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Biomedical subjects

Minoru Suzuki

Publications and source records attributed to Minoru Suzuki.

At least 55 records · Page 3Linked to original sources
PubMed2004

Biodistribution of 10B in a rat liver tumor model following intra-arterial administration of sodium borocaptate (BSH)/degradable starch microspheres (DSM) emulsion.

We reported that intra-arterial administration of borocaptate sodium (BSH)/lipiodol emulsion provided selectively high (10)B concentrations (approximately 200 ppm 6 h after administration) in experimental liver tumors. In the present study, we investigated the pharmacokinetics of BSH following intra-arterial administration of BSH with other embolizing agent, degradable starch microspheres (DSM). The (10)B concentration in the tumor at 1 h after administration of BSH with DSM was 231 ppm. At 6 h, the (10)B concentration in the tumor in BSH with DSM group was 81.5 ppm. The (10)B concentration in the liver at 1 h after administration of BSH with DSM was 184 ppm. At 6 h, the(10)B concentration in the liver in BSH with DSM group was 78 ppm. The tumor/liver (10)B concentration ratios (T/L ratio) in the "BSH+DSM" group were significantly smaller than those in the "BSH+lipiodol" group at 1 h (1.4 vs. 3.6) and 6h (1.1 vs. 14.9). BSH/DSM-boron neutron capture therapy (BNCT) was not suitable for treatment of multiple liver tumors due to the low T/L (10)B concentration ratio. However, the high (10)B accumulation in the liver tumors following intra-arterial administration of BSH/DSM emulsion suggests that BSH/DSM-BNCT has the potential for application to malignant tumors in other sites.

Animals↗
PubMed2004

Delivery of (10)boron to oral squamous cell carcinoma using boronophenylalanine and borocaptate sodium for boron neutron capture therapy.

Boron neutron capture therapy (BNCT) is a unique radiation therapy in which boron compounds are trapped into tumor cells. To determine the biodistribution of boronophenylalanine (BPA) in nude mice carrying oral squamous cell carcinoma (SCC), BPA was administered at a dose of 250 mg/kg body weight intraperitoneally. Two hours later, (10)B concentration in the tumor was 15.96 ppm and tumor/blood, tumor/tongue, tumor/skin and tumor/bone (10)B concentration ratios were 6.44, 4.19, 4.68 and 4.56, respectively. Two hours after the administration of borocaptate sodium (BSH) at a dose of 75 mg/kg body weight, (10)B concentration in the tumor was 3.61 ppm, and tumor/blood, tumor/tongue, tumor/skin and tumor/bone (10)B concentration ratios were 0.77, 1.05, 0.60 and 0.59, respectively. When cultured oral SCC cells were incubated with BPA or BSH for 2 h and then exposed to thermal neutrons, the proportion of survival cells that were capable of forming cell colonies decreased exponentially, depending on (10)B concentration. BPA-mediated BNCT was more efficient than BSH-mediated BNCT. Addition of boron compounds in the cell suspension during neutron irradiation enhanced the cell-killing effect of the neutrons. These results indicate that BPA is more selectively incorporated into human oral SCC as compared with normal oral tissues, and that both extra- and intra-cellular BPA contribute to the cell-killing effect of BNCT. BPA may be a useful boron carrier for BNCT in the treatment of advanced oral SCC.

Animals↗
PubMed2004

A real time non-invasive monitoring system for detection of hypovolemic state using RR interval variability in very low frequency ranges.

In offline analysis, very low frequency variability in RR interval and systolic arterial pressure has been reported below 0.1 Hz during head-up tilt (HUT) tests in conditions similar to hypovolemic states in humans. We designed a real time and non-invasive monitoring system of very low frequency RR interval variability to detect the hypovolemic state resulting from internal and external hemorrhages. Eight male Sprague-Dawley rats were subjected to monitoring before (normal state) and after withdrawal of 2 ml blood/100 g body weight over 15 minutes (hypovolemic state). Using one-channel electrocardiogram (ECG), the detection system monitored in real time the very low frequency components of RR interval variability using Fast Fourier Transform (FFT). Temperature mappings of rat abdomen were conducted simultaneously to monitor the hypothermic state after blood withdrawal using a local temperature mapping system with a deep body thermometer. This system demonstrated oscillation of the RR interval at 0.075 +/- 0.015 Hz in real time after blood withdrawal. The deep body temperature decreased significantly from 37.4 +/- 0.9 degrees centigrade to 35.5 +/- 1.2 degrees centigrade (p < 0.05) within 1 hour after blood withdrawal. Our monitoring system appears promising for the detection of hypovolemic state resulting from massive hemorrhage using a one-channel ECG monitor.

