    Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia. 03/2013;
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    ABSTRACT: To prospectively evaluate the feasibility of dual-energy (DE) split-bolus CT-urography (CTU) and the quality of virtual non-enhanced images (VNEI) and DE combined nephrographic-excretory phase images (CNEPI), and to estimate radiation dose reduction if true non-enhanced images (TNEI) could be omitted. Between August and September 2011, 30 consecutive patients with confirmed or suspected urothelial cancer or with hematuria underwent DE CT. Single-energy TNEI and DE CNEPI were obtained. VNEI was reconstructed from CNEPI. Image quality of CNEPI and VNEI was evaluated using a 5-point scale. The attenuation of urine in the bladder on TNEI and VNEI was measured. The CT dose index volume (CTDI (vol)) of the two scans was recorded. The mean image quality score of CNEPI and VNEI was 4.7 and 3.3, respectively. The mean differences in urine attenuation between VNEI and TNEI were 14±15 [SD] and -16±29 in the anterior and posterior parts of the bladder, respectively. The mean CTDI (vol) for TNEI and CNEPI was 11.8 and 10.9mGy, respectively. Omission of TNEI could reduce the total radiation dose by 52%. DE split-bolus CTU is technically feasible and can reduce radiation exposure; however, an additional TNEI scan is necessary when the VNEI quality is poor or quantitative evaluation of urine attenuation is required.
    European journal of radiology 05/2012; 81(11):3160-5. · 2.65 Impact Factor
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    ABSTRACT: The aim of this study was to determine the clinicopathologic significance of high-intensity areas in the ureter, urethra, prostate, and bone incidentally found on diffusion-weighted magnetic resonance imaging (DWI) for the staging of bladder cancer. Axial and sagittal DWI and T2-weighted imaging of the pelvis were evaluated in 157 patients with bladder cancer. Two observers assessed T2-weighted imaging with DWI independently. The observers pointed out 67 areas showing abnormal high signal intensity on DWI in the ureter (n = 17), urethra (n = 8), prostate (n = 20), and bone (n = 22). Of the 67 high-intensity areas, 33 lesions were confirmed histopathologically (ureter, n = 10; urethra, n = 7; prostate, n = 16), and 22 bone lesions were diagnosed using T1-weighted imaging and follow-up computed tomography. Thus, 55 lesions were evaluable for correlation with DWI findings. Of the 55 high-intensity areas, 28 (53%) were synchronous or metastatic urothelial cancer or invasion of urothelial cancer. The remaining 27 (47%) were a ureteral clot in one, a ureteral stone granuloma in one, prostatic cancer in six, granulomatous prostatitis in three, and normal red bone marrow in 16. DWI is useful to comprehend the extent of bladder cancer and to detect incidentally coexisting diseases. Other imaging, endoscopic, and clinical findings would be useful to reduce false positivity.
    Academic radiology 02/2012; 19(7):827-33. · 2.09 Impact Factor
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    ABSTRACT: To evaluate the compliance of linear-quadratic (LQ) model calculations in the high-dose range as used in stereotactic irradiation in a murine tumor model. Female 10-week-old Balb/c mice bearing 1-cm-diameter EMT6 tumors in the hind legs were used. Single doses of 10-25 Gy were compared with 2-5 fractions of 4-13 Gy given at 4-hour intervals. Cell survival after irradiation was determined by an in vivo-in vitro assay. Using an α/β ratio determined for in vitro EMT6 cells and the LQ formalism, equivalent single doses for the hypofractionated doses were calculated. They were then compared with actually measured equivalent single doses for the hypofractionated doses. These fractionation schedules were also compared simultaneously to investigate the concordance/divergence of dose-survival curves plotted against actual radiation doses and biologically effective doses (BED). Equivalent single doses for hypofractionated doses calculated from LQ formalism were lower than actually measured doses by 21%-31% in the 2- or 3-fraction experiments and by 27%-42% in the 4- or 5-fraction experiments. The differences were all significant. When a higher α/β ratio was assumed, the discrepancy became smaller. In direct comparison of the 2- to 5-fraction schedules, respective dose-response curves almost overlapped when cell survival was plotted against actual radiation doses. However, the curves tended to shift downward by increasing the fraction number when cell survival was plotted against BED calculated using an α/β ratio of 3.5 Gy for in vitro EMT6 cells. Conversion of hypofractionated radiation doses to single doses using the LQ formalism underestimated the in vivo effect of hypofractionated radiation by approximately 20%-40%. The discrepancy appeared to be larger than that seen in the previous in vitro study and tended to increase with the fraction number. BED appeared to be an unreliable measure of tumor response.
