Masao Takagaki - Academia.edu (original) (raw)

Papers by Masao Takagaki

Research paper thumbnail of Contents, Vol. 40, 1994

Chemotherapy, 1994

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Research paper thumbnail of Boron Neutron Capture Therapy (BNCT) for Malignant Glioma using ^ B-BPA

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Research paper thumbnail of Future Applications of Boron and Gadolinium Neutron Capture Therapy

New Technologies and Applications, 2011

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Research paper thumbnail of Potentially lethal damage repair by total and quiescent tumor cells following various DNA-damaging treatments

Radiation Medicine Medical Imaging and Radiation Oncology, 1999

After continuous labeling of proliferating (P) cells with 5-bromo-2'-deoxyuridine (BrdU) ... more After continuous labeling of proliferating (P) cells with 5-bromo-2'-deoxyuridine (BrdU) for 5 days, SCC VII tumor-bearing mice received various kinds of DNA-damaging treatments: gamma-ray irradiation, tirapazamine (TPZ, hypoxia-specific cytotoxin) administration, or cisplatin injection. From 0.5 to 72 hr after treatment, tumors were excised, minced, and trypsinized. Single tumor cell suspensions were incubated for 48 hr with a cytokinesis-blocker, cytochalasin-B. Then, the micronucleus (MN) frequency for BrdU-unlabeled cells, quiescent (Q) cells at treatment, was determined using immunofluorescence staining for BrdU. The MN frequency for total (P+Q) cells was obtained from tumors that were not pretreated with BrdU labeling. The sensitivity to each DNA-damaging treatment was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency). Treatment with gamma-rays or cisplatin resulted in a larger MN frequency in total cells than in Q cells. In contrast, TPZ treatment produced a smaller MN frequency in total cells than in Q cells. Regardless of the treatment used, Q cells showed greater repair capacities than total cells. However, TPZ caused much smaller repair capacity in both total and Q cells, compared with gamma-rays or cisplatin. Gamma-rays and cisplatin produced similar repair patterns. Differences in sensitivity between total and Q cells and repair patterns of the two cell populations were thought to depend on differences between the two cell populations in the toxicity of the DNA-damaging treatment and distribution pattern of the anticancer agent.

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Research paper thumbnail of Alteration of sensitivity of intratumor quiescent and total cells to γ-rays following thermal neutron irradiation with or without 10B-compound

Int J Radiat Oncol Biol Phys, 2000

Purpose: Changes in the sensitivity of intratumor quiescent (Q) and total cells to γ-rays followi... more Purpose: Changes in the sensitivity of intratumor quiescent (Q) and total cells to γ-rays following thermal neutron irradiation with or without 10B-compound were examined.Methods and Materials: 5-Bromo-2′-deoxyuridine (BrdU) was injected to SCC VII tumor-bearing mice intraperitoneally 10 times to label all the proliferating (P) tumor cells. As priming irradiation, thermal neutrons alone or thermal neutrons with 10B-labeled sodium borocaptate (BSH) or dl-p-boronophenylalanine (BPA) were administered. The tumor-bearing mice then received a series of γ-ray radiation doses, 0 through 24 h after the priming irradiation. During this period, no BrdU was administered. Immediately after the second irradiation, the tumors were excised, minced, and trypsinized. Following incubation of tumor cells with cytokinesis blocker, the micronucleus (MN) frequency in cells without BrdU labeling (= Q cells at the time of priming irradiation) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU before the priming irradiation. To determine the BrdU-labeled cell ratios in the tumors at the time of the second irradiation, each group also included mice that were continuously administered BrdU until just before the second irradiation using mini-osmotic pumps which had been implanted subcutaneously 5 days before the priming irradiation.Results: In total cells, during the interval between the two irradiations, the tumor sensitivity to γ-rays relative to that immediately after priming irradiation decreased with the priming irradiation ranking in the following order: thermal neutrons only > thermal neutrons with BSH > thermal neutrons with BPA. In contrast, in Q cells, during that time the sensitivity increased in the following order: thermal neutrons only < thermal neutrons with BSH < thermal neutrons with BPA. The longer the interval between the two irradiations, the higher was the BrdU-labeled cell ratio at the second irradiation. The labeled cell ratio at the same time point after each priming irradiation increased in the following order: thermal neutrons only < thermal neutrons with BSH < thermal neutrons with BPA.Conclusion: These findings indicated that the use of 10B-compound, especially BPA, in thermal neutron irradiation causes the recruitment from the Q to P population.

