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en: The value of diagnostic imaging in neoadjuvant chemoradiation therapy for non-small cell lung cancer

ja: 非小細胞肺癌に対する術前導入化学放射線療法における画像診断の有用性

en: Japanese Journal of Clinical Radiology

ja: (月刊)臨床放射線


en: Evaluation of the In vivo Radiosensitizing Activity of EtanidazoleUsing Tumor-bearing Chick Embryo

en: Chick embryos have been used as alternative experimental animals in various research fields, including virology, immunology, toxicology, oncology, and embryology. Until now, there have been no in vivo models using chick embryo to evaluate radiosensitizing activity. Here, the in vivo radiosensitizing activity of etanidazole, a well-known hypoxic cell radiosensitizer, was evaluated using tumor-bearing chick embryo. On the basis of tumor growth, drug administration and X-ray irradiation were performed on day 15 chick embryo, with the endpoint being day 18 chick embryo. In day 15 chick embryo, an X-ray irradiation dose of equal or less than 10 Gy did not cause significant tumor growth suppression. Intravenous administration of equal or less than 1.0 mg of etanidazole did not cause tumor growth suppression. Neither doses of equal or less than 8 Gy of irradiation nor 1.0 mg of etanidazole caused fatality of the chick embryo. On the basis of these results, we evaluated the radiosensitizing effect of a combination treatment with 8 Gy of irradiation and 1.0 mg of etanidazole. As noted above, 1.0 mg of etanidazole alone and 8 Gy of irradiation alone did not show tumor growth suppression. In contrast, a combination treatment with 8 Gy of irradiation and 1.0 mg of etanidazole showed 35% of significant tumor growth suppression. Thus, we succeeded in evaluating the in vivo radiosensitizing activity of etanidazole using tumor-bearing chick embryo. These results suggest that the use of tumor-bearing chick embryo may be part of a promising system for evaluating radiosensitizing activity.

en: Journal of Radiation Research

ja: Journal of Radiation Research


en: A newly designed cell-permeable SNARF derivative as an effective intracellular pH indicator.

en: We have successfully developed a new cell-permeable SNARF derivative that is activated inside the cell by ester hydrolysis and is notable for having reduced background fluorescence.

en: Chemical Communications

ja: Chemical Communications


en: Selection of endogenous 13C substrates for observation of intracellilar metabolism using the dynamic nuclear polarization technique

en: The aim of this study was to select a suitable substrate candidate for dynamic nuclear polarization (DNP) studies and demonstrate its utility for evaluating intracellular metabolism. Hyperpolarized substances included 1-(13)C-pyruvate (Pyr), 1-(13)C-glucose (Glc), and 1-(13)C-acetate. A DNP polarizer and a 600-MHz vertical small-bore scanner were used for (13)C-MR spectroscopic measurements. After polarization for 1 h, the dissolved solution was injected via a capillary line into the nuclear magnetic resonance tube in the scanner. The sequential spectra of the hyperpolarized (13)C-labeled substrates were acquired in durations of more than 120 s, and a thermal spectrum was obtained more than 1 h thereafter. FM3A cancer cells of mammary tumors were cultured for intracellular detection of the hyperpolarized (13)C-substances. The greatest sensitivity was found using Pyr with the longest T1 decay (51.5 s); and remarkably, the least sensitivity was observed using Glc with a signal decay of less than 2 s. An effective increase in sensitivity was shown using the other substances. The hyperpolarized intracellular study using (13)C-Pyr showed distinct elevation of lactate levels. The DNP technique is useful for evaluating intracellular metabolism. However, Glc is not suitable for use with the DNP technique.

