Biomedical subjects

Minoru Suzuki

Publications and source records attributed to Minoru Suzuki.

At least 37 records · Page 2Linked to original sources

PubMed2005

Capillary affinity electrophoresis using lectins for the analysis of milk oligosaccharide structure and its application to bovine colostrum oligosaccharides.

Animal colostrum and milk contain complex mixtures of oligosaccharides, which have species-specific profiles. Milk oligosaccharides have various types of structure related to the core structures of glycolipids and N- and O-glycans of glycoproteins and provide a good library to examine the binding of oligosaccharides to various lectins. Recently, we reported a capillary affinity electrophoresis (CAE) method for analyzing the interactions between lectins and complex mixtures of N-linked oligosaccharides prepared from serum glycoproteins. The present paper reports the interactions between 24 milk oligosaccharides and six lectins (PA-I, RCA(120), SBA, WGA, UEA-I, and AAL) analyzed using CAE. Based on the resulting data, we constructed a library that enables us to determine nonreducing terminal monosaccharides, such as Gal, GalNAc, GlcNAc, and Fuc, and to differentiate Gal- or Fuc-linked isomers, such as lacto-N-tetraose, lacto-N-neotetraose, and lacto-N-fucopentaose II and III. In addition, using the library, we show that a combination of the lectins can characterize the neutral oligosaccharides derived from bovine colostrum.

Animals↗

PubMed2005

Chemical synthesis of 23 kDa glycoprotein by repetitive segment condensation: a synthesis of MUC2 basal motif carrying multiple O-GalNAc moieties.

Peptide thioester corresponding to a MUC2 tandem repeat unit, which retains seven GalNAc moieties, was prepared by the Fmoc method followed by the low TfOH treatment to remove benzyl groups at the carbohydrate portions. The glycosylated peptide thioester was then consecutively joined by the activation of a thioester group by silver ions to obtain a MUC2 tandem repeat model composed of 141 amino acids with 42 GalNAc moieties.

Acetylgalactosamine↗

PubMed2005

Halogenated metabolites from Japanese Laurencia spp.

Further investigation of Laurencia species from Japanese waters, which were collected at three locations, yielded brominated metabolites, a labdane- type diterpene and a C15 acetogenin possessing a terminal bromoallene group. Their structures were deduced from analysis of spectroscopic data.

Acetogenins↗

PubMed2005

Evidence for universal signatures of Zeeman-splitting-limited pseudogaps in superconducting electron- and hole-doped cuprates.

We probe the "normal" state in electron-doped (n-type) Sm2-xCexCuO4-delta through interlayer tunneling transport in magnetic fields up to 45 T. The behavior of intrinsic high-field c-axis negative magnetoresistance (MR), which is accessed in small 30 nm-high mesa structures, is characteristic of the pseudogap state. It follows a universal correlation between the excess low-energy dissipation due to the pseudogap and its closing field Hpg and is in close correspondence with the hole-doped (p-type) Bi2Sr2CaCu2O8+y. The MR in the mesas and in the bulk crystals consistently gives a Zeeman relation between the pseudogap temperature T* and its closing field, pointing to a preeminent role of spin-singlet correlations in forming the pseudogap in cuprates, regardless of their n or p type.

Journal Article↗

PubMed2005

Importance of the initial volume of parotid glands in xerostomia for patients with head and neck cancers treated with IMRT.

OBJECTIVE: Our aim was to evaluate predictors of xerostomia in patients with head and neck cancers treated with intensity-modulated radiation therapy (IMRT). METHODS: Thirty-three patients with pharyngeal cancer were evaluated for xerostomia after having been treated with IMRT. All patients were treated with whole-neck irradiation of 46-50 Gy by IMRT, followed by boost IMRT to the high-risk clinical target volume to a total dose of 56-70 Gy in 28-35 fractions (median, 68 Gy). For boost IMRT, a second computed tomography (CT-2) scan was done in the third to fourth week of IMRT. Xerostomia was scored 3-4 months after the start of IMRT. RESULTS: The mean doses to the contralateral and ipsilateral parotid glands were 24.0 +/- 6.2 and 30.3 +/- 6.6 Gy, respectively. Among the 33 patients, xerostomia of grades 0, 1, 2 and 3 was noted in one, 18, 12 and two patients, respectively. Although the mean dose to the parotid glands was not correlated with the grade of xerostomia, the initial volume of the parotid glands was correlated with the grade of xerostomia (P = 0.04). Of 17 patients with small parotid glands (< or =38.8 ml) on initial CT (CT-1), 11 (65%) showed grade 2 or grade 3 xerostomia, whereas only three (19%) of 16 patients with larger parotid glands showed grade 2 xerostomia (P < 0.05). The mean volume of the parotid glands on CT-1 was 43.1 +/- 15.2 ml, but decreased significantly to 32.0 +/- 11.4 ml (74%) on CT-2 (P < 0.0001). CONCLUSIONS: Initial volumes of the parotid glands are significantly correlated with the grade of xerostomia in patients treated with IMRT. The volume of the parotid glands decreased significantly during the course of IMRT.

