Journal of Radiation Research
Online ISSN : 1349-9157
Print ISSN : 0449-3060
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Volume 53, Issue 2
Displaying 1-27 of 27 articles from this issue
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Biology
  • Millimeter Wave-induced Modulation of Calcium Dynamics in an Engineered Skin Co-culture Model: Role of Secreted ATP on Calcium Spiking
    Shan SUN, Igor TITUSHKIN, Jeffrey VARNER, Michael CHO
    2012 Volume 53 Issue 2 Pages 159-167
    Published: 2012
    Released on J-STAGE: April 17, 2012
    DOIhttps://doi.org/10.1269/jrr.11037
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    We have previously designed and characterized a 94 GHz exposure system that allows real-time monitoring of subcellular interactions induced by millimeter wave (MMW) stimulation. For example, studies of the calcium dynamics in neuronal cells in response to 94 GHz irradiation suggested that MMW stimulation increased calcium spiking. In this study, we engineered a 3D co-culture model that represents the major constituents of skin. We used this experimental model along with the custom-designed MMW exposure system to investigate the effects of 94 GHz irradiation in the skin-like tissue construct. Unlike typical non-excitable cells, keratinocytes exhibited calcium spikes in their resting state. Exposure to a 94 GHz irradiation induced a statistically significant increase in the calcium spiking. When co-cultured with neuronal cells in the 3D co-culture skin model, changes in the calcium spiking in neuronal cells depended on the MMW input power. Further, the 94 GHz irradiation caused ATP secretion by keratincytes. ATP is a major factor that modulates the calcium spiking in neuronal cells. Surprisingly, while a 5-fold increase in the ATP secretion enhanced the calcium spiking in neuronal cells, a 10-fold increase significantly hindered the calcium dynamics. Computational simulation of ATP-induced calcium dynamics was in general agreement with the experimental findings, suggesting the involvement of the ATP-sensitive purinergic receptors. The engineered co-culture skin model offers a physiologically relevant environment in which the calcium dynamics is regulated both by the cell-MMW and cell-cell interactions.
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  • Expression of p53-Regulated Proteins in Human Cultured Lymphoblastoid TSCE5 and WTK1 Cell Lines during Spaceflight
    Akihisa TAKAHASHI, Hiromi SUZUKI, Katsunori OMORI, Masaya SEKI, Toko H ...
    2012 Volume 53 Issue 2 Pages 168-175
    Published: 2012
    Released on J-STAGE: April 17, 2012
    Advance online publication: February 25, 2012
    DOIhttps://doi.org/10.1269/jrr.11140
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    The aim of this study was to determine the biological effects of space radiations, microgravity, and the interaction of them on the expression of p53-regulated proteins. Space experiments were performed with two human cultured lymphoblastoid cell lines: one line (TSCE5) bears a wild-type p53 gene status, and another line (WTK1) bears a mutated p53 gene status. Under 1 gravity or microgravity conditions, the cells were grown in the cell biology experimental facility (CBEF) of the International Space Station for 8 days without experiencing the stress during launching and landing because the cells were frozen during these periods. Ground control samples were simultaneously cultured for 8 days in the CBEF on the ground for 8 days. After spaceflight, protein expression was analyzed using a PanoramaTM Ab MicroArray protein chips. It was found that p53-dependent up-regulated proteins in response to space radiations and space environment were MeCP2 (methyl CpG binding protein 2), and Notch1 (Notch homolog 1), respectively. On the other hand, p53-dependent down-regulated proteins were TGF-β, TWEAKR (tumor necrosis factor-like weak inducer of apoptosis receptor), phosho-Pyk2 (Proline-rich tyrosine kinase 2), and 14-3-3θ/τ which were affected by microgravity, and DR4 (death receptor 4), PRMT1 (protein arginine methyltransferase 1) and ROCK-2 (Rho-associated, coiled-coil containing protein kinase 2) in response to space radiations. ROCK-2 was also suppressed in response to the space environment. The data provides the p53-dependent regulated proteins by exposure to space radiations and/or microgravity during spaceflight. Our expression data revealed proteins that might help to advance the basic space radiation biology.
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  • Analysis of the Cellular Stress Response in MCF10A Cells Exposed to Combined Radio Frequency Radiation
    Han-Na KIM, Na-Kyung HAN, Mi-Na HONG, Sung-Gil CHI, Yun-Sil LEE, Taeho ...
    2012 Volume 53 Issue 2 Pages 176-183
    Published: 2012
    Released on J-STAGE: April 17, 2012
    DOIhttps://doi.org/10.1269/jrr.11048
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    Exposure to environmental stressors can be measured by monitoring the cellular stress response in target cells. Here, we used the cellular stress response to investigate whether single or combined radio frequency (RF) radiation could induce stress response in human cells. Cellular stress responses in MCF10A human breast epithelial cells were characterized after exposure to 4 h of RF radiation [code division multiple access (CDMA) or CDMA plus wideband CDMA (WCDMA)] or 2 h RF radiation on 3 consecutive days. Specific absorption rate (SAR) was 4.0 W/kg for CDMA signal alone exposure and 2.0 W/kg each, 4.0 W/kg in total for combined CDMA plus WCDMA signals. Expression levels and phosphorylation states of specific heat shock proteins (HSPs) and mitogen-activated protein kinases (MAPKs) were analyzed by Western blot. It was found that HSP27 and ERK1/2 phosphorylations are the most sensitive markers of the stress response in MCF10A cells exposed to heat shock or ionizing radiation. Using these markers, we demonstrated that neither one-time nor repeated single (CDMA alone) or combined (CDMA plus WCDMA) RF radiation exposure significantly altered HSP27 and ERK1/2 phosphorylations in MCF10A cells (p > 0.05). The lack of a statistically significant alteration in HSP27 and ERK1/2 phosphorylations suggests that single or combined RF radiation exposure did not elicit activation of HSP27 and ERK1/2 in MCF10A cells.
