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Volume 51, Issue 1
Displaying 1-14 of 14 articles from this issue
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Review
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Takashi NAKANO, Tatsuya OHNO, Hitoshi ISHIKAWA, Yoshiyuki SUZUKI, Take ...2010 Volume 51 Issue 1 Pages 1-8
Published: 2010
Released on J-STAGE: February 20, 2010
JOURNAL FREE ACCESSRadiation therapy is one of the effective curative treatments for uterine cervical cancer. However poor clinical results for the advanced stages require further improvement of the treatment. Intensive studies on basic and clinical research have been made to improve local control, primarily important for long term survival in radiation therapy. Regarding current advancement in radiation therapy for uterine cervical cancer, the following three major subjects are pointed out; technological development to improve dose distribution by image guided radiation therapy technology, the concomitant anticancer chemotherapy with combination of radiation therapy, and radiation biological assessment of the radiation resistance of tumors. The biological factors overviewed in this article include hypoxia relating factors of HIF-1α, SOD, cell cycle parameters of pMI, proliferation factors of Ki67, EGFR, cerbB2, COX-2, cycle regulation proteins p53, p21, apoptosis regulation proteins Bcl2 and Bax and so on. Especially, the variety of these radiation biological factors is important for the selection of an effective treatment method for each patient to maximize the treatment benefit.View full abstractDownload PDF (226K)
Regular Papers
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Kazushige ATSUMI, Yoshiyuki SHIOYAMA, Katsumasa NAKAMURA, Satoshi NOMO ...2010 Volume 51 Issue 1 Pages 9-14
Published: 2010
Released on J-STAGE: February 20, 2010
Advance online publication: October 03, 2009JOURNAL FREE ACCESSThe purpose of this retrospective study was to clarify the predictive factors correlated with esophageal stenosis within three months after radiation therapy for locally advanced esophageal cancer. We enrolled 47 patients with advanced esophageal cancer with T2-4 and stageII-III who were treated with definitive radiation therapy and achieving complete response of primary lesion at Kyushu University Hospital between January 1998 and December 2005. Esophagography was performed for all patients before treatment and within three months after completion of the radiation therapy, the esophageal stenotic ratio was evaluated. The stenotic ratio was used to define four levels of stenosis: stenosis level 1, stenotic ratio of 0-25%; 2, 25-50%; 3,50-75%; 4,75-100%. We then estimated the correlation between the esophageal stenosis level after radiation therapy and each of numerous factors. The numbers and total percentages of patients at each stenosis level were as follows: level 1: n = 14 (30%); level 2: 8 (17%); level 3: 14 (30%); and level 4: 11 (23%). Esophageal stenosis in the case of full circumference involvement tended to be more severe and more frequent. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. The extent of involved circumference and wall thickness of tumor region were significantly correlated with esophageal stenosis associated with tumor regression in radiation therapy (p = 0.0006, p = 0.005). For predicting the possibility of esophageal stenosis with tumor regression within three months in radiation therapy, the extent of involved circumference and esophageal wall thickness of the tumor region may be useful.View full abstractDownload PDF (380K) -
Kazushige ATSUMI, Yoshiyuki SHIOYAMA, Satoshi NOMOTO, Saiji OHGA, Taka ...2010 Volume 51 Issue 1 Pages 15-20
Published: 2010
Released on J-STAGE: February 20, 2010