Adult↗

PubMed2005

Convenient and rapid analysis of linkage isomers of fucose-containing oligosaccharides by matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight mass spectrometry.

Matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight mass spectrometry (MALDI-QIT-TOF MS) was used to analyze three pyridylamino (PA)-fucosyloligosaccharides isolated from human milk: lacto-N-fucopentaose (LNFP) I [Fucalpha1-2Galbeta1-3GlcNAcbeta1-3Galbeta1-4Glc-PA], LNFP II [Galbeta1-3(Fucalpha1-4)GlcNAcbeta1-3Galbeta1-4Glc-PA], and LNFP III [Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-3Galbeta1-4Glc-PA]. These oligosaccharides are linkage isomers. MALDI-QIT-TOF MS provides MS(n) spectra, which we used to characterize these PA-oligosaccharides. MS/MS/MS analysis of the non-reducing end tri-saccharide ions generated by MS/MS was able to distinguish these oligosaccharide isomers. The MALDI-QIT-TOF MS is a very convenient and rapid method, therefore, it would be useful for high throughput structural analyses of various types of pyridylaminated oligosaccharide isomers.

Carbohydrate Sequence↗

PubMed2005

Increase in tumor oxygenation and potentiation of radiation effects using pentoxifylline, vinpocetine and ticlopidine hydrochloride.

The purpose of the present study was to investigate the effects of Pentoxifylline (PTX), Vinpocetine (VPT) and Ticlopidine Hydrochloride (TCD), used commonly for vascular disorders in humans, on the pO2 in SCCVII tumors of C3H/HeJ mice and on the radioresponse of SCCVII tumors. The pO2 in the SCCVII tumors, which were measured 30 min after intraperitoneal (i.p.) injection of PTX (5 mg/kg), VPT (5 mg/kg), or TCD (10 mg/kg) using polarography, was compared to that in saline-treated control tumors. All the three drugs, PTX, VPT and TCD, yielded significant increase of the pO2 in the SCCVII tumors from 25.6 to 26.9 mmHg, from 18.6 to 22.9 mmHg, and from 22.6 to 25.9 mmHg, respectively. Frequency histogram of the pO2 distribution in the saline-treated SCCVII tumors did not show hypoxic fraction of less than 10 mmHg. The radioresponses of the drugs were investigated by tumor growth delay assay. In the drug-treated groups, the SCCVII tumors were irradiated with a single dose of 15 Gy 30 min after injection of the drugs at the same doses as those used in the experiments for intratumoral pO2 measurement. Compared with the irradiation alone group, significant tumor growth delays were observed in all the drug-treated groups. The time required to reach a four-fold increase in the initial tumor volume were 4 days in the saline-treated control group, 22 days in the irradiation (IR) alone group, 28 days in the PTX + IR group, 29 days in the VPT + IR group, and 32 days in TCD + IR group. In conclusion, VPT and TCD are potentially promising drugs for increasing the intratumoral pO2 although the mechanism for radiopotentiation observed in the present study is unknown due to small hypoxic fraction in the SCCVII tumors. Further studies on other mechanisms for radiopotentiation of PTX, VPT or TCD, besides of increasing the pO2 in the tumor, are needed.

Animals↗

PubMed2005

Combination of the antivascular agent ZD6126 with hypoxic cytotoxin treatment, with reference to the effect on quiescent tumor cells and the dependency on p53 status of tumor cells.