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Research paper thumbnail of Time-course Change in Oxygenation Status of Total and Quiescent Cell Populations in Solid Tumors after γ-ray Irradiation, Tirapazamine Injection or Cisplatin Treatment

Journal of Radiation Research, Dec 1, 1998

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Research paper thumbnail of Clinical Experience with Bnct for Malignant Brain Tumors

Advances in Neutron Capture Therapy, 1993

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Research paper thumbnail of Boron neutron capture therapy: Preliminary study of BNCT with sodium borocaptate (Na 2 B 12 H 11 SH) on glioblastoma

J Neuro Oncol, 1997

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Research paper thumbnail of Boron Neutron Capture Therapy (BNCT) for Malignant Glioma using ^ B-BPA

Journal of Radiation Research, Dec 1, 1994

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Research paper thumbnail of Determination and Drug Modification Assessed by Micronucleus Frequency Assay of Potentially Lethal Damege Repair in Quiescent Cell Populations within Murine Solid Tumors

Radiation Medicine Medical Imaging and Radiation Oncology, 1997

We investigated potentially lethal damage repair (PLDR) by quiescent (Q) tumor cells in vivo. SCC... more We investigated potentially lethal damage repair (PLDR) by quiescent (Q) tumor cells in vivo. SCC VII tumor-bearing C3H/He mice were irradiated with 60Co gamma-rays after being given 10 injections of 5-bromo-2&#39;-deoxyuridine (BrdU) to label all proliferating (P) cells in their tumors, and the tumors were than excised and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (Cyt-B, a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling was determined using immunofluorescence staining for BrdU. Thus, the MN frequency was determined for cells not labeled by BrdU; for all practical purposes, such cells can be regarded as the Q cells in a tumor. The MN frequency in the total (P + Q) tumor cell population was determined from irradiated tumors that were not pretreated with BrdU. Assays were performed immediately after irradiation alone, 24 hours after the injection of cis-diaminedichloroplatinum(II) (CDDP), mitomycin C (MMC), misonidazole [1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol] (MISO), 3-aminobenzamide (3-AB), camptothecin (CPT) or caffeine (CAF) following irradiation, and 24 hours after irradiation alone. Q cells were more radioresistant and had a greater capacity for PLDR than the tumor cell population as a whole. CDDP and MISO (especially the latter) inhibited PLDR more strongly in Q cells than in the tumor cell population as a whole. However, CPT and CAF exerted similar inhibition of PLDR in Q cells and in the tumor cell population as a whole. This assay method appears to be useful for detecting the responses of Q tumor cells to various chemical agents.

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Research paper thumbnail of Alteration in the hypoxic fraction of quiescent cell populations by hyperthermia at mild temperatures

International Journal of Hyperthermia, 1997

We investigated oxygenation of quiescent (Q) tumour cells in vivo by mild heat treatment. C3H/He ... more We investigated oxygenation of quiescent (Q) tumour cells in vivo by mild heat treatment. C3H/He mice bearing SCC VII tumours received BrdU continuously for 5 days via implanted mini-osmotic pumps, to label all proliferating (P) cells. The tumours were then irradiated after treatment, and were excised, minced and trypsinized. The tumour cell suspension thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labelling was determined using immunofluorescence staining for BrdU. This MN frequency was then used to calculate the surviving fraction of unlabelled cells from the regression line for the relationship between the MN frequency and the surviving fraction of total (P + Q) tumour cells. Thus, a cell survival curve could be determined for the cells not labelled with BrdU, which can be regarded as the Q cells in a tumour for all practical purposes. The MN frequency in total tumour cell population was determined from the irradiated tumours that were not pretreated with BrdU. Assays performed immediately after irradiation of both normally aerated and hypoxic tumours showed that Q cells contained higher hypoxic fractions than the total tumour cell population. Mild heat treatment (40.0 degrees C, 60 min) before irradiation decreased the hypoxic fraction, even when is was combined with nicotinamide administration. In contrast, mild heating did not decrease the hypoxic fraction when the mice were placed in a circulating carbogen (95% O2/5% CO2) chamber. Therefore, mild heat treatment was thought to preferentially oxygenate the chronically hypoxic fraction.