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  • Plutonium Behavior after Pulmonary Administration According to Solubility Properties, and Consequences on Alveolar Macrophage Activation
    Anne VAN DER MEEREN, Olivier GREMY, Daniel RENAULT, Amandine MIROUX, S ...
    2012 Volume 53 Issue 2 Pages 184-194
    Published: 2012
    Released on J-STAGE: April 17, 2012
    DOIhttps://doi.org/10.1269/jrr.11112
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    The physico-chemical form in which plutonium enters the body influences the lung distribution and the transfer rate from lungs to blood. In the present study, we evaluated the early lung damage and macrophage activation after pulmonary contamination of plutonium of various preparation modes which produce different solubility and distribution patterns. Whatever the solubility properties of the contaminant, macrophages represent a major retention compartment in lungs, with 42 to 67% of the activity from broncho-alveolar lavages being associated with macrophages 14 days post-contamination. Lung changes were observed 2 and 6 weeks post-contamination, showing inflammatory lesions and accumulation of activated macrophages (CD68 positive) in plutonium-contaminated rats, although no increased proliferation of pneumocytes II (TTF-1 positive cells) was found. In addition, acid phosphatase activity in macrophages from contaminated rats was enhanced 2 weeks post-contamination as compared to sham groups, as well as inflammatory mediator levels (TNF-α, MCP-1, MIP-2 and CINC-1) in macrophage culture supernatants. Correlating with the decrease in activity remaining in macrophages after plutonium contamination, inflammatory mediator production returned to basal levels 6 weeks post-exposure. The production of chemokines by macrophages was evaluated after contamination with Pu of increasing solubility. No correlation was found between the solubility properties of Pu and the activation level of macrophages. In summary, our data indicate that, despite the higher solubility of plutonium citrate or nitrate as compared to preformed colloids or oxides, macrophages remain the main lung target after plutonium contamination and may participate in the early pulmonary damage.
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  • Effects of Ionizing Radiation on Proliferation and Differentiation of Mouse Induced Pluripotent Stem Cells
    Naoki HAYASHI, Satoru MONZEN, Koichi ITO, Tsuyoshi FUJIOKA, Yukio NAKA ...
    2012 Volume 53 Issue 2 Pages 195-201
    Published: 2012
    Released on J-STAGE: April 17, 2012
    DOIhttps://doi.org/10.1269/jrr.11138
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    The present study aimed to estimate the clonogenic and differentiation potential of induced pluripotent stem (iPS) cells exposed to ionizing radiation. Compared with mouse hematopoietic stem/progenitor cells, iPS cells were less sensitive to radiation. To examine the effect of ionizing radiation on the early differentiation pathway of iPS cells, we assessed embryoid body (EB) formation. Although EB formation was observed at all radiation doses, EB diameter decreased in a radiation dose-dependent manner. At the same time, we analyzed the expression of genes specific to differentiation in the initial iPS cells and cells of EB. The expression of the endoderm marker Afp increased remarkably in cells of EB derived from non-irradiated iPS cells; however, in irradiated cells, this expression significantly decreased in a radiation dose-dependent manner. Further, the expressions of the pluripotent stem cell markers Nanog and Oct-4 and the early mesoderm marker Brachyury significantly decreased. The results of the present study suggest that radiosensitivity with regard to gene expression differs at various stages in the early differentiation pathways of iPS cells that lead to the formation of the 3 germ layers; the sensitivity is the highest in the genes expressed during the differentiation pathways of iPS cells, leading to the formation of the endoderm.
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  • Combination of Radiotherapy and Adenovirus-Mediated p53 Gene Therapy for MDM2-Overexpressing Hepatocellular Carcinoma
    Woong Sub KOOM, Soo-Yeon PARK, Wonwoo KIM, Minjung KIM, Ji-Seong KIM, ...
    2012 Volume 53 Issue 2 Pages 202-210
    Published: 2012
    Released on J-STAGE: April 17, 2012
    DOIhttps://doi.org/10.1269/jrr.11110
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    The p53 gene plays a determinant role in radiation-induced cell death and its protein product is negatively regulated by MDM2. We investigated whether adenovirus-mediated modified p53 gene transfer, which blocks p53-MDM2 binding, is effective for radiation-induced cell death in hepatocellular carcinoma (HCC) at different MDM2 cellular levels. Human hepatocellular carcinoma cell lines expressing MDM2 at low levels (Huh7) and high levels (SK-Hep1) were used. Ad-p53 and Ad-p53vp are replication-deficient adenoviral vectors containing human wild-type or modified p53, respectively. The anti-tumor effect was highest for Ad-p53 + radiotherapy (RT) in the low-level MDM2 cells, whereas this effect was highest for Ad-p53vp + RT in the MDM2-overexpressing cells. In Huh-7 cells, Ad-p53 + RT decreased cell viability (32%) in vitro and inhibited tumor growth (enhancement factor, 1.86) in vivo. Additionally, p21 expression and apoptosis were increased. In contrast, in SK-Hep1 cells, Ad-p53vp + RT showed decreased cell viability (51%) in vitro and inhibition of tumor growth (enhancement factor, 3.07) in vivo. Caspase-3 expression and apoptosis were also increased. Adenovirus-expressing modified p53, which blocks p53-MDM2 binding, was effective in killing tumor cells overexpressing MDM2. Furthermore, the combination strategy for disruption of the p53-MDM2 interaction with RT demonstrated enhanced anti-tumor effects both in vitro and in vivo.
