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ABSTRACT: Photodynamic therapy (PDT) is a recently developed anticancer treatment that utilizes the generation of singlet oxygen and other reactive oxygen species in cancer tissue. In response to oxidative stress, NF-E2-related transcription factor (Nrf2) encoded by the NFE2L2 gene plays a key role in transcriptional upregulation of many target genes, including those for metabolizing enzymes and transporters essential for cellular defense. Recent studies have provided evidence that Nrf2 regulates the transcription of the human ABC transporter ABCG2 gene, which is critically involved in the cellular accumulation of porphyrins in PDT. Nrf2 interacts with the antioxidant responsive element (ARE) located in the promoter region of human ABCG2 gene. Nrf2-specific siRNA treatments suppressed the induction of ABCG2 expression after the photoactivation of porphyrins in vitro. One SNP (-617C>A; rs6721961) in the ARE-like loci of the human Nrf2 gene is considered to affect the positive feedback loop of transcriptional activation of the Nrf2 gene as well as its target genes including ABCG2. Since patients have demonstrated individual differences in their response to PDT, Nrf2-mediated transcriptional activation of the ABCG2 gene in cancer may affect patients' responses to PDT as well as chemotherapy. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
Journal of Pharmaceutical Sciences 05/2013; · 3.06 Impact Factor
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ABSTRACT: Background
Bevacizumab, an anti-vascular endothelial growth factor antibody, has been used for the treatment of radiation necrosis. Thus far, however, there has been no definitive report on its use for the treatment of symptomatic pseudoprogression. Here we report 2 cases of successful treatment with bevacizumab for symptomatic pseudoprogression after boron neutron capture therapy (BNCT) was applied for recurrent malignant gliomas.Methods
Two recurrent malignant gliomas received BNCT. Both cases were treated with intravenous administration of bevacizumab at the deterioration that seemed to be symptomatic pseudoprogression.ResultsThe first case was recurrent glioblastoma multiforme and the second was recurrent anaplastic oligoastrocytoma. Both cases recurred after standard chemoradiotherapy and were referred to our institute for BNCT, which is tumor-selective particle radiation. Just prior to neutron irradiation, PET with an amino acid tracer was applied in each case to confirm tumor recurrence. Both cases showed deterioration in symptoms, as well as on MRI, at intervals of 4 months and 2 months, respectively, after BNCT. For the first case, a second PET was applied in order to confirm no increase in tracer uptake. We diagnosed both cases as symptomatic pseudoprogression and started the intravenous administration of 5 mg/kg bevacizumab biweekly with 6 cycles. Both cases responded well to this, showing rapid and dramatic improvement in neuroimaging and clinical symptoms. No tumor progression was observed 8 months after BNCT.Conclusions
Bevacizumab showed marked effects on symptomatic pseudoprogression after BNCT. BNCT combined with bevacizumab may prolong the survival of patients with recurrent malignant gliomas.
Neuro-Oncology 03/2013; · 5.72 Impact Factor
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ABSTRACT: Since the ATP-binding cassette transporter ABCG2 plays a physiologically significant role of porphyrin efflux from living cells, the expression of ABCG2 may influences the efficacy of photodynamic therapy (PDT). In this study, we evaluated the effect of gefitinib, a potent ABCG2 inhibitor, on 5-aminolevulinic acid (5-ALA)-PDT in brain tumor cell lines in vitro.
Four human glioma cell lines (U87MG, U118MG, A172, and T98G) and a malignant meningioma cell line (IOMM-Lee) were incubated with gefitinib (0.01-1.0μM) before incubation with 5-ALA (1mM). The effects gefitinib on intracellular protoporphyrin IX (PpIX), mRNA and protein expression of ABCG2, and PDT were evaluated, in vitro.
At concentrations of 0.1μM or higher, gefitinib enhanced intracellular levels of PpIX in a dose-dependent manner in all those cell lines. Gefitinib decreased mRNA and plasma membrane protein expression of ABCG2, and efficiently enhanced the effect of 5-ALA-PDT in malignant brain tumor cells.