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Research paper thumbnail of Applicability of Combination with Tirapazamine in Boron Neutron Capture Therapy

Japanese Journal of Cancer Research Gann, Jul 1, 1998

SCC VII tumor-bearing mice were continuously given 5-bromo-2&#39;-deoxyuridine (BrdU) to labe... more SCC VII tumor-bearing mice were continuously given 5-bromo-2&#39;-deoxyuridine (BrdU) to label all proliferating cells. After injection of tirapazamine (TPZ), a bioreductive agent, combined with sodium borocaptate-10B (BSH) or dl-p-boronophenylalanine-10B (BPA) administration, the tumors were irradiated with thermal neutrons, and then isolated and incubated with cytochalasin-B (a cytokinesis blocker). The micronucleus (MN) frequency in cells without BrdU labeling (quiescent (Q) cells) was determined by means of immunofluorescence staining for BrdU, and that for total cells was obtained from tumors not pretreated with BrdU. Even when no 10B-compound was administered, TPZ increased the MN frequency of tumor cells including Q cells, resulting in reduction of the difference in MN frequency between total and Q cells, mainly by increasing the MN frequency of Q cells. TPZ increased the MN frequency of Q cells when combined with BPA administration, but TPZ showed no apparent effect on each cell population when combined with BSH. Namely, TPZ reduced the difference in MN frequency between total and Q cells caused by 10B-compound administration, especially when BPA was administered. From the viewpoint of the overall cell killing effect in boron neutron capture therapy (BNCT), combination with TPZ appeared to be useful in BPA-BNCT, but not in BSH-BNCT.

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Research paper thumbnail of Physical and Biological Characteristics of the Neutron Beam from Remodeled Heavy Water Facility of Kyoto University Research Reactor

Journal of Radiation Research, Dec 1, 1997

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Research paper thumbnail of Effectiveness of Borocaptate Sodium for Boron Neutron Capture Therapy in Malignant Brain Tumors

Cancer Neutron Capture Therapy, 1996

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Research paper thumbnail of Mutagenic Effects at HPRT Locus in Chinese Hamster Ovary (CHO) Cells Induced by Epi-Thermal and Thermal Neutrons

Frontiers in Neutron Capture Therapy, 2001

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Research paper thumbnail of Boron neutron capture therapy: preliminary study of BNCT with sodium borocaptate (Na2B1 2H1 1SH) on glioblastoma

Journal of neuro-oncology, 1997

To plan the optimal BNCT using BSH for glioblastoma patients, the 10B concentration in tumor and ... more To plan the optimal BNCT using BSH for glioblastoma patients, the 10B concentration in tumor and blood was investigated in 11 newly diagnosed glioblastoma patients. All patients received 20 mg BSH/kg body weight 2.5-16 hrs prior to tumor removal. The quantitative distribution of 10B was determined by prompt gamma ray spectrometry and/or alpha-track autoradiography. 10B distribution in tumors was heterogeneous, +/- 25% of scattering at the microscopic level, and the distribution was also heterogeneous at the tissue level. 10B concentration in blood decreased in bi-exponential decay as a function of the time after the end of the administration. The T/B ratio showed non-exponential increase with large variation. The maximum T/B ratio would be around 1. The tumor/normal brain (T/N) ratio of 10B concentration was 11.0 +/- 3.2. The 10B content in normal brain is originated in vascular 10B in parenchyma, since the 10B content in normal brain to blood (N/B ratio) being compatible with the b...