Advance online publication: September 16, 2009JOURNAL FREE ACCESSSmall cell esophageal carcinoma(SCEC) is a rare disease with aggressive behavior and poor prognosis. Because of the rarity of this disease, standard therapy has not yet been established. The objective of this retrospective study was to report the outcomes of SCEC treated with chemotherapy and radiotherapy from a retrospective study of 11 patients. We enrolled 11 SCEC patients who were treated with radiation therapy (more than 50 Gy) and chemotherapy between May 1996 and October 2007. Patients' age ranged from 44 to 77 years (mean: 69 years). In all patients, pathological examination of the specimen obtained by biopsy revealed small cell carcinoma. All patients were treated with chemotherapy and radiation therapy. The mean follow-up time was 14.7 months, and the median overall survival time of all patients was 13.2 months (range: 4.2-43.6 months). The 1-year and 3-year overall survival rates were 63% and 24%, respectively, while the 1-year and 3-year progression-free survival rates were 45% and 14%, respectively. Five of seven patients with complete response (CR) developed recurrent disease. Recurrence sites were distant metastases in four patients and lymph node outside the radiation field in one patient. Chemoradiation should be considered as one of the important treatment options for the loco-regional control in the patients with SCEC.View full abstractDownload PDF (312K) -
–Influence of the Addition of Platinum Atoms on DNA–Noriko USAMI, Katsumi KOBAYASHI, Ryoichi HIRAYAMA, Yoshiya FURUSAWA, E ...2010 Volume 51 Issue 1 Pages 21-26
Published: 2010
Released on J-STAGE: February 20, 2010
JOURNAL FREE ACCESSWhen energetic carbon ion beam (GeV range) goes through the matter, inelastic processes such as electronic ionization, molecular and nuclear fragmentation occur. For carbontherapy (hadrontherapy) purpose, it is of interest to compare the number of DNA breaks -single SSB or double DSB- for a given dose at the entrance channel and at the Bragg peak to look for a possible differential effect in the number of DNA breaks induced at these two locations. Samples of free plasmids DNA and complexes of plasmids DNA added with molecules containing platinum have been placed at different locations of an experimental setup simulating penetration depths of the ion beam in water and irradiated by carbon ions 290 MeV/amu. The DNA breaks have been quantified by subsequent electrophoresis on agarose gels. To disentangle the respective role of the direct and indirect effect, a free radical scavenger of hydroxyl radicals HO° -dimethyl sulfoxide DMSO- has been added in some of the experiments. In the range of Linear Energy Transfert -LET 13 - 110 keV/μm-, the number of the DSB was found to be constant versus the LET for a given dose. Contrary, the number of the SSB decreases at the Bragg peak compared to the entrance channel. In the presence of platinum, the number of single and double breaks was considerably enhanced, and follows a similar behaviour than in the free-DNA experiments. Quantitative results on DNA damages do not show significant enhancement due to the nuclear or to the molecular fragmentation in the present experiments.View full abstractDownload PDF (454K) -
Shin-ichiro MASUNAGA, Keizo TANO, Jun NAKAMURA, Masami WATANABE, Genro ...2010 Volume 51 Issue 1 Pages 27-35
Published: 2010
Released on J-STAGE: February 20, 2010
Advance online publication: October 03, 2009JOURNAL FREE ACCESSThe usefulness of hexamethylenetetramine as an adjuvant to radiation and cisplatin in the treatment of solid tumors and its dependency on the p53 status of tumor cells were examined. Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53), or with neo vector as a control (SAS/neo), were inoculated subcutaneously into both the hind legs of Balb/cA nude mice. The tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all proliferating (P) cells in the tumors. Then, they received hexamethylenetetramine (HMTA), intraperitoneally or continuously, combined with or without γ-ray irradiation or cisplatin treatment. Immediately after treatment following HMTA, the response of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The response of the total (= P + Q) tumor cells was determined from the BrdU non-treated tumors. A higher toxicity of HMTA to Q cells than total cells, especially in SAS/neo, was made less clear by continuous administration. There was no apparent difference in the radio- and cisplatin-sensitivity enhancing effects by HMTA combination between SAS/neo and SAS/mp53 tumors, with a slightly greater effect in SAS/mp53. In both SAS/neo and SAS/mp53 tumors, continuous HMTA administration produced higher radio- and cisplatin-sensitivity enhancing effects than intraperitoneal single administration. Therefore, the use of HMTA as an adjuvant to radiation or cisplatin might be promising in curing solid tumors with large fraction of hypoxic cells and also with frequent loss-of-function in p53.View full abstractDownload PDF (434K) -