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  • Protection of Mice against X-ray Injuries by the Post-irradiation Administration of Inosine-5'-monophosphate
    Nelli R. ASADULLINA, Anna M. USACHEVA, Sergey V. GUDKOV
    2012 Volume 53 Issue 2 Pages 211-216
    Published: 2012
    Released on J-STAGE: April 17, 2012
    DOIhttps://doi.org/10.1269/jrr.11050
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    The aim of the present study was to investigate the radiation modulating properties of inosine-5'-monophosphate (IMP). Mice injected introperitoneally (i.p.) with IMP 15 minutes after irradiation with a lethal irradiation dose of 7 Gy have better survival rates comparative to irradiated mice non treated with IMP. The dose reduction factor of the IMP is 1.22. Using a hematologdical test we demonstrated that administration of IMP alleviates the symptoms of radiation-induced leukopenia and thrombocytopenia. The DNA damage in bone marrow and thymus cells of irradiated mice was measured by flow cytofluorometry and micronucleus test (MN-test). The tests show that i.p. administration of IMP to irradiated animals leads to a significant reduction of the DNA damage level. In this paper we show that IMP substantially modulates the damaging effects of ionizing radiation protecting irradiated mice and it is a promising agent for a treatment of leukopenia.
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  • Long-term Sequential Changes of Radiation Proctitis and Angiopathy in Rats
    Hiroshi DOI, Norihiko KAMIKONYA, Yasuhiro TAKADA, Masayuki FUJIWARA, K ...
    2012 Volume 53 Issue 2 Pages 217-224
    Published: 2012
    Released on J-STAGE: April 17, 2012
    DOIhttps://doi.org/10.1269/jrr.11075
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    The purpose of the present study was to establish an experimental rat model for late radiation proctitis, and to examine the assessment strategy for late radiation proctitis. A total of 57 Wistar rats were used. Fourty-five of the rats were exposed to selective rectal irradiation with a single fraction of 25 Gy. These rats were sacrificed at the 4th, 12th, 24th, and 37th week following irradiation. The remaining 12 rats comprised the control group without irradiation. The rectal mucosa of each rat was evaluated macroscopically and pathologically. The number of vessels in the rectal mucosa was counted microscopically. In addition, the vascular stenosis was evaluated. In the results, the degree of clinical and macroscopic findings decreased following acute proctitis and developed later. In the pathological examination, mucosal changes and microangiopathy were followed up, as well. The absolute number of vessels in the rectum was the greatest at the 12th week following irradiation and was the lowest in the control group. The severity of the microangiopathy was also well evaluated. To conclude, we established an animal experimental model of late radiation proctitis, and also established an assessment strategy to evaluate objectively the severity of late radiation proctitis with focusing on microangiopathy using an animal experimental model. This model can be used as an animal experimental model of radiation-induced microangiopathy.
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  • Cell Killing and Radiosensitizing Effects of Atorvastatin in PC3 Prostate Cancer Cells
    Zhenhua HE, Lingegowda S. MANGALA, Corey A. THERIOT, Larry H. ROHDE, H ...
    2012 Volume 53 Issue 2 Pages 225-233
    Published: 2012
    Released on J-STAGE: April 17, 2012
    DOIhttps://doi.org/10.1269/jrr.11114
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    Recent studies have indicated that autophagy may be one of the important pathways induced by ionizing radiation. Atorvastatin (statin), an inhibitor of 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, may exhibit anticancer effects as an autophagy inducer. In our study, the cell killing and radiosensitizing effects of statin were analyzed in PC3 cell line. Activation of the autophagy pathway was analyzed using the GFP-LC3 assay and western blot to determine LC3-II expression. The radiosensitivity of PC3 cells was determined using the clonal survival assay, TUNEL assay, and the Annexin V apoptosis assay. The expression profiles of autophagy related genes were analyzed using a pathway specific real-time polymerase chain reaction (PCR) array. Autophagic response was induced in PC3 cells after exposure to statin and/or gamma rays. Inhibition of the autophagic process using small interfering RNAs (siRNA) targeting Atg7 and/or Atg12 significantly reduced radiosensitivity of PC3 cells. Statin also exhibited a significant apoptosis-inducing effect in PC3 cells, which can be partially suppressed by Atg7 siRNA. Cells treated with statin and gamma irradiation showed significantly reduced colony forming efficiency and increased number of Annexin V positive early apoptotic cells. Analysis of autophagy and its regulatory gene profile showed that the expressions of 22 genes out of 86 genes assessed were significantly altered in the cells exposed to combined treatment or statin alone. The data indicate that activation of the autophagy pathway may be responsible for apoptosis inducing effect of statin. Furthermore, combined treatment with radiation and autophagic inducer, such as statin, may be synergistic in inducing cell death of PC3 cells.
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  • NEIL1 mRNA Splicing Variants are Expressed in Normal Mouse Organs
    Ryohei YAMAMOTO, Mizuki YAMAMOTO, Hiroyuki KUSAKA, Hideaki MASATSUGU, ...