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Research paper thumbnail of Reduction of hypoxic cells in solid tumours induced by mild hyperthermia: special reference to differences in changes in the hypoxic fraction between total and quiescent cell populations

British journal of cancer, 1997

C3H/He mice bearing SCC VII tumours received 5-bromo-2'-deoxyuridine (BrdU) continuously for ... more C3H/He mice bearing SCC VII tumours received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps in order to label all proliferating (P) cells. The tumours were then heated at 40 degrees C for 60 min. At various time points after heating, tumour-bearing mice were irradiated while alive or after being killed. Immediately after irradiation, the tumours were excised, minced and trypsinized. The tumour cell suspensions obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labelling, which could be regarded as quiescent (Q) cells, was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P+Q) tumour cell population was determined from the irradiated tumours that were not pretreated with BrdU. The MN frequency of BrdU unlabelled cells was then used to calculate the surviving fraction of the unlabelled cells from the regression line for the relati...

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Research paper thumbnail of Mutagenic effects at HPRT locus induced in Chinese hamster ovary cells by thermal neutrons with or without boron compound

Mutation research, Jan 3, 1997

CHO cells were exposed to thermal neutrons and their mutation frequency was determined. The Kyoto... more CHO cells were exposed to thermal neutrons and their mutation frequency was determined. The Kyoto University Research Reactor (KUR), which has a very low level of contamination by gamma-rays and fast neutrons was used as a thermal neutron source. Cells were irradiated in the presence or absence of boric acid to determine mutation frequency and cell survival. Thermal neutron irradiation was 2.5 times as mutagenic as gamma-irradiation without boron. In the presence of boron, however, thermal neutron irradiation was from 4.2 to 4.5 times as mutagenic as gamma-irradiation. When the mutation frequency was plotted against the survival fraction, a higher degree of mutagenicity was observed in the presence than in the absence of boron. These results suggest that the enhancement of thermal neutron-induced mutation with boron is strongly associated with alpha-particles released by 10B(n, alpha)7 Li reaction.

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Research paper thumbnail of Alpha (α-) and beta (β-carboranyl-C-deoxyribosides: Syntheses, structures and biological evaluation

European Journal of Medicinal Chemistry, 2014

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

Journal of cancer research and clinical oncology, 2003

We evaluated the potential of a newly developed (10)B-containing alpha-amino alcohol of p-boronop... more 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. 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 determine...

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Research paper thumbnail of Contents, Vol. 40, 1994

Chemotherapy, 1994

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Research paper thumbnail of Boron Neutron Capture Therapy (BNCT) for Malignant Glioma using ^ B-BPA

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Future Applications of Boron and Gadolinium Neutron Capture Therapy

New Technologies and Applications, 2011

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Research paper thumbnail of Potentially lethal damage repair by total and quiescent tumor cells following various DNA-damaging treatments

Radiation Medicine Medical Imaging and Radiation Oncology, 1999

After continuous labeling of proliferating (P) cells with 5-bromo-2&#39;-deoxyuridine (BrdU) ... more After continuous labeling of proliferating (P) cells with 5-bromo-2&#39;-deoxyuridine (BrdU) for 5 days, SCC VII tumor-bearing mice received various kinds of DNA-damaging treatments: gamma-ray irradiation, tirapazamine (TPZ, hypoxia-specific cytotoxin) administration, or cisplatin injection. From 0.5 to 72 hr after treatment, tumors were excised, minced, and trypsinized. Single tumor cell suspensions were incubated for 48 hr with a cytokinesis-blocker, cytochalasin-B. Then, the micronucleus (MN) frequency for BrdU-unlabeled cells, quiescent (Q) cells at treatment, was determined using immunofluorescence staining for BrdU. The MN frequency for total (P+Q) cells was obtained from tumors that were not pretreated with BrdU labeling. The sensitivity to each DNA-damaging treatment was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency). Treatment with gamma-rays or cisplatin resulted in a larger MN frequency in total cells than in Q cells. In contrast, TPZ treatment produced a smaller MN frequency in total cells than in Q cells. Regardless of the treatment used, Q cells showed greater repair capacities than total cells. However, TPZ caused much smaller repair capacity in both total and Q cells, compared with gamma-rays or cisplatin. Gamma-rays and cisplatin produced similar repair patterns. Differences in sensitivity between total and Q cells and repair patterns of the two cell populations were thought to depend on differences between the two cell populations in the toxicity of the DNA-damaging treatment and distribution pattern of the anticancer agent.