Algorithms↗
PubMed2004

Tichocarpols A and B, two novel phenylpropanoids with feeding-deterrent activity from the red alga Tichocarpus crinitus.

Two novel phenylpropanoic acid derivatives, tichocarpol A (1) and tichocarpol B (2), were isolated along with floridoside and isethionic acid from the red alga Tichocarpus crinitus. The structures of these novel metabolites were elucidated using a combination of spectral (1D and 2D NMR techniques and ESIMS) and chemical methods. Compounds 1, 2, and floridoside exhibited feeding-deterrent activity against the sea urchin Strongylocentrotus intermedius.

Animals↗
PubMed2004

Involvement of proteases in glycosyltransferase secretion: Alzheimer's beta-secretase-dependent cleavage and a following processing by an aminopeptidase.

Alzheimer's beta-secretase (BACE1) cleaves amyloid precursor protein to produce amyloid beta-peptide, which is a crucial initiation process of the pathogenesis of Alzheimer's disease. We previously found that BACE1 also cleaves a membrane-bound sialyltransferase (ST6Gal I). Here we report that, when the protein A-ST6Gal I fusion protein, or ST6Gal I-derived peptide, was used as an in vitro substrate for BACE1, it cleaved the substrates between Leu(37) and Gln(38). However, a soluble form of ST6Gal I secreted from COS cells started from Glu(41), which was three amino acids shorter than the in vitro product. The results suggested that the BACE1 product was truncated by an aminopeptidase(s) before secretion. The aminopeptidase activity was successfully detected in detergent extracts of Golgi-membrane fraction. Taken together, we concluded that BACE1 initially cleaved ST6Gal I between Leu(37) and Gln(38), and the NH(2)-terminal three amino acids of the yielded product was further trimmed by the aminopeptidase.

Alanine↗
PubMed2004

Potent antibacterial activity of halogenated compounds against antibiotic-resistant bacteria.

Common Gram-positive clinical pathogens are showing an increasing trend for resistance to conventional antimicrobial agents. New drugs with potent antibacterial activities are urgently needed to remediate this problem. Halogenated compounds isolated from several species of the red algae genus Laurencia were examined for their antibacterial activity against 22 strains of human pathogenic bacteria, 7 strains of which were antibiotic-resistant bacteria. Four phenolic sesquiterpenes and a polybrominated indole showed wide spectra of antibacterial activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant Enterococcus faecalis and E. faecium (VRE). In addition, laurinterol and allolaurinterol displayed potent bactericidal activity against three strains of MRSA at 3.13 microg mL(-1), and three strains of vancomycin-susceptible Enterococcus, at 3.13 microg mL(-1) and 6.25 microg mL(-1), respectively.

Anti-Bacterial Agents↗
PubMed2003

Potential of alpha-amino alcohol p-boronophenylalaninol as a boron carrier in boron neutron capture therapy, regarding its enantiomers.

PURPOSE: We evaluated the potential of a newly developed (10)B-containing alpha-amino alcohol of p-boronophenylalanine-(10)B (BPA), p-boronophenylalaninol (BPAol), as a boron carrier in boron neutron capture therapy. METHODS: C57BL mice bearing EL4 tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously via implanted mini-osmotic pumps to label all proliferating (P) cells. After oral administration of L-BPA or D-BPA, or intraperitoneal injection of L-BPAol or D-BPAol, the tumors were irradiated with reactor thermal neutron beams. Some of the tumors were heated at 40 degrees C for 30 min (mild temperature hyperthermia (MTH)) right before neutron exposure, and/or tirapazamine (TPZ) was intraperitoneally injected 30 min before irradiation. The tumors were then 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, 6 h after irradiation, tumor cell suspensions obtained in the same manner were used for determining the apoptosis frequency in Q cells. The apoptosis and MN frequency in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. RESULTS: Without TPZ or MTH, L- and D-BPAol increased both frequencies markedly, especially for total cells. Although not significantly larger, L-BPA and D-BPAol increased both frequencies slightly more than D-BPA and L-BPAol, respectively. Combination with both MTH and TPZ markedly reduced the sensitivity difference between total and Q cells. CONCLUSION: Both L- and D-BPAol have potential as a (10)B-carrier in neutron capture therapy, especially when combined with both MTH and TPZ.

Amino Alcohols↗
PubMed2003

Feasibility study of the simultaneous integrated boost (SIB) method for malignant gliomas using intensity-modulated radiotherapy (IMRT).