Gefitinib can inhibit ABCG2-mediated PpIX efflux from malignant brain tumor cells to increase the intracellular PpIX and thereby enhance the PDT effect.
Photodiagnosis and photodynamic therapy 02/2013; 10(1):42-50.
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ABSTRACT: Bevacizumab is effective in treating radiation necrosis; however, radiation necrosis was not definitively diagnosed in most previous reports. Here we used amino acid positron emission tomography to diagnose radiation necrosis for the application of bevacizumab in treating progressive radiation necrosis. Lesion/normal tissue ratios of <2.5 on (18)fluoride-labeled boronophenylalanine-positron emission tomography were defined as an indication of effective bevacizumab treatment. Thirteen patients were treated with bevacizumab at a dose of 5 mg/kg every 2 weeks. Two patients were excluded because of adverse events. The median reduction rate in perilesional edema was 65.5%. Karnofsky performance status improved in six patients after bevacizumab treatment. Lesion/normal tissue ratios on (18)fluoride-labeled boronophenylalanine-positron emission tomography (P = 0.0084) and improvement in Karnofsky performance status after bevacizumab treatment (P = 0.0228) were significantly associated with reduced rates of perilesional edema. Thus, (18)fluoride-labeled boronophenylalanine-positron emission tomography could be useful for diagnosing radiation necrosis and predicting the efficacy of bevacizumab in progressive radiation necrosis.
Japanese Journal of Clinical Oncology 01/2013; · 1.78 Impact Factor
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Shin-Ichi Miyatake,
Shinji Kawabata,
Kunio Yokoyama,
Toshihiko Kuroiwa,
Hiroyuki Michiue,
Yoshinori Sakurai,
Hiroaki Kumada,
Minoru Suzuki,
Akira Maruhashi,
Mitsunori Kirihata,
Koji Ono
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ABSTRACT: We have applied boron neutron capture therapy (BNCT) to malignant brain tumors. Here we evaluated the survival benefit of
BNCT for recurrent malignant glioma (MG). Since 2002, we have treated 22 cases of recurrent MG with BNCT. Survival time was
analyzed with special reference to recursive partitioning analysis (RPA) classification, by Carson etal. (J Clin Oncol 25:2601–2606,
2007). Median survival times (MSTs) after BNCT for all patients and for glioblastoma as on-study histology at recurrence was
10.8months (n=22; 95% CI, 7.3–12.8months) and 9.6months (n=19; 95% CI, 6.9–11.4months), respectively. In our study, MST for the high-risk RPA classes was 9.1months (n=11; 95% CI, 4.4–11.0months). By contrast, the original journal data showed that the MST of the same RPA classes was 4.4months
(n=129; 95% CI, 3.6–5.4months). BNCT showed a survival benefit for recurrent MG, especially in the high-risk group.
Journal of Neuro-Oncology 04/2012; 91(2):199-206. · 3.21 Impact Factor
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11/2011; , ISBN: 978-953-307-284-5
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ABSTRACT: In photodynamic diagnosis, 5-aminolevulinic acid (5-ALA) is widely used for the fluorescence-guided resection of malignant brain tumors, where 5-ALA is converted to protoporphyrin IX, which exhibits strong fluorescence. Little is known, however, about the detailed molecular mechanisms underlying 5-ALA-induced fluorescence. To resolve this issue, we analyzed transcriptome profiles for the genes encoding enzymes, transporters, and a transcription factor involved in the porphyrin-biosynthesis pathway. By quantitative real-time (qRT)-PCR, we measured the mRNA levels of those genes in a total of 20 tumor samples that had been surgically resected from brain tumor patients at the Department of Neurosurgery of Osaka Medical College from 2008 to 2009. We selected 10 tumor samples with no 5-ALA-induced fluorescence, among which 2 were glioblastomas and 8 were metastatic brain tumors. Another 10 tumor samples were selected with strong fluorescence, among which 7 were glioblastomas and 3 were metastatic brain tumors. The qRT-PCR analysis study of these latter 10 samples revealed predominantly high levels of the mRNA of the coproporphyrinogen oxidase (CPOX) gene. The high mRNA level of CPOX expression was significantly well correlated with the phenotype of strong 5-ALA-induced fluorescence (P = .0003). These findings were further confirmed by immunohistochemical studies with a CPOX-specific antibody. It is concluded that induction of CPOX gene expression is one of the key molecular mechanisms underlying the 5-ALA-induced fluorescence of malignant brain tumors. The induction mechanism for the CPOX gene in brain tumors remains to be elucidated.