    2012 Volume 53 Issue 2 Pages 234-241
    Published: 2012
    Released on J-STAGE: April 17, 2012
    DOIhttps://doi.org/10.1269/jrr.11029
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    Oxidized pyrimidines are mainly repaired by base excision repair, which is initiated by damage-specific DNA glycosylases. NEIL1, the mammalian homolog of Escherichia coli endonuclease VIII and a major DNA glycosylase, initiates repair of oxidized pyrimidines. Here, we investigated the expression of two putative variant mouse NEIL1 (mNEIL1) mRNAs—variant 1 ("Neil1 protein" mRNA; BC043297 in the NCBI database) and variant 2 ("unnamed protein" mRNA; AK040802 in the NCBI database)—in normal mouse organs. Reverse transcription-PCR showed that both mRNAs were expressed in total RNA samples from 9 organs. Immunoblot analysis of a nuclear extract from normal mouse liver revealed three bands corresponding to full-length mNEIL1 protein and the two predicted variant proteins. However, neither variant protein, which included an N-terminal enzymatic activity domain deduced from the mRNA variants, were enzymatically active under multiple reaction conditions when expressed as his-tagged recombinant proteins. Nevertheless, recombinant variant 1 protein influenced mNEIL1 activity, while recombinant variant 2 protein had no influence. These results suggest that mNEIL1 mRNA variants are expressed in a variety of organs in normal mice and that variant 1 protein may regulate mNEIL1 activity.
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  • Low-dose Radiation Induces Drosophila Innate Immunity through Toll Pathway Activation
    Ki Moon SEONG, Cha Soon KIM, Byung-Sub LEE, Seon Young NAM, Kwang Hee ...
    2012 Volume 53 Issue 2 Pages 242-249
    Published: 2012
    Released on J-STAGE: April 17, 2012
    Advance online publication: February 25, 2012
    DOIhttps://doi.org/10.1269/jrr.11170
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    Numerous studies report that exposing certain organisms to low-dose radiation induces beneficial effects on lifespan, tumorigenesis, and immunity. By analyzing survival after bacterial infection and antimicrobial peptide gene expression in irradiated flies, we demonstrate that low-dose irradiation of Drosophila enhances innate immunity. Low-dose irradiation of flies significantly increased resistance against gram-positive and gram-negative bacterial infections, as well as expression of several antimicrobial peptide genes. Additionally, low-dose irradiation also resulted in a specific increase in expression of key proteins of the Toll signaling pathway and phosphorylated forms of p38 and JNK. These results indicate that innate immunity is activated after low-dose irradiation through Toll signaling pathway in Drosophila.
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  • Effects of Depletion of Dihydropyrimidine Dehydrogenase on Focus Formation and RPA Phosphorylation
    Masanori SOMEYA, Koh-ichi SAKATA, Yoshihisa MATSUMOTO, Hiroshi TAUCHI, ...
    2012 Volume 53 Issue 2 Pages 250-256
    Published: 2012
    Released on J-STAGE: April 17, 2012
    DOIhttps://doi.org/10.1269/jrr.11190
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    Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase (DPYD), partially inhibits homologous recombination (HR) repair and has a radiosensitizing effect as well as enhanced sensitivity to Camptothecin (CPT). DPYD is the target protein for radiosensitization by Gimeracil. We investigated the mechanisms of sensitization of radiation and CPT by DPYD inhibition using DLD-1 cells treated with siRNA for DPYD. We investigated the focus formation of various kinds of proteins involved in HR and examined the phosphorylation of RPA by irradiation using Western blot analysis. DPYD depletion by siRNA significantly restrained the formation of radiation-induced foci of Rad51 and RPA, whereas it increased the number of foci of NBS1. The numbers of colocalization of NBS1 and RPA foci in DPYD-depleted cells after radiation were significantly smaller than in the control cells. These results suggest that DPYD depletion is attributable to decreased single-stranded DNA generated by the Mre11/Rad50/NBS1 complex-dependent resection of DNA double-strand break ends. The phosphorylation of RPA by irradiation was partially suppressed in DPYD-depleted cells, suggesting that DPYD depletion may partially inhibit DNA repair with HR by suppressing phosphorylation of RPA. DPYD depletion showed a radiosensitizing effect as well as enhanced sensitivity to CPT. The radiosensitizing effect of DPYD depletion plus CPT was the additive effect of DPYD depletion and CPT. DPYD depletion did not have a cell-killing effect, suggesting that DPYD depletion may not be so toxic. Considering these results, the combination of CPT and drugs that inhibit DPYD may prove useful for radiotherapy as a method of radiosensitization.
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  • Radiosensitization by Inhibiting Complex I activity in Human Hepatoma HepG2 cells to X-ray Radiation
    Xin ZHANG, Xin ZHOU, Ruping CHEN, Hong ZHANG
    2012 Volume 53 Issue 2 Pages 257-263
    Published: 2012
    Released on J-STAGE: April 17, 2012
    DOIhttps://doi.org/10.1269/jrr.11124
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    The purpose of this study is to investigate the influence of mitochondrial respiratory chain complex I inhibition on the radiosensitivity of HepG2 cells. The complex I inhibitor rotenone was used to inhibit complex I activity on HepG2 cells before X-ray irradiation. The cytotoxicity of rotenone was analyzed by MTT assay at various doses. Rotenone induced dissipation of mitochondrial membrane potential and increase of intracellular ROS production were observed. Intracellular ATP production level was determined using luciferin-luciferase assay kit. We further analyzed cell survival and cell cycle distribution of a combined treatment which HepG2 cells underwent 0.5 μM rotenone pretreatment firstly and irradiated with different doses of X-ray radiation afterwards. Our results suggest rotenone pretreatment prior to X-ray irradiation could induce a sensitizing effect on HepG2 cells by enhancing X-ray radiation induced proliferation inhibition and cell apoptosis.