    International journal of radiation oncology, biology, physics 12/2011; 81(5):1538-43. · 4.59 Impact Factor
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    ABSTRACT: To investigate the reliability of the linear-quadratic (LQ) formalism and the magnitude of errors associated with its use in assessing biologic equivalence between single, high radiation doses and hypofractionated radiation doses. V79 and EMT6 single cells received single doses of 2-12 Gy or two or three fractions of 4 or 5 Gy, each at 4-h intervals. Single and fractionated doses to actually reduce the cell survival to the same level were determined by a colony assay. The alpha/beta ratio was obtained from the cell survival curves. Using the alpha/beta ratio and the LQ formalism, equivalent single doses for the hypofractionated doses were calculated. They were then compared with the actually determined equivalent single doses for the hypofractionated doses. The V79 spheroids received single doses of 5-26 Gy or two to five fractions of 5-12 Gy at 2 or 4-h interval, and then were assayed for cell survival. Next, equivalent single doses for the hypofractionated doses were determined, as were done for the single cells. The alpha/beta ratio was 5.1 Gy for the V79 single cells and 0.36 Gy for EMT6. In V79, the equivalent single doses for the hypofractionated doses calculated using the LQ formalism were 12-19% lower than the actually measured biologically equivalent single doses. In the EMT6 cells, this trend was also seen, but the differences were not significant. In the V79 spheroids, the calculated doses were 18-30% lower than the measured doses. Conversion of hypofractionated radiation doses to single doses using the LQ formalism could underestimate the effect of hypofractionated radiation by < or =30%.
    International journal of radiation oncology, biology, physics 10/2009; 75(2):482-8. · 4.59 Impact Factor
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    ABSTRACT: To prospectively evaluate the ability of diffusion-weighted (DW) magnetic resonance (MR) imaging to be used to determine the T stage of bladder cancer and to measure the correlation between the apparent diffusion coefficient (ADC) and histologic grade. This study was approved by the local institutional review board. All patients gave written informed consent. Forty patients with a total of 52 bladder tumors underwent MR imaging that included DW imaging. Histologic grade was determined for all tumors. Two radiologists interpreted four image sets (ie, T2-weighted images alone, T2-weighted plus DW images, T2-weighted plus dynamic contrast agent-enhanced images, all three image types together). Conventional criteria were used for interpreting T2-weighted and contrast-enhanced images. For DW images, new staging criterion developed on the basis of the hypothesis that tumors, submucosal tissue, and muscles show high, low, and intermediate signal intensity, respectively, was used. The McNemar test was used to examine differences in accuracy, sensitivity, and specificity. Differences in the performance were analyzed by comparing the areas under the receiver operating characteristic curves (A(z) values). To compare ADCs between three histologic grades, analysis of variance was used. The overall accuracy of T stage diagnosis was 67% for T2-weighted images alone, 88% for T2-weighted plus DW images, 79% for T2-weighted plus contrast-enhanced images, and 92% for all three image types together. The overall accuracy, specificity, and A(z) for diagnosing T2 or higher stages were significantly improved by adding DW images (P < .01). The mean ADC of G3 tumors was significantly lower than that of G1 and G2 tumors (P < .01). DW images provided useful information for evaluating the T stage of bladder cancer, particularly in differentiating T1 or lower tumors from T2 or higher tumors. The ADC may in part predict the histologic grade of bladder cancer.