Neuro-Oncology 08/2011; 13(11):1234-43. · 5.72 Impact Factor
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ABSTRACT: The cell type and localization of vascular endothelial growth factor (VEGF)-producing cells in human radiation necrosis (RN) are investigated from a histopathological and immunohistochemical standpoint using clinical specimens. Eighteen surgical specimens of symptomatic RN in the brain were retrospectively reviewed. These cases included different original histological tumor types and were treated with different radiation modalities. Histological analyses were performed using hematoxylin and eosin (H&E) staining, and anti-VEGF and anti-hypoxia-inducible factor (HIF)-1α immunohistochemistry. H&E staining showed marked angiogenesis and reactive astrocytosis at the perinecrotic area. The most prominent vasculature in this area was identified as telangiectasis. Immunohistochemistry indicated that HIF-1α was expressed predominantly in the perinecrotic area and that a large majority of VEGF-expressing cells were reactive astrocytes intensively distributed in this area. VEGF produced by the reactive astrocytes localized mainly in the perinecrotic area might be a major cause of both angiogenesis and the subsequent perilesional edema typically found in RN of the brain. The benefits of anti-VEGF antibody (bevacizumab) treatment in RN may be that VEGF secretion from the perinecrotic tissue is inhibited and that surgery would remove this tissue; both of these benefits result in effective reduction of edema associated with RN.
Journal of Neuro-Oncology 06/2011; 105(2):423-31. · 3.21 Impact Factor
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ABSTRACT: Bevacizumab is expected to constitute a new treatment modality for radiation necrosis. In the present cases, we observed a recurrence of radiation necrosis after temporary improvement by bevacizumab treatment. Re-treatment with bevacizumab controlled the necrosis again. A 39-year-old male and a 57-year-old female were diagnosed with glioblastoma and lung cancer metastasis, respectively. The former patient underwent partial resection of the glioblastoma, followed by boron neutron capture therapy (BNCT) and 30 Gy of fractionated X-ray radiotherapy. Eleven months after BNCT, he suffered from left hemiparesis and convulsions with enlargement of a perifocal edema. The latter patient underwent stereotactic radiosurgery twice for the same tumor. Three months after the second radiosurgery, she had an uncontrollable convulsion and right hemiplegia with a massive perifocal edema. Both lesions were suggested to be radiation necroses by positron emission tomography using amino acids as a tracer. Neither patient responded to corticosteroids, anticoagulants, or vitamin E. They underwent treatment with 5 mg/kg bevacizumab biweekly, for a total of 6 cycles. The size of the perifocal edema was clearly reduced in response to the treatments. The neurological status of the patients improved concomitant with therapy. However, the clinical status of both patients was aggravated several months after the bevacizumab was stopped, and the perifocal edemas enlarged again. The patients underwent a second treatment with bevacizumab, and the perifocal edemas again decreased. Although radiation necrosis may recur several months after bevacizumab treatment, repeated bevacizumab treatments also appear to be effective.
Journal of Neuro-Oncology 05/2011; 102(3):471-5. · 3.21 Impact Factor
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ABSTRACT: The present study aimed to demonstrate the features of fluorine-18-labeled boronophenylalanine positron emission tomography ((18)F-BPA-PET) to reveal oral cancer, as well as normal structures in the oral and maxillofacial regions. We analyzed (18)F-BPA-PET findings from 8 patients with histologically confirmed recurrent and/or advanced oral cancer scheduled for boron neutron capture therapy. The capacity of (18)F-BPA-PET to delineate tumor and normal structures was assessed qualitatively and quantitatively. Tumors were easily identified as high uptake areas in all cases. Although the eyes, which were depicted as a low uptake area, and tongue musculature were readily identified, major vessels were not noted in any of the cases. Areas corresponding to the surface of the dorsum tongue to middle pharynx were expressed as high uptake areas in all of the cases. Quantitatively, tumors were expressed as the highest uptake area in 6 of the 8 cases, while the dorsum tongue had the highest uptake area in the remaining 2 cases. (18)F-BPA-PET is useful in demonstrating the presence of a tumor. Thus, it is crucial to note the presence of a high uptake area corresponding to the dorsum area of the tongue when diagnosing a tumor using this technique.