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. Mice bearing the tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all proliferating (P) cells in the tumors. The mice then received a hypoxic cytotoxin, tirapazamine (TPZ) or TX-402, with or without a vascular targeting agent (VTA), ZD6126. Another group of mice given ZD6126 received a series of test doses of gamma-rays while alive or after tumor clamping to obtain hypoxic fractions (HFs) in the tumors. After each treatment, the tumor cells were isolated and incubated with a cytokinesis blocker (cytochalasin-B), and the micronucleus (MN) frequency in cells without BrdU labeling [quiescent (Q) cells] was determined using immunofluorescence staining for BrdU. The MN frequency in total (P+Q) tumor cells was determined from the tumors that were not pretreated with BrdU. Both hypoxic cytotoxins showed significantly greater toxicity toward SAS/mp53 and Q than SAS/neo and total tumor cells, respectively. The sensitivity to TX-402 was significantly higher than that to TPZ in both total and Q tumor cells of both tumors. The significant enhancive effect by ZD6126 combined with each hypoxic cytotoxin was similar irrespective of p53 status, and slightly greater for total than Q cells probably because of a more marked increase in the size of the HFs in total than Q cells on the use of ZD6126 in both tumors, resulting in a reduction of the difference in the sensitivity to the hypoxic cytotoxin between total and Q cells. In the treatment of conventional cancer therapy-resistant Q tumor cells or p53-mutated tumor cells, the use of hypoxic cytotoxin was very promising either alone or when VTA was co-administered. TX-402 might be more promising than TPZ, although further study of the toxicity to normal tissue is needed.

Animals↗

PubMed2004

Clinical, biochemical, and cytochemical studies on a Japanese Salla disease case associated with a renal disorder.

We report the first Japanese case of Salla disease. A 5-year-old male patient developed unique proteinuria with other clinical manifestations, including coarse facies, dysostosis multiplex, mild mitral valve regurgitation, umbilical and inguinal herniation, and mild developmental delay. Pathological analysis of biopsied kidney tissues showed marked vacuolation of podocytes, mesangial cells, capillary endothelial cells, and tubular cells. Biochemical studies involving thin-layer chromatography and mass spectrometry revealed increased excretion of free sialic acid (N-acetylneuraminic acid) into the patient's urine. Immuno- and lectin staining of the patient's cells demonstrated the accumulation of sialyl and asialyl glycoconjugates in lysosomes and late endosomes. A defect in sialyl glycoconjugate metabolism is thought to have occurred in the patient's cells, besides impairment of the lysosomal transport of free sialic acid residues. A renal disorder should be considered as an important manifestation, not only in infantile free sialic acid storage disease but also in Salla disease.

Biological Transport↗

PubMed2004

Combination of the vascular targeting agent ZD6126 with boron neutron capture therapy.

PURPOSE: The aim of this study was to evaluate the antitumor efficacy of the vascular targeting agent ZD6126 (N-acetylcochinol-O-phosphate) in the rodent squamous cell carcinoma (SCC) VII carcinoma model, in combination with boron neutron capture therapy (BNCT). METHODS AND MATERIALS: Sodium borocaptate-(10)B (BSH, 125 mg/kg, i.p.) or l-p-boronophenylalanine-(10)B (BPA, 250 mg/kg, i.p.) was injected into SCC VII tumor-bearing mice, and 15 min later, ZD6126 (100 mg/kg, i.p.) was administered. Then, the (10)B concentrations in tumors and normal tissues were measured by prompt gamma-ray spectrometry. On the other hand, for the thermal neutron beam exposure experiment, SCC VII tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells in the tumors, followed by treatment with a (10)B-carrier and ZD6126 in the same manner as the above-mentioned (10)B pharmacokinetics analyses. To obtain almost similar intratumor (10)B concentrations during neutron exposure, thermal neutron beam irradiation was started from the time point of 30 min after injection of BSH only, 90 min after BSH injection for combination with ZD6126, 120 min after the injection of BPA only, and 180 min after BPA injection for combination with ZD6126. Right after irradiation, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (quiescent [Q] cells) was determined using immunofluorescence staining for BrdU. Meanwhile, the MN frequency in total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU. The clonogenic cell survival assay was also performed in mice given no BrdU. RESULTS: Pharmacokinetics analyses showed that combination with ZD6126 greatly increased the (10)B concentrations in tumors after 60 min after BSH injection and after 120 min after BPA injection. The concentrations of (10)B from BSH in normal tissues were also raised by combination with ZD6126, although not so clearly as those in tumors. Combination with ZD6126 had almost no effect on the concentrations of (10)B from BPA in normal tissues. The clonogenic surviving fractions of total tumor cells and the MN frequencies of both total and Q tumor cells were reduced and increased by combination with ZD6126, respectively, whether BSH or BPA was employed. However, the degrees of these changes in the clonogenic surviving fractions and the MN frequencies were more obviously observed in tumors from BSH-injected mice than from BPA-injected mice, and in Q tumor cells than in total tumor cells regardless of the employed (10)B-carrier. CONCLUSIONS: Combination with ZD6126 was regarded as more promising in BSH-BNCT than BPA-BNCT, and more effective for enhancing the sensitivity of the Q tumor cells than that of the total tumor cells. This resulted in the decrease in the extended difference in the sensitivity between the total and Q tumor cells caused by the use of (10)B-carrier for BNCT.

