Meningiomas are often embolized before their surgical resection to reduce blood loss during surgery. Polyvinyl alcohol (PVA) particles have been the most frequently used material for embolization of meningiomas. We have used n-butyl cyanoacrylate (NBCA) as the first-choice material since 2001. Thirty-one meningiomas were embolized with NBCA. We report the result of embolization of meningiomas with NBCA in comparison with PVA particles.
meningioma, preoperative embolization, n-butyl cyanoacrylate
To evaluate the effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy (BNCT) by measuring the response of intratumour quiescent (Q) cells.
B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumours received reactor thermal neutron beam irradiation following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)] in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation.
BPA-BNCT increased the sensitivity of the total tumour cell population more than BSH-BNCT. However, the sensitivity of Q cells treated with BPA was lower than that of BSH-treated Q cells. With or without a 10B–carrier, MTH enhanced the sensitivity of the Q cell population. Without irradiation, nicotinamide treatment decreased the number of lung metastases. With irradiation, BPA-BNCT, especially in combination with nicotinamide treatment, showed the potential to reduce the number of metastases more than BSH-BNCT.
BSH-BNCT in combination with MTH improves local tumour control, while BPA-BNCT in combination with nicotinamide may reduce the number of lung metastases.
The aim was to evaluate the influence of bevacizumab on intratumour oxygenation status and lung metastasis following radiotherapy, with specific reference to the response of quiescent (Q) cell populations within irradiated tumours.
B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2-deoxyuridine (BrdU) to label all proliferating (P) cells. They received γ-ray irradiation following treatment with the acute hypoxia-releasing agent nicotinamide or local mild temperature hyperthermia (MTH) with or without the administration of bevacizumab under aerobic conditions or totally hypoxic conditions, achieved by clamping the proximal end of the tumours. Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In the other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation.
3 days after bevacizumab administration, acute hypoxia-rich total cell population in the tumour showed a remarkably enhanced radiosensitivity to γ-rays, and the hypoxic fraction (HF) was reduced, even after MTH treatment. However, the hypoxic fraction was not reduced after nicotinamide treatment. With or without γ-ray irradiation, bevacizumab administration showed some potential to reduce the number of lung metastases as well as nicotinamide treatment.
Bevacizumab has the potential to reduce perfusion-limited acute hypoxia and some potential to cause a decrease in the number of lung metastases as well as nicotinamide.
A 60-year-old man with direct carotid cavernous fistula (CCF) due to a motor vehicle accident underwent internal carotid artery trapping following high-flow external carotid to internal carotid artery bypass (EC-IC bypass). Follow-up angiography revealed ipsilateral complex indirect cavernous arteriovenous fistula. Although the traumatic indirect CCF angioarchitecture differs from cavernous-sinus dural arteriovenous fistula (CS-DAVF), the present indirect fistula was similar to the latter. Complex indirect CCF can occur after treatment of direct CCF caused by severe head injury.
traumatic CCF, dural arteriovenous fistula, endovascular treatment
We describe a case of subarachnoid hemorrhage due to a ruptured right vertebral artery (VA) aneurysm where endovascular therapy via a trans-femoral route was not feasible. Therefore we surgically exposed the VA and directly punctured it at the C4 level, followed by successful coil embolization. Direct access to the vertebral artery using an anterior surgical approach is an alternative in cases where the proximal side of the artery is occluded.
vertebral artery aneurysm, coil embolization, surgical exposure, direct puncture
In this article we report a case of desmoplastic ameloblastoma in which chronological changes in the early development can be observed on dental radiographs. The tumour grew very slowly and did not appear to have a strong potential for local extension like typical ameloblastomas. Radiological findings of our case suggest the tumour arose from the periodontal membrane. However, it was not possible to obtain conclusive histopathological evidence.