en: Japanese Journal of Radiology

ja: Japanese Journal of Radiology


en: Bystander Cell Killing in Normal Human Fibroblasts is Induced by Synchrotron X-ray Microbeams

en: Abstract The radiation-induced bystander response is defined as a response in cells that have not been directly targeted by radiation but that are in the neighborhood of cells that have been directly exposed. In the work described here, it is shown that bystander cell killing of normal human fibroblast WI-38 cells was induced by synchrotron microbeam X radiation. Cell nuclei in confluent WI-38 cells were irradiated with the microbeam. All of the cells on the dish were harvested and plated 24 h after irradiation. It was found that the bystander cell killing effect showed a parabolic relationship to the radiation dose when five cells were irradiated. At doses above 1.9 Gy, the surviving fraction increased to approximately 1.0. This suggests that induction of bystander cell killing may require some type of activity in the targeted cells, because the dose resulting in 37% cell survival was about 2.0 Gy. Bystander cell killing was suppressed by a pretreatment with aminoguanidine [an inhibitor of inducible nitric oxide (NO) synthase] or carboxy-PTIO (a scavenger of NO). These results suggest that NO is the chief initiator/mediator of bystander cell killing induced by X-ray microbeams.

en: Radiation Research

ja: Radiation Research


en: Design of a bioreductively-activated fluorescent pH probe for tumor hypoxia imaging

en: We have designed and evaluated UTX-12 as a novel fluorescent pH probe for tumor hypoxia imaging. UTX-12 consists of a p-nitro benzyl moiety, which is a latent hypoxia-selective leaving group activated by nitro reduction, directly linked to SNARF. Although UTX-12 itself is colorless and non-fluorescent in aqueous solution, nitro reduction triggers the release of SNARF which has well-characterized long wavelength absorption and fluorescence that is sensitive to pH. The resultant SNARF, released intracellularly by enzymatic reduction of UTX-12, allows measurement of pH by pH-dependent dual emission shifts. UTX-12 showed clear differences in fluorescence behavior between hypoxic and aerobic conditions in liver microsomes and inside V79 cells. These data are confirmation that UTX-12 is biologically reduced inside tumor cells and the released SNARF should monitor intracellular pH of tumor cells selectively with reduced background signal.

en: Bioorganic & Medicinal Chemistry

ja: Bioorganic & Medicinal Chemistry


en: 医療用自己遮蔽型PETサイクロトロン及び電子リニアックにおける中性子束の箔放射化法による測定

en: Japanese Journal of Radiation Safety Management

ja: 日本放射線安全管理学会誌


en: Design, synthesis, and radiosensitizing activities of sugar-hybrid hypoxic cell radiosensitizers

en: We have designed sugar-hybrid TX-1877 derivatives conjugated with sugar moieties including β-glucose (β-Glc), β-galactose (β-Gal), α-mannose (α-Man) and N-acetyl-β-galactosamine (β-GalNAc). Compound 1 (TX-1877) was glycosylated with appropriate peracetylated sugars using BF3-OEt2 to give acetylated sugar-hybrids, 5 (TX-2244), 6 (TX-2245), 7 (TX-2246), and 10 (TX-2243). Removal of the acetyl groups afforded the sugar-hybrids having free hydroxyl groups, 11 (TX-2141), 12 (TX-2218), 13 (TX-2217) and 14 (TX-2068). We evaluated their radiosensitizing activities by an in vitro radiosensitization assay. All free hydroxyl hybrids have lower enhancement ratio (ER) values (ER 1.43) and lower n-octanol/water partition coefficient (Poct) values (Poct < 1.00 × 10-2) than does 1 (TX-1877, ER = 1.75, Poct: 5.60 × 10-2). All acetylated hybrids have similar Poct values (3.55 × 10-2 1.05 × 10-1) to 1 (TX-1877) and have improved ER values (ER 1.47) compared to the hybrids having free hydroxyl groups. Among these, 5 (TX-2244) is the most active radiosensitizer (ER = 2.30). We found a good correlation (r = 0.866) between the magnitude of Poct (logPoct) and the ER value of 5 (TX-2244), 6 (TX-2245), 7 (TX-2246), 10 (TX-2243) and 1 (TX-1877), suggesting that increasing the hydrophobicity is reflected in increased in vitro radiosensitizing activity. In the present study, we have succeeded in producing sugar-hybrid hypoxic cell radiosensitizers that have an increased radiosensitizing activity that does not depend on increased hydrophobicity.