Animals↗

PubMed2004

Effects of mild temperature hyperthermia and p53 status on the size of hypoxic fractions in solid tumors, with reference to the effect in intratumor quiescent cell populations.

PURPOSE: To determine the effects of mild temperature hyperthermia (MTH) and p53 status of tumor cells on the size of hypoxic fractions (HFs) in solid tumors, with reference to the effect on intratumor quiescent (Q) cell populations. METHODS AND MATERIALS: 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 left hind legs of Balb/cA nude mice. Mice bearing the tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all proliferating (P) cells in the tumors. The mice then received nicotinamide injection or carbogen gas (95% O(2), 5% CO(2)) inhalation combined with or without MTH. Nicotinamide prevents intermittent blood flow that could induce perfusion-limited acute hypoxia. Chronically hypoxic cells in regions beyond the limitation of oxygen diffusion in tumors are oxygenated by increasing the oxygen transport capacity of circulating blood with carbogen gas inhalation. After each treatment, the mice received a series of test doses of gamma-rays while alive or after tumor clamping to obtain HFs in the tumors. Immediately after irradiation, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with a cytokinesis blocker (cytochalasin-B) to inhibit cytoplasmic division while allowing nuclear division. Tumor cells not labeled with BrdU were detected with immunofluorescence staining of BrdU for P cells, and the micronucleus frequency in cells without BrdU labeling [ = Q cells] was determined. The micronucleus frequency in total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU. RESULTS: SAS/mp53 tumors showed larger values for the size of not only the HF but also the diffusion-limited chronically HF than SAS/neo tumors. Q cell populations included a larger HF, particularly the chronically HF, than total cell populations in both tumors, especially in SAS/neo tumors. MTH could efficiently oxygenate the chronically HF, irrespective of p53 status. CONCLUSION: MTH is a useful combined treatment with a radioenhancement effect on intratumor Q cells, irrespective of the p53 status of tumor cells. The p53 status has the potential to affect microenvironmental conditions within solid tumors.

Animals↗

PubMed2004

SLI1 (YGR212W) is a major gene conferring resistance to the sphingolipid biosynthesis inhibitor ISP-1, and encodes an ISP-1 N-acetyltransferase in yeast.

ISP-1 (myriocin) is a potent inhibitor of serine palmitoyltransferase, the primary enzyme of sphingolipid biosynthesis, and is a useful tool for studying the biological functions of sphingolipids in both mammals and yeast (Saccharomyces cerevisiae). In a previous study, we cloned yeast multicopy suppressor genes for ISP-1, and one of these, YPK1/SLI2, was shown to encode a serine/threonine kinase which is a yeast homologue of mammalian SGK1 (serum/glucocorticoid-regulated kinase 1). In the present study, another gene, termed SLI1 (YGR212W; GenBank accession number CAA97239.1), was characterized. Sli1p has weak similarity to Atf1p and Atf2p, which are alcohol acetyltransferases. Although a sli1-null strain grew normally, the IC50 of ISP-1 for the growth of this strain was markedly decreased compared with that for the parental strain, indicating that Sli1p is a major contributor to ISP-1 resistance in yeast. On a sli1-null background, the increase in resistance to ISP-1 induced by YPK1 gene transfection was almost abolished. These data indicate that Sli1p co-operates with Ypk1p in mediating resistance to ISP-1 in yeast. Sli1p was found to convert ISP-1 into N-acetyl-ISP-1 in vitro. Furthermore, N-acetyl-ISP-1 did not share the ability of ISP-1 to inhibit the growth of yeast cells, and the serine palmitoyltransferase inhibitory activity of N-acetyl-ISP-1 was much lower than that of ISP-1. These data suggest that Sli1p inactivates ISP-1 due to its N-acetyltransferase activity towards ISP-1.

Acetylation↗

PubMed2004

Intra-arterial administration of sodium borocaptate (BSH)/lipiodol emulsion delivers B-10 to liver tumors highly selectively for boron neutron capture therapy: experimental studies in the rat liver model.