    Radiology 05/2009; 251(1):112-21. · 6.34 Impact Factor
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    ABSTRACT: To ascertain whether meloxicam used in a clinical setting as a non-steroidal anti-inflammatory drug (NSAID) warrants preclinical in vivo evaluation as an anticancer agent, we investigated its antitumor effects alone and in combination with radiation and/or 5-fluorouracil (5-FU) in cultured cells. Seven cell lines were examined for cyclooxygenase-2 (COX-2) protein expression by immunoblot analysis, and the HeLaS3, SCCVII and EMT6 cell lines were selected, expressing relatively high, intermediate, and relatively low COX-2 levels, respectively. Antitumor effects were examined using a colony assay. Among the three cell lines, the effect of meloxicam alone was strongest in SCCVII cells. With 24 h of drug exposure, meloxicam at concentrations of 250 and 1250 µM had a definite antitumor effect, dependent on the drug exposure time. The effect of meloxicam in combination with radiation and/or 5-FU was also investigated in the SCCVII cells. At a meloxicam concentration of 250 µM, the antitumor effect in combination with radiation or 5-FU was increased compared to the effect of radiation or 5-FU alone; however, the combined effect appeared to be additive. At lower concentrations, meloxicam had no radiosensitizing effect, nor did it enhance the effect of 5-FU. A meloxicam concentration of 250 µM is considerably higher than concentrations obtained in humans taking meloxicam as an NSAID. In conclusion, the antitumor effect of meloxicam was not correlated with the level of COX-2 protein expression. The effect of meloxicam in combination with radiation and/or 5-FU appeared to be additive. To evaluate the possibility of using meloxicam as an anticancer agent, in vivo investigations at clinically relevant drug dose levels are required.
    Molecular Medicine Reports 01/2009; 2(4):621-5. · 1.17 Impact Factor
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    ABSTRACT: The effect of pretreatment with various low doses of total-body irradiation (TBI) on tumor cell transplantability in syngeneic mice was investigated. Two cell lines, EMT6 and SCCVII, and two strains of mice, were used. First, Balb/c mice were sham-irradiated or irradiated at 200 mGy, and 6-48 h later, 1000 EMT6 cells were inoculated in the hind legs. Based on the results, 0-1500 mGy of TBI was given 6 h before inoculation of 100 or 1000 cells in the subsequent experiments. All mice were observed for 50 days after transplantation. Tumors were judged as grown when the volume of palpable nodules exceeded 200 mm(3). Tumor transplantability rate was significantly higher in the groups irradiated at 1500 mGy than in the sham-irradiated groups in both Balb/c and C3H/He mice. There were no differences in transplantability rates between the control group and the groups irradiated at various doses of 50-500 mGy. However, the mean time to tumor appearance was significantly elongated in Balb/c mice receiving TBI at 200 mGy and inoculated with 100 or 1000 EMT6 cells 6 h later. This phenomenon was also observed in Balb/c mice receiving 100 mGy TBI and inoculated with 1000 EMT6 cells. The present study might suggest that low-dose TBI to mice may delay tumor growth under certain conditions.
    Journal of Radiation Research 04/2008; 49(2):197-201. · 1.45 Impact Factor
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    ABSTRACT: In vivo effects of intermittent irradiation are influenced by recovery from sublethal damage (SLDR) and reoxygenation, so contribution of the two factors were investigated using murine tumors. 1-cm-diameter SCCVII tumors growing in the legs of C3H/HeN mice were used. First, effects of 5 fractions of 6 Gy given at intervals of 2.5-15 min were compared using an in vivo-in vitro assay, by clamping the tumor-bearing legs to exclude the influence of reoxygenation. In the second and third experiments, changes in the hypoxic fraction at 0-15 min after 13 or 5 Gy were assessed by a paired cell survival method. Fourth, effects of 5 fractions of 5 Gy given at intervals of 3-10 min under conditions of limited reoxygenation were compared using a growth delay assay. Cell survival from clamped tumors tended to increase with elongation of the intervals, but not significantly. The hypoxic fraction tended to decrease at 5-15 min from the level immediately after irradiation. Effects on tumor growth tended to decrease with elongation of the intervals. Reoxygenation occurring within 5-15 min appeared to compensate for SLDR in SCCVII tumors. When reoxygenation was limited, the decrease of radiation effect occurred due to SLDR.