desmoplastic ameloblastoma; imaging; diagnosis
The purpose of this study was to evaluate the influence of manipulating intratumour oxygenation status and radiation dose rate on local tumour response and lung metastases following radiotherapy, referring to the response of quiescent cell populations within irradiated tumours. B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. They received γ-ray irradiation at high dose rate (HDR) or reduced dose rate (RDR) following treatment with the acute hypoxia-releasing agent nicotinamide or local hyperthermia at mild temperatures (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the quiescent (Q) and total (proliferating + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour-bearing mice, 17 days after irradiation, macroscopic lung metastases were enumerated. Following HDR irradiation, nicotinamide and MTH enhanced the sensitivity of the total and Q-cell populations, respectively. The decrease in sensitivity at RDR irradiation compared with HDR irradiation was slightly inhibited by MTH, especially in Q cells. Without γ-ray irradiation, nicotinamide treatment tended to reduce the number of lung metastases. With γ-rays, in combination with nicotinamide or MTH, especially the former, HDR irradiation decreased the number of metastases more remarkably than RDR irradiation. Manipulating both tumour hypoxia and irradiation dose rate have the potential to influence lung metastasis. The combination with the acute hypoxia-releasing agent nicotinamide may be more promising in HDR than RDR irradiation in terms of reducing the number of lung metastases.
The advent of massively parallel sequencing (MPS) technology has lead to the development of assays which facilitate the study of epigenomics and genomics at the genome-wide level. However, the computational burden resulting from the need to store and process the gigbytes of data streaming from sequencing machines, in addition to collecting metadata and returning data to users, is becoming a major issue for both sequencing cores and users alike. We present WASP, a LIMS system designed to automate MPS data pre-processing and analysis. WASP integrates a user-friendly MediaWiki front end, a network file system (NFS) and MySQL database for recording experimental data and metadata, plus a multi-node cluster for data processing. The workflow includes capture of sample submission information to the database using web forms on the wiki, recording of core facility operations on samples and linking of samples to flowcells in the database followed by automatic processing of sequence data and running of data analysis pipelines following the sequence run. WASP currently supports MPS using the Illumina GaIIx. For epigenomics applications we provide a pipeline for our novel HpaII-tiny fragment enrichment by ligation-mediated PCR (HELP)-tag method which enables us to quantify the methylation status of ∼1.8 million CpGs located in 70% of the HpaII sites (CCGG) in the human genome. We also provide ChIP-seq analysis using MACS, which is also applicable for methylated DNA immunoprecipitation (MeDIP) assays, in addition to miRNA and mRNA analyses using custom pipelines. Output from the analysis pipelines is automatically linked to a users wiki-space and the data generated can be immediately viewed as tracks in a local mirror of the UCSC genome browser. WASP also provides capabilities for automated billing and keeping track of facility costs. We believe WASP represents a suitable model on which to develop LIMS systems for supporting MPS applications.
Dural arteriovenous fistula (d-AVF) is relatively rare. Some cases of atypical locations are often difficult to distinguish from other vascular disorders or tumors because those d-AVFs show various onsets, such as subcortical bleeding and venous infarctions. We encountered two cases of d-AVF with severe brain edema that took adequate time to distinguish from brain tumors. A 68-year-old man visited his local physician complaining of dizziness. He was diagnosed with a cerebral infarction due to the presence of an abnormal cerebellar signal on magnetic resonance imaging (MRI) and was treated by drip infusion. However, he did not recover and was admitted to our hospital with suspicion of a brain tumor. A 75-year-old woman with an onset of progressive dementia and gait disturbance showed severe edema of the right-front temporal lobe on MRI. Both these cases were examined by single photon emission computed tomography or positron emission tomography and were scheduled for craniotomy and biopsy based on the diagnosis of brain tumor. We performed preoperative angiography and found d-AVFs. We embolized the d-AVFs with liquid material and both patients recovered well.
Brain edema from d-AVF or a tumor can be distinguished by carefully reading the MRI with findings such as the distribution of the edemas, differences on diffusion-weighted images, and contrast-enhanced images. Therefore, it is important to provide initial accurate diagnoses to prevent patient mistrust and irreversible disease conditions.
dural arteriovenous fistula, magnetic resonance imaging, tumor, venous congestion
Cl− channels are widely found anion pores that are regulated by a variety of signals and that play various roles. On the basis of molecular biologic findings, ligand-gated Cl− channels in synapses, cystic fibrosis transmembrane conductors (CFTRs) and ClC channel types have been established, followed by bestrophin and possibly by tweety, which encode Ca2+-activated Cl− channels. The ClC family has been shown to possess a variety of functions, including stabilization of membrane potential, excitation, cellvolume regulation, fluid transport, protein degradation in endosomal vesicles and possibly cell growth. The molecular structure of Cl− channel types varies from 1 to 12 transmembrane segments. By means of computer-based prediction, functional Cl− channels have been synthesized artificially, revealing that many possible ion pores are hidden in channel, transporter or unidentified hydrophobic membrane proteins. Thus, novel Cl−-conducting pores may be occasionally discovered, and evidence from molecular biologic studies will clarify their physiologic and pathophysiologic roles.