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Research paper thumbnail of Alteration of sensitivity of intratumor quiescent and total cells to γ-rays following thermal neutron irradiation with or without 10B-compound

Int J Radiat Oncol Biol Phys, 2000

Purpose: Changes in the sensitivity of intratumor quiescent (Q) and total cells to γ-rays followi... more Purpose: Changes in the sensitivity of intratumor quiescent (Q) and total cells to γ-rays following thermal neutron irradiation with or without 10B-compound were examined.Methods and Materials: 5-Bromo-2′-deoxyuridine (BrdU) was injected to SCC VII tumor-bearing mice intraperitoneally 10 times to label all the proliferating (P) tumor cells. As priming irradiation, thermal neutrons alone or thermal neutrons with 10B-labeled sodium borocaptate (BSH) or dl-p-boronophenylalanine (BPA) were administered. The tumor-bearing mice then received a series of γ-ray radiation doses, 0 through 24 h after the priming irradiation. During this period, no BrdU was administered. Immediately after the second irradiation, the tumors were excised, minced, and trypsinized. Following incubation of tumor cells with cytokinesis blocker, the micronucleus (MN) frequency in cells without BrdU labeling (= Q cells at the time of priming irradiation) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU before the priming irradiation. To determine the BrdU-labeled cell ratios in the tumors at the time of the second irradiation, each group also included mice that were continuously administered BrdU until just before the second irradiation using mini-osmotic pumps which had been implanted subcutaneously 5 days before the priming irradiation.Results: In total cells, during the interval between the two irradiations, the tumor sensitivity to γ-rays relative to that immediately after priming irradiation decreased with the priming irradiation ranking in the following order: thermal neutrons only > thermal neutrons with BSH > thermal neutrons with BPA. In contrast, in Q cells, during that time the sensitivity increased in the following order: thermal neutrons only < thermal neutrons with BSH < thermal neutrons with BPA. The longer the interval between the two irradiations, the higher was the BrdU-labeled cell ratio at the second irradiation. The labeled cell ratio at the same time point after each priming irradiation increased in the following order: thermal neutrons only < thermal neutrons with BSH < thermal neutrons with BPA.Conclusion: These findings indicated that the use of 10B-compound, especially BPA, in thermal neutron irradiation causes the recruitment from the Q to P population.

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Research paper thumbnail of Time-course Change in Oxygenation Status of Total and Quiescent Cell Populations in Solid Tumors after γ-ray Irradiation, Tirapazamine Injection or Cisplatin Treatment

Journal of Radiation Research, Dec 1, 1998

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Research paper thumbnail of Clinical Experience with Bnct for Malignant Brain Tumors

Advances in Neutron Capture Therapy, 1993

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Boron neutron capture therapy: Preliminary study of BNCT with sodium borocaptate (Na 2 B 12 H 11 SH) on glioblastoma

J Neuro Oncol, 1997

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Research paper thumbnail of Boron Neutron Capture Therapy (BNCT) for Malignant Glioma using ^ B-BPA

Journal of Radiation Research, Dec 1, 1994

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Research paper thumbnail of Determination and Drug Modification Assessed by Micronucleus Frequency Assay of Potentially Lethal Damege Repair in Quiescent Cell Populations within Murine Solid Tumors