    Radiotherapy and Oncology 04/2008; 86(3):369-74. · 4.52 Impact Factor
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    ABSTRACT: We evaluated the results of postoperative mediastinal radiotherapy (MRT) for invasive thymoma and low-dose entire hemithorax radiotherapy (EHRT) for pleural dissemination. Sixty patients were treated with a nearly uniform policy. Generally, we administered 30 to 40 Gy MRT after surgery at 2 Gy daily fractions for Masaoka stage II tumors or suspected residual diseases, and 50 to 55 Gy MRT for stage III tumors and for highly-suspected or macroscopic residual diseases. Since 1992, we have administered EHRT in patients with pleural dissemination, with 11.2 Gy in 7 fractions or 15 to 16 Gy in 10 fractions after removal of disseminated lesions in addition to MRT. We treated 52 patients with MRT alone and 8 with EHRT and MRT. In addition, we gave EHRT to four patients who developed pleural dissemination later. For all 60 patients, the overall and cause-specific survival and local and pleural-dissemination control rates at 5 years were 79, 87, 86, and 69%, respectively. Both Masaoka stage and tumor resectability were associated with prognosis. In stage IVa patients, pleural dissemination control rate was 71% at 3 years after EHRT, whereas it was 49% in patients receiving MRT alone (p = 0.38). Grade 2 or higher radiation pneumonitis was observed in only 3 of 52 patients (5.8%) undergoing MRT initially. In 12 patients who underwent EHRT, 3 patients (25%) experienced grade 2 or 4 pneumonitis. Postoperative MRT appeared to prevent local recurrence with acceptable toxicity. EHRT is generally safe and may contribute to control of pleural dissemination.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 02/2008; 3(1):75-81. · 4.55 Impact Factor
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    ABSTRACT: Radioadaptive survival responses after relatively low doses of radiation were investigated in C57BL/6 mice. The 8-week-old mice received whole-body mid-lethal challenging irradiation (5.9 Gy) at various intervals after conditioning whole-body irradiation with 50-400 mGy. Thereafter, survival of the mice was observed for 30 days. The mice receiving 400 mGy at 6 h before the challenging dose had a lower survival rate than the control group, but it was not observed when the conditioning 400-mGy irradiation was given 24 h beforehand. The conditioning doses of 100 and 200 mGy did not influence the survival of mice after the challenging dose. The mice receiving 50 mGy at 1 day, 3 days or 1 week before the challenging dose had a higher survival rate than the control, although this adaptive response was not observed when 50 mGy was given 6 h, 12 h, 3.5 weeks, or 5 weeks beforehand. When 50 mGy was given 2 weeks before the challenging dose, the adaptive response was observed in an experiment in which the mice were caged in our laboratory at the age of 5 weeks, whereas it was not observed in another experiment in which the mice were caged at 3 weeks. This study confirmed the presence of radioadaptive survival responses at the dose of 50 mGy given relatively shortly before the challenging dose.