ClC; CFTR; bestrophin; tweety; volume regulation; Ca2+ activation; pharmacology; knockout mouse
The prevalence of colon cancer has seen strong demand in screening for colorectal neoplasia, and this has drawn considerable attention to the technological advances in Computed Tomographic Colonography (CTC). With the assistance of an oral contrast agent, an imaging technique known as Electronic Cleansing (EC), can affect virtual cleaning of the computed tomography (CT) images, to remove fecal material that is tagged by the agent. Technical problems can arise with electronic cleansing however, when the air lumen causes distortions to the tagged regions which result in partial volume effects.
Combining the simple image arithmetic of an electronic cleansing algorithm, with a vertical motion filter at the fluid level of the bowel, artifacts such as those caused by an air lumen are eliminated. Essentially, the filter becomes a vector for that carries the measurement of vertical motion to neutralise the artifact that is causing partial volume effects. Results demonstrate that despite its simplicity, this technique offers accuracy and is able to successfully maintain the normal intra-colonic structure, while supporting digital leaning of tagged residual material appearing on the colon wall.
Electronic cleansing; CT colonography
We describe a 24-year-old woman who presented with twice previously unverified subarachnoid hemorrhages from the conus me-dullaris spinal arteriovenous malformation with Parkes-Weber-syndrome.
Spinal MRI examination is considered to be necessary for the diagnosis of Klippel-Trenaunay-Weber syndro-me. For diagnosis of the spinal cord arteriovenous malformation, it is indispensable to search carefully for the presence of accompanying lesions. Transarterial glue embolization is effective for the management of the spinal vascular lesion.
spinal arteriovenous malformation, Klippel-Trenaunay-Weber, pseudoaneurysm, embolization
The expression and activity of the epidermal growth factor receptor (EGFR) are determinants of radiosensitivity in several tumour types, including non-small cell lung cancer (NSCLC). However, little is known of whether genetic alterations of EGFR in NSCLC cells affect the therapeutic response to monoclonal antibodies (mAbs) to EGFR in combination with radiation. We examined the effects of nimotuzumab, a humanised mAb to EGFR, in combination with ionising radiation on human NSCLC cell lines of differing EGFR status. Flow cytometry revealed that H292 and Ma-1 cells expressed high and moderate levels of EGFR on the cell surface, respectively, whereas H460, H1299, and H1975 cells showed a low level of surface EGFR expression. Immunoblot analysis revealed that EGFR phosphorylation was inhibited by nimotuzumab in H292 and Ma-1 cells but not in H460, H1299, or H1975 cells. Nimotuzumab augmented the cytotoxic effect of radiation in H292 and Ma-1 cells in a clonogenic assay in vitro, with a dose enhancement factor of 1.5 and 1.3, respectively. It also enhanced the antitumor effect of radiation on H292 and Ma-1 cell xenografts in nude mice, with an enhancement factor of 1.3 and 4.0, respectively. Nimotuzumab did not affect the radioresponse of H460 cells in vitro or in vivo. Nimotuzumab enhanced the antitumor efficacy of radiation in certain human NSCLC cell lines in vitro and in vivo. This effect may be related to the level of EGFR expression on the cell surface rather than to EGFR mutation.
epidermal growth factor receptor; non-small cell lung cancer; nimotuzumab; monoclonal antibody; genetic alteration; radiosensitisation
We describe the treatment and follow-up clinical symptoms and angiographic results in patients with dural arteriovenous fistula of the cavernous sinus treated by transvenous embolization (TVE). We have treated eight cases of dural arteriovenous fistula of the cavernous sinus by multi-staged TVE in two cases and TVE with sinus packing in six and three of six cases were treated with a combination of transarterial embolization. Multi-staged TVE was performed by occlusion from dangerous drainage veins to the cavernous sinus on several occasions.
Angiographical results showed disappearance or reduction of the arteriovenous shunt in all cases. Six patients presented with ophthalmic symptoms and two had tinnitus. Six cases had complete disappearance of clinical symptoms after treatment. There was a deterioration of ocular movement in one patient treated by TVE with sinus packing. Multi-staged TVE was performed to reduce the coil volume for the packing of the cavernous sinus in two cases without cranial nerve palsy. Embolization, especially multi-staged TVE, was considered a good treatment to occlude arteriovenous shunts at the cavernous sinus without cranial nerve complications.
arteriovenous shunt, cavernous sinus, multi-staged embolization
Background: Individual differences in T cell responsiveness to interleukin 12 (IL-12), resulting from inherited factors, may be responsible for differences in the intensity of cell mediated immune (CMI) responses in patients with leprosy, a disease with a wide clinical spectrum.