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Physics
  • Systematic Measurement of Lineal Energy Distributions for Proton, He and Si Ion Beams Over a Wide Energy Range Using a Wall-less Tissue Equivalent Proportional Counter
    Shuichi TSUDA, Tatsuhiko SATO, Fumiaki TAKAHASHI, Daiki SATOH, Shinich ...
    2012 Volume 53 Issue 2 Pages 264-271
    Published: 2012
    Released on J-STAGE: April 17, 2012
    DOIhttps://doi.org/10.1269/jrr.11135
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    The frequency distributions of the lineal energy, y, of 160 MeV proton, 150 MeV/u helium, and 490 MeV/u silicon ion beams were measured using a wall-less tissue equivalent proportional counter (TEPC) with a site size of 0.72 μm. The measured frequency distributions of y as well as the dose-mean values, y¯D, agree with the corresponding data calculated using the microdosimetric function of the particle and heavy ion transport code system PHITS. The values of y¯D increase in the range of LET below ~10 keV μm–1 because of discrete energy deposition by delta rays, while the relation is reversed above ~10 keV μm–1 as the amount of energy escaping via delta rays increases. These results indicate that care should be taken with the difference between y¯D and LET when estimating the ionization density that usually relates to relative biological effectiveness (RBE) of energetic heavy ions.
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  • A Treatment Planning Comparison of Passive-Scattering and Intensity-Modulated Proton Therapy for Typical Tumor Sites
    Yuki KASE, Haruo YAMASHITA, Hiroshi FUJI, Yuichi YAMAMOTO, Yuehu PU, C ...
    2012 Volume 53 Issue 2 Pages 272-280
    Published: 2012
    Released on J-STAGE: April 17, 2012
    Advance online publication: December 01, 2011
    DOIhttps://doi.org/10.1269/jrr.11136
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    Intensity-modulated proton therapy (IMPT) is expected to improve treatment results with fewer side effects than other proton therapies. The purpose of this study was to evaluate the tumor sites for which IMPT was effective under the same beam calculation conditions by planning IMPT for typical cases treated with passive scattering proton therapy (PSPT). We selected 16 cases of nasal cavity, lung, liver or prostate cancers as typical tumor sites receiving PSPT. The dose distributions and dose volume histograms optimized by the IMPT were compared with those optimized by the PSPT. We took particular note of the doses to the skin and organs at risk (OAR) when PSPT was replaced by IMPT. Furthermore, an improvement of the beam angles was also performed to obtain better dose distributions in the IMPT. The IMPT with the same beam angles resulted in near-maximum doses to the skin of average 78%, 64%, 84% and 99% of the PSPT doses for nasal cavity, lung, liver, and prostate cancers, respectively. However, it was difficult to improve the dose homogeneity of the target volume. The change of the IMPT beam angles could reduce the doses to OARs and skin in the case of the nasal cavity, while it had limited effect in the other cases. We concluded that IMPT was effective for reducing the doses to some OARs when treating nasal cavity, lung, liver and prostate cancers. The selection of beam angles was important in the IMPT optimization, especially for nasal cavity cancers.
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Oncology
  • The Effects of Two HDR Brachytherapy Schedules in Locally Advanced Cervical Cancer Treated with Concurrent Chemoradiation: A Study from Chiang Mai, Thailand
    Ekkasit THARAVICHITKUL, Pitchayaponne KLUNKIN, Vicharn LORVIDHAYA, Vim ...
    2012 Volume 53 Issue 2 Pages 281-287
    Published: 2012
    Released on J-STAGE: April 17, 2012
    DOIhttps://doi.org/10.1269/jrr.11038
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    Efficacy of different schedules of HDR brachytherapy in concurrent chemoradiotherapy was evaluated. The study compared the effectiveness of the two HDR brachytherapy schedules which have the same Biological Effective Dose (BED) in locally advanced cervical carcinoma that was treated with concurrent chemoradiotherapy. Included in the study were 377 randomly selected patients with advanced carcinoma of the cervix uteri who were treated during the period 2004–2006. Patients were divided into Group I: 7.2 Gy × 3 fractions and Group II: 6 Gy × 4 fractions. With a median follow-up time of 35 months, local control, disease-free survival and overall survival rates were 80.8%, 63.4%, 98.8% in group I and 86.7%, 63.8%, 97.3% in group II, respectively. There was no statistical significance in terms of local control, disease-free survival, overall survival and complication rates between the two treatment schedules which could be observed. Seven patients in group I developed acute grade 2–4 GI toxicities and two patients in group II. In GU toxicities, there were three patients in group I and three patients in group II who developed grade 2–4 toxicities. In late toxicity, no patient developed grade 3–4 GU toxicities in group I while two patients developed grade 3–4 GU toxicities in group II. In GI toxicities, there were five and six patients in group I and group II, respectively, who developed grade 3–4 severity. Both HDR schedules seem to be safe and effective for the treatment of locally advanced cervical cancer.
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  • Hemithoracic Intensity-modulated Radiotherapy Using Helical Tomotherapy for Patients after Extrapleural Pneumonectomy for Malignant Pleural Mesothelioma
    Takeshi EBARA, Hidemasa KAWAMURA, Takuya KAMINUMA, Masahiko OKAMOTO, D ...