    Journal of Radiation Research 12/2007; 48(6):455-60. · 1.45 Impact Factor
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    ABSTRACT: To investigate differences in visual evaluation of the hepatic arteries and contrast enhancement of the vessels and liver at 3-dimensional (3D) computed tomography (CT) angiography by 2 different concentrations of contrast materials. Eighty patients were randomly assigned into groups A and B receiving contrast materials with iodine concentrations of 300 and 370 mg/mL, respectively. The total iodine load (600 mg/kg), iodine injection time (25 seconds), and saline flush time (10 seconds) were identical. Seventy-two patients were evaluable. There were no differences between the 2 groups in visual evaluation of the hepatic arteries at 3D CT angiography. Contrast enhancement of the aorta at the late arterial phase and the liver at the portal phase was significantly higher in group B than in group A, but otherwise, there were no differences. Enhancement of the aorta and portal vein was higher in women than in men at some phases. With the same iodine dose and injection time, the concentration of contrast materials did not seem to be important in obtaining optimal images at 3D CT angiography of the hepatic artery.
    Journal of Computer Assisted Tomography 01/2007; 31(6):840-5. · 1.58 Impact Factor
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    ABSTRACT: A newly developed contrast material, CH3-DTPA-Gd (NMS60), a trimer containing 3 Gd(3+) atoms per molecule, has been shown to offer greater enhancement and longer vascular retention than gadopentetate dimeglumine (Gd-DTPA) in animals. We report on our early phase II study on NMS60 in brain tumor patients together with supplementary investigations. The longitudinal relaxation rate (R(1)=1/T(1)) and the transverse relaxation rate (R(2)*=1/T(2)*) of NMS60 and Gd-DTPA were determined at 20 degrees C in water at 1.5 T. An NMS60 dose of 0.1 or 0.2 mmol (Gd)/kg was randomly assigned and administered to 10 patients (five women, five men; mean age: 49 years) with brain tumors. Safety and contrast-enhancing ability of NMS60 were evaluated. Dual dynamic contrast-enhanced T(1) and R(2)* studies (DUCE imaging) were also carried out in two patients. Regarding the relaxivity per Gd, R(1) and R(2)* of NMS60 were 9.5 and 11.0 (mmol/L x s)(-1), respectively, compared to 4.8 and 7.2 (mmol/L x s)(-1) for Gd-DTPA. Although a transient slight increase of alanine aminotransferase was observed in one case, no other adverse reactions were observed after administration of NMS60. Contrast enhancement by NMS60 was excellent at both concentrations, and when tumor detectability was assessed with a five-point scale, the diagnostic usefulness was 4 or higher in all cases. In DUCE imaging, NMS60 appeared to show high signal intensity, when compared with the data obtained separately for Gd-DTPA. NMS60 had a high contrasting effect and little toxicity, and is expected to be clinically useful.
    Magnetic Resonance Imaging 07/2006; 24(5):625-30. · 2.06 Impact Factor
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    ABSTRACT: In stereotactic irradiation using a linear accelerator, the effect of radiation may be reduced during intermittent exposures owing to recovery from sublethal damage in tumor cells. After our previous in vitro study suggesting this phenomenon, we investigated the issue in murine tumors. We used EMT6 and SCCVII tumors approximately 1 cm in diameter growing in the hind legs of syngeneic mice. Three schedules of intermittent radiation were investigated. First, 2 fractions of 10 Gy were given at an interval of 15-360 min to investigate the pattern of recovery from sublethal damage. Second, 5 fractions of 4 Gy were given with interfraction intervals of 2.5-15 min each. Third, 10 fractions of 2 Gy were given with interfraction intervals of 1-7 min each. Doses of 15-20 Gy were also given without interruption to estimate the dose-modifying factors. Tumors were excised 20 h later, and tumor cell survival was determined by an in vivo-in vitro assay. In the 2-fraction experiment, the increase in cell survival with elongation of the interval was much less than that observed in our previous in vitro study. In the 5- and 10-fraction experiments, no significant increase in cell survival was observed after the intermittent exposures. Moreover, cell survival decreased at most points of the 5-fraction experiments by interruption of radiation in both EMT6 and SCCVII tumors. In the 10-fraction experiment, cell survival also decreased when the interruption was 3 or 7 min in EMT6 tumors. The results of the present in vivo studies were different from those of our in vitro studies in which cell survival increased significantly when a few minutes or longer intervals were posed between fractions. This suggests that recovery from sublethal damage in vivo may be counterbalanced by other phenomena such as reoxygenation that sensitizes tumor cells to subsequent irradiation.