Oncology letters 05/2011; 2(3):423-427. · 0.11 Impact Factor
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Shinji Kawabata, Shin-Ichi Miyatake,
Ryo Hiramatsu,
Yuki Hirota,
Shiro Miyata,
Yoko Takekita,
Toshihiko Kuroiwa,
Mitsunori Kirihata,
Yoshinori Sakurai,
Akira Maruhashi,
Koji Ono
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ABSTRACT: Recently, we reported our clinical experiences of boron neutron capture therapy (BNCT) for the newly diagnosed glioblastoma. The major differences of our protocol from the other past studies were simultaneous use of both sodium borocapate and boronophenylalanine, and combination with fractionated X-ray irradiation. These results showed the efficacy of combination therapy with external beam X-ray irradiation and BNCT. For our future study, we planned the multi-centric phase II clinical study for newly diagnosed glioblastoma patients in Japan (OSAKA-TRIBRAIN0902, NCT00974987).
Applied radiation and isotopes: including data, instrumentation and methods for use in agriculture, industry and medicine 03/2011; 69(12):1796-9. · 1.09 Impact Factor
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ABSTRACT: Boronated porphyrins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and easy synthesis with high boron content. Octa-anionic 5,10,15,20-tetra[3,5-(nido-carboranylmethyl)phenyl] porphyrin (H₂OCP) is a boronated porphyrin having eight boron clusters linked to the porphyrin ring. To evaluate H₂OCP's applicability to both PDT and BNCT, we performed an in vitro and ex vivo study using F98 rat glioma cells.
We examined the time-dependent cellular uptake of H₂OCP by measuring the boron concentration over time, and compared the cellular uptake/clearance of boron after exposure to H₂OCP in conjunction with boronophenylalanine (BPA) and sodium borocaptate (BSH), both of which are currently used in clinical BNCT studies. We evaluated the cytotoxicity of H₂OCP-mediated PDT using a colony-forming assay and assessed the tumorigenicity of the implantation of pre-treated cells using Kaplan-Meier survival curves. Fluorescence microscopy was also performed to evaluate the cellular uptake of H₂OCP.
H₂OCP accumulated within cells to a greater extent than BPA/BSH, and H₂OCP was retained inside the cells to approximately the same extent as BSH. The cell-surviving fraction following laser irradiation (8 J/cm², 18 hours after exposure to 10 µg B/ml H₂OCP) was <0.05. The median survival times of the pre-treated cell-implanted rats were longer than those of the untreated group (P < 0.05). The fluorescence of H₂OCP was clearly demonstrated within the tumor cells by fluorescence microscopy.
H₂OCP has been proven to be a promising photosensitizer for PDT. H₂OCP has also been proposed as a potentially effective replacement of BPA or BSH, or as a replacement of both BPA/BSH. Our study provides more evidence that H₂OCP could be an effective novel dual sensitizing agent for use in both PDT and BNCT.
Lasers in Surgery and Medicine 01/2011; 43(1):52-8. · 2.75 Impact Factor
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ABSTRACT: To achieve potent tumor-selective antitumor efficacy by boron neutron capture therapy (BNCT), it is important to have a significant differential uptake of 10B between tumor cells and normal cells. This should enable BNCT to reduce damage to normal tissues compared with other radiation therapies.
To augment the therapeutic efficacy of BNCT, we used transferrin-conjugated polyethylene glycol (PEG) (TF-PEG) liposome encapsulating sodium borocaptate and Iomeprol, an iodine contrast agent, with intratumoral convection-enhanced delivery (CED) in a rat glioma tumor model.