    2012 Volume 53 Issue 2 Pages 288-294
    Published: 2012
    Released on J-STAGE: April 17, 2012
    Advance online publication: February 25, 2012
    DOIhttps://doi.org/10.1269/jrr.11130
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    Postoperative hemithoracic irradiation is regarded as an important part of the curative treatment for resectable malignant pleural mesothelioma (MPM). Because the clinical target volume in postoperative MPM is irregular and surrounded by dose-limiting critical structures, intensity-modulated radiation therapy (IMRT) is thought to be suitable. However, postoperative hemithoracic IMRT remains experimental due to a high incidence of fatal pneumonitis. Therefore, a Phase I dose escalation study for hemithoracic IMRT using helical tomotherapy was planned, and the results of the first three patients are herein reported because this technique may provide benefits to such patients. For 3 patients with postoperative MPM, who were treated by extrapleural pneumonectomy (EPP), a radiation dose of 45.0 Gy in 25 fractions was given to cover 95% of the PTV. The lung V5s of the three patients were 14.3%, 10.0%, and 31.3%, respectively. The V5s of the present plans was smaller than that of the recent IMRT planning studies. The lung V20s of these patients were 2.4%, 2.2%, and 4.3%, respectively. Their MLDs were 4.3 Gy, 3.4 Gy, and 5.8 Gy, respectively. The follow-up periods of the patients were 26, 14 and 9 months from initiation of IMRT, respectively. All patients were alive, although local and contralateral recurrences had developed in 1 patient. Only 1 patient had Grade 2 acute esophagitis and nausea. There was no treatment-related pneumonitis. Hemithoracic IMRT using helical tomotherapy may play a crucial role in adjuvant treatment for MPM after EPP.
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  • Daily CT Measurement of Needle Applicator Displacement during Multifractionated High-dose-rate Interstitial Brachytherapy for Postoperative Recurrent Uterine Cancer
    Ken YOSHIDA, Mari UEDA, Tadashi TAKENAKA, Hideya YAMAZAKI, Tadayuki KO ...
    2012 Volume 53 Issue 2 Pages 295-300
    Published: 2012
    Released on J-STAGE: April 17, 2012
    Advance online publication: January 13, 2012
    DOIhttps://doi.org/10.1269/jrr.11165
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    We investigated daily needle applicator displacement during multifractionated high-dose-rate interstitial brachytherapy (HDR-ISBT) for postoperative recurrent uterine cancer. Eight patients with postoperative recurrent uterine cancer received HDR-ISBT with or without external beam radiotherapy using our unique ambulatory technique. To analyze displacement, we obtained daily computed tomography (CT) images for 122 flexible needle applicators at 21, 45, 69, and 93 hours after implantation. Displacement was defined as the length between the center of gravity of titanium markers and the needle applicator tips along the daily CT axis. For cases in which displacement was not corrected, we also calculated the dose that covered 90% of the clinical target volume (D90(CTV)) using a dose–volume histogram (DVH). Median caudal needle applicator displacement at 21, 45, 69, and 93 hours was 3, 2, 4, and 5 mm, respectively. More than 15 mm displacement was observed for 2% (2 of 122) and 17% (10 of 60) of needle applicators at 21 and 93 hours, respectively. Cases in which dwell positions were not changed to correct the treatment plan, 2 of 8 patients showed more than 10% reduction in D90(CTV) values compared with the initial treatment plan. Correction of dwell positions of the treatment source improves treatment DVH for multifractionated HDR-ISBT.
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  • Analysis of Post-exposure Density Growth in Radiochromic Film with Respect to the Radiation Dose
    Katsumi SHIMA, Kunihiko TATEOKA, Yuichi SAITOH, Junji SUZUKI, Yuji YAE ...
    2012 Volume 53 Issue 2 Pages 301-305
    Published: 2012
    Released on J-STAGE: April 17, 2012
    Advance online publication: January 14, 2012
    DOIhttps://doi.org/10.1269/jrr.11091
    JOURNAL FREE ACCESS
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    The post-exposure density growth (PEDG) is one of the characteristics of radiochromic film (RCF). In film dosimetry using RCF and a flatbed scanner, pixel values read out from the RCF are converted to dose (hereafter, film dose) by using a calibration curve. The aim of this study is to analyze the relationship between the pixel value read out from the RCF and the PEDG, and that between the film dose converted from the RCF and the PEDG. The film (GAFCHROMIC EBT) was irradiated with 10-MV X-rays in an ascending 11-dose-step arrangement. The pixel values of the irradiated EBT film were measured at arbitrary hours using an Epson flatbed scanner. In this study, the reference time was 24 h after irradiation, and all dose conversions from the pixel values read out from the EBT film were made using a calibration curve for 24 h after irradiation. For delivered doses of 33 and 348 cGy, the measured pixel values at 0.1 and 16 h after irradiation represented ranges of –9.6% to –0.7% and –3.9% to –0.3%, respectively, of the reference value. The relative changes between the pixel values read out from the EBT film at each elapsed time and that at the reference time decreased with increasing delivered dose. However, the difference range for all the film doses had a width of approximately –10% of the reference value at elapsed times from 0.1 to 16 h, and it showed no dependence on the delivered dose.
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  • Solitary Pulmonary Nodules Differentiated by Dynamic F-18 FDG PET in a Region with High Prevalence of Granulomatous Disease
    Yu-Erh HUANG, Hung-I LU, Feng-Yuan LIU, Yu-Jie HUANG, Meng-Chih LIN, C ...