Radjini RACINE, Line GRANDCOLAS, Eric BLANCHARDON, Patrick GOURMELON, ...2010 Volume 51 Issue 1 Pages 37-45
Published: 2010
Released on J-STAGE: February 20, 2010
JOURNAL FREE ACCESSThe Chernobyl accident released many radionuclides in the environment. Some are still contaminating the ground and thus the people through dietary intake. The long-term sanitary consequences of this disaster are still unclear and several biological systems remain to be investigated. Cholesterol metabolism is of particular interest, with regard to the link established between atherosclerosis and exposure to high-dose ionizing radiations. This study assesses the effect of cesium-137 on cholesterol metabolism in rats, after a chronic exposure since fetal life. To achieve this, rat dams were contaminated with cesium-137-supplemented water from two weeks before mating until the weaning of the pups. Thereafter, the weaned rats were given direct access to the contaminated drinking water until the age of 9 months. After the sacrifice, cholesterol metabolism was investigated in the liver at gene expression and protein level. The cholesterolemia was preserved, as well as the cholesterol concentration in the liver. At molecular level, the gene expressions of ACAT 2 (a cholesterol storage enzyme), of Apolipoprotein A-I and of RXR (a nuclear receptor involved in cholesterol metabolism) were significantly decreased. In addition, the enzymatic activity of CYP27A1, which catabolizes cholesterol, was increased. The results indicate that the rats seem to adapt to the cesium-137 contamination and display modifications of hepatic cholesterol metabolism only at molecular level and within physiological range.View full abstractDownload PDF (464K) -
Yuefen ZOU, Chao CHENG, Motoko OMURA-MINAMISAWA, Yun KANG, Takamitsu H ...2010 Volume 51 Issue 1 Pages 47-55
Published: 2010
Released on J-STAGE: February 20, 2010
Advance online publication: December 04, 2009JOURNAL FREE ACCESSBackground: The hypoxic microenvironment is closely associated with the radiation resistance of tumor cells. Hypoxia induces several genes such as hypoxia-inducible factor (HIF-1) and vascular endothelial growth factor (VEGF) to promote tumor cell growth and survival. The up-regulated expression levels of HIF-1 and VEGF in tumor cells also correlate with their resistance to radiation, suggesting that these genes are potential therapeutic targets for strategies designed to enhance radiation effects. To further investigate this possibility, we investigated the effects of suppressing these genes upon the radiation sensitivity of cancer cells. We conducted these experiments using multicellular spheroids as a three-dimensional in vitro tumor model and RNA interference as the method of gene suppression. Material and methods: SQ5 human lung carcinoma cells were treated with HIF-1/VEGF siRNA and/or radiation. Reversed transfection methods were employed for the spheroids. Gene expression was analyzed using quantitative RT-PCR and western blotting. Cell toxicity was qualified by colony formation assay. Results: Compared with monolayer cells, spheroids showed up-regulated expression of HIF-1 and increased radiation resistance. Hypoxic conditions elevated the expression of HIF-1 and VEGF and enhanced the surviving fraction of spheroids after exposure to radiation. However, when the expression of HIF-1 and VEGF was down-regulated by transfection of targeting siRNA, this did not influence the cytotoxic effects of the radiation under either normoxic or hypoxic conditions. Conclusions: We have established a method to transfect siRNA into spheroid cells. Our current data indicate that the functions of HIF-1 or VEGF are independent of radiation sensitivity in spheroids under either normoxic or hypoxic conditions.View full abstractDownload PDF (312K) -
Tomoteru YAMASAKI, Sachiko KOIKE, Akiko HATORI, Kazuhiko YANAMOTO, Kaz ...2010 Volume 51 Issue 1 Pages 57-65
Published: 2010
Released on J-STAGE: February 20, 2010