    International Journal of Radiation OncologyBiologyPhysics 03/2006; 64(2):619-24. · 4.52 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate radioadaptive response in 4 cell-lines under identical conditions using a colony assay. First, 4 cell-lines (V79, HeLa S3, EMT6 and SCCVII) were exposed to 8 Gy at various intervals after pretreatment with an adapting dose of 50 mGy or without it. Second, V79 cells were exposed to 8 Gy at 4.5 hrs after an adapting dose of 0 to 400 mGy. Third, V79 cells were exposed to 2, 4 or 6 Gy at 6 hrs after an adapting dose of 0 or 50 mGy. In the last experiment, an adapting dose was given either immediately after cell plating or 24 hrs later. Cell survival was assessed by a standard colony assay. Adaptive response was not observed in any of the 4 lines tested. In V79 cells, no adaptive response was seen even by changing the adapting dose, challenging dose, and timing of adapting radiation after cell plating. Although radioadaptive response has been reported for the V79 cell-line, we could not reproduce the result. We also failed to demonstrate the phenomenon in the other 3 tumor cell-lines in culture.
    The Kurume Medical Journal 02/2006; 53(1-2):1-5.
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    ABSTRACT: In intensity-modulated radiation therapy (IMRT) and stereotactic irradiation using a linear accelerator, radiation is administered intermittently and one treatment session often requires 30 min or a longer time. The purpose of the present study was to investigate the effect of fractionation and dose per fraction on cell killing by irradiation in intermittent exposure. Murine EMT6 and SCCVII cells were used. The cells were irradiated to a total dose of 8 Gy in 2, 5, 10, 20 and 40 fractions over 15, 30 and 46 min. The cells were also given 8 Gy in a single fraction over 15, 30 and 46 min using lower dose rates (continuous prolonged radiation groups). As compared with the control group receiving a single dose of 8 Gy at 1.55 Gy/min, the cell surviving fraction generally increased in groups receiving fractionated or continuous prolonged radiation. There was a general trend for cell survival to increase with the fraction number up to 20 or 40 fractions in both cell lines. The effects of IMRT and linear accelerator radiosurgery given over 15 min or longer may be less than those of 1- or 2-fraction irradiation. There was a trend for radiation effect to decrease with fraction number.
    Journal of Radiation Research 01/2006; 46(4):401-6. · 1.45 Impact Factor
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    ABSTRACT: Sanazole (AK-2123, 3-nitrotriazole derivative, N1-(3-methoxypropyl)-2-(3-nitro-1 H-1,2,4-triazol-1-yl)acetamide) and nimorazole (5-nitroimidazole derivative, 4-(2-(5-nitro-1H-1-imidazolyl)ethyl)morpholine) have been tested clinically as hypoxic cell radiosensitizers, mainly outside Japan. To determine if these sensitizers deserve clinical investigation in Japan, we reevaluated the radiosensitizing effects of these compounds in vitro and in vivo, in comparison with a fluorinated 2-nitroimidazole derivative KU-2285 (N1-(2-hydroxyethyl)-1,2-difluoro-3-(2-nitro-1 H-1-midazolyl)propanamide). KU-2285 is a known and established radiosensitizer, but is not suitable for clinical studies because of the high cost of synthesis. In vitro, the radiosensitizing effects of the three compounds on SCCVII (squamous cell carcinoma line in C3H mice) tumor cells were examined at 0.5 and 1 mM under aerobic or hypoxic conditions, using a colony assay. In vivo, SCCVII tumors grown subcutaneously in the hind legs of C3H/HeN mice were irradiated with or without prior intraperitoneal administration of 100, 200 or 400 mg/kg of the drugs. Thereafter, tumor growth delay was measured. In vitro, no sensitizing effect was observed under aerobic conditions at 1 mM. Under hypoxic conditions, the sensitizer enhancement ratio (SER) determined at 1% cell survival level for sanazole, nimorazole and KU-2285 was 1.55, 1.45 and 1.95, respectively, at 1 mM, and 1.40, 1.40 and 1.75, respectively, at 0.5 mM. In vivo, all three compounds had significant radiosensitizing effects; their effects appeared to decrease in the order of KU-2285, sanazole, and nimorazole. It was suggested that sanazole may be more suitable for clinical trials than nimorazole.