The in vitro (10)B concentration of F98 rat glioma cells was determined by inductively coupled plasma atomic emission spectrometry after incubation with either TF-PEG or PEG liposomes. For in vivo biodistribution studies, (10)B concentrations within blood, normal brain tissue, and intracerebrally transplanted F98 cells were measured with inductively coupled plasma-atomic emission spectrometry after CED of the compounds, and computed tomography was performed at selected time intervals.
(10)B concentrations of F98 cultured glioma cells in vitro 6 hours after exposure to PEG and TF-PEG liposome were 16.1 and 51.9 ng (10)B/10(6) cells, respectively. (10)B concentrations in F98 glioma tissue 24 hours after CED were 22.5 and 82.2 μg/g, by PEG and TF-PEG liposome, respectively, with lower (10)B concentrations in blood and normal brain. Iomeprol provided vivid and stable enhanced computed tomography imaging of the transplanted tumor even 72 hours after CED by TF-PEG liposome. Conversely, tissue enhancement had already washed out at 24 hours after CED of the PEG liposomes.
The combination of TF-PEG liposome encapsulating sodium borocaptate and Iomeprol and intratumoral CED enables not only a precise and potent targeting of boron delivery to the tumor tissue, but also the ability to follow the trace of boron delivery administered intratumorally by real-time computed tomography.
Neurosurgery 01/2011; 68(5):1380-7; discussion 1387. · 2.79 Impact Factor
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ABSTRACT: Systemic administration of high-dose recombinant human erythropoietin (rhEPO) is known to attenuate ischemic injury. However, high-dose rhEPO might aggravate ischemic lesions by increasing blood viscosity because of its erythropoietic effects. Asialoerythropoietin (asialoEPO), an EPO derivative with an extremely short plasma half-life, has considerably lesser erythropoietic effect than that of naive EPO. We attempted to determine whether asialoEPO exerts the same neuroprotective effect as naive EPO in a gerbil transient forebrain ischemia model.
Transient occlusion of both the common carotid arteries was performed in 23 adult gerbils. The drugs (asialoEPO or rhEPO, 10 U/g bodyweight) or phosphate-buffered saline (PBS) were injected intraperitoneally at three times (3 hours before, immediately after, and 24 hours after the ischemic insult). Learning and retention tests were performed on days 6 and 7, respectively, and histological analyses were performed on day 7.
Animals treated with asialoEPO and rhEPO showed significant neurological improvement compared to the PBS-treated animals. The number of viable neurons in the CA1 field of the rhEPO-treated (103.57 ± 27.90 cells/mm) and asialoEPO-treated (144.99 ± 34.87 cells/mm) animals was higher than that of the PBS-treated animals (19.53 ± 3.79 cells/mm). Terminal dinucleotidyltransferase-mediated UTP end labeling-positive cells were significantly lower in the rhEPO-treated (33.40 ± 8.13 cells/mm) and asialoEPO-treated (29.28 ± 14.91 cells/mm) animals than in the PBS-treated animals (76.67 ± 8.14 cells/mm). AsialoEPO treatment did not have any effect on erythropoiesis.
Multiple dosing of asialoEPO, like EPO, could protect the hippocampal CA1 neurons from ischemic damage without affecting erythropoiesis.
Neurological Research 05/2010; 32(9):957-62. · 1.52 Impact Factor
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ABSTRACT: The diverse characteristics of immunoliposomes provide advantages for utilization in drug delivery systems. In this study, we fused the antibody affinity motif of protein A (ZZ) with Gaussia luciferase (GLase). The fused protein conjugated with an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (GLase-ZZ-His-mAb) was effectively delivered into glioma cells expressing an activated EGFR mutant (EGFRvIII) and the bioluminescence was visualized in the cells. Immunoliposomes were further constructed with DSPE-PEG-MAL for covalent GLase-ZZ-His-mAb conjugation. A fluorescence dye (HPTS) encapsulated in immunoliposomes conjugated with GLase-ZZ-His-mAb was effectively delivered into EGFRvIII-expressing glioma cells. In a murine xenograft model of glioma, moreover, specific targeting of the immunoliposomes was visualized in the tumor. This new bifunctional immunoliposome system has the potential for drug delivery and imaging in vivo.