Aim: Polymorphisms in the 5′ flanking region of the IL12RB2 gene were analysed to determine potential immunogenetic factors affecting CMI responses, using leprosy as a model.
Methods: Polymorphisms in the 5′ flanking region of IL12RB2 were examined using direct sequencing techniques, and allele frequencies between patients with lepromatous leprosy and patients with tuberculoid leprosy were compared. The effect of these single nucleotide polymorphisms (SNPs) on IL12RB2 expression was estimated using the dual luciferase reporter gene assay in Jurkat T cells.
Results: Several SNPs, including −1035A>G, −1023A>G, −650delG, and −465A>G, were detected within the 5′ flanking region of IL12RB2. The frequency of haplotype 1 (−1035A, −1023A, −650G, −464A) was high in the general Japanese population, but was significantly lower in lepromatous patients compared with tuberculoid patients and healthy controls. Reporter gene assays using Jurkat T cells revealed that all haplotypes carrying one or more SNP exhibited a lower transcriptional activity compared with haplotype 1.
Conclusion: SNPs within the 5′ flanking region of IL12RB2 affect the degree of expression of this gene and may be implicated in individual differences in CMI responsiveness to mycobacterial antigens, leading to lepromatous or tuberculoid leprosy.
single nucleotide polymorphisms; IL12RB2; cell mediated immune responses; leprosy; mycobacterial antigens
To investigate the long-term biological effect of extreme low dose ionising radiation, we irradiated normal human fibroblasts (HFLIII) with carbon ions (290 MeV u−1, 70 keV μm−1) and γ-rays at 1 mGy (total dose) once at a low dose rate (1 mGy 6–8 h−1), and observed the cell growth kinetics up to 5 months by continuous culturing. The growth of carbon-irradiated cells started to slow down considerably sooner than that of non-irradiated cells before reaching senescence. In contrast, cells irradiated with γ-rays under similar conditions did not show significant deviation from the non-irradiated cells. A DNA double strand break (DSB) marker, γ-H2AX foci, and a DSB repair marker, phosphorylated DNA-PKcs foci, increased in number when non-irradiated cells reached several passages before senescence. A single low dose/low dose rate carbon ion exposure further raised the numbers of these markers. Furthermore, the numbers of foci for these two markers were significantly reduced after the cells became fully senescent. Our results indicate that high linear energy transfer (LET) radiation (carbon ions) causes different effects than low LET radiation (γ-rays) even at very low doses and that a single low dose of heavy ion irradiation can affect the stability of the genome many generations after irradiation.
low dose; low dose rate; senescence; DNA double strand break; high LET radiation
TZT-1027 is a novel anticancer agent that inhibits microtubule polymerisation and manifests potent antitumour activity in preclinical models. We have examined the effect of TZT-1027 on cell cycle progression as well as the anticancer activity of this drug both in vitro and in vivo. With the use of tsFT210 cells, which express a temperature-sensitive mutant of Cdc2, we found that TZT-1027 arrests cell cycle progression in mitosis, the phase of the cell cycle most sensitive to radiation. A clonogenic assay indeed revealed that TZT-1027 increased the sensitivity of H460 cells to γ-radiation, with a dose enhancement factor of 1.2. Furthermore, TZT-1027 increased the radiosensitivity of H460 and A549 cells in nude mice, as revealed by a marked delay in tumour growth and an enhancement factor of 3.0 and 2.2, respectively. TZT-1027 also potentiated the induction of apoptosis in H460 cells by radiation both in vitro and in vivo. Histological evaluation of H460 tumours revealed that TZT-1027 induced morphological damage to the vascular endothelium followed by extensive central tumour necrosis. Our results thus suggest that TZT-1027 enhances the antitumour effect of ionising radiation, and that this action is attributable in part to potentiation of apoptosis induction and to an antivascular effect. Combined treatment with TZT-1027 and radiation therefore warrants investigation in clinical trials as a potential anticancer strategy.
TZT-1027; radiosensitisation; microtubule; mitotic arrest; apoptosis; antivascular effect
chronic graft versus host disease