    Journal of Radiation Research 01/2006; 46(4):453-9. · 1.45 Impact Factor
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    ABSTRACT: Tumour hypoxia is a negative factor in cancer radiotherapy. In order to overcome the problem, various pharmacotherapies have been investigated as an adjunct to radiotherapy. The use of hypoxic cell sensitisers is a classical strategy, and many new compounds have been developed and investigated. Development of more efficient compounds than those currently available seems difficult and clinical studies to prove the efficacy of the existing compounds are encouraged, especially in combination with radiosurgery, intraoperative radiotherapy, and interstitial irradiation, in which a single high dose of radiation is used. Following the advent of hypoxic cell sensitisers, hypoxic cytotoxins have become available. Among them, tirapazamine has already gained success when combined with cisplatin in non-small cell lung cancer. The beneficial effect of tirapazamine when combined with radiation needs to be determined. As a third-generation compound in this field, antitumour prodrugs that are activated by irradiation under hypoxic conditions via one-electron reduction have been proposed. Prodrugs of 5-fluorouracil and 5-fluoro-2'-deoxyuridine have shown in vivo as well as in vitro activity. Although clinical evaluation of the compounds is not warranted due to a relatively low in vivo effect, this strategy appears promising if the prodrug design can be applied to more potent agents that shall be developed in future.
    Expert Opinion on Pharmacotherapy 01/2005; 5(12):2459-67. · 2.86 Impact Factor
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    ABSTRACT: In stereotactic irradiation using a linear accelerator and intensity-modulated radiation therapy (IMRT), radiation is administered intermittently, and 30 min or longer is often required in one treatment session. The purpose of the present study was to determine how different the dose delivered with such intermissions is from that delivered continuously and to estimate dose-modifying factors. Murine EMT6 and SCCVII cells in culture were used. First, two doses of 4 Gy were given with an interruption of 15 min to 6 h or 1-10 min, or without interruption. Next, five fractions of 1.6 Gy were given with interfraction intervals of 1 to 5 min each. Doses of 6.5-8 Gy were also given without interruption to estimate dose-modifying factors. Cell survival was determined by a colony assay. Furthermore, a total dose of 2 Gy was given in 5 or 10 even fractions at intervals of 1-5 min or 30 s-3 min each, respectively, and the results were compared with those obtained after 1.6-2 Gy delivered continuously by using a cytokinesis-block micronucleus assay. In the two-fraction experiments, a significant increase in cell survival resulting from recovery from sublethal damage (SLDR) was observed when the interruption time was 2 min or longer in EMT6 cells and 3 min or longer in SCCVII. With a 5-min interval, cell survival increased by 13% in EMT6 and by 18% in SCCVII. In the five-fraction experiments, SLDR was evident when the interfraction interval was 2 min or longer in both 8-Gy and 2-Gy dose experiments. In the 10-fraction experiment using a dose of 2 Gy, SLDR was evident when the interfraction interval was 1 min or longer. In the 5-fraction and 10-fraction experiments, the dose-modifying factors were between 1.08 and 1.16 when the total time for irradiation was between 20 and 30 min. The effects of stereotactic radiosurgery and IMRT that require considerably long beam interruption (e.g., 8 min or longer in total) may be less than those of the same dose administered continuously. In treatments that take 20 min or longer, dose modification appears necessary based on biologically estimated dose-modifying factors.
    International Journal of Radiation OncologyBiologyPhysics 09/2004; 59(5):1484-90. · 4.52 Impact Factor