Biomaterials 02/2010; 31(14):4139-45. · 7.40 Impact Factor
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ABSTRACT: Accumulating evidence indicates that ATP-binding cassette (ABC) transporter ABCG2 plays a key role in regulating the cellular accumulation of porphyrin derivatives in cancer cells and thereby affects the efficacy of photodynamic therapy and photodynamic diagnosis. The activity of porphyrin efflux can be affected by genetic polymorphisms in the ABCG2 gene. On the other hand, Nrf2, an NF-E2-related transcription factor, has been shown to be involved in oxidative stress-mediated induction of the ABCG2 gene. Since patients have demonstrated individual differences in their response to photodynamic therapy, transcriptional activation and/or genetic polymorphisms of the ABCG2 gene in cancer cells may affect patients' responses to photodynamic therapy. Protein kinase inhibitors, including imatinib mesylate and gefitinib, are suggested to potentially enhance the efficacy of photodynamic therapy by blocking ABCG2-mediated porphyrin efflux from cancer cells. This review article provides an overview on the role of human ABC transporter ABCG2 in photodynamic therapy and photodynamic diagnosis.
Advances in Pharmacological Sciences 01/2010; 2010:587306.
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ABSTRACT: Conventionary, we use 5-aminolevulinic acid (5-ALA) for photo-dynamic diagnosis in the removal of malignant gliomas. 5-ALA is converted to protoporphyrin IX (PpIX) in the body and emits red fluorescence, with the excitation of blue-violet light. As PpIX preferentially accumulates in the tumor tissue in comparison with normal tissue, this red fluorescence becomes a good hallmark for discrimination between normal and tumor tissues, especially in malignant gliomas, which have infiltrative characteristics. Approximately 80% to 90% of the malignant gliomas show this red fluorescence in surgery as mentioned above, while only a limited number of metastatic brain tumor cases do. In the surgery for metastatic brain tumor and lesionectomy for radiation necrosis and neurodegenerative disease, white matter around the lesion showed vague fluorescence, which also provided us with a hallmark in the surgery. Additionally, in meningioma, some tumors showed the red fluorescence, which is especially helpful in the removal of the infiltrative portion in the bone and normal parenchyma. In this paper, we also discuss high quality international reserch on 5-ALA-guided surgery for malignant gliomas. The most important point in 5-ALA-guided microsurgery is the use of good equipment that can provide sufficient operative fields even under fluorescence mode.
Brain and nerve = Shinkei kenkyū no shinpo 08/2009; 61(7):835-42.
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Shin-Ichi Miyatake,
Shinji Kawabata,
Kunio Yokoyama,
Toshihiko Kuroiwa,
Hiroyuki Michiue,
Yoshinori Sakurai,
Hiroaki Kumada,
Minoru Suzuki,
Akira Maruhashi,
Mitsunori Kirihata,
Koji Onoc
[show abstract]
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ABSTRACT: We have applied boron neutron capture therapy (BNCT) to malignant brain tumors. Here we evaluated the survival benefit of BNCT for recurrent malignant glioma (MG). Since 2002, we have treated 22 cases of recurrent MG with BNCT. Survival time was analyzed with special reference to recursive partitioning analysis (RPA) classification, by Carson et al. Median survival times (MSTs) after BNCT for all patients and for glioblastoma as on-study histology at recurrence was 10.8 months (n=22; 95% CI, 7.3-12.8 months) and 9.6 months (n=19; 95% CI, 6.9-11.4 months), respectively. In our study, MST for the high-risk RPA classes was 9.1 months (n=11; 95% CI, 4.4-11.0 months). By contrast, the original journal data showed that the MST of the same RPA classes was 4.4 months (n=129; 95% CI, 3.6-5.4 months). BNCT showed a survival benefit for recurrent MG, especially in the high-risk group.