PURPOSE: Boron neutron capture therapy (BNCT) is particle radiotherapy with alpha ((4)He) particle and recoiled lithium nucleus ((7)Li) derived from a reaction of boron ((10)B) and thermal neutron. We investigated applying BNCT to malignant liver tumors. The purpose of the present study was to reveal the efficacy for administration of emulsion of a boron compound (sodium borocaptate; BSH) and lipiodol via a hepatic artery using a rat liver tumor model. METHODS AND MATERIALS: Rat liver tumors were developed by direct injection of Walker 256 cells into the liver parenchyma. BSH (75 mg/kg)/lipiodol (0.3 mL/kg) emulsion was administered via the hepatic artery. Boron concentrations in the tumors, liver, and blood were measured at 1, 6, and 12 h after administration. Neutron capture radiography (NCR) was taken to confirm the selective accumulation of (10)B in the liver tumors. RESULTS: Boron concentrations in the liver tumors and the tumor/liver (T/L) boron concentration ratio at 1, 6, and 12 h after administration of BSH/lipiodol emulsion (concentration: T/L ratio) were 479.2 ppm: 4.0, 197.3 ppm: 14.9, and 96.5 ppm: 6.6, respectively. Highly selective irradiation was clearly demonstrated by the NCR images. CONCLUSIONS: Intra-arterial administration of BSH/lipiodol emulsion is effective method for delivering high concentration of (10)B selectively to the liver tumors.

Animals↗

PubMed2004

DES2 protein is responsible for phytoceramide biosynthesis in the mouse small intestine.

The C-4 hydroxylation of sphinganine and dihydroceramide is a rate-limiting reaction in the biosynthesis of phytosphingolipids. Mouse DES1 (MDES1) cDNA homologous to the Drosophila melanogaster degenerative spermatocyte gene-1 (des-1) cDNA leads to sphingosine Delta4-desaturase activity, and another mouse homologue, MDES2, has bifunctional activity, producing C-4 hydroxysphinganine and Delta4-sphingenine in yeast [Ternes, Franke, Zahringer, Sperling and Heinz (2002) J. Biol. Chem. 277, 25512-25518]. Here, we report the characterization of mouse DES2 (MDES2) using an in vitro assay with a homogenate of COS-7 cells transfected with MDES2 cDNA and N -octanoyl-sphinganine and sphinganine as substrates. MDES2 protein prefers dihydroceramide as a substrate to sphinganine, and exhibits dihydroceramide Delta4-desaturase and C-4 hydroxylase activities. MDES2 mRNA content was high in the small intestine and abundant in the kidney. In situ hybridization detected signals of MDES2 mRNA in the crypt cells. Immunohistochemistry using an anti-MDES2 peptide antibody stained the crypt cells and the adjacent epithelial cells. These results suggest that MDES2 is the dihydroceramide C-4 hydroxylase responsible for the biosynthesis of enriched phytosphingoglycolipids in the microvillous membranes of intestinal epithelial cells.

Animals↗

PubMed2004

Dosimetric study of boron neutron capture therapy with borocaptate sodium (BSH)/lipiodol emulsion (BSH/lipiodol-BNCT) for treatment of multiple liver tumors.

PURPOSE: We performed a computational study to investigate the feasibility of borocaptate sodium (BSH)/lipiodol-boron neutron capture therapy (BSH/lipiodol-BNCT) for multiple liver tumors using Simulation Environment for Radiotherapy Applications (SERA), a currently available BNCT treatment planning system. METHODS AND MATERIALS: Three treatment plans for BSH/lipiodol-BNCT using two or three epithermal neutron beams in one fraction were generated for 4 patients with multiple liver tumors using the SERA system. The (10)B concentrations in the tumor and the liver assumed in the study were 197.3 and 15.3 ppm, respectively; and were obtained from experimental studies in animals. The therapeutic gain factors for the liver tumors, defined as the minimum dose to the tumor/maximum dose to the liver, and the inhomogeneity index of the thermal neutron fluence for the whole of the liver, defined as the maximum neutron fluence - minimum neutron fluence/mean neutron fluence, were evaluated in each plan. RESULTS: Three epithermal neutron beams incident on the anterior, posterior, and right side of the patient can deliver the most homogeneous distribution of thermal neutron fluence to the whole of the liver and provide the greatest therapeutic gain factors for tumors in the right lobe and approximately equal therapeutic gain factors for tumors in the left lobe, compared with the two opposed (anterior-posterior) and two orthogonal (anterior-right) beams. CONCLUSIONS: From a dosimetric viewpoint, the BSH/lipiodol-BNCT treatment plan using three epithermal neutron beams is the most suitable for the treatment of multiple liver tumors.