BACKGROUND: Intensity-modulated radiotherapy (IMRT) using the simultaneous integrated boost (SIB) method was designed for treating malignant gliomas. The purpose of this study was to investigate feasibility of this treatment. METHODS: Between December 2000 and November 2002, six patients with malignant gliomas were enrolled in this study. IMRT delivered 70 Gy/28 fractions (fr)/daily 2.5 Gy to the gross tumor volume (GTV) and 56 Gy/28 fr/daily 2.0 Gy to the surrounding edema defined as the clinical target volume annulus (CTV-a). The feasibility of the treatment was assessed from both physical and clinical points of view. RESULTS: No delay due to acute radiation toxicity was observed in any of the patients. The tumor recurred locoregionally in five of the six patients. The glioblastoma (GBM) recurred in two patients during the radiotherapy and in three patients at 5.4, 4.0 and 7.0 months after the start of radiotherapy. The sites of recurrence or progression were local in the GTV in four patients and in one patient subependymal dissemination was observed. Three patients, two with GBMs and one with anaplastic astrocytoma, died of the disease at 4, 16 and 7 months after the start of radiotherapy, respectively. CONCLUSIONS: The treatment of 70 Gy/28 fr/daily 2.5 Gy to the GTV and 56 Gy/28 fr/daily 2.0 Gy to the CTV-a was feasible both physically and clinically.

Aged↗
PubMed2003

Phase I study of weekly docetaxel infusion and concurrent radiation therapy for head and neck cancer.

OBJECTIVE: This study was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly docetaxel in combination with concurrent radiotherapy for treating head and neck cancer. METHODS: Twelve patients with unresectable or postoperative head and neck cancers were enrolled in a dose-escalating phase I study. Eleven of the 12 patients were postoperative patients with intermediate or high pathological risk features. Radiotherapy was delivered as a standard fractionation regimen (2 Gy/day, 5 fractions/week) to a total dose of 60-70 Gy. The starting dose of docetaxel was 10 mg/m(2) (once per week) with a subsequent dose escalation of 5 mg/m(2) in cohorts of three patients. In 2001 and 2002, 12 patients completing three dose levels were included in the study. RESULTS: The MTD of docetaxel was 20 mg/m(2). With the third dose level (20 mg/m(2)), DLT was observed in two of three patients. One experienced grade IV mucositis and another suffered from prolonged grade III mucositis-enforced treatment delay for 13 days. Hematological toxicity was minimal. Mucositis was the DLT of concurrent chemoradiotherapy using weekly docetaxel administration for head and neck cancer. CONCLUSIONS: We identified the recommended phase II dose of docetaxel as 15 mg/m(2) administered weekly with concurrent radiotherapy for head and neck cancers.

Adult↗
PubMed2003

Concurrent chemoradiotherapy with protracted infusion of 5-FU and cisplatin for postoperative recurrent or residual esophageal cancer.

BACKGROUND: We carried out the present study to investigate the feasibility and effectiveness of concurrent chemoradiotherapy (CT-RT) for postoperative recurrent esophageal cancer, which are, at present, unclear. METHODS: Between 1998 and 2002, 16 patients with postoperative loco-regional recurrence of esophageal cancer, and two patients with incompletely resected esophageal cancer were treated with concurrent CT-RT. Patients received protracted infusion of 5-FU 250-300 mg/m(2) on days 1 to 14, 1 hour infusion of cisplatin 10 mg/body on days 1 to 5 and 8 to 12, and a concurrent radiotherapy (RT) dose of 30 Gy in 15 fractions over 3 weeks. This treatment schedule was repeated twice with a gap of 1 week, for a total RT dose of 60 Gy administered over 7 weeks. RESULTS: Of the 18 patients, 13 (72%) completed the CT-RT protocol. A total RT dose of 60 Gy was administered for all except two patients, and doses of chemotherapy were reduced for five patients. Although grade 3 hematological toxicities were frequently noted, non-hematological toxicities of grades 3 and 4 were few. Of the 18 tumors, five (28%) showed complete response (CR). For patients without prior chemotherapy, the CR rate was 40% (4/10). The 2-year survival rate of 13 patients without distant metastases was 19%, with a median survival time of 9.5 months. CONCLUSION: The concurrent CT-RT protocol appears feasible and effective for patients with postoperative recurrent or residual esophageal cancer.

Adult↗
PubMed2003

Usefulness of combined treatment with mild temperature hyperthermia and/or tirapazamine in the treatment of solid tumors: its independence of p53 status.