Applied radiation and isotopes: including data, instrumentation and methods for use in agriculture, industry and medicine 04/2009; 67(7-8 Suppl):S22-4. · 1.09 Impact Factor
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ABSTRACT: Pseudoprogression has been recognized and widely accepted in the treatment of malignant gliomas, as transient increases in the volume of the enhanced area just after chemoradiotherapy, especially using temozolomide. We experienced a similar phenomenon in the treatment of malignant gliomas and meningiomas using boron neutron capture therapy (BNCT), a cell-selective form of particle radiation. Here, we introduce representative cases and analyze the pathogenesis. Fifty-two cases of malignant glioma and 13 cases of malignant meningioma who were treated by BNCT were reviewed retrospectively mainly via MR images. Eleven of 52 malignant gliomas and 3 of 13 malignant meningiomas showed transient increases of enhanced volume in MR images within 3 months after BNCT. Among these cases, five patients with glioma underwent surgery because of suspicion of relapse. In histology, most of the specimens showed necrosis with small amounts of residual tumor cells. Ki-67 labeling showed decreased positivity compared with previous samples from the individuals. Fluoride-labeled boronophenylalanine PET was applied in four and two cases of malignant gliomas and meningiomas, respectively, at the time of transient increase of lesions. These PET scans showed decreased lesion:normal brain ratios in all cases compared with scans obtained prior to BNCT. With or without surgery, all lesions were decreased or stable in size during observation. Transient increases in enhanced volume in malignant gliomas and meningiomas immediately after BNCT seemed to be pseudoprogression. This pathogenesis was considered as treatment-related intratumoral necrosis in the subacute phase after BNCT.
Neuro-Oncology 04/2009; 11(4):430-6. · 5.72 Impact Factor
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Shinji Kawabata, Shin-Ichi Miyatake,
Naosuke Nonoguchi,
Ry Hiramatsu,
Kyoko Iida,
Shiro Miyata,
Kunio Yokoyama,
Atsushi Doi,
Yuzo Kuroda,
Toshihiko Kuroiwa,
Hiroyuki Michiue,
Hiroaki Kumada,
Mitsunori Kirihata,
Yoshio Imahori,
Akira Maruhashi,
Yoshinori Sakurai,
Minoru Suzuki,
Shin-Ichiro Masunaga,
Koji Ono
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ABSTRACT: Since 2002-2007, we applied boron neutron capture therapy (BNCT) to >50 cases of malignant gliomas (MGs) with epithermal neutron irradiations. Recently, we showed the early radiographical improvement of malignant glioma patients by our modified BNCT, with simultaneous use of BPA (borono-phenylalanine) and BSH (sodium borocaptate). In this time, we focused on the survival benefit from BNCT for the newly diagnosed glioblastoma patients.
BNCT group including 21 newly histological confirmed glioblastoma patients treated with surgical removal followed by BNCT in Osaka Medical College during 2002-2006 period. Ten patients were treated with BNCT only, and in the other 11 patients, 20-30 Gy fractionated external beam X-ray irradiation therapy (XRT) was performed after BNCT. No chemotherapy was administered until tumor progression was observed.
Treatments were well tolerated. Any kind of acute systemic or local severe toxicity were not demonstrated. Mean over all survival of the patients treated by BNCT was 20.7 and the median was 15.6 months with 2-years survival of 25%. Stratification by RPA criteria showed 6, 6, 8 and 1 patients, respectively, in classes III-VI. Three patients out of six in class III and one out of eight in class V are alive at the end point of this study. All the patients in classes IV and VI died. Median survival time for the BNCT group compared to the RTOG database was as follows: 20.6 months vs. 17.9 months for class III; 16.9 months vs. 11.1 months for class IV; 13.2 months vs. 8.9 months for class V.
The RTOG RPA prognostic criteria were helpful in establishing which class of glioma patients could potentially benefit from BNCT. BNCT showed a survival benefit in all of the RPA classes of the RTOG database not only for the good prognosis group.
Applied radiation and isotopes: including data, instrumentation and methods for use in agriculture, industry and medicine 03/2009; 67(7-8 Suppl):S15-8. · 1.09 Impact Factor