Borohydrides↗

PubMed2004

Erythropoietin/erythropoietin-receptor system as an angiogenic factor in chemically induced murine hepatic tumors.

BACKGROUND: To clarify the role of erythropoietin (Epo) in hepatic tumor angiogenesis, expression of Epo and its receptor (Epo-R) and content of Epo were investigated in murine chemically induced hepatic tumors. METHODS: To induce hepatic tumors and cirrhosis, diaminobenzidine was administered to Wistar rats for 5 months. In total, 30 hepatic tumors of greater than 3 mm in diameter were induced in 12 rats. The 30 hepatic tumors were resected with the surrounding hepatic tissues. The Epo content was measured by a radioimmunoassay (RIA) method. The number of tumor vessels in a definite area was counted in 100 areas of each tumor. To demonstrate the expression of Epo-R in tumors or surrounding liver tissues, immunohistochemical staining for Epo-R was performed. RESULTS: The Epo content of tumors ranged from 6.1 to 97.8 mU/ml, with a median of 21.8 mU/ml, which was significantly higher than that of the cirrhotic tissues adjacent to the tumors. Epo was not detectable in the normal or cirrhotic liver tissues without tumors. A significant correlation between Epo content and vascular density was noted in the 30 hepatic tumors (correlation coefficient, 0.480; P = 0.01). Immunoreactive Epo-R was detectable in the endothelium of intervening vessels of all hepatic tumors examined. CONCLUSION: The Epo/Epo-R system is related to the angiogenesis of murine hepatic tumors. To clarify the role of erythropoietin (Epo) in hepatic tumor angiogenesis, expression of Epo and its receptor (Epo-R) and content of Epo were investigated in murine chemically induced hepatic tumors.

Animals↗

PubMed2004

Comparison of outcomes between overlapping structure-based and non-overlapping structure-based optimization for simultaneous integrated boost IMRT for malignant gliomas.

BACKGROUND: Intensity-modulated radiotherapy (IMRT) can deliver different doses to two target volumes with high conformity. The purpose of the present study was to compare outcomes provided by two different optimization methods, overlapping structure-based and non-overlapping structure-based methods, for simultaneous integrated boost (SIB)-IMRT for malignant gliomas. METHODS: Treatment plans for three glioblastomas and one anaplastic astrocytoma were analyzed in the present study. The planning protocol was to deliver 70 Gy/28 fractions (fr) to the gross tumor volume (GTV) and 56 Gy/28 fr to the surrounding edema. Two different optimization methods were tested for optimizing dose distribution to the GTVand the surrounding edema. One method was the "including method", an overlapping structure-based (GTV and the clinical target volume [CTV]) optimization method. The other method was the "annulus method", a non-overlapping structure-based (GTV and the subtracted volume) optimization method. Dosimetric indexes derived from dose-volume histograms (DVHs) were used for the analysis. RESULTS: There was no significant difference between the two methods in the mean doses of the target volumes and the doses delivered to the 5% or 95% target volumes (D05 or D95). The mean dose to the brain by the including method was significantly higher than that delivered by the annulus method (P = 0.0001). The D05 of the brain showed no significant difference between the two methods. CONCLUSION: The two optimization methods provided comparable dose distributions within the target volumes and normal brain.

Brain Neoplasms↗

PubMed2004

Ascorbic acid reduced mutagenicity at the HPRT locus in CHO cells against thermal neutron radiation.

We investigated the biological effects of the long-lived radicals induced following neutron irradiation. It has been reported that radiation-induced long-lived radicals were scavenged by post-irradiation treatment of ascorbic acid (Koyama, 1998). We studied the effects of ascorbic acid acting as a long-lived radical scavenger on cell killing and mutagenicity in Chinese hamster ovary cells against thermal neutrons produced at the Kyoto University Research reactor. Ascorbic acid was added to cells 30 min after neutron irradiation and removed 150 min after irradiation. The biological end point of cell survival was measured by colony formation assay. The mutagenicity was measured by the mutant frequency in the HPRT locus. The post-irradiation treatment of ascorbic acid did not alter the cell killing effect of neutron radiation. However, the mutagenicity was decreased, especially when the cells were irradiated with boron. Our results suggested that ascorbic acid scavenged long-lived radicals effectively and caused apparent protective effects against mutagenicity of boron neutron capture therapy.

Animals↗