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 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 tirapazamine (TPZ) with or without mild temperature hyperthermia (40 degrees C, 60 min) (MTH), gamma-ray irradiation with or without MTH and/or TPZ, cisplatin (CDDP) with or without MTH and/or TPZ, or paclitaxel (TXL) with or without MTH and/or TPZ. After each treatment, the tumors were excised, minced and trypsinized. The tumor cell suspensions thus obtained were incubated with a cytokinesis blocker (cytochalasin-B), and the micronucleus (MN) frequency in cells without BrdU labeling (i.e., quiescent (Q) cells) was determined by using immunofluorescence staining for BrdU. Meanwhile, 6 h after gamma-ray irradiation or 24 h after other cytotoxic treatments, tumor cell suspensions obtained in the same manner were used for determining the frequency of apoptosis in Q cells. The MN frequency and apoptosis frequency in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. On the whole, gamma-ray irradiation and CDDP injection induced a higher frequency of apoptosis and lower frequency of MN in SAS/neo cells than SAS/mp53 cells. There were no apparent differences in the induced frequency of apoptosis and MN between SAS/neo and SAS/mp53 cells after TPZ or TXL treatment. MTH sensitized cells to TPZ-inducing cytotoxicity more markedly in SAS/mp53 and Q cells than in SAS/neo cells and total cells, respectively. In gamma-ray irradiation and CDDP treatment, the enhancement in combination with MTH and/or TPZ was more remarkable in SAS/mp53 cells and Q cells than in SAS/neo and total tumor cells, respectively. Also in the case of TXL treatment, the combination with MTH and/or TPZ induced a slightly greater enhancement effect in SAS/mp53 cells and Q cells. In view of the difficulty in controlling mutated p53 status tumors and intratumor Q cells, combination treatment with MTH and/or TPZ as a cooperative modality in cancer therapy is considered to have potential for controlling solid tumors as a whole.

Animals↗
PubMed2003

Pharmacological mechanism in slip-down behavior of mice.

Slip-down from a raised platform was previously found in mice treated with morphine, and this behavior was also recognized in mice treated with a monoamine releaser methamphetamine. Pharmacological examination on the slip-down indicated that the behavior was induced by receptor stimulations by D2 agonist PPHT and 5HT-2 agonist DOI. In mice treated with PPHT, antagonists of D1, alpha2, 5HT-2 and opioid mu and kappa suppressed the behavior. In mice treated with DOI, antagonists of D1, alpha2, 5HT-1A, 5HT-3 and opioid mu and delta suppressed the behavior. These present findings suggest that the slip-down was mainly induced by opioid mu receptor activity regulated with monoamine activities. When the slip-down is considered as an anxious behavior, it may be also suggested that the anxiety induced by 5-HT activities furthermore stimulated the behavior via the other opioid receptor activities.

Animals↗
PubMed2003

Additive effects of radiation and docetaxel on murine SCCVII tumors in vivo: special reference to changes in the cell cycle.

The purpose of the present study was to investigate the effects of a combination of docetaxel and irradiation in vivo with special reference to docetaxel-arrested G(2)/M-phase cells. At 24 and 48 h after intraperitoneal administration of docetaxel (90 mg/kg), tumor-bearing mice were irradiated with (60)Co gamma rays. Cell cycle distribution was analyzed by a DNA-Ki-67 double staining method using flow cytometry. An accumulation of cells in the G(2)/M phase of up to approximately 40% was observed 24 h after administration of docetaxel. Between 24 and 72 h, the percentage of cells arrested in G(2)/M phase that expressed Ki-67 decreased from 37.2% to 13.8%, in accordance with the increase in the Ki-67-negative G(2)/M-phase fraction. More than half of the cells arrested in G(2)/M phase lost their expression of Ki-67 protein between 24 and 72 h. The G(1)-phase fraction decreased from 28.4% to 8.6% at 24 h after docetaxel treatment; this remained unchanged at 72 h. These flow cytometry data suggested that docetaxel-arrested G(2)/M-phase cells did not enter the next cell cycle and were killed by docetaxel alone. Our data showed that arrest of cells in G(2)/M phase does not contribute to the synergism that has been reported for combinations of docetaxel and radiation in in vivo tumor models.

Animals↗
PubMed2003

[The biological effect of the phosphatidylinositol 3-kinase wortmannin following thermal neutron irradiation].

PURPOSE: Wortmannin, a phosphatidylinositol 3-kinase inhibitor, has been found to inhibit DNA-dependent protein kinase (DNA-PKcs) and to be an efficient radiosensitizer. We investigated the radiosensitizing effect of wortmannin on cell killing by thermal neutrons and the occurrence of mutations at the HPRT locus of CHO cells. MATERIALS AND METHODS: Wortmannin was added to cells at a final concentration of 20 microM two hours before irradiation. Cells were irradiated with thermal neutrons. The biological end point of cell survival was measured by colony formation assay. Mutagenicity was calculated from the mutation frequency at the HPRT locus. RESULTS: Wortmannin promoted cell death following thermal neutron irradiation especially in the absence of boron. However, mutagenicity was decreased by the wortmannin treatment. CONCLUSION: Our results suggest that the inhibition of DNA-PKcs by wortmannin would be an effective radiosensitizer for BNCT and might bring about a reduction in the frequency of mutation by blocking the mis-joining of DNA damage during the repair process.