Radiation Medicine Medical Imaging and Radiation Oncology, 1997

We investigated potentially lethal damage repair (PLDR) by quiescent (Q) tumor cells in vivo. SCC... more We investigated potentially lethal damage repair (PLDR) by quiescent (Q) tumor cells in vivo. SCC VII tumor-bearing C3H/He mice were irradiated with 60Co gamma-rays after being given 10 injections of 5-bromo-2&#39;-deoxyuridine (BrdU) to label all proliferating (P) cells in their tumors, and the tumors were than excised and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (Cyt-B, a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling was determined using immunofluorescence staining for BrdU. Thus, the MN frequency was determined for cells not labeled by BrdU; for all practical purposes, such cells can be regarded as the Q cells in a tumor. The MN frequency in the total (P + Q) tumor cell population was determined from irradiated tumors that were not pretreated with BrdU. Assays were performed immediately after irradiation alone, 24 hours after the injection of cis-diaminedichloroplatinum(II) (CDDP), mitomycin C (MMC), misonidazole [1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol] (MISO), 3-aminobenzamide (3-AB), camptothecin (CPT) or caffeine (CAF) following irradiation, and 24 hours after irradiation alone. Q cells were more radioresistant and had a greater capacity for PLDR than the tumor cell population as a whole. CDDP and MISO (especially the latter) inhibited PLDR more strongly in Q cells than in the tumor cell population as a whole. However, CPT and CAF exerted similar inhibition of PLDR in Q cells and in the tumor cell population as a whole. This assay method appears to be useful for detecting the responses of Q tumor cells to various chemical agents.

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Research paper thumbnail of Alteration in the hypoxic fraction of quiescent cell populations by hyperthermia at mild temperatures

International Journal of Hyperthermia, 1997

We investigated oxygenation of quiescent (Q) tumour cells in vivo by mild heat treatment. C3H/He ... more We investigated oxygenation of quiescent (Q) tumour cells in vivo by mild heat treatment. C3H/He mice bearing SCC VII tumours received BrdU continuously for 5 days via implanted mini-osmotic pumps, to label all proliferating (P) cells. The tumours were then irradiated after treatment, and were excised, minced and trypsinized. The tumour cell suspension thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labelling was determined using immunofluorescence staining for BrdU. This MN frequency was then used to calculate the surviving fraction of unlabelled cells from the regression line for the relationship between the MN frequency and the surviving fraction of total (P + Q) tumour cells. Thus, a cell survival curve could be determined for the cells not labelled with BrdU, which can be regarded as the Q cells in a tumour for all practical purposes. The MN frequency in total tumour cell population was determined from the irradiated tumours that were not pretreated with BrdU. Assays performed immediately after irradiation of both normally aerated and hypoxic tumours showed that Q cells contained higher hypoxic fractions than the total tumour cell population. Mild heat treatment (40.0 degrees C, 60 min) before irradiation decreased the hypoxic fraction, even when is was combined with nicotinamide administration. In contrast, mild heating did not decrease the hypoxic fraction when the mice were placed in a circulating carbogen (95% O2/5% CO2) chamber. Therefore, mild heat treatment was thought to preferentially oxygenate the chronically hypoxic fraction.

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Research paper thumbnail of Applicability of Combination with Tirapazamine in Boron Neutron Capture Therapy

Japanese Journal of Cancer Research Gann, Jul 1, 1998

SCC VII tumor-bearing mice were continuously given 5-bromo-2&#39;-deoxyuridine (BrdU) to labe... more SCC VII tumor-bearing mice were continuously given 5-bromo-2&#39;-deoxyuridine (BrdU) to label all proliferating cells. After injection of tirapazamine (TPZ), a bioreductive agent, combined with sodium borocaptate-10B (BSH) or dl-p-boronophenylalanine-10B (BPA) administration, the tumors were irradiated with thermal neutrons, and then isolated and incubated with cytochalasin-B (a cytokinesis blocker). The micronucleus (MN) frequency in cells without BrdU labeling (quiescent (Q) cells) was determined by means of immunofluorescence staining for BrdU, and that for total cells was obtained from tumors not pretreated with BrdU. Even when no 10B-compound was administered, TPZ increased the MN frequency of tumor cells including Q cells, resulting in reduction of the difference in MN frequency between total and Q cells, mainly by increasing the MN frequency of Q cells. TPZ increased the MN frequency of Q cells when combined with BPA administration, but TPZ showed no apparent effect on each cell population when combined with BSH. Namely, TPZ reduced the difference in MN frequency between total and Q cells caused by 10B-compound administration, especially when BPA was administered. From the viewpoint of the overall cell killing effect in boron neutron capture therapy (BNCT), combination with TPZ appeared to be useful in BPA-BNCT, but not in BSH-BNCT.