en: Human airway trypsin-like protease stimulates human bronchial fibroblast proliferation in a protease-activated receptor-2-dependent pathway.

en: Human airway trypsin-like protease (HAT) was isolated from airway secretions and localized to bronchial epithelial cells by immunohistochemistry. In the present study, we examined whether HAT could stimulate DNA synthesis and proliferation of primary human bronchial fibroblasts (HBF). HAT significantly stimulated the proliferation of HBF by 20-55%, a level similar to that of the mitogenic activity of lung mast cell tryptase (MCT). HAT also stimulated the incorporation of [3H]thymidine in HBF, and this HAT-induced DNA synthesis was abolished by leupeptin. Protease-activated receptor-2 (PAR-2) mRNA was expressed and localized to the cell surface in HBF. PAR-2 activating peptide (AP) also enhanced DNA synthesis, and both HAT and PAR-2 AP induced receptor internalization, similar to the response to trypsin. Pretreatment of HBF with anti-PAR-2 antibody significantly suppressed both HAT and PAR-2 AP-induced DNA synthesis. In addition, HAT and PAR-2 AP induced intracellular Ca2+ mobilization in HBF. The HAT-induced increase in Ca2+ was desensitized by pretreatment with trypsin or PAR-2 AP. U0126, a specific MAPK inhibitor, completely inhibited HAT-induced DNA synthesis as well as HAT-induced phosphorylation of MAPK. The effect of HAT and MCT together was additive, whereas the effect of HAT and insulin together on HBF DNA synthesis was synergistic. These results indicate that HAT stimulates fibroblast proliferation in bronchial airways through a PAR-2-dependent MEK-MAPK mediated pathway and that HAT is linked to airway processes involving fibroblasts.

en: American Journal of Physiology. Lung Cellular and Molecular Physiology


en: Development of microbeam irradiation system for radiobiology

en: Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment


en: Radiolytic products of bromodeoxyuridine in solids by Co-60 gamma-rays and monoenergetic soft x-rays at the k-absorption edge of bromine.

en: In order to investigate DNA damage due to Auger cascades in bromodeoxyuridine (BrdU), BrdU mixed with other nucleosides, as a model of DNA, was irradiated in solids by gamma-rays and monoenergetic x-rays at around the K-absorption edge of bromine (13.47 keV). The main products of BrdU were deoxyuridine produced through debromination, and bromouracil produced through the decomposition of a sugar group. The rates of the debromination and the nucleobases release of additives were markedly increased in the mixed sample. This observation indicated that the additives surrounding BrdU efficiently supplied protons and then decomposed. The major products by x-rays were the same as those by gamma-rays, indicating that Auger cascades in bromine atoms did not produce specific products. The production rates for all products from the mixed sample were about 2.5 times higher at 13.51 (above the K-absorption edge) keV than at 13.43-keV x-rays.

en: Acta Oncologica

ja: Acta Oncologica


en: Lethal effect of k-shell absorption of intracellular phosphorus on wild-type and radiation sensitive mutants of Escherichia coli.

en: The present study was conducted to clarify the lethality of Auger cascades induced by the K-shell photoabsorption of phosphorus in Escherichia coli. Killing of wild-type and radiation-sensitive mutants of E. coli was examined. Three x-ray energies were chosen for irradiation; at 2.153 keV: the resonance peak of K-shell photoabsorption of phosphorus; at 2.146 and 2.160 keV: off-peak. Enhancement ratio, which was defined as the ratio of the killing sensitivity of 2.153 keV to that at 2.146 keV, were 1.32 to 1.54 for examined strains. Increment of absorbed energy calculated in entire cells for 2.153 keV radiation could not explain the degree of observed enhancement of killing. Lethality of Auger cascades depended on the killing sensitivity with x-rays which did not induce Auger cascades. The lethality for wild-type was lower than that for recombination repair-deficient mutants. It was concluded that one part of damages produced by Auger cascades was repaired in wild-type strains.