Advance online publication: October 23, 2009JOURNAL FREE ACCESSWe aimed to determine the effect of carbon ion irradiation on the uptake of N-benzyl-N-11C-methyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([11C]DAC), a positron emission tomography (PET) ligand for the peripheral-type benzodiazepine receptor (PBR), in tumor cells and tumor-bearing mice. Spontaneous murine fibrosarcoma (NFSa) cells were implanted into the right hind legs of syngeneic C3H male mice. Conditioning irradiation with 290 MeV/u carbon ions was delivered to the 7- to 8-mm tumors In vitro uptake of [11C]DAC was measured in single NFSa cells isolated from NFSa-bearing mice after irradiation. In vivo biodistribution of [11C]DAC in NFSa-bearing mice was determined by small animal PET scanning and dissection. In vitro autoradiography was performed using tumor sections prepared from mice after PET scanning. In vitro and in vivo uptake of [11C]DAC in single NFSa cells and NFSa-bearing mice was significantly reduced by carbon ion irradiation. The decrease in [11C]DAC uptake in the tumor sections was mainly due to the change in PBR expression. In conclusion, [11C]DAC PET responded to the change in PBR expression in tumors caused by carbon ion irradiation in this study. Thus, [11C]DAC is a promising predictor for evaluating the effect of carbon ion radiotherapy.View full abstractDownload PDF (594K) -
Akira ONODERA, Sumino YANASE, Takamasa ISHII, Kayo YASUDA, Masaki MIYA ...2010 Volume 51 Issue 1 Pages 67-71
Published: 2010
Released on J-STAGE: February 20, 2010
Advance online publication: October 23, 2009JOURNAL FREE ACCESSThe time spent as a dauer larva does not affect adult life span in Caenorhabditis elegans, as if aging is suspended in this quiescent developmental stage. We now report that modest doses X-irradiation of dauer larvae increased their post-dauer longevity. Post-irradiation incubation of young dauer larvae did not modify this beneficial effect of radiation. Conversely, holding dauer larvae prior to irradiation rendered them refractory to this X-radiation-induced response. We present a model to explain these results. These experiments demonstrate that dauer larvae provide an excellent opportunity to study mechanisms by which X irradiation can extend life span.View full abstractDownload PDF (292K) -
Kohsei KUDO, Yong LIU, Kenji TAKAHASHI, Kohetsu TARUSAWA, Minoru OSANA ...2010 Volume 51 Issue 1 Pages 73-79
Published: 2010
Released on J-STAGE: February 20, 2010
Advance online publication: October 23, 2009JOURNAL FREE ACCESSThe effective treatments of radiation-induced intestinal injury are currently unavailable. Developing new treatments for radiation-induced intestinal injury is thus important. The present study investigated whether transplantation of mesenchymal stem cells (MSCs) is able to prevent radiation-induced intestinal injury. Intestines of female nude mice (ICR nu/nu) were irradiated at a single dose of 30 Gy. Transplantation of male MSCs (C57BL/6) was then immediately performed into the walls of irradiated intestine by direct injection for the irradiation + MSCs group. Mice were weighed daily and survival was recorded for 13 days after irradiation. From 13 to 27 days after irradiation, intestines of mice were obtained in order to assay histological changes by staining with hematoxylin-eosin and Masson trichrome. Mean body weight of the irradiation + MSC group was significantly higher than that of the irradiation-only group from 8 days after irradiation. In addition, survival rates were significantly higher in the irradiation + MSC group than for the irradiation-only group from 5 days after irradiation. Histological observation revealed that intestines of irradiation + MSC-transplanted mice were thick in the submucosal and muscle layers, and had almost fully recovered from radiation-induced intestinal injury at day 27. Specifically, ulcerated areas in the intestines of the irradiation + MSC-transplanted mice were smaller by 13 days after irradiation and were fewer in numbers at 27 days when compared with the irradiation-only group. Our results suggest that transplanted MSCs may play an important role in preventing radiation-induced injury and may offer a novel method to treat radiation-induced intestinal injury.View full abstractDownload PDF (596K) -
Izumi TANAKA, Mika TANAKA, Akiko SATOH, Ayako KUREMATSU, Akiko ISHIWAT ...2010 Volume 51 Issue 1 Pages 81-86
Published: 2010
Released on J-STAGE: February 20, 2010