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Research paper thumbnail of Physical and Biological Characteristics of the Neutron Beam from Remodeled Heavy Water Facility of Kyoto University Research Reactor

Journal of Radiation Research, Dec 1, 1997

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Research paper thumbnail of Effectiveness of Borocaptate Sodium for Boron Neutron Capture Therapy in Malignant Brain Tumors

Cancer Neutron Capture Therapy, 1996

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Mutagenic Effects at HPRT Locus in Chinese Hamster Ovary (CHO) Cells Induced by Epi-Thermal and Thermal Neutrons

Frontiers in Neutron Capture Therapy, 2001

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Boron neutron capture therapy: preliminary study of BNCT with sodium borocaptate (Na2B1 2H1 1SH) on glioblastoma

Journal of neuro-oncology, 1997

To plan the optimal BNCT using BSH for glioblastoma patients, the 10B concentration in tumor and ... more To plan the optimal BNCT using BSH for glioblastoma patients, the 10B concentration in tumor and blood was investigated in 11 newly diagnosed glioblastoma patients. All patients received 20 mg BSH/kg body weight 2.5-16 hrs prior to tumor removal. The quantitative distribution of 10B was determined by prompt gamma ray spectrometry and/or alpha-track autoradiography. 10B distribution in tumors was heterogeneous, +/- 25% of scattering at the microscopic level, and the distribution was also heterogeneous at the tissue level. 10B concentration in blood decreased in bi-exponential decay as a function of the time after the end of the administration. The T/B ratio showed non-exponential increase with large variation. The maximum T/B ratio would be around 1. The tumor/normal brain (T/N) ratio of 10B concentration was 11.0 +/- 3.2. The 10B content in normal brain is originated in vascular 10B in parenchyma, since the 10B content in normal brain to blood (N/B ratio) being compatible with the b...

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Research paper thumbnail of Reduction of hypoxic cells in solid tumours induced by mild hyperthermia: special reference to differences in changes in the hypoxic fraction between total and quiescent cell populations

British journal of cancer, 1997

C3H/He mice bearing SCC VII tumours received 5-bromo-2'-deoxyuridine (BrdU) continuously for ... more C3H/He mice bearing SCC VII tumours received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps in order to label all proliferating (P) cells. The tumours were then heated at 40 degrees C for 60 min. At various time points after heating, tumour-bearing mice were irradiated while alive or after being killed. Immediately after irradiation, the tumours were excised, minced and trypsinized. The tumour cell suspensions obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labelling, which could be regarded as quiescent (Q) cells, was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P+Q) tumour cell population was determined from the irradiated tumours that were not pretreated with BrdU. The MN frequency of BrdU unlabelled cells was then used to calculate the surviving fraction of the unlabelled cells from the regression line for the relati...

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Research paper thumbnail of Mutagenic effects at HPRT locus induced in Chinese hamster ovary cells by thermal neutrons with or without boron compound

Mutation research, Jan 3, 1997

CHO cells were exposed to thermal neutrons and their mutation frequency was determined. The Kyoto... more CHO cells were exposed to thermal neutrons and their mutation frequency was determined. The Kyoto University Research Reactor (KUR), which has a very low level of contamination by gamma-rays and fast neutrons was used as a thermal neutron source. Cells were irradiated in the presence or absence of boric acid to determine mutation frequency and cell survival. Thermal neutron irradiation was 2.5 times as mutagenic as gamma-irradiation without boron. In the presence of boron, however, thermal neutron irradiation was from 4.2 to 4.5 times as mutagenic as gamma-irradiation. When the mutation frequency was plotted against the survival fraction, a higher degree of mutagenicity was observed in the presence than in the absence of boron. These results suggest that the enhancement of thermal neutron-induced mutation with boron is strongly associated with alpha-particles released by 10B(n, alpha)7 Li reaction.

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Research paper thumbnail of Alpha (α-) and beta (β-carboranyl-C-deoxyribosides: Syntheses, structures and biological evaluation

European Journal of Medicinal Chemistry, 2014

Bookmarks Related papers MentionsView impact

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

Journal of cancer research and clinical oncology, 2003

We evaluated the potential of a newly developed (10)B-containing alpha-amino alcohol of p-boronop... more 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. 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 determine...

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