    2012 Volume 53 Issue 2 Pages 306-312
    Published: 2012
    Released on J-STAGE: April 17, 2012
    Advance online publication: February 25, 2012
    DOIhttps://doi.org/10.1269/jrr.11089
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    This study determined whether dynamic F-18 FDG PET imaging could differentiate benign from malignant solitary pulmonary nodules (SPNs). Histopathologically confirmed SPNs (10–35 mm), 24 malignant and 10 benign, from 34 patients were studied through both dynamic and static F-18 FDG PET imaging of all patients. Volumes of interest (VOIs) were placed over the pulmonary nodules using a 50% maximum pixel value threshold. The arterial input function was estimated from a left ventricle-defined VOI. Based on Patlak analysis, we calculated the net FDG phosphorylation rate (Ki) and glucose metabolic rate (MRGlu) of each nodule. The slope values of the time-activity curves (TACs) of the nodules were also determined. Based on the static PET images, maximum and mean standardized uptake values (SUVmax and SUVmean, respectively) were calculated. Benign and malignant SPNs had significantly different values for SUVmax, SUVmean, Ki, MRGlu, and TAC slope, with area under the receiver operating characteristic curves distinguishing benign from malignant nodules. McNemar's test of marginal homogeneity found all the predictors helpful to detect malignant nodules (all, p > 0.05), and combining Ki and MRGlu, which were generated by dynamic study, yielded a higher specificity of 90%, and a sensitivity of 79%. Among the 10 benign nodules, static SUV imaging correctly classified seven, while dynamic F-18 PET imaging correctly classified nine. Dynamic F-18 FDG PET imaging is valuable in differentiating benign from malignant SPNs, particularly for granulomatous disease.
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  • Preliminary Results of MRI-guided Brachytherapy in Cervical Carcinoma: The Chiangmai University Experience
    Ekkasit THARAVICHITKUL, Chate SIVASOMBOON, Somsak WANWILAIRAT, Vicharn ...
    2012 Volume 53 Issue 2 Pages 313-318
    Published: 2012
    Released on J-STAGE: April 17, 2012
    Advance online publication: January 21, 2012
    DOIhttps://doi.org/10.1269/jrr.11107
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    This study was performed to evaluate the feasibility of magnetic resonance imaging (MRI) in the treatment planning of image-guided brachytherapy for cervical carcinoma. Seventeen consecutive patients with locally advanced cervical cancer were enrolled in the study. Fifteen patients could be evaluated. When comparing the tumor at diagnosis (GTV-Dx) and the tumor at the first brachytherapy (GTV-BT), 11 of 15 patients showed a tumor regression of more than 80% while only four patients had less than 80% tumor regression. The mean D90 of HR-CTV and the calculated D2cc of the bladder, rectum, and sigmoid were 99.2 ± 11 Gy, 87.7 ± 5.7 Gy, 68.4 ± 5.4 Gy and 70.3 ± 6.8 Gy, respectively. No grade 3–4 acute toxicity was observed. The MRI can be a valuable tool for evaluating tumor response after external beam radiotherapy (EBRT) and is very helpful for prognosis prediction by residual GTV evaluation. Furthermore, MRI-guided brachytherapy allowed us to optimize the dose for both the target volumes and the OARs.
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  • Postoperative Radiotherapy for Incompletely Resected Non-small Cell Lung Cancer: Clinical Outcomes and Prognostic Value of the Histological Subtype
    Takayuki OHGURI, Katsuya YAHARA, Seung Dae MOON, Shinsaku YAMAGUCHI, H ...
    2012 Volume 53 Issue 2 Pages 319-325
    Published: 2012
    Released on J-STAGE: April 17, 2012
    Advance online publication: February 13, 2012
    DOIhttps://doi.org/10.1269/jrr.11082
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    The purpose of this study was to evaluate the efficacy and toxicity of the postoperative radiotherapy in patients with incompletely resected NSCLC, and to investigate whether the histological subtype is a prognostic factor. Forty-one incompletely resected NSCLC patients who underwent postoperative radiotherapy were retrospectively analyzed. The microscopic residual tumor (R1 group) was recognized in 23 patients, and the macroscopic residual tumor (R2 group) in 18. The postoperative pathological stages were I (n = 3), II (n = 8), IIIA (n = 17), and IIIB (n = 13). The histology included squamous cell carcinoma (n = 23), adenocarcinoma (n = 14) or other types (n = 4). The first site of disease progression was distant metastases alone for 3 (13%) of 23 with squamous cell carcinoma, and for 9 (64%) of 14 with adenocarcinoma (p < 0.01). The 5-year overall, local control, disease-free, and distant metastasis-free survival rates were 56%, 63%, 37% and 49%. Univariate analyses showed that squamous cell carcinoma histology, N0-1 stage and the R1 group were significant predictors for better disease-free and distant metastasis-free survival. Multivariate showed that squamous cell carcinoma and N0-1 stage were significant predictors for better distant metastasis-free survival. Toxicity was generally mild; Grade 3 toxicities occurred in 3 patients (neutropenia, radiation pneumonia and esophageal stenosis), and no acute and late toxicities of Grade 4 to 5 were observed. In conclusion, postoperative radiotherapy for incompletely resected NSCLC could achieve a relatively high local control rate without severe toxicity. However, different treatment strategies for non-squamous cell carcinoma should be considered, because of the higher risk for the distant metastases.