Advance online publication: October 23, 2009JOURNAL FREE ACCESSIt is well known that a pre-administration of proinflammatory cytokines alters hematopoietic progenitor cells to promote an increase resistance against radiation and increases the survival rate in mice irradiated with lethal doses of radiation. Inflammation stimulators, such as some bacterial constituents, are also reported to have similar radioprotective action. We found that pre-administration of heat-killed Lactobacillus casei (HLC) to mice increases the level of interleukin (IL)-1 beta in circulation as well as the survival rate following lethal dose of radiation. Since HLC stimulates early immune responses, effects by drugs to modify inflammation were studied. The increase of both blood IL-1 beta levels and survival rates by HLC were simultaneously accelerated by coadministration of mineralocorticoid and inhibited by glucocorticoids or corticotropin. Neither parameter was modified by non-steroidal anti-inflammatory or anti-rheumatoid drugs. This suggests that both expected radioprotective action and unexpected systemic action, realized as an increase in plasma cytokines, by inflammation-related radioprotectors can be controlled by the coadministration of drugs at least in C3H/He mice, based on consideration of their pharmacological properties.View full abstractDownload PDF (360K)
Technical Report
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Katsumasa NAKAMURA, Haruo YOSHIKAWA, Tomoharu AKAI, Satoshi NOMOTO, Yo ...2010 Volume 51 Issue 1 Pages 87-90
Published: 2010
Released on J-STAGE: February 20, 2010
Advance online publication: September 16, 2009JOURNAL FREE ACCESSWe have developed a new body fixation system for single patient use, which consists of a vacuum cushion, a thermoplastic fixation sheet which is used to suppress involuntary and voluntary patient movement, and a triple-wall corrugated fiberboard base plate to which both the vacuum cushion and the thermoplastic sheet are affixed. To evaluate the characteristics of the fiberboard as a patient-positioning insert, the photon beam attenuation of a fiberboard base plate, a carbon-fiber base plate, and a vacuum-formed cushion were compared. The strength of the fiberboard was also evaluated. The attenuation for the carbon-fiber base plate was 3.7% and 2.6% in 4 MV and 10 MV photon beams, respectively, while the results were less for the fiberboard base plate, i.e. 1.9% and 1.6%. The vacuum-formed cushion had a minimal effect on transmission. None of the materials subsided under the weight loading of 20 g/cm2. There was no difference between the thicknesses of the fiberboard before and after a 50 times daily load with the 60 kg weight of a volunteer. Corrugated fiberboard is a robust and low attenuating material that functions well as a patient-positioning insert.View full abstractDownload PDF (505K)
Short Communication
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Akihisa TAKAHASHI, Eiichiro MORI, Takeo OHNISHI2010 Volume 51 Issue 1 Pages 91-95
Published: 2010
Released on J-STAGE: February 20, 2010
JOURNAL FREE ACCESSRecently, there have been many reports concerning proteins which can recognize DNA double strand break (DSBs), and such proteins include histone H2AX phosphorylated at serine 139 (γH2AX), ataxia telangiectasia mutated (ATM) phospho-serine 1981, DNA-dependent protein kinase catalytic subunit (DNA-PKcs) phospho-threonine 2609, Nijmegen breakage syndrome 1 (NBS1) phospho-serine 343, checkpoint kinase 2 (CHK2), phospho-threonine 68, and structural maintenance of chromosomes 1 (SMC1) phospho-serine 966. Thus, it should be possible to follow the formation of DSBs and their repair using immunohistochemical methods with multiple antibodies to detect these proteins. When normal human fibroblasts (AG1522 cells) were exposed to 3 Gy of X-rays as a control, clearly discernable foci for these proteins were detected, and these foci localized with γH2AX foci. After heat treatment at 45.5°C for 20 min, these proteins are partially localized with γH2AX foci. Here we show that there were slight differences in the localization pattern among these proteins, such as a disappearance from the nucleus (phospho-ATM) and translocation to the cytoplasm (phospho-NBS1) at 30 min after heat treatment, and some foci (phospho-DNA-PKcs and phospho-CHK2) appeared at 8 h after heat treatment. These results are discussed from perspectives of heat-induced denaturation of proteins and formation of DSBs.View full abstractDownload PDF (692K)
Miscellaneou
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2010 Volume 51 Issue 1 Pages Cover01_1-Cover01_10
Published: 2010
Released on J-STAGE: February 20, 2010
JOURNAL FREE ACCESSDownload PDF (653K)
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