Androstadienes↗
PubMed2002

Characterization of alpha 2,6-sialyltransferase cleavage by Alzheimer's beta -secretase (BACE1).

BACE1 is a membrane-bound aspartic protease that cleaves the amyloid precursor protein (APP) at the beta-secretase site, a critical step in the Alzheimer disease pathogenesis. We previously found that BACE1 also cleaved a membrane-bound sialyltransferase, ST6Gal I. By BACE1 overexpression in COS cells, the secretion of ST6Gal I markedly increased, and the amino terminus of the secreted ST6Gal I started at Glu(41). Here we report that BACE1-Fc chimera protein cleaved the A-ST6Gal I fusion protein, or ST6Gal I-derived peptide, between Leu(37) and Gln(38), suggesting that an initial cleavage product by BACE1 was three amino acids longer than the secreted ST6Gal I. The three amino acids, Gln(38)-Ala(39)-Lys(40), were found to be truncated by exopeptidase activity, which was detected in detergent extracts of Golgi-derived membrane fraction. These results suggest that ST6Gal I is cleaved initially between Leu(37) and Gln(38) by BACE1, and then the three-amino acid sequence at the NH(2) terminus is removed by exopeptidase(s) before secretion from the cells.

Alzheimer Disease↗
PubMed2002

Prospective trial of concurrent chemoradiotherapy with protracted infusion of 5-fluorouracil and cisplatin for T4 esophageal cancer with or without fistula.

PURPOSE: A prospective trial of concurrent chemoradiotherapy (CT-RT) with a protracted infusion of 5-fluorouracil and cisplatin was performed to evaluate the safety and efficacy of this protocol for T4 esophageal cancer (UICC 1997). METHODS AND MATERIALS: Between 1998 and 2000, 28 patients with T4 esophageal squamous cell carcinomas were treated with concurrent CT-RT. Of the 28 patients, 15 had Stage III, 5 Stage IVA, and 8 Stage IV disease. Five of the T4 tumors had evidence of fistula before treatment. Patients received a protracted infusion of 5-fluorouracil 300 mg/m(2)/24 h on Days 1-14, a 1-h infusion of cisplatin 10 mg/body on Days 1-5 and 8-12, and concurrent radiation at a dose of 30 Gy in 15 fractions during 3 weeks. This schedule was repeated twice, with a 1-week split, for a total RT dose of 60 Gy during 7 weeks for 25 patients. For the remaining 3 patients, 30 Gy of preoperative CT-RT was administered. RESULTS: Of the 25 patients who were treated with the full dose of CT-RT, 14 (56%) completed the two courses of the CT-RT protocol, and 8 patients (32%) received the full dose of RT but a reduced dose of chemotherapy. Eight (32%) of the 25 tumors showed complete regression. Although Grade 3 hematologic toxicities were frequently noted, Grade 4 or more hematologic toxicities were few. Of the 5 T4 fistulous tumors, 2 demonstrated the disappearance of the fistula after CT-RT. However, the worsening or development of an esophageal fistula was noted in 5 patients. The 2-year survival rate for patients with Stage III was 27%, and the median survival time for those with Stage III and Stage IVA+IV was 12 and 5 months, respectively. CONCLUSION: Despite its significant toxicity for esophageal fistula, this concurrent CT-RT protocol of protracted 5-fluorouracil infusion and cisplatin appears feasible and effective for T4 esophageal cancer with or without fistulas.

Aged↗
PubMed2002

Brominated metabolites from an Okinawan Laurencia intricata.

Two halogenated C(15) acetogenins, itomanallenes A and B, with a terminal bromoallene moiety along with a halogenated sesquiterpene, itomanol, have been isolated from the red alga Laurencia intricata collected in Okinawan waters. Their structures were deduced from 1D and 2D NMR experiments including (1)H-(1)H COSY, HSQC, HMBC, and NOESY methods. The alcohol corresponding to itomanallene B seems to be a plausible precursor of itomanallene A, which has an unusual 2,10-dioxabicyclo[7.3.0]dodecene skeleton. Itomanol was found to be a selinane-type bromosesquiterpenoid, and is the first example of a selinane to be isolated from Japanese Laurencia species.

Bromine↗