en: Single- and double-strand breaks in pBR322 plasmid DNA by monochromatic X-rays on and off thr K-absorption peak of phosphorus.

en: Using a synchrotron irradiation system pBR322 plasmid DNA was irradiated under vacuum by monochromatic X-rays having five specific photon energies (2.147, 2.153, 2.159, 2.168 and 2.199 keV) both on and off the K-absorption peak (2.153 keV) of phosphorus. The single- and double-strand breaks (ssb and dsb) were measured as conversions of the closed circular form of DNA (form I) to open circular (form II) and linear (form III) forms respectively. Exposures to induce one strand break per molecule were lowest at the peak (2.153 keV), and highest at 2.147 keV; the ratios were 2.7 for ssb and 3.0 for dsb. The exposures for dsb were 21-26 times higher than those for ssb. When the exposures were converted to absorbed doses in grays the absorbed doses per ssb were almost independent of photon energy. This result indicates that a certain absorbed dose was necessary to induce a ssb, regardless of whether photons were absorbed by the K-shell of phosphorus or by other shells, or by other atoms. However, the absorbed dose per dsb at 2.147 keV was 1.17 times higher than that averaged over four X-ray energies above 2-153 keV, indicating that the K-shell absorption, and the subsequent Auger event, efficiently induce dsb. The results are also discussed concerning the number of photo-absorptions of the constituent atoms per DNA strand break.

en: International Journal of Radiation Biology


en: Californium-252 survival curve for model solid FSa-II tumor in vivo: dose per session and therapeutic efficacy.

en: Endocurietherapy/Hyperthermia Oncology

ja: Endocurietherapy/Hyperthermia Oncology


en: Synergistic effects of hyperthermia and intratumorous injection on anti-cancer drugs.

en: The Tokai Journal of Experimental and Clinical Medicine


en: Uracil-DNA glycosylase produces excess lethal damage induced by an Auger cascade in BrdU-labelled bacteriphage T1.

ja: International Journal of Radiation Biology


en: Radiosensitivity of mouse skin epithelial cell line established in serum-free culture: An alternative to animal use.

en: International Journal of Radiation Oncology*Biology*Physics


en: Comparative Study of Thermoradiosensitization by misonidazole and metronidazole in vivo: anti tumour effect and pharmacokinetics.

en: International Journal of Hyperthermia.

ja: International Journal of Hyperthermia.


en: Inactivation of bacteriophage T1 by the Auger wffect following phosphorus resonance absorption of monoenergetic synchrotron radiation.

en: Biophysical Aspects of Auger Processes. AAPM Symposium Series.


en: Iron(II) sulphate (Fricke solution) oxidation yields for 8.9 and 13.6 keV X-rays from synchrotron radiation.


en: Tripsin-like activities and human airway trypsin-like protease (HAT) levels in airway secretions from healthy subjects and patients with chronic airway diseases.

en: Proceeding of Airway Secretion Research

ja: Proceeding of Airway Secretion Research


en: Development of photon microbeam irradiation system for radiobiology

en: International Congress Series

ja: International Congress Series


en: Effect of human airway trypsin-like protease (HAT) on proliferation of normal bronchial epithelial cells and normal lung fibroblasts.

en: Proceeding of Airway Secretion research

ja: Proceeding of Airway Secretion research


en: Mutation induction, cell killing and in vivo skin reaction after fractionated irradiation with carbon ions.

en: Radiation Research


en: Synthesis and photophysical properties of new SNARF derivatives as dual emission pH sensors

en: We report the synthesis and properties of two new seminaphthorhodafluor (SNARF) derivatives, SNARF-F and SNARF-Cl. Both these derivatives exhibit typical red shifts of absorption and fluorescence, and higher cell permeability as compared to traditional SNARF, while the pH-dependent dual-emission characteristics are well retained. In particular, the lower pK(a) (7.38) of SNARF-F makes it more suitable than traditional SNARF derivatives for intracellular applications.

en: Bioorganic & Medicinal Chemistry Letters