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  • Changes of Tumor Size and Tumor Contrast Enhancement during Radiotherapy for Non-small-cell Lung Cancer May Be Suggestive of Treatment Response
    Hiroshi OKADA, Shigeto HONTSU, Sachiko MIURA, Isao ASAKAWA, Tetsuro TA ...
    2012 Volume 53 Issue 2 Pages 326-332
    Published: 2012
    Released on J-STAGE: April 17, 2012
    Advance online publication: February 13, 2012
    DOIhttps://doi.org/10.1269/jrr.11176
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    We evaluated sequential dynamic contrast-enhanced CT (DCE-CT) scans to assess the possibility of early prediction of treatment responses by quantifying the tumor size reduction and the change in tumor enhancement during and after a course of radiotherapy (RT). Thirty-nine patients with non-small-cell lung cancer were treated with RT for initial treatment. DCE-CT scan was performed within one week before the beginning of treatment, after 17 or 18 fractions (34 or 36 Gy), and 1 week and 1 month after the end of RT. The correlation between the relative decrease in tumor diameter and that in the attenuation value was evaluated. Nineteen patients were evaluated in this study. The median tumor size was 39.5 mm at the start of treatment, 30.8 mm at 34–36 Gy, and 16.1 mm 1 month after the end of RT. The relative decrease in tumor diameter at 34–36 Gy well correlated with that 1 month after treatment (r = 0.85, r: Pearson's correlation coefficient, p < 0.001). Relative change in the attenuation value at the rim of the tumor at 34–36 Gy did not significantly correlate with the change in tumor diameter 1 month after the completion of RT, but in the center of the tumor, the change of the attenuation value in the delayed phase correlated with the change in tumor diameter. The decrease of tumor diameter during RT may be predictive of treatment response. The relative change of tumor enhancement in the center of the tumor in the delayed phase correlated with tumor shrinkage 1 month after the completion of RT.
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  • Usefulness of 4D-CT for Radiation Treatment Planning of Gastric MZBCL/MALT
    Munetaka MATOBA, Kiyotaka OOTA, Ichiro TOYODA, Masataka KITADATE, Naot ...
    2012 Volume 53 Issue 2 Pages 333-337
    Published: 2012
    Released on J-STAGE: April 17, 2012
    Advance online publication: March 15, 2012
    DOIhttps://doi.org/10.1269/jrr.11127
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    It is well known that significant variations in stomach size, shape, and respiratory motion lead to uncertainties in target localization during treatment for gastric lymphoma. In this study, the usefulness of 4D-CT for radiation planning of gastric MZBCL/MALT was evaluated. Treatment planning using 4DCT (plan A) and conventional planning with a uniform margin (plan B) were compared using dose volume histograms (DVH) of the planning target volume (PTV) and the organ at risk, as well as the dose coverage of the clinical target volume (CTV) assessed by weekly online cone beam CT (CBCT) during the treatment course. In addition, regarding the image quality of CBCT , the interobserver agreement for the delineated volume of the CTV on CBCT was analyzed. The mean PTV of plan A was significantly smaller than that of plan B (p = 0.008). The mean doses to the liver and heart in plan A were significantly lower than those in plan B (p = 0.02 and 0.03, respectively). The reductions of V20 of each kidney in plan A compared with those in plan B were 4.8 ± 2.4% in the right kidney and 16.3 ± 10.4% in the left. There was no significant difference in the dose coverage of the CTV between the plans during the treatment course. The interobserver agreement for the volume of the CTV was moderate correlation. Treatment planning using 4DCT for gastric MZBCL/MALT was useful for effective and safe irradiation with minimizing exposure of the organ at risk.
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  • FDG-PET/CT-based Gross Tumor Volume Contouring for Radiation Therapy Planning: An Experimental Phantom Study
    Ryo TOYA, Ryuji MURAKAMI, Kuniyuki TASHIRO, Morikatsu YOSHIDA, Fumi SA ...
    2012 Volume 53 Issue 2 Pages 338-341
    Published: 2012
    Released on J-STAGE: April 17, 2012
    Advance online publication: March 04, 2012
    DOIhttps://doi.org/10.1269/jrr.10183
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    As there is continuing controversy over the role of F-18-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT-fused imaging in radiation therapy (RT) planning, we performed a phantom study to assess the feasibility of FDG-PET/CT-based gross tumor volume (GTV) contouring. The phantom set, consisting of an elliptical bowl and 6 spheres measuring from 10–37 mm in diameter, were filled with FDG to obtain 3 source-to-background ratios (SBRs) of 4, 8, and 16. The ratio to maximum intensity at 5% intervals was applied as the threshold for contouring. The ratio between contoured- and actual volumes (volume ratio) was calculated, and the threshold ratio was selected to provide a volume ratio close to 100%. To consider the clinical application, we applied the threshold value (maximum intensity × threshold ratio) for the largest 37-mm sphere to the 6 spheres. The threshold ratio and the volume ratio in 6 spheres with 3 SBRs were compared using the Friedman test. Threshold ratios ranged from 25–80%; they were higher for smaller spheres (p = 0.003) and lower SBRs (p < 0.001). The volume ratios with the threshold value for the largest 37-mm sphere were lower in smaller spheres (p = 0.010). These results suggest that smaller lesions and higher background activities require a higher threshold ratio and smaller lesions a lower threshold value. FDG-PET/CT-fused imaging should not be used as a single modality but rather to obtain supplemental information in RT planning. The contoured GTV should be adjusted based on clinical data including conventional images.
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